Faron Pharmaceuticals Oy (FARN) Earnings Call Transcript & Summary

Good day, ladies and gentlemen, and welcome to the bexmarilimab MATINS trial update webinar presented by Faron Pharmaceuticals. [Operator Instructions] I will now hand over to the CEO, Markku Jalkanen, to open the presentation. Please go ahead.

Thank you, operator. Thank you for all joining this webinar today. I'm here with Jussi Koivunen, Faron's Medical Director for Oncology. And Jussi's going to go over the updated MATINS data that was presented by Dr. Bono at the recent ESMO meeting during the weekend. He and I will be then available later on for the Q&A part, and that [ we will then explain on ] how we do that. But before I turn the word to Jussi, I would like to really thank all the people at Faron, all the investigators and especially the patients who participated in the trial. During this corona time, the recruitment has been challenging, but we have a significant effort really done by all the parties involved with the trial. And it has been a remarkable zone. And if you really think about what we have achieved during the last 12 months or so, it is remarkable, and we believe even stronger today that bexmarilimab treatment will be really beneficial for the cancer patients, as we have seen from these early results. This has clearly built in our strength and the development pathway for the bexmarilimab, really, all the way to the additional trials and studies and meanwhile, waiting also some of the [ bioanalytical ] data to come later this year to confirm maybe even further which patients are getting the most benefit out of this treatment. So with these words, really would like to provide Jussi to walk through the data. And then later on, we get back to the further questions, whatever you may have. Jussi, please.

Thank you, Markku, and it's an honor to share early update on the MATINS trial results. So where we're interested in macrophage is that macrophages are quite abundant in the tumors, and they can make up to 50% of the tumor mass. And these cells are not just device standards in the tumor, but they have been linked to tumor growth metastasis, and they can generate highly immunosuppressive environment in the tumor. And not all the macrophages are the same. We have the M2 type macrophages, which are highly immunosuppressive and tumor promoting. And then, we have the M1 type macrophages, which are -- and the inflammatory can cause on the tumor effects. So Clever-1 is the target of our lead compound bexmarilimab. Clever-1 is a large glycoprotein receptor expressed in the surface of immunosuppressive macrophages. It's a scavenger receptor and it's involved in tissue homeostasis and tolerance. The Clever-1 positive macrophages are highly immunosuppressive and high expression is seen only in cancer and pregnancy. Our lead compound bexmarilimab is a humanized anti-Clever-1 IgG4 antibody, which is currently investigated in solid tumors, and the trials are also expanded to hematological malignancies in near future. The proposed mechanism of action for bexmarilimab is that Clever-1 is expressed in these M2 type immunosuppressive macrophages, which result in high immunosuppression in the tumor and can also activate other immunosuppressive cells such as the regulatory T cells. When bexmarilimab finds the Clever-1, it reprograms the macrophages towards the M1 type and even activating macrophages, which can present antigens to T cells and also activate them. So the Clever-1 inhibition can turn cold tumors -- so cold tumors which do have a low number of activated T cells into hot tumors, having a large number of T cells in them. You see this phenomenon in mice models, where Clever-1 knocked down in macrophages results in a large infiltration of activated T cells to the tumors and immune-mediated T cell killing all the cancer cells. We see the same phenomenon also in the MATINS trial. This is a patient who was treated with bexmarilimab and we have the pre and post-treatment biopsies available, and we are seeing most treatment biopsies increased CD8-positive T cell infiltration in the tumor. We also see a robust B-cell activation in the circulation by day 14 after bexmarilimab initiation and interferon gamma response in about 1/4 of the patients. So then with the MATINS trial, this is a 3-part first-in-human Phase I/II study assessing safety and preliminary efficiency of bexmarilimab in patients with advanced solid tumors. The Part I was dose and safety finding study, which has been presented in numerous international congresses over the years. And now we are presenting the Part II, an expansion of the Part I from the trial. And this is assessing the safety and preliminary efficacy of the agent and the eligibility criteria for the Part II were confirmed advanced solid tumors, exhausted of treatment options [indiscernible] and we need adequate organ function and evaluable tumor pipe RECIST 1.1. And here are the endpoints listed as well. So then, the findings from the Part I of the MATINS trial, we could see a good safety profile. We didn't see any DLTs in the Part I. We saw promising preliminary signs of efficacy like in this colorectal cancer basin who received longer benefit with the PR response from bexmarilimab. We also saw positive changes in circulating biomarkers, such as increasing NK, CD8, CD4 and B cells and decreasing number of the regulatory cells and also chemokine switch from Th2 to Th1 type. And the recommended dose for Part II was 1 mg/kilo every 3 weeks. Here are the patient characteristics from Part II. There were roughly half and half males and females. ECOG 0 was at 41%, ECOG 1 59%. Median age was 60. Previous treatment line medium was 3. Medium duration of the previous treatment was 4.1 months. And all the cutaneous melanoma patients in the trial were previously treated with PD-1 or PD-L1 agents. We also saw some colorectal cancer patients, ovarian cancer patients, hepatocellular cancer patent and uveal melanoma patients to be created with these agents. And the cohort size were 10 of each tumor type, except the colorectal cancer, where we had 3 different dose levels tested. Then, the adverse event summary from the Part II. The agent remained well tolerated. We only saw 13 counts of Grade 3 to 4 treatment emerging adverse events. Of any great AEs, there were 706 counts. We also saw 6 counts of Grade 5 events, which were all disease progressions, which were listed as adverse events in the trial. Here are the list of the most common treatment-emergent adverse events of the Grade 1 to 2 events. Fatigue was the most common. And then of the Grade 3 events, we saw ascites and anemia as the most common events, and we didn't see any Grade 4 or 5 events in this category. Then, there will be investigator-assessed RECIST responses. We saw only 1 PR response in the trial, but we saw a quite number of SD responses, 17% of the patients treated in the trial. And here, below are the patients who had the clinical benefit from the bexmarilimab with PR or SV response by cohorts. And we could see a high number of CBRs in cutaneous melanoma, cholangiocarcinoma, gastric cancer, hepatocellular cancer and ER-positive breast cancer, where the CPR rates vary from 30 to 40. Here are some [indiscernible] plots from cancer cohorts of interest. We could see long-term treatments in cutaneous melanoma with the longest treatment was for 13 cycles and still ongoing. We see the same phenomenon also in the gastric and carcinoma. Here is a patient who has been treated for 12 cycles with the agent. Also, long-term treatments were seen in hepatocellular carcinoma, where the longest treatment was for 9 cycles. Here are the overall survival and progression-free survivals from all the patients treated in the Part I and Part II of the MATINS trial. The median OS was 151 days and median PFS was 59 days in the trial. We also carried out a landmark analysis for overall survival from cycle 4 on and divided the patients by clinical benefit to either having a PR or SD response with bexmarilimab compared to patients with PD response. And we could see a much longer overall survival for the patients having at least a PR or SD response with the agent. Since the seen survival difference in the landmark analysis could be accounted for slower tumor kinetics of an individual, we carried out some further analysis. It's not surprising that the progression-free survival is longer for the PR/SD patients compared to the PD patients in the MATINS trial. But we do not see the same phenomenon when we are looking at the treatment durations of the previous therapy line, prior entering to the trial. And basically, PR/SD response or PD response in the MATINS trial shared the same median times of previous line treatment duration. And then the summary and conclusion. Bexmarilimab, a novel macrophage re-programing antibody demonstrates good initial safety and tolerability in patients with advanced solid tumors, exhausted treatment options. We saw an evidence of promising antitumor activity of bexmarilimab monotherapy in several tumor types, 30% to 40% of CDR in cutaneous melanoma, cholangiocarcinoma, gastric cancer, hepatocellular cancer and ER-positive breast cancers. And clinical benefit was associated with long OS in the landmark analysis. Further trials will investigate monotherapy efficacy, patient selection and bexmarilimab in combination with other antitumor agents. Thank you, and I will hand this over to Markku for a Q&A session.

