Thank you very much. Hi, everybody. As you will notice, I lost my voice. I had meetings with 18 investors today, and we're not even raising money at the moment, so I lost my voice. I hope you can still hear me. Candel Therapeutics is focused on developing viral immunotherapies for difficult-to-treat solid tumors. You can find this language on our website, and here you see a summary of the company. Our lead asset is called aglatimagene, formerly known as CAN-2409. It has a unique mechanism of action. It's a first in class. It's an off-the-shelf prodrug. It's a pan-solid tumor therapy, but it leads to an individualized anti-tumor immune response specific for the patient's own tumor.
We feel quite comfortable that it is a pan-solid tumor strategy because we've shown mechanism of action, proof of mechanism, proof of concept, positive phase III placebo-controlled trial in prostate cancer. We have data in lung cancer, in pancreatic cancer, in other indications as well. I'll speak today mainly about newly diagnosed localized prostate cancer, and we'll very briefly mention the non-small cell lung cancer program. We are about to start a global phase III study in that indication as well. We also have data based on a small randomized control trial in borderline resectable pancreatic cancer, and we see a total separation of the overall survival curves. We got all the designations that we hoped for from the FDA, as you can see.
I will just briefly mention we also have another investigational medicine that's I think equally exciting but in an earlier stage of development, which is called linoserpaturev, formerly known as CAN-3110. It's a different mechanism of action. It's also a viral immunotherapy, but this is a true oncolytic virus, but it's a next generation replication-competent herpes simplex virus that has been designed to replicate specifically in the tumor while sparing the healthy tissue. We tested in probably the most difficult to treat form of cancer, which is recurrent glioblastoma. We've seen beautiful effects where we see even after a single injection, doubling of expected median overall survival. We've studied the molecular and immunological changes. We published this in Nature, and more recently, we presented data where we injected this multiple times, each preceded by a brain biopsy.
We've learned a lot about the tissue response in the brain of patients to linoserpaturev. We published this in Science Translational Medicine. We are on the cover. I think we've shown there the first pathological complete response in history in recurrent glioblastoma. This is a big unmet need, big commercial opportunity in an area that has been a graveyard for the industry, where we are planning now a randomized controlled phase II study. This is also an enabling indication for other tumors outside the brain. Here again, like for aglatimagene, the strategy could be to create a pipeline in a product. In terms of corporate highlights, we have a very strong executive team with decades of experience in drug discovery and development.
We are supported by a very strong research advisory board with people like Jim Allison, Carl June, Phil Kantoff, Roy Herbst, and many others. We are in a good financial situation. We have a runway into Q1 2028, and potentially we can get into commercialization based on the current financing. How does aglatimagene work? Very briefly, this is a replication-defective adenovirus that we use to deliver a gene that's actually derived from herpes simplex virus. It's the HSV thymidine kinase gene. For example, in prostate cancer, we inject this into the prostate. It's a very simple procedure, very thin needles like a flu shot, but then in the prostate, much less traumatic than a standard of care biopsy, and it leads to infiltration of the prostate by aglatimagene. We deliver this HSV thymidine kinase gene. That means you get local enzyme activity.
You get local activity of HSV thymidine kinase. We give the patient two weeks of a tablet, which is valacyclovir. This is a generic drug, and we use it as a prodrug because valacyclovir will be activated under the influence of HSV thymidine kinase, specifically in the injected prostate, and this will be converted into a toxic metabolite, a nucleotide analog that will be specifically incorporated in cells that exhibit DNA damage or that are proliferating, in other words, the tumor cells. There's a synergistic effect with radiotherapy because radiotherapy will induce DNA damage. That means you get highly immunogenic cell death in the tumor microenvironment, leading to the release of a whole variety of cancer antigens and cancer neoantigens that are specific for that tumor. At the same time, the adenoviral serotype 5 capsid proteins will give a very strong pro-inflammatory signal.
