Potential att bredda indikationen för Cereno Scientifics kandidat CS1
Som BioStock tidigare rapporterat har Cereno Scientific under våren etablerat en Scientific Advisory Board. Då rådet nyligen identifierat ett bredare indikationspotential för CS1 har vi nu talat med dess ordförande, Dr Bertram Pitt. Vi fick veta varför han anser att Cereno Scientific huvudkandidat CS1 – en förebyggande antitrombotisk behandling som snart ska påbörja fas II – kan vara intressant inom ett bredare indikationsfält och varför han valde att ansluta sig till bolaget.
När Cereno Scientific etablerade sin Scientific Advisory Board (SAB) i mars utsågs Dr Bertram Pitt, professor emeritus i medicin vid University of Michigan School of Medicine i Ann Arbor, USA, till rådets ordförande.
Rådet grundades i syfte att stödja bolagets vetenskapliga utveckling och målsättningen var att rekrytera världsledande experter inom bolagets fokusområde, trombosrelaterade kardiovaskulära sjukdomar. Tidpunkten är väl anpassad till avancemanget av CS1s kliniska utveckling, där en fas II-studie planeras att starta under första halvan av 2020.
Förutom CS1 inkluderar Cereno Scientifics pipeline den nyligen förvärvade prekliniska substansen CS014 som har innovativ potential inom kardiovaskulära sjukdomar.
Utökat potential inom kardiovaskulära sjukdomar
CS1 utvecklas för att förhindra blodproppar och ska användas som en förebyggande behandling för trombosrelaterade kardiovaskulära sjukdomar. När Dr Bertram Pitt accepterade rollen som ordförande i Cereno Scientifics SAB kommenterade han:
– CS1 provides a new opportunity to safely prevent thrombosis but in contrast to other currently available antithrombotic drugs it has additional potential that we are excited about. For example, not only could it prevent thromboembolic events but could also prevent the development of atrial fibrillation.
En världsledande expert
Rekryteringen av Dr Pitt, en världsledande forskare med ett grundmurat internationellt rykte, till Cereno Scientifics SAB var en viktig kvalitetsmärkning för bolaget. Han kommer att bli en värdefull resurs som komplettera och ytterligare stärka Cereno Scientifics interna expertis, t.ex. när det gäller att maximera projektportföljens potential och att utforma kliniska studier i enlighet med regulatoriska krav.
Men vad får Dr Pitt ut av det hela? BioStock har talat med Dr Pitt om hans tidigare uttalande om CS1, varför han är så entusiastisk gällande projektet och varför han valde att ansluta sig till Cerenos SAB.
»CS1 builds on a new concept in preventive antithrombotic therapy, namely, to restore (increase the capacity of) the body’s endogenous fibrinolytic system when and where needed. […] VPA also has other important properties that could potentially strengthen its use in cardiovascular disease and complement its use in thrombosis related conditions, e.g. in atrial fibrillation, heart failure and chronic kidney disease.« – Dr Bertram Pitt, professor emeritus i medicin vid University of Michigan School of Medicine
Dr Bertram Pitt, you have previously mentioned that CS1 is a new approach to thrombosis prevention. From your perspective, what is it that makes CS1 ground-breaking?
– I think that firstly, CS1 builds on a new concept in preventive antithrombotic therapy, namely, to restore (increase the capacity of) the body’s endogenous fibrinolytic system when and where needed. Secondly, it has a dual mechanism of action with increased storage and release of t-PA and reduction of PAI-1 levels. Thirdly, CS1 is an intelligent formulation of Valproic Acid (VPA) that maximise the effect of it to coincide with the circadian maximum of PAI-1. And, last but not least, it is a first-in-class mechanism with the potential of an antithrombotic therapy with a reduced risk of bleeding.
– This said, one also has to keep in mind that VPA has other important properties that could potentially strengthen its use in cardiovascular disease and complement its use in thrombosis related conditions, e.g. in atrial fibrillation, heart failure and chronic kidney disease.
»If a therapy like CS1 not only can prevent the thrombotic events per se, but also stop or reverse the progressive remodelling of the atrium, there is a potential to reduce the risk of atrial fibrillation or convert atrial fibrillation to sinus rhythm again.«
Like you said, it has been suggested that CSI, apart from thrombotic events, could prevent the development of atrial fibrillation. How are these connected?
– Atrial fibrillation (AF) is a disease which increases in number with age and is associated with a progressive remodelling of the left atrium. The remodelling of the atrium involves dilatation and fibrosis and is associated with an increased risk of thrombosis in the atrium and subsequent embolic stroke. The risk of embolic events is linked to the size/remodelling of the atrium.
