Immuno-oncology is an approach to fighting cancer that revolves around activating the immune system to attack tumors. Up to a quarter of dogs die of cancer, and its incidence is higher in older dogs. This approach has shown long-lasting efficacy in multiple human tumor types, making it an exciting line of investigation for Nexvet in canine cancer. In human medicine, blocking the interactions of PD-1 and PD-L1 has resulted in approved therapies, such as Opdivo® (nivolumab) and Keytruda® (pembrolizumab), with attractive safety profiles that demonstrate efficacy against multiple tumor types.
PD-1’s full name is programmed cell death protein 1. The PD-1 protein and a partner molecule, programmed death-ligand 1 (PD-L1), act in concert to reduce the immune system’s anti-tumor activity, allowing cancer growth and spread. In human medicine, blocking the interactions of PD-1 and PD-L1 has resulted in approved therapies with attractive safety profiles that demonstrate efficacy against multiple tumor types. These advancements have led to immuno-oncology (also called cancer immunotherapy) being hailed as a breakthrough for the treatment of cancer, and a major investment target. The first human PD-1 inhibitor received regulatory approval in late 2014, and PD-1 inhibitors alone are predicted to achieve human sales of approximately $14 billion by 2020.
Blocking canine PD-1/PD-L1 interactions has been shown to result in an increase of immune cell activity, via a similar mechanism to that observed in humans. In related research, high levels of PD-L1 expression were detected in a majority of tumor samples taken from several types of canine cancer, suggesting that PD-1/PD-L1 interactions may have an important role in tumor evasion.
Nexvet has entered a research and development collaboration with Zenoaq, a leading animal health company based in Japan, which involves applying PETization to convert mAb candidates identified by Zenoaq into 100% species-specific candidates in the areas of immuno-oncology and allergy/inflammation. This collaboration has yielded fully caninized, or ‘100% dog,’ mAbs that bind and potently inhibit canine PD-1.
Dogs are susceptible to many of the same types of cancers that afflict people. Epidemiological studies have indicated that cancer is the leading cause of death in dogs over 10 years of age, with 50 percent of older dogs developing cancer and approximately one in four dogs eventually dying from cancer.
Nexvet and Zenoaq believe the clinical successes seen in human disease can be replicated in canine disease to produce effective therapies for multiple tumor types in dogs. Successful cancer immunotherapies would be a new paradigm in veterinary oncology where current standards of care, including surgery, chemotherapy and radiotherapy, have exhibited significant treatment limitations.