Good afternoon, everyone, and welcome to the HC Wainwright Investment Conference. Next up, we have a presentation from Medicenna Therapeutics, and presenting for Medicenna is Dr. Fahar Merchant, CEO and President. Fahar, over to you.
Thank you very much. Thanks for joining, and thank you to HC Wainwright for inviting us to present today. I look forward to providing you all with a background on Medicenna. We are listed on the Toronto Stock Exchange and also on the OTCQX. Just to let you know that I will be making forward-looking statements, so a cautionary note to review our regulatory filings. Medicenna is a publicly listed clinical-stage immunotherapy company. Our focus is really on developing what we call evolutionary superkines, and the intent is to generate these revolutionary medicines, particularly to address unmet needs for patients, at least initially in the space of oncology. Today, I'll talk about three programs focusing mostly on our lead candidate, MDNA11. This is a best-in-class IL-2 superkine. It is the only not alpha-beta enhanced long-acting IL-2 super agonist.
We have seen that this drug, particularly in single agent and also in combination settings, has demonstrated response rates in the 30% to 50% range in checkpoint failed patients. The second program I'll talk about is MDNA113. This is a targeted anti-PD-1 bispecific. This is a first-in-class, the only tumor-activated anti-PD-1 IL-2 superkine that is targeting specifically a tumor-associated antigen known as IL-13 receptor alpha-2. This is currently in preclinical proof of concept with promising efficacy and safety data so far. Finally, a program that is the most advanced program called Bizaxofusp, previously known as MDNA55. This is a first-in-class IL-4 empowered superkine for targeting this particular therapy for patients with end-stage recurrent glioblastoma. Here again, we have shown survival that has doubled compared to standard of care.
In each of these cases so far, by the end of this year, we'd have generated clinical data from 250 patients with tumors that have an aggressive nature. They're metastatic, they're advanced, they're not resectable. The key highlights that we expect to report before the end of this year are first and foremost that we'll complete the phase 1/2 ability trial. We'll have the opportunity to disclose more data on our monotherapy setting with MDNA11, but also top-line data in combination with Keytruda®. We'll also have data with non-human primate testing of our bifunctional superkine before the end of this year. With the Bizaxofusp program, we are looking to partner that particular asset. Let me give you a bit of background around the platform itself, the Superkine™ platform. It basically powers our pipeline, particularly in the space of precision immunotherapy.
This is generating a library of the superkines that are either super agonists, super antagonists, or anything in between. The asset and the platform have been licensed from Dr. Chris Garcia's lab at Stanford. We further are taking those assets and generating additional next-generation molecules that are empowered superkines, that are bifunctional superkines, and they are also long-acting superkines. In all, therefore, to date, we have filed well above 100 patents around these programs with at least 70 or more patents issued globally in the major markets. If you look at our pipeline, we have really been successful in putting together a very robust pipeline that is balanced. It has those programs that are in early stage, but also mid and late stage assets. They cover not only oncology, which is what you see in the first three rows there, but we also have the ability to generate antagonists.
This is very relevant for autoimmune disease and inflammation. I will not talk about those today. Today, we'll talk about MDNA11, both as a single agent and in combination with Merck's Keytruda®, which is where we have the clinical collaboration with Merck. Finally, give you an overview of our phase 3 ready program, Bizaxofusp. Let's start with MDNA11. As I said, this is a clinical stage asset, phase 1/2 trials. We'll have data in north of 425 patients or so before the end of this year. Historically, if you look at this particular space, we know that IL-2 has been around for a long time in the form of Proleukin. Unfortunately, this particular drug did show some modest activity, but it comes with a very serious side effect profile that could be life-threatening for patients. Patients would have to be administered this drug in an intensive care unit.
This drug, Proleukin, has not advanced to the extent that one would have liked. Since then, there have been a number of attempts to generate the second generation IL-2s by major pharma biotech companies. Roche, for instance, started in 2015. Subsequently, Nektar and then collaboration with Bristol Myers. Then Synthorix is a drug also subsequently acquired by Sanofi. These were multi-billion dollar deals that took place with these particular programs. You can see that these drugs, although they were optimized for enhanced half-life, that extra half-life did not do much in terms of improving safety or providing any efficacy signals. This is where our next generation IL-2 superkine differentiates from all the others that are currently in the clinic.
It combines a series of changes or engineering that we've done to this molecule that allows this particular compound to have a much better safety profile, but at the same time be efficacious, have the right PK, half-life, and the ability to change the pharmacology of this IL-2. How is this molecule different than the others out there? Starting with the engineered IL-2 that you can see on this particular slide, on the left-hand side is the superkine that we have changed the molecule by inserting a couple of mutations so it will not bind to the alpha domain and therefore not cause toxicity issues or even boost your immunosuppressive T-reg population. What is different is that unlike anybody else, we have inserted certain mutations that dramatically increase the affinity of this IL-2 towards the beta domain.
