New PAH therapy to target disease drivers in upcoming global trial
CS1 will be tested for its effects on lung vessel resistance and exercise ability
The U.S. Food and Drug Administration (FDA) has cleared Cereno Scientific’s request to launch a global Phase 2b trial of CS1, an oral therapy for people with pulmonary arterial hypertension (PAH).
The company expects to begin enrolling patients in the second quarter of 2026, with top-line data anticipated around late 2028. The trial is expected to enroll about 126 people with PAH who are stable on their current therapy, across 65 sites in the U.S., Europe, and South America.
Cereno is now preparing for global study-start activities, including site selection and regulatory submissions in participating countries.
“Our goal with CS1 is to address the underlying mechanisms that drive PAH, not simply manage symptoms,” Rahul Agrawal, MD, Cereno’s chief medical officer and head of research & development, said in a company press release.
Why CS1 is designed to address underlying PAH biology
PAH occurs when the pulmonary arteries, the blood vessels that carry blood from the heart to the lungs, become narrowed and stiff, restricting blood flow and raising pressure in the lungs. PAH symptoms include shortness of breath, dizziness, and fatigue.
Pulmonary vascular remodeling, which refers to structural changes in the walls of the lung blood vessels caused by abnormal cell growth, is a major process that drives arterial narrowing in PAH.
CS1 is a formulation of valproic acid, a medication approved to treat seizures. In PAH, it is designed to counteract vascular remodeling by inhibiting histone deacetylases (HDACs), enzymes that reduce gene activity. This approach, called epigenetic modulation, adjusts gene activity without altering the DNA itself.
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.
In a Phase 2a clinical trial (NCT05224531) that tested CS1 as an add-on to standard therapy in 25 adults with PAH, the treatment was safe and well tolerated, which was the study’s main goal. Most participants also experienced stabilization or improvement in measures associated with disease severity and mortality risk, along with signals of reduced pulmonary arterial pressure.
Participants who completed the trial were able to continue receiving CS1 through an expanded access program (NCT06321705), which is collecting long-term data on safety and potential effectiveness.
During the first 36 weeks (about nine months) of the Phase 2b trial, participants will be randomly assigned to receive one of two CS1 doses or a placebo, taken once daily. After week 36, those initially on CS1 will either continue their dose or switch to placebo, while participants who started on the placebo will be assigned to one of the two CS1 dose groups.
What the Phase 2b trial will measure
The study will assess CS1’s effect on pulmonary vascular resistance — the resistance the heart must overcome to pump blood through the lungs — as well as changes in the six-minute walk distance, a standard measure of exercise capacity. Additional assessments will track biomarker changes, heart function, clinical worsening, and patient-reported outcomes.
“The planned Phase IIb trial is designed to determine the optimal dose for a Phase III trial and to assess CS1’s potential to meaningfully reduce pulmonary vascular resistance and improve functional capacity when added to today’s standard therapies,” Agrawal said.
“Receiving FDA clearance to proceed with our Phase IIb study is a significant catalyst for Cereno,” said Sten R. Sörensen, Cereno’s CEO. “This milestone strengthens the commercial potential of CS1, [and] supports our positioning as a leader in epigenetic modulation for rare cardiovascular diseases.”
The FDA has granted CS1 both fast track and orphan drug designation, which are intended to support the development of therapies for serious and rare diseases with unmet medical needs.
“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,” Sörensen said.
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