Good morning. I'd like to welcome everybody back to the H.C. Wainwright 28th Annual Global Investment Conference. My name is Andres Maldonado. I'm a Senior Biotech Analyst here, and it's my pleasure to welcome everybody. Continuing with the morning session, next up on the docket is Candel Therapeutics, and I'm so happy to have President and CEO, Paul Peter Tak, and Mark Sims, Chief Commercial Officer. Welcome, gentlemen. Thank you very much. Thanks. Great. A perfect primer to start is for investors less familiar with Candel Therapeutics' story. Could you briefly walk us through the pipeline and company priorities over the next 12- 18 months? Yeah, absolutely. Candel Therapeutics develops viral immunotherapies for difficult-to-treat solid tumors, and we have two investigational medicines in the clinic. The first is called aglatimagene, and we have positive phase III data pivotal trial in newly diagnosed localized prostate cancer. Area of huge unmet need. These patients that we focus on are treated with curative intent, and we try to increase the proportion of patients that will actually live free from evidence of recurrence of cancer. We have achieved that. We have achieved the primary endpoint supported by secondary and exploratory endpoints, and we are now preparing BLA submission. We're aiming for BLA submission at the end of this year, so that's the major catalyst. The interesting thing about aglatimagene is it's a bone solid tumor immunotherapy. We also have positive data in other indications that are difficult to treat, like therapy-resistant metastatic progressive non-small cell lung cancer. We have done a very interesting phase II-A study where we could show doubling of expected median overall survival in patients who had failed immune checkpoint inhibitors. We expect that the data will be published shortly in a scientific journal. We've started a global phase III clinical trial, pivotal trial in non-small cell lung cancer. We also have positive data in pancreatic cancer based on a small randomized controlled clinical trial in borderline resectable pancreatic cancer. You see a complete separation of the overall survival curves. We got Fast Track designation there, Orphan Drug designation. We've paused the program, however, because we have just too much, and we need to have a laser focus on value creation, but the program is still there. Then we will have new data for the aglatimagene in prostate cancer program in the near future. We've said we expect immunological biomarker data in Q3, and we may come back to this. The second investigational medicine is called linoserpaturev. Unlike aglatimagene, this is a true oncolytic virus, but it's a next generation replication-competent herpes simplex virus that is designed to replicate only in the tumor cells while sparing the healthy tissue. We test it in probably the most difficult to treat form of cancer, which is recurrent glioblastoma. We have very encouraging data there as well. We published this in Nature and more recently in Science Translational Medicine, and we are preparing a randomized control trial. We also expect in Q4 to come back to the catalyst. The question, are there any patients who live much longer than you would expect? Keep in mind that all these patients typically die within six-nine months. We're looking at the long tail of survival. I should mention that this is also an enabling indication for other tumors outside the brain. Think of sarcoma, gastrointestinal tumors, triple-negative breast cancer. We are creating another pipeline in a product at the right time, similar to what we've done for aglatimagene. Great. Seems like a very robust time for the company. Starting with aglatimagene in localized prostate cancer, what do you think that investors still underappreciate about the story and the idea essentially of using a localized administered therapy to generate a systemic durable anti-tumor immunity? Yeah, it's a great question. Let me first say the following. three years ago, we had a market cap of less than $50 million, and one week ago, we had a market cap of $1 billion. Institutional ownership has gone up to about 70%, if you include some of the key insiders like PBM Capital, but probably getting close to 80%. We are in a much better position than we are. At the same time, I also agree with you. I think this is still hugely undervalued, and the reasons include this is a completely new modality. It's even not an oncolytic virus, so people sometimes found it difficult to get their head around it. People have not seen any study that was focused on patients with localized prostate cancer treated with curative intent, so it's a completely new indication. People have not seen the use of disease-free survival as a primary endpoint for regulatory approval in prostate cancer. It has been used in other indications like breast cancer, other diseases, because there's been no successful treatment in the past for localized disease in patients who want to live free from cancer, free from local progression of the disease, free from metastases, free from long-term toxic treatments like long-term ADT, like this chemical castration. I think people did not get that immediately. But that also means that this is a vertical investment opportunity. I've