Kinnate Biopharma has lost over 90% of its value since floating in 2020, and the bad news just keeps on coming. Two delays to its lead project, exarafenib (KIN-2787), were followed yesterday by a move to cut 70% of the company’s staff. The cost-cutting plan is designed to enable Kinnate to exist on its current $204m cash balance until the second quarter of 2026, around a year longer than expected before, but what’s odd is that it comes just five months after the company trumpeted long-awaited exarafenib data, and brought two new projects, the MEK inhibitor KIN-7136 and the cMET inhibitor KIN-8741, into its pipeline. Yesterday it suspended development of the former, and said it would focus exarafenib development on a combo with Pfizer’s Mektovi. First-generation RAF inhibitors, including Maktovi, Roche’s Zelboraf and Novartis’s Tafinlar, work only in class 1 (also known as V600) BRAF mutations, but exarafenib is said to have activity in class 2 and 3 BRAF alterations. However, after two delays exarafenib monotherapy data showed an ORR of just 14% at the highest doses. This has presumably spurred the move to a Mektovi combo, where Kinnate claims a 38% ORR in BRAF inhibitor-naive patients. RAF inhibitors with possible activity beyond class 1 BRAF mutationsPorjectCompanyActivityClinical trialTovorafenib (DAY101)Day One (ex Sunesis/ Biogen/ Takeda)Pan-RAFPh3 1st-line RAF+ve gliomaNaporafenib (LXH-254)Novartis/ ErascaPan-RAFPh2 in 2nd-line melanomaFORE8394Fore (ex Daiichi Sankyo)*Class 1 & 2Ph2 in BRAF-altered cancersAvutometinib (VS-6766)Verastem (ex Roche)Dual RAF/MEK inhibitorPh2 in low-grade serous ovarian cancer Belvarafenib (HM95573)Hanmi/ RochePan-RAFPh2 in class 2 mutant or fusion +ve tumoursLUT014Lutris PharmaUnclearPh2 in colorectal cancerXP-102Xynomic (ex Boehringer Ingelheim)Pan-RAFPh1/2 is in V600 onlyExarafenib (KIN-2787)KinnateClass 1, 2 & 3Ph1 in various cancers, incl combo with MektoviBGB-3245 Beigene/ SpringWorksUnclearPh1, incl class 2 & 3PF-07284890PfizerUnclearPh1 includes substudy in class 2 BRAFNote: *Fore was earlier known as NovellusDx; Daiichi rights stem from acquisition of Plexxikon. Source: OncologyPipeline.
Kinnate Biopharma has lost over 90% of its value since floating in 2020, and the bad news just keeps on coming. Two delays to its lead project, exarafenib (KIN-2787), were followed yesterday by a move to cut 70% of the company’s staff. The cost-cutting plan is designed to enable Kinnate to exist on its current $204m cash balance until the second quarter of 2026, around a year longer than expected before, but what’s odd is that it comes just five months after the company trumpeted long-awaited exarafenib data, and brought two new projects, the MEK inhibitor KIN-7136 and the cMET inhibitor KIN-8741, into its pipeline. Yesterday it suspended development of the former, and said it would focus exarafenib development on a combo with Pfizer’s Mektovi. First-generation RAF inhibitors, including Maktovi, Roche’s Zelboraf and Novartis’s Tafinlar, work only in class 1 (also known as V600) BRAF mutations, but exarafenib is said to have activity in class 2 and 3 BRAF alterations. However, after two delays exarafenib monotherapy data showed an ORR of just 14% at the highest doses. This has presumably spurred the move to a Mektovi combo, where Kinnate claims a 38% ORR in BRAF inhibitor-naive patients.
RAF inhibitors with possible activity beyond class 1 BRAF mutations
