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. KL1333 has Orphan Drug Designation (ODD) in both Europe and the U.S. as well as Fast Track designation in the U.S.
- Read about the FALCON study
- Read about our KL1333 Phase 1a/b study
- Read about our KL1333 drug-drug interaction (DDI) study
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 both in the EU and the U.S. Given the prioritization of KL1333, no significant cost-intensive operational activities are planned for NV354 at this time.
Mitochondrial disease target population: Neurology
NV354 is being developed for mitochondrial disease with neurologic complications, in particular at insufficient activity in the mitochondrial protein complex I. The resulting deficiency in energy conversion contributes to clinical signs and symptoms in many types of mitochondrial disease, including neurologic complications seen in Leigh syndrome, MELAS, or LHON. There are also additional expansion opportunities outside of mitochondrial disease.
The drug candidate was discovered due to its ability to increase mitochondrial function in cells from mitochondrial Leigh syndrome patients. Leigh syndrome usually debuts at one to two years of age and includes psychomotor regression, hypotonia and developmental delays. The disease is fatal, and children with early-onset Leigh syndrome usually die before adulthood.
Mechanism of action: Energy replacement
Brain-penetrable NV354 is based on an 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.
Abliva has efforts ongoing to identify additional portfolio opportunities focused on the regulation and stabilization of cellular energy production.
Abliva develops medicines for the treatment of mitochondrial diseas. This congenital, rare and often very severe disease occurs when the cell’s energy provider, the mitochondria, do not function properly. The portfolio includes projects at different stages and ranges from early discovery phase to clinical phase.
Primary mitochondrial disease
Primary mitochondrial disease affects the ability of cells to convert energy. The disease can manifest itself very differently depending on the organs impacted and the number of dysfunctional mitochondria in that organ. Historically viewed as clinical syndromes, our knowledge about the various mutations underlying mitochondrial disease has increased, improving our ability to identify and treat these patients. It is estimated that 125 people per million have primary mitochondrial disease. It ofte …