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Roche gets value with GEMS
SOUTH PLAINFIELD, N.J.—PTC Therapeutics' GEMS—Gene Expression Modulation by Small-molecules, a screening technology for identifying small molecules that up- or down-regulate target proteins—will form the basis of a research collaboration and licensing agreement with Roche for the development of orally bioavailable small molecules active against four central nervous system (CNS) disease targets that will be jointly selected.
Under the terms of the agreement, Roche will make an upfront cash payment of $12 million and fund PTC's research efforts. Subject to achievement of several successive milestones, there is the potential for PTC to earn up to $239 million in research, development, regulatory and commercial milestone payments per target, putting the potential value of the deal at upwards of $950 million. In addition, if Roche exercises its option to add another four targets in other therapeutic areas, PTC would qualify for cash payments based on the same formula.
PTC is a privately held company with about 200 employees and no sales to date. The company name is derived from "post transcriptional control," which is functionally how compounds identified by the GEMS platform regulate the rate and timing of protein production vital to proper cellular function. Compounds identified through the GEMS technology target processes that act through the regulatory regions of messenger RNA molecules.
According to Cláudia Hirawat, senior vice president of business development at PTC, there is a general belief that the coding area of the gene is the only important region. The untranslated regions (UTRs) are frequently overlooked. It's much like a recipe, she says.
"The coding region provides the ingredients, while the UTRs tell you how to put them together," Hirawat says.
The GEMS platform identifies compounds that either inhibit or activate expression of the reporter protein. Compounds causing a statistically significant alteration in reporter expression in the primary HTS are confirmed to demonstrate dose-response activity and are immediately advanced to secondary functional screens designed to evaluate endogenous and physiologically relevant cell-based protein synthesis. Compounds that demonstrate activity against the endogenous target protein progress to follow-up assays that assess specificity with respect to similar targets. Confirmed hits are further characterized for pharmaceutical properties such as cytotoxicity, metabolic stability and bioavailability. Compounds demonstrating desirable activity profiles can then be advanced as leads in a drug discovery effort.
Morgan Conn, senior director of business development at PTC, notes that the company has successfully employed GEMS technology in several drug discovery programs across multiple therapeutic areas, including oncology, infectious diseases and neuromuscular disorders, with several programs either in the clinic or in the late stages of lead optimization. PTC299, a small-molecule inhibitor of VEGF expression, is undergoing multiple Phase 1b/2 clinical studies in cancer, he notes. GEMS is also being utilized in multiple therapeutic areas as the basis for collaborations with Schering-Plough (hepatitis C), Gilead (cardiovascular), Celgene (oncology), Pfizer (multiple areas) and CV Therapeutics.
"We are pleased to enter into this collaboration with PTC Therapeutics. PTC's expertise in small molecules addressing RNA biology and the demonstrated productivity of their GEMS technology platform make this an attractive collaboration," says Dr. Christer Nordstedt, head of CNS Discovery at Roche. "We believe that this novel and highly innovative technology will enable Roche to address important disease mechanisms that were intractable with conventional approaches. This may have profound impact on the treatment and management of several CNS disorders and therefore lead to great benefits for the patient."