Cereno Scientific has reported encouraging 12-month safety and clinical observations for CS1 in pulmonary arterial hypertension ahead of a planned global Phase 2b trial.

Cereno Scientific has reported additional analyses from its 12-month Expanded Access Program (EAP) evaluating lead drug candidate CS1 in patients with pulmonary arterial hypertension (PAH), with most patients completing treatment maintaining or improving their clinical status while demonstrating a favourable long-term safety profile.

The EAP, conducted under an FDA protocol, enabled patients who had completed the company’s earlier Phase 2a trial to continue receiving CS1 while providing additional long-term safety and tolerability data.

The programme enrolled 10 patients, six of whom completed 12 months of treatment. Four patients did not complete the programme, with none of the discontinuations considered related to CS1.

Two patients stopped treatment after developing atrial fibrillation and being prescribed anticoagulation therapy, which was not permitted under the EAP protocol. The company said atrial fibrillation is a recognised complication of PAH and was not considered related to CS1. One patient withdrew consent and another was lost to follow-up.

Among patients completing the programme, five of six maintained or improved their NYHA/WHO functional class, while five of six also demonstrated stable or improved NT-proBNP biomarker levels. Three patients improved their six-minute walk distance, three showed stable or improved REVEAL Risk Score 2.0, and three of five evaluable patients had stable or reduced mean pulmonary arterial pressure measured using CardioMEMS.

Because patients entered the EAP between six and 25 months after completing the Phase 2a study, and background therapies changed during that period, Cereno said the findings should be regarded as real-world clinical observations rather than controlled efficacy data.

Rahul Agrawal, chief medical officer and head of research and development at Cereno Scientific, said: “What is particularly meaningful to me is that these additional analyses provide important long-term clinical context for CS1 in PAH. The EAP further reinforces the favorable safety and tolerability profile observed in the Phase IIa trial and shows that patients completing 12 months of treatment were generally stable or improved across several clinically relevant measures. While conclusions regarding efficacy cannot be drawn from this small, non-controlled study, maintaining clinical stability over time in a progressive and fatal disease such as PAH is especially encouraging. These findings provide valuable momentum and support our continued conviction in the potential of CS1 as we advance the program into the planned Phase IIb study.”

CS1 is an HDAC inhibitor being developed as a potential disease-modifying treatment for PAH. The therapy is designed to target underlying disease mechanisms including vascular remodelling, fibrosis and inflammation, while being administered as a once-daily oral treatment.

The EAP also demonstrated that CS1 could be administered alongside approved PAH therapies, including sotatercept, supporting plans to investigate the candidate as an add-on therapy in future studies.

Cereno said the long-term safety observations strengthen confidence ahead of its planned global placebo-controlled Phase 2b trial, which is expected to enrol approximately 126 patients across around 65 investigational sites in 10 to 12 countries in North America, Europe and South America.

The study, developed in consultation with the FDA, will evaluate the safety, tolerability and efficacy of CS1 alongside standard of care while identifying the optimal dose for a future Phase 3 programme.