Good morning and good afternoon. Welcome to the Faron Pharmaceuticals webcast, coming to you live from ASCO, the annual meeting, one of the biggest oncology meetings in Chicago. Very excited to have you all with us today. Our presenters are going to be Dr. Juho Jalkanen, the CEO of Faron Pharmaceuticals; Dr. Amer Zeidan, who is the Professor of Medicine and Chief of Hematologic Malignancies at Yale School of Medicine and the Yale Cancer Center; and he will be our lead presenter, walking you through our data today. You'll see his disclosures there, as well as Dr. Petri Bono, who is the Chief Medical Officer for Faron Pharmaceuticals. We're excited to turn it over to Juho to walk you through the agenda. Please remember, there will be a Q&A at the end, as we usually do. Along the way, please submit your questions.
We will curate those, group them together, and ask them live at the end and have a discussion. Over to Juho.
Thank you, Julie. Super excited to be here and reporting on the phase two results out here at ASCO. I see it's been an amazing ASCO so far, still continuing. Want to go through the agenda today because key points here on today's agenda is going to be we are reporting for the first time also with the new 2023 criteria. How do the results look and what implications does it have further in our development? That's a key part of the data today. Professor Zeidan will be taking you through all that. It's super exciting. On to the next slide. I know in the audience, there's a lot of people who have followed us for a long time and have been waiting for this moment. Here it is.
This is a huge milestone for us as a company and possibly for high-risk MDS patients, bringing new hope to patients and their caregivers. Since there's also, I know, a lot of new people coming into the story, possibly hearing this for the first time. Just to recap, bexmarilimab, which we call b ex, is a first-in-class antibody. Now Phase 2 results out, both in last-line relapsed/ refractory MDS and first-line high-risk MDS. For us as a company, building up to this moment, and for a lot of our followers, the last-line Phase 2 data, since it's an open-label trial, has been looking good. For us, even for the first time, we're seeing the front-line data. We've been waiting that eagerly, and it looks also very good and supports our efforts and development plan already laid out by the FDA.
It looks like we're going to be tackling one of the deadliest cancers on the planet. We have very positive feedback from regulatory agencies recently: fast track or funds, possibility for accelerated approval. Next, we're going to go for prime and breakthrough, laser-focused on our mission to bring this to patients in MDS. Again, need to highlight that this is highly applicable in a number of cancers where macrophages are the source of treatment resistance. On to the next slide. Here, I will be handing over to Professor Zeidan, taking you through the landscape of MDS and what do we bring to the table with bex. Over to you, Professor Zeidan.
Yeah, thank you so much, Juho, and it's a pleasure to be here with you today speaking from Chicago, where we are seeing some of, I think, amazing developments in the general field of oncology. I think we are pleased about the progress we are seeing in MDS in particular. This is, I think, what we are going to be talking about today. A quick reminder that I'm speaking in my personal capacity, and I have consulted for Faron. Next slide, please. MDS basically is actually a form of cancer, as you just heard. Myelodysplastic syndromes or neoplasms, as the WHO have clearly renamed them to clearly reflect their malignant nature, are characterized by bone marrow failure, where the bone marrow, which produces the normal red blood cells, white blood cells, and platelets, becomes dysfunctional.
That leads to complications of infection, bleeding, as well as anemia. Ultimately, a significant number of those patients could develop into a more aggressive form, like acute myeloid leukemia. All of that will culminate in worsening survival of patients, especially in patients who have the more aggressive forms, what we call high-risk MDS, as well as impaired quality of life and increased health system costs from repeated visits and exposure to the health system. Next, please. This is a representation of the outcomes of MDS. I think this is important to show because MDS can happen on a spectrum. The patients who are, you can see in the lighter colors, are the patients who have the more advanced stages of MDS, what we call high-risk MDS. Those patients actually can have a survival of less than a year without treatment.
