SuperGen CLIMBs on board with GSK

DUBLIN, Calif.—Using epigenetics, the same process thatresults in cell differentiation in the zygote without any changes in theunderlying DNA sequence, SuperGen and GlaxoSmithKline PLC (GSK) have embarkedon a multi-year collaboration to discover and develop cancer therapeutics usingCLIMB, SuperGen's proprietary drug discovery engine. Epigenetic processes arewidely believed to play a central role in the development and progression ofalmost all cancers.

Under the terms of the agreement, SuperGen will progresscandidate compounds through early clinical proof-of-concept. GSK will then havethe option to develop further and commercialize resulting products worldwide.SuperGen will receive $5 million upfront, inclusive of a $3 million commonstock investment, priced at a premium to market. Total potential developmentand commercialization milestones payable to SuperGen could exceed $375 million,in addition to the potential for tiered double-digit royalties payable on netsales of any resulting products.

Dr. James S.J. Manuso, chairman, president and CEO ofSuperGen, notes that two-thirds of the $375 million is front-loaded, with thefinal third payable when a product is commercialized. GSK will pay $80 millionup to the time it exercises its option or declines to do so.

"GSK surveyed the market and found us," says SuperGen'sManuso, "and we are excited to be working with them. We believe thiscollaboration is a clear validation of our discovery platform, core expertiseand capabilities.

CLIMB—a database holding 1,021 chemistries, combinations andpermutations—is SuperGen's approach to small-molecule drug discovery. Accordingto Manuso, the in silico process mergesrapid screening of compound libraries with computational chemistry and systemsbiology techniques to rapidly and efficiently identify drug leads that bind totarget proteins.

"This is not a de novoprogram," Manuso adds. His company has been at the business of drug discoveryand development of novel cancer therapeutics that work via epigenetic and cellsignaling modulation for about 10 years. SuperGen develops products throughbiochemical and clinical proof-of-concept, then partners with companies such asGSK for further development and commercialization.

In traditional small-molecule screening, he notes, as manyas several million compounds may be tested in order to identify the few that interactselectively with a disease-related protein target.

"HTS is high-throughput," he notes, "but low-content."

CLIMB, on the other hand, has achieved results by screeningas few as several hundred rationally selected compounds, all of which exhibitconsiderable activity. This reduces the time from target identification toclinical candidate by several years, he states, and vastly decreases the costof drug development.

After lead identification, SuperGen will use proprietaryassays to winnow the number of leads down to "highly likely suspects," saysManuso, at which time GSK will enter the picture. He adds that partnering witha highly respected pharmaceutical giant such as GSK goes far to legitimizeCLIMB and SuperGen's capabilities to investors and the broader scientificcommunity. Plus, he adds, it provides SuperGen with enough resources to avoiddoing suboptimal deals.

Manuso points out that SuperGen's Dacogen, an injectablehypomethylating agent, is currently in use for treatment of myelodysplastic syndromesunder license to Eisai for North American markets and Johnson & Johnsonelsewhere in the world. SuperGen has two additional drugs in clinical trials:S-110, which is a pro-drug of Dacogen that is administered subcutaneously andcan be deployed against solid tumors, and a small molecule drug that can betaken orally. Dacogen is currently in clinical trials involving 485 patientswho suffer from elderly AML in a comparison study against Ara-C, the currentstandard of care.