Davunetide — catalogued also as NAP and AL-108 — is an eight-amino-acid peptide derived from activity-dependent neuroprotective protein (ADNP), a glial factor released in response to vasoactive intestinal peptide (VIP). Its clinical record is unusually instructive for a research peptide: rather than a thin set of small positive Phase 2 trials that were never confirmed, it culminates in a large, adequately powered pivotal trial that missed every pre-specified endpoint. The molecule has since been partially reintroduced for a rare genetic syndrome. This explainer sets out what the research does and does not show.

01 What davunetide is

Davunetide's sequence is NAPVSIPQ — Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln — an eight-residue fragment of ADNP. It was developed by Allon Therapeutics as an intranasal agent and is now associated with ExoNavis Therapeutics and Paladin Labs. It is not a hormone and not a receptor agonist; it is a short peptide studied primarily as a neuroprotective and microtubule-stabilising candidate.

02 The mechanism, and why tauopathies were the target

In preclinical work, davunetide promoted microtubule stability and reduced phosphorylation of tau. Because progressive supranuclear palsy (PSP) is a primary tauopathy, this provided a plausible mechanism linking the peptide to a disease that had no effective disease-modifying therapy at the time. As with most preclinical neuroprotection, that evidence rested on cell-culture models of toxic insult and transgenic mouse models carrying human MAPT mutations — a substantial distance from human disease.

03 The earlier human trials

Two smaller trials preceded the pivotal study:

  • A 12-week Phase 2 trial of intranasal davunetide in people with amnestic mild cognitive impairment reportedly improved measures of short-term and working memory.
  • A 2007–2009 Phase 2 trial in 63 patients with chronic schizophrenia missed one co-primary outcome (the MATRICS composite battery) while reportedly showing an effect on the other, the UCSD Performance-based Skills Assessment (UPSA), and on cortical thickness.

Neither trial was large enough to establish efficacy, and neither indication progressed.

04 The pivotal PSP trial

The Phase 2/3 PSP trial was a double-blind, placebo-controlled study run at 48 centres in Australia, Canada, France, Germany, the UK and the USA. A total of 313 participants meeting modified NNIPPS criteria for possible or probable PSP were randomised 1:1 to intranasal davunetide 30 mg twice daily or placebo for 52 weeks. The co-primary endpoints were change from baseline in the PSP Rating Scale (PSPRS) and the Schwab and England Activities of Daily Living (SEADL) scale.

The results, published in The Lancet Neurology in 2014, were negative across the board:

  • PSPRS change: median 11.8 (95% CI 10.5–13.0) with davunetide versus 11.8 (10.5–13.0) with placebo, p=0.41.
  • SEADL change: −0.20 (−0.20 to −0.17) versus −0.20 (−0.22 to −0.17), p=0.92.
  • No effect on the secondary outcomes, including the Clinical Global Impression of Change and the annual rate of brain atrophy measured by ventricular volume on volumetric MRI.

Nasal adverse events were more frequent with davunetide than with placebo (epistaxis in 18 patients [12%]). Serious adverse events were balanced (54 in each arm), with 11 deaths in the davunetide group and ten in the placebo group. Because both arms declined at the expected annual rate, the investigators concluded the trial was adequately powered to detect a treatment effect had one existed. Development in PSP was halted. (ClinicalTrials.gov identifier NCT01110720.)

05 A post hoc sex-difference claim

A later post hoc analysis of the PSP dataset reported that davunetide slowed progression in women but not men. Post hoc subgroup findings from a trial whose primary endpoints were null are hypothesis-generating only; they are not evidence of efficacy and have not been confirmed prospectively. This reference treats them as such.

06 Where davunetide stands now

In 2021 ExoNavis licensed davunetide from Tel Aviv University. A Phase 3 trial in 97 children with ADNP mutations reportedly began in October 2024; as of the AlzForum record (updated June 2025) it did not appear in public registries, so its status should be treated as company-reported rather than independently confirmed. Davunetide holds US FDA orphan-drug and rare-pediatric-disease designations and EMA orphan-drug status for ADNP syndrome — a jurisdictional comparison only; neither confers any UK authorisation.

07 UK regulatory position

Davunetide has no UK marketing authorisation and is not a licensed medicine. It is not controlled under the Misuse of Drugs Act 1971. As an unlicensed medicine it could only be supplied lawfully under the Human Medicines Regulations 2012, via a prescription from a qualified prescriber through a licensed supply chain. Research peptides sold to consumers as "not for human consumption" are not medicines, and their supply sits outside that route; the MHRA treats products marketed with medicinal claims as a compliance matter. Nothing here is consumption or dosing guidance, and no human-use protocol is implied.

08 Evidence grade

Peptide Data grades davunetide as Limited evidence. Human trial data exist across several indications, but there is no established efficacy in any of them: the pivotal tauopathy trial was definitively negative, and the earlier signals were small and unreplicated. That places the molecule well below the Strong and Moderate tiers, and closer to the many research peptides whose interest is mechanistic rather than clinical.

This article is AI-researched and editorially reviewed. It is provided for research and educational purposes only and is not medical advice. Research peptides are not licensed for human consumption in the UK.