How to interpret the strategic value of the 12-month EAP data for CS1 – clarity on what this means for investors

Cereno Scientific recently confirmed that CS1 met its primary endpoint of safety and tolerability in the 12-month Expanded Access Program (EAP) with CS1 in pulmonary arterial hypertension (PAH), confirming that CS1 was well tolerated with a favorable safety profile . While based on a limited number of patients, the EAP represents an important step forward by adding longer-term clinical data to the CS1 program. The initial analysis of the EAP has been focused on the primary endpoint of safety and tolerability. Further analyses will be conducted on data from the EAP and Fluidda imaging sub-study evaluating changes in the pulmonary vessels during Q2 2026.

Read full press release “Cereno Scientific Highlights Strategic Value of Meeting Primary Endpoint of Safety and Tolerability of 12-month CS1 Data in PAH” >

In this article, we explain what the results mean, why they matter, and how they support the continued development of CS1.

The key takeaway: Primary endpoint of safety and tolerability met, longer-term data further strengthens confidence in CS1

The most important message from the 12-month EAP is that CS1 continues to demonstrate a favorable safety and tolerability profile in total over 15 months of treatment. The 12-month EAP data are consistent with the earlier three-months Phase IIa results.

Together, the Phase IIa study and the EAP now provide up to 15 months of CS1 treatment data, which is highly relevant in a deadly disease such as PAH, where long-term treatment is required. This longer-term dataset is a valuable addition to the overall clinical package for CS1, strengthening confidence in its profile as an oral, once-daily disease-modifying treatment for patients with PAH.

Why this matters in PAH

PAH is a serious, progressive and deadly disease where patients require lifelong treatment. Many currently available therapies are associated with safety and tolerability challenges, which can impact how long patients remain on treatment.

At the same time, there is a significant unmet need for therapies that can address the underlying disease mechanisms, not only manage symptoms.

In this context, a therapy that combines:

• an oral, once-daily administration
• a favorable safety and tolerability profile
• disease-modifying properties

is particularly relevant for long-term effective treatment.

What the EAP data show in detail

The 12-month data from the EAP show that:

• CS1 was well tolerated with a favorable safety over long-term treatment:
  • No unexpected safety signals were observed
  • No deaths occurred
  • No treatment discontinuations were assessed as related to CS1

These findings are consistent with the Phase IIa results and further strengthen the overall beneficial clinical profile of CS1.

Comment from a clinician at a site that conducted the EAP

“These are encouraging results and consistent with what I have observed in my patients treated with CS1. The favorable safety and tolerability profile over longer-term use is particularly important in PAH, where patients require lifelong therapy. I look forward to following the continued development of CS1 as a potential new treatment option for patients living with this serious disease.” – Dr. Jason Guichard, Prisma Health-Upstate, investigator in the EAP and Phase IIa trial of CS1 in PAH.

Why do we use the term “favorable safety and tolerability profile”?

In communications around clinical studies, the term “favorable safety and tolerability profile” is commonly used rather than more everyday expressions such as “good” or “very good.”

This is because drug development follows established scientific and regulatory practices, where wording needs to be:

• precise and evidence-based
• balanced and comparable across studies
• aligned with how data are evaluated by regulatory authorities

For this reason, it is a standardized and widely accepted expression in clinical research.

For investors, this means that the results are positive, while the communication also adheres to the requirements for objectivity and precision that apply in drug development.

Understanding the discontinuations

Four out of 10 patients discontinued treatment during the EAP. It is important to understand the clinical context and underlying reasons behind these discontinuations.

Two patients discontinued treatment due to atrial fibrillation (AF), which is a known and relatively common complication in PAH. According to literature, AF develops in up to a third of patients due to the progressive nature of PAH, therefore the risk of AF is higher in more advanced stages of the disease.¹ This means that such events occur as part of the underlying disease rather than as a result of treatment. Patients with AF require anti-coagulation therapy, and must therefore leave the EAP in accordance with the study protocol.

One patient withdrew consent, which means the patient chose to stop participation in the program without giving any explanation and is a known occurrence in US clinical trials.

One patient was lost to follow-up, meaning the patient never came back to scheduled visits or responded to messages from the clinic. Therefore, no more data could be collected. This is a known and not uncommon phenomenon in longer-term clinical trials follow-up in the US.

It is also important to note that treatment discontinuations are common in PAH. A recent systematic review and meta-analysis reported that approximately 42% of patients discontinue PAH-targeted therapies over time, for a variety of reasons including disease progression, treatment burden, and adverse events, which helps put the observed discontinuations in context.²

Importantly, no discontinuations were reported as related to CS1, supporting the conclusion that CS1 was well tolerated with a favorable safety over long-term treatment.

Strategic value of the Expanded Access Program

The EAP is more than a continuation of treatment following the Phase IIa study. It plays an important strategic role in drug development and is highly valued by regulatory authorities.

By providing longer-term data beyond the initial Phase IIa study, the EAP:

• strengthens the overall clinical dataset
• supports the understanding of long-term safety and tolerability
• provides supportive data in regulatory interactions when preparing for later-stage clinical development
• supports ongoing partnering discussions

Supporting next steps: Phase IIb, regulatory pathway and partnering

The findings from the EAP are viewed as:

• contributing to supporting the regulatory pathway, by establishing a longer-term safety data
• supporting partnering discussions, as a more robust dataset strengthens the overall value proposition of CS1

Together, these elements help position CS1 for the next phase of development.

What happens next?

The next key milestones approaching for CS1 in Q2:

• EAP readout: Further analyses from the EAP and the Fluidda imaging sub-study to obtain insights into how long-term treatment of CS1 on top of standard therapy impact parameters relevant to PAH including REVEAL risk score, overall function, right heart function and quality of life are expected during Q2 2026.
• Phase IIb start: The preparations for the global Phase IIb study are ongoing according to plan, with first patient enrolment planned in June 2026.

Summary

The 12-month EAP data primary endpoint readout confirm that CS1 is well-tolerated with a favorable safety profile. The EAP has extended treatment experience to 15 months, representing an important step forward for CS1 by adding valuable longer-term clinical documentation.

While based on a limited number of patients, the results:

• confirm CS1 as a well-tolerated therapy with a favorable safety profile
• extend CS1 treatment experience to up to 15 months
• strengthen the overall clinical documentation
• support continued development, regulatory progress, and partnering discussions

Taken together, this reinforces the positioning of CS1’s as a disease-modifying treatment in PAH with a favorable safety and tolerability profile.

 

——-

References: 1. Sultan, D. et al., (2025). The Interplay Between Pulmonary Hypertension and Atrial Fibrillation: A Comprehensive Overview. Cells, 14(11), 839. https://doi.org/10.3390/cells14110839; 2. Qadus et al., Adherence and Discontinuation of Disease-Specific Therapies for Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis, 2023.