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

Thank you. Hello, everyone. Welcome to the Medexus Pharmaceuticals Key Opinion Leader Webinar to discuss the clinical data supporting treosulfan, a first-in-class conditioning agent allogeneic for hematopoietic stem cell transplantation. Before we begin, I would like to remind everyone that this presentation and discussion may contain some forward-looking information. I would encourage you to review the disclaimers on the slide presentation, which will be made available after the webinar. [Operator Instructions] Now I'll turn the call over to Ken d'Entremont, who's the CEO of Medexus Pharmaceuticals, for introductory remarks.

Thank you, Tina, and thank you to everyone for joining us on this call today. As you all know, on Tuesday of this week, we announced a transformative acquisition licensing deal for treosulfan from Médac GmbH in the United States. This is a very, very important addition to our portfolio, first and foremost, because this is an opportunity for us to help patients who are suffering from some very debilitating diseases. As you may know, we're excited also because this is a very near-term opportunity. Treosulfan has got a PDUFA date of August of this year, and so we're 6 months away from what we hope will be approval of the drug in the United States. This drug also has already received Orphan Drug Designation, so we certainly expect that, at approval, it will be afforded a 7-year period of exclusivity. We're also obviously clearly excited because this is a very innovative drug. Treosulfan will be the first drug in a new class of conditioning agents called Reduced Toxicity Conditioning. It basically combines the increased tolerability when compared to myeloablative strategies, with improved survival outcomes as compared to reduced intensity regimens. So this basically combines the positive aspect of those 2 strategies into 1 drug. So we're very excited at the innovative nature of this drug. This drug has got excellent clinical evidence, and that will be described by Professor Deeg, who is an expert in the field. And we're eager to hear his opinion on the drug. There is a new drug application, which has been filed. We have now passed the mid-cycle review. The data that the FDA is reviewing is the full data package from a pivotal Phase III study with 570 patients with AML and MDS, and this data package includes superiority testing. So the label that we may receive could be even stronger for treosulfan, if approved. The interim results of this same study have been published in Lancet in the past year or so. Our experience with the drug in Canada over the last couple of years via the SAP process, plus the extensive research that we've done in the U.S. makes us believe that treosulfan has the potential to become the standard of care in this area. And so we're very excited to hear from Professor Deeg. And before we go there, I'm going to turn it over to Mike Adelman, who is the General Manager of our U.S. affiliate, who can give you a brief summary of the market in the United States.

Thank you, Ken. Treosulfan was developed for use in allogeneic hematopoietic stem cell transplantation, or allo-HSCT, in which blood stem cells found in the bone marrow of matched donor are infused to the patient's blood. This procedure is the only potential curative treatment for several types of both malignant and nonmalignant diseases. Before receiving healthy blood stem cells from donor, patient's disease bone cell -- bone marrow cells must first be destroyed by using a conditioning therapy. These are regimens that typically combine multiple chemotherapy agents and also radiotherapy very commonly. Treosulfan is a water-soluble powder reconstituted for injection to the patients that belongs to a class of chemotherapy agents called alkylating agents, and treosulfan is used in conjunction with another chemotherapy agent called fludarabine as part of a conditioning treatment regimen. Alkylating agents briefly work by preventing disease cells from multiplying and proliferating by damaging the DNA of the disease cells. Treosulfan has demonstrated an increased rate of event-free survival and overall survival 2 years after allogeneic transplantation compared to the current standard of care in the pivotal Phase III study, and it's particularly associated with clinically meaningful survival benefits with higher-risk allo-HSCT patients like those with advanced age or comorbidities. Treosulfan has also demonstrated a favorable toxicity profile in multiple studies, supporting its safe use as an effective conditioning therapy for blood cancer patients, like those studied in our Phase III program with AML and MDS. Treosulfan is actually already available in both the EU and in Canada. Back in June of 2019, the European Commission granted marketing authorization to Medac for treosulfan in Europe. And currently, Medexus is distributing treosulfan in Canada via our Special Access Program during the ongoing regulatory review process, which started in 2020, and Health Canada had at that point granted an expedited review cycle for treosulfan. In the U.S., FDA granted Médac Orphan Drug Designation for treosulfan back in 2015 for conditioning treatment prior to allo-HSCT in malignant and nonmalignant disease in both adults and pediatric patients. So as Ken indicated, if approved, treosulfan will be the first and only alkylating agent clinically evaluated and approved for allo-HSCT conditioning. And then the PDUFA date, of course, is in August of 2021. Just a note on potential market size. According to the most recent data from CIBMTR, the Center for International Blood & Marrow Transplant Research, there were over 9,000 allo-HSCT procedures performed in the U.S. in 2018, the year most recently available, with year-over-year growth of around 3%. Incidentally, another 14,000 autologous HSCT procedures were done in that same year. This is a similar type of procedure, but not one in which treosulfan was studied, but one in which alkylating agents are typically used as part of conditioning regimens. So at this point, it is my distinct pleasure to introduce Professor Joachim Deeg to walk us through a summary of the data for the extensive Phase III clinical development program behind treosulfan. Professor Deeg is an oncologist at the Seattle Cancer Care Alliance, Professor of Medical Oncology at the University of Washington School of Medicine and Professor of Clinical Research at the Fred Hutchinson Cancer Research Center. He is internationally renowned expert in bone marrow transplantation as well as myelodysplastic syndromes and myeloproliferative neoplasms. And he's got over 40 years of clinical experience in treating blood disorders. In addition, he participated extensively in the clinical development program for treosulfan, and his center is currently conducting several investigator initiated studies of treosulfan. So welcome to Professor Deeg.

