NNZ-2591
NNZ-2591, cyclic glycine-proline analog
An oral IGF-1 metabolite mimic from the makers of trofinetide (Daybue), in the first-ever Phase 3 for Phelan-McDermid syndrome since February 2026.
Overview
NNZ-2591 is a synthetic analog of cyclic glycine-proline, a natural IGF-1 metabolite, and a sister molecule to trofinetide, which Neuren took to approval for Rett syndrome. It carries Fast Track, Orphan and Rare Pediatric designations. The 13-week Koala Phase 3 in Phelan-McDermid syndrome is dosing, and Phase 2 studies in Angelman and Pitt Hopkins syndromes are published. It is the nearest thing to a successor for davunetide in neurodevelopmental disease.
Mechanism of action
Normalizes IGF-1 and synaptic signaling in the brain, improving neuronal connectivity in neurodevelopmental disorders.
Key studies & citations
- Human2026
Koala: NNZ-2591 Phase 3 in Phelan-McDermid syndrome
First Phase 3 in the condition.
ClinicalTrials.gov NCT07281079 - Human2026
NNZ-2591 open-label extension
Long-term safety study.
ClinicalTrials.gov NCT07593391
Frequently asked questions
Is NNZ-2591 related to davunetide?
Only in spirit: both are short, brain-active molecules derived from natural neuroprotective peptides. Davunetide comes from ADNP; NNZ-2591 comes from an IGF-1 metabolite.