Ann: Positive Phase 1 Results of Phase 1 Study - LOXL2 Inhibitor, page-2

PHARMAXIS RELEASES POSITIVE RESULTS OF PHASE 1 CLINICAL TRIAL
FOR LOXL2 INHIBITOR COMPOUND
Pharmaceutical company Pharmaxis (ASX: PXS) today announced positive results from the Phase 1
clinical trial for the first of its Lysyl Oxidase Like 2 (LOXL2) inhibitor compounds being developed to
treat fibrotic diseases such as Non‐Alcoholic Steatohepatitis (NASH) and Idiopathic Pulmonary
Fibrosis (IPF).
The double‐blind placebo controlled study consisted of two stages. The first single ascending dose
stage was conducted in 48 healthy subjects divided into six groups with each taking a single dose
ranging from 10mg to 400mg or placebo. The second multiple ascending dose stage was conducted
in 24 healthy subjects divided into three groups which each received a single daily dose ranging from
100mg to 400mg or placebo for 14 days.
The excellent drug like properties demonstrated in earlier pre‐clinical testing were confirmed. There
were no adverse safety findings in either the first or second stages of the study and the
pharmacokinetic profile showed the expected dose related increases in exposure.
In addition to studying the safety and pharmacokinetic profile, the clinical trial also investigated the
degree to which the drug can inhibit the target enzyme LOXL2 which is implicated in several
different fibrotic diseases. Importantly, Pharmaxis has been able to demonstrate a large and highly
significant inhibition of this enzyme in blood serum for a full 24 hours from a single dose and that
daily dosing over a 14‐day period now meets our targeted effect of greater than 80% inhibition at
the 400mg dose.
Pharmaxis CEO Gary Phillips said, “I’m delighted that the excellent pharmacokinetic parameters and
the significant and long lasting inhibition of the target LOXL2 enzyme demonstrated in the single
dose stage of the study earlier this year completely translated into the profile we have seen in the
multiple dosing study. This drug profile has led to increased interest from major pharmaceutical
companies looking for good anti fibrotic programs to acquire. Today’s announcement that enzyme
inhibition is further enhanced after daily dosing over 14 days goes a long way to completing the data
package on which we will base continuing scientific and commercial discussions with potential
partners during the current quarter.”
The Phase 1 trial for a second Pharmaxis LOXL2 compound being studied has recently completed
dosing and will report in the current quarter.
The company’s LOXL2 program compounds are highly selective small molecule inhibitors of LOXL2
that can be administered orally. The ongoing pre‐clinical development program supports the
potential of both compounds to treat fibrotic disease in several organs. This support has been
enhanced by recent breakthroughs in Pharmaxis proprietary assay technology that have
demonstrated target engagement in animal tissue from the pre‐clinical studies as well as serum.
28‐day animal toxicity studies have been completed in two species for both compounds and the
remaining 3 month studies are due to be completed later this quarter.
Pharmaxis has previously announced its intention to partner the LOXL2 program after phase 1 studies are complete. Mr Phillips said, “We believe that the best in class LOXL2 inhibition and the
availability of two compounds with differentiated pharmacokinetic profiles make this program very
attractive and we look forward to concluding a licensing deal with a partner committed to develop
the compounds in indications where there remain a lack of treatment options and significant
commercial opportunities.