U44CA217482

Development of a Protein Drug for Pancreatic Cancer Treatment - Abstract

Pancreatic cancers are devastating diseases with a five-year survival rate less than 9%. Currently, there is no effective treatment for advanced disease. One major barrier to the 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 extracellular matrix (ECM) laid down by CAPSC is considered to be one of the major contributors to resistance to established therapies of the diseases. Depleting CAPSC and altering vessel density could significantly improve the 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 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 CAPSC and angiogenic endothelial cells express high levels of integrin V3, and since ProAgio is very effective in inducing apoptosis of integrin V3 expressing cells, ProAgio should both deplete CAPSC and eliminate new blood vessels in and around pancreatic tumors. This unique strategy may prove advantageous in the treatment of PDAC.

Our Small Business Technology Transfer (STTR) Phase I and II studies demonstrated the 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 and II studies provide proof of principle for future clinical tests. Results from our Phase II studies have led to an Investigational New Drug (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 the pharmacokinetic properties of ProAgio in cancer patients and 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 tumors to validate the mechanism of drug action in patients.

This study will explore a new therapeutic avenue for PDAC patients.

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]

Georgia United States

State-Wide

SBIR Phase IIB Bridge Awards to Accelerate the Development of Cancer-Relevant Technologies Toward Commercialization (R44 Clinical Trial Optional) (RFA-CA-20-033)

Amendment Since initial award the total obligations have increased 316% from $960,859 to $3,994,217.