LOX platform technology: LOX / LOXL2 inhibitors for multiple indications
There is significant interest among leading clinicians and pharmaceutical companies in the inhibition of LOX and LOXL2 to reduce fibrosis in a number of different diseases. Pharmaxis’ amine oxidase platform enables the synthesis of inhibitors with different pharmacological and pharmacokinetic profiles. The Company has developed first-in-class, mechanism-based small molecules that inhibits Lysyl Oxidase (LOX) and Lysyl Oxidase Like 2 (LOXL-2) for the treatment of fibrotic diseases and some cancers, including:
- Selective LOXL2 inhibitor: NASH, liver and kidney fibrosis
- Selective LOXL2 inhibitor: IPF (being developed in collaboration with Synairgen)
- Mixed LOX/LOXL2 inhibitor: cancer; severe liver and kidney fibrosis
Lead compounds with differentiated PK / PD profile have been identified and have demonstrated efficacy in pre clinical models of fibrosis and cancer.
In August 2015 Pharmaxis and UK biotechnology company Synairgen plc (LSE: SNG) announced 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). 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.