Good day, everyone, and Welcome to the Faron R&D Day. My name is Juho Jalkanen. I am the CEO and one of the founding members of Faron Pharmaceuticals. For those new to the story, Faron is a leading biotech in the fight against higher-risk myelodysplastic syndrome. Higher-risk MDS is one of the true unmet needs still in oncology, also known as the pancreatic cancer of hematology. We are listed both in London and Helsinki, so standard corporate disclaimer as we will be making forward-looking statements. It is our pleasure today to bring a comprehensive agenda on our activities and thinking. The first part will concentrate on our lead program in higher-risk MDS and slight update to the schedule. We will start with Professor Zeidan due to his tight conference schedule. The second part concentrates more broadly on the pipeline, the market opportunity, and the company vision.
Also, a bit on housekeeping. We will have a larger Q&A session at the very end, but that is for the Faron management. If you have specific questions for an external expert like Professor Zeidan, please type in your message and we will have a short Q&A after every external speaker so that we can let them go on their daily duties. So again, specific Q&A specifically for some expert, otherwise large Q&A at the end. That's all from me for now, your host, and I will give the floor to our esteemed chairman, Mr. Tuomo Pätsi.
Thank you, Juho, and welcome everyone also on my behalf. Thank you for joining this event. We have a great program today that Juho just shared, and I hope it addresses the request from many of you who have asked for more and more thorough information about our science and our R&D plans at Faron. I'm personally especially excited about our lead opportunity, so bexmarilimab in high-risk MDS. As early in my career, I held executive roles at some of the leading global biopharma companies, Amgen, Celgene, and Seagen. These are all companies that are involved with developing and commercializing cancer therapies and also for hematological cancers like AML and MDS. Over the 35 years that I've been in the industry, I've seen a lot of progress, a lot of progress in many cancer indications, also hematological cancers.
But there are some where the progress has been truly limited, and high-risk MDS is one such indication. The last significant improvement was probably the introduction of hypomethylating agents like azacitidine, and I was lucky to be part of launching that product internationally while I was at Celgene. But that was already 17, 18 years ago. So it is definitely time now for the next breakthrough in this indication, and we hope that we will be able to build on the current standard therapy and further improve the outcomes for patients with adding bexmarilimab. We can move on to the next slide, please. So 2026 has been, you could call it a clarity-building year for Faron. So we have now a clear focus plan, and the team is focused on executing this plan.
With longer follow-up of our BEXMAB study, we have continued to see excellent results with Bex in both first-line and relapse refractory high-risk MDS. That has given us conviction, and also to the clinical expert across the world, to move bexmarilimab now to the next phase of clinical development. There were also some external events late last year that impacted our plans. Namely fixed what was not working in terms of study design. We took these insights and modified our development plans accordingly. We are now focused on starting a randomized double-blind phase IIb trial as the next step. This will be a comparison of bexmarilimab plus azacitidine to placebo and azacitidine, and it will be in first-line high-risk MDS. We will hear more about this study and the plan in the minute.
To be able to execute this plan, we raised EUR 40 million through a rights offering earlier this year, and now we have the funding to get this randomized trial, to get to the readout of this randomized trial. Obviously, this will be a major value inflection point for the company. We have a clear plan. We have the funding needed for the next milestone. We have a great team at Faron, so we have strengthened the team recently, and very importantly, we have the support of the experts in the world's top research centers. Let's not forget, in addition to MDS, we have our program in solid tumors, and we will be hearing more of this as well. As we recently announced, we already have the first patients in these combination studies initiated.
An exciting year, and we have an exciting program ahead of us today. Let's now move on to our first expert presentation. Presentation will be by Professor Amer Zeidan from Yale School of Medicine, and he is broadly recognized as the leading global expert in MDS. He will share more details on the planned BEXERA study and the evolving MDS treatment landscape. Over to you, Professor Zeidan.
Yeah. Thank you so much, Tuomo, and it's a pleasure to be here with you today. A couple of disclaimers on my own that this represents my own opinions and not my employers, and I have consulted for Faron, but also I'm a little bit under the weather, so I apologize for my voice. There's a big thunderstorm behind me, so if you hear thunder, that's what it is. Can we go to the next slide? What I'm going to do today is I'm going to talk about MDS as a disease and the challenges in terms of drug development, and then talk about the evolving treatment landscape, in particular, some of the most recent phase III trials and their failures and how we have been working in the field in general.
But I have been working closely with the Faron team to design the trial in a way that we have learned a lot from the previous trials, so that we can optimize the chance of success in the BEXERA and hopefully in the subsequent phase III trial. Next, please. Next. So MDS, many of you have probably been following these calls, know the disease by now, but MDS is a cancer. It is a form of a blood cancer. It is associated with bone marrow failure and therefore symptoms of anemia, neutropenia, and thrombocytopenia, leading to infections, bleeding, and life-threatening complications. While patients with MDS, many of them will not progress to AML, they still often will die from complications related to the bone marrow failure.
Still, one-third of patients will progress to acute myeloid leukemia, and the survival with high-risk MDS really has been quite limited, as I am going to show you in the next slides. Next, please. Next. So you just heard from Tuomo, really the standard of care for MDS has not changed significantly over the last 20 years in any substantial fashion. Bone marrow transplant continues to be the only potential way to get a cure. However, with the median age of MDS patients being their early to mid-70s and with many patients having comorbidities related to age, most patients with MDS are not candidates for transplant. Real-life analysis actually have suggested that less than 5%-10% of patients undergo transplant. Therefore, the mainstay of treatment has been hypomethylating agents with azacitidine and decitabine for a long time.
In the U.S., both of those drugs are approved, plus an oral version of decitabine called decitabine cedazuridine. While in many countries around the world, only azacitidine has been approved because it has been the only drug to show a survival improvement in a randomized phase III trial. In the relapsed refractory setting, really there are no approved drugs outside of an IDH1 inhibitor that is approved in the U.S. based on a single arm phase I data. That really applies to less than 5% of patients with MDS who have this particular mutation. So for the vast majority of patients, really there are no treatment options. We know that intensive chemotherapy can be used in younger patients who have excess blast, but this is generally is used as a bridge to transplant and not as a definitive treatment by itself.
While hypomethylating agents have helped patients, there is a number of problems. First of all, less than half of the patients will achieve a response, so half of them will not have a response. When you talk about complete response, it happens in 20% or less of patients, so 80% will not achieve a complete response. Even those who respond typically will relapse usually within one to one and a half years. The median survival with hypomethylating agents is limited to around 18-20 months, as I am going to show you on some of the real-life studies. Importantly, many patients with MDS, even if they respond, they will eventually progress. So everybody will progress after some time on HMA. Once they progress, the median survival is less than six months.
We don't have a reliable way of predicting responders to hypomethylating agents. This really left an unmet need for all with the goal to increase the rate of complete response, but also to deepen the response, improve the quality so that it's more durable, and ideally reducing transfusion burden and improving survival as the main goals of treatment. Next, please. This paradigm for the treatment has not really changed over the last 20 years. As you can see, it's a much simpler paradigm compared to other diseases like myeloma or AML or CLL. Here, if the patient is a transplant candidate, the recommendation is go to transplant. But again, this is only 5% to 10% of patients. Sometimes we use bridging therapy. There's controversies on this. We can discuss that later.
But for the vast majority of patients who are not transplant candidates, the standard of care has been hypomethylating agent monotherapy, although a number of drugs looked at combinations, and we are going to show you some of the data. But unfortunately, all of them have failed. In the relapsed refractory setting, as I mentioned, only IDH1 inhibitor, ivosidenib, has been approved for only 5% of patients who have IDH1 mutations. Next, please. While the randomized AZA-001 study showed a median survival of 24 months, which was significantly longer than the 15 months with conventional care regimens, in real life, analysis has been very difficult to replicate those 24 months with azacitidine. Here you can see three different sets of real-life analysis that we have done, including pooling data from a number of frontline high-risk MDS studies.
What you can see is that the median survival ranges somewhere between 12 months in older patients, all the way to 19 months for patients who were included in clinical trials. So even worse than what was seen in the randomized clinical trial and clearly showing the need for improved therapies. Next, please. Now, bexmarilimab, you'll be hearing a lot during this session about bexmarilimab, but the activity with the combination with azacitidine, I think has really demonstrating very promising responses. In this slide, you can see a nutshell of all the top line data from the study that looked at patients. We studied 21 patients in the frontline setting, and the response rate, using the traditional 2006 criteria, was 45%. Using the IWG 2023, which emphasizes count recovery, the CR rate is 41%.
Many of those patients, 57%, who were transfusion-dependent became transfusion-independent, which is an important clinical benefit for patients. 67% of patients achieved MRD negativity using local assays. The median duration of response for CR patients was 16 months, and most of the patients achieved some blast reduction, as you can see in this latest data cut from EHA 2026. Next, please. In the relapse refractory setting, we studied also 33 patients, and again, this is a setting where, as you may remember, is a very difficult setting, no approved drugs for most patients. Median survival is around four to six months. So when we gave azacitidine with bexmarilimab, it did seem that bexmarilimab was resensitizing patients to Aza. So we saw complete responses and partial responses in 12% of those patients. The overall response rate was 64%.
Some of those patients were able to be bridged to transplant, which again, is the only way to try to cure these patients. But importantly, the median survival was around 14.5 months in the relapse refractory setting, which again, in that comparison, small study, but this looks much better than the expected six months after HMA failure. I think, given that these patients were already refractory to HMA, this provides very good proof of concept about the additional activity of bexmarilimab when it is combined with HMA, both in the front time, but also in the relapse refractory setting. Next, please. The safety profile of the drug in, remember, MDS patients, as I mentioned at the beginning, they are older patients. Most of them are in their 70s. They have number of comorbidities. So they are frail patients.
They often do not tolerate a lot of additional myelosuppression or combination drugs that kind of induce significant toxicities. Here with bexmarilimab, we saw a very good safety profiles. The hematologic adverse events were largely what you see with azacitidine by itself. Also, of course, in a single arm study, it is always difficult to kind of attribute 100%, but overall, given the solid tumor data, did not suggest myelosuppression with bexmarilimab. Historically, when you compare this data to azacitidine by itself, it does not seem the hematologic toxicities are increased with the combination. But importantly, bexmarilimab has low rates of infusion reactions, and no patients died from the drug so far in the clinical trials, and the incidence of infusion-related reactions and immune-related adverse events has generally been low, and the drug is well-tolerated. Next, please.
Here you can see kind of a comparison to the historical Aza data, as I mentioned. It does not seem the rates of thrombocytopenia and neutropenia looks worse. Actually, it does look a little bit better, but of course, this is a indirect comparison with the historical control. I think this gives reassurance that it is unlikely that adding bexmarilimab to Aza is leading to worsening hematologic toxicity. Next, please. Now, of course, these were all single agent or single arm trials, both in the frontline and the relapse refractory setting.
We need to go into a randomized setting, and we have spent a significant chunk of the last 1.5 years kind of working with Faron, but also with the regulators to kind of develop a randomized trial program, but also learn from the multiple failures that we have seen in combining azacitidine with other drugs. You can see here a listing of some of these trials with other drugs, including venetoclax, sabatolimab, magrolimab, pevonedistat, APR-246, and tamibarotene. You can see that they have used different endpoints, but the shared feature is that none of them have reached their primary endpoints. Next, please. What are the lessons? I think one lesson is overestimation of the treatment effect. This is something that we have seen, people kind of are too optimistic based on the initial small data in terms of the effect size.
I think when you power your randomized trial to a very large treatment effect difference, which is not replicated on the ground, that will lead to missing the primary endpoint. Also, there was not a lot of understanding of the subgroup analyses and the best dose and the biomarker kind of selection for patients. All of these have suffered across number of trials. Overall survival, I think, can be sometimes tricky in these early phase trials because there are different baseline disease characteristics. This means that what you try to power for can be challenging depending on how many patients go to transplant and the different operational and statistical assumptions.
There has been some trial or result variability by region and differences in the supportive care, for example, the use of antibiotic prophylaxis, as well as the robust assessment of responses, which sometimes can be tricky, so it really needs a sponsor involvement in making sure those responses are reflecting accurate results. Finally, I think trying to improve the design of the trial to account for variability that might occur, for example, allowing adaptive design to re-estimate the sample size based on evolving data, as we will talk later. Next, please. So we implemented all of these lessons in the design of the randomized phase II, which is a dose finding.