With the currently available treatments, which is azacitidine for high-risk MDS, the median survival can be somewhere between one and a half to two years. Some improvement, but clearly not applies to all patients. Most patients will progress at one point unless they go to bone marrow transplant. Now, bone marrow transplant is the only way to cure MDS, but it's applicable to less than 5%-10% of patients because MDS primarily happens in patients in their 70s, as you will see from our clinical data. Therefore, most patients are not able to have the potentially curative treatment, and they are therefore treated with hypomodulating agents. Once these drugs stop working, the median survival is somewhere between four to six months, again, reflecting how aggressive the disease can be in its higher-risk forms. Next, please.
You know, we have seen tremendous development and progress in oncology in general. In MDS, unfortunately, despite the increased understanding of the genetics and biology of MDS, we have not seen the same degree of therapeutic progress that we have seen in other cancers, especially in the high-risk forms. This schema that you can see here, which largely represents what happens in most developed countries for patients with high-risk MDS, has not really changed significantly in the last 15 to 20 years, where the standard treatment, as I mentioned, in the 5%-10% of patients who are eligible to transplant, is to go to transplant. For the vast majority of the other patients, around 90%, the treatment would be hypomethylating agents. Azacitidine is the most widely approved drug. Some other countries, like the U.S., also have decitabine and an oral version of decitabine.
In the 5% of patients who have an IDH1 mutation, there is an approved drug, an IDH1 inhibitor called ivosidenib in the US. This is very limited to a small percentage of patients who have these particular mutations. Treatment clearly is of limited success, and we need better options. Next, please. In the refractory lab setting, once those hypomethylating agents, especially azacitidine, stop working, it is even a worse situation because there are no approved treatments in this setting outside of the IDH1 inhibitor, which again is only applicable to 3%-5% of patients. The other patients, there are no approved treatments. We try to put them on clinical trials. Sometimes we try to give them other chemos like cytarabine or other forms of drugs, venetoclax, for example, as an off-label use.
Clearly, those patients are of very high unmet need and clearly of needing new therapies. Next, please. I think there has been an increased understanding in terms of how the response criteria should apply to the patients in what I would call patient-centric fashion, meaning that the response criteria should reflect a benefit that the patient can feel at their level. These response criteria, you can see, have evolved over years between the initial publication in 2000. The 2006 criteria have been used for a long time. In 2023, through a large consensus process from a large number of experts in the field, those have been revised.
The emphasis on these criteria has been to focus on blood count recovery, meaning that, as I mentioned at the beginning, having low blood counts, thrombocytopenia, neutropenia, and anemia is one of the biggest problems that we have in MDS and what leads to a lot of the complications. While it is important to reduce the number of the cancer cells, the blasts, what we call blast reduction, it is also important to get recovery of the good cells because those are the ones who are going to prevent the bleeding, prevent the infection, improve the anemia. This is why we introduced, in addition to what we call complete response, responses where there is some count recovery, but not to the full effect, what we call CRh and CRL, which is complete response with partial count recovery or limited count recovery.
Here, I would highlight in acute myeloid leukemia, complete response with partial count recovery has been actually already used to approve drugs in the AML space, again, reflecting that these are clinical benefits by themselves to be transfusion independent and reduce the risk of infection. Next, please. These response criteria have been validated in a number of settings now. This is a large Austrian database that was presented in EHA last year, which shows very nicely that the patients who achieve either overall response rate or composite CR, you can see that they have better survival than those who do not achieve these responses, but also that there is a nice correlation between the type of response, the CR, CR by lineage, you know, lineage, CRh, et cetera, and with the expected survival of the patient.
I think these criteria are clearly making their way to become, I think, the most widely used criteria going forward. Next, please. Now moving to bexmarilimab, which I will call bex for easy pronunciation. Next, please. You heard already about Clever-1. What is Clever-1? Clever-1 is a large glycoprotein. It's a transmembrane protein. It's a scavenger receptor. It removes debris and bacteria and cancer cells basically from the tumor. It has been shown to be expressed on the surface of immunosuppressive macrophages. High expression of this receptor has been associated with an immunosuppressive phenotype of those macrophages, and therefore, they are not as functional as they should be. That actually has been associated with increased expression of Clever-1 with occurrence of cancer, as well as in other immunosuppressed states such as pregnancy.
