Awards Registry

Pharmacology & Human Phase 1 Safety & Dose Escalation Studies Using Anti-GP88 in Aggressive Breast Cancer
Profile last edited on: 2/3/21

Program
SBIR
Agency
NIH | NCI
Total Award Amount
$1,221,480
Award Phase
2
Principal Investigator
Ginette Serrero
Activity Indicator

Company Information

A&G Pharmaceutical Inc (AKA:A and G Pharmaceutical Inc)

9130 Red Branch Road Suite U
Columbia, MD 21045
   (410) 884-4100
   N/A
   www.agpharma.com
Multiple Locations:   
Congressional District:   03
County:   Howard

Phase I

Phase I year
2018
Phase I Amount
$159,365
In 2017, ~200,000 new cases of breast cancer (BC) and ~40,000 related deaths are expected in the US. ~30,000 of these are patients with aggressive triple negative BC (TNBC) or anti-estrogen/aromatase inhibitor resistant (AE/AI) BC that do not have targeted therapy and rely on radiotherapy and aggressive chemotherapy. A new approach that benefits these patients and provides increased life expectancy needs to be developed. We have identified GP88, a glycoprotein that is produced by cancer cells and stimulates their growth and survival leading to formation of more aggressive tumors. GP88 is found in BC but not in normal breast tissue. There is compelling biological and clinical evidence to suggest that GP88 can be used to develop novel targeted therapy with companion diagnostics that could impact treatment and improve survival of TNBC and AE/AI BC patients. We have developed a tissue test to identify patients with tumors expressing GP88 and an anti-GP88 (AG1) to block the action of GP88 on tumor tissues to a) inhibit tumor growth and b) increase the efficacy of current BC drugs. We have safety and efficacy data in animals and will in our Phase 1 develop a dosing strategy in mice before moving into human studies as part of the Phase 2. Additionally, a blood test has been developed to monitor patients while on treatment. Using AG1 as the therapy with two companion diagnostic tests, we will carry out a phase IA/B clinical trial in humans to determine safety of AG1 manufactured under GMP in the Phase 2 and will collect tumor tissue and blood on all patients to evaluate for GP88 expression (tissue) and concentration (blood).

Project Terms:
Acute; Address; Adverse event; Animals; Antineoplastic Agents; Aromatase Inhibitors; autocrine; base; Biological; Biological Markers; Biological Response Modifier Therapy; Blood; Blood specimen; Blood Tests; breast cancer diagnosis; Breast Cancer Model; Breast Cancer Patient; Breast Cancer Risk Factor; cancer cell; Cell Line; Cessation of life; Chemistry; chemotherapy; Clinical; Clinical Research; Clinical Trials; cohort; companion diagnostics; Comprehensive Cancer Center; cost; cost effective; Data; Deposition; design; Diagnostic tests; Disease; Documentation; Dose; drug discovery; Drug resistance; Enrollment; Estrogen Antagonists; Estrogen receptor positive; Event; first-in-human; Formulation; Future; Glycoproteins; Growth; Hormones; Human; Image; immunogenicity; improved; in vivo; Individual; Injectable; innovation; Institutional Review Boards; intravenous injection; Investigation; Life Expectancy; Link; Liquid substance; malignant breast neoplasm; Malignant Neoplasms; Mammary Gland Parenchyma; Maryland; Maximum Tolerated Dose; Measurable; Measures; Monitor; Monoclonal Antibodies; Mus; Nature; neutralizing antibody; new therapeutic target; nonhuman primate; novel strategies; open label; Outcome; overexpression; Pathologic; Patient Monitoring; Patients; PGRN gene; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Pharmacology Study; Phase; Play; Population; Population Decreases; pre-clinical; precision medicine; preclinical development; preclinical efficacy; predictive marker; Process; Production; Radiation therapy; real time monitoring; Recombinants; Recurrence; Resistance; response; Role; Safety; Schedule; Serum; Small Business Innovation Research Grant; Solid Neoplasm; Stable Disease; success; targeted treatment; Testing; theranostics; Therapeutic; therapeutic target; therapy development; Tissue Banks; Tissues; Toxic effect; Toxicology; treatment choice; triple-negative invasive breast carcinoma; tumor; tumor growth; Tumor Tissue; tumorigenesis; Universities; Vial device; Xenograft Model; Xenograft procedure;

Phase II

Phase II year
2020 (last award dollars: 2020)
Phase II Amount
$1,062,115
In 2017, ~200,000 new cases of breast cancer (BC) and ~40,000 related deaths are expected in the US. ~30,000 of these are patients with aggressive triple negative BC (TNBC) or anti-estrogen/aromatase inhibitor resistant (AE/AI) BC that do not have targeted therapy and rely on radiotherapy and aggressive chemotherapy. A new approach that benefits these patients and provides increased life expectancy needs to be developed. We have identified GP88, a glycoprotein that is produced by cancer cells and stimulates their growth and survival leading to formation of more aggressive tumors. GP88 is found in BC but not in normal breast tissue. There is compelling biological and clinical evidence to suggest that GP88 can be used to develop novel targeted therapy with companion diagnostics that could impact treatment and improve survival of TNBC and AE/AI BC patients. We have developed a tissue test to identify patients with tumors expressing GP88 and an anti-GP88 (AG1) to block the action of GP88 on tumor tissues to a) inhibit tumor growth and b) increase the efficacy of current BC drugs. We have safety and efficacy data in animals and will in our Phase 1 develop a dosing strategy in mice before moving into human studies as part of the Phase 2. Additionally, a blood test has been developed to monitor patients while on treatment. Using AG1 as the therapy with two companion diagnostic tests, we will carry out a phase IA/B clinical trial in humans to determine safety of AG1 manufactured under GMP in the Phase 2 and will collect tumor tissue and blood on all patients to evaluate for GP88 expression (tissue) and concentration (blood).

