02
Jul
09

Israeli fund Accelmed invests in US co OIS

Ophthalmic Imaging Systems will merge with Israel’s MediVision Medical Imaging as part of the deal.

Gali Weinreb

Investment fund Accelmed has invested $6 million in California-based Ophthalmic Imaging Systems Inc. (Bulletin Board: OISI) (OIS). Accelmed chairman Dr. Uri Geiger and chairman of the investment committee Moshe (Mori) Arkin founded the Israeli investment firm.

Besides developing it own products, OIS owns a subsidiary that markets ophthalmic industry computer systems. As part of the deal with Accelmed, OIS will acquire the activities of Israeli ophthalmic products maker MediVision Medical Imaging Ltd. (EuroNM:MEDV), which is OIS’s controlling shareholder. The two companies have been working closely for a long time, and planned to merge a year ago, but did not go through with it. As a result of the present deal, MediVision will basically become a holding company, whose main asset will be about a third of OIS’s shares. OIS will forego a $4.7 million loan to MediVIsion and will also assume a $1 million loan to MediVision from Mizrahi Tefahot Bank (TASE:MZTF).

Accelmed’s investment in OIS is in two parts: $4 million was transferred in late June, and $2 million will be paid in April 2010, subject to OIS meeting certain conditions.

OIS’s board appointed Arkin and Geiger as directors, effective last month.

Geiger told “Globes”, “Accelmed intends to add to OIS a range of additional ophthalmic products.”

OIS was founded 20 years ago, and in addition to its ophthalmic business, it provides informatics solutions for managing patients’ medical reports.

Published by Globes [online], Israel business news – www.globes-online.com – on July 2, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

via Israeli fund Accelmed invests in US co OIS.

01
Jul
09

Stephen Quinn, in memoriam

Kerentech expresses its condolences to our friends at  the Ratner Biomedical Group and Beat Biotherapeutics, as well to Stephen’s widow, Katherin Min and their three children.  We  received this sad news on June 29 through Stephen’s friend, Robert Schumacher.

Stephen Quinn

Stephen Quinn

Follows an article published at  Xconomy, Seattle.

 

Stephen Quinn, Biotech and Medical Device Entrepreneur, Dies Suddenly at 46

Luke Timmerman 6/30/09

Xconomy is sad to report that Stephen Quinn, an emerging biotech and medical device entrepreneur in the Northwest, died suddenly at his home in Redmond, WA, on Sunday. He was 46.

The cause of death is unknown. Paramedics found Quinn at home on Sunday afternoon with no pulse, and rushed him to Overlake Hospital Medical Center, where doctors were unable to revive him, says Buddy Ratner, a University of Washington bioengineering professor. Ratner has collaborated with Quinn to start five local biomedical companies over the past three years.

“It’s a tragedy,” Ratner says. “I’m devastated.”

Quinn joined Ratner Biomedical Group in July 2006, after spending the previous nine years at Microsoft as a test manager in the SQL Server Business Intelligence Unit, according to his LinkedIn profile. Along with Ratner, Quinn played a founding role in starting Healionics, Calcionics, Inson Medical Systems, Ratner Biomedical Inc., and the latest spinoff company, Beat Biotherapeutics.

The news comes as a shock to me personally, because I spoke with Quinn at length over the phone just a couple weeks ago when I profiled BeatBio, a company that aims to make make stem cells to repair damaged heart tissue. Quinn sounded full of optimism that his new company had potential to treat millions of people with heart failure. He had found a creative way to support the company through a partnership with Bellevue, WA-based Hope Heart Institute, which he thought would help the company reach milestones needed to get venture capital in the future. He understood how difficult a stem cell company would be, and even told me at the time, “Somebody’s got to be crazy enough to take stem cell therapies to the market.”

“He felt life was a little tame at Microsoft, and at his age, he wanted bigger challenges,” Ratner says. “He had a fine job, but he wasn’t that excited about it. He became quite excited about the opportunities he saw being an entrepreneur.”

Greg Mahairas, an immunologist at the Fred Hutchinson Cancer Research Center who was collaborating with Quinn on BeatBio, says he’s still shocked by the news after he had dinner with Quinn to talk about their business plan a week ago.

“We had big plans, and he saw big potential,” Mahairas says. “He was always positive about things, and saw potential everywhere.”

Quinn is survived by his wife and three children. The family requests no flowers, although a memorial service is being scheduled for 6 pm on Thursday, with a location yet to be determined, Ratner said.

Luke Timmerman is the National Biotechnology Editor for Xconomy. You can e-mail him at ltimmerman@xconomy.com, call 206-624-2374, or follow him on Twitter at http://twitter.com/ldtimmerman.

30
Jun
09

Israeli Government biotech fund tender set for September

The government hopes to raise up to NIS 1 billion  ($ 250 M)  for the new fund.

Gali Weinreb

Sources inform “Globes” that the tender for the establishment of a government biotech fund will be published on September 15. The Office of the Chief Scientist today published the official announcement concerning the setting up of the fund. The announcement stipulated that the fund will be managed like a VC fund.

The Israeli government will invest NIS 250 million in the new fund (NIS 125 million from the Ministry of Finance and NIS 125 million from the Chief Scientist’s budget).

The aim is to raise more capital from private sources, mainly institutional investors, so that the total fund will reach NIS 750 million NIS 1 billion.

Published by Globes [online], Israel business news – www.globes-online.com – on June 30, 2009

via Govt biotech fund tender set for September « Catalonia-Israel Commerce Chamber.

30
Jun
09

Study shows therapeutic effects of Compugen peptide

Professor Markus F. Neurath : If these results continue to be confirmed in further studies, this molecule should represent a very exciting drug candidate for this substantial medical need.

Globes’ correspondent

Drug discovery company Compugen Ltd. (Nasdaq: CGEN; TASE: CGEN) said today that its CGEN-25007 peptide has shown positive therapeutic effects in an animal model of inflammatory bowel disease (IBD).

Prof. Markus F. Neurath

Inflammatory bowel disease is a commonly used term covering ulcerative colitis and Crohn’s disease.

CGEN-25007 is a novel peptide antagonist of gp96 with potent anti-inflammatory activity. It was initially discovered using Tel Aviv-based Compugen’s disease-associated conformation blockers discovery system. This system was designed to find peptides that block proteins from achieving certain disease-associated conformations, a capability that represents immense therapeutic promise in numerous fields.

In a recent study, administration of CGEN-25007 protected mice from the effects of lethal colitis. These results suggest that CGEN-25007 could have a potential therapeutic utility to treat IBD and other autoimmune diseases with a strong inflammatory component, such as rheumatoid arthritis.

University of Erlangen, Germany Professor Markus F. Neurath, who supervised the study, said, “If these results continue to be confirmed in further studies, this molecule should represent a very exciting drug candidate for this substantial, and largely unmet, medical need.”

Inflammatory bowel disease is a chronic, relapsing and remitting inflammatory condition, affecting around two million people. In the US, IBD is one of the most prevalent gastrointestinal disease burdens.

Compugen shares closed yesterday at $1.21, giving a market cap of $34.5 million.

Published by Globes [online], Israel business news – www.globes-online.com – on June 23, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

via Study shows therapeutic effects of Compugen peptide.

30
Jun
09

Protein may open door to new drugs

By John P. Mello Jr., Globe Correspondent 

 A protein found on brain cells, known to contribute to nicotine addiction, may also be the key to developing drugs for a wide range of diseases and medical conditions, including obesity, schizophrenia, and Alzheimer’s disease.

	Brown University professor Edward Hawrot is the studys lead author. (John Abromowski / Brown University)

Brown University professor Edward Hawrot is the study's lead author. (John Abromowski / Brown University)

 In a recent study, researchers at Brown University in Providence discovered the protein, called the alpha-7 receptor, has a previously unsuspected wide-ranging influence on processes within the body.

 It affects dozens of cellular interactions and interacts with 55 other proteins, including a separate class of receptor that is a target for about 40 percent of all therapeutic drugs.

 “These [receptors] as a group are very important because they control a lot of critical functions, like heart rate,’’ said Edward Hawrot, the study’s lead author and a professor of molecular science, molecular pharmacology, physiology, and technology at Brown. “What was surprising was that we saw a connection between [the] proteins, because these two receptor families are very, very different.’’

 Alpha-7 receptors have long been known, but their function was something of a mystery until the Brown researchers revealed their importance.

 “They’ve learned that these nicotinic receptors have a profound influence on other systems in the body,’’ said J. Donald deBethizy, chief executive of Targacept in Winston-Salem, N.C., which makes drugs that target receptors.

 DeBethizy said the Brown research shows “the alpha-7 receptor may be at the apex of many, many important biological responses.’’

 The alpha receptor is like a doughnut on the surface of a cell. The “hole,’’ normally closed, opens when it comes into contact with acetylcholine, a neurotransmitter, or a chemical that acts like a trigger for various activities within the cell. Acetylcholine occurs naturally in the body, but its effects can be mimicked by nicotine, which is why alpha-7 and its relatives are called nicotinic receptors.

 The Brown research indicated that alpha-7 drugs could provide a way to compensate for the loss of acetylcholine in Alzheimer’s disease and similar afflictions.

 “When you don’t have enough acetylcholine released to activate the receptors, people can’t remember and they have cognitive impairment,’’ said Merouane Bencherif, vice president at Targacept. “What we would do is provide a drug that is not metabolized that acts on nicotinic receptors. So essentially, you’re compensating for the deficit that exists in Alzheimer’s disease.’’

 DeBethizy said the “alpha-7 target is a very hot area in neuroscience,’’ but approved drugs aimed at the receptor have had an unforeseen downside: They react with another receptor system, causing nausea and gastrointestinal side effects.

 Targacept has had some success with drugs targeting other alpha class receptors, including one now in early clinical trials that has shown promise in treating the effects of aging, he said.

 The company is also working on an alpha-7 drug for treating cognitive dysfunction in schizophrenics, one of the leading reasons “schizophrenics can’t function better even when they’re being treated with [an] antipsychotic,’’ deBethizy explained.

 It’s estimated 90 percent of schizophrenics smoke. That’s because the nicotine has therapeutic effects for schizophrenics that it doesn’t have for others, said Tony George, a professor of psychiatry at the University of Toronto Centre for Addiction and Mental Health.

 “For schizophrenics, it will remedy deficits in memory and attention functions,’’ said George. He said a drug that could provide the benefits of nicotine to schizophrenics without tobacco would be beneficial.

 “Tobacco addiction is now the leading reason why people with schizophrenia die,’’ he said. “They succumb to tobacco-related illness.’’

29
Jun
09

Down to the bone

Posted by Elie Dolgin

A fusion protein that ferries a healthy version of a bone-related enzyme gone awry has shown early clinical success in treating a rare bone disorder with no known therapy, researchers reported earlier this month at the Endocrine Society’s annual meeting in Washington, DC. The drug — which is essentially a protein-based enzyme delivery mechanism — could open the door to treatments of other skeletal disorders that have so far been deemed untreatable.

“This is probably the most promising approach so far” for metabolic bone disorder therapies, Sundeep Khosla, an endocrinologist at the Mayo Clinic in Rochester, Minn., who was not affiliated with the work, told The Scientist.

The new therapy targets a rickets-like disease called hypophosphatasia (HPP), which is caused by a single mutation in the gene coding for an enzyme known as tissue non-specific alkaline phosphatase, or TNSALP. Developed by Enobia Pharma, a biotech company in Montreal, Canada, it is based on a fusion protein that contains the active portion of TNSALP merged with a small acidic peptide chain that targets the drug to bone, the site of enzymatic activity. In healthy people, TNSALP is normally tethered to the outside of bone- and cartilage-forming cells where it breaks down phosphate. But in HPP patients, the enzyme doesn’t fold properly, which leads to a build up of several phosphate-containing compounds in blood and urine, and produces a range of clinical symptoms including softer bones, shorter limbs, respiratory problems, premature tooth loss, and often infant death.

Michael Whyte, a medical researcher at Washington University’s School of Medicine in St Louis, Missouri, who consults for Enobia, announced the results of a Phase I trial involving afflicted adults and an ongoing efficacy trial in severely-affected HPP infants. In both studies, patients took to the medication well, and the first two infants to receive regular doses of the drug showed substantial bone mineralization and improved breathing abilities, Whyte reported at the meeting.

Enobia came up with the fusion construct in 2005. At the time, the company was working on a similar delivery vehicle to treat X-Linked Hypophosphatemic Rickets (XLH), a disease closely related to HPP that is also caused by a single aberrant enzyme. The XLH therapy, however, wasn’t effective in a mouse model of the disease. They then switched to HPP and the enzyme replacement therapy “worked right from the first experiment,” said Philippe Crine, Enobia’s chief scientific officer. “It was really spectacular.” Crine doesn’t know exactly why the drug platform worked for one disease and not the other, but he is confident that the same bone-targeting technology should be effective in treating other related bone disorders.

In the past, clinicians have tried several approaches to tackling HPP, including vitamin D supplements and bone marrow transplants, but all these therapies failed. Researchers also injected TNSALP intravenously, but again with no success; the infused enzyme “kind of gets into the bloodstream, but it goes all over the place,” said Khosla. “Being able to actually target therapeutic compounds to bone just hasn’t been easy. Part of technical problem has been finding the right carriers, and [Enobia] seems to have found one.”

Last year, a team led by Whyte, Crine, and José Luis Millán, a molecular geneticist at the Burnham Institute for Medical Research in La Jolla, Calif., published preclinical results showing that subcutaneous injections of their fusion protein drug mopped up phosphates floating in the blood and significantly improved survival and bone formation in knockout mice with a severe human infant-like form of HPP.

Enobia and its partners are now investigating the efficacy of different doses of the medication in their mouse models, as well as letting the mice develop for a couple of weeks before administering the drug, instead of treating them directly after birth. This is important because humans with the rare disorder often go months or years before being properly diagnosed. Early results show that the late-treated mice also have improved bone function and live longer, although not to the same extent as mice given the drug right away. “The bottom line,” said Millán, “is that treatment is good even if conferred very late.”

The drug — which is being manufactured by Princeton, NJ-based Laureate Pharma — was granted an orphan drug designation by the US Food and Drug Administration last October, and a fast track designation in May to help speed along its clinical development. The company plans to start Phase II adult trials later this summer.

29
Jun
09

Australian scientists kill cancer cells with “trojan horse”

By Michael Perry

SYDNEY (Reuters) – Australian scientists have developed a “trojan horse” therapy to combat cancer, using a bacterially-derived nano cell to penetrate and disarm the cancer cell before a second nano cell kills it with chemotherapy drugs.

Dr Jennifer MacDiarmid and

Dr Jennifer MacDiarmid and Dr Himanshu Brahmbhatt, who formed EnGenelC Pty Ltd in 2001

 The “trojan horse” therapy has the potential to directly target cancer cells with chemotherapy, rather than the current treatment that sees chemotherapy drugs injected into a cancer patient and attacking both cancer and healthy cells.

 Sydney scientists Dr Jennifer MacDiarmid and Dr Himanshu Brahmbhatt, who formed EnGenelC Pty Ltd in 2001, said they had achieved 100 percent survival in mice with human cancer cells by using the “trojan horse” therapy in the past two years.

 The scientists plan to start human clinical trials in the coming months. Human trials of the cell delivery system will start next week at the Peter MacCullum Cancer Center at the Royal Melbourne Hospital and The Austin at the University of Melbourne.

 The therapy, published in the latest Nature Biotechnology journal, sees mini-cells called EDVs (EnGenelC Delivery Vehicle) attach and enter the cancer cell.

 The first wave of mini-cells release ribonucleic acid molecules, called siRNA, which switch off the production of proteins that make the cancer cell resistant to chemotherapy.

 A second wave of EDV cells is then accepted by the cancer cell and releases chemotherapy drugs, killing the cancer cell.

 ”The beauty is that our EDVs operate like ‘Trojan Horses’ They arrive at the gates of the affected cells and are always allowed in,” said MacDiarmid.

 ”We are playing the rogue cells at their own game. They switch-on the gene to produce the protein to resist drugs, and we are switching-off the gene which, in turn, enables the drugs to enter.”

 DISARMING TUMOUR CELLS

 RNA interference, or RNAi, is designed to silence genes responsible for producing disease-causing proteins and is one of the hottest areas of biotechnology research. RNA was the basis of the 2006 Nobel Prize in medicine.

 Dozens of biotechnology companies are looking for ways to manipulate RNA to block genes that produce disease-causing proteins involved in cancer, blindness or AIDS.

 Brahmbhatt said that after treatment with conventional drug therapy, a large number of cancer cells die but a small percentage of the cells can produce proteins that make cancer cells resistant to chemotherapeutic drugs.

 ”Consequently, follow-up drug treatments can fail. The tumors thus become untreatable and continue to flourish, ultimately killing the patient,” said Brahmbhatt.

 ”We want to be part of moving toward a time when cancers can be managed as a chronic disease rather than being regarded as a death sentence,” he said.

 The Nature report said the mini-cells were “well tolerated with no adverse side effects or deaths in any of the actively treated animals, despite repeated dosing.”

 ”Significantly, our methodology does not damage the normal cells and is applicable to a wide spectrum of solid cancer types,” said MacDiarmid.

 ”The hope is that the benign nature of this EDV technology should enable cancer sufferers to get on with their lives and operate normally using out-patient therapy.”

 (Editing by Alex Richardson)

29
Jun
09

Transcend Medical Raises $35 Million Series B Round Towards Development of Novel Glaucoma Treatment

MENLO PARK, Calif., June 22 /PRNewswire/ — Transcend Medical, Inc., an ophthalmic device company dedicated to delivering breakthrough advances in the treatment of glaucoma, announced today that it has closed a $35 million Series B round and is continuing the rapid development of its Transcend CyPass(TM) System, a novel proprietary system for the minimally-invasive treatment of glaucoma.

Lead investor HLM Venture Partners, along with other new investors Canaan Partners, Technology Partners and Latterell Venture Partners made significant contributions to this round of financing, which was also strongly supported by current investors Morgenthaler Ventures and Split Rock Partners.

 ”Completing this round is a testament to the progress of our technology and a strong validation of its potential to impact the future of glaucoma treatment,” said Brian Walsh, President and Chief Executive Officer of Transcend Medical. “We are now well-capitalized to accomplish all initial clinical and commercial milestones for the company.”

 The Transcend CyPass System is being developed to both replace current glaucoma therapies, which either lack effectiveness or are very invasive, and to expand treatment to a much larger patient population. Transcend Medical is focused on a less invasive procedure using a novel, proprietary system that reduces intraocular pressure (IOP).

 ”There is a significant need to improve how we treat glaucoma,” commented Eugene de Juan, Jr., M.D., Jean Kelly Stock Distinguished Professor of Ophthalmology at UCSF and Founder of Transcend Medical. “Today’s treatment options for glaucoma are highly limited and only feasible in a limited portion of those affected by the disease worldwide.”

 ”We are encouraged by the CyPass System’s minimally invasive delivery which is of significant benefit to patients, provides important ease of use features for physicians, and could result in earlier intervention in the glaucoma disease process,” added Ike Ahmed, M.D., Assistant Professor, University of Toronto who is a world renowned glaucoma specialist and a clinical investigator of the CyPass System. “The CyPass System has shown promising initial results in a challenging population, with a very straight-forward procedure. We have been quite impressed with our experience to date in this growing patient group.”

 About Transcend Medical, Inc.

 Transcend Medical (www.transcendmedical.com) is focused on the research and development of medical devices for the treatment of glaucoma, the leading cause of adult irreversible blindness. It is estimated that nearly four million people in the U.S. and 70 million worldwide are afflicted with the disease today and the numbers are expected to grow to nearly six million in the U.S. and to over 80 million worldwide by the year 2013. Based in Menlo Park, Calif., Transcend Medical was the first company to be spun out of ForSight Labs (www.forsightlabs.com), an incubator solely focused on ophthalmic innovations.

 SOURCE Transcend Medical, Inc.

28
Jun
09

‘Surprise’ prostate result probed

Researchers are probing an unexpected success in a study of an experimental treatment for prostate cancer.

Prostate cancer kills 10,000 men in the UK each year

In three men with advanced disease, use of an immune drug called ipilimumab, shrank their tumours to such an extent surgeons were able to operate. The Mayo Clinic team in the US said the “startling” results in the study of 108 men had prompted them to set up a second trial using higher doses. One UK expert said there were currently few treatments for advanced disease In men with advanced prostate cancer, which has spread outside the prostate, surgery cannot usually be done. If these early and small scale results are replicated in larger trials, this represents a potentially very exciting development. Hormone therapy is usually given to try to shrink the tumour to some degree and buy some time. The trial was set up to see if MDX-010, a type of drug called a monoclonal antibody, would improve on hormone treatment. The idea is that the drug will encourage a strong immune response to attack the cancer cells. Half the men had normal therapy and half also received MDX-010. In three cases, where the experimental drug was given, the tumours shrank dramatically, enabling surgeons to operate and remove the tumour. There are 20 other patients who are showing improvements and who are being monitored by the surgeons.

If these early and small scale results are replicated in larger trials, this represents a potentially very exciting development.

John Neate, The Prostate Cancer Charity

‘Preliminary’

 Dr Eugene Kwon, a surgeon at the Mayo Clinic in Rochester, said the results in those men were well beyond their expectations.”Our surgeons had never seen this happen before and we were really taken by surprise.”They are now planning a trial in 30 men to test higher doses of the drug and hope to start much larger trials across many hospitals shortly after.Dr Michael Blute, study leader and the surgeon involved said: “I had never seen anything like this before. I had a hard time finding the cancer.”At one point the pathologist (who was working during surgery) asked if we were sending him samples from the same patient.” Until large scale studies are carried out it is unclear whether this response can be repeated in other patients or is an anomaly. But John Neate, chief executive of The Prostate Cancer Charity said they would wait for further results with anticipation. “If a cancerous tumour has spread beyond the prostate gland, it would currently be regarded as inoperable and alternative types of treatment, typically hormone therapy are necessary. “We urgently need a wider range of treatment options for prostate cancer which has spread outside the prostate gland. “It must be remembered that this is a small trial however, and the findings are preliminary.”

BBC

28
Jun
09

Glaxo CEO admits R&D overhaul has been traumatic

* Witty says morale a year ago was “terrible”

 * Now seeing quantitative and qualitative R&D benefits

 * Need for industry to be much more flexible on drug pricing

 By Ben Hirschler

 LONDON, June 19 (Reuters) – GlaxoSmithKline’s (GSK.L: Quote, Profile, Research, Stock Buzz) chief executive acknowledged on Friday that overhauling its drug discovery machine had been traumatic but said “turning back the clock” on R&D was now delivering results.

 ”It’s been a major upheaval and I’d be the first to admit that a year ago morale in our discovery organisation was not very good, in fact it was terrible,” Andrew Witty told a healthcare conference.

 Witty took over as head of the world’s second-largest drugmaker in May 2008 with a promise to create much smaller scientific teams and to move away from industrial-scale drug discovery processes.

 The upheaval involved job losses in the company’s core research and development (R&D) organisation, angering some staff.

 ”Many of the people we had in the discovery organisation left in the period of change, either through their own volition or because they were not up to operating in the kind of way I have described,” Witty said.

 ”Today, a year or so later, I’m shocked at how fast this has bedded down.”

 Glaxo is now synthesising more molecules against more disease targets than ever before and there are qualitative signs of improvement, with teams taking a more lateral approach to problem solving.

 It has been a radical shift.

 ”We’ve really thrown into reverse much of the trend of research organisation that had developed over the last 15 years,” Witty said.

 Over that time, the drugs industry was a big commercial success but it took a “wrong turn” by deciding that drug discovery was an industrial process based on large-scale application of technologies like genomics, proteomics and combinatorial chemistry.

 ”These were all supposed to transform productivity yet none of them did. It turns out, in my view, that research is much more of an art than a science,” Witty said.

 Pharmaceutical companies around the world are struggling to find a new business model as blockbuster drugs brought to market in the 1990s face patent expiry at a time when new ones prove harder and harder to develop.

 On top of that they are having to adapt to a period of austerity and healthcare reform in major markets — most notably the United States — which Witty reiterated would require a much more flexible approach to drug pricing. (Editing by Andrew Macdonald)

17
Nov
08

Solvay discontinues research into potential obesity compound

17 Nov 2008

Solvay has discontinued all research and development activities relating to a potential obesity treatment.

The company’s investigational compound SLV319 was in phase-two development and, according to the company, recent results had “confirmed its clinical activity and its efficacy”.

In the recent announcement of its financial results for the first nine months of the year, the firm had indicated that it was assessing its next step with regard to the compound.

“While the discontinuation is not related to any adverse events or the efficacy of the compound, we have made this decision after careful evaluation of the current regulatory environment ,” commented Dr Claus Steinborn, head of global research and development.

A compound in its class now faces “new and high regulatory hurdles”, he added.

Solvay recently revealed that its group net income for the first nine months of the year was down by 34 per cent compared to the same period in 2007.

It posted stable group sales of just over 7.2 billion euros (£6.1 billion

19
Nov
08

AstraZeneca Nobel Medicine Initiative to Increase Interest in the Nobel Prize in Physiology or Medicine

Global Initiative Will Highlight Benefits of Scientific Breakthroughs to Human Health and Feature Lecture Events, Interactive Educational Content, and Broadcast Documentaries to the General Public

 

STOCKHOLM, November 11, 2008 /PRNewswire/ — AstraZeneca AB, Nobel Media AB and Nobel Web AB today announced the launch of a global co-operation that aims to increase the general public’s understanding of and interest in the achievements of the Nobel Laureates within the fields of Physiology or Medicine and to further explain the benefits of the discoveries made. The AstraZeneca Nobel Medicine Initiative will enable the general public worldwide to learn directly from Nobel Laureates in Physiology or Medicine by combining live lecture events, interactive educational content and broadcast documentaries. The co-operation is for three years starting 2008.

“I am very pleased and proud of this collaboration” says Jan Lundberg, Executive Vice Pesident, Global Discovery Research, AstraZeneca. “It is truly an honour to be able to contribute to an increased understanding of what medical breakthrough science can mean for new treatments to enhance patient health and wellbeing – and to do this in partnership with Nobel Media and Nobel Web.”

“We are very happy for this great and promising co-operation with AstraZeneca supporting Nobel related programming reaching a global audience. We hope by this initiative, to enhance people’s interest for these discoveries and their impact on all our lives,” said Camilla Hylten-Cavallius, Chief Executive Officer, Nobel Media.

“Our exciting new co-operation with AstraZeneca supports and contributes to Nobelprize.org’s educational outreach mission to provide interactive tools to inspire and encourage interest about the achievements behind the Nobel Prize in Physiology or Medicine,” said Alf A. Lindberg, Chief Executive Officer, Nobel Web.

The AstraZeneca Nobel Medicine Initiative will consist of three core elements:

 

·         Lecture Events: AstraZeneca, in co-operation with Nobel Media and Nobel Web, will host a lecture event with the current year’s Nobel Laureates in Physiology or Medicine at selected AstraZeneca research centers worldwide.

·         Visiting Nobel Laureates will participate in an interview, lecture, and

·         Question and Answer session.

 

The lectures events will be made available on www.astrazeneca.com and Nobelprize.org.

 

Interactive Educational Content in Physiology or Medicine: Nobel Web will create, with the support of AstraZeneca, an educational Internet production per year called a Nobel Prize Narrative which will reflect the Nobel Prize in Physiology or Medicine and will place a series of related Nobel Prizes in a broader context, exploring the evolution of the discipline. The educational content will be accessible on Nobelprize.org.

