Clinical Program

Our clinical development strategy is to generate Phase 2 clinical and mechanistic proof of concept for Imprime PGG in combination with immune checkpoint inhibitors (CPIs).  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 activation at the tumor site, which is critical to CPI effectiveness.  Our clinical studies are designed to:

  • Explore the hypothesis that the addition of Imprime PGG to CPI therapy can provide clinically meaningful benefit,
    including increased Overall Survival, Disease Control and Overall Response Rates
  • Demonstrate continued safety of Imprime PGG in combination with CPIs
  • Utilize ABA biomarker prospectively to drive improved patient selection
  • Confirm Imprime PGG is effective when systemically administered

Our clinical studies focus on cancer indications where CPI monotherapy benefit is limited.  We utilize translational research to provide further evidence of Imprime PGG immune activation through analysis of tumor biopsies and peripheral blood samples collected pre- and on-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.

Details of Imprime PGG + Checkpoint Inhibitor Clinical Trials:

  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
KEYTRUDA®)
atezolizumab (Tecentriq®) + bevacizumab (Avastin®) pembrolizumab
(KEYTRUDA®)
pembrolizumab
(KEYTRUDA®)
Patients Progressive disease following chemotherapy, CPI naïve, biomarker positive*  PD during or following 2 separate lines of treatment for metastatic disease with chemotherapy + biologic agent  2nd line,
CPI naïve
Progressive disease following
 CPI treatment,
biomarker positive*
Number of Subjects  44

Stage 1: 15
Stage 2: 25

Stage 1: up to 12
Stage 2: 24

20
Primary Endpoint Overall Response   Overall Response Progression-Free Survival Overall Response
Additional Endpoints Safety, PFS, OS,  TTR, DOR, Immuno-PD markers  PFS, OS, DOR, Disease Control, Safety, PK and Immunogenicity 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 Enrollment complete,
study ongoing
NCT02981303 
Recruiting 
NCT03555149 
Recruiting
NCT03003468
Enrollment complete,
study ongoing
NCT02981303

* Patient selection criteria includes 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

Triple Negative Breast Cancer (TNBC) and Melanoma

  • 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 metastatic TNBC whose disease has progressed following treatment with one or more lines of therapy for metastatic disease. Primary data from this study was presented at the American Society of Clinical Oncology (ASCO) 2019 annual meeting. 
  • More than 271,000 breast cancer cases will be diagnosed in the U.S. this year. About 12% of breast cancers are triple negative, meaning these lack hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2).  TNBCs have a poorer prognosis than other breast cancer subtypes.
  • Melanoma is the most dangerous type of skin cancer.  The incidence of melanoma has increased rapidly over the past 30 years. According to the American Cancer Society, melanoma is now the fifth most common cancer in the United States. More than 96,000 new cases will likely be diagnosed in 2019.

Non-Small Cell Lung Cancer (NSCLC)

  • The Big Ten Cancer Research Consortium is conducting a Phase 1b/2 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. The American Cancer Society estimates that in 2019 there will be 228,000 new lung cancer diagnoses, of which approximately 85% will be NSCLC.
  • 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®) and bevacizumab (Avastin®) in patients with metastatic colorectal cancer. News release
  • More than 145,000 people in the U.S. will be diagnosed with colorectal cancer this year, the American Cancer Society estimates. It is the fourth most common type of cancer in the U.S., following breast, lung and prostate cancer.

Biomarker & Translational Research

  • Biothera’s Translational Research Program is designed to maximize learning from early clinical trials to enhance the ultimate likelihood of clinical/regulatory success.
  • Pre-treatment and on-treatment tumor biopsies and peripheral blood samples from patients in Biothera’s triple negative breast cancer and melanoma Phase 2 study are being analyzed for evidence of immune activation.
  • These translational data are providing molecular and cellular proof of concept, showing that Imprime PGG, as dosed clinically, activates innate and adaptive immunity in the periphery as well as at the tumor site.