It will involve bexmarilimab at two different doses, 1 mg and 3 mg /kg combined with azacitidine versus azacitidine with a placebo, and this will allow both to establish contribution of component, but also it would allow us to select the best dose to move forward. The effect size, what that was assumed in this trial, was realistic. So a small effect, the difference will allow the trial to move forward in terms of dose selection. The trial will stratify by things that are important to patient outcomes and that have been causing some problems when they are imbalanced in other studies, such as TP53 and blast percentage and IPSS-M.
I think this study also, again, will provide a lot of understanding about the differences in the dose activity as well as PK, PD, dose intensity, and hopefully biomarker predictors and subgroup analysis to inform the selection of patients for the randomized phase III trial. Next, please. So with that all in mind, we met with the regulators. I think we discussed the different options, and the program moved towards the BEXERA trial, which is a randomized phase II trial you can see here, which will, as you just heard, already enrolled the patient and is activating in a number of centers, including my center at Yale. Here, 90 patients will be randomized, 30 patients per arm to two doses of bex versus placebo, all of them combined with azacitidine. That will inform the design of the subsequent confirmatory trial. Next, please.
Of course, this trial will use a complete response plus CR equivalent as a primary endpoint and will introduce analysis focusing on the dose selection, but also other analysis looking at event-free survival and safety analysis. Next, please. This will be global study, many sites, as you can see, 35 sites across U.S., Europe, and U.K., which will allow very, hopefully, rapid accrual so that the results can result in late 2027, the trial. Next, please. This is more details about the trial.
I would mention that most of the sites that opened the BEXMAB, the phase I trial, are proceeding with the phase II, I think reflecting the confidence of the investigators in the drug and the good experience, but also, I think, helping with the logistics and since many of those investigators, including myself, have worked with Faron in the past. The other sites were selected for sites which have good experience with MDS to optimize the conduct of the study. Next, please. In summary, I think there is a significant high unmet need in all patients with MDS, high-risk MDS, including the frontline as well as the refractory relapse setting. HMAs and transplant continue to be standard of care, but transplant, most patients will not undergo it, and HMAs have limitations.
I think the BEXMAB study of bexmarilimab have shown very nice safety and efficacy data, including durable CR in 45% of patients. We saw good survival data in the relapse refractory setting, as well as good data in TP53. Therefore, I think we are ready to validate that in a randomized, placebo-controlled study of two doses of bexmarilimab compared to either with placebo to understand the contribution of component, but also to understand the dose selection to inform the subsequent phase III trial.
We have used the learnings from previous failed phase II and phase III randomized studies to design the BEXERA trial in a way that will optimize the chance of success, including discussions with the FDA about the use of endpoints, which will be complete CR here, plus CR equivalent, and the durability of the CR and stratifying the patients for important factors such as IPSS-M risk, blast percentage, and TP53 status. I believe this is the last slide. Happy to take any questions.
Amer Zeidan, wonderful talk. I have received a message that we have some questions from the audience, and we will be hearing them.
Thank you, Juho, and thank you for the excellent presentation. There are multiple questions, but we know that you have limited time today, so let's kick off. There is a lot of discussion about safety. How important is the safety in this setting and in this patient population when combining with Aza?
Yeah, this is very important because we have seen two things. One is that most of those patients are in their 70s, and they are frail and have comorbidities. It is very easy for them to get a drug that is combined with either that causes myelosuppression, and that can cause significant problems. We have seen some of that with venetoclax, we have seen some of that with magrolimab, and that really can derail the trial. So having a drug that is easy to combine and that can be administered on chronic, long-term basis without causing high rates of discontinuation is very important. So I think this is critical in any drug design for high-risk MDS.
Thank you. Based on the results seen so far, especially on the last line, do you think that we can establish a contribution of each agent from these results seen so far?
I think so. It's always difficult to make very solid conclusions from phase I studies with a relatively limited number of patients. I think all what we have seen in terms of the efficacy and the safety from the trial, but also in terms of my own personal experience with the drug, looked very promising. I think we are very well positioned to do the phase II randomized trial, which as I mentioned, is designed in a way to optimize the success of the trial. We don't end up in a situation where you have a drug that works, but because the trial is not very well designed, it leads to problems. I think here the trial is really designed to show the full benefit of the drug.
Thank you. What makes you confident about BEX, or what gets you excited? Is it TP53 safety profile or what makes you confident about BEX?
I think all of it. I think the CR rate, the durability in the frontline setting, the early activity we see in TP53, the safety profile. Also importantly, we are seeing some evidence of pharmacodynamic changes, like some immune activation suggesting the mechanism of action of the drug. Some early signals that you could predict responders using T cell subgroup or subset analysis, but also the survival in the relapsed/refractory setting of 14 months when only 20% of them went to transplant. This is quite good. I'm really hopeful and look forward to seeing these results replicated in the randomized study.
Thank you. For the last question, based on your experience and recent activities in the field, do you think that BEX is the one who can succeed or make it as a positive?
Yeah, I am someone who is optimistic by nature, and I certainly think all what we have seen so far with the drug is very positive. Ideally, from patient perspectives, we want not only one drug, multiple drugs. I am hoping there will be a number of drugs succeeding and helping our patients. But for bexmarilimab in particular, I think the data really looks as good as you can within a single-arm phase I study. Of course, the confirmation will be through our randomized studies, which we are going to do. I think we will find our answers hopefully by the end of next year.
Thank you, and over to you, Juho.
Thank you, Professor Zeidan. We will let you go.
Thank you.
Have a wonderful and productive day. As you mentioned, we are here to seek the truth, and that's what we're going for. Thank you. Next, actually, a great segue after that is, I'm going to invite our Chief Scientific Officer, Dr. Maija Hollmén, to the stage because she receives all these samples from the ongoing trials, analyzes them, and sees what's going on in these patients. It's something that Professor Zeidan also alluded to, that what we're seeing happening in these patients really validates the clinical activity of this drug. Over to you.
Thank you, Juho. Hi, everyone, and welcome also on my behalf. As Juho mentioned, I will be talking about what we know about bexmarilimab in MDS. First, I want to just briefly go to the basics of cancer and how it grows. For cancer to grow, it needs to gain several functions that are called the hallmarks of cancer, which include enabling replicative immortality, genomic instability. They have deregulated metabolic functions. They have tumor-promoting inflammation within the tumor microenvironment. They need to induce angiogenesis to grow bigger than 1 cubic millimeter. You can see all of these functions on the left-hand side of your screen. What is interesting and the current state now is that the pharmaceutical companies are trying to target these hallmarks by different drugs. They are developing drugs to each of the hallmarks separately.
I now want to introduce you something that we are trying to do, and it's on the middle of the graph, you can see the immunosuppressive myeloid cell. What is known about these cells is that they can support nine out of the 10 hallmarks that I'm representing here now. They're very powerful cells in supporting tumor angiogenesis, metastasis, and inflammation that promotes even more genomic instability. What can we do utilizing these cells to promote antitumor immunity and tumor destruction? We propose that we can reprogram these myeloid cells to actually activate anti-tumor immune responses, and therefore reduce tumor growth and impair metastasis events that are normally seen and that eventually kill tumor patients.
There you can see on the right-hand side, if we can then reprogram these macrophages to a pro-inflammatory anti-tumor myeloid cell, we can circumvent all of these nine hallmarks, except for the enabling replicative immortality that the cancer cells have themselves. That, of course, if you reduce all of the other hallmarks, you can really gain super powerful effects on the tumor growth itself. Going back to now our target and knowing what our target does based on preclinical and translational research that we have gained during the years. What normally the macrophage, this is now representing a macrophage that is expressing CLEVER-1, which is the target bexmarilimab binds to. CLEVER-1 scavenges acetylated LDL and oxidized lipids on the cell surface to take them inside the cell and induce these lipid nuclear receptor signaling pathways that promote tolerogenic macrophage subsets.
So basically, I can easily say that whatever the macrophage is eating, it's hiding it from the immune system. This can be seen as an increased secretion of IL-10 and regulatory T cell formation. What is also interesting within these macrophages is, which is shown on the left-hand side corner, that when macrophages eat different endogenous substances, it takes them very rapidly into phagolysosomes. So they acidify these lysosomes and degrade everything that they're eating and kind of hiding it. Now, when we target these macrophages with bexmarilimab, it binds to CLEVER-1, inhibiting the scavenging of, for example, these oxidized lipids, and they are not taken inside the cell that then impairs the induction of these tolerogenic macrophages.
While during this, bexmarilimab can impair the acidification of these lysosomes, coming to the promotion of antigen presentation via this impaired endosomal acidification so that it kind of has time to present the antigens, the immune system. It also activates NF-kappa B signaling, producing TNF-alpha, IL-12 and CCL3, CCL4 and CCL5, CXCL10s that are important molecules to supporting anti-tumor immune responses, for example, T cell activation towards cancer cells. And there you can see that that leads to an expansion of activated effector T cells. So why this is important in MDS? Because I want to highlight now that MDS is not only a clone of malignant cells. Also, these are myeloid cells that have gained malignancies. But one needs to always remember that malignant cells are within their tumor microenvironment.
And now we're discussing the bone marrow tumor microenvironment, where you have suppressive myeloid compartment that is supporting the tumor growth and that is suppressing the effective T cell response that you would normally have against the tumor. What you also get, of course, is that if you have this clonal expansion, you get dysfunctional hematopoiesis that causes all the side effects or the effects that Amer was just presenting, which are the anemia, neutropenia, and thrombocytopenia that is really severe and people get bleeding infections and so forth. So to understand this in the concept, I will go through what we know about CLEVER-1 and how it can support these activities for a better outcome for the patient. So I want to briefly tell you about CLEVER-1 and what we know about CLEVER-1 in myelodysplastic syndromes.
So basically, CLEVER-1 is a scavenger receptor expressed also by leukemic myeloid cells in addition to the normal monocyte macrophage subsets. You can see on the right-hand side a heatmap, where each dot represents one patient sample. And the more red that patient sample is, the higher the expression of CLEVER-1 is in these samples. So you can clearly see that you get a lot of red. AML is super red, MDS is also. So they are very good indications for targeting CLEVER-1. So CLEVER-1 is involved in the receptor-mediated endocytosis I was just explaining. But it also regulates leukocyte trafficking, inhibits T cell activation, and promotes tumor growth, which is demonstrated by different publications during the years. What is also known that high CLEVER-1 expression in cancer associated with poor prognosis and contributes to treatment resistance. So it's a very important factor regulating tumor growth and metastasis.
Now going back to HR-MDS and what we think is our very good approach why bexmarilimab works so well is that it kind of has a dual mode of action because CLEVER-1 is expressed on the monocyte myeloid compartment but also on the blast cells. That then, in one hand, induces immune activation by presenting the antigens to T cells and therefore affecting adaptive immune activation and killing of blast cells. On the other hand, on number two, bexmarilimab by binding to CLEVER-1 on the blast cells, it can impair their metabolic parameters and sensitize cells to azacitidine, for example. So how it's now shown, this is data from the bone marrow of the BEXMAB patients that were treated with combination of bexmarilimab plus azacitidine in the phase I/II study.
Now on the left-hand side, you can see HLA-DR expression on monocyte and blast populations that was measured from the patient bone marrow. HLA-DR is an antigen-presenting molecule that activates CD4+ T cells. Here you can see that on the monocytes, bexmarilimab is increasing the HLA-DR expression on the responding patients, which is very interesting that you can activate the immune system and get a response of the combination therapy. What is also happening, interestingly, is that the absolute numbers of CD8+ T cells increase in the bone marrow, and these CD8+ T cells are the killer T cells that kill the tumor cells very effectively. So by increasing these numbers, you can actually affect how the blast cells are getting killed.
On the right-hand side, you can see that during the treatment cycles, this observation of the absolute numbers of T cells is increasing significantly when you increase the doses of bexmarilimab. But going back to now the metabolic changes that we see in the blast cells. So what we see in the clinical trial is that there are some indications that bexmarilimab would help azacitidine treatment. So what we have done in the lab is that we have analyzed, for example, first, how does CLEVER-1 interact with other molecules in the cell? So in the A figure here, you can see the whole interaction map of the proteins that are interacting with CLEVER-1 inside the cell. So you can see it's quite big interaction map. Now when we treat these cells with bexmarilimab, you can see that there are no longer that many proteins that are interacting with CLEVER-1.