Hello. Thank you for the introduction, everyone, and good morning or good afternoon, depending upon where you are, I suppose. Yes. It is my pleasure to make a few comments from the practice point of few in regards to treosulfan as indicated. It has been tested now in a number of trials, the largest one being the randomized Phase III study conducted in Europe. But we have transplanted here at our center, I think, in excess of 400, 450 patients for both malignant and nonmalignant disorders, and I think that is not without importance because there is also a big indication there. One of the advantages, as also stressed already, of treosulfan is that it -- from a chemical point of view, it does not require activation, metabolization in the liver, that's sort of it avoids this first pass. That's why liver function is generally not an issue for this drug. It is for some other drugs that we use for conditioning of patients. It was stated that it is a "reduced toxicity" regimen, and I certainly agree with that. The important part, however, is that it is not a reduced intensity regimen, which is sometimes overlooked by my colleagues. In fact, it was initially, even prior to the development, as everyone was saying, for transplantation, it was used in Europe for treatment of solid tumors, in particularly ovarian carcinoma. And they have limiting effect -- side effect was marrow suppression, and that, of course, made it almost logical drug to be tested in the conditioning of patients for marrow or stem cell transplantation, if you wish. So it is a high intensity and quite efficacious drug with very little toxicity. In fact, we are carrying -- we have carried out at our center most of the transplant in the clinic, in the outpatient setting, patients not requiring treatment to the hospital, which, of course, patients like and certainly our health resources appreciate. In fact, it was so well tolerated that we could add, for some other indications, a low dose of total body radiation, which still did not induce any prohibitive toxicity. It is also important that the target in the European study in most studies here were AML, acute myeloid leukemia, and myelodysplastic syndrome, which are indeed the 2 most frequent indications for transplantation currently. And as you also heard, the use is growing -- approaching 10,000 patients per year in the United States. One comment on the toxicity, particularly in the pediatric population, where one major concern always has been for the decades that we have been doing transplant is impairment of growth and development. Treosulfan appears to have very little effect. And if our large animal preclinical models can be extrapolated, as we also have been doing for a long time, it may not even interfere with resuming reproductive activity after transplantation. It certainly has been tested in a large animal dog model at the NIH, as a matter of fact. So overall, our -- the community is very enthusiastic. We had countless calls, when can we use it, when can we participate in those studies, et cetera. So I think we are waiting for this drug to be available widely.

Professor Deeg, are you able to review some of the data on the slides that Tina is presenting here?

Do you want me to add some specific comments?

Yes, please. We're hoping to walk through the...

