Everyone, and thanks for joining today. I'm Tracy Sebastian with Oracle. We're here with Fahar Merchant, CEO and President of the Medicenna Team. I'll let you get started, Fahar.
Thank you very much. Thank you to Oppenheimer for inviting me to present today. Thank you all for joining the call this morning. I will be giving you some updates on Medicenna. We are a publicly listed company on the TSX, MDNA, and also on the OTC, MDNAF. Our focus is really on developing novel evolutionary cytokines to generate and commercialize revolutionary medicines. Before I proceed, let me just put forward a disclaimer that I will be making forward-looking statements and encourage you to review our filings on CDAR. As I mentioned, the company is really focused on cytokines, interleukins very specifically. The focus of the company is really on three different interleukins. These are including 2, 4, and 13. These superkines have been engineered so that they can be either super agonist, partially agonist, or super antagonist.
The one that I'll focus on today mostly is MDNA-11. It's our IL-2 super agonist, which is advancing in clinical trials in phase 1-2 studies in patients with advanced metastatic solid tumors. The second program I'll briefly talk about is our phase 3 rest-ready asset for recurrent glioblastoma, MDNA-55. It's an IL-4 receptor-targeted toxin. Finally, we do have a pipeline of really exciting assets in a deal-heavy space of autoimmune disease, inflammation, et cetera, where we are generating these bifunctional superkines for immunotherapy, or in short, BiSKITs. I won't have a chance to talk about these today, but nevertheless, just to briefly mention that. 2025 really holds a year of lots of news flow. We have a data-rich year, and multiple catalysts coming up around MDNA-11.
First and foremost, during the first half of this year, we'll be providing updates on our monotherapy expansion data that is currently enrolling. We also, in the first half of this year, will provide a set of results on our dose escalation, where we are combining MDNA-11 with Keytruda in collaboration with Merck. As part of that study, we will be expected, and we will expect to present results from our recommended dose for expansion in the combination arm in this first half. We will then have combination expansion ongoing throughout the year with top-line results available before the end of the year in the combination setting. We have multiple data readouts coming up in monotherapy combination data sets, both in the first and second half of this year, the bulk of them, of course, coming out during the first half of 2025.
We are pursuing with the phase 3 partnership with a potential collaborator or a commercial entity, where we would then be allowed to pursue phase 3 trials. This would be something that would be ongoing activity at our front. Finally, with respect to our BiSKITs program, we are advancing them so that there would be IND ready for IND enabling studies. Very briefly, the pipeline, as I mentioned, bizaxofusp for recurrent glioblastoma. We have key data readouts coming up with MDNA-11 the first half of 2025. In the combination setting, multiple readouts in the combination setting at first and second half of 2025, plus some updates on our earlier stage programs around the BiSKITs platform.
Moving on to our IND, sort of our MDNA-11 program, the IL-2, just to give you an introduction to those who are not familiar with this particular therapeutic agent, this drug has been approved since the 1990s for treatment of metastatic melanoma, as well as renal cell carcinoma. The drug was approved, but its uptake has been dismal, despite the fact that it has shown promising signs of activity with response rates in the 15%-16% range, with a fraction of those patients, about 6%-7%, having long-term durable complete responses. The problem with the native IL-2 or Proleukin is that, first and foremost, it does tend to preferentially stimulate your regulatory T cells, which are immunosuppressive.
By virtue of its ability to bind to a receptor known as IL-2 receptor alpha, it does indeed cause toxicity to such an extent that the drug needs to be administered in an intensive care unit. Finally, because of the size of the molecule, this drug needs to be administered every eight hours for up to five days due to the very short half-life of this particular molecule. What we have done here with MDNA-11 that you see on the right-hand side is really mitigate all those challenges, but at the same time, substantially improve the molecule so that it preferentially stimulates the cancer-fighting immune cells rather than the immunosuppressive Tregs, while at the same time avoiding toxicity associated with the binding to the alpha domain. Finally, to mitigate the short half-life, have this molecule so that we have an extended half-life.
To date, the data look very promising. We'll share some of this data later on. Very quickly, just to give you an overview about the molecule itself, first, this is MDNA-11, the first and the only beta-enhanced not-alpha IL-2 super agonist in clinical development. What we have done here is taken an IL-2, engineered it so that, first and foremost, by introducing a couple of mutations, we abolish binding to the alpha domain so that we don't stimulate Tregs, and we improve the safety profile of the molecule. Second, what we've done is, by inserting five mutations, we have dramatically improved the affinity of the molecule towards the beta-gamma receptor domains, which are really crucial for stimulating the cancer-fighting immune cells. These, in turn, result in a T cell memory response.
