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A-Alpha Bio Partners with Kymera Therapeutics to Discover Novel Interactions for Molecular Glue Discovery



A-Alpha Bio, a biotechnology company that works with pharmaceutical industry partners to enable and accelerate drug discovery with massively multiplexed measurements of protein-protein interactions, and Kymera Therapeutics, Inc., a clinical-stage biopharmaceutical company developing targeted protein degraders, today announced a partnership to discover and characterize novel pairs of E3 ubiquitin ligases and high-value therapeutic targets for the rational and prospective design and development of molecular glues.

The partnership is the first announced by A-Alpha Bio in the cutting-edge and rapidly growing area of targeted protein degradation and leverages the AlphaSeq platform to quantitatively measure protein-protein binding in a high-throughput manner along with a proprietary library of approximately 40 E3 ubiquitin ligases. Under the terms of the agreement, A-Alpha Bio will discover and characterize druggable interactions between a curated list of high-value targets and its library of E3 ligases that Kymera can use as an input to its Pegasus™ platform for the rational discovery and development of molecular glues. Kymera will have the option to take a license for up to two targets for further development. A-Alpha Bio will receive upfront and research payments and be eligible for downstream milestones.

Molecular glues, a new class of small-molecule drugs, are exciting for their potential to degrade previously undruggable protein targets, providing a valuable new tool to address areas of critical, unmet need. With over 600 human E3 ubiquitin ligases and numerous targets of interest, a major challenge for molecular glue discovery is prospectively identifying a ligase-target pair that has the potential for targeted degradation. The AlphaSeq platform can efficiently analyze up to millions of protein-protein interactions and measure each interaction strength, including very weak interactions that can be stabilized by a molecular glue. Once promising ligase-target pairs are discovered, AlphaSeq can again be used with mutagenic libraries of the ligase and target to further interrogate druggability and provide structural insights to aid in the subsequent rational discovery of a therapeutic glue.

“Use of rational approaches for the discovery of molecular glues have been limited to empirical exploration of Cereblon and IMiD glues with a small set of oncology targets mostly due to lack of broad understanding of how to enable novel interactions. A-Alpha Bio’s novel approach to identify weak protein-protein interactions at scale and ability to deeply characterize the molecular basis for new interactions is truly a game-changing innovation,” said Nello Mainolfi, PhD, Co-Founder, President and CEO, Kymera Therapeutics. “This collaboration presents a unique opportunity to discover those interactions and then use Kymera’s deep know-how in hit finding and degradation discovery to develop a new generation of molecular glues against new undrugged and un-ligandable targets as well as to expand the repertoire of E3 ligases that can be used for targeted protein degradation.”

A-Alpha Bio’s proprietary platform, AlphaSeq, represents the first high-throughput and quantitative approach for measuring protein-protein binding. To date, A-Alpha Bio’s partners have leveraged AlphaSeq to enable and accelerate antibody discovery by simultaneously measuring millions of interactions between antibodies and antigens or antigen mutants for high-throughput determination of properties like affinity, specificity, cross-reactivity, and epitope. The discovery of molecular glue targets for targeted protein degradation represents an exciting new application for AlphaSeq that expands its scope to address previously undruggable intracellular targets.

“We are thrilled to collaborate with the incredible Kymera team to discover and validate molecular glue targets. Kymera is a leader in the targeted protein degradation space and their pioneering work makes them an ideal partner for A-Alpha Bio,” said David Younger, PhD, Co-Founder and CEO of A-Alpha Bio. “Kymera and A-Alpha share a commitment to innovation and to expanding the potential of targeted protein degradation by unlocking new ligases and new previously undruggable targets. By combining Kymera’s deep domain expertise in targeted protein degradation and the multiplexing power and sensitivity of our AlphaSeq assay, we are confident that together we can unlock novel therapeutics against previously undruggable targets.”

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About A-Alpha BioA-Alpha Bio leverages synthetic biology to quantitatively measure millions of protein-protein interactions and machine learning to generate high-resolution models of protein binding and interaction networks.

The company has developed a proprietary platform technology, called AlphaSeq, that uses genetically engineered yeast cells to experimentally measure millions of protein-protein interaction affinities simultaneously at a library-on-library scale, generating enormous amounts of data to inform the discovery and development of potent, specific, and cross-reactive drugs.

A-Alpha Bio was founded in 2017 by a team of synthetic biologists from the University of Washington's Institute for Protein Design and Center for Synthetic Biology.

About Kymera Therapeutics, Inc.Kymera Therapeutics (Nasdaq: KMYR) 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 lead 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 global, 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 or follow us on Twitter or LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding its: strategy, business plans and objectives for its discovery and development efforts, and its relationships with its collaborators. The words "may," “might,” "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," “expect,” "estimate," “seek,” "predict," “future,” "project," "potential," "continue," "target" and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of COVID-19 on countries or regions in which we have operations or do business, as well as on the timing and anticipated results of our current preclinical studies and future clinical trials, strategy and future operations; the delay of any current preclinical studies or future clinical trials or the development of Kymera Therapeutics' drug candidates; the risk that the results of current preclinical studies may not be predictive of future results in connection with future clinical trials; Kymera Therapeutics' ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of the Company’s planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Quarterly Report on Form 10-Q for the period ended September 30, 2021, filed on November 10, 2021, as well as discussions of potential risks, uncertainties, and other important factors in Kymera Therapeutics' subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Kymera Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Kymera Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements###


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