estimated, and I've said this in public before, the probability of success ultimately for approval to be in the order of 90%, 90. Everybody can use their own favorite AI system to ask the question, if there's a pivotal phase III study, placebo-controlled trial that achieved the primary endpoint supported by secondary and exploratory endpoints, conducted under a Special Protocol Assessment agreed with the FDA that's intact, that got an RMAT designation after data read-out. But it's more or less the probability of success. In the end, it's always 0% or 100%, right? You get it or not, but this is how we think about it. We do believe that this is an asymmetrical investment opportunity, but we are happy with where we are. A very clear trajectory upwards. Great. Clinically, how do you see aglatimagene fitting differently across favorable, intermediate, unfavorable, intermediate, and high-risk disease? The question being, is the biggest opportunity is an alternative to treatment intensification in some patients or as another layer on top of the current therapy in the high-risk patients? Yeah. If a patient has intermediate or high-risk prostate cancer, and the decision is to undergo radical treatment because these patients want to eradicate that tumor, just think about it through the patient perspective, right? If you're diagnosed with cancer, you want to get rid of your cancer. You're not necessarily thinking about with a slowly growing tumor, will I be alive in 20 years? Also important, because if you don't have cancer anymore, you won't die because of prostate cancer 15 or 20 years later. But you want to have the immediate elimination. This is a patient population that has made that decision to accept the complications and side effects of either radical prostatectomy surgery or radiotherapy. Think of urinary incontinence, erectile dysfunction, loss of quality of life, what have you. The problem that we try to solve is that there's a chance of recurrence of 30%. 1/3 of the patients will face recurrence, and that's quite high if you realize this. We focus on the patients who have chosen to undergo radiotherapy. That's about 65,000 patients per year in the U.S. alone, and we want to increase the probability of living free from evidence of recurrence of cancer. At some point during the scientific advisory boards, I asked, "If we get approval, there will be three options, right? Your patients can choose radical prostatectomy or the current external beam radiotherapy or external beam radiotherapy plus aglatimagene." The key external experts said, "We disagree. There will be only two options, actually, in this scenario. It's either radical prostatectomy or EBRT plus aglatimagene because actually that leads to the best results." That's how we position it in intermediate or high risk prostate cancer. High risk defined as not more than a single risk factor because that was the ITT population. Great. Before we get into some of the mechanics that are left in the Q4 BLA filing, one thing I want to dive into is you had previously said that the FDA has requested a biodistribution and shedding study that's called PrTK05. Is this study on track for BLA submission? You also mentioned that you're planning to share immunological biomarker data in Q3. It would be great to get an update there. Yeah. That is correct. This is, again, an example of a program where we had a very tight timeline. The FDA did ask us to do a biodistribution and shedding study. We have done this in the past, or my predecessors actually, with older technology, and you would expect that the virus is cleared from the body within a few months, and that was shown at the time. But now the FDA asked, "Can you do that again with the most state-of-the-art technology?" Which is a completely reasonable request. This study is completely on track. We still aim to have all this data focused on biodistribution and shedding in Q4. That is great. I thought we are going to inject again in a group of patients aglatimagene into the prostate, which is a simple procedure, in patients with intermediate or high-risk prostate cancer to answer this question. It also gives us the opportunity to take some extra bio samples and ask the question, can we use that for sophisticated immunological biomarker research? Can we show evidence that we really changed the immune system long term, creating a new state of immune surveillance? While we speak, we have collected these samples. My team is doing the flow cytometry, and we are looking at questions like, can we show that there is an increase in the CD8 positive affected T cell population? Because we know that this is the key population for this mechanism of action. How do we know that? Because we have shown it in non-small cell lung cancer, in high-grade glioma. We also had high-grade glioma for aglatimagene program. Also in mouse models, if you deplete the CD8 positive T cells, it actually does not work anymore. This really works by educating the CD8 positive T cell population how to recognize and eliminate the tumor cells over time. We would love to see that. Along these lines, we would love to see that there is a change in CD8 positive effector memory cells. These T cells can continue to target potential, let us say, micro metastases in the body. That