Clinical Data Support Mechanism of Action and Patient Selection Biomarker for Imprime PGG, Biothera Pharmaceutical’s Phase 2 Cancer Immunotherapy

EAGAN, Minn.–(BUSINESS WIRE)– Biothera Pharmaceuticals, Inc. today announced the presentation of clinical
data demonstrating the mechanism of action of Imprime PGG, the
Company’s Phase 2 cancer immunotherapy drug, in healthy human
volunteers. These are the first data to show that when administered
intravenously to healthy human subjects, Imprime PGG drives the
immunopharmacodynamic (IPD) responses observed in ex vivo human
and in vivo mouse studies. Specifically, the study demonstrated
that formation of an immune complex between Imprime PGG and endogenous
anti-beta glucan antibodies (ABA) was critical to elicit Imprime-induced
immune activating events in humans. These findings provide additional
evidence that ABA levels may be a particularly useful biomarker for
selecting patients most likely to respond to Imprime-based therapy.
These data, as well as additional preclinical research demonstrating
Imprime’s ability to reshape the suppressive immune microenvironment of
the tumor and elicit robust anti-tumor immunity, were presented in
poster presentations during the CRI-CIMT-EATI-AACR International Cancer
Immunotherapy Conference, taking place in New York City, September
25-28, 2016.

“For the first time we are showing that Imprime PGG elicits multiple
innate immune-activating events after systemic dosing in humans. These
immune-activating events are the same events necessary for efficacy in
preclinical models,” said Jeremy Graff, Ph.D., Biothera’s Chief
Scientific Officer and Senior Vice President, Research. “These data also
further bolster our extensive research to show that pre-treatment ABA
levels represent a viable, non-invasive, mechanism-based patient
selection biomarker that will be deployed in our upcoming clinical
trials.”

Imprime PGG is a Pathogen Associated Molecular Patterning (PAMP)
molecule that acts therapeutically as an immunological “ignition switch”
to enlist the functionality of the innate immune system and to enhance
the efficacy of tumor targeting, anti-angiogenic, and immune checkpoint
inhibitor antibodies. Biothera and Merck are advancing a phase 2
clinical research collaboration to evaluate Imprime PGG and Merck’s
anti-PD-1 inhibitor KEYTRUDA^® (pembrolizumab) in patients
with either advanced melanoma or metastatic triple negative breast
cancer. Biothera and Merck are also collaborating with the Big Ten
Cancer Research Consortium to commence an Imprime PGG plus KEYTRUDA
Phase 1b/2 study in patients with non-small cell lung cancer.

In a second poster presentation at the conference, Biothera presented
preclinical data further demonstrating the ability of Imprime PGG to
re-orient the immunosuppressive tumor microenvironment, disabling the
immunosuppression that shields cancer cells from immune attack. Imprime
PGG promotes the differentiation of human myeloid-derived suppressor
cells (MDSCs), significantly upregulating the expression of
co-stimulatory molecules (iNOS, CD80, CD86) that drive anti-tumor
activity and relieving MDSC-mediated inhibition of T Cell proliferation.
Previous preclinical studies have reported that Imprime PGG also
promotes repolarization of M2 macrophages to an anti-tumor, M1-like
orientation while triggering maturation of critical antigen presenting
cells (i.e. dendritic cells) to enable antigen-specific T cell expansion
and the production of the potent anti-tumor cytokine interferon gamma.
Collectively, these data show that Imprime PGG treatment can reshape the
tumor microenvironment favoring robust anti-tumor immune responses.

About Biothera Pharmaceuticals, Inc.
Biothera
Pharmaceuticals is a privately held biotechnology company developing
Imprime PGG, a mid-clinical stage cancer immunotherapy that orchestrates
an integrated anti-cancer immune response in combination with checkpoint
inhibitors and tumor-targeting and anti-angiogenesis monoclonal
antibodies. Biothera and Merck have a clinical research agreement to
evaluate Imprime PGG and Merck’s KEYTRUDA^® (pembrolizumab) a
Phase 2 study in patients with either advanced melanoma or metastatic
triple negative breast cancer. The two companies are also collaborating
with the Big Ten Cancer Research Consortium on a Phase 1b/2 trial in
patients with non-small cell lung cancer. Biothera also plans to conduct
a Phase 2 clinical study with Imprime PGG and a checkpoint inhibitor in
squamous cell carcinoma of the head and neck. Imprime PGG has been well
tolerated and has established proof of concept in trials with more than
400 subjects.

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