Kymera Therapeutics, Inc. (NASDAQ:KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation to deliver novel small molecule protein degrader medicines, today presented positive late-breaking preclinical data demonstrating the IRAK4 degrader KT-474's superiority compared to a clinically active small molecule IRAK4 kinase inhibitor across a wide variety of immune-inflammatory preclinical in vivo models. The late-breaking data are being presented at the American Association of Immunologists' Virtual IMMUNOLOGY2021™ annual meeting, taking place from May 10 - 15, 2021 (Abstract 1307: IRAK4 degradation abrogates cytokine release and improves disease endpoints in murine models of IL-33/36- as well as Th17-driven inflammation).
"We have developed a first-in-class, orally bioavailable IRAK4 degrader, KT-474, to eliminate both the kinase and scaffolding functions of IRAK4 and thereby block TLR/IL-1R-mediated inflammation more broadly compared to other therapeutic approaches," said Jared Gollob, MD, Chief Medical Officer at Kymera Therapeutics. "These new data demonstrate both in vitro and in vivo the superiority of KT-474 over a clinically active small molecule IRAK4 kinase inhibitor in inhibiting inflammation driven by IL-1 family cytokines including IL-33 and IL-36, which are involved in diseases such as atopic dermatitis and hidradenitis suppurativa, as well as by Th17 cells involved in a variety of different autoimmune diseases including multiple sclerosis and inflammatory bowel disease."
Data highlights include:
- KT-474's efficacy and superiority to IRAK4 small molecule inhibitors were demonstrated across multiple mechanistic and disease models of inflammation
- In mouse models of skin inflammation induced by either IL-33 or IL-36 and an IL-33 intraperitoneal challenge model, KT-474 dose-dependently reduced IRAK4 levels in blood cells and inhibited skin inflammation and/or systemic as well as local cytokine production to the same extent as a potent corticosteroid (dexamethasone) and more potently than an IRAK4 small molecule inhibitor
- In a mouse model of Th17-mediated multiple sclerosis, KT-474 was superior to IRAK4 kinase inhibition and similar to FDA-approved fingolimod (FTY720) in significantly reducing clinical disease scores
"These KT-474 data demonstrate both the broad clinical potential and superiority over clinically active agents for the treatment of a wide variety of immune-inflammatory diseases," said Nello Mainolfi, PhD, Co-Founder, President and CEO, Kymera Therapeutics. "These findings and the recently disclosed non-interventional study data continue to support the breadth of our clinical development program and increase our confidence in the key de-risking dataset, expected in the fourth quarter, demonstrating pharmacokinetic, pharmacodynamic, and mechanistic proof-of-concept in our randomized, placebo-controlled study in healthy volunteers and patients with atopic dermatitis or hidradenitis suppurativa."
- Abstract: 1307
- Title: IRAK4 degradation abrogates cytokine release and improves disease endpoints in murine models of IL-33/36- as well as Th17-driven inflammation
- Session: Novel therapeutic approaches for the modulation of autoimmune and allergic diseases
- Session Time: 9:00 a.m. - 10:30 a.m. ET on Thursday, May 13, 2021
- Presenter: Cedric Hubeau, Ph.D.