Good afternoon. Welcome to join our presentation on year 2022. I'm here with our CFO, Toni Hänninen.
Good afternoon from my side as well, and welcome.
We are very happy really to describe the year 2022, which is so transformative for us, and excited about the prospects what we have for this year, and we plan to go over those with you. Obviously, as you are well aware, we are a public company, and we will be making a lot of forward-looking statements, and this is to disclaim really those. We move on, and I let Toni to start. Toni, please.
Thank you, Markku. Faron at a glance, just to recap who we are, Faron, a biotech company from Turku. We are dual listed in Helsinki and London. Our market cap roughly EUR 245 million. We are very pleased to see the development of the market cap in the last six months since we last spoke. The market cap has gone up roughly 80%, very pleased to see the results that are driving that. On the key financial and corporate information, cash balances, we had at the end of the year EUR 7 million, which is roughly the same as we had a year before, stable cash balances throughout the year. The loss for the financial period was EUR 28.7 million. As you see, it's quite a lot larger than we had a year ago.
This is mainly driven by the R&D expenses as we have accelerated our pipeline, we have really accelerated also our U.S. expansion as we communicated earlier. We currently have half a dozen people in the U.S. On the net assets side, we had EUR -11.5 Million of net assets. What's very important now to highlight at the end is the fundraising activities that we conducted. We had two fundraisers last year, one in June and one in October, totaling EUR 13.4 million. Here we welcomed The Leukemia & Lymphoma Society from the U.S. As a shareholder, we are part of their TAP program.
On top of that, in February, we obtained up to a EUR 30 million debt funding from IPF Partners, of which we drew EUR 10 million upon signing in February, and we have potential for further tranches of those EUR 20 million, which are possible under certain conditions. Post period, in the beginning of this year, we raised EUR 12 million from existing and new shareholders, here we are very happy that LLS participated with their second investment, which was a lot larger than the first investment earlier in the year. On the team side, we have really added a lot of very people in our team. Newest addition, Dr. Hollmén as the Chief Science Officer, then our Dr. Juho Jalkanen, sorry.
Marie-Louise joined in the beginning of the year as new CMO based in Boston, and she's been really driving the clinical programs that Markku will explain to you a little bit later. Dr. Juho Jalkanen promoted to COO, as well as Juuso Vakkuri and Vesa Karvonen in HR and in legal counsel capacity. On the board side, we welcomed Erik Ostrowski as a new board member, a great addition to our team. It's been very pleasure working with him. On the program, specific advisors, Dr. Mika Kontro, who's really supporting the BEXMAB program. With that, thank you from my side. I'll hand it over back to Markku.
Thank you, Toni. Obviously we have really focused now in our Bexmarilimab program. We have three our own trials ongoing and under design. You all know the MATINS, which are pretty much coming to the end, and we are really excited of the possibility to get the feedback from FDA during the Q1 or in April latest. We have this very exciting first hematological cancer with extremely interesting results, and I am going to spend some time with that as well. The combo with the PD-1 or PD-L1 blockade, it's also moving on, and that first protocol has been already approved by the Finnish authorities, and it's under review in U.S. at the moment. Very exciting thing.
I'd also say that you may have noticed that we are initiating a collaboration with Fred Hutch Cancer Center in Seattle in the US, and that is related to a cytokine release syndrome, which is very common side effect of any cell therapies given to the cancer patients. We are about to initiate a clinical trial collaboration with them based on the intravenous interferon beta use, and we will be announcing further during the year once we progress to the point when the trial is about to start. Wait that also during this year. The potential of Bexmarilimab in my mind is tremendous. The rationality here is really very simple. Roughly 90% of the cancer-related deaths are really related to the resistance of the treatments.
In order to really get that over, we have to learn to control the myeloid cells, which originally come from the bone marrow and build this resistance by setting up a immune suppressive elements to protect the cancer and their growth. We just believe that the solution is very simple. You reprogram these macrophages, and we do that with humanized antibody called Bexmarilimab, and I'm really focusing a lot of that. We already know the opportunity for us. We could go to the last line as we have very interesting results at the extension of the overall survival of those patients had no options anymore. The combination makes a lot of sense because the biomarkers indicate that we are helping those patients who are resistant to the PD-1 blockade.
