IMF Announces Research Agreement with Nobel Prize Winner Luc Montagnier and Howard Urnovitz of Chronix Biomedical

--Will Study Circulating DNA as a Marker for and Potential Cause of Disease Recurrence--

The International Myeloma Foundation (IMF) today announced plans to establish a research partnership between IMF chairman Brian G.M. Durie, M.D.; Luc Montagnier, M.D., co-recipient of the 2008 Nobel Prize in medicine; and Howard Urnovitz, Ph.D., CEO of Chronix Biomedical. The collaboration will study cancers that affect the immune system including multiple myeloma. The partnership will build on Dr. Montagnier's pioneering work with HIV; both AIDS and myeloma involve white blood cells in the immune system, and to date cannot be cured. Dr. Urnovitz studies genetic changes that take place over the course of a disease and uses the findings to aid in the diagnosis of cancer.

Their collaborative work will focus on circulating nucleic acids -- genomic sequences of DNA and RNA that travel in the blood stream - and the emerging understanding of their role in disease. In an abstract published in connection with the upcoming annual meeting of the American Society of Hematology, Drs. Durie and Urnovitz report they have identified specific DNA sequences circulating in the blood of myeloma patients that increase or decrease as the myeloma moves in and out of remission. While they look at DNA sequences that originate within the body, Dr. Montagnier will contribute new technology to the collaboration that can detect external DNA sequences related to infectious agents.

"These are intriguing biomarkers that point to processes underlying disease states," said Dr. Montagnier who is best known for his role in discovering the virus that causes AIDS. "They may be a sign of a persistent infectious process or may even be the cause. New technology I am developing to detect infectious disease agents at a new level of sensitivity is one of the key factors that will advance our ability to study diseases such as myeloma."

Dr. Durie added: "Tests for these DNA sequences circulating in the blood may become an important tool for physicians, telling them when disease is starting to recur so they know when to intervene. A greater understanding of these DNA sequences may also tell us whether we should be attacking the cancer cells, as we do now, or whether we should be looking for an underlying agent that may be the cause of the cancer and its recurrence."

Plans for the collaboration will allow all three partners to support each other, while each group will retain the rights to their own specific areas of research. For Dr. Montagnier this is the role of infectious agents, for Dr. Urnovitz the role of genetic changes, and for Dr. Durie this is applications of the findings to cancer.

Dr. Urnovitz says, "This work is made possible by powerful new technology. At Chronix we are publishing a paper about the first application of new mass-sequencing technology in the detection of chronic illnesses. Our approach coupled with Dr. Montagnier's new technology will give us new opportunities to measure genomic biomarkers while detecting infectious agents. This research partnership will utilize the combination of these new biotechnologic tools, allowing us to design new approaches in the treatment and prevention of cancer."

The relationship will be a global collaboration with Dr. Durie in the U.S., Dr. Montagnier based in France and Dr. Urnovitz based at Chronix Biomedical in Germany.

Using Computers to match drugs with genes

RevolutionariesMerck's Free RadicalMatthew Herper 11.10.08
Cancer drugs don't help 75% of the people who take them. Stephen Friend says he can use science to end the crapshoot

In the downtrodden drug industry, Merck cancer guru Stephen Friend may be one of the last great dreamers. His latest idea is one that would completely change the secretive and siloed way the pharmaceutical business fights cancer: create a giant, open-to-the-public database that will include every cancer drug and every patient and how that patient is doing. Track everything and over time we might be able to raise the abysmal success rate of treatment.

Friend, 54, has been a doctor who treated kids with cancer, an academic, an entrepreneur and a biotech chief executive. He helped develop a diagnostic test that predicts whether breast cancer will return after surgery. For five years he has been in charge of getting cancer drugs invented at Merck. Now 8 are in clinical trials, up from one, with 15 more preparing to enter trials. Friend is still unsatisfied. Why is it that, on average, three out of every four people who take a cancer medicine get lots of side effects but no benefit?

Researchers have been too willing to bet on hunches, he says, yet the technology to understand the complex biology of cancer is at hand. Spurred by Friend, Merck has spent billions on an arsenal of technologies for understanding how genes work. The resulting data stream is sent through the fastest supercomputer in the drug industry, a beast that consumes 64 kilowatts of power and is capable of 16 trillion calculations a second. Friend thinks he can accurately predict how groups of proteins in tumors work together and use that information to kill the cancer. He's trying to drag the secretive world of drug-discovery chemistry into the computer age.

The Friend way would take all the data collected each year from the thousands of cancer patients entered in trials, make it anonymous and put it into one database, preferably held by the government but definitely accessible to any physician or scientist. Right now those data are lost to the wind once the trial is over. But by keeping track of patients' genes, the genes in their tumors and what drugs they take, scientists will be able to discern patterns. Instead of trying drugs in order, from the ones that work most often to those that work least often, doctors will be able to pick the medicine that is most likely to help a particular patient. New medicines will get to market faster, along with diagnostic tests that will predict what will work. Friend predicts, somewhat optimistically, that prescribing decisions won't be based on "a promotional campaign." The database will decide.

"That future world is coming," says Friend. "And pharmaceutical companies can live in that world. If you develop the best drug and develop it for the right patient, all this does is get it to that right
patient."

