All right. Thank you everyone for joining. My name is Elliot Alper from TD Cowen, I have the privilege of introducing Candel Therapeutics today. Paul Peter Tak will be speaking with all of us today. Without further ado, I'll hand it over.
Thank you very much and good morning, everyone. It's a great pleasure to introduce Candel Therapeutics to you. We are focused on the development of viral immunotherapies for very difficult to treat solid tumors. This is language that you can find on our website, and here you see the summary of the company. We have two investigational medicines in the clinic. The first is called CAN-2409. It's a viral immunotherapy, but it's not an oncolytic virus. It's a first-in-class way to basically immunize the patient against the patient's own tumor at the site of the injection, but also against uninjected distant metastases. I'll show you the mechanism of action in more detail in a minute.
In December 2024, we announced positive data from a pivotal phase III clinical trial of aglatimagene besadenovec, or CAN-2409, in newly diagnosed localized prostate cancer, area of huge unmet need. There's basically no competition. Everybody else is focused on more late-stage disease, and I'll show you more detail about how we think about that and also what our goal is actually in terms of treatment. We achieved the primary endpoint supported by secondary endpoints. The clinical trial was conducted under a SPA, Special Protocol Assessment, agreed with the FDA, which is still intact, which was confirmed in writing in 2025. We got Fast Track designation.
With the data in hand, after data readout, we went to the FDA and applied for RMAT designation, Regenerative Medicine Advanced Therapy designation, which is like a breakthrough designation for gene therapy, which was granted, which is very important because it gives us many possibilities to engage with the FDA and also to accelerate the process. We do not only have positive data in prostate cancer, but because this is a pan-solid tumor therapy, we also have positive data in therapy-resistant non-small cell lung cancer. Here again, we got Fast Track designation. We had a very positive end of phase II meeting with the FDA. We've designed a large pivotal randomized controlled phase III clinical trial, which is expected to start enrollment in the next quarter. This is imminent.
We also announced that we have positive data based on the small randomized clinical trial in borderline resectable pancreatic cancer. We got Fast Track designation and Orphan Drug designation from the FDA as well as Orphan designation from the EMA. At this moment, we have paused that program because we cannot do everything. Top priority is to get the program in prostate cancer over the finish line and to start the non-small cell lung cancer program as soon as possible in metastatic progressive, non-squamous, non-small cell lung cancer patients who have failed immune checkpoint inhibitor treatment and platinum-based chemotherapy. Clearly we have a pipeline in the product strategy here. I will briefly mention CAN-3110, or glinosertib, as we call it now, which is a different type of viral immunotherapy, as you will see in a minute.
It's a replication-competent herpes simplex virus, so it's a true oncolytic virus. It's unique because it contains a gene that everybody else has deleted because of concerns about potential neurotoxicity, which is the ICP34.5 gene. The problem is if you delete that gene, you also sacrifice some of the efficacy. We reinserted 1 copy of that gene and put it under the control of a tumor-specific promoter, which is the nestin promoter. We've shown that after a single injection of CAN-3110 in recurrent high-grade glioma, most of these patients have recurrent glioblastoma, probably the most difficult to treat form of cancer, that we observe a doubling of the expected median overall survival with beautiful molecular and immunological biomarker data. We published this in Nature as well as in Science Translational Medicine.
This is an important indication, huge unmet need, also big commercial opportunity where many others have failed. It's also an enabling indication for other tumors that are characterized by the expression of a molecule called nestin. Think of melanoma, triple-negative breast cancer, and many others. Here again, there's the opportunity to, at the right time, create a pipeline in a product. Here again, we got Fast Track designation and Orphan Drug designation. In terms of corporate highlights, you can see this for yourself. We are in a stable financial situation, especially during the last six months or so. We did a large debt, a structured debt financing with Trinity. We announced a royalty deal with RTW and also very recently an equity deal. We're in a very stable position.
Let's now look in more detail at the mechanism of action. I'm going to show you this in a quick video.
Candel Therapeutics is developing viral immunotherapies for cancer that are able to kill tumor cells, modify the tumor microenvironment, and generate systemic immune activation against tumor-specific antigens.
