Good morning, everyone. Thank you for joining us at the 44th Annual Canaccord Genuity Growth Conference. I'm John Newman, one of the biotech analysts here at the firm. We're very excited to have Oncolytics with us today. Joining us are the Chief Financial Officer, Mr. Kirk Look, as well as the Chief Medical Officer, Mr. Tom Heineman, both to my left. So gentlemen, welcome. For those that may not have been following this story closely, I wondered if you could start by telling us about pelareorep's mechanism of action and how it activates the immune system for anti-tumor activity. Sure, John, I'll take that question. So pelareorep is an intravenously administered immunotherapeutic that is capable of targeting primary tumors as well as metastatic tumors directly. It has two complementary immunologic effects. First, it stimulates anti-tumor cellular immune responses, which includes the expansion of tumor-infiltrating lymphocytes that are then capable of attacking the tumor, and it also modifies the tumor microenvironment, essentially turning a cold tumor hot, which allows those cellular immune responses to then attack the tumor directly. Its mechanism of action has been established in many studies, both preclinical and clinical trials, including the recently concluded AWARE study in breast cancer and as well as various studies in different GI cancers. Mm-hmm. Okay, great. Thank you. Mm-hmm. I wondered if you could talk a bit more about the AWARE-1 study and also the importance of tumor-infiltrating lymphocyte counts that you've looked at with pelareorep. Sure. So the AWARE-1 study was a window of opportunity study in breast cancer, in which patients with early breast cancer were treated with pelareorep, and then later on, they had their tumors removed, which gave us a lot of information. We had So we had pre-treatment tumor samples and on-treatment tumor samples, and this allowed us to look both at the what was going on in the tumor and the blood in response to the pelareorep treatment. And so in the AWARE study, we, among other things, observed that there was an increase in the expansion of tumor-infiltrating lymphocytes, and that this was then correlated in different studies with an actual clinical response. So the AWARE data provided a huge amount of information, but the actual correlation between the expansion of tumor-infiltrating lymphocytes and clinical response actually came more from other studies in patients with more advanced disease. But the bottom line is that the AWARE study not only supported that part of the mechanism of action, the expansion of the tumor-infiltrating lymphocytes, but also provided a lot of information on what else was going on in the tumor microenvironment, including the upregulation of different chemokines and cytokines, such as PD-L1. Okay, thank you. Mm-hmm. So pelareorep has shown positive phase II data in combination with paclitaxel. Mm-hmm. In the BRACELET-1 study. Mm-hmm. And also, IND.213. Mm-hmm. I believe overall survival data are expected in the second half of this year. Just curious as to how you're thinking about what type of overall survival would be interesting, and are there other key data aspects that we should be looking for in that update? Yeah, sure. So the overall survival data for the BRACELET study will be coming shortly. Mm-hmm. In our discussions with people in the oncology community, investigators, KOLs, and similar individuals, we consistently hear that a 3 or 4 month improvement in overall survival would be interesting to the community. As a case in point, a year ago or so, the DESTINY-Breast04 overall survival results for Enhertu were presented at the ASCO meeting, and in that study, that was a study of Enhertu. In that study, a 6.3-month, I believe, overall survival benefit was observed, and that study received a prolonged ovation at the ASCO conference, right? The medical community was very enthusiastic about that 6-month improvement. The point being that if we see any overall survival results in that order of magnitude, we'd be very happy. As for other efficacy data that may come along, well, we will also have the final progression-free survival results from that study will be reported at the same time. Mm-hmm. Okay, thank you. Mm-hmm. What does the path to registration look like for the breast cancer indication? I know that you've recently been communicating with the agency. Mm-hmm. Just curious if you could, give us a brief summary about those conversations. Yeah, sure. So what we're targeting now as a path to registration would be a large phase II study. When I say large, I mean approximately 200 patients or thereabouts, phase II study, which would, a nd the path would follow the path that was used by Pfizer, for example, for the initial approval of Ibrance and by Daiichi Sankyo for the initial approval of Enhertu, wherein you would do a large phase II study that would then provide you with opportunities either for accelerated approval or for an opportunity to, at a very minimum, de-risk a subsequent study. We expect. We have talked to the agency about this and came away very encouraged with our, with our proposal for this next study in metastatic or advanced breast cancer patients. And if