BioStock article: Further steps in Aptahem’s phase I study

BioStock published an article on 28 February 2023 about Aptahem, which can be read in full below.

At the end of December 2022, biotech company Aptahem announced the completion of cohort 1 in healthy volunteers for the phase I study with the sepsis candidate Apta-1. Now, the second dose cohort is also ready and approved by the Dutch Ethics Committee and dose cohort three has started. BioStock talked to CEO Mikael Lindstam to learn more.

At the end of 2022, Aptahem reached its biggest milestone as a listed company – the initiation of a clinical phase I study with the drug candidate Apta-1. As a first step, Apta-1 is being developed as a new emergency treatment for sepsis, a condition that annually leads to about 11 million deaths. Preclinical studies indicate that the candidate has the potential to slow down the body’s uncontrollable inflammatory response, modulate the body’s own defences, and repair or inhibit the tissue breakdown that leads to leaky blood vessels and poor oxygenation in the body.

From these data, the company has concluded that Apta-1 could counteract blood pressure drops and poor oxygenation of vital organs and counteract the harmful effects that occur in sepsis. Sepsis is the company’s overall venture with Apta-1, but Aptahem also sees a potential in treating other critical inflammatory conditions.

More progress in 2022
Before Aptahem could start its first clinical study with Apta-1, the company first signed an agreement with the contract research organisation (CRO) The Centre for Human Drug Research (CHDR) in the Netherlands. Read more here.

The partner was chosen for several reasons. In addition to being a CRO, CHDR is also research centre with state-of-the-art facilities. According to Aptahem, it is staffed by experienced physicians and researchers who were excellent discussion partners in the effort to obtain ethical permission for initiating the study. In addition, the CHDR has extensive experience with LPS provocation studies, a controlled model used to characterise the early stages of a septic condition by provoking a variety of measurable symptoms.

After strengthening the team with Maria Ekblad as the new Chief Operating Officer (COO), Karin Aschan as Regulatory Affairs Director and Thomas Rupp as CMC Director, Aptahem was able to compile a solid clinical package, according to the company. It was also able to produce GMP-certified trial material. In addition to this, the team, headed by Chief Scientific Officer (CSO) Dr Luiza Jedlina, designed its full phase I study design, for which Aptahem received approval.

Soft funding and a new consortium
As previously reported by BioStock, Aptahem joined a new consortium with, among others, Örebro University in the spring of 2022 with funding from the Swedish KK Foundation. The collaboration, which is expected to last for four years, was initiated later in the year.

Aptahem contributes with its drug candidate Apta-1. The company also bring the expert competence of its CSO Dr Luiza Jedlina. She has the role of scientific advisor regarding aptamer-based drugs and especially for Apta-1’s inhibition of inflammation and thrombosis. Read more here.

Cooperation in Canada
Apta-1 has also attracted interest in wider circles outside of Sweden. In 2020, Aptahem initiated a collaboration with a research group at the University Health Network in Toronto, led by Professor Mingyao Liu. Read more here. Since then, the researchers have generated data in a coronavirus-induced lung injury model. It has so far shown that Apta-1 significantly reduces bleeding in the lung tissue, and it inhibits haemolysis and inflammatory responses while keeping vital organs stable.

Rights issue raised SEK 8 million
In the autumn of 2022, Aptahem carried out a rights issue of shares, with a subscription period that ended on 2 December. The rights issue was subscribed to approximately 32.8 per cent and Aptahem thereby received approximately SEK 8.3 million before issue costs, which amounted to approximately SEK 0.9 million.

Cohort 1 in healthy volunteers fully dosed by the end of 2022
A more resolute step towards the first clinical studies was taken on December 5, 2022, when the first healthy volunteers were screened for inclusion in the phase I clinical trial with Apta-1.

The randomised, placebo-controlled trial is led by The Centre for Human Drug Research (CHDR) in the Netherlands. It evaluates the safety, tolerability and pharmacodynamic effects of Apta-1 in healthy volunteers. Roughly a week later, the first patient was dosed, and on December 29, the entire first cohort was dosed without any treatment-related side effects. The stage was now prepared for the next step, cohort 2.

