Date: 2017-12-14
Type of information: R&D agreement
Compound: selective inhibitor to the lysyl oxidase type 2 enzyme (LOXL2)
Company: Pharmaxis (Australia) Synairgen (UK)
Therapeutic area: Lung diseases - Respiratory diseases - Rare diseases
Type agreement: R&D - research
Action mechanism:
- enzyme inhibitor/lysyl oxidase type 2 enzyme (LOXL2) inhibitor. The LOXL2 enzyme is being targeted because it is known to promote scar tissue which hardens and irreparably damages the lungs of idiopathic pulmonary fibrosis patients. It is hoped that the inhibition of LOXL2 will slow the build-up of scar tissue and improve survival rates that are worse than for many cancers.
- The LOXL2 inhibitor program comes from the same Pharmaxis chemistry platform as the SSAO inhibitor that was recently acquired by Boehringer Ingelheim. Under the terms of the agreement Synairgen will fund further activity of the program at Pharmaxis, use its BioBank and in vitro lung model platform, and collaborate with the IPF research team at the University of Southampton to complete pre-clinical and early clinical development. The IPF program will be managed by a joint steering committee through to the end of phase 1 or phase 2a clinical trials, at which time the collaboration will seek a license partner. Pharmaxis and Synairgen will share any licensing revenues in accordance with the ratio of total investment by the two companies at that time. The share of licensing revenues is expected to be approximately equal for a compound licensed for IPF after early clinical development. Pharmaxis will continue to develop compounds outside the collaboration for other indications where LOXL2 inhibitors have shown potential such as liver and kidney fibrosis, and metastatic cancer. The agreement does however allow for scenarios where the collaboration licenses its program for multiple indications.
Disease: idiopathic pulmonary fibrosis
Details:
- • On August 5, 2015, Pharmaxis and Synairgen announced they have entered into a research collaboration to develop a selective inhibitor to the lysyl oxidase type 2 enzyme (LOXL2) to treat the fatal lung disease idiopathic pulmonary fibrosis (IPF). The LOXL2 inhibitor program comes from the same Pharmaxis chemistry platform as the SSAO inhibitor that was recently acquired by Boehringer Ingelheim. Under the terms of the agreement Synairgen will fund further activity of the program at Pharmaxis, use its BioBank and in vitro lung model platform, and collaborate with the idiopathic pulmonary fibrosis research team at the University of Southampton to complete pre-clinical and early clinical development. The IPF program will be managed by a joint steering committee through to the end of phase 1 or phase 2a clinical trials, at which time the collaboration will seek a license partner. Pharmaxis will continue to develop compounds outside the collaboration for other indications where LOXL2 inhibitors have shown potential such as liver and kidney fibrosis, and metastatic cancer. The agreement does however allow for scenarios where the collaboration licenses its program for multiple indications.
Financial terms:
- Pharmaxis and Synairgen will share any licensing revenues in accordance with the ratio of total investment by the two companies at that time. The share of licensing revenues is expected to be approximately equal for a compound licensed for IPF after early clinical development.
Latest news:
- • On December 14, 2017, Pharmaxis announced it had taken full scientific and commercial control of the collaboration between Pharmaxis and Synairgen. Pharmaxis has expanded the scientific program on LOXL2 inhibitors to maximise its value to potential partners and at the same time substantially increased its interest in the program in return for a payment of £5 million to Synairgen.
- Pharmaxis has immediately doubled the program scope to encompass two lead candidates with unique properties that it intends to take to the end of phase 1 trials with additional toxicology data delivered in parallel to enable them to be phase 2 ready by mid?2018.
Pharmaxis has assumed full control of the ongoing partnering process and is targeting to conclude a deal after the phase 1 studies have reported.
Changes in the collaboration financial arrangements include:
- -Pharmaxis has significantly increased its share of any partnering deal for the LOXL2 program in fibrotic diseases to over 80%.
- -Synairgen has retained a reduced but fixed percentage share of all future partnering revenues.
- -Pharmaxis has assumed full funding responsibility for the ongoing collaboration program.
- -Pharmaxis will make a cash payment to Synairgen of £5 million (approximately A$9m).
- An extensive pre?clinical program identified two compounds that have all the characteristics of successful once a day, oral drugs, showing excellent efficacy in several different in vivo fibrosis models. In regulatory toxicity studies, the two compounds have been well?tolerated and shown good safety profiles. The LOXL2 inhibitor program has been the subject of discussions with large Pharma companies since the
beginning of 2016, and Pharmaxis expects that interest to intensify as the two compounds progress through phase 1 clinical trials and report in mid?2018. In parallel with the commencement of phase 1 clinical trials, Pharmaxis will therefore enable scientific due diligence of the program by select large Pharma companies interested in subsequent partnering discussions.
- Although Pharmaxis’ intention is to secure a partnering deal after phase 1 trials are complete, the amended agreement also includes measures to compensate Synairgen and/or Pharmaxis in the event that development and commercialisation activities do not proceed as intended, including in the event that Pharmaxis decides to independently advance the LOXL2 program into a Phase 2b study or is itself acquired prior to the program being partnered.
- • On September 6, 2017, Synairgen announced that, following the successful completion of preclinical pharmacology and toxicology studies, a compound from its anti-fibrotic Lysyl Oxidase type 2 (LOXL2) inhibitor programme, PXS-5382A, is being prepared to commence Phase I clinical development.
- • On March 22, 2016, Synairgen announced positive results from its ongoing collaboration with Pharmaxis to develop a lysyl oxidase type 2 enzyme (LOXL2) inhibitor as a novel treatment for idiopathic pulmonary fibrosis.
These results were generated in an in vitro model of IPF, developed in collaboration with scientists at the University of Southampton, using lung cells from IPF patients. The experiments showed that the Pharmaxis enzyme
inhibitors, by inhibiting LOXL2, are able to reduce cross-linking of collagen fibres in a dose dependent manner. Additionally it has also been found that collagen fibres were less organised in the presence of the inhibitors. It is hypothesised that this will result in less “stiff” lung tissue and that this may beneficially alter the course of this
devastating disease. Synairgen is now focussing on the pharmacology of the inhibitors and expects to progress one of these inhibitors into Phase I clinical trials during 2017.
Is general: Yes
