Yesterday, news came that Cereno Scientific had received approval for the planned Phase II study with CS1 in Bulgaria – the second and last country to host the phase II study with CS1. BioStock contacted CEO Sten R. Sörensen, currently at an “Anti-Fibrotic Drug Development” conference in Boston, for a comment.
In late September, Russia approved Cereno Scientific’s application to conduct a Phase II clinical trial with CS1 to evaluate the candidate’s ability to prevent thrombosis. Now, Bulgarian authorities have also approved the study application.
The plan is to start the prospective, randomized clinical trial in mid 2020. It will be conducted at about 30 clinics between the two countries and include both men and women between the ages of 55 and 90 who are to undergo orthopaedic knee surgery. The reason being that such surgery is associated with an increased risk of thrombosis during the time following the procedure, which is why this particular patient group enables a time-efficient evaluation of the candidate’s thrombosis prevention potential compared to existing treatments. Many of today’s well-established thrombosis treatments began their clinical development with this type of study.
New type of preventive antithrombotic therapy
CS1 works by activating and strengthening the body’s own intelligent anti-thrombotic system – the fibrinolytic system – to prevent blood clots from growing and clogging the blood vessels. As a result, the body’s own ability to dissolve blood clots is restored in individuals where it, for some reason, has been impaired, which is common in patients with e.g. cardiovascular disease.
The mechanism of action of CS1 is a new way to attack the risk of thrombosis compared to traditional anti-thrombotic therapy, blood thinners, which instead focuses on inhibiting the blood’s coagulation capability and/or inhibiting platelets. However, a subdued coagulation ability causes a constant increased risk of bleeding, which is not expected to be an issue with CS1 as it restores fibrinolytic capacity throughout the body, a capacity which is only triggered locally when needed. To manage the risk of bleeding, blood thinners are sometimes given in too low doses, or not at all, out of fear of excessive bleeding. Therefore, optimal anti-thrombotic treatment effect is seldom achieved. This is a very serious problem as thrombosis is the single most common cause of death worldwide.
The evaluation of CS1 in the upcoming phase II study
The end-game for Cereno Scientific is to be able to provide an effective and safe treatment alternative with reduced risk of bleeding for people who face a risk of thrombosis.
The planned Phase II study will thus evaluate CS1’s anti-thrombotic capacity in terms of the number of thromboembolic events after knee surgery and, at the same time, evaluate the risk of excessive bleeding measured as the number of bleeding episodes of varying levels of severity. In addition, further aspects of the candidate’s safety profile will be evaluated with standardized monitoring procedures.
There will be two parallel treatment arms and the patient will either be randomized to CS1 or to standardized thrombosis prophylactic therapy. CS1 will be given once a day, in two different doses, two weeks before surgery and four weeks after. The control group will be given standard treatment with Enoxaparin once a day.
The CEO comments
When the Bulgarian authorities’ study approval was announced, Cereno Scientific’s CEO Sten R. Sörensen was pleased:
– The fact that initiation of our Phase II clinical trial was approved in both Bulgaria and Russia is very positive as an important milestone now has been achieved. We are now working fully on the preparations and look forward to start the study next year.
Sörensen is currently on American soil to attend the Anti-Fibrotic Drug Development Conference (AFDD) in Boston. Today, he is invited to talk about the advances in the field of cardiovascular fibrosis as well as to participate in a panel debate on late clinical studies in fibrotic diseases.
After taking into account the time difference between Sweden and the US east coast, BioStock gave him a call to follow up on the study approval in Bulgaria and learn more about AFDD.
»All the work that has been done since the company was founded led us to the position we are in today.« – Sten R. Sörensen, CEO of Cereno Scientific
Sten R. Sörensen, CEO of Cereno Scientific, first and foremost congratulations on the approved study! Could you tell us about the work that has led up to the approval?
– Thank you so much! In fact, all the work that has been done since the company was founded led us to the position we are in today. Since our candidate CS1’s potential began to crystallize through well-conducted preclinical studies, it has been necessary for the company to find the strategically optimal way forward. Of course, the preclinical and clinical development has been essential, but as a smaller biotech company with a growing international focus, we are also dependent on continuous and solid business development activities. For example, we need to make the right contacts at the right time and bring in the right skills as the project develops, both in-house and through consultancy. In parallel with creating the conditions required to be able to raise capital, which in turn secures our operations, this is the basis for being able to drive the project forward in an efficient manner.
– Overall, I think we have done this in an exemplary way, which has resulted in a highly competent team, a world-leading Scientific Advisory Board with a fantastic network within our field and succeeding to keep our communicated timelines.
– Specific activities that have led up to the study approval includes a comprehensive compilation of all existing data relating to CS1 and the development of a study protocol that meets the authorities’ high set criteria and standards. In addition, there is a lot of administration associated the actual submission of the application and subsequent correspondence with the authorities. For the latter, we have had the assistance of our study partner, the clinical research organization OCT Group.
