# Amyloid-Beta and Tau/Glycosaminoglycan Dual Inhibitor for Alzheimer's Disease

> **NIH NIH R44** · GISMO THERAPEUTICS, INC. · 2024 · $1,192,768

## Abstract

ABSTRACT
The aim of this project is to support an IND application for GTC-3295 for the treatment of
Alzheimer's Disease (AD). Neurodegenerative amyloid diseases such as AD have common
underlying biochemical pathways leading to oligomerization and aggregation of amyloidogenic
peptides and prion-like spreading of amyloid proteopathic seeds throughout the Central Nervous
System (CNS). Recent data suggest that heparan sulfate glycosaminoglycans (HS-GAGs) are
the receptors responsible for internalization and spreading of amyloid-beta (Abeta) and tau
neuropathologies in the brain. We are developing a novel class of therapeutics,
Glycosaminoglycan-Interacting Small Molecules (GISMOs), for the treatment of AD. GISMOs
are drug-like small molecule compounds that inhibit Abeta and tau interactions with HS-GAGs,
each of which is a key molecule implicated in AD pathogenesis, and may reduce propagation of
these aggregated proteins in the Alzheimer's brain. GTC-3295 is a New Chemical Entity (NCE)
and has dual activity as it efficiently inhibits both Abeta as well as Tau interactions with HS-
GAGs. In previous studies in a transgenic mouse model of AD, GTC-3295 decreased amyloid
burden in the mouse brain by as much as five-fold, and significantly decreased
hyperphosphorylated tau levels in CA1 region of hippocampus. Initial preclinical studies indicate
that GTC-3295 is an orally available and brain penetrant compound possessing favorable
properties in in vitro ADME, pharmacokinetics, toxicity and other studies. These results provide
justification to continue developing GTC-3295. In this SBIR project, we will perform a number of
IND-enabling preclinical studies including GLP Toxicology studies in two species, scale-up
synthesis, formulation studies, and development of bioanalytical methods. We will also evaluate
efficacy of GTC-3295 in two transgenic models of AD, that separately address Abeta and tau
neuropathologies. Completion of these requisite development activities should position this
project towards a successful IND submission to the FDA and advancing into Phase I clinical
trials in humans.

## Key facts

- **NIH application ID:** 10891665
- **Project number:** 5R44AG056231-05
- **Recipient organization:** GISMO THERAPEUTICS, INC.
- **Principal Investigator:** Paul Gregor
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,192,768
- **Award type:** 5
- **Project period:** 2017-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891665

## Citation

> US National Institutes of Health, RePORTER application 10891665, Amyloid-Beta and Tau/Glycosaminoglycan Dual Inhibitor for Alzheimer's Disease (5R44AG056231-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10891665. Licensed CC0.

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