NEWS:Plexxikon and Phenomix to Develop Drug Candidate for Inflammation; R & D Team Expanded as Plexxikon's Second Drug Candidate Targeted for Clinical Trials

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Plexxikon and Phenomix to Develop Drug Candidate for Inflammation; R & D

Team Expanded as Plexxikon's Second Drug Candidate Targeted for Clinical

Trials

BIOWIRE2K

BERKELEY, Calif.--(BUSINESS WIRE)--Dec. 9, 2004--Plexxikon today announced

that PLX647, a dual c-Kit and FMS kinase inhibitor, developed in

collaboration with Phenomix Corporation, has been selected as a development

candidate for the treatment of inflammation. Preclinical testing of PLX647

has demonstrated preliminary safety in addition to anti-inflammatory

activity in several models of inflammation, including a collagen-induced

arthritis model. The collaborators expect to begin human clinical trials in

rheumatoid arthritis by the end of 2005, and will be seeking a licensing

partner for this program.

" With this novel compound for arthritis, Plexxikon has advanced a second

program into development in a very short period of time -- in less than

twelve months -- once again validating the power of our Scaffold-Based Drug

Discovery approach, " said K. Hirth, Ph.D., chief executive officer

of Plexxikon Inc. " We believe that by blocking two kinase targets, this drug

will be more efficacious, safer, and have the potential to be used both

alone and in combination with current therapies for patients with rheumatoid

arthritis. "

PLX647 appears promising as a novel oral drug, potentially useful in the

treatment of several inflammatory diseases. Inhibition of the c-Kit and FMS

pathways leads to a down-regulation of mast cell and macrophage activity,

thereby mitigating the inflammatory response. In addition to rheumatoid

arthritis, other potential disease targets include inflammatory bowel

disease, asthma, psoriasis and multiple sclerosis.

The compound is the result of a research collaboration between Plexxikon and

Phenomix established in November 2003, to discover and develop novel drugs

targeting specific kinase pathways critical in inflammation. During the

research collaboration, Plexxikon applied its proprietary Scaffold-Based

Drug Discovery platform to develop and optimize small molecule

inhibitors, while Phenomix conducted in vitro and in vivo pharmacology

studies to provide key biological insights in the discovery process.

Rheumatoid arthritis is one of the most common autoimmune diseases,

affecting approximately 2.1 million Americans and 6 million people

worldwide. It is a chronic disease characterized by inflammation of the

lining, or synovium, of the joints and causes chronic pain, loss of

function, disability and destruction of articular cartilage and bone.

R & D Appointments Made as Multiple Drug Candidates Advance to Development

Plexxikon today announced that it has expanded its research and development

executive team with the appointment of B. Nolop, M.D., as senior vice

president and chief medical officer, and the promotions of Dean R. Artis,

Ph.D., to vice president of lead generation and Gideon E. Bollag, Ph.D., to

vice president of discovery biology.

" With our continued success, 's development expertise in broad disease

areas will be instrumental in Plexxikon's next phase of growth as we move

multiple products into the clinic. In addition, the promotions of Rick and

Gideon reflect their significant contributions to the success of our

integrated discovery platform and expanding product pipeline as we now have

preclinical stage products in metabolic disease, inflammation and oncology, "

continued Dr. Hirth. " The expertise and talent of each of these team members

will strengthen Plexxikon's leadership and support the future growth and

productivity of the company. "

Dr. Nolop brings more than fifteen years of biotechnology and pharmaceutical

clinical development experience, including the filing of multiple

investigational new drug (IND) applications, three successful new drug

applications (NDA), and the approval of several labeling supplements. Dr.

Nolop comes to Plexxikon from CoTherix, where he was vice president of

clinical research. While at CoTherix, he led the clinical development of

iloprost for pulmonary hypertension, which has been accepted by the Food and

Drug Administration (FDA) for priority review and granted orphan drug

status. Prior to CoTherix, he held escalating positions within

Schering-Plough Corporation, where he initiated early to late stage clinical

programs successfully in multiple disease indications including allergic

rhinitis, asthma, COPD and hypercholesterolemia. Dr. Nolop holds an M.D.

from Vanderbilt University, and is a board certified physician in internal

medicine and pulmonary disease.

Dr. Artis was promoted to vice president of lead generation, responsible for

informatics, chemistry and structural biology. He joined Plexxikon in April

2002 as senior director of informatics. Prior to Plexxikon, Dr. Artis held

escalating positions with Genentech, most recently as senior scientist of

structural chemistry, and previously was staff researcher of computer-aided

drug design at Syntex. He holds a Ph.D. in organic chemistry from Yale

University.

Dr. Bollag was promoted to vice president of discovery biology, responsible

for screening, molecular biology, protein chemistry and in vitro

pharmacology. He joined Plexxikon as senior director of drug discovery in

June 2002. Prior to Plexxikon, he helped build drug discovery capabilities

at Syrrx, Inc., where he was the director of cellular pharmacology. Before

Syrrx, he held escalating positions at Onyx Pharmaceuticals, initially as

one of the founding scientists and eventually senior director of small

molecule therapeutics. While there, Dr. Bollag was involved in the Onyx

collaboration with Bayer to discover BAY 43-9006, a kinase inhibitor that is

currently in Phase III clinical testing in cancer patients. Dr. Bollag

earned his Ph.D. in biochemistry from the University of California,

Berkeley, and conducted post-doctoral research at Cetus Corporation.

About Plexxikon

Plexxikon is a leader in the discovery and development of novel small

molecule pharmaceuticals to treat human disease. Plexxikon's proprietary

Scaffold-Based Drug Discovery platform is being applied to build

therapeutic franchises in metabolic and cardiovascular disease, inflammation

and oncology. This discovery process utilizes a number of technologies,

including structural screening as one key component that provides a

significant competitive advantage to other drug discovery approaches. To

date, the company has discovered a portfolio of lead compounds in each of

these franchises, ranging from lead discovery to development stage.

Currently, the company's most advanced program is a PPAR pan-agonist for the

treatment of diabetes and related cardiovascular complications. Other

programs include a selective PDE 4B inhibitor for the treatment of chronic

obstructive pulmonary disease (COPD), a dual kinase inhibitor for the

treatment of rheumatoid arthritis and a b-Raf inhibitor for the treatment of

cancer. Plexxikon completed an initial human study in 2004 for PLX204, its

PPAR pan-agonist recently licensed as part of a broad collaboration with

Wyeth Pharmaceuticals. Plexxikon is seeking pharmaceutical and biotechnology

partners for a variety of collaboration opportunities. For more information,

please visit www.plexxikon.com .

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