Tularik was founded in 1991 based on a dream that dream took shape during a series of fly-fishing trips to western Alaska made over a period of years by Tularik's founders, Dave Goeddel, Bob Tjian and Steve McKnight. On the banks of the river for which the company was later named, an idea emerged that became the basis for the Tularik Biopharmaceutical Company. The vision was to create medicines that treat a broad range of serious human diseases by regulating gene expression. These medicines would be small molecules -- administered orally, convenient for patients to use and easy to manufacture. Tularik is presently a 429 person enterprise dedicated to this vision. Founding of Tularik

Advances in the field of molecular biology, some of which are based on the insights of Tularik's founders, have led to the recognition that inappropriate gene expression is a causal factor in nearly every major human disease. Tularik is a pioneer in the application of gene regulation biology to the discovery and development of new drugs. The power of Tularik's approach lies in its applicability to all disease categories. Mission Statement Tularik Inc Veterans Boulevard, South San Francisco, CA (tel) ; (fax)

TLRK (Nasdaq) decade stock performance

TLRK (Nasdaq) 12 month stock performance At 52 week high ( ), current 11.01, P/E = -5.21,

Drug Pipeline: 4 Candidates in Clinical Trials Tularik's drug discovery system is broadly applicable to a wide range of diseases. Its focus is on diseases that represent large markets that are underserved by current therapeutic products. The pipeline is concentrated in three broad disease areas: Cancer, Immunology, and Metabolic Disease. Tularik's integrated platform is highly productive. Scientists are employing a biology- based approach to drug discovery that frequently succeed in identifying multiple targets in a single gene regulation pathway. An integrated screening and lead optimization strategy has apparently identified high-quality lead compounds. Because the majority of leads act on targets for which there are no currently marketed therapeutics, they provide opportunities for producing first-of-class drugs. A benefit of the program diversity is thsat it provides a hedges against drug development risks. Tularik has identified lead compounds for 27 of company-validated targets. Thirteen of these lead compounds are being optimized by medicinal chemists and 6 are currently viewed as IND candidates. Tularik expects to file IND applications for one or more advanced leads in 2003, and to promote an equal number of optimized leads to "IND-candidate" status. The company publicizes that their pipeline will be replenished with new leads that will emerge this year from its research efforts.

Type 2 Diabetes According to the American Diabetes Association, nearly 17 million Americans have diabetes. Diabetes develops when the body can not effectively control the level of sugar (glucose) in the blood. When diet and exercise are not effective in controlling blood sugar levels in people with type 2 diabetes, oral medication(s), insulin injections or a combination are needed. According to Deutsche Bank estimates, the market for oral anti-diabetic drugs is expected to grow from over $5 billion in 2001 to $11.5 billion in Program Status In January 2003, Tularik initiated Phase 1 clinical testing to evaluate the safety and pharmacokinetic profile of T131, a drug candidate to treat type 2 diabetes. T131 activates PPAR  (peroxisome proliferator-activated receptor gamma), a target involved in the body’s ability to respond to insulin. The randomized, double-blinded, dose-escalation trial is being conducted in healthy adult volunteers in the United Kingdom. Current drugs that activate PPAR  including Actos TM and Avandia TM had combined sales in 2001 of $1.5 billion. T131 has a novel chemical structure and interacts with PPAR  differently from currently approved drugs. Animal studies comparing T131 to Avandia TM demonstrates that T131 has superior potency, equal efficacy and an excellent safety profile. T131 does not cause cardiac hypertrophy or a decrease in hematocrit, and causes less weight gain than Avandia TM in animal models. Tularik retains exclusive worldwide commercialization rights. Metabolic Disease: T131

Inflammation Under normal circumstances, inflammation is a defensive response to injury and infection. The process begins with the recruitment of leukocytes from the circulatory system to the site of damaged or infected tissue. Excessive or prolonged accumulation of leukocytes can lead to inflammatory conditions, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and asthma. Program Status Tularik hasinitiated a Phase 1 clinical trial to evaluate the safety and pharmacokinetics of T487. T487 is a small molecule designed to inhibit the chemokine activity underlying inflammatory diseases by binding to a single chemokine receptor without impairing other important immune system functions. T487 is expected to reduce inflammation in conditions such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. In preclinical models, T487 showed activity against certain inflammatory conditions and exhibited strong oral bioavailability, high potency and excellent selectivity with little or no pronblematic side effects. Tularik retains worldwide intellectual property and commercialization rights to T487 Inflammatory Disease: T487

Hepatocellular Carcinoma: HCC is a tumor type that is on the rise in the United States, principally in relation to the spread of hepatitis C infection. The National Cancer Institute estimates that HCC is the most common cancer in some other parts of the world. There are currently no approved systemic chemotherapeutic agents to treat HCC and surgical resection is feasible in a small percentage of patients. Program Status: Two drug candidates are in clinical development, T67 and T607. The most advanced candidate, T67, is a small molecule that binds irreversibly to ß- tubulin, a proven anti-cancer drug target. In Phase 1 and Phase 2 clinical trials, T67 showed activity against hepatocellular carcinoma (HCC; aka, primary liver cancer). Tularik expects to initiate a pivotal Phase 2/3 trial program in HCC in The phase 2/3 trial is expected to include approximately 750 1st line HCC patients and will be performed at numerous centers across the U.S., Europe and Asia. The study design will compare survival in patients who receive T67 every week to doxorubicin. T607 is a structural analog of T67, but, differs from T67 in that T607 does not cross the blood brain barrier and has a different tissue distribution profile. This may be a desirable feature for treatment of certain tumors. In Phase 1 trials, Tularik observed a partial response in HCC with T607, suggesting a mechanism of action shared by T67. Tularik is currently conducting Phase 2 clinical trials of T607 in patients with esophageal cancer, gastric cancer, HCC and ovarian cancer. Tularik discovered T67 and T607 and retains worldwide rights to both drug candidates.. Cancer: T67, T607

Cancer Gene Discovery In addition to 2 drug candidates in its oncology clinical development program, Tularik has an ongoing cancer gene discovery effort that intends to discover the full set of amplified oncogenes--genes that play a primary role in causing cancer. This research is producing potentially important new anti-cancer drug targets, against which the company intends to develop small molecule leads. Tularik has entered into a collaboration with Medarex, Inc. to develop therapeutic antibodies against three targets discovered in the cancer genomics program. Cancer Continued: DRUG DISCOVERY

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