The third one is really to target cells, cancer cells, which actually carry the same target molecules, and those are the hematological malignancies which have a myeloid background. Extremely interesting way of moving on. The mode of action of Bexmarilimab, which we have been studying for a long time, is really based on the fact that these macrophages, when they are in the tumor, can produce Do Not Show Me signal. In other words, they hide the cancer. This is a physiological situation in some of the physio-physiological regulatory pathways, one example being pregnancy. These tumor have just adaptive the same system as to hide the embryo. Now they hide themselves so that the host immune system can not recognize the tumor as a foreign material.
What we do with the Clever-1 blocking using the Bexmarilimab antibody is to reactivate immune activator gene read, and that will produce the activation and then produce a phenotype that can actually present the cancer to the host immune system. They produce Show Me signal in the presence of the Bexmarilimab. Obviously, this is what we have been aiming for a long time. Based on the work with the MATINS, we have really now set up the table for the progress. We know that Bexmarilimab is extremely well-tolerated. We have more than 250 patients already treated. We know what the dosing is, the range, and then we also have biomarkers which can help us really to enrich the patient selection where needed. We know for sure that Bexmarilimab ignites the immune reaction in cold tumors.
I have fresh data to demonstrate that even further, one we have provided previously. Out of this MATINS, we are looking what the last line structure would be, and that's the feedback from FDA, hopefully by latest by April. Obviously, we also learn from that feedback what the BEX combo actually would move on. Even we have that protocol already in, but there is a statement about the dosing. Then the BEXMAB, it's practically a separate from these because now we are dealing with the hematological malignancies, and it's very unique opportunity for us. This is the schematic presentation on the dual activity of Bexmarilimab in these type of the cancers. Obviously, we hope to able to activate the circulating monocytes to become immune activators.
We have seen that in humans already previously with the MATINS patients that it will take place. It should take place also with these malignant patients. Activation of the immunity. On top of it, we have a second direct effect on these leukemia cells, and that is blocking the Clever-1 on them. That will reduce the oxidation capacity, oxidative phosphorylation, and that will run out the cell from ATP. ATP for these cells is the fuel they need in order to maintain their shape and viability. When that happens, we have evidence that the combination of this BEX treatment with the standard of care will really reduce the viability of these cells. No wonder we have started to see the control of these cancer cells in those patients.
As you can see in this picture, there may be even a third mode of action, and that is that the Bexmarilimab can actually bring monocytes very close to the malignant cells because they are binding to the same receptor. Very interesting opportunity, mode of action-wise. Outsmarting cancer, a Clever approach. Let's look at what we have at the moment. We started everything with the MATINS trial. You are familiar with that one. Dose escalation, test indications and their expansion, and now we have a data that we have a benefit in the, in the overall survival in certain indications, not all of them. That material was sent to FDA, and looking forward really the interactions with them.
I'm not really going to say what that outcome will be, but it's very exciting time for us really to have a discussion with FDA during the H1 and then move on also with this one. Well-tolerated translational data show immune activation taking place in patients who have lost that. Clinical benefit observed up to 30%-40% in certain cancer indication within the last line patients and having biomarkers now available, including interferon gamma, but also the intratumor Clever-1 staining. That is becoming most likely connected to our next trial settings in all of those because obviously we would like to establish the way really to identify the patients who have the highest probability for the treatment. This is one example from the MATINS trial. On the right-hand side, you can see the extension of this overall survival.
We had roughly threefold longer survival those patients who had achieved the disease control. Remember, these patients had no options. Their average survival was only 4.2 months, which describes how desperate the situation with those patients really was. We extended that almost to 15 months. On the left-hand side, you can see that the ones who have the response, and that's the red curve, they increase the interferon gamma production. You can see how dramatic difference there are between these two. This really tells us that the innate immunity and the immune system is really now activated, and maybe that is really the benefit we really provide for the patients and maybe also for the PD-1 blockade.
