Faron Pharmaceuticals Oy (FARN) Earnings Call Transcript & Summary

Greetings, and welcome to the Faron Pharmaceuticals BEXMAB study update. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn the call over to your host, Dan Ferry of LifeSci Advisors. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to the Faron Pharmaceuticals conference call to discuss the positive BEXMAB data from Phase I/II trial cohorts in patients with relapsed/refractory AML and MDS and next steps for the program. A press release highlighting these updates is available on the Investors page of the corporate website at faron.com. We will be conducting a question-and-answer session at the end of the call. Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements regarding our regulatory product development and commercialization plans and research activities. These statements are subject to risks and uncertainties that could cause actual results to materially differ from those forecasted. A description of these risks can be found on the disclaimer page of our corporate investor presentation located on the company website. Presenting on the call today are Dr. Markku Jalkanen, Founder and Chief Executive Officer; and Dr. Marie-Louise Fjallskog, Faron Chief Medical Officer. Additional members of the Faron leadership team will be joining the question and answer session at the end of todays presentation and they also includes James O'Brien, Chief Financial Officer. I would now like to turn the call over to Dr. Markku Jalkanen, Chief Executive Officer of Faron. Markku?

Thank you, Dan. Good morning and afternoon, depending wherever you are. And we all know that cancer cells are very smart, and they do have a very clever way to hide our immune system. They do this by attracting immune suppressive cells around them so that they will change the microenvironment to hide our immune defense. And by doing that, that will allow them to grow and metastasis. The main cell pipe that can actually do that the myeloid cells grown in the bone marrow and then travel in the circulation and called monocytes and then they go to the tissue, they are called macrophages. This special type of immune suppressive megabases have a receptor called CLEVER-1. And the antibody called bexmarilimab or BEX like we call shortly, and lock the function of this CLEVER-1 molecule on the surfaces and then will convert these immune suppressive macrophages into the immune activators. The immune activation requires antigen presentation capacity, and we have shown that already in many occasions. And with that, we can actually activate the innate immunity and for that also the activation of immune cells. The CLEVER-1 antibody is a typical antibody used in the many occasions, IgC4 and it really blocks the antibody -- the receptor activation on the surface of these cells. And with that one, we can remove the immune suppression. We have a very good safety profile in more than 200 patients already is on, in the advanced solid tumors. But more interestingly, the hematologic malignancy is very good target because some of them really express the same receptor. Therefore, if I could get the next slide, I would like to present the mode of action, which is really evident with the patients we are now treating -- so we have a dualistic mode of action. We can activate immunity by activating these myeloid cells like shown on the left side of this slide. This activation could really lead a result in the activation of antigen presentation. And if CLEVER-1, if those are the cancer antigens, obviously, that will really target in the cancer cells. On top of it, these myeloid leukemia cells also expressed CLEVER-1, and now we have a direct target. And if you now block CLEVER-1 on the surface of this acute myeloid leukemia cells, to reduce their viability by preventing their Oxidative phosphorylation and ATP production. So this is a very attractive mode of actions really to prevent the blast proliferation and of leukemia cells, and that really is the target of our BEXMAB study, which will be soon introduced by our CMO, Marie-Louise Fjallskog. And then if you have a next slide, I just wanted to share with you 1 more thing before letting Marie-Louise to talk. And that is that we already have seen in these leukemia patients that we do activate the immune reaction to the point where the antigen presentation on the left-hand side has been increased by increasing the dose. Here, I have 1 mg per kg and 3 mg per kg. You can really see the increase in the ulceration capacity.But then at the same time, we have a increased number of lymphocytes, especially CD8 cells accumulating in the bone marrow. This really tells us we are activating this immune system in these leukemia patients. And obviously, that is exactly we want to reach. And now it's really time to look at what the outcome of this patient treatments have been over the time and obviously really looking at the most recent data from 6 per mg dosing cohort So with this I would like to really transfer the voice to Marie-Louise, please.

