Faron Pharmaceuticals Oy (FARN) Earnings Call Transcript & Summary

Welcome, everybody, to the Faron ASH Data Release Webcast. Early morning here in San Diego, but it gives us great pleasure to bring you the latest results, which were presented last night here at ASH in San Diego. Here with me today is our Chief Medical Officer, Petri Bono.

Hello, and good morning to everyone. 6:00 a.m. Pacific Standard Time, but very delighted to be here and tell about the results today.

And a beautiful day ahead. So let's go to the next slide, the agenda page, just opening remarks on my behalf, then I'll let Petri take you through the data that was presented and I'll be going through the other stuff we've seen here and some of the competitive landscape and future outlooks. So to the future outlooks, if we go to the next slide, standard disclaimer, but we will be making forward-looking statements. But over to you, Petri, on the data.

Thank you, Juho, and greetings really from us, and this is the largest ASH ever with 30,000 participants. And yesterday, PI of the BEXMAB study Dr. Mika Kontro presented the data. And here is the overview of what kind of patients were treated and what's the newest safety data. But before going into this, so just as a reminder that what we presented these 20 patients, these are MDS patients with relapsed or AZA refractory disease, difficult to treat patients with a very high unmet need. In the BEXMAB trial, we also have had relapsed AML patients and we have also frontline MDS patients. But at the end of July, when the abstract was submitted to ASCO. So the abstract included the r/r MDS patient population. And today, in the latest results, we have all the consecutive patients that have been treated in r/r MDS and that have at least 1 response evaluation available. And the data cutoff for this was as late as November '25, so that we could have 20 patients. And I want to remind you that the full end of Phase II data will include 35 r/r MDS patients. So over half of the patients, their efficacy results are already here. There are many more patients who are currently on treatment and of course, the full data will come in the stream. But then what kind of patients? On the left side here, the baseline characteristics, median age 72.5 years, a typical age for this quite elderly population. And then about the performance status, how fit the patients are? So 65% were performance status, one, meaning that these are also sick patients. These are not patients without symptoms. Then there's some international risk classification in the trial only patients with high-risk MDS were included. And out of this, we can actually see that 50% of the patients or 10 patients were very high-risk patients. And it's important when we report the results that also the risk classes are openly told because in various trials, the risk profile of the patients, so they differ. And about the mutations, the 2 most common mutations are shown here, TP53, which is a sign of an aggressive MDS. So 45% of the patients had TP53 mutation in the mutational analysis. And then how much pretreatment patients had received. So we can see here that 50% of the patients were actually not enrolled to the study after one line of azacitidine or HMA hypomethylating agent containing therapy, but many were at least 2 lines of therapy. And of interest, especially since in U.S., a lot of patients are also treated with HMA plus venetoclax. So 40% of the patients were also pretreated with the combination before entering the trial. And we have some patients, 15% of the patients who have received AZA plus immune therapy, meaning AZA plus PD-1 inhibitor or AZA plus CTLA-4 in their previous lines of treatment. Then about the safety. The latest safety data on the right side of the slide, if safety remains very good. BEX is very well tolerated. On the lower part of the right figure, you can see that bexmarilimab-related adverse events, 35% of the patients had BEX related adverse events, which is really low number. Typically, from the treatment, almost all patients over 90% or almost 100% received adverse events, and this can be also seen in the treatment-emergent adverse events row. So 95% of the patients also had a treatment emergent adverse events, meaning that a majority of them were coming from azacitidine. And then about the BEX related adverse events, those 35% of patients or 7 patients, what kind of adverse events there, where they were all Grade 1 or 2. So there were no Grade 3 or higher adverse events that were related to bexmarilimab treatment, meaning that the safety profile is excellent, also, meaning that what we've seen here, BEX is an ideal partner to combine with other agents, including not just azacitidine but also if we think beyond hematology, also together with PD-1 inhibitors or with chemo. Next slide, please. And here is the swim lane of the efficacy. The most important piece of data or a single number is the overall response rate that is 80% in this trial. We have also put all the different dosings there that are 1 or 3 or 6 milligrams per kilo. We have not made a statistical comparison between the different dosing. But at the moment, by my eye, which is not a formal statistical analysis since we are not at the full package yet -- the efficacy package yet, there doesn't seem to be major differences between the doses and the safety and outcome efficacy. In the middle, you can see there in the blue, the split out of the responses, what kind of responses were observed. Before going to those numbers, so the highest row or lane. So that's a patient who has been on treatment already 2.5 years and tolerates the treatment very well, meaning that also very long treatments are possible with BEX plus azacitidine. So CR, complete response in 5% of the patients, partial remission and 15% of the patients and marrow CR in 50% of the patients. And then 10% had hematological improvement as the best response. And then 15% had stable disease as best response and 5% progressive disease as their best response. Of note, out of these marrow CR patients, so