Kymera Therapeutics Presents Late-Breaking Preclinical Data Highlighting Superiority of Dual-Targeting Activity of IRAKIMiD Degrader KT-413 at AACR Annual Meeting 2021
KT-413-mediated degradation of IRAK4 and IMiD substrates has synergistic effect on MYD88-NFkB and IRF4-Type 1 Interferon pathways resulting in superior antitumor activity in MYD88-mutant DLBCL
models compared to IMiDs or selective IRAK4 targeting alone
Company anticipates IND submission and, if cleared, initiation of Phase 1 trial of KT-413 in relapsed/refractory B cell lymphomas, including MYD88-mutant DLBCL, in 2H 2021
WATERTOWN, Mass., April 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 late-breaking preclinical data showing how the dual targeting of IRAK4 and IMiD substrates by KT-413, its IRAKIMiD degrader currently in preclinical development, synergizes to impact signaling and cell killing in MYD88-mutant diffuse large B cell lymphoma (DLBCL) in a manner that is distinct from IMiDs or selective IRAK4 targeting alone. The data were presented today in a poster session at the American Association of Cancer Research (AACR) Annual Meeting 2021 (LB118: Mechanisms underlying synergistic activity in MYD88MT DLBCL of KT-413, a targeted degrader of IRAK4 and IMiD substrates).
IRAKIMiDs are novel heterobifunctional degraders designed to degrade both IRAK4 and IMiD substrates, including Ikaros and Aiolos, with a single small molecule. IRAKIMiDs synergistically target both the MYD88-NFkB and IRF4-Type 1 interferon pathways to enhance and broaden anti-tumor activity in MYD88-mutant DLBCL. KT-413 is being developed initially for the treatment of relapsed/refractory MYD88-mutant DLBCL, with the potential to expand into other MYD88-mutant indications and IL-1R/NFkB-driven malignancies. KT-413 is currently in preclinical development and Kymera plans to submit an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) and, if cleared, initiate a Phase 1 clinical trial in relapsed/refractory B cell lymphomas, including MYD88-mutant DLBCL, in the second half of 2021.
“KT-413 combines IRAK4 degradation with potent IMiD activity in a single agent in order to simultaneously target two signaling pathways central to the malignant phenotype of aggressive, poor prognosis MYD88-mutant DLBCL,” said Jared Gollob, MD, Chief Medical Officer at Kymera Therapeutics. “KT-413 has demonstrated broad activity against MYD88-mutant lymphomas in vitro and in mouse xenograft models, leading to rapid, complete and sustained tumor regressions, even when dosed intermittently. Our understanding of the molecular mechanism driving this remarkable antitumor activity allows us to further differentiate this dual-degrader approach from either IMiDs or selective IRAK4 targeting alone.”