Hi, good afternoon, everyone. Thank you for joining us at the 45th Annual Canaccord Genuity Growth Conference here in Boston. I'm John Newman, one of the Senior Biotech Analysts at the firm. We're very excited to have Candel Therapeutics with us today, along with Candel, the CEO, Dr. Paul -Peter Tak. Paul -Peter, welcome. Thank you. I'm wondering if you could start by talking about Candel's vaccine approach to address a variety of tumors. Most importantly, how is this different than what others have done in the past? Yeah, this is a whole new approach. That's also why people sometimes find it difficult to get their head around it. What is it? Is it gene therapy? Is it a vaccine? Is it an oncolytic virus? It's a new approach to immunize the patient against the patient's own tumor without the need to know the antigens. How does it work? We use a replication-defective adenovirus to deliver a transgene, which is the gene encoding HSV thymidine kinase. In patients with metastatic disease, you can just basically choose a tumor that you want to inject that's easy to reach. That will lead to local HSV thymidine kinase enzyme expression. We give the patient valacyclovir, which is a tablet for two weeks. Valacyclovir will be converted into a toxic metabolite into a nucleotide analog at the site of the local enzyme expression. That's where you get real specificity. This will be incorporated in cells that exhibit DNA damage or that are proliferating, in other words, in the tumor cells. It leads to a highly immunogenic cell death. Because we use an adenovirus to deliver this gene, the adenoviral capsid proteins will induce a very strong pro-inflammatory signal. That's what adenoviruses do. In other words, while you cause the release of a whole variety of cancer antigens in the tumor microenvironment specific for the patient's own tumor, you induce inflammation. You create the optimal conditions for immunization or vaccination against the tumor. That leads to a mainly CD8 positive T cell response that is specific. These T cells will migrate throughout the body, where they will be able to recognize and kill the tumor cells, as we've shown not only in mouse models but in patients. OK, great. I wonder if we could start in terms of the pipeline by talking about CAN-2409. You talked a little bit about the mechanism of action, but what are the indications that are currently under investigation and the stages of those clinical studies? Yeah, we see CAN-2409 as a pan-solid tumor therapy approach. We have data also in solid tumors that we currently do not pursue because we cannot do everything. We went through rigorous prioritization and only focused on the areas with the largest unmet need and the biggest commercial opportunity. Currently, we are focused on early localized non-metastatic prostate cancer. We are focused on borderline resectable pancreatic cancer and therapy-resistant non-small cell lung cancer. These patients have failed immune checkpoint inhibitors and often also chemotherapy. OK, great. For prostate cancer, you've already shown positive phase III data here, a very large study. I believe you're planning to submit the BLA by the end of 2026. I wonder if you could talk a little bit about those data and the activities to complete between now and the end of 2026. Yeah. Yeah, so we have completed a pivotal phase III trial that was conducted under a SPA, Special Protocol Assessment, agreed with the FDA, which is important because we wanted to make sure that there was agreement about the primary endpoint, which is disease-free survival. Here we have curative intent. We do not just want to make sure that patients live longer with cancer or that they maybe delay the development of metastases. We want them to get rid of their cancer because that's the goal in patients who elect to undergo radical therapy because of early, newly diagnosed prostate cancer. In 30% of the patients with current standard of care, there will be a recurrence of the disease leading to signs and symptoms due to progression and metastatic disease. Of course, these patients will get salvage therapies like long-term antigen deprivation therapy, basically chemical castration. Patients hate this, actually, because there's a lot of side effects and a negative impact on quality of life. That's the unmet need. Therefore, we agreed with the FDA that the primary endpoint would be disease-free survival, which means the absence of any evidence of remaining tumor cells, including in two-year biopsies of the prostate. This was a very high hurdle. We achieved that endpoint convincingly, so statistically significant improvement, 30% improvement in disease-free survival. Even if we count as event any cause of death, even if a patient gets a heart attack or a stroke or an accident, these would count as an event. You dilute the signal. Despite this, we have convincingly shown that we could achieve the primary endpoint. That brings me to the key secondary endpoint, which is prostate cancer specific disease-free survival. You eliminate all causes of death other than due to prostate cancer. We have a 38% improvement, highly significant. This is also supported by a higher proportion of patients achieving low levels of PSA, a nadir of less than 0.2 ng/mL. We've also shown this at the microscopic level because the FDA requested that we take biopsies at two years. We could show a pathological complete response at two years in 80%, H0, of these patients. That means the absence of any evidence of remaining tumor cells compared to 64% in the control group. This is what you would expect with current standard of care radiotherapy. OK, thank you. Maybe you could talk a moment about the