New Ways of Targeting Cancer: Q&A with Oncolytics Biotech

Thomas C. Heineman, MD, PhD
Chief medical officer
Oncolytics Biotech

Oncology is a quickly evolving space in the pharma sector, with researchers regularly discovering new and highly effective ways of treating tumors and cancers. Many of these new treatments are taking new approaches to fighting cancer and often rely on activating the body’s own immune responses against the disease. Oncolytics Biotech has a treatment in development for breast, pancreatic, and anal cancer. Pharmaceutical Executive spoke with chief medical officer Thomas C. Heineman, MD, PhD, and vice president of business development Christophe Degois about the company’s pipeline and financial status.

Pharmaceutical Executive: Let's discuss the MOA of pelareorep (pela)?
Thomas C. Heineman: Pelareorep is a non-genetically modified, natural, proprietary isolate of reovirus. It was originally considered to be a potential cancer therapeutic by virtue of the fact that it selectively replicates in and kills cancer cells but not normal cells. That remains true, but it's become increasingly clear over the years that its primary mechanism of action is not directly killing the cancer cells, per se, but by stimulating an anti-tumor immune response.

Its core characteristics include that it's not genetically modified, and it is delivered intravenously. Many agents of this type require direct administration into the tumor because they would be neutralized by antibodies in the blood if given intravenously. So, intravenous delivery is a big advantage because it allows pelareorep to directly target both the primary and metastatic tumor sites and also go to other places like lymph nodes, where there's a lot of immunologic activity. It also allows very convenient, safe, and simple dosing because it can be administered to patients in outpatient settings.

Pelareorep works primarily immunologically, and it has two key effects. First, it is a reovirus, which is a type of virus that has a double-stranded RNA genome. After infecting cancer cells, pelareorep’s double-stranded RNA is recognized as foreign by tumor cells and stimulates an inflammatory cascade, which makes the tumor visible to the immune system.

Christophe Degois
Vice president, business development
Oncolytics Biotech

For that to be helpful, the body must also have an immune response that can then attack the tumor. This highlights the importance of pelareorep’s second key immunologic activity, namely its ability to stimulate the expansion of tumor-infiltrating lymphocyte populations. These are T cells that are already in the tumor. They're tumor-specific, but they are either inactive or exhausted. Pelareorep causes these T cells to expand in the blood. The effect of this is that you now have these lymphocytes in the blood that are capable of attacking tumors, and because the tumor is visible to the immune system, these T cells can get into the tumor and kill it.

PE: What cancer clinical indications are you prioritizing as a primary focus for pelareorep?
Heineman: Breast cancer is our highest priority right now. We've done a lot of studies with pelareorep over the years, and obviously the cancers that we're prioritizing now are based on the results of those studies. Pelareorep has shown particular promise in breast cancer, and specifically the HR-positive/HER2-negative subset of breast cancer.

This is a huge subset, accounting for about 70% of all breast cancer. This is a large number of people, and these patients will get treated with all sorts of things when they have early-stage disease. If they have inoperable disease, they will eventually progress on these earlier therapies because they're not cures. At that point, there's a lot of medical need for continued good treatment.

In the last few years, the antibody-drug conjugates have come on the market, and these have substantial benefit for many breast cancer patients. The problem is that they don't work for all patients. Some patients are simply not appropriate for them to begin with, and others will start taking them but can't tolerate them because they're not easy drugs to take for some people. In addition, these drugs are not cures, so when patients who fail on these drugs, they will need better options at that point. There's a huge opportunity in breast cancer to improve the treatments in the patients who have exhausted their earlier options.

We also have some very compelling data in pancreatic cancer from a number of earlier studies. It’s not quite as advanced as the breast cancer data, but it is very promising. So, that’s the indication that we're targeting as a secondary priority.

PE: You have an impressive list of Pharma collaborations to advance your clinical development programs. How do you prioritize them?
Christophe Degois: We’ve put in place two collaborations for clinical development, one with Pfizer and one with Roche. In one of our phase 2 breast cancer studies, BRACELET-1, Pfizer was interested in looking at the impact of its checkpoint inhibitor, avelumab. So, they participated in that study and paid for half of it. This collaboration has come to an end since Pfizer has terminated its alliance with Merck KGaA. That being said, Pfizer is a very prominent player in the field of breast cancer, and they are still looking at the data.