Thank you very much, Markku. So the BEXMAB study is a Phase I/II study, where we are evaluating the additional back to standard of care in myeloid malignancy. So the study has 2 treatment arms. We call it the doublet. In the doublet, we have added back to standard-of-care azacitidine in the indications of MDS, relapsed/refractory AML and patients with MDS that failed prior HMA-based therapy. The study also has the triplet arm, where we have added back to standard of care asylycidine and beneficlax in indications such as azacitidine, venetoclax in indications such as newly diagnosed AML that do not tolerate chemotherapy. The study is actively enrolling, and enrollment is going fast. We have 4 very active sites in Finland and 2 in the U.S., City Of Hope and MD Anderson. We are very soon opening 2 additional sites in the U.S. Based upon the data that I will share with you from -- with the majority in from the government, we have decided to focus on patients that have HMA failed MDS and relapsed/refractory AML. So that was a quick background. Let's go to the data. Please go to the next slide. So I'm very, very excited to share the newest data from our ongoing BEXMAB study. So this is the third dosing cohort of the doublet in the dose escalation part of the study. So what you see here is the cohort in 6 mg per kg, 5 patients. You can see that 3 patients of these 5 have achieved objective responses. You can see a very nice mCR, and marrow CR, so complete remission of the blast in the bone marrow, we also see an mCR in a patient with a frontline MDS. And at the bottom of this slide is the SCR. So complete remission of the [ MAB blast ] in the bone marrow, but also complete recovery of the blood count. What I also want to share with you is that 4 out of these 5 patients received azacitidine before and they have failed. So reintroducing azacitidine alone to those patients would not lead to very good responses. And based upon this, we can conclude that bexmarilimab is adding to the patient clinical benefit. So I would like to walk you through with the patients one by one starting at the top, and you see the color coding to the right with the malignancy. The first patient on top is the patient with relapsed/refractory AML. So this patient received azacitidine and venetoclax prior to going to the study with the best response of progressive disease. So this is an azacitidine refractory patients. After 2 cycles on the study, the patient is doing well with a stable disease and is still ongoing. The next patient also received azacitidine and Venetoclax before, so relapsed/refractory AML received azacitidine and venetoclax, did well, had the CR and then relapse. Now on the study after 3 cycles, we see a nice stable disease and the patient is ongoing. If we go to the third patient, the blue bar, we see a patient with HMA failed MDS. So this patient had azacitidine before going into the study for a long time but relapsed. On our study with azacitidine and [ MAB ], we see a complete remission of the blast in the bone marrow, and we also see that all the blood counts are improving hemoglobin, neutrophils and platelets, not normalized, but improving. The next patient is an MDS patient frontline. So this patient did not receive any prior therapy. On our study after 1 cycle of therapy, we see complete remission of the blast in the bone marrow, and we also see normalization of the platelets and a near normal hemoglobin and neutrophils. And the last patient of this slide, you see a patient with MDS that failed prior HMA. So the patient actually had azacitidine and magrolimab and the best response was progressive disease. The patient was then put on decitabine and venetoclax and after failure came into our study. So the patient received 2 prior lines of HMA-based therapy and failed both of these lines. So on this study, we see after 1 cycle of therapy a complete remission, So this is like complete remission of blast in the bone marrow, but we also see a complete recovery of the blood count. So just to summarize, very excitingly, 3 out of 5 patients with objective responses, 4 of these patients had HMA-based therapy azacitidine before and are failed. So -- the benefits we see here is highly likely to come from bexmarilimab. So let's go to the next slide. We have already shared the efficacy data from 1 mg and 3 mg per kg from this study, but I want to share the totality of the data with you. So we have treated 15 patients so far. So 5 patients at 1 mg per kg by 5 patients at 3 mg per kg and 6 patients -- a 5 patients of 6 mgs per kg. We did see 3 objective responses in the first dosing cohort 2 objective responses in the second and 3 in the 6 mg per kg. So in total, we see 8 objective responses in 15 treated patients. And out of these 8 patients, half of them are azacitidine failed and should not respond to azacitidine again. But I would love to share a little bit more meat on the bones on these patients. So if you start at the top, this is a patient with relapsed refractory AML,this patient had azacitidine before going into the study but progressed during treatment and therefore, was enrolled into our study. After 3 cycles of therapy, you see a very nice PR followed by a deepening of the response to a CRI. So this is a complete remission of the blast in the bone marrow, but incomplete hematological recovery. I also want to share with you that at cycle 6, the patient actually had a complete blood count recovery. So normalization of the hemoglobin, neutrophils and platelets and the patient has not received any transfusions since last year. Patient has a very long-standing response and is still on study after 13 months. If we go down to patient # 4, in the 1 mg per kg cohort, the blue bar that is patients with MDS that trailed prior HMA. So this is a patient with a TP53 mutation, very high-risk MDS patients, received 2 prior lines of therapies, chemotheraphy and azacitidine and did not respond to any of these therapies. As you know, these patients only chance for cure is to have a good treatment result and to undergo stem cell transplantation. In our study after 2 cycles