If we now look what functions then this impaired interactome has on the cell, you can see that these cells are stressed. So they are increasing their mitochondrial RNA granules to produce mitochondrial respiration. This can be seen in the D part, where you can see impaired oxidative capacity. So the mitochondria cannot produce energy via oxidative phosphorylation. So this then translates to the viability arm in the E part, where you can see that a cell that is normally azacitidine resistant becomes sensitive to azacitidine if you add bexmarilimab to these cells. So this is basically telling us that bexmarilimab is priming the mitochondria to standard of care treatment so that they can more reliably gain impaired viability after standard of care treatment.
I want to also highlight, as Amer said, that BEXMAB was a combination trial, so it is very difficult to say what is bexmarilimab adding on to azacitidine treatment. When we look at this figure here, we have measured target engagement of bexmarilimab on soluble CLEVER-1 in an ELISA assay. Meaning that we can see how much of our drug is binding to CLEVER-1. This figure is now showing that the patients who get a complete response for the combination treatment have actually a higher target engagement of bexmarilimab on CLEVER-1. This kind of states to me that our drug is actually doing something because the complete response is associated with increased target engagement. Which is very hopeful, and we want to of course, study this further in the BEXERA trial. Then there was this interesting figure or data that Amer showed.
It is on the left-hand side, showing that there are some indications that actually the side effects in neutropenia, thrombocytopenia, and anemia would be reduced in the combination compared to azacitidine alone. This is interesting because when we go and see the bone marrow samples of the BEXMAB patients that were treated with the combination. You can see here two UMAP plots in the right-hand side of this screen. This UMAP plot is showing single cell RNA seq data from five patients that got a response for the combination. Each dot is one cell. The more closer the cells are together, the more similar they are in this map. We can annotate these cells, and you can see that we have annotated them as monocytes, granulocyte myeloid progenitors, and blast cells. This left-hand side UMAP is at entering the trial.
It took a bone marrow sample of the patients before they got the combination therapy. When we look at the same map or the UMAP map, you can see after three cycles of treatment, you get a robust reduction of cells on the monocyte lineage. These markers are telling us that these cells are very immunosuppressive and not good to have in the tumor microenvironment. We can reduce these cells a lot by the combination. What is also interesting is that you can see on the really right-hand corner, an increase in eosinophil, basophil, mast precursors, erythroid precursors, and the megakaryocyte precursors. They are increasing by the treatment, so this was after three cycles. We went back to the lab and actually asked the question, can bexmarilimab promote hematopoiesis by itself?
Just to look that this effect from the progenitor populations is not coming from the combination, but it is actually coming from bexmarilimab alone. We performed this colony forming assay. You can see here on the lower hand, or on the left-hand side, you can see these colonies that we are counting from this colony forming assay. You have a small, medium, large, and mixed colonies. You can see here that adding bexmarilimab into these colonies, compared to isotype control, we can see a significant increase in the colony formation of megakaryocyte colonies and different mixed colonies. That indicates to us that bexmarilimab is affecting these hematopoietic progenitor cells metabolically, so that it can induce their proliferation by itself.
I want to conclude the exciting scientific findings that we have found from the lab and from the patient samples, that bexmarilimab combined with azacitidine induces very broad hematopoietic and immune reprogramming in the bone marrow as it activates progenitor population, enhances lineage commitment and niche normalization. It increases complementary epigenetic and metabolic pathways in blast cells. These findings support the therapeutic potential of this combination in myeloid malignancies, which we are, again, then doing now in the BEXERA trial to actually really see the difference in placebo controls to define how bexmarilimab is really working. That was my last slide, and I am happy to take questions if there are any.
Thank you, Maija. Thank you. I am going to take this opportunity myself, if you may, because I have gotten to learn that you are a macrophage expert, and macrophages seem so thrilling, fascinating cells. Why do you love macrophages? Why are they so fascinating for you?
For me, the first time I actually became fascinated by them was that I understood that the tumor can consist half of the mass of macrophages. It was interesting to me, what were they doing there? Then I learned that people are calling them the Swiss Army knife of the immune system. That fascinates me, that they can do anything. They have the possibility to become everything and perform many, many tasks. That is why they are so fascinating to me.
It sounds like a tricky cell to target if it is a Swiss Army knife. Why is CLEVER-1 such an important target on macrophages then?
Of course, there are many scavenger receptors, many checkpoints on macrophages. But what we have learned from the lab is that CLEVER-1 has a really non-redundant function on macrophage immunosuppressivity.
Okay.
That's why we believe that targeting CLEVER-1, we can gain many multiple functions within the macrophage that supports antitumor immune responses.
Okay. Well, that's an important-
Yeah
important thing. Because what I've learned also from the field is that since there's been failures in macrophage targeting, people are talking, should we use two macrophage targets or even three macrophage targets? What do you feel about that?
Well, of course, it might benefit if you target macrophages in different angles. Let's say one is inducing phagocytosis and we are inducing antigen presentation. This, of course, might be a good approach, but I also want to emphasize that I think we should also consider other cell types like macrophage T cell activators so that we get both components activated. I think we still need to learn a lot, but I think CLEVER-1 is a very good target due to the fact that I said that it is regulating many of the functions that are needed for the antitumor responses.
CLEVER-1 alone could be enough on macrophages?
Yes. Yeah.
Okay. Well, we will get to the bottom of that.
Yeah.
Thank you, Maija.
You are welcome.
Do not worry, audience, Maija will be back for the management Q&A. Next, I want to take this opportunity to share the stage with an important partner for us, and it is Blood Cancer United and their Therapy Acceleration Program, the TAP program. Not that many may be aware of the good work and important work Blood Cancer United does, so we wanted to give them the chance to put the word out on what do they do and how have they been working with us to take the BEX program forward. With these words, I give the floor to Dr. Blaine Robinson, VP of the TAP program. Over to you, Blaine.
Thanks so much, Juho. Good to see you. Thank you so much for the opportunity to join Faron's R&D day today. It is a wonderful pleasure. As Juho mentioned, I am the Vice President of our Therapy Acceleration Program, or TAP for short. It is Blood Cancer United's venture philanthropy initiative. I have worked with this organization for more than 15 years, all as part of the TAP team. Before that, before coming to Blood Cancer United, I worked in a pediatric leukemia laboratory in the Children's Hospital of Philadelphia, so my connection to blood cancer really goes back more than 20 years. I will first start today with our mission and the research programs behind Blood Cancer United and then use MDS as a model to show how our mission can inform some of our commitments.
I'll introduce our TAP's investment and collaboration model before turning to the patient need and the history of our partnership with Faron, as Juho alluded to. My purpose today is not really to position one company over another, but really to show how a mission-driven organization like ours decides where to accelerate development. Before I speak about TAP and MDS, first I'd like to tell you a little bit about our nonprofit and why we're here at an R&D day. Next slide, please. Many of you may know us by our former name, the Leukemia & Lymphoma Society, or LLS. We recently rebranded about a year ago as Blood Cancer United, really to better reflect the full breadth of our patients, families, all the different blood cancer diseases in the communities that we serve. Our name has changed, but really our mission has not.
Our vision still remains a world without blood cancer, and our mission remains to cure blood cancer and improve the quality of life for all patients and their families. We do three things at the Blood Cancer United organization. We pioneer life-saving research worldwide, we help empower patients, caregivers, and providers with free information and support services, and we help amplify the voices of patients seeking access to quality, affordable care. For this audience today, research is the reason I'm here, but the other two pillars are really what make our perspective on any development program different from any other foundations or investors. Next slide, please. Our organization, Blood Cancer United, formerly Leukemia Society of America, and then Leukemia & Lymphoma Society, was founded more than 75 years ago, really on the goal of finding a cure for leukemia.
Today, we've become the world's largest non-profit health organization dedicated to blood cancer, funding research worldwide, providing education and patient services, and having leading policy and advocacy efforts, especially in the U.S. We have helped fund the vast majority of breakthroughs in blood cancer research over that period. Next slide, please. This slide really shows seven decades of what research investment has helped produce. We've seen dramatic improvements in five-year relative survivals in many of the major classifications of blood cancers from the '60s to today, and then especially accelerated by the explosion of new therapies over the past 20 years. Really exciting time to be in this blood cancer space and drug development. For example, myeloma, only 12% of patients survived five years in the '60s, to over 60% today, very similar to leukemia. Patients with non-Hodgkin's lymphoma have even better outcomes.
Almost 90% of patients are surviving five years. Recently, interestingly, our organization led a specific analysis, and it was published in Blood Advances just this past month. We've done this analysis that puts this progress in more human terms than just these numbers. What we've come to conclude was that over these years, advances in blood cancer treatment have helped save nearly 26 million years of life. That's really what our organization is about, saving life years. That's decades of science translated into something every patient and family can understand, more time together. These are obviously all of the field's numbers, not ours alone, so it takes our organization along with all the other organizations and companies in the world, but it really reflects the breakthroughs that have changed what's possible for patients.
Really, there's two well-known examples to help make this progress a little more tangible. For example, a drug called Gleevec changed the outlook on chronic myeloid leukemia by once turning a really fatal disease into one that many patients can manage for many years with their targeted therapy. In addition, rituximab is another good example that really reshaped B-cell lymphomas and other CD20-positive diseases, helping more patients achieve durable remissions. That type of track record is why a non-profit like us belongs in a conversation about drug development, and it's also a reminder that still there's a lot more work to do. Next slide, please. Shown here is kind of a snapshot of a lot of different numbers and our contributions to research. A couple I wanted to point out. As I mentioned, we're the largest non-profit funder of blood cancer research.
We funded more than $2 billion since our founding over all our different programs. Just today, we have over 330 active projects, spanning 43 different blood cancers. Obviously, immunotherapy is very key. We have 90 different projects in immunotherapy alone. We have several different grant programs focused on bringing trials into the community settings. We have 17 active TAP partnerships that I'll speak about a little bit later. Annually, we receive more than 600 grant applications a year and review them through a multi-step peer review process with blood cancer experts. This is really the portfolio behind the MDS work that I'll come to a bit later. Next slide, please. Shown here, this is how our research programs really map onto the development path, starting from just an idea through basic research, preclinical, drug discovery, and ultimately clinical research, and all the way up towards FDA approvals.
We have career development programs. These are awards that support the most promising emerging scientists in blood cancers. We have some discovery grants that fund the earliest science. Then we have a couple of grant programs, translational research and specialized centers of research. These help discoveries move a little bit closer to clinical application. Then we have a couple of programs focused on trials, academic clinical trials programs and impact programs, support trials, and access to community settings. Specifically today, our Therapy Acceleration Program, this is where we invest and work directly with biotech companies such as Faron, and these are typically on clinical-stage assets. Our organization also has several master clinical trials. One's called BeatAML. They are celebrating their 10th year, actually, and then a PEDAL trial, which is focused on pediatric leukemias. These are master trials where we're actually the sponsor of the trial.
We hold the IND. We run the trials with CROs and have dedicated sites committed to these diseases, especially in AML and for pediatric clinical development, respectively. We also run several special initiatives where there's a high unmet medical need. These include CMML, hairy cell leukemia, mantle cell lymphoma, and follicular lymphoma, and these are typically co-funded or supported by a specific donor or another disease foundation we work in collaboration with. For scale, our academic grant programs runs approximately $40 million-$50 million a year, and over the history of our organization, we have supported more than 4,000 projects in more than 80 institutions worldwide. Let me show you what that looks like at this current time in one specific disease, MDS. Next slide, please. This is what our MDS commitment actually looks like across the whole organization in biomedical research.
We have 28 active MDS-relevant awards. For TAP, where we focus with companies and invest, we have investments in four programs across three companies. We specialize centers of research. These are large multi-institutional grants, $5 million commitments. That includes multiple principal investigators, where they're working towards one overarching goal, and obviously these ones are focused in an area in MDS. We have 14 career development awards in the MDS space, along with three discoveries, two academic clinical trials, and these are really specifically funding investigator-initiated trials for using companies' drugs or drugs that have been developed by the academic institution running investigator-initiated trials and two impact access programs in the MDS space. Obviously, there's lots of different examples of what these programs are studying, but a few examples include RNA splicing, epigenetics, especially important in MDS, TP53 mutant disease, clonal hematopoiesis, and other metabolic vulnerabilities.
The message here really is we cover everything from the bench to the bedside, even to patient access, and really no single company or foundation can really cover that span like we do. This is what we bring to a partnership with any of our collaborators. One thing I did want to point out, just recently announced, we do have a collaboration with the Edward P. Evans Foundation. They focus on MDS. They have a program called EvansMDS, and they have, obviously, a commitment to do more collaborative MDS research. So we just announced that the Edward P. Evans Foundation and Blood Cancer United are going to be supporting a new SCOR grant, to bring together interdisciplinary teams together from around the world to focus on MDS translational research, try to bring more discoveries to the clinic.