Documentaries in Physiology or Medicine: Nobel Media will produce, with the support of AstraZeneca, one broadcast documentary per year on a topic related to the Nobel Prize in Physiology or Medicine.

 

23
Nov
08

Johnson & Johnson acquires Omrix Biopharmaceuticals

globes1

The US giant will pay $465 million for the Israeli company, which develops biosurgical sealants.
Shiri Habib-Valdhorn and Gali Weinreb 23 Nov 08 18:06
Sources inform ”Globes” that Johnson & Johnson Inc. (NYSE: JNJ) has acquired Israeli biopharmaceutical company Omrix Biopharmaceuticals Ltd. (Nasdaq:OMRI), bringing to an end eight years of partnership between the two companies and several months of acrimonious negotiations and endless rumors. Johnson & Johnson will reportedly pay $27 a share for Omrix, which develops and produces biosurgical sealants for the prevention of homeostasis in surgery, giving it a value of $465 million.The rumors of an imminent sale broke at the end of last week, after a team from Ethicon Inc. the Johnson & Johnson subsidiary partnering with Omrix arrived in Israel and began a thorough review of the company. The rumors sent Omrix’s share price up almost 30% on Friday to $21.20 in trading on Nasdaq.As first reported by “Globes”, Johnson & Johnson has been in talks on the acquisition of Omrix for a number of months, following an eight-year partnership between the two during which the idea of a sale was repeatedly broached.The atmosphere of the talks has been highly charged in recent months, with Omrix founder president and CEO Robert Taub initiating talks with other potential suitors in a bid to up the company’s price. Among the companies approached were German drug giant Bayer AG (LSE: BYR; XETRA: BAY), and Ofer Group, but these talks apparently did not progress to a concrete offer and did not pose a real threat to the deal with Johnson & Johnson.Omrix has confirmed the report. Taub will receive $100 million.Published by Globes [online], Israel business news – www.globes-online.com – on November 23, 2008© Copyright of Globes Publisher Itonut (1983) Ltd. 2008
23
Nov
08

Compugen: Rising Against the Storm

bio-it-world 

 By John Russell

Nov. 13, 2008| Technology company creation is such a craps shoot. One roll of the dice is nearly never enough to sort out the right business model or product mix, and Compugen, founded in 1993, has had a few tosses.

In February of 2005, this predictive informatics pioneer declared it would dump its technology licensing and fee-based services business model. It wasn’t working particularly well anyway – and not just for Compugen. Instead, the company would become a discovery engine. It would discover molecules (and markers) and license them to biopharma. It would only enter collaborations where revenue was predominantly based on milestones, royalties, and IP.

If this sounds like what many technology platform sellers were saying at the time, that’s because it is. Products (drugs) were hot. Services and software were not. Alex Kotzer, a longtime Serono executive, was brought in as Compugen president and CEO in April of 2005 and charged with delivering the new strategy. For background, see Compugen Transfoms Its Business).

So how’s it going?

That’s a tough question. Revenue is not yet gushing in. The company’s stock plunged – whose hasn’t? – and was trading under $1/share at this writing. This week, Chairman Martin Gerstel provided nervous investors with his plans for maintaining operations without seeking funds from an equity market which he says badly undervalues Compugen.

The company will cut costs 30 percent, reducing its burn rate to around $8 million; it has about $10.3 million in cash, enough for a year and a half or so. Layoffs are part of the cost-cutting. So is slowing plans for new discovery platforms and focusing more, at least near-term, on R&D collaborations and less on internal development. Plus, Kotzer is retiringfrom president and CEO in January although he will remain on the board, and Gerstel will assume those responsibilities.

Compugen is being battered by the same horrific financial storm that is pounding everyone.

That’s the bad news.

The good news is that Tel Aviv-based Compugen has very much to crow about. It has stuck largely to the new strategy. It increased the number of its in silico “discovery platforms” to 10; they are broadly divided between therapeutics and diagnostics,and include one for drug repositioning. Compugen has discovered several molecules which served the twin purpose of validating the predictive platforms and are now being shopped around. The company is working with nine collaborators, including heavyweights Roche and Merck.

That’s a lot of progress. The plate sounds almost too full – a criticism Kotzer has heard but dismisses: “People ask us why we are not focused on one area, or why we are not focusing on two molecules, which is common in this industry. We believe that this business model will give us a much higher chance to succeed.”

Compugen firmly believes it is leading a “paradigm shift” away from serendipitous high-throughput-screening based discovery to computationally-based true predictions. “The industry must get there, even if Compugen doesn’t,” said Gerstel on this week’s investor call.

The challenge now is to survive the storm and drive revenues; Kotzer and Gerstel are bullish about both.

“Basically the way we work is to identify an unmet need, identify our capabilities that can add value, and decide whether to do the discovery platform,” says Kotzer. Once a platform is built, “our computer (platform) predicts candidates and we select two of them and take them to the lab. So if it is a peptide, we produce them and we test them in vitro and in vivo in some animal or human disease models. Only when we have good results do we say we have a platform.”

For example, consider Compugen’s GPCR peptide ligand discovery platform. It has a proprietary ‘peptidome’ of thousands of novel human peptide sequences, expected to correspond to natural peptides based on computationally “predicted novel cleavage sites in precursor proteins.” Using machine learning techniques, Compugen mined the peptidome for likely activators. Thirty-three were screened against a panel of 152 GPCRs, and eight of the peptides activated six GPCRs, some for which there are no known endogenous ligands.

Two of the peptides – CGEN-856 and CGEN-857 – induced calcium flux in Mas-transfected cells and Compugen says they have no significant homology to known GPCR ligands or to each other. These peptides were later shown to have cardio-protective effects in vivo. Since then, Compugen has found another seven peptides that activate GPCRs.

Yossi Cohen, Compugen VP of research and development, says, “[The platform] can predict novel peptides in general, indigenous peptides, or given a long list of potential indigenous peptides, it can find a small subset that are likely to be GPCR related or GPCR agonists.”

The GPCR platform is one of six aimed at finding new therapeutics. Here is Cohen’s brief description of the others: 

Disease Associated Conformation (DAC) Peptide Blockers Platform. “[Here] we model segment-segment interaction in proteins. If the conformation of the protein is important for the protein activity, you may block the conformation by taking one of the segments and using it as an artificial peptide to block the folding and inhibit the protein. This discovery capability is unrelated to machine learning. It relies on all kinds of statistical analysis of multiple alignments of proteins.”

Viral Peptides Platform. Using viral DNA searching and analysis and other informatics tools, “we predict new peptides that are produced by viruses and search for those likely to have anti-inflammatory capabilities.” Others companies also do this. Cohen says Compugen’s ability to find the needles buried in the haystack of possibilities is distinctive.  

Novel Proteins Platform.“This is based on [our] LEADS platform looking for new splice variants that for all kinds of reasons we believe are likely to have therapeutic effects, and these proteins are novel proteins for which we have an IP position, and then we take them into the experimental laboratory.”

Targets for Monoclonal Antibodies Platform. “If you want to develop a new monoclonal antibody drug, having a very good target is a key. We use a variety of discovery capabilities to find novel targets. Basically, we are focusing on cancer-related indications and anti-inflammatory indications.”

The final therapeutics platform is Compugen’s new indication platform, launched a year and a half ago. “Given an already known molecule, we predict a new therapeutic indication. We make sure that this prediction is novel by looking at all the related patents and then we go into the lab and show that this molecule is indeed having the new therapeutic indication,” says Cohen.

Medarex (MAB targets for oncology and autoimmune disease) and Merck (GPCR activators) both have ongoing therapeutics-oriented collaborations with Compugen. Kotzer hopes to grow the number of collaborators substantially over the next 12 months. He won’t set a target but says something approaching 15-20 would be good. Like many in the biotech world, Compugen hopes downsizing in pharma will increase its R&D outsourcing.

Other current collaboratorsinclude Biosite, Ortho-Clinical Diagnostics, Roche, Siemens Healthcare Diagnostics, and Teva Pharmaceuticals.

It worth noting that for awhile, Compugen was really three companies. Evogene was created in 2002 to apply Compugen’s original LEADS technology to plant genomics. It went public (June 2007) on the Tel Aviv Stock Exchange and, roughly a year ago, Monsanto bought a big chunk ($18 million) of Evogene stock with an agreement to buy another $12 million in the future. The stock purchase diluted Compugen’s stake to about 10 percent. Compugen receives revenues but has no management role. It should be said that Gerstel is Evogene’s chairman, too.

Kotzer says the Monsanto-Evogene deal is a good model for Compugen. “Monsanto’s [stock] purchase was three-fourths higher than the current market value of the company, then Monsanto guaranteed to pay $5 million a year for discovery to be done for their behalf, and on top of it Monsanto will pay royalties and milestones for success.”

He bristles slightly at the suggestion this could be seen as a kind of takeover. “This is not what I said. I said once the industry realizes the value we have in-house, the different way we do discovery, the way we use predictive discoveries other than random or high-throughput screening or whatever it is, companies will want broader deals.

“All the collaborations we have made so far are based on specific discovery platforms. The next generation of collaborations we are looking for is wider,” Kotzer emphasizes. “A company will do a strategic agreement with us. They will put money in our company that we will spend on building discovery capabilities they would like us to build for them. This is where we are aiming at the end of the day.”

The third ‘piece’ of Compugen was Keddem Biosciences. It was first the company’s chemistry division (2000) and was later (2004) established as a small-molecule discovery subsidiary. “There are no ongoing activities at the moment. I think we discussed it in one of our conference calls. We have all the IP and all the rights and are looking for an opportunity to invest again in this,” says Kotzer.

Rounding out Compugen’s portfolio are its diagnostic discovery platforms, not surprisingly focused on biomarkers. There are four: genetic variation; drug induced toxicity; immunoassay; and nucleic acid testing.

Roche is working with Compugen on the genetic variation front, looking for drug response markers for rheumatoid arthritis patients.

Says Cohen, “We’ve also developed a capability to predict variation de novo, meaning given a DNA sequence we can quite successfully guess the area likely to be variable between individuals and go to that area specifically and look if there is a gene there, for example, which is relevant for the clinical problem we want to solve. I would say that about three-quarters of the capability is in silico and a quarter of it is laboratory related.”

The immunoassay effort looks for protein disease markers in the blood. The nucleic acid testing seeks markers that can be found in the diseased tissue. Both initiatives leverage Compugen’s LEADS technology. Current collaborators working on tox markers include Siemens, OCD, and Biosite. Compugen has even talked about licensing its tox-related platforms testing labs.

“With our inventory of 10 validated product candidate discovery platforms addressing key unmet needs in the drug and diagnostic markets, and the core capability to systematically approach other discovery needs, we feel we are now well positioned to enter into broader collaborations that will more fully leverage these capabilities and offer unique advantages to both Compugen and its partners,” says Gerstel.

To repeat: Technology company creation is often a craps shoot. One roll of the dice is nearly never enough and Compugen believes it’s ready to roll again. Place your bets.

25
Nov
08

Regenerating Neurons in Eyes

 mit-technology-review

 

Researchers stimulate the growth of new retinal cells in mice.

By Amanda Schaffer

Cells in the retina of mice can be coaxed to create new neurons following an injury, according to new research from the University of Washington. This is the most definitive demonstration to date that such regeneration is possible, given the right cues, for a specific type of neuron in the inner retina of a mammal.

If researchers could spur the development of different types of new neurons in the living human eye, they might be able to replace cells that are lost in diseases like macular degeneration and retinitis pigmentosa. Few or no treatment options are currently available for patients with these diseases.

“This is an excellent, clear demonstration that you can regrow cells of the inner retina,” says Stephen Rose, chief research officer at the nonprofit Foundation Fighting Blindness.

The retina, which is located in the back of the eye, has an outer layer of cells that detect light and translate it into electrical signals. It also has inner layers, which process the signals and send them to the brain.

In degenerative disorders like macular degeneration and retinitis pigmentosa, outer-layer cells, called photoreceptors, break down in the early stages of disease, leading to loss of vision. Extensive research has focused on replacing these cells, in an effort to restore sight. In people with advanced disease or blindness, however, the inner cell layers may also break down or become disorganized and need to be rebuilt, says Rose.

“The outer retina is like the CPU, and the inner retina is like the motherboard,” he says. “If I attach a new CPU to a dead motherboard, it won’t do any good, no matter how great a CPU it is.”

In the current work, developmental biologist Thomas Reh and his team first damaged the mice’s retinas, using a chemical known to destroy inner retinal cells. Then they injected a cocktail of proteins called growth factors. This process spurred some cells, called muller glia, to return to an immature state. Muller glia normally provide nutrition to other neurons and do not divide. Following chemical treatment, however, some of them returned to an undifferentiated state in which they resembled progenitor cells.

The immature cells then started to proliferate, some of them differentiating into mature neurons. In particular, they formed amacrine cells, which are located in the inner retina. These cells mediate electrical signals coming from the photoreceptors and are particularly important to motion detection and night vision, says Reh.

“We did not get a large number of new neurons,” he adds. “But we showed that we could make new amacrine cells, the cell type that had been lost to damage.” The findings were published this week in the online edition of the Proceedings of the National Academy of Sciences.

The current work may help build a foundation for future therapies in which cells of the inner retina–and potentially other cells, including photoreceptors–are regenerated in situ, in the living human eye, says Reh. In theory, such treatments might allow physicians to replace retinal neurons “precisely at the spot where they’re needed, without disruptions or discontinuities,” he says.

In lower vertebrates like fish and chickens, retinal cells are known to generate new neurons in response to damage, often restoring sight. While mammals do not have the same self-healing capacity, some previous research has suggested that under particular circumstances, mammals’ retinas might be able to generate new neurons. Reh’s current work offers more definitive evidence that immature cells, derived from muller glia, can differentiate again into mature neurons, says Michael Young of the Schepens Eye Research Institute.

More research is needed before retinal regeneration can be attempted in humans. “We need much more control over the basic cellular processes”–trying to regenerate different types of neurons and making sure that they function properly in vivo–”before we can treat real people with blinding disease,” says Anand Swaroop of the National Eye Institute.

For example, scientists need to show that regenerated neurons behave normally in the eye, integrating into circuits with other cells and contributing to vision. “It is hard enough to grow different cell types,” says Rose. “But will they function? Will they do what the cells they are replacing normally would do? That’s really tough.”

Reh says that growing new cells in the eye could be preferable to transplanting cells, an approach that his team is also working on. “Transplantation involves a tricky surgery; the cells may not go exactly where you want them to go,” says Reh, and some cells could cause an immune reaction. “Developing methods to stimulate regeneration may prove to be the best option in the long run.”

Copyright Technology Review 2008.

30
Nov
08

Merck chair: Our top three products have Israeli roots

The German company is involved with Israeli academic institutions and start-ups.
Gali Weinreb 27 Nov 08 18:41
“Our three lead products have Israeli roots,” declared Dr. Karl-Ludwig Kley, chairman of German pharmaceutical company Merck KGaA (XETRA: MRK), at the annual Chief Scientist R&D conference.Kley continued, “Rebif, our main product, originated in the Weizmann Institute. It was developed by a company jointly owned by the Institute and Serono, which was later acquired by us. Gonal-F. It enabled us to take the lead in the infertility market and is based on research conducted at Tel Hashomer. Erbitux, which is owned and marketed by ImClone, also owes part of its technology to the scientists at the Weizmann Institute. We are the international company that has paid the most royalties to Israeli scientists.”Merck continues to operate Interpharm, the company it jointly owns with the Weizmann Institute, as its R&D facility in Israel, although Serono closed its main plant in Israel even before it was sold to Merck.These three products have played their part in taking Merck to a market cap of $15 billion, so it is hardly any wonder that Kley enthuses about Israeli talent and is keen to expand his company’s collaborations, of which one example is the agreement it signed with the Chief Scientist in 2007.

Noting it was now a year since the signing of the agreement, Kley said that Merck was supporting five groups of scientists at the Weizmann Institute, as well collaborating with the Technion Israel Institute of Technology on cellular technology and with the Hebrew University of Jerusalem on nanomaterials. The company is also looking at 50 biomedical start-ups.

Published by Globes [online], Israel business news – www.globes-online.com – on November 27, 2008

© Copyright of Globes Publisher Itonut (1983) Ltd. 2008

globes1

01
Dec
08

Big biotechs surge while small developers struggle to survive

MedImmune, big biotechs plot major 2009 expansion

 

Published in FierceBiotech

Biotech companies are being rapidly divided among three distinct classes: growing biotechs worth more than a billion dollars, survivors with money in the bank and a growing segment of downsizing small and mid-sized companies.

MedImmune, for example, has blueprinted a 300,000-square-foot expansion of its corporate headquarters in Gaithersburg, MD, almost doubling the amount of HQ space it has. The expansion is largely new lab space, which will accommodate 600 employees. And MedImmune plans to go ahead and hire another 800 people next year, on top of the 800 it hired this year.

Meanwhile, even though much of the rest of Boston’s economy is in a tailspin, the city’s largest biotech companies are enjoying a surge in growth, with many hiring for dozens of open positions. Biogen Idec is hunting for new personnel to fill 106 positions, according to the Boston Business Journal, while Genzyme is advertising more than 100 jobs and Vertex is recruiting 89.

“We’ve added 10 percent to our workforce over the past year,” Scott Santoro, senior director for talent acquisition at Biogen, tells the Business Journal. The fast growth is happening at biotechs with a market cap north of $1 billion.

- check out the report [1] in the Washington Business Journal
- read the story [2] in the Boston Business Journal

 

Source URL:
http://www.fiercebiotech.com/story/medimmune-big-biotechs-plot-major-expansion-2009/2008-12-01

Links:
[1] http://washington.bizjournals.com/washington/stories/2008/12/01/story2.html?b=1228107600%5E1739254
[2] http://boston.bizjournals.com/boston/stories/2008/12/01/story7.html

01
Dec
08

Biotech’s Umbilical Cord Has Been Severed

Wall Street BioBeat

gen_logoCapital Will be More Expensive and Difficult to Obtain in the Next Twelve to Eighteen Months

Peter Winter

By and large, for the past 40 years venture capitalists and investors have been buying into the hopes and dreams of biotech companies and, as a result, biotechs have been able to gain access to reasonably easy and comparatively inexpensive sources of capital. Along the way the industry has also had to weather five severe market droughts (1983, 1986, 1991, 1995, and 2000) yet has lived to tell the tale when the capital markets rebounded. The meltdown in the financial markets that we witnessed in October has left industry executives wondering whether they will be able to recover once more from what is predicted to be a downturn that will last at least 12 to 18 months.The reason for the concern is that the root of the problem lies in the very sustenance of the industry—capital, which has been its umbilical cord since the industry’s inception. Now that the cord has been severed, the industry is entering a different world than it has previously experienced and capital, if available at all, will be more expensive and difficult to obtain. The more mature and blue-chip biotech companies will certainly do just fine since they have plenty of cash on hand, product revenue streams, strong pipelines and big pharma partners. It is the large universe of small public companies and private companies looking for venture capital that will feel the most pain.Almost overnight, it has become a buyer’s market with biotech public companies seeing their share prices fall to record lows. The focus of attention among successful private and public companies alike will be on those biotechs with a market cap well below their cash value but with $60 to $80 million in the bank. For private companies, with the IPO window firmly closed for them, it represents an opportunity to “go public” by merging into these companies that have fallen on hard times and have few or no options to undertake financing because of their low share price.The grim prognosis for the almost 200 publicly listed biotechnology companies (representing 55% of companies tracked by the monthly Burrill Biotechnology Report) that have seen their market cap drop to less than $100 million is that they will find the next 12 months challenging since they are trading at almost no multiple to their cash. These companies will need to find ways to extend their runway and stretch out the funds that they have remaining. Already we are seeing a flood of announcements that companies are restructuring by cutting their work forces and eliminating research and drug development projects in a desperate effort to extend their cash reserves. Some might have to sell themselves at fire sale prices. For example, Clinical Data acquired Avalon Pharmaceuticals recently in an all-stock transaction valued at approximately $10 million. At the beginning of 2008, Avalon’s share price was $3.25 representing a market cap of approximately $55 million.
By the Numbers
Analyzing biotech’s monthly and year-to-date performance, the Burrill Biotech Select Index, a price-weighted index tracking 20 of biotech’s blue-chip companies, finished October down 10% (the same YTD). In comparison, the Dow fell 14% (29.7% YTD) and the NASDAQ took a 17% hit (down 35% YTD). Overall, shares of blue-chip biotech companies have weathered reasonably well in one of the most turbulent periods in recent financial history. Investors have regarded biotech’s elite as safe havens in these times of economic uncertainty and have backed away from the traditional big pharma companies. This is seen in the fact that year-to-date, the American Stock Exchange Pharmaceuticals Index has declined 20%, twice that of the Burrill Biotech Select Index. The indices reveal the sheer magnitude of the fall off in the markets, and they reflect the realities that while investors still have faith in the blue-chip biotechs, they are staying well away from the more risky emerging biotech companies, with the stock values of the mid-cap and small-cap biotechs taking a pounding in October.
Financing
In terms of biotech IPOs in the U.S., 2008 is shaping up to be one of biotech’s worst in history with only one completed to date—Bioheart. Except for venture capital deals, which have remained at steady state for the past three quarters, generating about $1 billion each quarter, all other forms of financing have fallen compared to the first quarter of 2008 and comparative 2007 figures.Collectively U.S. biotech financings, both for public and private firms, raised $2.5 billion in the third quarter bringing the year-to-date total to almost $8.2 billion. The industry is on pace to generate about $10 billion in the year. You have to go back to 1998 to find a smaller amount that was raised by the industry.
Partnering Remains Steady
While slipping almost $1 billion in Q3’08 compared to Q2’08, partnering deals did generate over $2.9 billion for U.S. biotech companies. Notable deals in the quarter included a potential $820 million partnership between GlaxoSmithKline and Valeant Pharmaceuticals, and Pfizer inked a $725 million potential deal with Medivation to develop and commercialize Dimebon, the company’s investigational drug for treatment of Alzheimer’s and Huntington’s diseases.
What Will the Future Hold?
Looking to the future, we believe the markets will return in early 2010. At that time, however, we are likely to see a very different industry than currently exists today due to attrition through bankruptcies and mergers. These stressful times will force companies into looking at what assets they have and how they can be monetized. They will also have to look further afield for financing and potential partners than just the U.S., such as to the BRIC countries—Brazil, Russia, China, and India. The industry has been and will be as creative in its survival as it has been in its product development. From this will emerge an even stronger industry.

 

© 2008 Genetic Engineering & Biotechnology News, All Rights Reserved – terms of use | legal information | privacy statement | contact | about


02
Dec
08

New drug may put jet lag to rest

losangelestimesThe experimental medication, called tasimelteon, works like melatonin and restores normal sleep patterns, researchers say.

By Thomas H. Maugh II

 An experimental drug that mimics the effects of the hormone melatonin can reset the body’s circadian rhythms, bringing relief to jet-lagged travelers and night-shift workers, researchers reported Monday

In a study of 450 people who were subjected to simulated jet lag in a sleep laboratory, a team from Brigham and Women’s Hospital in Boston found that the drug restored near normal sleep the first night it was used.

There were no aftereffects from the drug, minimal side effects, and people who took it performed normally the next day, said Dr. Elizabeth B. Klerman, one of the co-authors of the study published online in the journal Lancet.

And unlike conventional sleeping aids such as Ambien or Lunesta, she added, the new drug, called tasimelteon, has no potential for addiction or abuse.

The main limitations of the study were the relatively small size and the researchers’ inability to measure performance and mood after the drug was used, experts said.

The study was designed and funded by Vanda Pharmaceuticals Inc. of Rockville, Md., which developed tasimelteon, and all of the researchers reported receiving funds from Vanda or other pharmaceutical companies.

“This is a very promising first step,” said Dr. Jay Udani, who runs the integrative medicine program at Northridge Hospital Medical Center and who was not involved in the study. But the research “does not prove that it works for jet lag or shift workers,” he added. “That needs controlled studies in the field.”

The body’s sleep-wake cycle is controlled by melatonin, which is produced by the pineal gland in response to patterns of light and darkness. Higher concentrations of melatonin in the blood are associated with greater sleepiness.

Some research has shown that administering melatonin can adjust sleep cycles in travelers and workers, but the results have been mixed.

Because melatonin can’t be patented, drug companies have been interested in developing melatonin mimics, such as tasimelteon, which can be patented.

In the first part of the study, 39 patients’ normal sleep habits were monitored for three nights in the laboratory before they were sent to bed five hours early.

They were then given one of four different doses of tasimelteon or a placebo 30 minutes before bedtime.

Researchers monitored their sleep efficiency — the percentage of time in bed they actually slept — and the amount of time required for them to fall asleep.

Although all the subjects benefited from the drug, those receiving the highest dose had a sleep efficiency of 89% the first night, virtually the same as the 90% efficiency before the trail started. Those receiving a placebo had an efficiency of 71%.

Patients taking the highest doses slept for an average of about 428 minutes, compared with 430 minutes before the trial and 324 minutes for those taking a placebo. It took an average of seven minutes for them to go to sleep, compared with 11 minutes before the trial and 22 minutes for those receiving a placebo.

Blood analysis showed that the melatonin cycle of those receiving the drug was altered to match the new conditions.

“They would be expected to sleep better because their internal clock is on the right time,” Klerman said.

Maugh is a Times staff writer.

thomas.maugh@latimes.com

http://www.latimes.com/news/science/la-sci-sleep2-2008dec02,0,6502985.story

03
Dec
08

Spain in the dock over research visas

Newsnaturenews

Failure to cut red tape for foreign scientists prompts legal action by the European Union.

Spain’s immigration procedures — still too bureaucratic for scientists. 

The European Commission is taking Spain to the European Court of Justice for failing to enact into national law the 2005 European Union (EU) directive on scientific visas. The directive aims to make it easier for researchers from outside the EU to work in an EU country and bring their families with them.

The United Kingdom and Denmark opted out of the directive, leaving Spain and Cyprus as the only member states bound by the directive that have yet to implement it.

Spain’s current immigration procedures are laborious and time-consuming, with visa applications sometimes taking months to process. The researchers’ visa would speed up the procedure and also allow scientists to attend meetings or conferences in EU states that have signed the Schengen Agreement, which abolishes border controls between participating countries. Researchers would also not have to leave their host nation to renew their visas.

Immobilized

Leonardo Acho, an electronics engineer from Mexico, is all too familiar with the problems of the current system. In February 2008, he was hired as a visiting professor by the Technical University of Catalonia in Barcelona. But during the visa application process, the Spanish authorities told him that they would not be able to grant residency permits for his whole family because the salary he was being offered was insufficient.

As a result, Acho was only able to apply on behalf of his wife and younger son. His older son, now studying at the Autonomous University of Barcelona, is living in Spain on the three-month tourist visa granted to Mexican citizens.

“From January on, the options I’ve been given for my son are either that he stays illegally in Spain or that he goes back to Mexico to renew his visa with no guarantees,” Acho says. “If I had known that I was going to be separated from my family, I’d have thought twice about ever coming to Spain in the first place.”

Coordinated by the Spanish Science and Technology Foundation (FECYT), regional mobility centres have been charged with helping non-EU researchers moving to the country. Esther Alsina, from the Catalan Foundation for Research and Innovation (FCRI) mobility centre, says they have identified a number of problems.

“Firstly, there is a lack of information in consulates for researchers,” she says. “Secondly, salary requirements by immigration authorities are not consistent with the salary researchers actually receive, and thirdly, the visa application clearance process takes too long, sometimes months.”

