Estuary Biotherapeutics has launched with $103 million in committed financing to develop genetic medicines targeting serious kidney diseases, beginning with autosomal dominant polycystic kidney disease. The financing includes a $93 million 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 financing, also participated.
The proceeds will support Estuary’s two lead programs, EST-201 and EST-101, through clinical proof of concept and further development of the company’s kidney-targeting platform. Both programs are designed to address the two most common genetic subtypes of ADPKD, an inherited disease characterized by progressive cyst growth in the kidneys.
EST-201 is a full-length PKD2 gene therapy delivered through an adeno-associated virus and is intended for patients with ADPKD caused by a PKD2 mutation. Estuary anticipates bringing the program into the clinic in 2027.
EST-101 delivers a functional region derived from the polycystin-1 protein using the same AAV approach and is intended for patients with PKD1 mutations. The company expects that program to enter the clinic in 2028.
Rather than targeting downstream pathways, Estuary’s programs are designed to address the underlying genetic causes of ADPKD. The company plans to use locally delivered AAV to target kidney epithelial cells and restore polycystin protein levels across the nephron while limiting systemic exposure.
The programs build on research from scientific co-founders Dr. Stefan Somlo and Dr. Michael Caplan of Yale School of Medicine. Their work demonstrated the potential to reverse structural and functional manifestations of polycystic kidney disease in preclinical models and helped establish the scientific basis for the company’s gene therapy approach.
ADPKD affects more than eight million people worldwide and is one of the most common inherited kidney diseases. More than 90% of patients have mutations in either PKD1 or PKD2. Estuary estimates initial U.S. treatment populations of approximately 100,000 to 140,000 rapidly progressing patients with PKD1 mutations and 10,000 to 15,000 with PKD2 mutations.
KEY QUOTES:
“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. 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. By pioneering fit-for-purpose local administration and an efficient global development strategy, our team is moving with urgency to bring these important medicines into the clinic.”
Wayne Sackett, Co-Founder and CEO of Estuary Biotherapeutics
“Estuary’s programs have the potential to transform the care of patients with ADPKD. The differentiated approach pairs a known gene therapy modality with focal, kidney-directed delivery designed to reach the nephron directly. Combined with compelling science demonstrating the potential to reverse disease, we believe this approach could fundamentally change what is possible for patients, and we are excited to support the team as it advances toward the clinic.”
Emily Minkow, Managing Director at RA Capital Management
“4BIO exists to back companies developing breakthrough therapies that can change the course of disease for patients who lack good options. Having partnered with Estuary early in its lifecycle by co-leading the company’s seed financing and helping shape the initial business plan, we have seen firsthand how effectively the team has translated ambitious science into a focused development strategy.”
Owen Smith, Partner at 4BIO Capital