PD-1 blockade works only with the patients who already have T-cells around the tumor, and you activate them and then make them to attack the tumor. This combination, what we are thinking. Changing cold tumor into hot one is a concept that is well accepted already in the literature that has to be done in order to really increase the efficacy of the PD-1 treatment with the various tumors. I promise you some exciting new data, and here it comes. This is what they call a volcano plot. This is the MATINS data looking at the patients who had response on the left-hand side and the patients who didn't on the right-hand side. These different eruptions in the left-hand side picture describe the situation prior BEX treatment. This is the biopsy from the intra-tumoral site of the tumor.
The right-hand side in the same picture indicates post-BEX treatment between the cycle three and four when the second biopsy was taken. The different names of these transcripts indicate on the left-hand side that there is a significant immune suppression in that tumor. Post-BEX treatment on the right-hand side, you get the readout of these genes, which mainly are the genes known to be in the active in inflammation and immune reaction. There are some very many well-known gene products. This conversion from immune suppression into a immune activation is localized in a intra-tumoral macrophages because that what they were analyzed and is a significant also statistically. If you look at the non-responding patients, it's totally flat. Nothing has taken place there.
The association is very strong in here. This is really the final evidence that we can activate the intra-tumoral macrophages like we have claimed for quite a while already. Very nice data. Obviously we are looking forward to publish this data later on this springtime. Very nice results really to move on. We also learn from that same kind of situation that if you have high Clever-1 expression within this tumor, the content is also reduced. There is no wonder that if we pre-stain these immunohistological sections, there is a statistical significant finding with the intra-tumoral presence of Clever-1 staining, not within the stroma or within the whole tumor. It has to be really intra-tumoral analysis of Clever-1 staining.
Obviously, this is something we are looking forward really to combine with our clinical trials and hopefully become a standard companion diagnostic tool for us and for next set of our trials. Very significant milestone achieved last year. Just looking one example of these last line patients, this is the bile duct cancer. You can see this dramatic difference between responder and non-responders. Obviously, this would be typical thing which we could actually further develop in our last line protocol after the FDA feedback. Let's see how we are going to learn and what we are going to learn from there. The BEX combo is really supported also from the findings in the literature. If you have high interferon gamma level, you have a response. That's the blue curve on the top.
If you have a low interferon gamma, those are resistant to the PD-1 treatment. Obviously, if we can now with Bex marilimab really increase the interferon gamma levels, they obviously have a chance really to react now to the PD-1 treatment. This combination therapy is really the target of the BEX combo. We would like to get to the first line and down on left side, you can see our candidate trials or indications we would like to move on. First, head and neck cancer, where the PD-1 blockade is not very effective. Urothelial cancer, also would like to move on to the lung because there are still space to help those patients as well.
This is almost ready to go and obviously we are looking forward really to have resources also to initiate this trial sometime this year. Another very exciting trial to move on. The hematological malignancies. We have known for some time that these myeloid-derived cancer types really express a Clever-1, and that is illustrated on the right-hand side where the different myeloid malignancies are analyzed, and you can see the red dots which actually illustrate individual cells, how they have been stained for the Clever-1 positivity. There are also information in the literature, higher expression you have Clever-1 on the surface of these cells, worse the outcome of the patient survival will be.
There is evidence already in the literature that by blocking the Clever-1, you actually could have a chances to help these patients. Again, this same picture. Activated immunity on the left side, blocking the Clever-1 function, to reduce the viability, and maybe even the third one to get the monocytes close to these cells. Obviously, if they are in the circulation, that is very easy to take place. With this treatment, we set up the BEXMAB study.
It's very simple in a way because we have a doublet study starting with azacitidine, which is the standard of care in many of these different myeloid AML. We also have possibility to move on to the triplet where we also combine the most recent chemo treatment on these patients, that is combining Azacitidine, Venetoclax, and BEX combo, BEX/Bexmarilimab. As we have already reported late in the year, this is a very interesting situation for us. Out of the first dosing cohort, which was 1 mg per kilo every week, we already have started to see a very positive response. We lost out of these five patients, one to another trial who had this IDH mutant.
