Roche and Cambridge, MA-based Biogen Idec are halting development of an experimental drug for rheumatoid arthritis because of safety concerns, according a report today by Bloomberg News. The drug, ocrelizumab, was designed to hit the same protein target on cells as the hit antibody ritxumimab, (Rituxan), albeit in a form thought to be more conducive for chronic autoimmune diseases than rituximab, which was originally developed as a cancer drug. Still, the new medicine was linked to “serious and opportunistic infections,” some of which were fatal, Basel, Switzerland-based Roche said today in an e-mailed statement cited by Bloomberg. The drug is still being tested for multiple sclerosis, according to the Bloomberg report.

Comments | Reprints | Share:        

One of the hot biotech startups from the Midwest is setting up shop in Boston. Lycera, the Ann Arbor, MI-based company with a novel idea for attacking autoimmune diseases, has decided to move its headquarters to Cambridge, MA and is naming a young management talent as CEO.

Lycera is announcing today it has hired Bill Sibold, the former senior vice president of U.S. commercial business at Biogen, to be its new CEO. Sibold, 43, is taking over at a company that made waves last year when it closed a Series A venture round worth $36 million from InterWest Partners, Arch Venture Partners, Clarus Ventures, and EDF Ventures.

The company was founded in 2006 to build on research from the University of Michigan laboratory of Gary Glick. He looked at the landscape of treatments for people with autoimmune disorders—conditions in which the immune system goes haywire and attacks healthy tissues—and saw room for improvement. A number of biotech drugs are effective against these disorders, such as Amgen’s etanercept (Enbrel) and Roche and Biogen Idec’s rituximab (Rituxan), but they and other drugs like them have the drawback of requiring injections and disabling some of a patient’s immune defenses, potentially making the patient vulnerable to infections. The concept at Lycera is to pursue different targets on cells, which make it possible to tamp down the autoimmune activity, without making people vulnerable to infection.

The market potential of any drug that really works for autoimmune diseases is enormous. About 80 diseases fall into this class, with names like rheumatoid arthritis, lupus, and psoriasis. The conditions collectively affect an estimated one out of every 12 people in the U.S., according to the National Institutes of Health. Rheumatoid arthritis alone is now a $10 billion a year market dominated by companies like Amgen, Johnson & Johnson, and Abbott Laboratories.

Bill Sibold

“Even though this is at an early stage, I think Lycera can be a great company that can compete with anybody,” Sibold told me, during a phone interview from the Ann Arbor offices.

Lycera envisions growing up over time from two bases of operation. Ann Arbor will remain the home to the drug discovery team, which is made up of about 15 people, many of whom used to work together at Pfizer before the company closed its research center there. Clinical development, regulatory affairs, business development, and executive leadership is being established in Cambridge, to take advantage of the region’s rich talent pool, Sibold says.

Sibold, 43, has the kind of background that venture capitalists want in an executive, and that is hard to find outside of Boston or the San Francisco Bay Area. He’s got a Harvard Business School …Next Page »

Comments | Reprints | Share:        

Adimab has an audacious goal for speeding up the way antibody drugs are discovered, and apparently it’s delivering the goods. The Lebanon, NH-based biotech company is announcing today it has collected milestone payments from its first two corporate partners, Merck and Roche, and built on that experience to grab a pair of additional partnerships with Pfizer and one other unnamed drug company.

Financial terms aren’t being disclosed, but I gathered the basic structure in a conversation yesterday with Adimab CEO Tillman Gerngross. Both Pfizer and the unnamed company have agreed to pay fees to support research at Adimab, as well as upfront cash, milestone payments, and royalties on sales for each drug or diagnostic that may someday be developed using the Adimab technology. Pfizer is using the Adimab technology to discover antibodies for a central nervous system disorder, while the unnamed partner is aiming to make antibodies against cancer.

While Adimab isn’t providing specific numbers, Gerngross tells me that securing these deals means that his 45-person company now has enough cash in the bank to operate for the next 10 years. The company is so confident that it has created something valuable to the pharmaceutical industry, that Gerngross vowed his company will secure two more partnerships before the end of March, plus two more by the end of June. Part of what’s driving it is that the pharmaceutical industry sees rapid growth in the $25 billion annual market for antibody drugs like rituximab (Rituxan) and trastuzumab (Herceptin), which can zero in on specific targets on diseased cells, while sparing healthy ones.

But that’s not the main reason the big players are beating a path to Lebanon, NH. They’re coming to Adimab for a method that can pump out hundreds of antibodies against a certain target in just two months of work, compared with six to 18 months of labor with the traditional methods used in biotech labs around the world, Gerngross said. The rest of the work in testing those drugs in animals and humans will be up to the major drug companies.

“People do a lot of promising in this business, and not a lot of delivering,” Gerngross said via phone from Nairobi, Kenya, where he was on vacation. “We take this very seriously. When we say we’re going to do something, we do at least that and more. It’s kind of embarrassing, but in this industry, that makes us stand out. We are doing these deals because we delivered.”

Gerngross can say stuff like that because he’s a proven player in the antibody drug business, after having sold his first company, Lebanon, NH-based GlycoFi, to Merck for $400 million in 2006. A year later, he started Adimab.

The idea, as Ryan has written about for Xconomy before, is to use a synthetic …Next Page »

Comments | Reprints | Share:        

If Seattle Genetics is destined to emerge a leading maker of antibody drugs that specifically target diseased cells, it will get there without the help of the world’s dominant player in the market for antibody drugs.

