Investment Conference. My name is Vivian, and I am an analyst on the Corporate Access team. HCW is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 19 publishing senior analysts in over 650 companies covered across all sectors. If you would like more information, please visit our website at hcwco.com. As a reminder, please reference your conference online portal that provides your individual links to your meetings and all company sessions. With that, I would like to introduce Dr. Paul Peter Tak, the President and Chief Executive Officer of Candel Therapeutics.
Thank you very much, Vivian. Hello, everybody. Candel Therapeutics is focused on the development of viral immunotherapies for difficult-to-treat solid tumors. You can find the forward-looking statements on our website. This is the summary of the company. We have two investigational medicines in the clinic. CAN-2409 is an off-the-shelf, pan-solid tumor therapy that leads to an individualized anti-tumor immune response. We have presented consistently positive data across various solid tumors, including, most recently, the readout of a Phase 3 pivotal clinical trial. This is a randomized, placebo-controlled clinical trial in newly diagnosed intermediate or high-risk prostate cancer. We achieved the primary endpoint, disease-free survival. We have curative intent here, supported by secondary endpoints. This study is conducted under a SPA Special Protocol Assessment agreed with the FDA.
That is important because this is an entirely new approach where we do not just try to let patients live longer with cancer or develop metastases at a later time point. We try to let them live without cancer. Therefore, it is very important that we have agreement in writing that the FDA is behind this endpoint. It is a high-hurdle endpoint. This is reinforced by the recent RMAT designation that we received from the FDA. RMAT means Regenerative Medicine Advanced Therapy designation. It is basically a breakthrough designation for gene therapy. We also have Fast Track designation for this program in prostate cancer, which allows us the opportunity to get a rolling submission before we get to the final BLA submission, which is planned for Q4 next year.
These data are supported by strong overall survival data in other indications with a high unmet need, namely borderline resectable pancreatic cancer and therapy-resistant non-small cell lung cancer. We will come back to this later during this presentation. For these programs, we also got Fast Track designation. We also got Orphan Drug designation for the program in pancreatic cancer. Most recently, we also started to reach out to the European regulators, the EMA . We got a similarly positive response, which translated into an orphan designation that we announced just a few weeks ago. Together, we have a pipeline in a product strategy for indications that all represent potential blockbuster indications. We also have a second investigational medicine in the clinic. I won't have the time to discuss it in great detail, but it is equally exciting.
This is a true oncolytic virus, but it works very differently compared to previously tested oncolytic viruses. It's a replication-competent herpes simplex virus 1 (HSV-1) that has been designed to replicate specifically in the tumor while sparing the healthy tissue. We are testing it in probably the most difficult-to-treat form of cancer, which is recurrent high-grade glioma. Most of these patients will have recurrent glioblastoma, brain cancer. We published the initial data after a single injection in Nature. We got a big grant on the basis of these data that allows us to ask the question, what would happen if you test multiple injections? We went up to six injections. We'll present data not later than in Q4 of this year. We have submitted this to a high-impact journal. This is currently under review. We hope to get results shortly.
Here again, we got Fast Track designation and Orphan Drug designation. This is not only a potentially big indication in an area where others have failed, where there's a huge unmet need for patients. It's also an enabling indication for other tumors that are characterized by NESTIN expression. NESTIN is the molecule that is upregulated in these tumors and that drives the activity of this virus. Think of triple-negative breast cancer, melanoma, sarcoma, other tumors. This is also an opportunity 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 know what it takes to get the medicine over the finish line.
We also know that it is not sufficient to be prepared for the regulators, which is, of course, critical, but also for the payers, for the health care professionals, and for the patients. We are also strongly supported by a very high-profile Research Advisory Board, the RAB, including Jim Allison, a Nobel Prize laureate, and other key leaders in the field who are also very close to our internal governance process and decision-making based on data. In terms of cash, we have announced actually in June that we have more than $100 million in the bank. We have an expected runway into Q1 2027. We have strong IP protection and data exclusivity, which will help us to create a wall of protection against both CAN-2409 and CAN-3110 so that we are able to advance this and to own this over time.
In terms of manufacturing, there's a lot of work going on in terms of manufacturing of CAN-2409, getting ready for the BLA submission. This is relatively straightforward. We are scaling up manufacturing. We put the product on stability. We will still aim to submit the BLA based on this in Q4. We will go as fast as possible. Meanwhile, we also conduct a variety of pre-commercialization activities. Let's focus on the lead indication, which is prostate cancer. What is it that we try to achieve? What is the patient population? Here we focus on early localized intermediate or high-risk prostate cancer patients who want to see their tumor eradicated. They want to be cured. They want to live free of cancer. These patients have two options. They can choose radical prostatectomy surgery or radiotherapy. Currently, about 65,000 patients per year in the U.S.
alone will choose to undergo radiotherapy in the context of radical therapy. What is the unmet need? In about 30% of the patients with the current radical prostatectomy or radiotherapy, there will be recurrence of the disease. We try to increase the proportion of patients that will be free of disease. We do this by combining CAN-2409 with radiotherapy. Why is that relevant for the patient? First, they choose to undergo treatments with long-term complications like surgery or radiotherapy because they want to get rid of their tumor. We try to help the patients to achieve that goal. Also, when there is recurrence, it will lead to signs and symptoms due to local progression of the disease, due to local regional progression. Ultimately, after prolonged follow-up, it will lead to the development of metastases. After 10- 15 years, this is associated with prostate cancer-specific mortality.
