Medexus Pharmaceuticals Inc. (MDP) Earnings Call Transcript & Summary

Okay. Hello, everyone. Thank you for joining the Medexus webcast this afternoon. Today, we are joined by Filippo Milano, a physician and scientist, whose research is focused on the use of umbilical cord blood as a source of stem cells for transplantation to treat various blood cancers. He is an associate professor in the Clinical Research Division at Fred Hutch and also a Director on the Cord Blood Transplant Program in the Clinical Research Division at Fred Hutch. Just a reminder for everyone, if I could please refer you to the forward-looking disclaimer in the press release Medexus issued this morning titled Treosulfan Pivotal Study Results Published. And with that, I'm going to turn it over to Filippo. At the end, we'll be back and we can answer a Q&A. Thanks, Filippo. Over to you.

Thank you, Victoria, and thank you, everyone, for the opportunity to be here with you and actually sharing some exciting news that have been recently released. One thing that I would like to add in terms of my area of expertise, yes, I'm the Director of Cord Blood Transplant, but as many of you know, at Fred Hutch, we pretty much treat any type of transplant type. So -- and I also have protocols in using haploidentical donors and related donors. As I said, very excited because it's been now over 2 years that we were waiting for this data to come up after the first study that was published in 2020 by [ Bill and colleagues ]. And at that point, the first study was including 476 patients and was -- mostly was a noninferiority study where they were comparing the [indiscernible] reduced intensity as we want to prefer to name it, busulfan fludarabine approach versus the treosulfan fludarabine approach. There was the first result that were reported, actually ended up in the plenary session at the TCT meeting, show non-inferiority of treosulfan compared to busulfan. There was the initial study, and everyone was very excited because it's already proving in an annualized fashion that treosulfan could be comparable to busulfan. But thanks to the leading authors and to the other center participating in Europe on this study, they decided to move forward and trying to change the aspect of this study from a non-inferiority to evaluate actually superiority of treosulfan. And that's actually what we are here today to speak about is the updated results, which now include not 476 patients but 570 patients. Of this 570, we have 280 patients who were randomized in the Treo/Flu arm versus 290, they were randomized in the busulfan flu arm. I would say that the primary endpoint of the study was evaluating event-free survival and event-free survival was defined by the authors as any type of disease progression, graph failure or any type of death, which is the most meaningful endpoint related to the -- related to a randomized study. What the others found was that a significantly better event-free survival in the group of patients receiving treosulfan, when compared to the patients receiving busulfan with a difference of 59% versus 49%, bringing to another ratio of 0.64, which basically means a 36% reduction in risk of any type of event correlated to survival in the group receiving treosulfan. The others then moved towards a -- towards analyzing secondary endpoints and the secondary endpoints, and what they found out is that overall survival was again, once again favorable to patients receiving treosulfan when compared to ones receiving busulfan was a difference of about 67% versus 56%. But once again, with a 36% reduction in risk of overall mortality among patients receiving treosulfan. There was no difference in terms of relapse, [indiscernible] details for relapse for both groups was pretty much the same. The difference that were noted in this study was mainly for non-relapsed mortality, which is significantly lower in the group receiving treosulfan. Those are the main points of the study, but as investigator and as Victoria said, my last time kind of give me away, my -- Milano tells you that I'm Italian, so I worked in Italy as a transplant doctor in University of Rome. Then I moved in Seattle in 2008. So it's been 14 years for me being in the United States. But when I came to the United States, one of the things that I was surprised is that treosulfan was not approved yet. While in Europe, I was already utilizing this drug, and I'm talking about 2007, 2006. So it's been around long enough in Europe and this study testify why in European colleagues, they use it as one of the main drug for conditioning regimen. I said all of that because I think other things that in this study was really appealing to me as a transplant physician, is the fact that also some of the secondary endpoints are very interesting. First of all, in the group receiving treosulfan, patients achieved a more stable and more sustained chimerism day 28. It's a very important point, which leads to another endpoint, which is GRPS or graft relapsed presurvival, which is now another endpoint of main interest for transplant decisions. GRPS at [ 2 year ] was significantly higher for patients receiving treosulfan when compared to the one receiving busulfan. I try to -- the announcement of the study is very recent. I tried to make up my mind of trying to understand this difference. But I do think that the fact that chimerism happens in a more robust way in patients receiving treosulfan, it might help also -- it might also help in terms of the tolerance in this patient because the GVHD prophylaxis was the same for both groups. And as a matter of fact, patients receiving treosulfan had less extensive chronic graft versus host disease when compared to patients receiving busulfan. I forgot to say one thing that's very important, again, too many things to share and in a very short period of time, this study was only for patients with AML and MDS, only for adult patients, it was 18 to 70 years old, and median age was 60 years old with median comorbidity score of 2. I think these are very important demographic data because they might come up in the discussion later on. As you know, transplant regulation is increasing over the years. So the approach of using conditioning regiment of reduced intensity of non-myeloablative, again, as you want to prefer to call it, it's very important because this is the main population that we treat these days. I think I will stop it here. I'll try to summarize, and I'm very happy to answer questions, if anything, that can -- from the audience. Thank you.