you like, I'd be happy to discuss some of the more specific points at, as you know, if you'd like. Sure. to hear about that. Yeah, that would be great. Yeah. Maybe you could walk us through some of the details of the registrational study design for HR-positive, HER2-negative metastatic breast cancer, including, for example, the timeline, the number of patients that you- Mm-hmm. ... are looking at enrolling, and then, key endpoints for the study. Sure. So I think the most important thing to define, at least initially, is well, the study design, of course, and then the population that- Mm. ... that we would target. So we would propose this study to be a randomized, controlled study in which we would evaluate the pelareorep combination therapy versus standard of care chemotherapy. The target population would be patients who have failed hormonal therapy, as all these patients in the, with HR-positive, HER2-negative inoperable breast cancer will initially get hormonal therapy. So we'd be targeting patients who had failed hormonal therapy and then had either failed also antibody-drug conjugate therapy or were unable to take antibody-drug conjugate therapy for whatever reason. We would target a progression-free survival primary endpoint, and we would power this study, as I mentioned before, to support at least—or at least to be very competitive for an accelerated approval if we achieve significance at the 0.05 confidence level. And if the study was successful but didn't quite meet that level of confidence, it would, at very minimum, provide a very sound basis for designing the next study and then de-risking the conduct of the next study by virtue of having succeeded in a large phase II study. But our primary goal is to target an accelerated approval pathway. Mm. Great. Mm-hmm. Where do you see pelareorep being utilized in the overall HR-positive, HER2-negative metastatic breast cancer space, given that the indication possesses a lot of different treatment regimen possibilities, and also different subtypes that you could address? Yeah. So I touched on this briefly a minute ago, but the patients who have inoperable, that is to say, metastatic or advanced HR-positive, HER2-negative breast cancer, which is a substantial population, will be treated with hormonal therapy, one or two lines of hormonal therapy. For certain subsets of patients for which it's appropriate, they may also receive different types of targeted therapy. But in any case, these treatments are not cures, and the patients will eventually progress on those treatments. Historically, those patients would then be treated with typical chemotherapy, things like paclitaxel, for example. With the success of Enhertu and other antibody-drug conjugates, those patients in the future are likely to receive the antibody-drug conjugate therapy immediately following their failure of hormonal therapy. Okay? But at some point, those they will also progress on those treatments because the antibody-drug conjugates, while very good, new therapies, are certainly not cures, right? And so once they progress on antibody-drug conjugate therapy, they will need options. And currently, that option—those options, I think, can be, are limited. And where we expect to enter the equation is to provide hopefully better options for patients who have either failed antibody-drug conjugate therapy at that point, or for the 20%-25% of the population for whom antibody-drug conjugate therapy is inappropriate to begin with. Mm-hmm. Right. So we are not planning on competing with the antibody-drug conjugate therapy, but rather to offer better options for patients who either fail that therapy or who can't take it to begin with. Mm-hmm. Pretty good. Mm-hmm. Pelareorep has also shown positive data in first-line advanced and metastatic pancreatic cancer. Mm. ... in the phase I/II GOBLET trial. Curious as to when we can expect a registrational study for this indication to begin? Yeah. So with respect to pancreatic cancer, we were excited to announce last quarter a collaboration with the Global Coalition for Adaptive Research, or GCAR. And what we're doing with GCAR is we're investigating inclusion into their adaptive design for pancreatic cancer approval. And so they run adaptive research, where it's this two-stage concept. Stage one enrolls a certain number of patients in a randomized setting and looking for a certain, you know, for lack of a better word, futility analysis. And once you get to that go or no-go decision, then you can expand enrollment and shore up the number of patients required to achieve the necessary success criteria for approval. And so we announced that back in Q2, and so we've been working with GCAR to design their master protocol. They have that in place already, but working with them to finalize that, to put into place the investigational arm that would include pelareorep, and then go to the FDA this year and seek their advice and support for such a concept. We expect that not to be an issue. This trial design has been done before with PanCAN, the Pancreatic Cancer Action Network, which GCAR has worked in collaboration with and actually has taken over their study concept in pancreatic cancer. So we don't expect that to be an