DANIEL J. O’CONNOR, PRESIDENT & CEO,

ONCOSEC MEDICAL INCORPORATED

"We want to have a natural immune response that avoids cytotoxic consequences for the patient experience, and our way of delivering IL-12 is getting a lot closer to that big idea."

Can you provide an overview of the key events that drove OncoSec’s market outperformance in 2020?

There was a convergence of good things that occurred for OncoSec in 2020, and it centered upon a preliminary data release we provided on KEYNOTE-696 at the Society for Immunotherapy of Cancer (SITC) annual meeting where we reported the tumor shrinkage response for the first 54 patients participating in the trial study. People appreciated the data as showing that the study was on track to meet its primary endpoint, which is a 20% response rate by BICR (blinded independent central review). The second positive item was closing a deal to begin collaboration with China Grand Pharmaceuticals (CGP) and Sirtex; two powerful drug development companies that we expect will flourish over time. The deal also provided OncoSec with US$30 million of capital to continue our ongoing and future clinical trials. Over the course of the year, we continued to raise capital binging in another US$15 million in August.

We want to give life to the concept, underpinning the paradigm of cancer immunotherapy, which is to use the body's natural immune response. We want to have a natural immune response that avoids cytotoxic consequences for the patient experience, and our way of delivering IL-12 is getting a lot closer to that big idea.

One of the problems with the biology of tumors is they are considered to be immunologically cold and we know checkpoints do not work well in this case. What is Oncosec’s approach to solve this problem?

First, it is important to understand what is happening vis-a-vis the checkpoint. In our study we are evaluating patients who used Keytruda or OPDIVO. These are both approved drugs in first line, late-stage metastatic melanoma or skin cancer. These are checkpoint inhibitors and they are monoclonal antibodies (MAB’s). In the case of Keytruda, it is a blocking antibody engineered to look like a protein that is capable of turning a T-cell off. Keytruda is an antibody that is able to mimic the protein and fit into that receptor, like gum in a lock. If the gum is in the lock, the natural protein cannot hit the receptor and turn the T-cell off, so it competitively inhibits the protein that would naturally be suppressive for turning the T-cell off.

Keytruda blocks the antibody that competitively inhibits the natural protein, which is otherwise immunosuppressant. Therefore, when a T cell then traffics to the tumor, it is not able to do its killing job because the tumor itself is immunosuppressed. Keytruda works well in hot tumors because there are T-cells that are kept activated through the blocking antibody trafficked to the tumor and can get in and do their killing job because the tumor itself is not immunologically suppressed. However, the majority of patients have some level of immunosuppression occurring in their tumor. IL-12 is a pro inflammatory signaling cytokine, and, as a signaler of inflammation, reintroducing IL-12 contextually into the tumor microenvironment has the ability to confirm if that tumor is immunologically suppressed, immunologically activated or active. We do that by coding IL-12 onto a DNA plasmid. By putting DNA plasmids into the tumor coded for IL-12 we are getting that DNA inside of cancer cells and other cells contextually located in the tumor. We are doing that using energy, which is why we call it gene electrotransfer. That DNA medicine is our way of causing the DNA plasmid to be put inside of the cancer cell, and that happens by the millions.

What are the main costs associated with developing cancer immunotherapy drugs?

The reality is that a lot of the newer techniques in development are expensive. Therefore, developing a system that is cost effective from the start is a consideration. That is why I favor our plasmid-based approach. Plasmids are very cost effective to make.

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