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 projects

KL1333: Blockbuster candidate heading to registrational study

Project status: IND (Investigational New Drug) approved for clinical Phase 2/3

KL1333 has been evaluated in both healthy volunteers and in patients, and has been granted orphan drug designation in both the United States and Europe. Abliva plans to recruit the first patient in a registrational Phase 2/3 study in 2022.

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⁺ modulation

KL1333 is a potent modulator of the cellular levels of NAD+, a central co-enzyme 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: Unique therapeutic approach heading to clinical development

Project status: Compilation of regulatory documentation to support clinical entrance

The project is estimated to enter clinical Phase 1 in 2022.

PMD 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 developed for a 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 on 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’s discovery projects focus on deeper understanding of the mechanisms for our unique chemistry platforms, and the development of next-generation compounds for primary mitochondrial diseases.