The Bothell, WA-based biotech company (NASDAQ: SGEN) said today that Roche’s U.S.-based Genentech unit has canceled a partnership the companies maintained for the past three years to co-develop dacetuzumab, an antibody for non-Hodgkin’s lymphoma and multiple myeloma. This means that Seattle Genetics will officially get back the full commercial rights to the treatment on June 8, six months after Roche served notice that it was ending the partnership.

The decision came after a portfolio review process at Roche, which has seen a lot of change this year. The Switzerland-based healthcare giant acquired South San Francisco-based Genentech, the world’s most valuable biotech company at the time, in March. Genentech is known as a biotech pioneer that developed or co-developed multi-billion dollar antibodies for cancer such as trastuzumab (Herceptin), rituximab (Rituxan), and bevacizumab (Avastin).

Genentech saw another opportunity in the antibody field when it struck a partnership with Seattle Genetics in January 2007. The bigger company agreed to pay Seattle Genetics $60 million upfront and potential milestone payments of $800 million over time for the right to co-develop daceutuzumab. One of the big ideas was to combine the new Seattle Genetics drug with Genentech’s rituximab. That was thought to be promising because the Seattle Genetics treatment was designed to hit a different target on cells, called CD-40, while the standard Genentech drug is made to block CD-20—and hitting two targets might be a more effective way to overcome resistance tumors eventually develop to treatment.

Seattle Genetics and its partner have seen mixed results with the new antibody this fall. Back in October, Seattle Genetics said it halted a clinical trial of dacetuzumab (formerly known as SGN-40) after an independent panel of safety monitors said mid-way through the study that it was unlikely to reach its goals. That was a big setback—the trial was set to enroll 224 patients with diffuse large B-cell lymphoma.

But this week, right before Genentech pulled the plug on the partnership, Seattle Genetics offered some new data that suggested dacetuzumab might not be toast. A study of 30 patients with diffuse large B-cell lymphoma, who got a different chemotherapy combination regimen than those in the other trial, found that half of the patients had their tumors partially or completely go away. Those new results were presented earlier this week at the American Society of Hematology meeting in New Orleans.

While losing a partner with the name cachet of Genentech is hard to spin around into a positive, Seattle Genetics CEO Clay Siegall did point out in a statement that dacetuzumab wasn’t really the company’s lead drug candidate anyway. That would be brentuximab vedotin, an “empowered antibody” that’s attached to a toxin to make it more potent against tumors. The empowered antibody is being tested in a pivotal clinical trial, and results are expected in the second half of 2010, the company has said. Seattle Genetics owns the full commercial rights to that product.

“We will evaluate available data as we consider possible next steps for the dacetuzumab program,” Siegall said in a statement. “We remain focused on advancing our lead product candidate, brentuximab vedotin.”

Seattle Genetics stock fell 5 percent at the opening bell this morning to $8.49 a share.

Comments | Reprints | Share:        

I groused last week that Seattle biotech news was slow, so naturally, this week I got swamped.

—Seattle-based Dendreon (NASDAQ: DNDN), the developer of a first-of-its-kind treatment to stimulate the immune system against cancer, is seeking to raise more than $400 million in a stock offering. The company plans to use the loot to build up its manufacturing and marketing muscle.

—ZymoGenetics (NASDAQ: ZGEN), the granddaddy of Seattle biotech companies, said it was cutting 52 workers, or about 15 percent of its staff. The company isn’t going to discover immunology drugs anymore. Interestingly, while Zymo made those cuts, its old corporate parent Novo Nordisk is going the opposite direction. Zymo sold one of its immunology drug candidates in animal testing to Novo for $24 million in upfront cash.

—Calistoga Pharmaceuticals, the Seattle-based developer of cancer and immunology drugs, showed off some impressive data for its lead drug candidate at the American Society of Hematology meeting in New Orleans. Results from the first 57 patients are compelling enough that Calistoga is preparing to leap ahead into a pivotal trial program next year.

—Gov. Chris Gregoire is making deep cuts in Olympia, but so far, she hasn’t recommended whacking the Life Sciences Discovery Fund (LSDF). The fund is still expected to get its $39 million budget allocation over this two-year budget cycle, says LSDF executive director Lee Huntsman.

—Arzeda, the Seattle-based company that makes designer enzymes on computers, said it has received a $149,000 grant from the National Science Foundation. The goal is to see if it can make an enzyme that can transform plant biomass into butadiene, a key ingredient in synthetic rubber tires. The grant’s not worth much, but it speaks volumes about the company’s strategy, which CEO Michael Martino explained in this exclusive interview.

—Seattle Genetics (NASDAQ: SGEN) suffered a setback with its antibody drug candidate dacetuzumab back in October, but now it may have some new life. The product, when given in combination with Roche and Biogen Idec’s rituximab (Rituxan) and chemotherapy, was able to completely or partially shrink tumors for 15 of 30 patients with diffuse large B-cell lymphoma, in a clinical trial. Results of the latest study were presented at the American Society of Hematology meeting.

—The Fred Hutchinson Cancer Research Center had a pretty lucrative week. The Seattle-based nonprofit research center said it won a multi-year, $55 million contract from the National Cancer Institute to run the only site of its kind that operates a cancer information service for the public. That contract will add 60 jobs. The next day, the Hutch raised $8.9 million at its annual Hutch Holiday Gala, mostly to support its research into stimulating the immune system to fight cancer cells.

—Stewart Lyman offered up another insightful observation in a guest editorial about how Hollywood is consistently portraying scientists as bad buys, largely inspired by a lot of corporate malfeasance in real life. If you’re not that familiar with Big Pharma’s tricks of the trade, you should check out the devastating list of industry wrongdoing Lyman has compiled from the past few years.

—Washington State University, along with Seattle-based Targeted Growth and Inventure Chemical, will share a $2 million federal grant to support research and development of algae as a source of biofuels.