Okay. Thanks, Filippo. I'm just going to add a few more participants. And so we can have a bit of a broader discussion. [Operator Instructions]. Michael can...

Hey everybody. Hey there, Mark. Just a couple of quick comments. Thank you very much to Professor Dr. Milano for his review of the top line information from our Phase III clinical study. As you saw in the press release, the manuscript of the results of the study have been accepted for publication by the American Journal of Hematology. Print Edition is still forthcoming, but the journal has made the results available on our website as of last week, and we've included the URL in the online -- to the online version in this morning's press release. Joining us from Medexus, you know Ken d'Entremont, our CEO; and also Mark Fosdal, our Director of Scientific Communications, who incidentally used to work at the same institution as Professor Milano. So thanks for joining us, and we'd love to open up the floor to questions from the participants in the audience.

So we do have one question that's come in so far. Is there any potential for any off-label use for any other patients?

Do you want me to answer these questions? Or I think I will leave this one to the -- maybe to Medexus because it's -- for me, I can tell you one thing, okay, let's put this way, maybe I'm going to set the stage. As I said to you, as European, I've been using this drug in Europe before coming here, and it's a very popular drug in Europe and it's becoming the one that we use the most among our colleagues in Europe. In the United States, we will be different. Fred Hutch actually has been very lucky to have available this for a long time for our collaboration with Medac, we have been treating more than 500 patients using treosulfan. I'm very happy to share this data with you and telling some of those are ready published. And I can tell you, our experience at Fred Hutch. Going to the question to set the stage, one of the study that we've been doing is, for example, using treosulfan patient with cord blood transplant. I was actually the PI on -- of that study, and we enrolled over 100 patients with the overall survival was approaching 70%, and everyone knows that cord blood is not an easy transplant to do. It's not really an off-label. It's not just a different stem cell source use. But there we know we do have other investigator at Fred Hutch, which are using treosulfan with very good success. Some of these have been already presented for nonmalignancies and it's becoming another area of interest where to use this drug. I'll stop it here. And I don't know if Medexus want to add anything else on this -- for this.

To your point, Dr. Milano, you mentioned the fact that there's many factors, many different types of donors, many different types of graft versus host disease prophylaxis and we are pursuing -- they're not only off-label per se, but there are different sources of, let's -- I think that's the one you're doing this as well with the haploidentical transplants and GVHD prophylaxis using post-transplant cytoxin, which is becoming more common. So it's not just MDS and AML, it's also different combinations of GVHD prophylaxis as well. And as Dr. Milano mentioned, nonmalignancies is another area of interest that has also been in Europe as well.

That's what the [ New York ] indication too, Mark, the nonmalignant. So we expect the label to reflect adult and pediatric use in conditioning before a hematopoietic stem cell transplant for both AML and MDS patients.

Okay. So a second question and nice data so far, given that the treosulfan data is superior to busulfan, can you envision anything on the clinical side that would prevent physicians switching to treosulfan use, if it were available?

Short answer, absolutely not. The -- I don't see any point why our colleagues should not switch. And I'm telling you that actually, again, as I said, we are very lucky here in Seattle because we had the chance of using this drug. And I have many colleagues of mine in the United States that are asking me to participate to my trials or how they can access to it. And unfortunately, the drug is not approved yet here and that they can be associated with my studies. But the interest is extremely high, especially because they know the results in Europe. And the practice in Europe is very similar to the practice in the United States. So we would like to do exactly the same here.

And then a follow-up question to that. Is busulfan still used in Europe? Or has it been replaced by treosulfan?

So very good question and it will be a very logical question. I can tell you that it's still used and some of the -- the reason behind it is because some of the centers that might acquire only busulfan, not necessarily -- especially the one that's more, the majority of the big centers that I know and I collaborate in, they have switched to treosulfan, not only based on this data but based on their experience.

So then in regards to the study, a question, why does event-free survival of treosulfan decrease further at 3 years versus 2 years by more than the decrease for busulfan?