Among patients with cancer, high Clever-1 expression has been associated with worse outcomes, as well as resistance to therapies, including immunotherapy. This receptor is involved in endocytosis and intracellular sorting. I think what is kind of neat about this is that it is not only related to the macrophages, which are part of the innate immune system, but also it relates to antigen presentation, as well as activating the adaptive immune system through the T cells. It is really, I think, a central receptor that is involved in many processes, and targeting it became, I think, a very rational way of going after malignancies, as we will discuss in the next few slides. Next, please. This is more about Clever-1. Kind of covered most of this data already.
The development of bexmarilimab, or bex, has been, I think, focused on trying to inhibit this receptor and has been associated with activation of these macrophages and converting them to the pro-inflammatory phenotype that is associated with tumor killing. There is actually some data suggesting that interfering with this receptor, Clever-1, which also is potentially present on some of the myeloid blasts, can interfere with the fitness and the energy production. I think this is an intriguing aspect that needs further analysis, but it could also point to potentially multiple mechanisms of action. Next, please. As we kind of alluded earlier, Clever-1 is highly expressed in cancers, especially in cancers which are resistant to treatment.
I think what is particularly interesting for our discussion today is that the expression in some of the aggressive hematologic malignancies, such as acute myeloid leukemia and MDS, is actually higher, as you can see here in red. Red is high expression. You can see acute myeloid leukemia, as well as MDS, as well as other forms of leukemias. In blue, you can see some of the normal myeloid cells where there is low expression. Next, please. This is some data from the ongoing study that we kind of will discuss later during the presentation. We are seeing pharmacodynamic evidence of activity of using bex in patients with MDS. This is from the refractory labs MDS part of the study.
What you are seeing here is that it is still early data with short follow-up, but it appears that the Clever-1 expression at the level of the bone marrow monocytes seems to correlate with the responses that we have seen within the trial, which is always very nice to have a biomarker potentially that can help you in guiding your treatment. We are also seeing evidence of immune activation by increasing the number of the monocytes, as well as the adaptive immune system on therapy, such as an increase in the number of CD8 T cells. Next, please. Now we are going to review some of the data that were presented. I presented some of the data in the MDS Foundation meeting last month. Some data were presented in ASCO.
Additional data will be presented later, actually, in our early part of June during the European Hematology Association. What you are going to see now is a combination of some of these different data sets. Next, please. This is a study design. This was, I think, designed in a way to kind of make the drug development as efficient as possible. It included a number of patient populations, including patients with myelodysplastic syndrome who have hypomethylating agent failure, which we mentioned is a very challenging situation, as well as refractory acute myeloid leukemia patients, as well as patients with newly diagnosed MDS who are higher-risk disease. In the dose escalation part of the study, the phase one, basically patients receive bex with azacitidine.
All of those patients received a combination of bex with the standard of care drug, which is azacitidine, in the frontline setting, as well as in the refractory labs setting. The Phase 1 was a dose escalation that tested three dose levels, 1 mg, 3 mg, and 6 mg. Phase 2 tried to do what we call dose optimization, trying to select the dose that would be most relevant for subsequent development. You can see here how we focus on two dose levels, the 3 mg and the 6 mg, and each one of those enrolled somewhere between 13- 16 patients, as we will talk about in a Simon's stage 2 design. Next, please. Next slide. These are the baseline characteristics. I'm going to show you two different sets here, right? The first one is the frontline diagnosed patients.
This is a relatively shorter cut because those patients were enrolled relatively later in the study, so you are not going to see as mature survival data like the relapsed/ refractory patients. Here you can see 21 patients who were treated. You can see that the age, there was a typical age, which was 72 years old, which, as I mentioned, patients with MDS typically have an age in the 70s. That is very representative of what we see in the real-life setting. You can see that most of them have advanced disease, high or very high risk by the IPSS-R, as well as increase in their blast count. Importantly, we did not talk much about this at the beginning, but many of those patients had TP53 mutations, which have been shown to be one of the worst actors in patients with MDS and AML.
