Tularik Inc. doesn't see itself as having the luxury that big pharmaceutical companies have of throwing multiple compounds into Phase I trials. The company is counting on its expertise in biology to improve the odds of any one compound being successful, and is building its discovery infrastructure in a stepwise fashion to turn its biological output into drugs.

TLRK, which is focused on the regulation of gene expression using small molecule orally available drugs, has programs in cancer, CMV, diabetes, obesity, inflammation, allergy/asthma, lipid disorders and bacterial diseases. The company has discovered and put 22 compounds into development on its own account, and has in-licensed one clinical-stage compound that fits its development model.

Lometrexol (T64), obtained from Eli Lilly and Co. (LLY, Indianapolis, Ind.), in July entered Phase II trials in a variety of cancers. T64 is an antifolate in the same class as methotrexate that inhibits purine biosynthesis.

Two of TLRK's internal leads for cancer are targeting beta tubulin, as taxol does, except that these bind irreversibly and thus are not susceptible to multiple drug resistance, according to Andrew Perlman, vice president of medical research and corporate development. T67 began a Phase I/II study in hepatocellular carcinoma in July. Another version, T607, has different tissue distribution and doesn't cross the blood-brain barrier, as T67 does. T607 is in Phase I trials in a variety of cancers.

The fourth compound, T2611 for CMV, is expected to enter the clinic this month.

Thus by year end, TLRK should have four compounds in the clinic, including two in Phase II and two about to start Phase II, with about 20 more leads across seven programs. The company hopes to pick one to two of those as INDs for 2001, and to in-license perhaps one additional compound every two years.

The platform

TLRK uses four principal steps in its drug discovery system: link diseases with aberrant expression of specific genes; biochemically elucidate the corresponding gene regulation pathway; develop specific biochemical and cellular assays for the best target(s) in these pathways; and automate assays and perform high throughput screening to discover lead compounds that regulate genes.