is one piece, and we are on track, I believe, if everything goes right with the biomarker assays in the next few weeks to give some high-profile disclosure about this data. We have also looked again at a randomized controlled trial where we have the biopsies, and we use digital pathology, including artificial intelligence, to ask the question, even in the patients who still have tumor cells, nobody cures everybody. Is there potentially a new state of interaction between the immune cells in the prostate and the tumor cells? We hope to disclose that data in the very near future. Wonderful. As you are thinking about the BLA filing, I guess the big question is what is remaining, what is on that path, and more importantly, as a follow-up, it would be great to get some initial clarity on how you are thinking about the launch. Yeah. I will speak very briefly about everything that is on the critical path because I spoke about it in great detail recently. We organized a meeting organized by your colleagues from Cantor, actually, where my chief technology officer and also Nicoletta Loggia, who oversaw all of cell and gene therapy manufacturing at Novartis and who is on our board, spoke in great detail about all the work streams. I would refer to that actually because of time. I spoke also about it last week, where we actually announced that we have just successfully completed the PPQ3 run, but now we need to test it and see can we use this in our conversations with the FDA. In terms of launch, I want to shift actually to the commercial side and give Mark the opportunity to respond. Yeah. First of all, I would like to say I am very excited to join the Candel team. I am the most recent member of the leadership team here after eight years leading some of the largest franchises in oncology at AstraZeneca. I am very excited about the opportunity to bring, first, our number one priority, bringing aglatimagene to the localized prostate cancer community and ensuring that it reaches its full potential. The approach that we are going to take, and I think this is something that we wanted to talk about, was really focus on accounts. What we have learned is that within the localized prostate cancer area specifically, we have the opportunity to actually have a concentrated focus on a certain number of accounts that are driving the primary patient opportunity. In fact, the top 200 accounts are really responsible for more than 80% of the patient opportunity in localized prostate cancer, which allows us to be very targeted, very focused. When you are thinking about the launch and the approach that we are going to take, we are going to be able to really focus on the customers that are going to drive the business. We are not talking about a very broad oncology execution. It is going to be able to be very precise and focused and hitting on the customers that are going to have as many patients as we need to reach. That is the approach that we are going to take to managing this opportunity. Wonderful. As many pre-commercial companies think about commercial launch, how do you view the biggest barriers to adoption of that launch? If you can touch upon, is it physician education, workflow, reimbursement? How are you thinking about some of those common headwinds? Yeah. We're working very hard right now to anticipate, understand, and be able to effectively overcome all potential barriers to launch uptake. I think the real focus for us, and I think it's a tremendous opportunity, is the integration of aglatimagene into radiation workflows. The key thing to remember here is we're talking about localized prostate cancer, and in that setting, these patients are primarily treated by urologists. The urologist is actually the quarterback, Paul Peter alluded to this earlier, where by their confirming the diagnosis, they're determining the risk and prognosis for these patients, but they're also very commonly working in concert and collaboration in a multidisciplinary fashion with radiation oncologists. We estimate that 65,000 patients a year with medium, intermediate to high risk localized prostate cancer are being treated with a radiation-based approach. These two stakeholders, these customers work very closely together. That's why the account-based approach is important because we have a range of different customers, community urology, large urology group practices, which are very sophisticated, community oncology practices and academic practices, et cetera. Understanding how they are working now and how we can integrate aglatimagene within the radiation workflows is the key opportunity for us. The great news so far is the feedback and the advice that we're getting from advisors is they feel that this can actually be very simply integrated within their workflows, and they're excited about the benefit that aglatimagene can bring to their patients. Great. Very helpful. Your payer work suggests relatively little price sensitivity with a strong NCCN recommendation. Help us understand what ultimately determines where aglatimagene should be priced, and how much does the strength of the initial guidance recommendation matter for uptake versus reimbursement? Yeah. So like you said, great news so far. The interactions that we've had with payers have been very