Gate Bioscience has inked a collaboration and license agreement with Eli Lilly to discover, develop, and commercialize molecular gate medicines, a new class of small molecules designed to eliminate disease-causing proteins at their source.
Gate, founded in 2021 and backed by Versant Ventures, a16z Bio + Health, ARCH Venture Partners, and GV, has placed its bets on developing molecular gates. These small molecules intervene at the Sec61 translocon, a channel used by newly synthesized proteins on their way out of the cell.
“The breakthrough came when we unlocked how to selectively stop one protein from passing through Sec61 without affecting other proteins that use the channel,” Jordi Mata-Fink, co-founder and CEO of Gate, told DDN. “Molecular gates eliminate disease-causing proteins by blocking their transit through a channel called Sec61, which newly made proteins use on their journey out of the cell.”
Recent advances in structural biology and computation have been key to moving the approach forward. “We take advantage of many newer technologies, from Cryo-EM to AI,” Mata-Fink said. “However, since our drugs are small molecules, we also benefit from all the accumulated expertise in conventional small molecule drug discovery.”
One advantage of the molecular gate approach is the ability to track its activity directly in early development. “We can tell if a molecular gate is working by detecting the elimination of the target protein,” Mata-Fink said. “We expect to be able to see this direct biomarker of drug activity very early in clinical development.”
Current strategies to eliminate secreted proteins often rely on biologic drugs such as antibodies or RNA-based therapies, which typically require injection, face limitations in tissue penetration, and can be difficult to manufacture and distribute. “In contrast, our small molecule medicines are pills that are easy for patients to take and the medicine can access all tissues in the body,” said Mata-Fink.
The collaboration gives Lilly access to Gate’s platform while providing Gate with resources to progress its first wave of candidates into development. Gate describes molecular gates as a new drug modality with the potential to address proteins that have remained out of reach for other therapeutic strategies.
Under the terms of the agreement, Gate will receive an upfront payment and an equity investment, with the potential to earn development, regulatory, and commercial milestones, as well as tiered royalties on future global sales. The total deal value could reach $856 million and Gate may also receive preclinical research support through Lilly ExploR&D, part of the company’s Catalyze360 initiative.
