Alligator Bioscience AB (publ)

Hello and welcome to Alligator Biosciences 2025 year-end report call. My name is Greta Hög. I am the IR and Communications Manager at Alligator and I will be introducing today's call. With me are our CEO Søren Reinholt and our CFO Johan Gilius. They will walk you through the latest developments from the previous quarter and the year. as well as the upcoming news flow. After this, they will be happy to take any questions you may have. You can post them in the Q&A function of this webinar, or you can send them by email to ir at alligatorbioscience.com. As you know, Alligator Bioscience is a publicly listed company, and I'd like to note that today's presentation may include forward-looking statements. Please refer to the disclaimer on this slide, which applies to the full presentation. With the formalities out of the way, I'm handing this over to you, Sarah.

Thank you, Greta, and it's a pleasure to welcome you all to this Q4 or end-year report call in alligator bioscience. What we will do today is go through some of the events of the fourth quarter, of course, and we will focus primarily on mitocelular map. And I'll also provide you some information about our partner program, HLX22. So Greta, if I could get the next slide just to get going. What has happened sort of on the high lines in the company, we have published two exciting papers, very exciting papers on metazolumab. all the biomarker data from the phase 2 study and we were published in cell reports and also data from the reactive 2 study which was an investigator-initiated study also in pancreatic cancer where we combined metazolamab with chemotherapy and also with a dendritic cell vaccine that was published in Nature Communications. And I'm of course not mentioning these two publications just for the sake of it, but of course to highlight the underlying strong data, both clinically and also mechanistically, and I'll share a little bit with you in just a few seconds. In addition, we have completed a rights issue of around 91 million in gross proceeds and as part of that, there is a number of outstanding warrants in the series TO14 and Johan will talk more about that later during the call. On the general portfolio, we further strengthened the IP position of yet another US patent approval on our bispecific molecule 804066, so the CD40-CCAM5 bispecific antibody. And then on the HLX molecule, HLX22, Henleus received the regulatory approval in China for their phase 2-3 trials in HER2-positive breast cancer.

And we'll talk more about those in just a second. If we go to the next slide, guys.

