In my last post (“Thanksgiving”), I wrote about the progress reported recently by Bionor, a small Norwegian company, in testing its therapeutic vaccine for HIV/AIDS (Bionor Nov PR). Given that yesterday was World AIDS Day, I thought I would continue in that vein and look at the other (too few) companies that are working on these vaccines. [In case you missed it, this year’s World AIDS Day theme is universal access, a good idea when treatment saves lives; the Day is on December 1 because back in 1988 a PR guy saw a news lull between elections and Christmas (Wikipedia article on WAD).] As I noted previously, therapeutic vaccines are intended to be given to HIV-positive individuals to increase cell-mediated immunity to both lower HIV viral load (viruses in the blood) and resist other potentially life-threatening pathogens and were once thought to be a dead end due to clinical failures in the 1990s (Nature article). This past year a handful of companies have reported promising early-stage clinical results.
The US company of the group is Argos Therapeutics of Durham, NC, (Argos) which is a 1997 spinout from Duke University and has raised about $120 million in private capital in four rounds (TechJournal article) in addition to receiving a $21 million NIH contract for platform development in 2006 (Argos platform) which is also funding the development of their HIV vaccine. The company’s approach is “personalized immunotherapy,” meaning a patient’s dendritic cells (antigen-presenting immune system cells) are harvested, transfected with the target cell or virus RNA, and then re-injected to boost the immune system response (an ex vivo vaccination). The upside is that the therapy is specific to all the genetic variants found in the patient; the downside is its costly and not suited for resource-limited settings. Argos’s lead product is for treating metastatic renal cell carcinoma which likely explains the investor enthusiasm. The FDA recently approved a similar approach, Dendreon’s Provenge for prostate cancer (a cancer of old guys who are likely to die of something else). Provenge extends survival about three months and costs about $93,000 per treatment or $23,000 per month of additional life (Xconomy article) or about what it costs to treat 133 HIV-infected Africans with antiviral drugs for a year. Argos’s HIV product, AGS-400, substantially decreased viral load in a Phase IIb trial involving about 40 patients who were temporarily not on antiretroviral drug therapy (Biotech Now article, Biotech Now article).
Of more interest to me is Genetic Immunity of Budapest, Hungary (GI), founded in 1998 by former NIH researcher and now Semmelweiss University professor, Julianna Lisziewicz. GI apparently has friend, family, and angel investor funding including a $2 million “bridge” investment (loan?) in 2007 (GI press release). The company’s lead product is DermaVir Patch consisting of: (1) a novel and proprietary plasmid DNA antigen that expresses the majority of HIV genes and doesn’t replicate or integrate; (2) a new “nanoparticle” formulation that targets dendritic cells and protects the plasmid from degradation; and (3) a new topical vaccine administration device, called DermaPrep Patch (NanoMed Cluster description). Despite the risk inherent in a product that depends on three novel and unproven technologies, GI’s Phase II trial in 36 infected but untreated patients resulted in decreased viral load and increased HIV-specific memory T-cells (Another GI press release). DermaVir is the company’s lead product, and it has preclinical programs for Chlamydia and papilloma virus infections and allergy (GI pipeline). Where GI will get the funding for further development is a question. The company is in the process of merging with another company that its founders also founded, the US-Italian ViroStatics (Virostatics), to form Immunacia, “a multinational biopharmaceutical company dedicated to developing treatments that partner with the immune system to improve human health” (GI About).
My favorite of the bunch, though, is FIT Biotech Oy which was established in 1995 and has 25 employees at its base in Tampere, Finland, and a 12-person r and d group in Tartu, Estonia (FIT). The company is funded by its founders, local private investors, and grants from the Finnish National Fund for Development and Innovation and the European Commission (FIT presentation). The basis of the company’s HIV vaccine is a proprietary DNA vector called the Gene Transport Unit which is loaded up with a lots (7?) of HIV-specific antigens (FIT technology) and, when injected into a patient, should stimulate multiple antigen presentation and a strong T-cell response (Wikipedia DNA vaccine article). The vaccine, called FIT-06, evidently also uses a liposomal delivery system licensed from ImmunoVaccine Technologies of Canada (Medical News article). Their Phase II study in 60 previously-untreated patients in South Africa reported decreased viral load and increased CD4-postive T-cell levels (FIT press release). Interestingly, FIT Biotech’s business model appears to be based on developing vaccines for neglected diseases, including tuberculosis, dengue, and malaria, and not-so-neglected HIV (a preventative vaccine) and influenza (Another FIT press release).
So what are the take-home lessons? 1) Biopharmaceutical product innovation is a long hard slog and only for the dedicated and self-motivated (these companies have been at it for 12-15 years). 2) And it may require concatenation of multiple novel technologies. 3) It is possible to reach Phase II trials of vaccines with relatively modest funding (like under $10 million). 4) The powers-that-be in AIDS research focus HIV vaccine development funding on conventional paths and ignore (or downplay) unconventional approaches (c.f., “These early trials involve small numbers of people,” says Carl Dieffenbach, head of the NIAID AIDS division. “It would be wrong to foster false hopes.” [Nature article]). 5) There are three companies in this space that are good investment opportunities (promising clinical results and low prices), Bionor, Genetic Immunity, and FIT (I exclude Argos whose current investors likely want 5X), and foundations, product development partnerships (PDPs like the International AIDS Vaccine Institute), and big pharma companies should get on board quickly. 6) There may be light at the end of the tunnel.