upstarts get injection of capital
By Jim Hopkins, USA TODAY
SAN FRANCISCO — Merck, the pharmaceutical giant racing to replenish its drug pipeline, hatched a $100 million partnership in November with a tiny biotech start-up in Cambridge, Mass.
Eli Lilly, another drugmaking stalwart, is plunging into the sizzling anti-impotence market ruled by Viagra with help from a young biotech near Seattle. Bristol-Myers Squibb, struggling to replace a cancer drug, is betting on a $2 billion deal with ImClone Systems — a biotech better known for its role in the Martha Stewart scandal.
More slow-growth pharmaceutical firms like these are partnering with fast-growth biotechs for a dose of new drugs battling cancer and other illnesses. Lilly, for one, has launched about 100 partnerships, mostly with biotechs, many in the last five years.
The trend underscores a power shift toward biotech in the drug and technology industries. Venture-capital investors are joining scientists in deciding what drugs get developed. Big pharmaceuticals are relying on biotechs to create new drugs for an aging population. And biotech is emerging as the next engine for innovation and jobs in the tech industry, long focused on computer chips and other traditional fare.
But there are risks. Venture capitalists are pickier about the biotechs they finance than they were 10 years ago during the last boom. That means discoveries with extra-high risk may get overlooked — and so won't reach patients. "There's no question that good ideas don't get funded," says Jim Tullis, CEO of Tullis-Dickerson, a biotech VC firm.
What's more, investors are betting on a highly regulated sector. The Food and Drug Administration slammed ImClone two years ago when it initially rejected its cancer drug. And the political debate over drug price controls makes VCs worry about paltry returns on start-up investments of $50 million or more.
The industry has been an investors' roller coaster since the start. "Anyone who has tried to make projections has many times been wrong," says Alan Goldhammer, a regulatory official at the Pharmaceutical Research and Manufacturers of America trade group.
Boom in biotech
Yet there is powerful fuel for the shift to biotech: Big drug companies are slowing research to focus more on marketing other companies' discoveries. Years of work in biotech labs are yielding drugs proven to tackle cancer and other elusive targets.
Even well-heeled investors such as Microsoft's Bill Gates are seizing on biotech as the tech industry's future.
Venture-capital investors, who invest on behalf of institutions and rich individuals, poured more money into biotech in the third and fourth quarters than into any other industry — including software, the perennial favorite. The share of venture capital going to biotech surged from 14% in 2002 to 19% last year, higher than in the last financing boom.
Biotech uses computer-powered genetic engineering to treat illnesses, create foods and improve manufacturing. Its high-tech promise is luring pharmaceuticals because of:
• Dry pipelines. The number of new drugs approved annually by the FDA has tumbled 45% since 1996 — the last peak year.
Ten years ago, traditional drugmakers were punching out 60 newly approved drugs a year. Biotech eked out just two to four, says Jim Broderick, a partner with Morgenthaler Ventures in Silicon Valley's Menlo Park.
By last year, the two sectors were about even, at 20 each. "Big pharma has fallen dramatically, and the biotech industry has grown dramatically," Broderick says.
That's caught pharmaceuticals' attention. For example, Lilly, running behind in developing an anti-impotence drug, formed a partnership in 1998 with Icos, the Seattle-area biotech, to develop and market Cialis.
Icos, whose early investors include Microsoft's Gates, started work on Cialis in the early 1990s. The FDA approved Cialis in November — pitting Lilly against Pfizer's blockbuster Viagra.
Experts debate why pharmaceuticals struggle to create new drugs. Their mammoth size may mean they've become too bureaucratic, so they chase only less-risky innovations more likely to produce a payoff, Broderick says. Also, they struggle to attract talent among biotech scientists who may think cutting-edge work can be better done at entrepreneurial start-ups.
• Patent problems. Pharmaceuticals are losing exclusive blockbuster drugs — those generating annual revenue of $1 billion or more — as patents expire. That lets competitors swoop in to make generic versions, cutting into revenue.
For example, Merck's top drug, the cholesterol-fighter Zocor, lost patent protection last year in Canada and some European nations. Since then, Zocor sales are down. Its USA patent expires in 2006. Zocor generated $5 billion, or about 23% of Merck's annual revenue, last year.
