# Development of a protein drug for pancreatic cancer treatment

> **NIH NIH U44** · PRODA BIOTECH, LLC · 2023 · $1,515,866

## Abstract

Abstract
Pancreatic cancers are devastating diseases with five year survival rate less than 9%. Currently,
there is no effective treatment for advanced disease. One major barrier to efficacy of anti-tumor
therapeutics is the dense desmoplastic stromal response. Evidence suggests that cancer
associated pancreatic stellate cells (CaPSC) produce the stromal collagen. The ECM laid down
by CaPSC is considered to be one of the major contributors of resistance to established therapies
of the diseases. Depleting CaPSC and altering vessel density could significantly improve efficacy
of existing pancreatic ductal adenocarcinoma (PDAC) treatments. However, currently, there are
no approved therapies that are able to deplete CaPSCs in PDAC. We have developed a novel
therapeutic protein (ProAgio) using rational protein design. ProAgio is designed to target integrin
αvβ3 at a novel site (not the ligand binding site). ProAgio specifically induces apoptosis of integrin
αvβ3 expressing cells with high efficacy by a novel mechanism of drug action (recruiting &
activating caspase 8 at cytoplasmic domain of β3). We reasoned that, since both CaPSC and
angiogenic endothelial cells express high levels of integrin αvβ3, and since ProAgio is very
effective in inducing apoptosis of integrin αvβ3 expressing cells, ProAgio should both deplete
CaPSC and eliminate new blood vessels in and around pancreatic tumors. This unique strategy
may prove advantageous in treatment of PDAC. Our STTR phase I&II studies demonstrated
efficacy of ProAgio potentially as a PDAC treatment via various cancer models. The studies
support our hypothesis that ProAgio can provide treatment benefit by simultaneously depleting
the collagen-producing CaPSCs that support tumor desmoplasia and cancer cell growth, while
also eliminating newly grown cancer associated blood vessels that feed cancer cells and enable
cancer metastasis. Data from our STTR phase I&II studies provides proof of principle for future
clinical tests. Results from our phase II studies have led to IND application of ProAgio as a
pancreatic cancer treatment drug. The main objective of this phase IIB application is to generate
a definitive dataset to enable the development of ProAgio as a viable therapeutic option for PDAC
patients. Aim 1 will characterize the toxicity and tolerability and determine the maximum tolerated
dose (MTD) and recommended phase II dose (RP2D) of ProAgio as a single agent and in
combination with G-nP. Aim 2 will characterize PK property of ProAgio in cancer patients and to
obtain preliminary anti-cancer activity data of ProAgio and ProAgio + G-nP in PDAC patients. Aim
3 will analyze the effects of ProAgio in patient tumor to validate the mechanism of drug action in
patients. This study will explore new therapeutic avenue for PDAC patients.

## Key facts

- **NIH application ID:** 10551992
- **Project number:** 5U44CA217482-05
- **Recipient organization:** PRODA BIOTECH, LLC
- **Principal Investigator:** Zhi-Ren Liu
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,515,866
- **Award type:** 5
- **Project period:** 2017-09-26 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10551992

## Citation

> US National Institutes of Health, RePORTER application 10551992, Development of a protein drug for pancreatic cancer treatment (5U44CA217482-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10551992. Licensed CC0.

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