Wasted opportunity

Spain’s failure to act is also affecting industry researchers. Satheesh Chinnapapagari, an Indian molecular biologist, started work for Bilbao-based genomics company Progenika Biopharma in June 2008.

After resigning from his post as a senior post-doctoral fellow at the University of Basel, Switzerland, in 2007, delays in obtaining his Spanish work permit forced him to go back to India, where he spent five months, until May 2008, unemployed and living on savings, waiting for his visa to arrive.

“Spain could be transformed into an attractive destination for highly skilled scientists of non-EU nationalities, if the visa procedures were less cumbersome,” says Chinnapapagari.

As an industry scientist, Chinnapapagari’s salary is higher than that of an equivalent academic researcher. But he still needed help from the Basque province of Vizcaya’s regional mobility centre to get his work permit. Spain’s Ministry of Labour and Social Security operates a service to help companies hire highly qualified staff from outside the EU. But the programme, called the Unidad de Grandes Empresas or Big Businesses Unit, is not well known, and many companies are deterred by the red tape that needs to be negotiated before they can get help.

“Spain hasn’t been able to transpose the European directive on scientific visas yet because in order to apply it, the current Spanish immigration law must first be changed,” Montserrat Torné, director of the science ministry’s International Cooperation Department told Nature News. “This is an organic law, and it’s very difficult to introduce modifications to it.” But Torné adds that the Spanish government now expects the new Immigration Law to come into effect before summer of next year.

Published online 2 December 2008 | Nature | doi:10.1038/news.2008.1269

 

06
Dec
08

H. M., an Unforgettable Amnesiac, Dies at 82

nytimesBy BENEDICT CAREY

He knew his name. That much he could remember.

He knew that his father’s family came from Thibodaux, La., and his mother was from Ireland, and he knew about the 1929 stock market crash and World War II and life in the 1940s.

But he could remember almost nothing after that.

In 1953, he underwent an experimental brain operation in Hartford to correct a seizure disorder, only to emerge from it fundamentally and irreparably changed. He developed a syndrome neurologists call profound amnesia. He had lost the ability to form new memories.

For the next 55 years, each time he met a friend, each time he ate a meal, each time he walked in the woods, it was as if for the first time.

And for those five decades, he was recognized as the most important patient in the history of brain science. As a participant in hundreds of studies, he helped scientists understand the biology of learning, memory and physical dexterity, as well as the fragile nature of human identity.

On Tuesday evening at 5:05, Henry Gustav Molaison — known worldwide only as H. M., to protect his privacy — died of respiratory failure at a nursing home in Windsor Locks, Conn. His death was confirmed by Suzanne Corkin, a neuroscientist at the Massachusetts Institute of Technology, who had worked closely with him for decades. Henry Molaison was 82.

From the age of 27, when he embarked on a life as an object of intensive study, he lived with his parents, then with a relative and finally in an institution. His amnesia did not damage his intellect or radically change his personality. But he could not hold a job and lived, more so than any mystic, in the moment.

“Say it however you want,” said Dr. Thomas Carew, a neuroscientist at the University of California, Irvine, and president of the Society for Neuroscience. “What H. M. lost, we now know, was a critical part of his identity.”

At a time when neuroscience is growing exponentially, when students and money are pouring into laboratories around the world and researchers are mounting large-scale studies with powerful brain-imaging technology, it is easy to forget how rudimentary neuroscience was in the middle of the 20th century.

When Mr. Molaison, at 9 years old, banged his head hard after being hit by a bicycle rider in his neighborhood near Hartford, scientists had no way to see inside his brain. They had no rigorous understanding of how complex functions like memory or learning functioned biologically. They could not explain why the boy had developed severe seizures after the accident, or even whether the blow to the head had anything do to with it.

Eighteen years after that bicycle accident, Mr. Molaison arrived at the office of Dr. William Beecher Scoville, a neurosurgeon at Hartford Hospital. Mr. Molaison was blacking out frequently, had devastating convulsions and could no longer repair motors to earn a living.

After exhausting other treatments, Dr. Scoville decided to surgically remove two finger-shaped slivers of tissue from Mr. Molaison’s brain. The seizures abated, but the procedure — especially cutting into the hippocampus, an area deep in the brain, about level with the ears — left the patient radically changed.

Alarmed, Dr. Scoville consulted with a leading surgeon in Montreal, Dr. Wilder Penfield of McGill University, who with Dr. Brenda Milner, a psychologist, had reported on two other patients’ memory deficits.

Soon Dr. Milner began taking the night train down from Canada to visit Mr. Molaison in Hartford, giving him a variety of memory tests. It was a collaboration that would forever alter scientists’ understanding of learning and memory.

“He was a very gracious man, very patient, always willing to try these tasks I would give him,” Dr. Milner, a professor of cognitive neuroscience at the Montreal Neurological Institute and McGill University, said in a recent interview. “And yet every time I walked in the room, it was like we’d never met.”

At the time, many scientists believed that memory was widely distributed throughout the brain and not dependent on any one neural organ or region. Brain lesions, either from surgery or accidents, altered people’s memory in ways that were not easily predictable. Even as Dr. Milner published her results, many researchers attributed H. M.’s deficits to other factors, like general trauma from his seizures or some unrecognized damage.

“It was hard for people to believe that it was all due” to the excisions from the surgery, Dr. Milner said.

That began to change in 1962, when Dr. Milner presented a landmark study in which she and H. M. demonstrated that a part of his memory was fully intact. In a series of trials, she had Mr. Molaison try to trace a line between two outlines of a five-point star, one inside the other, while watching his hand and the star in a mirror. The task is difficult for anyone to master at first.

Every time H. M. performed the task, it struck him as an entirely new experience. He had no memory of doing it before. Yet with practice he became proficient. “At one point he said to me, after many of these trials, ‘Huh, this was easier than I thought it would be,’ ” Dr. Milner said.

The implications were enormous. Scientists saw that there were at least two systems in the brain for creating new memories. One, known as declarative memory, records names, faces and new experiences and stores them until they are consciously retrieved. This system depends on the function of medial temporal areas, particularly an organ called the hippocampus, now the object of intense study.

Another system, commonly known as motor learning, is subconscious and depends on other brain systems. This explains why people can jump on a bike after years away from one and take the thing for a ride, or why they can pick up a guitar that they have not played in years and still remember how to strum it.

Soon “everyone wanted an amnesic to study,” Dr. Milner said, and researchers began to map out still other dimensions of memory. They saw that H. M.’s short-term memory was fine; he could hold thoughts in his head for about 20 seconds. It was holding onto them without the hippocampus that was impossible.

“The study of H. M. by Brenda Milner stands as one of the great milestones in the history of modern neuroscience,” said Dr. Eric Kandel, a neuroscientist at Columbia University. “It opened the way for the study of the two memory systems in the brain, explicit and implicit, and provided the basis for everything that came later — the study of human memory and its disorders.”

Living at his parents’ house, and later with a relative through the 1970s, Mr. Molaison helped with the shopping, mowed the lawn, raked leaves and relaxed in front of the television. He could navigate through a day attending to mundane details — fixing a lunch, making his bed — by drawing on what he could remember from his first 27 years.

He also somehow sensed from all the scientists, students and researchers parading through his life that he was contributing to a larger endeavor, though he was uncertain about the details, said Dr. Corkin, who met Mr. Molaison while studying in Dr. Milner’s laboratory and who continued to work with him until his death.

By the time he moved into a nursing home in 1980, at age 54, he had become known to Dr. Corkin’s M.I.T. team in the way that Polaroid snapshots in a photo album might sketch out a life but not reveal it whole.

H. M. could recount childhood scenes: Hiking the Mohawk Trail. A road trip with his parents. Target shooting in the woods near his house.

“Gist memories, we call them,” Dr. Corkin said. “He had the memories, but he couldn’t place them in time exactly; he couldn’t give you a narrative.”

He was nonetheless a self-conscious presence, as open to a good joke and as sensitive as anyone in the room. Once, a researcher visiting with Dr. Milner and H. M. turned to her and remarked how interesting a case this patient was.

“H. M. was standing right there,” Dr. Milner said, “and he kind of colored — blushed, you know — and mumbled how he didn’t think he was that interesting, and moved away.”

In the last years of his life, Mr. Molaison was, as always, open to visits from researchers, and Dr. Corkin said she checked on his health weekly. She also arranged for one last research program. On Tuesday, hours after Mr. Molaison’s death, scientists worked through the night taking exhaustive M.R.I. scans of his brain, data that will help tease apart precisely which areas of his temporal lobes were still intact and which were damaged, and how this pattern related to his memory.

Dr. Corkin arranged, too, to have his brain preserved for future study, in the same spirit that Einstein’s was, as an irreplaceable artifact of scientific history.

“He was like a family member,” said Dr. Corkin, who is at work on a book on H. M., titled “A Lifetime Without Memory.” “You’d think it would be impossible to have a relationship with someone who didn’t recognize you, but I did.”

In his way, Mr. Molaison did know his frequent visitor, she added: “He thought he knew me from high school.”

Henry Gustav Molaison, born on Feb. 26, 1926, left no survivors. He left a legacy in science that cannot be erased.

 

09
Dec
08

Brain stem cells could be transplanted to cure hearing loss, say scientists

Stems cells in the brain could be “transplanted” into the ear to reverse hearing loss in some people, researchers have claimed.

telegraphcouk
By Richard Alleyne, Science Correspondent
Last Updated: 10:38PM GMT 08 Dec 2008
Damage to hair cells in the inner ear due to ageing and exposure to excessive noise is a major cause of deafness, affecting 10 per cent of the worldwide population.
The cell loss is irreversible because the cells have a limited capacity to regenerate.
But a new study suggests that a part of the brain called the lateral ventricle contains stem cells which share characteristics with inner ear hair cells and which have the potential to reproduce.
According to the scientists, these cells could potentially be transplanted from a person’s brain into their ear, where they would undergo a functional switch to enable them to replace the damaged ones.
The study said that as the production of new ear hair cells is a rare event, “considerable efforts have been made to identify a renewable cell source able to reconstruct damaged inner ears”.
Ebenezer Yamoah, who led the team at the University of California, said the brain cells “have the potential to give rise to inner ear hair cell-like phenotypes”.
“These cells share many morphological and functional characteristics with inner ear hair cells,” he added.
“We surmise that cells of the adult forebrain germinal zone might be potential candidate cells to be transplanted for the replacement of non-renewable hair cells.”


The scientists analysed the structural, molecular and functional criteria of the brain cells to provide evidence.


The authors, who published their results in the Proceedings of the National Academy of Sciences, concluded that transplanted cells could alter their functions to work as inner ear hair cells and thus restore hearing.
They suggested their findings on the flexible function of certain cells could also be extended to offer treatment for other problems affecting the nervous system.
“The functional plasticity of renewable cells revealed in this study may open a new therapeutic avenue for other neural degenerative diseases,” they add.

10
Dec
08

The Placebo Effect: Not All in Your Head

By Rachel Zelkowitz
ScienceNOW Daily News
2 December 2008

To get a drug to market, pharmaceutical companies have to show that it works better than a placebo. But sometimes the placebo is just as powerful as the real thing. Just why our bodies respond so strongly to fake medicine has long been a mystery, but researchers are a step closer to solving that riddle, having picked out a particular gene that may be responsible for one type of placebo effect.

The placebo effect works because patients believe they are actually receiving treatment. Expecting treatment is similar to anticipating reward, studies have shown, and reward anticipation triggers the release of the neurotransmitter dopamine in the brain, which can help alleviate symptoms of chronic pain and depression. But what about placebo effects for other conditions?

Tomas Furmark, a psychologist at Uppsala University in Sweden, suspected that a different neurotransmitter plays a role in placebo responses to social anxiety disorder (SAD)–an abnormal fear of being judged by others. Brain imaging studies have shown that the amygdala, an area of the brain that regulates the fear response, is unusually active in patients with SAD. What’s more, healthy people with certain variations of two genes that regulate the neurotransmitter serotonin have more active amygdalas.

Based on these results, Furmark and his colleagues–in collaboration with the pharmaceutical company GlaxoSmithKline–ran a placebo-controlled trial with 108 patients who had been previously diagnosed with SAD. The volunteers were randomly assigned to receive either a new serotonin medication or a sugar pill for 8 weeks. At the beginning of the trial, the patients had to prepare and deliver a speech in front of small group of people–an anxiety-triggering event–while the researchers tracked their amygdala activity using positron emission tomography. The technique allows researchers to track blood flow–and thus activity–in different areas of the brain. The study participants had to give a similar speech at the end of the treatment period, so researchers could assess whether their patterns of brain activity had changed.

Even sugar was enough to conquer some cases of SAD. Of the 25 patients who received the placebo, 10 reported reduced anxiety by the end of the study. (Numbers for the treatment group were not released because the trial is ongoing.) Brain scans during the second speech showed their amygdalas were also less active. Genetic analysis revealed that eight people who got relief from the placebo had a particular version of a gene that regulates serotonin production called the tryptophan hydroxylase-2 promoter (TPH2), the researchers report tomorrow in the Journal of Neuroscience. This is one of the same genetic variants linked to heightened amygdala activity in healthy people. TPH2 is the first genetic marker tied to any placebo response, the team reports.

Finding genetic markers for the placebo effect could raise ethical questions about how companies design their clinical trials, Furmark says. For example, “it could be tempting to screen all individuals and … select only those with [the] nonresponsive phenotype [for the trial].”

Psychiatrist Helen Mayberg of Emory University in Atlanta, Georgia, who has studied the placebo effect in depression, agrees that the findings could have major implications for research design. But first, more research is needed to determine if the genetic markers for placebo relief from SAD can be generalized to other diseases, and what other genes might contribute to the phenomena, she says.

 

 

10
Dec
08

BioMarin’s Kuvan wins European approval

San Francisco Business Times – by Ron Leuty

Kuvan, BioMarin Pharmaceutical Inc.’s treatment for patients with a rare genetic condition in which the body can’t break down a certain type of amino acid, won approval from European regulators.

As a result of approval by the European Commission, Novato-based BioMarin (NASDAQ: BMRN) will receive a $30 million milestone payment from marketing partner Merck Serono of Switzerland. It also will receive net single-digit royalties on sales in Europe.

BioMarin officials assumed approval and the $30 million milestone when they told analysts in October that 2008 net income would be $30 million to $42 million.

Kuvan treats abnormally high levels of the amino acid phenylalanine, or Phe, in the blood. The condition, called hyperphenylalaninemia, is caused by genetic metabolism errors in patients with phenylketonuria, also known as PKU, or in BH4-deficient patients.

High levels of Phe, toxic to the brain, can result in mental retardation and behavioral problems. Treatment historically has centered on diet, restricting foods that contain Phe.

Kuvan is supposed to be used in conjunction with a Phe-restricted diet.

About 35,000 people each year are diagnosed with hyperphenylalaninemia due to PKU or BH4 deficiency.

Kuvan won orphan drug designation from the U.S. Food and Drug Administration in December 2007. That gave it tax advantages and market exclusivity for seven years.

The drug will have 10 years of patent protection in Europe.

BioMarin said in October that net product revenue from Kuvan will be $45 million to $65 million this year.

 

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http://sanfrancisco.bizjournals.com/sanfrancisco/stories/2008/12/08/daily31.html

10
Dec
08

Valeant to Acquire Dow Pharmaceutical Sciences, Inc. for $285 Million

Acquisition Significantly Expands Valeant’s Dermatology franchise in U.S. 

ALISO VIEJO, Calif., Dec. 10 /PRNewswire-FirstCall/ — Valeant Pharmaceuticals International (NYSE: VRX) today announced that it has signed a definitive agreement to acquire Dow Pharmaceutical Sciences, Inc., a privately held dermatology company that specializes in the development of topical products on a proprietary basis, as well as for pharmaceutical and biotechnology companies. The transaction significantly enhances Valeant’s dermatology franchise in the United States through the acquisition of a specialized dermatology research and development organization including a newly approved product and a robust pipeline of five dermatology products, three of which are in Phase II clinical development. Current annualized revenues are approximately $45 million, of which approximately $20 million represents royalty payments from products already out-licensed by Dow.

Dow recently received approval from the Food and Drug Administration (FDA) for Acanya(TM), a novel topical prescription medication indicated for the treatment of mild to moderate acne. Acanya(TM) is expected to be launched in the United States in early 2009. Dow has products in clinical development for the treatment of rosacea, moderate to severe acne, fungal infections and common warts. We expect one or more products to enter a Phase III trial in 2009, with an expected launch as early as 2012. In addition, Dow operates a well-regarded topical products services business dedicated to working with external sponsors for the formulation and development of topical therapies.

Under the terms of the agreement, Valeant will pay Dow $285 million, subject to certain closing adjustments. Approximately $8 million in cash will be retained from current Dow accounts, making the net amount paid $277 million. Valeant will make the first payment of $250 million upon closing ($242 million net of cash). In the six month period following closing, Valeant will fund an escrow account of $35 million, which will be subject to indemnification claims from Valeant for a period of eighteen months following closing. The transaction is expected to be accretive in 2009. Additionally, Valeant will pay future milestones, based predominately on the achievement of approval and commercial targets for certain pipeline products still in development.

The transaction was approved by the boards of directors for both companies and is subject to customary closing conditions, including the expiration or early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvement Act of 1976, as amended. The transaction is expected to close at year end.

“This acquisition grows our scale and capabilities in dermatology thus solidifying Valeant’s future as a leading company in the development and commercialization of dermatology medications,” stated J. Michael Pearson, chairman and chief executive officer. “Gordon Dow, the founder of Dow Pharmaceutical Sciences, and his team are highly regarded with innovative formulation and development expertise, exemplified by having worked on ten dermatology approvals from the FDA in the past few years and with projects underway in eight of the top ten dermatology diagnoses. We are excited that they will be joining the Valeant team as we believe the synergies between our newly acquired Coria franchise and Dow’s business will provide sustainable growth for many years to come.”

Conference Call and Webcast and Presentation:

Valeant will host a conference call today at 11:00 a.m. EST (8:00 a.m. PST) to discuss the transaction. The dial-in number to participate on this call is (877) 295-5743, confirmation code 76913148. International callers should dial (973) 200-3961, confirmation code 76913148. A replay will be available approximately two hours following the conclusion of the conference call through December 17, 2008 and can be accessed by dialing (800) 642-1687, or (706) 645-9291, confirmation code 76913148. The company will also webcast the conference call live over the Internet. The webcast, as well as the investor presentation, may be accessed through the investor relations section of Valeant’s corporate Web site at http://www.valeant.com.

About Acanya(TM)

On October 23, 2008, the Food and Drug Administration approved the Dow NDA for a combination product, Acanya(TM) Gel (clindamycin phosphate 1.2% and benzoyl peroxide 2.5%), indicated for the treatment of mild to moderate acne vulgaris in patients 12 years and older.

About Valeant

Valeant Pharmaceuticals International (NYSE: VRX) is a multinational specialty pharmaceutical company that develops, manufactures and markets a broad range of pharmaceutical products primarily in the areas of neurology and dermatology. More information about Valeant can be found at http://www.valeant.com.

About Dow

Dow Pharmaceutical Sciences, Inc. is a privately held company that specializes in the development of topical drug products for pharmaceutical and biotechnology clients. Dow provides a full range of product development services including formulation and regulatory consulting, formulation optimization utilizing state-of-the-art in vitro permeation models, full analytical support, cGMP clinical manufacturing and clinical labeling. Dow conducts dermatology studies at clinical sites in California, and in Europe through its Bioskin Division, a full-service dermatology CRO. More information about Dow can be found at http://www.dowpharm.com.

FORWARD-LOOKING STATEMENTS

This press release contains forward-looking statements, including, but not limited to, statements regarding the future growth in Valeant’s dermatology franchise, the impact of the Dow Pharmaceutical Sciences, Inc. acquisition on Valeant’s business, the timing and potential success of clinical trials and the approval of product candidates. These statements are based upon the current expectations and beliefs of Valeant’s management and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include, but are not limited to, risks and uncertainties related to Valeant’s ability to successfully integrate the Dow assets, risks and uncertainties relating to the clinical development of product candidates, regulatory approval processes, the potential that competitors may bring to market products or treatments that are more commercially attractive than existing or future Dow products, and other risks and uncertainties discussed in the company’s filings with the SEC. The company cautions the reader that these factors are among the factors that could cause actual results to differ materially from the expectations described in the forward-looking statements. The company also cautions the reader that undue reliance should not be placed on any of the forward-looking statements, which speak only as of the date of this press release. The company undertakes no responsibility to update any of these forward-looking statements to reflect events or circumstances after the date of this press release or to reflect actual outcomes.

 


Source URL:
http://www.fiercebiotech.com/press-releases/valeant-acquire-dow-pharmaceutical-sciences-inc-285-million

21
Dec
08

In Defense of Finders

trendlines

 

 

 


It’s the truth. Raising money is hard work. It’s one more full-time job for a CEO who already has several full-time jobs. So, are you making it harder on yourself that it need be? Let’s consider one of the classes of professionals, semi-professionals (and unprofessionals) who offer to help “do” your raise — the “finder.”

The “finder.” This sounds like a guy who stumbles upon opportunities, making money from his luck and occasional knowledge of phone numbers. Sometimes, that’s the case. Some finders, though, are true professionals. Finders — to my definition — do not ask for retainers. They work on a commission and are paid as they succeed. Some finders will ask for both a cash commission and warrants. While the term “finder” is often used derisively, I believe that as a group they are an important part of a fund-raising plan.

We are privileged to work with finders around the world who are honest in their dealings and successful for their clients. Professional finders have relationships with investors they know well; they are always prospecting for new investors to add to their portfolios.

Typically, finders spend little time with your business plan and other support materials. If they don’t find your presentation or business plan acceptable, they will tell you to fix it. Their focus is on getting you to investors — not on strategies and plans.

Whatever you call them — finders, machers, investment bankers — these “connectors” can make the difference between success and death for a company. At all times — and especially during these times — I encourage you to speak to many and engage — non-exclusively — those whom you feel comfortable with and will work to help you and your company.

And because you should engage them non-exclusively and because they cannot commit to any investment — they can only bring you an investor for your consideration. I beg you: Don’t get overly focused on the fees that they request from you. Get focused on the investors that they bring you and the total cost of the deal — their commission and warrants are part of the total cost of the deal. I see companies spending more time negotiating with finders than they spend talking to investors. That’s the wrong balance.

You can only understand what a deal costs when see the valuation offered and the full set of terms presented. The finder who asks you for 7% cash plus 7% options is a bargain when he brings you the money that you need at the valuation that you want. Focus on the total cost of the deal.

Remember, you can always (and you must) say “no” to a bad deal — and a bad investor. Say “yes” to your finder and deal with the investor when he is at hand. Stop thinking that the finder is getting lots of money “just for making a phone call,” and start thinking that you will be thrilled to write him a big check.

D. Todd Dollinger, CEO
The Trendlines Group

22
Dec
08

St. Jude buys Israel’s MediGuide for $300 million

Batya Feldman

Israeli start-up MediGuide has been bought for $300 million cash by medical technology and services giant St. Jude Medical (NYSE: STJ).
Under the deal, the acquiring company is taking on MediGuide’s liabilities, to the tune of $17 million, so that MediGuide’s shareholders will in fact receive $283 million in cash. This sum will be paid in three installments: $138 million on the signing of the agreement, $111 million in November 2009, and up to $34 million in April 2010.

MediGuide was founded in 2000 by Gera Strommer, president and CEO, and Uzi Eichler, vice president technology, as a spin-off from Elbit Systems (Nasdaq: ESLT; TASE: ESLT), which owns 41.3% of the company, and with backing from Israeli venture capital fund Vitalife. Since it was founded, the company has raised $45 million from a small number of investors, among them Eliezer Fishman’s Fishman Group, Docor International Management, and Elbit Systems. Philips and Boston Scientific have also invested in the company.

Sources inform “Globes” that the negotiations over the acquisition were short, and that St. Jude was advised by Bank of America. MediGuide did not have advising bankers.

MediGuide has developed technology and products for minimally invasive navigation and tracking within the human body. Its devices are for use in cardiac procedures and catheterization. The system consists of sensors mounted on a catheter introduced into the body, with the locating done on the basis of the distance of the sensors from several sources of magnetic radiation, with an accuracy of fractions of a millimeter.

The information from the sensors is combined with an image of the interior of the body, in a way that is similar to the way locating using a GPS device works. Since in catheterization or other invasive procedure, the human body undergoes changes, the device measures physiological indications from the body breathing, EKG, and so on and amends the picture accordingly.

Elbit Systems president and CEO Joseph Ackerman said, “We believe the acquisition provides MediGuide an excellent opportunity to continue its growth, while allowing Elbit Systems to focus on its core business areas.”

Since its foundation, MediGuide has sought collaboration agreements with large market players. The company now has agreements with Medtronic, Siemens, Asahi Intecc of Japan, Boston Scientific, and Philips. It has yet to make substantial sales.

2008 will certainly be remembered as a good year for MediGuide. In January, the company signed a collaboration agreement concerning its Medical Positioning System (MPS) intra-body navigation products with medical device giant Medtronic (NYSE: MDT). The companies will jointly develop products on the basis of MediGuide’s technology. Initially, the joint development will not involve any cash element, but the agreement provides an option for future investment by Medtronic, investment that it seems will not now be required.

Vitalife jumped in, the other funds missed out

When MediGuide’s two entrepreneurs were just beginning to formulate the idea and trying to raise money, they approached most of the venture capital firms that invest in healthcare companies. All, except for Vitalife, gave them the cold shoulder, among other things because the entrepreneurs were inexperienced in the medical field. More than one partner in the local venture capital industry must now be looking back eight years with frustration and regret. It is estimated that MediGuide’s investors, particularly the early-stage ones, will see returns of 15-20 times their investments, a huge achievement by any standards, but particularly remarkable in the light of the returns venture capital firms have been making on sales in the past few years.

Eliezer Fishman is the controlling shareholder in “Globes.”

Published by Globes [online], Israel business news – www.globes.co.il – on December 22, 2008

© Copyright of Globes Publisher Itonut (1983) Ltd. 2008
globes1

23
Dec
08

EPIX Pharmaceuticals Announces FDA Approval of Vasovist® (gadofosveset trisodium)

First Imaging Agent Approved for Magnetic Resonance Angiography (MRA) in the U.S. epix-logorgb-345x230_3

LEXINGTON, Mass.–(BUSINESS WIRE)–EPIX Pharmaceuticals, Inc. (NASDAQ:EPIX), a biopharmaceutical company focused on discovering and developing novel therapeutics through the use of its proprietary and highly efficient in silico drug discovery platform, today announced that the U.S. Food and Drug Administration (FDA) has approved for marketing its novel blood pool magnetic resonance angiography (MRA) agent, Vasovist® (gadofosveset trisodium), to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease. AIOD occurs when iliac arteries become narrowed or blocked and may prevent the sufficient transport of oxygen and/or blood throughout the body.

Vasovist is the first contrast agent approved for marketing in the United States for use with MRA, a non-invasive modality for imaging blood vessels. In 2007, there were approximately 1.3 million MRA procedures performed in the United States using contrast agents not specifically approved for this procedure. MRA is a less invasive procedure than x-ray angiography, allowing for reduced patient discomfort and recuperation time and unlike x-ray angiography, MRA does not expose patients to ionizing radiation. Vasovist had previously been approved for marketing in 34 countries outside the United States based on data from four multi-center, Phase 3 clinical trials that showed that Vasovist’s overall accuracy was similar to that of catheter-based x-ray angiography, as determined by blinded readings.