Thank you, Jussi. We will now open the lines for the questions. And operator, could you guide people really how to make questions over the phone?

[Operator Instructions] We have our first question that comes from the line of Miles Dixon from Peel Hunt.

So I remain intrigued by the kind of progress that you're making, particularly in Part II. Could you expand on -- we've seen some of the disease control states have improved, particularly in the addition of breast cancer, but also in hepato. Can you just run through why that is? Is it better analysis of the data? Is it because you're adding more patients? How am I supposed to think about it?

Miles, I'll let Jussi to comment as well. But obviously, now we have a full-size of cohorts that was the original plan to have a 10 patients at each of the cohorts at 1 mg/kilo dosing. And now it's now completed so we are able to do the whole analysis. And obviously, then the numbers are final. But I also ask Jussi to comment why some of the other cancers would be more sensitive for this treatment than the other ones. Do you have an opinion, Jussi, on that?

I don't think I have a true answer of what is the reason behind some tumor types responding and some not. But I guess the accumulating number of the patients kind of makes a difference that we can make at least some suggestions that which are the tumor types where bexmarilimab is the most efficient and promising.

Great. And perhaps just one additional question on soluble Clever-1 [ at its use as a ] potential diagnostic. Is there any additional progress since last time we spoke here, Markku?

Thank you for asking that. And now when we have the data from these full cohorts, obviously, we are very interested in learning additional kind of changes in those and also the baseline characteristics. Hopefully also, to build an understanding, can we redefine the responders from non-responders. And obviously, if we can do that, and we should be able to do it with this material, that will be really exciting, and we are looking forward. And we are assuming that we should have this data last quarter of this year.

We have another question that comes from Julie Simmonds from Panmure Gordon.

Markku, I'm just wondering -- I mean, clearly, when you started Part II of the trial, you were expecting better data from colorectal cancer based on what you've seen in Part I. And that's where the sort of variation in dosing was looked at. I mean I'm assuming there wasn't enough responders in that part of the study to sort of tell us anything about dosing. Do you think that the 1 mg/kg is the right dose to go forward or do you think there still needs to be some additional work done on that in 1 of the cancers where you've shown efficacy?

