With that, the floor is yours.
Thank you very much, Sarah. As you just heard, we are focused on tipping the balance in favor of the immune system to fight cancer, and we develop our therapies for very difficult to treat solid tumors. This is language that you can find in more detail on the website. As you well know, that there's an increased interest in the development of intratumoral immunotherapies that may lead to systemic anti-tumor immune responses. This is now a new frontier in cancer care, and we've seen examples that were positive from Replimune, CG Oncology, other biotech companies. Importantly, also, big pharma companies are moving into this space. For example, Johnson & Johnson announced recently the creation of the so-called Interventional Oncology Unit, and they also recently initiated a phase I clinical trial of their viral immunotherapy that they're testing in non-small cell lung cancer.
We, Candel Therapeutics, are focused on three platforms: two clinical-stage platforms and a discovery platform. So first, CAN-2409, which is an investigational medicine in late-stage development. It's an off-the-shelf pan-solid tumor therapy that leads to an individualized anti-cancer immune response. Second, CAN-3110, which we're testing in a very difficult-to-treat form of cancer, which is recurrent high-grade glioma. Most of these patients will have glioblastoma. Here, like for CAN-2409, we can create a pipeline in a product, and we have proof of concept for both assets for every indication that we currently pursue.
Then we've created the enLIGHTEN Discovery Platform , that we partner part of this platform with, UPenn, with Carl June's group, and we try to, help to design viral immunotherapies that may assist CAR T cells to get into, pancreatic solid tumors and then promote their function at the site of the, of the tumor. Let's now discuss the mechanism of action of CAN-2409. This is a viral immunotherapy that has been designed for in situ vaccination against the patient's own tumor at the site of the injection, but also against the uninjected distant metastases. This is not an oncolytic virus. It's an in situ vaccination approach. Let's look at the mechanism in more detail.
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 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.
We have proof of concept for every indication that we currently pursue, which are early, localized, non-metastatic prostate cancer, area of huge unmet need, where no new treatments have been approved in the last more than 25 years. Everybody else is focused on more late-stage disease. We will have to read out of two large randomized clinical trials, phase II-B and phase III, later this year in 2024 , so in a few months from now. We've presented data based on the phase II-A clinical trial, an open-label clinical trial in therapy-resistant non-small cell lung cancer. Most of these patients had progressive disease at baseline, despite optimal standard of care, chemotherapy, and immune checkpoint inhibitor treatment, and most of these patients had metastatic disease, so you don't see placebo effects in these patients, and we presented very encouraging results. I'll come back to it.
We also presented data this year based on the randomized clinical trial in borderline resectable pancreatic cancer. Here again, we focus on the hardest endpoint, which is overall survival, and we see a complete separation of the survival curves between active treatment with CAN-2409 compared to standard of care therapy. We've dosed more than one thousand patients, so we have enormous experience in terms of feasibility, safety, and tolerability. This approach is generally well-tolerated and is actually easy to administer and aligned with normal clinical practice. You just need two to three administrations, which are typically done in an outpatient clinic setting, and it leads to durable anti-tumor immune responses. We got Fast Track designation for every indication: prostate cancer, pancreatic cancer, lung cancer. We also got Orphan Drug designation for pancreatic cancer, and we have shown that there's monotherapy activity, as you can see on this slide.
But we can also combine this approach where appropriate from a medical perspective with chemotherapy, with radiotherapy, with immune checkpoint inhibitor treatment, and or surgery, based on the current standard of care. This year, we have presented the following data for CAN-2409, based on the phase II-A clinical trial, randomized trial, in borderline resectable pancreatic cancer. We could demonstrate in the active treatment group, a median overall survival of 28.8 months, compared to only 12.5 months in the control group. So this is a very, very encouraging result. This forms the basis for the design of a future phase II-B randomized clinical trial, with very much the same design as this current trial. We presented data at ASCO in non-small cell lung cancer.
As I mentioned, these patients had stage three or stage four disease that was not responsive to immune checkpoint inhibitor treatment. While standard of care docetaxel chemotherapy will lead to median overall survival of not more than 10-12 months, which has been reported consistently in the literature, we observed in the per-protocol population, the patients who received two administrations of CAN-2409, median overall survival of 20.6 months. This is an extremely encouraging result, and forms the basis for the design of a phase II-B/phase III randomized clinical trial that we are designing while we speak. Then again, we hope to see, based on the fully enrolled phase II-B clinical trial in the so-called active surveillance population, patients with low to intermediate risk prostate cancer, we hope to see significant improvement in progression-free survival.