—Lastly, I got a good reminder this week of how prevention of illness can sometimes be a better business than treatments. Seattle-based Free & Clear, which had received $17 million in venture capital, was honored with the “Deal of the Year” award by the Evergreen Venture Capital Association. The company, which has a coaching program for smoking cessation, was acquired in September for $130 million. It may not be as lucrative as creating a blockbuster drug for lung cancer, but 800,000 people have voluntarily enrolled in the program, and Free & Clear estimates that its work has helped the population add a total of 2 million years of extra life.

Comments | Reprints | Share:        

Some of the most successful biotech drugs ever created are designed to hit just one specific target on diseased cells, while sparing all sorts of markers found on healthy cells. But if Biogen Idec scientist Tony Manning and his colleagues are right, antibodies that specifically hit two targets could someday be better than one.

Cambridge, MA-based Biogen Idec (NASDAQ: BIIB) has long been a leader among companies that make monoclonal antibodies, which are made to specifically home in on a single specific target found on diseased cells. This is the mode of action behind one of Roche and Biogen’s classic hits, rituximab (Rituxan). Other biotech drugs, including products from Cambridge, MA-based Genzyme, are engineered proteins that replace something essential in the body. Still others like those from Amgen stimulate production of essential red and white blood cells.

But if your goal is to hit a specific target on diseased cells and you believe that say, certain autoimmune diseases and cancers are really complicated and involve cells with many different markers of disease, then wouldn’t it make sense to see if a drug can specifically block two targets? Essentially, as the old cliché goes, wouldn’t that be like killing two birds with one stone?

That’s how Manning sees it.

“These are next-generation biotherapeutics that could transform the business of biotech products,” says Manning, Biogen’s vice president of inflammation and autoimmune disease research.

Rituximab was approved by the FDA as the first monoclonal antibody for cancer back in 1997, and that opened the floodgates for an antibody boom. Biotech companies are estimated to rake in more than $30 billion in sales next year from these little Y-shaped proteins that treat all kinds of diseases like non-Hodgkin’s lymphoma, lung cancer, rheumatoid arthritis, and multiple sclerosis.

Tony Manning

Ever since genetically engineered antibodies were first synthesized in the 1970s, scientists have sought ways to make them better. Earlier this week, I described how Waltham, MA-based ImmunoGen (NASDAQ: IMGN) is working with Roche on what those companies hope will be the first commercially successful drug that attaches an antibody to an extra-potent toxin.

Taking a different approach, Manning spearheads a group at Biogen who dream of engineering a new class of antibodies that can hit two disease targets on cells, not just one. These are so-called “bispecific” antibodies. This is all at a very early stage of research, and none of these drug candidates have yet advanced into clinical trials, but to hear Manning talk, they will be a big deal someday not too far in the future.

The potential advantages of such a two-pronged antibody are pretty clear. Take rheumatoid arthritis, for example. Researchers know that drugs that block targets on cells called TNF and IL-6 can be effective at dampening the excess inflammation in the disease. It could be hypothesized that giving both types of drugs together might increase overall effectiveness, but that would also add a number of injections that patients might not want, and the two drugs could increase side effects …Next Page »

Comments | Reprints | Share:        

Seattle Genetics gets attention for its “empowered” antibody that targets tumor cells with a potent toxin, but today it presented some impressive data from a more typical “naked” antibody that doesn’t carry an extra lethal toxin.

The Bothell, WA-based biotech company (NASDAQ: SGEN) said today that half of the 30 patients with diffuse large B-cell lymphoma had their tumors completely or partially go away when they got the company’s experimental antibody, dacetuzumab. The trial was conducted in patients who had relapsed after prior therapies, and the experimental drug was given in combination with a common antibody, rituximab (Rituxan) and chemotherapy. The results were presented today at the American Society of Hematology’s annual meeting in New Orleans.

The results represent a comeback for the Seattle Genetics drug, which failed in a larger trial of 224 patients that was halted two months ago. Still, the drug has been a high priority for the company since January 2007, when it struck a partnership with Genentech, which is now owned by Roche. Both Genentech and Roche are deeply familiar with rituximab, which hits a target on tumor cells called CD20. The original drug, first approved in 1997, has become a commercial hit, generating $2.59 billion in U.S. sales last year. Yet as good as it is, patients eventually see their disease spread, and relapse. So Seattle Genetics moved to combine its antibody with rituximab. The Seattle Genetics drug designed to hit a different target, CD40, found on many types of malignant B cells and acts in a complementary way.

The data in the early-stage trial, which combines the Seattle Genetics drug with rituximab were “remarkable,” said David Miller, president of Seattle-based Biotech Stock Research, who covers Seattle Genetics. He attended the presentation in New Orleans, and summarized the data in a note to clients.

While the trial didn’t have any control group to offer a solid comparison, the researcher presenting the data said that patients at this stage of disease who get Eli Lilly’s chemotherapy agent gemcitabine (Gemzar) in combination treatments are expected to have tumor shrinkage rates of around 20 percent, far below the 50 percent seen in this study, Miller wrote in a note to clients.

Side effects have been known to derail companies that gave patients more than one antibody drug at a time, but Seattle Genetics said the majority of side effects were mild to moderate in this trial. Nausea, fatigue, and a depletion of platelet cells in the blood were the most common side effects.

Researchers found that eight out of 30 evaluable patients on the drug had their tumors completely disappear, and another seven of them had partial shrinkage. The tumor shrinkage lasted a median of 5.1 months, researchers said.

Based on the findings, Seattle Genetics and its partner, the Genentech unit of Roche, will decide what to do next based on findings in 2010 from a pair of additional early-stage trials in follicular lymphoma and multiple myeloma. The companies are also developing a gene signature test which is supposed to predict which patients are more likely to respond to treatment with dacetuzumab, and which ones won’t be helped.

