Firstly, thanks to the members of the Research Advisory Board and other key external experts who join us today. Thank you very much for sharing your wisdom and insights during the year, but especially also today. Of course, I want to thank the analysts, some of the best analysts in the industry from the banks who are joining us today to ask us the questions that may be on the mind of many, many people. I want to thank my team and my employees for all the hard work, and especially a big thank you to all the patients and their families. They are the main focus we try to improve the life of patients with huge unmet needs. I'm Paul Peter Tak. I'm the CEO of Candel Therapeutics since more than five years now, and I would like to introduce our programs to you.
Before I do so, you can see on the next slide the forward-looking statement, so I will refer to the website where you can see all the details and get straight into the business. Candel Therapeutics develops viral immunotherapies for very difficult-to-treat solid tumors, and we have basically two clinical platforms. First, CAN-2409, which is a pan-solid tumor off-the-shelf immunotherapy where we have consistently shown positive proof of concept. We have a positive large phase III clinical trial that we're going to discuss in more detail, focused on an area of huge unmet need, which is newly diagnosed localized prostate cancer. We met the primary endpoint based on a large clinical trial in 745 patients supported by secondary endpoints. The study is conducted under a SPA, Special Protocol Assessment agreed with the FDA. That means there is agreement about the design and the primary endpoint.
We got Fast Track designation as well, and then with the data in hand, we went to the new FDA, as I call them, and we got the so-called RMAT designation, Regenerative Medicine Advanced Therapy designation, which is like a breakthrough designation for a gene therapy. We also presented this year positive data based on a small randomized clinical trial in another difficult-to-treat disease, which is borderline resectable pancreatic cancer. This is where we focus on overall survival, which is the hardest endpoint in pancreatic cancer, and we have shown dramatic separation of the overall survival curves between CAN-2409 plus standard of care versus standard of care alone. Based on the data, we got Fast Track designation, we got Orphan Drug Designation from the FDA, and we've started to engage with the European regulators, the EMA, and this was rewarded with an orphan designation from the EMA as well.
In this study, we could start to think in a whole new way about post-progression survival in this very difficult-to-treat form of cancer. And we've replicated these data that we will discuss in more detail in therapy-resistant non-small cell lung cancer. Most of these patients, as you will see, had progressive metastatic disease despite first-line treatment with an immune checkpoint inhibitor. Most of these patients had also been treated with chemotherapy, sometimes multiple lines of chemotherapy, so they have a very poor prognosis with standard of care. We've shown doubling of the expected median overall survival. Here again, we got Fast Track designation from the FDA. We had a very positive End of phase II meeting, which led to the design of a controlled, randomized controlled clinical trial that we expect to start in Q2 of next year, and we're going to discuss this in far more detail.
We also have data in other solid tumors that we don't include in the slide deck, but with a consistently positive result. That's why we feel quite comfortable calling this a pan-solid tumor approach, and we create a pipeline in a product for CAN-2409. So this is our lead asset. The second investigational medicine is called CAN-3110. It works in a different way. It's a replication-competent herpes simplex virus. It's a true oncolytic virus, unlike CAN-2409, which is not an oncolytic virus. It's an approach used for vaccination against the patient's own tumor. But CAN-3110 also has very interesting data in a completely therapy-resistant disease. We'll show you some of the data. This is recurrent high-grade glioma. Most of these patients will have recurrent glioblastoma.
They failed neurosurgical resection and chemotherapy and radiotherapy, and then we injected CAN-3110 with very promising results, which were published recently in very high-impact journals, so we believe that this is an opportunity for Candel where many others have failed, unfortunately, but also this is an enabling indication for other tumors outside the brain that are characterized by the expression of a molecule called nestin. Think of triple-negative breast cancer, potentially melanoma, sarcoma, other tumors, so here again, there's an opportunity at the right time to create another pipeline in a product. In terms of corporate highlights, we're in a good financial situation. We have cash and cash equivalents of $87 million as of the end of September 2025, as we have published, with an expected runway into Q1 2027.
And then very recently, we announced that we entered into a term loan facility with Trinity Capital of up to $130 million, and this was announced last month. We'll speak about IP protection. We tried to create a wall of protection around our assets. Cost of goods, we'll discuss that probably in more detail, are expected to be really low for CAN-2409. It's comparable to many of the vaccines that are out there. So think of the AstraZeneca vaccine for COVID-19 or the Janssen vaccine at the time for COVID-19. These are replication defective adenoviral gene constructs that are not very costly to manufacture. And then we used the time to get ready for BLA submission, also for quite a lot of pre-commercialization activities that we are going to discuss in more detail.
Since I joined this company a little bit more than five years ago, we have consistently done what we promised to the external world, and we intend to try to do this again in the next year. It's going to be a super important year for Candel. You can see that we expect updated clinical data in the next quarter for non-small cell lung cancer. We follow the patients who turn out to be long-term survivors. Again, these are patients who have failed standard of care. So we'll present data in the next few months based on the non-small cell lung cancer phase II clinical trial. Then we expect updated clinical data in Q2, so the next quarter, based on the phase three study that we're going to present in more detail. We have already hit the primary endpoint supported by secondary endpoint.
So the key data are from Q4 last year. Having said that, I think it's good practice to continue to follow these patients over time. And we're going to start to look at the time to biochemical failure, the time to the need to use salvage therapies, typically salvage androgen deprivation therapy, chemical castration, which has a lot of negative impact on quality of life in patients. We want to avoid that or at least to delay it, the time to metastasis. So we hope to present such data in Q2 of next year. Then also in Q2, we hope to involve the first patient into the pivotal randomized controlled phase III clinical trial of CAN-2409 in non-small cell lung cancer.
Then we'll do a study that we will discuss briefly later during this session where we are looking at biodistribution and shedding of CAN-2409 using the most sophisticated and up-to-date biomarkers. That means we're going to inject CAN-2409 into the prostate in a small number of patients, probably about 25 patients. There are no clinical endpoints that we are waiting for, but we are using the occasion actually to take biosamples from these patients to also learn more about the mechanistic immunological biomarker data, similar to what we've done already for CAN-2409 in glioblastoma. It's not an active program, but we had very encouraging data that we published earlier this year in Neuro-Oncology. It just doesn't make sense to have two different assets in glioblastoma. We have data in non-small cell lung cancer, deep biomarker data that we just submitted to a high-impact journal.
We will use the occasion to basically create new scientific data also in newly diagnosed prostate cancer. It's not critical for the BLA submission at all, but it will be important in the future for strategic discussions. Then we talk to pharmaceutical companies. They like to see mechanistic data. It'll also be important in terms of the commercialization efforts. Just think of the sales force that will be able to talk deep science with the treating physicians based on the data that we hope to release in Q3 of next year. And then Q4 is probably going to be the most important for now in the history of Candel Therapeutics. We will have updated overall survival data for CAN-3110 in recurrent glioblastoma. Here again, we are starting to think about long-term survivors, even if that's a minority of the patients.
This is a unique concept in a completely therapy-resistant form of cancer, so we hope to have exciting data at that time. But most importantly, we anticipate BLA filing for CAN-2409 in Q4 next year for newly diagnosed localized prostate cancer. The first thing that I did when I joined this company five years ago was to bring together a brand new executive team that has decades of experience in drug discovery and development, and you can see their background. Since then, we have been together operating as a high-performing team. But even if you believe that you are the top leaders in the field, also scientifically, I think you always need to be aware of potential blind spots, and you always need to embrace peer review. That's why I created the Research Advisory Board, RAB, with the top leaders in the field in oncology and immuno-oncology.
Several of the members are actually on the call today and will present. I should also mention that Ed Benz and Gary Nabel are also members of the board of directors of Candel. This RAB is critically important to us, and they always keep us on the ground with the best science. This was my introduction into Candel. Let's get straight into the next session. You see the overview of what we're going to discuss today. We are not going to spend a lot of time on introductions. Actually, I could speak an hour about the background of the key external experts that we have today on the call, but we'd rather put it actually in the press release. Probably many of these people, or most, do not need an introduction anyway because they're famous.
But you can also see a brief background on the slides that I will present. So what we're going to focus on now is immuno-oncology. What's the next wave of innovation? And I'm going to welcome Doctors Allison, June, Sharma, and Nochomovitz. And I'm going to ask Yigal Nochomovitz to chair this session. Over to you, Yigal. Okay, Yigal, I'm going to hand over to you to moderate this session. Thank you very much.
Great. Thank you very much, Paul Peter. And I am Yigal Nochomovitz, biotech analyst at Citi. And it's very nice to meet all of you, Jim, Carl, and Pam. Thank you very, very much for doing this. So let's just start out with a big high-level question, which is, what makes an immunotherapy target good? And two sort of sub-questions behind that. First of all, why do some IO targets that seem very promising in research labs end up having such different real-world clinical impact and value? And secondly, how does the industry get better at predicting which ones will have the best clinical outcomes? Jim, maybe we can start with you and then move to Pam and to Carl, please. Thank you.
Yeah, I think that the best targets are those that when you either block them or give an agonist signal results in induction of your own immune cells so that you have long-living immunity after whatever drug you used is gone. I think that should be the goal of all immunotherapies. And I think that the reason that we're off sometimes is that things change when you give something, and treatments are based on baseline biopsy, not on treatment biopsies. And I think it'd be useful to really get an idea of what the changes are downstream and get some idea of how the immune system has changed in the local environment of the tumor. We know what a good response looks like.
That can give you not only ideas by knowing what's happened, you can not only get an idea of what you've done, but also what you may be missing because we know what a successful therapy looks like at this point. I would suggest that, although we're getting to the next question, but building an atlas of all the spatial omics data that's beginning to be available from different treatment groups would be a very valuable resource for companies to have so they know a little bit more than just what they see on a TCGA analysis to predict their outcome because that falls way short for many, many reasons of being a predictor. So it's just inducing long-term immunity. That should be the goal.
Thanks. Pam, would you like to add to that?
So I think one of the issues that we're facing right now is that a lot of our model systems are basically in mouse models where we're injecting the tumors, and then a few days later, we're coming in with the treatment. And obviously, in patients, these cancers have been around much, much longer. And so the immune system has had a much longer time to adapt. And so it's important that we take the basic biology that we get out of the laboratory, but it has to be integrated with human data sets, right? I mean, the human immune response longitudinally and what happens over time and collecting the blood samples, the microbiome samples, the tumor samples, and looking at all of that longitudinally so we understand how the immune response is changing and when we can come in with a therapy.
So I mean, again, the immune system, when you perturb it, will always try to have other changes. And so we don't know always what those changes are because we haven't studied things longitudinally in the human immune response. And if we can do that and have a better way of looking at that, then we'll know which combinations to give when because we'll know when the target shows up and when the target is not present because it may only come up after you perturb the system. And that, I think, will help us to then have better results in the clinic compared to what we're getting in mouse models in the lab. So I think integrating is great.
And then I think in terms of biomarkers, we need to start to think about combinatorial biomarker approaches because I think we're always looking at either a genomic biomarker such as MSI status, for example, or an immunologic biomarker such as PD-L1. But what we really need to do is think of things of how these two affect each other. So for example, in certain mutations, for example, ARID1A mutation, you're going to see that that affects the interferon gamma response. And so then you can combine things like the mutations and the immunologic status and try to put that together. So can we have combinatorial biomarkers that can help predict which patients will do better? So I think these are the ways in which the field can move forward.
Carl, what are your thoughts?
Thanks, Yigal. So my point of view would be my interest, how would you combine cell therapies with checkpoint therapies, oncolytic viruses? And so in the case of cell therapies, where we've had a lot of success has been when there's lineage-dependent targets. And we don't have that in solid tumors where we really need to go. And so I think one emerging issue is being able to have targets that are drivers in the tumor. One huge advance now is potentially targeting things like mutated KRAS, and we'll have less escape. But I think we're going to need to have, as Jim said, the ability to trigger an immune response against the total tumor. And that requires the tumor mutational burden. But we need to start the fire and then need to have it be catalytic to broaden out.
All right, great. Well, the second question is sort of tied into the first, and I think you've all alluded to it a bit. But if I could just press a little further, how do we get smarter at predicting which patients will respond best to immunotherapy? And beneath that, is there more than just IO target expression to addressing that? And what other biomarkers or clinical features would you consider important, setting aside, of course, some of the obvious ones like the degree of prior therapy and disease burden, ECOG status, things like that?
I think one of the important things to consider here too is what stage of disease that we're always going in, right? I think a lot of times we've been very focused on stage four disease where patients have got multiple metastatic disease. Obviously, their tumors have gone through multiple variations of mutations as the immune system is trying to keep up. The tumor has learned how to evade the immune response in multiple different ways. Each tumor that's there in the patient's body, whether it's a bone metastasis versus a lung metastasis, has now got its own different niche and microenvironment. And so I would like us to start to think about how to move immunotherapy into earlier disease settings where patients are at high risk for recurrence just from surgery alone.
Maybe we need these neoadjuvant approaches to really get the immune system going while the patient has localized disease. The immune system can take care of metastatic disease if it tries to occur at some point. We need to educate and give the therapies earlier for the immune system to have a chance of really eradicating any metastatic disease that may arise. That comes by coming into the earlier disease setting. How do we select patients in the earlier disease setting? Again, it should be patients who maybe have a higher risk of recurrence from their surgery alone. We certainly know how to stratify patients in many tumor types from that way, especially in solid tumors.
And then again, selecting biomarkers that we know tend to give information about a good immune response, whether, again, interferon gamma, T cell responses, and mutation status of the tumors. And that can help us to select patients better.
I would add that I think we need to take into consideration what happens when you hit the target. And so that, again, would take data looking after the drug is given and taking into account the whole, even before you could, to some extent, anticipate that maybe just marker expression on the tumor or one marker in the tumor is not going to inform what the total microenvironment would be like. It would be useful, for example, to know what the myeloid infiltration is and what the nature of the myeloid cells is to design other drugs or other treatments that might be included. So I think just looking at just the target is really short-sighted. A lot of things could happen that we know are going to happen when you give it, and a lot of things that you're not going to know until you look.
So I think that's very important. It's not just tumor burden. It's what's in that tumor, what the microenvironment looks like before and after you've given your drug.
Carl, is your answer different?