Those patients tend to do very poorly. There is a tendency to over-enroll them on clinical trials. What you can see here is that both actually in this cohort, as well as the relapsed/ refractory cohort, there were a significant number of patients with TP53 mutations. Next, please. This is the refractory relapsed cohort. Here we have 32 patients in addition to the 21 patients in the frontline. Similar characteristics, you can see the age is actually a little bit older here, 74. Advanced disease, again, all of these patients have received at least hypomethylating agents. Some of them have received more than one previous line of therapy, including venetoclax. Those are patients who have received kind of all the existing standard of care drugs. Next, please.
I think one interesting kind of quick observation is the fact that the drug, which we already have seen this in the dose escalation part of the study, and now we are showing the data across the dose escalation and the dose expansion, that most patients have, I think, tolerated the drug quite well. Safety was, I think, a good thing because remember, again, these are older patients, generally frail, so you cannot give them treatments that are very kind of tough. You can see that there is a high incidence of blood counts suppression, but this is very common in MDS and AML trials because the disease itself is associated with low blood counts, as well as febrile neutropenia.
When you look specifically at bex -related adverse events that were attributed by the investigators to the drug itself, you can see that most of them were Grade 1 and Grade 2, while Grade 3 and 4 were rare. The rate of discontinuation generally on the study was low, 13%, but discontinuation from any bex-related adverse events was only 2%. Importantly, there were no Grade 5, there were no bex-related basically mortality that were attributed to bex by the investigators. You can see here that the other side effects were primarily focused on low blood counts and generally were manageable, which is pretty standard in kind of when we work with patients with MDS. Next, please. This is a safety profile, again, across the entire cohort, the 53 patients in the dose expansion, as well as the dose escalation.
You can see here similar trends of kind of the tolerable safety. Here the focus is to show, I think one of the important kind of conclusions from the work so far is the choice of the dose, which we have chosen to kind of proceed with further development, which is 3 mg per kg, which offers the best balance between efficacy and safety. That is based on the similar efficacy between the 3 mg and the 6 mg. We will talk about efficacy in the next few slides. On the safety front, it appears there were more side effects with the 6 mg, including three deaths that happened on the higher dose, but they were again not called related to bex in this particular setting. Next, please. Here you can look at the safety—oh, sorry, at the efficacy data.
I know this can get confusing because you are seeing efficacy noted in two different formats, one by the 2006 criteria and one by the 2023 criteria. Just as a quick reminder, because this is important, the focus of the 2023 criteria is not only on reducing the blast count, but also to have some meaningful recovery of the blood counts. What you can see here, looking at the 2006 criteria, is that the overall response rate among the 18 evaluable patients—so out of the 21 patients, 18 of them had been evaluable at the data cut of April 25th. The overall response rate was 72%. By the 2023 criteria, it was 67%. The composite CR, which looks at CR equivalent and CR with limited and partial count recovery, was 56% of the cohort, which again, I think, is promising data. Next, please.
Here in the refractory lab setting, which again, remember, those are patients who are sicker. They have already seen hypomethylating agents and progressed on them. You would generally not expect much activity in the setting. Remember, there are no approved drugs in this setting. We generally do clinical trials or venetoclax. Any kind of responses in this setting actually is considered meaningful. You can see here by both criteria, we observed, I think, a good number of responses. The overall response rate in the 2006 criteria was 63%. The 2023 criteria was 47%. The composite CR—so we had patients actually who achieved CRs and CR with limited count recovery, which again, I think, is quite nice in the refractory relapse setting. I would note in both cohorts, refractory labs and frontline, again, there were a lot of patients who had TP53 mutations, around 40%.
