Kymera Therapeutics sweetened news of a setback Wednesday, revealing that Sanofi is pulling back from its lead IRAK4 degrader alongside details of the selection of a follow-up prospect and a $750 million deal with Gilead Sciences.
Sanofi took its original lead IRAK4 degrader, which is called SAR444656 or KT-474, into phase 2 trials in atopic dermatitis and hidradenitis suppurativa in 2023. The studies were scheduled to wrap up next year, but the Big Pharma has rethought its plans before reaching the milestones. Rather than advancing KT-474, Sanofi has decided to prioritize the preclinical IRAK4 degrader KT-485, according to a June 25 press release from Kymera.
In the release, Kymera said the new candidate showed increased selectivity and potency with a favorable safety profile in preclinical testing. The biotech expects KT-485 to enter the clinic next year, five years after it started a phase 1 trial of KT-474.
Sanofi will pay a milestone when KT-485 starts clinical development. The fee is part of a total package that is worth up to $975 million in potential clinical, regulatory and commercial milestones. Last month, Kymera said it was eligible to receive up to $1 billion in development and regulatory milestones, plus up to $400 million tied to commercial successes, as part of the Sanofi deal.
Kymera shared news of changes to the Sanofi collaboration minutes after disclosing an oncology deal with Gilead. The Big Biotech has committed up to $85 million in upfront and potential option exercise payments for a chance to license a CDK2-directed molecular glue degrader. The idea is to remove the protein from cells, taking out a tumor growth driver without causing the side effects associated with CDK2 inhibitors.
Companies including AstraZeneca, Incyte and Pfizer have CDK2 inhibitors in clinical trials, reflecting the potential for medicines that inhibit the protein to address resistance mechanisms to CDK4/6 inhibitors in breast cancer. First-generation candidates had tolerability problems, potentially because they hit other proteins as well as CDK2.
Advocates of molecular glue degraders argue the modality could avoid the dose-limiting toxicities seen in some CDK2 inhibitor trials by more selectively targeting the protein. Monte Rosa Therapeutics shared preclinical data on its CDK2-directed molecular glue degrader late last year.
Kymera will lead all research activities for the Gilead-partnered CDK2 program. Gilead has an option to exclusively license the program in exchange for a financial package that could total $750 million plus royalties.