This application window is now open, and we hope to fund a new MDS-focused SCOR grant next year. Now as I transition to more about the Therapy Acceleration Program, this is the part of the organization that works directly with companies. Let me now turn to that model and how it operates. Next slide, please. I know there's a lot here on the slide, but I'll walk you through it. TAP is our venture philanthropy program, and we've been supporting companies developing novel blood cancer therapies since 2007, so we are approaching our 20th year next year. The different sections. First I want to bring your attention to the circular bullseye on the right. This is a snapshot of all the biotech companies TAP has ever supported. There's over 50 of them there.
Some of them might be on the slide more than once, because they might have different assets in blood cancers. They either show the current stage of development or where the program ultimately ended. The outer ring represents preclinical stage companies. As we move toward the center, you see phase I, phase II, and phase III, and ultimately FDA-approved therapies, of which several have been completed with TAP-supported therapies. The blue boxes highlight recent or incremental investments over the last couple of years, and we have a couple other partners that are actually still in active development in blood cancers. The main goal here is our mission. We invest to accelerate therapies to help cure blood cancers and improve patient outcomes. As I mentioned, in the center of the bullseye are six approved therapies that have either been FDA approved or included in the NCCN guidelines.
These include in diseases AML, lymphoma, rare blood cancers called BPDCN, and T-cell lymphomas. One of our most recent examples of an approval where TAP had a contribution was ziftomenib. It is one of the new class of therapies called menin inhibitors. It was approved last November. When TAP makes an investment, we invest as part of a syndicate with other like-minded investors. We take an equity position in the company.
The model is really designed to both impact mission for accelerated development for therapies and also a possible financial return. We have invested more than $120 million to date in over these 50 companies, and there is more than 30 active clinical trials running across the portfolio with TAP-supported therapies. Strategic transactions, financings, and financial returns do matter, because these returns that then come back to us, we recycle into the mission and help fuel the next generation of TAP investments.
Over the years, we have been doing this for quite some time, we have built up a pattern recognition to distinguish companies that best fit our thesis for investments and have the potential to impact patient care, which is our primary driver. The next slide shows this thesis and what we look for before deciding to partner with and invest in a company. Next slide, please. These criteria are what we look for in a company during due diligence, and they are the same ones we have applied to Faron. First and always first, we really look for the unmet medical need. What are the existing emerging patient populations where patients have very few good options? Is there a real gap in the current emerging treatment landscape? We look for innovative science, things that are first in class.
If others or other companies in pharma are well covering a development target or particular diseases, we may be less likely to invest there. We can use our dollars to invest in a space where there is really that unmet need and lacking of a standard of care. We look for, is there a plausible path forward, either through a first in human study or even through registration-enabling studies, making sure that the plan, the company has an alignment with the FDA, how we can assist with them and make sure they have the best chance for success. Additionally, beyond the science, we look into the company. We will make sure that the company has got the proper intellectual property, the management team is in place, they have expertise, they want to work well with us, and they have the ability to finance and execute the development plan.
An important framing point when we look at these opportunities, we are just looking for ones that fit these criteria. We have a due diligence process shown here. We typically look at over 100 inquiries a year. We are not really ranking ones. We are looking for all the different companies that fit. If we have the dollars to make an investment, we will. We are looking through a mission lens first, not looking for the best winners, looking to see which companies can have the best impact for patients. We have a very strict due diligence process. We have a number of staff members with expertise that do our initial due diligence. Ultimately, we do work with some KOLs to provide additional feedback.
We do have an oversight committee called the TAP Committee, where any of the opportunities we want to make an investment with, they oversee our program, and they have to give the go-ahead if we are to proceed with an investment. A lot of these national board members have investing, finance, and scientific expertise. Some of them have been former CEOs, some are investors in other VC groups, so they have a lot of expertise and also help us due diligence on these investment opportunities. Very, very rigorous. We have been told sometimes we do much more rigorous due diligence on the scientific and management than other investors. A lot of companies, if they make it through our due diligence process and become a partner, they really look at us as for a seal of approval, and can be used as a catalyst for additional financing.
We only make several investments a year, typically bring on one to two new partners, and we are also reinvesting or following investing with some of our current portfolio partners. As I showed, this funnel shows a broad set of inquiries down to smaller investments. We look through investment inquiries year-round, and once a company is selected for investment, that is part of their syndicated financing. That is really where our true partnership begins. I will speak about that more in a little bit. Next slide. This is our current portfolio of companies that we have invested in across the blood cancers. It really illustrates sort of the breadth of the different partnerships. We certainly have a concentration in myeloid diseases, particularly AML, MDS, which obviously have a lot of high unmet medical need.
Boxed in red are our current MDS portfolio for TAP, which includes Faron, Oran, and the two crossbow programs. What I want you to see is not just different company logos, but it is really a living pipeline. We are always hoping to come when we join a company investment, whether it is preclinical or in phase I or phase II, we want to see them sort of moving toward the right into pivotal trials and ultimately for an approval. There is a whole host of different modalities, stages of development, so we are really agnostic to those. We have cell and immune therapies, targeted small molecules, antibodies, and other different approaches all selected because they sort of address difficult blood cancer settings where better options are needed for patients. Really the concentration is not accidental. It really follows sort of leading with unmet need.
This sort of gives you the portfolio view, but the next slide I am going to show you is looking at our commitment through a different type of lens, how many dollars we have invested in the particular disease areas. Next slide, please. Putting the portfolio into context where we have committed our resources across all the different blood cancers, this chart shows our historical commitment over time, as I mentioned, is over $120 million, looking at five-year survival for a lot of the large buckets of blood cancers and their annual incidence, which is the size of the bubble. It shows how unmet need really aligns where we put our substantial commitments in diseases where survival is the poorest. Shown here, those areas are AML, MDS, and aggressive non-Hodgkin's lymphoma. This is just provided for context. It is not really a formula.
We are not saying we can only invest in these areas, but this is how it has played out over time, where we have made all our historical investments. Really focusing on MDS, we have invested nearly $120 million in MDS alone in several different companies, including Faron. Behind those commitments are patients that have very limited options. Let me now reframe the unmet need in MDS before we can get to talking about our Faron partnership. Next slide. Earlier on today's program, Amer Zeidan covered the clinical science of MDS in much greater depth from the perspective of physicians who actually treat these patients. My role here is a little bit different.
Just want to explain from our perspective why high-risk MDS is the kind of unmet need, it is urgent, and it is patient-centric that drives us, our commitment to making these types of investment decisions in these blood cancers. High-risk MDS is a disease of older adults. Many are too frail for intensive therapies or transplant. The standard of cares are HMAs, which produce overall response rates roughly 40%, 50%, but only 10% - 16% have received complete responses, and many of those are transient. The harder number is really what happens after you fail the initial therapy. Once HMAs stop working, there is really no approved therapy, and overall survival is only several months. For most patients after they fail HMA, the next conversation is supportive care, not really what is the next therapy they can go after. Underneath survival statistics is really patients' daily lives.
Patients have to deal with cytopenias, transfusions, infections, going back to the clinic multiple times. It is really quality of life in addition to being a survival story. Also there are some adverse molecular subgroups in an MDS, right? We have talked about before TP53 alter disease, these patients fare worst of all. Having therapies that can address these patients is critical. That is really the gap we are looking to address when we evaluated Faron. Before I walk through the partnership timeline, let me first sort of explain how the program fit our mission and development lens. Next slide, please. This slide sort of shows, highlights five reasons why Faron's program fit our mission lens. First, unmet need, as I mentioned, that is the first thing we look for, substantial in both frontline and higher risk failure MDS. Second, there is great science.
There is bexmarilimab targets CLEVER-1, a novel target, unique biology. There is a distinct mechanism involved, especially including with an HMA-based resident in combination. Third, there is clinical data. There are clinical signals from the BEXMAB trial, including some response observations in TP53 alter disease. As we will go through the partnership in a little bit, this has informed us to make several different funding reviews, and we continue to be encouraged by the development and have made three investments in Faron so far. Fourth, development path now includes a randomized follow-up study really to test these early signals. This is always critical as you are moving forward to determine if it has a chance to get towards approvals to see if there is meaningful patient benefit.
And five, we are looking for companies, we see a role for our organization at TAP to help companies through disease insight or providing our patient perspective, getting expert inputs from some of our KOLs and help with development networks. So these are sort of the five areas that we thought Faron fit and happy to go through the partnership in a second with Juho. And really, just to be clear, still bexmarilimab remains investigational. Randomized studies need to be conducted to establish additional patient benefit. So really, let us now go through the partnership to show everyone how it is developed through the time through several different reviews and our stage investment process. So next, I would like to have Juho join me for the next couple slides.
Thanks for having me, Blaine. Happy to be here with you and discuss the partnership. So next slide, please. The audience to really understand how we have been working together and how our partnership has evolved. So it actually all began in 2022 when we were wrapping up our first-in-human trial with Bex in solid tumors. And the most important learning out of the first-in-human was that those patients benefited who had a CLEVER-1 positive macrophages in the tumor microenvironment. So we screened a lot of databases, and we learned that AML and MDS, basically everybody is CLEVER-1 positive, and that is an area we need to move into. But we had limited experience in the Heme space, so that is when we reached out for the first time to Blood Cancer United and started the dialogue.
Yeah, exactly, Juho. And it is interesting, so that is when we made our first investment in June of 2022. I actually looked back this morning, and I found that we actually first connected at a JP Morgan conference in January of 2021, during COVID. So we actually worked and engaged with Faron for over 18 months, looking at a strategy, the data, connecting the experts, and ultimately, given all that preclinical data and rationale, like Juho mentioned, especially moving into AML and MDS, we made an initial $500,000 investment, took Faron through the entire stage diligence process. This is one of our few investments made coming out of COVID, when dollars were limited. And that investment helped support expansion of the existing MATINS trial, going into AML now and high-risk MDS and helped support clinical protocol development.
Yeah, and ultimately, that initial investment then that resulted in the BEXMAB protocol, and then early on, already in dose escalation. In phase I dose escalation, we saw very strong signals and blast reductions in relapsed/refractory patients, where usually you do not see anything happen, and we were seeing this. And again, we sat together and, "Hey, we need to move on to the phase II part," and we needed further investment. So comes up to 2023 then.
Yeah, exactly. When we made the initial investment in June, obviously, we were collaborating together, we were following the data. I have to say, from being in the organization for quite some time, making a subsequent investment, we have done several times, but doing it within seven months later, that sort of goes to show that the company is able to execute. All those early signs are really promising. So we took through our stage due diligence process again, and we took the company, Faron, had to present in front of a TAP committee and get approval. We ultimately, yes, we agreed to do a larger investment this time, another $3 million, to help support part of the BEXMAB study and also to start enabling expansion into the U.S. sites, where we think TAP could be helpful given our network and experience.
Yeah, it was very essential because that way we were able to expand to the U.S., get more sites, get things going for the phase II part, and execute on the phase II part. Ultimately, the phase II then confirmed those early signals seen in phase I, which then led to a successful end-of-phase-II meeting with the FDA in the fall of 2025.
Exactly. We were following all along and very excited to hear the engagement with the FDA and coming up with plans to move forward. Based on that meeting, we again brought our. Sometimes we bring portfolio companies to the TAP committee to give them updates on how things are going. Thinking things are going really well. They are engaging. They are developing a plan to move forward. We were discussing the registration study. So both our TAP team and the committee expressed continued support for another investment in the near future. We would continue to follow the data and development plans. We knew the company was preparing to present some data at ASH, so we were looking forward to getting those updates and hearing more about their plan. After those checkpoints happened, the ASH data came out. The company came up with a financing plan.
They revised the plan. So we brought the opportunity back to the committee. The committee was supportive again, and we made a third investment of EUR 3 million as part of Faron's financing at that period to finance the randomized BEXERA trial.
Exactly. This is how I see that what we're looking at in this slide and in this four-year period, Faron emerged as the leading company in high-risk MDS. How would you, Blaine, summarize this?
Yeah, I have to say, it's really been a wonderful partnership as the years have progressed. It really reflects sort of the continuity over these different columns showing here. 4 years of collaboration, successive reviews of encouraging data, the development plan moving forward, execution. This has led to different investments. Every milestone along the way has given us the opportunity to evaluate the science. How's the Faron team executing the plan? What's the path forward? It was never just really about a single check. It's really about the relationship with the company, and it deepened as the data matured.
