Oncolytics Biotech Inc.

are ongoing business development initiatives, and other statements related to anticipated developments in the company's business. These statements are based on management's current expectations and beliefs and are subject to a number of factors which involve none and unknown risks, delays, uncertainties, and other factors not under the company's control that may cause actual results, performance, or achievements of the company to be materially different from the results, performance, or expectations implied by these four looking statements. In any forward-looking statement in which oncologists express an expectation or belief as to future results, such expectations or beliefs are expressed in good faith, and our beliefs have a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. These factors include results of current or pending clinical trials, risks associated with intellectual property protection, financial projections, actions by regulatory agencies, and those other factors detailed in the company's filings with CDAR and the SEC. Unclaims does not undertake any obligation to update these forward-looking statements except as required by applicable laws. Now, I'm pleased to introduce the members of our management team who are joining me to discuss the important progress we made during the third quarter. These are Chair of Unclaims Board of Directors and Interim CEO, Wayne Pisano, Chief Medical Officer, Dr. Tom Heinemann, Chief Financial Officer, Kirk Look, and Vice President of Business Development, Christophe Degois. Wayne will start our conversation this morning, so I'll hand it off to him. Wayne?

Thank you, John. Good morning. Also, thanks to everyone who's joining our call today, especially because we've had several meaningful news events since our last update. Following my brief introduction, Tom will provide a recap of the Bracelet One data and our plans for a clinical trial designed to support the accelerated approval of Pell-O-Rio Rep and metastatic breast cancer. He will also expand upon our plans for Pell-O-Rio Rep and gastrointestinal cancers. Christoph will discuss our large, addressable market opportunities and partnership efforts. Kirk will review the financials. And finally, we will end by taking your questions. In the third quarter of 2024, we reached a critical milestone in our development of Pella-Riorep, or Pella as we often call it, our leading immunotherapeutic agent. The BraceFoot1 breast cancer study reported its final data and the combination of Pella plus Paclitaxel showed substantial improvement compared to Paclitaxel monotherapy in critical metrics like progression-free survival, overall survival, and 24-month overall survival rate. Progression-free survival and the 24-month overall survival rate nearly doubled, while overall survival showed an approximate 14-month benefit. We believe these data provide us the opportunity to significantly impact the lives of patients with HR-positive, HR-negative metastatic breast cancer, and we believe the next appropriate step is a registration-enabling study utilizing Bracelet 1 outcomes as the basis for an accelerated approval development path. Now, before Tom provides a more comprehensive update, I would also like to highlight that we are continuing enrollment in the safety run-in phase of Goblet Cohort 5 in newly diagnosed patients with metastatic pancreatic destructal adenocarcinoma, supported by the Pancreatic Cancer Action Network. Additionally, we continue to work with GCAR on finalizing the master protocol and seeking FDA feedback for the registration-enabling study in pancreatic cancer. With the potential for two registrational studies ahead, we believe 2025 will be an exciting year for Pella and for Oncolytics. Now, I'd like to turn the call over to Tom to provide a more detailed update. Tom?