The beta domain on your immune cells, particularly your CD8 T cells and NK cells, gets activated. What we find is a substantial enhancement of the effector cell activation, meaning that we are stimulating the cancer-fighting immune cells preferentially. With that, we are also seeing that this particular molecule is able to stimulate certain other immune cells in generating memory responses. I think this novel pharmacology that I'll share with you shortly. We have, instead of using pegylation or the Fc domain, extended the half-life of this molecule by fusing it to albumin. By doing so, we've not only increased the half-life, but we know that albumin tends to accumulate in the tumor and in the tumor draining lymph nodes. This is where your immune cells get activated. This is where your immune cells get trained so that they are able to subsequently attack the tumor.
This is the approach ideally to achieve, we believe, durable long-term responses that are a challenge with other therapies. We have, as I said, with this ability phase 1 to clinical trial, currently in progress. We've completed the dose escalation phase of the study in a monotherapy setting. We've also completed the combination portion of the study in terms of the escalation portion. In both cases, we observed that the recommended dose for expansion was the same in both. It was 90 micrograms for both, indicating that combining with Keytruda® does not inadvertently affect the safety profile of this particular molecule. We are now expanding patients and enrolling patients in the expansion cohorts, the focus being really in the monotherapy and combination arms in three different tumor types.
Primarily, we're looking at cutaneous melanoma, where we know what the benchmarks are for seeking approval in a phase 2-based registration trial, which is trying to achieve a 30% response rate. We also have MSI-high, TMB-high tumors. These tumors are really biomarker driven. They are sort of cancer agnostic, and therefore, the ability to treat multiple tumor types as long as these particular biomarkers and these patients would have failed a checkpoint inhibitor. Just as a brief note here, as I was talking about the safety, we actually tested the drug at doses of 3 to 120 micrograms per kilogram. Under no circumstances did we see any dose-limiting toxicities. That is a promising safety feature of this drug. From a safety profile, what you see in this particular slide is more than 90% of the adverse events were grade one or two.
There were just a few of grade three events. Most of them were lab. They were asymptomatic and therefore did not require any intervention. When we look at the pharmacology of this drug, what is really exciting here is on this particular side, on the left-hand side, that you can see on the left-hand side, the lower yellow or sort of the orange plot showing that we are not stimulating T-regs. We are stimulating the NK cells, but most importantly, we are boosting the CD8 T cells the most efficiently. What is also very exciting about this drug is not the quantity of CD8 T cells, but it's the quality of the CD8 T cells. On the right-hand side of this slide, what you see is that we are stimulating the stem-like memory T cells. Those are important because they are the ones that are responsible for durability.
They stay in the bloodstream for a prolonged period of time, enabling the immune cells to attack the tumor should they come back. What we also observed in this clinical trial, at least, is that patients that had a substantial increase in the stem-like population, those are the patients that responded to treatment. There is a good indicator for us here. When we look at the durability of these responses in these patients, we are really excited to see that this drug is working in multiple tumor types. I'll give you just one example. If you look at the top, which is the first plot, this is a patient with pancreatic cancer. The patient had surgery, and thereafter, the patient then had spread of the tumor to the liver.
Once it spread to the liver, the patient received a combination of four chemotherapies that continued to aggressively allow the tumor to metastasize, but also proliferate. Subsequently, the patient got into a combination of two chemotherapies, and that patient was not able to tolerate that therapy. Finally, the patient got Keytruda®. With Keytruda®, the patient continued to progress. This is when MDNA11 was administered as a single agent. This patient then had what we say or show you is response after the first two CT scans. That response continued to deepen until the patient then decided to go away on vacation for eight weeks, came back, and unfortunately, there was a new lesion that was observed. That patient got a single cycle of radiation and started again on MDNA11 and continued to receive until all the target, non-target, and the new lesions disappeared.
Since December 2023, this patient has not received any therapy, not received MDNA11, and still remains tumor-free. This is really exciting that we are able to potentially, hopefully, have a curative potential with this kind of therapy. When we look at the response rates, we're seeing response rates of anywhere from 30% to 50%, depending on different tumor types. We are seeing this in patients with MSI-high tumors, patients with cutaneous melanoma, et cetera, and we're seeing the durability in these patients as well. When we look at the combination setting, again, testing the drug in tumor types that is not normally what you would do with Keytruda®, for instance, even anal squamous cell carcinoma, has single-digit response rates. We're seeing a complete response. In patients with endometrial cancer, we've seen two out of four patients responding.