• Merger mania. A wave of big pharmaceutical mergers and acquisitions in the past five years has left fewer competitors to gobble up, depleting a quick source of revenue growth.
At least 20 deals have been announced or completed since 1999, including the record $115 billion combination in 2000 of Pfizer and Warner-Lambert.
One of the rare deals more recently, still developing, is the $58 billion hostile bid announced in January by Sanofi-Synthelabo for its French rival, Aventis.
• Big risk. Drug-development costs have soared as disease targets get more complex — and regulatory reviews grow longer.
Development costs for all drugs, from lab to FDA approval, average $802 million per drug — more than double the cost in 1987, says the Pharmaceutical Research and Manufacturers of America. New drugs take as long as 15 years to reach FDA approval.That means big pharmaceuticals, under pressure from Wall Street to boost profits, are more skittish about investing in new drugs. That's another reason to cut risk by linking with biotech start-ups.Still, alliances have risks, too. That was the story at Bristol-Myers soon after it signed a marketing agreement for ImClone's cancer drug, Erbitux. The FDA, citing poor research data, rejected Erbitux in December 2001 — sending ImClone stock tumbling and threatening Bristol-Myers' $2 billion marketing deal with the biotech.Last month, acting on new data, the FDA finally approved Erbitux — boosting ImClone stock 29% in one day and winning Bristol-Myers a return on its gambit. It will get 61% of Erbitux revenue. The ImClone partnership is one of more than 190 that Bristol-Myers has signed with biotech and other firms.
A higher bar Risks, amid higher investment costs, are one reason VCs are now choosier about biotechs. Last year, they invested an average $11.2 million per biotech deal, nearly three times the average 10 years ago.More VCs are looking for biotechs with drugs deeper in development. The best candidates are those close to, or already in, the first phase of human testing, says James Golden, research vice president at Life Science Insights, an industry tracker.A recent example: GenPath Pharmaceuticals — Merck's new biotech partner. Founded by two Harvard University scientists, GenPath hopes to begin Phase 1 testing next year, says CEO Tuan Ha-Ngoc. That timetable attracted eight VCs and several private investors. They pumped $42.7 million into the Cambridge company in October. The Merck partnership came the following month.Merck has ramped up the number of such partnerships in the last year. It has more than 80, mostly with biotechs; 47 were formed last year.Ha-Ngoc says GenPath is talking to other pharmaceuticals about deals. GenPath's workforce is growing, underlining biotech's job-building potential. The company, with 65 employees, expects to add 35 by the end of the year.Certainly, these partnerships aren't a one-way street. Biotechs gain pharmaceuticals' expertise in guiding drugs through the labyrinth of human testing, which can account for half of development time. "It's very difficult to clear all the hurdles," says Icos CEO Paul Clark.Moreover, Lilly and other pharmaceuticals are skilled at marketing and distribution. Icos has 165 newly hired sales representatives. Lilly will assist with its own sales force.The growing number of partnerships is luring more investors. New Enterprise Associates, an influential VC firm in Silicon Valley, just raised $1.1 billion partly for health investments. Venrock Associates, the Rockefeller family's investment arm, raised $550 million in January. About 30% will go to biotech and other health start-ups.Traditional tech is still profitable, but product life cycles are shorter, reducing investor returns.Yet a biotech with a successful drug can generate $500 million in annual revenue — with 95% gross profit margins for years, says Bryan Roberts, Venrock general partner in Menlo Park."Like getting a winning lottery ticket," he says.
# # #
Venture capital investors last year pumped $3.4 billion into biotech start-ups, a risky industry barely reaching adolescence.
Biotech has fewer than 1,500 companies and fewer than 200,000 workers. Only about 100 biotech drugs reached the market in the past 30 years. Genentech and Amgen are among the few big, profitable biotechs whose names are well-known.
Many biotech drugs fail, leaving the industry swimming in red ink. Global losses in 2002, the most recent year available, more than doubled to $12.5 billion from $5.8 billion in 2001, Ernst & Young says. Too many companies are chasing too few investor dollars, the consultant says.
