Eli Lilly and Seed Therapeutics Enter $790M Collaboration to Develop Novel Ubiquitin-Mediated Targeted Protein Degradation Therapies

New York – November 12, 2020: Seed Therapeutics, Inc. (a subsidiary of Zai Lab Limited, hereinafter referred to as “Seed”), a global R&D company focused on the development of unique “molecule glue” therapeutics designed to target and degrade disease-causing proteins, today announced that it has entered into a research collaboration and license agreement with Eli Lilly and Company (“Lilly”) to jointly research and develop a class of new chemical entities (NCEs) that exert therapeutic effects through targeted protein degradation (TPD).

Leveraging technologies in the field of targeted protein degradation (TPD), hundreds of proteins associated with human diseases that were previously considered undruggable can be transformed into drug targets. Seed Therapeutics has independently pioneered a technology known as “molecular glues,” which harnesses the ubiquitous protein degradation machinery present in all cells to identify and degrade pathogenic proteins that are typically not regarded as viable drug targets. More importantly, Seed Therapeutics’ molecular glue programs focus on new chemical entities (NCEs) with chemical properties more conducive to druggability. This approach differs from the development strategy employed for proteolysis-targeting chimeras (PROTACs), and is designed to maximize the likelihood of successful drug development in subsequent research stages.

Under the terms of the agreement, Eli Lilly will pay Seed Therapeutics milestone payments totaling up to $790 million, including an upfront payment of $10 million. Meanwhile, Seed Therapeutics will also receive sales royalties based on the net sales of the products during the collaboration period. In addition, Eli Lilly will make a $10 million equity investment in Seed Therapeutics.

The R&D team of Seed Therapeutics is led by Avram Hershko, the 2004 Nobel Laureate in Chemistry and discoverer of the ubiquitin-mediated targeted protein degradation system, and Dr. Lan Huang, CEO of Seed Therapeutics. The R&D team at Seed Therapeutics has accumulated profound technical expertise in this field over many years: On November 12, 1999, Dr. Lan Huang solved the first structure of an E3 ligase in the protein degradation system worldwide and published the findings in a scientific journal (Note 1); exactly 21 years later to the day, a collaboration agreement was signed with Eli Lilly and Company. The core technical experts also include Professor Ning Zheng and Professor Michele Pagano. In 2014, Professor Ning Zheng first solved the innovative structure of CRL E3 ligases and published the results in Nature Reviews Drug Discovery (Note 2). Building on this foundation, the R&D team has engaged in continuous development and accumulation of expertise for over a decade, seeking to construct more unique compounds as potential therapies for various diseases.

“This agreement enables us to continue advancing our company’s innovative platform to develop novel molecules targeting human disease-causing proteins,” added Dr. Lan Huang. “Our collaboration with Eli Lilly serves as a catalyst, empowering Seed Therapeutics’ world-class global team to initiate the development of our TPD product pipeline, aimed at treating diseases that are refractory to conventional therapies.”

Dr. Utpal Singh, Vice President of Drug Discovery Chemistry at Eli Lilly, stated, “Our collaboration with Seed Therapeutics in preclinical research and product licensing enables both parties to comprehensively, rapidly, and deeply explore the application prospects of targeted protein degradation, thereby supporting further drug development in this field.” The novel therapy jointly advanced by the two parties will utilize novel E3 ligases to induce specific protein degradation, thereby functionally inhibiting pathogenic proteins or those associated with resistance to other therapies. This breakthrough development strategy is expected to significantly benefit thousands of patients suffering from serious diseases.

Note 1: Huang L, et al. Structure of an E6AP-UbcH7 complex: Insights into ubiquitination by the E2-E3 enzyme cascade. Science 286:1321–1326 (1999)

Note 2: Skaar, J. R., Pagan, J. K. & Pagano, M. SCF ubiquitin ligase-targeted therapies. Nat. Rev. Drug Discov. 13, 889–903 (2014)

Note: The original text has been abridged.