“Vasovist is a first-in-class contrast agent with several unique characteristics that we believe will allow it to become a market leader in the United States,” said Elkan Gamzu, Ph.D., interim chief executive officer of EPIX. “It offers good resolution angiography, a high signal per dose, a long imaging window timeframe and single-dose imaging of multiple vessel beds. We believe the resulting high-quality image will allow physicians to fully utilize MRA as a meaningful diagnostic and therapeutic tool. In addition, the albumin-binding properties of Vasovist make it ideal for vascular imaging as opposed to other gadolinium agents that are rapidly cleared from the blood stream and have a narrow imaging window. There are no other imaging agents approved for MRA in the United States and we believe Vasovist will be well-received by the physician community as a valuable, safe tool for MRA. Our strategy remains to monetize this asset and we believe these characteristics and market dynamics make Vasovist an appealing opportunity for a company interested in building or augmenting its competitive position in the imaging market.”

The approval was based on the positive results from a blinded, independent re-read of images of Vasovist from previous Phase 3 studies. The re-read, which was conducted earlier this year, met all pre-specified endpoints prospectively agreed to with the FDA. In the re-read Vasovist was demonstrated to have:

  • statistically greater sensitivity – readers of images using Vasovist more accurately detected disease when disease was present, compared with non-contrast MRA;
  • statistically greater specificity – readers of images using Vasovist more accurately excluded disease if it wasn’t present at a rate that was not worse than non-contrast MRA;
  • for scans deemed uninterpretable, Vasovist was demonstrated to have sensitivity and specificity that was significantly better than chance alone.

About Vasovist

Vasovist is an injectable intravascular contrast agent designed to provide improved imaging of the vascular system through magnetic resonance angiography imaging (MRA). Vasovist has been approved for marketing in the United States and in 34 countries outside the United States, including all 27 member states of the European Union, Switzerland, Turkey, Australia and Canada. Global marketing rights to Vasovist are held by Bayer Schering Pharma until March 1, 2009 at which time they transfer to EPIX. Vasovist is currently marketed in Canada and 18 European countries, including Germany, the Netherlands, Italy, all Nordic countries, the United Kingdom and Switzerland.

About AIOD and Peripheral Vascular Disease

Aortoiliac occlusive disease (AIOD) occurs when iliac arteries become narrowed or blocked. Arteries are normally smooth and unobstructed on the inside, but with age, plaque can build up in the walls of arteries and cause them to narrow and stiffen. Those affected with AIOD may not receive the blood and oxygen they need throughout their legs, causing pain, sores or gangrene, which can result in the loss of a limb. Peripheral vascular disease refers to diseases of blood vessels outside the heart and brain and includes functional peripheral vascular disease, which doesn’t have an organic cause or involve defects in blood vessels’ structure and organic peripheral vascular disease, which is caused by structural changes in blood vessels.

About MRA

Magnetic resonance angiography uses a powerful magnetic field, radio waves and a computer to produce detailed images of major blood vessels throughout the body. MRA may be performed with or without contrast material and is used in many diagnostic medical procedures including the identification of disease, aneurysms, and atherosclerosis; it is also used to guide surgeons making repairs to diseased blood vessels and plans for surgical operations.

About EPIX

EPIX Pharmaceuticals is a biopharmaceutical company focused on discovering and developing novel therapeutics through the use of its proprietary and highly efficient in silico drug discovery platform. The company has a pipeline of internally-discovered drug candidates currently in clinical development to treat diseases of the central nervous system and lung conditions. EPIX also has collaborations with leading organizations, including GlaxoSmithKline, Amgen and Cystic Fibrosis Foundation Therapeutics.

This news release contains express or implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are based on current expectations of management. These statements relate to, among other things, our expectations and assumptions concerning the commercial success of Vasovist, our ability to successfully monetize Vasovist and management’s plans, objectives and strategies. These statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, among other things: risks that Vasovist may not be successfully marketed or manufactured; failure to obtain the financial resources to commercialize or monetize Vasovist; competing products may be more successful; our inability to interest potential partners in our technologies and products; our inability to achieve commercial success for our products and technologies; our inability to successfully defend against litigation, including any appeal or re-filing of the shareholder class action lawsuit; our inability to protect our intellectual property and the cost of enforcing or defending our intellectual property rights; our failure to comply with regulations relating to our products and product candidates, including FDA requirements; and risks of new, changing and competitive technologies and regulations in the U.S. and internationally. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. We undertake no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. For additional information regarding these and other risks that we face, see the disclosure contained in our filings with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q.

23
Dec
08

Archemix signs $1.42B collaboration with Glaxo

GlaxoSmithKline and Archemix Form Strategic Alliance to Develop Aptamers to Treat Inflammatory Diseases archemix_logo

LONDON–(BUSINESS WIRE)–GlaxoSmithKline and Archemix Corp. today announced a worldwide strategic alliance to discover, develop and commercialise aptamer therapeutics to treat inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease. Aptamers are synthetised oligonucleotides, or short nucleic acid sequences, that bind to proteins with high affinity and specificity.

The alliance leverages Archemix’s unique expertise and intellectual property position in the discovery and development of aptamer therapeutics and provides GSK with an option to license product candidates directed at seven different aptamer targets with relevance in inflammatory disease.

Under the terms of the agreement, Archemix will receive $27.5 million in upfront payments from GSK, including a $6.5 million equity investment by GSK in the company. Archemix could also be eligible to receive up to $200 million in development, regulatory and sales milestone payments for each of the seven aptamer therapeutics which may be discovered and developed as part of the alliance. Archemix would also receive tiered royalties up to lower double digits on worldwide sales of products that may result from the alliance.

“We are very excited about this collaboration with GSK. GSK is an outstanding partner with leadership and expertise in inflammation, and we look forward to expanding our efforts in inflammation where aptamers could offer novel options to treat disease,” said Errol DeSouza, Ph.D., President and Chief Executive Officer of Archemix. “This is another step forward in our strategy to leverage our intellectual property estate together with our significant internal capabilities in order to develop aptamers for a variety of therapeutic areas with key partners who are experts in their field.”

Archemix will be responsible for the discovery and development of the aptamer therapeutics through completion of clinical proof of mechanism, unless GSK chooses to exercise its option earlier. After exercise of the option, GSK will have an exclusive license to drug product candidates developed under each programme by Archemix for the relevant aptamer target for further development and commercialisation on a worldwide basis. Archemix will have the right to further develop and commercialise any aptamer therapeutics which GSK chooses not to develop or commercialise.

“This innovative multi-target drug-discovery deal is an important extension of our externalisation strategy and provides GSK with an outstanding opportunity to work with the world leader in aptamer discovery and development,” said Jose Carlos Gutierrez-Ramos, PhD., Senior Vice President and Head of the Immuno-Inflammation Centre of Excellence for Drug Discovery in GSK. “The application of aptamers with their unique properties is an exciting opportunity that holds enormous potential for the treatment of many devastating diseases of the immune system.”

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com

Aptamers are synthetically-derived oligonucleotides, or short nucleic acid sequences, that bind to protein targets with high affinity and specificity and can be designed to have a specified duration of action. Aptamers represent an emerging class of potential therapeutic agents that Archemix believes may have broad application to treat a variety of human diseases.

Archemix – is a biotechnology company focused on discovering, developing and commercialising aptamer therapeutics. Using Archemix’s processes for discovering aptamers, which are protected by its broad patent portfolio, Archemix is developing aptamer product candidates for rare haematological diseases. In addition, Archemix has licensed its intellectual property to third parties to develop their own aptamer product candidates in other areas. Currently, Archemix’s licensees are evaluating five different aptamer product candidates in human clinical trials; two in Phase 2 and three in Phase 1. Archemix has additional partnerships with several pharmaceutical and biotechnology companies, including Merck Serono, Pfizer, Takeda, Eli Lilly and Isis Pharmaceuticals.

On November 18, 2008, Archemix announced that it had entered into a merger agreement with NitroMed, Inc., (NASDAQ: NTMD) pursuant to which Archemix has agreed to merge with NitroMed in an all-share transaction. The merger is subject to approval by Archemix’s and NitroMed’s shareholders, consummation of the sale of NitroMed’s BiDil and BiDil XR drug business and other customary closing conditions. As a result of the $27.5 million in upfront payments received by Archemix from GSK, Archemix now estimates that cash and cash equivalents for the combined company at the closing of the merger will be approximately $78-88 million.

Important Additional Information Will Be Filed with the SEC

In connection with Archemix’s proposed merger with NitroMed, NitroMed has filed with the SEC a Registration Statement on Form S-4 containing a joint proxy statement/prospectus. Once the Form S-4 is declared effective by the SEC, the joint proxy statement/prospectus will be mailed to shareholders of NitroMed and Archemix. The joint proxy statement/prospectus will contain important information about NitroMed, Archemix, the transaction and related matters. In addition, NitroMed has filed with the SEC and mailed to its shareholders a definitive proxy statement in connection with the previously-announced proposed sale of its BiDil and BiDil XR drug business to JHP Pharmaceuticals, LLC. The definitive proxy statement contains important information about NitroMed, the proposed sale of the BiDil and BiDil XR drug business and related matters. Investors and security holders of Archemix and NitroMed are urged to read carefully both the joint proxy statement/prospectus relating to the merger, when it is available, and the definitive proxy statement relating to the proposed sale of the BiDil and BiDil XR drug business.

Investors and security holders of Archemix will be able to obtain free copies of the joint proxy statement/prospectus for the merger (when it is available) by contacting Archemix Corp., Attn: Secretary, 300 Third Street, Cambridge, MA 02142. In addition, investors and security holders of NitroMed will be able to obtain free copies of the definitive proxy statement for the proposed sale of the BiDil and BiDil XR drug business and the joint proxy statement/prospectus for the proposed merger (when it is available), and other documents filed with the SEC by NitroMed through the website maintained by the SEC at www.sec.gov and also by contacting NitroMed, Inc., Attn: Secretary, 45 Hayden Avenue, Suite 3000, Lexington, MA 02421.

Archemix and NitroMed, and their respective directors and executive officers, may be deemed to be participants in the solicitation of proxies in respect of the transactions contemplated by the merger agreement with NitroMed. In addition, NitroMed, and its directors and executive officers, may be deemed to be participants in the solicitation of proxies in respect of the transactions contemplated by the purchase and sale agreement with JHP Pharmaceuticals relating to the sale of the BiDil and BiDil XR drug business. Information regarding NitroMed’s directors and executive officers is contained in NitroMed’s Annual Report on Form 10-K for the fiscal year ended December 31, 2007 and its proxy statement dated April 16, 2008, which are filed with the SEC. As of November 30, 2008, NitroMed’s directors and executive officers beneficially owned approximately 33% of NitroMed’s common stock. In addition, information regarding Archemix’s directors and officers and a more complete description of the interests of NitroMed’s directors and officers will be available in the joint proxy statement/prospectus relating to the merger. A more complete description of the interests of NitroMed’s directors and officers is also available in the definitive proxy statement relating to the sale of the BiDil and BiDil XR drug business.

Cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK’ s operations are described under ‘Risk Factors’ in the ‘Business Review’ in the company’ s Annual Report on Form 20-F for 2007.

23
Dec
08

Biomedical researchers create artificial human bone marrow in a test tube

physorg(PhysOrg.com) — Artificial bone marrow that can continuously make red and white blood cells has been created in a University of Michigan lab.

This development could lead to simpler pharmaceutical drug testing, closer study of immune system defects and a continuous supply of blood for transfusions.

The substance grows on a 3-D scaffold that mimics the tissues supporting bone marrow in the body, said Nicholas Kotov, a professor in the U-M departments of Chemical Engineering; Materials Science and Engineering; and Biomedical Engineering.

The marrow is not made to be implanted in the body, like most 3-D biomedical scaffolds. It is designed to function in a test tube.

Kotov, principal investigator, is an author of a paper about the research currently published online in the journal Biomaterials. Joan Nichols, professor from the University of Texas Medical Branch, collaborated on many aspects of the project.

“This is the first successful artificial bone marrow,” Kotov said. “It has two of the essential functions of bone marrow. It can replicate blood stem cells and produce B cells. The latter are the key immune cells producing antibodies that are important to fighting many diseases.”

Blood stem cells give rise to blood as well as several other types of cells. B cells, a type of white blood cell, battle colds, bacterial infections, and other foreign or abnormal cells including some cancers.

Cancer-fighting chemotherapy drugs can strongly suppress bone marrow function, leaving the body more susceptible to infection. The new artificial marrow could allow researchers to test how a new drug at certain potencies would affect bone marrow function, Kotov said. This could assist in drug development and catch severe side effects before human drug trials.

Bone marrow is a complicated organ to replicate, Kotov said. Vital to the success of this new development is the three-dimensional scaffold on which the artificial marrow grows. This lattice had to have a high number of precisely-sized pores to stimulate cellular interaction.

The scaffolds are made out of a transparent polymer that nutrients can easily pass through. To create the scaffolds, scientists molded the polymer with tiny spheres ordered like billiard balls. Then, they dissolved the spheres to leave the perfect geometry of pores in the scaffold.

The scaffolds were then seeded with bone marrow stromal cells and osteoblasts, another type of bone marrow cell.

“The geometrical perfection of the polymer molded by spheres is very essential for reproducibility of the drug tests and evaluation of potential drug candidates,” Kotov said. “The scaffold for this work had to be designed from scratch closely mimicking real bone marrow because there are no suitable commercially products.

“Certain stem cells that are essential for immunity and blood production are able to grow, divide and differentiate efficiently in these scaffolds due to the close similarity of the pores in the scaffold and the pores in actual bone marrow.”

The researchers demonstrated that the artificial marrow gives a human-like response to an infectious New Caledonia/99/H1N1 flu virus. This is believed to be a first.

To determine whether the substance behaves like real bone marrow, the scientists implanted it in mice with immune deficiencies. The mice produced human immune cells and blood vessels grew through the substance.

The paper is called “In vitro analog of human bone marrow from 3D scaffolds with Biomimetic inverted colloidal crystal geometry.”

Provided by University of Michigan

30
Dec
08

Israeli High-Tech Company Capital Raising Q1-Q3/2008 Summary

by Efrat Zakai, IVC Research Center, 12/30/2008

Introduction

Israel is considered by some to be one of the most advanced countries in Southwest Asia in terms of economic and industrial development. After the United States, Israel has the second-largest number of startup companies in the world and the largest number of NASDAQ-listed companies outside of North America.

Stanley Fischer, the Governor of the Bank of Israel was recently quoted as saying, “We are in very good shape.” Despite the turmoil in the American and world financial markets, the Bank of Israel Governor has expressed confidence that the economic situation in Israel will remain strong. Merrill Lynch demonstrated its confidence in the Israeli economy this year by applying for remote membership to the Tel-Aviv Stock Exchange (TASE).

This month Merrill Lynch was approved as TASE’s first remote member, providing the clients of the global financial services firm with direct access to the bourse while increasing the exposure of Tel Aviv-listed companies to a broad spectrum of foreign investors.

IVC Research Center is Israeli’s leading research center supplying business leaders with an unmatched wealth of data on Israeli venture capital, private equity and high-tech industries. In this week’s Buzz article, the IVC Research Center shares with us the results of its recent quarterly survey which indicates more good news for the Israeli economy.


Summary of Israeli High-Tech Company Capital Raising

Q1-Q3/2008 Survey

IVC Reports: $600 million raised in Q3, 45% above Q3/07 levels 2008 capital raising expected to reach an 8-year record high

Tel Aviv, Israel, November 10, 2008. The following are the findings of the Quarterly Survey conducted by the IVC Research Center, which for more than ten years has been at the forefront of venture capital and private equity research in Israel. This Survey reviews capital raised by private Israeli high-tech companies from Israeli venture capital funds and from other investors. The Survey is based on reports from 72 venture investors of which 46 are Israeli management companies and 26 are other – mostly foreign – investment entities.

One hundred and twenty-four Israeli high-tech companies raised $600 million in the third quarter of 2008 from venture investors – both local and foreign. The quarterly amount was the highest reported in the last eight years – 45 percent above the $414 million raised in the third quarter of 2007, and up 29 percent from the $465 million raised in the previous quarter.

“Q3 capital raising reached a record eight-year high, exceeding all projections for the quarter,” said Efrat Zakai, Director of Research at IVC. “We don’t expect the same rate of investment in the coming quarters. However, 2008 will be logged as a record year, even if the fourth quarter comes in considerably below average”, Zakai concluded.

The average financing round was $4.84 million, compared to $3.83 million in the third quarter of 2007 and $4.04 million in the second quarter of 2008. Eighty companies attracted more than $1 million each. Of these, 14 companies raised $5 million to $10 million each, 12 companies raised $10 million to $20 million, four companies raised $20 million to $40 million and two companies raised more than $40 million each.

In the three first quarters of 2008, Israeli high-tech companies raised $1.68 billion, 34 percent above the $1.25 billion raised in the corresponding period of 2007.

Israeli VC Investment Activity

In Q3, Israeli VCs invested $206 million in Israeli companies, compared with $172 million invested in Q3/2007 and $161 million invested in the previous quarter. The Israeli VC share of the total amount invested in Israeli high-tech was 34 percent, with the remainder of capital coming from foreign investors as well as non-VC Israeli investors.

First investments by Israeli VC funds were 28 percent of their total investments in the third quarter, compared to 51 percent and 22 percent in Q3/07 and Q2/08, respectively. The average First investment by Israeli VCs was $2.76 million, while the average Follow-on investment was $1.22 million.

Zeev Holtzman, Chairman of IVC Research Center and Giza Venture Capital said: “Israeli high-tech companies, responding to early signs of market changes and the falling dollar-shekel rate, have been raising follow-on capital to help them navigate through the long-anticipated global crisis. Now that the crisis is here, a similar rate of investment won’t be maintained.”

In the first three quarters of 2008, the Israeli VC fund share of investments in Israeli high-tech companies was 37 percent, compared to 43 percent in the corresponding period in 2007.

Capital Raised by Sector

The Communications sector led capital raising in Q3/2008 with $134 million or 22 percent of capital raised, followed by the Internet sector with $126 million or 21 percent – the highest Internet share since the fourth quarter of 2000. In the first three quarters of 2008, Internet companies attracted $247 million or 15 percent of total capital raised, which compares with $181 million or 14 percent in the first three quarters of 2007, $65 million or 6 percent in Q1-Q3/2006 and only $21 million or 2 percent in Q1-Q3/2005. 

Capital Raised by Stage

Fifteen Seed companies attracted $16 million, 3 percent of the total amount raised in Q3. During the first three quarters of the year, Seed companies attracted $73 million, just 4 percent of the total funds, which compares with $133 million or 11 percent in Q1-Q3/2007. These figures clearly indicate that seed activity has markedly slowed from the previous year period.

Chart 1: Capital Raised by Israeli High-Tech Companies ($m)

 


For more information: www.ivc-online.com

IVC Research Center is Israel’s leading research center providing business leaders with an unmatched wealth of data on Israeli venture capital, private equity and high-tech industries. IVC products and services are used regularly by venture capital funds, private investors, high-tech companies, financial investors and institutions, as well as public entities such as the Office of the Prime Minister, the Central Bureau of Statistics, the Bank of Israel and the Office of the Chief Scientist. IVC publishes the most comprehensive guide to Israeli venture capital and high technology companies – the IVC Yearbook. Among IVC products and publications are the Quarterly Survey, which examines capital raising trends by Israeli high-tech companies; the quarterly Israel Venture Capital Journal (IVCJ), which reviews developments in the venture capital, private equity and high-tech industries; and a comprehensive online database (www.ivc-online.com) containing over 8,000 Israeli high-tech companies, venture capital funds, investment companies and technology incubators, as well as news updates and lots more.

For additional information, please visit: www.ivc-online.com or contact

Efrat Zakai, +972-3-640-2337, efrat@ivc-online.com

01
Jan
09

Universities struggle as value of endowments falls

Tough decisions need to be made about how to cut costs.

Eric Hand

 

Some large research universities have suffered double-digit declines in their multibillion-dollar endowments since the autumn credit crunch and stock market collapse. The endowments have also become increasingly cash-poor precisely when they might be expected to compensate for downward pressures on academic budgets. The declines are presenting universities with tough choices: fire sales of endowment assets, or budgetary trimming in the form of pay cuts, freezes on hiring and deferred construction projects.

“It’s a very big problem,” says John Walda, president of the National Association of College and University Business Officers (NACUBO) in Washington DC. “A good number [of endowments] are seeing about a 30% decline since last year.”

Harvard University announced in December that its endowment, the world’s largest and worth $36.9 billion at mid-year, had dropped 22% from that amount by the end of November – with worse expected to come. As of mid-December, the world’s second-largest endowment, that of Yale University, had fallen 25% since mid-year, when it stood at $22.9 billion.

In some ways, the big universities have been a victim of their own success. As endowments experienced double-digit increases nearly every year through the 1990s and 2000s, universities have become ever more dependent on them in their overall budgets – even as endowment payouts remained roughly constant at around 5% per year. Ten years ago, Harvard’s endowment paid for a third of the operating budget of the school of arts and sciences; now it covers more than half of the $1.16-billion budget.

Endowments are suffering now partly because of the very investment methods they used to beat the broader markets year after year. Universities with endowments bigger than $1 billion – there were 76 of them in the United States in 2007, according to NACUBO – kept much of their money in more volatile ‘alternative’ investments that are ‘illiquid’, or difficult to convert into cash quickly, such as hedge funds and venture capital. By comparison, institutions with endowments of less than $25 million had a nearly opposite, more conservative approach, with much of their money being kept in cash and fixed-income assets (see chart).

John Nelson, an analyst with Moody’s in New York, says the alternative-investment approach is smart: even in the bear market, when share prices are falling, the stock portfolios of big universities have fared better than the Standard and Poor’s 500 share index, which dropped 31% from 30 June to mid-December.

“When are we going to be forced to sell some of these assets in the down market?”

But alternative investments, in addition to being illiquid, can also suck up cash from elsewhere. Hedge-fund managers, for example, require periodic new investments known as ‘cash calls’. These represent a problem at a time when universities need cash for salaries and construction projects and credit is hard to come by. “The tough choice that endowment managers face now is, ‘when are we going to be forced to sell some of these assets in the down market?’” says Nelson. Some managers, such as those at Harvard, are already trying to sell assets off for far less than they had been worth, according to reports in The New York Times and The Wall Street Journal.

Even knowing what the alternative assets are worth is a challenge. Yeshiva University in New York City revealed that $110 million in investments – 8% of the university’s endowment – had evaporated in the investment scheme created by Bernard Madoff, who was arrested on 11 December and charged with fraud that may have cheated investors of $50 billion (see ‘Medical charity folds after investment losses’). The current climate, says Walda, “will lead to more scrutiny of the underlying value of investments”.

The effects on departmental hallways have been varied and will probably play out over several years, as most endowments base their payouts on a principal amount smoothed by a three-year rolling average. Harvard has put a partial hiring freeze in place. Stanford University in Palo Alto, California, will trim its budget next year by 5% by postponing new construction, controlling salaries and cutting some jobs. The chancellor of Washington University in St Louis, Missouri, has promised to take a symbolic pay cut of nearly 10% off his half-a-million-dollar salary. The Georgia Institute of Technology in Atlanta is trimming its landscaping budget; the University of Hawaii is turning off its weekend air-conditioning; and the Field Museum of Natural History in Chicago, Illinois, is cutting its budget by 15% after the value of the museum’s endowment plunged by nearly US$100 million (31%) in the past six months (see ‘Downturn hits Chicago’s natural history museum’).

Making do

At the California Institute of Technology in Pasadena, endowment managers had started putting more money into cash and cash-equivalent assets in September, says spokesman Jon Weiner, and the university expects to weather the storm without a hiring freeze.

Few, however, are as optimistic about their prospects. In a survey released on 18 December by the National Association of Independent Colleges and Universities, half of the 371 college and university presidents who responded reported freezing new hiring. In addition, 22% reported freezing salaries, and more than two-thirds were planning to raise tuition fees for the next academic year. Their manoeuvres stem partly from falling endowments, but also from concerns such as greater difficulty in raising funds and declining student enrolment numbers.

The endowment phenomenon is largely American, where there is a long tradition of private fund-raising in higher education. In Europe, the only two universities with multibillion-dollar endowments are Oxford and Cambridge in the United Kingdom. By and large, big research universities outside the United States are much more dependent on public funding, says Thomas Estermann of the European University Association in Brussels. “Losing a higher percentage of public funding will be much worse for them,” he says. That is also the case for small universities in the United States, which are worried about budget cuts at the state level because their endowments won’t be bailing them out. The 1,600 private US institutions have a median endowment of only $16 million, according to 2007 data from the US Department of Education. Most public universities have similarly small endowments, with the exception of a handful of monster-sized ones, such as those of the University of Texas and the University of California systems.

Nearly a year ago, in a very different climate, universities were facing scrutiny in the US Congress. Representatives wanted to know why college tuition fees kept rising even though some universities, bolstered by successful endowments, seemed to be getting richer. They proposed legislation that would mandate state universities to spend 5% of the value of their endowment assets each year – for instance to reduce tuition fees – as is the case for private foundations. But that legislation has not yet got anywhere. Many will be watching to see if endowments, the cash cows for universities for so long, can sustain them through the long economic winter

 

 naturenews

Published online 31 December 2008 | Nature 457, 11-12 (2009) | doi:10.1038/457011a

05
Jan
09

Beyond the crunch

nature-reviewsThe effects of the credit crunch have been prominent in many industries in the past year, and, of course, the biopharma industry is not immune, especially companies that need funding. Nevertheless, many of the challenges for drug discovery and development in the next year and beyond are more familiar, but hopefully some potential solutions are emerging.

At the end of 2008, a group of high-profile figures associated with the UK biotech industry joined the growing number of leaders from other industries around the world asking for a government bailout — in this case involving the establishment of two UK£500 million funds. Without such funding soon, a host of biotech companies will fail in the next year, say the supporters of the proposal.

Although predicting the effects of the credit crunch on the biopharma industry in the coming year is a risky endeavour, some broad possibilities such as this seem to have become generally recognized. On one hand, smaller, less mature, companies are increasingly having to cut staff and terminate projects to stretch out their rapidly dwindling cash supplies, even in the United States, which has generally had a much more positive environment for biotech funding than the UK and elsewhere. Indeed, it has been reported that more than 100 public US biotech companies have less than 6 months’ worth of cash left.

Large biotech and pharma companies, on the other hand, generally have considerable cash reserves, and several have already stated their intentions to harness this position through licensing deals and acquisitions. For example, Novo Nordisk recently announced that they might spend as much as US$2 billion on takeovers in the next 12 months. Thus, the general impression is that for larger companies the credit crunch could provide opportunities to replenish pipelines through deals on terms that are considerably more favourable for them than would have been likely a year or so ago.

However, regardless of whether the credit crunch represents a serious threat or a potential opportunity for a particular company, a crucial challenge for the biopharma industry in general is still lacklustre late-stage pipelines. This challenge is made particularly acute by the widely acknowledged ‘patent cliff’, which is now close to reaching its steepest point. According to Datamonitor, between 2007 and 2012, the top 50 pharma companies face patent expiries on $115 billion worth of drugs1. The losses in sales are anticipated to be particularly severe from 2011/2012 onwards: products that lose patent protection in the key US market in these 2 years alone include the multibillion-dollar blockbusters Lipitor (Pfizer), Advair (GlaxoSmithKline), Plavix (Sanofi–Aventis/Bristol–Myers Squibb) and Seroquel (AstraZeneca).

