Thanks for joining us to have a conversation. Good morning, and thanks for joining us to have a conversation with Fahar Merchant, CEO of Medicenna. Medicenna is a clinical stage biotechnology company developing highly selective versions of IL-2, IL-4, and IL-13 superkines. The company is currently evaluating MDNA11 and IL-2 superkines in a phase I/II study. The company also has a phase III asset, MDNA55, that has shown efficacy in treating GBM. And on top of these, the company has a platform called BiSKITs, which is a fusion of superkines and an antibody that can be used as an immunotherapy. So to talk about the clinical development programs of all these assets, I invite Fahar to this fireside chat. So Fahar, I'm glad to see you here, and appreciate you coming down and talking to the audience today.
So for starters, Fahar, to help people understand what Medicenna is and what's the development strategy, you know, please highlight, you know, some of those for us.
First and foremost, thank you, RK, for inviting us to present and participating in this fireside chat. Really appreciate that, and thank you for the background that you provided on Medicenna. As you mentioned, clearly we have three different superkines: IL-2, IL-4, and IL-13. Each one of them, of course, have multiple potential development pathways, the majority being currently in the oncology sector. We also have opportunities outside oncology, in autoimmune disease, et cetera, with our other superkines as well. The approach, clearly, as far as the company is concerned, we are looking to advance these programs to achieve proof of concept in humans, particularly in the oncology space, and then in the non-oncology space, looking at demonstrating robust preclinical data, and see if there might be opportunities for partnerships, et cetera.
That is the purpose of Medicenna right now. We believe that the platform is incredibly versatile, allows us to not only pursue as a single agent and/or in combination with other immune therapies, but potentially incorporate, let's say, our IL-2 superagonist in cell-based therapies, as well as developing our BiSKITs or bispecific superkines. As you know, that's sort of a really hot space right now.
Yes. So in terms of, you know, the pipeline, the current pipeline, and starting especially with MDNA11, you know, can you discuss the design of the molecule itself, and how is it differentiated, you know, from other IL-2 molecules, which are actually in the clinic at this time?
Yes, that's a really good question. I think, as you know, there have been so many different versions of IL-2s having been developed over the past three to five years. There's others that are in the clinic, just like ours. But I think the key thing here with MDNA11, first and foremost, is that we have engineered the molecule so that it does not bind to the alpha domain.
By not binding to the alpha domain, you're not going to stimulate your immunosuppressive Tregs. Also, it will help from a safety perspective, because we have clearly seen that in our case, unlike others that have the alpha binding domain, we don't see eosinophilia.
Eosinophilia generally tends to be a precursor for vascular leak syndrome, so we're not seeing that. That's one important aspect about what we've done. The second thing is that, unlike anybody else in the IL-2 space, we are the only company, and our IL-2 is the only one, where there is a very dramatic increase in the affinity for the beta gamma receptor, which is, this receptor is overexpressed and generally in your effector CD8 + T cells and NK cells that attack the tumor. It allows us to have that selectivity.
And finally, what we've done with our IL-2 is, instead of using other traditional approaches of extending half-life, we fused it to albumin, and that albumin extends the half-life, but more importantly, it allows the drug to also be accumulating in the tumor, in the tumor microenvironment, in tumor-draining lymph nodes, et cetera. And that's why we believe we are seeing that differentiated safety, but also differentiated activity of the drug.
Very good. And, you have been conducting, as I said, phase I/II study, which you call ABILITY, to evaluate MDNA11. What's the design of this study, and what are the endpoints that you're trying to achieve in the study?
Right. So the ABILITY Study, as you explained, is a phase I/II trial, and there are really four sort of parts to it. The first part being the single-agent MDNA11 monotherapy dose escalation portion of the study, which was open to all different solid tumor types in patients that had advanced cancer. And that portion of the study has been completed, where we have established the recommended dose for expansion at 90 mcg/kg . So that's one part.
