U44CA268345

A Treatment Drug for Triple Negative Breast Cancer - Summary

Triple negative breast cancers (TNBC) are devastating diseases with a median survival of less than 1 year for patients with metastatic disease. TNBC patients with a tumor of high fibrotic stroma have an even worse prognosis. There are no specific targeted therapies available for TNBC, and the only treatment option is broadly cytotoxic chemotherapy drugs, despite their less effective and strong unwanted side effects.

One major barrier to the efficacy of anti-tumor therapeutics is the dense fibrotic stromal and dysregulated tumor blood vessels, which contribute to the failure of therapies. Evidence suggests that cancer-associated fibroblasts (CAF) produce the stromal collagen. The extracellular matrix (ECM) laid down by CAF is considered to be one of the major contributors to resistance to established therapies of the diseases. TNBC has high angiogenic activity, and dense tumor vasculature is associated with a shorter time from diagnosis to relapse and from relapse to death. The dysregulated vessel structure in TNBC tumors often leads to resistance to blood flow into the tumor, which is another important barrier for drug delivery.

Depleting CAF and abrogating tumor angiogenesis could significantly improve the efficacy of existing TNBC cancer treatments. However, currently, there are no approved therapies that are able to deplete CAF and tumor angiogenesis in TNBC cancer.

We have developed a novel therapeutic protein (ProAgio) using rational protein design. ProAgio is designed to target integrin V3 at a novel site (not the ligand binding site). ProAgio specifically induces apoptosis of integrin V3 expressing cells with high efficacy by a novel mechanism of drug action (recruiting and activating caspase 8 at the cytoplasmic domain of). We reasoned that, since both CAF and angiogenic endothelial cells (AEC) express high levels of integrin V3, and since ProAgio is very effective in inducing apoptosis of integrin V3 expressing cells, ProAgio should both deplete CAF and eliminate intratumoral angiogenic blood vessels in and around TNBC tumors. This unique strategy may prove advantageous in the treatment of TNBC.

The main objective of this direct Phase II SBIR application is to generate a definitive dataset to enable the development of ProAgio as a viable therapeutic option for TNBC patients. Characterization of the toxicity and tolerability and determining the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of ProAgio as a single agent is ongoing. Aim 1 will characterize the toxicity and tolerability and determine the recommended Phase II dose (RP2D) of ProAgio in combination with gemcitabine (GEM). Aim 2 will obtain preliminary anti-cancer activity data of ProAgio and ProAgio + GEM in TNBC patients. Aim 3 will analyze the effects of ProAgio in patient tumors to validate the mechanism of drug action in patients.

This clinical study project will explore a new therapeutic avenue for TNBC patients. Our goal is that, through our study, we will introduce a new treatment approach for TNBC with a novel mechanism of drug action.

Proda Biotech

TO DEVELOP THE MEANS TO CURE AS MANY CANCER PATIENTS AS POSSIBLE AND TO CONTROL THE DISEASE IN THOSE PATIENTS WHO ARE NOT CURED. CANCER TREATMENT RESEARCH INCLUDES THE DEVELOPMENT AND EVALUATION OF IMPROVED METHODS OF CANCER TREATMENT THROUGH THE SUPPORT AND PERFORMANCE OF BOTH FUNDAMENTAL AND APPLIED LABORATORY AND CLINICAL RESEARCH. RESEARCH IS SUPPORTED IN THE DISCOVERY, DEVELOPMENT, AND CLINICAL TESTING OF ALL MODES OF THERAPY INCLUDING: SURGERY, RADIOTHERAPY, CHEMOTHERAPY, AND BIOLOGICAL THERAPY INCLUDING MOLECULARLY TARGETED THERAPIES, BOTH INDIVIDUALLY AND IN COMBINATION. IN ADDITION, RESEARCH IS CARRIED OUT IN AREAS OF NUTRITIONAL SUPPORT, STEM CELL AND BONE MARROW TRANSPLANTATION, IMAGE GUIDED THERAPIES AND STUDIES TO REDUCE TOXICITY OF CYTOTOXIC THERAPIES, AND OTHER METHODS OF SUPPORTIVE CARE THAT MAY SUPPLEMENT AND ENHANCE PRIMARY TREATMENT. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.395 - Cancer Treatment Research

National Cancer Institute (NCI) [HHS - NIH]

Atlanta, Georgia 303032921 United States

Single Zip Code

PHS 2021-2 Omnibus Solicitation of the NIH and CDC for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Required) (PA-21-260)

Amendment Since initial award the total obligations have increased 100% from $999,562 to $1,999,124.