Plexxikon Announces PLX4032 Phase 1 Data Showing Objective Responses in Metastatic Melanoma Patients

--Personalized Medicine for Deadliest Form of Skin Cancer --

ORLANDO, Fla. & BERKELEY, Calif.--(Business Wire)--
Plexxikon Inc. today announced preliminary data from a Phase 1 clinical study
investigating PLX4032 (R7204). PLX4032 is a novel, oral and highly selective
drug that targets the BRAFV600E cancer-causingmutation that occurs in most
melanomas and about eight percent of all solid tumors. In patients whose cancer
harbors this mutation and who were treated with therapeutic doses of PLX4032,
tumor shrinkage and extended progression-free survival have been observed.
Currently, two extension studies are being conducted in mutation-positive
melanoma and colorectal cancer patients. Following the initial positive findings
announced today, larger clinical trials to support a registration program for
product approval are targeted to start later in 2009. Plexxikon and Roche are
co-developing PLX4032 under their 2006 license and collaboration agreement.

"PLX4032 has shown both tumor shrinkage and delay in tumor progression in
patients whose tumors harbor a BRAF mutation as well as reports of clinical
symptom improvement in some patients," stated Keith T. Flaherty, M.D., assistant
professor at the Abramson Cancer Center of the University of Pennsylvania and
principal investigator for the PLX4032 Phase 1 clinical trial. "Seven years
after BRAF mutations were first identified, we have validation that this
mutation is a cancer driver and therapeutic target. This is a new and important
chapter in the story of targeted therapy development in cancer, and we are
especially excited for our melanoma patients, for whom there are currently few
treatment options." Link to video clip of Dr. Flaherty

In the dose escalation phase of the study, 55 cancer patients have been treated,
including 24 mutation-positive melanoma patients and 3 mutation-positive thyroid
patients, as well as 28 melanoma, rectal and ovarian cancer patients who did not
have the mutation or whose mutation status was not known.

In 16 BRAF mutation-positive melanoma patients treated with PLX4032 doses at or
above 240 mg twice daily (BID), representing targeted drug exposure levels, data
show:

* PLX4032 is well tolerated at very high doses, with 960 mg BID under evaluation
as the maximum tolerated dose
* Partial responses in 9 patients showing greater than 30% tumor regression by
RECIST (Response Evaluation Criteria in Solid Tumors) criteria, with 7 confirmed

* Regression of metastatic lesions in every site to which melanoma commonly
spreads, including liver, lung and bone
* Minor responses in 4 patients showing tumor regression greater than 10% but
less than 30%
* Disease control lasting up to 14 months with continuous therapy, with many
patients still receiving treatment
* Interim median progression-free survival of at least six months, with many
responding patients still receiving treatment

By contrast, no treatment response was observed in a small group of patients
without the mutation, and progression-free survival was less than 2 months,
consistent with historical data.

Dose-limiting toxicities, primarily rash, fatigue and joint pains, were seen at
1120 mg BID. Drug-related adverse events have been predominantly mild in
severity and transient, including rash and photosensitivity. Serious adverse
events were observed in some patients after chronic treatment, including
possibly drug-related cutaneous squamous cell carcinoma. A risk management plan
has been implemented for baseline evaluation of the skin and monitoring of all
patients while on study. Cutaneous squamous cell carcinoma is typically excised
by a patient`s dermatologist.

"This is a significant day for us at Plexxikon. The clinical data for PLX4032 so
far support our hypothesis that a truly selective drug can target tumors
harboring this cancer-causing mutation, while at the same time, deliver a
treatment that is well tolerated by patients," stated K. Peter Hirth, Ph.D.,
chief executive officer of Plexxikon. "In conjunction with bio-response markers
and a companion diagnostic test, PLX4032 has all the hallmarks of an ideal
personalized medicine. Plexxikon`s pipeline includes several highly selective
kinase inhibitors, including novel therapies for other cancers as well as other
chronic diseases such as rheumatoid arthritis where such precision is
anticipated to provide a safety advantage."

Companion Diagnostic in Parallel Development

Along with the development of PLX4032 therapy, a diagnostic test to identify
patients with the BRAF mutation is being co-developed by Plexxikon and Roche,
under a separate 2005 agreement. This test is already being used to identify
mutation-positive patients for ongoing clinical trials. Most importantly, this
companion diagnostic enables the identification of mutation-positive cancer
patients considered most likely to respond to PLX4032 treatment.

