Top suggestions

Pan-RAF Inhibitor (JZP815)

Sold to Jazz Pharmaceutical, July 2019, currently in Phase 1

Pan-Raf inhibitor programme: Overcoming drug resistance mechanisms

The 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 developed a pan-RAF inhibitor programme. The lead chemical series 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.

Redx is eligible to receive further development, regulatory and commercial milestone payments throughout the course of the programme should it successfully reach these milestones. Redx is also eligible for tiered royalties of mid-single digit percentages, based on any future net sales.

Pan-Raf inhibitor programme: Overcoming drug resistance mechanisms

The 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 developed a pan-RAF inhibitor programme. The lead chemical series 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.

Redx is eligible to receive further development, regulatory and commercial milestone payments throughout the course of the programme should it successfully reach these milestones. Redx is also eligible for tiered royalties of mid-single digit percentages, based on any future net sales.