Morning, everybody. Welcome to the Jefferies Global Healthcare Conference. My name is Brett Gallagher with the Healthcare Investment Banking Team. It's now my pleasure to invite Paul Peter Tak, from Candel Therapeutics, up to the stage.
Thank you very much. A very good morning, everybody. It's great to be here and to present our programs at Candel Therapeutics. We are focused on the development of viral immunotherapies for very difficult-to-treat cancers. Let's see if this works. These are the forward-looking statements that you can find on the website. This is the company just at a glance. The lead compound is called CAN-2409. I'll discuss it in more detail. It's a pan-solid tumor approach. It's not an oncolytic virus, but it's a whole new first-in-line viral immunotherapy that, as you will see, leads to immunization against the patient's own tumor. We got all the designations you can dream of for the different indications that we pursue, including RMAT last week. The second investigational medicine that I will not discuss in more detail just because of time is CAN-3110.
This is a true next-generation HSV oncolytic virus that will replicate specifically in the tumor while sparing the healthy tissue. We test it in the most difficult-to-treat form of cancer, which is recurrent glioblastoma. With very encouraging results, we published the data in Nature that a single injection could double the expected median overall survival. We are now exploring the effects of multiple injections. This is a big indication in itself where others have failed. It is also an enabling indication for other tumors outside the brain that we can leverage the same pathway that actually, or the same molecule that triggers the activation of the virus, which is called Nestin. Think of triple-negative breast cancer, sarcoma, melanoma, et cetera. We got a very big grant from the Break Through Cancer foundation. This program pays for itself. It is also great external validation.
For the remainder of this talk, I will focus on the lead asset, which is called CAN-2409. I'm going to play a quick video that will explain the mechanism of action.
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 pro-drug state to a form that is toxic to cancer cells. Incorporation of activated valacyclovir and 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.
This is the summary of CAN-2409 from a clinical development perspective. We've dosed this investigational medicine to more than 1,000 patients. We have huge experience in terms of safety and tolerability. We got fast-track designation for prostate cancer, pancreatic cancer, and non-small cell lung cancer. We got orphan drug designation for pancreatic cancer. We conducted the phase III study that I'm going to show you in a minute under a SPA, special protocol assessment agreed with the FDA. That basically means that the FDA has agreed in writing to the design of the study, including, this is critical, the new primary endpoint, which is disease-free survival. You'll see we have curative intent. Last week, we also got the RMAT, the Regenerative Medicine Advanced Therapy designation that gives us all the benefits of a breakthrough designation plus more.
As you can see on the right side, we have shown monotherapy activity across multiple indications. This is a patient with a newly diagnosed non-small cell lung cancer. This is a huge tumor, as you can see. We just gave CAN-2409 once in this case, followed by the pro-drug, similar to what you've seen in the video. You see three weeks later, there's already a 50% decrease in the size of the tumor. We have also shown that CAN-2409 can be combined with surgery, chemotherapy, immune checkpoint inhibitor treatment, radiotherapy, where appropriate from a clinical perspective. Let's now focus on the lead indication, which is early localized non-metastatic prostate cancer. Everybody else is focused on more advanced disease. That is why they focus on metastases, free survival, overall survival, et cetera.
We are focusing on the earliest stages of the disease in patients with intermediate or high-risk localized prostate cancer who elect to undergo radical treatment. Patients basically have two choices. One, they can choose radical prostatectomy or surgery, major operation, or they can choose radiotherapy. Until now, the clinical outcomes in terms of disease-free survival are similar. There are different reasons why patients may prefer surgery versus radiotherapy or the other way around. About 50% of the patients will elect radiotherapy. You can see the numbers in terms of incidence. These are very significant numbers. As you know, this is the second most common cause of cancer in men in the US and many other parts of the world. The first would be all the skin cancers together, actually, including relatively innocent skin cancers.