work you've done in preparation for the commercial launch of CAN-2409 in prostate cancer, and just tell us a bit about how the product will fit in with the current treatment landscape. Yeah. Maybe I should briefly come back to the point, what are we doing between now and BLA submission in Q4 next year? This is all based on scaling up commercial manufacturing. We deliberately made a decision that we did not want to spend tens of millions of dollars before we had seen the data readout of the phase III program because we have many other very promising programs. If the data would have been negative, then we would have pivoted to the other programs. At that time point, the probability of success was in the order of 35% based on industry metrics. Now, having a SPA primary endpoint supported by all the secondary endpoints and an RMET that we got after we've seen the data, we have a probability of success that we estimate to be 92%. We are now scaling up manufacturing with our partner, SAFC, in California. That's basically Merck Millipore. This is focused on the GMP runs and the PPQ runs, putting the product on stability, et cetera. Meanwhile, we also use this time for pre-commercial activities. We've done extensive market research over the years, actually, but now most recently with the data in hand in May of this year, both in the U.S. and in Europe, both in academia and in community centers. We received consistently positive feedback from the physicians who treat these patients. Who are they? They are urologists and/or radiation oncologists. They treat newly diagnosed prostate cancer. 100% of the respondents indicated that they would actually adopt this approach and combine CAN-2409 with standard of care radiotherapy to increase the proportion of patients that will achieve their goal, which is to eradicate the tumor, not to live with cancer, but to live without cancer. We started a lot of this work in an externalized model. I think it's important to emphasize this. We work with Globe Life Sciences in the U.K., one of the best companies, I think, in this field in the world. We work with IDEA Pharma. This is a company that was founded by Mike Rea, a very big name in the commercial world. He was involved in some of the most successful launches, including that of Nivolumab at the time, and a third undisclosed party, which helps us to get access to the brightest minds in commercialization, payer research, medical affairs, patient engagement without building a big infrastructure in-house prematurely. That's what we are focused on at this moment. We also got very positive initial payer feedback, both in the U.S. and in Europe. It's sort of attractive, actually, because it's a one-off treatment. It's not a recurring cost year after year. It's very well tolerated, apart from minor flu-like symptoms in a very significant proportion of patients. We don't see an increase in serious adverse events. Of course, there will be the avoidance of future costs to the health care system with this approach. OK, great. I know you're focused on the BLA submission in prostate cancer, but I also wanted to talk about the work that you've done in non-small cell lung cancer and the data there that have been generated. Yeah. In non-small cell lung cancer, we focus actually on the other side of the spectrum, patients who have failed standard of care. We enroll patients with unresectable stage III or stage IV non-small cell lung cancer. In fact, we ended up with 90% of the patients with stage IV, so metastatic disease. Most patients had progressive disease despite chemotherapy, despite immune checkpoint inhibitor treatment. These patients will typically get second-line docetaxel chemotherapy. They have a life expectancy at that time of less than a year, which has been consistently reported. We did not change anything to the regimen. We kept them on the immune checkpoint inhibitor that they basically failed on. We gave them two administrations of CAN-2409 into one of the tumors or in two of the tumors. We could demonstrate the median overall survival in the 46 patients who were treated per protocol. They received two injections of CAN-2409 without changing anything else of more than 24 months. This is very low in this population. It's a doubling of the expected median overall survival. We are not aware of any data that come even close to this in the pipeline of the industry. We also found that if you compare the patients with non-squamous histology, which is about 70% - 75% of the patients, compared to patients with squamous histology, it looks even better if you focus on the non-squamous subgroup. That will be the group that we will focus on moving forward. This is all supported by deep biomarker research where we can see that we changed the T cell responses. We see massive infiltration into the tumors, but also very clear evidence, both on the clinical level and on an immunological level, of a systemic anti-tumor immune response. That means you don't need to inject the tumors again and again, two times, actually, twice in a patient's life. It's done during bronchoscopy. You don't need to inject all the tumors because of the very clear evidence of an epsilon effect. We got Fast Track designation from the FDA based on these data. We recently had a very constructive meeting with the FDA end of phase II meeting. We are now preparing a large, potentially registrational, phase III clinical trial in therapy-resistant non-small cell lung cancer. Again, patients who have failed immune checkpoint inhibitors. Moving forward, we will focus on non-squamous histology. Have you talked about any kind of a timeline there in terms of when you might proceed to a pivotal