Cereno Scientific announces positive topline results of Phase IIa trial with lead candidate CS1 in Pulmonary Arterial Hypertension

• Primary endpoint of safety and tolerability met successfully
• Positive impact on exploratory clinical efficacy parameters:
  • REVEAL risk score:
    • 43% (9/21) of the patients improved risk score
    • 71% (15/21) of the patients improved or had stable risk score
  • Functional Class:
    • 33% (7/21) of the patients improved functional class
    • 86% (18/21) of the patients improved or had stable functional class
  • Mean pulmonary arterial pressure (mPAP, AUC):
    • 67% (14/21) of the patients had sustained pressure reduction
• CS1 Phase IIa study data, together with preclinical information, is consistent with reversing pathological remodeling
• Clear path forward - Engaging with regulatory authorities in pursuing a pivotal trial
• Webcast scheduled for Monday September 30, 2024 at 14:00 CET will provide more details of the topline results

Cereno Scientific (Nasdaq First North: CRNO B), a pioneering biotech developing innovative treatments for rare and common cardiovascular disease, today announced positive topline results from the Phase IIa trial of CS1 in Pulmonary Arterial Hypertension (PAH). The results demonstrate that CS1 is safe, well tolerated and has positive impact on clinically relevant parameters such as risk, functional class and hemodynamics.

“I am delighted to share the topline data from the Phase IIa trial of CS1 in PAH. Key results from the study demonstrate both that the primary endpoint was met with good safety and tolerability of CS1 in patients with PAH, and, in addition, we also show a positive impact already after 12 weeks on clinical parameters meaningful to patients and regulatory authorities. These results, together with our foundation of preclinical data, strengthen our conviction that CS1 is a disease-modifying therapy for PAH. We are excited to now move forward with the next development phase with CS1. Our mission is to deliver a drug addressing the pathological remodeling which is progressing the PAH disease and to provide a valuable addition to the PAH toolbox of therapeutics”, said Sten R. Sörensen, CEO, Cereno Scientific.

Pulmonary Arterial Hypertension
PAH is a debilitating and fatal disease with no spontaneous improvement. Epigenetic mechanisms through histone deacetylase (HDAC) drive disease progression and continuous deterioration. The disease pathology is defined by endothelial dysfunction, inflammation, vasoconstriction, hypertrophy and remodeling of pulmonary small arteries, leading to poor lung function, right heart failure and ultimately death. Existing treatment alternatives are insufficient and do not address the root cause of the disease.

The goal of PAH treatment is to improve risk score status (measured by amongst others REVEAL risk score), symptoms and physical capacity (measured by functional class) and hemodynamics (measured by mean Pulmonary Arterial Pressure, mPAP and Pulmonary Vascular Resistance, PVR), to ultimately improve both patients’ quality of life and extend survival.

“PAH is a rare and devastating disease for patients suffering from it. Despite advances in treatment options there is still a pronounced need for effective, safe and disease-modifying therapies for these patients. The results presented today with primary endpoints met regarding safety and tolerability and supporting signs of clinical efficacy including improvement in risk score, improvement of functional class and impact on mean pulmonary pressure are promising,” said Dr. Raymond Benza, Network Director of Pulmonary Hypertension at Mount Sinai Icahn School of Medicine, New York; and Principal Investigator of the Phase IIa trial of CS1.

CS1 and the CS1-003 Phase IIa trial
CS1 is an HDAC inhibitor that works through epigenetic modulation, being developed as a safe, effective and disease modifying treatment for PAH. CS1 targets the root cause of the disease, aiming to reverse the pathological vascular remodeling of the small lung arteries.

CS1-003 is a Phase IIa trial evaluating the safety, tolerability, pharmacokinetics, and exploratory efficacy of CS1 on top of standard-of-care in patients with PAH. The study initially had as an objective to recruit 30 patients. In June, recruitment was stopped after the Study Clinical Steering Committee concluded that there was sufficient data for evaluating the next steps in development. The study, which was performed at 10 clinical sites in the US, randomized 25 patients to CS1 treatment, out of which 21 patients completed the treatment without protocol deviations.

CS1 – Phase IIa safety data – Primary endpoint of safety and tolerability met successfully
The primary endpoint of safety and tolerability was met successfully:

• No CS1-related serious adverse events, including hospitalizations/mortality
• No changes in liver lab values or clinically significant drug-related platelets decrease or bleedings, were seen in the study
• CS1 was well tolerated.

CS1 Phase IIa – Compelling positive impact on exploratory clinical efficacy parameters

Efficacy data from the three doses were pooled together due to therapeutic drug exposure (i.e. plasma concentration) also in the low dose group. 