Yes. We thought also it would be then beneficial that we will talk a little about, what actually in practice does this mean? How do you work, not just with Faron, because this is not just about Faron, it's the amazing work that's being done in Blood Cancer United. How do you work with companies actually in practice? Again, it's with us, but also with other companies. Could you explain?
Yeah, exactly. This is a really important piece. We're just not giving dollars and checks out and just waiting to see what happens. We want to work and find companies that want to collaborate with us, and we really think that our organization and TAP brings a more partnership and a value add beyond just the dollars. It's really about the continuing collaboration with whomever the biotech partner is. This is where our value proposition really becomes a little bit more concrete. For every partnership we form a research advisory committee. We form it between when we make our first investment.
It's a really structure that's put in place so that we can have recurring dialogue all throughout the year, typically quarterly, both virtually and in person as possible at some of the scientific meetings, really to touch base to make sure we're assisting the company however we can. Every company's a little bit different. Some need more expertise on the science side, KOL connections, others might need me more business development side.
Absolutely, and I think one of the key things that really differences or sets Blood Cancer United and TAP apart from anything else that I've seen is actually your engagement and network to leading U.S. KOLs and sites. You can really tap into the best minds of the field, and then companies can benefit from that for you. I think that's the real key, how you differentiate and your uniqueness.
Exactly. As I mentioned, we engage KOLs in several different ways. We utilize some during our review process, as we do with every company. Some of the KOLs may be more experts in the target area or the particular disease or development plan. Once we become partners with companies, we can help convene the right voices, clinical voices around trial design, endpoints, selecting patients, and those types of things. We've organized events at ASH, bringing in KOLs to meet with companies. We've made specific introductions to companies, saying, "Hey," and hearing from us, is an easier connection from a company just trying to reach out to some expert they want to connect with, right? If it comes from us say, "Hey, we know this company. They're doing really great things. They had a presentation at ASH. Maybe you weren't able to see it.
What do you think about it?" All the times the KOLs are like, "Hey, this looks really great. Put me in contact with the company," and maybe they become a site, maybe they become an advisor, or maybe just someone they can sort of bounce some ideas off of. It's really been a wonderful collaborative aspect that we bring to all of our partnerships. Not only like KOLs, we have other resources within our organization, like Blood Cancer United. We have a clinical trial support center, for example, where nurse navigators, we have almost 20 of them. They speak directly with patients and caregivers. They're always looking for what trial are they eligible for. Are there slots open and access, how do they get access to these sites? Are there any barriers to enrollment?
We always encourage our TAP partner companies to speak with the nurses, give them the most updated information about the trials, what's going on, so that obviously the trial support center is. Their job to put more patients on clinical trials than people can get, because we all know these are all much more beneficial than just going on the standard of cares in many of those cases. It's really the patient-facing perspective that we can bring for companies, helping refine their clinical development plans, enrollment strategies, and obviously, moving forward with companies that are getting closer to the finish line, discussing their registration strategy has become a really a great discussion point between us and the TAP partners.
Absolutely. Maybe just to sum up what I see here, and again, it's one of the specialties of Blood Cancer United and TAP. There's this very operational side. We're working together even on a site's KOL level, meeting frequently on an operational level. But then there's, again, the TAP committee that makes ultimately the investment decisions. Through a continuous operational partnership, we've then repeatedly gone back to the TAP committee, keeping them up to dated on the evidence as it's building up, on the development plan as it builds up, which has ultimately led to this, I would say, amazing and very flourishing partnership.
Yeah, exactly. We make the investment, but our role really is to help collaborate, advise, and convene whatever the companies need. The company, Faron, in this case, they own the program. They make their decisions. We're just the advisors. We're not taking board seats and those types of things. That's how we do this all sort of our collaborative research advisory committee model, trying to make those connections. Even as beyond them, we've done connections with companies sort of on the business side, introducing them to other investors. Our organization works with many of the large pharma companies. We can try to make introductions and those types of things. We kind of bring a full engine to all these partnerships to try to obviously bring the science forward and impact patient lives as best we can.
Wonderful. A true partnership, if I may add, in its truest sense.
Yeah, exactly. That is what I always like to talk about, our TAP partners. We always say TAP partners. It is a partnership. If there is a company that wants to take our money but do not really want to work with us, that really works for our model, right? We really want to be very collaborative and true partners with it. We are contributing just alongside our investment, which is a sort of unique angle was how venture philanthropy should work and how we operate.
Thanks a lot, Blaine. Let us move on to the next and last slide and you can wrap it up. Again, amazing work. We want to raise awareness of this work that Blood Cancer United is doing. Over to you, Blaine, to wrap it up.
Thank you. Yes. First, thank you for the opportunity today. Just a couple take-home points from today. Blood Cancer United, our organization really exists for patients to cure blood cancers, improve the quality of life for patients and their families. Our venture philanthropy program, TAP, can help accelerate mission-aligned innovation, providing capital plus expertise and collaboration in a patient-centric perspective. Third, high-risk MDS remains a major unmet need. There are new therapies needed for patients. They need more tolerable therapies, more effective therapies, and to be tested in rigorous studies. Fourth, Faron is a current TAP partner, that this program aligns with the MDS unmet need, has unique biology and unique mechanistic rationale, and it has got the clinical data so far that is very encouraging and a promising clinical development path moving forward. It fits all the checkboxes.
If you really take one thing away, our MDS commitment runs from starting from the bench to some early science to bedside and patient access and Faron fits all those boxes and really sits inside of all that. Shown here today, really wanted to acknowledge some of our supporters. We have been looking for supporters to help financially provide dollars to TAP to make additional investments and to grow our program. I want to acknowledge a recent partnership with Royalty Pharma and a couple foundations, the Butler Family Foundation, and also Blood Cancer UK. They are all our supporters now. They are helping to expand our reach and impact, fueling our growth, and trying for our TAP program to become a self-sustaining venture philanthropy. The goal is simple, to help move promising science to patients who urgently need better therapies.
Thank you very much for the opportunity to present today.
Thank you, Blaine. Awesome work. Just checking any questions from the audience to Blaine or shall we let Blaine go?
There are few questions for Blaine. There is sort of discussion that how do you see the data as overall? How would you describe the data? How promising is the data which we have seen so far?
I am not going to speak about the data today. Obviously, I think from my perspective, the TAP program has made several investments in the company. I think that is a sure suggest that we are encouraged by the data and looking forward to the registration study starting.
Thank you. There is the second question about TAP philosophy that do you support broad range of programs hoping to find one that will make the change, or are you very selective doing with these investments and you need high level of conviction?
I think if I understand the question right, when we make investments, we're very selective in programs. They have to check off a lot of the boxes as I sort of discussed before. We're really looking for high conviction programs and for us to make a subsequent investment in the company. We're not like another investor and we just keep pouring dollars into a company, just to maintain our shares and our levels on the cap table. We only make investments in the companies where we feel like there's a forward momentum in blood cancers to justify an additional investment.
Thank you. That was the last question. Over to you, Juho.
Okay. Thank you, Blaine. We're up on time, so wishing you-
Thank you.
A wonderful day. I think we are up to the break. We will now again align our timetable with another external expert coming soon. We will now have a 20-minute break, so continuing 16:45 Finnish time, 15:45 Central European time. Thank you and see you soon. Welcome back, everybody. I hope you had a good break, a fresh cup of coffee. Next is what else is happening in Faron, and here to tell us all about it is our Chief Medical Officer, Petri Bono, on pipeline review and ongoing other trials. Over to you, Petri.
Thank you, Juho, and good afternoon, everyone, and good morning to U.S. Really delighted to tell about our pipeline review. Let us start. Progress recently, and this is the current pipeline. You can see the second trial is BEXMAB, where we already a year ago stopped enrollment of new patients. Good to remember that although the enrollment is closed, the study data continues to mature. We released in July newest OS data to the market, and in an upcoming major hematological meeting, we will then present the newest data in more detail. Then Amer Zeidan presented the design of the BEXERA trial that is in the treatment-naïve, higher risk MDS patient population. We are on track. We have earlier told to the market that the study will start enrolling patients in Q4 this year, and we are on track with that.
Very excitingly, we have BLAZE and BEXAR that are not anymore just in planning. Both are up and running, both have received all regulatory approvals. Actually, we have released to the market also that first patients have already been enrolled to both BEXAR and BLAZE. In BEXAR, it is metastatic soft tissue sarcoma, and we will hear today more in detail about it by the study principal investigator, Dr. César Serrano from Barcelona. Then I will update the BLAZE situation and BLAZE design. BLAZE is a trial where we try to overcome secondary resistance to PD-1 inhibitors in metastatic melanoma and non-small cell lung cancer patients. What I am so proud to tell you, actually, that today we received information that the first cohort in BEXAR, that is fully enrolled, and the second cohort has been opened for enrollment.
In the BLAZE, we have already two patients that have started on their treatment, one in London in Royal Marsden Hospital and the other one at the Christie Hospital in Manchester. Both trials in solid tumor, these investigator-initiated trials, they are also progressing very nicely. As mentioned, BLAZE and BEXAR, they are not just anymore first patient in but up and running. When they have had so good and strong start, it means that we can expect to have results from this trial at H2 2027 next year from the first part of the trial or first stage. Then we have also another two IIT trials that are progressing also the preparations. The other one is the Nordic AML trial, BEAM trial, that is led by Dr. Mika Kontro from the Helsinki University Hospital together with The Karolinska Institute.
It's bexmarilimab plus azacitidine in MRD- positive AML patients after transplant. That trial is currently at the submission stage. Then the other trial that is an investigator-initiated trial run in California, the City of Hope Comprehensive Cancer Center, that's in relapsed and resistant MDS patients combining Bex for the first time with an oral agent. This time it's INQOVI, that is a combination of decitabine plus cedazuridine. These are progressing. We are finalizing the full protocol with the City of Hope trial and then the other one, BEAM, to be submitted extremely soon. Then couple of words, what's the rationale actually behind these IITs? We'll go a little bit more in depth into that. Let's start what we have learned from MATINS trial. As a reminder, MATINS was a single agent bexmarilimab treatment for patients with advanced metastatic solid tumors.
At that time, when MATINS was started, I was working still at the Helsinki University Hospital Comprehensive Cancer Center and had the privilege to be the global PI of the MATINS trial. Altogether, 216 patients were enrolled to the trial from various large European cancer centers, and we got lots of learnings from the trial. First of all, good to remember, patients were really late-stage patients. They had received a median number of previous treatment lines of three before entering the trial. It wasn't a frontline metastatic trial at all. Why this is important, when we're talking about novel immune oncology agent, you need also to have good immune system, so that immune system shouldn't be too exhausted to get the benefit from IO treatment.
In that way, MATINS wasn't the optimal setting, but this is always how it goes with first in human trials, if late-stage cancer patients are enrolled. What we were able to show, actually, in these MATINS patients, that we were inducing macrophage activation that was leading to treatment benefit in solid tumor patients. We observed that with some cohorts in 25%-35% percentage of the patients, including liver, gastric, melanoma patients that were benefiting from the treatment. We also learned that targeting CLEVER-1 with Bex is extremely well-tolerated. The rate of immunological adverse events were extremely low, and also the rate of any treatment emergent adverse event was not either high, and treatment-related adverse events. We only had in less than 10% grade three or higher treatment-related adverse event.
Then we were able to show that it is realistic to get a disease control in late stage cancer patients with single agent bexmarilimab treatment. Very importantly, we were able to show that low baseline immune activation is associated with bexmarilimab treatment benefit. Why this is important, those patients who have low baseline immune activation status are typically patients who do not respond to PD-1 inhibitors. Also we were able to show in the translational studies that Bex converts intratumoral macrophages to support adaptive immune responses. Also, based on the translational results, we were able to show that we have a good biomarker candidate that is the intratumoral CLEVER-1 positivity by immunohistochemical staining.
When we talk about checkpoint inhibitors within solid tumor patient treatments, it is important to remember that although there has been a lot of bustle for the last 10 years, how they have transformed the treatment of cancer. Actually just 20% of the patients do respond to checkpoint inhibitors. On the right side of the slide, this is from a Lancet review. You can see that the reasons for that, the mechanisms of resistance. There are several mechanisms, and actually many of these are related to the macrophage function. On the left side, we can see how many patients actually respond to checkpoint inhibitors. You can see that for example, Hodgkin's lymphoma, melanoma, they have 50% or more of patients who do get benefit from PD-1 inhibitors.
