Good afternoon, all in Europe, and good morning for those on the other side of the pond. I'm Markku Jalkanen, founder and CEO. I'm here today with our director for medical affairs, Inka Pawlicki. We are going to present you the recent update of the BEXMAB data. Very exciting one. I hope you really like it. And as just a reminder, after the presentations, you have a chance to really make questions, and you can already do it during the presentation. Just connect to the link, which was in the invite, and send the questions in, and then they will be presented to us post-meeting. So welcome again, and we will move on. I will show the mandatory disclaimer because we will be making forward-looking statements. As you know, the lead product we have is this bexmarilimab.
It regulates the function of Clever-1 molecule, which is the major immune suppressive elements on macrophages or, or monocytes or myeloid cells. By that matter, it can generate a significant suppressed immune environment to control the host defense system. Obviously, cancer is typically one disease group that actually would like to utilize that in order to grow in us and then metastasize. We also know that this regulatory pathway can generate a interferon signaling, and this signature is known to be really important for the current immune therapies. Without it, they have lousy effi-e-efficacy levels, and obviously, that is very interesting to us. Having said that, we have really focused recently, this lead program we have with the myeloid leukemia. Why it is so interesting is really the fact that now we have the same receptor of the surface of these cancer cells.
We have made significant progress, and we tell the results in a minute, but on the background, we have also made significant interactions with the regulators. And obviously, when you are in the drug business, in the development business, you have to really coordinate and align with the regulators like FDA, EMA, and the Finnish authorities. And those, some of those we have already announced, but I'm pretty sure that there will be further information available later this fourth quarter of this year. So bexmarilimab, blocking antibody for Clever-1, and we know, and we have shown this previously, this is almost like engineered to be in this position, to activate the immunity by controlling the monocyte phenotypes. When they are in the circulation, these myeloid cells are called monocytes.
When they penetrate to the tissue, they are macrophages, but at the same time, also block the Clever-1 on the surface of the acute myeloid leukemia cells. Just to remind you all right away, right away now, there's no really good treatment for this myeloid leukemia at the moment. When Clever-1 receptor is blocked on the surface of these myeloid leukemia cells, it will cause a signaling change for the cells, and that would decline the use of oxidative phosphorylation. When you do that, you shut off the gas production, and gas for the cells is ATP. Obviously, when cell runs, runs out of the gas, you lose your viability.
So this combination of activating our immune system and then, declining the viability is a perfect example, really, to be utilized now against the acute myeloid leukemia cells born in the bone marrow and then spread all over the body, and then replacing our really important ancestral blood cells, and that causing then usually severe infections and obviously death of the patient. So we also learned that by combining with standard of care, which is now practiced with the acute myeloid leukemia, we can even synergize this, viability drop effect. And obviously, that could really explain why we have so excellent results from this BEXMAB trial we have been conducting now a bit more than a year. I want to say this is not too complex, but the take-home message is twofold.
As you see from the uncertain, giving Bex to the patients, these leukemia cells, we do activate the bone marrow immunity. We can see that in the increased antigen presentation capacity of the cells, we can also see on the right-hand side, increased accumulation or a lymphocyte into the bone marrow. Both are clear signs that the activation of immunity is increased. You can see also from the figure, if you look at carefully, that there are dosing levels of our current trial indicated, and it looks to us that the jump from 1 mg per kg to 3 is a significant one, and it's not necessarily any more increased. The dosing we selected already during the MATINS trial and post-MATINS trial is pretty much predicting the outcome of the trial also at this point.
Obviously, we are very happy for it because then we know that we have a similar principles really also applied as we had with the solid cancer patients. Very exciting. Then I would like to ask Inka to continue from here, please.
Perfect. So I'm gonna recap, our BEXMAB study, which is investigating bexmarilimab when combined with standard of care therapies....So the BEXMAB study is a phase I/II study. The phase I is a dose-finding study, and then this is followed by a phase II, which is the efficacy evaluation of the combination treatment. And like Markku already mentioned, in the dose-finding, we have now evaluated 3 different dose levels. And I think we have, or we think that there is sufficient data to analyze, to now move rather swiftly into the phase II. And we will focus, of course, on the doublet arm, which is on top, shown in the yellow bar, where we are investigating 3 different population of patients. One is, frontline MDS patients, who has never received treatment for their disease.