Diffuse Large B-cell Lymphoma makes up about 30 percent of the cases of patients with non-Hodgkin’s lymphoma, making it the most common subtype of that malignancy. About 66,000 new cases of non-Hodgkin’s lymphoma are expected to be diagnosed this year in the U.S., and about 19,500 people are expected to die from the disease, according to the American Cancer Society. Diffuse large B-cell lymphoma is the form of cancer that Microsoft co-founder Paul Allen was diagnosed with last month.

Comments | Reprints | Share:        

Few doctors knew much about a rare brain infection called PML back in 2005, when two patients on a hot new multiple sclerosis drug from Biogen Idec and Elan died from the side effect. The infection, at the time, was generally considered a death sentence. But now with three years of data from more than 60,000 patients worldwide who have taken natalizumab (Tysabri) under strict monitoring by physicians, a new picture is emerging that shows PML is still very much a serious threat, but that it isn’t nearly as deadly as first feared.

While each and every confirmed case of PML, known formally as progressive multifocal leukoencephalopathy, scares investors in Cambridge, MA-based Biogen (NASDAQ: BIIB) and Ireland-based Elan (NYSE: ELN), I sought to assemble a big picture view of exactly how deadly PML really is when I interviewed Al Sandrock last week. He’s the senior vice president of neurology R&D at Biogen, and an assistant clinical professor of neurology at Harvard Medical School.

Before diving too far into the numbers about the risk of Tysabri, a little background is required. This drug, an antibody treatment designed to block certain white blood cells that cause MS when they attack nerves, has a history of also making patients vulnerable to infection. Biogen and Elan yanked it off the market in February 2005 after two cases of the brain disease were confirmed among patients taking the drug; a month later, a third case was confirmed. But legions of patients still demanded the drug, considered to be the most effective medicine on the market at reducing the disabling nerve damage from multiple sclerosis flare-ups. The FDA allowed the drug to return to the market in July 2006 after determining its benefits outweighed the risks, but it also forced doctors into a strict monitoring program to keep an eye out for the early signs of PML.

This matters not just for doctors and patients, but for Biogen’s and Elan’s financial futures. The drug, Biogen’s fastest-growing product, generated $560 million in sales in the first nine months of this year. (The importance of this drug is one reason why investors get so ticked at Biogen when it isn’t exactly forthcoming about every newly diagnosed case, but that’s a bone to pick another day.)

When the drug came back on the market, its FDA-approved prescribing information contained a prominent warning that about 1 out of every 1,000 patients on the drug were likely to get PML. But that was really just a forecast, and the actual risk-benefit balance for this drug is really a moving target that shifts over time when a new case is confirmed. So I sought to build a simple chart when I spoke to Sandrock that provides a snapshot of PML cases in February 2005, when the drug was pulled off the market because of the PML risk, versus those confirmed as of yesterday. Here’s what I gathered:

The February 2005 figures came from clinical trial data and formed the foundation for the FDA-required warning of the 1-in-1,000 chance of getting PML. The more recent figures include all the experience of patients who have gotten the drug since it was returned to the market in July 2006. The thing that jumped out at me was the fact that only five of the 27 confirmed patients with PML have died—meaning that the current survival rate stands at over 80 percent.

That curious fact has been buried under a rash of scary headlines …Next Page »

Comments (37) | Reprints | Share:        

Seattle-based Calistoga Pharmaceuticals has taken another peek at preliminary results from an ongoing clinical trial of its drug that’s made to block one of the hottest targets in cancer biology, and it continues to like what it’s seeing.

Researchers saw that five of 17 evaluable patients (29 percent) with chronic lymphocytic leukemia had at least partial tumor shrinkage after a single one-month cycle of therapy on Calistoga’s CAL-101 drug candidate by itself, without help from combination therapy, according to data presented over the weekend at a leukemia research meeting in Barcelona. All of the patients had gotten standard treatments before enrolling, and half of them had relapsed before entering the Calistoga trial, researchers said.

The new findings strengthen Calistoga’s body of evidence in a year in which it has started to create some buzz on the national stage. The company raised $30 million in venture capital in May from Frazier Healthcare Ventures, Alta Partners, Three Arch Partners, and Amgen Ventures. A few weeks later, it became clear why Calistoga attracted that much cash. It reported at a pair of cancer meetings that its drug was causing tumor shrinkage in about half of the first 24 evaluated patients in its first clinical trial, even at less than ideal doses, for patients with non-Hodgkin’s lymphoma, acute myeloid leukemia, and chronic lymphocytic leukemia.

The latest data also confirms that Calistoga, along with a number of tough competitors, is pursuing what biologists consider one of the hottest targets in cancer biology. It’s called the PI3 kinase pathway, which controls critical cell processes like proliferation, migration, and cell survival. When these normal functions get flipped into an overactive mode, it’s a hallmark of cancer cells growing out of control as well as an immune system going haywire and attacking healthy tissue.

“We’re seeing robust responses,” in relapsed patients, says Carol Gallagher, Calistoga’s CEO, who I reached by phone while she was attending the meeting in Barcelona. “This is very encouraging data.”

Carol Gallagher

Encouraging as it may be, Calistoga has also learned some important things about side effects. Patients got either a 200 milligram or 350 milligram dose of CAL-101, and saw some signs of elevated liver enzymes in the bloodstream at those doses, which can be a sign of liver damage. The side effects were reversible when patients quit taking the drug, but that effect has gotten Calistoga thinking about whether patients would be better off taking a lower dose in subsequent trials, to strike the best balance between safety and effectiveness, Gallagher says. The company has seen tumor shrinkage with doses as low as 50 and 100 milligrams, she says.