Study will read out in a few months from now, and this would mean that we can stop the progression of the disease, so that patients don't need to undergo radical therapy, think of radical prostatectomy surgery or radiotherapy over time, because these treatments are associated with significant complications and a negative impact on quality of life. Then we'll also see the readout of a phase III clinical trial data this year, based on the phase III trial in intermediate to high risk prostate cancer, where we hope to see significant improvement in disease-free survival. In other words, the curative intent. So let's discuss non-small cell lung cancer in a little bit more detail.
Still a huge unmet need, because we know that the standard of care, immune checkpoint inhibitor treatment, there will be progression of the disease after one year in about 60% of the patients, and over time, that percentage goes up, right? It's a huge unmet need. As I mentioned, these patients will get docetaxel chemotherapy, which is associated with median overall survival of less than a year at best. Huge, medical unmet need, also very big commercial opportunity. This is the design of this open label clinical trial. We focus on stage three or stage four non-resectable, non-small cell lung cancer with an inadequate response to immune checkpoint inhibitor treatment. In fact, in our trial, most patients have stage four disease, and most patients are in cohort two, which means they have progressive disease at baseline, so they have the most unfavorable prognosis.
We have 41 patients who got two administrations of CAN-2409 in cohort two, which is very much the focus moving forward from here in terms of development. This is the biggest unmet need. We also have five patients in cohort one. These patients had stable disease at baseline, but we wanted to explore, could you actually induce improvement in these patients? That's still a small cohort. I should also mention that we do deep mechanistic biomarker work in all of our experimental medicine clinical trials like this one. Here, supported by PACT, Partnership for Accelerating Cancer Therapy. Big financial support, but most important, importantly, scientific validation, and it gives us access to the brightest minds in academia focused on biomarker research.
When you look at the table, you can see that we had most patients in cohort two, patients who had progressive disease at baseline, and we observed a disease control rate of 70%, seven zero, which means that we could stop these tumors from growing, although they had progressive disease, despite optimal standard of care. And on the left, you can see what that means for individual patients. So when we look at the blue bars, which are the patients in cohort two, you can see that actually, in a small majority of the patients, there was even a decrease in the size of the tumor. You don't expect a huge decrease with this mechanism of action, because basically, we are replacing cancer cells by immune cells, as we've shown by histologic examination of the biopsies across multiple solid tumors.
So let's now look at cohort one, patients who had stable disease at baseline, shown by the green bars. We maintained disease control in all of these patients. We actually had an overall response rate, so a RECIST response, which means decrease in the size of the tumor of at least 30% in 40% of these patients. And you can see all the green lines go down. But more importantly is the question: How does that translate into what really matters to patients and to the regulators, which is median overall survival? So when we pool these patients, cohort one and two, together, we have 46 patients, and you can see that we observed. Well, you can't see it here. We observed more than 22 months in this population.
When we focus on the patients with the worst prognosis, cohort two, we have 41 patients, and that's what I show here. We still have the median overall survival of more than twenty months, which is a very, very high number, actually, compared to optimal standard of care... and also actually compared to other experimental treatments that are in the pipeline of the pharmaceutical industry. Again, you see the comparison to the publication by Reckamp; you expect less than 12 months. So very promising. What does that mean to a patient? This is a representative example of a patient in this clinical trial. When you look at the top right of this figure, you see the real diameter of the tumor. This is a huge tumor of more than 11 centimeters, despite optimal standard of care.
So this is where you start to have end-of-life discussions with the patient. You can see the tumor is growing until we give the first administration of CAN-2409, the small orange arrow. You can see there's a decrease in the size of the tumor. It's not an RECIST responder, but which you do not expect, so there's no decrease of more than 30%. But the tumor was growing, now it's reducing in size. Then we give the second injection. That's well, when you start to see a mature immune response developing against the tumor, and you can see there's further stabilization and continuous regression of the tumor. The patient becomes a partial responder according to the RECIST criteria over time, but more importantly, the patient is still alive after more than 30 months of follow-up and is still doing fine.