study? We have not announced a timeline. What we are doing and what's included in the current budget for lung cancer, actually the same is true for pancreatic cancer, is what I call all the enabling work. That takes more time than it costs money. Think of protocol development, engagement with the key experts in academia, engagement with the FDA, as I just mentioned, like an end of phase II meeting with the FDA. That's all included. We expect to have that protocol ready in Q1 of next year. That's all in what I call committed spend. We will not trigger the initiation of the enrollment of patients before we have secured additional funding because that's not in the current runway. That will be done only if we are able to get access to non-dilutive funding. The same is true for pancreatic cancer. OK, great. In pancreatic cancer, I wondered if you could describe the data here thus far as well. You talked briefly about the plans for that program going forward. If you had to prioritize lung versus pancreatic, I'm just curious as to which program you might like to take forward. In pancreatic cancer, we've conducted a small randomized clinical trial in so-called borderline resectable pancreatic cancer. That's a clinical diagnosis. The only hope for a patient with pancreatic cancer to be cured is to be able to have the tumor removed completely. This is a big resection, typically a Whipple procedure. We focus on the patients where there's typically a tumor invading a blood vessel, an artery, or a vein. Therefore, they are not resectable yet. These patients will get chemotherapy induction treatment followed by chemoradiation. The hope is to shrink the tumor so that they may become resectable, which is the case in about half of the patients. We randomize patients to receive this standard of care regimen that I just described or the same regimen, but then on top of that, two to three administrations of CAN-2409. Two in everybody, and the third, if patients would become resectable, would be delivered during surgery. We don't know whether you need that third injection. It's like a second booster. You're in the abdomen, and it's very easy to inject. We looked at the hardest endpoint in this indication, which is overall survival. We saw a complete separation of the overall survival curves. There's an estimated median overall survival in the active treatment group of more than 32 months compared to 12.5 months in the control group. Complete separation of these overall survival curves is supported, again, by deep biomarker research. We can show that this very cold, from an immunological perspective, tumor, which is sometimes called an immunological desert, could be converted into a tumor microenvironment containing tertiary lymphoid structures, like immunologically active organs, which explains, in part, the very remarkable effects. We've also seen post-progression survival much, much longer, 22 months, compared to what you would expect in normal clinical practice of about 6.5 months. We got Fast Track designation and Orphan Drug designation from the FDA on the back of these data. We just announced a few weeks ago that we also got Orphan designation from the EMA. We are now starting to interact with the European regulators as well with a similar positive outcome. Now we are designing a phase II-B/phase III adaptive clinical trial, potentially registrational clinical trial. We'll follow the same path as I just described for non-small cell lung cancer. To come back to your question about prioritization, when I joined this company almost five years ago, we went through a very rigorous prioritization exercise where we kept everything where we felt there was a very strong scientific rationale, big clinical unmet need, clear regulatory path forward, and a big commercial opportunity. These indications are in. If you would still need to prioritize, number one would be to get to approval and launch and commercialization in prostate cancer, number one. Number two, non-small cell lung cancer. Number three, pancreatic cancer. We have a pipeline in a strategy, a pipeline in a product strategy. Ideally, you want to advance these all rapidly, actually, because the clock starts ticking at the moment of your first approval of data exclusivity. From a commercial perspective, and that's also the feedback that we get from Chief Commercial Officers from very big pharma companies with a strong presence in oncology, you can extract most value if you are able to start all these programs in parallel. If needed, we'll prioritize. We'll only do this if we get sufficient access to non-dilutive funding. Great. Can you describe the manufacturing process for CAN-2409? Do you currently have manufacturing capacity to support the commercial launch? Yes, the answer is yes. This is a replication-defective adenovirus. Compare it to, for example, the AstraZeneca vaccine for COVID-19 or the Janssen vaccine. These are also replication-defective adenoviruses that are used to deliver a gene, in our case, the HSV thymidine kinase gene. In the case of COVID-19, for example, the spike protein for the coronavirus. It's the same technology. There's huge capacity in the industry. This is not like CAR T cells or tumor infiltrating lymphocytes. It's relatively straightforward. We have a product that has been shown to be stable in the fridge for more than 10 years. It's stable, and not in the fridge, in the freezer. It's stable in the fridge at 4 degrees centigrade for several months. There's no complex cold chain here compared to, for example, T-VEC or Imlygic. Cost of goods are low. It's relatively straightforward. You just need to do the work of scaling up manufacturing because you