You can see what we try to achieve here. We try to prevent the recurrence of the disease, which is clinically very important because patients do not want to live with cancer. That is why they are willing to accept the long-term complications of these therapies, surgery or radiotherapy. Think of urinary incontinence, erectile dysfunction, loss of quality of life, depression. They are willing to pay that price because they want to get rid of that tumor. The reality is that in 30% of the cases, there will be recurrence, both for surgery or radiotherapy. We try to increase the proportion of patients that will stay free from tumor. We just came back from ASCO. I am going to show you the oral presentation that we gave just two days ago. It was delivered by Ted DeWeese, who is the Dean and CEO of Johns Hopkins.
You see the authors on the paper. This is a pivotal phase III clinical trial. I'm going to show you the design in a second. Key takeaways, CAN-2409 plus pro-drug, which is valacyclovir, improves disease-free survival by 30%. We achieved statistical significance. This is the primary endpoint compared with placebo when added to standard of care and state-of-the-art radiotherapy. We believe this could offer a real paradigm shift in our thinking about prostate cancer. This would be the first new development in early localized disease in more than 20 years. As I mentioned, the goal here is prevention of cancer recurrence. This is the design of the clinical trial. We involved 745 patients. This is the ITT population. Everybody got, by definition, standard of care radiotherapy.
We randomized patients to receive either three injections of CAN-2409 into the prostate or three injections of placebo into the prostate, followed by valacyclovir, which in itself does not do anything for the cancer. As I mentioned, the primary endpoint was disease-free survival. How about the procedure? There are some people who think that it's very difficult to inject something into a tumor. It's actually very simple and straightforward and aligned with normal clinical practice. We inject in total 2 ml into the four quadrants of the prostate. We infiltrate the whole prostate with CAN-2409. The reason is that prostate cancer is often a multifocal disease. There may be small lesions in the tumor that may even have been missed with the diagnostic biopsy. We infiltrate the whole prostate. You can see we are able to do that.
If you look at the green color, you see the diffuse distribution here of the labeled virus. The whole procedure takes 15 to 20 minutes in an outpatient clinic. You don't need anesthesia. You don't even need local anesthesia. It's often better tolerated than a standard of care prostate biopsy. You only need to do it three times in a patient's life to get durable anti-tumor immunity. This is a very patient-friendly approach. It's aligned with normal clinical practice. The treating physicians are radiologists, radiation oncologists, or urologists. They put needles into prostates every day. No special equipment required for this procedure. Here you see the concert diagram. You can find all the details on our website. You go to the corporate deck. As you can see, we screened 774 patients. The ultimate intensity to treat analysis population consists of 745 patients.
This is a really very big program that took many years to complete. Here you see the baseline characteristics of these randomized patients. Nothing out of the order. This is the population that you would expect. You can see that we had about 85% of the patients who had intermediate-risk prostate cancer. About 15% had high-risk prostate cancer. You can see the groups are nicely balanced between active versus control. 85%, more or less, had a Gleason score of 7. The other patients had higher scores, 8 or 9. Very aggressive disease. We left it to the discretion of the treating physician whether patients would receive short-term, defined as less than six months, ADT, androgen deprivation therapy, which is hormonal therapy. As you can see, about 50% of the patients received ADT. We stratified for this in the analysis.
We know that this is well tolerated. We've published this before based on other programs. If you focus on the adverse events shown in the red box, these are those that are related to CAN-2409. We typically see flu-like symptoms that are mild, that last less than 24-48 hours, very comparable to, let's say, COVID-19 vaccination. We try to induce inflammation so patients may feel the flu-like symptoms. Otherwise, you see the other side effects on the bottom are all related to radiotherapy. This is well established and also comparable between the two groups. How about serious adverse events and adverse events thought to be related to treatment? In fact, we found trends towards lower numbers of serious adverse events in the CAN-2409 group compared to placebo. Frankly, I don't know how to explain that. The bottom line is really that this is probably statistical noise.