Yeah, I mean, I agree with that. I think we need to understand more about the stroma and what the immunosuppressive mechanisms are in a given tumor. And the huge innovation there is what Jim mentioned, spatial biology. If we have huge databases on that, it's going to really accelerate the entire field. And right now, we're not having cross-learning, really. I don't think enough between different trials and what the tumor microenvironments were and then understanding the escape and resistance mechanisms. So that would be something that everyone would benefit from if we had an atlas of spatial biology of various tumor microenvironments.
All right, very, very helpful. So I guess getting into a little bit more specifics, where do you all see the next wave of innovation for immuno-oncology-based therapies? Are there specific novel targets that you believe are interesting and worth pursuing? If you'd like to highlight any, what do you think about some of the dual-targeting approaches? Of course, we're very familiar with some of the novel bispecifics. Any thoughts on antibody engineering in terms of Fc silent versus Fc active, which has, of course, been a very significant debate in the TIGIT field, as you well know, or anything else that you'd like to highlight that I didn't mention? Jim, maybe you could start.
Yeah, I think novel targets would be those that, again, contribute to giving a healthy overall antibody and T cell response while minimizing negative regulatory input that would shut it down. I think that to the extent that bispecifics work, it's fine as long as, particularly the ones that are coupled to chemotherapeutic agents, I don't think by themselves are going to be curative. If we're going to do that, we need to take advantage of the cell death. And I think that the bottom line, checkpoint blockade, at least, what starts the whole process that you're playing on is cell death. And so ways of achieving that, as with oncolytic viruses, is really a good place to start with almost everything.
Just get some tumor cell death, get the neoantigens and whatever the immune system has a potential to see out there, and then shape the response by knowing the key things that'll play a role in elaborating that response as it plays out so that you get durable immunity. I think that anything that just focuses on killing the tumor cell without doing more is going to fail, and so we need to look for the appropriate combinations that will give more than just a several months prolongation of life or something, but something that will induce the sort of immune response that we know could be curative that we've seen so much with checkpoint blockade.
I want to highlight that I think there are two important pieces that we're going to see moving forward, and we need to really make sure we understand. One are epigenetic pathways and how do epigenetic pathways regulate immune responses? Because I think these epigenetic programming can then be taken advantage of to target these pathways in combination with immune checkpoint therapy, in combination with CAR T cell therapy. Because I think if we can epigenetically reprogram cells, not just T cells, but myeloid cells and other cell types, then we're going to see a great step forward in the immuno-oncology space. The other thing I want to highlight is that RNA vaccines are turning out to be very powerful. Obviously, we saw the COVID mRNA vaccine have impact.
I only think RNA vaccines in the cancer immunotherapy space are also showing a great deal of promise and how we can take advantage of the pathways that mRNA vaccines initiate, right? These sort of danger pathways, these innate immune response pathways that mRNA vaccines can then initiate, and then we can bring in the adaptive immune response with sort of the T cell therapy treatments that we're giving, so I think these are two things that I see moving forward in the future, and I hope we can take full advantage of them to bring benefit to patients.
Yeah, and I would just expand on that. I think in addition to this emerging area of oncolytic viruses, engineered viruses, we're going to see an explosion of in vivo therapies, as Pam mentioned. RNA vaccines, targeted lipid nanoparticles, in vivo CAR manufacturing, and so on can all happen now with the new in vivo delivery approaches, and I think that will be able to boost responses from both cell therapies and IO checkpoint therapies. So I think we're really going to have a convergence that way with these new toolboxes in addition to the increasingly sophisticated bispecific antibodies.
Great. Well, you all sort of pre-answered my next question, which is fine. I was going to ask about the combo approaches with non-IO-based therapies and which tend to be most effective. You mentioned a lot of things, including the oncolytic viruses, T cell therapies, the RNA vaccines, LNPs, in vivo LNPs, in vivo CARs. Maybe just spend a little bit of time talking about which of those may seem more promising in combination with IO. Do they all have to be tried? Do they all have different advantages or different disadvantages? If you could just expand on that line of thinking, please.
I do think that they're all going to have to be tried in some ways, right? Because although all of these look promising in preclinical settings, I think we need the clinical data, at least 10 or 20 patients. I'm a big proponent of saying 10 or 20 patients to test the concept, collect all the samples from those patients to understand whether you really targeted the appropriate biologic pathways and immunologic pathways to get outcomes for our patients. That needs to be looked at. So I think we can do small trials where we ask the question, did this combination effectively change the immune response in a way that we would like to see? And did we see any clinical outcomes that's a signal for then expanding that into larger numbers of patients to look at? So I think those are the things that will need to be done.
I don't know that we can haphazardly just choose which one will go just based on the preclinical data, because I have to say the preclinical data is looking very good in many of these different combinations. It's just whether or not they'll translate in the clinic. The one other thing I want to highlight is that let's not forget that we have our known treatments in cancer, right? Surgery, radiation therapy, chemotherapy. These are known pillars that work well in cancer patients, and how do we combine immunotherapy with these becomes very important, so recently, we were able to show that surgery, for example, even in the metastatic disease setting, if you take out a single lesion, usually we wouldn't do that because surgeons don't like to take out a single lesion and leave a lot of other metastatic lesions around because what's the point in removing one lesion?
But what we're showing is that by removing a single lesion, you are changing the immune response and the antigen load. And so you can get benefit then with surgery and immune checkpoint therapy. And so we showed some of this data in a pilot study, and I think this needs to now move on to larger studies. So I do think combinations that can get us in that direction, how do we combine these different things and why combine them? What's the mechanism behind combining them becomes important.
Great. As we kind of wrap up here in the last few minutes, I'd be curious to get your thoughts just at a high level. What has surprised you most as all of you as pioneers in the field of immunotherapy? What has surprised you most in terms of what's worked unexpectedly, what hasn't worked that you may have expected should work? And then more specifically, I'd be curious to get your thoughts on, Jim, you mentioned oncolytic viruses, but I'd be curious to get all of your thoughts on viral immunotherapies for solid tumors and what you think of the potential of that modality.
Go ahead.
As we've talked a little bit, we've hit on mouse models and how they can be a little bit informative, but don't tell the whole story. My lab has quite a bit of experience of different ways of combining ways of killing tumors with immunotherapy. It's amazing how well most of them work, I think. The oncolytic viruses definitely have a good place, and there's a good, pretty clean way of doing it while causing other things that could come along.
But I think that what we need to do is, while we're thinking of all these new agents and everything, is also perhaps think, and Pam sort of hinted at this, so the way we do trials of phase I, phase II, phase III, that sort of paradigm in immunotherapies is kind of not really so useful anymore because with the monotherapies, you can see some efficacy in phase I and stuff. But as you go on, it's going to become, I think it's becoming apparent that we could do a lot by combining two or three things. But we've got to get beyond the idea of basing a treatment on baseline biopsies, treating a few patients for safety, and then doing a huge phase III trial. It makes no sense.
You should be starting off with smaller trials, as Pam said, doing whatever you think you can do, adding a combination, seeing the effect. After a while, you learn what's there, what's missing, including epigenetic changes, all this stuff, and just a way of looking more clearly. I think some of the things, some very good agents have been just dropped because they were tried as single agents to start out with when there are things that you might see in an analysis of a tumor, but they're not there at the start. They're induced by something else you do, and it would be good to hit these secondary targets.
But when people say, "Oh, that's a good target," and try it by the normal way, it fails, and you reject it, and you've killed a drug, which might be very useful if you just added it to the other one or used it afterwards. So we've got to use our brains a little bit more because we're throwing away useful drugs that could be useful and wasting a lot of patients by doing 500-patient, 700-patient phase III on things that mechanistically are unsound or untested. I think we need to take a close look at that and get more out of our patients and more out of our trials.
Yeah, I'd just like to say we have, it's been, in my experience, very difficult to do these combination trials that we need, as what Jim just pointed out.
There's this issue of the paradigm that the so-called binary funding black hole, where when you get these trials started, it's twice the technical risk for a single clinical payoff. It's very hard to get companies to do this. I think we need a new kind of IIT trial system so that we can do academic trials like this that Jim was pointing out at our advanced cancer centers. And they have that in China. We can't do it here. It would very much accelerate this if we would change our regulatory paradigm.
Okay. You mentioned combos and being able to test multiple things at once. Would that suggest that bispecifics or even trispecifics, there's some of these trispecific T cell engagers out there, do those become more interesting because you can test multiple things at once and sort of get around some of these operational challenges, as you've alluded to?
I think one of the issues with trying to put everything all together as in trispecific or bispecific, right? We don't understand sometimes all of the steric interferences that may come with having these agents combined rather than giving them singly. Also, we don't have all of the biology that we understand from the single agent alone, much less coming in with bispecific and trispecific, right? We don't know how the human immune response is changing in response to a single agent. We may not even know what the target and ligand or receptor ligand pairs are. You mentioned TIGIT, for example, and everyone is disappointed about the TIGIT failures that we've seen. But I mean, I think the biology of TIGIT and how TIGIT, what's the receptor ligand paired that's most important in that TIGIT pathway and what's the signaling downstream is still unknown.
So I think sometimes we move so quickly to bispecific, trispecifics without understanding some of the biology behind a single agent by itself that that may also hamper us as we get into clinic. But again, it's a matter of trial in the patients and then seeing what that data points to before we can make next decisions. So I do think those are things we have to look at. I'm very convinced that combination therapies are going to be the way to move forward. And obviously, we all have seen data where good combinations can be meaningful in patients.
And again, in order to test those combinations, I think small 10 or 20 patient trials put together the combination that you see that the biology made sense in a preclinical data set, take that into 10 or 20 patients and make sure that the biology replicates from that preclinical data set into human data and then move that forward into larger trials. And I think those are the pieces that we have to put in place.
All right. And last question here, just literally in the last four minutes, we can kind of go rapid fire. Jim, you mentioned TCGA not being enough. Carl, you mentioned AI and spatial biology. I'd be just curious what each of you are doing at your respective institutions with respect to big data, with respect to machine learning, AI to sort of solve for this massive data question and uncover hidden signals in tumors and in tumor progression and how tumors respond to therapies that could benefit patients.
We've taken a step, I guess, in that direction by sharing all the spatial data, all the data that we have with the group here that does data science analysis and giving all the data, coupled with all the patient data and everything to them so they can, down the road, maybe use an AI approach to putting it all together. But I think it's sharing the data, especially all this mechanistic data, with the patient in clinical outcome to just see what's going on in an objective way where we could start making informed decisions about more complicated issues than just whether something is safe and works better than the standard chemo.
Yeah, I would think, in addition, I mean, we have in our comprehensive cancer centers, our databases and emerging spatial biology, very large data sets.
We need to have ways to encourage companies when they do these post-treatment biopsies so that those can come into analysis and not just treating patients. But if we have samples after treatment, then it's really going to, I think, really uncover these mechanisms of resistance that right now we just can't understand. And so we need a coordinated response. This is something that I think the NCI in the U.S. could take leadership on to help fund this because we each have our own foxholes at our cancer centers. But to tie them all together would be, I think, a really large value add. Yeah.
Yeah, I want to stress that I think it's so important now that computational biologists, bioinformaticians become a part of our daily lab work that we're doing, right? Biology, computational, and bioinformatics expertise have to sit together at the same lab bench and the same labs and help to make all of this move forward. I also think it's so important that we bring multiple stakeholders at the table from the federal government, the NCI, these academic centers, and the big groups who are so good at looking at data, right? The Googles of the world, the Microsofts of the world. We have to bring all of this. I mean, I think about all the things we can do on the internet and the way OpenAI and the world is changing.
They have to be a part of our conversations as we're developing these therapies and as we're looking for how to interpret the data. We need to bring down the silos and the walls that separate academic medicine from the computational experts that exist out there. So we have to really try and come up with a new paradigm for how to work between these different fields that we haven't seen before.
All right. Well, on that forward-looking and optimistic thought, Pam, thank you very much. Jim, Carl, thank you all very, very much for doing this. And I will turn it back to Paul Peter to continue the session.
Thank you.
Yeah, thank you very much for this super interesting session. Some of the key points while we move to the next session include the importance potentially of inducing immunogenic cell death. That's exactly what we are doing, as we will discuss in a minute with CAN-2409, the importance of small clinical trials where you try to learn as much as possible, a concept that we call experimental medicine clinical trials. We'll give you an example today, or two actually, in non-small cell lung cancer, phase II A clinical trial, open label in completely therapy-resistant disease. There's no placebo effect there. There's no regression to the mean, no impact of expectation bias. So if you see something, you know it's real. It provides the rationale to do the large conventional clinical trials that you will need for the regulators. Same is true for recurrent glioblastoma.
We also heard the importance of the combination with standard of care therapies, and that's what we're going to discuss now for newly diagnosed localized prostate cancer. Everything that works in end-stage disease will probably work even better in earlier disease. So this is a big unmet need where we focus on newly diagnosed patients and where we combine CAN-2409 versus placebo with standard of care radiotherapy to improve outcomes. So it's a real pleasure to welcome the next set of speakers. I need to make sure that I go to the next slide. We have here Dr. Gejerman, Kantoff, Nichols, Tutrone, and this session will be moderated in the discussion by Oliver McCammon. Before we go there, I'm going to ask Garrett Nichols, our CMO, to take us through some of the highlights of the data.
Thank you, Paul Peter. So Candel is addressing a clear unmet patient need, and the opportunity in the United States alone is quite large for CAN-2409. There are over 150,000 patients that are diagnosed with newly diagnosed localized prostate cancer with intermediate- or high-risk every year, and approximately 65,000 of these currently receive radiotherapy. But these patients basically have suboptimal standard of care options, including the risk for recurrence, which is anywhere between 30% to up to 50% in high-risk patients, and the toxicities that are associated with long-term ADT and the costs related thereof. Next slide. So the target product profile for CAN-2409 is shown here. We look for an indication in newly diagnosed localized prostate cancer in patients with intermediate- to high-risk disease. This drug is administered in combination with standard of care external beam radiation therapy with or without short course ADT or androgen deprivation therapy.
