# Novel Dopaminergic Stimulant Prodrug for the Treatment of Apathy in AD

> **NIH NIH R44** · PRAXIS BIORESEARCH, LLC · 2022 · $50,000

## Abstract

PROJECT SUMMARY
The goal of this project is to develop PRX-P4-003 as a safer “first-in-class” FDA-approved
therapy for apathy in Alzheimer’s Disease (AD). Apathy is one of the most common
neurobehavioral symptoms of AD (>70% of patients) and is defined as loss of initiative and
interest in daily activity in the absence of depression or other mood changes. These symptoms
are associated with reduced quality of life, increased functional impairment, greater caregiver
burden, earlier institutionalization and higher costs of care. The central role of dopamine in
motivation is well appreciated mechanistically and promising clinical data with methylphenidate
(MPH), a dopaminergic stimulant drug, suggests that apathy in AD is treatable. Three published
clinical studies have shown meaningful improvement in apathy symptoms by 4 weeks and
additionally a promising finding of gradual improvement in cognition by 12 weeks. However,
MPH is a Schedule II-controlled drug which, like opiates, has a high risk of diversion, addiction,
and abuse. PRX-P4-003 is a novel dopaminergic prodrug of a known stimulant fencamfamine, it
has a potential to improve symptoms of apathy as a convenient low risk, once-a-day, Schedule
IV treatment. The unique structure of PRX-P4-003 results in a water insoluble prodrug with dual
protection properties: it is inactive following intravenous administration and has delayed
absorption properties with oral administration. These protection properties were accomplished
by chemically formulating the prodrug as a substrate specifically activated by pancreatic lipase,
which is almost entirely (>99%) located in the pancreatic duct and small intestine. Praxis has
obtained both in vitro and in vivo safety and efficacy data demonstrating the feasibility of PRX-
P4-003 for the next stage of development. Successful completion of the work in this proposal
will provide key evidence needed to pursue this drug for treating apathy in AD. Activities will
focus on large scale GMP manufacturing and FDA approved regulatory studies for eventual
human dosing and investigation into patients with apathy in Alzheimer’s Disease.

## Key facts

- **NIH application ID:** 10657261
- **Project number:** 3R44AG066378-03S1
- **Recipient organization:** PRAXIS BIORESEARCH, LLC
- **Principal Investigator:** Sandeep Patil
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $50,000
- **Award type:** 3
- **Project period:** 2022-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657261

## Citation

> US National Institutes of Health, RePORTER application 10657261, Novel Dopaminergic Stimulant Prodrug for the Treatment of Apathy in AD (3R44AG066378-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10657261. Licensed CC0.

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