Kymera is developing a selective orally administered IRAK4 degraders for the treatment of toll-like receptor (TLR)/interleukin-1 receptor (IL-1R)-driven autoimmune and autoinflammatory diseases.

Kymera Therapeutics Inc. has started  enrollment in a non-interventional trial evaluating IRAK4 expression in patients with hidradenitis suppurativa (HS) and atopic dermatitis (AD).

Kymera is developing a selective orally administered IRAK4 degraders for the treatment of toll-like receptor (TLR)/interleukin-1 receptor (IL-1R)-driven autoimmune and autoinflammatory diseases. Kymera has plans to advance its lead compound into the clinic in healthy volunteers in the first half of 2021.

"We are thrilled to have started enrollment in this non-interventional trial at York Dermatology Clinic, working closely with Dr. Afsaneh Alavi, one of the world's leading experts in HS and inflammatory skin conditions," says Jared Gollob, MD, Chief Medical Officer of Kymera Therapeutics, in a news release. "The information from this study will further our understanding of the role of IRAK4 in the pathogenesis of HS as well as AD, another TLR/IL-1R-driven inflammatory skin disease and set the stage for future interventional trials in these patient populations using our IRAK4 degraders."

Conducted in collaboration with Dr. Alavi at York Dermatology Clinic and Research Center in Ontario, Canada, the non-interventional trial in patients with HS and AD is designed to examine IRAK4 expression in both diseased and normal skin and blood and its relationship to inflammatory biomarkers and disease stage.

"We have a commitment to patients to further define the central role of our targets in diseases of high unmet need before advancing to the clinic. This study will further our understanding of the biology while optimizing our drug development platform through determination of target expression and PK/PD relationships in patients as early as possible," sadds Nello Mainolfi, PhD, co-founder, President and CEO of Kymera Therapeutics.

The trial will enroll up to 30 HS patients with mild, moderate and severe disease, as well as up to 10 AD patients. Patient participation in the study will consist of a single visit to the clinic for evaluation of disease status, skin biopsies, blood draws, and collection of medical history. IRAK4 levels and production of proinflammatory cytokines, chemokines, and acute phase reactants will be measured in skin and blood. Tissues will also be treated ex-vivo to determine Kymera's IRAK4 degrader effects on IRAK4 levels and on the production of proinflammatory cytokines and chemokines.

"TLR stimulation and IL-1 family cytokines play important roles in the biology of both HS and AD, making IRAK4 an attractive target for the treatment of these diseases," says Dr.  Alavi. "We welcome this opportunity to study the expression of IRAK4 and its relationship to inflammation in these patients, as this knowledge will facilitate the development of promising IRAK4-targeted therapeutics such as IRAK4 degraders."