Our most advanced candidate, CAN-2409, is an adenovirus that has been engineered to deliver a gene encoding an enzyme called thymidine kinase into the tumor cells. The enzyme converts valacyclovir, an FDA-approved oral small molecule drug, from its inactive prodrug state to a form that is toxic to cancer cells. Incorporation of activated valacyclovir in tumor cell DNA results in termination of DNA synthesis and permanent cell damage and death. When administered together, CAN-2409 and valacyclovir cause immunogenic cell death where tumor cells release tumor-specific antigens that are recognized by the immune system. At the same time, the adenovirus itself provokes the release of inflammatory mediators that recruit immune cells, which are educated how to recognize the patient's tumor neoantigens. This effectively results in vaccination against the injected tumor and the uninjected distant metastasis.
CAN-2409 is currently in late-stage clinical trials, and it has been designed to improve patient survival while maintaining quality of life.
We are in a unique position, I think, because we've dosed already more than 1,000 patients. We've learned a lot about the safety and tolerability. I mentioned some of the solid tumors where we've shown efficacy, but we've also shown it in other that are even not included in this slide deck. Huge experience. We've shown monotherapy activity. You see an example on the right side of this slide. This is from a patient with newly diagnosed non-small cell lung cancer, huge tumor. We injected CAN-2409 followed by valacyclovir in the absence of any other treatment during a three-week period. You can see that in three weeks only, there's already a 50% decrease in the size of the tumor. We've also shown this in other indications like in children with retinoblastoma complicated by tumor microseeds and others.
We've also shown that this approach can be combined with optimal standard of care, which gives us a lot of flexibility. Think of radiotherapy, as I will show you in a minute, in newly diagnosed localized prostate cancer or chemotherapy or immune checkpoint inhibitor treatment, as we've done in first-line treatment of glioblastoma. We published this in Neuro-Oncology, but also in other indications. There's a lot of flexibility where we try to optimize the results of standard of care. Let's now spend a few minutes on CAN-3110, which is actually equally exciting, but it's in an earlier stage of development.
Candel Therapeutics is developing cancer immunotherapies based on engineered viral gene constructs able to modify tumor microenvironment, kill tumor cells, and generate systemic immune activation against tumor-specific antigens. CAN-3110 is a modified herpes simplex virus carrying a single copy of a viral gene known as ICP34.5 that enables the virus to replicate despite cellular defense mechanisms. This gene is engineered to be under the control of the promoter for nestin, a protein that is highly overexpressed in high-grade glioma and other aggressive cancers outside the brain, but not in healthy tissue. This modification allows CAN-3110 to replicate almost exclusively in tumor cells, causing immunogenic death. The ability of CAN-3110 to replicate specifically within the tumor leads to significant tumor oncolysis with release of tumor antigens and local inflammation, resulting in a long-lasting immune response against the tumor in both injected and uninjected lesions.
CAN-3110 is currently in an early-phase clinical trial in recurrent high-grade glioma.
We call this a phase I-b trial, but it has grown over time. In fact, we've dosed now more than 60 patients. You could easily see it as a phase II program. In this completely therapy-resistant condition, we see very remarkable clinical outcomes. On the right side, you see for illustrative purposes, you see a more extended version in our corporate slide deck. You see an example of a patient who had failed neurosurgical resection and chemotherapy and radiotherapy. Unfortunately, that's a typical story of a patient with glioblastoma. This patient refused all further standard of care, including even the use of corticosteroids. He did agree to a single injection of CAN-3110 into one of the two tumors that you see on the scan on the left.
You see one with a red arrow, big white lesion, and then next to it, there's another white lesion. This is multifocal recurrent glioblastoma, extremely poor prognosis of less than 6 months. We gave a single injection. Nothing else was done from a therapeutic point of view. You don't need to be a radiologist to see that if you go from the left to the right, there's a very strong improvement in the injected lesion and the uninjected lesion. The patient could go back to work. Although it's still exceptional because it's in the minority of the patients, this is what we're starting to see. Recently, I invited one of these patients into our company because I find it important that my employees hear the story from the patients directly. This was a patient with a similar story.
Her whole memory was wiped out, just close to dying. She got a single injection of CAN-3110, she walked into our office almost five years later. This is ongoing. She lives a normal life. She goes snow skiing. Her memory came back. Her husband said all the memories came back, including the memories that I had hoped that she would have forgotten, right? This is very remarkable. We asked the question also based on molecular findings that we describe in Nature, and more recently in Science Translational Medicine, could it be even better if you give multiple injections? We went up to six injections, and we take serial biopsies from the brain. We learn a lot about the brain tissue response. Nobody else has done this before.
