"We are pleased to have completed the Clinical Study Report, successfully concluding the Phase IIa trial and enhancing our understanding of CS1's reverse remodeling effects. PAH is a progressive and fatal disease with pathological changes to the pulmonary vasculature and the right-heart. Despite the trial's short duration, CS1 showed improvement of right-ventricular function signaling a disease-modifying effect by halting disease progression or through the reversal of pathological vascular remodeling. Based on these encouraging findings and the completed Clinical Study Report, we have now initiated a Type C meeting with the FDA to align the next development steps of CS1 and in parallel we are pursuing the publication of our scientific data," said Rahul Agrawal, CMO & Head of R&D at Cereno Scientific.

The Phase IIa trial was conducted over 12 weeks with a total of 25 patients of which 21 were evaluated for efficacy parameters. The trial successfully met its primary endpoint of safety and tolerability, with no drug related serious adverse events. CS1 was also shown to have a positive impact on exploratory clinical efficacy parameters consistent with disease-modifying effects in PAH. Treatment with CS1 lowered patients' REVEAL 2.0 risk score, a key predictor of clinical worsening and mortality, where 43% (9/21) showed an improved REVEAL 2.0 risk score and 71% (15/21) improved or had stable risk score after the 12-week treatment period. Patients reported functioning better in daily life when treated with CS1 as reflected in the 33% (7/21) of patients with improved NYHA functional class and 86% (18/21) of patients with improved or stable NYHA functional class after the treatment period. 67% (14/21) of the patients had sustained pressure reduction reflected in mean pulmonary arterial pressure (mPAP, AUC) when treated with CS1.

Further analysis conducted after the trial's top-line reporting showed:

• CS1 showed a significant improvement of right-ventricular Global Longitudinal Strain (RVGLS), a sensitive measure of right heart function and treatment response. The RVGLS is a highly predictive indicator of right-ventricular remodeling at early stages of disease and future mortality.  
• Alongside RVGLS, an improvement and/or stabilization in tricuspid regurgitation (TR)-a condition in which the valve fails to close completely during right ventricular contraction, leading to increased pressure-was also observed over the 12-week treatment period.
• CS1 further demonstrated a gradual improvement over time on the REVEAL 2.0 risk score and the NYHA functional class in the 12-week treatment period.
• CS1 also demonstrated a positive impact on quality of life (QoL) in patients with PAH as measured by PAH-SYMPACT and Minnesota Living with Heart Failure Questionnaire.
•  A sub-group of patients were identified being in the early stage of PAH disease who experienced marked improvement of pulmonary vascular resistance (PVR).

"All signs are pointing toward our epigenetic modulating HDACi CS1 having a real potential to be a disease-modifying game-changer in the treatment of PAH, a fatal rare disease with high unmet need. We are excited for the next part of the journey to further evaluate CS1's transformative potential as a treatment for PAH. We view CS1 as a strong candidate for commercial partnering given the exciting preclinical and clinical data on reverse remodeling effects, good safety and tolerability, oral administration and market exclusivity of seven and ten years with an ODD in the US and Europe, respectively. In parallel with our regulatory and clinical preparations for further development, we foresee an even further increase in our partnering activities," said Sten R. Sörensen, CEO of Cereno Scientific.

The clinical development plan for CS1 is to continue the evaluation of CS1 as a safe, well-tolerated oral therapy with disease-modifying effects in PAH. A larger placebo-controlled Phase IIb trial is being planned, and interactions with the U.S. Food & Drug Administration (FDA) has been initiated following the recent submission of a Type C meeting request.

For further information, please contact:

Tove Bergenholt, Head of IR & Communications

Email:  tove.bergenholt@cerenoscientific.com

Phone: +46 73- 236 62 46

Sten R. Sörensen, CEO

Email: sten.sorensen@cerenoscientific.com

Phone: +46 73-374 03 74

Webcast to present the Phase IIa data

A webcast is planned to share the Phase IIa data of CS1 with a presentation and Q&A session on March 4, 2025. An invitation with information on registration for the virtual event will follow.

About CS1

Drug candidate CS1 is a Class 1 HDAC inhibitor (HDACi) that works through epigenetic modulation, being developed as an oral, safe and well-tolerated treatment with disease-modifying capacity for the rare disease pulmonary arterial hypertension (PAH). CS1 has a completely new approach to the treatment of PAH by more profoundly targeting the pathophysiology of the disease, aiming to reverse the pathological vascular remodeling of the small lung arteries.  

CS1 is a proprietary novel reformulation of repurposed valproic acid (VPA) protected by three patent families and orphan drug status in both the US (ODD) and EU in PAH. In a recently concluded Phase IIa study, CS1 successfully met the primary endpoint of safety and tolerability. CS1 further showed compelling data supporting a disease-modifying capacity, based on epigenetic modulation, on top of standard therapy in PAH over the trial's 12-week treatment period. FDA approved an Expanded Access Program (EAP) as an extension of the Phase IIa trial in PAH, where about half of the patients (10) are currently enrolled to continue CS1 treatment. A sub-study of the EAP is currently ongoing using medtech Fluidda's non-invasive imaging technology Functional Respiratory Imaging (FRI) on certain patients to visualize how long-term use of CS1 on top of standard therapy may impact disease characteristic changes in small pulmonary arteries. The long-term safety and efficacy data obtained by the EAP supports required regulatory interactions and planning future Phase IIb trial.

CS1's unique efficacy profile aligns well with the underlying mechanisms of disease that drives the progression of PAH, positioning it to address the critical unmet need for more effective treatment options. CS1 is part of Cereno's HDACi portfolio, untapping the potential of epigenetic modulation in rare cardiovascular and pulmonary diseases.

About Cereno Scientific AB

Cereno Scientific is pioneering treatments to enhance and extend life. Our innovative pipeline offers disease-modifying drug candidates to empower people suffering from rare cardiovascular and pulmonary diseases to live life to the full.

Lead candidate CS1 is an HDACi that works through epigenetic modulation, being developed as an oral, safe, well tolerated and effective disease modifying treatment for rare disease Pulmonary Arterial Hypertension (PAH). A Phase IIa trial evaluating CS1's safety, tolerability, and exploratory efficacy in patients with PAH demonstrated that CS1 was safe, well-tolerated and showed a positive impact on exploratory clinical efficacy parameters. An Expanded Access Program enables patients that have completed the Phase IIa trial to gain access to CS1. HDACi CS014, in Phase I development, is a new chemical entity with disease-modifying potential. CS014 employs a multi-modal mechanism of action as an epigenetic modulator, targeting key unmet needs in patients with rare disease Idiopathic Pulmonary Fibrosis (IPF). Cereno Scientific is also pursuing a preclinical program with CS585, an oral, highly potent and selective prostacyclin (IP) receptor agonist that has demonstrated the potential to significantly improve disease mechanisms relevant to cardiovascular diseases. While CS585 has not yet been assigned a specific indication for clinical development, preclinical data indicates that it could potentially be used in indications like Thrombosis prevention without increased risk of bleeding and Pulmonary Hypertension.

The Company is headquartered in GoCo Health Innovation City, in Gothenburg, Sweden, and has a US subsidiary; Cereno Scientific Inc. based in Kendall Square, Boston, Massachusetts, US. Cereno Scientific is listed on the Nasdaq First North (CRNO B). The Certified Adviser is Carnegie Investment Bank AB, certifiedadviser@carnegie.se. More information can be found on www.cerenoscientific.com.