The drug is given as three courses of intraprostatic injections, two mL total volume per injection course, followed by 14 days of valacyclovir orally after each injection course, so CAN-2409 is an investigational, off-the-shelf, replication defective adenovirus. This is designed to deliver the herpes simplex virus thymidine kinase gene directly into a patient's tumor. We inject it intratumorally, and once into the tumor, the thymidine kinase enzyme converts the oral prodrug valacyclovir into DNA incorporating nucleotide analogs that lead to immunogenic cell death in the dividing tumor with the release of a variety of different tumor antigens. The adenovirus capsid protein also inflames the tumor microenvironment through the induction of pro-inflammatory cytokines, chemokines, and adhesion molecules, and together, this regimen is designed to induce an individualized and specific CD8 T cell mediated response against the injected tumor and the uninjected metastasis via in situ immunization against the patient's own tumor antigens.
We conducted a phase III clinical trial of CAN-2409 in 745 patients with newly diagnosed intermediate to high-risk localized prostate cancer. These patients were randomized two to one to three courses of CAN-2409 injections plus valacyclovir or three courses of placebo injections plus valacyclovir, both in combination with standard of care radiotherapy with or without short course ADT, which was a stratification factor. The primary endpoint was disease-free survival, which was the time to cancer recurrence or death due to any cause, and the study was conducted under agreement with the FDA under a Special Protocol Assessment. The injection procedure is shown here. It's a routine and well-tolerated outpatient procedure that is delivered by urologist or radiation oncologist in an outpatient clinic. The injections are given via ultrasound-guided injections as shown on the schedule on the right. Course one is approximately two to three weeks before the start of radiotherapy.
Course two is in conjunction with the start of radiotherapy, and course three is approximately two to three weeks after the prior injection. So when we ask patients, "How did you tolerate the study procedure compared to a prostate biopsy?" Most patients indicated that regardless of transperineal or transrectal approaches, they tolerated the intraprostatic injections the same or better than their routine prostate biopsies. Here we're showing the primary endpoint of the phase III study. CAN-2409 significantly improved disease-free survival with a 30% risk reduction in disease recurrence, including death from any cause compared to standard of care alone. The hazard ratio, again, was 0.7, and the p-value was 0.0155. This was after a median of approximately 50 months of follow-up.
When one looks at prostate cancer-specific disease-free survival, we showed an even greater effect with a 38% reduction in the risk for prostate cancer recurrence or prostate cancer-related death. This was highly statistically significant with a p-value of 0.0046. Other key secondary endpoints were also supportive. There was a significant increase in the proportion of patients achieving a prostate-specific antigen nadir of less than 0.2 nanograms per mL in the treatment arm compared to the placebo arm, 67% versus 58.6% with a p-value of 0.0164. As expected over this short period of follow-up, overall survival was similar by treatment arm. Only two deaths were due to prostate cancer in this timeframe. 50 patients did die due to other causes but unrelated to treatment. In an exploratory analysis, we also looked at the rate of pathologic complete response compared to the placebo arm.
At two years after the completion of radiotherapy, 80.4% of patients treated with CAN-2409 were free of prostate cancer in the two-year biopsy versus 63.6%, and this was highly statistically significant. This is important because positive biopsies greater than two years after radiotherapy are predictive of metastasis and cancer-related mortality after long-term follow-up of 10 to 15 years. In the meta-analysis presented here, patients with a positive biopsy greater than two years after radiotherapy had a tenfold higher odds for developing biochemical failure, threefold higher odds of developing distant metastasis, and fivefold higher odds of dying from the prostate cancer.
In conclusion, our phase III clinical trial of CAN-2409 achieved a statistically significant primary endpoint, improving disease-free survival in patients with intermediate- to high-risk localized prostate cancer with supportive secondary and supplemental endpoints as shown here and presented previously, and also with a very compelling safety profile with a lower incidence of serious adverse events and treatment-related SAEs in the active arm versus control. At this time, I'll hand it over to Oliver to chair the presentation.
Thank you, Dr. Nichols. My name is Oliver McCammon, and I'm one of the equity research analysts at LifeSci Capital. I'd like to thank each of the experts for joining us today, Dr. Gejerman, Dr. Tutrone, and Dr. Kantoff. Perhaps we can get right into questions. It'd be helpful, I think, to hear a view from each of you on what is the goal in patients who seek curative treatment for their localized prostate cancer? Again, I'll open this up to the group if there's anyone who wants to take a first stab at it.
Sure, I'll jump in. I'm an outlier here. I'm a medical oncologist, but I was fortunate during my career to see a lot of patients who were diagnosed with localized prostate cancer. So I just want to make it clear that there are many patients who are diagnosed with prostate cancer who don't need to be treated. Low-grade prostate cancer, for the most part, is something that can be observed. It's really the patients with intermediate or high-grade prostate cancer or high-risk prostate cancer. And the goal of treatment is at least optimally to cure the patient, to render the patient free of disease for the rest of his life. If not, to avoid recurrence as long as possible because once a patient recurs, there's an increased need for subsequent therapies.
And the most immediate subsequent therapy after relapse from localized prostate cancer is androgen deprivation therapy, sometimes known as hormonal therapy, and that's associated with significant side effects. So if that can be avoided, that is a significant breakthrough. So once again, for those that need to be cured, cure. If not, delay the time until subsequent therapies. Thank you.
Dr. Tutrone and Dr. Gejerman, anything to add there?
Sure. So I mean, that was a great summary. You know, it's fascinating that we've made so many strides in the management of localized prostate cancer. So let's take the extremes. Let's start with the low risk and then the high risk. So for low-risk patients, we've really learned to sort out which patients need therapy, which ones do not. So improvements in imaging with MRI, PSMA scans, improvement in looking at genomic classifiers to really better assess the risk beyond just Gleason score and PSA. That's really helped us sort out which patients at the lower end of the spectrum can be safely observed. Similarly, for the high-risk patients, we've made great strides with our medical oncology colleagues in terms of doublets, triplets, when to add systemic therapy to local therapy.
It's more of the middle ground, the intermediate group, which, as it turns out to be, it's the largest group of patients that we encounter. There haven't been as many strides. So research like this where we can try to improve the local control is extremely important. And I think that patients really flock to this innovation in that when we sit down with them and say, "Look, we have an ability to treat you, improve your chances for long-term cure, and keep your quality of life high," that was something the patient was very interested in.
I'd like to dovetail. Those are great summaries Phil and Glen gave, but I'd like to dovetail. That's the goal of treatment is cure, and with surgery, we have a very simple objective measure, which is the PSA. It should be undetectable. The challenge we have is that in patients who choose radiation, which is almost half of the patients with intermediate and high risk, the PSA is not as accurate. It's black and white with surgery that it should be zero undetectable, but with radiation, the definition is a little more gray. It's having a PSA less than one, and a lot of patients following radiation will have a bounce of their PSA. It will go up and down, and that creates a lot of stress in their lives.
And so that's where the challenge is in trying to calm patients down and not worry so much about the PSA and all the anxiety of it. And as Dr. Nichols nicely showed that the PSA in patients who receive CAN-2409 is significantly lower compared to placebo.
That's a nice segue to my next question, which is, what is the impact of the fear of recurrence and cancer-related anxiety on patients? And how do you think this reads into the choice of definitive upfront therapy for their localized prostate cancer? Again, I'll open it up to the group if there's anyone who wants to start.
I ended with the talking about the patient's anxiety, so I'll continue. I see a lot of patients in my busy clinical practice, and it's tangible. They really do worry. When patients usually come in after their radiation annually, they are just hovering and just have a lot of anxiety attached to what their PSA value is. Again, in surgery, it's black and white. If the PSA is undetectable, great. But following radiation, the PSA may go from 0.2 to 0.4, and patients literally will freak out about that. So there's a lot of anxiety with it. I'll turn it over to Phil and Glen.
Sure. As a medical oncologist, the diagnosis of cancer is devastating. There's a lot of fear, anxiety associated with it. So with other cancers, we use imaging for the most part as the biomarker of recurrence. In prostate cancer, we use the PSA. The PSA has been a fantastic advance with regard to diagnosis and management of patients. But as Ron pointed out and Glen pointed out, the anxiety associated with a rising PSA after local therapy is really significant. So the ability to diminish the likelihood of recurrence from a psychological quality of life standpoint cannot be understated.
Yeah, these are great comments. I mean, I think the key word is anxiety. When patients are diagnosed invariably, they say, "Just remove it. I want it out of me." Patients in their 50s, patients in their 80s, "Just remove it." And then as they begin to layer on more information, they begin to assimilate what they're hearing from their physicians, from their consultations, is that, "Wait a minute, I probably can be, certainly if I'm in the intermediate group, I can expect a good long-term survival." And I want to look at quality of life as well. But quality of life is not just, "Are they sexually active? Are they good in terms of urine control?" It's also the psychological piece of it, which is the anxiety. And so patients really want to maximize the ability to achieve a cure.
That's why these interventions that we can add and layer on to either surgery, active surveillance, or radiation are super important.
Very helpful. So I think for the next question, could you remind us just of the rate of recurrence after radiotherapy or radical prostatectomy in the context of initial definitive therapy? And then in patients who do face recurrence, generally, how are you approaching treatment there? Maybe Dr. Tutrone will start with you again.
Overall, I tell patients the rate of recurrence is roughly 30%. One out of three patients is going to recur with a PSA recurrence, but certainly in patients with higher-risk cancer, that could be up to 50%. It's challenging with treatment options when they do recur. As Dr. Kantoff pointed out earlier, the mainstay has been androgen deprivation therapy, but in a lot of patients following surgery, we may do salvage radiation. Following radiation, there's a lot of options, including salvage radiation with brachytherapy or seeds or external beam radiation. We have high-intensity focused ultrasound and cryotherapy, but these treatments have a lot of negative side effects that really negatively impact patients' quality of lives and really could be devastating, and so anything we can do to reduce that risk of a 30%-50% recurrence is tremendous.
I think that's a great summary, Ron. The only thing that I would add is traditionally, the type of patient who gets radiation therapy for their prostate cancer tends to have a slightly more, I'm going to use the word aggressive, for lack of a better word, than patients who are treated with surgery. That may be evolving. I'd love to hear what Glen and Ron have to say about that. But for the most part, patients treated with radiation have a higher disease burden and maybe higher-grade cancer, so their recurrence rates are higher. And that's the population that we're targeting with this therapy. So anything that can reduce the recurrence rates, and Ron, I agree with your estimates with regard to recurrence rates, anything that can be done to reduce the rate of recurrence in patients treated with radiation is really an important advance.
Excellent points. And you know it's an interesting question you asked. It should be straightforward. And the published data is very clear. It's about 30% after radiotherapy. But there's more nuance to that, right? So decades ago, we did not have PSMA scans. And we're finding so many patients now that we think are great candidates, all localized, when we put them through the scanning, find that there is micrometastatic disease. And so I think that as we're getting better with our imaging techniques, we're probably going to sort out which patients are truly localized, and perhaps that 30% number comes down. Maybe it won't be 30% recurrence. Maybe it'll be 20%.
Additionally, now with genomic classifiers and looking at things like being able to really dive in just more than just Gleason score, but sorting out which patients have best risks for achieving a complete cure, perhaps that number changes. Again, it's not something that we can avoid, though. I mean, I tell patients all the time, "Look, you've got a great chance. If we really see that you're localized, you've got a great chance to cure." But everything we do now to maximize that upfront is better because all the additional therapies that we use for salvage, as was pointed out, are quite toxic.
Very helpful. We all touched on ADT briefly. Can you remind us just of the safety profile of ADT based on your clinical experience, as well as some of the potential long-term consequences of this therapy for the localized prostate cancer group? Perhaps Dr. Kantoff, starting with you.
Thank you. So traditionally, ADT was giving a drug that lowers the production of testosterone.
Comments on that?
I think it was a great summary. It's certainly not a benign medication. It's a great drug when it's necessary, but there are real impacts, and I would say probably about 20% of my practice is managing post-ADT symptomatology, so whether that's erectile dysfunction, we have a very active bone health clinic where patients go for DEXA scans, bone density studies, and I would say about 30%-40% of them, we do find that have osteoporosis or osteopenia with a high risk for a bone fracture, and we have to manage these patients with Prolia and other medications, so the goal of eliminating ADT is a very important goal when we can't safely.
Dr. Tutrone?
Yeah, I'd just like to add that when I sit there and tell patients they have prostate cancer, the first thing I'll say to them is most men with prostate cancer don't die from prostate cancer. They die with it. And the leading cause of death in men with prostate cancer is, in fact, heart attack. And so putting patients on ADT, in addition to all the side effects Dr. Kantoff had mentioned, it increases your risk of a major adverse cardiac event by 30%. And that's defined as a heart attack, stroke, or a blood clot. So adding ADT significantly puts patients at risk for death from cardiac events.
Very helpful. So turning to Candel's phase III trial data, I'll just open it up to the group again. How meaningful are the data from CAN-2409 in terms of preventing recurrence? Dr. Kantoff?
Yeah, I mean, first of all, it's a remarkable study. I think biologically, it's fascinating to me. And the evidence that's positive here is, number one, a reduction in the number of positive biopsies after treatment, which denotes that the therapy being used here has a greater chance of curing patients. The second piece here that's really very interesting is the nadir, the lowest point that PSA gets after therapy. And it's clearly significantly lower with the combination using CAN-2409 than without using it. So it's my anticipation that this will translate eventually into significant clinical benefit, let alone the issues of anxiety associated with PSA recurrence. But it's my anticipation that this will translate into a low rate of metastasis and an improvement in overall survival.
Dr. Tutrone?
Sure. I think Phil gave a great overview of the positive results. But I'd like to step back from 30,000-foot view and say back in the early 2000s, I was involved with a trial on immunotherapy for prostate cancer called Provenge, which got FDA approval in 2010. And it was the first immunotherapy for any cancer. And it was for prostate cancer. But these men had very advanced metastatic castrate-resistant prostate cancer. What's exciting to me is that this therapy, immunotherapy, is being brought in way earlier in the disease state. So it's exciting. And anything we could add to local therapy, like radiation, and we know that adding immunotherapy earlier in the disease will translate to better long-term overall survival. And that's what got Provenge FDA approved, was based upon an increase and improvement in overall survival. Now, this study is a little young. It was four-year data.
But we know that the PSA nadir was much better in these patients. They had a lower positive biopsy rate when they received CAN-2409. And they had almost a 40% reduction in disease recurrence. So that's really exciting to me, is getting this therapy, immunotherapy, in earlier.
