Sugen's new class of signal transduction inhibitors block key molecular pathway to ras oncogene; Company discovers inhibitors for GRB2, key target for R&D Programs, as reported at IBC conference.

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Aug. 17, 1995--SUGEN, Inc. (Nasdaq: SUGN) today announced that Company researchers have identified a novel class of signal transduction inhibitors that block the function of the GRB2 adapter protein.

GRB2 represents a molecular bridge between receptor tyrosine kinases (RTKs) and the intracellular ras oncogene pathway. As reported at the International Business Communication's Second Annual Signal Transduction Therapy Conference, this proprietary class of compounds under development at SUGEN may have significant utility in the treatment of RTK-dependent tumors, by intervening at a critical step prior to the activation of ras.

Dr. Joseph Schlessinger, a scientific founder of SUGEN and Professor and Chairman of NYU Medical Center's Department of Pharmacology, was the first to discover and clone GRB2. SUGEN believes it should receive strong patent protection on both this target and the new class of compounds.

"By finding selective inhibitors of GRB2, SUGEN's drug discovery team has added an important new component to the Company's portfolio of signal transduction inhibitors for the potential treatment of cancers," commented Stephen Evans-Freke, chairman and chief executive officer of SUGEN. "SUGEN's mission in cancer is to develop and bring to market a family of target-specific signal transduction inhibitors addressing subsets of major cancers defined by their particular signalling dysfunction."

GRB2 and the ras Oncogene

GRB2 has been a target for many pharmaceutical and biotech R&D programs because it is an activator (or, "adapter protein") for the ras oncogene. Excessive activity of ras has been implicated in many cancers. The current evidence shows that SUGEN's GRB2 inhibitors act as cytostatic agents, causing cancerous cells to cease multiplying or self-destruct ("apoptosis").

GRB2 and the ras oncogene are key elements of intracellular pathways that are linked to a family of proteins found on the surface of the cell, known as receptor tyrosine kinases. When an RTK is activated by the binding of specific growth factors, it conveys a biochemical "message" to nearby proteins, which in turn activate the ras pathway through GRB2. Scientists believe that this activation process can lead to runaway cell proliferation resulting in cancer.

SUGEN's R&D teams simulated the effect of GRB2 inhibition by the application of genetically engineered models, termed "dominant negatives". "Our dominant negative models predicted that inhibiting GRB2 would be effective in blocking the cancerous growth of tumors using this pathway," commented Jerry McMahon, Ph.D., Director of Drug Discovery at SUGEN. "We are pleased that the predictive value of these target validation models has been demonstrated, in that the activity profile of our novel GRB2 inhibitors reflects faithfully our expectations from the dominant negative studies."

SUGEN, Inc. is a biopharmaceutical company pioneering the development of a new class of small molecule drugs which interact with key signal transduction molecules, known as tyrosine kinases and tyrosine phosphatases, and their signalling pathways. These pathways are involved in a number of human diseases and disorders, including cancer and diabetes, as well as hematopoietic and neurodegenerative disorders. SUGEN's shares are traded on the Nasdaq Stock Market's National Market System under the symbol SUGN.

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