One of the key points in Q4 was, the release of the readout of the 30-month data that was actually in Q3. And we published these data at ASCO GI in January. And I thought I wanted to share with you sort of the entirety of the phase two population treated in the phase two study. So what you see here on the slide is a so-called waterfall plot. of the best clinical response for all the individual patients treated with either the low-dose 405 micrograms or the high-dose 900 micrograms of metazolamab in first-line metastatic pancreatic cancer. And even though the slide looks incredibly busy, I think there's a couple of key points that we need to take from this. Key point number one is that when you compare the light green, the 450, with the dark green, the 900, I think we can all agree that the 900 dose gives more responses in more patients, meaning that that 900 is, and all the statistics show this, better than 450, hence the the FDA's and EMA's recommendation and endorsement of 900 microgram as the phase three dose. But what is equally important is that when we can see when patients actually do respond to 450, we have clinical responses that still shows that even at this dose, Although in fewer patients, the drug is still active. And most notably, as you can see to the right-hand side, we actually now have additional two complete responders. So now a total of five patients have complete responses to metazolamab in this very hard-to-treat indication. And in addition to this, you can see that we have two patients with more than 80, and one of them close to 90% reduction in tumor burden. So together, this data tells us three things. It corroborates sort of the clinical benefit of mitocidolimab. It shows us that we consistently get deep and long responses. And it also shows us clearly that 900, the phase three dose, is better than 450, meaning that we have a clear dose response in this phase two study with mitocidolimab. And that's, of course, something that we are happy to see. If we go to the next slide here, you have seen these data before. On the left-hand side here, we have a significant effect of META on the immediate normal survival and on the durability of response. And when you look at the hallmark data, as we've discussed previously, we increase the probability of being alive at 18 months by a factor of two, at two years by a factor of three, and at two and a half year by a factor of four of metacetamol in comparison with the chemotherapy backbone. And when we look at the combination of the clinical profile of mitosalimab with a safety profile that is consistent with fulfirinox, which allows combination with this chemotherapy and dosing for extended periods of time. We have several patients that have been on the drug for more than two years and some patients even longer. When we compare that with the deep and curable responses with five patients with complete responses, We maintain our position that we have a drug here that in itself, together with chemotherapy, can play a significant role in first-line therapy of pancreatic cancer, but definitely also in combination with other molecules, synthetic lethals like KRAS inhibitors that are becoming a player in at least in second line metastatic pancreatic cancer. So a strong suit of clinical data today with a focus on adding additional patients to the pool of complete responders. If we take the next slide, just not to overburden you with technicalities here, but just to remind us all that We previously discussed a strong correlation between the hypothesized mechanism of action of metazolamab and its ability to activate the immune system and have a direct link of that with the long-term clinical benefits of the drug. And then today we add for the For the sake of it, the lower right-hand corner of the graph here, data coming out of the Phase I study done together with the Dutch University and recently published in Nature Communications, very clearly showing that when you provide mesosalimab to patients with pancreatic cancer, one of the mechanisms that we have hypothesized is the decrease in in connective tissue or stroma in the tumors. And these data clearly shows a significant decrease in that particular and important aspect of the disease. So again, building on the mechanistic evidence that metacelumab is doing exactly as we wanted to do in these patients. If we then go to the next slide, and as I said, we have now completed OPTIMIZE 1. There are still a little handful of patients on treatment. both at 900 and at 450, these patients will continue to receive metazerolamab as this is a medication that keeps them alive. But other than that, we are not collecting data in the study any longer, and there will be no more data readouts. Where we will get data readouts is for the number of phase 1 and phase 2 studies that we have started, both in the US and in Europe, based on the very strong investigator interest in Mr. Salimab. We have a number of studies that are open and recruiting both in oral pre-reglutinances in pancreatic cancer and breast cancer on US Ivory League University. As these trials are investigator-led, Alligator is not really in complete control of when the first and subsequent patients are being enrolled into the trial, but we will keep you updated when that happens and there are major events in these studies. What I do want to emphasize, of course, and we've spoken about this before, is the study in biliary tract cancer that will be run by the French group called Unicancer. If we can have the next slide, Greta. That is basically a randomized phase two study run by at Institut Curie and a few other hospitals across France enrolling 112 patients in biliary tract, randomized two to one. So every time there's two mesoselomab patients, there will be one control patients. And we expect this study to start in the second quarter of this year. So biliary tract is a rare and highly lethal gastrointestinal cancer. It's orphan drug. It qualifies for orphan drug with around 30,000 cases a year in the US and in Europe and around 200,000 cases worthwhile. The median OS remains around a year. Even with the approved IO combinations in first line, hence the unmet medical need is significant and there are really few effective systemic treatment options. So why is this trial being run? It's being run because the investigators that have familiarized themselves with metazolamab in pancreatic cancer, to a large extent, is also the same physicians that are treating other gastrointestinal cancers. And the activities that we have seen in pancreatic cancer together with Folfirinox have led to the conclusion that is relevant to dry metasalumab in combination with Folfox, so a subset of the Folfurinox frontline, so Folfox and metasalumab in second line in binary tract. So just to remind you, the study is a randomized phase two study. It gives the opportunity to actually add a phase three arm if the phase two study is positive and that alligator is providing metacetamol to the investigators and minimal financial support in terms of scientific support. a little bit of insurance and pharmacovigilance. But other than that, a cost-free study for alligator. With that, I think we'll continue with HLX22. For those of you who are not familiar with HLX22. It's an innovative HER2 monoclonal antibody that is currently being developed by a Chinese company, Shanghai Helios Biotech, under license from Apclone, and the molecule was discovered following a collaboration with Alligator, and we have a certain financial potential upside by HLX22. And without going too much into the financials, our conservative estimate of a potential royalty stream annually between 150 and 400 million SEK remains unchanged. I think that it's fair to say that based on the data that has been published, the probability of the progress in the phase three study, I think we can say that the probability that this will materialize has increased. Why do I say that? First of all, the phase three study is ongoing and I will show some of the data in the next slide. But if you look at the table here, we have listed all the ongoing studies and planned studies that Henleus have announced. So the phase three study in gastric cancer is ongoing. It's a 550 patient global study. It's based on a very strong set of phase two data that I'll show you within a second. There is a breast cancer phase two study ongoing that hopefully will be completed soon. if not already. And that has led to the initiation or the planned initiation of two additional studies in breast cancer, a study in the neoadjuvant setting and a study in recurrent breast cancer. And you can see from the table here that you expect to enroll approximately 1,500 patients across across these trials. And then it's also worth noting that the company is planning to start recruiting in a small pancreatic cancer study, just like we've been running with metacernumab. So a strong expansion of the HLX22 program that of course is expanding the clinical footprint and of course also the commercial opportunity for hemios and hence the commercial opportunity for alligator going forward. Then before we jump into the HLX2 data and the phase three trial, I thought it would be interesting just to mention that a new molecule has materialized called HLX49, which is a bispecific antibody-derived, or antidrug conjugate, sorry, partly derived from HLX22. Let's see where that is going, but as per the HLX22 agreement, Alligator also holds a certain financial interest in this follow-up molecule. It's early, so we don't really ascribe any tangible value to that in our current financial modeling. So, if we go to the next slide, Greta, just to sort of even the playing field here, so we have the same set of information when we talk about HLX22, the company reported the phase two data at ASCO-GI, and you can see that in general, and you can see them in the upper left-hand corner of your screen here. And basically what you can see is that compared to the control group, which is a complex treatment of an antibody, in chemotherapy called C-LOX plus or minus pembrolizumab When you add HLX22 to that combo, that is the orange line there, you can see a very strong separation. And when you run the statistics, HLX22 actually infer up to an 80% reduction in the risk of disease progression or death. So a very strong phase two clinical data that we, of course, not only for the patients, but also for the valuation of the company that we hope will translate in the phase three study. So, in summary, good progress on mitosalumab, which is in alligators' control, and also strong progress on HLX22, driven by Henleus. And with those notes, I will leave the word to you, Johan.

