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CAMBRIDGE, Mbad., March 29, 2019 / PRNewswire / – Kymera Therapeutics Inc., a pioneering biotechnology company focused on targeted protein degradation to create breakthrough drugs for patients, will present new preclinical data on its first oral IRAK4 protein degrading agent, KYM- 001, in the mutant lymphoma MYD88. The data will be presented during a last-minute research session at the American Association for Cancer Research's annual meeting on April 3 of 8h – 12 (Poster n ° 18, Session: Experimental and Molecular Therapeutics 2). The study showed that KYM-001 resulted in highly selective degradation of IRAK4 and tumor regression after oral administration, both alone and in combination with BTK inhibition.
"IRAK4 degradation agents offer a whole new therapeutic approach to treat MYD88 B-cell lymphoma, which is often aggressive and has a poor prognosis." Nello Mainolfi, PhD, co-founder and scientific director, Kymera Therapeutics and co-author of the study. "IRAK4 kinase and scaffolding functions are essential for Myddosome signaling driven by MYD88. In contrast to conventional kinase inhibitors, our new KYM-001 degrader suppresses both kinase and scaffold function of IRAK4 to effectively block Myddosome signaling, resulting in tumor growth arrest and subsequent regression. The team was able to quickly identify active oral degraders with ease and flexibility of dosing. "
MYD88 activating mutations occur in 30-40% of patients with diffuse B-cell diffuse B-cell (ABC). This study evaluated the antitumor activity of Kymera orally active small molecule degradation agents in human ABC DLCBL cell lines. in vitro and in tumor xenograft models in vivo, alone and in combination with ibrutinib, an inhibitor of BTK.
Highlights of the study "KYM-001, a first-clbad oral IRAK4 protein degrading agent, induces tumor regression in the ABC DLBCL mutant MYD88 xenograft models, alone and in combination with BTK inhibition. ":
- KYM-001 induced potent and selective degradation of E3 ligase-dependent IRAK4 in several cellular models, resulting in 90% degradation at concentrations below 100 nM.
- KYM-001 induced comparable levels of IRAK4 degradation in the cell lines of both MYD88 mutant and MYD88 WT ABC DLBCL human.
- KYM-001 affected the viability of ABC DLBCL cell lines of mutant MYD88, but not WT, inducing apoptotic effects within 72 hours.
- The oral dosage of KYM-001 showed antitumor activity dependent on the ABC DLBCL ABCDBCL cell line of MYD88 L265P, with a> 80% degradation of IRAK4 correlated with tumor regression in xenograft-bearing mice.
- KYM-001 was synergistic with the inhibitor BTK inhibitor ibrutinib in vitro in ABC DLBCL cell lines carrying both MYD88 L265P and CD79 mutations. In vivothis combined activity resulted in tumor regression at suboptimal concentrations in single-agent studies, further exploring combinations that target oncogenic NFKB signaling.
About Kymera Therapeutics
Kymera Therapeutics is a biotechnology company that is developing a new transformative approach to treating previously incurable diseases. The company is advancing the field of targeted protein degradation by accessing the innate machinery of protein recycling in the body to degrade the dysregulated proteins that cause the disease. Powered by Pegasus ™, a revolutionary integrated degradation platform, Kymera accelerates drug discovery with unmatched ability to target and break down the most intractable proteins and offer new treatment options to patients. For more information, visit www.kymeratx.com.
About Pegasus ™
Pegasus ™ is Kymera Therapeutics' proprietary protein-degrading platform, created by its team of experienced drug researchers to improve the efficiency of targeted protein degradation and generate a portfolio of new treatments. for previously insoluble diseases. The platform includes computer-based target identification, new E3 ligases, exclusive ternary complex predictive modeling capabilities and degradation tools.
SOURCE Kymera Therapeutics Inc.
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