Good morning and welcome to the Jefferies 2025 Healthcare Conference. It's my pleasure now to introduce Paul Peter Tak, CEO of Candel Therapeutics. Just a reminder, there will be a 20-minute presentation following with 5 minutes of Q&A.
Thank you very much and very good morning, everybody. We have a lot of new data and a lot of new plans, actually, new catalysts, so I won't be able to elaborate on everything. For all the details, I refer to our website where you will find the most up-to-date slide deck. Candel Therapeutics is focused on the development of viral immunotherapies for very difficult-to-treat forms of cancer. This is standard language that you can find on our website. Candel has two investigational medicines in the clinic. First, CAN-2409, which is a first-in-class approach for in situ vaccination, in situ immunization against the patient's own tumor. At the site of the injection, you can just choose one or two tumors in patients with metastatic disease. You don't need to inject all the metastases, and you don't need to do it again and again.
You give two to three administrations in a patient's life to get durable anti-tumor immunity, as we've shown not only in mice but in many, many patients. And CAN-2409 is an off-the-shelf product, and it's a pan-solid tumor strategy. We've shown proof of concept based on a large pivotal phase III clinical trial in newly diagnosed localized prostate cancer. We've shown proof of concept in a randomized clinical trial in pancreatic cancer and in an open-label clinical trial in completely therapy-resistant progressive metastatic non-small cell lung cancer, and also other tumors that we even don't include in the slide deck anymore because we have a lot of data. We got all the designations from the FDA that we wished for: fast-track designation in prostate cancer, pancreatic cancer, lung cancer, orphan drug designation from the FDA in pancreatic cancer, orphan designation for pancreatic cancer from the EMA.
The pivotal phase III trial in prostate cancer was conducted under a SPA, special protocol assessment, agreed with the FDA, which is still intact, and which was reinforced by what I call the new FDA with the data in hand when we had the data readout of the phase III trial by an RMAT designation, Regenerative Medicine Advanced Therapy designation, which is like a breakthrough designation for gene therapy. I'll come back to CAN-2409 in a minute. The second investigational medicine in the clinic is CAN-3110, which is a true oncolytic virus, but it's a next-generation replication-competent herpes simplex virus that will only replicate in the tumor while sparing the healthy tissue. We develop it in probably the most difficult-to-treat form of cancer, which is recurrent high-grade glioma. Most of these patients have recurrent glioblastoma.
They will have failed neurosurgical resection and chemotherapy and radiotherapy, so they're basically at the end of their lives. We have very encouraging data that we published in Nature and in Science Translational Medicine just a few weeks ago. I'll show you some examples from these clinical experiences that we have. We're in a very good financial situation. We just announced that we did a significant deal with Trinity Capital. We also raised an equity deal in December last year and then again later during the first half of this year. We brought in a very strong executive team with decades of experience in drug discovery and development in immunology and oncology. We know what it takes to get a medicine over the finish line and to get it to approval.
I've been global head of development of GlaxoSmithKline, of GSK, and the Chief Immunology Officer of the company. We know what it takes, actually, not only to do R&D but also to get the medicine ultimately to patients. I'm also a big fan of independent peer review because the assumption always needs to be that you may have blind spots. We work with the best of the best in oncology and immuno-oncology in the research advisory board that we created. You will see this reads like the who is who in oncology, including Jim Allison, the Nobel Prize laureate. Very recently, Carl June joined us, the father of the field of CAR-T cells. You will see that there's a leader for each of the indications that we pursue, world-class leaders. These people are very close to our programs.
They participate in our internal governance process where we make decisions about data, the Science and Investment Board, as we call it, and Advance and Gary Nabel are also members of the board of directors of Candel. They are very close to us and also very supportive of our programs. How does CAN-2409 work? I refer to the video that we have online, and you can see actually the address to access it yourself. Basically, it is a form of in situ vaccination where we combine a replication-defective adenovirus that delivers the HSV-thymidine kinase gene to the site of the injection, which is a simple procedure aligned with normal clinical practice. There is nothing complicated about this procedure. Again, you do not need to inject all the tumors at all.
We use that tumor actually to educate the patient's own immune cells how to recognize and eliminate the tumor cells throughout the body. We combine CAN-2409 with a course of two weeks of a tablet, valacyclovir, which is a generic medicine which was actually developed by GSK in the past. It leads to the formation of nucleotide analogs that will lead to highly immunogenic cell death at the site of the injection. Because we use an adenovirus to deliver it, the adenoviral serotype 5 capsid proteins will promote inflammation, value induce the release of a whole variety of cancer antigens in the tumor that are specific for the patient's own tumor. It leads to a largely CD8-positive cytotoxic tumor-infiltrating lymphocyte reaction in the context of immune surveillance. We have shown this leads to a durable anti-tumor immune response.
