NNZ-2591
IGF-1-related peptide
Also NNZ2591, NNZ 2591, Cyclic glycine-proline analog, cGP analog
- Evidence
- CAnimal and cell studies
- FDA status
- In clinical trialsas of 2026-10-27
- Route
- Oral
- Studies cited
- 1 human0 animal or cell
It is a pill being tested for rare genetic conditions linked to autism. The one trial had 18 children and no comparison group, so it cannot show the drug works.
Sold for
NNZ-2591 is talked about as a follow-on to trofinetide, a possible oral treatment for several genetic autism-related syndromes at once.
Studies say
One small uncontrolled trial found the drug was tolerated and that scores moved in a favorable direction, which is the kind of evidence that justifies a placebo-controlled trial but does not show the drug works.
Why grade C. The only published trial is a single-group, open-label phase 2 study in 18 children with Phelan-McDermid syndrome, designed mainly to test safety and drug levels. Without a placebo group, the reported improvements on caregiver and clinician scales cannot be separated from expectation effects. A controlled trial is the missing piece. 12
FDA. Not approved by the FDA for any use. NNZ-2591 is an investigational oral drug from Neuren Pharmaceuticals being tested in rare neurodevelopmental disorders, and the published human data are from an open-label phase 2 trial in Phelan-McDermid syndrome. A randomized, placebo-controlled phase 3 trial in children with Phelan-McDermid syndrome started in November 2025 and is recruiting.
Written from 3 cited sources. Fact-checked 2026-10-27: 12 claims checked, 1 corrected, 1 sources unreachable. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Rare genetic brain development conditions
- Can a US doctor prescribe it?
- Not yet; it is still in trials.
- Properly tested in people?
- Not properly: animal or lab studies, or small uncontrolled human reports. One report of 18 children.
Evidence checklist
- Randomised controlled trial Open-label, single-group phase 2no
- Human study over 100 people 18 childrenno
- More than one research group Article does not sayno information
- Clinical outcomes, not surrogate markers Caregiver and clinician rating scalesno
- Human safety data beyond case reports 13-week trial; no safety withdrawals; shortyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
NNZ-2591 is a small synthetic molecule modeled on cyclic glycine-proline, a natural breakdown product of insulin-like growth factor 1 (IGF-1). Neuren Pharmaceuticals, the Australian company behind trofinetide, developed it as an oral liquid that is more stable in the body than the natural compound. 1
The company is testing it in Phelan-McDermid syndrome, Pitt Hopkins syndrome, Angelman syndrome and Prader-Willi syndrome, all rare genetic conditions that cause intellectual disability and autism-like features. The Phelan-McDermid trial is the one with published results. 12
How it works
IGF-1 signaling helps regulate how neurons grow, connect and prune their connections. In several genetic neurodevelopmental disorders this signaling appears to be out of balance. Cyclic glycine-proline is thought to normalize IGF-1 activity by affecting how much of the hormone is free to act on its receptor; it does not simply add more hormone. NNZ-2591 is designed to do the same thing in a form that survives digestion and lasts longer in the bloodstream. 1
What human research shows
The published phase 2 trial enrolled children aged 3 to 12 with Phelan-McDermid syndrome, a condition caused by loss of the SHANK3 gene. Eighteen children received oral NNZ-2591 twice a day for 13 weeks in a single-group design with no placebo arm. The primary endpoints were safety and pharmacokinetics, meaning how the drug was absorbed and cleared. Fourteen secondary efficacy measures were collected from caregivers and clinicians. 12
Most adverse events were mild to moderate and no serious safety concerns emerged. On the efficacy measures, significant improvement from baseline was reported on 10 of the 14 scales, and 16 of 18 children improved on the clinician-rated global impression scale. Because the trial was open-label, caregivers and clinicians knew every child was receiving the drug, so part of this could reflect expectation. The company has reported that a similar open-label trial in Pitt Hopkins syndrome also met its goals, and has said a placebo-controlled phase 3 trial is planned. 13
| Study | Model | Finding |
|---|---|---|
| PMS-001 phase 2 (Neumeyer 2025) | Humans, n=18 children with Phelan-McDermid syndrome, single-group open-label | NNZ-2591 was tolerated over 13 weeks, with improvement reported on 10 of 14 secondary efficacy scales in the absence of a control group. 1 |
| NCT05025241 registration | Humans, children aged 3 to 12, open-label | Trial registry entry describing the design, primary safety and pharmacokinetic endpoints. 2 |
Safety
In the 13-week trial, treatment-emergent adverse events were mostly mild or moderate, and there were no deaths or discontinuations for safety. That is reassuring but limited: 18 children over three months cannot reveal uncommon side effects or anything about long-term use. There are no data in adults and none on effects outside the trial populations. 1
Questions for your clinician
- Is a placebo-controlled trial running?
- How can improvement be told apart from expectation in an open-label study?
- What is known about use beyond three months?
Questions people ask
How is NNZ-2591 related to trofinetide?
Both come from Neuren and both are synthetic versions of natural IGF-1 fragments. Trofinetide is based on the N-terminal tripeptide of IGF-1 and is approved for Rett syndrome; NNZ-2591 is based on cyclic glycine-proline, a different IGF-1-related molecule, and is still in trials. 1
Did the trial show NNZ-2591 works?
It showed the drug was tolerated and that scores improved on most scales. Because every child received the drug and families knew it, the improvement cannot be distinguished from the expectation and attention that come with being in a trial. Only a placebo-controlled study can answer whether it works. 1
Is NNZ-2591 sold online as a research peptide?
It appears on some research-chemical sites, but it is a small molecule, not a classic peptide, and has been tested only in children with specific genetic syndromes. There are no data on its effects in anyone else. 1
Citations
- Neumeyer 2025 (published online December 2025; Feb 2026 issue), Neurology Genetics: NNZ-2591 in children and adolescents with Phelan-McDermid syndrome, single-group open-label phase 2 trial doi.org
- ClinicalTrials.gov NCT05025241: an open-label study of oral NNZ-2591 in Phelan-McDermid syndrome (PMS-001) clinicaltrials.gov
- BioWorld 2024: Neuren's NNZ-2591 meets phase 2 endpoints in Pitt Hopkins syndrome (company report) bioworld.com