Kymera Therapeutics Presents Late-Breaking Preclinical Data on IRAK4 Degrader KT-474 at IMMUNOLOGY2021™ Annual Meeting
- Category: Small Molecules
- Published on Monday, 10 May 2021 17:09
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New in vivo data demonstrate the broad anti-inflammatory activity of KT-474 and its superiority compared to a clinically active small molecule IRAK4 kinase inhibitor in preclinical immune-inflammatory models
KT-474 is in Phase 1 clinical development as a first-in-class oral IRAK4 degrader for the treatment of immune-inflammatory diseases, such as atopic dermatitis, hidradenitis suppurativa, rheumatoid arthritis, and potentially others
WATERTOWN, MA, USA I May 10, 2021 I 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.
The presentation is available for download at https://www.kymeratx.com/scientific-resources/.
About IRAK4 and KT-474
IRAK4 is a key protein involved in inflammation mediated by the activation of toll-like receptors (TLRs) and IL-1 receptors (IL-1Rs). Aberrant activation of these pathways is the underlying cause of multiple immune-inflammatory conditions. KT-474, a potential first-in-class, orally bioavailable IRAK4 degrader, is being developed for the treatment of TLR/IL-1R-driven immune-inflammatory diseases with high unmet medical need, such as atopic dermatitis, hidradenitis suppurativa, rheumatoid arthritis, and potentially others. KT-474 is designed to block TLR/IL-1R-mediated inflammation more broadly compared to monoclonal antibodies targeting single cytokines, and to enable pathway inhibition that is superior to IRAK4 kinase inhibitors by abolishing both the kinase and scaffolding functions of IRAK4. In February 2021, Kymera initiated dosing of healthy volunteers in a first-in-human Phase 1 single and multiple ascending dose trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally administered KT-474 in adult healthy volunteers and patients with atopic dermatitis or hidradenitis suppurativa.
Kymera is collaborating with Sanofi on the development of degrader candidates targeting IRAK4, including KT-474 (SAR444656), outside of the oncology and immuno-oncology fields.
Pegasus™ is Kymera Therapeutics’ proprietary protein degradation platform, created by its team of experienced drug hunters to improve the effectiveness of targeted protein degradation and generate a pipeline of novel therapeutics for previously undruggable diseases. The platform consists of informatics-driven target identification, novel E3 ligases, proprietary ternary complex predictive modeling capabilities, and degradation tools.
About Kymera Therapeutics
Kymera Therapeutics (Nasdaq: KYMR) is a clinical-stage biopharmaceutical company founded with the mission to discover, develop, and commercialize transformative therapies while leading the evolution of targeted protein degradation, a transformative new approach to address previously intractable disease targets. Kymera’s Pegasus™ platform enables the discovery of novel small molecule degraders designed to harness the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on undrugged nodes in validated pathways currently inaccessible with conventional therapeutics. Kymera’s initial programs are IRAK4, IRAKIMiD, and STAT3, each of which addresses high impact targets within the IL-1R/TLR or JAK/STAT pathways, providing the opportunity to treat a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. Kymera’s goal is to be a fully integrated biopharmaceutical company at the forefront of this new class of protein degrader medicines, with a pipeline of novel degrader medicines targeting disease-causing proteins that were previously intractable.
Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” biotechnology company by FierceBiotech and has been recognized by the Boston Business Journal as one of Boston’s “Best Places to Work.” For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn.
SOURCE: Kymera Therapeutics