Exploring PLX4032 in Colorectal and Other Cancers

The prevalence of the BRAF mutation is about eight percent of all solid tumors.
Preclinical studies in colorectal cancer models also suggest that PLX4032 causes
tumor regression, either as a single agent or in combination. Hence, future
clinical trials may evaluate PLX4032 in tumor types beyond melanoma.

Currently, one of two extension cohorts is recruiting mutation-positive
colorectal cancer patients in order to evaluate PLX4032 in this target
population. In a retrospective study of 600 patients with colorectal cancer,
including all stages and both genders, tumor tissue was tested for the presence
of the BRAF mutation and correlated with outcomes. The data confirmed that
approximately 10 percent of colorectal cancer patients carry this mutation,
which is independent of the KRAS mutation, and those BRAF mutation-positive
patients have a much poorer prognosis than patients with wild-type BRAF (ASCO
2009 Abstract #1103).

Additionally, in the Phase 1 dose escalation study which enrolled patients with
several different tumor types, one mutation-positive thyroid patient showed a
confirmed partial response, while two others showed stable disease with
prolonged therapy.

Biomarkers Enhance Development of Personalized Medicine

The development of PLX4032 has employed a variety of translational tools,
including bio-response markers and an in vitro diagnostic test. These tools can
potentially enable early detection of targeted pathway modulation and treatment
response, as well as identification of the targeted patient population for this
treatment.

Biomarker data from patient tumor biopsies before and after PLX4032 treatment
showed early target modulation and when dosed at higher levels, have shown
nearly complete inhibition of the desired target (ASCO 2009 Abstract #9021).

About PLX4032 (R7204)-A Personalized Medicine for Cancer Treatment

PLX4032 is a novel, oral small molecule for the treatment of melanoma and other
cancers harboring the V600E mutation of the BRAF kinase gene. This defect is
present in approximately 60 percent of melanoma skin cancers, and occurs in
about eight percent of all solid tumors, including melanoma, colorectal, thyroid
and other cancers. Preclinical data suggest that Plexxikon`s novel anti-cancer
compound selectively targets and inhibits tumor cells which contain this
cancer-causing mutation. In contrast to many other kinase inhibitors available,
PLX4032 is highly selective for its primary target, and does not have
significant activity on other kinase targets.

About Melanoma

Melanoma is the most serious type of skin cancer. More than 50,000 people in the
U.S. are diagnosed with melanoma each year, but the percentage of people in the
U.S. who develop melanoma has more than doubled in the past 30 years. Worldwide,
about 160,000 new cases of melanoma are diagnosed annually. Melanoma is
treatable if caught early but is very deadly when it becomes metastatic. The
median progression-free survival for a patient with metastatic melanoma is less
than 60 days, and the median overall survival for these patients is less than 12
months. Patients who develop metastatic disease are rarely cured with available
treatments.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused
healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is
the world`s largest biotech company with truly differentiated medicines in
oncology, virology, inflammation, metabolism and CNS. Roche is also the world
leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in
diabetes management. Roche`s personalized healthcare strategy aims at providing
medicines and diagnostic tools that enable tangible improvements in the health,
quality of life and survival of patients.

In 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion
Swiss francs in R&D. The Group posted sales of 45.6 billion Swiss francs.
Genentech, United States, is a wholly owned member of the Roche Group. Roche has
a majority stake in Chugai Pharmaceutical, Japan. For more information:
www.roche.com.

About Plexxikon

Plexxikon is a leader in the structure-guided discovery and development of novel
small molecule pharmaceuticals to treat human disease. The company`s clinical
stage programs include PLX4032 for the treatment of melanoma and colorectal
cancer, PLX5568 for the treatment of polycystic kidney disease and PLX204 for
the treatment of diabetes. Among the company`s preclinical development programs,
candidates are being developed for the treatment of rheumatoid arthritis,
multiple sclerosis and other autoimmune diseases as well as for the treatment of
pancreatic and metastatic breast cancer.

Plexxikon`s proprietary Scaffold-Based Drug Discovery platform integrates
multiple state-of-the-art technologies, including structural screening as one
key component that provides a significant competitive advantage over other drug
discovery approaches. To date, the company has discovered a portfolio of
clinical and preclinical stage compounds being developed to address significant
unmet medical needs in cardio-renal disease, CNS disorders, inflammatory and
neuro-inflammatory diseases and oncology. For more information:
www.plexxikon.com.

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Plexxikon Inc.
Kathleen Sereda Glaub, President, +1-510-647-4009
kglaub@plexxikon.com
or
For Plexxikon Inc.
Jennifer Cook Williams, +1-360-668-3701
jennifer@cwcomm.org

Copyright Business Wire 2009