That said, there were other interesting findings from this trial. To put it in context, Gallagher first explained the “partial responses” that are reached when scientists saw at least a 50 percent shrinkage in lymph node tumors, in addition to a 50 percent decline in lymphatic cancer cells circulating through the bloodstream.

That’s important to physicians, but what’s particularly intriguing is the next finding. Calistoga …Next Page »

Comments | Reprints | Share:        

Some unexpected bad news out of Seattle Genetics is driving down its stock 14 percent this morning. The Bothell, WA-based developer of antibody drugs for cancer (NASDAQ: SGEN) said a mid-stage clinical trial of an experimental lymphoma drug was halted midway through enrollment after an independent panel of data monitors determined the experimental drug was unlikely to reach its goal of beating the control group.

The Seattle Genetics antibody drug, called dacetuzumab or SGN-40, was being studied in a trial of 224 patients with diffuse large B-cell lymphoma, in combination with rituximab (Rituxan) and standard chemotherapies. Patients in the control group got the same treatment, except a placebo instead of the Seattle Genetics drug. About two-thirds of the patients were enrolled in the randomized, blinded trial before it was closed. Seattle Genetics didn’t say anything in its statement today about the safety profile of its drug.

The trial failure is a setback for Seattle Genetics, which has been developing this drug since January 2007 in partnership with Genentech and now Roche. The new antibody is designed to hit a different target found on cells, called CD40, which is found on many types of malignant B cells and is supposed to be complementary to the standard rituximab antibody that hits another target called CD20. Rituximab, the pioneering antibody for cancer, generated $2.59 billion in U.S. sales last year as it has become a standard lymphoma treatment. Yet as good as it is, patients eventually see their disease spread, and relapse after getting rituximab. Seattle Genetics pointed out in its release that it has four other smaller clinical trials of its dacetuzumab treatment for non-Hodgkin’s lymphoma and multiple myeloma, a cancer of the bone marrow.

“We are disappointed that the interim analysis of the phase IIb clinical trial resulted in discontinuation of the study, especially given the unmet medical need for DLBCL patients,” said Clay Siegall, CEO of Seattle Genetics, in a statement. “In collaboration with Genentech, we will conduct a detailed analysis of data from the SeaGen MARINER trial.”

Seattle Genetics shares fell $1.79, or about 14 percent, at the opening bell this morning to $11.83.

Comments | Reprints | Share:        

Drug companies usually have a hard time recruiting cancer patients in clinical trials, and some dirty little financial reasons for it were exposed last week in The New York Times. Another little secret is that biotech companies often overpromise, and under deliver, when they tell investors they will hit their clinical trial deadlines.

That makes it all the more surprising to hear what’s going on at Bothell, WA-based Seattle Genetics (NASDAQ:SGEN). This company, the developer of an “empowered antibody” against Hodgkin’s disease, said recently its pivotal study is recruiting patients so fast that it is now six months ahead of schedule. That sets off a chain reaction that means it should have results sooner, apply for FDA approval quicker, and reach the market six months earlier, possibly as soon as the end of 2011.

Seattle Genetics has been able to pull this off because of pent-up demand from very sick patients with relapsed forms of Hodgkin’s disease, who are searching for new treatment options. Top cancer doctors hopped on the bandwagon after the American Society of Clinical Oncology meeting in June 2008, when the company released preliminary results showing its experimental treatment was able to completely wipe out or partially shrink tumors for 12 of 38 patients, with mild to moderate fatigue, cough, and nausea as side effects. The preliminary results for brentuximab vedotin (formerly known as SGN-35) started looking even better when longer-term follow-up data was presented at a medical meeting in December.

“More investigators wanted into the trial than we could really let in to participate,” said Tom Reynolds, the chief medical officer at Seattle Genetics, in an interview on Aug. 3. “You usually have to work really hard to get them interested. There seems to be a good buzz going in the oncology community.”

Investors like it too. JP Morgan analyst Cory Kasimov, a Seattle Genetics bull, headlined his note to investors on July 23 with “SGN-35 Momentum Continues to Pick Up Steam.”  Seattle Genetics seized on some of that momentum this week, raising $118 million in a stock offering that priced yesterday afternoon.

Exciting as it all was, drug development is highly regulated and slow. But Seattle Genetics has been pushing hard to move as quickly as possible. One month after producing that stellar data at the American Society of Hematology in December, Seattle Genetics clinched an agreement with the FDA on …Next Page »

Comments (1) | Reprints | Share:        

Biogen Idec, as avid biotech readers know, is the world’s largest maker of multiple sclerosis drugs. Not the world’s largest maker of cancer drugs. Not even close.

Yet the Cambridge, MA-based biotech company (NASDAQ: BIIB) has its sights on carving out a bigger niche in the fiercely competitive field of cancer drug development. It’s a market with plenty of room—growing from $66 billion in worldwide sales in 2008 to more than $84 billion by 2012, according to Cowen & Company.

Right now, Biogen has one slice of that, which comes solely from its partial ownership, along with Roche and Genentech, of rituximab (Rituxan). That drug was the original trailblazer in the field of targeted antibodies, made to seek out cancer cells and avoid healthy ones, when it was first approved by the FDA in 1997 for patients with non-Hodgkin’s lymphoma. It generated $2.6 billion in U.S. sales last year. But that drug cracked into the market 12 years ago, and there’s no second-generation, or third-generation version yet on the market. The company didn’t have much to brag about a few weeks ago at the American Society of Clinical Oncology annual extravaganza. I wanted to know what Biogen is really doing to improve upon that, so I spoke to Greg Reyes, the company’s senior vice president of oncology R&D.

