Our Pan-RAF inhibitor programme aims to overcome resistance mechanisms associated with clinically approved B-RAF selective drugs

Mutations leading to uncontrolled signalling via the RAS-RAF-MAPK pathway are seen in over one third of all cancers. The RAF kinases (A-RAF, B-RAF and C-RAF) are an integral part of this pathway, with B-RAF mutations commonly seen in the clinic. Although most B-RAFV600E/K mutant skin cancers are initially sensitive to approved B-RAF selective drugs, treatment resistance often leads to disease progression. Moreover, B-RAFV600E mutant colorectal cancers are surprisingly insensitive to these B-RAF selective agents due to the functions of other RAF family members. Importantly, B-RAF selective therapies fail to show clinical benefit against the more prevalent RAS-mutated tumours.

To overcome these resistance mechanisms our scientists are developing a Pan-RAF inhibitor programme. Our lead chemical series has demonstrated monotherapy in vivo efficacy in a B-RAFV600E mutant colorectal cancer xenograft model, where approved B-RAF selective drugs are ineffective as monotherapy. In addition, this series shows monotherapy in vivo efficacy in a RAS-mutant colorectal cancer xenograft model.

On 10 July 2019, Redx Pharma announced that it has signed a definitive agreement with Jazz Pharmaceuticals under which Jazz has acquired Redx’s pan-RAF inhibitor programme for the potential treatment of RAF and RAS mutant tumours. Jazz will be responsible for all future development, regulatory, manufacturing and commercialisation activities.

Under the terms of the agreement, Jazz will pay Redx an upfront payment of $3.5 million in cash for all rights, title and interest relating to Redx’s proprietary pan-RAF inhibitor programme, including all related patents. Redx is eligible to receive up to $203 million in development, regulatory and commercial milestone payments from Jazz, with the next milestones being initiation of IND enabling studies, followed by a further milestone at IND submission to the FDA.  Redx is also eligible for incremental tiered royalties in mid-single digit percentage, based on any future net sales. As part of a separate collaboration agreement, signed in parallel, Jazz will pay Redx to perform research and preclinical development services with the goal of completing IND-enabling studies.

This transaction validates Redx’s excellence in drug design and represents the company’s second oncology deal in the last two years, following the sale of our BTK inhibitor programme to Loxo Oncology in 2017 (now owned by Eli Lilly), of which the lead candidate (LOXO-305) has now progressed into a phase 2 clinical trial.