The second part is where we are enrolling patients now, is in the monotherapy dose expansion, where we're looking at a select group of patients or tumor types, namely, melanoma, patients with MSI-high tumors, and third, patients that have non-melanoma skin cancer. So those are the three tumor types. And then separately, we have the combination portion, where we have a clinical collaboration with Merck, where we are combining MDNA11 with Pembro. And, Pembro, as you know, sort of a blockbuster, drug out there.
Yeah.
We are currently conducting a combination escalation study, where Pembro is being administered 400 mgs every six weeks. MDNA11 is being administered every two weeks. Both of them are IV administrations and the important thing here is that we are already past the 60 mcg/kg dose, and are currently enrolling in the combination group at 90 mcg/kg , which is the same dose as the monotherapy expansion. So really happy with the safety profile we've seen so far. We've not seen any overlapping toxicities or signs of immune-mediated adverse events. And then finally, once we establish the dose and the combination, we'll be looking at expansion in the combination as well.
So, you know, in terms of the data that you have released so far, as you said, you know, you released you know tranches of data at different times. But can you, especially the recommended dose where you're taking to the expansion phase, at that particular dose, what's the efficacy that you're seeing? And also, you know, what's the safety you're seeing?
Correct. Yeah, that's a good question. So this is really exciting for us. As you know, there have been a number of challenges in the IL-2 space. Previously, some of the first, second generation of IL-2s were not showing single-agent activity, and we've been demonstrated that, in the 14 patients that we've treated so far, and these are patients who have failed, multiple therapies. In fact, all the patients, of the 14 patients, have all failed at least one, if not two, immune checkpoint inhibitor therapy. So these are really patients that generally are the focus in three different tumor types. And we've seen response rates of nearly 30%, just under 29%, in fact, where we have seen four patients with responses out of 14. And of those four patients, one is a complete responder.
The second patient, a pancreatic cancer patient, a partial response, but now the patient has completed and is not receiving any treatment, continues to show complete remission of the treatment. And we have got a small bowel cancer patient, again, a PR. This is an 85-year-old lady. And finally, another patient with melanoma who's a partial responder. So we've seen four out of 14 responses.
I think the key thing here to note is that typically, as you know, PROLEUKIN, the traditional IL-2, has been approved for melanoma and renal cell carcinoma. What is very unique here is that we're seeing that two patients, one, a pancreatic cancer patient, another, small bowel cancer. Previously, neither of these tumor types have shown any where IL-2 has never shown any activity before. So really encouraged to see this kind of activity in these different tumor types.
Of these two tumor types, you know, the pancreatic and the small bowel, you know, is there a way to amend the protocol and try to expand that patient population, or does that come later?
Right. So good question. Just to add to the story that, about, you know, pancreatic cancer and, and, small bowel cancer, both of these patients had, have a tumor, which is the MSI-H.
Mm.
Patient populations. Now, patients with MSI-H tumors, this sort of includes a whole range of different tumor types. These are generally patients with gastrointestinal cancers or gynecological tumors, for instance. And these patients routinely get Pembro as first-line therapy for them, and Pembro has worked in a good number of patients. However, there are patients, for instance, the pancreatic cancer patient that we enrolled, that patient simply did not respond to checkpoint inhibitor such as Pembro, and responded. The second patient, which is a small bowel cancer, also a MSI high patient, previously did respond to Pembro, but eventually the tumor progressed and advanced.
So the potential here is that if we continue to see this kind of data, and if we see, let's say, over the next, say, 10 patients or so, response rate in or above 30% in this patient population, we may look at potentially expanding that particular study, and in a new protocol, look at a potential for a pathway, a registration pathway in a phase two setting in patients who failed checkpoint inhibitors with MSI-H tumors.
In terms of the safety, I know you.
Right.
You alluded to PROLEUKIN and its issues.
Yeah.
In general, with IL-2 therapies, not only PROLEUKIN, but other therapies which are out in the clinic, what have you seen in terms of safety concerns, and how does MDNA11 differentiate itself against the other molecules in the clinic?
