"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."

Daniel J. O’Connor

PRESIDENT & CEO, ONCOSEC MEDICAL INCORPORATED

April 22, 2021

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.

2020 was not only successful as it related to our data set. People also began to appreciate the potential of our technology. 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. A patient that falls into that category will likely receive one or both of these drugs. These are called checkpoint inhibitors and they are monoclonal antibodies (MAB’s). How do these MAB's work? In the case of Keytruda, it is a blocking antibody. The antibody has been 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 is the benefit of electroporation and why is this an approach that OncoSec prefers?

The benefit is there is a cytokine like effect without exposing the patient to the cytokine like side effects. This is done through Gene Electrotransfer (GET), because you are not trying put it into an antibody or a virus, and having the virus interact with immune responses. You are putting it onto DNA plasmids and forcing that plasmid back into cancer cells and getting those cancer cells to express IL-12 for a couple of days.

We are using a non-physical, non-toxic, non-chemical approach that spares the immune response from having to do something with a bacteria, virus or monoclonal antibody that is going to travel throughout the bloodstream, and elsewhere in the body.

What are the main costs associated with developing cancer immunotherapy drugs and to what extent should companies plan for these factors from the beginning?

There should be scrutiny on prices because patients need affordable medicines. Manufacturers should be looking to develop products that can deliver on that. Cancer is a terrible disease and researchers are doing great work to try to figure out a way to tame or cure it. However, the reality is that a lot of the newer techniques in development are expensive. If you look at autologous treatments that require the extraction of cells from a patient, manipulation of those cells in a cGMP facility, and then a one-to-one reintegration from treatment to patient costs US$100,000. It can work, but it is expensive, and those costs must be paid eventually. 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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