»We can proceed with our set plan for conducting the study, together with OCT Group. Their extensive experience and well-developed strategy are based on the participation of established and experienced orthopaedic surgical clinics in both Russia and Bulgaria.«
When the study was approved in Russia, you said that it was the company’s biggest milestone to date. How does the Bulgarian approval relate?
– It is obviously very important to get the study approved in at least one country, as it was in Russia. At the same time, the approval from the authorities in Bulgaria are perhaps even more important as it means that we can proceed with our set plan for conducting the study, together with OCT Group. Their extensive experience and well-developed strategy are based on the participation of established and experienced orthopaedic surgical clinics in both Russia and Bulgaria.
Has it already been decided which clinics will be conducting the study? If so, what can you say about them?
– OCT has already established contact with most clinics that will participate in the study. OCT has visited the clinics, documented their conditions for participation, that they operate on enough patients per year, evaluated their past experiences of participating in clinical studies and other relevant study-related conditions that my colleagues on our team have been briefed about. Most of the clinics selected by OCT have previous experience participating in similar studies.
What additional steps remain to enable you to start the Phase II study according to the scheduled timetable, i.e. in mid-2020?
– The fact that we now have approval from the relevant authorities in both Russia and Bulgaria means that we have achieved a significant milestone, which we are very pleased about. What remains is that we, together with our partner Galenica, will succeed in scaling up production of test material. Although it is a very complicated process, we currently have no reason to believe that it will not be done within the set time frame.
»We try to be active and attend conferences. This has several advantages, in particular it gives an opportunity to both maintain existing, and make new, important contacts in the cardiovascular field. In addition, these conferences showcase presentations and discussions in the very latest cardiovascular research advances«
We will follow the development with interest. Meanwhile, you also seem to be investing in becoming more visible in the cardiovascular field. Right now, you are in Boston for this year’s AFDD conference. What brings you there?
– It is true that we try to be active and attend conferences. This has several advantages, in particular it gives an opportunity to both maintain existing, and make new, important contacts in the cardiovascular field. In addition, these conferences showcase presentations and discussions in the very latest cardiovascular research advances, and we get insights and knowledge that we can then bring home and apply to our own projects.
– However, one could wonder why I am attending a conference on the development of drugs for the treatment of fibrosis. I believe that Cereno Scientific was invited to the meeting because the fact that our treatment concept has favourable effects on fibrosis, through epigenetic modulation in several organs, has been recognized.
– The importance of fibrosis in the body should not be underestimated as almost half of all chronic diseases, many cardiovascular, are associated with fibrosis. Moreover, fibrosis is associated with a significant mortality, similar to that of thrombosis. In fact, there are many links between thrombotic and fibrotic development in the body.
What, then, is epigenetic modulation?
– It is the body’s way of changing the reading of the genetic code without changing the basic code itself. It can be compared to being able to play the right melody on a piano by tuning individual keys where the melody is the genetic code. Epigenetic modulation then becomes ”gene therapy” at the population level. This increasing insight into our treatment concept can lead to the development of opportunities in both major cardiovascular diseases and rare diseases, or “orphan drug diseases.”
»Our CMO Björn Dahlöf will represent – and present – Cereno Scientific at the prestigious Global Cardio Vascular Clinical Trialists Forum in Washington D.C. in early December. There, we will, once more, have the opportunity to present our potentially expanded treatment options related to fibrosis in front of world leading KOLs in the field, and, not the least, US decision makers.«
What does your participation at AFDD entail?
– I appear in the program twice, both times being later today. Firstly, I will present our treatment concept under the theme ”Advancements in Cardiovascular Fibrosis.” My talk will touch on the potential we see in our treatment concept, not least from the aspect that scientific studies indicate that VPA (valproic acid) has the potential to inhibit, or even decrease, already-established fibrosis development and, at the same time, affect inflammation and elevated blood pressure both in the lungs as well as in the rest of the body. This is very exciting as it opens up for the treatment of further cardiovascular indications for Cereno Scientific, e.g. heart failure, chronic kidney damage, atrial fibrillation and even for rare diseases treated with orphan drugs. This is something that has captured a great deal of interest in the industry.
– In addition, I will participate in a panel discussion called “Spotlight on Fibrotic Disease Areas & Later Stage Clinical Trial Design,” where we will discuss how to best utilize the knowledge of fibrosis development and its consequences in future studies where Cereno Scientific hopes to be able to contribute with some innovative studies in the field of fibrosis.
Is Cereno Scientific planning on any other conference attendances in the near future?
– Yes, our CMO Björn Dahlöf will represent – and present – Cereno Scientific at the prestigious Global Cardio Vascular Clinical Trialists Forum (CVCT) in Washington D.C. in early December. There, we will, once more, have the opportunity to present our potentially expanded treatment options related to fibrosis in front of world leading KOLs in the field, and, not the least, US decision makers.
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