Cereno Scientific reports positive results from the data quality control review initiative in the Phase II study of CS1 in rare disease pulmonary arterial hypertension (PAH)

Cereno Scientific (Nasdaq First North: CRNO B), a company developing innovative treatments for common and rare cardiovascular disease, today announced that the initiative to control the data quality produced from the cutting-edge technology CardioMEMS HF System (Abbott Inc.) used in the Phase II study of CS1 in pulmonary arterial hypertension (PAH) has successfully been concluded with positive results. The Data Quality Control Review (DQCR) found the data quality of the CardioMEMS measurements satisfactory with adherence to study protocol and with timely data transfers from the patient's home to the clinic. Efficacy findings show a clinically meaningful reduction of pulmonary pressure in several patients included in the data quality control already after 3 weeks of treatment with CS1, in line with the results from the previously communicated Patient Case. Cereno emphasizes that these reported initial findings of the DQCR may differ from the Phase II study’s final results. The top-line results of the completed Phase II study are expected in Q1 2024.

As communicated on June 26, 2023, an investigator-initiated Patient Case review showed remarkable efficacy data in the first patient completing the Phase II study of CS1. The results from right heart catheterization showed that the patient’s mean pulmonary arterial pressure (mPAP) was reduced from 33 mmHg at baseline to 23 mmHg at the end of the 12-week treatment period. Cardiac output was increased from 4.7 L/min at baseline to 5.6 L/min. Right ventricular (RV) stroke volume (SV) also increased when treated with the highest dose of CS1 over time, together with SV index and RV efficiency. These changes were accompanied by reductions in RV stroke work and total pulmonary resistance (TPR). With CardioMEMS HF System, there was a sustained reduction in mPAP over time measured as the Area Under the Curve (AUC) mmHg days. The patient required no changes to her PAH medication during the study, and her status was improved from NYHA/WHO functional class II to functional class I at the end of the 12-week treatment period.  

This month a Data Quality Control Review (DQCR) initiative was performed with the aim of correcting potential deviations from the set protocol or identifying issues around data transfer from the patient’s home to the clinic to increase standardization of the data and also obtain an early indication of CS1’s efficacy. The DQCR was performed on blinded data regarding the individual patient dosing. The review included data obtained by the CardioMEMS HF System from the first 16 patients enrolled in the Phase II study.

Key findings from the DQCR:

1. The DQCR concluded no concerning issues with digital data transfer and patient/physician protocol adherence.
2. The DQCR shows several patients with a reduction in mPAP of similar or greater magnitude as the initial Patient Case as measured with CardioMEMS HF System over time (AUC mmHg days). This indicates a clinically meaningful efficacy potential with CS1 in reducing mPAP in patients with PAH on top of standard-of-care drug therapy.
3. The DQCR shows that more than 60% of patients on CS1, all doses included, have a sustained reduction in mPAP evaluated as the AUC.
4. Reductions of mPAP (AUC) as so far seen in several patients in this study are clinically meaningful for patients with PAH.
5. The DQCR indicates an efficacy response compatible with a dose-response pattern. As the analysis was performed with dosages blinded, the final assessment of a dose-response relationship will need to await unblinding of the data at the end of the study.
6. The DQCR indicates an early onset of action with drug therapy of CS1 as measured by the reduction of mPAP. This early onset was observed already after 3 weeks for several patients.
7. The DQCR showed a sustained reduction of mPAP in the 2-week follow-up period after the 12-week period of therapy with CS1 was discontinued. 

“I am excited to see a clinically meaningful mPAP reduction in several patients, on top of Standard of Care in the PAH patients included in the DQCR. Measurement of the AUC for mPAP with CardioMEMS is a powerful way of evaluating the unloading of the right heart ventricle, which should have significant prognostic implications. We were intrigued by the remarkable improvement in the Patient Case and now we find several patients with similar or greater reduction in mPAP as measured by CardioMEMS. I am eagerly awaiting the final results at completion of the study,” said Björn Dahlöf, CMO, CSO and Head of Clinical Development of Cereno Scientific.