can only get a BLA submission if you can show that you have the commercial batches ready to go and that they are stable. This is all on track. OK, great. I wonder if we could pivot to CAN-3110. Just in terms of the mechanism of action, is there any difference there versus CAN-2409? Yeah, this is a different approach, although there are some similarities. CAN-3110 is a true oncolytic virus. It's a replication competent herpes simplex virus. It's a next-generation oncolytic virus. It's unique in its mechanism of action because it contains a gene that everybody else has deleted, which is the ICP34.5 gene. If you think, for example, of T-VEC or Imlygic, which was the first approved oncolytic virus in the Western world, it lacks the 34.5 gene. Why? Because it is associated with neurotoxicity. It makes a lot of sense. The problem is that if you do that, you also sacrifice efficacy. We inserted one copy of this gene and put it under the control of a tumor-specific promoter, which is the Nestin promoter. Nestin plays a role in embryogenesis, but it's completely absent from the healthy adult brain. It's upregulated in every glioblastoma. We have injected the first herpes simplex virus containing a 34.5 gene into humans. Nobody has done this before. Actually, we injected it into the brain of humans, and we've shown that this was safe and well tolerated. We've not reached dose-limiting toxicity, and we've shown that just after a single injection in recurrent glioblastoma, these patients have failed neurosurgery and chemotherapy and radiotherapy, and they have a life expectancy of less than six to nine months. We've shown doubling of the expected median overall survival after just a single injection, with several patients living much longer than a year, all supported by deep immunological and molecular biomarker research. We published the initial data in Nature. We got a very big grant from the Breakthrough Cancer Foundation based on these data, a grant of $16 million, one-six. That's quite a lot for an extension of a phase I-B trial. That allows us now to ask the question, we believe that we have a medicine even after a single injection. Could it be even better if you give multiple injections? We've now started to explore whether it's feasible and/or useful to go up to six injections. We presented data last year in an oral presentation at the International Oncolytic Viral Immunotherapy Meeting that we could show that this is feasible. We also take brain biopsies before every injection, so we're going to learn a lot about the tissue response to CAN-3110 in the brain. We could also demonstrate that half of these patients were still alive after one year, and this is ongoing. We expect to have additional clinical activity data and biomarker data in the next quarter. In fact, some of these data are currently under review at a very high impact journal. OK, great. Just a follow-on question there in terms of the upcoming data here in glioblastoma. Yeah, recurrent glioblastoma, yeah. Do you have any sense as to, just roughly speaking, how many patients you might have and how much follow-up time you might be able to report? Yeah, we have deliberately not given the real details about how many patients and why is that because we run this company like an investigator-sponsored study. It's a little bit more difficult to control than when it's a study sponsored by Candel Therapeutics. We do know that we will have data about survival and that we will have very interesting data about the relationship between histologic changes after CAN-3110 versus what you see on imaging. I will just highlight that ORRs, et cetera, and progression-free survival are not great surrogate markers for the evaluation of immunotherapies. This is also consistent with the CICD guidelines. I feel quite supported by the new FDA from that point of view. You need to wait for the hardest endpoint, which is really overall survival. We'll have very detailed data. We've not announced the exact number of patients because we don't know it for sure ourselves until we get these data from our academic principal investigator. The PI is Nino Chiocca, who is the Head of Neurosurgery at the Brigham and Women's Hospital, one of the key experts in the field. I should also say we got, based on the initial data, again, Fast Track designation and Orphan Drug designation from the FDA. We are preparing a phase II clinical trial, which could be a registrational clinical trial in this indication. We see this also not only as a huge opportunity where others have failed. This has been a graveyard for the industry. Everything always fails until something works. We also see it as an enabling indication for other tumors outside the brain that are characterized by Nestin overexpression. Think of melanoma, triple negative breast cancer, sarcoma, gastrointestinal tumors, thyroid cancer, what have you. You see in all of these indications upregulation of Nestin, which means that the virus would be active in these tumors while sparing the healthy tissue. Interesting. We've got just about a minute left. Just want to see if there are any questions from the audience at this point. Looking, looking. All right. I'll have one additional question, not nearly as exciting as what we've been talking about, but interesting nonetheless. Could you remind us of the last reported cash position for Candel and potential cash runway? Yeah, we've announced a runway into Q1 2027. This is still correct, and we'll announce the data in the 10-Q shortly. Great. I wanted to say thank you to everyone in the audience today. Also, thank you to Candel. Thank you, Paul- Peter, for joining us today. Thank you very much. Thank you all.