All right, I can say let me try and do that. Well, as indicated here, listed on this slide are 3 by now completed trials. And again, most of -- as you see in AML and MDS patients, I have essentially said already what is relevant here as well, tremendous tolerability at various dose levels, usually between 10 and 14 grams per dose with excellent tolerance. And as I said, I emphasized that we have done, in fact, most of this transplant in the clinic outpatient settings. The next one, MC fludarabine T7 AML trial was a Phase II, as indicated here, and yielded very promising, encouraging results in regards to anti-leukemic effect and long-term survival. And the same is true for the third study listed here focusing on MDS with very similar outcome, maybe even slightly better than in patients with AML, which may have to do with the disease pathophysiology. Well, this is just more of the same, not to bore you with unnecessary details. As we said already, there have been Phase I, II and Phase III trials. I referred to the doses, and they are shown in bold here, the range between 10 and 14 grams per meter square per day as part of the regimen, usually in combination with fludarabine and other profoundly immunosuppressive drug that is also used for non-transplant purposes in patients with malignant diseases. And as we have been saying and the results in all these studies were really positive. I try not to say encouraging because I think if they hadn't been encouraging, we wouldn't be going where we are going now into a broader indication. As emphasized by others before, this treosulfan, there is only one narrow indication for any other drug that has been used -- approved for conditioning.,, That was busulfan for chronic myeloid leukemia. But since we see very few patients with CML for transplantation, currently, the availability of treosulfan as an indication for a different disease group is very relevant. Well, this summarizes data on studies, which enrolled patients with different diseases, as listed here, but again, mostly AML, MDS and then also some mature B cells. Combined total, as indicated here, 563 patients and with excellent safety outcome. I think we have another slide on that, if I'm not mistaken. No? Well, I'm not sure how much I should comment on the text that is shown here. You can certainly read it. There was a temporary suspension after 330 patients had been enrolled. There were discussions about the optimum dose, but that decision really was dependent upon what the comparator would be if we use treosulfan at higher doses. Eventually, of course, you will get toxicity. But if you want to compare it to a regimen with what is thought to have comparable efficacy, then it turned out a lower dose of treosulfan was absolutely sufficient, and that is also what allowed us, and I have said that already, to do many transplant in the clinic outpatient setting. The rest of the text is sort of administrative stuff. It was -- the study was completed, and the remaining patients were treated at a reduced dose of treosulfan. I don't think that requires any additional comments, and the data have been published. Initially, there will be a follow-up papers by the European group led by Dr. Beelen in -- as indicated here. The paper came out in Lancet Hematology last year. And as you can see here in the 2 columns headed treosulfan and busulfan side-by-side comparison, the patient populations were very comparable. Most of the patients received peripheral blood progenitor cells, and only a few received bone marrow as a source of stem cells. So it's more convenient way of obtaining the stem cells by collecting them from peripheral blood. The engraftment, as indicated here, by complete chimerism, which we usually determine at 1 month, 28 days and around day 100 was, in fact, slightly higher with treosulfan. We do not have later time points, let's say, 6 months or so to compare again, but that was certainly a very important finding and that there was no problem with engraftment, which some people had feared would be the case because we didn't really see much toxicity. The question came out, one, is that an indication that we have less efficacy. Obviously, not for engraftment, and you see even a p-value given for both time points, day 28, and day 100. The overall survival is shown here, 71% versus 56%. As was said before, the study was originally designed as an inferiority -- non-inferiority, sorry, study. And clearly, the treosulfan combination was not inferior. In fact, it turned out to be superior. Also reflected in an improved 2-year survival at 64%, the transplant-related mortality at 2 years was only 12%, which, in some studies, in fact, it was only 10% or 9%, definitely lower than with busulfan. Hence, as emphasized repeatedly before, a reference to this regimen as a reduced toxicity regimen with comparable efficacy. The relapse incidence was similar, 24% -- 23% at 2 years, graft-versus-host disease. If anything was -- extensive chronic graft-versus-host disease, if anything, was somewhat lower with treosulfan, which may have to do with the fact that, not to go into great details here, if you have less toxicity of the conditioning regimen, apparently, you do less tissue damage, almost by definition. And having less tissue damage is a situation where you have -- you are not as favorably setting the stage for developing GVHD as if you have a lot of tissue damage with all kinds of cytokines floating around. GVHD-free survival is shown here also, and both GVHD and relapse-free survival, as many people like to refer to now, GRFS, was superior with treosulfan. Very few side effects, as you can see.

Yes. Joachim Baumgart speaking. May I add a short comment to...

Please, go ahead.

To the presentation. If you go back, please, yes. I only want to mention, Joachim, that from Medac speaking that we submitted prior results on the basis on the non-inferiority estimation, as mentioned by Joachim Deeg. This submission was done in Europe at the EMA. But for the U.S. submission of our New Drug Application, we included the prior results of all 570 patients with a longer follow-up as submitted to the European authorities. And we have included a superiority testing in this submission, which is under review by the FDA currently. So we are hoping that the FDA will follow our final results submission with a longer-term follow-up compared to the European submission and will hopefully confirm a superiority claim as submitted by our company. This is, I think, important to mention for the slightly different data base, which was submitted on the request of FDA for our new drug application here in the U.S. Thank you for this short comment.