Two CAN-3110, recently we were on the cover of Science Translational Medicine, where we report a pathological complete response in this condition. Just imagine this never happens in the natural course of the disease. We believe that this is very exciting. We're going to optimize the dosing regimen. We are designing a randomized controlled phase II clinical trial, which could be a registrational clinical trial. Meanwhile, we have the option at the right time to also expand into other indications outside the brain. Here you can see that we've de-risked our portfolio on the portfolio level, our Timogen, CAN-2409. We're getting ready for a BLA submission in Q4 of this year. We're getting ready for commercialization. I'll come back to it.
We're ready to start a phase III clinical trial in non-small cell lung cancer, which is going to be a randomized controlled global clinical trial. CAN-3110, we will continue to deliver data. We're going to look at the long-term survivors in Q4 of this year, while we prepare a randomized controlled clinical trial. The company is led by a team with decades of experience in drug discovery and development in immunology and oncology. We know what it takes to get the medicine over the finish line. In my previous life, I was the Chief Immunology Officer and the Global Head of Development of GSK, big pharmaceutical company. My team brings a lot of experience, but I'm also a big fan of independent peer review because you can always have blind spots.
Therefore, I created the Research Advisory Board, which reads like the who is who in oncology, including Jim Allison, the Nobel Prize laureate, Carl June, the father of the field of CAR T-cells, Pem Sharma, Phil Kantoff, and many others. These people are very close to our internal governance process, and, two of them are also members of the board of directors of Candel. They're very close to our programs and very supportive. Let's now zoom in on the lead program, CAN-2409 in prostate cancer. What is it that we try to achieve? Our goal here is not to extend the life of patients with advanced prostate cancer. There are other therapies that have been quite successful in doing so, although there's still a huge remaining unmet need.
This is typically a slowly growing tumor, after 10, 15 years, this is still the second most important cause of mortality due to cancer in men. That's still a big unmet need. Our goal is to increase the proportion of patients with localized, newly diagnosed prostate cancer that will achieve their goal of living free of cancer. Therefore, if you translate that into regulatory terms, the primary endpoint is disease-free survival, the absence of any evidence of recurrent or persistent cancer. Why is that important? Well, first, I think everybody can understand this in an intuitive way. If you had cancer and you choose to undergo radical treatment, you hope that the disease will not come back.
There are the signs and symptoms due to a locally growing tumor, due to local regional progression, due to metastatic progression over time, and also the side effects and the toxicity of the currently available salvage anti-cancer therapy. Think of long-term hormone treatments like androgen deprivation therapy, or chemotherapy, or additional radiotherapy, or additional surgery. That's what we try to achieve. If a patient is diagnosed with intermediate risk or high risk localized prostate cancer and want to eradicate the tumor, there are basically two options. One is radical prostatectomy, which is major surgery. The other is radiotherapy. In about 50/50, you'll choose either of these options.
We focus on the patients who choose radiotherapy as part of radical treatment, but we know that there's a risk of recurrence of about 30%, which is quite high when you think about it, despite the long-term complications of the standard of care treatments that these patients are willing to accept. We combine CAN-2409 with optimal standard of care. It's a huge market. Some people think that there's something difficult about intratumoral approaches. I'm a physician who has treated patients for decades. This is very simple, especially in prostate. The whole procedure takes like 15, 20 minutes in an outpatient clinic. It's easier than a standard of care diagnostic biopsy. Often even no local anesthesia are required, and the patient walks out of your clinic again. We only do it 3 times in a patient's life, so it's very patient-friendly approach.
Here you can see that in this procedure, we basically infiltrate the four quadrants of the prostate. Within 15-20 minutes, we achieve diffuse distribution across the prostate, as you can see shown by the green color on the top right of this slide. You can see the typical regimen on the bottom right. This is like a vaccination regimen without being a vaccine, right? We cause the release of all these tumor antigens in the tumor microenvironment while we cause inflammation, and that leads to a T-cell, a CD8-positive T-cell-mediated response, as you've seen. The treating physicians who do this are mainly the urologists. They are surgeons. Can also be the radiation oncologist. These patients are not seen by medical oncologists. They see patients with more advanced, often metastatic disease, and they are used to do procedures.
