Verastem announced a global licensing agreement with Chugai Pharmaceutical. Verastem Oncology is obtaining worldwide development and commercialization rights to the RAF/MEK inhibitor CH5126766 (CKI27) from Chugai currently under development for the treatment of KRAS mutant solid tumors.
CH5126766 in combination with Verastem Oncology’s focal adhesion kinase (FAK) inhibitor, defactinib, is currently the subject of a clinical study (Phase I followed by expansion cohorts) with the expansion cohorts now ongoing in patients with KRAS mutant advanced solid tumors, including low grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). This clinical study of the defactinib/CH5126766 combination is supported by the single-agent Phase 2 studies of defactinib in KRAS mutant NSCLC2 and CH5126766 in KRAS mutant NSCLC and LGSOC.
“Based on the single-agent defactinib results in KRAS mutant NSCLC, we conducted an internal pre-clinical effort to identify drug classes that were synergistic with defactinib and saw the highest level of synergy in combination with MEK inhibitors and, specifically, with CH5126766,” said Dan Paterson, President and Chief Operating Officer of Verastem Oncology. “The exciting early clinical results led to our decision to enter into a partnership with Chugai for CH5126766 and accelerate the combination development program for patients with KRAS mutant cancers, which are highly aggressive and recurrent. We plan to initiate discussions with regulatory authorities about our development plans and to define the registration path early this year.”
“We found that MEK blockade activates FAK signaling as a potential escape mechanism,” said Professor Udai Banerji, Professor of Molecular Cancer Pharmacology at The Institute of Cancer Research and Honorary Consultant in Medical Oncology, MBBS, MD, DNB, PhD, FRCP at The Royal Marsden NHS Foundation Trust, London, England, and lead investigator of the clinical study. “Based on the synergy between FAK and MEK inhibitors observed in preclinical KRAS mutant models, we have been assessing the combination of defactinib and CH5126766 for treatment of patients with KRAS mutant cancers. The results to date have been encouraging and we look forward to sharing our clinical findings, including the response rate in an upcoming scientific presentation.”
“CH5126766 is a unique and particularly promising inhibitor of the RAS/RAF/MEK signaling pathway,” said Neal Rosen, MD, PhD, Memorial Sloan Kettering Cancer Center, NY, NY. “In contrast to other MEK inhibitors in development, CH5126766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows CH5126766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The clinical data with the combination of defactinib and CH5126766 are striking and suggest promise for patients with KRAS mutant solid tumors.”
Under the terms of the agreement, Verastem Oncology is responsible for the development and worldwide commercialization of CH5126766. The Company will make an upfront payment of $3M and pay royalties to Chugai.