Deploying Immunologic Viral Agents To Target Cancers With Oncolytics Biotech's Thomas Heineman

A significant challenge in delivering immuno-oncology therapies intravenously is evading neutralization in the blood while the therapeutic agents are on their way to target sites. In this episode of Sit and Deliver, host Tom von Gunden talks with Oncolytics Biotech’s Chief Medical Officer Thomas Heineman about deploying oncolytic viral agents to ensure successful arrival at lymph nodes and at primary and metastatic tumor sites.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Sit and Deliver, the series in which we hear from thought leaders in the drug delivery space about innovations and advancements that they're working on. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader and your host for this series. Today I am joined by Chief Medical Officer Thomas Heineman from Oncolytics Biotech, which is working on immunological therapies primarily for the treatment of cancer.

Welcome, Tom.

Thomas Heineman, Chief Medical Officer, Oncolytics Biotech:

Thank you very much, Tom. It's a pleasure to be here.

Well, it's my pleasure to have you here, so thanks for joining us. So, let's start off by, if you can tell us a little bit about the current landscape of the patient populations and the therapeutic areas and patient needs that you're targeting. And then, in addition to who you're targeting, can you tell us a little bit about, up to this point, what would their options for treatment have been and their experience with those options? So, the target population and areas, and what's available to them today or what traditionally has been?

I'd be happy to discuss that. So, at present we are actually focusing on two specific cancers. These are metastatic pancreatic cancer and breast cancer, and specifically the HR+ HER2- subset of breast cancer.

We're developing an agent called Pelareorep which has shown promise in several different cancers. But the data that we've collected over a number of clinical trials over the years has really pointed us in the direction of these two cancers, HR+ HER2- breast cancer and pancreatic cancer as our primary focuses at the moment.

So, both of these cancers, as you may be aware, are very challenging therapeutic targets for different reasons. For example, and this is perhaps particularly telling, over the past decade or so, as I'm sure you're well aware, the immunotherapeutics have become extremely impactful in cancer and have really revolutionized the treatment of a lot of different cancers.

But both of these cancers have actually proven resistant to immunotherapies. And so, one of the things that we are hoping to accomplish, and which our data seems to tell us is possible with our agent, is to allow an immunotherapeutic approach to improve the treatment of these two very difficult cancers from that perspective.

Gotcha. And so, I know that you're working on therapies that would be delivered by infusion, or intravenously. And I believe that the therapy itself is actually a proprietary virus. So, can you tell us a little bit about the choice of route of administration and also the use of that proprietary virus as the actual therapeutic agent?

So, the traditional treatment for these cancers, for the pancreatic cancer and breast cancer, have been chemotherapies of one sort or another. In pancreatic cancer, the treatment for that disease has really not changed. The options have not really progressed dramatically for most patients over the past, oh, 12, 15 years or so. And it's not for lack of trying, I might add.

There have been many efforts made [that have] just proven unsuccessful, as I mentioned with the immunotherapeutics, for example. In breast cancer, there's been more success in developing new therapeutic agents, but there remains a point in time at which the patients begin running out of good options. And we feel that our agent can fit in well in both of these instances and fill some of these gaps.

Now, with regard to the choice of the agent: Our agent is called Pelareorep. It's actually an oncolytic reovirus. But as you mentioned, it's a proprietary isolate of reovirus. It is not genetically modified in any way.

So oncolytic viruses, as a class, are typically agents that have been modified in some form genetically, either to target them to the tumor or to improve their efficacy once they get to the tumor. But Pelareorep has some very specific characteristics that don't make modifications necessary for either of those reasons.

So, Pelareorep by nature is oncolytic, right? It selectively infects cancer cells. And it is targeted to the tumors through intravenous administration. Many oncolytic virus-based agents require direct inoculation into the tumor because, primarily, they are neutralized in the blood if they're given intravenously. Right. Pelareorep has the ability to associate in the blood after intravenous administration with mononuclear cells — monocytes, lymphocytes, and so forth.

And when it associates with these cells in the blood, it is transported to the tumor and shielded from neutralization. Okay. So, we've shown in many different studies in many different cancers that intravenously delivered Pelareorep will find its way to tumors even after repeat administration. So even after you give it a number of doses over many cycles, it continues to evade neutralization in the blood, and so it can be delivered intravenously.

