Progress in Cancer Therapy Following Developments in Biopharma Faculty of Biology June 2015 Danielle Neufeld & Anna Rabinovich

Cancer Treatment Targeted therapies Non-targeted therapies Biopharma Small molecules Chemotherapy Radiation Small molecule compounds are typically developed for targets that are located inside the cell since such agents enter cells relatively easily by diffusion. Advantages Disadvantages Low cost of production Limited number of small molecules can be synthesized Not specific Cancer cells can develop resistance Multiple side effects

Biopharma A biopharma, also known as a biopharmaceutical, is a biologic medical product, and refers to any medicinal product manufactured in, extracted from, or semi-synthesized from biological sources. Hormone therapies Angiogenesis Inhibitors Epigenetics Signal transduction inhibitors Gene expression modulators Apoptosis inducers Immunotherapies Monoclonal antibodies

Monoclonal Antibodies Monoclonal antibodies (mAbs) recognize specific molecules on the surface of cancer cells. Binding of the monoclonal antibody to the target molecule results in the immune destruction of cells that express that target molecule. Other monoclonal antibodies bind to certain immune cells and help these cells kill cancer cells. Receptor Ligand mAbs InhibitionReceptor

Monoclonal Antibodies Advantage Disadvantage Make the cancer cell more visible to the immune system Side effects: Allergic reactions Flu-like signs Nausea, diarrhea, skin rashes Block growth signals Stop new blood vessels from forming Deliver radiation to cancer cells Deliver chemotherapy to cancer cells

The Majority of Cancer Drugs in the Pipeline Have the Potential to Be First-in-class

Melanoma The most dangerous form of skin cancer which forms from melanocytes, these cancerous growths develop when unrepaired DNA damage to skin cells (most often caused by ultraviolet radiation from sunshine or tanning beds). About 60% of melanomas contain a mutation in the proto-oncogene B-Raf. More than 30 mutations of the BRAF gene associated with human cancers have been identified.

Unsuccessful Melanoma Drugs in Development

KEYTRUDA is a monoclonal antibody that binds to the PD-1 receptor and blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Upregulation of PD-1 ligands occurs in some tumors, and signaling through the PD-1 pathway can contribute to inhibition of active T-cell immune surveillance of tumors.

KEYTRUDA Clinical Trial Results Caroline Robert, et al, April 2015   Improves Overall Survival in Patients with Advanced Melanoma 

The Biopharmaceutical Pipeline: Evolving Science, Hope for Patients There are challenges in developing biopharmaceutical cancer drugs. Today’s pipeline of biopharmaceutical innovation represents an important part of the solution to health care problems facing our nation. There are challenges in developing cancer medicines. Adjustment of treatment according to individual needs: personal medicine. The continued discovery and development of new treatments saves and improves patients’ lives

Thank you for listening