私营公司 Estuary Biotherapeutics 完成1.03亿美元融资出隐身，推进ADPKD肾病AAV基因疗法EST-201/EST-101

Estuary Biotherapeutics has swum out of stealth with $103 million in funding to power a pair of gene therapies into clinical trials for an inherited kidney disorder.
Having already secured $10 million in seed funding, the biotech has now raised a $93 million series A led by RA Capital Management. Other investors included Deep Track Capital, Biogen New Ventures and UPMC Enterprises. 4BIO Capital and GV, which co-led the $10 million seed financing, also participated.
The money will be used to generate clinical proof-of-concept data for EST-201 and EST-101, two gene therapies targeting the root cause of autosomal dominant polycystic kidney disease (ADPKD). The program is built on research from the labs of two professors at the Yale School of Medicine, Stefan Somlo, M.D., and Michael Caplan, M.D., Ph.D.


Alongside Somlo and Caplan, the company's other founders are Xavier Anguela, Ph.D.—vice president for gene therapy at Eli Lilly—and Estuary's CEO Wayne Sackett.
ADPKD, a genetic disease that causes cysts to grow large enough to affect kidney function, is the most common inherited kidney disease. Around 90% of patients with the disease harbor mutations in one of two genes, PKD1 or PKD2. Both genes usually work together to form an ion channel complex on the surface of kidney and liver cells that regulate the flux of ions and control downstream signaling pathways involved in cell proliferation and formation of cysts.
Mutations in either PKD genes disrupt this complex, leading to impaired ion signaling and increased cyclic AMP, causing uncontrolled cellular proliferation and the fluid-filled kidney cysts seen in ADPKD.

“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,” CEO Sackett said in the release. “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.”
EST-201 is a full-length PKD2 gene therapy delivered through a modified adeno-associated virus (AAV). Estuary's ambition is to take EST-201 into the clinic next year.
Meanwhile, EST-101 uses the same AAV delivery technology to deliver a polycystin-1 (PC1)-derived functional region, the protein encoded by the PKD1 gene, with hopes to enter the clinic in 2028. The AAVs will be locally delivered to transduce kidney epithelial cells with the goal of targeting the organ of interest and restoring protein levels across the entire nephron.
“We are developing our programs as potentially one-time, locally delivered AAV gene therapies with the goal of achieving long-term, durable gene expression,” Sackett told Fierce. “If successful, we believe this approach could move treatment beyond slowing disease progression toward potentially halting or reversing it.”
Otsuka Pharmaceutical’s tolvaptan is the only FDA-approved drug in the ADPKD space. The arginine vasopressin V2-receptor antagonist is designed to lower the elevated levels of cyclic AMP in kidney cells, reducing cyst cell proliferation, fluid secretion and overall kidney volume enlargement.
Last year, Novartis committed another $1.7 billion to its ambition to become a kidney disease leader by buying Regulus Therapeutics for its phase 3-ready oligonucleotide therapy farabursen, which is being developed for ADPKD.