So, the fact that Pelareorep can be delivered intravenously gives it a substantial advantage both in terms of its mechanism of action and in terms of, simply, the ease of administration. So, clearly, intravenous administration is simple, safe, because it's not a genetically modified agent. It doesn't require any particular biohazard precautions or anything like that.

So, it could be administered in [an] outpatient setting, oncology suites, etc. But, in addition to that, the fact that it can be delivered intravenously is really integral to its mechanism of action as well, because it allows it to directly target not only sites of the primary tumor — for example, the pancreas or the breast or whatever — but also any metastatic sites that may exist in the liver, lungs, or other places.

And it also will deliver the virus to lymph nodes, where a lot of the activity of the immune system takes place, which is very important to establishing the immune response as necessary to attack the tumor.

Right. Thanks for the detail there. And so, maybe this varies by patient condition or stage or something, but what's a common kind of treatment regimen that patients would expect for receiving these therapies in this manner?

So indeed, it does vary according to the cancer that we're treating. Now, the thing to keep in mind about Pelareorep, in addition, is that it does have monotherapy activity in some cancers. So, if you just give it low, it will have activity against some cancers, including breast cancer.

But we've done a number of studies over the years across different diseases, and we've observed that its therapeutic effect is both more prolonged and more profound when it's given in combination with chemotherapy and/or an immunotherapeutic agent, such as a checkpoint inhibitor.

And so, when delivering Pelareorep — and for the sake of the patient’s convenience, we make every effort when possible to deliver it at the same time, or at least in sequence with whatever chemotherapy. For example, they may be receiving in combination with the Pelareorep.

So, for example, in our breast cancer studies, the patients are receiving the chemotherapy paclitaxel,  which is given on days one, eight and 15, typically, of a 28-day cycle. So, when we provide the Pelareorep, we will give that sequentially, immediately following the paclitaxel administration on the same days and, in some cases, on subsequent days, as well.

But the point is that we will do everything we can to mesh the treatment regimens so that the patients have as few clinic visits and spend as little time in the oncology suites or whatever as possible.

Gotcha. And so, I like to finish up these episodes with a look to the future, out onto the near or far horizon, whichever is closer [on the development timeline]. As you look out there, Tom, assuming that the advances and the innovations that you're working on there at Oncolytics Biotech take hold and provide the benefit to the patients that you are working toward, what can you say about what patients’ health and lives and experience might be like, and hopefully different and improved, once that happens?

Well, I think one thing that's important to mention about Pelareorep, and I think this is probably obvious from the fact that we're treating very different cancers, such as pancreatic and breast cancer, is that it's not an agent that is specific for a given cancer. It's not targeting a specific modification or mutation, or something in this or that cancer.

It's an immunologic agent that works by stimulating immune responses that can attack cancers more generically. In other words, it directs the body's immune system, that is already trying to attack the cancer, to attack that cancer more effectively. Okay, so with that in mind, Pelareorep has a lot of potential applications above and beyond even the cancers that we are currently studying.

So. we're focusing on the breast and the pancreatic cancer based on the very strong data that we've seen in our prior clinical trials, that point us in that direction as the first optimal targets to address with the Pelareorep. But Pelareorep has the potential, and we do have some data across a number of other cancers where it could provide benefit.

For example, other gastrointestinal cancers, such as colorectal cancer, anal cancer. We've done studies in patients with certain types of brain cancer, blood cancers like myeloma, and so forth. And you know, to your question, we think that Pelareorep has a lot of potential to really provide some additional benefit in situations where patients are really beginning to run out of good treatment options. Okay.

And in many of these cancers — pancreatic, the HR+ HER2- breast cancer, and looking to the future, maybe certain types of brain cancer and other things — these are very difficult-to-treat cancers that have been historically resistant to some of the newer immunotherapeutic approaches. So, we think Pelareorep can live up to its promise as an immunotherapeutic that can address these otherwise resistant cancers.

It can really be a game-changer in terms of providing these patients with an opportunity for treatment approaches that they have simply not been able to access otherwise. So, we're very optimistic that this can provide substantial benefit across a wide range of diseases.

Well, that all sounds very promising. I want to thank you, Tom, for joining me to share the work that's being done there at Oncolytics Biotech. And I want to thank our audience for joining us for another episode of Sit and Deliver. And we'll see you here next time.