it's of interest that how many of these patients actually had hematological improvement although it was not shown in the poster, so we have done subanalysis and 60% of the marrow CR patients, they also got hematological improvement. And then when we go to other subgroups. So the TP53 aggressive patients about their overall response rate, this is a question that has been asked yesterday many, many times for Mika Kontro. So the response rate is 56% among the TP53 mutants. Then the HMA pretreated patients that were those 40% of the 20 patients. So the overall response is there also very, very encouraging 63%. And of all the patients, 20% or 4 patients were able to move forward to stem cell transplantation, which is an excellent result. And it's shown here by the black dots, meaning that the end reason for the BEX treatment in the trial was the stem cell transplantation, which is the only curative treatment available for the patients. But it's good to remember that it's not always easy to find a suitable donor for that and then another one. Many of these patients are so fragile that although the efficacy would be good enough from the treatment to continue to stem cell transplantation, their performance status is too low so that cannot be done. But they tolerate this treatment well and can continue, of course, when they get a response. And then also about the overall survival. We don't have a Kaplan-Meier estimate of the survival curve in this presentation. But we have updated the numbers since October also, and it remains unchanged, 407 days or 13.4 months, which is a lot more than traditionally these patients survive it's something between 4 to 6 months, the overall survival in different studies for r/r MDS patients. Next slide, please. Then if we have a look at the waterfall plot. So we can see that over 50% of the patients, they have over 50% reduction in the bone marrow blast number on average when compared to the baseline. And this waterfall plot is shown here. And as you can see, majority of the patients, their blast numbers are getting reduced while on the treatment. And as a reminder, they have received combo AZA plus BEX but they were AZA refractory and resistant that was an inclusion criteria to the trial. So if they would continue just with the single agent AZA, the predicted response rate should be 0% or 2%. So we can really anticipate that this is coming fully from the addition of BEX to the treatment that can be seen here in the waterfall plot. On a general level, so the blast count is a key indicator of disease severity and these higher levels are associated with an increased risk of disease progression and progression into AML and the reduction of what we see here. So it not only slows the disease progression but also, of course, improves the patient prognosis and importantly, also the quality of life. And it was not yet presented, but we are working to get from the data. The exact number will be reported in future scientific meetings but noteworthy proportion of patients also became transfusion independent while on the BEXMAB trial but for those details, we will present that in later scientific meetings to come. Then on the left side of the figure, these 2 patients mark with an asterisk there, so who are having increase in the blast number while on treatment, meaning that they were not responding to the treatment. So their relative dose intensity was low, they received only one cycle of treatment in the trial and due to BEX unrelated adverse events had to interrupt the treatment, and that's likely to be one of the reasons why they didn't have a good response to the treatment. Next slide, please. And about nonclinical findings, 2 slides. The first one here that supports the data. On the left side, we can see HLA-DR expression on bone marrow monocytes and blasts and we see at the end of cycle 1, an increase in the HLA expression on monocyte and the exact number is 189%. It's a very good number, meaning that we can improve the antigen presentation by the BEX treatment. Then importantly, also, when we think about the mechanism of action of BEX is that can we see an increase in the number of CD8+ T cells in the biopsies and there, we can see that a cycle -- at the end of cycle one there's a 63% increase on average in the number of infiltrating T-cell amount, which is also nicely showing that also on a translational study, we can show support for the mechanism of action that, of course, we see as an end result as a clinical response to the patients. Altogether, these 2 figures such as enhanced immune activation and antitumor response in these patients and add to the rationale for this treatment to modulate to a microenvironment and to improve the disease control. And as you may remember, so in MDS, so it's a dual mode of action we are hitting the tumor microenvironment, but also at the same time directly sensitizing the blast cells back to azacitidine since the blast cells are basically all positive for CLEVER-1 expression and therefore, we have a direct effect with the antibody, although on their sensitivity to the treatment. Next slide, please. And then another piece of nonclinical data, this is -- starts to be a bit more scientific but what we were able to show here is that we can identify sensitive blast cells for the treatment and that's important. And the other issue about this that CLEVER-1 is expressed in all 3 bone marrow myeloid populations and which can be seen by the red, green and blue color in the upper left corner figure. And if we go and then to the left lower level, which is showing the CLEVER-1 mRNA expression per cycle among those populations. So the red spots there, so they remain basically fairly unchanged during the treatment cycles, meaning that we don't see any change in the expression of CLEVER-1 mRNA during the treatment, which is important. There might be an effect with the antibody that it would down regulate significantly CLEVER-1 expression on the blast, but that doesn't seem to happen. The expression remains their constant. Then in the middle, there are 3 different