CS1 showed compelling positive impact on exploratory clinical parameters already over a 12-week treatment period:

• REVEAL risk score:
  • 43% (9/21) of the patients improved risk score
  • 71% 15/21) of the patients improved or had a stable risk score
• Functional Class:
  • 33% (7/21) of the patients improved functional class
  • 86% (18/21) of the patients improved or had a stable functional class
• Mean pulmonary arterial pressure (mPAP, AUC):
  • 67% (14/21) of the patients had sustained pressure reduction

“I am very pleased with the positive outcomes we are seeing in our patients following treatment with CS1. Their improvements in health and well-being are encouraging and reflect the potential effectiveness of the therapy. The majority of my patients have expressed interest in enrolling into the Expanded Access Program. This progress reaffirms my commitment to advancing treatments that can make a meaningful difference in patients' lives with PAH,” said Dr. Jason Guichard, Advanced Heart Failure and Transplant Cardiology, Department of Medicine, Division of Cardiology, Prisma Health-Upstate, Assistant Professor of Medicine, University of South Carolina School of Medicine Greenville and investigator in the Phase IIa trial of CS1 in PAH.

CS1 phase II a study clinical data, together with preclinical information, is consistent with reversing pathological remodeling
An in-depth analysis made on a subgroup of patients with a remarkable response showed:

• 25% (5/21) of patients responded to CS1 with remarkably large reductions in pulmonary vascular resistance (PVR reduced by >30%, range 35–51%, mean 45%) consistent with the proposed reverse vascular-remodeling mechanism of action.
• These large reductions in PVR were strongly associated with robust increases in right ventricular stroke volume.
• Findings suggest the lower dose range in the trial (480–960mg) as optimal.

The data from the CS1-003 trial, together with recently announced preclinical data from our HDAC inhibitor program, directly demonstrating our HDAC-inhibitor program’s dose-dependent positive impact on reverse vascular remodeling in small lung arteries, provide a basis for assuming that CS1 may act with a disease-modifying capacity in PAH.

Clear path forward to develop a disease-modifying therapy for PAH​
Cereno will be initiating discussions with regulatory bodies based on these encouraging results and will progress pursuing a pivotal trial of CS1 in PAH. 

A comprehensive analysis of the complete CS1-003 data will be conducted, with the findings to be presented at upcoming medical conferences and published in a reputable medical journals.

“We are excited to take the next steps in our journey to make a meaningful impact for patients with PAH. Our plans include engaging with regulatory authorities to in pursuing a pivotal trial for CS1 and to continue enrolling patients in our Expanded Access Program. The CS1-003 trial demonstrated compelling signs of clinical efficacy already over a 12-week treatment period and we expect to see additional positive impact of CS1 with longer use of our drug in patients with PAH” said Dr. Rahul Agrawal, CMO and Head of R&D, Cereno Scientific

Webcast presentation on Monday, September 30
Cereno Scientific will host a webcast including a Q&A session where CEO Sten R. Sörensen, CMO and Head of R&D Dr. Rahul Agrawal, CSO Dr. Björn Dahlöf and Head of Preclinical Development, Nicholas Oakes, will present the CS1-003 topline results.  

Date and time: Monday, September 30, 2024, at 14:00 CET

How to join: https://ir.financialhearings.com/cereno-scientific-2024

The webcast and presentation will be available on the Company’s website after the webinar at: https://cerenoscientific.com/events-presentations/

For further information, please contact:

Henrik Westdahl, Director IR & Communications

Email: henrik.westdahl@cerenoscientific.com

Phone: +46 70-817 59 96

Sten R. Sörensen, CEO

Email: sten.sorensen@cerenoscientific.com

Phone: +46 73-374 03 74

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 20:40 (CET) on September 27, 2024.

About the CS1-003 trial
The CS1-003 trial titled “A Phase II, Prospective, Randomized, Open-label, Blinded Endpoint, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of 3 Doses of CS1 in Subjects With Pulmonary Arterial Hypertension” (NCT05224531) randomized adult PAH patients with WHO Functional class II or III, stable on standard of care therapy for 90 days, to one of three total daily doses of CS1; 480 mg, 960 mg or 1920 mg. Subjects were enrolled for up to 22 weeks including a treatment period of 12 weeks. The trial was conducted at 10 specialist clinics in the US. 25 patients were randomized to CS1 treatment out of which 21 patients completed the treatment without protocol deviations.

The study’s primary endpoint was to evaluate the safety and tolerability of CS1 treatment in patients with PAH. Other relevant standard endpoints used in previous studies of this patient group have been measured and evaluated in an exploratory fashion. A collaboration agreement with global healthcare company Abbott has allowed Cereno to use their cutting-edge technology CardioMEMS HF System in the trial, to measure mean Pulmonary Arterial Pressure (mPAP) and other hemodynamic parameters.

CS1-003 is a Phase IIa trial that is not powered for statistically significant detection or exclusion of efficacy-related parameters.