Second, these patients, if there is recurrence of the disease, will get salvage therapies like salvage ADT, androgen deprivation therapy, hormonal therapy. This is basically chemical castration. Many patients hate this, actually, because of the side effects, the big impact, negative impact on quality of life in the majority of the patients. It is relevant to increase the proportion of patients who will achieve a state of disease-free survival. What follows is the trial design. We have enrolled 745 patients. This is a really large clinical trial. All patients got, by definition, radiotherapy, standard of care. Patients could get short-term ADT, which is sometimes given. For example, if there is a high risk, we included patients with a single high-risk factor. There may be contraindications. This is based on shared decision-making between the patient and the treating physician.
We left it to the treating physician in this clinical trial to be as close as possible to normal standard of care. Short-term ADT is defined as less than six months. We enrolled 745 patients. We randomized them to receive either three injections of CAN-2409 into the prostate, each followed by two weeks of valacyclovir. This is a tablet. Or three injections of placebo into the prostate, again followed by valacyclovir. As agreed with the FDA, in writing under the SPA Special Protocol Assessment, the primary endpoint was disease-free survival, which basically means the absence of any evidence that there is remaining tumor, including in a biopsy at two years, as requested by the FDA. This was generally well tolerated, as we've also shown previously. We have dosed CAN-2409 across our programs to more than 1,000 patients. This is quite unusual for a biotech company.
We have huge experience with this investigational medicine. We know it's generally well tolerated. Many patients will develop minor flu-like symptoms that typically last less than one to two days. Let's now look at serious adverse events. You see these on the right side of the slide. You see that the % of patients that received CAN-2409 that developed treatment-related serious adverse events or serious other definitions of serious adverse events were similar, or maybe even a trend towards lower. I would say that's statistical noise. They were similar and low compared to placebo. Generally speaking, this is extremely well tolerated, which gives us a lot of flexibility to also give it during an early stage of the disease. This is the primary endpoint. This is an event-driven endpoint. If a patient has positive tumor cells in the prostate biopsy, that's an event.
If the patient has a rising PSA, which you can measure in the blood, and it leads to additional diagnostic workup, imaging, and/or biopsy, and it's shown that there is tumor recurrence, that's an event. If a patient would die because of any cause, that would also be an event. Here I should mention that we have a median follow-up of 50.3 months. That's a long time, but that's not long enough to show the benefit in prostate cancer mortality. We've always known that. That's why we agreed to the disease-free survival as the primary endpoint. That means that the death in this clinical trial remained due to causes unrelated to prostate cancer, such as a heart attack or a stroke or an accident.
That means that we have diluted the signal, and still, we see this beautiful 30% improvement in disease-free survival, which was statistically significant with a p-value of 0.155. What follows from what I just said is the key secondary endpoint, which is prostate cancer-specific disease-free survival. Here we exclude death due to causes not related to prostate cancer, and then you can see there's an even further improvement. We see a 38% improvement in prostate cancer-specific disease-free survival, which is highly statistically significant with a p-value of 0.0046. This is supported by various secondary endpoints. Here I show you an exploratory analysis. This study was not powered nor designed to explore statistical significance in different subgroups, but you can do a descriptive analysis where you hope to see that the HR, the hazard ratio, is lower than 1 in different subgroups.
As you can see, when we focus on the patients who did not receive ADT, which is about half of the patients, the HR was 0.56. When we look at the patients who did receive short-term ADT, HR is 0.69, and you see similarly for other subgroup analysis that the HR is lower than 1. The conclusion is we've shown statistically significant improvement in disease-free survival comparing CAN-2409 to placebo on top of standard of care radiotherapy, independent of the use of ADT, and independent of the question whether the patient had an intermediate favorable risk profile or intermediate unfavorable, as you can see on this slide.
We've also shown using the gold standard to detect tumor cells in the two-year biopsies, as requested by the FDA, that we could achieve a pathological complete response in 80.4% of the patients that received CAN-2409 compared to 63.6% in the placebo group that, of course, received standard of care radiotherapy. That's what you would expect, actually, in standard of care, but you see this highly statistically significant improvement. What is a pathological complete response? It means the absence of any tumor cells in the two-year biopsy. That's a high hurdle, and it is relevant because we know based on previous work that has been published extensively. This is based on a meta-analysis based on 22 studies that a positive biopsy at two years is highly predictive of subsequent biochemical failure.
