MIPS Project Detail:
Company
Company Description:
A&G is focused on the identification of biomarkers involved in the development of cancer cells and using such biomarkers as targets, developing theranostic (diagnostic and therapeutic combination) products useful in the diagnosis, treatment and monitoring of cancer. The company is comprised of two divisions, an R&D division focused on theranostic products, and the Precision Antibody division, recognized worldwide as a provider of high-quality, customized antibodies to pharmaceutical and biotech companies, as well as federal laboratories.
A&G has grown from an incubator company with four employees to a 12,000 sq.-ft. facility with 30 employees, of whom >50 percent are Maryland graduates. A&G’s financing is a mix of equity funding and profits from Precision Antibody. Non-dilutive funding has been obtained from NIH and Avon Foundation grants. The MIPS funding of studies at the University of Maryland have been important in the company’s goal of developing diagnostic kits for its theranostic portfolio.
A&G’s lead products in development, based on a unique biomarker called GP88 (progranulin), target both lung and breast cancer, as well as several other cancers. GP88, a glycoprotein, is produced and required by cancer cells for growth, proliferation and survival. In clinical studies, GP88 was detected in >80 percent of breast cancer tumors. High levels of GP88 in such tumors are statistically associated with a five-fold increase in the risk of recurrence, compared with patients with low or no GP88 detected in tumors. GP88 blood levels have been shown to be statistically elevated in breast cancer patients with progressive disease, compared with healthy individuals. Concurrent with the development of GP88 diagnostic kits for detecting GP88 in tumor tissue and blood, A&G is pursuing the development of an associated anti-GP88 monoclonal antibody therapeutic. In pre-clinical xenograft models, the antibody was demonstrated to inhibit tumor growth and promote tumor regression. Toxicology and safety studies demonstrated anti-GP88 is safe and showed no toxicities in either acute or repeat dose studies. Thanks to an SBIR/NCI grant ($2 million), this therapeutic will enter Phase 1 clinical trials in 2018. The two diagnostic products will be used in this study to identify patients for treatment with the anti-GP88 and subsequently for monitoring patients during and post-treatment.
MIPS Project
Cancer Theranostic Biomarker
Project #
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MIPS Round
58
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Starting Date:
Jan 2010
MIPS Project Challenge:
Of ~210,000 U.S. patients annually diagnosed with breast cancer, 80 percent are estrogen receptor positive (ER+) and 25 percent Her-2 overexpressing with available targeted therapies. Tamoxifen and Herceptin®, two successful therapies, block targets expressed by cancer cells that can be measured by laboratory tests to identify subsets of eligible patients. These drugs, with companion diagnostic markers, have had a dramatic impact on the survival of BC patients and heightened demands for similar combinations. Not since these two therapies were FDA-approved in 1977 and 1997, respectively, has any other ground-breaking drug with a companion diagnostic product been approved. In spite of these successes, ~40,000 breast cancer patients die annually, partly due to the fact that the cancer cells become resistant to these therapies. A&G’s focus has been on discovering and developing a theranostic target that has both diagnostic and therapeutic applications in drug-resistant breast cancer. Ginette Serrero, A&G’s CEO, identified GP88 as being actively involved in the development and proliferation of cancer and has developed a product pipeline that will stratify, treat and monitor patients with elevated GP88. The challenge is to develop and implement a diagnostic and therapeutic product combination that will identify, treat and monitor such patients with the realistic goal of improving overall survival.
Project Scope:
With the collaboration of Tkaczuk, through the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC), A&G performed a clinical study with newly diagnosed breast cancer patients with all stages of the disease. Objectives of the study were to determine if serum GP88 could be used to identify more aggressive subtypes of breast cancer by measuring GP88 serum and tissue levels at the time of diagnosis, and ascertain whether or not GP88 serum levels could be used to follow the response to anticancer therapy and time to progression of the disease for stage-4 patients undergoing standard anticancer therapies. GP88 assays were conducted at A&G using its proprietary test kits.
Results:
Correlations of GP88 serum levels with clinical parameters such as stage, therapy response and survival, established the clinical utility of the GP88 tissue and serum assay to identify more aggressive behavior of disease in breast cancer patients. In A&G’s published work, the company demonstrated that such patients have elevated levels of GP88 when compared to healthy individuals and breast cancer patients with disease that was responding to therapy. Subsequently, A&G has identified a GP88 level in blood that is able to stratify patients on therapy that have improved prognosis over those with a higher risk of a poor outcome. This initial MIPS work is now being further evaluated as part of an NCI/ SBIR grant.
In 2010, A&G received a $1.2 million Phase II Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI) for the GP88 program. This work focused on the development of a neutralizing therapeutic antibody against GP88. A&G received two further grants. The first, in 2014, was for $1.4 million to manufacture and study the safety of the anti-GP88 in pre-clinical studies. Following the success of this 2014 grant, A&G will receive a $2 million to move its therapeutic antibody into a “first in human” Phase I clinical trial.
A&G has sought to license its technology outside of the field of cancer and in 2012, the Mayo Clinic acquired a license to use reagents for the measurement of progranulin in blood. This agreement enabled the Mayo Clinic to develop a commercial blood test to predict progranulin mutation status in patients suspected of frontotemporal dementia (FTD).
Principal Investigator:
Katherine
Tkaczuk
Professor of Medicine
Project Manager:
Ginette
Serrero
Co-Founder and CEO
Technologies:
Biotechnology / Genetic Engineering
