Estuary Biotherapeutics, Inc. has launched with $103m in total committed financing.
The financing will support advancement of the company’s two lead programmes, EST-201 and EST-101, through clinical proof of concept and to further develop its kidney-targeting platform. Estuary’s lead programmes are designed to target the most common genetic subtypes of ADPKD, an inherited, lifelong, progressive disease characterised by the growth of cysts in both kidneys. Over time, these cysts enlarge, displacing functioning tissue until the organs fail, requiring dialysis or transplant.
“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. 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.”
Estuary’s programmes build on research from its scientific co-founders, Stefan Somlo and Michael Caplan of Yale School of Medicine.
Somlo established the in vivo reversal biology underlying Estuary’s approach, demonstrating that restoring polycystin expression in kidneys with established cystic disease can reverse both the structural and functional hallmarks of disease in mice. Caplan further demonstrated a compact functional region of the polycystin-1 (PC1) protein is sufficient to suppress cystic disease in mice, providing the scientific basis for an adeno-associated virus (AAV)-based approach to ADPKD-PKD1.
The company said the discoveries have redefined what’s possible from a therapeutic standpoint: moving beyond slowing disease progression to potentially halting or reversing it, with distinct therapies that have the potential to treat all patients with a given genetic mutation. Estuary is also advancing locally delivered genetic medicines for ADPKD, starting with its two lead programmes.
EST-201 is a full-length PKD2 gene therapy delivered through AAV, which will be evaluated in patients with ADPKD with a PKD2 mutation and is anticipated to enter the clinic in 2027. EST-101 is a gene therapy delivering a PC1-derived functional region via the same AAV as EST-201. EST-101 will be evaluated in patients with ADPKD with a PKD1 mutation and is anticipated to enter the clinic in 2028.
While other ADPKD therapies target pathways downstream of the causal biology, EST-201 and EST-101 are designed to address the underlying genetic root cause directly, using a potentially one-time, locally delivered AAV to transduce individual kidney epithelial cells, with the goal of restoring polycystin protein levels across the entire nephron. This kidney-confined approach is designed to avoid many of the challenges that have complicated the overall risk-benefit profile of systemically delivered AAV gene therapies to date. Further, Estuary plans to extend its leadership position by further expanding its pipeline to target both monogenic and common kidney diseases.
A $93m Series A was led by RA Capital Management and included 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). 4BIO Capital and GV, which co-led the company’s $10m seed financing, also participated in the Series A.