EVP-0334 / Forum Pharmaceuticals - LARVOL DELTA

Effect of the Histone Deacetylase Inhibitor FRM-0334 on Progranulin Levels in Patients With Progranulin Gene Haploinsufficiency: A Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P2 | "International multicenter clinical trials of FTD-GRN are feasible. ClinicalTrials.gov Identifier: NCT02149160."

Clinical • Epigenetic controller • Journal • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • CSF NfL • CSF T-tau • FDG PET

The effect of HDAC2 inhibition on cognitive measures in C57/BL6 mice: Assessing pharmacological, antisense oligonucleotide, and genetic manipulations (Neuroscience 2017) - "...We then tested a more selective HDAC2 inhibitor, FRM-0334, after daily dosing for 1, 3, or 10 days prior to training, but again, no enhancement of contextual fear was observed under any dosing regimen...Thus, these observations are not consistent with the premise that HDAC2 inhibition is a viable strategy for cognitive enhancement. As these studies were all conducted in healthy, relatively young mice the possibility remains that HDAC2 inhibition could be effective in instances and circumstances in which cognitive performance is impaired due to age, disease, or neurodegeneration."

Alzheimer's Disease

Phase 2a Randomized, Double-Blind, Placebo-Controlled Trial of the Histone Deacetylase Inhibitor (HDACi), FRM-0334, in Asymptomatic Carriers of, or Patients with Frontotemporal Lobar Degeneration (FTLD) Due to, Progranulin Gene Mutations (AAIC 2019) - "FRM-0334 was safe and well tolerated in GRN mutation carriers but had no effect at doses tested on PGRN levels. Systemic and CSF FRM-0334 levels were lower than expected suggesting insufficient FRM-0334 exposure. Therefore the hypothesis that HDAC inhibition can increase PGRN expression in humans was not fully tested."

Clinical • P2a data