There's no increase in the active treatment group. That is the key message here. It's very safe, very well tolerated. This is the key slide that shows you the primary endpoint. This is an event-driven endpoint. If there are tumor cells in the prostate biopsy after two years, that's an event. If there's any evidence of local progression of the disease or development of metastasis, that's an event. If a patient dies independent of the cause, then that's an event. Many of these patients who die will die because of cardiovascular disease, right, in men of this age. There were also accidents, right? Somebody fell off a ladder in the active treatment group and died. Somebody was murdered even in the active treatment group. We don't believe it's related to treatment. Of course, this dilutes the signal.
Despite that, if you take all causes of death in your primary endpoint, we still see this highly significant improvement in disease-free survival. Let's now look at the secondary endpoint where we focus on, oh, sorry, I missed this slide. I'll show this first. Focus on prostate cancer specific disease-free survival. You can see the results look even better. We have a 38% improvement in prostate cancer specific disease-free survival. You can see the p-value. This is highly significant. We did an exploratory analysis. We look at different subgroups. I need to highlight that this study is not designed from a statistical point of view to detect any significant difference in these subgroups because they're just too small. We look at this in an exploratory way. What you would like to see is that the hazard ratios are less than 1, right?
That the midpoint of your forest plot shows that everything is a little bit to the left. That's, generally speaking, what we see. Let's focus on the patients who did not receive androgen deprivation therapy. This is very important. You see that the hazard ratio was 0.56. Again, I want to look at this in a descriptive way without making claims that are too big. Of course, this is extremely encouraging. In the clinic, you actually want to try to avoid the need of ADT because patients hate it. Two-thirds of them will have reduced quality of life. There is a distinction between favorable and unfavorable. You see that both midpoints are to the left. Let's now look at the patients who received androgen deprivation therapy. There are the patients who had unfavorable prognostic factors. That's where it's currently indicated.
You see that the hazard ratio is 0.81, so still the scope. Then we look at the patients who have favorable prognostic factors. Actually, they are not candidates for ADT. They should not get ADT. You see a hazard ratio at first sight of 2.26. Think, oh, what's going on here, right? In the first place, these patients should not have received ADT. In the second, these numbers are really small. You look at the confidence interval. It ranges from 0.27 to 1893. That is how we get to 2.26. We do not think that we learn anything useful here. The key point is that CAN-2409 appears to work better than placebo, independent of the use of ADT, and offers the opportunity, actually, potentially, to avoid ADT. Let's now look at, sorry, I am still struggling with my clicker.
I hope I don't make you dizzy. Let's now look at the other secondary endpoints. If these patients are followed in normal clinical practice, PSA levels are measured, right? Easy, soluble biomarker. The goal is to get undetectable PSA levels. That means with a sensitive test, a value of less than 0.2 ng per mil. This was achieved in a higher percentage of patients who had received CAN-2409 compared to the placebo group. You see it's statistically significant. How about overall survival? We had a median follow-up of about 50 months, so close to five years. It's quite long. It's not long enough to show that patients will live longer because they don't get prostate-related mortality. You need a follow-up of a median of about 10 years. This is well established in the literature.
I put one of these papers on the bottom of the slide from The New England Journal of Medicine. We only had two deaths due to prostate cancer during this follow-up period, as expected. Fifty patients died due to other causes, and I mentioned some of them. This is very important. The FDA requested that we would look at the recurrence of the disease in the most sensitive way possible, which is by taking a biopsy two years after treatment. If there would be any evidence of tumor cells, that would be an event. We looked at the pathological complete response. That means total absence of any evidence of cancer. It was achieved in more than 80% of the patients in the CAN-2409 group, 80. It is really high compared to about 64% in the control group. Again, you see this is statistically significant.