Reyes, a pharmaceutical and biotech veteran who joined the company in October, is based in San Diego. He oversees a cancer research operation with 230 people. They are responsible for a pipeline that now includes 12 different drug candidates at various stages of development. Speaking broadly, the company is pouring a lot of its energy into understanding how its drugs work, crafting really rigorous clinical trials at earlier stages to separate the wheat from the chaff, and studying biomarkers that might offer clues into which patients are likely to repond to therapy, and which won’t, Reyes says. Investors, doctors, and patients will find out in coming years whether this effort will bear any fruit.

“If we are having this same conversation five years from now, and we’re still talking …Next Page »

Comments (1) | Reprints | Share:        

Agios Pharmaceuticals has landed a big fish in the world of cancer drug development. The Cambridge, MA-based company has hired David Schenkein, the senior vice president in charge of cancer drug development at Genentech, to be its first permanent CEO, starting in August. He will replace Kevin Starr, a partner with Third Rock Ventures, who has been serving as its interim CEO in the company’s early days.

It’s a coup for Agios, which debuted with a $33 million initial round of venture capital last Fourth of July weekend. Schenkein will join Duncan Higgons, formerly the president and chief operating officer of Cambridge, MA-based Archemix, who has recently signed on as the chief operating officer at Agios. As I explained in earlier stories about the company last July and November, the idea at Agios is to throw a wrench into the overactive metabolic enzymes that allow cancer cells to grow and thrive. Essentially, the startup hopes to starve cancer cells to death.

Schenkein, 52, has been responsible for clinical development and regulatory work on numerous cancer therapies at South San Francisco-based Genentech over the past three years, as it asserted itself as the largest U.S. maker of cancer drugs. He has worked on efforts to expand usage of top-selling antibody drugs like bevacizumab (Avastin), rituximab (Rituxan), and trastuzumab (Herceptin). Schenkein also has roots in Boston. He played a key role at Millennium Pharmaceuticals in the development of bortezomib (Velcade), and prior to that was the director of the cancer center at Tufts Medical Center.

“David is one of the most sought after executives in the biotech/pharma industry. This speaks volumes about the science and vision of Agios,” Starr says.

Comments (1) | Reprints | Share:        

Some of biotech’s most innovative drugs emerged under the worst financial conditions. Two big breakthroughs in the 1990s, Enbrel for rheumatoid arthritis and Rituxan for lymphoma, came from small biotech companies that toiled for years, and survived brushes with extinction, before they made it.

This history lesson came up in conversations I had with entrepreneurs after the Xconomy Forum: Tomorrow’s Biotech—Innovators and Innovations, which we held yesterday at Biogen Idec in Cambridge, MA. The people who enter this business need a rare combination of intellect and tenacity to survive in a business where 9 out of 10 drugs that enter clinical trials fail, and where it takes more than a decade and hundreds of millions of dollars to develop a drug, even in good times. So it was fascinating to hear people describe the grim realities of the economy as simply another obstacle they need to overcome—and not an insurmountable one.

Startup founders and CEOs participating in the forum covered a lot of ground about creative ways biotech companies are seeking to clear these hurdles by raising money, improving the odds in drug development, and lowering costs. Of course there’s no one simple way to build and sustain a new company, and indeed the forum highlighted some completely opposite strategies.

Meanwhile, the heads of some of the most innovative programs at public biotechs—Biogen Idec’s Gilmore N. O’Neill, Genzyme’s Sam Wadsworth, and Vertex Pharmaceuticals’ Eric Olson, moderated by GlaxoSmithKline’s Michelle Dipp—shared their perspectives on what it takes to foster new ideas and treatments in the public-company context. (FYI, none of them officially condone submarine projects, wink wink nudge nudge.) We also heard from some pioneers of the biotech industry—Walter Gilbert and George Church—during a keynote chat, although I’m saving up highlights from an interview with Church for next week, so watch this space.

Thanks to all who joined the conversation yesterday. And if you missed it, here are some of the highlights from the entrepreneurs at the Forum:

—Peter Hecht, CEO of Cambridge, MA-based Ironwood Pharmaceuticals, talked about his secret for being able to raise $281 million over the past 11 years to build his company, which now has 160 employees. “We’re crazy-passionate about building a great company and doing it over the long haul,” he said, with a sense of purpose that made it sound like more than a platitude.

This guiding principle has enabled Hecht to pull together investors like Polaris Venture Partners and Venrock Associates to support the company—without agitating for a quick acquisition to get fast returns. By sticking with this consistent …Next Page »

Comments | Reprints | Share:        

Biogen Idec is the world’s biggest maker of drugs for multiple sclerosis, and it wants to keep things that way. But every drug that’s born eventually dies, and the last remaining patents on Biogen’s biggest-selling drug, interferon-beta1a (Avonex), run out in 2011 and 2013. To protect this $2.2 billion-a-year MS franchise—which generates more than half of Biogen’s sales—the company has cooked up a modified version (with a fresh new patent, of course). The new drug is supposed to last longer in the bloodstream, require fewer shots, and maybe even work better.

The idea—attach a polymer to the end of this type of interferon protein—has been tried by chemists for years with no luck, but it would be a big deal if Biogen or anybody else could find a way to make it work. Biogen is so jazzed about this concept that it is leapfrogging from the first phase of clinical trials to the final stage. I spoke with Biogen’s president of research and development, Cecil Pickett, this week for more insight into the company’s strategy in pursuing this “pegylated” version of its workhorse interferon drug.

