# A novel monobody-drug conjugate to treat mutant KRas pancreatic cancer.

> **NIH NIH R41** · TEZCAT LABORATORIES LLC · 2022 · $209,986

## Abstract

Project Summary: TEZCAT Laboratories LLC is an early-stage, Austin-based biotechnology
company developing novel biologics with a unique mechanism of action to treat the most
recalcitrant cancers, such as mutant KRas pancreatic cancer. As an alternative to targeting
mutant KRas itself, much attention has been paid to targeting cellular events that are a result of
mutant KRas. New efforts are underway to exploit previously unrecognized vulnerabilities. We
have observed that mutant KRas pancreatic cancer cells display high levels of a protein
scavenging process. Harnessing this metabolic adaptation, we have created protein-drug
conjugates that carry an FDA-approved cytotoxic payload. In vitro and in vivo assays demonstrate
that the protein-drug conjugates show selectivity for mutant KRas cancer cells and maintain
potency in the low nanomolar range. The protein-drug conjugates display relatively fast systemic
clearance but maintain beneficial characteristics of biologics such as decreased systemic
toxicities and tumor accumulation. Thus, we hypothesize that our novel conjugates will reduce
on-target and off-target effects often seen with traditional antibody-drug conjugates and fill a void
of therapeutic options for patients with mutant KRas pancreatic cancer. We have proposed a
Phase I STTR program for investigators at TEZCAT Laboratories and New York University
Langone Health to advance this lead through Specific Aims that evaluate the ability of the lead
drug candidate to control cancer growth in mouse models of pancreatic cancer. We further
propose to use an Administrative Supplement to 1) test our lead against other proprietary protein-
drug conjugates that utilize the same mechanism of action, and 2) test our lead in combination
with immunotherapy in the most clinically-relevant mouse model of pancreatic cancer. The
commercialization strategy will be based on establishing initial efficacy and nontoxicity of the lead
compound in relation to mutant KRas status in Phase I STTR studies, further development
towards IND status in Phase II SBIR studies, and then first-in-human clinical trials. Thus, we
expect Phase I STTR and the Administrative Supplement to provide the basis for pursuit of
additional data in Phase II aimed at GMP protocols and further non-GLP and GLP safety and
toxicity studies.

## Key facts

- **NIH application ID:** 10666997
- **Project number:** 3R41CA265512-01S1
- **Recipient organization:** TEZCAT LABORATORIES LLC
- **Principal Investigator:** DAFNA BAR-SAGI
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $209,986
- **Award type:** 3
- **Project period:** 2022-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10666997

## Citation

> US National Institutes of Health, RePORTER application 10666997, A novel monobody-drug conjugate to treat mutant KRas pancreatic cancer. (3R41CA265512-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10666997. Licensed CC0.

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