issue, but we, of course, are working with the FDA, and we'll seek their advice. Once we have their advice and their input, we'll incorporate that, and we would expect to start to put the operational pieces in place early next year to start enrollment in a registrational concept trial, the first half of next year. Okay, great. The GOBLET study demonstrated approximately 62% overall response rate, which is quite high versus historical controls. It's a meaningful improvement. Just curious as to what you think is driving the response. Is this related to tumor-infiltrating lymphocytes, which have been shown to increase in patients undergoing your therapy, or could it be related to another immune function? Yeah, I think the GOBLET study provided some very interesting data, both clinical data and translational data. Just to remind people, the GOBLET study treated—in that study, we treated patients with metastatic pancreatic cancer with a combination of pelareorep, standard of care chemotherapy, and the checkpoint inhibitor atezolizumab. And that—and as John mentioned, we had a 62% overall response rate, which was very high. In looking at the translational results from that study, we observed that in all the—in every case for which we had data, the patients who had the who had a significant expansion of their tumor-infiltrating lymphocytes were also the patients that had strong tumor responses. So there is a clear correlation between the expansion of TILs and the tumor responses. So I think we do believe that's critical for the clinical effect. In addition, in that study, we did observe changes to the tumor microenvironment. So as I mentioned before, this is kind of the two-pronged immunologic effect of pelareorep. One is to stimulate cellular immune responses, including the expansion of TILs, and second, to modify the tumor microenvironment to allow those TILs to then act upon the tumor. In the GOBLET study, we also had a checkpoint inhibitor, as I mentioned, and part of the response to pelareorep is to increase the expression of PD-L1. So we also believe that that increase in the expression of PD-L1 is likely to have allowed the checkpoint inhibitor to also act more effectively and act synergistically with the pelareorep. Mm-hmm. I believe you are running several cohorts for the GOBLET study. I'm curious as to when we might see expanded data from Cohorts 1 and 5 for pancreatic cancer. Okay. So, Cohort 1 is—that's the, that is the cohort that I was just describing, and we are not collecting more data on that, with that combination from the GOBLET study. But as Kirk mentioned, that combination therapy will move forward through our collaboration with GCAR. Mm-hmm. Okay? So we're moving that forward directly. The Cohort 5, that's a different combination therapy, also in first-line metastatic pancreatic cancer patients. So cohort, in Cohort 5, we are combining pelareorep with a different chemotherapy, and the reason for that is that in pancreatic cancer, some physicians prefer to use FOLFIRINOX, which is a different chemotherapy than what we used in cohort one. And so if we succeed with the pelareorep- FOLFIRINOX combination, it will give us an opportunity to treat an even broader spectrum of pancreatic cancer patients. That's the enrollment into that arm of the study began a couple months ago. We expect the initial safety data from that. We hope to be able to update people on the initial safety data from that arm of the study, later this year or early next year, with an additional efficacy data from that arm of the study coming later next year. Mm-hmm. Okay, great. Mm-hmm. I believe pelareorep- Mm-hmm. ... is also being tested in second-line unresectable anal cancer, with positive phase I data shown here thus far. We're expecting follow-up data from the ongoing phase II expansion study in combination with atezolizumab, I believe, in either 2025 or 2026. Just curious if you could talk a bit about whether that timing makes sense and what types of initial data you might be discussing. Yeah. So in the second line or later, anal carcinoma, that's a population for which there are very limited treatment options. Those patients are currently treated with checkpoint inhibitors alone. They have response rates in the 10%, 12%, 14% range, which is very low. The data that we presented last year on an initial subset of patients from that, from our study had a 37.5% response rate, so obviously much better. It's a rare disease. So it tends to enroll patients relatively slowly. We will update the efficacy results from that study as the patients accumulate. That could happen, we could have updates early next year or sometime next year. But for the final data, we'd expect probably in 2025. The type of data again would be response rate data relative to the historical controls, which are well established. I believe the basket GOBLET study. Mm-hmm. ... included first-line and third-line metastatic colorectal cancer, if I'm not mistaken. Mm-hmm. Just curious if you're looking to carry out any further studies in that indication? Yeah, I think in the third- line colorectal, we actually met the success criteria established at the beginning of the study for the combination of pelareorep