Background

This small molecule is a potent and selective PDE-1 phosphodiesterase inhibitor that increases neuronal levels of cyclic nucleotide second messengers. Lu AF88434 is intended to enhance neuroplasticity, intracellular signaling, and cognitive functioning.

Findings

In 2019 and 2020, Lundbeck completed two Phase 1 studies in healthy adults. One investigated single ascending doses or placebo in 68 young men against endpoints of safely, pharmacokinetics, and food effects. The second measured brain penetration in eight men by PET scan using a [11C]-Lu AF8843 tracer.

A Phase 2 trial for negative symptoms of schizophrenia was discontinued in August 2020 (press release), and at the end of 2020, Lundbeck dropped Lu AF88434 from their development pipeline.

For details on Lu AF88434 trials, see clinicaltrials.gov.