Understanding the Additional 12-Month EAP Analyses for CS1 – What This Means for Investors

Cereno Scientific has announced additional analyses from the 12-month Expanded Access Program (EAP) with its lead drug candidate CS1 in pulmonary arterial hypertension (PAH). The findings provide further long-term clinical experience with CS1 and add important context as the company prepares to initiate its global Phase IIb study, where CS1’s potential disease-modifying profile in PAH will be further evaluated in a controlled setting.

The EAP enrolled 10 patients who had completed the previous Phase IIa trial. Six patients completed 12 months of CS1 treatment. The analyses are based on these completing patients and should be understood as descriptive, real-world clinical observations, not as controlled efficacy results generated from a clinical trial.

While the EAP was not designed or powered to demonstrate efficacy, the findings contribute to a broader understanding of how CS1 performs over an extended treatment period and in combination with modern PAH therapies in real world setting.

Below, we explain what the findings mean and why they are relevant for investors.

What was the purpose of the EAP?

The Expanded Access Program was initiated following requests from physicians and patients who had participated in the previous Phase IIa study. Its purpose was to enable continued access to CS1 while collecting additional long-term information regarding safety and tolerability.

The program’s primary objective was met, with no unexpected safety concerns and no deaths reported during the treatment period.

Of the 10 enrolled patients, six completed 12 months of treatment. Two patients discontinued CS1 because their treating physicians prescribed anticoagulation therapy following atrial fibrillation. Anticoagulant use was an exclusion criterion under the EAP protocol, meaning these patients had to discontinue CS1 treatment. Atrial fibrillation is a known complication in PAH, particularly in later stages of disease, and was not considered related to CS1 treatment. One patient withdrew consent and one was lost to follow-up. Importantly, no discontinuation was assessed as related to CS1.

What do the new analyses show?

The additional analyses provide further descriptive insight into the clinical course of patients who completed the 12 months of treatment.

Among the six patients who completed 12 months of CS1 treatment:

• Five of six had stable or improved NYHA/WHO functional class
• Five of six had stable or improved NT-proBNP levels
• Three of six improved six-minute walk distance
• Three of six had stable or improved REVEAL Risk Score 2.0
• Three of five evaluable patients had stable or reduced mean pulmonary arterial pressure measured by CardioMEMS

  These measures are relevant because they reflect different aspects of PAH disease status, including functional capacity, cardiac strain, clinical risk and pulmonary pressure. In a progressive disease such as PAH, stability or improvement across several of these measures over 12 months is supportive of CS1’s proposed disease-modifying profile, although it cannot establish treatment effect due to the limited number of patients.

  The EAP also showed that CS1 could be administered alongside currently approved PAH therapies, including concomitant treatment with sotatercept. This is relevant because the upcoming Phase IIb study will evaluate CS1 as an add-on therapy to standard of care in a modern PAH treatment setting.

  Why is clinical stability important in PAH?

  Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Even with currently available therapies, many patients deteriorate over time and symptoms continue to worsen. For this reason, maintaining clinical stability over a longer treatment period can be meaningful, particularly when combined with a favorable long-term safety and tolerability profile.

  CS1 is being developed as a disease-modifying therapy that targets underlying mechanisms of PAH, including vascular remodeling, fibrosis and inflammation. In this context, maintained or improved clinical status over 12 months is clinically relevant.

  The findings should therefore be viewed as supportive clinical observations that are consistent with the disease-modifying profile previously observed in the Phase IIa study.

  Why should the results be interpreted with caution?

  The EAP was designed to provide continued access to CS1 and collect additional long-term clinical experience. It was not designed or statistically powered to demonstrate efficacy.

  The program included 10 patients and was conducted in an open-label setting. In addition, patients did not transition directly from the Phase IIa study into the EAP. The time between studies varied considerably, and patients received changes to their standard PAH treatment during that period.

  As a result, the findings should be interpreted as real-world clinical observations of individual patient responses, not as controlled evidence of treatment effect.

  The EAP also included an exploratory Fluidda imaging sub-study. However, only three patients were included, no consistent imaging results were observed and no conclusions can be drawn from this sub-study.

  What conclusions cannot be drawn?

  The EAP was not designed or powered to establish efficacy. Therefore, no definitive conclusions can be drawn about CS1’s treatment effects from these data.

  This is also why the upcoming placebo-controlled Phase IIb study remains the critical next step in the development of CS1.

  Why are these findings still relevant to investors?

  Although the EAP cannot answer the efficacy question, it does provide valuable information in several areas.

  First, the findings provide longer-term clinical context that is supportive of CS1’s disease-modifying profile in PAH.

  Second, it provides additional clinical experience from patients treated for up to 12 months in a real-world setting.

  Third, it supports the continued evaluation of CS1 as an add-on therapy alongside currently approved PAH treatments, including recently introduced therapies such as sotatercept.

  Fourth, the observations are consistent with the profile seen in the Phase IIa trial and provide additional context ahead of the planned Phase IIb study.

  Finally, the program further strengthens the long-term safety and tolerability profile of CS1.

  Taken together, these observations help strengthen the overall clinical package supporting the continued development of CS1 in PAH.

  How does this fit into the next stage of development?

  The EAP represents an important bridge between the completed Phase IIa trial and the planned global Phase IIb study.

  The planned Phase IIb study is expected to enrol approximately 126 patients across approximately 65 investigational sites in 10–12 countries in North America, Europe and South America. It has been developed in dialogue with the FDA and is designed to evaluate the safety, tolerability and efficacy of CS1 when added to standard of care, while also further assessing CS1’s potential disease-modifying effects and identifying the optimal dose for Phase III development.

  Unlike the EAP, the Phase IIb study will be placebo-controlled and designed to generate the type of clinical evidence needed to assess CS1’s potential treatment effect.

  The additional EAP analyses do not replace the need for Phase IIb data. However, they provide encouraging long-term clinical context as CS1 moves into its next and most important development stage to date.

  Summary

• The additional EAP analyses provide longer-term clinical context supportive of CS1’s disease-modifying profile in PAH.
• Most patients completing 12 months of treatment were stable or improved across one or more clinically relevant measures.
• In a progressive disease such as PAH, maintained or improved clinical status over time is clinically relevant and directionally consistent with the Phase IIa observations.
• The EAP was not designed to establish efficacy, and no conclusions regarding treatment effect can be drawn.
• The findings support continued evaluation of CS1 as an add-on therapy in a modern PAH treatment setting.
• The planned global Phase IIb study remains the critical next step to evaluate CS1’s safety, tolerability, efficacy and potential disease-modifying effects in a controlled setting.