KRAS Inhibitors
Sold to Jazz Pharmaceutical, February 2024
KRAS Inhibitor Programme: Targeting mutations beyond G12C
The KRAS inhibitor programme is targeting KRAS to inhibit oncogenic signaling and suppress KRAS mutant tumour growth. To date a number of inhibitors of the G12C variant of KRAS are in clinical development – Redx is targeting the next generation by focusing on a profile against G12D and also a multi–KRAS profile which would inhibit other mutant forms of KRAS.
Currently launched KRAS inhibitors Lumakras (sotorasib) and Krazati (adagrasib) selectively target the KRAS G12C mutation, Redx is targeting next generation KRAS inhibitor profiles, including a selective inhibitor of the most prevalent KRAS G12D mutation. In addition, a -pan-KRAS profile that inhibits a broad range of KRAS mutants and also wild-type KRAS, which could help prevent the reported resistance observed with KRAS mutant selective agents.
Rat sarcoma virus (RAS) is the most frequently mutated oncogene across different cancer types, with KRAS mutations accounting for approximately 85% of these mutated oncogenes. Therefore, KRAS inhibitors targeting multiple commonly-occurring mutations may offer a treatment option for large segments of colorectal, pancreatic and lung cancer patients who currently have limited treatment options. Developing orally-bioavailable agents with dosing that allows for long term target coverage, and thus reduced risk of resistance, is a key opportunity for the next wave of KRAS-targeting agents that act beyond the G12C mutation.
KRAS Inhibitor Programme: Targeting mutations beyond G12C
The KRAS inhibitor programme is targeting KRAS to inhibit oncogenic signaling and suppress KRAS mutant tumour growth. To date a number of inhibitors of the G12C variant of KRAS are in clinical development – Redx is targeting the next generation by focusing on a profile against G12D and also a multi–KRAS profile which would inhibit other mutant forms of KRAS.
Currently launched KRAS inhibitors Lumakras (sotorasib) and Krazati (adagrasib) selectively target the KRAS G12C mutation, Redx is targeting next generation KRAS inhibitor profiles, including a selective inhibitor of the most prevalent KRAS G12D mutation. In addition, a -pan-KRAS profile that inhibits a broad range of KRAS mutants and also wild-type KRAS, which could help prevent the reported resistance observed with KRAS mutant selective agents.
Rat sarcoma virus (RAS) is the most frequently mutated oncogene across different cancer types, with KRAS mutations accounting for approximately 85% of these mutated oncogenes. Therefore, KRAS inhibitors targeting multiple commonly-occurring mutations may offer a treatment option for large segments of colorectal, pancreatic and lung cancer patients who currently have limited treatment options. Developing orally-bioavailable agents with dosing that allows for long term target coverage, and thus reduced risk of resistance, is a key opportunity for the next wave of KRAS-targeting agents that act beyond the G12C mutation.
KRAS inhibitor programme sold to Jazz Pharmaceuticals (“Jazz”)
On 7 February 2024, Redx Pharma announced that it had signed a definitive agreement with Jazz under which Jazz acquired Redx’s KRAS inhibitor programme, which includes G12D selective and pan-KRAS molecules, for the treatment of KRAS mutant driven cancers. In parallel, an additional collaboration agreement was signed with Jazz under which Jazz will pay Redx to perform research and preclinical development services with the goal of completing IND-enabling studies.
Under the terms of the agreement, Redx received an upfront payment of $10m, for all rights, title and interest relating to Redx’s proprietary KRAS inhibitor programme, including all related patents. The next milestone payment would be payable with an IND clearance from this programme from the U.S. Food and Drug Administration. Redx is also eligible to receive up to a further $870 million in development, regulatory and commercial milestone payments from Jazz as well as mid-single digit royalties.
KRAS is a well-validated oncology target and there remains a high unmet need for innovation in this area based on challenges in developing molecules to target specific KRAS mutations. Redx has discovered a number of preclinical KRAS candidates and we plan to leverage our collective oncology development expertise to identify and advance the most promising molecules toward the clinic. This transaction further expands our early-stage oncology pipeline, and we are excited to explore novel approaches to improving treatment options for cancer patients.