Kymera Therapeutics Presents New Data Demonstrating Proof-of-Degradation Using Novel Tissue-Restricted E3 Ligase

Novel E3 ligase identified by Kymera’s Whole-Body Atlas is expressed in selected tissues while broadly expressed in cancer cells

Novel STAT3 degrader enabled by PegasusTM platform, and based on identified novel ligase, demonstrates proof-of-concept degradation across multiple in vitro cancer cell lines

New preclinical findings presented today at inaugural Ligase Targeting Drug Development Summit

WATERTOWN, MA, USA I May 26, 2021 I Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation to deliver novel small molecule protein degrader medicines, today presented new data demonstrating proof-of-concept for its PegasusTM platform, including the identification and characterization of a novel and previously unliganded E3 ligase with restricted expression in healthy tissues while broadly expressed in cancer cells, as determined by proteomics. Kymera discovered novel ligands for this ligase using state-of-the-art hit finding techniques and subsequently designed a novel proof-of-concept STAT3 degrader compound based on this novel E3 ligase. The degrader demonstrated potent and dose-dependent degradation of STAT3 across multiple cancer cell lines. These data are being presented by Chris De Savi, PhD, Vice President, Head of Drug Discovery at Kymera, today at the inaugural Ligase Targeting Drug Development Summit, taking place virtually from May 25-27, 2021.

“Kymera was founded and empowered to push the boundaries of targeted protein degradation to discover and develop novel, life-changing therapies. A key initiative in our discovery efforts is to discover a new generation of tissue-selective or -restrictive degrader medicines with the goal of drugging an entirely new set of protein targets. We believe the future of targeted protein degradation will rely on exploiting novel E3 ligases with diverse tissue expression profiles, enabling medicines with selective degradation in disease-relevant tissues, and potentially unlocking a therapeutic paradigm shift," said Nello Mainolfi, PhD, Co-Founder, President and CEO of Kymera Therapeutics. “We look forward to building on these findings as we expand our pipeline of innovative therapeutic candidates and advance our novel E3 ligase-enabled pipeline.”

Kymera has identified the expression profiles of approximately 600 naturally-occurring unique E3 ligases across different tissues with its E3 Ligase Whole-Body Atlas. This knowledge enables Kymera to match a target protein with the appropriate E3 ligase based on expression, distribution, intracellular localization, and biology. Kymera has the ability to determine E3 ligase expression across both healthy and diseased tissues and can identify selective pairings of E3 ligases with therapeutic targets of interest, including tissue-selective or tissue-restrictive pairings. Kymera is building a proprietary toolbox of differentiated E3 ligase binders to enable the design of next-generation disease-specific degraders that target selective degradation in disease-relevant tissues, with the potential of sparing healthy tissues for an improved safety profile.

“The current field of drug development in targeted protein degradation has been limited to a handful of well-understood ubiquitously-expressed E3 ligases. These data presented today provide support for our differentiated ability to identify and utilize previously unliganded E3 ligases, particularly those with selective or restrictive expression, and design highly active and selective heterobifunctional degraders to target and degrade disease-causing proteins using our PegasusTM platform," said Richard Chesworth, DPhil, Chief Scientific Officer at Kymera.

Presentation highlights include:

  • The abundance, characterization, and validation of novel chemical matter for a previously undrugged cullin-RING E3 ligase with ligandable domains and high ‘ligandability’ score
  • This novel E3 ligase is a tissue-restricted ligase, but is broadly expressed in multiple cancer cell lines
  • Potent ligand binders identified using Pegasus™ platform, leading to design of degrader series across Kymera targets including proof-of-concept examples with IRAK4 and STAT3
  • STAT3 degraders based on novel ligase demonstrate broad and potent degradation across multiple in vitro cancer cell lines

“This case study of a previously undrugged cullin-RING E3 ligase demonstrates how we think about both ‘ligandability’, the likelihood of identifying a small-molecule ligand binder to a novel E3 ligase, and ‘druggability’, the likelihood of converting the ligand into a heterobifunctional degrader with therapeutic potential. Our lead discovery strategies are designed to identify, validate, and optimize these novel E3 ligands through a comprehensive, industry-leading approach integrating bioinformatics-driven target identification, diverse screening strategies, and ternary complex predictive modeling,” said Chris De Savi, PhD, Vice President, Head of Drug Discovery at Kymera.

The presentation is available for download at https://www.kymeratx.com/scientific-resources/.

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.

About Kymera Therapeutics
Kymera Therapeutics (Nasdaq: KYMR) is a clinical-stage biopharmaceutical company founded with the mission to discover, develop, and commercialize transformative therapies while leading the evolution of targeted protein degradation, a transformative new approach to address previously intractable disease targets. Kymera’s Pegasus™ platform enables the discovery of novel small molecule degraders designed to harness the body’s natural protein recycling machinery to degrade disease-causing proteins, with a focus on undrugged nodes in validated pathways currently inaccessible with conventional therapeutics. Kymera’s initial programs are IRAK4, IRAKIMiD, and STAT3, each of which addresses high impact targets 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. Kymera’s goal is to be a fully integrated biopharmaceutical company at the forefront of this new class of protein degrader medicines, with a pipeline of novel degrader medicines targeting disease-causing proteins that were previously intractable.

Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” biotechnology company by FierceBiotech and has been recognized by the Boston Business Journal as one of Boston’s “Best Places to Work.” For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn.

SOURCE: Kymera Therapeutics

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