But on the lower side of the left side figure, you can see that these big tumor types like liver cancer, colorectal cancer, ER hormone receptor-positive breast cancer, actually it is less than 15% who get benefit for PD-1s. From the patient's perspective, there is really a lot of need for further improvement of the treatments. What do we know about CLEVER-1 mRNA expression and its association with survival of patients from large databases? On the left side, you can see Kaplan-Meier survival curve that shows that CLEVER-1 or the mRNA coding for that STAB1, so the expression level. It is associated among all cancer patients with worse prognosis. The high CLEVER-1 patients shown in red. Their Kaplan-Meier curves are clearly inferior to the blue ones who are CLEVER-1 low. On the second panel from left, you can see separated IO therapy-treated patients.
The difference is even higher there, so that the ones who are CLEVER-1 high, they are actually the ones with the worst prognosis. On the right side, we have also done a split between the IO treatment between PD-1 inhibition and between CTLA-4 blocking, and the same result holds true there. I would like to spend a little time with this slide that is taken from a very elegant Chinese paper that was published last year in the Journal of Immunotherapy of Cancer. This is one of the good reasons why we want to study in solid tumor clinical trials the combination of Bex, for example, with PD-1 inhibitors.
Maija has shown earlier mouse tumor work also supporting that, but this is an external validation from gastric cancer patients and gastric cancer data showing that CLEVER-1 expression is actually related to clinical resistance to nivolumab. It is related to CD8+ T cell functioning and also related to tumor cell killing. On the left side, the patient numbers in that paper were still fairly small, but patients were treated with a combination of 5-FU plus oxaliplatin plus nivolumab. Gastric cancer patients. Not all patients do get a response. When the tumor-associated macrophage infiltration was analyzed, the responders versus the non-responders. Non-responders in orange. They had much higher CLEVER-1 positive rates than the responders, indicating that CLEVER-1 expression is really related to the treatment resistance to a PD-1 inhibitor.
In the middle graph, what they did, they actually isolated tumor cells from gastric cancer tumors and put them on a Petri dish and then treated those cells either with control antibody, nivolumab, PD-1 antibody or with anti-CLEVER antibody or the combination. As you can see in purple, the combination. The dual blockage, it produces the strongest interferon gamma response in these tumor-infiltrating CD8 + T cells. This is a really good rational interest. A single agent anti-CLEVER-1 antibody was at least as efficient as nivolumab, if even a little bit better. The same direction or trend can be seen on the right panel also. This was not measuring T cell reprogramming. The right panel is measuring apoptosis. Tumor cell killing and how that is enhanced best in CLEVER-1 positive tumor microenvironment, high tumors with the combination.
In summary, this elegant Chinese work makes a really good rationale to move forward also with the patients. Where are we actually, and how do the IITs look like? BLAZE. BLAZE is a melanoma, non-small cell lung cancer study in second-line treatment after the patients have failed their frontline checkpoint inhibitor or PD-1 inhibitor therapy. It is testing whether addition of bex can overcome the secondary resistance of these patients. In order for a patient to be enrolled to the trial, they need to have received PD-1 inhibitor, get a response to that, and then before entering, they need to have received the latest PD-1 treatment within three months. This is a phase I, phase II investigator-initiated study, where the part one will include approximately 10 - 12 patients, and the part two will then include 25 melanoma patients and 25 non-small cell lung cancer patients.
The primary objective is safety and overall response rate in this trial. With re-challenge with the PD-1 inhibitor, for example, in melanoma, you do not expect more than 5% response rate there. Within the first 10 patients, even one response would mean a green light to proceed to the phase II part of the trial. Then BEXAR. This one I will do very shortly since César will go through. Just want to highlight that by purpose, this is in frontline patients. In frontline because the immune system of the patient is optimal to be treated with bexmarilimab. This trial, it is a combined phase I-B, II trial, and the first phase I-B trial will include up to 46 patients with PFS and safety as primary endpoints. Then the City of Hope trial, which is extending BEX evidence to an oral hypomethylating agent backbone.
The rationale, of course, from BEXMAB, we know that combining BEX with azacitidine, it has really encouraging efficacy. But at the same time, we know that oral use of HMAs will be increasing. With BEX, of course, we will need evidence that its activity can be translated from IV or subcutaneous AZA also to oral agents such as decitabine, cedazuridine or INQOVI as a brand name. This trial has 34 patients that are planned. It is an open-label, phase II investigator-initiated trial that will be run in the network of City of Hope. They have satellites elsewhere also in the U.S. in a couple of major cities. The primary objective of this trial is to measure OS rate at 12 months and also overall response rate.
As we know when patients fail HMA in frontline, basically you do not get any responses, or it is again less than 5% of the responses. The overall survival rate at 12 months, we talk typically about 25%, and the plan is to increase that from 25%- 50%. BEAM is a setting that we have a low disease burden that will allow BEX driven immune and hematological effects to be detected before an overt disease relapse, so that patients after transplant, AML patients, when they become MRD positive with sensitive measures, they will receive azacitidine plus BEX in an open label phase II investigator initiative trial. Planned trial size is 24 patients, and the primary objective is MRD negativity at 24 weeks. This was my last slide about the pipeline and the activities related with these trials.
Really proud what kind of progress we have been doing for the last couple of months with these ones and by purpose did not touch too much today the BEXERA trial since that will be presented by the next presenter, Dr. César Serrano, who is a Group Leader of the Sarcoma Translational Research Program at the prestigious Vall d'Hebron Hospital in Barcelona. Cesar is also an ESMO faculty member also this year at ESMO in two weeks leading sessions there as a moderator and has been long involved with both translational and clinical research of sarcoma treatments and certainly represent a true key opinion leader within Europe in this disease type. Without further introduction, Cesar, please, stage is yours.
Thanks so much, Petri, for your very nice introduction, and hi, everyone. Over the next few minutes, my idea is just to transmit you why it is important to target CLEVER-1 in patients with sarcoma and why I think this is a low-hanging fruit. Maybe you have heard before, but CLEVER-1 is a type of a protein that is mainly and basically uniquely expressed in cells of myeloid lineage. In physiological conditions, CLEVER-1 has multiple functions that help the body. But the problem comes when there is a context of a tumor type where it actually promotes tumor growth, mostly through altering leukocyte trafficking and inhibiting T cell activation, basically stating an immune suppressive microenvironment, which is, you may know already, that it is pro-tumorigenic.
What is known already quite well is that high CLEVER-1 expression in cancers is associated with poor prognosis, and also it contributes to tumor resistance. This is based on clinical studies making association between expression of CLEVER-1 protein, STAB1 gene, that is the same as CLEVER-1, and a patient's outcomes. Next, please. The fundamental for working on a STAB1 gene inhibition or CLEVER-1 protein inhibition in sarcoma is actually very rational. What we did at some point was to study across all the tumors that have been profiled under the TCGA is to check for the expression of STAB1 gene that is responsible for CLEVER-1 protein expression. We observed that among solid tumors, basically sarcomas is the second, together with mesothelioma, there's two first, and with a big range of expression of STAB1 gene, which establish a very nice and interesting rationale for targeting STAB1 in sarcomas.
It also comes under another observation for many papers published in the field in the recent years. Basically, the main immune infiltrate that we have in sarcomas are macrophages that promotes a tumor microenvironment that is immune suppressive. So it's quite well connected, this immune suppressive microenvironment in sarcomas with a big predominance of macrophages together with this high STAB1 gene expression. Next. There are multiple sarcoma subtypes you'll see in a minute, but these six that you can see here are basically the most common sarcoma subtypes representing up to 80% of sarcomas. We could observe in this same study, preliminary study of RNA expression of STAB1, that there are differences in this STAB1 expression across the different sarcoma subtypes. Basically the three in your right are those that express more quantity of STAB1 gene.
Basically these three subtypes are the most common sarcoma subtypes that are typically treated by chemotherapy in our daily routine clinic. These findings are actually foundational for what is going to come in the trial design that I will speak about to you in a minute. Next, please. What are sarcomas? Sarcomas are tumors of mesenchymal subtypes, 150 tumors of mesenchymal origin. The big problem that we have with these patients is that the main treatment is for localized disease, surgery, perhaps radiotherapy too. Then when disease is metastatic, is that occurs in more than half of the patients, we've been treating these patients the same for the past three decades. Basically, doxorubicin, anthracyclines, the most typical, common one that everyone knows.
The problem with the doxorubicin is first, the activity is relatively modest, with an overall response rate of 10%-15%, median progression-free survival of around six to eight months. The very last two clinical trials challenging doxorubicin as single agent that you can see those in the table up in the right, basically, just they were negative for the endpoints, which transmit us first that they weren't the right combinations, but it's feasible to do in the sarcoma community, trials challenging the doxorubicin first-line combination. There are a big array of sarcoma subtypes that can be treated with different type of somewhat specific drugs against those subtypes, but we don't truly have a biomarker that can direct all these different TKIs or agents that you can see in the table bottom right, linking those with subtypes.
We have big troubles in treating these patients, and we haven't improved outcomes of sarcoma patients, again, for the past two, three decades. Here, this is the mindset why targeting CLEVER-1 in sarcomas is such a low-hanging fruit. First, because of the rationale about CLEVER-1 that you heard before, is the solid tumor with the highest expression with some specific sarcoma subtypes that we know that they express more, a STAB1 gene expression, and that they're actually the most common sarcoma subtypes. And other that, in the second part, is that these patients have poor outcomes with drugs that are the same for decades, and that they have a very, very modest activity. Why combining then chemotherapy with bexmarilimab? Well, there have been few clinical trials, two, three clinical trials combining chemotherapy with checkpoint inhibitors that has shown very limited efficacy in soft tissue sarcoma.
Basically, because as you've seen before, the microenvironment is already quite immunosuppressive for PD-1 inhibitors as monotherapy or in combination to help to do any type of effect. Also, we know that chemotherapy can prime tumors for immune responses and upregulates already CLEVER-1 expression. You'll see that in a minute. There is this strong biological rationale that combining cytotoxic chemotherapies with immune therapies may offer maximization of the therapeutic response and improve patient's outcomes in the short term. Some data that I wanted to share with you regarding some of these affirmations I just made. First is that CLEVER-1 blockage in combination with chemotherapy can have a broad potential, and sarcoma is or can be one of the main paradigms.
We know that, as there have been many reports already that chemotherapy and many types of chemotherapy can actually increase the infiltration of STAB1 expressed in macrophages, which actually leads to a more tumor immune suppressive tumor microenvironment. Then there is also some other clinical data, as you can see in the upper part first, that high STAB1 expression after neoadjuvant chemotherapy in ovarian cancer decreases patients outcomes. And in the lower part, you can see the Zhongshan cohort from Shanghai in China, which finds that actually, CLEVER-1 high expression in the tumor microenvironment infiltration is associated with poor outcomes, regardless of the stage of the disease in gastric cancer. We also have some data from in vivo studies performed in different types of mice. But basically, here, what you can see is the feasibility, first, of combining chemotherapy, in this case, 5-FU with bexmarilimab.
Second, we can see actually the analysis of how the addition of bexmarilimab to the chemotherapy improves the tumor microenvironment, the infiltrate, making it less immune suppressive, and it can be, it was assessed in the left, you can see by flow cytometry in the blood, and then in the right within these knockout mice. We have this proof of how, first, this occurs in patients, the increase of a more immune suppressive tumor infiltrate mediated by macrophages expressing CLEVER-1. And second, that the combination of chemotherapy plus bexmarilimab is feasible, and then it rewires the tumor microenvironment.
Altogether, the evidence in sarcomas about CLEVER-1 expression, the knowledge about chemotherapy inducing CLEVER-1 and this in the clinical amendment, actually, that we have in sarcomas and the feasibility to do these trials led up to this phase I-B, phase II trial that we have currently active in Spain. Here, what we are combining is studying the combination of first-line doxorubicin, so doxorubicin with bexmarilimab. We have first, and this is what we have ongoing now, the dose escalation, which is followed by a dose expansion, and then if this is positive, the endpoints that we've set, we will follow by a phase II randomized clinical trial. Basically, in the dose escalation now we just opened the second cohort of the escalation. We said doxorubicin 75, this is the standard dose. Why?
