Pan-RAF Inhibitor (JZP815)
Sold to Jazz Pharmaceutical, July 2019
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.
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.
Pan-RAF inhibitor programme sold to Jazz Pharmaceuticals (“Jazz”)
On 10 July 2019, Redx Pharma announced that it had signed a definitive agreement with Jazz Pharmaceuticals under which Jazz 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 paid Redx an upfront payment of $3.5 million for all rights, title and interest relating to Redx’s proprietary pan-RAF inhibitor programme, including all related patents. A milestone payment of $3 million was earned in September 2021 following the initiation of IND-enabling studies, and a further $5 million was earned in June 2022 with the clearance of the IND application. Jazz announced in November 2022 that JZP815 had commenced Phase 1 clinical studies. Redx is also eligible to receive development, regulatory and commercial milestone payments from Jazz and incremental tiered royalties in mid-single digit percentages, based on any future net sales.
Read the press releaseWe’re excited to advance JZP815, a precision pan-RAF inhibitor with a differentiated mechanism of action, into a clinical trial programme. JZP815 may represent a significant advancement in the pan-RAF inhibitor class by not inducing paradoxical pathway activation that can stimulate the growth of certain cancers. The JZP815 programme exemplifies our continued progress in expanding our early-stage oncology pipeline, and in developing therapies with the potential to address unmet patient need. Redx has an exceptional team of research and development scientists and together we have formed an outstanding collaboration, leveraging the strengths of both companies.