Thank you, Wayne. Just to quickly refresh anyone who hasn't heard our story for a while or is new to what we're doing, Pella is an intravenously delivered immunotherapeutic that acts systemically. It introduces double-stranded RNA into the tumor, which promotes an inflammatory response that makes the tumor visible to the immune system. At the same time, it stimulates anti-tumor cellular immune responses that can attack the now-visible tumor. Our main priorities are to advance our planned registrational studies in breast and pancreatic cancer, so that is where we will focus our discussion today. Starting with our breast cancer program, we recently shared efficacy results from the BRACE-LOOK-1 study, which exceeded our expectations across the board, including both progression-free survival, PFS, and overall survival, OS. The median PFS nearly doubled from 6.4 months in the control arm to 12.1 months in the Pella arm. Similarly, while median OS was 18.2 months in the control arm, it could not even be calculated in the Pella arm because more than half the patients were still alive at the end of the study. Nonetheless, using the conservative assumption that all the Pella patients would have passed away at the time of their next clinic visit, the median OS would have been 32.1 months, well more than a year longer than the control patients. Perhaps even more telling, the proportion of patients who lived two years or longer nearly doubled from 33% in the control arm to 64% in the Pella arm. It's important to note that the patient populations were well-balanced across the study groups with no substantial differences that would be expected to bias results in favor of Pella. Safety results from the BRACE-L1 study were in line with Pella's well-understood and favorable safety profile based on more than 1,100 treated patients. The next question is where we go from here. After discussions with key opinion leaders, our biopharma collaborators, and the FDA, we have identified an approach that can generate primary endpoint results within two years of the start of patient enrollment. Accordingly, our next planned breast cancer study is anticipated to be a registration-enabling large Phase II study of around 180 HR-positive, HER2-negative metastatic breast cancer patients. We would use progression-free survival as a primary endpoint and would power the study to achieve a Phase III level of success if the expected clinical benefit is achieved. If Pella-based therapy demonstrates a progression-free survival benefit comparable to that seen in bracelet one, we anticipate seeking licensure, potentially through the accelerated approval pathway. This approach has been used to achieve the initial approvals of other breast cancer treatments, including Pfizer's, Ibran's, and Daiichi's, and HER2. We believe this is a cost-effective and efficient strategy for the development of Pella in breast cancer. I would now like to move to the Goblet study and our opportunity in gastrointestinal cancers. So far, we have evaluated Pella-based therapies in first-line metastatic pancreatic ductal adenocarcinoma, or PDAC, third-line metastatic colorectal cancer, and second-line or later, later anal cancer. Despite the difficulty of treating these specific cancers, Pella-based combination therapy met the initial predefined efficacy success criteria for each of these indications. Our highest priority in GI cancers is pancreatic cancer. We've seen exciting efficacy signals in previous studies, and the objective response rate we reported in the pancreatic cancer cohort of the GOBLET study was more than double historical objective response rates. The strength of these results attracted the attention of multiple potential partners. One of these collaborators is the Global Coalition for Adaptive Research, or GCAR, which specializes in the design and conduct of cost-effective, innovative, adaptive clinical trials intended to support licensure. We are currently collaborating with GCAR to develop an adaptive registrational enabling study to evaluate Pella-based combination therapy and metastatic PDAC, and we expect to seek, with GCAR, FDA guidance on the study design. We look forward to continuing our collaboration with GCAR on this exciting opportunity, and we will provide an update as this program advances. As a compliment to our work with GCAR, we also received a $5 million grant from the Pancreatic Cancer Action Network, also known as PANCAN, to evaluate a different Pella-based combination therapy in PDAC. Historically, the two most common standards of care in metastatic pancreatic cancer are the chemotherapy regimens of gemcitabine nabpaclitaxel or modified fulfirinox. The gemcitabine nabpaclitaxel regimen is the focus of our work with GCAR, while the PANCAN grant is funding the evaluation of Pella combined with modified fulfirinox. This is an attractive opportunity because if Pella-based therapy demonstrates benefit when combined with both commonly used chemotherapy regimens, it may lead to improved therapeutic options for nearly all metastatic pancreatic cancer patients. Earlier this year, we announced the dosing of the first patient in the new Goblet cohort evaluating Pella combined with modified Fulfironox. Enrollment into this cohort of the Goblet study is ongoing, and we will provide additional updates when they become available. Did the combination of Pella and modified Fulferinox produce a positive outcome if it resulted in another registrational opportunity for Pella in this challenging indication? Before I turn the call over to Christoph to expand on our business development efforts as well as our most recent commercial assessments, I would like to briefly summarize our immediate priorities. First, we plan to pursue an accelerated approval pathway for Pella in HR-positive, HER2-negative metastatic breast cancer to a large registration-enabling study that compares paclitaxel plus Pella to paclitaxel alone. Since we've already demonstrated Pella's clinical benefit in two prior randomized studies, we are confident in this approach. Secondly, we are working with GCAR to finalize the protocol for the metastatic pancreatic cancer trial, evaluating Pella, gemcitabine, nabpaclitaxel, and atezolizumab, and we will seek guidance from the FDA on this approach, which we believe will open another registrational pathway for Pella. And finally, we continue to enroll patients into the Goblet Study cohort evaluating Pella combined with modified fulfirodox, which is in newly diagnosed pancreatic cancer patients. Our conviction in Pella's broad therapeutic benefits grows stronger with each positive dataset, as does our belief in Pella's potential to improve the lives of cancer patients. With that, I will turn the call over to Christoph to discuss Pella's market opportunity, our ongoing collaborations, and future partnership opportunities. Christoph?

