Abliva har rapporterat positiva interimsanalysresultat för den potentiellt registreringsgrundande FALCON-studien, som utvärderar KL1333 hos patienter med primär mitokondriell sjukdom. Samtidigt som studiedesignen valideras och KL1333:s starka säkerhetsprofil bekräftas, utlöser den också en konvertering av konvertibellån, vilket ger Abliva en likvid om 42 miljoner kronor före transaktionskostnader.
– The interim analysis is an important de-risking event for the program, säger Ablivas vd Ellen K. Donelly.

Abliva utvecklar terapier med målet att förbättra mitokondriernas funktion. Huvudkandidaten KL1333 är en läkemedelskandidat som utvärderas i fas II-studien FALCON för behandling av mitokondriell DNA (mtDNA)-relaterad mitokondriell sjukdom hos vuxna patienter som lider av funktionsnedsättande trötthet och muskelsvaghet.

Positiv interimsanalys

Abliva uppnådde full rekrytering i Wave 1-delen av FALCON-studien under Q4 2023 och den 30 maj 2024 hade den sista patienten avslutat sitt 24-veckorsbesök. Den oberoende dataövervakningskommittén (DMC) har nu granskat 24-veckors interimsdata från Wave 1-patientkohorten, där den oberoende gruppen granskade en förspecificerad villkorsstyrd poweranalys för de två primära effektmåtten efter 24 veckors dosering.

Båda effektmåtten klarade futilitetstestet och DMC rekommenderade att inkludera totalt 180 patienter, vilket ökar sannolikheten för ett positivt resultat efter slutförandet av den fullständiga studien. DMC betonade att KL1333 har en god säkerhetsprofil och inga säkerhetsproblem eller läkemedelsrelaterade allvarliga biverkningar (SAE) sågs under 24 veckors dosering.

Abliva siktar på att starta den sista vågen av FALCON-studien under andra halvåret 2024.

Erhåller 39 miljoner kronor

Samtidigt har Abliva också meddelat att det konvertibla lånet från kapitalanskaffningen tidigare i år kommer att konverteras till aktier i bolaget. Denna konvertering, som föranleddes av den positiva interimsanalysen, kommer att ge Abliva ytterligare 42 miljoner kronor i tilläggslikvid före transaktionskostnader om cirka 2,9 miljoner kronor.

Vd kommenterar

För att få veta mer om betydelsen av de positiva resultaten från interimsanalysen kontaktade BioStock Ablivas vd Ellen K. Donnelly.

Could you begin by discussing the positive interim analysis results and the significance of the 24-week interim data for KL1333?

– The interim readout is great news as it not only confirms that the program has passed futility, but it also provides an important de-risking step for the program as we now have more information regarding the potential efficacy of the two endpoints and the safety profile of KL1333.  When we started the FALCON study we had only dosed 6 patients with KL1333 (2 on placebo) for 10 days with 50 mg KL1333/day.  The interim analysis reviewed data from 35 patients dosed with 50 – 100mg/ day for 24 weeks.   So knowing that KL1333 continues to have a good safety profile at a higher dose over six months of treatment is very important.  To know that both of our primary endpoints, fatigue and myopathy, are still ‘in play’ is very encouraging and takes us one step closer to the market.

Can you elaborate on the independent primary endpoints in the FALCON study?

– Our study focuses on the two symptoms that patients with primary mitochondrial disease cite as the most debilitating – fatigue and myopathy.  We are evaluating fatigue with a mitochondrial-disease-specific patient-reported questionnaire that we developed with patients, and myopathy with a simple test where you count the number of times you can stand up and sit down from a chair in 30 seconds (30 Second sit-to-stand test). The FALCON study is designed so that only one of these independent (alternative) endpoints needs to show a statistically significant improvement in the patients for the study to be positive. And now, after this positive interim readout, we are even more confident with this primary endpoint design, knowing that we still have two chances to be successful.

How does KL1333’s novel mechanism of action contribute to its potential success?

– KL1333 specifically targets an underlying cause of mitochondrial disease – a decreased NAD⁺/NADH ratio, crucial for energy conversion in the mitochondria. By converting NADH to NAD⁺, KL1333 restores the ratio and has the potential to normalize cellular energy production.

Can you explain the expedited path to market for KL1333?

– The regulatory agency in the US that approves new medicines, the Food & Drug Administration (FDA), has a number of programs that facilitate the development of medicines for rare diseases with high unmet medical need.  One example is the requirement for only one (versus two) late-stage study for approval. Another example is Fast Track Designation, a program that helps accelerate the development and review of programs with serious conditions with a high unmet need.  We have already taken advantage of the opportunity to meet with the FDA frequently to discuss key aspects of the program, and we look forward to taking advantage of the rolling review of our new drug application when, if the study is successful, we seek approval of our medicine upon completion of this study.

Finally, the positive interim analysis has triggered a convertible loan conversion, providing additional proceeds of 42 million SEK before transaction costs. How will the money be used?

– The convertible loan conversion completes the financing round of SEK 80M announced earlier this year.  The proceeds from this conversion will support completion of the first wave of the study, continue the preparations of the new countries for the final wave of the study, and  elongate our runway, providing us time now after the positive interim readout to continue discussions with investors and potential partners.

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