# GMP Manufacturing and IND Enabling Studies of Extended-Release PNA5: A  Novel Therapeutic for Treating Cognitive Impairment in Patients at-risk for Alzheimer's Disease-Related Dementias and Vascular

> **NIH NIH R43** · PRONEUROGEN, INC. · 2023 · $499,545

## Abstract

Vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer’s disease related dementias
(ADRD) significantly contribute to the 47 million people world-wide who suffer with dementia. This number is
estimated to increase to over 130 million people by 2050. Several studies have shown that VCID and conversion
to ADRD are strongly correlated with vascular disease, inflammation and decreased cerebral brain blood flow.
The relationship between vascular disease, cognitive function and progression to dementia and possible AD
have been recently reviewed 1 and conversion rates of VCID to dementia have been reported to be approximately
45% within 5 years of diagnosis of VCID. To date, there are no approved therapies for VCID. ProNeurogen has
been working to develop PNA5, a novel Angiotensin 1-7 (Ang-1–7) derivative, to treat cognitive impairment in
persons at for risk ADRD and VCID. The goal of the present SBIR Phase I project is to complete GMP
formulation of our extended-release (ER) subcutaneous injection formulation of PNA5 and begin GLP
repeat-dose toxicology studies for the administration of our novel peptide therapy, PNA5ER, for VCID.
These novel peptide formulations are designed to act on Mas receptors (MasR) within the neurovascular unit
including brain vascular endothelium, neuronal cells and microglia to decrease brain reactive oxygen (ROS)
production, neuroinflammation and improved brain blood flow. We have begun to translate these preclinical
findings into novel peptide therapeutics to treat cognitive impairment in patients with heart disease who are at
risk for ADRD or VCID. With support from NIA, we are currently completing our formal IND enabling toxicology
studies required to advance PNA5 to human clinical trials for VCID and expect to submit our IND application by
Q4 2023. Our current planned treatment protocol for VCID patients is once a day, subcutaneous 100 microg/kg
injection using a standard needle and syringe for 85 days. However, to increase patient compliance as well as
accelerate commercialization we are currently investigating new formulations that are more patient friendly and
require fewer injections. We will take advantage of Pace Labs (formerly DDE) extensive experience in the
formulation of GMP poly(lactic-co-glycolic acid) (PLGA) sterile injectable in-situ gel formulations and
manufacturing expertise to complete the 3 principal objectives of this project.
Objective I: Develop GMP manufacturing processes for PNA5ER required for IND submission.
Objective II. Conduct IND enabling repeat-dose GLP toxicology studies in rats to determine the toxicokinetic
and TK profiles for subcutaneously administered PNA5ER.
Objective III: Complete CMC regulatory assessments and documentation for an IND amendment.
Following successful completion of these studies, in Phase II we will complete GLP long-term PD/PK studies
and safety studies required for IND submission.

## Key facts

- **NIH application ID:** 10819329
- **Project number:** 1R43AG085713-01
- **Recipient organization:** PRONEUROGEN, INC.
- **Principal Investigator:** Meredith Hay
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $499,545
- **Award type:** 1
- **Project period:** 2023-09-18 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819329

## Citation

> US National Institutes of Health, RePORTER application 10819329, GMP Manufacturing and IND Enabling Studies of Extended-Release PNA5: A  Novel Therapeutic for Treating Cognitive Impairment in Patients at-risk for Alzheimer's Disease-Related Dementias and Vascular (1R43AG085713-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10819329. Licensed CC0.

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