The current batch of interferons, the standard of care for MS, are effective at reducing flare-ups from the chronic neurodegenerative disease, generating about $4 billion a year in revenue for Biogen, Bayer, and Merck KGaA. But patients say they can be a nuisance. The drugs cause flu-like symptoms and suffer from peaks and valleys of concentration in the bloodstream that are thought to weaken their effect and require them to be taken with more than one injection a week. Many patients struggle to stick with their meds, especially when it’s hard to tell for sure when the drugs are working.

There is a precedent for making a pegylated version of interferon—a related molecule for hepatitis C called interferon alpha. Modified forms of this drug, for hepatitis C, have been shown to boost their effectiveness and increase convenience for patients, and have become billion-dollar franchises for Roche and Schering-Plough. Since multiple sclerosis treatment is becoming increasingly competitive with convenient oral drugs from Novartis and Merck KGaA emerging in late-stage clinical trials, Biogen sees the long-lasting interferon-beta as an important way to defend its turf. There are at least two venture-backed startups, Seattle-based Allozyne and San Diego-based Ambrx, working on longer-lasting interferons for MS, but neither has yet entered clinical trials. Biogen believes it is still in the lead, and it might be able to strengthen its grip on the market by combining the longer-lasting interferon with an oral MS drug of its own, Pickett says.

“We felt comfortable with the dose and response we saw in the Phase I study,” Pickett says. “I think we’re in the lead, and given the expertise we have in MS and our ability to make these kinds of molecules, I’m bullish about this.”

Pickett says he’s been an in-house advocate for this program since he joined Biogen in September 2006, because he’s “biased” from his previous experience at Schering-Plough. That Kenilworth, NJ-based drugmaker (NYSE: SGP) attached a polymer to a different kind of interferon, the alpha variety, and turned it into a $914 million hit marketed as PEG-Intron for hepatitis C. What’s more, that compound works in combination with an oral hepatitis C drug, ribavirin. That’s gotten Biogen thinking about one day combining its long-lasting interferon beta with BG-12, an oral MS drug it has in development, Pickett says.

Chemists have traditionally had a hard time making a long lasting interferon beta, because attaching polymers in standard manufacturing techniques is easier said than done. Past techniques caused the polymer to attach to different parts of the protein, rendering it an inconsistent product in the vial, which is a big no-no …Next Page »

Comments | Reprints | Share:        

Trubion Pharmaceuticals (NASDAQ: TRBN), said today it has started a clinical trial of a drug for lupus, an autoimmune disease. The drug, SBI-087, is made to hit a target called CD20, that’s currently blocked by Genentech and Biogen Idec’s rituximab (Rituxan) for patients with a different form of autoimmune disease, rheumatoid arthritis. The Trubion drug-which is also being tested for rheumatoid arthritis—is being developed in partnership with Madison, NJ-based Wyeth.

Comments | Reprints | Share:        

Rituxan, the hit lymphoma drug from Genentech and Biogen Idec, has failed in yet another bid to expand into treating other diseases. The drug fell short of reaching the main goal in a final-stage study of 144 patients with lupus nephritis, an inflammatory disease of the kidneys.

The study, called Lunar, showed that patients who got a combination of immune-suppressing drugs in addition to rituximab (Rituxan) didn’t do significantly better those who got a placebo, Genentech said today in a statement. No new or unexpected safety issues popped up, the company said.

The two life sciences companies first formed a partnership to co-develop, and co-market the drug back in 1995, when rituximab’s developer, San Diego-based Idec Pharmaceuticals, was low on cash and needed help from Genentech to finish clinical trials for non-Hodgkin’s lymphoma. Genentech is based in South San Francisco, CA, and operates a manufacturing facility in Oceanside, CA, about 35 miles north of San Diego. Biogen Idec, based in Cambridge, MA, merged with Idec in 2003 and still retains a presence in the region.

Rituxan, approved in 1997 by the FDA as the world’s first targeted antibody drug for cancer, won an additional approval from U.S. regulators in 2006 for rheumatoid arthritis. The drug is designed to block excess B-cells of the immune system, which are culprits in non-Hodgkin’s lymphoma, as well as autoimmune diseases. After showing positive early signs in clinical trials, the drug failed last year in the final phases of development for multiple sclerosis, lupus that circulates throughout the body, and now lupus of the kidneys. The drug is a major revenue driver for both Genentech and Biogen Idec—it generated $2.6 billion in U.S. sales in 2008.

Genentech and Biogen Idec plan to continue to hunt for treatments of lupus nephritis based on findings from the study. “We plan to analyze the full set of data from this study and share the findings at an upcoming scientific meeting,” said Evan Beckman, Biogen’s senior vice president of immunology R&D, in a statement.

An estimated 1.5 million to 2 million people in the United States have lupus, a disease in which the immune system goes haywire and starts attacking healthy tissue like it would a virus. About one-third are estimated to have the form that attacks the kidneys, Genentech and Biogen said.

The failure of rituximab is just the latest in a string of setbacks for lupus treatments. An experimental drug called Riquent from La Jolla Pharmaceutical failed last month in a study of 730 patients with lupus nephritis.

Comments (2) | Reprints | Share:        

Seattle-based Trubion Pharmaceuticals said today it is cutting one-fourth of its workforce, about 25 jobs, leaving it with a staff of about 75. The company says it expects the cuts will help it conserve enough cash to operate into the second half of 2010.

The Trubion (NASDAQ: TRBN) cuts will affect “most areas of the company,” a spokeswoman said. The restructuring is designed to invest in the company’s “strongest near-term opportunities,” including TRU-016 for chronic lymphocytic leukemia, and select drug candidates in animal testing that it says could become valuable over time. Trubion says it will “continue to support” the programs it has in a collaboration with Madison, NJ-based Wyeth, TRU-015 and SBI-087, a pair of experimental drugs for rheumatoid arthritis.