Yes. Again, a really good focus here, because in the end, as you know, PROLEUKIN has been a challenge because of the toxicity issues. The drug, you know, has to be administered, in most cases, in an intensive care unit for a period of five days or so, which is a problem with PROLEUKIN. We haven't seen those kind of toxicities with MDNA11. In fact, the majority of events that are drug-related, 95% of those have been grade one or two. Most of them are generally the ones that don't last more than 24- 48 hours. Only 5% of the patients had grade three events, and these were expected with IL-2's mechanism.
So we do see, for instance, elevation of liver enzymes, but we did not see any symptomatic effects of the drug. And what is very interesting is that these patients with grade three events were again transient. So from that perspective, we are happy to see that we are not observing any immune-related adverse events. And these immune-related adverse events are generally the ones that are caused by checkpoint inhibitors. So the concern always is that you might add the two, you know, toxicity profiles and make things worse, which is really something we are not seeing in our situation. So that's really important. And I think the other thing is also that as patients receive MDNA11, they become more tolerant-
Mm.
To MDNA11, so that subsequent administrations of the drug does not cause that issue. So unlike others, where we have seen, for instance, with alpha-driven IL-2s, for instance, that are in the clinic right now, tendencies for eosinophilia, for instance. And that sort of grade three eosinophilia is generally a precursor to vascular leak syndrome. So that's one problem. The second is with another, competing IL-2 program, where we've seen, patients that received the second cycle of treatment, immune-mediated adverse events, such as colitis and so on.
Mm-hmm.
And that is also potentially a concern, particularly when you are then going to look at combination strategies. So thankfully, we haven't seen any of those and really encouraged with the safety profile. As you know, we are administering the drug IV once every two weeks, and we've seen activity even at 60 mcg/kg . So really excited with the data so far.
One more question on the safety side of things. Have you seen any discontinuations or either drug holidays or people lowering the doses?
We did have a patient in pancreatic cancer who actually went on holidays, not specifically for drug. But the patient had a really good, you know, PR, went away for holidays. But unfortunately, after eight weeks, having missed four cycles of treatment, came back with a new lesion, which had to be very quickly treated with a single cycle of radiation and then went back onto MDNA11, and thankfully, MDNA11 was able to eventually restore and then sort of the efficacy, and therefore, the patients had complete regression of all target and non-target lesions. That was one instance. We have not seen any drug-related, sort of treatment-related discontinuations, and we will be providing more updates at the upcoming conferences next, sort of, in the month of November.
Okay, perfect. So in terms of you moving on and going to the second in phase II of this study.
Right.
So what's the strategy there, both for, monotherapy and combination therapy, and also the confidence that you have that you want to go there?
Yeah, I mean, the thing is that we are already, as I said, you know, if in a monotherapy setting, anything above 20% response rate would really trigger for us a really solid set of data, and therefore identify opportunities where we might look at progressing the drug. For instance, I mentioned to you the MSI-H patient.
Mm-hmm.
Population, for example. In the combination setting, of course, we are evaluating the combo, looking at the dose escalation. This is sort of very open. It's open to all different tumor types. We will revisit after we've completed the dose escalation and determine which tumor types we should pursue. But certainly, one of the ones that we want to look at so that we are able to compare single agent activity is in the melanoma patients. So we'll at least look at melanoma in a combination setting. Again, these will be patients that have had previous failure to checkpoints.
So in terms of data expectations, you know, what should investors have, not only for the rest of this year, but also in 2025 from the MDNA11 program?
Yes. So we expect, at SITC, which is sort of eight weeks away from now, we expect to provide an update. This will be the monotherapy expansion update, including patients that we have reported in the past. So we will be providing an update on those patients, as well as new patients that have been enrolled. And then in the combination setting, as you know, we've been treating patients at the 90 mcg/kg in combination with Pembro. We'll have determined if we are seeing any DLTs in that, so we'll be reporting on that as well. And therefore, that will help us make a decision going forward in terms of combination expansion. And in sort of 2025, we're sort of expecting presenting at maybe AACR or ASCO, so we're looking at sort of springtime.