Moreover, it is well acknowledged that many of the larger companies are not favourably positioned to offset this vast loss of revenue through the introduction of new drugs. For example, an analysis of the predicted performance of the 14 largest biopharma companies forecasted that, by 2012, the group overall would generate only $0.26 in new product revenue for every dollar of revenue lost owing to issues such as patent expiries2. Indeed, of the 14 companies, only two had a forecasted replacement ratio — the ratio of new-product revenue to established-product revenue lost — greater than 1.0 in 2012.

Unsurprisingly, despite the ongoing cost-cutting programmes — which have recently seen more than 50,000 jobs cut or planned to be cut from large biopharma companies — some industry analysts are speculating that the dual pressures of imminent patent expiries and lack of new drugs will be the catalyst for another wave of large-company mergers and acquisitions. However, given that past experience with mega-mergers suggests that productivity often suffers considerably for a long period post-merger, such short-term strategies could further damage the industry’s long-term chances of regaining its vitality.

Nevertheless, as highlighted in our traditional yearly news round-up on page 5, some promising novel alternatives for improving overall R&D productivity are emerging, perhaps most notable of which are a new breed of partnerships. For example, this year has seen the establishment of a range of closer and more collaborative relationships between large pharma companies and academic institutions, which might help to more effectively and rapidly link basic research advances in academia to the translational expertise of pharma. Furthermore, collaborations between companies in areas that might have previously been considered competitive, such as identifying biomarkers of toxicity, have reported their first successes. It must be hoped that some of these innovative partnerships will help provide a solution to the fundamental problems that had been plaguing the biopharma industry for years before the credit crunch took hold.

References

  1. The Pharmaceutical Industry 2008 (Datamonitor, March 2008).

  2. Goodman, M. Nature Rev. Drug Discov. 7, 795 (2008).

Nature Reviews Drug Discovery 8, 3 (January 2009) | doi:10.1038/nrd2802

09
Jan
09

BioLineRX in collaboration talls with Merck

The deal for BioLine’s schizophrenia drug could be worth several hundred million dollars.
Gali Weinreb 8 Jan 09 10:36
Sources inform “Globes” that drug development company BiolineRX Ltd. (TASE:BLRX) is negotiating with US pharmaceutical giant Merck for the commercialization of one of its two leading drugs, BL 1020 for the treatment of schizophrenia. BioLineRX declined to comment on the report.Senior representatives of Merck have already visited BioLine and have begun the due diligence process, and the two companies have already reached understandings regarding the commercialization conditions for the deal. Agreement is now dependent on the scientific due diligence that Merck is carrying out, during which the global pharmaceutical company will conduct its own trials. At the same time BioLine is also holding talks with others.If and when a deal is signed, it will earn BioLineRX an initial payment of more than $10 million, full funding of development, and milestone payments worth several tens of millions of dollars, even before the product reaches the market. Subsequently, the company would receive royalties from sales so that the deal could be worth hundreds of millions of dollars. The drug is in Phase IIb clinical trials, with interim results expected in the third quarter of 2009.In a presentation made by BioLine several weeks ago, the company said that it aimed to commercialize at least one of its two most advanced drugs by the end of 2009. The company’s second leading drug is BL 1040 for rebuilding heart tissue for heart attack sufferers. It is possible that both drugs will be commercialized by the end of the year.

There are many schizophrenia drugs on the market, both patented and without patents. But although the market is very competitive, there is no existing product which is thought to provide a fully successful solution to the problem. There are two families of effective medications, but each one has harsh side effects.

BioLine will be able to compete successfully on this market only if can present results, which are as effective as existing drugs, but with significantly less side effects. The IIa phase of the clinical trial, which involved 36 patients, showed outstanding statistical effectiveness and a small number of side effects. Previous safety trials were also completed with a small number of side effects.

BioLine shares rose 12% yesterday on the Tel Aviv Stock Exchange, and are up 4.55% in late morning trade today.

Published by Globes [online], Israel business news – www.globes-online.com – on January 8, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

09
Jan
09

Vanderbilt University Announces Partnership with Janssen Pharmaceutica N.V. for Schizophrenia Drug Research

vanderbilt-university

 

Vanderbilt University is pleased to announce a licensing and research agreement with Janssen Pharmaceutica N.V., focusing on discovery of novel drugs for the treatment of schizophrenia. Under the terms of the agreement Vanderbilt University grants Janssen Pharmaceutica N.V. a worldwide exclusive license to existing compounds acting on a neurotransmitter receptor target, and provides a mechanism for the discovery and licensing of additional novel compounds over the next three years.

The licensing and research agreement provides for a total of $10 million in upfront payment and committed research funding to the laboratory of Jeffrey Conn, Ph.D., Director of Vanderbilt’s Program in Drug Discovery. Additional payments will be made based on meeting certain milestones and through royalties on product sales.

Vanderbilt will use its state-of-the-art drug discovery infrastructure, including high throughput screening, medicinal chemistry, molecular biology, and pharmacology testing, to create novel compounds with properties compatible with becoming schizophrenia drugs. In addition to carrying selected compounds from the collaboration into clinical development and through commercialization, Janssen Pharmaceutica N.V. will bring its expertise to the partnership through input on compound design, synthesis and later -stage safety and pharmacokinetic studies.

“This is another milestone for our Program in Drug Discovery and we are excited to be teaming up with one of the world’s leading developers of drugs for treatment of schizophrenia, said Conn. “It is also a testament to Vanderbilt’s commitment to new approaches to drug discovery and developing new models by which academic institutions work closely with industry partners to deliver new breakthrough medicines that have a fundamental impact on human health.”

Stef Heylen, M.D., Chief Medical Officer, CNS Research and Early Development at Janssen, said, “Academic collaborations are an important part of our drug discovery strategy. This collaboration underscores the synergies between industry and academia that can help to create solutions for addressing unmet medical needs. It is a great example of how we can work together with academia to better understand complex diseases and hopefully bring improved treatments to patients.”

 

Media Inquires:
John Howser
Deputy Director / Director of Media Relations
Vanderbilt Medical Center – News and Public Affairs
Phone: 615-322-4747
Email: john.howser@vanderbilt.edu  
http://www.mc.vanderbilt.edu/npa  

 

 

13
Jan
09

Impact of Ovarian Hormones on the Modulation of the Serotonin Transporter by Fluvoxamine

Abstract

Most preclinical studies examining the mechanism(s) of action of antidepressants are carried out using male animals. Blockade of serotonin transporter (SERT) function by selective serotonin reuptake inhibitors (SSRIs) is the initial event that triggers a not completely understood process that results in clinical improvement in depression. To investigate whether there are differences in the ability of SSRIs to inhibit the SERT between male and female rats at different phases of the estrous cycle, clearance of locally applied serotonin (5-HT) was measured by in vivo chronoamperometry. Local application of the SSRI, fluvoxamine, directly into the CA3 area of hippocampus increased significantly 5-HT clearance time parameters in male rats and female rats in estrus or diestrus, but not in proestrus. The contribution of ovarian steroids to this result was investigated in ovariectomized (OVX) rats treated with estradiol benzoate (EB) and/or progesterone (P). In OVX-control rats, fluvoxamine increased clearance time parameters, whereas EB and/or P treatment blocked this effect, consistent with what was seen in female rats in proestrus. This effect was gender-specific, since treatment of castrated rats with EB/P had no effect on the ability of fluvoxamine to slow 5-HT clearance. The time course of hormonal effects showed that 1–60 min after local application of 17-beta-estradiol (E2) into the CA3 region of OVX rats, fluvoxamine had no effect on clearance time of 5-HT. E2–BSA mimicked E2’s effects at 10 min but not at 60 min. Pretreatment with estrogen receptor antagonists blocked the effects of E2. The finding that acutely both estradiol and progesterone can inhibit the ability of an SSRI to slow the clearance of 5-HT, may have important implications for the use of SSRIs in women.

Keywords:

serotonin transporter, estradiol, progesterone, fluvoxamine, chronoamperometry, hippocampus

 

Neuropsychopharmacology (2009) 34, 555–564; doi:10.1038/npp.2008.23; published online 5 March 2008

Saloua Benmansour1, Jonathan P Piotrowski1, Alfonso V Altamirano1 and Alan Frazer1,2

  1. 1Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
  2. 2South Texas Veterans Health Care System, San Antonio, TX, USA
Correspondence: Dr S Benmansour, Department of Pharmacology (MC 7764), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Tel: +1 210 567 4203; Fax: +1 210 567 4303; E-mail: benmansour@uthscsa.edu

Received 5 September 2007; Revised 10 January 2008; Accepted 28 January 2008; Published online 5 March 2008.

13
Jan
09

Short Onset of Action of a Serotonin Reuptake Inhibitor When Used to Reduce Premenstrual Irritability

Several studies suggest that serotonin reuptake inhibitors (SRIs) exert a more rapid effect when used for the treatment of symptoms such as anger and irritability then when used for depression, obsessive-compulsive disorder, or anxiety. In line with this, premenstrual irritability can be effectively dampened by intermittent administration of an SRI, from ovulation to menstruation, indicating an onset of action of 10 days or less. How fast this effect appears, in terms of hours or days, is of considerable theoretical interest, but has previously not been studied in detail. To explore this issue, 22 women with marked premenstrual irritability, who previously had responded to paroxetine, were given this compound during two menstrual cycles and placebo during one cycle in a double-blind, cross-over fashion. The women were asked to start medication in the midst of the luteal phase when irritability had been intense for 2 days. The paroxetine cycles differed significantly from the placebo cycle as early as 14 h after drug intake with respect to the number of subjects experiencing sustained reduction in irritability. When the different cycles were compared with respect to irritability-rating scores for each time of assessment, the difference was significant at day 3. The side effect nausea had an even more rapid onset (4 h), but usually disappeared within 4 days. To summarize, this controlled trial shows that an SRI reduces premenstrual irritability already within a few days after the onset of treatment.

Keywords:

irritability, premenstrual syndrome, premenstrual dysphoric disorder, serotonin reuptake inhibitor, paroxetine, onset of action

 

 

Mikael Landén1, Helena Erlandsson2, Finn Bengtsson3, Björn Andersch2 and Elias Eriksson4

  1. 1Department of Clinical Neuroscience, Section of Psychiatry S:t Göran, Karolinska Institutet, Stockholm, Sweden
  2. 2Department of Gynaecology and Obstetrics, Göteborg University, Göteborg, Sweden
  3. 3Department of Medicine and Care, Division of Clinical Pharmacology, Linköping University, Linköping, Sweden
  4. 4Department of Pharmacology, Institute of Neuroscience and Physiology, Göteborg University, Göteborg, Sweden

Correspondence: Dr Mikael Landén, Department of Clinical Neuroscience, Section of Psychiatry S:t Göran, Karolinska Institutet, SE 112 81 Stockholm, Sweden, Tel: +46 (8) 672 23 71, Fax: +46 (8) 672 19 08, E-mail: mikael.landen@cns.ki.se

Received 10 December 2007; Revised 27 April 2008; Accepted 8 May 2008; Published online 2 July 2008.

13
Jan
09

FORMA Therapeutics Announces Collaboration with Novartis Corporation (NVS) to Develop Inhibitors of Protein-Protein Interactions; FORMA Eligible to Receive Over $200 Million

CAMBRIDGE, Mass. — FORMA Therapeutics announced today that it has entered into a license and option agreement through the Novartis Option Fund. Under the terms of the agreement, FORMA will leverage its transformative biology and chemistry platform to develop inhibitors for an undisclosed protein-protein interaction target in the field of oncology. The agreement includes an upfront fee and potential milestones totaling over $200 million as well as royalties.

“Protein-protein interactions represent important target opportunities in the field of oncology drug discovery, but have been highly elusive to date,” stated Reinhard Ambros, Head of the Novartis Venture Funds. “Novartis is very excited to be collaborating with FORMA to access their biology and chemistry expertise and powerful discovery tools to unlock this challenging target class.”

“Working collaboratively with Novartis on these targets provides us with the opportunity to fully leverage our integrated drug discovery platform to accelerate the advancement of oncology programs into clinical development,” said Steven Tregay, CEO of FORMA. “We believe that this collaboration provides important validation for FORMA’s unique approach to drug discovery for challenging targets.”

About FORMA’s Integrated Drug Discovery Platform

FORMA is uniquely positioned through its unprecedented combination of technological capabilities and oncology expertise to access such novel target space and to develop a new generation of breakthrough oncology drugs. Some of the key features of FORMA’s discovery capabilities include:

  • Versatile cell-based screening platform which allows the screening of discrete targets in cells and quantitative genome/proteome-wide profiling and target identification.
  • Accessing new chemical space through structure guided drug discovery (SGDD) approaches leveraging proprietary computational and structural biology combined with our integrated chemistry platform which incorporates Diversity Orientated Synthesis (DOS). DOS combines the high stereochemical and structural diversity found in natural products with traditional combinatorial chemistry techniques. This approach has been proven to work for challenging targets and will allow the rapid optimization of lead therapeutic candidates.

FORMA Therapeutics is integrating transformative biology and chemistry to unlock the best targets and pathways that genomics medicine has revealed. FORMA builds on the vision of its academic founders: Stuart Schreiber, Todd Golub, Michael Foley, each of the Broad Institute of Harvard and MIT and leverages its innovative drug discovery platform to address challenging targets and develop a robust internal pipeline of targeted breakthrough oncology drugs. FORMA is a global company headquartered in Cambridge, MA with additional research operations in Connecticut, Singapore and Beijing. www.formatherapeutics.com

The Novartis Option Fund (NOF) is a $200 million fund which is part of the Novartis Venture Funds (NVF), which were established in 1996 and currently manage over $550 million in committed capital and is invested in more then 50 private companies. The objective of the $200 million Novartis Option Fund is to seed innovative companies through financing their initial investment. The investment is coupled with an option to a specific therapeutic program early validation for the start-up company’s technology/programs by large Pharma. The NVF team of nine investment professionals located in Basel, Switzerland and Cambridge, MA brings together extensive experience in pharmaceutical R&D and venture capital. For more information, visit www.venturefund.novartis.com

13
Jan
09

Young blood fights cancer

 

“New blood” can revitalize a company or a sports team. Recent research by Tel Aviv University finds that young blood does a body good as well, especially when it comes to fighting cancer.

The TAU researchers, led by Prof. Shamgar Ben-Eliyahu from the Department of Psychology’s Neuroimmunology Research Unit, discovered that a transfusion of “young” blood — blood which has been stored for less than 9 days — increased the odds of survival in animals challenged with two types of cancer. This finding, reported in the journal Anesthesiology, may solve an age-old mystery as to why some blood transfusions during cancer-related surgeries may lead to an increased recurrence of cancer and others do not.

“There is anecdotal evidence pointing to the fact that some surgeons really prefer to use younger blood units. They insist on it. Our research shows their reasoning might be sound,” says Prof. Ben-Eliyahu, explaining that the oldest blood in a blood bank usually sits on the shelf anywhere from 40 to 42 days before it expires.

Using an animal model, the researchers conducted tests on rats with leukemia and breast cancer. The odds of surviving the cancer, they found, were only compromised if the transfusion blood had been stored for nine or more days.

Can Transfusions Cause More Cancer?

“I don’t think this study will or should change the practices of surgeons in hospitals, but it is definitely something that needs to be investigated further in human clinical studies,” says Prof. Ben-Eliyahu. “It might have a serious impact on the survival of prostate or colon cancers — two cancers that are associated with a lot of bleeding. If our research proves to be true in human trials, it should revolutionize the way we look at transfusion in cancer patients.”

The study, Prof. Ben-Eliyahu points out, also led to one other interesting finding. Surgeons commonly transfuse blood from which white blood cells have been removed, believing that these cells can cause harmful effects in the recipient.

“However, we found that it was the red blood cells, not the white blood cells, which caused the negative effects,” he says. Because red blood cells carry oxygen to the body, transfusions cannot be withheld, but using fresher blood might be better for cancer patients, the professor maintains.

Banking Your Own Blood May Not Be Helpful

While Prof. Ben-Eliyahu urges that further studies need to be done in this potentially life-saving practice, he believes that in most cases of cancer, donor blood might be healthier for the recipient than one’s own blood, because such a supply is commonly built up in a bank weeks before an operation. “The age of the blood itself impacts survival. The best recipe for transfusions might be fresh blood from other people. We found no differences between autologous blood and blood from other donors. The latter can be stored for much shorter durations before use.”

The idea that transfusions of “older” blood may increase cancer metastasis remains controversial, Prof. Ben-Eliyahu notes. Negative effects might be limited to specific cancers or special circumstances. He suggests that researchers investigate not just any database relating blood transfusions to cancer, but only those that include data in which the transfusion itself was a risk factor in metastasis.

In other words, Prof. Ben-Eliyahu recommends that one should first establish, in a given dataset, that blood transfusion is a risk factor for cancer progression, and only then it will make sense to test whether the storage duration of blood affects survival rates. Alternatively, it is possible that blood transfusion is a risk factor in some types of cancer, but not in others, and it will thus be wise to test whether the storage duration of blood affects survival rates only in these specific types of cancer, he says.

If proven true in human studies, Prof. Ben-Eliyahu’s research — done in collaboration with Shir Atzil, a doctoral student — could broadly impact the healthcare system. Blood banks are already dealing with severe blood shortages in America, and the increased use of fresher blood will make it even harder to keep blood on the shelf. Cost is another factor, but a lower mortality rate may outweigh the price in dollars and cents.

###

American Friends of Tel Aviv University (www.aftau.org) supports Israel’s leading and most comprehensive center of higher learning. In independent rankings, TAU’s innovations and discoveries are cited more often by the global scientific community than all but 20 other universities worldwide.

Internationally recognized for the scope and groundbreaking nature of its research programs, Tel Aviv University consistently produces work with profound implications for the future.


15
Jan
09

Japanese BioAlliance Strategies Evolving

Changes are Necessary as Collaborations with U.S. Firms Often Run into Cultural Roadblocksgen_logo

Tom Burger
James E. Foley, Ph.D.

Significant transformations are occurring within Japan’s leading pharmaceutical companies as they consider strategic alternatives to doing business in the U.S. Traditionally, Japanese companies, other than the four largest—Takeda, Daiichi Sankyo, Astellas, and Eisai, have focused on two major types of strategic transactions: in-licensing or acquiring a compound for the purpose of developing and marketing it in Japan and Asia with perhaps some type of copromotion right in the U.S., which is almost never exercised, and out-licensing in-house developed compounds after completing Phase II trials in Japan. The in-licensing of U.S.-developed compounds to Japan is unlikely to change in any meaningful way as Japanese pipelines continue to weaken in spite of significant increases in domestic R&D investment. Japanese companies tend to lack critical mass and mainly focus on two or three therapeutic areas. They have always found it politically difficult to drop programs that have been championed by members of top management or influential community thought leaders. Loss of face is a greater consideration than loss of cash. In short, U.S. innovation is, and will continue to be, needed and valued. Japan’s track record of out-licensing developed compounds to U.S. or global companies has been spotty at best. Alliances with larger pharmaceutical companies have far too often resulted in the Japanese company getting the short end of the stick. One example is Shionogi’s 1998 license deal with AstraZeneca for Crestor®. Shionogi would be better off today if it owned 100% of an $8 billion drug in the U.S. alone. Partnering with a smaller specialty pharma is difficult given the tremendous cultural differences in addition to the conflicting short and long term objectives—U.S. companies typically dream of getting taken out at an enormous premium. Whereas Japanese companies dream of building a large global company that will be respected within society. These two wildly differing views of the world seldom result in a harmonious relationship. Faced with this “damned if we do, dammed if we don’t” scenario, a new model has begun to emerge. Strategic Alternatives Two recently announced deals, Shionogi/ Sciele Pharmaceuticals and Kowa/ProEthic Pharmaceuticals, demonstrate that the strategic path for maximizing the value of the U.S. market is changing. This trend will fundamentally change the way small- and mid-sized U.S. firms think and may well make it more difficult for Big Pharma to complete traditional transactions with Japanese counterparts. Shionogi currently has several strategic partnerships in the U.S. Its interest in globalization commenced in 1997 with the initiation of a U.S.-based R&D center near Boston. The company reversed course in 2002 and announced that it planned to cease R&D operations in the U.S. After quickly selling off pieces of its business, it returned to the traditional model of doing R&D in Japan and out-licensing after Phase II data was available. In 2001–2002, Shionogi restarted independent U.S. operations intending to market products developed in Japan directly in the U.S. rather than through “less than optimal” partnering deals. The acquisition of Sciele Pharmaceuticals represents a pattern that we believe will be repeated by more and more Japanese companies in the next few years. Why would Shionogi pay $1.4 billion for Sciele Pharmaceuticals? Sciele has a collection of marketed compounds that are losing market share and seeing falling revenues. So why, then, did Shionogi pay a 57% premium over the previous day’s closing price? Two words: sales force. “It’s easier to buy these assets than to build them. Sciele’s current drugs will be used as a bridge, providing Shionogi with U.S. revenue as it develops its own drugs, which have greater commercial potential but are several years away from reaching the market,” said Ken Trbovich, analyst at RBC. Additionally, it has become even easier to justify these hefty prices given the 30% increase in the value of the Japanese Yen during the past 18 months. Simultaneous to the dramatic change in the relative value of the dollar vs. Yen, U.S. companies have found it nearly impossible to finance growth. Day after day we have all read the barrage of Wall Street Journal articles telling us that the IPO market is completely shut; banks aren’t lending; and VC funds are being inundated with requests for withdrawals. Meanwhile, Japanese pharmaceutical companies have been hording cash at levels that we would never see in the U.S. These three events (strong Yen, closed financial windows in the U.S., and cash- heavy companies in Japan) have made for the perfect storm and will continue to create tremendous opportunities for strategic collaborations that play off of both parties’ relative strengths and weaknesses. In the past when a Japanese company has tried to build a sales presence on its own, it has quickly found that adapting to the motivation methods that work in the U.S. are simply too difficult to get passed by a Japanese board of directors. Almost without exception, each of these efforts has failed. Of late, though, dramatic changes are being seen in the backgrounds of Japanese pharmaceutical executives. Isao Teshirogi, Ph.D., president of Shionogi, has spent considerable time in the U.S., speaks fluent English and worked at McKinsey & Co. rather than traditionally working his way through positions at Shionogi. The acquisition of ProEthic Pharmaceuticals by Kowa Pharmaceuticals similarly focuses on sales presence. Among Kowa’s pipeline of products, pitavastatin will play a key focus in its U.S. growth plans. What do these changes mean for U.S.-based specialty pharmas? As we see it, developing one’s own sales force will become as important, if not more important, than successful development of lead compounds in terms of building value in the enterprise—particularly if M&A is the preferred exit. These changes will make it more difficult for large pharma and specialty pharma to in-license attractive candidates from Japan as Japanese firms now have a cleaner, more attractive alternative. Transactions among Big Pharma for attractive late-stage opportunities will clearly become more competitive as the number of deals decreases. It remains to be seen, however, whether a Japanese company can successfully recruit, manage, and motivate a U.S.-based sales organization. For this reason, the next step in this on-going evolution will involve strategic partnerships resembling a JV structure rather than full acquisitions. Hiring and retaining top talent, whether sales or management, has always been a significant problem—a situation unlikely to change anytime soon. Japanese companies would be wise to carefully consider the value of an acquisition when the assets have the ability to walk out the door every night.

 

http://www.genengnews.com/articles/chitem.aspx?aid=2737

21
Jan
09

Biotech sector ponders potential ‘bloodbath’

graveyardPeter Mitchell

 

Introduction

 

The economic downturn and lack of financing is sending many a small firm to the graveyard.

 

A large proportion of small public biotech companies now find themselves at serious risk of going out of business, with not enough cash to see them through the next 12 months and negligible prospects of refinancing. As banks have run out of lending money, as hedge funds and private equity investors have shut up shop and the public equity markets spiraled into a free fall, financing options for cash-hungry biotech companies have dwindled. By the end of November, total capital raised by the industry had fallen by 56% from the previous year, according to data from BioCentury. By the end of this year, the global biotech landscape could look vastly different from the past.

“The current crisis is unparalleled in its scope and severity,” says Gautam Jaggi, senior manager at Ernst & Young Global Biotechnology, in New York, and it will lead to substantial consolidation, restructuring, layoffs and delistings (Box 1). According to the Biotechnology Industry Organization (BIO; Washington, DC), 180 quoted US biotech companies have less than a year’s cash in hand—the level at which most CEOs, employees and investors find themselves swallowing hard and considering less palatable options for fueling a company. Of these, 120 have less than six months’ breathing space (the majority are microcaps, Box 2 and Figs. 1 and 2).

Figure 1: Percentage of biotech firms operating with less than one year’s cash.

 

 

 

 

 

 fig11

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 2: Percentage of cash-poor microcaps in various regions.

 

 

 

“Some companies have already gone under as a result of the credit crunch, while others have had to scale back their research,” says BIO president and CEO Jim Greenwood. Five US biotech companies sought bankruptcy protection during November alone, after October’s high-profile default and bankruptcy of inflammatory disease research firm Atherogenics, located in Atlanta. Twenty-four small public biotech firms laid off workers in the eight weeks between November 1 and December 5, Greenwood adds (Table 1).

Table 1: Public companies restructuring

 table

 

 

 

 

 

What’s more, average market valuations have collapsed. BIO reports that, as of November 24, valuations of small caps (it defines small cap as a market capitalization of less than $1 billion) were down 53% from their January 1, 2008, values. In fact, BIO says about 35% of the 270 US small-caps were trading at below cash in early December, meaning stock markets valued the firm at less than their cash on hand.

These depressed valuations mean acquisition opportunities for the larger pharma firms, which are looking for products and companies to plump up pipelines at bargain prices. Johnson & Johnson’s purchase of New York–based Omrix, which makes human plasma-derived surgical products such as fibrin sealants, and thrombin, as well as immunoglobulins to treat immune deficiencies and infections is a case in point. The $438 million paid in November by the New Brunswick, New Jersey–based pharma occurred after Omrix’s shares had fallen about 40% over the course of 2008.

But sitting on their slush funds, pharma is likely to wait some time longer before it pounces. Dennis Purcell, senior partner of venture capital (VC) firm Aisling Capital of New York, agrees big pharma is circling, but he doesn’t expect the mass consolidation that some are predicting. Pharma companies typically do one deal at a time, he says, and “they are all going through strategic reviews of their own, aimed at narrowing down their therapeutic areas.” Purcell expects investors in many cash-starved biotech firms to insist on survival at all costs, by trimming activities to match cash reserves and thereby living to fight another day. “Companies are taking pretty drastic measures: delaying projects, cancelling early-stage projects, putting capital where they get most bang for the buck,” says Purcell.

The European scene, with its historically weaker financing infrastructure, is suffering even more than the US. Willy de Greef, head of the trade organization EuropaBio in Brussels, says next year could be a “bloodbath.”

“[2008] was already not the best of years for new financing rounds, with fewer deals being done,” says de Greef. “As for 2009, some of these companies are now in deep trouble. If the banks are beginning to put down the phone on the General Electrics and General Motors of this world, with their huge cash flows, what chance do we have in the biotech industry?” He adds that biotech is “going to be punished with oblivion for reasons over which they have exactly zero control.”