Again, remember, those are patients who generally do very poorly with all existing treatments. Next, please. Overall survival, here we have the more mature data from the refractory labs cohort, where you can see the median overall survival is around 13 months on these patients. I mentioned at the beginning, historically, the overall survival after HMA failure was around six months. Maybe some of the more recent data suggested eight to nine months. To see 13 months, I think, is quite encouraging. Also among patients who have TP53, the ones who have, again, the worst outcomes, the median survival was around nine months. I think this is encouraging. Relatively small sample size, but I think everything is trending the right way, including bridging some patients to transplant, which, remember, is the only way you can cure this disease.
Whenever we have the chance to get someone to transplant, we try to do it. Next, please. Here you can see separation of the survival for the refractory MDS patients according to the dose levels. You can see clearly in blue line is that the 3 mg bex dose seems better than the 6 mg. Again, this supports the decision of why we decided to go with the 3 mg dose going forward as the best combination of optimal efficacy while trying to reduce the rate of complications because one of the, I think, important principles in treating patients with MDS is to try to avoid early discontinuation when you give drugs that are leading to a lot of side effects and the patients have to discontinue relatively quickly in the trial. This has been a problem in some of the previous Phase 3 trials.
Also, even the long-term administration of the drug is important. For that, you really need to have the most tolerable dose so that the patient can continue receiving that for treatment because in this setting, we treat patients until progression. The patient is on treatment for the rest of their lives as long as they are responding, as long as they are not having an acceptable toxicity. Clearly, if they do not go to transplant, which most patients will not be going at this point. Next, please. Here showing kind of some just for reference, some comparison to some of the existing drugs that are being tested. Clearly, there are not many great drugs in the refractory lab setting. Venetoclax is one drug that is approved in AML and used off-label in the refractory lab setting in the U.S. and other countries.
Of course, there's interest also in venetoclax in the frontline setting, and we are waiting the results of this trial as well. In the refractory lab setting, you can see here clearly that on most indicators, we are seeing relatively comparable or even better activity with bex and aza, including the overall response rate, the median survival, as well as safety profile. Remember, venetoclax is very myelosuppressive. It lowers the blood counts. I think one of the problems when using it is to strike the balance between reducing the blast and allowing the blood counts to recover, which does not seem to be a big problem right now with bex. I think that could be an advantage for bex. Next, please.
I think in conclusion, we are seeing so far from the 53 patients that we have data on for the last data cut-off, including the presentations, the MDS Foundation, ASCO, and the upcoming presentation, EHA, that the data coming together suggests that bex is well tolerated. Generally, the side effects are what you expect in patients with MDS in general, focusing on blood count suppressions. We're not seeing significant infusion reactions or high-grade immune-related side effects, which are things that we think about always for immune checkpoint treatments. The patients are able to stay on treatment. The early efficacy data in terms of responses and overall survival is encouraging both in the refractory and the frontline setting.
I think putting all this data together provides a strong rationale to move to kind of registration intent studies, including hopefully a pivotal Phase 3 trial using the optimal dose that has been selected, which is the 3 mg per kilogram. I will have Dr. Bono talk about the subsequent steps in the drug development process. Thank you.
Thank you, Professor Zeidan. Could we get the next slide, please? The clinical path forward, the clinical development of bex in MDS. Some of you may remember that actually we had a Type D meeting with FDA last summer. When we got the minutes from that, actually they suggested that we should follow the Project FrontRunner that FDA has launched in 2023. Just a quick reminder, what is this FrontRunner?
It's an initiative to transform the evaluation of cancer drugs in earlier lines of therapy rather than doing the traditional way to go into really late-stage settings and patients. It is really aiming to enhance the patient access to new innovative treatments and then also to strengthen the evidence and quality of the data and, of course, to accelerate also the drug development path forward. What does this then mean actually to us? What did they say to us last year? They said that don't go to r/r MDS to a randomized study there, but rather go to the frontline according to the FrontRunner guidance. There actually one single Phase 3 would be enough for both frontline and r/r high-risk MDS approvals.