Then we are also investigating MDS patients that had prior HMA-based therapy, and we are investigating relapsed-refractory AML patients. The combination that we are investigating, we are calling the doublet, and that is Bexmarilimab plus azacitidine, and azacitidine is actually an HMA-based therapy. So this is the current status of our trials, where we are finishing up the dose-finding part. We are working together with six clinical sites, four in Finland and two in the U.S., and we are anticipating to open an additional three sites in the U.S. still this year. Based on the emerging data, our current focus is to move the MDS HMA failed population as well as the relapsed refractory AML population into the phase II.
Maybe the most exciting or the update on where we are in October versus where we were in July. Basically, since July, mid of July until now, we have actually enrolled a total of 28 patients, but efficacy data is presented here in the graph from 22 patients, because 6 patients have not completed at least two treatment cycles. We have now, in total, 7 additional patients since July, where we also have efficacy and safety data that we will present. Just a high-level summary, in green, you can see on the slide where these patients are based on the best change in their percentage of bone marrow blasts.
You can maybe appreciate that, first of all, bexmarilimab continues to function rather well directly in the bone marrow of the majority of patients, because we can see a blast reduction also in the majority of patients. Maybe the next slide. Here we are showing you basically, out of the 22 patients that we are presenting the efficacy data today, 11 actually show an objective response, and these 11 patients are summarized here in the Swimmers plot. The different populations or malignancies are shown based on the color of the bar.
If you maybe focus on the blue bar, these are the MDS patients that had prior HMA therapy, meaning these patients have previously been exposed to azacitidine, which is a combination partner that we are investigating in the BEXMAB trial. You can appreciate that the majority of these patients actually respond to remain on treatment. We put at around four months the median overall survival of the MDS failed population as it is reported currently in the literature. You can see that we are basically three of the five patients or four patients that are shown here have an extended overall survival versus what the median overall survival of this population would be.
And then if you maybe focus on the purple bar, this is the relapsed refractory AML patient population. It's a very difficult to treat population with no standard therapies around. So also here, we are seeing rather promising long duration of responses in the two patients that we are showing here as responders. And to highlight again, the MDS HMA failed population of patients. Also, that population is basically without any standard of care of therapy. So the combination treatment again extends, you know, potentially the overall survival of three out of the five patients.
One patient is rather, rather new in the study, so it-- this is the, the fourth patient at 6 mg per kg, where we see disease stabilization, but also this is accompanied with blood count recovery. Otherwise, I think this is really, in a really promising data for this patient population. Again, as there's no standard of care of therapy for this population. Then moving, of course, we are in a dose-finding phase of the safety, is the primary endpoint for this phase I of the BEXMAB study. Here we are providing you the updated safety that we are observing. Overall, bexmarilimab continues to be well-tolerated in combination with azacitidine. As mentioned, we now evaluated three dose levels, 1, 3, and 6 mg per kg.
On the left side, you can see the treatment-related adverse events. These are adverse events that are related to bexmarilimab, and out of the total adverse events observed so far in the BEXMAB study, these are around 8% of all adverse events, and the majority of these 18 single events is of grade one and two in severity. We do observe, in total, 5 events that are either grade three or above, and two of these related events also led to discontinuation of the patient. If you look closely, again, now on the left side, the blue table, we are listing here now all of these 18 events.
And for us, these results indicate, again, that we are not seeing any different safety pattern as has been observed previously with bexmarilimab at these doses, for instance, in the MATINS trial. So there's no related adverse event that hasn't been observed before. But I do want to highlight that we are observing related events that are immune-related. So there we have three events. This is basically the COP, then the CLS and the HLH. It's written out what this event or what these diseases or conditions mean. And these are of, again, they're immune-related, and they are of grade three or higher that we have observed. And it's not a surprise, in the end, because bexmarilimab is an immunotherapy.
So, we also, during the dose escalation for the three dose levels, have not observed a dose-limiting toxicity. As I said, bexmarilimab in combination with azacitidine remains well tolerated in the patient populations. To summarize our update as of today, we do see very encouraging data in the patients, especially in the indications of high unmet medical need, like relapsed refractory AML and MDS patients that have failed prior HMA therapies. Again, bexmarilimab remains well tolerated in the combination setting with azacitidine, and we are particularly, yeah, encouraged also in observing these durable responses in the combination. A- and that's really, I think, something, you know, that patients derive the most benefit from.
