The bad news just keeps coming for Kinnate
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
Porject | Company | Activity | Clinical trial |
---|---|---|---|
Tovorafenib (DAY101) | Day One (ex Sunesis/ Biogen/ Takeda) | Pan-RAF | Ph3 1st-line RAF+ve glioma |
Naporafenib (LXH-254) | Novartis/ Erasca | Pan-RAF | Ph2 in 2nd-line melanoma |
FORE8394 | Fore (ex Daiichi Sankyo)* | Class 1 & 2 | Ph2 in BRAF-altered cancers |
Avutometinib (VS-6766) | Verastem (ex Roche) | Dual RAF/MEK inhibitor | Ph2 in low-grade serous ovarian cancer |
Belvarafenib (HM95573) | Hanmi/ Roche | Pan-RAF | Ph2 in class 2 mutant or fusion +ve tumours |
LUT014 | Lutris Pharma | Unclear | Ph2 in colorectal cancer |
XP-102 | Xynomic (ex Boehringer Ingelheim) | Pan-RAF | Ph1/2 is in V600 only |
Exarafenib (KIN-2787) | Kinnate | Class 1, 2 & 3 | Ph1 in various cancers, incl combo with Mektovi |
BGB-3245 | Beigene/ SpringWorks | Unclear | Ph1, incl class 2 & 3 |
PF-07284890 | Pfizer | Unclear | Ph1 includes substudy in class 2 BRAF |
Note: *Fore was earlier known as NovellusDx; Daiichi rights stem from acquisition of Plexxikon. Source: OncologyPipeline.
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