By Jim Hopkins
# # #
Find this article at:
no ARGENTINA studies are top secret! or should i say another waste of
years and time. remember 20 years of ........promises or bull and were
still at .15 and starting testing again and maybe fda submissions. you
got to luv it go advr and new boss 2004 should make us or break us
What is Bregman clamoring about anyway? funny.
I dinnot think that's what he's askin':
Advanced Viral Research Corp. (ADVR)
Dec. 3, 2003
Reports AVR118 Inhibits Inflammatory Arthritis In Animal Model And In Rheumatoid Arthritis Patients In Human Clinical Trial
YONKERS, N.Y., Dec. 3 /PRNewswire-FirstCall/ -- Advanced Viral Research Corp. (BULLETIN BOARD: ADVR) today announced that its novel immunomodulator AVR118 (formerly known as Product R) has exhibited therapeutic effects in both an animal model of inflammatory arthritis and in a clinical trial of patients with rheumatoid arthritis. In experiments with an animal model of inflammatory arthritis, performed at The Weizmann Institute of Research in Rehovot, Israel, the administration of AVR118 significantly suppressed the development of inflammation in the animals' joints compared to non-treated control animals. The results in the animal model were validated by an open-label clinical trial conducted in Argentina in 27 patients. All patients in the trial had improvement in quality of life including resolution or significant decrease in intensity of pain, the ability to exercise, to perform housework, and to engage in social activities. In addition, all patients showed objective signs of decreased inflammation, and increased mobility, of affected joints.
"These positive results highlight the anti-inflammatory properties of AVR118 and underline the potential of AVR118 as an anti-inflammatory therapeutic agent," said Eli Wilner, Chairman of the Board of ADVR.
In the Weizmann Institute animal model, inflammatory arthritis was induced by injecting complete Freund's adjuvant containing inactivated Mycobacterium tuberculosis into rats. AVR118 was administered for 14 days out of the twenty-four days that the animals were observed for the full development of inflammation. The anti-inflammatory effects of AVR118 were evident even for the ten days following the discontinuation of the drug. This adjuvant arthritis model in animals serves as an experimental model for human rheumatoid arthritis.
In the clinical trial, 27 female patients, ranging in age from 29 to 50 years, with mild to moderately severe rheumatoid arthritis, were treated with AVR118 for a period of 90 days. These patients had previously been treated with other anti-inflammatory drugs such as aspirin. By day 90, all patients had either complete regression or significant decrease of joint swelling. Measurements of joint mobility showed improvement in all patients. All patients showed decreases in the level of the erythrocyte sedimentation rate (ESR) by day 90 of therapy and most patients showed decreases in the latex fixation test. There were no significant side effects of AVR118 observed in this study.
"Inflammation and cachexia are inextricably linked by metabolic pathways that have common origins and targets; areas where modulation can occur for maximum impact on the process," said James T. D'Olimpio M.D., a clinical consultant to ADVR and expert in the treatment of cachexia. "In addition, the pathways involved with inflammation are not just confined to separate and distinct disease entities, but are a common thread that impacts on quality of life in many unrelated diseases such as AIDS, Cancer, Rheumatoid Arthritis and other conditions in which weight loss, weakness, poor outcomes and non- compliance to treatment are major clinical concerns. These results appear to confirm the potent anti-inflammatory properties of AVR118."
Cytokines and chemokines play important roles in the progression of rheumatoid arthritis. The development of clinical rheumatoid joint inflammation is associated with increase of the chemokine interleukin-8 (IL-8) in joint tissue. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are present at high levels in arthritic joints and their blood concentrations increase with the severity of the disease. Monocytes migrate into the joints from the blood and are activated to differentiate into macrophages in the joint tissue by inflammatory cytokines and chemokines such as IL-1, IL-6, IL-8, and TNF-alpha. Activated macrophages play an important role in joint inflammation and destruction. The joint tissue attracts the monocytes into the joints through the production of the chemokines monocyte chemoattractant protein-1 (MCP-1) and IL-8. In laboratory experiments ADVR scientists have shown that AVR118 modulates the synthesis of cytokines and chemokines including MCP-1, IL-8, IL-1 beta, and IL-6. Although AVR118 stimulates the synthesis of the pro-inflammatory chemokines MCP-1 and IL-8 by native monocytes in cell culture, highly activated macrophages are turned off with decreased synthesis of MCP-1 and IL-8.