Overall, we have observed 11 responses out of 22 patients where efficacy data is available across the three dosing cohorts. If you particularly focus on the 1 milligram per kilogram, there we have observed one response each: one is a complete remission, then a complete remission with incomplete blood recovery, and a partial remission. At the 3 milligram per kilogram, we have observed two complete remissions and one complete remission with incomplete blood recovery. At the 6 milligram, again, two complete remissions and one marrow complete remission. This is very encouraging data for us now to take forward into the phase two, where we will further evaluate the efficacy of the combination setting.
I think, the most encouraging also, this is what we hear from the investigators, is that, you know, for instance, we have one patient, actually the first patient that entered the trial, that now remained on treatment, more than 16 months and continues to play golf. This is the comment we get from the investigator. So it's really, you know, it's, it's, yeah, very interesting, also really, yeah, encouraging for us to see that there is really the potential to provide the benefit to the patients. Yeah, as I mentioned already, we will now focus to move further swiftly into the phase two, and we will focus on the MDS population that failed prior HMA therapy, as well as the relapsed refractory AML population.
We did obtain orphan drug designation from the FDA for AML. We are planning, I think, or we are putting all the pieces in place in terms of clinical and regulatory strategy to have a BLA application filing planned for 2025.
Thank you, Inka. In order to understand the severity of this condition, I wanted to show this slide. This is looking at the outcome of this MDS treatment therapies, what, and which are available at the moment. If you look at the outcome after two years, there are various treatment choices, and on the right-hand side, you can see the outcome. With all of them, which are currently used, the end result is pretty much the same. More than 90% of the patients die, and that is illustrated with these figures, blue and white ones. The only way to get rid of this condition is to have a transplantation. As you may have noticed, we already have one in our trial, which went to the transplantation procedure, which is always a good sign.
If you get a transplant, you have a 50/50 chance, is really, to continue your life. It is rather amazing that, in 2023, we have a situation that we don't have really good care of these patients, to keep them alive. Yet, if you look at this slide, especially the third bullet points, it tells you how expensive these patients actually could be for the society or for the insurance companies, because almost $1 million could be really spent in order to help the patients, and yet the outcome is this bad.... Obviously, we have been using this pharma venture report, which we ordered from a U.K.-based consultancy company, also to evaluate the market itself and pricing opportunities, and obviously, this is a very good guidance for us.
This is also meant to prepare us for possible partner interactions, which will be very heavy this fall. We have Bio-Europe, we have ESMO, and in December, the American Society of Hematology meeting, for which, by the way, we do have a poster now accepted, and obviously, around at that time, there will be further announcement of this data as well, because that will be part of that meeting. So very interesting situation, high unmet need, very high efficacy at the moment. You saw those green columns in those new patients, indicating also that they have a very fast response because all those patients came rather late to the trial.
We maybe really have a right dosing at the moment and a right population, and if that continues, we really believe that in 2025, we have a possibility to file the marketing approval application. Just looking, what happens next is really to complete the analysis, take the data to the dose escalation committee, and then make the decision how we are going to continue with the phase two. We already have phase two protocol accepted in Finland. We are expecting to get the same from the U.S., from FDA. We may announce that once that is done, and then just initiate the phase two, and maybe along that time, we will increase also the site number in the U.S., because there is a list of sites actually would like to come in.
We have been wondering why we are so popular, and the popularity is very easy to explain, very safe track, very effective in these populations where there are nothing really available, so I understand why the clinicians really would like to help. And obviously, we need to take advantage of that and expand the trial, then really move on, and then make the phase 2 recruitment really fast. And sometime, you know, maybe a year from now, or maybe even shorter time, we have the results of that. And at the same time, interact with the regulators. I mentioned FDA, but Fimea and EMA, EMA are as important for us, and then build the program that actually could go all the way to the marketing approval application.
That's very important for us, it's very important for our partner candidates, and that obviously will be something that, will be intensified after these results because they are so damn exciting. So with this, really would like to thank you for your time and listening us, and we are happy to be able to take any questions you may have. Please.
Thank you, Marco. As a reminder, to participate in the Q&A session, please type your question in the box at the bottom of your screen. Our first question from the audience: Congratulations on another set of strong data. Can you offer biological rationale that might explain higher overall response rate in MDS patients that previously failed HMA therapy?
