New Data Strengthens Correlation between Biomarker and Cancer Immunotherapeutic Imprime PGG

Research to be Presented at AACR Cancer Conference

EAGAN, Minn.--()--At the AACR Tumor Immunology and Immunotherapy: The Next Chapter conference today, Biothera will present data describing the presence and distribution of a biomarker that may predict the ability of subjects to respond to its immunotherapeutic Imprime PGG®.

Imprime PGG is a novel innate immune cell modulator currently in late-stage development for colorectal and non-small cell lung cancer. Imprime PGG primes neutrophils, monocytes and macrophages through a complement receptor 3 (CR3)-dependent mechanism to exert anti-tumor activity against tumor cells that have been opsonized with complement following targeting with anti-tumor monoclonal antibodies.

Previous research has shown that Imprime PGG-induced functional activities occurred predominantly in individuals with higher levels of anti-beta-glucan antibodies (ABA), either immunoglobulin G (IgG) or IgM. These ABA form immune complexes with Imprime PGG that are essential for binding CR3. Data generated using prototype enzyme-linked immunosorbent assays (ELISAs) to measure IgG and IgM ABA suggested correlations between ABA levels, Imprime PGG binding to neutrophils in whole blood, and consequent induction of functional immune responses.

The new study sought to further optimize and qualify these ELISAs, in a larger cohort of healthy subjects (n=143), and to confirm the significance of elevated ABA levels with respect to binding of Imprime PGG to neutrophils and monocytes, and Imprime PGG-induced functional changes.

Results
Results showed that samples from 52% of healthy subjects demonstrated high binding of Imprime PGG to neutrophils (>5% of cells). Samples from these same subjects also exhibited high Imprime PGG binding to monocytes. ABA levels in these high binding individuals were significantly greater than those in the low binding individuals (p<0.0001 for IgG ABA, and p=0.0099 for IgM ABA, and p<0.0001 for the combination of IgG and IgM ABA). Subjects with high ABA levels also demonstrated positive immunological responses to Imprime PGG.

“These new data using a larger, healthy population confirm that serum ABA levels correlate with Imprime PGG binding to neutrophils as well as monocytes in vitro and with the induction of functional immune responses by these cells,” said Jeremy Graff, Ph.D., Senior Vice President, Research, Biothera Pharmaceutical Group. “We can also select ABA cutoffs that will identify the majority of healthy individuals whose cells demonstrate these responses.”

Biothera is continuing to investigate the value of ABA as a potential clinical biomarker for Imprime PGG response in cancer patients.

Biothera Presentation Time & Location
Biothera will present poster number A 08 at 1:15 pm on December 2, 2014 in Fantasia H of Disney’s Contemporary Resort in Orlando. The poster is entitled, “Distribution, Cutoff, and Functional Significance of a Potential Biomarker for Imprime PGG, an Experimental Cancer Immunotherapeutic, in a Healthy Subject Population.”

Authors of the presentation are Biothera researchers Diane McMurray, Ben Harrison, Katie Ertelt, Richard Walsh, Lindsay Wurst, Steven Leonardo, Nadine Ottoson, Adria Bykowski Jonas, Xiaohong Qiu, Nandita Bose and Peter Maimonis.

About Biothera
Biothera, a privately held U.S. biotechnology company, is developing Imprime PGG, a late clinical stage biologic that modulates the immune response to cancer. Data from the most recent randomized phase 2 study of Imprime PGG in first line non-squamous NSCLC was featured as a late-breaking abstract in the Immunotherapy of Cancer session at ESMO 2014. In this study, which evaluated the addition of Imprime PGG to bevacizumab and carboplatin/paclitaxel versus bevacizumab and chemotherapy alone, objective response rate was 60.4% versus 43.5%, duration of response was 10.3 months versus 5.6 months and median overall survival was 16.1 months versus 11.6 months. Similarly encouraging data have been observed in both squamous and non-squamous subjects in a second randomized Phase 2 study in 1st line NSCLC in combination with cetuximab and in studies in high-risk chronic lymphocytic leukemia and metastatic colorectal cancer. Imprime PGG directly modulates the key effector cells of the innate immune system, neutrophils and monocytes/macrophages, enabling them to recognize and kill antibody-targeted cancer cells. In addition, on-going research points to a secondary, bystander effect of Imprime PGG on both innate and adaptive immune cell types known to exist in the tumor microenvironment, including T-cells, dendritic cells, M-2 macrophages and myeloid derived suppressor cells. Imprime PGG is being evaluated in a phase 3 study in late stage metastatic colorectal cancer and planning is underway for an approvable study in NSCLC.

More information is available at www.biothera.com/pharma or follow us on Twitter.

Contacts

Biothera, the Immune Health Company
David Walsh, 651-256-4606
SVP Marketing & Communications
dwalsh@biothera.com

Release Summary

New data strengthens the correlation between a predictive biomarker and Biothera's cancer Immunotherapeutic Imprime PGG. The research will be presented today at an AACR conference.

Contacts

Biothera, the Immune Health Company
David Walsh, 651-256-4606
SVP Marketing & Communications
dwalsh@biothera.com