clusters of the upper left corner. And if we go to the lowest part, that is the monocyte macrophage cluster. So what is shown there is that it's actually here where we can see the difference in the intensity of the dots meaning that it's actually these macrophages that are responding to the BEX treatment in this analysis. There are 2 other myelocyte precursors and the blasts shown above the Moma figure. So there is fairly -- especially in the blasts, so it's not that large the change in the expression, but in the monocyte macrophage cluster, we can see that change really highlighting that they are the cell types responding to BEX treatment. Next slide, please. Then the key conclusion with this very exciting and encouraging latest data, as shown here, objective response rate in 80% of the patients treated with BEX plus AZA, 55% of the patients had over 50% reduction in bone marrow blast count. CR/PR, marrow CR in 70% of the patients, 63% in veneto-HMA pretreated and median survival long 13.4 months, and 20% of the patients were received a stem cell transplant after the treatment highlighting the potential long-term benefit and impact on overall survival of the patients. Majority of the patients also had hematological improvements and 60% of the marrow CR patients had the hematological improvement. This further highlights the differentiated biology and benefits related BEX compared to myelosuppressive and cytotoxic drugs. About the safety, very well tolerated across all the doses in this trial with the 3 different dose levels. No dose limiting toxicity issues and BEX continues to show a highly favorable risk/benefit ratio. And in my opinion, about all the results that I have seen so far at ASH either oral presentation or poster presentations, we have the best or most favorable risk-benefit ratio of any trials that have been reported here. So it looks very good at the moment for the BEX with these results with the treatment that is so well tolerated also. Then about the translational highlights, there's about that what kind of blasts which features, which changes in the gene expression we can see there. But we've been able to identify the sensitive blast and we now know one of the changes that are impairing mine cells. Energy production and from other translational highlight is that we can really promote the immune activation evidenced by increased antigen presentation measured by HLA-DR expression on blasts and monocytes and then in the -- by the enhanced CD8+ T cell density in the biopsies. And then the enhanced bone marrow macrophage proinflammatory phenotype, so it supports our dual mechanism of action in hematological malignancies and the CLEVER expression is linked to treatment response, which reduced malignance blasts and immune cells. And next slide, please. And then if we move forward to regulatory updates that where we're going at the moment, so just as an update here so that the trial, the enrollment is going well. We have also just recently told that, we have 2 sites in U.K. that have been added to the BEXMAB trial. We have still all the old sites open, 4 sites in Finland, 4 sites in U.S. And especially during the fall, U.S. has been very active in enrolling patients. And of course, I want to thank all the U.S. principal investigators at the sites for their efforts with the trial and enrolling patients for this trial. The next data readout, so that will be at the end of March '25, and this will be the end of phase -- basis for the end of Phase II package. And then we have made a decision that we will enlarge the trial that we will start enrolling also CML patients that will be the trial to gather more data also in this malignancy. These patients, they all also expressed very highly CLEVER-1, the target of bexmarilimab and therefore, it makes sense to enroll them, too. It doesn't require any amendment to the protocol. It's already prohibiting in the current version of the protocol. And after the enrollment is full in the r/r and frontline MDS, we will then open the CMML patients. So the patients from this 10 participating sites in U.S., U.K. and Finland will be able to enter the trial. In addition to the engagement with FDA, so of course, we are planning to bring the results to EMA and the U.K. authorities prior to potential long-term benefits and then we have partnered with U.S. MDS Foundation have met them also here to enhance patient and physician engagement and then we are already in the preparation of the MDS Phase III trial. And of course, that will be a major issue in 2025 to get prepared to the trial that we are planning with the combination of azacitidine and BEX in the frontline patients in a Phase III study. And I think the next slide, please. And then about these regulatory designations, very important. We received in August, FDA Fast Track designation, very good external -- sign of an external analysis an impact of the treatment for patients, which accelerates the development and review process and then most recently, we have also received a green light from U.K. and we have MHRA Innovation Passport designation that was granted I think, 2, 1.5 weeks ago. And this -- in U.K., this provides early engagement also with the U.S. regulators to optimize the clinical development and offers also a tool like rolling review in U.K. too. And of course, for BEX, about the overall implications, so this recognize the potential as a potential transformative therapy for these patients, which are in very high medical need for novel treatments. These are desperate patients. They die fast without proper treatment after AZA and of course, these designations, so they enhance global regulatory alignment and accelerate the time lines for our communications. I think this was the last slide for my part. And as a summary, so brilliant results presented here with 20 r/r MDS patients, top notch benefit risk ratio, top notch efficacy. And of course, we are really excited to continue enrollment and to get prepared for the full Phase II readout in the spring. So thank you very much, and I give over the word to Juho.