There is a separate treatment protocol for that one, so we couldn't do anything for that one. The third patient had a fatal and unrelated adverse event, infection, which it's rather normal with these patients, so couldn't do there was nothing. If you look the three other ones, one complete responder at this time point and two partial responders. It's like three out of five already have a response to these patients. This trial is now moving on, obviously, and we are looking forward later in the spring to look at the second cohort that is 3 mgs per kilo. Our dose escalation committee did recently a decision to move on to the 6 mgs per kilo because there are no dose-limiting toxicity yet. Maybe we stop there because we already have this high efficacy.
The triplet, the first triplet, a cohort has been recruited. We have very promising situation here if you look at also this is from that one because these patients can be also monitored from the blood samples as they can be monitored from the bone marrow. Here is an example of a patient where the patient is losing these cancer cells. They are called blasts. You can see down the stainings and loss of these cells and then on top of it, the number counts. Here we can see how the remission has been produced. As you can see below 5%, representation of these blast cells in the blood actually indicate that we have enter remission. In other words, the cancer have been under control. This is really example from the Helsinki University Hospital patient.
Nothing else really to say about that. The whole point here is that we have MATINS trial extension possible using last line randomized trial. Would that be bile duct or something else? Depends on the feedback from FDA. They may also propose all comers, but let's see what they say. The combination initiate that, and then accelerate the BEXMAB as much as we can because obviously that is where we have the fastest way to the market at the moment, as there are no that many treatments to help these patients and roughly 90% of the patients will die with the diagnosed AML within the first five years. The medical need is tremendous over there, and we are really looking forward to help these patients.
All with this setting, we believe that we have a very interesting news flow during the first half of the year, maybe also on the second one, but this we pretty much know at the moment. There will be additional information provided with the MATINS data and also especially with the BEXMAB data on these hematological malignancies. We believe that this illustration of the outcome of these different trial and the data, and then building that into three different programs will be significant for us during 2023. We are really working hard in order to get there. As Toni already indicated, we have really expanded our activities on the U.S. side. For the BEXMAB, we will add a additional four sites during the springtime in order to really have access to the U.S.-based patients.
All those four sites we are activating are the major U.S.-based sites and also very well known. Really looking forward also, to provide additional data, on those patients who are recruited on the U.S. side. With this, I'm really now closing our presentation today, and we want to thank you. Obviously we are very happy to answer to any of the questions you may have. Please, you have, the link to type in your questions, provided earlier today and use that one really to send them and we will then discuss further on whatever is bothering your mind. Thank you again.
Okay. To the questions. There has already been a couple of questions, starting with BEXMAB. How is BEXMAB recruitment progressing, and has it been difficult to get patients from Finland? Related, when will the first site or sites open in the US?
It's been amazing effect after announcing the first response results with the BEXMAB trial. I don't know if the word goes around, but we have a line-up of patients here in Finland at the moment. As soon as we opened the new cohort 6 mgs per kilo, we believe that we can recruit that in few weeks time. We opened the first site in U.S. That is a City of Hope hospital close to L.A., really well-known hospital over there. The second one will be MD Anderson in Houston, again, very well known. Third one will be Yale. You must recognize that one. Third one, a University of North Carolina Hospitals. We had a meeting at ASH meeting, American Society of Hematology, in December.
When the same data I presented here today was shared with them, we had a line-up of sites who wanted to join the trial. We believe that the progress of BEXMAB will be extremely fast. Obviously, the acceleration is good for us, but also I want to remind that it also will increase our cost. Obviously every patient will be carefully controlled when they come in. Hopefully with the data and with the other ways, we can move on as fast as we can possibly do. Also with that data, have further discussion with the regulators on the possible pathway all the way to the market. That remains to be seen, and obviously we will be announcing all those steps later this year.
Okay. Continuing with BEXMAB, an analyst question. In BEXMAB, which malignancies will you focus on? Do you expect some to recruit faster moving forward, and how do you intend to monitor these patients? How long do you intend to monitor these patients?
The refractory or remission relapse patients would be way forward for us. If you really think about, there is a significant population and those patients do not have any options. We have had those already in our trial. They come in the second cohort, which I have seen what they are. It's a kind of a strategy we have to think about once we have a little bit more data on these patients, which of the form of AML we actually would like to take further, because the treatment protocols are a little bit different on all of those. Also, the combination of Azacitidine and BEX has been completely safe. BEX has not added any risk of having additional adverse events.
