BioWorld Today Columnist
Academic and company scientists have been working since the beginning of the biotech industry (and long before) to understand how to generate the ultimate desirable manipulation of the immune system - turning off the disease-causing reactions while turning on the good reactions.
In the 1890s, William Coley found that shooting up cancer patients with a slurry of bacterial cell walls generated a powerful immune response that delivered a tumor-torturing cocktail of cells and factors to the cancer sites.
Scientists then spent the next 100-plus years trying to isolate the individual factors that were ultimately responsible for that nifty antitumor response. Many of the first-generation biotech firms focused on just that task - tracking down thymosin, lymphotoxin, the myriad interferons and my personal favorite: tumor necrosis factor. Scientists wanted to create narrowly targeted therapies and vaccines, but it seemed the more they tried to get down to a single molecule, the more elusive the clinical response became.
That same pattern showed up all over the place: trying to find the single neurotrophic factor that could cure degenerative brain diseases, the growth factor that could treat heal wounds and bone fractures quickly, the subunit vaccine that could protect as powerfully as the old whole-virus vaccines.
But the more we narrowed things down, the less significant the biological response. In many cases, there simply wasn't a way to deliver those specific factors so they could reproduce the desired in vivo response. Vaccines aimed at infectious disease and cancer just couldn't generate a strong enough response to be protective.
Let's Get Non-Specific
Jeff Fairman was working at Valentis, a gene therapy company in Burlingame, Calif., looking for a way to deliver specific genetic information to cells to fight disease. One of the delivery methods used fats to surround the gene, hoping to sneak it in into cells where it could do its therapeutic thing.
There was a small problem. That approach generated a whopping immunostimulatory reaction when given I.V., pretty much negating its ability to deliver gene therapy. Valentis decided to drop the approach in favor of others.
But Fairman and a Valentis collaborator, Steve Dow at Colorado State University, thought that this very flaw made the fat/DNA complex a great way to deliver a generalized kickstart to the immune system.
They tweaked the system to include non-coding DNA wrapped in the lipid coat to create a powerful immune stimulant that did not require a specific antigen. Mice challenged with virus and then treated with the general immunostimulant were able to chase the virus out just fine.
Dow also found that addition of antigens could direct the immune response against a target antigen from a tumor or microbe. Dow has treated dogs with naturally occurring tumors using a mixture of tumor cell lysate plus the immunostimulant fat/DNA combo and has seen a significant improvement in the survival rate (about 40 percent vs. zero survival in the non-treated group).
Fairman said they are seeing a very robust increase of at least 10-fold vs. competing technologies in immune response driven by the lipid/DNA mixture in a range of systems. They licensed the technology from Valentis and created Juvaris in 2003.
John Warner, the former vice president of research and development at Valentis and now chief scientific officer at Juvaris, helped recruit Martin Cleary and his extensive management experience in biotechnology companies to take the CEO slot.
The Outcast Chasing Dollars
Ever been the least popular kid at school? Try raising venture money when you not only don't look like the current fad business model, but also the VCs define your technology as "failed!"
The Juvaris team faced a huge challenge in convincing investors that a fat/DNA combo could in fact deliver the desired clinically significant response in vivo - especially since gene therapy companies were trying to convince them of just the opposite. There are too many variables involved in why the "same" product gives completely different reactions in different settings, and investors usually don't like complicated stories.
So Juvaris took a route that is gaining in popularity for startups. Using Cleary's track record of building shareholder value, they raised $2 million in angel funding and started writing grant proposals. They set up labs in the Molecular Medicine Research Institute in Sunnyvale, where they could take advantage of a turnkey setup at a great price. (See BioWorld Today, March 13, 2006.)
To date, the company has been awarded more than $1.6 million in grants to support development of vaccines for Pseudomonas, influenza A and HIV and are waiting to hear about funding for a Rift Valley fever program, an acute myelogenous leukemia program and Tularemia as well as the Phase II SBIR for Pseudomonas. All of those programs involve prestigious collaborators, including the University of California at San Francisco, Stanford and the Centers for Disease Control and Prevention.
Juvaris has seen significant responses in animal models using either the general immune stimulant or an antigen-driven version in hepatitis B, influenza A, various biodefense and infectious disease models. It also has seen tumor reduction and increased survival in a range of cancer models and canine patients with naturally occurring tumors.
The great thing about the Valentis licensing deal is that it gave Juvaris a huge leg-up in the downstream development of products from the technology, including a full manufacturing package, validated vendors ready to produce for clinical testing, and a track record of safety with the FDA. Fairman said, "We are somewhere between traditional startups and these specialty pharma companies. We are actually close to the clinic in glioblastoma and hepatitis B, and know a lot about the product."
Juvaris is well on its way to exploiting a field with a sordid past - immunotherapy - by going back to basics. After decades of focusing on giving patients that single, genetically engineered molecule and not getting the desired clinical impact, Juvaris is giving the immune system a swift kick with something that more closely resembles Coley's long-ago microbial mixture than current more-defined immunotherapy approaches, and trusting the body to sort it out and generate the right mix of cytokines and cells at the right spot in the body.
After Glaxo picked up Corixa essentially for the old Ribi Immunochem adjuvant technology, we shouldn't be surprised if Juvaris hooks up soon with some of the strategic corporate partners who have come knocking on its door after reading about the grant programs. With renewed interest in financing companies focused on biodefense and pandemic flu, who knows - maybe the VCs will step up to the plate?
Robbins-Roth, Ph.D., founding partner of BioVenture Consultants, can be reached at email@example.com. Her opinions are her own and do not necessarily reflect those of BioWorld Today.