CS1, an innovative formulation of a promising histone deacetylase inhibitor called valproic acid (VPA), is Cereno Scientifics lead candidate and has demonstrated the ability to treat a broad spectrum of cardiovascular diseases (CVD) in both preclinical and Phase I studies. CS1 was granted Orphan Drug Designation (ODD) by FDA in March 2020 for the treatment of the rare cardiovascular disease pulmonary arterial hypertension (PAH), and in August 2021 the company filed a so-called Investigational New Drug (IND) application to the FDA for approval to initiate a Phase II study in PAH.
IND application approved
Last week, Cereno Scientific announced that the FDA has approved the IND application, which means that final study preparations and patient recruitment can be initiated. The purpose of the study will primarily be to demonstrate the safety and tolerability of CS1, but the study will also perform a validated risk assessment and evaluate dose, pharmacokinetics and exploratory efficacy measures in PAH patients. The study will be conducted at approximately six different clinical sites in the US and include approximately 30 patients.
»This is a very important milestone for Cereno. The team has been working tirelessly throughout this year including over the summer together with our partners to prepare the documentation required to submit the IND application and we are very happy that we are now able to initiate the phase II trial. Importantly, this is also a great step for patients living with PAH as CS1 has the potential to completely change how these patients are treated« — Sten R. Sörensen, CEO Cereno Scientific
Preparations for the phase II study have been made in collaboration with Worldwide Clinical Trials, a global CRO that Cereno entered into a collaboration with earlier this year. Worldwide's expertise has played a key role in supporting and guiding Cereno in the final preparatory steps towards the Phase II study, and the CRO will continue to support the conduct of the study.
Key people in the study
A key person in the upcoming study is Dr. Raymond Benza, who will be the principal investigator of the study. Dr. Benza, the newest addition to Cereno's Scientific Advisory Board (SAB), is a global opinion leader in PAH, and has been working as an advisor to Cereno to plan the clinical aspects of the upcoming Phase II study program with CS1.
»It is very satisfying that we can now move forward with the phase II study. I believe CS1 has the potential to drive a paradigm shift in PAH due to its unique mechanisms of action and I am very much looking forward to supporting the execution of the trial« — Dr Raymond Benza, SAB Cereno Scientific
Another key player, both before and during the study, is Cereno's partner, the global life science company AbbottEarlier this year, Abbott collaborated with Cereno to prepare the IND application. In addition, Abbott will provide Cereno with its pulmonary artery blood pressure monitoring system, CardioMEMS HF System, in the upcoming study. The system has previously been approved for use in severe heart failure and can help healthcare professionals remotely and proactively monitor pulmonary and right heart hemodynamics, including pulmonary artery blood pressure. It will also be possible to evaluate the condition of the right heart, which ultimately fails in many PAH patients. At the same time, the study provides Abbot with the opportunity to test its CardioMEMS HF System in a new indication, PAH.
»For dose finding, the CardioMEMS will be key with its remote continuous monitoring of pulmonary arterial blood pressure. The numerous exploratory efficacy parameters, including those that have been used in previous PAH studies and a validated risk score, will give a good estimate of potential effect sizes on important parameters. This will enable us to calculate the number of patients needed in a next study« — Björn Dahlöf, CMO Cereno Scientific
Panel discussion
BioStock assembled a panel consisting of Cereno's CEO Stone R Sorensen and CMO Bjorn Dahlof, as well as Dr. Benza to discuss the details of the upcoming Phase II study and its implications.
Sten R Sörensen, how important is this milestone for Cereno Scientific?
- This is a very important milestone for Cereno. The team has been working tirelessly throughout this year including over the summer together with our partners to prepare the documentation required to submit the IND application and we are very happy that we are now able to initiate the phase II trial. Importantly, this is also a great step for patients living with PAH as CS1 has the potential to completely change how these patients are treated.
Would you say this acceptance is a form of validation for your rare disease strategy?
– Obtaining FDA's clearance is an important step in further realizing our rare disease strategy for CS1. With the ODD which was granted to us by the FDA in 2020 we see great potential in the business opportunity for our investors while at the same time fulfilling some of the serious unmet needs for PAH patients.
Björn Dahlöf, could you speak to the work put into preparing the necessary documentation and steps needed to start the clinical phase II study?
- It all starts with the design of the study and the protocol development. The protocol is the core document for the IND application to the FDA and basically all other documents necessary for the application relate to different parts of the protocol. To develop a clinical study protocol is an elaborate process since the protocol needs to include background rationale, all relevant questions to be answered, which patients can be included in the study and which should be excluded, relevant safety information, all clinical investigations to be made, a detailed step by step schedule of events for each patient, all relevant aspects of documentation of laboratory parameters and clinical investigations.
– In addition, detailed documentation of every part of the protocol is provided all the way from patient informed consent to all previous preclinical and clinical documentation of the medication as well as documentation of all previous safety information, documentation of formulation and production of the medication. Everything is provided to FDA in a special electronic format where all parts are cross referenced. After the IND application has eventually been submitted, the FDA has 30 days to respond.
What implications will this study have on future studies with CS1?
– This study has the primary goal of looking at safety and tolerability since this is the first time CS1 is given to patients with PAH. However, we will also be able to determine the best dose(s) and relevant pharmacokinetics for future studies. For dose finding, the CardioMEMS will be key with its remote continuous monitoring of pulmonary arterial blood pressure. The numerous exploratory efficacy parameters, including those that have been used in previous PAH studies and a validated risk score, will give a good estimate of potential effect sizes on important parameters. This will enable us to calculate the number of patients needed in a next study.
Dr. Benza, as scientific advisor to Cereno and principal investigator to the upcoming phase II trial, how does it feel to be able to initiate this study?
- It is very satisfying that we can now move forward with the phase II study. I believe CS1 has the potential to drive a paradigm shift in PAH due to its unique mechanisms of action and I am very much looking forward to supporting the execution of the trial.
What will be the overall timeline for this study?
- Now that we have clearance from the FDA, we are looking forward to initiating patient recruitment across our US clinical sites. We expect to have top-line results from this phase II trial ready during the second half of 2022.
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