Cohort 2 implemented and approved by the Ethics Committee
Since then, Aptahem has advanced further by having dosed and completed the second cohort in healthy volunteers. The next step has now begun as cohort 3 has been initiated following approval from the Dutch Ethics Committee. Aptahem’s intention is to initiate a phase Ib study as soon as the preliminary results from the phase Ia study are ready. The company expects this to happen later this year. The goal is to conclude the phase Ib study in the fourth quarter of 2023, with reliable results in early 2024.

Comments from the CEO
Progress in 2022 and 2023 has mainly been about the company’s first clinical study. Aptahem’s CEO Mikael Lindstam spoke with BioStock about the ongoing phase I study, as well as the steps needed on the way to phase II.

Mikael, your goal is for Apta-1 to become the world’s first specific emergency treatment for sepsis. For those who may not be so familiar with sepsis, why is an emergency treatment needed for this indication?

– It is needed for several reasons, where the simple and short answer is that there is no single working treatment today or treatments not enough effective. Then, of course, it’s not quite that simple because patients diagnosed with sepsis or septic shock are given antibiotics, often in combination with some form of treatment to keep blood pressure up in order for oxygenation to the body’s organs to continue to function. As antibiotics only work on bacteria-induced infections, it does not help against a viral induced sepsis. Even when using antibiotics it will sometimes not help or if given too late, will not have an effect. As an example of a virus, the recent covid pandemic, had many of the deaths caused by septic conditions when the body could not cope with the infection despite SOC (Standard of care) treatments.

– The reason why we believe that Apta-1 will be the treatment that healthcare demands for acute, inflammatory conditions such as sepsis, is that our candidate addresses both coagulation and inflammation-related problems and reaches the problems within minutes from what we observed in our pre-clinical studies. In fact, sometimes the course from a ‘common’ infection to a death-threatening condition is very short, and the healthcare providers neither have the time for a proper diagnosis nor have an adequate treatment for this extremely acute condition.

– There are ongoing clinical trials with different drug candidates right now. But from what we can see, they only act on either coagulation or inflammation, not both, contrary to our candidate Apta-1, which potentially acts on both.

– I also mentioned that time is an important factor, and, in the worst case, the course of a life threatning septic condition can take only a few hours. That is why there is not always time to wait for the antibiotics to work. Apta-1, on the other hand has been shown in our preclinical studies to be fast-acting, which is another reason why it has the potential to become a long-awaited emergency treatment for sepsis.

Right now, you are conducting the first studies with Apta-1 with the aim of evaluating its safety and tolerability at different doses. You have recently started patient cohort 3. Your comments?

– Yes, the study continues completely according to the plan we have developed, which we are very pleased with so far. After each completed cohort, the ethics committee reviews the data to ensure that the candidate for medicinal products is safe enough to continue to administer at a higher dose. After every other cohort, they will also look at some more comprehensive data on pharmacokinetics, i.e., the amount of Apta-1 at different time-points. It is also the reason why it takes longer to get a response from the committee after every other cohort.

Could you brief our readers about the steps that remain before you can enter phase II studies?

– The first part of the study, phase Ia, which is the mandatory part for studying safety and tolerability, will be completed by the summer, provided that we receive continued green light from the ethics committee after each completed cohort and we can get all cohorts completed. When phase Ia is completed, and a preliminary report is in place, we proceed to the voluntary phase Ib study. It is a provocation study where we will study the effect of Apta-1 in healthy volunteers who have been dosed with a bacterial toxin called LPS first. Apta-1 will then be administered as a treatment which can be seen as more realistically mimicking of a proper treatment in a sharp, acute situation.

– If everything goes according to plan, the entire phase I, i.e., both phase Ia and Ib, will tentatively be completed in late autumn this year. Once the entire study has been compiled and reported in a final report, we will be able to focus even more on the next phase, clinical phase 2 for studies in patients. This preparatory work has already been initiated but it will take significantly more time than the previous Ia/Ib study plan as well as new regulatory handling times have been almost doubled, something we need to factor in. This is completely normal if we are to be able to maintain a pace of development with the clinic without having a waiting period. The internal discussion is since long ongoing and much can be done before we have a final report on the Ia/Ib study, which will eventually give us the indications to be carried into the study design for phase II.

Read the article at biostock.se

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