The British government has already announced fiscal measures to boost innovative industries, whereas countries like Germany are hesitating but at least making encouraging noises. Meanwhile, UK biotech firms are taking matters into their own hands. Twenty-two leaders from its biotech sector signed a dossier sent to the UK Prime Minister and the Business Secretary. Entitled The UK Biotechnology Sector—Recommendations To Transform the Industry, the dossier calls for the creation of a national biomedical public-private partnership, including a National BioMedical Consolidation Fund and a National Super Growth Biomedical Fund—each worth at least £500 ($742.7) million (see Editorial, p. 1).

In the US, BIO is lobbying Congress for emergency measures to stimulate biotech investment. It wants capital gains tax on invested funds to be temporarily cut or suspended and emerging companies to be allowed to receive a refund of their net operating losses to set them against research expenses. It also wants more flexibility on the use of R&D tax credits. But Greenwood insists BIO is not asking for a capital infusion.

“Entrepreneurs who go into biotech are survivors, they knew going in it was a highly risky enterprise,” he says. “For the most part companies will survive, they will skinny down through the lean times and wait for the recovery.”

 

 Even if most of the industry weathers the storm, the effects could ripple out for years. If investors aren’t funding today’s startups, it could mean a lack of innovation and a dearth of early-stage products five years down the line. Aisling Capital’s Purcell notes that venture capitalists’ main priority now is to keep their existing portfolios healthy. “There is not enough capital for everybody in the portfolio, so VC companies are triaging to decide where to spend it where it makes most difference,” he says. And that doesn’t mean startups.

If every downturn has a recovery, then the biotech sector must simply hold on. But it will not come tomorrow, as most estimates put any reversal at least six months if not more than a full year away. Those companies not already affected are anticipating the blade (Box 3 and Figs. 3 and 4). However, E&Y’s Gautam Jaggi believes that when the turn does come, it will be big: “There will be a lot of pent-up demand and investors will ultimately return to the IPO [initial public offering] market in a big way,” he says. “There will be fewer biotech companies, but the survivors will be the stronger for it.”

Figure 3: Department of company in which respondents expect layoffs.

 

 

 

 

 

 

 

fig-32

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 4: Ways in which respondents expect company to acquire funding.

 

 

 fig-4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Box 1

 

 Off the exchange

Nasdaq delisted 81 companies for regulatory issues or noncompliance in 2008 through the end of November (268 firms delisted overall, including for reverse mergers and acquisitions). Of those, 19 were biotech firms (63 biotechs were delisted for all reasons), meaning that 23% of Nasdaq’s regulatory or noncompliance delistings were from the biotech industry. BIO says another 86 biotech companies were facing delisting as of the beginning of October.
Against this backdrop, and facing as many as 344 potential delistings across all sectors as of October, Nasdaq has said it will ease enforcement in hopes of helping keep companies on the exchange.

Box 2

The smallest are the weakest

 

Box 3

Sampling Industy opinion

 

A survey conducted by Avance’s Ralph Villiger drew 142 respondents from the drug development and affiliated sectors—47 of them from biotech firms. More than half of the respondents said they anticipated being affected by the financial downturn. Most did not anticipate laying off employees, but of those who did, the biggest cuts are expected in R&D (Fig. 3).
Considering financing, most respondents felt that future money would come through joint ventures, licensings and collaborations (Fig. 4).

Nature Biotechnology examined the financial reports of more than 400 public biotech firms (mid-year filings for the most part) to discern where the trouble lay, and data show the situation is particularly dire for the microcap firms (Figs. 1 and 2). More than 40% of the microcaps studied were operating with less than one year’s cash in reserves, based on their most recent financial disclosures as Nature Biotechnology went to press. In comparison, fourth-quarter filings for 2005, 2006 and 2007 show that 31.7%, 34.6% and 27%, respectively, of microcaps were in that same precarious position.
With the equity markets dead, the mood for these small firms is “dark,” says Ralph Villiger, a partner at service and solution provider Avance, in Basel. A survey from his firm shows that the majority of respondents feel the economy will not turn around for one to two years, and most expect to be affected. They anticipate more mergers, smaller total value for deals and an increase in deals that reward the back end. More than half feel raising capital would be “impossible.”
Not only is the cash drought disproportionately hitting microcaps, but it is also likely to persist longer for those firms, says Stelios Papadopoulos, chairman and founder of Exelixis in S. San Francisco, California, and a long-time investment banker focused on biotech. “When the market does come back, it will look first at the robust, solid, dividend-paying major industrial concerns,” Papadopoulos says. “It will be a long time before the $100 million company with 20 employees gets its moment of happiness.” He predicts that the crisis could wipe out as many as one in five biotech firms with market caps less than $200 million. “They will either go bankrupt or they will be taken over for nominal amounts of money,” says Papadopoulos, citing as an example London-based GlaxoSmithKline’s $57 million buyout of Redwood City, California–based Genelabs in November.
A sinking valuation and shrinking cash pile pushed Montvale, New Jersey–based Memory Pharmaceuticals to find a buyer. Roche, of Basel, is acquiring all outstanding shares of Memory for $0.61 per share, or about $50 million—a far cry from the valuation the company received when it went public in spring 2004, raising $35 million by selling 5 million shares at $7 a piece. But it’s also a 319% premium to the share price before the Roche announcement. The companies were already partnered on two programs, but before Roche stepped in, Memory spent 2008 watching its cash position dwindle, its auditor label it a going concern and Nasdaq threaten delisting.
Pro-Pharmaceuticals of Newton, Massachusetts, has a similar problem but as of publication had not found a solution. The company had $816,000 in cash at the end of the third quarter and had lost $2.3 million over the first nine months of the year. It was looking to raise money in November through a rights offering to current shareholders but was also seeking a partner for its colorectal cancer drug, Davanat (carbohydrate polymer), which is close to regulatory submission.
The microcap layer is pocked with these stories, and it is from here that biotech will see most of its losses. Licensing deals might save some, and acquisitions rescue others, but those that are unable to find money or a lifeboat one way or the other will simply “vanish,” says Villiger.

 

Nature Biotechnology 27, 3 – 5 (2009) doi:10.1038/nbt0109-3

20
Jan
09

Teva and Lonza link to tap biosimilar drugs market

* Move underlines growing interest in field by major firms

 

* Joint venture to start up in first quarter 2009

 

By Ben Hirschler

 

LONDON, Jan 20 (Reuters) – Israel’s Teva Pharmaceutical Industries (TEVA.TA), the world’s biggest maker of generic drugs, is joining forces with Swiss-based Lonza (LONN.VX) to exploit the emerging market for so-called biosimilar medicines.

 

The two companies said on Tuesday they had formed a strategic partnership to become a leading global provider of biosimilars, or generic versions of biotechnology drugs.

 

Their joint venture — to develop, manufacture and market a portfolio of products — is expected to commence activities in the first quarter of 2009.

 

Financial details of the agreement were not disclosed.

 

Shlomo Yanai, Teva’s chief executive, said biosimilars were a major growth driver for Teva, and Lonza was “an ideal partner” given its experience in manufacturing antibodies and other complex biotech drugs for pharmaceutical companies.

 

Bernstein analyst Ronny Gal agreed, arguing the combination of Lonza’s large manufacturing base and Teva’s drug development capability meant the joint venture had a complete platform.

 

Teva and Lonza did not specify which products they intended to copy but Gal said he suspected they were primarily targeting Amgen (AMGN.O) and Wyeth’s (WYE.N) rheumatoid arthritis drug Enbrel and the cancer drug Rituxan, or MabThera, from Genentech (DNA.N), Biogen Idec (BIIB.O) and Roche (ROG.VX).

 

Biosimilars are viewed as a promising new market, given the pent-up demand for cheaper versions of extremely expensive biotech drugs, some of which are coming to the end of their patent life.

 

 

HOT AREA

 

In Europe, the first such biosimilars have already been approved and on the market.

 

The United States, the world’s biggest and most lucrative pharmaceuticals market, is still discussing a regulatory pathway for follow-on biotech treatments but the new Obama administration is expected to push for their introduction.

 

“There is no doubt that biogenerics has become very sexy with the beginning of the government of Barack Obama and Democratic control in both houses of Congress,” Yoav Burgan, an analyst at Israeli brokerage Leader Capital Markets, said in a note to clients.

 

“It’s possible that in 2009 we will finally see the hoped-for creation of a regulatory path for approving biogeneric drugs in the United States.”

 

Burgan said the Lonza tie-up reinforced Teva’s commitment to biosimilars, following the purchase of CoGenesys and Pliva’s biogeneric activities, the latter being part of its acquisition of Barr.

 

Teva’s shares were 0.9 percent higher by 1230 GMT while Lonza added 0.6 percent.

 

Because they are complicated to manufacture, biosimilars are expected to enjoy higher margins than conventional “small molecule” generic drugs — a fact which means some branded drugmakers are also interested in making them.

 

Merck & Co (MRK.N) announced a big push into biosimilars last month and other big drug companies, such as Eli Lilly (LLY.N) and AstraZeneca (AZN.L), have also recently expressed interest.

 

The growing interest from major players is set to ratchet up the pressure on companies such as Amgen that rely on older biotech drugs, which are likely to be the first generic targets. (Additional reporting by Tova Cohen in Tel Aviv; Editing by Jon Loades-Carter and Elaine Hardcastle)

 

 

 

© Thomson Reuters 2009 All rights reserved.

 

 

20
Jan
09

Stroke patients to be treated with tailor-made brain cells.

Green light for UK stem-cell trialstem-cells

 

 

Helen Pilcher

 

 

Stem cells will be grafted into the brains of patients during the new trial. Researchers have been given the go-ahead for a clinical trial to assess the use of stem-cell transplants for stroke. Twelve people will take part in the preliminary safety study, the first time that brain-derived stem cells have been used to treat stroke patients.

 

The trial, due to start later this year, will see different doses of cultured human neural stem cells grafted into the brains of patients who have had a stroke — often caused by a blood clot blocking one of the vessels leading to the brain. The study will assess how safe the procedure is, but will also monitor changes in mobility and brain function.

 

“I’m cautious but hopeful,” says neurologist Keith Muir of the University of Glasgow, UK, who will coordinate the trial. “We’ve tried a lot of things in stroke over the years, most of which haven’t been helpful.”

 

Stroke is the leading cause of death and the single biggest cause of adult disability in the developed world. Around half of all stroke survivors are left with permanent disabilities. Although clot-busting treatments can help restore blood flow if given soon after the stroke, most treatment focuses on rehabilitation such as physiotherapy.

 

So researchers are searching for other therapies. Stem-cell transplants are an attractive option because the primitive cells have the potential to form many other cell types, and may be able to repair or replace damaged brain cells.

 

Human stem cells have been grafted into the brains of stroke patients before, but the results were inconclusive. Because those cells came from an embryonic tumour, scientists were concerned that they might become cancerous in the patients’ brains.

 

Chemical switch

The cells in this study, developed by UK biotechnology firm ReNeuron, have been tailor-made for transplantation. Originally isolated from a human fetus, the cells have been modified by the addition of a gene that promotes cell growth. This helps them to divide in culture in the lab so they can be grown up into the vast numbers required for the trial.

 

Crucially, the gene’s activity can be switched on and off by adding or removing a chemical in the culture dish. When the chemical is removed, the cells stop dividing and are ready for transplantation without the risk of tumour formation. The UK Medicines and Healthcare products Regulatory Agency has given the green light for the use of these cells in the study.

 

 “It’s exciting to see things that we’ve worked on for many years coming to trial,” says Steve Dunnett from Cardiff University, UK, who studies cell transplantation.

 

ReNeuron researchers have already tested the therapy in stroke-damaged rat brains, in which the cells prompted new blood vessels and neurons to form. The animals also regained control of movement in their front paws.

 

The cells will be transplanted into patients around six months after their stroke, by which time any remaining brain damage is thought to be permanent. “But it’s hard to imagine that once you’ve got an area of dead tissue, transplanting cells into it will make much difference,” says Roger Barker from the University of Cambridge, UK, who studies transplantation therapies for neurodegenerative diseases. It may be that the cells will work better if transplanted earlier, he adds.

 

Published online 19 January 2009 | Nature | doi:10.1038/news.2009.41

 

 

naturenews

20
Jan
09

Keep That 1876 Journal Handy, It Just May Help Treat Diabetes

klinische-wochenschriftBy JACOB GOLDSTEIN

A Harvard researcher hopes an old arthritis drug, which he read about in a 19th century German medical journal, could be a cheap new treatment for diabetes.

This 1876 paper from the Berliner Klinische Wochenschrift suggested salsalate could help diabetics control their blood sugar.

In the late 1990s, Steven Shoelson’s research suggested that the drug, called salsalate, might also help diabetics. The idea sent him into the basement stacks of a Harvard library to see whether anyone else had pursued the notion.

He found an 1876 article published in a German medical journal that suggested salsalate might improve diabetics’ ability to control blood sugar. “It was then that I said, ‘Aha! We’re on to something big,’” Dr. Shoelson recalled.

Since that rediscovery, Dr. Shoelson and his colleagues at the Harvard-affiliated Joslin Diabetes Center have seen promising results from several small studies of Type 2 diabetes — the most common form of the disease. A large study funded by the National Institutes of Health was launched late last year.

If the research bears fruit, the use of an inexpensive and already familiar drug like salsalate could benefit patients not only in the U.S., but also in developing countries where diabetes is on the rise and where costly medicines are unaffordable for many.

Diabetes raises the risk of everything from heart attacks to kidney failure, and the rapid spread of the disease is a key driver of health costs in the U.S. and beyond. But using medicine to control the disease can radically reduce many of the risks.

“It’s a cheap, generic drug that has the potential to add to our tools for improving glucose control in diabetics,” says Myrlene Staten, an NIH scientist who has overseen some of the agency’s funding for the research. “Improving glucose control lowers the cost of diabetes treatment and the risk of complications and hospitalizations.”

Salsalate is an anti-inflammatory drug. It blocks a chemical pathway Dr. Shoelson believes may be a key link between inflammation and diabetes. But diabetes experts disagree over whether inflammation is an important factor in the disease.

Stephen O’Rahilly, a diabetes researcher at Cambridge University and self-described “inflammo-skeptic,” points out that about a dozen genes have been identified as risk factors for Type 2 diabetes-and none seems to be related to inflammation. For the most part, the genes relate to the ability of the pancreas to produce insulin, a protein that is essential for the body to process sugar. Dr. O’Rahilly, who consults for several pharmaceutical companies, has a friendly bet with Dr. Shoelson — a bottle of champagne — over whether the inflammation hypothesis will pan out.

Inflammation traditionally has been seen as the body’s response to infection or injury. But as researchers have identified the chemical pathways associated with inflammation, they have found signs of inflammation connected to other factors. Obesity, for example, tends to cause chronic, low-grade inflammation.

That inflammation, Dr. Shoelson believes, makes insulin less effective. Most people are able to produce more insulin to overcome this problem, but those with genetic risk factors for diabetes aren’t able to do so, and they develop the disease. Using salsalate to reduce inflammation could break this chain.

In a set of small studies with about 30 diabetic patients, the drug significantly lowered spikes in blood sugar, according to a 2008 article in the journal Clinical and Translational Science by Dr. Shoelson and his colleagues.

Another study was conducted last year and included more than 100 diabetics randomly assigned to receive either salsalate or a placebo. The results haven’t been published yet, but they were promising enough to convince the NIH to fund a yearlong trial with more than 400 patients.

That study is likely to provide the clearest picture yet of whether salsalate holds promise in treating diabetics. But it probably won’t be enough to provide the clear answers about both safety and effectiveness that would be required to win salsalate’s approval from the Food and Drug Administration as a diabetes treatment.

Since salsalate already is sold as an inexpensive, generic arthritis medicine, pharmaceutical companies have little financial incentive to fund research. The Joslin center, which has received at least two patents based on Dr. Shoelson’s research, is considering seeking support from foundations for the large, multiyear studies that could be required for FDA approval. Dr. Shoelson says he has no financial stake in salsalate’s development.

“We really want to see it remain inexpensive,” says Allison Goldfine, who is overseeing much of Joslin’s clinical research into salsalate.

Salsalate carries a safety warning, shared by many painkillers, that it may increase the risk of heart attacks and strokes. But the drug works differently than the other painkillers in the class, and there is no clear evidence that it shares that risk.

In fact, another NIH-funded study Dr. Shoelson’s group is working on seeks to determine whether the drug lowers the risk of heart disease by slowing the buildup of plaque in the arteries around the heart.

 wsj_print

Write to Jacob Goldstein at jacob.goldstein@wsj.com

22
Jan
09

Teva recruiting 100 new employees

 Teva has also been taking in employees fired by other companies. teva

Einav Ben-Yehuda 

 While most companies are announcing layoffs, Teva Pharmaceutical Industries Ltd. (Nasdaq:TEVA; TASE:TEVA) is recruiting 100 new employees. Teva corporate VP human resources Isaac Abravanel told “Globes” that the company had also taken in employees who have been laid off from other companies. He said “We want to recruit 100 new people for our production activities in Jerusalem. In recent months, following the wave of lay offs in the Israeli economy, we initiated contacts with various companies who had fired employees like ECI, Intel, Tnuva, Alliance, Ampa, Kodak and Orbotech and we took in employees for our activities in Jerusalem and Kfar Saba. We are also striving to take in workers from the ultra-orthodox Jewish sector, new immigrants from Ethiopia and Iran and returning Israelis.” However, Abravanel admitted that there was a slowdown in recruitment, taking into account that Teva had hired 2,000 new people over the past two years. He said, “the slowdown in recruitment is mainly because of the acquisition of Barr Pharmaceuticals.” At the same time Abravanel stressed that there will be no layoffs or salary cuts. “We have no reason to fire employees. Employment stability is one of Teva’s strategic values. There is no need to change anything relating to the company’s human resource management. We will carry on hiring, carry on raising salaries and carry on getting rid of employees who are not so good.”

Published by Globes [online], Israel business news – www.globes-online.com – on January 21, 2009 © Copyright of Globes Publisher Itonut (1983) Ltd. 2009globes1

22
Jan
09

J&J to invest as much as $13M in Enlight Biosciences

Enlight Biosciences and Industry Giant Johnson & Johnson Forge Partnership

 Ryan McBride

Enlight Biosciences, a Boston-based biotech firm advancing new technologies used in the discovery and development of drugs, said today it has gained a commitment from Johnson & Johnson to invest up to $13 million in its programs. Johnson & Johnson, the New Brunswick, NJ-based healthcare giant (NYSE:JNJ), is the latest drugmaker to form a partnership with Enlight. The list of Enlight’s partners now includes Eli Lilly, Merck, and Pfizer. Enlight now has attracted as much as $52 million to direct toward technologies intended to help its Big Pharma partners improve their chances of bringing breakthrough drugs to the market. “When you’re developing technologies where you’re trying to drive industry adoption, having multiple big pharmas around the table from the very beginning has a great impact,” says David Steinberg, founding CEO of Enlight. Steinberg is part of the team at Boston’s PureTech Ventures, which co-founded Enlight and manages the company. Enlight aims to address a crucial need among pharma companies to develop technologies in such fields as molecular imaging, drug formulation, and drug synthesis—all of which could improve R&D needed to fill the pharma firms’ ailing pipelines with new drugs. Johnson & Johnson and its peers are struggling to find new drugs to replace the revenues from older products that face present or future competition from generic drugs. (In fact, J&J got a call to action to launch new drugs this week when it reported a 67.4 percent decline in fourth-quarter 2008 sales of blockbuster schizophrenia drug risperidone (Risperdal), which the company blamed on generic drug competition.) Luke captured the ongoing dilemma facing the pharma industry in his story about the public launch of Enlight in July 2008, in which he wrote that drug companies are pumping record-high billions of dollars into research and development while actual U.S. drug approvals are lagging. Johnson & Johnson hopes to collaborate with Enlight’s other pharma partners to identify technologies that could help all of them overcome R&D hurdles. “Participation in this initiative will allow us to work with our consortium peers to identify technology needs and influence future industry standards,” says Gary Neil, corporate vice president of J&J’s Office of Sciences and Technology, in a statement. Enlight’s pharma partners get to choose the programs in which they invest, while Enlight tracks down the technologies worthy of their investment from multiple academic and industry sources. Enlight has already launched a virtual startup, Endra, which develops technology that combines the capabilities of ultrasound and optical imaging to, for example, show researchers whether a drug is shrinking tumors during clinical trials, Steinberg says.

http://www.xconomy.com/boston/2009/01/22/enlight-biosciences-and-industry-giant-johnson-johnson-forge-partnership/

22
Jan
09

S*BIO and Tragara Announce an Exclusive Worldwide License Agreement for Novel Multi-kinase Inhibitor SB1317

SINGAPORE and SAN DIEGO, Jan. 21 /PRNewswire/ — S*BIO Pte Ltd and Tragara Pharmaceuticals Inc. today announced that S*BIO has granted a worldwide exclusive license to Tragara to develop and commercialize its novel multi-kinase inhibitor SB1317.

tragara

Under the terms of the agreement S*BIO is eligible to receive up to US$112.5 million in payments. This includes an upfront fee, development and sales milestone payments and up to double-digit royalties. Additionally, S*BIO will perform certain preclinical activities for Tragara under a defined workplan in return for research fees. Tragara is responsible for all IND enabling, development and commercialization activities under the agreement.

SB1317 is a novel orally-available, multi-kinase inhibitor with excellent pharmacological and pharmaceutical properties. SB1317 development will be initially focused on the treatment of hematologic malignancies and Tragara will also explore the therapeutic potential of the compound’s activity in solid tumors.

“Our entire Tragara team is excited about adding SB1317 to our product pipeline,” said Thomas M. Estok, President and CEO of Tragara. “S*BIO successfully identified a promising compound for the treatment of hematological and potentially solid tumors and we look forward to further profiling the compound and moving it toward clinical development.”

“We are pleased to work with Tragara in rapidly advancing SB1317 through IND enabling studies to the clinic. We chose Tragara as a partner due to a combination of their experience, exciting clinical development plans and commitment to speed. Together we will determine the full breadth of the compound’s competitive advantages in a series of preclinical profiling studies prior to Tragara advancing this product through parallel tracks of clinical development,” said Dr. Jan-Anders Karlsson, CEO of S*BIO.

About Tragara Pharmaceuticals Inc

Tragara Pharmaceuticals, Inc. is a privately-held pharmaceutical company based in San Diego, Calif. The company is focused on the clinical and commercial development of proprietary medicines for the treatment of cancer and inflammation. Tragara strives to provide much-needed therapies that will contribute to patient health through better survival and an increase in the quality of life. Tragara’s lead program, Capoxigem(R) (apricoxib, TG01), is currently in Phase II clinical development in lung, breast and pancreatic cancers and has completed a Phase II study in inflammation/pain. A second program, an oral multi-kinase inhibitor, TG02 (SB1317), is in late stage preclinical development.

Tragara is managed by a team of entrepreneurs with both Big Pharma and Biotech experience in the development and commercialization of oncology therapeutics. More information about Tragara can be found at www.tragarapharma.com.

About S*BIO Pte Ltd

S*BIO is a privately-held biotech company focused on the research and clinical development of novel targeted small molecule drugs for the treatment of cancer with leading programs around histone deacetylases (HDAC) and kinases. S*BIO’s lead candidate, SB939, entered the clinic in 2007. SB1518, S*BIO’s potent and orally-active JAK2 inhibitor, also entered the clinic in 2008 and has received orphan drug designation from the U.S. FDA. S*BIO has entered into a development collaboration, and option & license agreement with Onyx Pharmaceuticals, Inc. to develop and commercialize SB1518 and its other novel JAK2 inhibitor, SB1578. S*BIO’s SB1317, a novel multi-kinase inhibitor, is in pre-clinical development and under a worldwide exclusive license with Tragara Pharmaceuticals, Inc. for its development and commercialization.

In line with its vision to be a leading fully-integrated oncology-focused biotech company in Asia Pacific, S*BIO has established a state-of-the-art R&D infrastructure, complemented by a strong clinical development team. S*BIO has strong links with a network of medical oncologists in Asia Pacific . More information about S*BIO can be found at www.sbio.com.

SOURCE S*BIO Pte Ltd

23
Jan
09

A stretcher for the 21st century

By David Shamah  

It’s called the “golden hour” – the immediate aftermath of an injury, when medical care makes the most difference. According to many emergency room doctors, patients heal more quickly and efficiently if they are treated within the first 60 minutes after sustaining an injury or trauma.

In the hospital, the golden hour is easy to beat; there’s a full staff of care workers, and the hospital has the life-saving equipment and supplies doctors need to treat patients properly. In the field, though, it’s a different story; every minute counts, and if the patient is in a spot that ambulances or medical workers can’t get to, the golden hour can quickly pass – and with it, the chances for a patient to fully recover.

Thanks to Herzliya’s Fisher Institute for Air and Space Strategic Studies, more injured people will be able to receive golden hour treatment – even if they’re stuck in a location that doctors and ambulances can’t get to.

To expand the range of patients who can be treated in this first hour, Tal Inbar, and Dr. Eran Schenker, head of the Fisher Institute’s Aerospace Medicine Research Center, have designed the MedUAV concept vehicle – an unmanned air vehicle that can hover, land, or take off vertically without the need for a runway or a landing pad.

Flying in aid, flying out patients

A revolutionary device in the area of field medicine, the MedUAV can deliver medical supplies and advanced gear into the field, or transport patients to nearby medical facilities.

The idea for the MedUAV came as a result of research carried out by Schenker on battlefield medicine. “Under battlefield conditions, it’s almost impossible to ensure proper care when injuries occur,” he tells ISRAEL21c.

“The challenge is getting the soldier to the treatment area. Evacuating patients in time to take advantage of that first hour where treatment is so vital, is very difficult, because often helicopters or other modes of transport can’t get to the field because of the ongoing battle – and it’s impossible to take all the equipment that would be needed for proper care right to the front,” he explains.

In fact, the most practical method for transporting injured soldiers – the stretcher – dates back to World War I. “There have been some improvements in the basic model since then, but the concept is the same,” says Schenker, adding that the MedUAV is designed to be the 21st century answer to the stretcher.

The strength of the device, which is already at prototype stage and will be launched in the coming months, is that it can fly in all the gear necessary for treatment of the injured – like a flying first aid kit – enabling field medical workers to administer treatment, even if the patient can’t be transported to a field hospital right away.

“In addition, the equipment can be monitored remotely by a doctor, so when a patient is hooked up to a device in the field, the doctor at the medical center can see readings and measurements – and guide the field worker to use the equipment to its best advantage,” says Schenker.

And, once the initial treatment is completed, the patient can be strapped into the MedUAV for transport back to the medical center.

A safer alternative to helicopters

So how is the MedUAV different from, say, a helicopter? For one thing, it’s safer, says Schenker, because it doesn’t require a crew to fly directly into a battle zone. “Where military commanders might be afraid to send a helicopter because of the danger it would be shot down, they would be more willing to send an unmanned UAV. Besides being unmanned, it’s a much smaller target, and thus harder to shoot down and more likely to get to where it has to go,” he explains.

That, combined with the MedUAV’s ability to hover, launching and landing vertically with little (if any) open ground space, makes it a more practical solution for emergency battlefield treatment and transport than helicopters, he says.

And what works on the battlefield will work in civilian emergencies as well – like earthquakes, where it’s likely that the debris from toppled buildings would make it very difficult to fly in medical help.

The MedUAV could also be used in the event of train and bus crashes, where victims are often stuck in ravines – such as the recent bus accident near Eilat, where 25 Russian tour guides were killed. The concept could also be used in situations where civilians find themselves under fire.

US Navy expresses interest

The flexibility of the device is already attracting interest from overseas. The US Navy and other military organizations have approached the institute to find out more.

