Estuary Biotherapeutics launches with $103M and two AAV programs for inherited kidney disease

Estuary Biotherapeutics has launched with $103 million in committed financing to develop genetic medicines for serious kidney diseases, starting with autosomal dominant polycystic kidney disease (ADPKD). The financing includes a $93M Series A led by RA Capital Management, with participation from Deep Track Capital, Biogen New Ventures, UPMC Enterprises, Pivotal bioVenture Partners, the National Kidney Foundation Innovation Fund and a family office connected to an individual living with ADPKD. 4BIO Capital and GV, which co-led Estuary's $10 million seed round, also participated.

The proceeds are earmarked for Estuary's two lead programs, EST-201 and EST-101, which the company intends to take through clinical proof of concept, along with further development of its kidney-targeting platform. Both programs address the two most common genetic subtypes of ADPKD, an inherited condition marked by progressive cyst growth in the kidneys.

EST-201 is a full-length PKD2 gene therapy delivered via adeno-associated virus, intended for patients whose disease is caused by a PKD2 mutation; Estuary expects to bring it into the clinic in 2027. EST-101 delivers a functional region derived from the polycystin-1 protein using the same AAV approach, targeting PKD1 mutations, with a planned clinic entry in 2028.

Rather than going after downstream pathways, the company is designing its programs to address the underlying genetic causes of ADPKD. Estuary plans to use locally delivered AAV to target kidney epithelial cells and restore polycystin protein levels across the nephron while limiting systemic exposure — a delivery strategy the company frames as the field's key remaining obstacle.

"ADPKD is one of the world's most common genetic diseases, yet patients are still awaiting a therapy that can transform the course of their disease," said Wayne Sackett, co-founder and CEO. "We paired our scientific co-founders' landmark breakthroughs in disease biology with a dedicated and passionate team focused on solving the most crucial remaining barrier to kidney gene therapy: delivery."

The programs build on research from scientific co-founders Dr. Stefan Somlo and Dr. Michael Caplan of Yale School of Medicine, whose preclinical work demonstrated the potential to reverse structural and functional manifestations of polycystic kidney disease.

The market is large: ADPKD affects more than eight million people worldwide and is among the most common inherited kidney diseases, with more than 90% of patients carrying mutations in either PKD1 or PKD2. Estuary estimates initial U.S. treatment populations of roughly 100,000 to 140,000 rapidly progressing patients with PKD1 mutations and 10,000 to 15,000 with PKD2 mutations.