with the chemotherapy and the checkpoint inhibitor. For now, however, we are not planning new studies in that population, simply because we are focusing on our very strong data and the for the indications I mean, the indications for which we have even stronger data, the breast cancer and the pancreatic cancer. It's entirely possible that at some point we'll circle back to the colorectal, but for now, we're not pursuing that in the immediate future. Okay. Mm-hmm. I believe Oncolytics is now effectively running two registration trials simultaneously, if you will. The pancreatic cancer indication, which received $5 million from PanCAN, Mm-hmm. ... and also, the modified FOLFIRINOX study in newly diagnosed pancreatic cancer. Just curious if there's any other funding that might be needed to complete these studies? And a potential additional investigation in with modified FOLFIRINOX. Yeah. So with respect to the modified FOLFIRINOX cohort in the GOBLET study, we did receive the $5 million grant, the Therapeutic Accelerator Award from PanCan. That fully funds the modified FOLFIRINOX cohort for GOBLET, so that will take us through to some decision-making points. We'll understand the safety profile, we'll understand the efficacy data that comes out of that cohort, and that will inform us the next steps with respect to modified FOLFIRINOX. And so our expectation is, we'll take that data, if it is as strong or as we've seen in Cohort 1 with the Gem-N ab backbone, we would look to move that into a registration concept, similar to what we're doing with GCAR. So another adaptive design. We feel that that's the most effective and efficient way forward, for an indication like pancreatic cancer, to use the adaptive design concept. And so once we have that information and that data, and we can then properly plan out a, a phase, you know, adaptive design, phase III study in the modified FOLFIRINOX cohort, we would then look to see what the, what the capital cost would be, and, and we would look to address that, at, at that time. Mm-hmm. The BRACELET-1 study, I believe, was in partnership with Pfizer and Merck. I'm just curious, when you're thinking about a registrational study in breast cancer, are you thinking about running that in conjunction with a partner, a collaboration group, or potentially on your own? So the value of the BRACELET study to Oncolytics really came last year with our PFS data that we announced at ASCO. And this was the first time in a randomized setting where we saw, you know, a strong PFS benefit. And that really opened up the opportunity for us to seek approval through, you know, the non-traditional overall survival large study pathway. Tom touched on our large phase II, seeking accelerated approval concept, and that's the value of BRACELET that BRACELET's brought forth to Oncolytics. And so now we feel quite confident that this pathway will be effective both from a science standpoint, but also from a resource standpoint. And so with respect to pharma and the need for pharma, you know, we now we don't necessarily need to rely on pharma to move forward. If we wanted to do a large 600-patient overall survival study, you know, that's a very big undertaking for a company like Oncolytics. When you're looking at a sub 200-patient phase II study, that is something that is well within our abilities. It's, you know, we have the horsepower to do that, and we feel confident that that's something that we can put into place and move forward quite quickly. So our plan is to, you know, move forward. We can go it alone if we want to, and then, and at the same time, we can move pharma along, we can move Pfizer, we can move Roche along, and get them, get them fully up to date with, with the clinical data that we expect this second half of the year on the overall survival, and then start to talk about and, and discuss how they can get involved and, and help us move, the program forward. Okay, great. We've got just a minute left here, just one last question. So on the financials, Oncolytics has been very judicious over time with the use of cash, and I was just curious if you could just give us a sense as to your cash runway and just kind of how you think about financing the clinical studies going forward. Yeah, so we announced, a little over a week ago, our second-quarter results, you know, CAD 24 million on our balance sheet. That moves our financial runway out, into 2025, into, you know, kind of late, first half, Q2 concept. And those funds will allow us to move, the program along. We, you know, we'll be able to move the GCAR study forward to get to the FDA, to, and to get their feedback. We'll get through the survival data on the, on BRACELET in the metastatic breast cancer. But we don't have the funds to move, either registration program, forward, as of today. So moving forward, we'll be looking to address that situation. We'll be looking at partnering opportunities. We'll be looking at the equity capital markets and ways to deal with the funding requirements for both of these opportunities. Okay, great. Well, thank you very much, Tom and Kirk, for joining us, and thank you very much to our audience. Thanks, John. We really appreciate the opportunity. Thank you, John.