Having spent nearly a decade at NASH-focused NGM Bio, Aetna Wun Trombley knew it would take some really compelling science to lure her away: “I was at NGM for nine years and I still love that company,” she told FierceBiotech. “Obviously, it would have to be something very special for me to even consider an opportunity outside of NGM.”
In March, she made the leap, leaving her post as NGM’s chief operating officer and president to take the helm of a mystery biotech. Months later, that mystery is ready to reveal itself: Lycia Therapeutics is launching out of Versant Ventures with $50 million to develop drugs targeting protein degradation in a new way.
Other companies are working to expand the pool of druggable proteins by taking advantage of the body’s protein degradation machinery, which tags unneeded or damaged proteins for destruction. But there remain proteins that elude those players.
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“A lot of companies are developing PROTAC-type [proteolysis-targeting chimera] molecules and are really advancing in expanding the druggable proteome,” she said. “But even with all of those advances, PROTACs rely on machinery that’s inside the cell, in the cytosol.”
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That means proteins outside the cell, either on cell surfaces or circulating in the blood, are out of reach. Enter Lycia’s lysosomal-targeting chimeras, LYTACs. Based on the work of Carolyn Bertozzi, Ph.D., a professor of chemistry and an investigator at the Howard Hughes Medical Institute at Stanford University, LYTACs are designed to “grab” proteins from cell membranes, or proteins that are in circulation, and “drag” them into the cell, where they are degraded by the lysosome.
LYTACs are bifunctional molecules with two arms, Trombley said. One arm binds to a lysosomal target receptor, while the other arm binds to the target protein. Lycia can mix and match the arms, so it can target receptors that are expressed in specific tissues—or, more broadly, across many different tissues—with the appropriate molecule to grab the protein target, including antibodies, small molecules and peptide inhibitors.
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Now that it’s coming out of stealth, Lycia will work to expand its LYTAC platform, develop a pipeline, build its team in San Francisco and consider early-stage partnerships to advance its work.
The company is looking broadly at applications for LYTACs, separating them into three main buckets: diseases where membrane or circulating proteins are hard to drug, diseases that are driven by protein aggregation and diseases in which autoantibodies play a role.
Lycia’s approach could be useful in cancers where patients develop resistance against treatments such as tyrosine kinase inhibitors, or it could help treat autoimmune diseases in which the body produces antibodies that attack its own tissues. It could even be used to make gene therapies accessible to more people. By Trombley’s count, about half of patients can’t undergo gene therapy delivered by adeno-associated viruses because they are immune to the viral vectors.
“We have a few programs in each of those buckets that we are looking to advance development candidates from. And we can imagine that we will be building out a lot of the platform as we are doing that,” Trombley said. “I think that’s a lot for our team to work on, so I think it’s important for a small company to focus. We can always expand as we go.”