Although this is not a routine test, and I would not recommend doing it in routine clinical practice, for research, it is very, very important because this underpins, actually, what we have shown in terms of disease-free survival. Why does it matter what you find in your two-year biopsy? This is actually quite standard in many radiation clinical trials because it is known from the literature. What I show you here is based on a meta-analysis based on 22 trials that there is a very significant relationship between having tumor cells in the biopsy at two years and subsequent biochemical failure, as shown by increased PSA levels, subsequent development of distant metastases after prolonged follow-up, and also of dying because of prostate cancer after typically 10 years, which is, of course, intuitive. If you do not have prostate cancer anymore, you will not die because of prostate cancer.
Concluding remarks so far, we've shown a significantly improved disease-free survival by 30%, significantly improved prostate cancer disease-free survival by 38%, significantly increased the proportion of patients achieving a PSA nadir of less than 0.2 ng per mil. We significantly improved the rate of the pathological complete response in a two-year biopsy. It may sound like a boring story. Everything is significant. That we hit all the primary and the secondary endpoints of importance. This is very well tolerated. You don't need to inject tumors again and again. It's just three courses, and off they go to get durable anti-tumor immune responses. Again, if approved, CAN-2409 will be the first new therapy for men with localized prostate cancer in more than 20 years. Now we are getting ready for BLA submission. That's expected in Q4 next year.
Some people ask me, so why are you now delaying the BLA submission? You have these stellar data. We are not delaying anything. This is all based on commercial manufacturing. We deliberately did not scale up manufacturing until we had seen the data readout of the phase three trial. Why? Because phase three trials may also be negative, right? You do not know. That is why you do the trial. We want to use the shareholder money in the most prudent way, also because we also have other programs that are very encouraging. Now that we know that the data are positive, we are going full speed ahead. We have announced that we work with an external partner, SAFC, in California. That is Merck Millipore, one of the largest manufacturers of adenoviruses in the U.S. and in the world.
We oversee this with a very senior team that we brought into Candel. That is all on track. We also use the time to do all the pre-commercialization work in a highly innovative model, which I believe should be the model for biotech. We are not going to create a huge commercial infrastructure at this time. We work with different external parties, and we have created multiple work streams. A lot is going on already behind the screens. We have announced that we work with IDEA Pharma, the organization started by Mike Rea, who has been involved in the most successful launches in the industry, including Nivolumab. We work with Globe Life Sciences, which is an outstanding company doing market research and payer research with very positive feedback that we received.
We also work with a third undisclosed external partner doing the medical affairs work, the patient advocacy, et cetera. We will be ready for launch excellence at the time that we get approval. That is what we hope for, right? You can see here some of the work streams at the high level. This is a previous iteration of the payer research that we have done in the U.S . and in Europe. We have just completed it now with the data in hand, actually, and it looks even more positive. Here you can see work that we have done in the past in the U.S. We have a representative mix of payers here. You can see some of the quotes. There was a very positive response to this concept because it is patient-friendly.
It's only treatment during one year, basically a very short period, more like a gene therapy approach than a continuous treatment. You would avoid future costs to the healthcare system using this approach. We got very positive feedback. Here you can see that people really like the endpoint of disease-free survival, one-off treatment, long-term cost savings. There was the view that physician panels may be particularly supportive because this is a very patient-oriented approach. Here, I want to show you a slide about price. Of course, we do not know the price yet, and we're doing a lot of thinking and a lot of work to think about the best price. There is no example of early localized prostate cancer treatments at this moment from a medical perspective. Here you can see some of the benchmarks for currently available treatments in more advanced disease.
You see it's in the order of $130,000-$260,000, which is given for more than one year. We are going to model because we are seeking a broad label because it's a very big group of patients. We don't want to have an extraordinarily high-priced, let's say, gene therapy positioning because it would limit the number of patients that would get access to this treatment. I also want to remind you that CAN-2409 is a pan-solid tumor therapy. I highlight here the data for prostate cancer because it's our top priority, and we've de-risked this very largely at this time. We also presented very interesting data in other indications. I'll just show two slides. This is based on data that we announced even after the release of the prostate cancer data. This is a small randomized clinical trial in so-called borderline resectable pancreatic cancer.
