# Project 2: Clinical Development of the Pancreatic Cancer Drug Conjugate SW v-49

> **NIH NIH P50** · WASHINGTON UNIVERSITY · 2020 · $473,179

## Abstract

PROJECT SUMMARY
Pancreatic cancer is a devastating disease that is refractory to standard chemotherapies, as demonstrated by
the low five-year survival rate of 6%. The objective of this proposal is to clinically evaluate a novel therapeutic
for the treatment of pancreatic cancer with in order to improve survival rates
The sigma-2 (S2) receptor is overexpressed in pancreatic cancer, and small molecule ligands to this receptor
localize to these tumors. In addition, PDAC cancer cells rapidly internalize selected sigma-2 ligands. This
finding prompted us to explore the possibility of using these ligands to deliver a therapeutic payload to PDAC
tumor cells via chemical linkage with our ligands. We have successfully used S2 ligands to deliver structurally
diverse compounds including both peptides and small molecule therapeutics (classic chemotherapeutics
[rapamycin] and peptidomimetics), into the cancer cells both in vitro and in vivo. In each case, the activity
profiles of the conjugates were far greater than the isolated components or their equimolar combinations.
Based on this delivery mechanism, we combined the tumor selectivity of the S2 ligand with a promising drug
cargo that induces cell death selectively in PDAC, to create a single small molecule conjugate (SW V-49). We
have shown that this conjugate efficiently kills tumor cells in stroma-rich pancreatic cancer tumor models with
limited systemic toxicity.
This project will perform pharmacology and toxicity assays, and test the conjugate in a clinical trial.

## Key facts

- **NIH application ID:** 9982233
- **Project number:** 5P50CA196510-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** WILLIAM G HAWKINS
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $473,179
- **Award type:** 5
- **Project period:** — → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982233

## Citation

> US National Institutes of Health, RePORTER application 9982233, Project 2: Clinical Development of the Pancreatic Cancer Drug Conjugate SW v-49 (5P50CA196510-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982233. Licensed CC0.

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