# Scale-up Manufacturing and IND Enabling Studies of Extended-Release Formulation of Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Alzheimer's Disease-Related Dementias

> **NIH NIH R43** · PRONEUROGEN, INC. · 2022 · $499,598

## Abstract

A growing body of evidence indicates that decreased brain blood flow, increased reactive oxygen
(ROS) and pro-inflammatory mechanisms accelerate the progression of neurodegenerative
diseases such as Alzheimer’s Disease and Related Dementias (ADRD) including Vascular
Contributions to Cognitive Impairment (VCID) 1, 2,3,4, 5. ProNeurogen has been working with our
University of Arizona collaborators to develop novel Angiotensin 1-7 (Ang-1–7) formulations to
treat inflammation-related cognitive impairment in heart disease patients at for risk ADRD and
VCID. These novel peptide formulations are designed to act on Mas receptors (MasR) within the
brain vascular endothelium and neuronal cells to decrease brain ROS production,
neuroinflammation and improve cerebral vascular blood flow. We have begun to translate these
preclinical findings into novel peptide therapeutics to treat inflammation related cognitive
impairment in patients with heart disease who are at risk for ADRD or VCID. We have an
approved FDA IND # 125320 and support for Phase 2a trials for native Ang-(1-7) for treatment of
cognitive impairment in heart failure (HF) patients and NIH support for our trial in cardiac bypass
surgery patients (CABG). We are currently enrolling in these studies. Our current approved
treatment protocol is once a day, subcutaneous 100 microg/kg injection using a standard needle
and syringe for 85 days in our HF patients. However, long-term administration of Ang-(1-7)
peptides to protect cognitive function will require injections over multiple months. To increase
patient compliance as well as accelerate commercialization we are currently investigating new
formulations and injection methods that are more “patient friendly” and will decrease the number
of injections required. We have recently completed feasibility studies and identified our lead
extended-release Ang-(1-7) formulation (PNA1-ER) and are progressing towards IND submission
for this new formulation. The goal of the present SBIR Phase I project is to 1) scale-up batch
development of our extended-release poly (lactic-co-glycolic acid) (PLGA) in-situ gel formulations
for subcutaneous injection of PNA1-ER, 2) begin formal PK and pharmacotoxicity studies of
PNA1-ER required for IND submission.
Objective 1: Scale-up batch development of our lead candidate extended-release in-situ gel
formulations for subcutaneous injection of Ang-(1-7) (PNA1-ER).
Objective 2: Single-dose Pharmacokinetics and Local Tolerability Study of PNA1-ER in
Rats.
Objective 3: Repeat-dose PK and Tolerability Study of PNA1-ER in Rats.

## Key facts

- **NIH application ID:** 10543390
- **Project number:** 1R43AG079647-01
- **Recipient organization:** PRONEUROGEN, INC.
- **Principal Investigator:** Meredith Hay
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $499,598
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10543390

## Citation

> US National Institutes of Health, RePORTER application 10543390, Scale-up Manufacturing and IND Enabling Studies of Extended-Release Formulation of Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Alzheimer's Disease-Related Dementias (1R43AG079647-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10543390. Licensed CC0.

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