Research & Development

Abliva’s objective is to improve life for patients suffering from primary mitochondrial diseases, meaning diseases caused by a genetic defect in mitochondrial function. These diseases often cause great suffering for both patients and family members. The symptoms worsen over time and, in many cases, the diseases lead to a far too early death. Today, a very limited number of treatment options are available, which means there are major unmet medical needs.

Our projects

KL1333: Blockbuster candidate heading to pivotal study

Project status: Patient studies initiated

KL1333 is currently being evaluated in patient studies and has been granted orphan drug designation in both the United States and Europe. Abliva intends to start a pivotal clinical Phase II/III efficacy study during 2021.

PMD target population: MELAS-MIDD and KSS-CPEO

The KL1333 project is in clinical development stage intended to document the use for chronic oral treatment of primary mitochondrial disorders, in particular MELAS-MIDD spectrum disorders, mainly caused by the mutation m.3243A>G in the mitochondrial DNA (mtDNA) and affects about 35 in 1,000,000 people. An additional group is KSS-CPEO spectrum disorders caused by a deletion of a large part of mtDNA which affects 15 in 1,000,000. Common symptoms include fatigue, myopathy (muscle weakness), and an intractable form of diabetes.

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 been demonstrated to increase mitochondrial energy output, have long-term beneficial effects on energy metabolism, strengthen muscle function and improve biomarkers of mitochondrial disease. KL1333 has been in-licensed from Yungjin Pharm, a Korean pharmaceutical company.

NV354: Unique therapeutic approach heading to clinical development

Project status: Preclinical safety studies ongoing

NV354 undergoes preclinical pharmacology and safety studies. The goal is to enter into clinical phase during 2021.

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 the treatment of Leigh disease, a severe primary mitochondrial disease that usually debuts at one to two years of age. Patients usually die at two to three years of age. Symptoms include developmental delay, psychomotor regression, and hypotonia. There are currently no approved medicines.

In a second step, NV354 may also be developed for the treatment of MELAS in children and adolescents with neurological symptoms, and LHON. MELAS is a very serious disease with symptoms such as muscle weakness, 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. Succinate bypasses the dysfunctional Complex I and acts directly on Complex II, to replace the energy lost. NV354 has shown favorable properties in tolerability, oral bioavailability, plasma stability and organ delivery, specifically to the brain. The drug candidate is intended for long-term oral treatment.

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.