Tolvaptan

A new biotech is stepping into the spotlight with a vision to transform how a common inherited kidney disease is treated. Berkeley-based Renasant Bio raised $54.5 million in seed funding to develop the first truly disease-modifying therapies for autosomal dominant polycystic kidney disease (ADPKD), a condition marked by the progressive formation of fluid-filled cysts in the kidneys that can ultimately lead to end-stage renal failure.The financing round was co-led by founding investor 5AM Ventures, with backing from Atlas Venture, OrbiMed and Qiming Venture.ADPKD is caused by mutations in the genes that encode polycystin proteins PC1 and PC2 that are needed for normal kidney function. When these proteins misfold or malfunction, fluid-filled cysts grow in the kidneys, eventually impairing organ function. Currently, the only approved treatment is tolvaptan, which can slow cyst growth, but doesn't tackle the root cause of the disease.Renasant wants to change that. The company is developing oral small molecule correctors and potentiators that target the underlying protein dysfunction across the disease's highly heterogeneous mutation spectrum, where no single mutation affects more than 2% of patients."Our preclinical data show that we can restore polycystin trafficking across a broad range of ADPKD mutations," CEO Emily Conley told FirstWord. "That gives us confidence that our approach has the potential to benefit a wide spectrum of patients, regardless of their specific genetic variant."Renasant's lead corrector programme aims to stabilise and properly fold the PC1 and PC2 proteins, promoting proper cellular trafficking to help restore kidney function. The company has also developed proprietary assays to measure polycystin trafficking and other key mechanisms, tools it believes will enable a precision-guided approach to developing novel therapies for ADPKD.Conley, who previously served as CEO at Federation Bio after a decade in business development as an early employee at personal genetic testing company 23andMe, said Renasant expects to nominate a development candidate from the corrector programme in 2026, with the goal of advancing into the clinic within a few years.Meanwhile, Renasant is simultaneously advancing discovery efforts for its first-in-class potentiator programme, which enhances ion flux through the polycystin channel. "Correctors and potentiators can act as stand-alone therapies, or they can be combined for synergistic effect," the company said in a release Thursday.In a recent big-ticket deal in the space, Novartis acquired Regulus Therapeutics for approximately $800 million to gain access to farabursen, an miR-17–targeting oligonucleotide that recently completed a Phase Ib multiple-ascending dose trial in ADPKD (see – Spotlight On: Novartis doubles down on kidney disease).

The drug industrys efforts to develop a treatment for a rare kidney condition known in shorthand as ADPKD have come in fits and starts.People with ADPKD, or autosomal dominant polycystic kidney disease, can use an Otsuka drug, Jynarque, that U.S. regulators cleared in 2018 to slow the decline in organ function thats brought on by the condition.They have few other good options, however. Sanofi was developing a drug, venglustat, around the same time as Jynarques approval, but stopped clinical testing in 2021 after negative study results.The disease stayed on some drugmakers radars. In April, Novartis agreed to pay $800 million to acquire Regulus Therapeutics and an experimental therapy, farabursen, that the Swiss pharmaceutical company said showed promising clinical efficacy and safety. And a new biotechnology company launching Thursday is trying its hand at developing another.Called Renasant Bio, the company raised $54.5 million in seed financing from blue-chip investors 5AM Ventures, Atlas Venture, OrbiMed and Qiming Venture Partners USA.Renasant is the brainchild of a pair of University of California, San Francisco professors, Jeremy Reiter and Markus Delling, who sent 5AM a cold email in 2022 with a pitch built from their research into the diseases biology. It's now headed up by Emily Conley, a Stanford University scientist who previously led Federation Bio, a gut microbiome biotech, and oversaw business development at the genetic testing company 23AndMe.Renasant draws inspiration from drug development in cystic fibrosis. While cystic fibrosis is a disease of the lungs, both conditions are linked to malformed ion channels. As in cystic fibrosis, where drugs like Vertex Pharmaceuticals Trikafta work by correcting and boosting the activity of those channel proteins, Renasant believes it can develop corrector and potentiator treatments that restore and open up the channels relevant to ADPKD.What a corrector does is it helps that misfolded protein fold properly, said Conley. Once the protein gets into the right shape, then it can go where it needs to go, and then the potentiator holds the channel open.We know what's broken, Conley added. If we can fix it with correctors and potentiators, then we could have this very dramatic effect on patient outcomes.Renasants lead drug candidate, which is currently in preclinical testing, is a small molecule corrector the company hopes can work in patients with any of the wide range of mutations that cause ADPKD. While Renasant envisions this molecule working as a standalone treatment, its also developing a potentiator that could be used in tandem to prevent cysts from forming or growing in the kidney.The company plans to enter clinical testing in the next few years.Overseeing Renasants scientific work is Gus Gustafson, a veteran of large pharmaceutical firms like Johnson & Johnson and Merck & Co. Its board of directors is led by Natalie Holles, the former CEO of Third Harmonic Bio, and includes Charlotte McKee, chief medical officer of cystic fibrosis drugmaker Sionna Therapeutics, as well as venture investors.Renasant has assembled the right team, with years of research experience in polycystic disease that has informed the right scientific approach, Deborah Palestrant, a partner at 5AM, which incubated the biotech, said in a statement.Renasant estimates that some 12 million people have ADPKD worldwide. In addition to Novartis and Regulus, Vertex is also developing a drug for the disease. '