No need for separate Phase 3 for relapsed/ refractory MDS and no need for separate Phase 2 for frontline high-risk MDS, which means that the development cost and also time required for the approval will be faster and would allow patient access also faster to this treatment. Next slide, please. We are actually on track exactly what FDA told us last year. They said that do and treat more frontline patients, treatment naive patients, then do a dose optimization part to randomize patients between the recommended Phase 2 dose and the recommended Phase 2 dose minus one, which were the 6 mg and 3 mg per kg doses. That is exactly what we have done. Now we have the results in our hands. Based on the results, we are now moving forward to the FDA end of Phase 2 meeting.
What we're going to do there is that we're going to propose, first of all, we're going to tell all the detailed results. We're going to tell also all the data we have from the drug behavior, including receptor occupancy, pharmacokinetic data, pharmacodynamic data, PK modeling data. We're going to then also go through the proposed study design, discuss that with the agency. The study design in big picture is shown here. We're going to propose a very classical randomized placebo-controlled double-blind Phase 3 trial to compare bex 3 mg per kilo plus aza according to standard of care versus placebo plus aza. It's worth also mentioning that with the safety profile of bex, it's possible to do also a true placebo-controlled trial and not an over-label trial, which will be a strength in the Phase 3 trial setting.
The first interim analysis, so that's after 164 patients. The total study size would be 428 patients. We are going to discuss with FDA the primary endpoint and also the difference and power calculations, what's required to show the benefit of bex. The primary endpoint, as Professor Zeidan mentioned, which is strong in our data, is the composite CR. We will discuss that with FDA. We believe that we can show an increase from the 25% with single-agent aza to 50% with bex plus aza. The final analysis of the trial, so that will be for the overall survival. That is also then the confirmatory part for the possible accelerated approval that in the Type D meeting, FDA suggested for us.
They told that if we see in the interim analysis a difference favoring bex addition to aza, that would then trigger the accelerated approval for r/r MDS, but also perhaps also to the frontline setting. These all we're going to discuss with FDA in the upcoming meeting. Of course, we as a company are very much looking forward to that and working hard to get that meeting by end of summer completed and also the minutes probably end of sometime in August. This was the overall design of the phase three study. We do have, of course, exact power calculations. We do have exact alpha values. We do have adaptable design also for the study inbuilt. These are all aspects that will be discussed with FDA.
After the FDA meeting, we will, of course, tell them more in detail how we are going to move forward to the Phase 3. Based on the data that we have now seen and that was presented by Professor Zeidan, we can see very nice robust efficacy. We can see good safety profile. We know now the dose, that is the 3 mg per kg according to FDA's guidance. If there is no difference in the efficacy or safety, you should select the lower dose. That is what we are going to propose. Next, getting prepared to go and have this discussion together with FDA. Thank you. I had only to. Yes, you have.
Yes, thank you, Petri. We are going to move on to Q&A, but just to wrap it up before we get the questions in.
You know, here going around ASCO, talking to a lot of people, there's not that much new spectacular stuff out there. That's what I've heard people say. Then there's us, then there's bex here, which is truly exciting, something new, something possibly game-changing. It is looking extremely good from that perspective. The area needs something new, and we have it. Over to you, Julie.
Oh, Juho. And thank you to the presenters. Very good overview. Yes, lots of key points. We've got some questions that have come in, excuse me, on the chat. We're going to start, maybe, Petri, we'll come back to you just quickly to just make sure on those Phase 3 endpoints, just a little FDA discussion on the Phase 3 endpoints. What do you think those, where do you think those will end up?
There was a question, and I think you covered it, that has this new data gone to the FDA yet? Some has, some has not, I think, but why do not you clarify on that? We will start there.
Okay, thanks, Julie. We believe that primary endpoint of the trial could be composite CR, and a second primary endpoint could be overall survival, and then plenty of secondary endpoints. To answer whether this has been submitted, not yet. We believe we will submit this, if not this week, then next week. Very, very soon, we are ready to submit the whole package to FDA.
