Kymera Therapeutics

Kymera Therapeutics to Present New Preclinical Data for its First-In-Class Oral IRAK4 Degrader in MYD88-Mutant B Cell Lymphoma at the 15th International Conference on Malignant Lymphoma

KYM-001 causes potent and selective IRAK4 protein knockdown and regression of OCI-LY10 tumor xenografts, both alone and in combination with BTK inhibition

Cambridge, Mass. (June 19, 2019) – Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to create breakthrough medicines for patients, will present new preclinical data demonstrating its first-in-class oral IRAK4 protein degraders cause tumor regression in MYD88-mutant B cell lymphoma. Data will be shared during an oral presentation at the 15th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland on Thursday, June 20 at 5:45 PM CEST.

“We are highly encouraged by the data, which strongly supports clinical advancement of our orally active IRAK4 protein degraders in MYD88-driven B cell malignancies, both as monotherapy and in combination with drugs targeting complementary pathways,” said Jared Gollob, MD, CMO, Kymera Therapeutics. “We look forward to sharing our findings and engaging with an international group of lymphoma experts at this year’s ICML meeting to define the path forward into the clinic in 2020.”

Activating mutations in MYD88 are frequent across multiple subsets of aggressive B cell lymphomas, including activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL, 30-40%), primary central nervous system lymphoma (30-70%), and primary extranodal lymphoma (45-75%), as well as Waldenström Macroglobulinemia (>90%). Myddosome signaling triggered by MYD88 is dependent on both the kinase activity and scaffolding function of IRAK4. Kymera is using a chemical knockdown strategy to develop heterobifunctional small molecule IRAK4 protein degraders such as KYM-001 for the treatment of B cell malignancies driven by MYD88 mutations.

ICML Study Highlights

ABSTRACT #083: “KYM-001, a first-in-class oral IRAK4 protein degrader, induces tumor regression in xenograft models of MYD88-mutant ABC-DLBCL alone and in combination with BTK inhibition”

Presented by Duncan Walker, PhD, VP of Oncology, Kymera Therapeutics

  • Kymera’s IRAK4 degrader achieved potent and selective E3 ligase-dependent degradation of IRAK4 in both MYD88 mutant and MYD88 wild-type (WT) ABC-DLBCL cell lines.
  • Cell viability was impacted in MYD88 mutant but not WT ABC-DLBCL cell lines, whereas an IRAK4 kinase inhibitor had no effect.
  • Orally dosed KYM-001 caused in vivo tumor regression in a dual MYD88/CD79 mutant OCI-LY10 mouse xenograft model of ABC-DLBCL associated with ≥75% IRAK4 knockdown in tumors.
  • Subtherapeutic doses of KYM-001 in combination with the BTK inhibitor ibrutinib increased OCI-LY10 apoptosis in vitro and drove tumor regression in vivo in the OCI-LY10 mouse xenograft model.

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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.

About Pegasus™

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.

Media Contact:
Lissette Steele
Verge Scientific Communications
lsteele@vergescientific.com
202.930.4762