Biothera, a US biotechnology company dedicated to improving immune health, has enhanced innate immune responses to its cancer immunotherapy drug candidate Imprime PGG in subjects regardless of biomarker status, demonstrating the opportunity to treat a larger patient population. The in vitro research will be presented at the Cambridge Healthtech Institute’s Antibody-Drug Conjugates/ Engineering Targeted Therapeutics conference in Palm Springs, California.

Biothera developed an Imprime PGG-antibody conjugate that induced similar immune modulation effects in immune cells from biomarker-negative subjects as Imprime PGG alone does in biomarker-positive subjects. By attaching or conjugating antibodies directly to Imprime PGG, the combination was able to bind to innate immune cells from biomarker-negative subjects and initiate biological activity. This included the production of beneficial chemokines that are necessary for neutrophils and monocytes to join the fight against cancer.

“This research shows that there is an opportunity to significantly expand the cancer patient population that can respond to Imprime PGG therapy, regardless of biomarker status,” said Dan Conners, president of Biothera’s Pharmaceutical Group. “Our previous research demonstrated the potential for Imprime PGG combination therapy to treat a wide range of cancer types and the results of our proof-of-concept clinical trials are confirming that in the biomarker-positive patient population. Now, we are confident that this treatment option can be made to work in the vast majority of cancer patients.”

Biothera recently reported the results of its phase II clinical trial evaluating the effectiveness of its experimental cancer immunotherapy Imprime PGG in combination with cetuximab (Erbitux), carboplatin and paclitaxel compared with the monoclonal antibody and chemotherapies alone in previously untreated patients with advanced non-small cell lung cancer. During the study, Biothera researchers discovered a biomarker that identified subjects who were most likely to best respond to Imprime PGG. The objective overall response rate, the primary endpoint of the study, was 67 per cent for biomarker-positive patients compared with 23 per cent for the control group patients. The median overall survival for biomarker-positive patients was 16.5 months compared with 11.2 months for the control group patients.

The predictive biomarker that identifies which patients would respond best to Imprime PGG is a naturally occurring antibody to Imprime PGG. These antibodies bind to Imprime PGG forming an antibody-Imprime PGG complex that is required for binding to innate immune cells that the drug engages and directs to recognize and kill antibody targeted cancer cells. Using a quantitative serum assay, Biothera can determine which patients are biomarker positive for these naturally occurring antibodies and may respond to Imprime PGG. Biomarker-negative patients, however, lack sufficient levels of the necessary antibodies for their innate immune cells to respond to Imprime PGG therapy.

Michael E Danielson, Ph.D., Biothera senior director of Chemistry Research, will present the company's new research at the Renaissance Hotel and Palm Springs Convention Centre. The presentation is entitled, “The Use of Carbohydrate Antibody Conjugates to Stimulate and Direct Innate Immune Cells to Recognize and Kill Cancer Cells.” The authors are Biothera researchers Michael E Danielson Ph.D., Nandita Bose Ph.D., Kyle S Michel, Xiaohong Qiu, Nadine C Ottoson, Mary Antonysamy, Ph.D., Andrew S Magee, Ph.D., and Paul M Will.

Imprime PGG is a novel immunomodulatory drug in development as a cancer therapy. Innate immune cells are the most abundant immune cells in the body and are normally responsible for pathogen killing, but not anti-tumor activity. However, Imprime PGG has been shown to bind to neutrophils and monocytes and redirect their killing ability to reduce tumor growth and enhance long-term survival. This targeted mechanism is synergistic with multiple anti-tumor monoclonal antibodies, providing the potential to improve patient outcomes in a wide range of cancer indications. Imprime PGG has demonstrated marked improvements in overall response rates in multiple clinical trials for colorectal cancer, KRAS-mutant colorectal cancer and chronic lymphocytic leukemia. Imprime PGG is currently in a phase III clinical trial for advanced colorectal cancer and a phase II NSCLC study with bevacizumab (Avastin).

Biothera is developing pharmaceuticals that engage the innate immune system to fight cancer.