# Discover HTT-lowering small-molecule drugs to treat Huntington's disease

> **NIH NIH R43** · RGENTA THERAPEUTICS, INC. · 2020 · $400,034

## Abstract

ABSTRACT
Rgenta has developed a robust, innovative, target and lead discovery platform that has identified small molecules
that can lower the levels of HTT through a novel mechanism-of-action in RNA-targeting. In this Phase I SBIR
project, we aim to develop first-in-class drug candidate compounds for HTT lowering as a new therapeutic
approach for treating HD. Our Phase I SBIR proposal has three aims: Aim 1. We will perform chemical hit
expansion and medicinal chemistry to improve the potency and refine Structure-Activity Relationships (SARs) of
our three novel pharmacophores. Aim 2. We will characterize pharmacological effect of lead molecules in HD
patient derived iPSC neurons on HTT lowering, preventing HTT aggregate formation induced by proteasome
inhibitors, and selectivity profiles Aim 3. We will test up to five compounds from each chemical series in well-
established in vitro absorption, distribution, metabolism, excretion (ADME) assays including cell permeability,
and in vitro metabolic stability. We will then determine mouse in vivo pharmacokinetics (PK) on the best
molecules. Aim 4. We will determine the in vivo HTT lowering efficacy of our best compounds in HD mouse
models.

## Key facts

- **NIH application ID:** 10157094
- **Project number:** 1R43NS120782-01
- **Recipient organization:** RGENTA THERAPEUTICS, INC.
- **Principal Investigator:** Travis Wager
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,034
- **Award type:** 1
- **Project period:** 2020-09-30 → 2021-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157094

## Citation

> US National Institutes of Health, RePORTER application 10157094, Discover HTT-lowering small-molecule drugs to treat Huntington's disease (1R43NS120782-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10157094. Licensed CC0.

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