# IND Enabling Studies for RASRx 1902, a novel Mas receptor agonist, for treatment of cognitive impairment in patients at risk for Alzheimer's disease.

> **NIH NIH U01** · UNIVERSITY OF ARIZONA · 2021 · $1,531,012

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer’s disease (AD) is a progressive multifactorial disease affecting more than 50 million people worldwide,
and is the most common dementia of late-life. To date, no interventions have demonstrated substantial
therapeutic efficacy to prevent, delay or treat AD. In recent years, both cardiovascular disorders (CVD) and
genetic factors (ApoE4) have been attributed to an increased risk of developing AD. The pathological arm of the
Renin Angiotensin System (RAS) has been implicated in both CVD and AD, whereas the protective arm,
including Angiotensin (1-7)[A(1-7)], Mas receptor and ACE2 are known to counter-regulate these effects. A(1-
7), through the Mas receptor, is known to reduce inflammation and oxidative (OS) in several disease states and
it also has regenerative effects by upregulating endogenous stem cell populations. Data from clinical studies
have shown that both A(1-7) and ACE2 are reduced in AD patients and several in-vivo studies support the
efficacy of A(1-7) in treating AD. While the effects of A(1-7) in AD models have been extremely promising, its
short half-life and lack of oral bioavailability make it challenging to develop as a therapeutic modality. In order to
overcome this shortcoming, our lab has developed an equipotent small molecule analogues of A(1-7),
RASRx1902 and RASRx1911. RASRx1902 and RASRx1911 have been shown to reduce inflammation and OS
in target organs as well as having a regenerative effect on damaged tissues. A recent study from our lab showed
that RASRx1902 and RASRx1911 were able to improve cognitive function as well as reduce OS in the brain in
a mouse model of hypertension induced cognitive dysfunction (transverse aortic constriction [TAC]). Since Mas
agonism is known to have a beneficial effect in AD, we hypothesize that these molecules can be developed as
a potential new therapeutic for the treatment of AD and related dementias. The primary objective of this proposal
are to advance development of one small molecule Mas agonist to submission of an Investigation New Drug
Application (IND) for the treatment of AD and related dementias through: 1. Evaluation of the oral efficacy of
RASRx1902 and RASRx1911 in TAC and AD mouse models (5xFAD & ApoE4); 2. Assessment of the efficacy
of RASRx1902 in TAC-ApoE4 mice, 3. Scale up of one Mas agonist manufactured under Good Manufacturing
Practices (GMP); 4. Development of a formulation of one Mas agonist for Phase I clinical trial; 5. Completion of
ADME, (PK) and IND-enabling Toxicology studies; 6. Preparation Pre IND and IND Documentation; 7. Conduct
of a Pre IND meeting; and 8. Filing of an IND. Research proposed herein is responsive to PAS 18-820 to develop
and evaluate therapies “that prevent Alzheimer's disease (AD), slow its progression or treat its cognitive and
behavioral symptoms”.

## Key facts

- **NIH application ID:** 10151579
- **Project number:** 5U01AG063768-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** KATHLEEN E. RODGERS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,531,012
- **Award type:** 5
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151579

## Citation

> US National Institutes of Health, RePORTER application 10151579, IND Enabling Studies for RASRx 1902, a novel Mas receptor agonist, for treatment of cognitive impairment in patients at risk for Alzheimer's disease. (5U01AG063768-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10151579. Licensed CC0.

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