# Preclinical Development of a Novel Therapeutic to Rejuvenate Aging Muscle Stem Cells and Enhance Muscle Strength and Function Post Hip Fracture

> **NIH NIH U44** · RIDGELINE THERAPEUTICS, LLC · 2024 · $236,538

## Abstract

ABSTRACT
Ridgeline’s U44 award (U44AG074107) from the National Institute on Aging has supported critical therapeutic
development studies of RT-002, a novel oral therapeutic to accelerate full functional recovery and enhance
quality-of-life after traumatic hip injuries in adults ≥65 years of age. The majority of the proposed milestones for
our clinical candidate drug RT-002 were completed in the past 2.5 years (award start: 09/01/21), including (i)
essential studies that identified the necessary rodent and nonrodent species for human-predictive toxicology
assessments, (ii) translational mechanistic and target-engagement validations in aged human muscle-derived
progenitor cells and aged mice and rat preclinical models, (iii) process optimization and scale-up synthesis of
~4-kilogram GMP-like batch of drug substance, (iv) non-GLP and GLP toxicity and safety pharmacology studies
in rats, (v) oral dosing tolerability and toxicokinetic (TK) assessments in male and female dogs that justified dogs
as a non-ideal toxicology species, and (vi) non-GLP in vivo PK, dose escalation, and repeated-oral dosing
tolerability studies in male and female minipigs that fully justified minipigs as the ideal nonrodent toxicology
species. The latter study was funded by an administrative supplement award (No. U44AG074107-02S1), with
the results described in this proposal.
This administrative supplement project will enable us to complete FDA-mandated GLP toxicity/TK study in
minipigs, the appropriate nonrodent species, and related bionalytical activities. Our pivotal cross-species
metabolism studies demonstrated that RT-002 was metabolized similarly in rat, minipig, and human hepatocytes,
with consistent in vivo results showing substantial systemic exposures of RT-002’s primary metabolites in rats
and minipigs following oral dosing. Recently completed non-GLP dose-range finder and 14-day repeated-oral
dosing toxicity/TK studies in male and female minipigs validated a maximum tolerated single dose (MTD) of at
least 500 mg/kg RT-002 and an MTD of 100 mg/kg/day over 14 days (once-daily [q.d.] dosing regimen as
intended in the clinical program). The steady-state RT-002 exposures were similar between sexes after 14 days
of daily dosing (AUClast males = 15,000 ng*h/mL; AUClast females = 12,400 ng*h/mL), with unremarkable cardiac
toxicity findings. These results support the planned pivotal GLP toxicity/TK studies in male and female minipigs
to establish the no observable adverse effect level (NOAEL) and MTD of RT-002 and evaluate dose-limiting
toxicities following q.d. oral dosing of RT-002 over 28 days. Outcomes from these final GLP studies will be
compiled into an investigational new drug (IND) briefing package and submitted to the U.S. FDA, enabling
Ridgeline to reach a crucial value-inflection point and begin clinical trials at the end of this project

## Key facts

- **NIH application ID:** 11080486
- **Project number:** 3U44AG074107-03S1
- **Recipient organization:** RIDGELINE THERAPEUTICS, LLC
- **Principal Investigator:** Harshini Neelakantan
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $236,538
- **Award type:** 3
- **Project period:** 2021-09-30 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11080486

## Citation

> US National Institutes of Health, RePORTER application 11080486, Preclinical Development of a Novel Therapeutic to Rejuvenate Aging Muscle Stem Cells and Enhance Muscle Strength and Function Post Hip Fracture (3U44AG074107-03S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11080486. Licensed CC0.

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