These patients have a tumor that will typically invade a blood vessel, an artery, or a vein, and therefore they are not resectable yet. Resection is the only hope for cure in pancreatic cancer, as you know, right? These patients will get chemotherapy, induction treatment, followed by chemoradiation with the goal to shrink the tumor. Therefore, the patients may become resectable potentially, which is the case in about half of the patients. That is the population we focused on. Everybody got this standard of care that I just described. Then we randomized them to receive two to three administrations of CAN-2409 plus standard of care or standard of care alone. We followed these patients over time. On the right, you see the median overall survival. You see the complete separation of these overall survival curves.
When we do a landmark analysis at two years, 71.4% of the patients in the CAN-2409 group are still alive compared to what you would expect in clinical practice, 16.7% in the control group. We look at the estimated median overall survival, and these are mature data. We found in the test group, in the CAN-2409 group, as you can see, 31.4 months compared to only 12.5 months in the control group. This is huge separation. Of interest, we're starting to see a new paradigm that patients who have recurrence of the disease or progression of the disease or even develop metastatic pancreatic cancer may still be alive. We create a new balance between the tumor and the anti-tumor immune response, which is a completely new paradigm in pancreatic cancer. For example, there's one patient who was considered to be resectable after chemotherapy and chemoradiation.
The abdomen was opened, and it turned out during surgery that there were liver metastases. The patient was classified as stage four pancreatic cancer. This patient is still alive five years later. We did not cure this patient. Nobody can. It is extremely unusual that the patient would still be alive after five years. Another patient did undergo a RIPPLE procedure, and it turned out that the margins were positive. There was remaining tumor. This patient is still alive after three years. This is also ongoing. We are starting now to show the data about post-progression survival, and you will find that on our website. Similarly, and completely aligned with these data, we recently presented very encouraging data in therapy-resistant non-small cell lung cancer. These patients have unresectable stage three or stage four non-small cell lung cancer. They failed chemotherapy. They failed immune checkpoint inhibitor treatment.
These tumors are growing. Some of them are very large, actually. They have an expected median overall survival with the best standard of care, which is docetaxel chemotherapy, which is also quite toxic, of less than one year. You can see that we've presented data recently that in the patient with progressive metastatic disease, we observed a median overall survival of 25.4 months in the patients with non-squamous histology. That's the patient group that we are focused on. This is better than any data that have been presented in the pipeline of the industry. We are designing now the phase three protocol. We will engage with the FDA. In our runway is all the money to do the enabling work, both in pancreatic cancer and in lung cancer.
We will not press the button until we have, for example, non-dilutive funding to do these trials that are, of course, significant in size. I think these data need to be seen in their totality. We are creating here a pipeline in a product for the palm-solid tumor approach. We have consistently delivered on every catalyst during the last years since I joined the company at the end of 2020. This year, we will present new data for CAN-3110, the investigational medicine tested in recurrent glioblastoma. We will have clinical activity in biomarker data. There will be a continuous stream of news about CAN-2409 as well. We will, of course, have new presentations, publications, and other news that's relevant for the company. I want to thank my team and everybody reporting into them.
It's a small company that we did bring in a very senior team with decades of experience in drug discovery and development. We know what it takes to get the medicine over the finish line, to get it to approval and beyond, because we've done it in the past. I also want to acknowledge our research advisory board. I'm a huge fan of independent peer review. You can see this reads like the who is who in oncology, including Jim Allison, the Nobel Prize laureate. These people are very close to our internal governance process where we make decisions based on data, and Gary Nabel is also a member of the board of directors. This is my summary. I'm not going to read this again. I think we're in a very good place. I will just highlight this. We are on track with the manufacturing of CAN-2409.
Cost of goods are going to be low. There's no complex cold chain. We can put this in the fridge at four degrees Celsius, and it's stable for several months. We are looking forward to bringing this to patients. Thank you very much for your attention.