# Long-term toxicology studies for Posiphen; 6 month in rats and 9 months in dogs

> **NIH NIH U01** · ANNOVIS BIO, INC. · 2020 · $975,429

## Abstract

PAR 18-820
Summary
Long term toxicology studies for Posiphen®; 6 months in rats and 9 months in dogs
Posiphen tartrate is a small molecule of 487.5 molecular weight, with a Log P of 2.22 resulting oral
availability and high blood-brain barrier penetrability. It is a translational inhibitor of neurotoxic proteins,
APP, tau and α-synuclein. By inhibiting these proteins, posiphen normalizes axonal transport, lowers
inflammation and protects nerve cells from dying. This novel mechanism promises stop or slow the
course of neurodegeneration and to give people with cognitive difficulties the possibility of living a
healthy and independent live way into old age.
In order to study this drug in Alzheimer’s and/or Parkinson’s patients we need long term tox studies in
animals. We propose to conduct two animal toxicology studies: a 6 month rat study with 1 month
recovery and a 9 month dog study with 1 month recovery. During the study the animals will be
monitored for behavior and safety and after the study the organs and the brain will be evaluated for
toxicological findings.
We have already progressed posiphen through 3 human phase I safety studies and ADCS started a
pharmacodynamic SILK phase IIa study in mild to moderate AD patients in summer of 2016.
The data from the phase IIa together with the data from the proposed animal tox studies will allow us to
enter posiphen into a 2 to 3 year pivotal phase II/III study in AD patients to show efficacy.
The Alzheimer’s field has been dominated by approaches that prevent the processing to Aβ or remove
Aβ in one of its many forms. Posiphen prevents the synthesis of APP and hence of Aβ. Accordingly the
Parkinson’s field uses similar approaches to inhibit levels of α-synuclein or LRRK. Again posiphen
prevents the synthesis of α-synuclein. By normalizing the levels APP/Aβ, tau/phopho-tau and α-
synuclein posiphen prevents the formation of toxic products and prevents death of nerve cells.
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## Key facts

- **NIH application ID:** 10018610
- **Project number:** 5U01AG056437-02
- **Recipient organization:** ANNOVIS BIO, INC.
- **Principal Investigator:** Maria Maccecchini
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $975,429
- **Award type:** 5
- **Project period:** 2019-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018610

## Citation

> US National Institutes of Health, RePORTER application 10018610, Long-term toxicology studies for Posiphen; 6 month in rats and 9 months in dogs (5U01AG056437-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10018610. Licensed CC0.

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