“It is great to observe that the CardioMEMS HF System seems to provide useful information in the PAH patient population. Frequent remote assessment of pulmonary arterial pressures to evaluate medication effect has the potential to enhance management and understanding of the disorder. We are pleased to see the results from the quality initiative and continue to monitor the safety of using the CardioMEMS HF system in patients with PAH,” said Philip B. Adamson, MD, MSc Divisional Vice President and Chief Medical Officer of the Heart Failure Division, Abbott. 

“I am pleased to receive confirmation about the quality of data and adherence to protocol in our study. It is indeed also very exciting that a reduction in mPAP, similar or greater to what was observed in the previously reported Patient Case, is seen in additional patients with CS1 therapy, measured as reduction of AUC mmHg over time. These findings, combined with the Patient Case study, provide valuable information for us to initiate planning of a pivotal clinical study for CS1 in PAH while the Phase II study will continue to run to completion according to plan. We are now confident that top-line data, once reported, will comprise optimal data quality for efficacy data on CS1, which strengthens both our scientific and business case moving forward,” said Sten R. Sörensen, CEO of Cereno Scientific.

Disclaimer:

Based on the observed findings in the review, the Phase II study will continue to completion without any changes to the study protocol. Top-line results are expected in Q1 2024. The now-published information is not based on data from all patients participating in the Phase II study and some patients in this analysis have not completed the full study period. The final results of the study may differ from the now-published findings in this DQCR. The above information and findings shall not in any way be seen as a guarantee regarding the outcome and conclusions of the upcoming final Phase II study results.

For further information, please contact:

Eva Jagenheim, CFO
Email: info@cerenoscientific.com
http://www.cerenoscientific.com/

This information is information that Cereno Scientific AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 22.55 (CEST) on October 13, 2023.

About the Phase II study of CS1

The Phase II study of CS1 in the rare disease pulmonary arterial hypertension (PAH) is actively recruiting patients at 9 specialist clinics in the US, and two new clinics are planned to open. An investigator-initiated patient case study performed on the first patient having completed the study at the clinic the investigator was based showed remarkable efficacy data. In 12 weeks of treatment with CS1, the patient showed a 30% reduction in PAH and a 20% increase in cardiac output. The patient’s overall functional status was changed from NYHA/WHO functional class II to I at the end of the treatment period, meaning that she had next to normal functional physical capacity. A data quality control initiative was conducted confirming the utility of the CardioMEMS HF System (Abbott Inc.) and showed that CS1 has a clinical meaningful reduction of pulmonary pressure, a key marker of the PAH disease burden, in several patients analyzed already after 3 weeks of treatment. The study is designed to randomize 30 PAH patients and the top-line result of the Phase II study is estimated to be reported in Q1 2024.

About Cereno Scientific AB

Cereno Scientific is a clinical-stage biotech company within cardiovascular diseases. The lead drug candidate, CS1, is a Phase II candidate in development for the treatment of the rare disease pulmonary arterial hypertension (PAH). CS1 is an HDAC (histone deacetylase) inhibitor that acts as an epigenetic modulator with pressure-reducing, reverse-remodeling, anti-inflammatory, anti-fibrotic and anti-thrombotic properties, all relevant for PAH. A clinical Phase II study is ongoing to evaluate CS1’s safety, tolerability, and efficacy in patients with PAH. A collaboration agreement with global healthcare company Abbott allows Cereno to use their cutting-edge technology CardioMEMS HF System in the study. Cereno also has two promising preclinical drug candidates in development for cardiovascular disease through research collaborations with the University of Michigan. Drug candidate CS014 is a novel HDAC inhibitor with epigenetic effects, selected for prevention of thrombosis as target indication. In preclinical studies, it has been documented to regulate platelet activity, fibrinolysis and clot stability for prevention of thrombosis without increased risk of bleeding. Thrombosis prevention in venous or arterial and cardiovascular disease has been selected as the first indication area for CS014. Drug candidate CS585 is a prostacyclin receptor agonist that has been documented in preclinical studies to target the IP receptor for prevention of thrombosis without increased risk of bleeding. The company is headquartered in Gothenburg, Sweden, and has a US subsidiary Cereno Scientific Inc. based in Kendall Square in Boston, Massachusetts, US. Cereno is listed on the Nasdaq First North (CRNO B). More information on www.cerenoscientific.com.