# Preclinical Development of ACXT-3102 for the Treatment of Pancreatic Adenocarcinoma (PDAC)

> **NIH NIH R42** · ACCURONIX THERAPEUTICS, INC. · 2022 · $1,019,186

## Abstract

Project Summary/Abstract
Pancreatic cancer is a devastating disease with a very low (8%) 5-year survival rate. Therapeutic options are
limited in efficacy and many have substantial toxicity. Targeted drug delivery may improve the therapeutic
index of cancer drugs by enhancing drug localization to the cancer cell while minimizing off-target side effects.
Sigma-2 receptors (S2R) are highly expressed in pancreatic and other cancers compared to healthy cells.
Accuronix Therapeutics is developing ACXT-3102, a molecule with therapeutic potential licensed from
Washington University School of Medicine in St. Louis (WUSM). ACXT-3102 is comprised of a S2 ligand
covalently bound to the ferroptosis-inducing molecule dm-erastin. Preliminary data show that ACXT-3102
increased the cytotoxicity against pancreatic tumor cells in vitro by 35-fold compared to dm-erastin alone.
ACXT-3102 has tremendous potential as a novel treatment option for pancreatic and perhaps several other
types of cancer. Drug optimization strategies were conducted in a Phase I STTR which resulted in a better
yield during drug synthesis, identification of a mesylate salt with high aqueous solubility and improved physical
properties suitable for oral drug administration, demonstration of good oral efficacy and discovery that tumors
lacking malic enzyme 1 (ME1) are even more sensitive to ACXT-3102.
For this Phase II STTR program, Accuronix Therapeutics will continue to work with our research colleagues
from WUSM to prepare ACXT-3102 for Investigational New Drug (IND) submission and eventually testing the
compound in pancreatic cancer patients. We will conduct a series of preclinical studies to optimize the dosing
regimen in murine pancreatic cancer models – understanding if once, twice or three times per day drug
administration improves plasma exposure and anti-tumor efficacy while maintaining safety, i.e., avoiding dose-
limiting side effects. Studies will also explore if efficacy of our drug can be further improved when given in
combination with gemcitabine, a current standard-of-care for pancreatic cancer. Chemical and metabolic
stability of ACXT-3102 will be established using in vitro assays to guide storage conditions of the drug and
understand which preclinical species best represents metabolism in humans. To obtain data required for the
pharmacology and safety sections of the IND package, preclinical studies will be conducted according to Good
Laboratory Practice (GLP) guidelines to generate pharmacokinetic (PK) and pharmacodynamic (PD) data for
correlating plasma exposures in different species to what is predicted in human. Similarly, formal GLP
toxicology studies will be completed using three different doses in rats and dogs to establish the “No Observed
Adverse Effect Level” (NOAEL). These data will be used to model exposure levels in humans and establish a
safe, first-in-human (FIH) dose for starting our clinical trials in cancer patients. At the conclusion of the Phase
II STTR gran...

## Key facts

- **NIH application ID:** 10435565
- **Project number:** 5R42CA239853-03
- **Recipient organization:** ACCURONIX THERAPEUTICS, INC.
- **Principal Investigator:** WILLIAM G HAWKINS
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,019,186
- **Award type:** 5
- **Project period:** 2019-09-23 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435565

## Citation

> US National Institutes of Health, RePORTER application 10435565, Preclinical Development of ACXT-3102 for the Treatment of Pancreatic Adenocarcinoma (PDAC) (5R42CA239853-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10435565. Licensed CC0.

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