Thank you, Petri. As Petri said, I can say that this is the best data set out there for this very hard-to-treat population. But we also thought will bring to you what else have we seen here. And with this slide, I want to bring you that before going into the data that we've seen here from other agents just want to highlight the importance of the risk/benefit ratio. In other words, the safety and efficacy is key for approving any drug and the commercial uptake, the willingness to prescribe a drug from a physician. There is a first bullet there, an investigator initiated trial running in MD Anderson with bispecific T cell engager, glofitamab in relapse refractory MDS 16 patients were reported. Objective response rate was 56%, 0% CRs and PRs, so majority being MCR, but a pretty low number of hematogical improvement, median overall survival, 10.3 months, treatment-related adverse events, 68%. So pretty high treatment-related adverse events. And this drug actually was previously discontinued by the actual developing companies and currently the IIT in MD Anderson was done with reduced dosing and it's been better tolerated that way. Then if we move to -- if we can call it our main competitor, VEN/AZA also reported latest data in relapsed refractory MDS, 32 patients treated, objective response rate, 48%, basically on MCRs, 12% moved out to transplant, median overall survival 7 months. Everybody is waiting for the Phase III frontline study named VERONA. It's been postponed. Another development is that they've actually changed their primary endpoint from CR to median overall survival, which can mean a lot of things, and I can't speculate too much about it. But have to say that in the Phase II data, the CR rate was around 30% when it could be 20% for AZA alone and from the Phase II data, you couldn't really get out a clear survival benefit. And with the AZA/VEN combination, treatment-related adverse ment over 90% often severe and even leading to death. So whenever thinking of a drug, it's just not about the efficacy, it's also about the safety and what we've heard a lot here at ASH for MDS, especially high-risk MDS. It's also a lot about the hematological improvement the drug can bring. So last bullet their, RYTELO, a recent approval based on a Phase III study in the low-risk population. It's telomerase inhibitor, basically the results in a nutshell, no remissions, but 40%, we're able to achieve transfusion independence from getting red blood cells. And as Petri mentioned, we, even in a very much harder to treat population achieve a significant amount of transfusion independence. So that's pretty much the wrap up. So if we go to the next slide. The data is looking amazing and nothing really out there for the relapsed refractory population. We will be pushing the envelope towards the FDA to see that when should patients actually be getting this drug because for us and a lot of doctors here, it looks that it may be a game changer for this population. Especially with the hematological improvement and the blast reductions and the safety profile we see. So a very action-packed year ahead of us will have, as Petri mentioned, in January, both frontline and relapsing factory enrollment completed around end of March, the response rate readout, yes, we will be going for breakthrough designation for the relapsed refractory population. We will be going to an end of Phase II meeting that would then kick off the Phase III development and as the duration of response data, the survival data and all that, which is pending good constantly for this relapsing/refactory, we will be approaching the FDA on when should these patients be allowed to go to a treatment and not wait for a frontline Phase III to start and give us some more data. So very exciting year ahead of us. That's all from us from San Diego. Wishing you a lovely evening to Europe and an amazing start to the day here. Thank you, everybody.

Thank you.