Clinical Program

Biothera Pharmaceuticals is developing Imprime PGG as a combination therapy with immune checkpoint inhibitors (CPIs) for multiple cancer indications with high unmet clinical needs. CPIs are antibodies that block checkpoint proteins and restore the ability of T cells to kill cancer cells.  Imprime PGG is an innate immune trigger that repolarizes the immunosuppressive tumor microenvironment and increases T cell infiltration and activation at the tumor site, which is critical to CPI effectiveness.

Clinical research collaborations with Merck & Co. and Genentech will evaluate Imprime PGG with both anti-PD-1 checkpoint inhibitors (pembrolizumab/KEYTRUDA®) and anti-PD-L1 checkpoint inhibitors (atezolizumab/TECENTRIQ®) in four ongoing Phase 2 clinical trials.In several studies, Biothera will test for a mechanism-based biomarker that may help identify patients with the best probability of responding to the combination of Imprime PGG and CPI therapy.

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.

  Triple-Negative
Breast Cancer*
Colorectal
Cancer
 
Non-Small Cell 
Lung Cancer
Metastatic
Melanoma*
Phase Phase 2  Phase 1b/2  Phase 1b/2 Phase 2
Combination Therapy Pembrolizumab  Atezolizumab + Bevacizumab  Pembrolizumab Pembrolizumab
Patients Progressive disease following chemotherapy 
– CPI naive 
PD during or following 2 separate lines of treatment for metastatic disease with chemotherapy + biologic agent  2nd line  
– CPI naive
Progressive disease following
 CPI treatment
Number of Subjects  41 40  36 29
Primary Endpoint Overall Response   Overall Response Progression-Free Survival Overall Response
Additional Endpoints Safety, PFS, OS,  TTR, DOR, Immuno-PD markers  Safety, PFS, OS,
DOR, Disease Control 
Safety, ORR, OS, 
Immuno-PD markers
Safety, PFS, OS, TTR, DOR, Immuno-PD markers
Collaboration Partner Merck  Genentech/Roche The Big Ten Cancer Research Consortium Merck
Status Recruiting
NCT02981303 
Recruiting 
NCT03555149 
Recruiting
NCT03003468
Not Recruiting
NCT02981303

* 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
TTR – Time to Response
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.

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. News release
  • More than 140,000 people in the U.S. will be diagnosed with colorectal cancer this year, 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