# I-Corps Project plan for:STTR Phase I Development of therapeutics to treat fentanyl overdose using a validated animal model

> **NIH NIH R41** · TORRALVA MEDICAL THERAPEUTICS, LLC · 2022 · $54,960

## Abstract

Project Summary
According to the Centers for Disease Control (CDC), synthetic opioids are currently the most
common cause of overdose death in the U.S, while heroin and prescription opioid deaths have
decreased significantly since 2017. Despite the widespread availability of naloxone, deaths from
fentanyl and fentanyl analogues (F/FA) continue to rise in parallel with increasing reports of
F/FA resistance to naloxone. High doses of rapidly injected F/FA cause airway obstruction from
vocal cord closure (VCC) and severe chest wall rigidity (CWR) within 2 minutes, effects that
persist for up to 10 minutes and appear to be resistant to naloxone. In contrast, morphine-
derived opiates (e.g. heroin) cause respiratory depression and mild muscle rigidity that is
responsive to naloxone but are not known to cause VCC in humans. This suggests distinct
pharmacological mechanisms underlying F/FA-induced VCC, compared to morphine-induced
respiratory depression mediated by mu opioid receptors. In support of this hypothesis,
off-site targets our published pharmacological data demonstrate F/FA, but not morphine or
naloxone, have affinity for models of brain lipid concentrations for F/FA. Additionally, we have
demonstrated in our animal model that that may regulate these F/FA-induced effects. The in
vitro data include F/FA concentrations that may be physiologically relevant to humans, based
on available these fentanyl-induced effects are resistant to high dose naloxone and may involve
these off-site receptor targets. This preliminary data suggests the development of effective
therapies for overdose require a biological model that re-conceptualizes the underlying causes
of F/FA to include VCC, in addition to respiratory depression. There is currently no Federal
Drug Administration development of a new class of therapeutics, specific to F/FA overdose.
Under the I-Corp project, the team will seek to validate or modify its hypotheses regarding the
market, target customers, and critical market need.

## Key facts

- **NIH application ID:** 10541304
- **Project number:** 3R41DA055409-01S1
- **Recipient organization:** TORRALVA MEDICAL THERAPEUTICS, LLC
- **Principal Investigator:** Phillip Randolph Torralva
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $54,960
- **Award type:** 3
- **Project period:** 2021-09-30 → 2022-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10541304

## Citation

> US National Institutes of Health, RePORTER application 10541304, I-Corps Project plan for:STTR Phase I Development of therapeutics to treat fentanyl overdose using a validated animal model (3R41DA055409-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10541304. Licensed CC0.

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