CGEN-15001, Predictive Discovery and the Choice Facing Big Pharma

In recent months, Israeli drug discovery company Compugen has issued two press releases concerning a new therapeutic drug candidate, CGEN-15001, targeting multiple sclerosis ("MS") and other autoimmune diseases. As stated by Compugen in its July press release:

"[A]dministration of CGEN-15001 in an animal model of multiple sclerosis (MS) has been shown to completely abolish spontaneous relapses. In addition, administration of this novel molecule prior to disease onset demonstrated a pronounced delay of disease onset and a significant decrease in disease symptoms. These results, together with complementary results from earlier studies, strongly support a significant potential therapeutic utility for CGEN-15001 in the treatment of multiple sclerosis and other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes."

http://www.cgen.com/Content.aspx?Page=press_releases&NewsId=498

Although there can be no assurances whether these very early stage, preclinical results will ultimately translate into a new drug destined to alleviate the symptoms and suffering associated with MS and other autoimmune diseases, Compugen, in my opinion, has nevertheless achieved something quite remarkable:

• Compugen predicted and verified the existence of CGEN-15001T, a heretofore unknown member of the B7/CD28 protein family, which has been intensively picked over in the search for immune regulation candidates.
• CGEN-15001T in and of itself constitutes a promising antibody therapeutics target for cancer.
• The discovery of CGEN-15001T promptly led to the identification by Compugen of CGEN-15001, a soluble recombinant fusion protein comprised of the extracellular region of CGEN-15001T, which, as reported in the above Compugen press release, underwent testing in an animal model of MS.

As commonly known, autoimmune diseases entail the body attacking its own cells, and treatment usually consists of drugs intended to weaken the body's immune response with all the attendant dangers. Compugen, however, has stated that CGEN-15001 is expected to be devoid of general immunosuppressive effects and therefore have a decreased risk of opportunistic infections. How is this possible?

CGEN-15001 is thought to act as a "negative costimulator", and like other negative costimulators, it is thought to target tolerance breakdown, i.e. eliminate activated autoreactive cells and directly block the deleterious effects of self-reactive immune cell function in autoimmune diseases. This anticipated specificity, which does not target the B7/CD28 pathway, is expected to eliminate general immunosuppressive effects.

Equally remarkable, as reported in Compugen's July press release, Professor Stephen Miller of Northwestern University has stated with respect to CGEN-15001:

"These studies have also demonstrated that CGEN-15001 has the unique ability to inhibit proliferation, differentiation, and cytokine production of pro-inflammatory Th1 and Th17 responses while at the same time sparing or actually promoting regulatory Th2-derived cytokines. As far as I am aware, this potentially very beneficial pattern of inhibiting Th1/Th17 while promoting Th2 responses is unique among the reagents targeting the B7 family of co-stimulatory molecules that have been published to date.”

Shifting from a Th1 to a Th2 immune response would clearly prove beneficial in MS and other autoimmune diseases, since Th2 cells limit the proliferation of Th1/Th17 autoreactive pro-inflammatory cells and thereby protect the central nervous system.

But what about the bigger picture? Quite apart from their modes of action, the discoveries of CGEN-15001T and CGEN-15001 amount to powerful validation of the coming of age of predictive discovery. How is Big Pharma to react?

Obviously, there will be those R&D departments that feel threatened by this new science, capable of rendering their methodology, built over the course of decades at a cost of hundreds of millions of dollars, anachronistic. These departments will rejoice at any perceived failure or shortcoming involving the new science.

Other R&D departments, however, will embrace predictive discovery and seek out new modes of collaboration, particularly involving their cutting-edge testing capabilities.

In my opinion it's ultimately going to come down to a matter of accepting the inevitable, and those organizations willing to adapt to the rigors of predictive discovery are most likely destined to succeed.

[As noted in prior blog entries, I am a Compugen shareholder, this blog entry is not a recommendation to buy or sell Compugen shares, and in mid-September 2009 I began work as a part-time external consultant to Compugen. The opinions expressed herein are mine and are based on publicly available information. This blog entry has not been authorized or approved by Compugen.]