They also like this. It's also, after approval, commercially attractive to them. It's also important to ask the patients, how do they think about this? We did. We asked you in the last part of the phase III trial, basically the key question, you underwent diagnostic biopsy in the past. That's how you established the diagnosis. How did the study procedure, where we injected CAN-2409 into your prostate compare to the standard of care biopsy? You can see when you look at the orange bars that most patients indicate it's the same or better tolerated. Why is it better tolerated? Because it's less traumatic. It's a very thin needle, the same that's used for COVID-19 vaccination. You probably know that that's very thin. This was the design of the trial. Everybody got standard of care radiotherapy.
The patients could get short-term ADT based on the NCCN guidelines. It's a large trial, 745 patients, we randomized them 2 to 1 to receive either three injections of CAN-2409 into the prostate or three injections of placebo into the prostate. Everybody got the prodrug, valacyclovir, which is a generic tablet, for two weeks. The primary endpoint, as I discussed, is the absence of any evidence of persistent or recurrent cancer. In other words, disease-free survival, as agreed with the FDA. This is an event-driven endpoint. We took a per protocol two-year biopsy, as agreed with the FDA, because that's the most objective and most sensitive way to detect cancer after two years. If there would be tumor cells in the two-year biopsy, that's an event.
If there are rising PSA levels, prostate-specific antigen, which you can measure in the blood, that would lead to additional diagnostic work-up like biopsy and/or imaging, and it was positive and confirmed, that would be an event. If the patient had signs of metastasis, which is unlikely in this timeframe, we had a median follow-up of 50.3 months, that would be an event. If the patient would die because of prostate cancer, that would be an event. It's again, very unlikely in that timeframe. If the patient would die because of something else, like an accident, it would also count as an event. In a way, we diluted the signal. Despite that, we still achieved the primary endpoint, as you will see. In terms of demographics and baseline characteristics, this was the typical population that you would expect.
85% of the patients had intermediate risk prostate cancer, and 15% had high risk, but they could only have not more than a single high risk factor according to the protocol. Most importantly, the treatment groups are completely comparable in terms of demographic and clinical baseline features. This was very well tolerated. We do see quite a lot of flu-like symptoms that are typically minor. Again, completely comparable to, let's say, COVID-19 vaccination. If you look at serious adverse events on the bottom right of this slide, you can see that there's no difference between CAN-2409 versus placebo. Some people may say, "Well, it's even less for CAN-2409." That must be statistical noise. There's no mechanistic rationale. I think it's fair to say that this is very well tolerated.
What follows from what I described when I spoke about the events is that the key endpoint is prostate cancer-specific disease-free survival. First, I show you here the data for disease-free survival, statistically significant, and then for the patients where we basically eliminate causes of death other than related to prostate cancer, then you see it looks even better. A very significant improvement in prostate cancer-specific disease-free survival. What we show here, this is exploratory descriptive subset analysis, but it's very consistent that this is independent of the use of short-term ADT. It was upon the physician's discretion whether the patient would get short-term ADT. For example, in high risk, you give ADT. In patients with intermediate risk, unfavorable disease, as it's classified nowadays, you would give short-term ADT, defined as less than 6 months.
You can see all the hazard ratios tend to be smaller than one, and it was also independent of the specific type of radiotherapy that was used. This is external beam radiotherapy, EBRT. Over time, there was a new form that was introduced in clinical practice, which is called hypofractionated EBRT. Basically, you give the same overall radiation dose but in fewer sessions. It's known that this does not impact outcome, but it's more patient-friendly because the patient doesn't need to go to the radiation therapy center all the time. Therefore, in 2019, we allowed patients through an amendment, which was approved by the FDA, so the SPA was still intact, to get moderate hypofractionated EBRT. You can see here that the hazard ratios are again smaller than one for both.
Maybe it's even better for hypofractionated EBRT, again, study was not powered to detect these differences. Independent of the subset and of the use of short-term ADT and the specific type of radiotherapy, we found that CAN-2409 performed better than placebo in terms of recurrence on top of optimal standard of care. This was supported by other important secondary endpoints like the proportion of patients that would achieve a really low level of PSA, statistically significant difference. As expected, with a median follow-up of 50.3 months, overall survival was similar as you would expect. It would need another 5-10 years of follow-up to start to see the separation. I think it's logical to say that if you don't have prostate cancer anymore. You will not die because of prostate cancer 10 years later.