We're seeing the same 30% to 50% response rates in patients who have failed checkpoint inhibitors or are not eligible to receive checkpoint inhibitors. Why are we pursuing these particular three tumor types that I initially showed you: melanoma, MSI-high, and TMB-high patients? The market opportunity is substantial, but again, there is an unmet need because patients that have a recurrence of melanoma, they don't have many options at that point. We feel that MDNA11 could fit in that space, particularly with the data we've seen in a single agent setting. With respect to the combination or even single agent setting with MSI-high and TMB-high, those patients typically receive checkpoint inhibitors, but unfortunately, they do not all respond. Those that do respond will eventually have the tumor relapse. This is the patient population that's available for us to treat.
Finally, I think it's important to probably note that with checkpoint inhibitors, we believe that combining with an interleukin-2 will be a prerequisite if you're going to improve response rates in first-line therapies from 30% to 40% to hopefully 60% to 70%. This is where we believe MDNA11 could play a major role. Moving on to using the same approach, which is the IL-2 that we have used in our MDNA11 program, is our bispecific or bifunctional superkine or a BiSKIT called MDNA113. This particular molecule is being developed. There's obviously a considerable amount of interest in this particular space, a deal-heavy space, as you can see here. At the same time, we know the checkpoint inhibitors, the two big blockbusters, Merck's Keytruda® and Bristol Myers' Opdivo, are going off patent in 2028 and combine their sales of over $40 billion right now.
If we can find somehow to develop next-generation checkpoint inhibitors with better functionality, we feel that this would really be a great thing for patients. So 113, what is it? We have two components to it that are critical. First and foremost is the anti-PD-1, and we are not working with some experimental or new anti-PD-1. We are focused on one of the two commercially approved mega blockbusters of anti-PD-1. The second portion is the green circle that you see is our IL-2 superkine, the same superkine that you find in MDNA11. Again, we have demonstrated that that particular superkine is active. By fusing the two molecules together, we are getting the best of both worlds. We know that the dosing in these situations can be different.
The best way for us to do this is to create a masked version of this particular bifunctional molecule with the ability to be switched on at the tumor site. What we've done is we have attached IL-13 superkines to either side of this IL-2, so it keeps the molecule relatively inactive in systemic circulation. Once it gets into the tumor, the pink boxes, which are your IL-13s, get cleaved off and you switch on the drug, which then binds in a cis format to your T cells. The reason is, why are we using IL-13? The reason we are using IL-13 is, first and foremost, obviously, we're getting masking with IL-13. Second of all, we know that this is expressed in so many solid tumors. We know that high expression of this particular target is associated with poor survival outcomes.
We can see that there is a huge opportunity for this particular molecule. You can see on the right-hand side, two tumor types, colon cancer, lung cancer. You can see clearly that patients that have high expression of the target have poor survival outcomes. When we look at our competitor Innovent, for instance, they have an anti-PD-1 IL-2. What you do see is there is toxicity associated with this particular molecule. There is mortality in some patients. I think these grade 5 events don't bode too well because they don't have the masking or the targeting capability. This is something that we are doing with our molecule, where we have proven the checkpoint inhibitor is a commercial mega blockbuster. The IL-2 is clearly active, as we see in MDNA11. We know that the IL-13 target is something that's been well validated. That is essentially where we are.
I'll quickly summarize by talking about our MDNA55. This is a program that we're looking to partner. This is an IL-4 empowered superkine. It's administered once to these patients. It's got an interleukin-4 engineered with a payload that delivers a toxin directly into the tumor. What we've seen in a phase 2b clinical trial is a very dramatic improvement in survival outcomes when you compare to an extremely well-matched propensity-scored patient population that received the standard of care versus Bizaxofusp. Here we see a doubling of survival from about 7 months to nearly 14 months. This is a program that we're looking to partner. The opportunities are beyond recurrent GBM into other CNS tumors, etc., but also metastatic tumors as well. Ending the story here around our superkine space is really to tell you where we are from a company finance perspective. We are headquartered in Toronto.
As I said earlier, listed on the Toronto Stock Exchange and OTCQX. We have a cash of $21 million. This is based on our projected runway. It takes us into Q3 next year. We have about 83 million shares outstanding, with insiders owning about 22% of those. We're covered by David Martin and Kathryn Novak at Bloom Burton and Jones Research. At RK and Andre at HC Wainwright and Research Capital. To summarize, we have a number of catalysts coming up before the end of this year. We'll be completing enrollment with MDNA11 in monotherapy and combination settings. We'll have data from over 250 patients with not only MDNA11, but with Bizaxofusp in total. We'll have top-line data on the combination setting and MDNA11 in a single agent setting before the end of this year.
We would have some non-human primate data before the end of this year with our BiSKITs™ with the intent to go into the clinic next year with MDNA113. We continue to progress on the Bizaxofusp partnership. This is where I'll end. Thank you very much. Any questions? All right. Thank you very much.