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For Swedish biopharma company Abliva the first half of the year was dominated by two important news events – the change of CEO to industry veteran Ellen Donnelly in January and the positive results from the company’s phase Ia/b study with lead candidate KL1333. BioStock spoke with the Chief Medical Officer Magnus Hansson to get his take on the past six months and on what we can expect from Abliva during the rest of 2021.

Lund-based Abliva focuses on the development of treatments for rare primary mitochondrial diseases (PMD). This is a group of diseases where the mitochondria, responsible for creating the energy needed by the human body to function optimally, malfunction. For the patients this often leads to severe symptoms, such as difficulties moving and breathing, and a shortened lifespan.

The company is developing two candidates. The lead candidate, KL1333, for the treatment of primary mitochondrial disease in adults (including MELAS and similar conditions), is currently on its way to a phase II/III study start. The second compound, NV354, targets the paediatric disorder Leigh Syndrome, and is also moving towards clinical studies which are expected to begin in 2022.

KL1333 continues to advance

The first half of 2021 was focused on the continued advancement of lead candidate KL1333. The accelerated plan can be traced back to summer 2020 when the FDA provided positive feedback on Abliva’s clinical development plan and recommended the company conduct a single phase II/III study. Abliva decided to follow this recommendation in order to shorten the time to market for KL1333. The merged phase II/III study is planned to begin during the second half of 2021, but before it can start several companion studies are necessary. A number of these companion studies, including an important drug interaction study (DDI study), have already been completed with encouraging results.

In May 2021, Abliva reported positive results from the phase Ia/b study with KL1333, an important step in the candidate’s clinical development. The study consisted of 64 healthy volunteers as well as eight patients with primary mitochondrial disease. The inclusion of these patients marked another significant milestone in KL1333’s development as it was the first time the candidate was given to PMD patients. Overall, the study showed positive safety and pharmacokinetic data as well as signals of efficacy in relevant clinical outcome measures in PMD patients. Read more about the phase Ia/b results here.

New CEO to take Abliva to the next level

The advancement of KL1333 also played an important role in 2021’s other big news from Abliva. In January, the company announced that CEO Erik Kinnman was stepping down and that Dr. Ellen Donnelly was taking over the position. In Donnelly, Abliva secured a CEO with the credentials needed to take the company to the next stage of development. Donnelly not only has previous experience in later-stage development, but, from her time as CEO of Modus Therapeutics, also has experience in the development of treatments for rare diseases. Read an interview with Ellen Donnelly here.

Strengthened finances

It is also worth noting that Abliva, during the first half of 2021, made sure to strengthen the coffers ahead of further clinical development. In April the company completed a share issue to several Swedish and international investors, including Hadean Ventures, a leading Nordic life science investor that invested significantly in Abliva during 2020. The financing round brought in 80 MSEK before costs, funds that will be used primarily on the clinical development of KL1333.

BioStock spoke to Ablivas CMO Magnus Hansson to get his view of the first half of 2021 and what is next for Abliva.

Magnus Hansson, CMO, Abliva

Magnus, first of all, in your opinion, what has been the most important news from Abliva during 2021 so far?

– The most important news for the company was definitely the readout of the phase Ia/Ib study. The study not only showed that KL1333 is safe in healthy volunteers and patients, but also gave us a clear signal of efficacy in patients suffering from PMD. Even though this was a small study, we wanted to run it in a ‘blinded’ fashion, meaning that we gave some patients a placebo pill (without the active ingredient) and other patients a pill including KL1333. Both pills in the study looked identical and neither the patients nor the physicians knew which patients had been given KL1333 and which patients had been given the placebo pill.

–  In all of the key efficacy endpoints there were greater improvements in the patients receiving KL1333 compared to the patients receiving placebo. The endpoints we explored, debilitating fatigue and muscle function, address issues that patients with primary mitochondrial disease find most important to improve, and the magnitude of improvement in those receiving KL1333 versus placebo was in the range considered clinically meaningful. These disease expressions, fatigue and muscle weakness, will be a focus in the phase II/III study, so these results gave us further confidence that we will be able to generate the data required to show that KL1333 is effective and then, most importantly, seek approval so we can get KL1333 into patients.

Much of 2021 has been about the clinical development of KL1333. You achieved positive results in the phase Ia/b study, what can you tell us about the other studies you are conducting prior to the start of the merged phase II/III study?

– Concurrent to the phase Ia/Ib data release, we announced results in our drug-drug interaction study, where KL1333 was given to healthy volunteers, along with other commonly prescribed drugs. Seven drug-metabolising enzymes were analysed and no concerning interactions were found. This means that we do not anticipate having issues with recruiting patients on commonly used medicines into the upcoming phase II/III study.

– We have also conducted a patient registry study in partnership with Newcastle University in the UK. The investigators in Newcastle have access to a unique patient registry and have extracted important data about the prevalence of different symptoms and combinations of symptoms in PMD patients – data that has helped us in the design of our upcoming study.

– Another important study is an ongoing patient study which will validate fatigue as a clinical endpoint. This interview study, planned in close discussion with the US Food and Drug Administration (FDA), is being run in PMD patients in the US.  This study will establish a fatigue endpoint that is relevant and validated in PMD patients, something that until now has not been done.

– Finally, we have now initiated long-term toxicological studies that will continue to run in parallel to the phase II/III study.

 What remains to be done before the merged phase II/III study can start?

– A key upcoming milestone for Abliva and KL1333 is the submission and approval of our Clinical Trial Application (CTA) / Investigational New Drug (IND) application. We have previously discussed our clinical plan with both US and European regulators and have appreciated their guidance. This input, combined with input from patients and key opinion leaders, has been instrumental as we finalised our clinical trial design. In parallel to finalising the regulatory submissions we are intensively evaluating and selecting the study sites for the upcoming study.

You have previously communicated that the plan is to initiate clinical studies with NV354 during the second half of 2021. What is the status in the NV354 project?

 – The preclinical pharmacology and safety studies for NV354 are in the final stages. Towards the end of the year we will complete regulatory documentation to support clinical study start. We expect that phase I studies will commence in early 2022.

What milestones can we expect from Abliva during the rest of 2021?

– The first half year has been very intense, and the next half promises to be even more exciting. The Abliva team will have full focus on KL1333 and the start of the phase II/III study will be a major milestone in the second half of the year.

 

The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.

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