Dr. Gejerman?
Yeah, great comments. Look, in terms of the primary endpoints and secondary endpoints, it was a great study. But many patients say to me, "You had me at immunotherapy," because patients are aware of immunotherapy for other tumor models. And it captures their imagination. We're going to put this drug directly into where your tumor is, that appeal to them. And what really appeals to many of them is that, "Wait a minute. I have a choice. I can avoid ADT and still maximize my chance of cure." It was very easy to enroll patients on this study. And I think that's going to have a major impact in terms of patients and physicians embracing this as an additional modality.
Really appreciate that. And I wanted to check in, too, on the administration profile. Is the intratumoral administration of CAN-2409 difficult? Does it need to be done in specialized centers? And how do you overall think about the safety and tolerability profile? Maybe Dr. Gejerman, we'll go back to you.
Yeah, it really was straightforward. I mean, this is really our wheelhouse, whether it's urology or radiation oncology. We're constantly using ultrasound-guided transperineal, either for a biopsy or for implanting fiducial markers to help aim the radiation or for rectal spacers. So it's something that we do every day. And it doesn't really add a lot in terms of procedures because patients are going to be getting, if they're getting radiotherapy, they're going to get fiducials and a rectal spacer anyway, typically done in either one or two procedures. So we're not adding a lot of procedures. It was extremely well tolerated. We had very, very little toxicity from it. The only significant toxicity is just maybe taking the valacyclovir. But even that was a little bit of minor renal issues. And once we adjusted the medication, we had no problems.
Very helpful. Dr. Tutrone and Dr. Kantoff, I'd be curious to hear from you and as well whether this administration profile you think could fit within the community setting in particular. Dr. Tutrone?
Yes, I'm going to just echo what Glen just said. It's very simple and right in the wheelhouse. It's like doing a block, a numbing of the prostate prior to doing a biopsy. So it's nothing like a biopsy. It's much, much simpler, and anyone could perform it.
Very helpful. Dr. Kantoff, anything to add?
Not really. I did not participate in the study. I'm not a urologist. I don't inject prostates. I'll leave that to Ron and Glen. From what I can see of the toxicity profile, it's really pretty minimal compared to many of the other therapies that we use in oncology.
Very helpful. The final question for me is, would you expect that after extended follow-up, CAN-2409 will be able to prevent or delay development of metastasis and the need for salvage therapies, recognizing that we've seen DFS data so far, and potentially avoid long-term or salvage therapies such as ADT? Dr. Kantoff, maybe we'll go back to you.
Yeah. So first of all, I think very strongly that it will diminish the need for salvage therapies. We've talked about that. If you diminish the frequency of recurrence, you'll decrease the need for androgen deprivation therapy, and I think that that is highly likely to be the case. As Ron pointed out, and Glen as well, these are people that live, particularly intermediate risk patients, live 10 to 15 years after diagnosis, so there are significant competing causes of mortality, and as Ron pointed out, cardiovascular disease is a leading cause of that, so although I'm optimistic that it will diminish metastasis and prostate cancer-specific survival, I think time will tell whether that will, in fact, be the case.
And anything from Dr. Tutrone and Dr. Gejerman?
I fully echo Phil's comments, and I say to patients, I'm in a race with their cardiologist to see who's going to win, whether they're going to die from a heart attack or the prostate cancer, and I will say that having CAN-2409 in our armamentarium is going to very much favor urologists winning this race and radiation doctors.
I agree with those statements.
I'd like to thank you all for the time today. Really appreciate it.
Thank you.
Thanks.
Thank you all for a great discussion. So we have achieved the primary endpoint, as you heard. It's clinically meaningful. This is supported by secondary endpoint. So people asked us, why are you not actually filing the BLA yet? But more work needs to be done. We're doing a lot of work, actually, in the background in terms of regulatory work, but also getting ready for commercial manufacturing, which we summarize as the roadmap to Biologics License Application. So it's a great pleasure to introduce the next session where we're going to give you more insight into all the work that has been going on and that is going on and that is on track. So welcome to Sue Stewart, the Chief Regulatory Officer, Seshu Tiagarajan, the Chief Technical Officer, and the moderator, Andres Maldonado.
Before we get into the discussion, I'm going to hand over to Sue Stewart, who will then hand over to Seshu to take us through some of the data.
Thank you, Paul Peter. I'm really happy to be able to present the progress we've made on getting to a BLA filing and pleased to say that we are on track for submission, as we've been stating, at the end of next year. I wanted to remind everyone, and I know Paul Peter mentioned it earlier, that we have been granted Fast Track designation and also Regenerative Medicine Advanced Therapy, RMAT designation this year, which are these elevated designations that help FDA work with us to accelerate, where possible, our development toward BLA. I pulled out this box here, just a reminder of what the benefits are and what we will be able to take advantage of in terms of the RMAT designation.
Everything that you hear about gaining through Breakthrough Therapy designation, often given to drug products, are available under the RMAT, which is specific to cell and gene therapy with CBER. And that is, again, working very closely with FDA, with their more senior people, in many cases, to ensure that we are all operating to the most efficient guidelines and pathways. The opportunity to be able to conduct a rolling submission process within the BLA, which would get sections to the FDA earlier than the final BLA full submission, which could give potential from some early reviews there. Expedited review, which is an additional review under the jurisdiction of reviewers that could cut the time even shorter. And that is sort of a nuance that is only available in the FDA's own regulatory SOPs, to understand it.
In some cases, this is where people are able to potentially get accelerated approvals. That is not something that we're pursuing. All meetings get converted now to mostly Type B, which you know is one of the more quick meetings to get, or even a Type A, depending on the circumstances. To the left is just a little update on where we've been already leveraging advantage under the RMAT. We have had a pediatric plan waiver granted already. I mean, this is prostate cancer. We are eligible for Priority Review, which shortens to six months once the BLA is accepted for filing. I mentioned an expedited review is possible at the discretion of reviewers. Rolling reviews are eligible. We will be eligible to file a small business fee waiver request at the time we file.
I think, as you know, the current 2026 filing fee is over $4 million. So we'd like to waive that. You could move the slide. Thank you. Just to give you an idea, leveraging the RMAT designation is really important. We've been just utilizing this to meet with FDA on a number of topics so that we can risk mitigate and continue to know that when we get to BLA, we will have achieved the goals. We've had certain elements that are very important. For instance, the RCA spec we've had discussions about and the assay. And Seshu will go into much more detail about what this means. And also, we've cleared the way for our tox plan and biodistribution and shedding in clinical environment. Also cleared our proposal for a comparability protocol.
Just to bring in the lung program for a minute, we had a really highly successful End of phase II/pre-phase III meeting this year, which paves the way with a green light toward a registration study. I will tell you a little bit more of the outcomes there. The reason that I bring this together is anything we learn with prostate or lung contributes to the other program. Next slide. This is a really high-level diagram to show all the swim lanes. A BLA is made up of modules. Primarily, we are looking to provide non-clinical information, clinical, CMC, some administrative-type information. This maps what you can tell are the different activities within each of these swim lanes that are all moving us toward a filing. At the very bottom is places where either we've had meetings or we're planning meetings.
We want, again, to continually utilize this availability of the FDA team as we continue moving forward in the BLA with an anticipated submission in Q4 next year. Thank you. So to give you an overview of the key takeaways from the meetings to date, as I said, we're utilizing the RMAT to the extent possible. FDA's aligned with us on RCA. FDA's aligned with us on this is critical that we get early agreement on what our toxicology package is going to look like and also how we will evaluate clinical biodistribution and shedding. FDA is also aligned with us in how we're approaching comparability, which is really important, moving from clinical to commercial-stage material. And again, Seshu will cover this in a little more detail. And we're in ongoing discussions even on procedural things so that there's no bump in the road once we file.
Okay. Shall I take it from here soon?
Yes, please.
Okay. Thank you very much, and a very good morning and a good afternoon to everyone. I'd like to start with technical successes from the technical operations group, especially it's a large effort from not only just Candel folks, but also our CDMOs and CROs. At the beginning, in the first half of this year, we had a successful GMP run, which was actually scheduled for quarter three. With the help of the CDMO, we were able to move it into May and June of this year and complete it successfully. Following that, we had some successful DP fills. Currently, as we speak, our second GMP run is ongoing. This uses the new commercial, not the new, but the commercial master cell bank and the commercial working cell bank, which have been vialed, and the testings are ongoing for them.
Similarly, commercial viral bank has been vialed, and the testing is ongoing for that. And this commercial viral bank was actually produced from the first GMP one run that I mentioned just a minute ago. In addition to that, our relative potency assay has been qualified ahead of schedule, and it's currently undergoing validation. Other assay qualifications and validations are also on track. RCA assay is a critical assay, and that assay development is complete, and it's moving into qualification and validation stage. As Sue mentioned, we've had a couple of meetings with the FDA on RCA and comparability, and these were hugely successful and very productive. As a result of that, we now have a clear roadmap and alignment for executing analytical comparability. And we've also aligned with FDA on the PPQ strategy. So how does all this convert into a timeline slide? So the next slide, please.
We've been working with our manufacturing partner, that is SAFC, since quarter four of 2022. And by the end of 2023, we had already tech transferred the process, scaled it up from a three titer to 10-liter to 50-liter, locked the process, and then performed and executed a large-scale run in the PD area. This was by December 2023. Moving forward, in 2024, we completed an engineering run. And then the minute the phase three became positive, we triggered all the CMC activities that you will see now, here, now, here, and in other places. I already started mentioning some of those earlier. So we successfully completed the GMP run in May, June of this year. And the reason this is very critical is because this generated the commercial viral bank, which is now being used in the GMP two run that is happening right now.
The GMP two run uses the commercial working cell bank and the commercial viral bank, and it is our commercial process, and it sets the basis for our PPQ runs next year and for all the commercial runs coming in future, so these are the main activities that have happened so far, and what is coming up in next year is PPQ runs, which is process performance qualification or process validation runs and comparability testing. These are two high-level, high-ticket items, and these all will go into the BLA filing for quarter four of next year, but next slide, we'll talk about all the critical work streams and just some of them because there's so much going on. We can't really present all the work streams here.
So if we were to take another look at the manufacturing progress, we've completed four large-scale runs, three that have been completed, and the fourth that's ongoing as we speak. These are at the commercial scale of 200 liters. We've also had a few 50-liter runs under our belt completed at SAFC. As I mentioned, we completed two DP fills earlier in this year, and we are scheduled to do three more DP fills between December and January. I've mentioned about the master cell bank and the working cell bank and the commercial viral bank. From a PPQ perspective, all activities are on track. Master validation plan is currently ongoing, and process characterization is currently ongoing. From an analytical perspective, the assay qualification and validation is on track. The comparability plan is aligned with the FDA, and the comparability protocol is currently being drafted.
Now, as I mentioned, there are a lot of work streams that are going behind all of this. So I just chose a few to mention. All these work streams are priority one. So it's very hard to choose some and not the others. But some other critical work streams are supply chain and launch readiness, shipping validation studies and stability studies, extractables and leachables, and PAI readiness. And all of these are important for a successful BLA and approval and launch. Next slide, please. In addition to the CMC progress, we've also had some very good success with the FDA. And this slide talks about that. In 2023 and 2024, I talked about the process development and engineering runs. First half of this year, we had a very successful meeting with the FDA on the RCA strategy and the RCA assay and the control.
How are we going to work with the RCA and control it? The 200-liter GMP run was successful in generating the commercial viral bank. Second half of this year, we had another successful meeting with the FDA on comparability, and I'll come back to that in just a second. The 200-liter GMP run that's ongoing right now has the commercial working cell bank and the commercial viral bank, and it sets the stage for our commercial process, and this is what will carry forward into 2026 for the three PPQ runs that are scheduled for quarter two of next year. Now, with the FDA meeting on comparability, some of the key wins that I'd like to share with the group today are that we have complete alignment on the analytical comparability plan for the BLA.
This also means that we've confirmed with the agency that at this point in time, no additional clinical or preclinical studies are needed to support comparability for the BLA. We also reconfirmed our agreement on RCA strategy. And finally, the agency allowed us to pool materials from prior processes without further testing to generate acceptance criteria for the comp protocol. Next slide, please. And all this, obviously, we have lots of CROs that we have to thank for. I have to thank the Candel team that is working diligently day in and day out. I'd like to mention our manufacturing partner here briefly. That is SAFC at Carlsbad, California, part of MilliporeSigma. All activities are on track there. For example, the small-scale model is complete. We are in process characterization stage, and PPQ readiness is ongoing there.
From the very beginning, SAFC has shown a very collaborative approach to Candel, and we have had lots of successes with them, and they are committed to meet the BLA timelines. They are a very engaged team. They've increased the cadence of meetings, hired extra resources, and are committed to maintain the PPQ timelines, so in short, they continue to be a very good partner for Candel, and Candel has also put person in plant for all critical activities at SAFC. With that, Andres, I turn it over to you.
Great. Thank you, Susan and Seshu, for that great and informative session. My name is Andres Maldonado, Senior Biotech Analyst at H.C. Wainwright. Good afternoon to everybody, and let's jump right into some of the questions we have for you guys. So I guess the roadmap shows several parallel gating items: biopsies, CRC completions, non-clinical studies, comparability testing. I guess if you can give us additional color on which single component is the most determinative for hitting that 4Q 2026 timeline. Obviously, all of them are important. But if you had to assign weight to a single one or two, and what is the contingency plan once you highlight what those one or two are if you encounter any kind of delay on any of those variables there? I'll leave it to either of you.
So I will take that question. Andres, thank you for the question. So the BLA timeline was developed based upon CMC's ability to perform all the critical activities and then submit a comprehensive Module 3 for the BLA. So obviously, as you've seen in the slide as well, the two remaining activities that are very critical for CMC are PPQ and comparability. We are aware that it's very critical. So what are we doing in order to make sure that we are on track currently and we deliver on track? So we have increased. We've ensured that we have FTEs and resources available, not just in Candel, but also at our CDMO to make sure that we can meet the timelines. We have a risk register internally that we continue to update and monitor and ensure that we have risk mitigation strategies for the risks that we have identified.