Mm-hmm.
Where we will have, at that point, not only a fuller set of data on monotherapy expansion, but we'll have a good set of data on, combination expansion as well.
Perfect. And then, your other program, which is the BiSKITs program.
Yes.
Which is a preclinical at this point. You know, you have been developing molecules there, and I know that you recently came back from Paris attending.
Yeah.
The promise of IL-2 conference there. And you had data presentations over at Paris as well. Can you highlight the program?
Sure
And also the specific data that you has presented in this two molecules.
Yeah. So the one we mentioned is MDNA113, which is a BiSKIT. This is a bifunctional or a bispecific superkine, where we have fused our IL-2 superkine, which is the same IL-2 As we have in MDNA11.
Mm-hmm
And instead of fusing it to albumin, we have fused it to a checkpoint inhibitor, anti-PD-1. So this way, we've got a bifunctional molecule, bispecific molecule, very much in sort of line with what you've heard from, let's say, Summit Therapeutics.
Yeah
Where they have an anti-PD-1 with VEGF. And as you can see, those kind of bispecific molecules do exceptionally well. So we're really excited about this molecule. The good thing with MDNA113 is that it is directed towards tumors that are extremely sort of cold tumors that don't respond to checkpoint inhibitors. And we have, within this molecule, a masking domain and a targeting domain. So this is where we use our IL-13 to essentially localize the drug right at the tumor site. So that's our MDNA11 program - sorry, MDNA113, the BiSKITs.
Mm-hmm.
The other program is really exciting. We've seen some really remarkable results in patients, sorry, not in patients, but in mice, with graft-versus-host disease. This is really a molecule that evolved from MDNA11, where we've taken MDNA11, and instead of making it a super agonist, we've made it a super antagonist. So the purpose here is really to drive and, you know, sort of, treat autoimmune disease, where we know that in autoimmune disease, our own immune system attacks our own organs. Now, by calming the immune system down with something like MDNA209, would really help these patients with autoimmune disease. As you know, it's a huge market. There's been a number of transactions at the preclinical stage with, you know, autoimmune therapies.
So we're looking forward to you know, advancing those two programs and hopefully have them in the clinic.
Mm-hmm.
Or enter a partnership with other companies.
So yeah, so talking through that, you know, what is the development strategy? Because you have MDNA55, MDNA11, which is obviously, you know.
Mm-hmm.
Has progressed really well through the clinic so far. So when it comes to BiSKITs, you have multiple programs. So.
Yeah.
Which ones would you prioritize?
Yeah.
You know, what should we think could come to the clinic the soonest?
MDNA113, I would say, is the BiSKITs that we would be looking at from an oncology perspective. That's one. With again, this would likely not commence until towards another 12-18 months from now, so we certainly are not looking to advance that in the short time frame. The focus is really on MDNA11, get that study completed. We are also making advances with MDNA55 from a regulatory perspective. We've looking to get breakthrough therapy designation, get alignment with the European Medicines Agency on MDNA55, so that those two key regulatory milestones will allow us to hopefully get a transaction completed with MDNA55 and commence a phase III trial. With any other assets, I think MDNA209 is our autoimmune program.
Mm-hmm.
Based on the plans, we continue to do preclinical work. We have sufficient cash into mid-2026. Our current cash balance, CAD 36 million. We sort of burn between CAD 4 million and CAD 5 million a quarter, so that gives us a pretty good runway. We look forward to, most importantly, advance MDNA11 to its, you know, key data endpoints or data readouts, which will be middle of next year. Then, of course, look at advancing the other pipeline assets. But for that, of course, we'll be looking to have to need additional capital. Right now, we have sufficient funds for MDNA11 and MDNA55.
Good.
Okay?
Fantastic. Thank you very much. Appreciate you coming down, and good luck.
Thank you. Thanks a lot.
Thanks.
Bye-bye.