Excellent. A related question in the chat as a follow-on, and maybe this is for Professor Zeidan or Petri, is about the VERONA trial. You hit on that in one slide.
A little bit more about the 20%-25% cCR bar that you expect for aza. What's your confidence that bex will be better than that? Is it really—I love this question. Is venetoclax, is it really a competitor given your impressive safety? Meaning, how would you position bex in the 1L landscape should VERONA succeed? A nice kind of recap there of the VERON topic.
I'm going to reply to this question.
Yeah, sure. Yeah, I think I would start by what Juho said is that this is a very challenging field, and there has been a lot of drug failures, and the MDS community is in desperate need really of new drugs. Big picture, as physicians and as patients, we'd love to have multiple agents. I mean, if we get more than one agent, that would be even fantastic.
We are waiting to see the results of the phase three trial with venetoclax, of course. I think big picture is that there seems to be differences in the profiles of these drugs. As I mentioned, venetoclax is a little bit more myelosuppressive, at least for patients on the AML experience, and there has to be a lot of count monitoring as well as supportive care, etc., based on the early Phase 1 and Phase 2 data and our own experience in AML. Patients who are older, who are more frail, patients who might not be going to transplant, those patients could also benefit from a drug that has an easier kind of profile when it comes to blood count suppression. From what we have seen so far, bex does not seem to have an additive significant myelosuppressive effect.
I think this is something that's difficult to ascertain from a single-arm trial like what we have right now, but that's our sense. I think once we go to the randomized setting, we will have a better sense of that. I think the short answer, in my view, is that having multiple drugs is not a big problem because there are certainly a lot of patients, and they are in need of drugs. I would finish by, if somehow you have both drugs available, the next step would be to combine them. This is what we always do when we have multiple good drugs. I think that that would be a good win for patients. Hopefully, both or at least one of them will make it forward.
Excellent.
Petri, I think for you, were there any surprises in the data, either that you expected, did not expect, positive, negative, any surprises? Or for Amer as well, whichever one of you wants to mention.
I can maybe answer here first. I think the safety looks so good. That 36% bex-related adverse event, 36% in any cancer trial with a novel agent, that is a low number. Of course, this is judged by the investigators. It really seems that there are no surprises. We treated with bex in solitary first-in-man trial, 216 patients. Basically, what we have seen here is that the safety profile of bex remains very good. This was the first time bex was combined with anything. It also seems to work very well when you combine with another agent.
Of course, if we think also beyond MDS to other settings like AML, this makes it possible to combine bex with also other agents. This is also important when it comes to solitary development. Of course, it's always nice when the patient numbers increase to see that the promising efficacy also continues to be on a high level. The numbers, when the patient numbers change, of course, efficacy numbers slightly change also. The big picture is that we do see very nice clinically meaningful-looking efficacy with the treatment. This is a good basis to move forward to Phase 3.
Yeah, I would add to this that kind of having treated a number of patients myself on the trial and kind of seeing them on a regular basis, my experience with the drug tolerability is in line with what we just saw in terms of the data. The patients do not seem to have anything beyond what you typically see with azacitidine. The patients are, again, not reporting these chronic toxicities that might not—sometimes you can see these chronic toxicities that might not get captured very well on these databases, like significant fatigue or rashes or other things. In my experience, we are not seeing that. Patients seem to tolerate the drug quite well. Also, as someone who has been involved in several immune checkpoint inhibitors over the last decade, one thing I pay particular attention to is immune-related adverse events.
Again, the data in my mind has been reassuring both, again, in my personal experience treating patients on the trial, but also on the dataset. It seems like infusion reactions and immune-related adverse events are not a big kind of problem, which has derailed some other immune checkpoint inhibitors in the past.
Any additional comments on the frequency of treatment dose adjustments for aza and bex in the BEXMAB study? Not sure who wants to take that one.
No, they were as expected. Of course, if a patient is having febrile neutropenia, that needs to be treated, that causes some delay for the next treatment cycle. Nothing unexpected there.
