Cereno Scientific (CRNO) Study Update summary

Study background and objectives

• CS1 is a proprietary Class I HDAC inhibitor reformulation of valproic acid targeting pulmonary arterial hypertension (PAH), a rare and fatal disease with high unmet need.

• The phase 2A trial aimed to assess safety, tolerability, and exploratory efficacy in PAH patients, with a primary endpoint of safety and tolerability.

• Exploratory endpoints included standard PAH efficacy measures, validated risk scores, pharmacokinetics, and dose-finding.

• 25 patients were randomized across three dose levels at 10 US sites, with a 12-week treatment period; 21 were included in per protocol analyses.

• CS1 has orphan drug designation and market exclusivity in the US and Europe, with patent protection upon approval.

Mechanism and rationale

• CS1 acts as a class I HDAC inhibitor, targeting epigenetic modulation to address the root cause of PAH.

• HDAC inhibition is linked to reversing pathological vascular remodeling, antifibrotic, anti-inflammatory, pressure-reducing, and antithrombotic effects.

• The approach aims to modify disease progression rather than just provide symptomatic relief.

Phase 2A study design and results

• The study used Abbott's CardioMEMS system for hemodynamic monitoring.

• Primary endpoint of safety and tolerability was met: no serious drug-related adverse events, hospitalizations, or deaths; non-serious adverse events were dose-dependent and consistent with valproic acid profile.

• No clinically significant abnormalities in laboratory or ECG findings; vital signs remained stable.

• Exploratory efficacy showed 43% improved REVEAL Risk Score, 86% improved or maintained NYHA functional class, and 67% had sustained reduction in mean pulmonary artery pressure.

• Right ventricular function improved or stabilized in most patients, as measured by global longitudinal strain and tricuspid regurgitation.