Research & Development

Abliva’s in-house R&D capabilities have been instrumental in creating and delivering a portfolio that includes several projects with mechanisms of action suitable for a wide range of primary mitochondrial diseases

Our portfolio

KL1333: Innovative therapy in late-stage development

Project status: Dosing in patients is ongoing in the FALCON study

KL1333 has been evaluated in both healthy volunteers and patients and has been granted orphan drug designation in both the United States and Europe. The global FALCON study with KL1333 was initiated in late 2022. The company will recruit patients in two waves, and an interim analysis will take place after the completion of Wave 1 towards the middle of 2024.

Mitochondrial disease target population: MELAS-MIDD, KSS-CPEO and MERRF

KL1333 is being developed as a treatment for a subset of adult primary mitochondrial disease patients suffering from multiple debilitating symptoms, including chronic fatigue and myopathy. Diagnoses can include MELAS-MIDD and KSS-CPEO spectrum disorders as well as MERRF syndrome.

Mechanism of action: NAD⁺/NADH modulation

KL1333 is a potent modulator of the cellular levels of NAD+ and NADH, central co-enzymes in the cell’s energy metabolism. KL1333 has in preclinical models demonstrated to increase mitochondrial energy output, have long-term beneficial effects on energy metabolism, strengthen muscle function and improve biomarkers of mitochondrial disease.

NV354: First-in-class therapeutic targeting high unmet need

Project status: Preclinical development completed

The program has completed preclinical development and has been granted Orphan Drug Designation in the U.S.

Mitochondrial disease target population: Leigh syndrome, MELAS, and LHON

One of the most common causes of mitochondrial diseases relates to Complex I dysfunction, i.e. when energy conversion in the first of the five protein complexes in the mitochondrion that are essential for effective energy conversion does not function normally. This is apparent in disorders including Leigh syndrome, MELAS, or LHON.

NV354 is initially being developed for chronic oral treatment of Leigh syndrome, a severe primary mitochondrial disease that usually debuts at one to two years of age. The disease is fatal and children usually die before age 5. Symptoms include developmental delay, psychomotor regression, and hypotonia. There are currently no approved medicines.

The unique mechanism of action and high brain uptake may be utilized to develop NV354 for the treatment of MELAS in children and adolescents with neurological symptoms, and for the treatment of LHON. MELAS is a serious disease with symptoms such as muscle weakness, diabetes, fatigue, epilepsy, other severe neurological effects, and shortened life span. LHON is a disease that causes sudden severe permanent visual impairment and can lead to blindness in both eyes.

Mechanism of action: Energy replacement

The project is based on an Abliva innovation in which the body’s own energy substrate, succinate, is made available in the cell via a prodrug technology. A prodrug is an inactive drug that is activated first when it enters the body by the transformation of its chemical structure.

Early programs

Abliva has efforts ongoing to identify additional portfolio opportunities focused on the regulation and stabilization of cellular energy production.