That means PSA levels are rising, a threefold higher odds of developing distant metastases after prolonged follow-up, and a fivefold higher odds of dying from prostate cancer after 10, 15 years. You see on the top left of the slide the p-values. This is extremely statistically significant. We are doing the scaling up of the manufacturing, as I discussed. We put the product on stability. We used that time also to do a lot of work with payers, with health care professionals, with patients. In other words, there's a lot of work in terms of pre-commercialization activities that will get us ready for all the key stakeholders at the right time. These data are reinforced by our data in borderline resectable pancreatic cancer, another area of huge unmet need. We did a small randomized clinical trial in this indication. You see the key findings on this slide.
We're looking here at the hardest endpoint that's relevant for patients and for the FDA, which is overall survival in this indication. You see that we observed a median overall survival of 31.4 months in the patients who received CAN-2409 combined with standard of care compared to only 12.5 months in the control group that received similar standard of care but no CAN-2409. We've seen patients who lived much longer than you would expect. For example, a patient who was diagnosed in this study with stage IV, that means metastatic pancreatic cancer, who's still alive after five years. Another patient underwent radical surgery, Whipple procedure. There was resident tumor in the tumor sections in the margins, which means that the tumor was not removed entirely. The patient is still alive after more than three years. This is extremely unusual in pancreatic cancer.
We can start to think about post-progression survival in this indication. We changed the balance between the tumor and the anti-tumor immune response. In other words, we changed progressive cancer into a chronic disease. We've shown the same in non-small cell lung cancer. In patients who failed standard of care, immune checkpoint inhibitor treatment, in most cases, also standard of care chemotherapy, 90% of these patients had metastatic disease. Most patients had unfavorable prognostic factors. Normally, in standard of care, you would switch them to second-line chemotherapy, which is docetaxel. As you can see on this slide, you see the references. This is associated with, A, a lot of toxicity, and B, a median overall survival consistently reported in the literature of less than one year.
In contrast, we observed that after two administrations of CAN-2409, while we did not change anything to the ICI regimen that they had an adequate response to, we observed a median overall survival of 24.5 months. This is a doubling of the expected median overall survival. The data are extremely encouraging and are in line with what I described for pancreatic cancer. This is post-progression survival in most of these patients. Here you can see what that means for a patient. We have a patient with metastatic disease with metastases in the lymph nodes. We injected only the subcarinal lymph node twice with six weeks in between. This is a relatively straightforward and simple procedure done in an outpatient clinic. We did not change the immune checkpoint inhibitor regimen, which was in this case nivolumab.
You can see when you go from baseline to six months that there was a decrease in the size of the injected tumor, but also in the uninjected supraclavicular involved lymph node. This is stabilized over time. You see the target diameter on the top right of this slide. This patient had progressive metastatic disease. Despite optimal treatment with nivolumab and cisplatin-based chemotherapy, you would expect a very poor prognosis. The patient is still alive after more than 44 months. This was ongoing at the most recent data cutoff. This is a representative example. We've seen in the majority of the patients, in about 2/3 of the patients, there's clear evidence of a systemic anti-tumor immune response, as shown by clinical benefit supported by deep biomarker research.
We found that if you focus on the subset of patients with non-screeners, non-small cell lung cancer, this is about 70%- 75% of the patients, that it looks even better with a median overall survival of 25.4 months. Moving forward, that's the target population that we will focus on. We had a very constructive meeting recently, end of Phase 2 meeting with the FDA. It's very clear on our minds what the protocol would need to look like for a potentially Phase 3 registration of clinical trial. We do all the enabling work with the academic key experts and the FDA to have this ready. This will create value for the company. We will start this clinical trial after securing non-dilutive funding. That will be trigger spend, as I define it. Having this protocol ready will create value for the company. We do the same for pancreatic cancer.
We are doing the enabling work to get ready for a Phase 2B/Phase 3 adaptive design clinical trial. We will interact with the key experts in the field, as well as the FDA. We will have this protocol ready. This is all in the current budget. We will trigger the spend only if we have secured at least a significant non-dilutive funding to support this. I will briefly mention we have CAN-3110 in high-grade glioma. This is an area where others have failed. Huge commercial opportunity. This would be extremely relevant for patients. I'll just show one case report of a patient who had failed neurosurgical resection and chemotherapy and radiotherapy. This is completely therapy-resistant disease. This patient refused all further standard of care, including corticosteroids, but did agree to a single injection of CAN-3110 into one of the two tumors.
One tumor with a red arrow next to it, another white lesion. You don't need to be a radiologist to see that if you go from the left to the right, there's a very clear improvement in the injected tumor and in the uninjected tumor. The patient could go back to work. We've seen examples of long-term survival, which is extremely survival, if it ever happens, in this indication. We've seen two patients where we believe they may have been cured. We see in a small subset of the patients very encouraging results. We'll have new data based on repeated injections in the very near future. This is the summary. Two investigational medicines with the opportunity to create real pipelines in a product. The company is in a good position from a financial perspective with a runway into Q1 next year.
We are on track for BLA submission Q4 next year. I want to thank you for your attention.
Dr. Tak, thank you for leading a productive and informative presentation on behalf of Candel Therapeutics. We appreciate the time that went into putting this together and are grateful for the team's participation in our conference this year.
Thank you very much.