The promise of educating and activating the immune system as a protective mechanism dates back conservatively to the late 18th century, with the observation that exposure to cowpox could prevent smallpox.  While the technology of immunization has become more elegant, the broad concept of harnessing the power of the immune system to fight disease is rooted in history and has been proven repeatedly.

 

Cancer is a spectrum of devastating diseases with a common feature, genetic mutations. These mutations and other changes in cancer cells differentiate them from normal cells and create the prospect for cancer-eradicating immune responses. While recent advances in preventative vaccines have been remarkably successful (e.g., vaccines against the human papillomavirus to protect against cervical cancer), their efficacy is both limited to prevention and to a narrow subset of cancers.

 

Activation of the immune system in patients with established cancers has been the subject of numerous clinical trials over the years. Perhaps the earliest success was the use of interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma over 30 years ago. However, the balance of risk and benefit of such an approach remains equivocal and the percentage of patients who benefit has been fairly limited.

 

More recently, blockade of CTLA-4 – a known inhibitor of T cell activity – has been shown to stimulate the immune system to recognize and destroy established tumors. This approach has been proven in randomized clinical trials, resulting in the approval of ipilimumab for the treatment of advanced melanoma. However, the number of patients with shrinking tumors was limited, and treatment-related adverse events were common. Similarly, more recent attempts to inactivate immune-repressive mechanisms, such as the interaction between PD-L1 and its receptor (PD-1), have resulted in preliminary but promising results in a growing number of cancer types. However, responses (tumor shrinkage) are still only observed in a minority of patients.

 

These data prove that the concept of subduing repressive mechanisms in the immune system can be efficacious in patients with advanced cancers. Yet, a high unmet medical need for improved strategies remains. At Flexus, we believe the promise of immune therapy to be vast but largely untapped with current approaches. Accordingly, new approaches are needed to expand both the number of patients who benefit and the breadth of cancer types for which this strategy can be translated to reality.

 

We are actively pursuing a number of different and complementary strategies to unleash a therapeutic immune response to fight cancer. Leveraging years of remarkable basic science research, scientists at Flexus have initiated multiple unique drug discovery programs with the goal of empowering physicians with the tools to modulate immune responses to maximize clinical benefit while reducing potential risks.