This is Joachim Deeg again, one more comment. Most of these studies, I don't think we explicitly stated that we are done with HLA identical donors using peripheral blood or bone marrow. I would like to add that, similarly, encouraging results have been obtained with umbilical cord blood as a source of stem cells and which is -- has been -- is still an important source of stem cells, particularly for patients from ethnic minorities, where it is sometimes difficult to find an HLA-matched donor. And very importantly, studies are ongoing now using a treosulfan-based conditioning for patients who are to receive an HLA-haploidentical transplant, for example, from a child or sometimes from a parent, a patient is very young, which is a development over the last 5, 8, 10 years by now, but really gaining tremendous momentum as another aspect of allogeneic transplantation because almost, almost anyone has an HLA-haploidentical donor, so further widening the ability of applying that strategy. You want me -- there's not much to comment on that. I mean, we have said all that before, but just show it graphically. Shown in blue here from the trial as indicated is the survival among patients given the treosulfan-based regimen, 64%, 2-year survival, and in purple broken line, the results with busulfan showing a 50% 2-year -- 24-month survival. And this is -- can you go back to the previous slide? Sorry. Yes. This is the event-free survival, so no relapse. And the next one -- the next slide is the overall survival, similar difference, somewhat higher because a number of patients were rescued by additional therapy, and indicated here is the treatment related or what we often call non-relapse mortality, as we said earlier, was in the range of about 12% for the treosulfan, shown in blue here and was some 25% or thereabout, 28% actually for patients conditioned with busulfan, shown in purple. Well, just to read through that, there is good evidence that a treosulfan-based conditioning regimen is associated with a very favorable outcome of transplantation. And apparently, based on all the studies that have been done and which we have discussed, outcome superior than what is otherwise, probably the most widely-used regimen, busulfan and fludarabine, or busulfan and Cytoxan, although that was not the direct comparison here. Just repeating what we have been saying, the outcome overall survival was significantly higher in this AML and MDS patients. In all fairness, one will have to say that it will remain to be seen whether this superiority occurs also in patients with other indications. But as we emphasized before, AML and MDS are currently the most frequent indications of malignant diseases for allogeneic transplantation. And the last paragraph is, I think, of interest, if I can go back one more time, is that a match pair analysis done by the European Bone Marrow Transplant group shows, again, a superiority of treosulfan, which was also shown in an analysis conducted by the Center for International Blood & Marrow Transplant Research with a seat in Milwaukee. Yes. I don't think I have to comment. The studies on the previous slide were done -- studies done on this continent. In fact, in the U.S., in both adult and pediatric patients, all coming out with a favorable assessment of treosulfan, and here are various centers that participated in those studies. And I have said that already, too. It also includes pediatric patients and, importantly, as emphasized before, nonmalignant diseases. And this not -- lack of toxicity and, hopefully, a lack of a negative effect on growth and development in these young patients is a very important aspect we're looking at. We'll continue to follow, of course, since we need longer follow-up with patients -- with more patients going through puberty and see what their recoveries.

So thank you, Professor Deeg. Great insight into treosulfan, and I appreciate you coming on with us today to discuss some of the clinical data that you've done, and appreciate all the work that you've done behind this drug. So yes, thanks so much for being on here. We'll open up to question and answers. [Operator Instructions]

So I guess, Professor Deeg, if we can get you back on for a moment, maybe we can talk about the autologous market, which I know that the company is looking for approval for allo-HSCT, but there is this other market that could be potentially quite large as well. Can you provide some color on the potential in that market?

For autologous transplants, you mean?

Yes.

Yes. Well, autologous transplants are not really transplants since you infused the cells to the same person from whom you have collected them. So that is not just the question of works. That's the term that people use. It's really here in the autologous setting, what we do when we do a "transplant" is we give high-dose therapy and then rescue basically the patient by reinfusing cells previously collected. But this is, once again, where the very important aspect has to be emphasized that the original observation was that the dose-limiting factor of treosulfan without stem cell rescue, autologous cell infusion was marrow suppression in these patients with ovarian cancer. So that can be taken now to different disease indications as long as we are able to harvest sufficient cells for an effective rescue following the high-dose therapy. Whether that would be in the autologous setting only with treosulfan or in combination with other modalities, I think that's an open question. What we do not need here is a component that will suppress the recipient's immune system. In other words, we don't have to be concerned about rejection, which theoretically at least and in practical, that could be an issue with allogeneic transplantation. So with the patient's own cell, that is not an issue. Hence, here, the emphasis is on as effective and ablation of the disease and then salvage by the infusion of the previously collected stem cells. An important part, of course, as far as disease eradication is concerned, an important difference from the allogeneic transplant setting is the fact that we will not have a "graft versus tumor" effect since the cells are identical toward the patient, although there are studies going on modifying autologous cells, genetically engineering the cells so that we could add such an effect even in the autologous setting.

Is busulfan currently being used for the autologous -- in the autologous setting?

I don't think anyone is using busulfan in the autologous setting, no.