In other words, you create the optimal conditions for in situ immunization against the patient's own tumor, which lead to a local anti-tumor immune response and also a systemic anti-tumor immune response. You don't need to do this again and again. In prostate cancer, this treatment is basically a one-off treatment consisting of three courses, almost like a vaccination approach. In non-small cell lung cancer, we just administered this twice by bronchoscopy, again, aligned with normal clinical practice, simple procedure, takes less than an hour. We've dosed aglatimagene to more than 1,000 patients, so we feel quite comfortable when we speak about safety and tolerability. I spoke already about the designations. On the right side, I just show you that we've also shown clear monotherapy activity. This is a patient actually with newly diagnosed lung cancer. You see this enormous tumor. We only injected aglatimagene followed by valacyclovir.
Three weeks later, you see a reduction in size by 50%. Very briefly, linoserpaturev, I mentioned it. We tested in recurrent glioblastoma. We got Fast Track designation and Orphan Drug designation in this indication as well. We've now dosed it to 62 patients. We call it a phase I-B trial, but I would say it's actually a phase II trial by now. We added arms. You see on the right the responses that we get in terms of clinical outcomes. You see here a patient with recurrent multifocal glioblastoma. You see two tumors, one with a red arrow, and then next to it there's another white lesion. This patient refused all further standard of care, but he'd only agreed to a single injection of linoserpaturev in the large lesion with the red arrow.
You don't need to be a radiologist to see that if you go from the left to the right, there's a dramatic improvement at the site of the injection, but also at the uninjected lesion. This patient could go back to work. Some of you may have seen that there was recently an interview by a patient, who participated in this trial, who gave an interview to Parade, which is a journal that's read by tens of millions of people. This is an exceptional patient, but this patient had a similar story. Recurrent glioblastoma. The memory was wiped out. She was close to dying. She got the single injection of this replication-competent virus, and she's still alive after almost six years and leads a normal life. I'm not saying that we see this in all patients. This is an exceptional case. We see a few of these cases.
We try to learn how can we optimize this? Together, we've created a pipeline focused on value creation, which is largely de-risked with proof of concept in humans for each of these indications and for each of these investigational medicines. I also want to highlight that since I joined this company almost six years ago, we've always done what we said that we would do. We've never missed a single catalyst. I'm not going to say that it will never happen, but I will do anything we can to identify risk and mitigate risk. You can see we're also on track this year. In the red square on the right, you can see what we are planning for the rest of this year.
Initiation of a phase III clinical trial in metastatic progressive non-small cell lung cancer, new biomarker in Q3 in newly diagnosed localized prostate cancer. In Q4, an update of the potential long tail of survival after linoserpaturev in recurrent glioblastoma. Just imagine that we're even starting to think about this, because these patients typically all die within six to nine months. Most importantly, BLA filing in Q4 of this year. We're still on track for aglatimagene in newly diagnosed localized prostate cancer. Why are we focused on newly diagnosed localized prostate cancer, and what is the problem that we try to solve? We focus on patients with intermediate risk or high risk with a single high risk factor, newly diagnosed localized prostate cancer, who want to be cured.
These patients elect to undergo radical treatment with curative intent. They can choose between radical prostatectomy, which is surgery, or radiotherapy. We focus on the patients who choose radiotherapy. The outcomes in terms of recurrence are similar. There's a risk of recurrence of about 30%. How the complications kick in, that difference, and the patients are able to undergo surgery, all these factors determine are they going to choose one over the other. We are focused on the 65,000 patients per year in the U.S. alone that will choose radiotherapy with curative intent. The problem is, as I said, in 30% of the cases, the disease will come back. We want to increase the proportion of patients that will achieve their goal of living free from cancer. This is not about living longer with cancer. This is about living without cancer.
We try to delay or avoid the need to use long-term salvage anti-cancer therapies like long-term ADT, androgen deprivation therapy. This is chemical castration. Patients hate this. We try to avoid the local or metastatic progression of the disease. It may still be alive with prostate cancer, but it may be alive with a very strongly impaired quality of life. That's a treatment goal. There's no competition in this space. Nobody's done such a study. One of the reasons is it takes forever to do such a study. It took us more than 10 years. The good news is it's behind us, and it's positive. This field is wide open. It's a very big opportunity. This was the design of the clinical trial. By design, everybody got external beam radiotherapy, standard of care.