The goal here is not really focused on survival, but on living free of cancer and without salvage therapies. We took two-year biopsies, which allowed us to look at the pathological complete response. In other words, the absence of any evidence of cancer cells in a two-year biopsy. You can see here that we achieved a statistically significant improvement in the proportion of patients that achieved this 80.4%, which is really high compared to 63.6% in the placebo group, and that's what you would expect based on the literature. The placebo group, of course, still got the optimal standard of care radiotherapy. Why is a two-year biopsy important? This is not part of normal standard of care. It's a procedure. It's a research procedure, right? To have the most objective evidence.
Why is it not part of standard of care? Because it's not pleasant to undergo a prostate biopsy. Normally these patients are followed by looking at PSA levels, and if then over time, the PSA levels go up, then it will lead to a biopsy and/or imaging studies. This is quite common in radiation oncology studies in prostate cancer. Therefore, we know a lot based on the literature. This is based on a meta-analysis comprising 22 clinical trials. You can see that seeing tumor cells in a two-year biopsy is highly predictive of subsequent biochemical failure and after prolonged follow-up, development of metastases, and after more extended follow-up, prostate cancer-specific mortality. You see on the top left the P values that are extremely low.
We also, although we have already achieved our primary endpoint, consistent with the SPA, supported by the secondary endpoints, in exploratory way, we will continue to follow these patients for the time to metastasis and the time to salvage anti-cancer therapies, and we hope to present this data in Q2 of this year. Meanwhile, we do not only want to get ready for the regulators, but also for the payers. We've done deep payer research for the healthcare professionals and for the patients. We have a very innovative commercial strategy where we work with external partners and where we will bring in-house what we need at the right time. This is an example of some of the pricing based on other treatments that have been approved in later stages of prostate cancer. You can see the typical price range.
We know that based on the payer feedback, there's been very positive response to the concept of CAN-2409. What did they like? They like the clinical data. They have a very consistent data package. They like the safety and tolerability profile, but they also like that this is not a recurring cost that comes back year after year. In fact, it's a bunk of treatment, basically consisting of three courses, and that's it. That's very attractive to the payers. What kind of milestones? I spoke about it. Just to summarize it, we'll see new data for potential long tail of survival in lung cancer before April this year. We expect additional exploratory data from the phase III study in prostate cancer in Q2, like time to metastasis, time to salvage therapy, a continued follow-up for prostate cancer-specific disease-free survival.
In Q3, we expect to announce new biomarker data in prostate cancer. In Q4, we expect to announce a potential long tail of survival in some patients with recurrent glioblastoma for CAN-3110. Most importantly, we are on track to submit the BLA in Q4 of this year. This is the summary. I won't repeat all of this again, and I would like to thank you all for your attention. Thank you very much. Any questions from anyone? If not. Yes, go ahead.
In many ways, this is immunotherapy before there was immunotherapy, right? It is. Why is this approach now coming to fruition?
Yeah.
where, you know, many have struggled with that?
Yeah. It's a great question because the concept of viral immunotherapies has been around for a long time, and now it's coming to fruition, as you said.
I think it's not unusual in the history of progress in medicine because CAR T-cells took actually quite a while. C-cell and gene therapy, bispecific antibodies have been around for a long time, the concept of ADCs and radioligand. I think this is about the world of paradigm shifts that may take a long time. Not all viral immunotherapies are the same, so you need to have the right virus with the right promoter, the right prodrug, if any, in the right indication with the right statistical plan. It's no different from, let's say, let's go back a few decades, antibodies for autoimmune diseases. I'm a rheumatologist, and I was intimately involved in the development of the anti-TNF therapies actually a long time ago now for diseases like rheumatoid arthritis.
I remember that people said, "Well, we don't believe in this." Actually, I also did many trials that were completely negative with depleting anti-CD4 antibodies, non-depleting anti-CD4 antibodies, Campath, IL-10 subQ, what have you. Nobody would ask now the question, well, do you believe in antibodies, right, for autoimmune diseases? It has transformed the field at the moment that people figured out what is the right antibody against which antigen in which indication, et cetera. That's probably behind it. I think we have now shown, based on the data, that this works. We are not alone. A company like CG Oncology is doing really interesting work in bladder cancer, Replimune in melanoma. Also the first big pharma companies are going full in into this space, like Johnson & Johnson.
They created a big unit focused on intratumoral approaches, including viral immunotherapies. They are in phase 1 with their viral immunotherapy in non-small cell lung cancer. I think this is now the cutting-edge new paradigm in this field. We are supported by people like Jim Allison, who published about this concept before he got the Nobel Prize for his immune checkpoint inhibitors. Thanks for the question. Yeah. Thank you very much for your attention.