Interview with the Chairman of the Scientific Advisory Board, Dr Anders Bylock
”Aptahem’s drug candidate shows sensationally good results in sepsis studies”
The scientific advisory board has now been in place for almost a year, and we have interviewed the president of the board, Dr. Anders Bylock, about what has happened since he assumed his appointment.
Anders Bylock, could you describe your role and the role of the scientific advisory board in the development work that has been conducted this year? How do you think Aptahem is doing now compared to when you first started working with us?
The scientific advisory board has had, and will have, a very strong significance for ongoing and future development. We have been central in the shift of the indication area to, as we see it, an area of extremely high medical need, namely the life-threatening pre-shock that is caused by various very serious disorders in human functions. This includes conditions where there is a loss of control over normal and functional defence mechanisms such as coagulation and inflammation which, instead, overreact and become counterproductive, sometimes even fatal by nature.
The European Medicines Agency, EMA has announced that they intend to review the use of drugs with hydroethyl starch. These drugs, such as Voluven, aim to maintain blood volume in order to counteract shock in patients following acute bleeding. How do you see this in relation to our development of Apta-1?
It would be very good if more drugs were to be developed in this area, since it affects a very large number of people every minute in the world. Maintenance of the circulating fluid volume is central, but in a large proportion of cases where life-threatening shock is imminent, it needs to be supplemented with anticoagulation and / or inflammation attenuation during the time that it is needed for example to give antibiotics a chance to take effect.
Over the year we presented very positive study results. What can we say for sure about Apta-1 today, which we were not previously aware of?
We are now able to summarize an exciting year, where we saw completely new effects which could have very significant clinical relevance. We have seen a combination of promising clinical parameters, such as improved circulation, strong indications of positive effects of Apta-1 in the laboratory, and perhaps most importantly, a dramatically improved survival, which is ultimately by far the most important biomarker. In fact, from the first animal study; a sepsis in mice study, which is a very common model of survival, we could hardly believe the results were possible to achieve. We repeated the study with an even larger number of animals, as well as other doses and regimens, and saw the same results! It would be deeply unfortunate if we were not able to quickly proceed both with further animal models and at the same time documentation in humas, which would initially be focused on safety but as soon as possible on the clinical effect in an intensive care situation, where measurement of biomarkers can quickly show if there are also positive effects in humans.
Improved survival is a clear measure of effectiveness. To what extent can you draw conclusions about what we expect to see in humans based on the preclinical model? Is this the only animal model?
At the moment we see both extreme benefits in effects and side effects, so to complement not only other animal models but also the rapid testing of pharmacokinetics and pharmacodynamics in humans as soon as possible is most desirable.
The study design in the second study was somewhat different from that we used in the first study. Would you care to tell me how and why?
The classical things one looks for when considering a project for a larger company are the dose-response curve as well as the timing of the drug administration. These must be adapted to the type of drug and its pharmacokinetics. In the case of Apta-1, this is especially important as it is essential that in this first stage of development, the drug should be administered directly into the patient’s fluid volume, and furthermore, this should be relatively often. Therefore we took the opportunity to test more dose levels and other dosing intervals. Since we saw both a dose response within the intended dose range and a possible additional effect due to the later distribution of the drug, we believe our clinical trial plan is further strengthened.
”In fact, from the first animal study; a sepsis in mice study, which is a very common model of survival, we could hardly believe the results were possible to achieve. We repeated the study with an even larger number of animals, as well as other doses and regimens, and saw the same results!” – Anders Bylock
If we choose to look forward into the future, what will happen next in the development of Apta-1 and what important milestones are to follow in the development programme?
We will need to recruit both preclinical and clinical expertise in the pre-shock / sepsis areas, produce more substance, initiate a phase I study in humans as soon as possible, and in parallel to this, perform tests on more animal models for sepsis.
We participated in BioJapan where we received very good response from several important players. How important is Japan as a market in sepsis?
