# Therapeutics to prevent aminoglycoside-induced hearing loss

> **NIH NIH R44** · TING THERAPEUTICS, INC. · 2024 · $524,299

## Abstract

Project Summary
Ting Therapeutics LLC is a pharmaceutical company developing drugs to prevent and treat hearing loss.
Aminoglycosides are one of the most widely used drugs to treat Gram-negative bacterial infections. However,
aminoglycoside therapy causes hearing loss in 40-60% of the patients. To date, no drugs have been approved
by the Food and Drug Administration for protection from aminoglycoside-induced hearing loss (AGIHL). Most
candidate compounds currently in pre-clinical and clinical trials are related to antioxidants, vitamins, and
glutathione metabolism, such as ebselen or N-acetylcysteine. We have performed high throughput screens for
otoprotectants against AGIHL in zebrafish and identified TT003, known as piperlongumine, a natural product
extracted from the pepper Piper Longum. TT003 attenuates hearing loss in adult mice treated with kanamycin
(700 mg/kg twice a day for 14 days) when delivered intraperitoneally (IP) at 40 mg/kg/day for 17 consecutive
days. Interestingly, TT003 seems to be protective against excitotoxicity in a zebrafish model that mimics
glutamate overexposure. In this SBIR Phase II, we will perform Investigational New Drug-enabling experiments
to test TT003’s effect on aminoglycoside’s bacteria killing efficacy in vivo and to conduct efficacy studies to define
an optimal dosing regimen and therapeutic index in an animal model that mimic the pathophysiological
environment of patients with Gram-negative bacterial infections. The long-term goal is for TT003 to become a
standard otoprotective drug of aminoglycoside-based therapies. For this purpose, we will identify TT003’s no-
observed adverse effect level and demonstrate TT003’s efficacy in a mouse model of inflammation that mimics
the physiological environment of cystic fibrosis patients (Aim 1). We will determine pharmacokinetics and
pharmacodynamics profiles in blood and perilymph, as well as efficacy, in a guinea pig model for aminoglycoside-
induced hearing loss (Aim 2). This Aim will be performed under contract with an independent and reputable
Contract Research Organization, Turner Scientific LLC. Finally, we will test drug-drug interactions in vivo to verify
that TT003 does not interfere with aminoglycoside’s anti-bacterial activity in mouse model for acute
Pseudomonas aeruginosa infections (Aim 3). By successfully completing these studies, Ting Therapeutics will
obtain critical data necessary for the initiation of Investigational New Drug enabling complaint preclinical studies
and subsequent clinical trials. Ting Therapeutics has filed a Patent Cooperation Treaty (PCT) for both the US
and international rights. The completion of this proposal will allow Ting Therapeutics to initiate conversations
with pharmaceutical companies and venture investments for the commercialization of TT003.

## Key facts

- **NIH application ID:** 11228816
- **Project number:** 6R44DC019065-03
- **Recipient organization:** TING THERAPEUTICS, INC.
- **Principal Investigator:** JIAN ZUO
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $524,299
- **Award type:** 6
- **Project period:** 2020-07-17 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11228816

## Citation

> US National Institutes of Health, RePORTER application 11228816, Therapeutics to prevent aminoglycoside-induced hearing loss (6R44DC019065-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11228816. Licensed CC0.

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