of therapy, we see a very nice PR and this PR continue to deepen. At the last PRs you can see on this slide, the patient had a blast count of 7%, and the investigator decided to take the patient off study to offer a potential cure. So the patient underwent a transplantation in February. The last patient in the [ 1 make or take ] cohort is an MDS patient that is treatment naive. It's a very high-risk patient with mutations that make it more difficult to treat. As you can see here, it took a while for the patient to respond. But after 4 cycles and naive PR that deepen into CR and the patient was on study almost 1 year. Unfortunately, now transformation to AML and the patient is off study. The 3 objective responses and 1 mg per kg cohort and 2 of these patients had received prior azacitidine. If we go to the 3 mg per kg cohort, the second patient there is a patient that received azacitidine for more than 1 year and actually did well and had a complete remission. After relapse, azacitidine was tried again, but the patient progressed very quickly. So no response to single agent azacitidine. On our study, we see a very nice CRI after 2 cycles of therapy. So complete remission all the blasts in the bone marrow, but incomplete hematological recovery. Patient is doing great and is still on study after more than half a year. If we jump down to the last patient in the 3 mg per kg cohort, we see a patient with frontline MDS, high-risk after 3 cycles, a very nice objective response with an improvement of the platelets. And then we have the 6 mg per kg data -- and just a reminder, we have the MCR in the patients with MDS HMA failed, and this patient is doing great, improvement of blood counts, the second patient, MCR frontline MDS, we have recovered platelets and almost normalization of hemoglobin and neutrophils. And the very last patient received 2 prior therapies of azacitidine based therapy failed and got to CR very quickly on our study. So just to summarize again, 8 out of 15 objective responses, 4 of these patients had azacitidine and failed and are not expected to respond to azacitidine alone. So therefore, it's highly likely that bexmarilimab has contributed to these nice responses. So let's go to the next slide. So on this slide, you see a waterfall plot with the bone marrow blast reductions in our patients. And as you can see, most of the patients, a majority of the patients have very nice reductions of the blast count in the bone marrow. And this is important because we want to understand that the drug is really getting into the bone marrow to have the effect there. Very impressive data. So let's go to the next slide. I also want to share a little bit about the safety data. So what you see on this slide is adverse events that are potentially related to Bexmarilimab based upon the investigator's knowledge of the patients. I want to share that we did not see any dose-limiting toxicities in the first 3 dosing cohorts. So in 15 patients, no dose-limiting toxicities. If you look at the table to the left, -- we see that most of the treatment-related adverse events are low grade. So grade 1 or grade 2, mild to moderate adverse events. You also see that we have one Grade 3 and 1 Grade 5 event. So if we go to the table to the right side, you see that the patient with a Grade 3 event had a capillary leak syndrome. So these patients responded very promptly within days to steroid treatment. The patient is completely recovered and is still ongoing in the study. We also have a patient with Hemophagocytic lymphohistiocytosis also called HLH. So this is the condition that is pretty rare, but it occurs in about 1% of all malignancies. It is more common in hematological malignancies. So reports show that up to 10% of patients with AML getting intensive chemotherapy can get HLH. There are also some reports on patients getting HLH on azacitidine and venetoclax. We have evaluated bexmarilimab in more than 200 patients as a single agent in solid tumors, and we did not see any events of HLH. However, since BEX is a macrophage activator, and we know that HLH is characterized by an over activation of macrophages. We cannot rule out that BEX has something to do with this event. So let's go to the conclusion on the next slide. So 3 out of 5 patients in the latest 6 mg per kg cohort responded with CRs and MCRs. 2 of these patients had failed HMA and are not expected to respond to azacitidine alone. 18 (sic) [ 8 ] of the 15 patients that we have treated so far in the dosing cohort, had objective responses, 4 of these are HMA failed and should not respond to azacitidine alone. We have seen some durable responses in the study and the very first patient on the study, the patient with relapsed/refractory AML has actually stayed on treatment for 13 months now. We are focusing on the HMA failed MDS or relapsed/refractory AML patients moving forward with our development and our intent is to gather sufficient data to apply for BLA in H1 2025. So let's go to the last slide showing a little bit about how we're thinking about the development of that. So as I mentioned, we are focusing on 2 different indications. HMA failed relapsed/refractory AML or HMA failed MDS. So we are currently in the left part of the gantt chart. So we are in the Phase I dose escalation. We are hoping to decide on the doses to move forward with in Phase II by the end of the year. Per the FDA new guidance on dose optimization, we're going to pick 2 doses from the Phase I part of the study to evaluate in the first part of the Phase II to decide on the RP2D. So we're going to pick 2 doses, randomized between those doses. Just look at the safety data and the efficacy data and then decide on the RP2D, the recommended Phase II dose. We're going to add an amendment or we're planning to add an addendum to the protocols to turn this into a pivotal trial to be able to file for an accelerated approval in H1 2025. Then we're planning to add a part to the study, a confirmatory trial part to the study to be able to potentially apply for full approval. So with that, I would like to turn back to the Q&A session. Thank you.

