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, Mass., May 10, 2021 (GLOBE NEWSWIRE) -- 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.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding its: beliefs regarding the potential clinical impact of KT-474, including resulting datasets, and plans to present new data; strategy, business plans and objectives for the IRAK4, IRAKIMiD and STAT3 degrader programs; beliefs regarding the roles of IRAK4 and the potential of an IRAK4 degrader to improve patient outcomes; and plans and timelines for the clinical development of Kymera Therapeutics' product candidates, including the therapeutic potential and clinical benefits thereof. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of COVID-19 on countries or regions in which we have operations or do business, as well as on the timing and anticipated results of our current preclinical studies and future clinical trials, strategy and future operations; the delay of any current preclinical studies or future clinical trials or the development of Kymera Therapeutics' drug candidates; the risk that the results of current preclinical studies may not be predictive of future results in connection with future clinical trials; Kymera Therapeutics' ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of the Company’s planned interactions with regulatory authorities, including the resolution of the current partial clinical hold for KT-474; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Annual Report on Form 10-Q for the period ended March 31, 2021, filed on May 6, 2021, as well as discussions of potential risks, uncertainties, and other important factors in Kymera Therapeutics' subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Kymera Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
VP, Investor Relations and Communications
Lissette L. Steele
Verge Scientific Communications for Kymera Therapeutics