Because as you've seen before by Petri and others, the tolerability of bexmarilimab is wonderful, actually. It makes this easy to combine, and we establish the dose as the standard one with increasing levels of bexmarilimab. Once the dose escalation is over, we will start with the expansion and later with the phase II. In this expansion, basically, we will allow only the soft tissue sarcoma cases that were included in the TCGA. We have a control about the potential expression of CLEVER-1 and the activity that these patients will have with the combination. We have a cap design, so we will be able to have, despite relatively modest numbers, some very interesting data about the activity.
If this is positive, we will move to a randomized setting with basically the same design, and these are six cycles of doxorubicin together with bexmarilimab, and then followed by bexmarilimab after doxorubicin is finished. The endpoints are basically the typical ones about MTD tolerability and those about efficacy. For the phase II, of course, it will be PFS. That is such a very common endpoint and objective for sarcoma trials. Next. This is the clinical trial. We are actually in the finishing line of 2026, and we already included three patients in the trial in the first dose level. We cleaned it up, and now we are starting the second dose level. Already three slots has been able. Investigators have applied already to four slots. We are recruiting very rapidly, and we aim to have initial results around April, May of the next year.
Very rapid results, but this is actually what we want to move on this trial, that we aim also to squeeze this time, but probably by the beginning of 2029, we will have the full data set that will be moved towards the phase II trial. The timelines are being committed. The investigators here, we are very excited because this is such a rationale behind this clinical trial, and also, we think that we may have, finally, a compound that can challenge, in three decades, doxorubicin, a single agent, a standard of care in sarcoma. Thanks so much, and happy to take any question.
Thank you, César. Fantastic progress. First cohort already full. Time to take some questions. Do we have any questions online?
Thank you, Petri. We have a few questions. After years of working in sarcoma research, what gives you confidence that targeting CLEVER-1 with bex may succeed where many previous approaches have delivered only limited benefits? What gives you confidence?
Thanks for the question. What gives me most the confidence is that soft tissue sarcomas are the solid tumors with the highest expression of the STAB1 gene. There is a strong, sound biological rationale that we actually lacked in the past. Prior combinations with avelumab, we never had a biomarker there. Other chemotherapies, we never had biomarkers there. Even PD-1 inhibitors in small trials, we never have a true biomarker there. Here we know that, especially some entities that are those sarcomas with complex genomes that are actually the most common, they do express very high levels of the STAB1 gene. This is what gives me most the confidence, the biological and sound rationale behind.
Thank you. Next one. What would be clinically meaningful improvement over historical outcomes seen with chemotherapy alone that you would like to see in this combination treatment?
May I add a little bit, César? In the phase Ib, in the dose escalation and dose expansion part of the trial, not the latter part, the randomized part, but what would you consider a very positive result in the phase Ib part?
There are two positive results. I am saying that because of the response rate. Sometimes we pay attention to response rate that is quite low, 10%-15%, with doxorubicin as a single agent. Something that we can even close to double, like 25% of response rate, will be high. Just imagine that 25% of response rate is we can make it with the combination of doxorubicin and ifosfamide in some settings with two chemotherapies. That will be a good one, but I am saying that we have a double expectation because immunotherapy, what we know in the field is that there is established a long delay for coming back the disease. If we move from six, eight months of PFS to something like 12 months, one full year, that will be already a lot.
That will be a lot, because these patients, they progress quite rapidly. Again, PFS is a very common surrogate marker for overall survival in sarcomas, widely accepted by regulatory authorities.
Thank you, César. No further questions on this point.
Okay.
Thank you.
Thank you, César, so much.
Thank you.
This was a brilliant presentation. Finally, one comment. You will be presenting at ESMO, Trials in Progress poster about bexmarilimab in Madrid in ESMO.
The same here. See you in Madrid soon. Bye bye. Thanks so much.
Next, we're going to move forward with our program, and it's about bexmarilimab market opportunity. Ralph Hughes, our Chief Business Officer, will go through this market opportunity with you. Ralph, please.
Thank you very much, Petri. Thank you. Thank you for having me today. I wanted to spend a little bit of time today talking about the bexmarilimab market opportunity and how Faron sees the market opportunity for Bex as we move forward through the trials towards launch. The MDS market is expected to grow significantly in the coming years. This is being driven by multiple factors. First of all, and probably most importantly, an aging population. MDS is a disease of older patients, and that's important because it sees the population growing in Western markets. We're also seeing growth come from the launch of reformulations of azacitidine, reformulations of decitabine, but also from drugs in the lower-risk MDS market.
However, all of this and these market projections are probably a significant underestimate of how the market will grow in the coming years because it doesn't include the enormous potential of something like bexmarilimab coming into the market and seeing that market grow in a very significant and disruptive way. As we've heard many times, there have been no new treatments in this indication for the past 20 years. However, for the first time in a long time, we are now seeing multiple assets in early clinical development for higher-risk MDS. Many of these assets are, however, using previously failed modalities, such as BCL-2 inhibitors and CD47s. Faron is actually one of the only assets that's bringing novel biology and a new biological approach to this space. It's not just the new biology, but it's Faron itself.
By observing and learning, we are able to advance our clinical program considering really important factors, such as understanding how to deal with TP53, how to adapt the clinical trial numbers as a result of various interim analyses, and how to make sure we hit the right endpoints to meet the needs of our development plan. We at Faron are viewing higher-risk MDS as the new multiple myeloma, an area of developmental difficulty that is now delivering excellent returns to investors, delivering drugs to patients. We really see bexmarilimab as the head of a wave of new and exciting innovations in this space.
Now, I thought it would be really important to just spend a little bit of time understanding how at Faron we understand the market potential for bexmarilimab when we come to launch, and how we believe that the conditions are incredibly favorable for Bex when we bring it to market. Drug pricing. This is a topic that is in the news a lot, and it is something that we spend a lot of time thinking about what will happen when Bex comes to the market. We have done extensive qualitative and quantitative research, so much of what I am about to talk about is based on that, but there is also additional lots of publications out there around things like this as well.
In terms of pricing, there are some established benchmarks in the field, such as Onureg, which is an oral azacitidine, which is essentially a branded oral version of an HMA, and that is priced around $25,000 per month in the U.S. That is about $300,000 per year. We also have Rytelo and Reblozyl, both assets in the lower-risk MDS space, and they are also priced similarly. When tested with U.S. payers, they will view these as something of a benchmark or an analog for our asset. However, in both of these situations, these are. In the Onureg situation, this is a reformulation of an existing asset. In the lower-risk MDS, these are drugs to treat anemia, not treat the underlying condition, and are therefore not disease-modifying. They are also launching into an area where there exist treatments already.
Potentially a better analog or an analog that is on a lot of people's minds at the moment would be Rasonk in the very, very high unmet need pancreatic cancer. This is an area where there has been no new launches for a long time, extremely high unmet need, and here we see pricing of around $40,000 a month, which equates to about $420,000 per year in the United States. Another question that we get a lot, and that I think is very interesting, is epidemiology. As mentioned before, high-risk MDS and MDS is a disease of older patients. I think Amer earlier today said it was in patients around 70 years old. That really matters because when we are talking about epidemiology, a lot of the published figures that are used very frequently are quite old, and therefore do not reflect the demographics of an aging population.
Certainly in Western markets, the U.S. and Europe, we see the population aging, and as a result, the incidence is increasing of MDS. We did some internal analysis. We looked at all the publications out there on this, or the most commonly cited publications out there, and we updated them using today's demographics. Then quality control took the most appropriate publications. Here we end up with epidemiology of around 5.3 per 100,000 incidents in the U.S. and 6.3 per 100,000 in Europe. In terms of uptake, we did extensive qualitative and quantitative research. As a result of that research, we believe and we are predicting in our various models a very rapid uptake of around four to five years and with a very high uptake in the region of 60%-70% of the market share.
A very significant opportunity and a very favorable opportunity for Bex when it ultimately comes to market. The opportunity doesn't just stop there with MDS, as we've heard from Petri and Dr. Serrano. We're also seeing massive potential to be unlocked by Faron as a result, or by bexmarilimab, as a result of the additional studies that we're running. Soft tissue sarcoma, probably a population size not too dissimilar from higher risk MDS and a potentially quite similar market opportunity. We've also got PD-1 refractory melanoma and non-small cell lung cancer, which potentially have much bigger market possibilities as well, both in terms of patient population and in terms of the dollar value of the market size as a whole. If we zoom the camera back a little bit and look at the biopharma deal-making sector as a whole, biopharma had a really tough year in 2024.
In 2025, we saw a bit of a rebound back to kind of normal levels of capital inflow and M&A. In the first half of this year, 2026, we saw capital flooding back into the biotech sector. It's a good sector to invest in right now because of all the M&A that's going on at the moment. In the first half of the year, we saw an absolutely bumper year in terms of that. M&A is strong, deal-making is very active, and we're ready to take advantage of that when the moment comes. We see this as a really very exciting opportunity in terms of the market potential of bexmarilimab. Thank you very much. Over to you, Juho, to take us out.
Let's have a little Q&A, just you and me, buddy, because this is a great slide. I go out a lot to meet investors and see where the industry is. It seems to be thriving, and it's beating general markets. The biotech market sector has been growing while other markets have been suffering from the geopolitical stuff going on. Biotech has kind of been protected from that for some odd reason. How do you feel about that?
Well, I think it's interesting. We look at 2024 as it was a very rough year. I think that meant that there was quite a bit of dry powder still around. Therefore, there was a lot of activity and a lot of hunger to do a lot of deals. I think there was also potentially some of the companies that couldn't survive probably went under. We saw the cream rising to the top, I suppose, the better companies or the companies that really have true value to add surviving. I think that's a large part of why we saw such an extraordinary amount of M&A happening in the first part of this year.
Wonderful. Thanks. Another question or topic I really want to a little bit dive into, which I've seen in the past, especially from a kind of physician lens, is that when you go into an indication where there's really not much available, like high-risk MDS, especially relapsed refractory MDS, where there's and people are even left without treatment or without diagnosis because there is simply nothing. How do you feel is that somewhat reflected in your numbers or our numbers, or how do you see the RR in frontline populations? Are they underestimated possibly?
Yeah. A brilliant question. I've spent a large part of my career both at Pfizer, Mundipharma, and PharmaVentures modeling indications and trying to figure out the distribution between different indications and sub-indications and how different launches at different times affect these things. I think you raise a really good point. I think when you have an area of very high unmet need, what you often then see is clinicians very keen to use the medicine that is new and that is coming into a market. So in a situation like this where we have a relapsed refractory population and a frontline population, one would predict a heavy overlap between the two. If you have an approval in one indication, and it's very close, you would expect a certain amount of cannibalization of one indication from the other, a massive amount of overlap into the other indication as well.
Yeah, I think generally estimations are probably an underestimation in this space. We've seen it time and time again, when you haven't had anything, and you have all this pent-up enthusiasm, I suppose, from clinicians to use a drug in a space. Yeah, I think that's part of the reason why we had such strong feedback during our quantitative research. Actually, the numbers that we're predicting are slightly lower than what the KOLs wanted, because we're trying to be a little cautious.
Realistic cautious.
Realistic cautious, yeah. I think for us, it's important to be a little conservative. But yes, I would say this is probably an underestimate.
Wonderful. Thanks a lot, Ralph. Thanks for being here. And on we go. If you've made it almost to the very end, this is how I boil all this down. We've seen a lot, we've heard a lot, but I'm a simple-minded guy, and I think the first question is, well, how did a practicing physician join a biotech? It's because of cancer. Eventually, cancer will profoundly touch us all. If not ourselves, a loved one, a family member, somebody we know. When it does that, it will leave a permanent mark. I've experienced that myself, and this has given me the drive, the energy to go further, explore further. We need to do more. Cancer continues killing. We need to solve this problem. I don't take no for an answer. But why does cancer still kill? We've made great advances, PD-1, checkpoint inhibitors.
Now the new RevMed stuff in pancreatic cancer, amazing. Absolutely amazing. We have hundreds and hundreds of treatments, a lot of studies going on. But why does cancer still kill? It's because of treatment resistance. It's what our CSO Maija talked about. A key cell in treatment resistance is the macrophage or the myeloid cell. They are basically the same thing. We're going to talk macrophages here. This is not us saying it. You can go look at it in AI. The literature's full of it. Macrophages remain the key source of treatment resistance. As Maija pointed out, usually 50% of a non-responsive tumor is made of macrophages. I've talked a lot about this with pharma. Pharma goes, "Oh, macrophages, they're so difficult. They don't seem to work." I'm like, "So are we going to just go around and pretend that they're not there?" No.