Trubion was dealt a big dose of uncertainty last month when the world’s largest pharmaceutical company, New York-based Pfizer, reached an agreement to acquire Wyeth for $68 billion. Trubion has no marketed products of its own, so it depends heavily on the partnership with Wyeth to support its research and development. A clinical trial of 270 patients who took Trubion’s lead drug, TRU-015, or a placebo, disappointed investors in the fall of 2007 because it didn’t show conclusive superiority over Genentech’s rituximab (Rituxan) for rheumatoid arthritis.

Wyeth has shown willingness to stick with Trubion’s plan, pushing forward another mid-stage trial that’s expected to produce results by the end of 2009, but investors have run low on patience. Trubion had about $61.6 million in cash and investments left at the end of September, the last time it reported financial results, yet investors are saying the company is worth a whole lot less than that, giving it a market value of $23 million. Trubion stock fell 87 percent during 2008.

For an updated look at job cuts at Seattle high-tech and life sciences companies, check out our updated layoff tracker.

Comments | Reprints | Share:        

Pfizer rocked the business world yesterday with its $68 billion bid to acquire Madison, NJ-based Wyeth (NYSE: WYE), and the ripple effect was felt here in the Northwest. Nobody in town has a bigger stake in this deal than Seattle-based Trubion Pharmaceuticals (NASDAQ: TRBN).

Trubion’s lead drug candidate for rheumatoid arthritis, TRU-015, has been part of a collaboration with Wyeth since December 2005. That deal brought Trubion $40 million in upfront cash, shifted the drug’s development and commercialization bills onto Wyeth, and made Trubion eligible for as much as $800 million in milestone payments, plus royalties on sales if the drug made it all the way to become an FDA-approved product. Last June, Wyeth elected to extend the research part of the collaboration through Dec. 22, 2009.

Pfizer, the world’s largest drugmaker, didn’t say in its announcement of the proposed Wyeth takeover what will happen to partnerships like the one with Trubion. On the plus side, Pfizer did say the acquisition is supposed to make it “a top-tier player in biotherapeutics and vaccines,” through acquiring multi-billion dollar products like Wyeth’s pneumococcal conjugate vaccine for infants (Prevnar) and its stake in the world’s best-selling biotech drug, etanercept (Enbrel) for rheumatoid arthritis. Then again, Pfizer has also said it wants to cut costs—and eliminate 8,000 jobs—so it’s hard to say exactly what the new bosses will do with any experimental drugs if they complete the deal and send Wyeth’s executives to the exits. A definite answer isn’t coming right away—the deal isn’t supposed to close until the third or fourth quarter of this year.

“It is far too early to tell if or how it will impact Trubion. As of right now, our collaboration agreement with Wyeth is still in effect,” said Trubion spokesman Jim DeNike, in an e-mail. “While we cannot speculate on the ultimate disposition of our programs until after the transaction closes and after information is confirmed, we are encouraged by Pfizer’s stated strategic initiatives as outlined in the merger press release, many of which appear very synergistic with our business objectives.”

Still, I had to ask what the terms of Trubion’s deal say about what happens in the event of a Wyeth takeover. The terms of the partnership agreement call for the new owner of Wyeth to offer Trubion an exclusive opportunity to buy back its stake in the licensed products “on commercially reasonable terms.” If they can’t agree to terms, then the new owner could divest the license to another company, as long as it doesn’t end up offering better terms than it did to Trubion.

Pfizer doesn’t appear to have any drugs in its development pipeline for rheumatoid arthritis, according to a survey by the Pharmaceutical Research & Manufacturers Association. What’s more, Pfizer doesn’t appear to have any drug of its own in development designed to work like Trubion’s TRU-015, which blocks a target on B cells known as CD-20, DeNike says. Rheumatoid arthritis drugs are certainly the kind of market that can get the attention of a company as large as Pfizer, since the class of treatments generated an estimated $10 billion in sales in 2006, according to IMS Health.

Still, the uncertainty over what Pfizer will do this year has to be an unwelcome headache for Trubion. The company is already coming off a brutal year. Its stock has collapsed …Next Page »

Comments | Reprints | Share:        

It’s tough times for biotech entrepreneurs in search of new funds to launch startups, with early-stage investors conserving capital for their existing portfolio companies. Yet one venture group that isn’t hurting for capital nowadays is Biogen Idec New Ventures, the San Diego-based VC arm of big biotech company Biogen Idec (NASDAQ:BIIB).

Biogen this year committed an additional $100 million to its VC outfit, adding to the initial $100 million allocated to the group when it was formed in 2004, says John Dunn, executive vice president of New Ventures. The Biogen venture group also operates in Cambridge, MA, where Biogen is headquartered.

Dunn says the tough economic climate creates opportunities for New Ventures. “It would just seem obvious that because of the economic climate, traditional venture is pulling back a little bit, but companies still need the capital,” he told me . “The deal flow has never been a problem, but we see [inquiries from startups] increasing a little bit.”

While many traditional venture firms scale back on investment activities, New Ventures plans to invest at about the same pace as it has since 2004. Dunn says he expects to invest the new $100 million allocation from Biogen over a four-year period, give or take six months.

Dunn says his group, governed by a board of top Biogen executives, is authorized to invest up to $7.5 million in a single financing round and a total of $10 million in each portfolio company. He doesn’t like to talk about the 13 companies in his portfolio, keeping Biogen’s investment strategy close to the vest. But here are our descriptions of several of them in the Boston area and San Diego:

Hydra Biosciences — Cambridge, MA

Hydra aims to develop new drugs to home in on …Next Page »

Comments | Reprints | Share: