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Plexxikon - News
September 3, 2008
Plexxikon Initiates Phase 1 Trial for PLX5568
–First-in-Class Drug for the Treatment of Pain and Polycystic Kidney Disease
BERKELEY, Calif. - September 3, 2008 -- Plexxikon Inc. today announced
that it has initiated a Phase 1 human clinical trial for PLX5568, a novel kinase
inhibitor targeted for the treatment of at least two major indications with unmet
medical needs: pain as well as polycystic kidney disease (PKD). PLX5568 has
demonstrated robust preclinical efficacy in multiple pain models, including
neuropathic pain as well as acute and inflammatory pain. In addition, PLX5568
has demonstrated compelling efficacy in multiple preclinical models of PKD.
Dosing has been completed in the first cohort of healthy volunteer subjects in
the single ascending dose, double-blind, placebo-controlled trial, which will enroll
approximately 30 subjects. This study will be followed by a multiple ascending
dose, double-blind, placebo-controlled trial, which will enroll approximately 32
healthy volunteer subjects. Together, these studies are being conducted to
evaluate the safety and tolerability of PLX5568 as well as to gain insight into the
pharmacokinetic profile of the drug candidate. Preliminary pharmacokinetic data
from the Phase 1 trial indicate that the exposure in blood achieved with the initial
dose is in the target range required to show efficacy with once-a-day capsule
dosing.
“PLX5568 represents the fifth Investigational New Drug (IND) from our discovery
platform to enter the clinic in four years, and expands our therapeutic portfolio
now also to pain and renal disease with this first-in-class agent, underscoring our
early development capabilities as well as the productivity and breadth of our
discovery platform,” stated K. Peter Hirth, Ph.D., chief executive officer of
Plexxikon. “Additionally, PLX5568 is a highly selective drug candidate and yet
another example of Plexxikon’s hallmark capability to design very selective
kinase inhibitors. Given this capability, we are uniquely positioned to explore
kinase drug candidates for the potential treatment of chronic indications where
safety is paramount.”
PLX5568 is a very selective and potent kinase inhibitor. Non-clinical GLP
toxicology studies which included doses up to 2000 mgs per day over a period of
28 days, have confirmed the attractive safety profile of our selective kinase
inhibitor, and that such selectivity potentially confers safety to our drug
candidate. Kinases represent a large family of potential drug targets through
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Plexxikon - News
which a broad range of chronic diseases could be treated with safe and selective
drugs that inhibit their activity.
About PLX5568 in Pain
PLX5568 is a first-in-class, oral, non-opioid agent with opiate-like efficacy, and a
rapid onset of action. Kinases play a key role in the signaling pathways that
control the sensation of pain and the transmission of pain sensing signals.
Preclinical efficacy in various types of pain models demonstrated clear analgesic
responses to treatment with PLX5568, comparable to gabapentin or morphine
even at low doses of PLX5568, but without the side effects of an opiate.
Following the successful completion of the Phase 1 trial, Plexxikon plans to
initiate a Phase 2 clinical trial in neuropathic pain patients in 2009.
As a non-opioid and oral pain agent, PLX5568 could address significant unmet
needs in chronic pain, cancer pain and neuropathic pain, addressing substantial
markets with an estimated 7.8 million patients with neuropathic pain alone.
There is a significant opportunity for novel pain treatments, since most currently
available pain therapies suffer from suboptimal efficacy, intolerable side effects
or long-term safety concerns, including sedation and addiction.
About PLX5568 in Polycystic Kidney Disease
PLX5568 has also demonstrated impressive efficacy in orthologous models of
both forms of PKD, including effects on cyst size and renal function. Following
the successful completion of the Phase 1 trial and chronic toxicology studies,
Plexxikon plans to initiate a Phase 2 clinical trial in PKD patients in 2009.
PKD is a genetic disease in which cysts form in the kidneys, causing them to
become enlarged and infected, or burst, ultimately leading to loss of kidney
function. Currently, there are no treatments for this disease, and patients
eventually progress to kidney transplant or dialysis. PKD is the most common lifethreatening genetic disease, affecting approximately 600,000 patients in the U.S.
and over 12 million patients worldwide.
Plexxikon Profile
Plexxikon is a leader in structure-guided discovery and development of novel small
molecule pharmaceuticals to treat human disease. The company’s clinical stage
programs include PLX204 for the treatment of diabetes, PLX4032 for the treatment
of melanoma and colorectal cancer and PLX5568 for the treatment of pain and
renal disease. Among the company’s preclinical development programs, candidates
are being developed for the treatment of rheumatoid arthritis, multiple sclerosis
and other autoimmune diseases.
Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform is being applied
to build a pipeline of diverse product opportunities for the treatment of metabolic
and cardiovascular disease, inflammation, oncology and CNS disorders. This
discovery process integrates a number of 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 in multiple
disease areas addressing significant unmet needs in each therapeutic category.
Plexxikon is seeking pharmaceutical and biotechnology partners for select
collaboration opportunities. For more information, please visit www.plexxikon.com.
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