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Kymera Therapeutics Presents Preclinical Data on IRAKIMiD and STAT3 Programs at ASH

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WATERTOWN, Mass., Dec. 07, 2020 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a biopharmaceutical company advancing targeted protein degradation to deliver novel, small molecule protein degrader therapeutics, today announced the company presented preclinical data that further support development of its highly selective and potent IRAKIMiD and STAT3 protein degraders scheduled to enter the clinic in 2021. Data were presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting, Dec. 5-8, 2020 in three separate poster presentations.

  • KT-413 selectively degraded IRAK4 and IMiD substrates in peripheral blood mononuclear cells and activated type I interferon signaling in MYD88MT DLBCL.
  • KT-413 showed superior activity in vitro compared to the potent IMiD CC-220 across MYD88MT DLBCL cell lines, irrespective of co-mutations such as CD79B, TNFAIP3, IRF4, and/or BCL6.
  • PK/PD in tumors showed sustained >80% degradation of both IRAK4 and IMiD substrates associated with tumor regressions irrespective of co-mutations in multiple MYD88MT DLBCL mouse CDX and PDX in vivo models with intermittent PO or IV dosing.
  • KT-413 is on track for initiation of a Phase 1 trial in advanced lymphoma in 2H 2021.

“KTX-120, A Novel IRAKIMiD Degrader of IRAK4 and IMiD Substrates, Shows Preferential Activity and Induces Regressions in MYD88-Mutant DLBCL Cell and Patient Derived Xenograft Models,” presented by Duncan H. Walker, PhD, Vice President of Oncology at Kymera Therapeutics. Poster Session II: Sunday, Dec. 6th (7:00 AM - 3:30 PM PT)

  • IRAKIMiDs are novel, heterobifunctional degraders in development for MYD88-mutant (MYD88MT) diffuse large B cell lymphoma (DLBCL) that selectively target and degrade both IRAK4 and IMiD substrates to elicit more profound and durable anti-tumor activity than targeting IRAK4 or IMiD substrates alone. New data presented on Kymera’s IRAKIMiD development candidate, KT-413 (formerly KTX-120), continue to support the potential for a first-in-class targeted therapy in MYD88MT DLBCL.

“Targeting MYD88-Mutant DLBCL with IRAKIMiDs: A Comparison to IRAK4 Kinase Inhibition and Evaluation of Synergy with Rational Combinations,” presented by Jennifer K. Lue, MD of Columbia University Irving Medical Center. Poster Session III: Monday, Dec. 7th (7:00 AM - 3:30 PM PT)

  • IRAKIMiD degraders KTX-475 and KTX-582 demonstrated potent cell killing across a panel of MYD88MT DLBCL cell lines that was superior to clinically-active IMiDs or IRAK4 kinase inhibitors. In addition, KTX-475 showed synergistic killing of MYD88MT DLBCL in combination with BTK, PI3K, or BCL2 inhibitors in vitro.

“Mechanisms of Anti-tumor Activity of STAT3 Degraders in Lymphoma,” presented by Haojing Rong, PhD, Vice President of Pre-Clinical Development. Poster Session II: Sunday, Dec. 6th (7:00 AM - 3:30 PM PT)

  • STAT3 hyperactivation is prominent in numerous solid and liquid tumors, including clinically aggressive lymphomas. Kymera’s potent and selective STAT3 degrader, KTX-201, has been shown to strongly repress cancer cell growth in preclinical models of STAT3-dependent heme malignancies, including ALK+ ALCL. Data presented for the first time at ASH revealed the molecular mechanisms (both tumor cell-intrinsic and -extrinsic) underlying the anti-tumor effect of STAT3 degradation in mouse models of lymphoma as well as the PK/PD/efficacy relationship of KTX-201 in vivo.

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