We left it to the treating physician, whether the patients would get short-term ADT, defined as not more than six months, and we ended up with about 50% of the patients getting ADT, and the other 50% did not, and we stratified for this in the statistical analysis. We had 745 patients, and we randomized them 2 to 1 to receive either three administrations of aglatimagene into the prostate or three administrations of placebo into the prostate. Everybody got valacyclovir, which is the product, which does nothing in itself on cancer. As agreed under the SPA, the Special Protocol Assessment, agreed with the FDA, the primary endpoint is disease-free survival, which basically means the absence of any evidence of cancer. This is the right endpoint in a curative setting. Here you can see the procedure.
This is a simple procedure in the hands of a urologist or a radiation oncologist. This can be done in an outpatient clinic. You don't need to give sedation. In many cases, you even don't need to give local anesthesia. We basically infiltrate the prostate by giving 0.5 mil in each of the four quadrants of the prostate. The reason is that prostate cancer is often a multifocal disease. There may be small lesions, and we have shown that if you use this approach, if you look at the bottom left of this slide, all the green color represents, as shown by immunofluorescence, the distribution of aglatimagene after local administration. This was the treatment regimen. We started by giving the first administration of aglatimagene, which can often be combined with, for example, the placement of a spacer that's increasingly used.
We give two weeks of the tablets, valacyclovir. You see the start of the radiotherapy. Patients come to the clinic anyway, so at that moment they get the second administration of aglatimagene, another two weeks of valacyclovir, and then the third, just like a second booster of aglatimagene, again followed by valacyclovir. The primary endpoint was disease-free survival, as I mentioned. What does that mean? This is an event-driven endpoint, and per protocol, we took a two-year biopsy of the prostate, which is not part of normal standard of care. Why not? Because it's not very pleasant to undergo a prostate biopsy. It's the most objective and sensitive way to detect cancer cells, and it will actually precede biochemical failure, so PSA levels going up.
Also, PSA levels in themselves are not completely reliable, so the PSA was not accepted by the FDA as an endpoint. This is the gold standard to detect cancer cells, is take a biopsy and look under the microscope. If the biopsy was positive at two years, that's an event. Patients are in normal clinical practice, followed by PSA measurement. If there's a continuous rise in PSA, it will lead to additional diagnostic workup, imaging and/or biopsy. If that was positive, that's an event. If the patient would develop metastases, which is unlikely in this timeframe, it would be an event. On the right side, if the patient would die, independent of the cause, that would be an event. If a patient died in a car accident, as happened, that was counted as an event.
If a patient overdosed on drugs, as happened actually one and a half year after the trial, people do crazy things. That's an event. That also means we diluted the signal with events that have nothing to do with prostate cancer, but still, we achieved our endpoint. This is generally well-tolerated. You can see a lot of detail actually in the paper in The Lancet Oncology that was published yesterday. This is really very new. You can see that you see flu-like symptoms in about one-third of the patients. These are typically mild, last one or two days. That's it. You can just compare it actually to, for example, COVID-19 vaccination in terms of these flu-like symptoms. Otherwise, if you look at the serious adverse events, as shown on the top of this slide, there's no increase when you compare aglatimagene compared to placebo.
Some people will say, "Numerically, it looks even better in the aglatimagene group." That is statistical noise, but there's no increase. This is the primary endpoint, which we convincingly achieved. Hazard ratio of 0.7, P value of 0.055. That means basically a 30% risk reduction or a 30% improvement in disease-free survival. From how I described DFS follows the key secondary endpoint, which is prostate cancer-specific DFS. This is shown here. Here you exclude the death that are completely unrelated to prostate cancer. I should mention, we had only two prostate cancer-related death in this trial with a median follow-up of 50.3 month. That's what you would expect. One in the active treatment arm, one in the placebo. I want to remind you, 2: 1 randomization. We should not read too much into this at this time.