Again, we administer this only twice or three times in a patient's life to get durable anti-tumor immunity. It is fundamentally different from an oncolytic virus like Imlygic, where you need to inject again and again in all the metastases. At the end of last year, we announced that we have met the primary endpoint in a large randomized clinical trial, placebo-controlled in newly diagnosed prostate cancer, supported by secondary endpoints. I will not have the time to go through all the details of the clinical trial, but we convincingly reached our endpoints. This is the problem that we try to solve. First, everybody else is focused on more advanced disease, which makes a lot of sense because it takes a long time actually to show the benefits in terms of disease-free survival.
We have curative intent here, and therefore biotech companies and pharma companies will focus on more advanced disease. The good news is we have done this. It's behind us, and it has been successful, and therefore there's no competition in this space of newly diagnosed localized prostate cancer. We have focused on patients with intermediate or high-risk prostate cancer who want to get rid of their cancer. They want to be cured. They have two choices. They can choose radical prostatectomy, which is major surgery, or they can choose radiotherapy. The outcomes are similar in terms of clinical efficacy. There are differences in terms of tolerability of the procedure, the nature of complications over time. In terms of efficacy, there's a chance of recurrence of about 30% for either radical prostatectomy or radiotherapy, and about half of the patients will choose for radiotherapy.
That's our target population. We want to help these patients to achieve their goal of living without cancer, living free of cancer. Therefore, as agreed with the FDA, the primary endpoint is disease-free survival. Why is that relevant? If there is recurrence of the disease despite the long-term complications of either radical prostatectomy or surgery, it will lead to obviously cancer-related anxiety, fear of recurrence, the local signs and symptoms due to progression of the disease, local progression, local regional progression, metastatic disease, and the need for salvage therapies, which is typically salvage long-term androgen deprivation therapy, chemical castration, which has a very negative impact on the quality of life in at least two-thirds of the patients. Patients hate this, actually. We try to avoid this. We try to avoid the development of metastasis. We try to avoid the need to use therapies like long-term ADT.
This is the design of the clinical trial. We stayed as close as possible to normal clinical practice. We choose by definition on the patients. We focus on the patients who choose radiotherapy with curative intent. They could get short-term ADT defined as not more than six months upon the discretion of the treating physician because, for example, in intermediate-risk unfavorable prostate cancer, according to the guidelines, there is an indication for short-term ADT. We left that upon the discretion of the physician, and we ended up actually with about half of the patients getting short-term ADT, and the other half did not get it, and we stratified for this in the statistical analysis. We randomized these patients two-to-one to receive either three administrations of CAN-2409, each followed by two weeks of valacyclovir, or three injections of placebo into the prostate, followed by valacyclovir.
As I mentioned, the primary endpoint, as agreed with the FDA, was disease-free survival. We want to see that patients can live without cancer, and if they do not have cancer, they will not die because of cancer, let's say 15 years later. This was done under the SPA. I will just mention here because there is a lot of misunderstanding about intratumoral injections that this is a super simple procedure that takes 15-20 minutes in an outpatient clinic. Who are the treating physicians? Typically, urologists. They are surgeons, right? They put needles into prostates every day. Think of standard of care diagnostic biopsies, which are much more traumatic, bigger needles, more invasive procedure. It is completely implemented in normal clinical practice. It is very often done repeatedly. Here we use a 22-gauge needle. That is the same needle that is used for COVID-19 vaccination.
Most of you will know that that's a super thin needle. It's not very traumatic. Urologists and also radiation oncologists are able to do this without actually any equipment that's not available in their outpatient clinic. Patient walks out of the clinic 15, 20 minutes later, even very often no local anesthesia required, and you only do it three times in a patient's life. I would argue a single injection of CAN-2409 into the prostate is typically better tolerated than an intravenous administration of an immune checkpoint inhibitor because it doesn't lead to cytokine release syndrome. It doesn't lead to the induction of autoimmunity, et cetera. This is a real vaccination regimen that we use. Of course, we can think about this as physicians, but you also need to ask the patients, how do you think about it?