Public Health Relevance Statement:
Significance: Of ~220,000 cases of breast cancer (BC) diagnosed in the US in 2017 ~175,000 cases will be estrogen receptor positive and 25% Her-2 overexpressing for whom targeted therapies are available as well as biomarker tests to identify those who may benefit from such drugs. However, there are 2 major at risk BC groups who have limited treatment choices: anti-estrogen/ aromatase inhibitor resistant population (AE/AI) and triple negative BC population (TNBC). The PI’s discovery of a theranostic target that is a driver of tumorigenesis and has therapeutic and companion diagnostics applications, will address both BC populations. Hypothesis: We identified GP88, an 88 kDa glycoprotein autocrine growth /survival factor involved in deregulated growth leading to aggressive tumor formation. The PI demonstrated GP88’s critical role in the process of cancer tumorigenesis & survival, its overexpression in BC tumors but not in normal breast tissue & its secretion into biological fluids at increased levels in BC patients compared to healthy individuals. Using a tissue test to identify patients with GP88 positive tumors and treating such patients with an antibody that neutralizes GP88 and blocks its autocrine effect on cancer cells will inhibit tumor growth and increase efficacy of current BC drugs. Evidence: Pathological studies established GP88 tumor expression as a predictive marker for recurrence. Clinical studies showed BC patients with progressive BC have elevated GP88 serum levels compared to healthy individuals. In Vivo studies demonstrated AG1, a recombinant anti-GP88 can reduce growth of human BC xenografts in mice and potentiate the effect of SOC drugs. GMP manufacturing of AG1 has been developed. 2 lots of AG1 have been produced and formulated as injectable. Repeat dose toxicology study in non-human primates established AG1 safety. Strategy & Approach of Fast Track SBIR: Phase 1 specific aims will collect pharmacology data in mice to link our efficacy & safety data to identify a dose and schedule for AG1 in human studies. Phase 2 will focus on a phase IA/B clinical trial to determine safety of AG1 in humans. Tumor tissue collection and serial blood sampling will evaluate GP88 tissue expression and blood concentration in enrolled TNBC and AE/AI BC patients demonstrated to express GP88 correlated with outcome. The IHC test measures GP88 expression in tumor tissue to identify GP88 positive patients. The serum GP88 EIA provides real time monitoring of disease status. The Phase 2 Specific Aim 1 manufacture 500gms of GMP AG1 for Phase IA/B clinical studies. Specific Aim 2 perform a Phase IA/B clinical study in (a) patients with solid tumors to determine maximum tolerated dose/ optimum biological dose and (b) expansion cohorts with TNBC and AE/AI BC patients with GP88 positive tumors. Overall Impact: Blocking action of GP88 in aggressive cancer using a first-in-class neutralizing antibody will 1) inhibit tumor growth 2) potentiate SOC drugs. There is compelling biological and clinical evidence to suggest GP88 is a therapeutic target with companion diagnostics for BC that could impact treatment and improve survival of patients with TNBC and AE/AI BC.

Project Terms:
Acute; Address; adverse event monitoring; Animals; Antineoplastic Agents; Aromatase Inhibitors; autocrine; base; Biological; Biological Markers; Biological Response Modifier Therapy; Blood; Blood specimen; Blood Tests; breast cancer diagnosis; Breast Cancer Model; Breast Cancer Patient; Breast Cancer Risk Factor; cancer cell; Cell Line; Cessation of life; Chemistry; chemotherapy; Clinical; Clinical Research; Clinical Trials; cohort; companion diagnostics; Comprehensive Cancer Center; cost; cost effective; Data; Deposition; design; Diagnostic tests; Disease; Documentation; Dose; drug discovery; Drug resistance; Enrollment; Estrogen Antagonists; Estrogen receptor positive; Event; first-in-human; Formulation; Future; Glycoproteins; Growth; Hormones; Human; Image; immunogenicity; improved; in vivo; Individual; Injectable; innovation; Institutional Review Boards; intravenous injection; Investigation; Life Expectancy; Link; Liquid substance; malignant breast neoplasm; Malignant Neoplasms; Mammary Gland Parenchyma; Maryland; Maximum Tolerated Dose; Measurable; Measures; Monoclonal Antibodies; Mus; Nature; neutralizing antibody; new therapeutic target; nonhuman primate; novel strategies; open label; Outcome; overexpression; Pathologic; Patient Monitoring; Patients; PGRN gene; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Pharmacology Study; Phase; Play; Population; Population Decreases; pre-clinical; precision medicine; preclinical development; preclinical efficacy; predictive marker; Process; Production; Radiation therapy; real time monitoring; Recombinants; Recurrence; Resistance; response; Role; Safety; Schedule; Serum; Small Business Innovation Research Grant; Solid Neoplasm; Stable Disease; success; targeted treatment; Testing; theranostics; Therapeutic; therapeutic target; therapy development; Tissue Banks; Tissues; Toxic effect; Toxicology; treatment choice; triple-negative invasive breast carcinoma; tumor; tumor growth; Tumor Tissue; tumorigenesis; Universities; Vial device; Xenograft Model; Xenograft proced