At least me, I cannot live my life that way. Something has to be done for the macrophages. We've worked in this field for over two decades. This is writing new biology. AI will never write us new biology. What the patients and the pharma industry actually needs is new targets. AI will not give them to us. CLEVER-1, understanding its biology and how to tackle it is a result of over 20 years of simple, old-fashioned, hard work. It doesn't come easy, does it? AI is good in designing and characterizing molecules. But again, it doesn't give us new targets. It requires good old-fashioned science and understanding and writing new biology. We've learned CLEVER-1 is essential for targeting macrophages or trying to make them work for us.
To tackle CLEVER-1, we have bexmarilimab, the first-in-class anti-CLEVER-1 antibody, which again, has, in our belief, the best-in-class activity and safety when targeting macrophages. Again, a lot of stuff that's successful. But so far what we see is that this has the best-in-class, again, activity and safety when targeting macrophages. What is our vision? We aim to establish BEX as the cornerstone of cancer care in cancers where CLEVER-1 positive macrophages are the source of treatment resistance and cancer progression. That's a bold statement, but that's what we want to do. What does this actually mean? Well, how many patients? What kind of cancers? Basically, simplifying this means that we could, if successful, be able to help around 20%-30% of patients suffering from treatment resistance. That's screening biobank data. That's around where roughly cancers vary on how CLEVER-1 positive they are.
That's our bullish estimate. But then again, we have to be realistic. We are a small biotech. How are we going to accomplish this? Everything starts from focus. This is what I call how to eat the elephant slide. We are prioritizing all our resources where we see the best bet and that is, or the biggest need, and that is high-risk MDS, because everybody is CLEVER-1 positive, excellent results, low bar possibly for approval. Meanwhile, given with our resources and working with world-leading KOLs, CRO, CDMOs, we're expanding into new, where again, as César said, the low-hanging fruits may be like sarcoma, like check refractory melanoma and lung. We're expanding again as much as we can. Currently what we're actually receiving more investigator-initiated trial proposals than we can handle at the moment. Unfortunately, we cannot turn them all sponsored.
Eventually, as we get into revenue making through the MDS program, we'll start turning these other trials sponsored and push them to approval as well within our resources again. All of this, what we're doing will then result to even the stuff we've been looking at today is what we believe significant shareholder value. We will be producing, again during 2027, data from not one, not two, not three, but four, possibly even five new indications of data. Now show me another biotech that's going to do all this with the resource size of us. That's what we're made about. We are here to tackle macrophages in cancer. Thank you. Now we're going to take the management back and have little questions from the audience. I hope you've stayed awake until the very end and have typed a lot of questions in. Come on, team.
Thank you, Juho. There is plenty of questions, but let's take the first one as there is a few questions about partnering. Could you please elaborate the current partnering situation? Possibly for Ralph.
Thank you. Yes, good question. Like any biotech, we are engaged in regular and ongoing dialogues with various partners of different types. Certainly, something that we're exploring very openly, and very keen to ensure that we have good partners as we move the program forward.
Thank you. Also next one for Ralph about uptake. What uptake do you estimate in high-risk MDS, and what supports this estimate for uptake?
In high-risk MDS, in our models, we estimate around 60%-70% in front line. Similar in relapse refractory. However, relapse refractory based on the current plan, would be an overspill or essentially, as a result of There is a certain cannibalization of the second-line market as a result of that. That's based on extensive quantitative research that we've done both in the U.S. and in Europe. We predict that uptake to take around four to five years to reach peak. Obviously, price growth, and inflation and so on, we'll continue to see additional growth, but in terms of the actual pure market share, that's where we would put it. There is also the aging population, which is another factor within there, as I've talked about, and it is a very real effect because the incidence in the general population is around 5%, 5.3%, 6.3%.
But the moment that you look in patients over 65, it shoots up by about tenfold. So it is a very significant factor in any kind of forecast modeling.
Thank you. And I believe this next one goes for Petri. How widely accepted is complete response as an endpoint in high-risk MDS, and has the field view changed with these endpoints?
Thank you. Excellent question. FDA published the guidance for industry a year ago, and in the guidance, they officially say that complete remission plus partial remission is an endpoint. It's not just the regulatory agencies, but also clinicians and also key investigators who feel the same way that OS is not the only endpoint we need to look at, that approval should be based on durable CR. Of course, at the same time, need to show that there's no detrimental effect on OS when you produce a lot of durable CRs.
Thank you. And next question about single agent activity. As bexmarilimab hasn't been tested as a single agent in frontline setting, why should investors still be confident in it? Maija or Juho?
I can take it first.
All yours.
Maybe. It has been tested now in the last line for single agent, and there you have a very big tumor burden and metastatic disease. What we know about immunotherapies is that they usually work better when the tumor load is less. That's even for anti-PD-1s, for example. Therefore, I believe that if the closer you have for the first line, the better responses you get. Also, these patients, when they're in first line, they haven't been treated with all the lympho-depleting therapies. Their bone marrows are not exhausted, so they have the better ability to have anti-tumor responses because they have higher levels of adaptive immune cells, like lymphocytes. This is why I believe that it would work very nicely in the first-line setting. Anybody else wants to add?
Yeah, maybe to also add, because again, when disease burden is very high, for example, if we're thinking MDS to AML, disease burden is already very high in AML, and Bex is not a cytotoxic agent, hence the relatively good safety profile. So Bex as a single agent could be very good in low disease burden settings, but again, in high disease burden settings where you ultimately start drug development in, it's not the best optimal situation. Petri?
No.
These were the most important ones. But in the clinics with PD-1 inhibitors, it's been shown in multiple tumor types that you don't get good efficacy in late stage or late line treatments, so that you get the optimal, actually not just in the frontline treatment of metastatic patients, but the best results, for example, in melanoma are in the neoadjuvant before the surgery. So that, I think, tells everything, and there's no reason to believe based what just Maija told that would be different with Bex.
Thank you. And few questions about BEXERA timing, and also that has there been any surprises? But first, when do you expect the first patient to be enrolled in the BEXERA, and is everything according on the timelines that we have communicated previously?
Maybe I can take this. We are progressing well. We have already told that the first patients will be treated in Q4. And as Amer had in his slide, so first sites are opening now in October, and we are well on track, and we expect first patient to be treated soon.
Thank you. And as a follow-up, has there been any surprises since we started the BEXERA trial and the preparations for that?
We have a superb CRO that we working together, Parexel. Of course, as an experienced CRO, there are all the time surprises every week. But we tackle them little by little every day. As I just mentioned, we are very well on track to get the first patient treated soon.
Thank you. About the mode of action. The mechanism of action is very novel. Given that there has been a lot of setbacks in the field of macrophage targeting, what gives you the confidence that CLEVER-1 as a target will continue to stand out? To Maija or Juho.
Yeah, so we have a very novel mode of action. As I mentioned in my talk and when we were doing the QA with Juho previously, I believe that CLEVER-1 is a non-redundant molecule on macrophages. What we have seen in the lab is that if we block with Bex, CLEVER-1, we see a downregulation of other checkpoints. This is on the T cells and on the macrophages. So we kind of lower those that are already inhibited by other drugs. So with one drug, we can accomplish this, meaning that we have a very good safety profile, but we get all the good things that we can have on a macrophage to support anti-tumor responses.
I just say it's a master regulator.
Maybe I can have an add here. Although we discussed that the last line patients were treated in the MATINS trial, we are going to have at ESMO overall survival results from the melanoma cohort with 25 patients, the overall survival update of those patients. Although 100% of them were PD-1 refractory, I think it nicely shows the encouraging activity that we see with Bex as single agent, even in late stage tumors.
There was also one question about that. Could Petri please remind us about the melanoma results that you know in the MATINS?
The most important result is related to overall survival, and they are under embargo to ESMO. But in two weeks, we will present them. But they are very positive.
Thank you.
There will be also translational data showing how the tumor microenvironment, also the cytokine environment has an impact also on the outcome of the patients when they treated with Bex, which fits very nicely with the mode of action that we showed in the MATINS trial.
Thank you. Patients who responded to Bex and those who didn't.
This was something that Petri already mentioned in his talk, that the biomarker studies that we did was that the patients who got a response in the MATINS trial had higher levels of intratumoral CLEVER-1-positive macrophages. It seems to matter how much you have them, and therefore, we are using that maybe in the future trials to enrich patients based on the histology for CLEVER-1.
From BEXERA and BLAZE, we will get extremely important validation, what we saw in the MATINS. After that, hopefully we'll be able to also start using a selection criteria. There are quite strict regulations what is a ready test to be used for patient selection in a prospective form of clinical trial. We need to validate the MATINS result of the biomarker in these upcoming trials.
Maybe to chime in here again for the audience, MATINS was the first in human study in solid tumors as a single agent BEX treatment. Again, how we see it is that the ones that had CLEVER-1 positive macrophages got the clinical benefit. Again, when you go to large heterogenic solid tumors like breast or lung, patient selection ultimately will be needed. For example, we know in melanoma that PD-1 resistant patients are more abundant with CLEVER-1, and then in sarcomas, it is a very CLEVER-1 high cancer. So we will look to establish possibly a threshold for patient selection. Will one be needed, for example, in sarcoma? Remains to be seen, and that is why this study is also super important to learn that.
Thank you. Few quite scientific questions maybe for Maija. Do you have evidence that BEX restores normal hematopoiesis independently of blast reduction, or could the observed recovery simply be a consequence of disease control?
So this observation that I told about or made this hypothesis is based on mouse experiments that we have done in the lab. So we have treated the mice with 5-fluorouracil for one dose and then looked at the recovery after anti-CLEVER-1 blocking. If we block CLEVER-1 in these mice, they have much improved recovery faster and improved recovery of platelets, lymphocytes and granulocytes. So it seems to hold true, at least in our models, that it can induce hematopoietic recovery regardless of blast count. These mice that we were using in our experimentation were healthy mice, so they did not have tumors.
Thank you. Next question for Juho. Could you please remind us the status of the CMC production, where we are today?
Yes, absolutely. We are very well on track on that. We are already at commercial scale, 2,000 liters with a robust process representing what we believe to be the commercial manufacturing process. We are good on that.
Thank you. As a last open question to all of you, what are you waiting most next? What are the reason that why you are excited, what data you are expecting and so on?
I am going to let the team go first. I will go last.
I can go first. I am really waiting to see the contribution of components in the BEXERA trial. I have been asking quite many years that I would want to have seen a single arm study or the bexmarilimab alone in the MDS to just scientifically compare what Bex can do in the disease. But now we are getting the placebo control. I am really waiting for the patient data that we will be getting an analysis of that data.
Maybe to continue, of course, BEXERA results are super exciting. That's the final proof of concept that the randomized setting that the benefit for the patients is coming from the addition of Bex. I am a solid tumor guy at the same time, so love to wait for the data from these BLAZE and BEXAR. Can we overcome resistance in BLAZE? Even one good deep response among the 10 first patients is a clear sign to proceed. Then also, we didn't talk that much in the BEXAR, but the hematopoiesis effect. We know very well with single agent doxorubicin how deep neutropenia patients develop, how long lasting neutropenia they have, and then how much infections requiring hospitalization they have. So all these data points we will gather from the combination of doxorubicin plus Bex.
Of course, we believe that that's also in addition to BEXERA from that trial, we can show that actually the benefit for the patients from the increased hematopoiesis is a true phenomenon.
I think obviously BEXERA, the readout is incredibly exciting, but I am so completely convinced that it's going to be positive that actually I like Petri, am most excited about how big can this opportunity get, how these additional solid tumor trials, how much will we be able to expand into new indications and help new patients.
Well, that's well said. I like to talk, so maybe I'll say what I feel. Actually, from a physician perspective, I am absolutely it's kind of crazy. Hey, the safety profile looks better than with single agent Aza. Everybody's like, "Yeah, yeah, right. Yeah. Well, its efficacy is the thing." No, but imagine if we have the efficacy and we even improve on safety, and now it's going to be really tested against single agent Aza. If that's there, it's an amazing drug. I am really thrilled about that. Then ultimately, what I am super excited about, like I mentioned there now, 20 years of work is put to the bench, and we'll see what does it deliver. The opportunity, how many patients, which cancers. It's coming together.
Thank you, those were all the questions.
All right then. Well then, we are absolutely well. Basically, that probably was good closing remarks at 20 years of work, research, put to the bench, randomized trial. Here we go, everybody. Super exciting times. Stay tuned.