Lund-based Abliva is dedicated to addressing the profound impact of primary mitochondrial diseases. These are diseases that disrupt cellular energy conversion, resulting in severe symptoms such as stroke-like episodes, muscle weakness, and heart failure. With limited treatment options currently available, Abliva addresses a significant medical need.

NV354 targets neurologic mitochondrial disease

This year, much focus has been on lead candidate KL1333 which is currently being evaluated in a potentially registrational phase II-study. But KL1333 is not Abliva’s only promising candidate within the PMD space. In the pipeline we also find NV354, a candidate being developed for the treatment of mitochondrial disease with neurologic complications. Such diseases include Leigh syndrome, a rare paediatric disease which inflicts severe symptoms, often leading to early death in children. There is no cure, and most children affected die before age 5. Other diseases that may benefit from NV354 are Leber’s hereditary optic neuropathy (LHON), leading to vision loss, and mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a disorder characterised by a combination of neurological and metabolic symptoms.

NV354 targets the root cause of the diseases by addressing energy conversion issues, specifically Complex I dysfunction. By utilising succinate, an existing energy substrate, NV354 aims to restore energy production, providing a potential breakthrough for patients with mitochondrial disease who have neurological complications.

Orphan designation granted in EU

Abliva has finished preclinical testing of NV354 with promising results. In April 2023, FDA granted the drug candidate orphan drug designation in the US for the treatment of mitochondrial disease. Further advancing NV354’s position, Abliva recently received orphan designation from the European Commission for the treatment of Leigh syndrome. This designation provides Abliva with advice on studies, reduction in fees, and access to grants. Upon marketing approval of NV354 for Leigh syndrome, orphan drug status will provide Abliva with market exclusivity  for the drug candidate in the EU for ten years and in the US for seven years.

CEO comments

BioStock took the opportunity to speak to Abliva’s CEO Ellen K. Donnelly about the orphan designation and its significance.

 Ellen, can you elaborate on the significance on having orphan designation in both the US and the EU for NV354?

-Orphan drug designation is great validation of the molecule and the mechanism of action by both sets of regulators.  Having this designation for NV354 not only means that we have better access to regulatory advice and the potential for lower fees, but it is also worth noting that the likelihood of success for orphan drugs is much higher than for non-orphan drugs.

The orphan designation given by the European Commission relates to Leigh syndrome specifically, but your press release also mentions LHON and MELAS as targets for NV354. Can the orphan designation be extended to cover indications other than Leigh syndrome?

– Yes, we will add to the orphan designations as needed to match the clinical indication and the label we will seek for marketing approval. The EMA has historically granted orphan designations in primary mitochondrial disease according to historically described syndromes, such as Leigh syndrome. This is in contrast to the FDA which has implemented a more modern view on mitochondrial disease and already given us a broad designation for NV354 that covers any sub-set of mitochondrial disease. The initial orphan designation is important in Europe at this stage, and then we have plenty of time to extend the designation to match the clinical strategy.

Finally, what is the next step in the development of NV354?

 -We have completed the preclinical program for NV354 and have taken the opportunity to discuss the details with the regulatory authorities in the UK (MHRA) who were supportive of us moving the compound into clinical development and Phase I studies.  We have also met with our scientific advisory board to evaluate different options for the clinical plan and are encouraged by the different paths forward for the program.  Our primary focus in the company, however, must continue to be our ongoing FALCON study, the global, potentially pivotal Phase II study evaluating KL1333 in adult patients with mitochondrial disease.  For this reason, all resources are currently directed to KL1333, and there are no cost-intensive activities ongoing for NV354.