Thank you, Julie, for asking that. Yes, the work is ongoing at the moment and we are testing increased frequency of dosing in those cohorts where we have seen the highest respond rates. Colorectal originally was still exciting, but as you see, there are very few responses out of those. And that is the reason also why we have now designed what we call the neoadjuvant study, only focusing on colorectal or renal cancer. That would allow us to analyze the pretreatment biopsy and post-surgical samples to really see the increasing of dosing can activate the influx of leukocytes, lymphocytes in the tumor. And that is really important also for the matter that then we have [ intact cancer ] patients. In other words, we believe that their immunosystem is more responsive really to react any of these start treatments. And once we have that and if we can really demonstrate that you can turn these cold colorectal cancer types into hot ones, they then become also assessable for [ PD-1 ] treatments. And obviously, that is really pushing us really to move on to the combinations. So yes, there are a lot of things going on at the moment and hope to learn those various combinations as soon as possible and dosing phases.

There are no further questions on the conference line. We will now take questions submitted through the webcast page. We have a question that's come through. It says how confident are you that the DCR will deliver a strong OS in the MATINS trial? Are you using personalized medicines in this trial to ensure patients being delivered this treatment are good candidates? I know that [ Traumakine, ] you later discussed stronger efficiency in certain genetic groups. Is this the same?

Jussi, would you like to take this question?

Yes. I guess of course. We would like to see maybe more PR or see our responses in the trial. But then again, we're talking about an agent, which is kind of completely novel, and we don't really know what to expect and what kind of results to expect with an agent like this. And I -- at least, we are kind of -- we really feel that these results are quite promising that we see very long-term treatment and we don't see any kind of initial difference in the tumor kinetics of an individual, which is actually benefiting from bexmarilimab. So we're quite confident. And of course, there's a lot of uncertainties in a Phase I/II trial.

Can you discuss in more detail the updated survival data and compare it to the previous data part?

Well, as said, now we have full size of those cohorts completed at the cycle 4, where the RECIST analysis is carried out. So this is really based on the case reports from the patients. And now we can look at the outcome and then make further analysis. So I don't expect to see too much of the readouts from these patients, but I really expect to get additional data from those where we have increased the density or the frequency of the dosing and also we increased even the dose a little bit in order to see the receptor occupancy and also how complete the removal of soluble Clever-1 from those patients is during the treatment. That is essential and most likely also to get a full response. So all these are ongoing at the moment and we really are looking forward to have additional information as soon as it becomes available.

The next question, it says, when do you expect to talk to the FDA about the updated data and the design of Part III studies? Do you expect the patient population at the Part III studies to be the same as Part I and II?

We anticipate to have that meeting during the first half of next year. It is really important that we have as clear data as possible because, obviously, that is the way we can justify the next steps, including the design of the pivotal part. There, the important part is really to consider would we like to continue with these last line patients. If so, do we randomize them? What is the control setting and all these important questions. Then on top of it, we need to also, at the same time, really look at the data carefully and try to understand if the combinations actually would be the better way forward. But to remind you that all the melanoma patients are refractory for PD-1 inhibition, who came to our trial. So maybe there, we actually may have a possibility to demonstrate increased efficacy when we go directly to the combinations or maybe even to the first line, which is the aim we do with the lung cancer later -- starting later this year. So we need to keep price open and really look at the data and try to get the readout as soon as possible to help us to design all the questions and information to the regulators.

We have another question. It is, are you planning to move all 5 of the tumor types that had a strong DCR rate forward in Part III?

I would say the other way around that we probably do not focus on those who had a lower response rates. Would it be a combination of all of those 5 in 1 same trial, that we need to consider carefully and use some opinion leaders because the current treatment regimens for those cohort [indiscernible] are different. So we have to again consider. Then comes to the point that the response rate what we see today, can we enrich that from any of the biomarkers, and maybe that could actually guide the selection even further and make it less dependent on the tissue type of the cancer origin.

The next question is what is the state of the biomarker data? And when do you expect to share results of your analysis?

It's all getting to be analyzed during the last quarter of this year. I can't say exactly the day when it comes, but it is massive amount of data from several cycles of these treatments. But now we have a significant group of responders we can put into a group and then convert the non-responders. This amount of the patient data from 150 patients or so would really tell us the likelihood of having able to select also the future patients even more carefully than we do today.

Our next question, how do you plan to fund the continued development, the expansion cohort, neoadjuvant studies, combo studies and [ hypoalergic ] [indiscernible] study.

Right. I don't ask Jussi to answer this one. I will do it. We have several options and Board is well aware about the lead for the additional resources. So we will let people know as soon as those are completed. Thank you.

Thank you. There are no more questions at this time. This concludes our question-and-answer session. I will now hand over the presentation to the CEO Markku Jalkanen for closing remarks.

Thank you very much for all the participants and thank you for the questions. And I'm really looking forward to see some of the people face to face soon. We really are getting exciting data and happy to share with you in due course. Thank you again, and goodbye at this point.

Thank you. So this concludes the conference call for today. You may now disconnect. Thank you for joining, and have a very good day.