CS1, an HDAC Inhibitor, Appears to Reverse Remodeling in PAH

Cereno Scientific says its lead therapeutic candidate, CS1, appears to be able to reverse vascular remodeling associated with pulmonary arterial hypertension (PAH). The findings are based on new data from the company’s phase IIa trial.

“All in all, the key results are we have met the primary endpoint that our CS1 is safe and well-tolerated,” said Rahul Agrawal, M.D., the company’s chief medical officer, during a company webcast announcing the findings.

In addition to meeting its primary endpoints, the data also showed participants experienced improvements in right-ventricular function and in risk parameters.

CS1 is a new formulation of valproic acid that inhibits histone deacetylase (HDAC). Sten R. Sörensen, the company’s CEO, noted that the therapy has long been used to treat epilepsy. However, he said the therapy also holds the potential to modify cardiovascular diseases like PAH through epigenetic modulation.

The trial was a 12-week study in which 21 of 25 enrolled patients were evaluated to test the therapy’s safety and tolerability. There were no serious drug-related adverse events, no hospitalizations or deaths, and no significant abnormalities in laboratory parameters.

The investigators said the trial showed that CS1 led to improved REVEAL 2.0 risk scores in 9 of 21 patients and improved or stabilized risk scores in 15 patients. The New York Heart Association functional class improved in 7 patients, and 18 saw either improvements or stable scores. Two-thirds of patients had improved sustained mean pulmonary arterial pressure reductions.

Sörensen said the data suggest CS1 could be an important player in the PAH market.

“We believe that our drug, CS1, will transform treatment for PAH,” he said. "[PAH] is rare, fatal and very progressive, and there is a high unmet need to address this vascular remodeling that is happening.”

Part of the reason Sörensen sees market potential is that the PAH armamentarium remains relatively small and the disease remains incurable. However, the pipeline of PAH therapies appears to be growing. A report published last year in Drugs in R&D found more than a dozen novel therapies under clinical investigation as possible treatments for PAH. One of those therapies, the subcutaneously injected Winrevair (sotatercept), was approved last year.

Sörensen and Agrawal noted that CS1 is an oral therapy, a fact that they believe will give the drug an edge in the marketplace should it eventually emerge from trials with a favorable regulatory decision.

“The market has a void of safe and well-tolerated treatments that are oral and are addressing the underlying pathophysiology of PAH,” Sörensen said.

In the webcast announcing the phase IIa results, Sörensen made clear that the company is eager to find partners to help get the therapy across the regulatory finish line.

“We’re looking forward to continued talks with potential partners here, and we’ll report back when we have something to say about that,” he said.

He said the company is interested in a variety of partnerships or a merger or acquisition.

In the meantime, Cereno is continuing its study of CS1. The company said it started an expanded access program for CS1 with 10 patients and expects to have interim data available in the second quarter of this year. They are also planning a sub-study of that expanded-access program in which they will evaluate the use of Fluidda Inc.’s non-invasive functional respiratory imaging technology to better visualize changes in small pulmonary arteries that occur during therapy. That study’s results are expected in the first quarter of 2026.

Cereno is also working on a phase 2b trial of CS1. The trial is expected to start in the first half of next year.