In addition, we have a very solid team of expert SMEs that have years of experience in this area, and we rely on them heavily to ensure that we are prepared for any kind of contingencies. We also have additional budget in our budget for extra PPQ runs should we need. So far, I can comfortably say that we have delivered everything that we said two years ago, right on target, and we are continually delivering on that, and we are prepared for any kind of contingencies in this manner, and Sue, if you want to add something, please go ahead.
No, I think you've covered that.
No, absolutely great. Thank you for the color. So maybe a quick question on DFS as a clinically meaningful endpoint under the SPA. So DFS was central to the SPA and is now viewed favorably by clinicians and payers, as we know. Can you give us a little bit more color on how the FDA has characterized the magnitude of durability of DFS improvement in your recent interactions, particularly so in the context of long-term prostate cancer-specific outcomes shown in your two-year biopsy data?
Yeah, I think this would be a better question for Garrett Nichols.
He's not here.
Oh, no problem.
Garrett is not here as well. I'll just be very brief, right, and I'll just step in. We've hit clearly the primary endpoint, agreed with the FDA. You've heard actually in the previous session how the key external experts, both in academia and in community centers, think about this, so there's statistical significance. There's alignment with the FDA. This is what they wanted to see. This is what we've shown them, and then there's very strong support from the medical community that this is clinically meaningful, and we will continue to follow these patients, although not required by the FDA, to show, especially for strategic and commercial discussions, that at some point we expect to see separation in terms of time to ADT, time to metastasis, and time to biochemical failure, and we hope to present such data in Q2 of next year.
Great. And I think in the minute we have left, maybe we can sneak one quick one in. I said it's obvious you guys are prepared for commercial readiness. Any additional color you want to highlight to us on the remaining scale-up factor yield or raw material constraints that could pose any risk to PPQ or that first commercial supply, just to reassure us that the team is ready?
So as we said, we are ready. We are on track for PPQ. Currently, there are no high-risk raw materials in our process. So it's more a question of ensuring that we order all of them ahead of time, ensuring that we have backups on site available for any contingencies. And SAFC is already doing that. And other than that, we don't see from our raw material or any other points that you just raised as a risk to commercialization or PPQ.
Great. And with that, thank you, Susan, and thank you, Seshu. I'll turn the conversation over back to Paul Peter.
Thank you.
Thank you so much, and Andres, this was a great segue to the next topic, which is really about the pre-commercialization effort, so we used the time needed for the regulatory work and CMC work that we just discussed in great detail to be ready not only for the regulators, but also for the payers and the healthcare professionals and the patients, so this is what we call the pre-commercialization roadmap, and we do this in a highly innovative model, so in terms of the pre-commercialization activities, we have created a fluid asset-centric ecosystem that integrates pricing, market access, evidence planning, and only channels stakeholder engagement without building a big fixed infrastructure prematurely, so basically, we are mirroring the CRO and CDMO revolutions that we've seen in the past in clinical development and manufacturing, respectively.
We use specialized external commercialization networks that allow us to scale expertise instantly without delay. We find the value positioning continuously and redirect the resources in a dynamic way as data mature. I mentioned we do not only plan to be ready for the regulators, but also for all the other key stakeholders. We'll discuss this in a little bit more detail in this session. That said, we will start the search for a Chief Commercial Officer because there's so much work going on at this time. We'll start this in the very near future to oversee this pre-commercialization variety of work streams. We will also be able to bring the capabilities in in terms of a sales force in a very short period of time after approval. We'll prepare for all of this.
So I think this is an example of what I like to call adaptive commercialization. And two of our partners in this model are IDEA Pharma and Globe Life Sciences. So it's really a great pleasure to introduce Jackie Poot and Jonathon Mitchell, who will share some of their findings and their approach in this model during this session. So some of the key activities that have been ongoing are shown on this slide as a high-level overview. So activities that are underway today and that have started already in the last year: strategic roadmap and positioning, scientific presentations. Almost every other week, we give a keynote lecture somewhere, as you may have noticed, scientific publications. We just had a paper in Science Translational Medicine. We have prepared also the papers for CAN-2409 in newly diagnosed localized prostate cancer and in non-small cell lung cancer.
So these are all ready for submission. And then pricing and reimbursement assessments. And then other work that's ongoing, planned pre-launch activities, as you can see summarized on this slide. And then you can see what we will be ready for at launch. So all of this work is done in parallel while we are getting ready for the BLA submission.
Thank you, Paul Peter. In the first half of the year, Globe Life Sciences conducted a comprehensive commercial evaluation of CAN-2409 in prostate cancer based on detailed desk research and in-depth primary research with a large sample size of physicians and payers. And this was actually the latest in a series of market research activities conducted by Globe around CAN-2409 in prostate cancer over the past few years. And I'll just start by covering a couple of topics relating to the market environment into which CAN-2409 is launching. So firstly, what is the goal of treatment for patients electing to undergo radical therapy? That is very clear. And we heard this from the panel earlier. It is to cure patients and prevent recurrence and to achieve that cure in a way which best preserves the long-term quality of life of the patient.
That is a view which is held highly consistently among this physician group. I would just clarify as well that these treating physicians here are urologists and radiologists. This is generally not a medical oncologist customer group. Next slide. A clear finding of our market research is the significant burden associated with recurrence to primary treatment in localized prostate cancer. As we heard earlier, that occurs in 30% of patients, up to 50% actually in high-risk. What drives that burden of recurrence? Actually, the number one factors cited by physicians are the burden of future treatments, as well as the psychological cancer anxiety associated with failing primary therapy and return of the cancer.
These patients will then have to commit to a long-term treatment plan, typically with androgen deprivation therapy, which has significant side effects and a very negative impact on quality of life. And it's notable that at the point of recurrence from primary treatment, this is the number one concern of physicians, rather than thinking about this purely in terms of the overall survival outlook of that patient. And as a consequence of the burden of recurrence and the high recurrence rate, physicians consider that to be a very clear unmet need for a novel adjunctive therapy for localized prostate cancer, which can improve cure rates and long-term outcomes without introducing additional side effects or a negative quality of life burden. And that view is very consistently shared, regardless of whether it is a radiologist, a urologist, a community-based, or an academic physician. Next slide.
What is clear is that this is a substantial market size. This has been touched upon earlier today, but we estimate there to be 65,000 patients in the U.S. with intermediate to high-risk localized prostate cancer who are treated with radiotherapy each year. Actually, an additional roughly 70,000 patients who are treated with radical prostatectomy. This is a growing market as well. Not only is this an area of very high unmet need, it's a substantial market size which is potentially addressable with CAN-2409. Next slide. When we introduced the CAN-2409 treatment concept to this customer group, there was an extremely favorable reaction. Actually, with the majority of physicians we spoke with, scoring their interest or excitement around the product is either a nine or 10 out of 10.
This was, again, consistent among radiologists and urologists, regardless of whether they're from an academic or community practice. What drives that positive reaction? Really, it's a combination of two factors: a recognition of the unmet need and an excitement around the modality itself and the potential introduction of an innovative immunotherapy medicine into a space which has actually seen relatively limited innovation in recent years or even decades. Next slide. Crucially, the phase III data was similarly met with an overwhelmingly positive response from this customer group. Firstly, the DFS primary endpoint was viewed as absolutely appropriate for this patient population. I'll refer back to what I said earlier about the goals of treatment for these patients being achievement of cure and preventing recurrence, which is very nicely captured by the disease-free survival endpoint.
And then secondly, with respect to the magnitude of benefit achieved by CAN-2409, so a 30% improvement in disease-free survival or a 38% improvement in prostate cancer-specific DFS, 100% of those we spoke with physicians viewed that magnitude to be clinically meaningful and a valuable benefit. And actually, nearly 50% of those we spoke with classify this data as potentially transformative. Next slide. And in recognition of the strength of the clinical data and the value proposition that CAN-2409 brings to this patient population, physicians anticipate broad adoption of CAN-2409 actually across the breadth of its anticipated label, and they expect it to become a standard of care. So on average, physicians anticipate using the product in a majority of their patients receiving radiotherapy with very high uptake in unfavorable intermediate and high-risk disease driven by the elevated risk of recurrence in these groups.
But actually, also CAN-2409 is seen as a compelling proposition as a safe, effective adjunct for favorable intermediate risk patients where ADT actually is not recommended due to its risk-benefit profile in those patients. And next slide. And the payer story here is very encouraging too. I think from our own study, we found payers to be highly receptive to the product and the phase III results, where the trial design endpoints used were viewed as completely appropriate for this patient population, with payers also perceiving that the magnitude of benefit to be clearly clinically significant. And based on the recognition of the clinical value of CAN-2409, payers have been receptive to attractive price points, very much in line with the annualized cost of the more premiumly priced other prostate cancer therapies.
And particularly if a strong NCCN guideline recommendation is achieved, which we've been very hopeful for, these payers anticipate quite unrestrictive coverage at these attractive price levels. And I should say, actually, that these findings from our study have also since been validated by another group as part of the ongoing market access activities being conducted by Candel. So overall, we've seen a very favorable response to CAN-2409 from both the customer group and payers, which underscores an exciting commercial outlook for the product in prostate cancer. Next slide.
Thank you. And building on the clear unmet need and compelling market opportunity just outlined by Jonathon, I'd like now to share how we are positioned to capture this value. On the clinical side, CAN-2409, as we've heard, brings really advantages of an individualized anti-cancer immune response coupled with the scalability of the off-the-shelf therapy. This strength, also the strength of the phase three program, the FDA's RMAT, as well as the fast-track designations coupled with our broad indication strategy, are a compelling profile for all healthcare stakeholders. But we also know that strong clinical evidence alone is not enough to ensure commercial impact. So what matters now is how we translate the scientific advantage into real-world adoption and commercial value. And that's what I'll cover in the next section. Next slide.
So as we transition from a clinical-focused company to a fully end-to-end commercial organization, our strategy is anchored in three cross-functional aligned critical success factors. These will determine our performance success as well as also the long-term value for CAN-2409. Regarding the first critical success factor, CAN-2409 represents a transformative new option that advances the standards of care, as we've been discussing. And this is the foundation for adoption. We need to ensure that all stakeholders not only understand the strength of the data, but also internalize the relevance for their real-world practices. The second critical success factor gives the off-the-shelf nature, given the off-the-shelf nature of CAN-2409, is important to ensure timely therapy in localized prostate cancer. And we want to make sure that there's ease of ordering, predictability in availability of the product, and also reimbursement pathways that minimize friction for payers, for providers, and patients.
The last one regarding CAN-2409's differentiated value story, we want to make sure that we include and communicate the durable clinical benefit, the potential for disease-free survival as meaningful endpoints, as also outlined earlier. These three pillars, belief, access, and value, will work together to drive commercial success and are underpinned by strong commercial workstreams. Next slide. Our pre-commercialization program is deliberately structured around the fastest path to value creation. Looking at this chart for the next 12-18 months, you can see multiple catalyst events, data readouts, and regulatory interactions. As we look ahead, it's important that we make sure that we are tightly coordinated around these events and have disciplined execution. That brings me to the U.S. launch planning and key activity.
In terms of the pre-commercial strategy and planning that is well underway, we've defined the strategic positioning, our value story, our go-to-market model that has been aligned with customer needs. In terms of launch readiness, spanning into 2026 and 2027, we're establishing medical affairs, market access, commercial operations, and field team plans in order to be ready for our launch. The field team recruitment is timed to begin late 2026 through 2027. We need to ensure that the field force will be fully trained, compliant, and ready to engage with our top priority customers. The increasing presence that you can see at the bottom of the slide across major scientific and customer-facing conferences are really critical touchpoints for us to further shape the perception, share further data regarding CAN-2409's clinical relevance, but also make sure the market is prepared for adoption when the product becomes available for commercialization.
So taken together, this commercial roadmap demonstrates really a cross-functional approach and disciplined execution towards launch. Next slide. Double-clicking on our field strategy, as we already mentioned earlier, it's really designed to drive rapid penetration in community and hospital-based urologic and oncology practices. These two settings represent the core decision-makers for localized prostate cancer. And our approach is built on primary market research to make sure that it's also aligned with clinical practice. In terms of our commercial focus, we'll focus on coordinated data-driven education across all stakeholder groups. So for example, for the urologist, it focuses on ensuring strong education around CAN-2409's product profile, as well as the alignment with unmet medical patient needs, disease-free survival. And then for the radiation oncologist, our goal is really to reinforce the clinical and operational alignment with their role in the treatment sequence.
Patient engagement is a critical component, and we've mentioned also our key insights regarding the patient experience several times, which is built into our go-to-market strategy to make sure that our messaging is rooted in also the meaningful outcomes patients seek. This will help in terms of establishing CAN-2409 as a viable treatment option, as we know that they also have a big influence in terms of the treatment decision, as well as support broader demand generation. Next slide. And with all of these different activities focusing and prioritizing what we would call our anchor launch in prostate cancer, we are building a scalable commercial infrastructure. Obviously, as I mentioned, for the anchor launch, it's about medical affairs, field teams, market access, and distribution pathways, covering all the operational capabilities needed to introduce a novel therapeutic modality as CAN-2409.
Then in terms of the second part, in terms of the regulatory pathways, the CMC and quality systems, but also supply chain and payer frameworks and processes, we're not deploying that just as prostate cancer specific. They will become repeatable processes we can apply efficiently also for other indications. And lastly, lifecycle management and expansion into other tumor types can benefit from this infrastructure and architecture, making sure that also the learnings and the experience are pulled through as we plan ahead. Thank you. Next slide.
Great. At this point, I'd like to thank Jacqueline and Jonathon for that excellent overview and have a few quick brief questions in the little time we have remaining. Just maybe, can you give us a little color on how you're approaching the coordinated educational effort for both urologists and oncologists so that you ensure alignment, given that they have different incentives and workflows, any kind of granularity on how the approach may be different between the two while telling the same story at the same time?
Yeah. So we are having our pre-launch activities that drive uptake across community and academic settings. So we make sure that we work on understanding their workflows, how they select patients, and then align our strategy and communications in terms of positioning CAN-2409 for fast adoption as the new standard of care. So it's really rooted in a deep understanding of the workflows in different clinical settings.