If they failed previously, they have generated a way to get around with that kind of a burden they have on themselves. Now, when Bex comes in and we reduce the viability, it may be that they could not maintain this resistance anymore. And we have some ex vivo data to support this when we combine these components in ex vivo setting on human cells. So we believe that this synergy is actually rather important, really, to move on further. And as that is a standard of care, we actually basically have a setting really to move on with that combination, and really looking forward really to expand the process optimization part next.
Thank you. When could we expect additional details on Faron's plan to expand into pivotal phase 3 study?
I think we are getting very close. I can't say the month when we have it, but having all these discussions during the early fall and late summer, and then interactions what we have with the regulators, I believe that we have better understanding by the end of the year. But let's wait that we really get a proper alignment with the regulators, and then we can talk about more.
Thank you, Marco. Another clinical outcome question: What would Faron consider to be a positive outcome on the data readout in Q4 2024?
That's, that's actually quite an easy one.
It's very easy. So we already have quite strong data that makes us comfortable moving into phase 1. So the readout of the additional ongoing 6 patients will further strengthen this data. But also, in the same time, you know, this is a very biomarker-heavy study, so we are really analyzing the bone marrow and the peripheral blood of these patients very carefully to support, of course, the mechanism of action of bexmarilimab, and then, you know, also monitoring to potentially identify the patients, you know, that might be the best responders, let's say, you know, just to put it into context. So, you know, potentially for patient selection, but also for the timing of the treatment. So you have to take each patient, you know, with the patient history. So these patients are coming in, they have had prior therapies....
You know, and now we have to evaluate also the risk group that are coming in with the mutational status of their disease and so on. So this will all be, you know, put together comprehensively, and of course, the more patient data that we have, the stronger that data will help us also then to advance the program.
I have a feeling that the person who did this question wants to have a rather straightforward answer.
Oh.
And here it comes. We now have in HMA MDS efficacy level of 80%. I showed you a graph that the other treatments, what we are available today, it's less than 10%. That would mean that we have an eightfold increase in the outcome, in the response rate. That could really even be reduced down to 50%, and it's still remarkable result. So somewhere along there, we cannot continue the trial forever because at one point it, the P values really comparable for the historical efficacy levels will become so significant that then we are ready to really move on to the pivotal part and to the confirmatory part, and then hopefully get the approval at one point. So these results, for me, almost I found them unbelievable, but that's what they are, and we should utilize them maximally.
So we are not anticipating to have a significant size of the trial to complete this process. Definitely less than 100 patients, but would that be 60, 70, 50? I cannot really commit myself yet to say that, but maybe having additional data, then we can do it. Thank you. It's a very good question. Thank you very much.
Thank you, Marco and Inka. The next question: How is Bex differentiated from other agents currently in development in the space, specifically anti-CD47 magrolimab?
I thought that I'm not going to mention anti-CD47, but as when it was now asked, and we all know that magrolimab has some problems of taking it forward and it was put on hold. I don't know what will happen to that one. But the mode of action is completely different, and we do have evidence, which I didn't have here in my talk, that the activation pathways they activate are completely different among the microenvironment of tumor or cancer. So there is, there's really nothing in common with them. So don't eat me signal is not at all close to our mode of action. We really activate and reprogram the macrophages from the immune suppressive profile into immune activators, which then can actually activate number of other genes.
When we have looked these other genes, you find some very interesting molecules like TREM-1, MARCO, TGF-beta. So, when I saw that, I felt that, you know, gee, CLEVER-1 is the master genes for these other genes, so, and we can regulate the CLEVER-1. So that, that is very important point I wanted to say, and I'm not saying more about the anti-CD47, but I think we are in the front line at the moment with, with, with anti-CLEVER antibody.
Thank you. The next question comes and wants us to touch on the possible partnering negotiations and conversations.
They are ongoing, like I have said, and I hope that this data will stimulate them, even further. What I can say is that we have inbound discussions nowadays, and obviously that is the sign that the data has been recognized. Already after the July report, and obviously this will activate that even, even more. All those meetings, what is around in this fall, a small Bio-Europe, ASH meeting, and then J.P. Morgan, even in January, where we got the invitation already. These are the places where we can meet the new ones, but the existing ones which already have been discussing with us, those discussions will be intensified. Can't give a precise, you know, timing when...
I'm more after a good return for the shareholders than timing at this point.
The next question, on biomarkers. What biomarker data would Faron need to see to help to move BEXMAB into early lines of treatment?
