PRAX-020 / Praxis Precision Medicines, UCB - LARVOL DELTA

An iPSC line (FINi102-A) carrying a heterozygous R950Q variant in KCNT1 from a boy with early-onset epilepsy. (PubMed, Stem Cell Res) - "This iPSC line displayed normal hiPSC morphology, expression of pluripotency markers, ability to differentiate into all three embryonic germ layers, and no high-density SNP array-detectable aneuploidies. This line can be used for modelling of, and the development of precision therapies for, debilitating early-onset epilepsies and other conditions caused by the variants in KCNT1."

Journal • CNS Disorders • Epilepsy

Praxis Precision Medicines and UCB Announce Epilepsy Research Collaboration (GlobeNewswire) - "Praxis Precision Medicines, Inc...announced a strategic collaboration, based upon Praxis’ PRAX-020 program, for the discovery of small molecule therapeutics as potential treatments of KCNT1 related epilepsies....Under the terms of the collaboration, UCB retains an exclusive option to in-license global development and commercialization rights to any resulting KCNT1 small molecule development candidate."

Licensing / partnership • CNS Disorders • Epilepsy

Kna1.1 antagonism with PRX2904 suppresses epileptiform activity due to a heterozygous mutation in Kcnt1 (Neuroscience 2022) - "Kcnt1+/R455H mice were tested with pentylenetetrazole (PTZ) 50 mg/kg IP administered 1 or 2 hours after administration of either PRX2904 75 mg/kg SC or vehicle control. Baseline epileptiform spike rates on EEG were variable between animals, but there was a marked per-animal reduction in the 24 hours following PRX2904 administration (p=0.005, N=12). These results suggest that KNa1.1 antagonists may be an effective treatment for KCNT1 epilepsy."

CNS Disorders • Epilepsy • Psychiatry • PRDX2

Praxis Precision Medicines to Present Data from Rare Disease Programs at the American Epilepsy Society 2021 Annual Meeting (GlobeNewswire) - "Praxis Precision Medicines, Inc...announced that data from its rare disease programs will be delivered in three presentations at the American Epilepsy Society 2021 Annual Meeting, held December 3-7, 2021 in Chicago."

Preclinical • CNS Disorders • Epilepsy

Discovery of the First Orally Available, Selective K1.1 Inhibitor: In Vitro and In Vivo Activity of an Oxadiazole Series. (PubMed, ACS Med Chem Lett) - "Effective treatment options for KCNT1-related disease are absent, and novel therapies are urgently required. We describe the development of a novel class of oxadiazole K1.1 inhibitors, leading to the discovery of compound 31 that reduced seizures and interictal spikes in a mouse model of KCNT1 GoF."

Journal • Preclinical • CNS Disorders • Epilepsy