"Rheumatoid arthritis is a systemic disease that serves as a model for other auto-immune diseases. The anti-inflammatory activity of AVR118 in the animal model, and in the rheumatoid arthritis patients in the clinical trial, including the amelioration of the systemic manifestations of the disease, suggests the possibility of treating not only Rheumatoid Arthritis with AVR118 but also a broad range of inflammatory processes associated with human diseases," explained Shalom Z. Hirschman, M.D., Chief Scientist at ADVR. "In the laboratory, AVR118 modulates the synthesis of pro-inflammatory cytokines and chemokines implicated in the inflammatory process in patients with Rheumatoid Arthritis. If these clinical results are validated by future clinical trials, then AVR118 would represent an important advance in the treatment of this systemic disease marked by crippling arthritis."
"The potential of a non-toxic immunomodulator such as AVR118 in the therapy of Rheumatoid Arthritis could be significant, as AVR118 appears to lack the often toxic effects of currently used mainstay therapies such as corticosteroids, COX inhibitors, gold compounds and methotrexate," stated Irach Taraporewala, Ph.D., ADVR's head of structural chemistry. Dr. Taraporewala is an experienced research scientist in the design of anti-inflammatory small molecules for the treatment of rheumatoid arthritis.
Rheumatoid Arthritis Market
Rheumatoid arthritis usually begins between the ages of 25 to 55 years. More than 85% of patients with rheumatoid arthritis are over the age of 50. Among patients with rheumatoid arthritis, women outnumber men by three to one. In the United States, approximately 1% of the population, or 2.5 million people, have rheumatoid arthritis. It occurs in of all ethnic groups and in all parts of the world. As the population in the developing world ages, and with a rising incidence of the disease, the world market for safe and effective rheumatoid arthritis treatment is projected to reach $6.6 billion annually by the year 2009.
ADVR's AVR118 represents a biopolymer chemistry that possesses novel immunomodulator activity. This peptide-nucleic acid, which to date has shown no indication of human toxicity, appears to stimulate the proinflammatory responses required to combat viral infections such as AIDS and human papilloma virus and to dampen aberrant autoimmune-type inflammatory responses, such as occur in patients with rheumatoid arthritis. Therefore, AVR118 has been termed a "switch-type" immunomodulator. AVR118 is in clinical trials in Israel for the treatment of cachexia (body wasting) in patients with AIDS.
For further information regarding Advanced Viral Research Corp., please visit our website at http://www.adviral.com/.
Advanced Viral Research Corp., based in Yonkers, New York, is a biopharmaceutical firm dedicated to improving patients' lives by researching, developing and bringing to market new and effective therapies for viral and other diseases.
Note: This news release contains forward-looking statements that involve risks associated with clinical development, regulatory approvals, including application to the FDA, product commercialization and other risks described from time to time in the SEC reports filed by the Company. AVR118 (Product R) is not approved by the U.S. Food and Drug Administration or any comparable agencies of any other countries. There is no assurance that the Company will be able to secure the financing necessary to continue and/or complete the clinical trials of AVR118 or satisfy certain other conditions relating to clinical trials including obtaining adequate insurance on terms acceptable to the Company. The Company undertakes no obligation to update or revise the information contained in this announcement whether as a result of new information, future events or circumstances or otherwise.
Contact: Eli Wilner 914-376-7383
Advanced Viral Research Corp.
CONTACT: Eli Wilner Advanced Viral Research Corp., +1-914-376-7383
Web site: http://www.adviral.com/
Company News On-Call: http://www.prnewswire.com/comp/903002.html
Only a very brief summary of the Argentina arthritis study appeared in a
corporate update last year. It was very sketchy and did not mention
when, at which hospital or medical center in Argentina the studies were
done or by which physicians. In the past, for other studies in the U.S.
and Israel the complete details have been provided, but the Argentina
studies seem to be more hush-hush as regards the specifics and the
- - - - -
View Replies »
Mind-Body and the Immune System
North Shore-LIJ Scientist Gains Support For Theory On Mind-Body Connection To Controlling Immune System
Source: North Shore-Long Island Jewish (LIJ) Research Institute
Through years of painstaking research on the immune system's response to the often-fatal illnesses of sepsis and septic shock, Kevin J. Tracey, MD, of the North Shore-Long Island Jewish (LIJ) Research Institute, and colleagues worldwide made several incremental discoveries that led to a new theory he coined "the inflammatory reflex" -- a theory that is gaining increasing support internationally as additional research uncovers new findings.
