Clinical Program

Biothera Pharmaceuticals is leveraging its knowledge of Imprime PGG’s mechanism of action and its extensive clinical experience through the IMPRIME cancer immunotherapy clinical trials. Biothera initially is targeting cancer indications with high unmet clinical needs for which the standard of care is evolving toward combination therapy with checkpoint inhibitors. The Company has announced four clinical trials that will evaluate Imprime PGG in combination with pembrolizumab (KEYTRUDA®), Merck’s anti-PD-1 checkpoint inhibitor, or atezolizumab (Tecentriq®), Genentech’s anti-PD-L1 antibody, in five cancer indications.

In the melanoma, triple negative breast cancer and head and neck cancer Phase 2 studies, Biothera will test for a mechanism-based biomarker
that may help identify patients with the best probability of responding to the combination therapy of Imprime PGG and pembrolizumab.

Details about the clinical trials evaluating Imprime PGG combination therapies, including patient enrollment criteria and trial site locations, is available on ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

  Non-Small Cell 
Lung Cancer
Metastatic
Melanoma*
Triple-Negative
Breast Cancer*
Head and Neck 
Cancer*

Colorectal
Cancer

Phase Phase 1b/2 Phase 2 Phase 2 Phase 2 Phase 1b/2
Combination Therapy Pembrolizumab Pembrolizumab Pembrolizumab Pembrolizumab

Atezolizumab + Bevacizumab

Patients 2nd line  
– CPI naive
Progressive disease following CPI treatment Progressive disease following chemotherapy 
– CPI naive
(1) PD following CPI treatment or (2) stable disease after 3+ months on Pembrolizumab

TBD

Number of Subjects 36 29 41 87 40
Primary Endpoint Progression-Free Survival Overall Response Overall Response Overall Response TBD
Additional Endpoints Safety, ORR, OS, 
Immuno-PD markers
Safety, PFS, OS, 
Immuno-PD markers
Safety, PFS, OS, 
Immuno-PD markers
Safety, PFS, OS, 
Immuno-PD markers
TBD
Collaboration Partner The Big Ten Cancer Research Consortium Merck Merck Merck Genentech
Status Recruiting
NCT03003468
Recruiting
NCT02981303
Recruiting
NCT02981303
Recruiting 
NCT03246685
TBD

* Anti-beta glucan antibody (ABA) biomarker > than 20 μg/ml

CPI – Checkpoint Inhibitor
Immuno-PD markers – ImmunoPharmacodynamic markers of innate immune activation
PD – Progressive Disease
PFS – Progression-Free Survival
ORR – Overall Response Rate
OS – Overall Survival
DOR – Duration of Response

Imprime PGG’s clinical trials address the following four therapeutic indications:

Melanoma and Triple Negative Breast Cancer (TNBC)

  • Biothera and Merck have entered into a clinical research collaboration to study the combination of Imprime PGG and pembrolizumab (Keytruda) in a Phase 2 clinical trial in patients with either advanced melanoma who have progressed on treatment with a checkpoint inhibitor therapy, or with TNBC whose disease has progressed following treatment with one or more lines of therapy for metastatic disease. The study is currently enrolling patients. News release
  • Melanoma is the most dangerous type of skin cancer, and the incidence of melanoma has increased rapidly over the past 30 years. According to the American Cancer Society, melanoma is the fifth most common cancer in the United States and more than 87,000 new cases will be diagnosed in 2017. 
  • About 12% of breast cancers are triple negative, meaning they lack hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2).  TNBCs have a worse prognosis compared with other breast cancer subtypes.

Squamous Cell Cancer of the Head and Neck (SCCHN)

  • Biothera and Merck are collaborating on a Phase 2 clinical study investigating Imprime PGG and pembrolizumab in head and neck cancer patients. The study will include two distinct cohorts of patients: (1) SCCHN patients with progressive disease following prior treatment with an immune checkpoint inhibitor and (2) patients with stable disease, who have failed to demonstrate an objective response after at least three months of pembrolizumab monotherapy. News release
  • According to the World Health Organization, the annual incidence of head and neck cancers worldwide is more than 550,000 cases with approximately 300,000 deaths each year.  About 90% of all head and neck cancers are squamous cell carcinomas.  

Non-Small Cell Lung Cancer (NSCLC)

  • The Big Ten Cancer Research Consortium is conducting a Phase 1/b2 clinical trial evaluating Imprime PGG and pembrolizumab in NSCLC patients. The study is open for patient enrollment. Funding is provided by Merck. News release
  • Lung cancer is the second most common cancer in the U.S., with an estimated 222,500 new cases in 2017, according to the National Cancer Institute.
  • According to the American Cancer Society, it is estimated that more than 222,000 Americans will be diagnosed with lung cancer in 2017, and NSCLC accounts for 85 percent of all lung cancers.
  • It is estimated that approximately 60 percent of lung cancer diagnoses in the U.S. are made when the disease is in the advanced stages.

Colorectal Cancer

  • Biothera and Genentech have entered into a clinical trial collaboration to assess the safety and efficacy of Imprime PGG in combination with atezolizumab (Tecentriq®, Roche/Genentech) and bevacizumab (Avastin®, Roche/Genentech) in patients with metastatic colorectal cancer. The study is expected to begin in the first half of 2018. News release
  • More than 135,000 people in the U.S. will be diagnosed with colorectal cancer in 2017, according to National Cancer Institute estimates.  It is the fourth most common type of cancer in the U.S., behind breast, lung and prostate cancer. 

Biomarker & Translational Research

  • Biothera’s advanced translational research capabilities may help elucidate Imprime-induced immune activity
  • Immuno Proof of Concept measures are important early clinical indicators of immune response and potential long-term clinical benefits
  • Pre-treatment and on-treatment tumor biopsies and blood samples will be analyzed for evidence of:
    • Repolarization of myeloid cells in tumor microenvironment
    • Improved dendritic cell function, including T cell infiltration and activation