The FDA has accepted Cereno Scientific’s Investigational New Drug application for the company’s lead drug candidate CS1. This allows Cereno to start the planned phase II study in patients with pulmonary arterial hypertension at clinical sites in the US. BioStock was able to put together a panel discussion to learn more about the importance of this milestone. The panel includes Cereno’s CEO Sten R Sörensen as well as CMO Björn Dahlöf, and the Principal Investigator of the study Dr Raymond Benza.
CS1, an innovative formulation of a promising histone deacetylase inhibitor (HDACi) called valproic acid (VPA), is Cereno Scientific’s lead candidate and it has shown, in both preclinical and phase I stages of development, the ability to treat a wide range of cardiovascular diseases (CVDs). CS1 was granted ODD (Orphan Drug Designation) by the FDA in March 2020 for the treatment of the rare CVD pulmonary arterial hypertension (PAH), so, in August 2021, the company sent in an Investigational New Drug (IND) application to the FDA seeking acceptance for initiating a phase II trial in PAH.
IND application accepted
This week, Cereno Scientific announced that FDA has accepted the IND application, meaning final study preparations and patient recruitment can be initiated. The aim of the study will primarily be to demonstrate CS1’s safety and tolerability but also evaluate dose and pharmacokinetics, validated risk scores and exploratory efficacy endpoints in PAH patients. The study will be run at approximately six different clinical sites in the US and include about 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
Preparation for the phase II trial has been done in collaboration with Worldwide Clinical Trials, a global CRO with whom Cereno partnered 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 in the execution of the study.
Important contributors to the study
A key person in the upcoming trial is Dr Raymond Benza, who will be the principal investigator in the study. Dr Benza, the latest addition to Cereno’s Scientific Advisory Board (SAB), is a global thought leader within PAH, and he has been working as an advisor to Cereno for planning the clinical aspects of the upcoming phase II study programme 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 in the leadup to the trial, as well as during the trial is Cereno’s partner, the global life science company Abbott. Earlier this year, Abbott collaborated with Cereno to put together the IND application; moreover, Abbott will provide Cereno with its pulmonary artery pressure monitoring system CardioMEMS HF System in the upcoming study, which previously has been approved for use in severe heart failure. The system can help healthcare professionals remotely and proactively monitor pulmonary and right heart haemodynamics including pulmonary arterial 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, Abbot will get the opportunity to test their CardioMEMS HF System in a new disease indication, PAH, through this Phase II study.
»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 riskscore, will give a good estimation 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
BioStock put together a panel with Cereno’s CEO Sten R Sörensen and CMO Björn Dahlöf, as well as Dr Benza to discuss the details of the upcoming phase II trial 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 relates 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 eventually has 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 riskscore, will give a good estimation 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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