Finally, as far as natural killer cells are concerned, they reduce the exhaustion of natural killer cells by virtue of these mutations. Those are the key changes that have been made to the molecule. What we have further done is we have fused the molecule to human albumin, first, to extend the half-life of the molecule. Second of all, we know that albumin tends to accumulate in tumor draining lymph nodes. It accumulates in the tumor as well. By virtue of that, we are able to train the immune cells in the tumor draining lymph nodes to attack the cancer. Overall, this provides us with a superior anti-cancer response, allowing us to administer the drug once every two weeks instead of three times a day. We have an ongoing clinical trial, ABILITY-1.
It's a phase 1-2 monotherapy and combination study with Keytruda in collaboration with Merck. What we have is four portions of four different cohorts in this particular clinical trial. The first one, which we have completed, is the monotherapy dose escalation, where we have arranged and tested the dosing from 3 all the way to 120 micrograms per kilogram with no signs of dose-limiting toxicities. By virtue of seeing that we've been able to demonstrate better immunodynamics at 90 micrograms per kilogram, we have taken that into as our recommended dose for expansion and are currently pursuing with the second phase of the study, where we are looking at administering this drug q2 weeks at 90 micrograms per kilogram in three different tumor types, namely melanoma, non-melanoma skin cancer, and then irrespective of organ MSI high or DMMR tumors. Third, we have started the combination trial with Keytruda.
This is a dose escalation portion of the study, where we started at 60 micrograms per kilogram, where we have seen clinical activity of MDNA-11 in a single agent setting. We have now advanced to the 90 micrograms per kilogram, which was also cleared by the Safety Review Committee, and currently are evaluating MDNA-11 at the 120 micrograms per kilogram at either q2 weeks or every three weeks in combination with Keytruda. We will be reporting data in the coming weeks and months on the combination portion of the dose escalation portion of this trial. We will set a recommended dose for expansion in the combination setting and identify tumor types, which will be part of the expansion phase, which is the fourth cohort of this study.
If we look at the safety profile that we have generated to date, both in the monotherapy setting and the combination, we're really impressed with the fact that the bulk of the adverse events, 90% or more of these are just grade 1 and 2, the majority of them lasting less than 24 hours. Although we have seen transient liver increases in laboratory tests with liver functions, these are also transient, asymptomatic, and generally return back to baseline within a few days. Similarly, with the combination set, we've not seen any new toxicities or new safety signals in the combination arm, which is really encouraging. We look forward to sharing more data on the safety as we complete the dose escalation portion of the combination study.
Going back to the monotherapy portion of the trial, we have clearly seen, as designed in the molecule itself, really robust stimulation of CD8 T cells and NK cells without seeing an expansion or minimal expansion of the Tregs. This is really encouraging, as you can see from this data on this particular slide, that as we increase the dose from 30 to 60 to 90 to 120 micrograms per kilogram, the expansion that is occurring predominantly is with CD4 and CD8 effector T cells and also NK cells to an extent, but not much as far as Tregs are concerned.
Furthermore, when we look at the pharmaco or immunodynamics, again, what we see on the left-hand side of this slide is that in the monotherapy setting, we see a dramatic increase at the recommended dose for expansion at the 90 micrograms per kilogram, a huge expansion of the CD8 T cells, NK cells, but hardly any expansion of the Tregs. I think most importantly, now this is in systemic circulation, it is important to see that the quality of the CD8 T cells is impressive. What we are seeing is a dramatic increase in the population of the CD25 positive, namely the activated CD8 T cells. We are also seeing CD8 T cells with a high portion of these being with stem-like properties.
Finally, at the bottom of the slide, you can see that we are also expanding very significantly the population of effector and central memory T cells. These are essential to ensure that we have durable responses with IL-2 treatment with this drug. Not only in systemic circulation, but when we examine the tumor microenvironment, we see something very similar as well. In this patient with melanoma at the really low dose of just 10 micrograms per kilogram, although the patient had disease progression, the patient volunteered for PET biopsies. What you can see on the right-hand side is that also in the tumor, we see a substantial enhancement in the population of the CD8 T cells, but also the majority of those that we see expansion that is occurring in is the activated CD8 T cells with CD25 positivity.