Merck has not done much so far to open its trial data to the world, nor have its rivals, but Merck has less to lose here and more to gain. It has fewer cancer drugs in human tests than Pfizer or AstraZeneca, and its shares have dropped by half this year. Friend is powering ahead, building a first stab at the big database with the H. Lee Moffitt Cancer Center in Tampa, Fla. Over the next five years every patient who walks through Moffitt's door will be asked to put genes and tumor samples in a database that will number 100,000 patients; 5,000 are already in. The database will provide information to the doctors doing research there and, eventually, to patients. If it turns out you have a gene that tells researchers what drug will work for you, Merck and Moffitt plan to let you know. Experiments that would have required weeks of thawing tumor samples now take a matter of hours.

"Right now most of medicine is based on a bunch of gray-haired guys who say, 'This is the way I do it and it seems to work,'" says Moffitt Director Bill S. Dalton. "We need to determine over time what is useful and what isn't. The only way to do that is to study 100,000 patients."

The database idea is taking root elsewhere. The U.S. government is funding a Cancer Genome Atlas, in order to figure out how a large database would work. The Multiple Myeloma Research Consortium has funded the collection of 1,900 patients' bone marrow samples that are being studied by the mit-Harvard Broad Institute, a genetic research center. New data from that effort will be available within months.

A megadatabase "could save me months or years of trying to collect patient information," says Oregon Health & Science University oncologist Brian Druker, who helped get Novartis' potent tumor-fighter Gleevec to the market. But he questions whether researchers understand cancer biology well enough for Friend's highly computational approach to pay off in the short term. "Over the long term the Merck strategy will be the winning strategy," says Druker. "But right now I don't think we're quite there."

Merck has spent the past few years trying to dig out of one of the toughest periods of its 120-year history. In 2003 several experimental drugs for various diseases failed, all at once. In 2004 the blockbuster painkiller Vioxx was yanked because it caused heart problems. Merck settled its Vioxx liability claims last year for $5 billion.

The stock recovered as eight drugs were approved in two years, but the revival was short-lived. Sales of its Vytorin cholesterol pill, produced with Schering-Plough, have crashed under doubts about its effectiveness at preventing heart attacks. Cervical cancer vaccine Gardasil has hit a growth wall, and the Food & Drug Administration rejected a promising cholesterol drug because Merck had not collected enough safety data.

Merck hopes fighting cancer is one way out of this funk. Friend was put in charge of Merck's cancer research efforts in 2003, two years after Merck bought the company he was running, Rosetta Inpharmatics. Friend had cofounded Rosetta in 1996 with Leland Hartwell, now director of the Fred Hutchinson Cancer Research Center in Seattle, and Leroy Hood, now president of the nearby Institute for Systems Biology. Like rival Affymetrix, Rosetta began selling tiny DNA chips that could be used to figure out how often cells were accessing their genes.

Merck bought Rosetta in 2001 for $620 million. Hood and Hartwell gave their shares to their institutions. Hartwell won the Nobel Prize six months later for other work. Friend made $10 million on the sale and built himself a solar-powered, off-the-grid house on Stuart Island.

The first fruits of Rosetta's technology began to emerge with a 2002 article in the New England Journal of Medicine. Dutch researchers using Rosetta's software found a particular pattern of genetic signals within breast cancer tumors that could predict whether or not the cancer would return after surgery. The test is not a significant product for Merck but was approved by the FDA in 2007. It and a similar test made by a rival, Genomic Health of Redwood City, Calif., are widely used to guide post-op treatment strategy.

Merck has been making big acquisitions to augment Friend's technology. In 2006 Merck spent $1.1 billion in cash to buy tiny Sirna Therapeutics, a leader in a field called RNA silencing, which uses small molecules to shut off genes. These molecules can't be used as drugs because the body destroys them. But they can be used in petri dishes to turn genes on and off to find out which are important.

This technology identified a gene last year called KRAS that predicts whether targeted cancer drugs like ImClone Systems' Erbitux will work in a given cancer patient. Clinical trials confirmed this finding this year, and it turned out that 40% of the patients who were receiving Erbitux were getting no benefit. In the past this would have hurt the chances for a drug like Erbitux, but the new test makes doctors more eager to use the drug when it makes sense. Eli Lilly is now buying ImClone for $6.5 billion.

Friend has identified three families of cancer drugs that he thinks his technology can accurately understand: drugs that destroy DNA; those that mess up cell division; and drugs that block some of the most important signals in cancer cells. Noticeably absent are drugs such as Genentech's $2 billion (annual sales) Avastin, which stanches tumor blood supply. These are too complicated to understand.

He's been buying the rights to drugs that fit his interests. In 2004 Merck bought Aton Pharmaceuticals for its drug Zolinza, used to treat cutaneous T cell lymphoma. In 2007 it pledged up to $1 billion for a cancer pill from Ariad Pharmaceuticals.

All of these bets are based on what Friend's giant computer tells him. "This is going to have to be the path taken by pharma in the future," says Hood of Friend's current work. "It's a gamble, but I think it's one that if Merck sticks with it, they'll win big."

Recently Friend took a detour on his way to a research conference in Chicago. He flew to Florida, rented a 1972 Chevy Chevelle and drove to Cape Canaveral to watch the space shuttle launch. He says it wasn't just that he wanted to recapture the feeling of the space race, when scientists were treated like heroes, but that he wanted to get a sense of a project that massive and complex. Creating a cancer drug is not that different.

"The puzzle's gotten big," he says of the cancer drug hunt. "But I think there is only one way to solve it."