# IND-enabling safety and toxicity testing of a subcutaneous formulation of the PTP1B inhibitor MSI-1436, a novel strategy for treating fatal cardiomyopathy in Duchenne muscular dystrophy patients

> **NIH NIH R44** · REVIDIA THERAPEUTICS, INC · 2024 · $1,358,179

## Abstract

PROJECT SUMMARY
 Heart failure caused by progressive dilated cardiomyopathy is the primary cause of death in
patients with Duchenne muscular dystrophy (DMD), a fatal inherited muscle wasting disorder defined by
the FDA as an orphan disease. Cardiomyopathy is detectable in children as young as 10 years old and is
present in most patients by their late teens. Most DMD patients die in their late 20s from heart failure.
 There are no approved medications for DMD cardiomyopathy. Little effort has been devoted to
cardiomyopathy therapeutic development despite it being the main cause of DMD patient mortality. The vast
majority of DMD therapies in development focus on treating skeletal muscle degeneration. Current standard of
cardiac care for DMD patients utilizes steroids and off-label anti-hypertensive and heart failure drugs to reduce
heart inflammatory damage, workload, and tissue remodeling.
 Revidia Therapeutics, Inc. is a cardiac regenerative medicine company developing small molecules that
reactivate endogenous cardiac repair and regenerative processes. We are advancing a novel subcutaneous
formulation of our lead small molecule MSI-1436 into clinical trials as a treatment for DMD cardiomyopathy.
 MSI-1436 has already proven human safety. It functions by inhibiting the tyrosine phosphatase
PTP1B via a novel allosteric mechanism. PTP1B normally inactivates endogenous tissue repair and
regeneration processes. MSI-1436-induced inhibition of PTP1B reactivates these processes, which in turn
reverses tissue damage. Using blinded and randomized experimental and data analysis protocols, we have
shown that MSI-1436 stimulates heart muscle regeneration, improves heart function, and reduces infarct size
in wild type adult mice following myocardial infarction; improves left ventricle ejection fraction in a mouse
pressure overload dilated cardiomyopathy model; slows cardiac degenerative changes in young D2.B10-
Dmdmdx/J DMD mice; and improves left ventricle ejection fraction in aged DMD animals. Doses of MSI-1436
that reverse cardiac injury are up to 50-times lower than the maximum well tolerated human dose.
 Revidia has completed multiple IND-enabling workstreams including 1) FDA pre-IND meetings, 2)
efficacy testing in multiple animal models, 3) in vitro safety pharmacology, 4) ADME studies, 5) dose-range
finding, 6) CMC development and 7) Good Laboratory Practice (GLP) manufacturing. The final IND-enabling
workstream that must be completed is FDA-required GLP-compliant safety and toxicity testing of
subcutaneously administered MSI-1436. Proposed studies will validate subcutaneous MSI-1436 dose
formulations and bioanalytical methods and perform repeat dose toxicology and genotoxicity testing and CNS,
respiratory and cardiovascular safety pharmacology testing. Completion of these studies will allow IND
application submission in early 2025 and initiation of clinical trials later that year. Treatment of DMD
cardiomyopathy with MSI-1436 has significant potentia...

## Key facts

- **NIH application ID:** 10913659
- **Project number:** 1R44HL174171-01
- **Recipient organization:** REVIDIA THERAPEUTICS, INC
- **Principal Investigator:** KEVIN STRANGE
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,358,179
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-03-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913659

## Citation

> US National Institutes of Health, RePORTER application 10913659, IND-enabling safety and toxicity testing of a subcutaneous formulation of the PTP1B inhibitor MSI-1436, a novel strategy for treating fatal cardiomyopathy in Duchenne muscular dystrophy patients (1R44HL174171-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10913659. Licensed CC0.

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