We also collaborate with Roche, who is providing its checkpoint inhibitor, TECENTRIQ® (atezolizumab) for the GOBLET study, which includes arms in pancreatic and anal cancers.

PE: Please elaborate on how you are prioritizing combination clinical trials with pelareorep + checkpoint inhibitors?
Heineman: We are focused on getting our next breast cancer study off the ground, which we anticipate will be a study to evaluate pelareorep in HR-positive, HER2-negative metastatic breast cancer patients and could pursue regulatory approval through an accelerated approval submission. We are continuing to do a lot of work in pancreatic cancer and are moving forward through a collaboration with the Global Coalition for Adaptive Research (GCAR), who are interested in getting into the pancreatic cancer space and were impressed with our data. We're working actively with them to develop a protocol to move forward with the pelareorep combination therapy, which includes the checkpoint inhibitor atezolizumab and chemotherapy for pancreatic cancer as well.

Pelareorep is a very good combination partner for a wide variety of agents, including chemotherapy, but also specifically immunotherapy. For example, patients with relapsed anal cancer have no good treatment options, but we've seen some very compelling early results for the combination of pelareorep plus a PD-L1 inhibitor. As these data evolve, this may become another registrational path. More to the point, it illustrates the ability of pelareorep to provide benefit through synergy with immune therapies, including checkpoint inhibitors.

I should point out that in our pancreatic cancer studies, our best data have come in studies where we have combined pelareorep with both chemotherapy and a checkpoint inhibitor.

We also have an active collaboration with academic investigators at the Mayo Clinic to look at potential combinations of pelareorep with CAR-T therapies. This has not gone into people yet, but the pre-clinical data are very promising, and we're exploring our options for moving that forward in a solid tumor setting.

PE: What is your timeline for BLA filings with FDA for pelareorep and how are you prioritizing them? When do you anticipate pivotal data in your lead clinical indications?
Heineman: We've met with the FDA a number of times over the years to discuss various aspects of our breast cancer program. Most recently, we met with them in the middle of last year to discuss the proposed next breast cancer study going forward. Of course, the FDA will never make any guarantees on licensure, but they voiced no concern regarding key elements of the proposed study. Specifically, they were happy with the endpoint, and they provided us with some very clear guidance on the magnitude of the clinical effect that they think would make a compelling case for a new drug. I think we've checked all the boxes that we need to check on the regulatory side to move forward into the next study in breast cancer.

In pancreatic cancer, we're working with GCAR to develop a protocol to move forward there, and we anticipate going to FDA to get their thoughts on the final version of that protocol. That's still in the planning stages, so I would hesitate to say anything timeline-wise in the pancreatic cancer side until have spoken with the FDA.

PE: Please elaborate on the GOBLET "family" of clinical trials in anal cancer, PDAC, etc.
Heineman: The GOBLET study is a platform study that includes two pancreatic arms and an anal cancer arm.

The results of the initial pancreatic cancer arm looked very promising, and that's what we're moving forward with through our collaboration with GCAR. In addition, the Pancreatic Cancer Action Network (PanCAN) and its experts looked at those data and our earlier results in pancreatic cancer and considered them very compelling. Based on that, they awarded Oncolytics a grant to expand the concept beyond what we did in the first arm of the study and add another pancreatic cancer arm in which we could explore a different pelareorep chemotherapy combination. We wanted to expand the pelareorep combination therapy approach to cover pretty much all the bases, so that the broadest range of patients, in theory, could benefit from pelareorep-based therapy. That arm of the GOBLET study, which is pelareorep combined with modified FOLFIRINOX with and without atezolizumab, is still ongoing, and we're hoping to have the initial efficacy results later this year.

PE: What are the financial objectives for Nasdaq: ONCY in the near-term? Pharma M&A to drive growth? BD&L out-licensing based on robust clinical data packages?
Degois: Our financing strategy is focused on raising the capital necessary to fund our upcoming registration-enabling Phase 2 breast cancer study. If successful, it is expected to support an accelerated approval submission. We are committed to increasing the company's value by executing on this Phase 2 trial, effectively addressing a critical gap in the breast cancer treatment landscape. Simultaneously, we are actively engaging with major pharmaceutical and biotech companies, exploring strategic partnerships that will enable us to pursue multiple indications for pelareorep. We are confident that these collaborations will greatly enhance our capabilities and impact the market.