– In their analysis, the DMC will review the safety profile of KL1333 and the potential of the study to achieve statistical significance after the full 48 weeks of dosing, says Abliva’s CEO Ellen Donnelly.
Abliva is developing therapies that restore mitochondrial function. Lead candidate KL1333 is a drug being evaluated in the phase II FALCON study for the treatment of mitochondrial DNA (mtDNA)-related mitochondrial disease in adult patients suffering from debilitating fatigue and muscle weakness.
Abliva moves toward interim analysis with FALCON study
During Q1, the company has made significant progress with the FALCON trial. Since achieving full enrollment in the Wave 1 part of the trial late last year, Abliva has been working around the clock to reach interim analysis in a timely yet efficient manner, working closely with clinical sites to ensure everything is on track.
One of the key steps towards the interim analysis is sending the data to the Independent Data Monitoring Committee (DMC) once the last patient completes their 24-week visit. The committee will review the safety profile of KL1333 and evaluate the potential of the study to achieve statistical significance after the full 48 weeks of dosing. If the DMC’s recommendation is to continue the study into Wave 2, they will also make a determination as to the final size of the study, up to 180 total patients.
Keeping close ties with the mitochondrial disease community
As part of Abliva’s long-term goal to become a leading global company focused on discovering therapeutics for mitochondrial disease, the company also makes a point of actively engaging with the mitochondrial medicine community.
For example, in early February Abliva met with physicians and FALCON investigators at a national mitochondrial disease meeting in Strasbourg, France. Then, the team attended the Mitochondrial Medicine – Therapeutic Development meeting in the UK. They are now preparing for the Mitochondrial Medicine Conference in the US, an event that brings together key stakeholders in the field.
Investor outreach is a priority
As the interim analysis approaches, the company has been making sure to reach out to the investor community, giving them a detailed overview of what Abliva can bring to the table in terms of value for future shareholders. Part of that outreach came in the form of hosting a virtual Key Opinion Leader (KOL) event, featuring Dr Amel Karaa, a specialist in mitochondrial disease from Massachusetts General Hospital, and her patient with mitochondrial disease. The event provided an overview of primary mitochondrial disease, the challenges in developing treatments, and detailed insights into KL1333.
The team has also been actively meeting with investors at events like the Van Lanschot Kempen Life Sciences Conference and BioEquity. Upcoming participation will include BioInternational, and also the BioStock Global Forum, where Abliva’s CMO Magnus Hansson will showcase the company.
Successful capital raise
In February, Abliva announced a successful financing round, comprising a preferential rights issue and a convertible loan. The rights issue raised SEK 46 million before transaction costs, and many guarantors opted to receive their fees in shares, indicating strong confidence in the company. The convertible loan of SEK 42 million (before transaction costs) will convert if the interim analysis is positive.
»I am confident that we have designed a study that will properly test the safety and efficacy of KL1333 in patients with primary mitochondrial disease«
CEO insights
BioStock reached out to Abliva’s CEO Ellen Donnelly to get her take on Q1 and the expectations for the FALCON interim analysis.
Ellen, what is the take-home message from Abliva’s Q1?
– The take-home message is that we remain on track for the interim analysis early in the third quarter. The team has worked tirelessly making sure all of the necessary data is being collected and prepared so that the interim analysis can proceed as seamlessly as possible.
Could you tell us more about what needs to be done between the last 24 week visit and the announcement of the outcome?
– The interim analysis involves a review of the data from all Wave 1 patients across 6 different countries and 18 sites. To ensure high quality data, the Abliva team works closely with our Contract Research Organization, ICON, and the clinical sites, to design an optimal process to ensure the data set is correct and complete. The data is collected and recorded in a central database, verified against source data during monitoring visits, and then analyzed and assembled into a clear output for review by the Data Monitoring Committee (DMC).
– The DMC is an independent group of medical and statistical experts who will come together to review the data and give their opinion on the safety profile of KL1333 and recommend the final size of the study. Once Abliva receives the recommendation we will issue a press result detailing the outcome.
How confident are you in a positive decision by the DMC?
– It is impossible to predict the outcome of any interim analysis or clinical trial. What I am confident in, however, is the data package for KL1333 and the design of our currently study. First, the preclinical data package for KL1333 clearly demonstrates that KL1333 has a positive effect on the underlying disease mechanism of primary mitochondrial disease. Second, the results from our phase Ib study in mitochondrial disease patients indicated that KL1333 had an effect on fatigue and myopathy, the two endpoints being evaluated by the DMC. I am also confident that our study was designed in an optimal manner to give KL1333 the best chance to succeed.
– For example, the alternate endpoint approach allows us to independently evaluate both fatigue and myopathy as primary endpoints, giving us two opportunities for a successful study. We also included a long screening period in the study which allowed us to confirm that the patients we dosed were all patients that met our stringent inclusion criteria. And I think the study duration (48 week) will give us time to see the impact of KL1333 on mitochondrial function. And thus, based on our preclinical and clinical data, I am confident that we have designed a study that will properly test the safety and efficacy of KL1333 in patients with primary mitochondrial disease.
Have you experienced good engagement with investors at recent events?
– The team has been very active this year in participating in conferences where we can further spread the word about Abliva and our efforts to develop medicines for primary mitochondrial disease. We are working in a space that is very attractive to both investors and strategic partners as we have a late-stage asset in a rare disease with a relatively uncrowded competitive landscape. So yes, we have been quite busy at the recent meetings. This week Magnus will be attending the BioStock Global Forum in Lund and I will head to BioInternational (San Diego, CA) on Sunday, so we are looking forward to continuing our discussions with biotech and pharma executives as well as life science investors.
How critical is the financial boost you got recently?
– We are thankful for the continued support of our shareholders, who clearly saw the importance of our latest financing round, a novel type of financing that included a preferential rights issue (now completed) and a convertible that will be triggered upon a positive (non-futile) interim readout. This round was crucial as it will allow us to continue moving KL1333 towards the market as we review the data from the interim analysis and progress discussions with potential partners and investors.