Yes. It's a good point. I don't think that the data allow us to kind of tease out yet. The reason of that less decrease, I would say, though, that the percentage of patients alive at 2 years is pretty high for such population. And I think that's why I think we see a bit -- maybe a bigger decrease in the busulfan arm. I can tell that here in Seattle, we are actually now analyzing the data. We have data from 2009. We're talking about 12 years of data in trying to analyze if there is anything specific related to treosulfan. So far, we have not find any signal. So I would say that this is just something that needs to be better investigated, but I don't see as a detrimental effect, honestly.

And then is data being collected for event-free survival past the 3-year point on treosulfan?

From my side, yes, I have a -- as I said, I have plenty of data. I cannot speak for these authors, but I suppose they are.

Once Medexus' response to the CRL is considered complete by the FDA, when would Medexus expect to launch treosulfan assuming FDA approval?

So I'll jump in on that one in Victoria. The study, of course, is the basis for the new drug application that's currently with the FDA and the basis of our plans for communication. So we're looking forward to it being approved. We do expect there to be up to 6 months from the time of complete resubmission to FDA approval, and we are working on tightening up supply chains and timelines as much as possible to minimize the delay, but it will take us a few months.

Okay. [Operator Instructions] Those were all the questions that we've had come in so far. So I'm not sure if there's any general or closing comments that anyone here would like to make.

I might -- I tried to summarize the paper, if I may. And I am -- as an expert in the field, I really think that as I said, I was very surprised when I came in, in 2008 in Seattle with my broken English that treosulfan was not approved in the United States. I was using in Europe already, and I knew the results. And it's been a little bit of struggle to understand why this drug is not in the market yet because it's definitely a drug that we love as a transplant physician. And I'm telling you why we love it. We love it because it's associated with less liver toxicity. That's where it really comes down, and that's what the studies are showing at the end of it, the difference is non-relapsed mortality. The reason why is that -- the reason why is because it's -- this complication is called -- in the past, it was called VOD, veno-occlusive disease, which is a mortal complications after transplant, happens in the first few weeks post-transplant. Busulfan drug is metabolized in the liver, so it affects the liver and create toxicity in the liver. Treosulfan has 2 different molecules, there are 2 hydroxyl groups in its molecule, which bypass the liver and bypassing the liver doesn't bring the toxicity. And as a matter of fact, and as I said to you, we've been treating now over 500 patients. And I don't even think we can count on one end, patients having complications like the one I'm describing. Why when you use busulfan, it is a complication that we need to always be aware. And unfortunately, there's not that many drugs, only one on the market, it doesn't work all the time and patients end up dying after conditioning regimen. That's why I really would like to have this drug available, not only for me, I have it right now in a clinical study, but for all my colleagues. And I would also add another thing that is important. I said it before, but the majority of our patients now are older patients. And so adding a drug that allows what is a nonmyeloablative regimen is what we are looking for. We want to create a regimen that is not toxic for our patients, that make establish engraftment so that we can have the desired outcomes. And the study is only on AML and MDS, sorry, that I'm talking very much, but because, again, the experience that we had in Seattle has been outstanding so far. And we also tried treosulfan in patients with acute lymphoblastic leukemia, and the effect seems to stand also and therefore, that disease.

Okay. Yes. Thank you so much for that. Two other questions that come in. These are more geared toward Medexus. Are you able to clarify what additional data the FDA has requested and why it wasn't sent originally?

I'll take that, Victoria. So we said in our press release that the FDA was reviewing the resubmission, that a question came up that couldn't be answered within the time frame that we had available, which was 30 days. And so that really caused the delay that we're experiencing now. It's a very straightforward data collection, but it has to come from the institution. So we do feel like it can be accomplished and certainly within the time frame, that we have available prior to the 1-year anniversary of the CRL, which is July 30. So we do believe that we will -- or that act will have a resubmission submitted prior to that deadline.

And then the last question, the data that was presented in the study that was just released, has this been included in the application?

Yes. So I think that's why it's important to have this discussion with Dr. Milano and here in his experience and his interpretation of the data because this is the data that the FDA is reviewing. And so this will be the data from which Mike and his team will promote treosulfan. So we think it's really important that investors understand that what's been presented here today is the information that the FDA is reviewing and will form the basis of our label upon approval assuming approval is granted.

Okay. Well, that's it for the questions. So thank you, everyone, for joining today. Thank you, Dr. Milano so much for coming on here and giving your opinion. And with that, unless there's any more comments from many of you, I will end the call.

We thank Dr. Milano for sharing his vast experience. It's very much appreciated.

My pleasure. Thank you so much for having me.

Okay. Thank you, everyone.