WATERTOWN, MA, USA I November 04, 2020 I Kymera Therapeutics, Inc. (NASDAQ: KYMR), a biopharmaceutical company advancing targeted protein degradation to deliver novel small molecule protein degrader therapeutics, today announced the company will present new preclinical data for its IRAKIMiD and STAT3 degrader programs at the 62nd American Society of Hematology (ASH) Annual Meeting taking place virtually from Dec. 5-8, 2020.

“We are excited to share for the first time preclinical data of our IRAKIMiD development candidate KT-413 (formerly KTX-120) as well as an expanded preclinical investigation of our STAT3 degrader program which have allowed us to uncover important insights into their therapeutic potential across a variety of hematologic cancers,” said Jared Gollob, MD, Chief Medical Officer, Kymera Therapeutics. “The results also establish the potential for intermittent dosing schedules for both programs as we guide their advancement into the clinic next year.” 

IRAKIMiD Program

ABSTRACT #2088, “KTX-120, a Novel IRAKIMiD Degrader of IRAK4 and IMiD substrates shows Preferential Activity and Induces Regressions in MYD88-Mutant DLBCL CDX and PDX 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).

ABSTRACT #3013, “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).

Data to be presented show:

  • Deep and Sustained Tumor Regressions with Intermittent Dosing in MYD88-mutant DLBCL: KT-413 was well tolerated and exhibited potent and sustained antitumor activity in multiple MYD88-mutant mouse CDX and PDX models of DLBCL across a range of both PO and IV intermittent dosing schedules.
  • Preferential Anti-Tumor Activity in MYD88-mutant DLBCL Irrespective of Co-Mutations: KT-413 anti-tumor activity was specific to MYD88-mutant cell lines (relative to WT cell lines) and was independent of a variety of common co-mutations that further activate the NF-kB and IRF4 pathways.
  • Superiority to IMiDs and IRAK4 Kinase Inhibitor: In MYD88-mutant models of DLBCL, IRAKIMiDs showed superior cell killing compared to either IMiDs or an IRAK4 kinase inhibitor alone.
  • Synergistic Combination Potential: Rational combinations of IRAKIMiDs with either BCL2, BTK, or PI3K inhibitors showed synergistic in vitro activity in MYD88-mutant DLBCL.

STAT3 Program

ABSTRACT #2090, “Mechanisms of the 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).

Data to be presented show:

  • Tumor Regressions in STAT3-dependent ALK+ ALCL with Intermittent Dosing: Weekly dosing with KTX-201 achieved complete tumor regressions at doses that lowered tumor levels of STAT3 by >90% and maintained that lowering for up to 4 days post-dose.
  • Antitumor Mechanism of Action: Proteomics showed that STAT3 degradation in vitro by KTX-201 in ALK+ ALCL was associated with inhibition of cytokine signaling, G1 cell cycle arrest and induction of apoptosis.

These findings build on results reported at the 2020 American Association for Cancer Research (AACR) Virtual Annual Meeting II, which highlighted the potent anti-tumor effects of Kymera’s selective IRAKIMiD and STAT3 degraders in multiple animal models of cancer.

About Kymera Therapeutics
Kymera Therapeutics is a biopharmaceutical company focused on a transformative new approach to address previously intractable disease targets. Kymera is advancing the field of targeted protein degradation, accessing the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. Kymera’s Pegasus targeted protein degradation platform harnesses the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on un-drugged nodes in validated pathways currently inaccessible with conventional therapeutics. 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. Kymera’s initial programs target IRAK4, IRAKIMiD and STAT3 within the IL-1R/TLR or JAK/STAT pathways, providing the opportunity to treat a broad range of immune-inflammatory diseases, hematologic malignancies and solid tumors. 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.

SOURCE: Kymera Therapeutics