Kymera Therapeutics announces publication of Phase 1 trial results for KT-474

Kymera Therapeutics announced that results from the positive Phase 1 clinical trial from its lead program, KT-474, a potent, highly selective, orally bioavailable IRAK4 degrader, were published in Nature Medicine. The results showed a reduction of disease-relevant inflammatory biomarkers in the blood and skin of HS and AD patients associated with improvement in skin lesions and symptoms. The full manuscript, “IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial,” was published online on November 13, 2023, on the Nature Medicine website. The data reported in the publication show that KT-474 administered to HS and AD patients had safety, pharmacokinetics and pharmacodynamics similar to healthy volunteers, achieved robust IRAK4 degradation in blood and skin lesions associated with a systemic anti-inflammatory effect, and showed activity in HS and AD. The Company previously reported Phase 1 results in December 2022 and at the European Academy of Dermatology and Venereology Symposium in May 2023. The publication also highlights preclinical data on KT-474, including the first publication of the compound’s chemical structure. KT-474 was studied in a Phase 1 randomized, placebo-controlled, single and multiple ascending dose trial to assess safety, pharmacokinetics, pharmacodynamics and clinical activity. 105 healthy volunteers were enrolled in the placebo-controlled single and multiple ascending dose escalation cohorts and 21 HS and AD patients were enrolled into an open-label patient cohort. KT-474 was administered as a single dose and then daily for 14 days in the fasted state in HVs followed by dosing for 28 days in the fed state in patients with HS or AD. Degradation of IRAK4 was observed in HV blood, with mean reductions after a single dose of greater than or equal to93% at 600-1600 mg and after 14 daily doses of greater than or equal to95% at 50-200 mg. In patients treated with 75 mg of KT-474, similar IRAK4 degradation was achieved in blood, and IRAK4 was normalized in skin lesions where it was overexpressed relative to HVs. Reduction of disease-relevant inflammatory biomarkers was demonstrated in the blood and skin of HS and AD patients associated with improvement in skin lesions and symptoms. KT-474 was well-tolerated with no drug-related infections. These results from the first published clinical trial using a heterobifunctional degrader provide initial proof of concept for KT-474 in HS and AD to be further confirmed in placebo-controlled Phase 2 trials.