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

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Founding of Tularik
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.
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Tularik Inc. 1120 Veterans Boulevard, South San
Francisco, CA 94080 (tel) 650.825.7000 (fax)
650.825.7303
Mission Statement
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.
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TLRK (Nasdaq) decade stock performance
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TLRK (Nasdaq) 12 month stock performance
At 52 week high (3.61 - 11.90), current 11.01,
P/E -5.21,
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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.
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Metabolic Disease T131
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 2005. 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 bodys 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.
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Inflammatory Disease T487
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
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Cancer T67, T607
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 2003. 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. .
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Cancer Continued DRUG DISCOVERY
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.  
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Product Development Rights and Partnering
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