Thank you, Søren. Perfect, thank you. So this is a snapshot of the financials for the Q4 2025. And as expected, we are seeing decreasing expenses due to the fact that we have, you know, more or less closed the clinical trial for phase two. And we also have completed the IMP production as communicated earlier. The second thing that I would like to point out is the net financial items that are quite huge and it's an effect out of the TU14 and previous to that the TU12 and TU13 and also the FENIA renegotiation that we have done during 2025. All of that, if you're interested, you can see quite extensive disclosures in the Q4 report and previous report as well, so if you want to dig in deeper to that. But all in all, it's mainly effects of should it go through the P&L or go directly to equity, if you want to summarize it. Can we have the next slide, please? Here is more of an optical graph of the decreasing cost and we are coming down to a baseline that is between 15 and 20 million per quarter in 2026 then given that we're not doing anything additional to this baseline then. The liquidity position of the company is now 62.2 million and we can then also conclude and communicate that all of the money from the proceeds have now arrived before the year end. So that's the total amount. And then of course, we had some bridge financing and repayments to be made. That's why the total liquidity position is lower than the actual capital raised. And as we sort of mentioned before, we also have the upcoming TU14 that I will cover on the next slide. Finally, then of course, We understand that this will take us then to Q2 2026. But of course, we are looking into various means of extending our runway and financing activities going forward. But let us come back on that. Next slide, please. So here we have the TU14 in a snapshot and we can the maximum raise additional 61 million gross and this is due to the quite narrow interval that we now know about for the subscription and so it's between 20 and 25 euro. And we are just now in the pricing period and so we will know in a week or two exactly the subscription price. And of course the uptake will determine the proceeds that we can raise. And as you can see to the right, then we do have the subscription period coming in the beginning of March, up to mid-March. And I think that's good for you to know that, so you at least know to act on your subscriptions or your TU14s then. And you can also then trade a TU14, buy or sell additional TU14s then up to 17th of March. With that, I think I will hand over to you, Søren, before we take any questions.

Thank you, Johan.