positive. They see the benefit that aglatimagene is going to bring to their patients. And it all comes down to value proposition. So clinical benefit versus risk in the context of the unmet need. The issue around clinical belief and impact doesn't seem to be much of the driver here because they're seeing that aglatimagene does address that unmet need very clearly. Then the other side of it that's quite important is the fact that there's potential for cost offset here because we're talking about a very limited duration of therapy. So localized treatment that's delivered in an outpatient setting, just three administrations, and then you're done over a four-six week period, and that's it. You get the benefit of reducing the rate of recurrence or reducing recurrence of prostate cancer. We're also seeing in some of the data that was recently presented at AUA, an improvement in lengthening the time to metastases, and then also an increase in the time to salvage therapies, which is really important here in the context of payers, because what that means, the most common salvage therapy that's used in these patients is long-term hormonal therapies like androgen deprivation therapy, which is medical castration. Those therapies, not only is it long duration of treatment that you're offsetting, but it's all the associated toxicity. So there's a lot of burden on patients from these treatments. That value proposition reduction recurrence, improvement in time to metastases, improvement in time to salvage therapy. That package together is very compelling from a payer perspective, and all the pricing work that we've done to date, is showing us that the quarters for pricing that we would like to see is something that will be acceptable to the payer audience. Great. And maybe to summarize that really quickly, if you could just talk briefly about outside of the initial revenue expectations, what are some of the two or three commercial metrics that investors should be closely paying attention to that may be underappreciated within the first six- 12 months of launch? And afterward, Paul Peter Tak, it would be great to just overview the quick catalyst in that few minutes we have left. Just quickly, one of them that is really important that actually we are working on and trying to drive right now is really awareness, and that can happen prior to launch to a certain degree. Obviously, we cannot be selling, but from a medical education perspective, we can build awareness through our scientific affairs team, and that has already started the expansion of our engagement with medical congresses. We cannot say the abstracts that are being presented this fall, but trust me, we are going to be active at each of the major urology and prostate cancer conferences that are upcoming. We have recently published The Lancet Oncology publication, which is in a really exciting in June. We are expanding that reach. Awareness is important. The next thing that we will see at approval, we are patient, where we have a plan to really support patient access. We hope to have a hub, a patient hub. One of the early elements of uptake is you will see enrollments in the hub. What that reflects is really physician desire to prescribe and initiate navigation for reimbursement. That is where our patient access hub will be able to support them. The third area, of course, is just vial shipments. What we are going to be looking for, again, we will be focusing on our large volume accounts. We want to see vial shipments first breadth, which means we are reaching a lot of customers in as far as prescription and utilization, and then we want to see depth, so repeat use, repeat prescription, repeat administration in those patients. Those are some of the key ones we will be looking for.</seg <seg id="3">Yeah, very briefly maybe, the key catalyst coming up, right? We hope to see immunological biomarker data for prostate cancer this month. We are aiming for BLA submission at the end of this year. Still many things going on in parallel. We hope to see a long tail of survival in a subset of patients with recurrent high-grade glioma. Most importantly, everything is focused, of course, on aglatimagene in prostate cancer. We also make plans for the future that we will disclose later. It is really about having a laser focus on being ready for the regulators, for the payers, the healthcare professionals and the patients. We do all of this in parallel. Great. Yeah, very briefly maybe, the key catalyst coming up, right? We hope to see immunological biomarker data for prostate cancer this month. We are aiming for BLA submission at the end of this year. Still many things going on in parallel. We hope to see a long tail of survival in a subset of patients with recurrent high-grade glioma. But most importantly, everything is focused, of course, on aglatimagene in prostate cancer. Well, we also make plans for the future that we will disclose later. But it's really about having a laser focus on being ready for the regulators, for the payers, the healthcare professionals and the patients. And we do all of this in parallel. Great. So on behalf of myself and the whole HCW family, thank you so much for joining us. Congrats on the progress, and we look forward to future updates. Thank you. Thank you so much.