NEWTON, Mass. — Estuary Biotherapeutics, a biotechnology company developing genetic medicines for serious kidney diseases, has launched with $103 million in committed financing to advance experimental gene therapies targeting the underlying causes of inherited kidney disease.
The financing includes a $93 million Series A round 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 autosomal dominant polycystic kidney disease (ADPKD).
Existing investors 4BIO Capital and GV, which co-led the company’s $10 million seed financing, also participated.
Estuary plans to use the funding to advance its two lead programs, EST-201 and EST-101, through clinical proof of concept and expand its kidney-targeting gene therapy platform.
The programs are designed to treat ADPKD, a progressive inherited condition characterized by the development of cysts in both kidneys. As the cysts enlarge, they damage healthy kidney tissue and can eventually lead to kidney failure requiring dialysis or transplantation.
“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 of Estuary.
“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,” Sackett added.
The company’s technology builds on research by scientific co-founders Dr. Stefan Somlo and Dr. Michael Caplan of Yale School of Medicine.
Somlo demonstrated in mice that restoring polycystin protein expression in kidneys with established cystic disease could reverse structural and functional damage. Caplan subsequently identified a functional region of the polycystin-1 protein capable of suppressing cyst formation in mice, providing a foundation for developing gene therapies targeting mutations in the PKD1 gene.
Estuary’s lead candidate, EST-201, uses an adeno-associated virus (AAV) to deliver a functional PKD2 gene to patients with mutations in that gene. The company expects the program to enter clinical development in 2027.
Its second program, EST-101, uses the same viral delivery platform to introduce a functional region derived from polycystin-1 in patients with PKD1 mutations. Clinical development is expected to begin in 2028.
Unlike existing treatments focused on slowing disease progression, Estuary’s experimental therapies aim to address the underlying genetic causes of ADPKD. The company is developing a localized delivery method intended to target kidney cells directly while reducing potential complications associated with systemic gene therapy.
The approach remains investigational, and its ability to halt or reverse kidney disease in humans has not yet been established.
“Estuary’s programs have the potential to transform the care of patients with ADPKD,” said Emily Minkow, managing director at RA Capital Management. “The differentiated approach pairs a known gene therapy modality with focal, kidney-directed delivery designed to reach the nephron directly.”
The company also plans to expand its pipeline beyond ADPKD to address other inherited and common kidney diseases.
Estuary’s leadership team includes Chief Scientific Officer Dr. Jeremy Duffield, Chief Medical Officer Dr. Uptal Patel, Senior Vice President of Chemistry, Manufacturing and Controls Christopher Morrison, and Head of Regulatory Kiley Keelin.
Its board of directors includes independent chairman Jake Bauer, Minkow, Owen Smith of 4BIO Capital and Sackett.
The company’s scientific and medical advisers include Spark Therapeutics co-founder Jeff Marrazzo, gene therapy specialist Karen Kozarsky, former Sanofi clinical development executive Vijay Modur, nephrologist Frank Czerwiec, Mass General Brigham nephrologist Lou Brenner and former Eli Lilly and Janssen scientist Matthew Breyer.
Estuary said its longer-term objective is to develop potentially one-time genetic treatments capable of providing lasting benefits to patients with kidney disease.
