Estuary Biotherapeutics, a California-based genetic medicines developer, officially launched on Friday, backed by nine figures worth of funding and a management team stocked with former Biogen leaders.
Forged in 2022, Estuary is built around research conducted by its scientific co-founders Stefan Somlo and Michael Caplan, both professors at the Yale School of Medicine. Somlo’s lab has made major discoveries about an inherited disorder where certain genetic mutations cause cysts that progressively damage the kidneys and often lead to renal failure. Through a landmark study published in the journal Nature Genetics, Somlo’s team found that, in mice, reactivating proteins called polycystins could shrink the cysts and reverse kidney inflammation and scarring.
And in Caplan’s lab, scientists determined that only a small piece of the full polycystin protein is needed to suppress this “autosomal dominant polycystic kidney disease.” Those findings suggest that helpful genetic material can be successfully packaged up and delivered to the kidneys with the standard “viral vectors” used for gene therapy.
Taken together, Estuary believes its technology and expertise will bring about the first-ever treatment that can halt or reverse, rather than just slow, the most common inherited kidney disorder. Estimates hold that ADPKD affects about 1 in every 400 to 1,000 people. Just one drug, tolvaptan, is specifically approved to treat it.
Patients “are still awaiting a therapy that can transform the course of their disease,” said Wayne Sackett, Estuary’s co-founder and CEO, in a statement.
The focus now, Sackett added, is solving “the most crucial remaining barrier to kidney gene therapy: delivery.”
Estuary’s lead programs target the two main drivers of ADPKD, though in different ways. The first, codenamed EST-201, is designed to deliver a functional, full-length version of a polycystin-producing gene known as PKD2. The second, EST-101, provides just the most useful bits of the protein made by the PKD1 gene. They are meant to be one-time, locally administered treatments that restore polycystin levels in the microscopic components that make up the kidneys.
Estuary expects these therapies to enter human testing in 2027 and 2028, respectively. Fueling their development is a $93 million Series A round that was led by prominent life sciences investor RA Capital Management and saw participation from Deep Track Capital, 4BIO Capital, Alphabet’s GV venture arm and several other backers. Two of those firms co-led a $10 million seed financing for the company as well.
Biogen’s early-stage investment arm was also involved in the bigger round. At least three members of Estuary’s management team previously worked at Biogen: Jeremy Duffield, who was a vice president of R&D; Kiley Keelin, who was a director of regulatory affairs; and Uptal Patel, who was head of the big biotech’s west coast hub and, formerly, chief medical officer at HI-Bio. Biogen acquired HI-Bio for nearly $1.2 billion in 2024.
Estuary’s board includes Sackett, RA Managing Director Emily Minkow and 4BIO partner Owen Smith. The company’s fourth co-founder, Xavier Anguela, was a vice president of gene therapy at Eli Lilly and had held scientific leadership roles at Nava Therapeutics, Spark Therapeutics and Bayer-acquired AskBio. Among Estuary’s advisers are Frank Czerwiec, who led the clinical development of tolvaptan, and Jeff Marrazzo, co-founder and former CEO of Spark Therapeutics, which sold to Roche for almost $5 billion in 2019.
Estuary isn’t the only drug developer to set its sights on ADPKD. Last year, Swiss pharmaceutical giant Novartis agreed to acquire Regulus Therapeutics for $800 million to take control of an experimental, RNA-targeting medicine that had shown promising signals in an early-stage clinical trial. Only a few months after that deal announcement, Renasant Bio emerged from stealth mode. The startup, which hopes to treat ADPKD through ion channel research, came equipped with $55 million in seed funding from prominent investors 5AM Ventures, Atlas Venture and OrbiMed.
Sanofi had a candidate, too, though it flunked in a vital study.