You see it looks even better. Hazard ratio of 0.62, it's very highly significant. There's actually a better way of looking at it. It means 38% reduction for prostate cancer-specific events. We did an exploratory descriptive analysis, again, I want to warn that we should not read too much in it. This study was not statistically powered to detect differences in subsets. What you hope to see is that all the trends are more or less in the same direction, that the hazard ratios tend to be lower than one, that's exactly what we see. If you look at the patients who did not receive androgen deprivation therapy, you see hazard ratio is 0.56. If you look at the patients who did get ADT, hazard ratio of 0.69.
The conclusion is we observed the benefit of aglatimagene compared to placebo on top of standard of care radiotherapy independent of the use of short-term ADT. The same is true for the use of the specific type of radiotherapy because there has been evolution, and there was what we now call conventional EBRT, but later there was a new regimen, which is called hypofractionated EBRT. That means you give exactly the same overall dose, but you give it in fewer sessions, which is more patient-friendly because they don't need to come that often to the clinic. It does not impact outcome. It does not improve outcome. It's just more patient-friendly. Therefore, in 2019, we submitted an amendment to make it possible to use moderate hypofractionated EBRT. Then again, we interacted with the FDA that confirmed in writing that the SPA remained intact.
Here you can see that in the same exploratory descriptive way I looked at the hazard ratios, does it actually have an impact whether you use hypofractionated EBRT versus conventional EBRT? You look at the hazard ratios, they all look smaller than one. Some people might say it looks even better for hypofractionated EBRT. Again, I want to caution against over-interpreting the data. My conclusion is we've shown the benefit of aglatimagene versus placebo, independent of the specific type of radiotherapy. I spoke already about the pathological complete response that we looked at. We took a two-year biopsy, and this basically means the total absence of tumor cells in your biopsy. As you can see in the placebo group, this was achieved in 63% of the patients. This is what you would expect based on the literature.
We saw a statistically significant increase in the proportion of patients that had pathological complete response at two years with a value of 80%, 8-0, which is very high. Why does this matter? Because it's known based on previous studies, and I'm showing you a published meta-analysis comprising 22 clinical studies where two-year biopsies were used in radiation therapy studies in localized prostate cancer, that there's a highly significant relationship between having a positive biopsy at two years and subsequent biochemical failure. If you look at the top of the slide, 10-fold higher odds of developing biochemical failure over time, threefold higher odds of developing metastatic disease, and after even more extended follow-up, a fivefold higher odds of dying from prostate cancer.
Many people will say, "Well, prostate cancer, many of these patients die with prostate cancer." Which is true, because it's also associated with cardiovascular disease and other conditions. At the same time, it's true that this is the second most common cause of death due to cancer in men. It just takes longer than when you look at pancreatic cancer or lung cancer and other cancers, but after 10, 15 years, it's still a major killer. That's not the main goal of our treatment. We want to achieve cure, and I would say if you're cured, you won't die because of prostate cancer 15, 20 years later. Here you can see that the two-year biopsy is very predictive. I said in December 2024, when our data read out, I believe that over time, we're starting to see a separation between aglatimagene versus placebo.
If you look at biochemical failure, time to metastasis, and the time to salvage anti-cancer therapies, that's exactly what we just presented. These are data that we presented two weeks ago at a plenary oral session at the AUA, American Urological Association meeting. A very big session. You can see that the impact on prostate cancer-specific DFS is durable. The hazard ratio even looks a little bit better. Still very statistically significant. 39% improvement in prostate cancer-specific DFS after prolonged follow-up. Here we have a median follow-up of 58 months. Here I'm showing you the time to salvage anti-cancer therapy on the left and showing you the time to biochemical failure on the right. It's almost boring. All these figures look the same. You see the consistent separation between aglatimagene versus placebo. This is also interesting.
We're looking here at the time to metastasis, and you see here a hazard ratio of 0.58. Again, very clear trend towards improvement if you compare aglatimagene versus placebo. I asked my team, "Well, let's now look at the largest subset, which is 85% of the patients, had intermediate-risk prostate cancer." It's still a very large group. We have here 635 patients with intermediate-risk prostate cancer. Again, I just show you one slide because all the others show also the separation. I just want to highlight here, we look at the time to metastasis. Look at the hazard ratio. It's 0.1. We're showing here a 90% improvement in the time to metastasis, which actually achieved already statistical significance if you look at the confidence interval as shown on the bottom.