We also see a dramatic increase in the population of natural killer cells. Finally, high-quality CD8 T cells that are highly efficient in targeting tumors that are I-COS positive CD8 T cells also expanding. All in all, we've seen, as expected, as per redesign, the molecule really encouraging signs from a PK, safety, immunodynamics characteristics of this particular molecule. What is really encouraging for us now is to see durable tumor responses in patients that have all failed checkpoint inhibitors. In this data set that you see on your slide right now, we can see that these patients have all failed checkpoint inhibitors. About 70% of these had failed checkpoint inhibitors, at least two different lines of checkpoint inhibitor therapies. Among the patient population that we are pursuing in the expansion cohorts, we see in the expansion cohort to date a response rate of 30%.
Amongst all patients, irrespective of expansion cohort and including patients in the dose escalation cohort receiving the higher doses above 60 micrograms, we're seeing a response rate of about 25%. Importantly, I think what we need to look at is right at the top, where you see the second bar, which is a pancreatic ductal cancer patient who had a partial response all the way towards the end of his first year of treatment. Unfortunately, upon taking vacation, the patient had a new lesion, which was treated by a single cycle of radiation, but thereafter, the patient resumed MDNA-11 treatment, and thereafter, the tumor essentially resolved with the patient now in remission for more than 11 months without having received any treatment. We also see a melanoma patient that initially had a confirmed partial response, graduating eventually to a complete response.
We also see additional patients in this monotherapy arm, where we have partial responses among patients with melanoma and another patient with pancreatic cancer as well showing a partial response. These are really exciting. Outside the space of melanoma and renal cell carcinoma, we are seeing really encouraging signs of activity of the drug in tumor types that we were not expecting MDNA-11 to demonstrate robust activity. In this waterfall plot, it gives you a good idea as to what we are seeing to date. We have seen one complete responder, including a partial response patient that eventually became a complete response. We have also seen that amongst the patients with partial response, these responses tend to be durable. Stable disease patients, you can see that we're seeing durability there as well.
To date, we see a disease control rate of about 55%, a clinical benefit rate of 40%, and an objective response rate of 25% amongst all patients and 30% amongst patients in the expansion cohort of this clinical trial. These patients continue to receive therapy. We will update reports on these. Of course, a lot more patients that we have been enrolling in the dose expansion cohort of this trial. When we now move on to the combination portion of the study, we will be reporting more PK, PD data, and immunodynamics with respect to the combination arm of the study. Very quickly here, just to demonstrate that we are seeing a dose-dependent expansion of lymphocytes, looking at 60 versus 90 micrograms per kilogram. That is, again, consistent with what we saw in the single agent monotherapy study.
We are also really excited that in this dose escalation portion of the study, which is historically not designed to demonstrate efficacy per se, but in addition to seeing promising safety of this particular molecule, we've again seen responses in patients that generally do not respond to checkpoint inhibitors. To give you two examples, we have first a complete response patient, a patient with anal squamous cell carcinoma. This patient had progressed on two different prior lines of treatment. The patient had no prior treatment with immunotherapy simply because immunotherapy or checkpoint inhibitors are not approved for this kind of tumors. What we found is within the first scan, eight weeks post-starting the combination treatment, the patient achieved a complete response, and the patient continues on treatment. The second, which we find really exciting also, is a partial response in a patient with colorectal cancer.
This patient has a microsatellite stable tumor, which we know does not respond to checkpoint inhibitors. This patient had prior lines of chemotherapy and progressed on those. The patient now continues to receive treatment after having seen a partial response. There are really two encouraging signs in the dose escalation portion. We will report more data at the 90 micrograms as well as 120, which is currently enrolling every two weeks with MDNA-11 and also every three weeks. Finally, what we have is a summary of the advances we have made with MDNA-11. We believe that MDNA-11 is potentially a best-in-class IL-2 based on its safety profile, its immunodynamics, which is consistent with what we are hoping for. Already in a monotherapy setting, we are seeing a response rate of 30% and 25% amongst high-dose phase two eligible patients.
On the combination set, very early, based on just nine patients to date, we've already seen two patients responding, including a complete response in tumor types that do not generally respond to checkpoint inhibitors. Quickly here, I'll briefly talk about bizaxofusp. It's our MDNA-55 molecule. This is an IL-4 targeted therapy. We have data here to share with you in treating patients with recurrent glioblastoma. This is by far the most aggressive form of cancer out there, with recurrent patients generally not responding to therapy with no approved therapies currently available. Despite patients having first had surgery, radiation, chemo, et cetera, these patients unfortunately invariably recur. When the tumor comes back, this tends to be a lot more aggressive, where the survival expectations in these patients are between six and nine months.