Very helpful. And then as you move from pre-launch planning to operational readiness, I guess any kind of context you want to give us additionally from that great talk about which components you guys are thinking about remaining internal versus external and how you ensure continuity of institutional knowledge across potential future partners?
Yeah. As I mentioned in my introduction, we'll do this in a very fluid model. It's very comparable to working with the CDMO, except that after approval, we will bring in our own sales force because for different reasons, that is probably better. But at the same time, we will actually have an external sales force ready at that time as well. So actually, we'll work temporarily in a hybrid model where we may have actually a double sales force. It's not that large because we know actually that most patients are treated in a limited number of centers. But we want to make sure that we really hit the ground running and that we get to peak year sales as fast as possible.
Great. And in the last minute, maybe a little last color on what are your initial GTM plan focus on these centers of excellence and how you envision expanding to community practices where logistics and training may need a little bit more variation there?
Anyone who wants to take that question?
Feel free to elaborate.
Yeah. So probably you heard during the discussion with the key external experts who actually treat these patients, there actually is no specific training needed here. The procedure is very simple in the hands of a urologist or radiation oncologist. There's no special equipment needed that's not available in these centers. You just need a 22-gauge needle and an ultrasound machine that is in the outpatient clinic of every urology or radiation oncology treatment. We will make sure that they understand how to handle actually the product. But then again, you will have heard that this product is stable at four degrees centigrade for several months actually, so just in the fridge. So there's no complex cold chain. But we are working through all these details, but in this case, they are pretty much straightforward.
So these are all great questions, and we will be prepared for all of this at the time of launch.
Thank you.
Yeah. Thank you so much, Andres. So because of time, we are moving to the next topic. And we've spoken about early localized disease. Just to bring this back to the first session today, right? Everything will work better in early disease. But the remarkable finding is that we found that there's also efficacy of CAN-2409 in late-stage disease, both in pancreatic cancer and in non-small cell lung cancer. And that's what we're going to discuss today. We also spoke about the importance of relatively small experimental medicine clinical trials, which will lead to go-no-go decisions. Well, clearly, you will see that the findings that we have lead to a go-decision. So I would like to welcome Charu Aggarwal, Roy Herbst, and Daniel Sterman, who are key leaders in this field. And the moderator is John Newman, and that is from Canaccord Genuity.
I'm going to ask Charu to take us through some of the key findings in the clinical trial.
Great. Thanks, Paul Peter. And I don't have to give this group any more introduction on CAN-2409. So we'll go right into the design of the clinical trial. This is a phase II clinical trial of CAN-2409 in combination with continued immuno, sorry, ICI or checkpoint inhibition in patients with stage three or four advanced non-small cell lung cancer. We studied the efficacy of this compound in two cohorts: one who had stable disease or inadequate response to ICI after more than 18 weeks of therapy. These are patients who had stable disease but really didn't have a clear partial or complete response. And then cohort two, which is more pressing need, is those patients who had progressive disease after first-line chemoimmunotherapy. As you know, CAN-2409 was administered into the tumor either bronchoscopically or with an interventional radiological procedure.
Valacyclovir was given for two weeks with continued standard of care anti-PD-1 or PD-L1 therapy that the patients had been on with or without maintenance chemotherapy. You can see at the bottom schema of how this was administered, so the two administrations of CAN-2409 were about six weeks apart. We did capture pre and post-treatment biopsies when safe and feasible, and there were a lot of analyses for biomarkers with a blood-based analysis. In March of this year, we had final overall survival data, and we'll look at some of these in the next few slides, so this patient population was exceptionally high risk. We know that patients who have PD-L1 low non-small cell lung cancer or PD-L1 negative non-small cell lung cancer tend to have overall poor outcomes with immunotherapy.
As you can see, approximately half of the patients on this trial who were enrolled had PD-L1 negative disease. The majority were smokers. About 20% had liver metastasis. The great majority of these patients had been treated with platinum-based chemotherapy with pemetrexed. Next slide. This is how the patient enrollment broke out. We started with 76 patients who were enrolled, which are our treatment safety population. Then we defined our per protocol population as those patients who completed two injections and completed two full courses of valacyclovir and completed a 12-week study assessment. So we were left with 46 patients who were included in our per protocol population. Cohort one, again, to remind you, these were patients who had inadequate response to ICI, were the small majority of the patients, with the majority of patients in the second line or the patients who had progressed after first-line treatment.
Next slide. So when we look at the treatment characteristics, next slide. Am I able to advance the slides? Did we just come back off stage?
I don't see the slides anymore, Charu.
Yeah. I think we lost the conference.
So this is the patient we can go back. So when we look at the patient characteristics as well as disease-related attributes, we find that the per protocol population is well matched with the total enrolled population. So it's just important to think about this as we look at the results. Most of these patients, as we have previously mentioned, received platinum-based chemotherapy with either pemetrexed or a taxane. And majority of these patients had PD-L1 low, either negative or one to 49%. Next slide. You can see that in our overall population, most common treatment emergent events reported in greater than or equal to 5% of the patients are listed here by grade of toxicity. And you can see that most of these are single-digit numbers. Most treatment-related AEs were grade one to two. Grade three treatment-related AEs were seen in less than 5% of the patients.
There were no grade four or higher treatment-related AEs. We did see chills and pyrexia, which speaks to the immune activation profile of this agent, but we did not see any significant AEs that limited patient participation. Next slide. And here is the key outcome, which we'll look at in some different flavors. But median overall survival for the per protocol population, that is, those patients who completed two cycles of the valacyclovir, two injections, and had a 12-week assessment, was over two years. Next slide. You can see amongst patients who had second-line treatment or cohort two, this is the patient with the greatest unmet medical need. Remember, these are patients who are progressing on maintenance ICI with or without pemetrexed. And you can see that the median overall survival is close to two years amongst these 41 patients.
Just for reference, again, this is not an intra-trial, but a cross-trial comparison. Standard of care chemotherapy with docetaxel or docetaxel and ramucirumab usually gives us a median overall survival of about a year. So this is definitely some interesting signal that should be followed. Next slide. I want to just represent a case that was actually treated by Dr. Sterman, who's on this call here. I want to illustrate that nodal injections are feasible with this model of CAN-2409 delivery. And in fact, CAN-2409 can sustain and induce long-term systemic anti-tumor activity with some abscopal effect, as seen in this patient after 52 months of follow-up. So you can see on the baseline, injection was performed in the lymph node. And you can see that there were responses not just at six months, but also at 17 months.
At the top, you can see the target, the sum of the target lesions with an ongoing response, which is quite characteristic for this patient and representative of many others that have been treated on this trial. Next slide. You can see that regression of uninjected lesions was seen in about two-thirds of the patients presenting with multiple lesions. So of course, the injected lesions showed some response. But we were actually really pleased to see that we were noticing a real abscopal effect here.
Phase II trial. It's hard to compare to phase III. I can tell you in a trial that we ran called Pragmatica-Lung, which was a very similar group of patients, the median survival of both groups of patients, those treated with a VEGF inhibitor plus the IO versus standard of care, both groups had about 10 months on the median.
Of course, much less at two or three years, as we're seeing here. So I think this is a very impressive result. But you have to remember, it is a phase II trial. So there's always selection in a phase II trial. There's always a little bit of selection. You have to get the patient to the procedure and so forth. But that said, when Dr. Aggarwal showed us the demographics, these are patients who had had a significant amount of prior treatment, as we saw. Many of them were PD-L1 negative. So these were patients with bad disease. And this is the thing about immunotherapy, as attractive as it is and as much progress that we've made in lung cancer, it's amazing. Still, most patients have this sort of fate where they either progress right through.
And those are very tough patients to deal with because they probably have other reasons why they're not having an adaptive immune response. Those that have the adaptive immune response and then continue to progress, I think we're seeing very strong signs of activity here that now will be verified in phase III studies.
Okay. Great. And Dr. Aggarwal, I'm also curious as to your view here if you think that something like CAN-2409 could have utility, perhaps across prognostic factors, maybe not just in patients that are very ill?
Absolutely, and I think this is going to open the doors for several other applications. I think, could we use this in the early curative setting? Could we use it in patients who are undergoing neoadjuvant chemoimmunotherapy as an adjunct to improve the immune activation and immune responsiveness? What we've seen from the safety profile doesn't seem concerning to add this agent in a curative setting. So I think there can be a variety of different applications that I'm actually very excited about.
Okay. Great. Thank you. And Dr. Sterman, an additional question for you. Only two administrations of CAN-2409 were given here. Could you talk about how that could make things potentially more convenient to patients? And also, I'm curious, would there be situations where you would actually extend the number of treatments?
Certainly, so very convenient in terms of the interval between the two procedures, somewhere around six to eight weeks between the two procedures for our patients, and then in terms of the ability to give additional doses, absolutely, and we've discussed this several times. I think the idea is essentially if what we're doing is in situ vaccination, vaccinating patients against their own tumors and stimulating the immune responses and rejuvenating the immune responses, it may well be that for those patients, especially those patients who are still alive at one, two, and several years beyond, that they may need another dose to reinvigorate that immune response that may well be terminating for a variety of reasons, including to induce tolerance, so I think there are roles for additional injections, and certainly, technically, it would not be complicated to give additional injections in the future.
What's interesting is where we should be giving the injections. And I think we still have to learn should these patients be administered directly into the primary tumor or other lesions within the lung parenchyma, in lymph nodes, or in distant metastatic sites, and in what sequence. Should they both be given to the same location or in different locations? And those are things that we hope to learn from the phase III trial.
Okay. Great. Thank you. A question for Dr. Herbst. What is the standard of care for patients with progressive metastatic non-small cell lung cancer despite first-line treatment with immune checkpoint inhibitors, as you discussed previously? And how does the overall survival data, which was presented by Dr. Aggarwal, compare to the overall survival for that current standard of care?
Right, so there really isn't anything that wonderful to offer here, despite many years of research. That's why this approach does stand out. I mentioned that the standards would probably be docetaxel, quite toxic taxane. In the U.S., it's used with the VEGFR-2 antibody ramucirumab, not so much in the rest of the world. Some people use the drug gemcitabine, very little activity in lung cancer. But there really isn't that much in early phase trials, and remember, a lot of these tumors are probably cold. They don't have T cells in the immune microenvironment. Now, the best experiment, recent experiment, is a trial called SWOG-1800A, which was part of the Lung-MAP trial that took pembrolizumab and the VEGFR-2 antibody ramucirumab in the same population, and that study showed some hints of activity.
But in the phase III trial, the median survival was 10.1 months, significantly less, more than half what we're seeing here. The standard of care, which is what you specifically asked me about, came in about the same. And a little bit worse, by the way, in squamous than non-squamous, as we're seeing here. So at least, again, phase II versus phase III, it has to be confirmed. But more than two, two and a half times the result here, I think, is very exciting and suggests that this is certainly an approach that is worthy of much more study in the future.
Okay. Great. And then also curious, in terms for Dr. Sterman, what is your view on the clinical relevance of what you've seen with some of the individual patients that you've treated? And what I'm curious about here is, do you tend to see tumor shrinkage, tumor stabilization, or both? How do you think about those outcomes, and how do they translate into clinical benefit?
Certainly. I think what's been most impressive for us in following some of our patients have been the abscopal responses. So the fact that we've seen significant, measurable, in some cases with supraclavicular lymph nodes, palpable regression of tumors in areas where we have not injected. I think that for anyone who's interested in local therapies, and we study a variety of local therapies at our institution in lung cancer, the fact that we would see responses in distant sites that have been untreated really is a hallmark of this. And what we do know is those who do get responses at distant sites that have not been injected have a correlate in terms of their survival advantage as well. So that, to me, has been the most impressive, the correlation between abscopal responses, the high number of those responses, and the correlation with survival.
Okay. Great. Thank you. And just to finish up the Q&A here, Dr. Aggarwal, I wondered if you could discuss the design of the phase III trial for CAN-2409 in non-small cell lung cancer. Just curious what the treatment population is here. Will the study focus on both non-squamous and squamous histologies? Primary endpoint? And also, how do you think the results could inform the treatment paradigm?
It's a great question, and this is what we've been alluding to all along, that we see such a strong signal in phase II that I think this needs to be confirmed in a phase III trial. Based on the biomarker analyses, and this is why we do phase II trials, we noticed that patients with squamous histology don't quite mount the same level of immune responsiveness that the non-squamous tumors do. We are still trying to understand why that may happen, but we know that squamous histology tumors tend to have a tougher immune microenvironment to begin with. For the purposes of the phase III trial, patients with non-squamous histology who have progressive disease following chemoimmunotherapy for stage four non-small cell lung cancer will be enrolled.
The idea is that we will be able to graft on CAN-2409 with ongoing immunotherapy and compare it to physician-preferred standard of care, which most likely is going to be docetaxel. Follow these patients on for survival outcomes, such as PFS and overall survival. I do think that this is the kind of trial we want to do. As you know, there have been several trials looking at antibody-drug conjugates in the second-line setting, two of which were mentioned on the slide deck. antibody-drug conjugates against TROP2 with both sacituzumab as well as datopotamab deruxtecan both unfortunately failed to reveal an improvement in overall survival that was statistically significant. We also found that actually patients with non-squamous histology tended to do numerically better with ADC. Again, a trend that is emerging that distinguishes these two histologies.
I'm very excited at the prospect of having a phase III trial.
Excellent. Thank you very much, all the speakers.
I want to thank you all. As you probably noticed, my internet went down completely. So thank you for being very flexible. We also like to be prepared for any scenario. So I hope that everybody is also seeing that we had a backup plan in case the internet would go down. So it's a real pleasure to move to the next session. Of course, we had a very strong focus today on CAN-2409. But actually, we should not forget that there's another very exciting investigational medicine, which is CAN-3110, which we test in probably the most difficult to treat form of cancer, which is recurrent high-grade glioma. Most of these patients will have recurrent glioblastoma. So I welcome Francesca Barone, Henry Brem, and Kemp Dolliver. And I'm going to ask Francesca, our Chief Scientific Officer, to take us through some of the key data.