Same seems to be case also with the BCL-2 inhibitor Venetoclax. Venetoclax and Azacitidine combination can produce toxic or adverse events, so we have to be careful how fast we actually going to develop that one. We'd probably like to start on the later stages of the patients, but consider all the time, can we really move on in the front and initiate a separate cohort? That obviously requires an amendment to the protocol, but we are ready to do that if the data is supporting that really strongly.
Related question still from analyst. How does Bexmarilimab compare to other AML, MDS therapies that are being pursued?
If you think about the biologics, I don't often want to say that some of is worse or better than ours, but if you think about anti-CD47 treatment, it actually never showed a stand-alone activity like we have already seen with the BEXMAB. Obviously the mode of action, don't eat me signal, is targeting a different pathway than Bexmarilimab. One of the strategies actually could be here that we actually combine them. Again, that has to be based on the data what we obtain for our own trial, and luckily that is accumulating really fast. Other than that, what is ongoing, we just all of us need more data. Something has to be really taking place in order to this help these patients within the next 10 years or so.
Okay, good. A bit more general question on Bexmarilimab. How do the companion diagnostics compare across the different patient groups, I mean, in liquid and solid tumors, and are the blood markers similar?
If it start with the solid tumors, we have seen a correlation between intratumoral positivity of the Clever-1 and the outcome of the Bexmarilimab efficacy. That correlation is already there, obviously we have provided this information to the authorities. We are ready to set up the assay to the trials. It's already verified, it's suitable for the standard hospital diagnostic system. I don't want to say the commercial systems used at the moment, but it's available to us. Obviously we will continue to use that. The solid the hematological malignancies are a bit different, but they are easy to analyze, just looking the cell surface, a Clever-1 positivity, that is developing at the same time while we do it.
Obviously would like to learn if the correlation is as strong as we have seen on the solid tumor part also with the hematological malignancies. Maybe we can one point also to select these patients based on the Clever-1 positivity. That analysis is rather standard also at the university hospitals or hospitals that treat these patients.
Yeah. Then from another analyst, a related question. In the phase III trial for Bexmarilimab in the monotherapy, do we expect to be selecting patients with a biomarker?
As I said earlier, we are also waiting the response from the regulators on that matter. These patients, last line patients had very few options, and as we have seen, we have highest responder rates in certain indications and less in the other ones. They may propose us that you take all of them in, and then you just follow and have built up a statistical system for those who are Clever-1 positive and those who have less expression of Clever-1, and the outcome could be different. Remember that these last line patients have no options anymore, and we all want to help them. I'm open to both of these, and also would that be 1-to-1 randomization or 2-to-1 randomization could also be advised by the regulators. Let's see later in the spring what the outcome will be.
I can tell you more about it.
Okay. still on the monotherapy trial going forward, do you have a confirmed date for the meeting with FDA? How long after the meeting do you expect to get their formal feedback?
It's in March and post-meeting, they have 30 days, time to provide a written opinion. It's usually just a letter they send out.
Okay. Still, one more question regarding BEX. Are there clinical observations of antibodies against BEX? If so, can the problem or any problem there be solved by increasing the dose of BEX?
Dosing with, uh, uh, with the solid advanced tumor patients showed that if you start to go higher up, I'm now sa- meaning like ten mgs per kilo up to thirty mgs per kilo, we start to see bell shape. So it's not helping us really to increase, uh, the BEXMAB uh, the Bexmarilimab dosing. Uh, the frequency itself has not shown that much of a difference, is it once a week or every three weeks. And if you think about the mode of action, we need to ignite the immunity. We don't need to maintain that once it has been ignited. So you then have a pharmacodynamic effect later on, and if that ends up or results in activation of naive cells, uh, to recognize the tumor antigens, that's kind of a vaccination against the tumor antigens, and that does not disappear. It will stay with the patient.
The dosing could be something that we may have a range, and once we are using that within the range, it will not help us if we increase the dosing. Obviously, this is also very good on the economical side because you don't need to go high up with the, with the Bexmarilimab. If it's only one mg per kilo, it's very decent dose and will reduce also the risk of any side effects. We have seen very few antibodies being born against the Bexmarilimab, and also that is very good because usually the regulators want us or want to people to really also measure the neutralizing antibodies against your drug, which is known to take place against the antibodies. We really haven't seen that much in those patients we have been measuring from the MATINS trial.
