by David Holley | Published October 11, 2011 at 11:25 AM
Had Ralph Steinman lived for three more days, he would have seen the culmination of 30 years of scientific research that is just now reaching commercialization and will soon begin to make an impact on dealmaking.
Steinman was awarded the Nobel Prize for medicine on Oct. 3 for his discovery of dendritic cells, a type of immune cell that can be manipulated to spark disease-killing T cells and B cells at nearly peerless levels. Yet the validation of Steinman's efforts -- he spent years as one of the few, if not only, people espousing the promise of dendrtic cells, a promise that often fell on deaf ears -- comes amid tragedy. Three days before he was announced as a Nobel winner, the New York-based immunologist died of pancreatic cancer, the same illness that led to Apple Inc. co-founder Steve Jobs' death and a focal point of his research.
"The word of the day is 'bittersweet,'" Sarah Schlesinger, an immunologist and biologist who worked with Steinman on dendritic cells at The Rockefeller University since the late 1970s, said in an interview. "I wish I could say he knew or had an inkling. If he did, I think he would have held on."
Though Steinman never learned of his victory, he did know that his work was creating tangible products, such as Seattle-based Dendreon Corp.'s Provenge, the first Food and Drug Administration-approved cancer vaccine.
Provenge, approved in 2010 for prostate cancer, is made by taking a variety of cells, primarily dendritic cells derived from white blood cells, out of a patient's body and activating a chemical part of the dendritic cells known as antigens. The cells are then infused back into the patient's body. Depending on what type of antigen it is, it can trigger an immune response that targets a specific disease. In the case of Provenge, the dendritic cell's antigen causes T cells to target and kill prostate tumors.
Use of Steinman's dendritic cells extends far beyond Dendreon, however. Needham, Mass.-based Celldex Therapeutics Inc. is an early-stage biotech closely associated with Steinman and Rockefeller considering a partnership with Big Pharma. Celldex licensed intellectual property from Rockefeller that was discovered by Steinman as a follow-on of sorts to dendritic cells. Celldex gives patients a protein with a monoclonal antibody that seeks out a specific receptor, or antigen, on dendritic cells known as DEC-205. Through the receptor, the antibody causes the killer T cells to attack. Celldex's executives praise the process, which is in Phase 2 trials for cancer and Phase 1 for a drug meant to treat HIV, as potentially easier and cheaper.
Celldex is considering partnerships with larger drug makers as a method of funding its work. "We have active discussions with those companies you recognize that are involved in immunotherapy," Tibor Keler, the company's founder and chief scientific officer, said in an interview with The Deal Pipeline at a cancer immunotherapy conference in New York hosted by MD Becker Partners.
Exactly who a partner could be is up in the air. Some large pharmaceutical companies work in the vaccine and monoclonal antibody space, such as Bristol Myers Squibb & Co. and Sanofi SA. Bristol and Celldex have history together, however, which could be good reason for a partnership. Celldex is a spinout of Princeton, N.J-based Medarex, which Bristol bought for $2.4 billion in 2009.
Because Celldex's process is different than Provenge, it may not experience similar problems. Provenge sales since 2010 have been far below what Dendreon expected. Part of the difficulty, analysts say, has been getting urologists and oncologists to front the $93,000 for the treatment and then wait for reimbursement from insurance providers, which is how the sales process currently works.
Those commercialization and sales risks have made some investors skeptical of cancer immunology treatments. A panel of investors, venture capitalists and investment bankers at the MD Becker conference said there is still substantial interest in the space if companies have data that shows a drug will work.
Argos Therapeutics Inc., a Durham, N.C., biotech also associated with Steinman's work, is in the midst of gathering that data. Argos' process on surface appears similar to Provenge, but chief executive and president Jeff Abbey said that Argos' process has a higher potency of dendritic cells, causing a reaction among a certain type of T cell known as "elite controllers."
"No one else to our knowledge is showing this in active immunotherapy," Abbey said at the New York immunology conference.
With its lead candidate nearing the end of Phase 2 trials, Argos filed documents in August to begin the process of an initial public offering, in hopes of rasing money to fund Phase 3 trials. Shortly after, however, Dendreon announced its sales problems, sending a shockwave of uncertainty through those considering investments in vaccine immunotherapy. Then the stock market began to tumble. Most companies with plans for an IPO, even those not involved in the risky biotech sector, have put plans on hold.
Abbey said he can't comment on Argos' future strategy. In need of money, it's easy to guess that Argos will likely look to venture capital or partnerships with another company -- anyone from Dendreon to GlaxoSmithKline plc -- to continue its work.
Argos has one other connection to Steinman. It produced a full-course dose of its product, approved by the FDA through its compassion-use program, for Steinman to use against his pancreatic cancer. It was one of eight different experimental vaccines or personalized therapies that Steinman tried after he was diagnosed with the disease in 2007.
Though they're not certain what it was, Abbey and Schlesinger -- Steinman's colleague at Rockefeller -- believe something helped Steinman survive. Most people who are diagnosed with pancreatic cancer die after weeks or months.
"He lived for four and a half years," she said. "He was an amazing and remarkable man, unbelievably passionate about his work."
Steinman was in essence a true biologist: someone who believes in the potential of the science, whether or not it were ever proven definitively useful.