MDNA-11, or rather bizaxofusp, is a fusion protein of an engineered interleukin-4 with a payload, which is essentially there to design to target not only the tumor, but also the tumor microenvironment. By administering the drug directly in the tumor using a single procedure, we are able to bypass the blood-brain barrier. The results from this clinical trial were really impressive. We've seen a dramatic increase in survival outcomes. Instead of 7.2 months in a balanced external control arm that matched the patient population in the phase IIb trial, we find that the treatment with bizaxofusp, a single administration, nearly doubled the median survival in these patients.
With those data, we received clearance from the FDA to pursue a novel study design, which would allow us to enroll the majority of patients in a control arm from hospital databases, namely an external control arm that would be the portion of the study allowing us to recruit faster, but also reduce the cost of the clinical trial. This was based mainly around the fact that the impact or the effect size with MDNA-55 or bizaxofusp was really substantial in this clinical trial. We are currently looking to partner this asset, and we'll keep you updated as we progress on that front. The market opportunity is huge, not only for recurrent GBM at about $800 million, but as we extend to other tumors in the CNS, we see a potential market of about $4 billion.
Finally, looking at the key catalysts coming up for 2025, we have multiple readouts. It is a data-rich 2025, mostly in the first half of this year, with the monotherapy expansion data being presented at conferences in the first half of this year, including combination escalation data and the recommended dose for expansion in the combination arm. At the same time, we will also disclose the tumor types that we will be pursuing in the combination arm of the study. We will commence with the combination expansion phase of the study again in the first half of this year, with data expected throughout the second half of 2025. With bizaxofusp, we will continue our efforts in partnering the program, and we will advance our BiSKITs so that they are IND enabling ready before the end of the year.
The key financial highlights: we are a Toronto-based company listed on the TSX and OTCQX. Market cap is CAD 100 million, with currently CAD 32 million in cash as per our last quarter, with no debt, no preferred shares, with insider ownership of about 22% based on the basic shares outstanding, 83 million total outstanding, with fully diluted just above 100 million shares. Based on our current cash position, we have sufficient cash to take us right through mid-calendar 2026, allowing us to reach all our key milestones coming up this year. Thank you very much for participating, and happy to answer any questions.
Thank you, Fahar. Moving on to Q&A. For MDNA-11, you're mainly focused on melanoma, but showed data indicating positive signs in other cancer types. How are you thinking about other potential indications there, and what kind of prioritization do you have?
Right. What we are quite impressed about is the biomarker-specific tumor type, mainly tumors that are MSI high tumors, for instance. That is where we have seen two out of three patients responding to treatment. That is, despite the fact that all these three patients had failed checkpoint inhibitors. That is really exciting for us. We feel encouraged by the fact that the MSI high patient population is unique in the sense that those that fail checkpoint inhibitors have really no other options. There might be a pathway for this particular tumor type, particularly the failed patients, where we could proceed or look at a potential phase two registration trial. Similarly, around MDNA-11, either alone or in combination, looking at other tumor types, for instance, patients with TMB high or patients that might have tumors of different biomarker categories or even different tumors that are tissue or organ specific.
What is really encouraging is that we're seeing responses even in patients with liver metastasis. As you know, those tend to be really challenging tumor types to treat, being such a highly immunosuppressive organ. Obviously, as we generate more data in the coming weeks and months, we will be contemplating what our registration pathway might be, what tumor types should we be looking at, particularly as we generate more data around the combination portion of the study, with the monotherapy clearly demonstrating robust activity in melanoma as well as in patients with MSI high tumors.
Thank you. I think we have time for one more quick question. Can you elaborate more about your criteria for an ideal combination agent, and are you considering other potential combinations?
Yes. Indeed, the checkpoint inhibitor is the first obvious one with the majority of patients receiving checkpoints. Unfortunately, two out of three patients do not respond to checkpoints. Therefore, we feel that that is potentially the biggest market opportunity that we can pursue. There are other therapies out there. We feel, for instance, combinations with antibody drug conjugates or bispecific T cell engagers. Those are really potentially other combination strategies that we might look at. Really, the real low-hanging fruit is how do we combine our therapy with other cell-based therapies, such as TILs or CAR-Ts, et cetera, that need continuous propagation of the TILs in the patient and expansion of the CARs, whether they be NK or T cell-based tumor treatments.
Those are other obvious combination strategies that we are currently evaluating, either through collaborations with academia or through material transfer agreements with other corporate entities.
Thank you. That brings us to the end of our Q&A. Thank you, Fahar, and thank you, everyone, for joining today.
Thank you.