On June 28, 2024, Cereno announced the decision to close patient recruitment to the Phase IIa trial CS1-003 by July 1st, 2024, after the Study Clinical Steering Committee concluded that there was sufficient data for evaluating the next steps in development.

About PAH

Pulmonary Arterial Hypertension (PAH) is a rare disease and diagnosed with high blood pressure in the pulmonary circulation. Globally, the disease affects approximately 10 in 100,000 people. It is a severe, debilitating disease with no spontaneous improvement. The disease is characterized by a progressive narrowing of the pulmonary arterial vessels ultimately leading to right heart failure and death. Life expectancy is 2.5 years without therapy and 7.5 years on current standard of care.

PAH has a major impact on quality of life and causes shortness of breath, fatigue, chest pains, reduced ability to work, unnatural swelling, fainting and heart palpitations. This has significant implications for a patient's physical, mental, and social well-being.

There is currently no cure available for PAH with the exception of lung transplantation, which patients are often too seriously ill to undergo. Current standard of care, mainly vasodilators, improves the patient's symptoms and involves, at best, a moderate slowing of the disease progression. There is therefore a great need for safer therapies with disease-modifying capacity that address the root causes of PAH and that can give patients an increased opportunity for an improved quality of life and a longer life.

About CS1

Drug candidate CS1 is an HDAC inhibitor that works through epigenetic modulation, being developed as a treatment for the rare disease PAH. CS1 holds the potential to be an effective, safe and disease-modifying drug, targeting the root cause of the disease by reverse remodeling.

In preclinical cardiovascular disease models, HDAC inhibitors have shown disease-modifying potential through reverse pathological remodeling, as well as anti-fibrotic, anti-inflammatory, pulmonary pressure-reducing, and anti-thrombotic effects. CS1’s unique efficacy profile aligns well with the underlying mechanisms of PAH, positioning it to address the critical unmet need for more effective treatment options. The goal of CS1's development is to improve quality of life and extend survival for patients with PAH. CS1 is part of Cereno’s HDACi portfolio, untapping the potential of epigenetic modulation in CVD. CS1 has been granted orphan drug status in both the US and EU.

Since January 30, 2024, CS1 is approved by the FDA for Expanded Access, as an extension of the ongoing Phase IIa trial CS1-003 evaluating CS1 in PAH. The EAP gives patients that have completed the Phase IIa trial the opportunity to, after being judged suitable and to benefit from CS1 treatment by investigators, continue CS1 treatment of PAH when no comparable or satisfactory alternative therapy options are available. The EAP allows Cereno to, under a formal FDA-approved protocol, collect safety and efficacy data from long-term exposure to CS1 in patients with PAH. As such, this initiative not only supports the treatment of PAH patients but also enables Cereno to gather additional CS1 usage documentation for regulatory discussions and Phase IIb/III pivotal study design planning. On August 30, 2024, the Company announced that the first patient had been dosed under the EAP. 

About Cereno Scientific AB
Cereno Scientific develops innovative treatments for rare and common cardiovascular disease. The lead drug candidate, 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. A Phase IIa trial evaluating CS1’s safety, tolerability, and exploratory efficacy in patients with the rare disease pulmonary arterial hypertension (PAH) demonstrated that CS1 was safe, well-tolerated and showed a positive impact on exploratory clinical efficacy parameters. CS1 study data, together with preclinical information, is consistent with reversing pathological remodeling. A collaboration agreement with global healthcare company Abbott allowed Cereno to use their cutting-edge technology CardioMEMS HF System in the trial. Since January 2024, we are delighted that the FDA´s Expanded Access Program will enable patients with PAH, a serious life-threatening disease condition, to gain access to CS1 where no comparable alternative therapy options are available. Cereno’s pipeline comprises two additional programs in development through research collaborations with the University of Michigan CS014 is a new chemical entity with a multi-fold mechanism of action as an epigenetic modulator – regulating platelet activity, fibrinolysis, and clot stability for the prevention of thrombosis without an increased risk of bleeding as documented in preclinical trials. The drug candidate has also demonstrated a favorable profile in preclinical models of other cardiovascular diseases, such as PAH, with reverse remodeling of pulmonary arterial vessels and effects on vascular fibrosis. On 28th of June, 2024, Cereno initiated a first-in-human Phase I trial of CS014. Preclinical candidate CS585 is an oral, highly potent and selective prostacyclin (IP) receptor agonist that has demonstrated the potential to significantly improve disease mechanisms relevant to cardiovascular disease. 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 Pulmonary Hypertension and thrombosis prevention without increased risk of bleeding. CS585 was in-licensed from the University of Michigan in 2023. 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 is listed on the Nasdaq First North (CRNO B). The Certified Adviser is Carnegie Investment Bank AB, certifiedadviser@carnegie.se. More information is on www.cerenoscientific.com.