That is very interesting, and with the MDS side, we already learned how we move on into combination with PD-1 blockade, and that protocol has been accepted already by, by Fimea and FDA, so we are ready actually, take that off. So would we really need additional kind of information with hematological malignancies? That's under the analysis at the moment. But having this efficacy level already with the refractory population, we may just move on into a first line. But I would think that we may want to have a partner before we do that, because then it's important also to consider what combination you may be using in that front line. And if the partner has their own product, they probably will favor that one. So let's see. That is part of the discussions, and we need to consider that along the other development.
That is a good question as well, but we are prepared also for that.
Thank you, Marco. The next question: can you expand on the significance of the blood count recovery for the patients?
That's everything. You know, if you don't have your normal blood count, you die. That's very simple, and that's the reason why these patients are getting substitutions of the blood, some of them every week, some of them are rarely, depending on the values. The blood recovery, what we have been using in the presentation, that requires certain levels of recovery. Hemoglobin, for example, 100 mg per ml, neutrophils, 1 million per ml. So that is defining that we have reactivated the bone marrow to produce cells for that individual, and that is only explained by the disappearance of these cancer blasts.
So the cancer blast is not looking the size of the tumor because tumor is liquid one, so we look at the number of the cells, and that means that if you have a 50% reduction in the blast, that is a partial remission, and then when it goes below 5, it's a complete remission.
Thank you. We've got two regulatory questions. One is, Faron got orphan drug designation for AML. Have you applied for MDS for orphan drug? And the second question-
It's in the process. It's in the process. Thank you.
The second regulatory question: how many patient, how many patients is sufficient to apply for the FDA fast track designation?
We may already have it. I don't know the precise one, because now you need to also consider the efficacy outcome. If you have a this dramatic difference on the current treatments, they will favor it and not push really the higher number of the patients. I hope that they agree with this.
We are coming close to the end of the Q&A session. As a reminder, if the audience has more questions, please feel free to type them in the box below. Our next question is: Can you discuss in more detail the safety and tolerability profile you've seen in the data up to date?
For Inka.
Sure. As I said, during the dose escalation, the endpoint is a safety evaluation to then determine a safe dose, also to move forward to take forward into the phase two. So far, between the dose levels, we have not really seen a trend of accumulating related adverse events. That means basically, the bexmarilimab is tolerated well at all of the three dose levels. That's why we have also not observed a single dose-limiting toxicity in the study. If you look at the related events for bexmarilimab, as I mentioned, they are very much in line with the MATINS data, so we observe similar events.
And then, of course, we have these immune-related adverse events that are related to bexmarilimab, and that, you know, is based on the mechanism of action of bexmarilimab by activating the immune system. In some patients, you know, that might then trigger an immune-related adverse events, and we have seen these at the 3 milligram and at the 6 milligram dose level. You know, that's the safety profile, you know, in a nutshell. Of course, we are considering, you know, to carefully, you know, keep monitoring, patients that are participating in our BEXMAB study, you know, to, basically catch early if an immune-related adverse event occurs, and then these patients will be treated. As I said, basically, these immune-related adverse events are, once you stop the drug, they basically recover. So it's, it's not...
For us, so the safety profile remains basically that bexmarilimab is well tolerated. And just one more sentence, also, the safety profile of azacitidine, of course, is well known, and if you compare our safety data to the safety profile of azacitidine, we don't see an increase in the, in the severity or in the number of adverse events that are related to azacitidine. Again, supporting this, well-tolerated treatment of the combination.
Thank you, Inka. I just want to add to here. One of the reasons why the recruitment has been so successful and fast is really due to the fact that the clinician liked this so much, as there are no additional risk or is already known among these clinicians who treat these patients. So I think it's really good way to move forward and obviously spread the word. Safe, effective drug, patients are not losing their hair. It's just marvelous.
Thank you both. Our final question: what are your plans to apply for the breakthrough status for bex?
Well, the plan is to file. But obviously, maybe some additional information, making sure that we actually get it. We are applying fast track rather soon. So this is a continuation of the discussion with the FDA and the same also in Europe. So some of the similar opportunities are on the European side as well. So moving on with those, and then those are really part of these activities because the trial itself moves on now really nicely. Thank you again, Inka.
Thanks.
The audience, good questions. Keep watching us. New news will arrive. Can't tell, but they will arrive. Thank you.