Because shock, which is sometimes caused by sepsis, is one of the most common conditions that leads to premature death in all countries, this project would be of utmost importance, no matter where in the world you are and no matter what market you are thinking about. In fact, this is one of the clinical areas that has the greatest need for better treatments.
During this week, Aptahem will participate in BioEurope, Europe’s largest partner conference, as part of an active effort to form a successful partnership for the company’s drug candidates. As an industry veteran with experience of in-licensing, what factors do you think will make Aptahem stand out this week?
I feel that the concept we have documented so far is so extremely strong compared to the many dozens of projects I have previously evaluated. Uniquely strong preclinical results, so far with a very low documented toxicity and in an area of enormous medical need makes the package extremely interesting.
”This is one of the clinical areas with the greatest need for improved treatments.” – Anders Bylock
Could you give us some insight into the ongoing preclinical development work and how current activities support the continued clinical development of Apta-1?
With regard to the details of the preclinical development work, I would refer to other expertise within the company. What we have seen so far is that the first biomarker studies have shown both good anticoagulant and anti-inflammatory effects, which were then supplemented by sensationally good results in two large sepsis studies where mortality and the “clinical” condition were studied. We need to confirm these results in more animal species as soon as possible, but unfortunately, I am unable to provide further information on the subject at the present time.
When can we expect to hear more about upcoming preclinical milestones?
We are working on publishing the results that we have seen so far in our preclinical models, and hope to have articles published in early 2018. Parallel to this work, new studies are being prepared in other animal models, as well as the first human studies.
Aptahem has on several occasions been asked by shareholders why Apta-1 will be launched as a drug for sepsis, given that no one has so far managed to get an effective product on the market. What would be your comment here?
These days, all areas with a major medical need are generally considered to be difficult given the enormous resources that have been pumped into medical research over the past decades. However, the results we saw in the summer of 2017 are so good that we hope we will be able to offer uniquely effective therapy in an area where the need is acute, critical and of great human and economic value. The combination of properties that Apta-1 exhibits is unique, and has not been tested before in an acute life-threatening sepsis-like situation, a clinical condition which is rapidly fatal and, moreover, very common. Our dream would be to be able to offer therapy which could work as a supporting bridge between a severe critical state for the patient and over to a situation where causal therapy, like antibiotics, anti-inflammatory medicines, anticoagulants, thrombolytics etcetera, would start to take effect on the actual disease state.
In this context, it is important to emphasise the fact that some patient groups cannot be expected to have a therapeutic response, for example those who have lost a lot of blood or have a severe heart/lung failure or the like, where one should not expect Apta-1 to have a dramatic effect. With the careful analysis of the very positive results we have seen from many of the biomarkers, we should be able to define the target groups which can be expected to react most favourably to Apta-1, and therefore we should be able to avoid the pitfalls which have been previously described, which in many cases are likely to have been dependent on the fact that the patient groups have been overly heterogenous.
Finally I would like to reconnect to your role as chairman of the company’s scientific advisory board. With full speed ahead into the preclinical work, the company’s need for clinical and industry expertise will only increase. How do the expansion plans look for the scientific advisory board perspective and what type of expertise will you be looking for?
We are looking for clinical intensive care specialists from all over the world, preferably with experience in drug development. Bringing in experts with experience in animal models which are relevant for pre-shock and sepsis in humans is also of value.
For further information
Mikael Lindstam, CEO
Tel: 0766-333 699
Aptahem AB (Aktietorget: APTA) is a biotechnology company which is developing aptamer-based drugs for the treatment of life-threatening conditions in which coagulation and inflammation work together in the process of the disease. Apta-1, the company’s main drug candidate, is an acute drug which is in development with the goal of stopping the organ and tissue damage which leads to the very high mortality rate in, among others, patients with sepsis. The company holds patent protection on strategic target markets and carries out active business development work towards future partners.