– If a therapy like CS1 not only can prevent the thrombotic events per se, but also stop or reverse the progressive remodelling of the atrium, there is a potential to reduce the risk of atrial fibrillation or convert atrial fibrillation to sinus rhythm again. This could reinforce the antithrombotic effect as such and also improve the well-being of the patient having less symptoms of rapid/irregular beats. Importantly, CS1 reduces PAI-1 and PAI-1 is associated with fibrosis, this perspective is interesting when looking at atrial fibrillation both in relation to prevention of thrombotic/embolic complications, and in relation to the importance of an antifibrotic effect for stopping progressive atrial remodelling.
– I also want to mention that there is a recently published study that shows that VPA, in transgenic mice that are prone to remodelling and subsequent atrial fibrillation, could improve on both remodelling and prevent/delay future atrial fibrillation. This study from researchers in Germany is a preclinical Proof of Concept for CS1s ability to prevent atrial fibrillation.
Speaking of AF, it is the most common indication for prescribing NOAKs today. Why are NOAKs suboptimal for AF treatment, and in what way could CS1 be a better alternative?
– NOAKs have the same problem as all current antithrombotic therapies; suboptimal dosing due to fear of bleedings or actual bleedings. Even though being a simplified regimen compared to vitamin K antagonists, they are still a suboptimal therapy. CS1 could be a game-changer with improvement of fibrinolysis only when and where needed instead of putting the body in constant risk of bleeding. Providing a first-in-class therapy based on enhanced fibrinolysis with a reduced incidence of bleeding, CS1 would be a powerful contribution to future preventive antithrombotic therapy.
– In addition, the antifibrotic/prevention of pathological remodelling capacity that CS1 seems to have adds a whole new dimension to treatment of atrial fibrillation that NOAKs do not have.
»In addition to being an improved therapy for atrial fibrillation, CS1 could be useful in the remodelling associated with myocardial infarction (MI).«
Are there any additional cardiovascular disease prevention methods that CS1 could be relevant for, and, if so, what is the reasoning behind it?
– VPA has, in addition to an antithrombotic effect, shown interesting and potentially very useful properties for cardiovascular disease associated with thrombosis. I have already mentioned some of the potential antifibrotic properties of CS1 in atrial fibrillation. In addition to the antifibrotic effect shown with VPA, anti-inflammatory properties have been shown as well as the fact that VPA can lower increased pulmonary artery pressure.
– This opens up a whole menu of other potential CV indications. In addition to being an improved therapy for atrial fibrillation, CS1 could be useful in the remodelling associated with myocardial infarction (MI), and actually there is a recent publication from my institution that shows that VPA can reduce remodelling and infarct size (up to 50%) after coronary ligation in animals.
– Furthermore, there is a huge need for preventing renal fibrosis where VPA has shown interesting results.
– Finally, there is huge unmet need in rare thrombotic diseases, where CS1 might have additional potential.
You met with the other SAB members at the Heart Failure conference in Athens on May 24. What was on the agenda for your meeting?
– Basically, this first meeting of the Scientific Advisory Board was to get to know each other and unprejudiced get to know CS1 and its potential. The meeting was also about starting to explore the further potential of CS1 and CS014 beyond traditional antithrombotic therapy, which in itself is a huge potential game-changer.
– Furthermore, I think we will start to explore the potential of this first in class therapy in atrial fibrillation, renal fibrosis and potentially secondary prevention of MI.
– In future SAB meetings we will most likely also discuss the potential of this technology beyond cardiovascular diseases.
»The potential of Cereno Scientifics technology fascinates me; having a huge potential in thrombosis related disease and beyond. It could potentially be the therapy of choice in the future.«
If you could sum up your reasons for accepting the position as chairman of Cereno Scientific’s SAB in a few words, what would you say?
– The potential of Cereno Scientifics technology fascinates me; having a huge potential in thrombosis related disease and beyond. It could potentially be the therapy of choice in the future.
– Based on my experience, there are several new areas to explore and I look forward to potentially advancing this exciting new technology forward into new indications.
Where do you see Cereno Scientific in three years’ time?
– Having successfully shown the potential of CS1 as a future anti-thrombotic agent in a proof of concept study Cereno Scientific has other candidates in the pipeline for other indications in CV.
– As the development of Cereno Scientific’s concept progresses, I believe that it would be an interesting target for being partnered/outlicensed or acquired by a major pharmaceutical company in order to take advantage of the full potential of this new and I believe unique therapeutic concept which combines antithrombosis with antifibrosis.
Läs också: Cereno Scientific rekryterar internationellt toppnamn till sin nyinrättade Scientific Advisory Board (11 mars 2019)
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