Kymera Therapeutics to Present Preclinical Data on its First-in-Class IRAK4 Degraders Demonstrating Robust Inhibition of Inflammatory Responses and Superiority to IRAK4 Kinase Inhibitors
Data will be shared in an oral presentation at the 2019 American College of Rheumatology’s Annual Meeting in Atlanta
Cambridge, Mass. (November 11, 2019) – Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to discover breakthrough medicines for patients, today announced the company will present new preclinical data showing its first-in-class selective and potent oral IRAK4 degraders demonstrate broad and robust in vitro and in vivo inhibition of the toll-like receptor (TLR) and Interleukin-1 receptor (IL-1R) pathways underlying the pathogenesis of many inflammatory and autoimmune diseases. Data will be shared during an oral presentation (Abstract #1768) at the American College of Rheumatology Annual Meeting in Atlanta on Monday, November 11 at 3:30 PM EST.
“IRAK4, a key component of the myddosome complex that mediates innate immune activation by TLRs and IL-1Rs, has kinase and scaffolding functions, both of which must be drugged to effectively inhibit proinflammatory cytokine and chemokine induction by those stimuli,” said Jared Gollob, MD, CMO, Kymera Therapeutics. “Our data showing broader and more potent inhibition of cytokine and chemokine induction by TLR agonists and IL-1β using IRAK4 degraders compared to IRAK4 kinase inhibitors support the further development of IRAK4 degraders for the treatment of dermatologic, rheumatic and gastrointestinal diseases caused by IL-1 family cytokines including IL-1a, IL-1β, IL-36, IL-18 and IL-33, as well as by toll-like receptor activation.”
“The TLR/IL-1R pathway has been extensively clinically validated by multiple biologics blocking individual IL-1 family cytokines with impact across a diverse set of autoinflammatory and autoimmune diseases,” said Nello Mainolfi, PhD, Founder, President & CSO, Kymera Therapeutics. “We are excited to advance this program into the clinic in 2020 and provide, with a single oral small molecule, a powerful and convenient solution to patients in need.”
ACR/ARP Study Highlights
ABSTRACT #1768, “A First-in-class Selective and Potent IRAK4 Degrader Demonstrates Robust in Vitro and in Vivo Inhibition of TLR/IL-1R Activation and Inflammation,” presented by Veronica Campbell, Principal Scientist at Kymera Therapeutics.
- Unbiased proteomics with a depth of >10,000 proteins showed exclusive degradation of IRAK4 in human PBMCs.
- Selective degraders led to greater than 90% IRAK4 reduction in lymphocytes and monocytes that correlated with inhibition of IL-6 induction by the TLR 7/8 agonist R848.
- IRAK4 degradation led to more effective inhibition of R848 and LPS (TLR4 agonist) stimulated cell signaling compared to IRAK4 kinase inhibitors.
- IRAK4 degraders inhibited R848, LPS and IL-1β induced production of pro-inflammatory cytokines at low nanomolar concentrations – exceeded what can be achieved with IRAK4 kinase inhibitors.
- IRAK4 degraders also exhibited potent inhibition of cytokine and chemokine induction by the combination of LPS + IL-1β that was superior to IRAK4 kinase inhibitors.
- Oral administration of an IRAK4 degrader in the mouse MSU air pouch model led to dose-dependent IRAK4 degradation and a marked decrease in neutrophil infiltration and IL-1β production.
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About Kymera Therapeutics
Kymera Therapeutics is a biotechnology company pioneering a transformative new approach to treating previously untreatable diseases. The company is advancing the field of targeted protein degradation, accessing the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. Powered by Pegasus™, a game-changing integrated degradation platform, Kymera is accelerating drug discovery with an unmatched ability to target and degrade the most intractable of proteins, and advance new treatment options for patients. For more information visit, www.kymeratx.com.
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.