We sent out surveys to the patients asking the question, you underwent a prostate biopsy in the past. How does the study procedure where we inject CAN-2409 compare to your standard of care diagnostic biopsy? When you look at the orange bars, you can see that most patients indicate it's the same or better tolerated than a standard of care diagnostic biopsy. Let's go straight to the primary endpoint. This is an event-driven endpoint. If the patient would have tumor cells in a two-year biopsy, which was agreed with the FDA as a very sensitive way to detect cancer, this is the gold standard to detect tumor cells, this would be an event. If the patient would develop local signs of recurrence or persistence of cancer and it was confirmed by imaging and/or biopsy, that would be an event.
If the patient would die because of whatever cause, right? These patients with a median follow-up of 15 months will not die because of prostate cancer because it's typically a slowly growing tumor. In fact, we had only two deaths due to prostate cancer in the high-risk group. In this time frame, you would need 10 or 15 years of follow-up to show that. This has been consistently reported in the literature, and one of the famous papers was from the New England Journal of Medicine. Let's say a patient died because of a heart attack or a stroke or an accident, that would be an event. We diluted the signal by including events that have nothing to do with prostate cancer. Despite this, we convincingly achieved the primary endpoint with a 30% improvement in disease-free survival.
What follows from what I just described is the key secondary endpoint, which is prostate cancer-specific disease-free survival, where you exclude all the events that are not related to prostate cancer in any way. As you can see, we could demonstrate a 38% improvement in prostate cancer-specific disease-free survival, highly significant. We also showed an increase in the proportion of patients that achieved really low levels of PSA, which you can measure in the blood. Importantly, when you look at the pathology, we could demonstrate at two years an 80.4% pathological complete response in the CAN-2409 group compared to 63.6% in the control group, the placebo group that, of course, still received standard of care radiotherapy. That is what you would expect based on the literature. A highly significant result.
Why do these two-year biopsies matter, which are actually not part of standard of care because it's not necessarily pleasant to undergo a biopsy? It will be done if PSA levels go up. This is quite standard in radiation oncology clinical trials in prostate cancer. Therefore, we know that there's a very highly significant relationship between seeing tumor cells in a two-year biopsy and subsequent biochemical failure, so PSA levels going up, subsequent development of metastases after extended follow-up, and after even more prolonged follow-up, a very strong relationship with prostate cancer-specific mortality. Prostate cancer is still the second major cause of mortality due to cancer in men. It just takes a long time, but it's not great to live with cancer for a long time, have all the side effects of therapy, and then 10, 15 years later, you're still dying because of prostate cancer.
This is a very important slide. We plan to submit the BLA in Q4 next year. Some people ask me, why are you actually delaying the submission of the BLA? You have these data. We met the primary endpoint supported by the secondary endpoints. We are not delaying anything. This is all based on scaling up commercial manufacturing, putting the product on stability, doing biodistribution and shedding studies. This is all straightforward production of a biopharmaceutical. There is no big pharma company that could do this faster than we do. I know that because I have a big pharma background. We work with the best of the best in this field, SAFC in California, right? Merck, Millipore is producing this, overseen by senior leaders that we brought in from Novartis and Merck, who have been in charge of cell and gene therapy manufacturing at Novartis at the time.
We will also use this time to not only be ready for the regulators in Q4 next year, but to also be ready for the payers and the healthcare professionals and the patients. There is a lot of work going on in terms of pre-commercialization activities because I know if you want to hit the ground running and really get to approval, hopefully, and then also sell, right, and get to your peak year sales as fast as possible, you need to be prepared in all these things. There is a lot of work going on in the background. I briefly want to speak about the second indication for CAN-2409 that we are pursuing, which is therapy-resistant non-small cell lung cancer.
This was a very important reason to sign the Trinity Capital deal that we announced just a few weeks ago with up to $130 million of funding, which allows us to start the phase three pivotal clinical trial in non-small cell lung cancer. These are patients who have failed immune checkpoint inhibitors and chemotherapy. They have metastatic progressive non-squamous disease. There is an element of stratified medicine because we found that the immunological and clinical response is better in non-squamous disease than in squamous disease, and it's still 70-75% of the patients. I just want to bring this to life with a representative example of a patient who participated in this trial. We're looking here at the patient who was on stable nivolumab, immune checkpoint inhibitor, and chemotherapy with metastatic progressive disease.
These patients will typically get dose ETAC cell second-line chemotherapy, and typically they die within a year. The prognosis in these patients is very, very poor. We did not change anything to the background therapy that the patient had failed on. We just gave two administrations of CAN-2409 into the tumors or into one tumor, actually, which was the subcarinal lymph node, the affected lymph node. We did not touch the other affected lymph node, the supraclavicular lymph node. You can see here that we stabilized the tumor. Actually, the immune system started to control the tumor. You see there is a consistent decrease over time. Most importantly, the hardest endpoint, and both CITC and the FDA, the new FDA, agree completely that the hardest endpoint is overall survival. This patient is still alive after more than 52 months, and this is ongoing. We just checked this.
