# DT-EGF Toxic Fusion Protein for the Treatment of Bladder Cancer

> **NIH NIH R44** · AURORA ONCOLOGY, INC. · 2020 · $1,000,745

## Abstract

Project Summary/Abstract
Bladder cancer causes over 165,000 annual deaths worldwide with 70,000 new cases and 16,000 deaths
reported in the US. Treatment of superficial bladder cancer by resection and BCG administration is
unsuccessful in 40% of cases with recurrences eventually requiring cystectomy or other aggressive therapy;
new therapies are needed. The role of Epidermal Growth Factor Receptor (EGFR) in bladder cancer
pathogenesis has been well established and its pathologic expression on the luminal side of uroepithelial cells
in 70% of patients provides an ideal target for intravesical targeted therapy. We have previously demonstrated
DTEGF—a single chain protein, encoding modified diphtheria toxin (DT) that has replaced the B-chain
sequence normally enabling cell entry with that of Epidermal Growth Factor—was efficacious in a syngeneic
rodent model of bladder cancer, as well as in a number of xenograph explants of human bladder cancer in
nude mice. Toxicity was not observed in these murine studies, nor in a pilot study in dogs demonstrated
intravesical DTEGF was well tolerated at concentrations well above those needed for efficacy. IND-enabling
studies are needed for DTEGF to move into the clinical testing. While we have preclinical proof-of-concept with
DTEGF, another company has demonstrated Phase II clinical proof-of-concept with an EpCAM-toxinA fusion-
toxin demonstrating 40% complete response in superficial bladder cancer patients. Their work provides a
proven developmental path for our EGFR targeted toxin. The present grant application proposes to optimize
intravesical administration and subsequently complete IND-enabling safety studies, hold a pre-IND meeting
and complete an IND application. Completion of this work would position our agent as one with a very high
likelihood success to be ready for clinically testing. We anticipate DTEGF to address the unmet need of
patients that fail BCG (40%) and over express EGFR (70%) and eventually become a first line therapy that will
likely work with EpCAM-targeted and other therapies to benefit the majority of patients.

## Key facts

- **NIH application ID:** 10235431
- **Project number:** 4R44CA232963-02
- **Recipient organization:** AURORA ONCOLOGY, INC.
- **Principal Investigator:** Mike Glode
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,000,745
- **Award type:** 4N
- **Project period:** 2018-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235431

## Citation

> US National Institutes of Health, RePORTER application 10235431, DT-EGF Toxic Fusion Protein for the Treatment of Bladder Cancer (4R44CA232963-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10235431. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*