Thanks, Tom. Since joining Oncolytics, I've focused on saturating business development opportunities as well as working to articulate the broad opportunity we have with Pella to potential strategic industry partners. We continue to have conversation with our current collaborators, Pfizer and Roche, in addition to potential biopharma partners. With the announcement of the final data from bracelet one, including a 5.7-month progression-free survival benefit and nearly 14 months overall survival benefit, I anticipate we'll be able to have an enhanced discussion about Pella going forward, as this is an asset that is clearly ready to move to registration or setting. that members of potential partners could be interested in the progress we're making and in our plans for the future. We just completed a robust analysis of the HR-positive O2-negative metastatic breast cancer population and are encouraged by the potential PELA may have in this indication. Using the assumption that PELA could be ready for an accelerated approval in 2027, We anticipate an addressable population of around 55,000 patients in the U.S. at that time. We derive these numbers by factoring in patients who would have progressed under cream therapy and who are ineditable for, not responsive to, or progress on Nr2, which is an antibody conjugate that's becoming part of the breast cancer treatment paradigm. If we then project sales going forward to the U.S. and Europe, Assuming a 15 to 20% market penetration by the year 2033, we see the potential for $2.4 billion in annual sales for U.S. plus EU5. This would create a meaningful breast cancer drug franchise to just about any battle from our partners, and that is what we're offering in our discussion going forward. A multi-billion dollar potential drug with the potential for accelerated approval in a few years. While we are obviously very excited about the breast cancer data and opportunity, data has shown exciting efficacy in multiple cancer indications. The pancreatic cancer data has been reported is very compelling as well. In the second quarter, we entered into a collaboration with GCAR, and last year received funding from PanCan via the therapeutic accelerator award. Both of these strategic relationships provide external validation of the potential of PELLA-based combination therapy. GCAR selected the combination of PELLA, gemcitabine, napaclitaxel, and atezolizumab for investigation in the inaugural pancreatic cancer program after a thorough vetting process, which included meetings with key opinion leaders and multiple committees. We're working with them to finalize the master protocol and have GCAR submitted to the FDA for guidance. Importantly, the GCAR Alliance will provide access to trial sites, rapid patient enrollment, and control arm drug supply. PANCAM is a nonprofit organization dedicated to finding pancreatic cancer in a comprehensive way by advancing scientific research, building community, sharing knowledge, and advocating for patients. Pancan Therapy Accelerator grant is funding Code 5 of the Goblet Study, which is Pellab plus modified Folfirinox with and without atezolizumab. As Tom mentioned earlier, modified Folfirinox is the other chemotherapy backbone that is most often used besides gemcitabine plus naphthaxetaxel. So a meaningful response with a Folfirinox combination would create significant opportunity to improve the treatment outcomes for a large number of patients. With that, I'll bring on Kirk to cover our Q3 2024 financial highlights.

Kirk?

Thanks, Christophe, and good morning, everyone. I'd like to discuss our financial results for the third quarter of 2024, which will be provided in Canadian dollars unless otherwise noted. A full summary of our financial results can be found on the investor section of our website under filings and reports or in the press release issued earlier this morning. As we start to ramp up our efforts to put Pella on the path to registration, we continue to be efficient with our cash resources and keep our critical milestones in mind. As of September 30, 2024, the company reported $19.6 million in cash and cash equivalents. Net cash used in operating activities for the nine months ended September 30, 2024 was $19.1 million, compared to $22.3 million for the nine months ended September 30, 2023. The decrease reflects non-cash working capital changes partly offset by higher net operating activities in 2024. The general and administrative expenses for the third quarter of 2024 were $3.1 million compared to 5.2 for the third quarter of 2023. The decrease was primarily due to lower investor relations activities and transaction costs that were part of our 2023 public offerings. Research and development expenses for the third quarter of 2024 were $6.8 million, compared to $5.8 million for the third quarter of 2023. The increase was primarily due to higher manufacturing expenses and clinical trial expenses. Increased manufacturing expenses were related to completing a CGMP production run in the quarter. Increased clinical trial expenses were associated with our GCAR collaboration, bracelet one study closeout costs, and the clinical data management of legacy studies. This increase was partly offset by lower goblet study costs as we focus on enrolling cohort five, which is supported by the PANCAN grant. The net loss for the third quarter of 2024 was 9.5 million compared to the net loss of 9.9 million for the third quarter of 2023. The basic and diluted loss per share was 12 cents in the third quarter of 2024 compared to a basic and diluted loss per share of 14 cents in the third quarter of 2023. Now, we are very excited to move Pella further along the path to registration, and we are looking at multiple upcoming milestones. We are moving forward with our registration-enabling study of HR-positive HER2-negative metastatic breast cancer based on the clinical benefits observed in IND213, Bracelet 1, in addition to the feedback we received from the FDA. Our collaboration with GCAR is continuing to progress, and we are nearing the finalization of the master protocol. Cohort 5 of the GOBLET study, the combination of Pella and modified falferinox with and without atezolizumab, continues to enroll, and we expect safety data in early 2025, followed by efficacy data later next year. We are also looking for updated efficacy data from cohort 4 of GOBLET next year. That is the cohort evaluating Pella and atezolizumab in second line or later, So we always try to end our calls by expressing our gratitude to the people who are instrumental in helping us continue our mission of giving cancer patients the opportunity to live longer, better lives. This includes the entire Oncolytics team, our investors, our patients, and their families.