Maybe to chime in on that, because I think what the question is referring to is that since we now have a lot of these patients a year, two years, one of the patients is nearing three years on the drug, and it's given every week in the protocol, we do allow that they can switch to biweekly to make it easier for the patient and not coming in so often to get their infusion. We do allow that, but what we've seen is that the disease tends to be coming back, and then they've come back to weekly dosing. That's allowed in the protocol to try to make it easier for the patient.
Somewhat preference.
Yeah.
Okay, next question too. Can you tell me if it would be worth doing a trial in myeloid leukemias, AML solely with the TP53, given the exciting data thus far?
Thanks for that.
I'm going to hand it over to the doctors.
Yeah, I think when it comes to new trials, we didn't go too much into detail, but in BEXMAB, we saw in the front line 80% response rate in TP53 mutants, which is really encouraging. This merits also further evaluation of bex in other disease types, including AML. Actually, Scandinavian Sarcoma Group has already done a proposal with bex about how that could be used in an investigator-initiated trial to improve the treatment in AML.
I would add to this that certainly initial data looks promising. I think TP53 is clearly the most difficult subset of patients with MDS and AML, clearly. They certainly need new therapies. Generally, those patients also at the same time do very poorly with a lot of treatments, especially in the refractory relapse setting.
In my opinion, I think you have to have a lot of very robust data, longer follow-up to go for a trial dedicated to this patient population. Certainly, including them in the Phase 3 is something that, in my opinion, should be done. In my opinion, also trying to balance in between the arms is probably a good idea because, again, those patients generally tend not to do well. This has been an issue in previous Phase 3 trials in the past.
Let's pivot a little bit to future plans and commercialization and all of that planning. A great question about looking ahead with regulatory alignment now on the single-pivotal trial, given the impressive data demonstrated to date, how are you thinking about early access pathways, pricing strategy, pair positioning in both the EU and the U.S. for HR-MDS?
That maybe the Juho is for you to talk a little bit about just the overall commercial planning and know that that is ramping up with this exciting news and where we go next?
Exactly. That's something we started working on now and recent new CBO hire to start that work, actually. We're ramping that up, work in progress. We'll come back in due course on how it's progressing, how's it looking. Very interesting times ahead. There's going to be a lot of KOL interactions, for example, at EHA and in multiple meetings coming up.
Excellent. Of course, the fast-following question to that is conversations with the strategics and a partner deal. What's happening with that? What's the latest?
That's a hot topic. Intense conversations. I'll have to come back to that. It couldn't be better, I would say, at the moment.
Cannot talk too much about those, though, unfortunately.
Excellent. Conversations ongoing. Another question related to how patients who have undergone bone transplants or how are they treated with calculating CR, mOS, etc.
I could answer here that patients who have undergone stem cell transplants, so we do have a plan that we will collect separately all that data. Of course, we want to also report that in upcoming scientific meeting. This is now the first look at the efficacy data in the Phase 2 part. We have not yet collected that data from the investigators, but this has already been suggested by some investigators that we should separately analyze those stem cell transplanted patients, their outcome, what were the responses, whether everything went well with the safety after the transplant and so on. We will definitely do that collection.
Excellent.
Do we need to give a little bit more guidance? There's a question on updating on the Phase 3 timing and when you feel the study might complete?
I can't reply to that, the Phase 2 timing. After we get the FDA written feedback, we're going to finalize the protocol and start preparations for that. In H1 next year, planning to initiate the Phase 3 and to enroll 428 patients to a Phase 3. Probably the enrollment time would be something 16-18 months. Sorry, 20-24 months.
Excellent. Okay, that wraps up most of the questions from the chat. Thank you all for joining. Again, very exciting time, one of the most deadly cancers that are around and an absolute excellent efficacy and safety profile that we're seeing so far. Ideally, as Professor Zeidan said, allowing patients to possibly get to a cure.
Very exciting times for Faron. Thank you, everyone, for joining. Appreciate your time and the engagement. Have a good rest of your day.
Thank you.
Thank you.
Thank you. Bye-bye.