Kymera Therapeutics, Inc. announced that the first patient has been dosed in the randomized Phase 2 clinical trial in hidradenitis suppurativa (HS) evaluating KT-474 (SAR444656), a first-in-class, investigational IRAK4 degrader. The Phase 2 study will evaluate the efficacy, safety, pharmacokinetics, and biological effects of KT-474 compared with placebo in adult patients with moderate to severe HS. Kymera?s partner Sanofi is conducting the Phase 2 study in HS, and has initiated a second randomized Phase 2 trial in AD.

Under the terms of the collaboration, dosing of the first patient in the HS trial generated a milestone payment of $40 million. Dosing of the first patient in the AD trial will also generate a milestone payment to Kymera. KT-474 is an oral IRAK4 degrader, in development for the treatment of IL-1R/TLR-driven complex inflammatory diseases where there is an opportunity to significantly advance the standard of care, including HS and AD.

In the Phase 1 trial, KT-474 showed evidence of robust IRAK4 degradation in the blood and active skin lesions of HS and AD patients and was generally well tolerated. Treatment with KT-474 was associated with a systemic anti-inflammatory response and improvement in skin lesions and symptoms in both HS and AD patients, with internal consistency between the effect on inflammatory biomarkers and impact on clinical endpoints. KT-474 was generally safe and well-tolerated, with no serious adverse events, no drug-related infections, and no dose interruptions or discontinuations due to adverse events.

The safety and efficacy of KT-474 (SAR444656) is currently being evaluated in double blind, placebo-controlled, randomized Phase 2 clinical trials in adult patients with moderate to severe HS and AD. Sanofi, which is collaborating with Kymera on the development of KT-474 outside of the oncology and immune-oncology fields, is conducting the Phase 2 studies. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that causes painful lumps deep in the skin.

It results in painful nodules and abscesses that can persist and worsen over time. It can affect daily life and emotional well-being, especially as the disease progresses. HS tends to start after puberty, usually before age 40.

There are no FDA approved oral treatments for HS.