We've seen this across this program in multiple patients. We've also shown very clearly in this trial in lung cancer, a systemic anti-tumor immune response. So you don't need to inject all the tumors. You can just choose one or two to educate the T-cells how to recognize the patient's own tumor, and it leads to a change in the immune cells that will continue to attack and recognize the tumor cells. Similarly, we have very encouraging data based on the randomized clinical trial in borderline resectable pancreatic cancer. Here, we could show a complete separation of the overall survival data. As you can see here, median overall survival of 28.8 months, compared to only 12.5 months in the control group, while the patients are actually comparable in terms of baseline prognostic factors.
In fact, there's one patient in the active treatment group, as you can see in the table, shown by the orange font, are the patients in the active treatment group. One patient had stage four disease, so this patient had metastatic disease and is still doing fine after a continued follow-up. This is all explained by the fact that we are fundamentally changing the tumor microenvironment in these patients. We've demonstrated the formation of lymphocyte aggregates that resemble so-called tertiary lymphoid structures in the pancreatic tumors, and this is known to be associated with improved survival. Let's now focus on the other investigational medicine in the clinic, which is equally exciting, but in earlier stage, which is a true oncolytic virus. It's a replication-competent HSV. It's a second-generation HSV. It's designed to replicate specifically in the tumor while sparing the healthy tissue.
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've presented the data for the first 41 patients with recurrent high-grade glioma. Most of these patients have recurrent glioblastoma who failed neurosurgical resection, and chemotherapy, and radiotherapy recently in Nature, so a very high-impact publication describing the doubling of the expected median overall survival after just one injection. Also, beautiful biomarker research, and I would invite you to read this paper. Since then, we have completely replicated these findings in an independent cohort of an additional nine patients with identical results, so now that we know that we have these very promising effects after just a single injection, we started to ask the question: Could it be even better if you would give multiple injections? and at ASCO, we presented the feasibility and the tolerability of multiple injections, up to six injections into the tumor in the first six patients.
The data are encouraging. This is a daycare procedure. Patients will undergo a procedure that takes about 45 minutes, and they can go home the same day. Again, you see dramatic improvements in some of these patients. You see an example on this slide of a patient who had failed neurosurgery, chemotherapy, radiotherapy. This patient had multifocal disease. You can see two tumors. He refused all further standard of care, which gave us the opportunity to observe monotherapy activity in a completely therapy-resistant disease with a very poor prognosis. When you go from the left to the right, you can see that after just one injection. There was a dramatic improvement in the injected tumor and the uninjected tumor as well. This patient could go back to work.
So this is a very big opportunity, as you can understand, because there's been very little progress in this field. Our work is now completely funded by the Breakthrough Cancer Foundation with a very big grant. It's also great scientific validation. In the sequential dose escalation clinical trial, we did not observe dose-limiting toxicity, and we found only the replication of the virus in the tumor, but we could not detect CAN-3110 in the healthy brain tissue of the same patients. I've shown you this example in the short version. Here, you can see more scans. We have several other patients with a very similar pattern, and this is what we see on the group level, which we published in Nature, doubling of the expected median overall survival after just one injection.
Now, we ask the question: What could that look like if you give multiple injections? Together, we have created a pipeline focused on value creation, two assets in the clinic, proof of concept for both assets across multiple indications, and then we've also created the enLIGHTEN Discovery Platform, and we had multiple presentations already at SITC and the AACR, then we have a partnership with UPenn, and then we are open for a partnership with Big Pharma. We have consistently delivered what we said that we would do since I joined this company, end of 2020. You can see this year has been very important, but the readout of two large randomized clinical trials, Phase II-B and Phase III, fully enrolled in prostate cancer, are imminent.
We will see these top-line data in the next few months, and then the beginning of next year, we will have updated overall survival data in non-small cell lung cancer and also in borderline resectable pancreatic cancer. This is my summary. You will find much more data in the corporate deck, which you can find on the website, and I would like to thank you all for your attention. Thank you very much.
Great. Thank you, Paul, and the whole Candel Therapeutics team for an informative presentation. We're very grateful for your flexibility and your presence at our conference this year. Thank you again from the H.C. Wainwright team.