Thank you, Paul Peter. So there is a significant unmet clinical need and also a great opportunity to develop a medicine in recurrent high-grade glioma. Glioblastoma is the most common form of high-grade glioma. It's rare, but it's also a deadly disease. I mean, only 10% of the patients will survive past five years. And actually, survival post-recurrence has got an extremely dire prognosis with only a survival of less than six to nine months. This standard of care for recurrent patients includes surgical resection and, in some cases, chemotherapy with a very poor quality of life. And the reason for this is that these tumors are extremely immunosuppressive in their microenvironment. So there is really an opportunity to create a new medicine that, while killing the tumor, will be able to activate this tumor microenvironment. And that's why we developed CAN-3110.
This is a fast-acting oncolytic virus where the two genes responsible for viral replication, the ICP34.5, have been deleted, and only one copy has been reinserted under the nestin promoter. This modification allows the virus to replicate and therefore kill specifically tumor cells that express nestin. Nestin is a cytoskeleton protein. It's highly expressed during development, but in adult tissue, in healthy tissue, it's not expressed. While it's highly expressed in tumor cells, Paul Peter alluded to that before in his introduction, this protein is highly expressed in aggressive tumors, and in particular in high-grade glioma, for which it was originally developed. This really enables us to replicate and kill tumor cells while keeping the rest of the brain healthy. This is the case of a patient that has been treated with CAN-3110.
We've actually reported this case and the results of the first cohorts of our phase IB trial with single injection of CAN-3110 in Nature in 2023. You see here a patient with a classical story of high-grade glioma. This patient presented two recurrences and underwent multiple resections. And just after the second resection, and I want to point it out, the time between these resections, a very short period of time, the patient was treated with CAN-3110. And after 90 days, the MRI scan seems to suggest another recurrence. And you can see the enhancement in the scan. This patient was brought back to the operating table, and the tumor was removed. But actually, instead of being tumor, in this case, the tissue was full of tumor-infiltrating lymphocytes recruited at the site of the tumor after the injection with CAN-3110.
You see the follow-up scan for this patient that had no further tumor growth, and there is only an empty cavity there. This patient is a lady. She was able to survive for more than two years after the injection of CAN-3110. Actually, she died. She passed away in a motor vehicle accident where she wasn't driving. It wasn't because of disease recurrence. This patient was considered cured. As I mentioned before, we reported the median overall survival for this patient population. In 2023, we also reported some very interesting biomarker findings for this patient population treated with CAN-3110. In particular, the fact that a patient that had the prior immunity against HSV-1 virus was characterized by better survival.
This patient, you can see here, has a median overall survival of up to 14 months, so largely exceeding the median overall survival reported for these patient populations. The other biomarker that we found that was associated with survival was the broadening of the T cell repertoire after injection. This is extremely exciting because it really suggests that this virus is not only exerting an oncolytic activity, but really a strong immunomodulatory activity with the capability of activating the T cells in the tumor microenvironment to react against multiple antigens, the virus in one case, so developing an antiviral response that will burst the anti-immune response, but also against potentially a tumor antigen. We will see how this is important. This beautiful biology translates actually in improved survival for the patient. That is the most important element.
You can see here that we're starting to look at this long tail of survival that was mentioned before. We see two patients in the single injection cohort that I mentioned before that are still alive after 59 months and 42 months. What we are also exploring is that leveraging that capability of the patients to have a survival advantage once they have immune capability to mount an immune response against the virus, that we've seen happens not only for patients that have positivity against HSV-1 at baseline, but also patients that develop the positivity of the antibody response against the virus after the first injection. We are now exploring what happens if we have multiple injections of CAN-3110. We show that multiple injections are well tolerated even when they are coupled with biopsies that occur prior to the injection.
We've seen now starting to observe these long tails of survival also on these patients. We will report additional data on survival at the end of 2026. What we have reported, though, very recently is the first two cases of patients treated with multiple injections of CAN-3110. This is an extension of the trial that is funded by the Break Through Cancer Foundation. We've reported very recently in Science Translational Medicine. You see here the cover actually of that journal that was dedicated to this publication, how two patients that were treated respectively with four and six serial injections of CAN-3110 have improved survival, but also profound changes in the tumor microenvironment with a significant activation of the immune cells there. We confirm reactivity against the tumor antigen. You see here the reactivity against nestin. That is also the other name for CAN-3110.
And you can follow in the patient in these serial biopsies performed in the brain how these clones are found. These T cell clones of effector cells are expanding in the brain. The other reactivity of these cell clones is, as we suspected, but now we have the confirmation, are mounting against the antigens of the tumor. And you see here the immunopeptidomes that highlight the presence of clones that are against the antigens associated with glioma. So we have clear data that there is a survival advantage in patients with recurrent high-grade glioma that are treated with CAN-3110. We've seen this in single injection, but we started to see this also in multiple injections. And we want to really develop in the future stage of development trials that will enable us to interrogate what is the right regimen in terms of number of injections.
And we've seen that the biology is there to confirm activation of the tumor microenvironment. And we need to be mindful of the fact that this expansion of the immune cells can be misleading and think that the patient undergoes progression when actually they are mounting an immune response and they are responding to CAN-3110. And I'm going to pass it back to Kemp for the moderation.
Great. Thank you so much, Dr. Barone. So Dr. Brem, what are your thoughts on these data?
I'm very excited by it. Just by way of background, I've been in this field for a long time. When I first began my career in neuro-oncology, I was discouraged by people who said that glioblastomas, being the most devastating disease probably that's treated in medicine, had really not had, you know, was sort of invulnerable to whatever we threw at it, and early on in my own career, together with Bob Langer at MIT, we developed chemotherapy wafers that were successfully able to get through FDA approval and a successful product that changed the outcome for glioblastomas. And that is still used worldwide now and has impacted on the survival. This is the most exciting new approach that I have seen since that time, and I think that the ability to modulate the immune system and use the herpes simplex virus delivery as an oncolytic virus is extraordinarily powerful.
And we're seeing in patients results that are stunning, which is long-term survivors in the refractory end-stage glioblastomas that it's being looked at. So given that the patient population, I think I can't emphasize enough what a refractory group of patients this is. And yet we're seeing a change in the environment, immune cells being modulated and really destroying the tumors. And consequently, this tail of long-term survival, I think that this is a very viable product that will really change the way we approach malignant gliomas. So very positive, very excited, very much looking forward to helping with the next stages of the clinical research that needs to be done. And optimistic based on what we've seen that we will have a successful product.
Great. Thank you for that. So Dr. Barone, based on the data that you have so far, what do you expect will be the optimal number of administrations of CAN-3110?
Thanks for this question. I think that we want to run a trial to understand what would be the best administration. We've seen very encouraging data even after a single injection, but we really want to see if we can leverage this, acquire the immunity against the HSV-1 to modulate and improve the response against the tumor, so we want to run a randomized trial to interrogate that, and probably we won't need four or six injections that we've done in this expansion cohort that was an experimental medicine part of the trial. We will probably need two injections, maybe three injections to leverage this sort of priming booster mechanism that some of these viruses have shown. We've seen that in CAN-2409, and we think it could work also for CAN-3110.
Thank you very much for that. Turning back to Dr. Brem and noting that we have only a couple of minutes left, what would you like to see from the mature overall survival data from Arm C of the phase IB trial that's expected by year-end, which is obviously within the next few weeks? And what constitutes a clinically significant improvement in overall survival?
You know, first I want to say that although this is an elaborate study that needs to be done, that this patient population, in my experience over a career of taking care of these patients, is that nobody shuns away from these very difficult procedures because it's a uniformly fatal disease. And so people are willing to undergo multiple injections into the brain if that's what's necessary. And we've done many trials that require that. So I'm optimistic that we'll accrue quickly. I think what we want to see and what we expect to see is more long-term survivors because that's an extraordinary finding. And that's what we've seen in the—that's unexpected, if you will. And we're seeing it.
If we continue to see that, and there's no reason not to, in the next phase study, I think we'll have a home run here because people will be willing to undergo this therapy if there's a chance even of long-term survival. I think that's what we're seeing, and that's what I would hope to continue to see.
Great. Thank you again. Given the time remaining, Paul Peter, I'm going to hand back the microphone to you.
Thank you so much. This was also a great session. Let's move to the next slide. I'm now going to invite, as you see, many analysts from leading banks to open up the Q&A. I'm going to pause here, and maybe you can raise your hand if you have a question, and we'll take it from there. I'm joined here, I hope, by my whole leadership team and the people who have presented today on behalf of Candel. Thank you so much. I'm going to listen to the first questions. Oliver.
Thank you for taking my questions and congratulations on putting together this event. I just wanted to see if you could remind us on the additional efficacy data from the phase III localized prostate cancer trial that Candel has guided to sharing next year? And then related to that is how you think the community or the treating community views data like time to metastasis and time to salvage therapy in the context of DFS and what you've previously shared?
Thank you again.
Yeah, that's a great question. So I want to remind everybody that the goal of treatment for these patients is to be free of cancer. These patients accept the risk of long-term complications of current standard of care, whether it's radical prostatectomy, major surgery, or radiotherapy. The population that we focus on, think of urinary incontinence, erectile dysfunction, loss of quality of life. They're willing to accept that risk because they want to eradicate that tumor. And we help them actually to achieve that goal in a significantly higher percentage when you give CAN-2409 versus placebo on top of standard of care radiotherapy. So I think we've achieved that, supported by secondary endpoints. In radiation oncology trials, you often see that the two-year biopsy is included. This is not part of standard of care, but it's the most sensitive way to detect tumor cells. It's also the gold standard.
If you see cancer cells under the microscope, you know it's there, and we know, and Garrett has shown this in a beautiful way based on a large meta-analysis based on 22 clinical trials, that seeing tumor cells in a two-year biopsy is predictive of subsequent biochemical failure, so PSA levels going up, development of metastasis, local progression of the disease, all associated with clinical signs and symptoms, and then the need for salvage therapies in the first place, long-term androgen deprivation therapies. We've heard the downside of that, so we would expect, based on this meta-analysis and what we demonstrated in the two-year biopsy, that over time, after extended follow-up, we will start to see a separation between CAN-2409 versus placebo when you look at biochemical failure, development of metastasis, and the need for salvage therapies.
We don't have these data yet, but we hope to be able to see the first trends in Q2 of next year, and we will continue to follow these patients over time. Thank you for the question, Oliver.
Thank you. Appreciate it again.
Next is Andres.
Hi, everyone. Thanks for taking my questions and congrats on this great event. Really appreciate you including everybody here so maybe one question that tries to tie all the programs together. Across tumor types, a lot of your tumor level analyses have suggested a biomarker-based precision framework that's starting to emerge across programs so could you outline how you envision potentially integrating these potential biomarker data sets, any unique kind of IO strategy, and whether this could influence future label expansion or trial design? Any high-level thought there would be helpful. Thank you.
Yeah, thanks for the great question. I spent a lot of my career, actually, on developing precision medicine approaches, not only in oncology, but also in immunoinflammation, autoimmunity, and the interesting thing is that now we are developing a pan-solid tumor therapy that seems to work in all comers that we've treated, although there may be differences, for example, based on the histology, as we've shown in non-small cell lung cancer, so I would not call that necessarily precision medicine, but stratified medicine. We know that there is a large population that's basically, from a pathological point of view, a different disease entity, namely non-squamous disease versus squamous disease. And that's what we will focus on, so we do deep biomarker research in all the trials that we do, trying to find out what is the best population.
But the unique aspect of CAN-2409 is that, generally speaking, it seems to be a pan-solid tumor therapy. That means that we don't expect to see baseline biomarker features that will say, well, this patient will get CAN-2409, and this patient won't get CAN-2409. Having said that, we're starting to see changes in serial measurements of biomarkers early on. For example, in the evaluation of soluble granzymes, cytotoxic enzymes produced by cytotoxic T cells and natural killer cells, key effector cells killing the tumor. And then we see there's very strong increase early on in soluble granzyme levels after initiation of CAN-2409 that seems to be associated with improved overall survival. So that may lead development in the following way.
Post-approval, we may start to think about maybe there's a benefit in patients who don't see the same profound increase early on in giving them a booster. Maybe in patients where you see that granzyme levels are going down over time, maybe there's a benefit of an annual booster, which would be interesting from many perspectives, including a commercial perspective. So I think this is for post-approval in lung cancer and in other tumors. But this is clearly on our mind, and we collect all the material to be able to answer these questions.
Thank you for the question, Andres.
Thank you.
So next is John. And now I lost John. John Newman.
Hey, Guys. Hey, you're welcome.
Really great event today. Really great commentary by the physicians. I also thought the section on manufacturing was extremely well put together and useful, so thank you for that. And my question is actually about manufacturing, Paul Peter. I wondered if you could just remind us what type of manufacturing capacity for CAN-2409 do you expect to have at launch and then also, say, one to two years post-FDA approval?
Yeah, great question. I'm going to hand over to Seshu because the beauty of a high-performing team is that I should not answer all the questions. Seshu, over to you.
So thank you. So John, I think we will meet the demand. And so the capacity will meet the demand. We have enough reassurance from our CDMO that we can scale up manufacturing to meet the demand. Currently, as you know, we are manufacturing a GMP batch right now, PPQ batches next year, maybe a few more batches the year after. But we are well situated to meet the demand as it comes, not just for the next two years, but five years, 10 years. All that planning is happening as we speak.
I thank you, Seshu. And the beauty of this approach is that it's quite different from, let's say, development of cellular therapies or very complex gene therapies, right? It's relatively easy and straightforward, although it's work that needs to be done to scale this product up. The next in line is Alec.
Hey, guys. Really impressive host of speakers today. Appreciate you putting this together and for taking our questions. Two, actually, on the CMC information, which I agree was really helpful today. I guess first on the biodistribution and shedding study, how large should we expect this to be, sort of the kind of endpoint there? And was this kind of the expectation going in? And then second, just on slide 32, it was mentioned that you're allowed to pool materials from prior processes for establishing comparability. I was hoping you could maybe expand upon, I guess, why this is important. And is it just easing logistics or maybe something on the data side as well?
So I'm going to hand it over to Seshu as well and leave it to her whether she also wants to bring in Francesca.
I will have to bring in Francesca for the first question. But maybe we'll change the order. I'll answer the second question, and then Fran will come in. So in our clinical studies, even though it is a similar process, there were some differences between the processes that were used for the prostate trial and the lung trial. So there was a big discussion internally for some time before we got the alignment with the FDA that how do we pool them together, what kind of risk assessments are needed, what kind of tests are needed. But upon questions from the FDA and us providing them all the data, they were pretty comfortable to say that you can go ahead and pool this material without additional testing. That was the key. And then use that as pre-change material for comparability studies.