The Fisher Institute is a non-profit research organization that funds air and space technology projects. It is modeled on the Rand Institute in the US, according to Brigadier General Asaf Agmon, the institute’s CEO.

Among the Fisher Institute’s missions, Agmon says, is working on research to enhance air and space travel, developing position papers on the issues in order to promote discussion and research, organizing conventions and forums for international researchers to gather and discuss ideas, and running educational programs to raise awareness on advances in air and space research.

One project the Fisher Institute has underwritten, says Agmon, has been research into how birds and planes can coexist in increasingly crowded skies, and how to handle medical emergencies in the air.

The institute also runs dozens of after-school “flying clubs,” where kids learn about aviation and space, and participate in a science contest, in which they build prototypes of devices that will make air travel safer.

In May last year, the MedUAV concept was selected as one of the best 60 technology projects at the “Facing Tomorrow” exhibition, part of the Israel Presidential Conference 2008.

This project is exactly the type of thing Israel excels at,” says Schenker. “We’re one of the top countries in the world in the field of UAV development, medical devices, and tele-medicine – remote treatment of patients. The MedUAV is a meld of these three areas of distinction, and we expect the project to succeed and do well.”

 

Published in Israel21C                                                                                     

23
Jan
09

Pfizer in Talks to Buy Wyeth for $60 B

 

By MATTHEW KARNITSCHNIG and JONATHAN D. ROCKOFF

 

 

Pfizer Inc. is in talks to acquire rival drug maker Wyeth in a deal that could be valued at more than $60 billion, said people familiar with the matter.

A combination of these two U.S. pharmaceutical giants would redraw the boundaries of the global drug industry, which has suffered from flagging product development and high fixed costs. It would also represent a high-stakes gambit for Pfizer, which has been stung in the past by expensive acquisitions.

The two sides have been in discussions for months and a deal isn’t imminent, the people said. Given recent market volatility and overall economic uncertainty, the talks are especially fragile and could collapse, the people warned.

Pfizer spokesman Raymond F. Kerins Jr. said the company doesn’t comment on “market rumors and speculation.” A Wyeth spokesman said, “We don’t comment on marketplace rumor.”

 

Joining New York-based Pfizer and Madison, N.J.-based Wyeth would create a behemoth with combined revenue of about $75 billion and a line of blockbuster drugs including Pfizer’s cholesterol drug Lipitor and Wyeth’s pediatric vaccine Prevnar.

Pfizer, the world’s largest drug maker by revenue, would likely use a combination of cash and stock for the acquisition. Details on price haven’t been worked out, but Wyeth has a market capitalization of about $52 billion and premiums in the sector have averaged just over 20%. That would put the value of the deal at well over $60 billion.

If completed, a deal could create billions in cost savings through the combination of back-office operations, research and development, sales and manufacturing. Like other major pharmaceutical companies, Pfizer and Wyeth face the looming expiration of patents on their most lucrative products as well as intense competition from makers of generic drugs. In addition, a tougher regulatory environment in the U.S. and overseas has made it more difficult to win approval for new treatments, forcing companies to narrow their research focus.

Those realities have prompted calls for industry consolidation from the investment community. For years, companies have withstood pressure to merge, hoping that new discoveries would allow them to maintain independence. But with drugs generating an estimated $30 billion in sales losing patent protection over the next several years, many analysts have been saying industry consolidation is inevitable.

Unlike other sectors of the economy, the pharmaceutical industry has historically been buffered from downturns because patients typically don’t stop seeking treatment for major ailments. While there are growing signs that this recession has triggered a decline in prescription-drug consumption among cash-strapped consumers, major companies nonetheless have streams of cash they can use for acquisitions.

Pfizer alone had more than $27 billion in cash and equivalents on its balance sheet at the end of 2008, Goldman Sachs estimated in a recent note to investors. Analysts believe that most of that money is outside the U.S. and Pfizer would suffer a tax hit if the company repatriated the funds. Many in the industry have been waiting to see what Pfizer does before pursuing deals of their own.

Pfizer posted revenue of $48.4 billion and a profit of $8.1 billion in 2007, the most recent year for which data are available. Wyeth’s revenue totaled $22.4 billion and its profit $4.6 billion in 2007.

The stocks of both companies have held up fairly well over the past year compared with the rest of the market. Pfizer’s shares have fallen about 23% while Wyeth’s stock is down 7.5%. The S&P 500 is off 37% over the same period.

Combining major drug companies doesn’t solve the industry’s short-term need for new drugs, but it would allow the industry to slash research-and-development spending, which accounts for nearly 20% of sales at many companies.

With more scale, drug companies would also be better positioned to acquire biotech companies, which many believe will be a source of future treatments. Many pharmaceutical companies have already begun to buy or strike drug-development deals with smaller biotech firms. While promising in the long term, such deals tend to bring too little revenues and profits in the short term to make up for the loss of blockbuster drugs.

 Mr. Kindler has been cutting costs, firing more than 15,000 employees since January 2007. A person familiar with the matter say Pfizer is planning to cut as many as 2,400 sales-force jobs in the first quarter of 2009. The chief executive has also been revamping drug-research efforts, shuttering laboratories and selling manufacturing pla

Pfizer Chairman and CEO Jeff Kindler, in November 2008

Pfizer Chairman and CEO Jeff Kindler, in November 2008

nts.

Investors and analysts have grown increasingly frustrated that these steps aren’t enough to return Pfizer to the kind of profitability that made it a stock-market star in the 1990s and early 2000s. Since Mr. Kindler took over, Pfizer stock is down 34%, compared with a drop of 20% for the Dow Jones Wilshire Pharmaceuticals Index.

Critics have lambasted Pfizer’s 2006 sale of its consumer business, which included the Listerine, Visine and Lubriderm brands, as well as nonprescription drugs Sudafed and Nicorette. That unit is now helping its buyer, Johnson & Johnson, weather problems in its own prescription drug business.

Of big drug makers, Pfizer in particular has been built through big acquisitions. It gained full control of Lipitor after a $116 billion takeover of Warner-Lambert Co. in 2000. But Pfizer’s deal-making history also suggests the pitfalls of what analysts say is a reliance on big takeovers over strong in-house research and smart licensing.

Pfizer bought Pharmacia in 2003 largely for painkiller Celebrex, but sales plunged after a rival drug, Vioxx, was withdrawn in 2004 over heart risks.

“The record of big mergers and acquisitions in big pharma has just not been good. There’s just been an enormous amount of shareholder wealth destroyed,” said Gary Pisano, a Harvard Business School professor who has written about the issue.

Bernard Poussot, Wyeth, in October 2007.

Bernard Poussot, Wyeth, in October 2007.

Nonetheless, analysts have named Wyeth as a likely target because the company has products and businesses that complement Pfizer’s lineup. It’s not clear what role Wyeth CEO Bernard Poussot would play in the combined company.

Wyeth has already established a foothold in biotechnology. The company has had strong success with Prevnar, its pediatric pneumococcal vaccine, which brought in $2.11 billion in sales in the first nine months of 2008, a 12% increase over the year-earlier period. The company’s pipeline includes a new version, Prevnar-13, that is designed to offer enhanced protection against pneumococcal disease. Another strong biotechnology seller in Wyeth’s portfolio is the anti-inflammatory biologic Enbrel, which Wyeth co-markets with Amgen Inc.

Wyeth also would bring with it an animal-health business and consumer-health unit whose brands include Advil, Robitussin and ChapStick. Those businesses would help offset the cyclicality and risks of the drug business.

 

In the absence of big merger deals, pharmaceutical companies have tried to buy time by slashing costs. Most notably, the industry has eliminated about 15,000 sales jobs since pharmaceutical sales-rep ranks reached a peak of about 105,000 in the first quarter of 2006, according to ZS Associates, a sales and marketing consulting firm.

 

Consultants say the industry still hasn’t cut costs nearly enough, and analysts have increased the pressure on executives like Mr. Kindler. Investors are especially keen on acquisitions from cash-rich pharmaceuticals companies now that values of smaller companies have shrunk.

“There is no major payday in R&D coming in the next several years, and the personal makeovers will not be enough,” Deutsche Bank analyst Barbara Ryan wrote in a recent note to investors.

—Dana Cimilluca and Sarah Rubenstein contributed to this article.

Write to Matthew Karnitschnig at matthew.karnitschnig@wsj.com and Jonathan D. Rockoff at jonathan.rockoff@wsj.com

Printed in The Wall Street Journal, page A1

Copyright 2008 Dow Jones & Company, Inc. All Rights Reserved

 wsj_print

27
Jan
09

Astellas Proposes to Acquire CV Therapeutics for $16 Per Share in Cash

Proposal Values CV Therapeutics at $1.0 Billion and Represents a 41% Premium for CV Therapeutics Stockholders       astellas

TOKYO–(BUSINESS WIRE)–Astellas Pharma Inc. (”Astellas”) today announced that it has submitted a proposal to the Board of Directors of CV Therapeutics, Inc. (Nasdaq: CVTX) to acquire all outstanding common shares of CV Therapeutics for $16.00 per share in cash. The proposal represents a 41% premium to the closing share price of CV Therapeutics on January 26, 2009, and a 69% premium to CV Therapeutics’ 60-day average closing price. The proposal is not subject to any financing condition and represents a total equity value of $1.0 billion on a fully diluted basis.

This proposal was previously submitted to the Board of Directors of CV Therapeutics in a letter dated November 14, 2008 and Astellas was informed on November 21, 2008 that the CV Therapeutics Board had rejected the proposal. CV Therapeutics has subsequently declined to engage Astellas in any meaningful discussions regarding a transaction.

“We are disappointed that the CV Therapeutics Board of Directors has rejected outright what we believe is a very compelling all-cash proposal that would deliver stockholders significant immediate value that we believe far exceeds what CV Therapeutics can achieve as a standalone company,” said Masafumi Nogimori, president and CEO of Astellas. “CV Therapeutics’ product portfolio, including its angina treatment agent Ranexa®, would complement Astellas’ US based hospital and cardiology business, and our established infrastructure and proven track record in drug development and commercialization provide an ideal platform to increase the value inherent in CV Therapeutics.

“We are surprised that the CV Therapeutics Board has refused to engage us in meaningful discussions about our proposal; however, we remain committed to working cooperatively with CV Therapeutics to reach a mutually agreeable transaction should the Board reconsider our proposal and decide to engage us in discussions promptly.”

Included below is the full text of the letter sent to the CV Therapeutics Board of Directors earlier today:

January 27, 2009

CV Therapeutics, Inc.

The Board of Directors

c/o Dr. Louis G. Lange, Chairman of the Board & CEO

3172 Porter Drive

Palo Alto, CA 94303

Gentlemen:

I am writing to express our disappointment that you have rejected Astellas’ proposal of November 14, 2008, to acquire CV Therapeutics, Inc. for $16.00 per share in cash, and that you have subsequently refused numerous requests – made both directly and through our advisors since then, and as recently as January 13, 2009 – to engage in substantive discussions about a combination that would deliver substantial and immediate value to your stockholders.

We remain enthusiastic and committed to a transaction with CV Therapeutics, and we continue to believe our proposal provides your stockholders with significant immediate value that we believe far exceeds the value CV Therapeutics could reasonably expect to achieve as a standalone company in the foreseeable future.

We believe our proposal takes into full account the future potential of CV Therapeutics – with no execution risk to your stockholders. Our offer represents a 41% premium to CV Therapeutics’ share price as of January 26, 2009, and a 69% premium to its 60-day average price.

Astellas has built a productive partnership with CV Therapeutics around Lexiscan over several years, and we have watched and helped the company grow during this time. We are enthusiastic about Ranexa, but we believe it will be a significant challenge for CV Therapeutics to deliver the full value of Ranexa to your stockholders given CV Therapeutics’ limited commercial presence and the difficult macro environment. We believe Astellas is better positioned to maximize the value of CV Therapeutics, and Ranexa in particular, by leveraging Astellas’ infrastructure and marketing expertise.

I want to emphasize that our proposal is not subject to any financing condition, and we expect the transaction would receive regulatory approvals in a timely manner. While we have conducted a substantial amount of due diligence to date, our proposal remains subject to confirmatory due diligence, execution of definitive agreements and the satisfaction of customary conditions to be set forth in such agreements.

For over the past year we have attempted to discuss a possible acquisition transaction with CV Therapeutics that would maximize the value of CV Therapeutics for your stockholders. Our desire continues to be to work together with the CV Therapeutics Board of Directors to reach a mutually beneficial transaction but we have been very disappointed that you have refused to engage us in such discussions.

We remain prepared to meet immediately with you and your advisors to discuss our proposal. We believe that we could conclude our due diligence review and execute a definitive agreement in approximately three to four weeks. We have retained Lazard as our financial advisor and Morrison & Foerster as our legal advisor.

We are very enthusiastic about the prospects for a combination between CV Therapeutics and Astellas. We hope you will reconsider our proposal and we look forward to your prompt response.

Yours sincerely,

Masafumi Nogimori

President and CEO

About Astellas

Astellas Pharma Inc., with global headquarters in Tokyo and US headquarters in Deerfield, Illinois, is a pharmaceutical company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. The organization is committed to becoming a global pharmaceutical company by combining outstanding R&D and marketing capabilities and continuing to grow in the world pharmaceutical market.

Astellas was formed by the historical merger of Japan’s third and fifth largest pharmaceutical companies – Yamanouchi, founded in 1923, and Fujisawa, founded in 1894. Today, Astellas is one of the largest pharmaceutical companies in Japan with a market capitalization of approximately $17.7 billion as of January 26, 2009, and, for the fiscal year ended March 31, 2008, net income of approximately $1.8 billion.

The company has approximately 14,000 employees worldwide. This includes 7,500 in Japan, 3,300 in Europe, 2,200 in North America and 1,000 in Asia. Some of Astellas’ core products in the US are: Lexiscan® (regadenoson) and Adenoscan® (adenosine injection), pharmacologic stress agents indicated for radionuclide myocardial perfusion imaging/scintigraphy (MPI/S) in patients unable to undergo adequate exercise stress; Prograf® (tacrolimus), an immunosuppressant indicated for the prophylaxis of organ rejection in patients receiving organ transplants; and VESIcare® (solifenacin succinate), indicated for the treatment of overactive bladder with symptoms of urgency, frequency, and urge incontinence.

Astellas is publicly traded on the Tokyo Stock Exchange. For more information about Astellas Pharma Inc., please visit www.astellas.com. For more information about Astellas Pharma US, Inc., please visit http://www.us.astellas.com/.

For further information regarding Astellas’ offer for CV Therapeutics, please visit www.cvtxvalue.com.

This press release is neither an offer to purchase nor a solicitation of an offer to sell securities of CV Therapeutics. Subject to future developments, additional documents regarding a transaction with CV Therapeutics may be filed with the Securities and Exchange Commission (the “Commission”) and, if and when available, would be accessible for free at the Commission’s website at http://www.sec.gov. Investors and security holders are urged to read such disclosure documents, if and when they become available, because they will contain important information.

Astellas is not currently engaged in a solicitation of proxies or consents from the stockholders of CV Therapeutics. However, in connection with Astellas’ proposal to acquire CV Therapeutics, certain directors and officers of Astellas may participate in meetings or discussions with CV Therapeutics stockholders. Astellas does not believe that any of these persons is a “participant” as defined in Schedule 14A promulgated under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), in the solicitation of proxies or consents, or that Schedule 14A requires the disclosure of certain information concerning any of them. If in the future Astellas does engage in a solicitation of proxies or consents from the stockholders of CV Therapeutics in connection with its proposal to acquire CV Therapeutics, Astellas will amend the information provided above to disclose the information concerning participants in that solicitation required by Rule 14a-12 under the Exchange Act.

No assurance can be given that the proposed transaction described herein will be consummated by Astellas, or completed on the terms proposed or any particular schedule, that the proposed transaction will not incur delays in obtaining the regulatory, board or stockholder approvals required for a transaction, or that Astellas will realize the anticipated benefits of any proposed transaction.

Any information regarding CV Therapeutics contained herein has been taken from, or is based upon, publicly available information. Although Astellas does not have any information that would indicate that any information contained herein is inaccurate or incomplete, Astellas does not undertake any responsibility for the accuracy or completeness of such information.

Astellas does not undertake, and specifically disclaims, any obligation or responsibility to update or amend any of the information above.

28
Jan
09

Cutting calories may improve memory

 

Cutting calories by 30% for three months has boosted memory and reduced insulin concentrations in a group of healthy elderly people.

Previous research on the possible benefits of calorie restriction has yielded mixed results. Some studies have found no benefits. Others have found that calorie restriction protects rats and mice against age-related memory loss and some neurodegenerative diseases. In humans, cutting calories has been linked to prolonged health, but there have been no previous reports of an effect on memory.

Now, neurologist Agnes Flöel and her colleagues at the University of Münster in Germany have filled that gap. The group looked at 50 people divided into three groups: one maintained its usual diet, one was told to cut calories and the third was was asked to eat more polyunsaturated fatty acids — nutrients found in foods such as fish and olive oil that have previously been linked to reducing the risk of cognitive impairment. The participants were either of normal weight or overweight, and averaged just over 60 years old.

Three months later, the researchers found that those who cut calories were 20% better at remembering a list of words than those who either maintained the same diet or ate more polyunsaturated fatty acids. Their work has been published in the Proceedings of the National Academy of Sciences1.

“It is an important advance,” says Mark Mattson, chief of the laboratory of neurosciences at the National Institute on Aging in Baltimore, Maryland. “It is taking something that was predicted from animal studies and showing that it works in humans.”

Sweet success

Memory improved in both normal and overweight people, but the number of participants was too small to allow a thorough comparison of the two groups, says Flöel. She and her colleagues plan to repeat the study in a larger group, and to study the effects of cutting calories in patients with mild cognitive impairment.

Why would cutting calories improve memory? One possibility is that the body becomes more efficient at processing sugar. Participants who cut calories also had lower concentrations of the hormone insulin, which regulates levels of sugar in the blood. Lower insulin suggests that the participants had become more sensitive to the hormone, and previous work has suggested that improved insulin responses can benefit the brain.

In addition, Flöel and her colleagues found lower concentrations of a protein associated with inflammation in the patients who followed a restricted diet. Preliminary studies of that protein, called C-reactive protein, have shown that low concentrations are associated with improved memory in elderly people.

Flöel’s study relied on questionnaires filled out by the participants to ascertain whether everyone was sticking to their diets. That has led some to wonder whether the participants really cut calories by 30%. Andrzej Bartke of the Southern Illinois University School of Medicine in Springfield notes that although participants on a reduced-calorie diet lost weight, he might have expected them to lose a little more on such a strict regimen. “Most people would not stick to 30% below what they normally eat,” he says. “That’s pretty severe. People get hungry.”

If some participants broke the rules, however, it suggests that less-draconian measures might also be effective, he says. “It doesn’t take very much weight loss to get, in some regard, significantly healthier,” says Bartke.

•        References

1.       Witte, A. V., Fobker, M., Gellner, R., Knecht, S. & Flöel, A. Proc. Natl Acad. Sci. USA 106, 1255–1260 (2009).

 

·         Published online 26 January 2009 | Nature | doi:10.1038/news.2009.57

 

naturenews

27
Jan
09

Wyeth Deal May Slow Pfizer Biotech Acquisitions

By ANDREW POLLACK

 

This month Pfizer’s chief executive, Jeffrey B. Kindler, held a breakfast for venture capitalists atop a hotel in San Francisco. Some guests took it as a sign that Pfizer was serious about buying young biotechnology companies or licensing their technology.

But Pfizer’s deal to buy a big pharmaceuticals rival, Wyeth, raises questions about how willing — or able — Pfizer will be to enter deals anytime soon with biotechnology companies, many of which are struggling to stay in business.

Wyeth itself will also now be unlikely to buy other companies. On Monday, it withdrew from talks about buying Crucell, a Dutch vaccine maker, sending Crucell’s shares tumbling about 14 percent in Nasdaq trading.

In deciding to buy one of its Big Pharma brethren, albeit one with considerable expertise in biotech drugs, Pfizer dispelled the hopes of some investors that it would acquire a major biotechnology company like Amgen or Biogen Idec.

Amgen’s shares fell nearly 4 percent on Friday, when news of a possible Wyeth deal surfaced, while Biogen shares, also hurt by positive news about a competitor’s drug, fell 7 percent. Both stocks recovered somewhat on Monday.

But Amgen and Biogen are big enough to fend for themselves. More precarious is the condition of many smaller biotechnology companies, those without revenue-producing products and profits. With capital markets frozen, many of these companies are running out of cash and looking to sell themselves or their products to a larger company.

“There are probably 5,000 biotech companies out there that are waiting for a deal to save them,” said Oleg Nodelman, portfolio manager at the Biotechnology Value Fund, which invests in smaller biotechnology companies. Pfizer executives say they remain interested in alliances and deals. “We are going to continue to look at opportunities for innovative drugs and technology,” Corey S. Goodman, the president of Pfizer’s Biotherapeutics and Bioinnovation Center in South San Francisco, Calif., said Monday.

But others say the debt that Pfizer took on to buy Wyeth might preclude it in the short run from buying any but the smallest of biotech companies. And when two big companies merge, talks for deals with smaller companies tend to get put on the back burner, as management’s attention is diverted and the newly combined company assesses its research pipeline.

“It will just drag people’s attention away, and they will want to do only the critical things,” said Jonathan MacQuitty, a partner at venture capital firm Abingworth. With small, unprofitable private biotech companies unable to go public, venture capitalists’ hope for a payout are typically based on selling the companies they start to pharmaceutical companies.

Matt Geller of Geller Biopharm, a boutique investment bank, says that because Wyeth is so science-oriented, it has been seen as a good potential partner for smaller and middle-size biotechnology companies. “Unfortunately,” he said, “it does take a potential buyer of smaller biotech companies off the market.”

Pfizer, on the other hand, had a reputation for paying top dollar for products or for smaller companies. It raised many eyebrows last September, for instance, when it agreed to pay $225 million initially, and possibly hundreds of millions of dollars later, for the rights to an Alzheimer’s disease drug being developed by Medivation, a San Francisco company.

Pfizer is behind many of the other large pharmaceutical companies in moving into biologic drugs, which are made in living cells and are more immune to generic competition. But it is trying to make strides.

In late 2007 it hired Mr. Goodman, an academic neuroscientist and biotechnology entrepreneur, to lead its move in that direction, in part by arranging alliances with smaller companies and with universities. To keep the operation nimble, Mr. Goodman reports directly to Mr. Kindler, the chief executive, and has a fair degree of autonomy.

Some experts say Pfizer’s purchase of Wyeth might actually spur other pharmaceutical companies to buy biotechnology companies. One reason Pfizer was interested in Wyeth was the latter’s expertise in manufacturing biotech drugs and vaccines.

“I think it’s just further evidence of how valuable these assets are,” said Kris Jenner, portfolio manager of the T. Rowe Price Health Sciences Fund. “There are plenty of buyers outside of Pfizer who are interested in biotech assets.”

Moreover, Pfizer’s ability to arrange $22.5 billion in debt financing from five banks for the Wyeth acquisition raises the chances that Roche will be able to raise the money it needs to acquire the 44 percent of Genentech that it does not already own.

Roche, a Swiss pharmaceutical giant, first proposed to pay $43.7 billion for those shares in July, an offer Genentech rebuffed as too low. Analysts expect Roche to raise its bid, but its difficulty in arranging financing has slowed negotiations.

Big pharmaceutical companies are not the only ones who can buy companies or drugs. In some cases, mid-size biotech companies like Cephalon and Myriad Genetics are outracing larger companies to snap up some drugs.

That is why Mr. Nodelman, at the Biotechnology Value Fund, said he did not expect the Pfizer-Wyeth deal to have much of a braking effect on acquisitions of small companies or their drugs. “All it means is there is one less company that might do a deal with them,” he said.

28
Jan
09

Norwegian biotech industry thrown a lifeline

By John O’Doherty

Norwegian biotechnology has been thrown a lifeline after the country’s government made explicit provision for life sciences and innovation research within the NOK20bn ($2.87bn) stimulus package unveiled on Monday.

The biotechnology component of the stimulus, valued at just under £300m (€318m, $418m) will prevent half of the company’s biotechnology groups from going bankrupt.

“This is the most active political move in Europe regarding support to the biotech industry,” said Bjarte Reve, chief executive of the Oslo Cancer Cluster, which represents 25 Norwegian biotech groups that employ about 1,000 people.

“At this point, these seem to be the necessary measures to bring the Norwegian biotech companies through the financial crisis.”

As part of the package, Innovation Norway, a state development agency, will increase the amount of loans it makes to research-intensive companies – principally biotech and information technology groups – from £32m to £95m a year.

Argentum, the Norwegian government fund which invests in private equity groups and has €500m (£473m, $658m) under management, will also get £200m ($279m, €212m) to invest in innovation-focused companies, also explicitly focused on biotech and IT.

More than 80 per cent of Norway’s biotechnology industry is focused on cancer research and are based in and around Oslo. Mr Reve said that if support for the biotech industry had not been forthcoming, many of those companies would have gone bust, threatening the loss of 50 cancer products currently in clinical trials.

“Last December, half of our biotech companies said in a survey that they would run out of cash in the next 12-18 months if nothing happens, so this has been crucial in stopping half of our companies from going under,” said Mr Reve.

 

 

27
Jan
09

Pharmas offer gloomy 2009 forecasts

It’s that time of year again: Earnings season. Yesterday, all the deal hoopla squeezed out Pfizer and Wyeth’s results, but we have them for you today. Plus, get the numbers on Amgen and Bristol-Myers Squibb. Just for fun, we’ll put them in order by percentage change, from the biggest declines to the biggest leaps.

  • Pfizer reported a whopping 90 percent drop in fourth-quarter profits to $266 million, or 4 cents per share, mostly because of a one-time charge related to its Bextra settlement (see above for more on that). But revenues also fell, by 4 percent, to $12.35 billion. That’s from generic competition on Norvasc, Zyrtec and Camptosar, MarketWatch reports. And 2009 forecasts look grim: Pfizer predicts a revenue decline to between $44 billion and $46 billion, from $43.8 billion in 2008. (That’s without Wyeth, natch.)
  • Wyeth income dropped by 5.6 percent to $960.4 million, with sales down 7 percent to $5.35 billion. Pharma sales in particular also dropped 7 percent, to $4.41 billion; much of the revenue drop was because of currency effects, the company said. Wyeth’s best-seller remains the antidepressant Effexor, though its sales also fell by 7 percent to $902 million. And with Effexor soon to face more generic competition, that’s likely to continue. The Prevnar vaccine, however, saw an 8 percent revenue boost to $603 million, and Enbrel sales grew 6 percent to $598 million.
  • Amgen’s 15 percent rise in fourth-quarter profits–to $961 million–puts it right at the middle of today’s pack. Revenue was essentially flat at $3.75 billion, up from a 3.5 percent drop during the same period last year. A 15 percent drop in Aranesp sales, along with disappointment in the company’s 2009 forecast, spooked investors, however; Amgen forecast revenues of between $14.8 billion and $15.2 billion for the year when analysts had expected $15.4 billion. 
  • Bristol-Myers Squibb posted a whopping 50 percent-plus increase in adjusted earnings, as net income rose to $1.24 billion from a year-earlier loss of $89 million. (Now, last year’s loss was generated by a variety of special charges, but percentage-wise we’re looking at the adjusted EPS, which rose to 46 cents from 30 cents.) Sales grew by 3.8 percent to $5.25 billion, just shy of analyst estimates of $5.42 billion. Plavix revenues rose by 7 percent, helping to take up the slack from a 70 percent loss of Pravachol sales because of generic competition.

