The U.S. Food and Drug Administration (FDA) has granted clearance to Cereno Scientific to launch its global phase 2b trial of CS1 for the treatment of pulmonary arterial hypertension (PAH). The FDA has previously granted CS1 Orphan Drug Designation and Fast Track Designation.
CS1 is an oral therapy (generic name: valproic acid) that targets key disease-driving mechanisms, such as vascular remodeling, fibrosis and inflammation. Acting through epigenetic modulation, it blocks histone deacetylases (HDACs) and modifies gene activity without altering the DNA.
“Our goal with CS1 is to address the underlying mechanisms that drive PAH, not simply manage symptoms,” said Rahul Agrawal, CMO and head of R&D at Cereno Scientific, in a press release. “The planned phase 2b trial is designed to determine the optimal dose for a phase 3 trial and to assess CS1’s potential to meaningfully reduce pulmonary vascular resistance and improve functional capacity when added to today’s standard therapies.”
In phase 2a of the clinical trial, the developmental drug was safe and well-tolerated as a standard therapy add-on in 25 adults with PAH. CS1 also stabilized or improved measures associated with disease severity and mortality risk in most participants.
“Building on the encouraging signals observed in our phase 2a study, we believe CS1 could offer a differentiated and disease-modifying approach for patients living with this rare and fatal disease,” Agrawal said.
The trial, “A Phase 2b, Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study to Compare the Efficacy and Safety/Tolerability of CS1 Versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH),” will include approximately 126 patients with PAH who are stable on background therapy.
During the first 36 weeks of treatment, participants will randomly receive once-daily capsules of CS1 at one of two dose levels or matching placebo. At week 36, all participants will be re-randomized: those initially receiving CS1 will be assigned to either continue their CS1 dose or switch to a placebo, while those initially receiving placebo will be assigned to one of the two CS1 dose groups. Participants will complete a second treatment period and follow-up.
This design ensures that all participants will receive active treatment at some point of the trial and allows researchers to further evaluate the drug’s previously observed disease-modifying signals in a larger, controlled group. The total study duration is 60 weeks, including screening and follow-up.
The phase 2b study will evaluate the effects of CS1 on pulmonary vascular resistance (PVR) at week 36 via right-heart catheterization, changes in six-minute walk distance and a range of additional evaluations, including measures of heart function, biomarker changes, clinical worsening, patient-reported outcomes and pharmacokinetics.
The dose-finding trial is expected to be conducted across 10 to 12 countries in the United States, Europe and South America at approximately 65 investigative sites.
“With Fast Track Designation and global site participation, we see clear opportunities to accelerate our path toward a potential disease-modifying therapy that can enhance and extend the lives of patients with PAH,” said Cereno Scientific CEO Sten R. Sörensen.
Currently, the Swedish biotech company is advancing global study-start activities, including site selection, regulatory submission in participating countries and operational readiness. First patient in (FPI) is planned for Q2 2026, with top-line results anticipated around Q4 2028.