Now I would like to open the call for Q&A. Operator?

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Wanted to check on the upcoming San Antonio breast cancer update. Should we expect any closer data cut or what kind of details should we expect there?

Tom Heinemann here, Chief Medical Officer. The data that we presented in this call are in fact the final results. Because of the timing and of the meeting, we will not have anything any update at San Antonio, but the results presented are, in fact, the final results, so there is no more updated cut expected.

Got it. And a quick one on the HER2 negative status is, could you remind us they were, I'd say, two and below, or what?

Well, when this study was started, The antibody drug conjugates were not on the market and they were not being used, right? So there was no reason to test specifically the HER2 status. All of the patients in the study fell into the classic characterization, however, of HER2 low. So they were all two or lower according to the standard definition.

Okay. Thank you again for taking the questions. Sure. Next question comes from Louise Chen with Gandor.

Please go ahead.

Hi. Good morning, everyone. Thank you for taking our questions. First, on your breast cancer registration enabling study, can you provide additional color on a potential to achieve accelerated approval? How early were you able to achieve this or do we have to wait until the trial completion for regulatory action? And I do have a follow-up. Thank you.

Okay. Well, I'll start. Tom Heinemann again. So the path for regulatory approval and accelerated approval is based on our prior feedback with the FDA and on precedent, right? And so we think that the study as designed will provide a clinically meaningful benefit. And if it does provide a clinically meaningful benefit comparable or even anywhere close to what we saw in the bracelet study, that would result in a statistical level of a p-value of less than 0.05 okay and so in other words with that study we would hit all the main points that the fda is looking for when they consider an approval so one we would have a clinically meaningful benefit two we would have statistical a highly statistically significant study and three if it performs as it has in all our previous studies we would have a solid safety profile which are the three main things the fda is looking for Okay, so the FDA, of course, will never tell you in advance that they will approve anything before they see the data, but if this study performs as we expect it to, we would hit on all the points that we think would be compelling for the FDA to support a regulatory approval following in the precedent set by many drugs, but including such drugs as Ibrans and HER2. Okay. And with regard to the timing, perhaps I can hand that off to Kirk to discuss the timing explicitly, if you don't mind, Kirk.

Yeah, in terms of timing, we would, once we can get the study up and running and enrolling, we expect enrollment to happen over an 18-month period, and then data maturity is expected to be six months after the last patient's on, and then we would expect to be in a, subject to the data, of course, we expect to be in a filing position after that point in time.

Great, thank you. My follow-up question is, on your first upcoming major milestone, which is finalizing the master protocol for your adaptive registration enabling trial, given this is for first-line PDAC patients, We're wondering how quickly we'll be able to complete patient enrollment.

Thank you.

Well, once the, so we need to finalize the protocol as we mentioned. It will need to be discussed with the FDA. In other words, there are some upstream steps. Once that study starts enrolling, we would have to map out the timelines precisely based on the parameters of the study at that time. But we expected to enroll quickly because this is a, this is not a rare disease. This is a, unfortunately, relatively common cancer. And we would be expecting to work with all of, well, or many of the best, highest potential, recruiting potential sites in the U.S. and maybe even elsewhere. So while I hesitate to put a precise timeline on it, we expect this study to evolve very efficiently. And, Kirk, maybe you'd like to expand on that. I don't know.

No, I think that's exactly right. Okay. Great. That's helpful. Thank you so much.