The last question related to the drugs, and then we go to the regulatory and corporate questions. Would it be possible to give BEX as an intramuscular or subcutaneous injection in the future?
Thinking that you would like to get the antibody to penetrate to tissues, you may be better off if you give it in a IV formulation because then the concentration peak would help it to penetrate into tissues. Technically, it would be possible to really develop a IM or SC form and that has been also developed for some other antibodies. In our case, we may not think about it that way because we really would like to get the antibody to penetrate into tumor as well, and there, higher plasma concentration will help really to take that place.
Okay. A question about regulatory. Could further positive BEXMAB data lead to an European application?
Yes. I talk about lots of FDA. Obviously, we focus on both of them. We, as we said, we are increasing our activities in U.S., and FDA is more close regulator there. Maybe also, I don't know if it's more dynamic, but anyway, you get a opinion that holds up to the end of the development. If they advise us to do a certain pivotal pathway all the way to the BLA, biologicals application, in order to get the marketing authorization, if you have that advice, you can trust that it holds up to the very end unless something really dramatic will happen. Yes, both Europe and U.S. are in our mind, but as said, U.S. is very interesting market as well for us at the moment.
There are a couple of questions or multiple questions relating to funding and licensing strategies. The questions actually, if you combine them, can you elaborate a bit about the usage of the remaining debt facility, the likelihood, the potential licensing deal discussions, and also eventually, whether there is plans for Nasdaq listing?
Toni, would you like to answer?
Yeah, sure. Thank you. That's a great question. As mentioned earlier, so we have a debt facility with IPF, which consists of three tranches. We drew the first tranche, EUR 10 million last year. There's a second tranche, which is EUR 5 million defined by certain conditions, and then a third one, which is EUR 15 million. We are in active discussions, of course, about the second and the third tranche, so that is definitely an option. Regarding licensing, maybe like if you wanna, Markku, say a few words about the licensing, and I can talk about the question on the Nasdaq.
Thank you. Yes. Thank you. With the data what we have obtained recently, as I said, we got the clinician excited, but we have also got excited the different licensing candidates which have been discussing with Orro in the past. We can already see the increasing intensity over there. We will be present in many of the conferences this spring where we meet not all of them, but many of these partner who have been interested in this new mode of action to treat the cancer patients. If you think about the situation in the market at the moment, there are, I guess, eight approved PD-1 inhibitors at the moment.
They all start to run out of their patent period. Obviously they all want to protect their product or even increase their sales. The one who comes with the new combination that can increase the efficacy of the PD-1 blockade would be the winner. Obviously we are looking that winner as well. Having said that, we would also have a situation that we can use BEX with all of these PD-1 inhibitors, because that would put our position in a much better commercial position. Then I definitely can say that the upside will be humongous. That upside is tremendous if you think about how much PD-1 blockers are selling at the moment. We have to be careful with the future decisions, but the interest definitely is there.
Maybe to come back to the Nasdaq listing question. What we have always done, we looked at the U.S. market very closely. We have a track record here in Europe of fundraising successfully since the beginning of the company in 2006. We always look at the option of the U.S. listing. Clearly we are building the activities over there. We are building the capabilities if we choose to pursue such listing, we continue to follow that and keep that as one option for future funding.
Finally, one corporate matters related question. Can you expand on the reasons for the proposed appointment of Tuomo Pätsi as a member of the board?
That's extremely easy. Tuomo is one of the few people who have really made a significant career out from Finland. Even he's Swiss citizen nowadays. He has really go over number of oncology commercializations in his career in small biotechs, but especially in the big pharma. He brings in the commercial experience to the board, which we value high at the moment when we are entering these licensing discussions and plans how we are going to commercialize our Bexmarilimab opportunity. That was really the main reasons. And Tuomo is also very pleasant person, I'm really looking forward to work together with him.
Yeah. No further questions from the audience. Thank you.
Thank you very much for following us, and hope to see you soon with the good additional data from Bexmarilimab trials. Thank you very much again. Bye now.
Thank you.
Bye.