On June 19, 2019 Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to create breakthrough medicines for patients, reported that it will present new preclinical data demonstrating its first-in-class oral IRAK4 protein degraders cause tumor regression in MYD88-mutant B cell lymphoma (Press release, Kymera Therapeutics, JUN 19, 2019, View Source [SID1234537183]). 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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.