Thank you. Thank you very much, Marie-Louise.

Thank you. At this time, we'll be conducting a question-and-answer session. [Operator Instructions]. Our first question comes from the line of Asthika Goonewardene with Truist Securities.

This is [ Gene ] speaking for Asthika. So I have a question regarding about your -- this -- we can see there's -- some response was not responded by some patients. So do you have any good biomarkers which can help to predict that their response to this drug and also how about the level of other cytokines, such as from Gamma and TNF-alpha or IL-6, IL-8 or also, especially the PD-L1 CLEVER-1,all this kind of ratios correlated to the clinical benefit of this drug. That's my first question. My second question I want to ask. So what do you think this drug could be compared combo study could be compared with other immunotherapy or some novel agents in the development of R&R, AML or MDS. That's my question.

Thank you very much. I can take the first one. We know from a solid tumor patients that if the baseline levels of the immune indicators are low, you have a better chance to have a response from those. And obviously, we are looking all of these biomarkers at the moment from these patients. I can just tell that we have seen also [indiscernible] increase in some of the patients, and those have been that have already responded to their blast number. So the trend is very much the same. And then we also are measuring the CLEVER-1 content from these patients that actually could predict also the outcome. And all this is really underway at the moment. So it's a bit too early really to pinpoint something that is a specific. But as we have been advancing with the solid tumor patients, somewhat similar approach will be applied also here. And for the second question, Marie-Louise, would you take opinion on what kind of combinations would be really good for us in the future?

Yes. Thank you very much. So what I think is very special for us is that we're going in the last line setting. So there are really no good standard of cares in this setting. I think our mechanism of action is very unique, but I do think it would be very interesting to combine with potential other macrophage targeting therapies like for instance magrolimab, but for now, we're focusing on this study, but a lot to come in the future.

Okay. Great. I just have a quick follow-up question regarding about the duration. So do you have any comments about the response duration in this study from the latest update?

Yes. Thank you so much. Yes. So if you look at this swimmer's plot, you see that we do have -- so remember that the patients that have been longest on the study are the 1 mg per kg patients and the patients in the 6 mg per kg, they -- I mean, they have actually only been on for 3 to 4 months. All of the patients are ongoing in the latest cohort. And if we look at the duration of the responses or duration of treatment in the 1 mg per kg and 3mg per kg, we see very long duration. So in the patient with 13 months on study, that is much longer than expected, and we have several other patients as long. When you are HMA failed both in AML and MDS the median survival is around 5 months. So I think we have very interesting duration of therapy so far, but we look forward to maturation of the data.

Okay. also congratulations on the update. Thank you.

Welcome.

[Operator Instructions] Our next question comes from the line of Miles Dixon with Peel Hunt.