"The literature shows that for centuries, doctors, monks, shamans, priests, acupuncturists and even laymen believed that individuals' state of mind influenced their health. But nobody could explain how, until now," said Dr. Tracey, who was the recipient Wednesday of the Richard L. Simmons Lectureship in Surgical Science at the University of Pittsburgh Medical Center.
Credited with initiating a new field of investigation based on therapeutically targeting systemic inflammation, Dr. Tracey first outlined his breakthrough work on the inflammatory reflex in a January 2003 Nature article (first published online in December 2002).
One of the immune system's weapons is tumor necrosis factor, or TNF. A "big gun," TNF can cause a local response to an injury or infection, such as pain and redness. This is good to a point, but in excessive amounts TNF affects the whole body and can cause shock and death.
Dr. Tracey and his team of researchers discovered that the vagus nerve, which wanders through the heart, liver, lungs, spleen and kidneys, inhibits TNF production. In particular, they identified the specific binding site on immune cells that receives specific chemical messages to inhibit TNF release sent by the brain via the vagus nerve. In other words, the vagus nerve is the conduit through which the brain directly controls the immune system -- and prevents excessive TNF, shock and death. This is the inflammatory reflex.
In April, a team of neuroscientists at the University of South Florida (USF) in Tampa published findings in the Journal of Neurochemistry that support Dr. Tracey's work. The USF research team showed that the same binding site is also found on certain brain cells that become excessively active in diseases such as Alzheimer's and Parkinson's, giving rise to persistent inflammation and a worsening of the disease.
The inflammatory reflex is the foundation for the mind-body connection, and Dr. Tracey next wanted to apply this theory for practical use. Because the vagus nerve normally controls the heart rate, and research has demonstrated that biofeedback and meditation slow the heart rate, he has begun investigating the effects of these relaxation techniques on the immune system.
By studying patients with chronic inflammatory diseases who use biofeedback techniques to relax, he has recently found that these individuals have higher vagus nerve activity and lower levels of an important "proinflammatory cytokine" -- an immune system chemical that promotes inflammation -- that is typically elevated during inflammation. The implication is that people with chronic inflammatory diseases such as Crohn's, rheumatoid arthritis and peripheral vascular disease may be able to "think" their way to feeling better.
Last year, a University of California at Los Angeles (UCLA) study in older adults showed that tai chi, a centuries-old Chinese exercise described as "meditation through movement," improved immunity to shingles, a painful nerve disease that results from a re-emergence of the chickenpox virus.
Dr. Tracey is director of the Laboratory of Biomedical Science, director of the Center for Patient-Oriented Research and program director for the National Institutes of Health (NIH)-sponsored General Clinical Research Center at the North Shore-LIJ Research Institute.
About the North Shore-Long Island Jewish (LIJ) Research Institute
Located in Manhasset, NY, and part of the North Shore-LIJ Health System, the North Shore-LIJ Research Institute is among the top five percent of institutions nationally that receive funding from the National Institutes of Health. Building on its strengths in immunology and inflammation, oncology and cell biology, human genetics, and neurodegenerative and psychiatric disorders, its goal is to understand the biological processes that underlie various diseases and translate this knowledge into new tools for diagnosis and treatment.
CONTACT: Christina Verni, +1-516-562-1232, for North Shore-Long IslandJewish (LIJ) Research Institute
Actually Dr D Olimpio is Director of Supportive Oncology and Palliative
Care Service of North Shore University Hospital, Manhasset.
That hospital along with North Shore-Long Island Jewish (LIJ) are both excellent Hospitals and very well known.
I lived near both and know from personal experience, also. Excellent care and attention. The finest doctors.
Have a great weekend!