This is called an abscopal effect. It clearly illustrates you do not need to inject all the lesions, and we really extend the life of these patients with a good quality of life very significantly. This is a representative example. We see this in two-thirds of our patients. That is the trial that we are going to do in 500 patients, and it is going to start in Q2 of next year. We will have an update about our overall survival data in Q1 of next year. 2026 is going to be very rich in terms of catalyst. This is from an earlier data cut where you can see that we do not only see an improvement in median overall survival, where we actually achieved 24.5 months in patients with an inadequate response to immune checkpoint inhibitors.
We are not aware of any data that come even close to it in the pipeline of the industry. We also start to see here a long tail of survival. In 37% of the patients, we're still alive after more than two years. Actually, they all have non-squamous disease, so that's very interesting. We also found the immunological basis for this, and we're going to submit this to a high-impact journal shortly. The last few minutes I want to spend to talk about CAN-3110. This is a different mechanism of action. It's also a viral immunotherapy, but it's a true oncolytic virus. It's replication competent HSV. Unlike everybody else that has deleted the so-called ICP34.5 gene, so think of Imlygic, think of Replimune programs and others, everybody has knocked out the 34.5 gene. Why? Because it is associated with neurotoxicity.
That makes a lot of sense. However, if you do that, you create a virus that's less effective. What we've done is we have inserted one copy of this gene but put it under the control of a tumor-specific promoter, which is the Nestin promoter. Nestin plays a role in embryogenesis. It's completely absent from the healthy adult brain, but it's upregulated in every glioblastoma. We went for recurrent glioblastoma, the graveyard of industry where everything has failed. I'll show you just one example. Here we have a typical disease course of a patient with recurrent high-grade glioma. You see the initial lesion. The patient went for a subtotal resection. At some point, and that's always the case, unfortunately, there's recurrence of the disease. There is rapid progression. When you look at day minus 14, the patient underwent actually a second resection.
Two weeks later, the tumor was growing again. These patients are going to die within weeks, definitely not more than a month. On day zero, we gave a single injection of CAN-3110 into the tumor. You can see the timelines are changing. Three months after that, there appears to be, again, tumor progression on imaging. We took biopsies, and it appeared that it was largely pseudo-progression. We were replacing tumor cells by immune cells. The patient went for another debulking at day 96. The patient was still alive. After that, the patient was considered to be cured. You see on the right, day 630, there is a very long timeline here. You see this big empty space. The patient lived a completely normal life until she died in a car accident while she was even not driving. This is just one example.
We just announced just a few weeks ago that even in the patients who have received a single injection, we have a patient who's still alive after 59.2 months, the other 42.4 months. These are extreme timelines. We're starting to see long-term survivors even after a single injection. Now we've asked the question, what would happen if you give multiple injections? We went up to six injections. This is ongoing. We see very encouraging results. We're starting to see the first long-term survivors. We just published data where we took serial biopsies from the brain. I mean, this is pretty amazing. This has been never done before. We ended up on the cover of Science Translational Medicine just a few weeks ago. What you can see here in red, you see this big tumor.
In the middle, you see the yellow area, which represents necrosis, cell death in these tumor cells. You see four green dots. These are the four injections of CAN-3110. This was a pathological complete response, which I think has never been described in recurrent glioblastoma. We'll have an update about this in Q4 next year, where we're starting to look at long-term survival for CAN-3110. In summary, CAN-2409, one solid tumor therapy where we have positive data, including pivotal phase 3 data. We're preparing for BLA submission in Q4. We're going to use this time also to generate a lot of data, including biodistribution and shedding, which is all straightforward work requested by the FDA. We will use that actually to also create new immunological biomarker data, which is not requested by the FDA.
We are a deeply scientific company, and we want to generate these data, which will be important for strategic discussions and also for commercialization in the future. I spoke about CAN-3110, which is very promising. We see this as an enabling study also for other tumors outside the brain characterized by Nestin expression. Finally, I want to close on this. These are the catalysts that we just announced for next year. It's going to be another busy year. New overall survival data, including long-term survival for non-small cell lung cancer. We will start the clinical trial in non-small cell lung cancer planned for Q2 next year. We expect new data based on the prostate cancer trial where we continue to follow these patients. You can see more data about CAN-3110 and the BLA submission. I want to thank you all for your attention.
Thank you very much.