Cereno’s phase IIa results positive, clear path forward
Recently, Cereno Scientific announced positive topline results from the phase IIa trial of CS1 in pulmonary arterial hypertension. The results demonstrate that the candidate is safe, well tolerated, and has a positive impact on clinically relevant parameters. The phase IIa clinical trial data, together with preclinical information, are consistent with reversing pathological remodeling, which is in line with the development goals for CS1.
Cereno Scientific focuses on developing cutting-edge therapies to enhance the quality of life and prolong the lives of individuals affected by common and rare cardiovascular diseases. Its portfolio includes three innovative drug candidates — CS1, CS014, and CS585— currently undergoing evaluation in separate, parallel development programs.
On Friday, September 27, the Swedish biotech company announced its most significant milestone to date, showing positive phase IIa results with the leading drug candidate, CS1. The candidate is a histone deacetylase (HDAC) inhibitor acting through epigenetic modulation and is being developed as a safe, effective, and disease-modifying treatment for the rare disease pulmonary arterial hypertension (PAH). It targets the root cause of the disease, aiming to reverse the pathological vascular remodeling of the small lung arteries.
Strong safety and compelling signs of efficacy spark PAH hope
The phase IIa trial evaluates the safety, tolerability, pharmacokinetics, and exploratory efficacy of CS1 in addition to standard-of-care in patients with PAH. The primary endpoint of safety and tolerability was met successfully, with no CS1-related serious adverse events, including hospitalizations/mortality, changes in liver lab values, clinically significant drug-related platelets decrease, or bleeding. Overall, CS1 was well tolerated.
The study initially aimed to recruit 30 patients. In June, recruitment was stopped after the Study Clinical Steering Committee concluded that there was sufficient data to evaluate the next steps in development. The study, which was performed at ten clinical sites in the US, randomized 25 patients to CS1 treatment, out of which 21 patients completed the treatment without protocol deviations.
CS1 showed a compelling positive impact on exploratory clinical parameters already over a 12-week treatment period. In the REVEAL risk score parameter, 43 per cent of the patients improved risk score and 71 per cent of the patients improved or had a stable risk score. In the functional class parameter, 33 per cent of the patients improved functional class and 86 per cent improved or had a stable functional class. This is important since PAH management goals are to improve the risk score measured by REVEAL improvement of symptoms and improve physical capacity measured by functional class. Published literature states that a 1-point reduction in risk score in 12 weeks is associated with a 23 per cent reduction in of death at 12 months.
Moreover, in the mean pulmonary arterial pressure (mPAP) AUC measurements with the remote monitoring platform CardioMEMS, 67 per cent of the patients had sustained pressure reduction, which is also great news as even a small change, in the same order of magnitude as seen in the trial, in pulmonary artery diastolic pressure (ePAD) is associated with decreased mortality risk.
Remarkable responders
Additionally, an in-depth analysis of a subgroup of patients with a remarkable response showed that 25 per cent of patients responded to CS1 with remarkably large reductions in pulmonary vascular resistance (PVR reduced by >30 per cent) consistent with the proposed reverse vascular-remodeling mechanism of action. These significant reductions in PVR were strongly associated with robust increases in right ventricular stroke volume, which is clinically very relevant because right ventricular failure is often the cause of death in these patients.
“The data from the CS1-003 trial, together with recently announced preclinical data from Cereno’s HDAC inhibitor program on an established model of PAH, directly demonstrate a dose-dependent positive impact on reverse vascular remodeling in small lung arteries, which provide a basis for assuming that CS1 may act with a disease-modifying capacity in PAH”, said Sten R. Sörensen, CEO, Cereno Scientific.
Clear path forward to develop a disease-modifying therapy
Going forward, Cereno will initiate discussions with regulatory bodies based on these encouraging results and will progress toward pursuing a pivotal trial of CS1 in PAH.
A comprehensive analysis of the complete CS1-003 data will be conducted, with these and further findings to be presented at upcoming medical conferences and published in reputable medical journals.
“We are excited to take the next steps in our journey to meaningfully impact patients with PAH. Our plans include engaging with regulatory authorities to pursue 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.
Agreement signed to use Fluidda’s FRI technology
On September 30, Cereno Scientific announced an agreement with medical technology company Fluidda on respiratory imaging solutions. The aim is to visualize signs of reverse remodeling of lead drug candidate CS1 in PAH in a clinical setting.
To deepen the exploration of CS1’s impact on pathological vascular remodeling of small pulmonary arteries, as seen in preclinical, phase I and Phase II trials, Cereno is actively engaging with a leading PAH specialist to launch an investigator-initiated trial (IIT). This trial aims to harness Fluidda’s technology to visualize how long-term use of CS1 influences structural changes in pulmonary arteries. The trial seeks to provide valuable insights into CS1’s potential to transform PAH treatment.
“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 of Cereno Scientific.
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