Stay tuned: We have yet to hear from several other Big Pharma firms.

- see Pfizer’s results [1] at MarketWatch
- get the numbers [2] on Wyeth from PharmaTimes
- check out Amgen’s details [3]
- read the Bristol story [4] from Dow Jones

Source URL:
http://www.fiercepharma.com/story/pharmas-offer-gloomy-2009-forecasts/2009-01-27


29
Jan
09

Abbott buys Advanced Medical Optics

 By Julie MacIntosh in New York

Abbott Laboratories is set to buy Advanced Medical Optics, a top provider of cataract and laser eye surgery devices, for $1.4bn, in an attempt to increase its share of the growing global eye care market. Abbott is set to launch a cash tender offer within two weeks to buy a majority of Advanced Medical’s shares for $22 each. If that offer is successful, the deal would be worth $2.8bn, including Advanced Medical’s net debt. In spite of a general dearth of mergers and acquisitions, the healthcare industry is defying the broader slump. The biggest drug companies are diversifying their portfolios and decreasing their exposure to blockbuster drugs that will eventually lose patent protection. Abbott, which is based in the US, sells everything from cholesterol and arthritis drugs to baby formula and drug-coated stents. With the acquisition of Advanced Medical, Abbott would immediately become a force in the global eye care market at a time when ageing populations in the west are generating a greater demand for cataract operations and other eye surgeries. The popularity of corrective laser eye surgery has also skyrocketed over the past decade, though difficult economic times have prompted some patients to reduce their spending on laser, plastic surgery and other medical procedures that are viewed as discretionary. Advanced Medical Optics provides equipment for laser corrective eye surgery. Abbott offered a premium of nearly 150 per cent to Advanced Medical’s most recent closing share price. In 2007, Advanced Medical made a $4.2bn unsolicited takeover bid for Bausch & Lomb, another top eye care company. However, the company dropped the bid after one of its largest investors decried the deal. Instead, Bausch & Lomb was bought by Warburg Pincus, the private equity firm. Monday’s deal comes less than a year after the Swiss drugmaker Novartis said it would buy up to a 77 per cent stake in Alcon, the eye care market leader, from Nestlé in a two-step transaction worth as much as $39bn. Alcon sells over-the-counter contact lens products but generates most of its revenue by selling products and devices that are used for eye surgery. Abbott has a history of making acquisitions to strengthen its portfolio, including its acquisition of Knoll Pharmaceuticals in 2001 and its late 2006 announcement that it would buy Kos Pharmaceuticals.

Copyright The Financial Times Limited 2009

30
Jan
09

Lilly, Novartis sales flat; Novo’s rise 15%

As promised, another raft of pharma earnings reports today, ranging from a $3.63 billion loss at Eli Lilly–because of its big acquisition of ImClone Systems–to a 138 percent hike in profits at Novo Nordisk. Here we go.

  • Lilly booked a $4.73 billion charge on its ImClone deal, pushing its fourth-quarter operating results into the red by $3.31 per share. That compares with $854.4 million in profits for the same period last year. Net sales were essentially flat, rising 0.4 percent to $5.21 billion; analysts had expected $5.42 billion. One culprit: Zyprexa, which saw a 10 percent drop in sales, 4 percent in the U.S. and 15 percent internationally.
  • Fourth quarter revenue doubled at Celgene, to $623 million, fueled largely by the blood cancer drug Revlimid, which posted a robust 49 percent sales growth. In fact, it accounted for more than half of the company’s sales for the quarter. The company isn’t forecasting such a large growth spurt this year: Only 28 percent for 2009 Revlimid sales, which would amount to about $1.7 billion.
  • Novartis reported a 70 percent hike in fourth-quarter profits, to $1.54 billion. (Without a big charge against last year’s numbers, though, the growth amounted to only 14 percent). Sales rose by a paltry 1 percent, however, to $10.8 billion, so the profit gains stemmed from cost-cutting. Perhaps more significant, CEO Daniel Vasella (photo [1]) is predicting 5 percent sales growth for the coming year, one of the more optimistic Big Pharma forecasts we’ve yet seen.
  • Novo Nordisk takes the prize for profit growth: 138 percent. Unfortunately, like Novartis, Novo took a big charge against earnings for the same period last year, so the percentage is skewed. But sales leapt by 15 percent globally, and 24 percent in North America. For the full year, profits grew 13 percent on an 11 percent hike in revenues to about $5.6 billion.

Who are we missing? Merck, for one, which will report its 2008 results on Feb. 3.

http://www.fiercepharma.com/story/lilly-novartis-sales-flat-novos-rise-15/2009-01-29-0

31
Jan
09

Novartis Phase III promise for oral multiple sclerosis therapy

 

Novartis has released the first results from a Phase III trial of FTY720 (fingolimod), a novel oral therapy for multiple sclerosis (MS). They show that FTY720 reduced relapse rates compared with intramuscular injections of interferon-Beta-1a, which is a current standard treatment.

This 1 year, double-blind, randomized study involved 1,292 patients with relapsing–remitting MS, who received either 0.5 mg or 1.25 mg FTY720 or interferon-Beta 1a (Avonex; Biogen Idec). Participants receiving interferon-Beta-1a had an annualized relapse rate of 0.33, whereas the corresponding rates for those receiving the low and high doses of FTY720 were 0.16 and 0.20, respectively. FTY720 was generally well tolerated, but two fatal cases of herpes infections were reported among patients receiving the 1.25 mg dose. Both cases involved confounding factors, although the possibility of involvement of FTY720 could not be ruled out, given its immunosuppressive effects.

Current disease-modifying therapies for MS, a chronic inflammatory disorder in which autoreactive T cells and macrophages cause demyelination of nerve cells in the central nervous system (CNS), also act by suppressing the immune system (Nature Rev. Drug Disc. 7, 909–925; 2008). However, finding the optimal balance between effective immunosuppression and the risk of adverse events is a particularly challenging task. As Ludwig Kappos, Chair of the Department of Neurology, University Hospital, Basel, Switzerland, points out: “Approved first-line drugs [for MS] have demonstrated modest efficacy in suppressing the inflammatory activity of the disease, reducing relapse frequency and severity, and in slowing down disease progression. Improved efficacy without additional risks would be highly appreciated.”

FTY720 binds to the sphingosine-1-phosphate receptor, which is predominantly expressed on lymphocytes and regulates their migration from secondary lymphoid tissues to sites of injury or infection. FTY270 initially acts as an agonist, but promptly induces downregulation of receptor expression, therefore blocking the signal required for lymphocyte migration and preventing systemic trafficking of self-reactive T cells to the CNS (Pharmacol. Ther. 108, 308–319; 2005). A differential effect on particular subsets of T cells, or potential direct effects on oligodendrocyte and dendritic cell maturation, myelinogenesis and astroglia proliferation, might account for its therapeutic effectiveness and adverse-effect profile.

Importantly, compared with interferon-Beta products, which are administered by injection, the oral availability of FTY720 would “certainly increase acceptance and the necessary long-term compliance to treatment,” says Kappos. “FTY720 is one of five orally administered drugs currently in Phase III testing,” adds Howard Weiner, Professor of Neurology at Harvard Medical School, suggesting that we may be on the verge of a new era of oral treatments for MS.

Further analyses of the trial are expected to be reported later this year, and two Phase III placebo-controlled trials are also ongoing. Novartis is aiming to submit regulatory applications for FTY720 by the end of 2009.

 

Nature Reviews Drug Discovery 8, 98-99 (February 2009) | doi:10.1038/nrd2821nature-reviews

31
Jan
09

Lead discovery: Tailoring nuclear receptor activation

Peter Kirkpatrick

Agents that target multiple disease-related metabolic parameters, such as insulin sensitivity, dyslipidaemia and weight gain, could provide more effective and convenient treatment for type 2 diabetes. Writing in PNAS, Artis et al. describe how such agents targeting the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors can be designed using a fragment-based lead-discovery strategy.

Two classes of marketed drugs already target specific members of the PPAR family, which have a key role in regulating metabolic processes and inflammation. Fibrates, which activate PPAR-Alpha, are used as lipid-lowering agents, whereas glitazones, which activate PPAR-Gamma, have insulin-sensitizing properties. Furthermore, PPAR-Delta activators have also been investigated as potential drugs for dyslipidaemia and weight loss.

So, compounds that can stimulate all three PPARs could target the multiple risk factors that are commonly present in patients with diabetes and reduce the need for polypharmacy and its associated risks and inconvenience. In addition, tailoring the level of receptor activation could be important in addressing the cardiovascular risk that has recently been associated with full PPAR-Gamma agonism.

To tackle the challenge of identifying such compounds, the authors applied a lead-discovery approach that they had previously successfully applied to the kinase and phosphodiesterase enzyme families. First, 170 low-molecular mass ‘fragments’ that activated one or more of the PPAR receptors, albeit weakly, were identified from a biochemical screen. Co-crystal structures of these compounds with at least one of the PPARs were obtained where possible, which led to the identification of a promising scaffold on which to build compounds that activate all three PPARs.

A computational structure-based approach was then used to guide synthesis of derivatives of this scaffold for testing in cellular assays. One such derivative, indeglitazar, which activated all three PPARs (acting as a partial rather than a full agonist of PPAR-Gamma) and possessed excellent drug-like properties, was selected for development.

In rodent models of diabetes, indeglitazar had strong beneficial effects on levels of glucose, triglycerides and cholesterol. Furthermore, it led to weight loss in both rodents and primates. In this respect, compared with the full PPAR-Gamma agonist rosiglitazone, indeglitazar was less potent in stimulating an adiponectin response, which might be linked to the undesirable weight gain that is observed with glitazones.

On the basis of this promising therapeutic profile, indeglitazar has progressed to Phase II trials in patients with type 2 diabetes. The compounds and approach described could also be valuable for future investigation of the effects of varying levels of activation of PPARs, and could provide more potential drugs for patients with metabolic disorders as subpopulations become better defined.

 

References and links

ORIGINAL RESEARCH PAPER

1.      Artis, D. R. et al. Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent. Proc. Natl Acad. Sci. USA 106, 262–267 (2009)

FURTHER READING

1.      Hajduk, P. J. & Greer, J. A decade of fragment-based drug design: strategic advances and lessons learned. Nature Rev. Drug Discov. 6, 211–219 (2007)

2.      Tsai, J. et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl Acad. Sci. USA 105, 3041–3046 (2008)

3.      Card, G. L. et al. A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nature Biotechnol. 23, 201–207 (2005)

Nature Reviews Drug Discovery 8, 107 (February 2009) | doi:10.1038/nrd2807nature-reviews

01
Feb
09

Systemic lupus erythematosus

James Wentworth1 & Clare Davies2

Systemic lupus erythematosus (SLE) is a complex, chronic, autoimmune disorder that involves multiple organ systems including the skin, joints, heart, lungs, blood, kidneys and, in the most severe cases, the brain. The disease mainly affects women from Afro-Caribbean, Asian or Hispanic descent; Caucasians are affected to a lesser extent. The diagnosis of SLE is a significant challenge, as symptoms can fluctuate and sometimes mimic those of other diseases. Furthermore, there is currently no test available that can diagnose SLE with certainty.

The difficulty in defining and diagnosing SLE, and the lack of appropriate epidemiological studies makes estimating the patient population problematic. The Lupus Foundation of America suggests that lupus may affect 1.5–2 million people in the US1. However, some, possibly more rigorous, epidemiology studies disagree with this number and estimate that SLE actually afflicts about 0.3 million people in this country2. We conservatively estimate that in 2008, there were 0.24 million patients with SLE in the US (Fig. 1), and 0.4 million in the seven major markets (France, Germany, Italy, Spain, UK, Japan and US).

 

Figure 1 | Systemic lupus erythematosus (SLE) epidemiology.

 

 

There is a large unmet need in both the diagnosis and treatment of SLE. The US FDA has not approved a treatment for SLE in decades, even though current treatments lack specificity and can often cause considerable side effects. The heterogeneous and flaring nature of the disease makes assessment of drug efficacy in clinical trials difficult, and a lack of clarity from regulatory agencies has stifled SLE drug development in the past. However, recent insights into the biology of autoimmune diseases that extend to SLE, coupled with a better understanding of SLE pathogenesis, have renewed interest in this disease area. Product candidates are in development for different subcategories of SLE including lupus nephritis (LN), a kidney disorder associated with more severe SLE, and cutaneous lupus erythematosus, which affects the skin and has a broad spectrum of clinical manifestations.

Current treatment

The treatment of SLE is highly individualized and physicians (mainly rheumatologists) determine optimal therapy by assessing disease type and severity. Steroids, particularly prednisone, which is highly genericized, are often the key to controlling SLE. They are used as a rescue therapy and as maintenance for short periods, and effectively treat the symptoms of SLE. However, long-term steroid treatment can cause severe side effects and force physicians to use various drugs with other mechanisms of action.

Antimalarial drugs, such as hydroxychloroquine (Plaquenil; Sanofi–Aventis), are commonly prescribed for the treatment of SLE. An estimated 40% of patients with SLE plus multiple organ involvement receive products from this class (Table 1). Furthermore, although most immunosuppressants are restricted to off-label use in SLE, we estimate that at least half of all patients with lupus receive a drug from this class, especially those with LN or CNS involvement. Azathioprine, methotrexate and cyclophosphamide are commonly used immunosuppressants for SLE. Tacrolimus (Prograf; Astellas Pharma) shows particular benefit in LN, and the drug was approved for this indication in Japan in January 2007.

 

Table 1 | Percentage of patients with SLE treated with each drug class*

Subtype of SLE Cortico-steroids Anti-malarials Immuno-supressants§ Anti-inflammatories|| Biologics
Multiple areas 60 44 59 43 6
Cutaneous 56 56 26 11 2
Joints 37 49 39 56 3
Blood 57 30 50 14 5
CNS 62 21 72 16 8
Kidney 69 24 92 9 10
*Figures are based on Datamonitor primary research and will not add up to 100% as patients with each subtype of systemic lupus erythematosus (SLE) can receive more than one therapy.Corticosteroids include both systemic and topical corticosteroids.§Immunosuppressants include immunomodulators, cytotoxic agents and disease-modifying antirheumatic drugs.||Anti-inflammatory drugs include salicylates, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase 2-specific NSAIDs.

 

 

 

 

 

 

The transplant-rejection drug mycophenolate mofetil (CellCept; Aspreva/Roche) also showed some promise in SLE, particularly for LN. However, its development is on hold after a Phase III trial failed to show superiority over cyclophosphamide, another immunosuppressant commonly prescribed off-label in LN. Nevertheless, our data indicate that physicians prefer to prescribe mycophenolate mofetil over cyclophosphamide owing to safety concerns.

B-cells as the target of the future

The current focus for new SLE drugs is targeted therapies aimed at cytokines, and B and T cells. B cells are a particularly attractive target as autoantibodies often cause considerable pathology in SLE. There are now six products that specifically target B cells in the late-stage SLE pipeline (Table 2).

 

Table 2 | Products in development for lupus indications 2008

Generic (brand) name Company Mechanism Lupus indication Country
      LN SLE CLE  
B cells
Rituximab (Rituxan/MabThera) Biogen Idec/Genentech Murine–human chimeric anti-CD20 mAb III II/III NA US
Belimumab (LymphoStat-B) Human Genome Sciences/GSK mAb against human BLyS NA III NA US/EU
Ocrelizumab Biogen Idec/Genentech Humanized anti-CD20 mAb NA III NA US
Epratuzumab Immunomedics/UCB Humanized anti-CD22 mAb NA III NA US
Atacicept/TACI-Ig Merck Serono BLyS ligand inhibitor II/III II/III NA US/EU
Veltuzumab/IMMU-106 Immunomedics Anti-CD20 mAb NA II NA US
T cells
Abatacept (Orencia) Bristol–Myers Squibb CTAL4–Ig fusion protein II/III II NA US/EU
CTLA4–IgG4m/RG2077 Repligen CTLA4–Ig soluble protein II I NA US
IPP-201101 ImmuPharma CD4 modulator NA IIb NA US/EU
Cytokine
CNTO-136 Centocor Human anti-IL-6 mAb NA II II US
Other
Prasterone (Aslera/Prestara) Genelabs Oral dehydroepiandrosterone and NO modulator NA III NA US/EU
Abetimus sodium (Riquent) La Jolla Immunosuppressant III NA NA US
R-salbutamol sulphate Astion Pharma Anti-inflammatory NA NA II EU
Edratide/TV-4710 Teva Synthetic peptide immunomodulator NA II NA US/EU
BLyS, B lymphocyte stimulator; CLE, cutaneous lupus erythematosus; CTLA4, cytotoxic T-lymphocyte-associated protein 4; GSK, GlaxoSmithKline; Ig, immunoglobulin; IL-6, interleukin 6; LN, lupus nephritis; mAb, monoclonal antibody; NA, not applicable; NO, nitric oxide; SLE, systemic lupus erythematosus.

 

 

 

 

Rituximab (Rituxan/MabThera; Biogen Idec/Genentech/Roche), a chimeric anti-CD20 monoclonal antibody, was tipped to be the first therapy approved for SLE in decades, but it failed to meet the primary and secondary end points in the EXPLORER trial in SLE in April 2008 (Ref. 3). An ongoing LN study could still result in rituximab’s approval for SLE with specific kidney involvement. Despite an FDA safety warning (December 2006) of progressive multifocal leukoencephalopathy in patients with SLE receiving rituximab, there is evidence for continued off-label use4.

Other B-cell therapies in Phase III trials that are competing with rituximab include the monoclonal antibodies belimumab (Human Genome Sciences/GlaxoSmithKline), targeted at the B-lymphocyte stimulator (BLyS), and epratuzumab (UCB), targeted at the B-cell specific surface receptor CD22. After rituximab’s recent SLE trial failure, belimumab is the most advanced agent seeking SLE indication approval; enrolment and initial dosing in two Phase III trials was completed by August 2008. Belimumab has the potential to overtake rituximab as the first biologic to reach the market for SLE. Atacicept is a soluble fusion protein that inhibits B-cell activation and is being developed for both SLE and LN. Merck Serono recently acquired the exclusive development rights for atacicept from ZymoGenetics, which will provide a boost to its commercialization prospects. Genentech and Biogen Idec are key players in the autoimmune disease area and are looking to follow-on from rituximab with ocrelizumab, a humanized monoclonal antibody targeting CD20.

Outlook

From a stalled pipeline 10 years ago, there are now targeted products that have the potential to change the way that SLE is treated. The late-stage pipeline shows promise and the market is primed for growth over the next 10 years. However, the main stumbling block will continue to be the ability to prove efficacy to regulatory authorities, as the recent disappointments of rituximab in SLE and mycophenolate mofetil in LN have shown.

Datamonitor estimates that the lupus drug market in the seven major markets was worth at least US$330 million in 2007. Despite failing its Phase III trial in SLE, rituximab, which we believe generated lupus sales of $125 million in 2007, will continue to be prescribed off-label and sales will increase even further if it is approved for LN.

The key opportunities to drive future market growth will come from the approval of higher-priced targeted therapies. There are a number of companies pursuing targeted drug therapies for lupus indications (Table 2). Furthermore, greater patient potential exists in emerging markets because of racial differences in disease prevalence. Datamonitor estimates that the SLE patient population in China, India and Mexico is over 2.2 million. It is likely that only a small percentage of patients will be able to afford the expensive biologic therapies, but opportunity certainly exists for the cheaper small molecules.

 

Nature Reviews Drug Discovery 8, 103-104 (February 2009) | doi:10.1038/nrd2743nature-reviews

 
 
 suplementary-information-about-sle
03
Feb
09

Saifun founder buys biotech firm

Boaz Eitan acquired electronic drug delivery systems maker Q-Core from its receiver and aims to keep it as a going concern.

Gali Weinreb

Saifun Semiconductor founder Dr. Boaz Eitan and his wife, Tally Eitan, have acquired electronic drug delivery systems maker Q-Core Ltd. from its receiver for NIS 5.6 million. They plan to inject an additional NIS 20 million into the company in order to keep it as a going concern and save the jobs of its 40 employees. The Receiver General still has to approve the deal, but is expected to do so in a few days. Boaz Eitan declined to comment on the report. This is apparently Eitan’s first deal as a private investor. He currently serves as VP at Spansion Inc. (Nasdaq: SPSN), which acquired Saifun, which he founded and led. Tally Eitan is a founder and partner of the Eitan Mehulal Law Group Q-Core has four product lines, all of which have US Food and Drug Administration (FDA) approval. They include an infusion pump, an enteral feeding pump, a veterinary infusion pump, and a range of accessories. Q-Core went into receivership when its shareholder, Core Capital, which mainly comprised a group of private North American Jewish investors, unexpectedly fell into financial difficulties and stopping funding the company. The cut-off happened just when Q-Core was about to begin sales, having completed the development and certification stages of its products. Q-Core has an immediate $900,000 order for its products and an orders backlog amounting to $12 million for the next two years, but lacked the cash to finance the production of the goods ordered. The orders are from the US, Europe, and Japan. Q-Core was founded in 1996 at Incentive Technological Incubator, and raised $15 million to date from Core Capital. The company was unable to find new investors in the short time needed following the cut-off of funding from Core Capital, and went into receivership before its debts could accumulate. Q-Core has NIS 1.9 million in liabilities, mostly employee salaries, bank debts, which are guaranteed by the company’s shareholders, and debts to the shareholders. Eitan beat Ilex Medical Ltd. (TASE:ILX) and other bidders for Q-Core.

 Published by Globes [online], Israel business news – www.globes-online.com – on February 2, 2009 © Copyright of Globes Publisher Itonut (1983) Ltd. 2009globes1

03
Feb
09

Israel Ministry of Finance allocates additional NIS 400M to assist high-tech and biotech sectors

The Ministry of Finance will allocate an additional NIS 400 million to assist these sectors.
   

 Adrian Filut

Minister of Finance Ronnie Bar-On today announced a stimulus plan for the high-tech and biotechnology sectors. The Ministry of Finance will

Dr Eli Opper, Israels CSO

Dr Eli Opper, Israel's CSO

allocate an additional NIS 150 million to the Office of the Chief Scientist, which will all be invested in the first quarter of 2009. This allocation is explicitly designed to provide an immediate response to the crisis in financing for promising R&D companies, which due to the global credit crisis are struggling to find funding sources.The new NIS 150 million allocation will be added to the Office of the Chief Scientist’s regular annual budget of NIS 1.2 billion. However, because the government’s 2009 budget has yet to be approved, the Chief Scientist is only permitted an allocation of NIS 100,000 per month.This is in addition to the extra NIS 200,000 allocated to the Chief Scientist in the Ministry of Finance’s previous stimulus plan, which was approved by the Knesset Finance Committee in December 2008.The Ministry of Finance will also allocate NIS 250 million for the setting up of a fund specializing in biotechnology investments. The fund will be leveraged by the private sector and will reach a total of between NIS 750 million and 1 billion. The fund will be managed by an experienced management body with expertise in the biotech R&D sector. The new fund’s investments are expected to enable the sector to realize its potential and provide employment opportunities for university graduates, and an estimated 600 Israelis returning from abroad.Published by Globes [online], Israel business news – www.globes-online.com – on February 1, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

03
Feb
09

Multiple sclerosis treatment seems to reverse symptoms.

Monya Baker

Bone marrow stem cells may have helped patients with multiple sclerosis.MedicalRF.com / Alamy

Bone marrow stem cells may have helped patients with multiple sclerosis.MedicalRF.com / Alamy

 

A stem-cell therapy appears to help some patients with early-stage multiple sclerosis recover, according to results from a preliminary study.

Multiple sclerosis (MS) is a chronic disease where the body’s immune system attacks the central nervous system. White blood cells in the body attack the protective myelin sheaths surrounding nerve fibres in the brain and spinal cord. Although symptoms of the disease wax and wane, they generally grow worse over time and include fatigue, blurred vision and difficulty walking.

In the new trial, the patients’ immune cells were first destroyed and they were then injected with blood stem cells taken from their bone marrow. Seventeen of the 21 patients treated in his study improved, suffering fewer problems with their balance or vision, and none declined over the 2-4 years they took part in the study.

This marks the first time a technique “has actually shown reversal” of neurologic loss caused by this disease, says Richard Burt of Northwestern University in Chicago, who led the study.

Normally, when MS drugs fail to calm the immune system, doctors may adapt a strategy currently used for blood cancers: a combination of toxins and radiation to destroy the bone marrow — which contains the patient’s blood-forming system — followed by a transplant of healthy cells to restore it.

Though such techniques can be effective, they carry the risk of serious side-effects and death.

 Early chance

The current work uses less toxic drugs to primarily kill one type of immune cell — the white blood cells known as T-cells. Burt and colleagues were also able to administer the stem cells at earlier stages of MS, when the brain is more capable of repairing damage.

Edwin McClure, a 24-year-old advertising student at Virginia Commonwealth University, was one of the patients treated. He says his neurologist referred him to the study after he’d tried “three different drugs over three years that were all pretty much ineffective”. Before the study, he says, he had to give himself a shot every other day; nonetheless, fatigue, poor balance and dimmed vision limited his activities. Now, McClure says, he no longer has those problems or takes medications for MS.

A lot of research suggests that the early “relapsing-remitting” stage of MS is the most treatable, says Patricia O’Looney, vice president for biomedical research at the National Multiple Sclerosis Society in New York. This is when the inflammation that destroys myelin sheaths is at its peak.

“To try to stop progression and loss of tissue, you have to try to get that inflammation under control,” she says. Safer, earlier ways of destroying and replacing the immune system might do that, she says, but, she still recommends caution about the transplantation technique. “It’s not an easy procedure,” she says. “Although they are impressive results, it’s a preliminary study.”

 Larger trial

Burt’s therapy is probably less toxic than other forms of intense immunosuppression, says Gianluigi Mancardi of University of Genova in Italy, who wrote a commentary accompanying the study2. But, he says, “Burt’s therapy cannot be considered gentle, because there are certainly side-effects of some importance”.

Burt believes that the risk of death from this procedure is less than 1%. In comparison, the MS drug Tysabri (natalizumab), a monoclonal antibody, has about a 1 in 1000 chance of causing a serious viral infection, but those risks were considered so serious that it was initially withdrawn from sale by the manufacturer. It is now only prescribed under a special prescription programme in the United States and carries serious warnings in Europe.

 Walter Royal, director of the Maryland Center for Multiple Sclerosis at the University of Maryland, Baltimore, highlights some of the study’s strengths. He notes the researchers tried to control for the wide fluctuations often observed in MS, by recruiting patients only after their condition stabilized following a relapse. The patients were also monitored over an average of three years, he says, “which certainly was long enough to know if improvement was transient”. Nonetheless, larger studies in multiple centres are now needed, particularly to assess risks, Royal adds.

Burt agrees that his team’s study is small and lacked a control or comparison group. He is currently recruiting patients for a larger, randomized trial. Even if further work shows that the treatment is effective for the early stage of the disease, the technique does not help patients with later “progressive” MS, says Burt. Though bone marrow stem cells reboot the immune system, they cannot repair myelin after axons have been very badly damaged.

 

References

Burt, R. K. et al. Lancet Neurol. Advanced online publication doi:10.1016/S1474-4422(09)70017-1 (2009).

Mancardi, G. Lancet Neurol. Advanced online publication doi:10.1016/S1474-4422(09)70018-3 (2009).

 

Published online 30 January 2009 | Nature | doi:10.1038/news.2009.71