Anti Fibrotic LOXL2 Program in Phase 1 Clinical Trials
Pharmaxis consolidated its position as a significant competitor in the NASH market as the Company's LOXL2 inhibitor joined its SSAO inhibitor in the clinic late in 2017 and with the first stage of phase 1 studies demonstrating a best in class profile for two compounds.
Extensive pre‐clinical showed the compounds displayed all the characteristics of a successful once a day, oral drug showing excellent efficacy in several different in vivo fibrosis models including fibrosis of the liver, lung, kidney and heart.
In October 2018 positive Phase 1 clinical trial results were reported on the first compound with a multiple dosing study involving a total of 72 patients confirming long lasting inhibition of the target LOXL2 enzyme.
The Pharmaxis drug discovery group has developed a number of selective small molecule inhibitors to the LOXL2 enzyme utilising the same amine oxidase platform that delivered the anti-inflammatory drug that was acquired by Boehringer Ingelheim in 2015. The LOXL2 enzyme is fundamental to the fibrotic cascade that follows chronic inflammation in the liver disease NASH, cardiac fibrosis, kidney fibrosis, and idiopathic pulmonary fibrosis (IPF), and it also plays a role in some cancers.
The extensive pre‐clinical program performed on the program compounds confirmed that they have all the characteristics of a successful once a day, oral drug showing excellent efficacy in several different in vivo fibrosis models including fibrosis of the liver, lung, kidney and heart. In regulatory toxicity studies, our compounds have been well tolerated and shown a good safety profile with long lasting inhibition of LOXL2 enzyme after a single oral dose.
The phase 1 trial for the second Pharmaxis LOXL2 compound being studied has completed dosing and will report in the current quarter.
Pharmaxis Earns A$15 Million Milestone Payment as Boehringer Ingelheim Clinical Trial in Diabetic Retinopathy Doses 1st Patient
In January 2018 Pharmaxis Ltd announced dosing of the first patient in Boehringer Ingelheim’s Phase 2a clinical trial in patients with diabetic retinopathy (DR), triggering a €10 million (~A$15 million) milestone payment to Pharmaxis. DR is the second disease to be targeted with the drug known as BI 1467335 which was discovered by Pharmaxis. BI 1467335 is also in an ongoing Phase 2a clinical trial for non-alcoholic steatohepatitis (NASH). Both studies are due to report in the first half of 2019.
The Phase 2a clinical trial of in diabetic retinopathy will randomise 100 patients to either drug or placebo for a 12-week treatment period with an additional 12-week follow-up period. A subsequent Phase 2b study will seek to confirm and extend these findings.
Diabetic retinopathy is the leading cause of vision-loss in adults aged 20-74. Of an estimated 285 million people with diabetes mellitus worldwide, approximately one third have signs of the disease.
Boehringer Ingelheim’s two-pronged clinical program with BI 1467335 is focused on tackling the common diseases related to the complications of diabetes which affect millions of people worldwide. The drug was acquired by Boehringer Ingelheim in 2015 with an upfront payment of A$41m to initially study the chronic liver condition NASH.
The milestone payment of $15 million for the commencement of a phase 2a trial in a second disease brings the total payments received by Pharmaxis from Boehringer to €57 million (~A$86 million). The total of all potential development milestones payable to Pharmaxis if both indications in the deal are approved is approximately A$625 million.
Both development plans attract the same total development payments through to approval, with the 2nd indication milestone payments weighted more towards approval. The next milestones from BI are payable if they choose to commence phase 3 trials, at which time the two indications would attract a total of €62 million in milestones.
Details of the DR clinical trial can be found here.
Watch a 5 minute video with Pharmaxis CEO Gary Phillips discussing the clinical program with Boehringer: https://www.youtube.com/watch?v=OSB0fGkW5Kk
Pictured above : Pharmaxis CEO Gary Phillips and Boehringer Ingelheim MD Australia & NZ Wes Cook mark the start of a new clinical trial in diabetic retinopathy.
Pharmaxis Announces $24 million Placement
Pharmaxis has secured $24 million in funding after receiving commitments from sophisticated and institutional investors for a two-tranche share placement. The second tranche required and on 17 September 2018 received shareholder approval. (Read the Notice of Extraordinary General Meeting here). The placement price at 32.5 cents represented a 3.1% premium to the last closing price.
The placement received strong support from specialist global healthcare investors including the first Australian investment for UK-based Arix Bioscience plc (LON:ARIX), a global healthcare and life science company. Arix will invest $14.2 million to take a 11.1% shareholding in Pharmaxis post approval.
Existing shareholder BVF Partners LP also committed to invest a further $7.1 million to increase its holding to 22.9% post approval, the maximum currently allowable.
The funds will further strengthen the Pharmaxis balance sheet as the company conducts partnering negotiations for its clinical development program into lysyl oxidase 2 inhibitors (LOXL2), expected to occur in 2H18.
Pharmaxis CEO Gary Phillips said the success of the capital raising and the addition of a new specialist healthcare investor as a major shareholder was a vote of confidence in the company’s ability and expertise in generating value from a business model which prioritises the development of first in class drugs that are attractive to multinational pharmaceutical companies.
Read the full announcement here.