Terrapin Technologies Inc. this week provided details on someof the technology that is the basis of its development of tumor-specific cancer therapies. On Tuesday, the company's founderand chief scientific officer, Lawrence Kauvar, told those at theCancer Progress '94 conference in New York about thecompany's research concerning glutathione S-transferases(GSTs). The conference was sponsored by Communitech MarketIntelligence Inc.
Terrapin of South San Francisco, Calif., has developedcompounds, or prodrugs, that can be targeted to GSTs, carryinga toxic alkylating agent that is inactive until it reaches thetumor. The alkylating chemotherapeutic is "cloaked," orbiologically inactive, while it is attached to the GST analog,Terrapin's president and chief executive officer, ReinaldoGomez, told BioWorld. When the prodrug reaches the GSTsexpressed at cancerous tumor sites, the enzymatic interactionof the GST analog with the GSTs causes the prodrug to divide,freeing the alkylating agent, which then kills cancer cells.
The company is planning to begin studies of its prodrugsagainst human colon carcinoma and breast tumors in SCID mice.It is currently studying the agents' effectiveness against certainmouth tumors in mice, said Amy Morgan, senior scientist of cellbiology. Terrapin is concentrating on two prodrug compounds,she added, and plans to file an investigational new drugapplication to begin Phase I clinical trials of one of these agentsin early 1995.
GST isozymes act to detoxify harmful compounds theyencounter, including chemotherapeutics. Because this naturalprocess can reduce the effectiveness of chemotherapy agents,Terrapin is also developing a GST inhibitor that blocks theisozymes from detoxifying therapeutic drugs. During SCIDmouse testing of the agent in human colon cancer tumors,Gomez said it was found that the GST inhibitors generallydoubled the effectiveness of alkylating agents alone.
The GST program is the lead technology coming out of thecompany's TRAP technology, which was developed by Kauvaras a means of rapidly classifying molecules. TRAP essentially"fingerprints" molecules by testing their binding affinity with arange of other molecules, Morgan said, and can be used topredict the binding properties of drug candidates in chemicallibraries. The resulting characterization is predictive of thebinding similarities between molecules and how molecules willbind to other targets, Gomez said. The company has two issuedand one allowed U.S. patent on the TRAP technology.
Terrapin was founded in 1986 with seed funding from Kauvar'sfamily and Jerrold Glick, a member of the company's board ofdirectors and chairman of the board as well as a generalpartner of Columbia Group Ltd. The company's first formalventure financing came in 1992 when it raised $8.5 millionfrom a number of investors, including Alpha Partners; Burr,Egan and Deleage; Delphi BioVentures; Sofinnova; and Weiss,Peck & Greer. Terrapin's director of finance and administration,Larry Strauss, said the company is currently planning anotherprivate financing for later this year.
Terrapin's name was chosen by Kauvar, who took it from theGrateful Dead song "Terrapin Station" because he admired thelyrics about creativity and innovation.
-- Karl A. Thiel Business Editor
(c) 1997 American Health Consultants. All rights reserved.