Estuary Biotherapeutics launches with $103 million to advance gene therapies for severe kidney disease

Estuary Biotherapeutics, a company developing gene medicines for patients with severe kidney disease, announced on the 16th that it has secured $103 million in funding commitments to begin operations.

The total funding combines a $93 million Series A round led by RA Capital Management with a $10 million seed round co-led by 4BIO Capital and GV.

Participating in the Series A were Deep Track Capital, Biogen New Ventures, UPMC Enterprises, Pivotal bioVenture Partners, the National Kidney Foundation Innovation Fund, and a family office involved with autosomal dominant polycystic kidney disease (ADPKD) patients. 4BIO Capital and GV also continued their investment.

The funds will be used to advance the company's two lead programs, EST-201 and EST-101, to proof-of-concept in the clinic, and to develop a platform for delivering drugs to the kidneys.

ADPKD is a genetic, progressive disease in which cysts form in both kidneys. The cysts grow over time, displacing normal tissue, and eventually the kidneys lose function, requiring dialysis or transplantation.

According to the company, existing ADPKD treatments target pathways that are more "downstream" of the disease's root cause. In contrast, the company's two programs are designed to directly address the underlying genetic problem.

Both programs use adeno-associated virus (AAV) vectors administered directly to the kidneys to deliver genes into kidney epithelial cells, aiming to restore levels of the protein polycystin across the entire nephron. A single dose may be sufficient, and limiting administration to the kidneys is intended to avoid many of the issues that have arisen with systemically delivered AAV gene therapies.

EST-201 is a gene therapy that delivers the full-length PKD2 gene via AAV. It targets ADPKD patients with PKD2 mutations and is expected to enter clinical trials in 2027.

EST-101 delivers the functional region of the polycystin-1 (PC1) protein using the same AAV vector. It targets patients with PKD1 mutations and is expected to enter clinical trials in 2028.

Both programs are based on research by Stefan Somlo and Michael Caplan, scientific co-founders at Yale University School of Medicine. Somlo demonstrated in mice that restoring polycystin expression in advanced cystic kidneys reverses both structural and functional features of the disease. Caplan showed that a small region of the PC1 protein responsible for its function can suppress cystic disease in mice.

The company plans to expand its pipeline to cover both single-gene kidney diseases and more common kidney diseases.

BRIDGE, a media outlet operated by THE BRIDGE, reported this story.