This is a very exciting, supportive piece of information that we do not necessarily need for the file because we had the readout of our data in December 2024. All of this is very supportive from a scientific engagement perspective and shows the meaningfulness of the two-year biopsy. This is what I just showed you. We also have other secondary endpoints that were all positive. You can find far more detail in The Lancet Oncology paper, and also on our website. I just want to speak briefly about non-small cell lung cancer. Here we start actually at the other side of the spectrum. In prostate cancer, after approval, hoping that we will get there, and planning for success, we will probably move into oligometastatic disease, and after that, into metastatic disease.
In fact, we have already some evidence that it also works in advanced prostate cancer patients who had failed radiotherapy. In non-small cell lung cancer, we have the reverse strategy. We start with progressive metastatic non-small cell lung cancer, and this is a big unmet need, as you see on the right side of the slide. Immune checkpoint inhibitors have really changed the field and have really improved outcomes. Still, it's a huge unmet need. After one year of immune checkpoint inhibitors, 60% of the patients will actually show progression. There's a lot of activity in this field, but we don't believe that there are great compounds in the pipeline of the industry that I'm aware of that show very promising benefit risk for the patients. To make a long story short, you can find it in far more detail on our website.
This is what we find. This is a representative patient in our trial. You see this huge tumor, more than 11 cm at baseline, growing despite KEYTRUDA and despite chemotherapy. You see the real diameter of the tumor on the top right of this slide. Before the first injection with aglatimagene, you can see this tumor is growing, and this patient has an extremely poor prognosis. We give the first administration, as shown by the red arrow. You see that the tumor is starting to decrease in size, right? It's not an immediate dramatic decrease because it's an immunotherapy. We replace tumor cells by immune cells. There's an element of pseudoprogression, as we've shown in serial biopsy samples. We give the second administration that's like the booster, right? You see the second red arrow, and you see that there is consistent control.
We basically change progressive cancer into a chronic disease with an acceptable quality of life. This patient lived until 56.4 month, which is extremely long, right? We've seen very clear abscopal effect. You don't need to inject all the metastases. You just choose one or two tumors that are easily accessible, typically by bronchoscopy, to educate the patient's own immune cells how to recognize and eliminate, the tumor cells and create a new state of immune surveillance. These data were presented very recently. We've shown that we have observed doubling of expected median overall survival, even a little bit more than that, with just two administrations of aglatimagene without changing anything else. We ask the question, is there a long tail of survival?
These patients will get a normal standard of care, docetaxel second time chemotherapy, which has quite a lot of toxicity, and the median overall survival with standard of care has consistently been reported as less than one year. Here we showed that after two years, 50% of the patients were still alive, which is very long. You see several were alive three, four, up to almost five years. The interesting thing is all these really long tail survivors have non-squamous, non-small cell lung cancer. We've shown that there's a differential immunological response if you compare non-squamous to squamous. If you focus here on the population with progressive disease at baseline with non-squamous disease, you can see we observed a median overall survival of 25.4 month. If anyone has seen better data in the industry, please drop me an email, because we are not aware of it.
These data are extremely promising, and we got Fast Track designation from the FDA, and we've designed this phase III clinical trial that is going to start imminently. We will include 500 patients with metastatic, progressive, non-squamous, non-small cell lung cancer, who failed on KEYTRUDA and cisplatin-based chemotherapy. You know they have a very bad prognosis. We randomized them to either stay on the KEYTRUDA that they failed on, but we give them two administration of aglatimagene to convert non-responders into responders, as we've shown in the phase II study. You stop the immune checkpoint inhibitor, KEYTRUDA in this case, and then you give the patients docetaxel, as you would do a normal standard of care, and the primary endpoint is overall survival. I'll stop here. This is my summary, and I would like to thank you for your attention. Thank you very much.