So what this does is it gives us an advantage to generate some data that we can then put into our comparability protocol and then use that for conducting the study next year. So that was the reason. And it's a pretty big assurance from the agency for us.
So I'll take the second part of the question, Alec. Basically, the biodistribution study is a small study. I just want to clarify something that Seshu mentioned. This was not a requirement to validate, to cross-check the comparability of the product. This is all done through analytical comparability. We don't want it to provide a very clear guidance in terms of shedding. And this is what this study will address. And so the plan is only to collect 30 patients. We already know that this is a replication defective adenovirus. The shedding is going to be extremely limited. We did have some data from our very early studies, but those were done with methodologies that were not up to date. And so we decided to redo it. So 30 patients is the target in order to actually have longitudinal data on 20 patients.
And then, because we do like an experimental medicine study, we're going to add 10 control patients, not treated with CAN-2409. And we're going to evaluate. We're going to use these patients to do a comparison for biomarker analysis. That is more of our own driver to provide additional mechanistic data in the prostate cancer, similar to what you see in the other indications.
OK, very helpful. Thank you for taking my questions.
Thank you for the question, Alec. Next is Imogen.
Great. Thank you, Paul Peter. And thank you all. It was a really excellent session and a stellar roster of experts from Candel and outside. A question from me on what we've been hearing about the challenges of ADT, both in terms of managing patients who are on it, but then also the adverse effects. Do you think that you're going to be able to show cardiovascular benefits from CAN-2409 from reduced use of ADT as salvage therapy? And is that something that we could maybe see in the long-term follow-up? And when will we be able to see that?
Great question. I'm going to ask Garrett to answer this.
I think that if we had designed the study in order to compare 2409 to ADT in patients with prostate cancer, we might be able to answer that question a little bit more readily. In this setting, we're basically depending on patients having recurrence and being treated with long-term ADT. It's possible that with long-term follow-up, we'd be able to see some benefits on that side, but it's going to take more time. We're now following those patients for recurrence. We're following patients for the need for salvage therapies. We're also intending to follow those patients in terms of their quality of life, particularly when they have recurrence, and comparing those to the patients on 2409 who do not. Some of this information will be available, but I think a future study potentially comparing 2409 to ADT may be something that would be of interest.
And in addition, we will continue to follow these patients. I completely agree with Garrett. It will take time before you start to see that. We will see the immediate benefits, I think, in terms of not needing ADT or delaying the need for ADT in terms of the immediate side effects that were discussed today. But this is a significant risk factor for cardiovascular disease. And we know that there's a metabolic component to prostate cancer. So these patients are already at increased risk. So the expectation would definitely be that there will be a difference based on the phase three trial. But it will take at least another five or 10 years, I think, before we start to see that. Thank you for the question, Imogen.
Thank you.
Next is Sudan.
Hi, Paul Peter. Thank you so much for the time here today. Very robust conversations with all the KOLs and with the rest of the Candel team, so I really appreciate all the transparency, so my question is regarding the first quarter 2026 update in the ICI refractory non-small cell lung cancer. How should we think about the quality of the median overall survival and the long tail signal beyond the headline median, particularly in the cohort two? For example, what proportion of patients do you expect to still be on study event-free at 24, 30, or 36 months? And how sensitive are those tail estimates to censoring and post-progression therapies? And will you share any pre-specified analysis, such as treatment beyond progression data, to help investors gauge how robust that apparent survival plateau really could be?
Thank you, Sudan. That's a long list of questions. So let's see if we can remember it. I'm going to ask Francesca to respond to this.
Thank you, Paul Peter. These are very interesting questions. We are following this patient for a while. We know that the long tail of survival that we've observed, we believe that this is going to continue. The patient in study, they are still there. We haven't looked at the data yet. Obviously, we monitor the patient over all time, but we haven't done a formal data cap. I cannot really answer to you. We have not had very significant deaths, in particular in the front side of the curve or on the left side of the curve. We are still confident that we will see this long tail of survival continuing through. In terms of post-treatment, the first thing to say is that a lot of the treatment in this stage of disease has shown no advantage in terms of survival.
So we are not expecting those to have a significant impact. Nonetheless, we are following the patient. We are following the type of treatment that they take. And we will continue reporting them. We've just compiled the manuscript that reports, in fact, for each patient which kind of second-line treatment. But just to remind you, none of the treatment has so far beat standard of care, that is 12 months, those outcomes. So we are not expecting really to make a difference. But we will report those. And we will definitely follow this post-treatment survival, post-failure survival that we've observed so far.
Yeah, and the interesting thing is, well, we've shared already two patients today, right? Charu Aggarwal showed these data of patients who lived now like four or five years after having metastatic progressive disease despite immune checkpoint inhibitor treatment and chemotherapy, so we know that there's a subset that lives much, much longer. We don't do a data cut because otherwise we would need to share it, so we don't have this information, but we will have it shortly in the next several months.
Thank you for the question, Sudan.
Thank you, Paul Peter.
Next is Francesca. Next is Kemp.
Yeah, thanks. So my question relates to 2409 in prostate cancer. And your sense of the awareness of the data and the drug's potential in the broader medical community, but also the patient population, just given that this is the first real advance in this particular setting for many years?
Yeah, I may ask Jackie to comment on this in a minute and also comment on our strategy. But it's a good question. This is a completely new approach. It's a new paradigm. So it always takes a little bit of time before people can get their head around it. First, it's a completely new modality. Actually, it's not an oncolytic virus even. It's a way to vaccinate the patient without being a vaccine and get a laid-out mechanism. And the second point is people have not seen any medicine approved for the treatment of early localized disease, right? The options are surgical or radiotherapy. So we've spent quite a lot of time presenting this at large, significant meetings. And we are very happy that our abstracts were accepted for oral presentations at ASTRO , which is a big honor, right?
It was presented by the dean and CEO of Johns Hopkins. Then we had an oral presentation that was accepted at ASTRO, also a high-profile meeting, the big radiotherapy meeting. We presented the data at SITC. Just a few weeks ago, I opened the session in the ballroom where we spoke about the next wave of innovation. And it was focused on prostate cancer. I presented the data at a large meeting in Europe, 5,000 people, with keynote lecture, et cetera. You've seen on the slide from Jackie some of the key presentations that we've given. So that all helps to educate. So that's one part. Second, of course, it takes some time to write up all the data, right, and do it in the most rigorous way. So we have a manuscript ready to be submitted to a high-impact journal in the very near future.
So that's going to be important. And then we have started to have scientific advisory boards, for example, at the Prostate Cancer Foundation, which is probably the most high-profile network in prostate cancer in the U.S., maybe in the world. So again, there was an oral presentation, an invited oral presentation that I gave there. But we also had an SAB with some of the key leaders, including Phil Kantoff, who you've seen today, but also the CMO and the CSO of the Prostate Cancer Foundation. So we do a lot of scientific engagement. Then we get feedback and input, but which also helps to educate the community, first, actually, the key leaders in the field. So I'm now going to hand over to Jackie to maybe elaborate a little bit on our strategy to make sure that everybody knows about this program at the time of BLA submission.
Thank you, Paul Peter. And as you've already established our presence towards, you could say, the clinical and scientific community, I would like to pick it up indeed with the patient community because we also want to make sure we demonstrate the value of CAN-2409 to them and to the patient organizations. And through our launch process, obviously aligned also with regulatory approval and compliance requirements, we will educate both health care professionals, but also payers about the new mode of action, but then making sure that they also have educational materials for patients. We will help, and we've identified health care professionals who have high patient populations of patients with prostate cancer to make sure we target them first. And then we can use also their learnings from discussing CAN-2409 as a treatment option, take those lessons into expanding access and education.
We also want to make sure that we understand patient goals and their needs and how CAN-2409 can then help them live life without cancer. We are already engaging with patient association groups in order to establish really that relationship, but also to learn from their members and from their activities. And they've also shared with us that they see CAN-2409 as an important new treatment option. And over the next year, we will be increasing our engagements with patient organizations so that we can further learn about their experience in a more in-depth manner. We talked about also the positive benefits of CAN-2409 in terms of psychological impact, quality of life. And we want to make sure that that becomes highly specific and relevant rather than staying in generic terms, as we sometimes see.
Yeah, thank you, Jackie, so as I said earlier during this meeting, we do not only want to be ready for the regulators, which is, of course, key, but also for the payers, for the health care professionals, so I gave you some examples of work that we are doing, educating people, engaging, right, scientific engagement, getting also their input. At the same time, you really raise awareness by doing so. Also, we've started strategic activities, actually, to identify, and we've done this already, the key experts who are also close to the NCCN guidelines, right, which will be very important to press the button the day after approval to submit our files, actually, for inclusion in the NCCN guidelines, which will be very important, and then again, I want to echo what Jackie said. We are an organization where a patient-in-partnership strategy is critical.
And also, the patient voice is going to be important because they also will talk to their urologist and radiation oncologist and ask about this new therapy. So thank you for the question, Kemp. So I would invite everybody who still has a burning question to ask it right now. There's no problem raising your hand again. You can do another round. So there we go. Yigal.
Great. Thank you very much, Paul Peter. I was curious about sort of some market dynamics. I think in the past, you've talked about how the market was split approximately 50/50, radiotherapy and prostatectomy. And given your data and potential changes to practice paradigms, would you expect the market to shift to a greater use of radiotherapy?
Yeah, that's a great question. I think there is a group of patients where there's a very strong conviction that they want to undergo radical prostatectomy, right, surgery. And that may not change. And it's also culturally dependent. For example, that's more common in, let's say, Germany than in the United Kingdom. So that group will probably still be there. Then there's the group that chooses radiotherapy as their radical treatment. That's our current target population. But then there are many patients who are on the fence, actually, right, who are somewhere in between. Shall I choose radical prostatectomy? Shall I go for radiotherapy? Both have their pros and cons. And that is in the context of shared decision-making between the physicians and the patients who will often see both a urologist and a radiation oncologist to seek their advice.
That's the population where we hear that actually this may shift, and it may be more attractive here to choose radiotherapy, so overall, the group of patients who will elect to undergo radiotherapy may grow, and that is supported by the market research that we've done, and Jonathon has, I think, spoken about this because we've now shown that the benefit-risk for this combination option of CAN-2409 plus radiotherapy may lead to better outcomes over time and a reduced risk of recurrence. Thank you for the question.
And then you mentioned NCCN guidelines a little bit a second ago. In this situation, you've had the phase III data for a while. And given the manufacturing timelines, you have a lot of time to work on getting those guidelines. Is there any possibility that you could get those even before the launch? Or that's not realistic?
No, that's not realistic. But we will be ready, actually, to have everything in place. Probably the most important is to be engaged with the key influencers in the field. So we spend a lot of time already. We use this time to our benefit to make sure that we will have a very steep uptake of CAN-2409. But you cannot submit, is my understanding, before approval by the FDA. Thank you very much. Alec.
Yeah, great. Thanks for the follow-up, Paul Peter. We talked about a lot of really good science here and obviously the unmet medical need. But as a company, you'll need money to push these endeavors forward. Maybe you could just speak about the term loan from Trinity in October, how this maybe adds flexibility for your launch prep and pipeline progression that you talked about today.
Yeah, absolutely. Great question. I'm going to hand over to Charles, our Chief Financial Officer.
Thanks, Paul Peter. So as a reminder for everyone, the Trinity loan provided for up to $130 million of non-dilutive financing over the next two years. The first tranche was a $50 million upfront payment, which was received in October of this year and allowed us to initiate the phase III trial in non-small cell lung cancer that we've been talking about. The remaining $80 million will be split between three potential future tranches that are tied to achievement of certain regulatory milestones. These tranches will provide additional non-dilutive capital at key inflection points in the company's future and will fund the company past our launch and into commercialization. So in summary, the Trinity loan has already strengthened our balance sheet.
It's allowed us to initiate another key phase three trial and will significantly reduce the amount of additional capital required to fund the company past our launch and into commercial and profitability.
Thank you very much, Charles. Imogen.
Thanks, Paul Peter. So obviously, the decision of radical prostatectomy or EBRT is very much up to the patient and the physician and independent of the costs of these procedures. But at the moment, it is more lucrative for urologists to do a prostatectomy than EBRT. So could you talk about how CAN-2409 changes or potentially even equalizes the economics of that decision, given the potential for buy and bill and shorter procedure times in high-volume centers?
Yeah, great question. So based on the work that we've done, it appears that this is very attractive to urologists because the patients who have made up their mind and they want to undergo radical prostatectomy, that's not going to change. But in all the patients who undergo radiotherapy, there will be an additional procedure. And in most patients, this will actually be performed by the urologist. So there will be more like teamwork, I think, between the radiation therapist, radiation oncologist, and the urologist. And the urologist is expected to have a reimbursable procedure. So they're quite interested in that part. And I think it will be like pushing against an open door. So that's a great question. I'm aware that we have two more minutes. So probably Sudan is going to be the person who's going to ask the last question. Sudan, over to you.
Hi. I really appreciate you taking the follow-up on keeping it snappy here. So I remember I saw the conversations you had with IDEA Pharma during the conversation, during the presentations. Across the work you've done with them and Globe Life Sciences and your pricing partner, what has emerged as the single most important commercial insight for CAN-2409, whether around positioning, payer willingness to reimburse the novel immune gene therapy, or defining the patient segment that derives the greatest perceived value?
Maybe you can comment on this, Jonathon.
Yeah, absolutely. So I mean, I think the whole story is positive. But I think for us, it's the response to the clinical data and the consistency of that positive response to both the trial design and the clinical meaningfulness of that data from the perspective of both physicians and payers, particularly against the context that Paul Peter was talking about earlier, that this is a patient population where actually there's been limited precedent for the development of innovative therapy, which in often, in many cases, can then open the door to questions on trial design and whether it's appropriate for this patient population. And it's just that consistency of positive feedback has been, I think, so encouraging, certainly for us to see.
Thank you very much, Jonathon. I don't think we have time for a third round of questions. Please drop me an email, Yigal, with the last question. I'm going to close the meeting again by thanking everybody who contributed to this.