Just needed to get the technology to work here. Yeah, thanks. So if I can have the next slide, I just want to... We emphasize a few points that the phase two trial with metazolamab in pancreatic cancer is now completed. We have seen unprecedented landmark survival data at 30 months, 21% survival versus an estimated five for the chemo backbone. And that very nice set of data has now sort of been accompanied by another set of complete responders, bringing that number up to five. And it's very clear that this data warrants registrational development in the indication. That's not only something that the aggregator thinks, but that is the widespread belief with our key opinion leaders, both in Europe and the US. And the drug is phase three ready and we have established a regulatory path to approval. And of course, we continue to speak with potential partners about global deals and also, in certain extent, regional deals. Then we are exploring and executing development options beyond PDAC. As we just discussed, we are the most The most tangible, not tangible is not the right word, but the most prominent now is the randomized phase two study in biliary tract cancer that we will expect to start in the second quarter this year, which we really believe the fact that it's a parallel indication It's parallel disease biology, parallel chemotherapy, and the fact that it's a large randomized study really is a true development option for metazolamab in addition to pancreatic cancer. And then, as we discussed, the HLX22 program developed by Henleus, strong Phase II clinical data in gastric cancer leading into a a global trial that is creating some attention. And based on the phase two study in breast cancer, we also see the clinical program expanding in that indication with two new phase two, three trials in breast cancer. And then finally, I introduced you to HLX49, a bispecific antibody drug conjugate that is partly delivered from from HLX22. So a steady quarter, rounding up a very significant year for alligator, moving mitocelular map forward, reading out good data yet again, and closing down the trial as expected. And as Johan just mentioned, bringing down down the burn rate to a relatively low level of between 15 and 20 million sec per quarter. And with that, we'll take a couple of questions. Remember, you can always use the chat as we speak. We have a couple of questions here. from Philip from Red Eye. And I can see that there is a small little handful here. Philip writes that the RAS inhibitors or KRAS inhibitors, if you will, have taken a center stage in drug development in pancreatic cancer and other solid tumors. And Philip then asked, it seems like mitosalimab can be a useful combination partner with these inhibitors. And what are my thoughts? What are our thoughts on that? And do you have any discussions with potential partners? I think that's a very timely and thoughtful question. So thank you for that, Philip. Yes, KRAS inhibitors are most likely getting approved in second line probably already this year. And the leader in that drug class, Revolution Medicine, has announced that they will start a couple of phase 2 tree studies with their various inhibitors also in first line this year. So at least we know that Ras inhibitors will change the second-line landscape, and I think we can be fairly certain that they will also have some impact on the first-line landscape, absolutely. We will see how it pans out. I think what is clear from, to your point here about combination, what is clear from a number of independent preclinical studies combining KRAS inhibitors with CD40s, not done by alligator, but by independent researchers, It's clear that mechanistically the two drug classes work nicely together in CD40 agenists, giving deeper and also more durable responses in combination with the KRAS inhibitors than the KRAS inhibitors alone. So that's clearly a yes. We believe that metacelumab would be a very good combination partner with KRAS inhibitors as it is with chemo alone, both because of the mechanism, but also because of its benign safety profile. It's of course important when you combine drugs and you keep stacking drugs on each other in first and second line that these drugs have a safety profile that allows that to happen. Then the second part of the question is that do we have any discussions with potential partners about that? I would say we not only have discussions with partners about that, but we're also talking to a number of clinicians that have asked themselves exactly that question that Philip has, and we're exploring opportunities to actually run clinical studies in that combination. in the IIT setup that we just described. So that was a long answer to a very important question. Then we have a couple of questions here. all on the same theme. It's one from Joseph Hedden from RxSecurity. There's one from a gentleman called Banksy. I know his full name, but anyway. And we also have a question from Philip around the the milestone coming from or earned or to be earned from the Phase 2 study with HLX22. And AppClone's CEO has announced that he expects that milestone to be paid during the first half of 2026. I'm not necessarily commenting on his comments, but yes, that is definitely a probability. And I'm not free to let you know what amount that's going to be. But I can tell you, and I think I said this before, that it's relatively modest. It's based on the fact that the drug was licensed at a very early stage. And the clear upside to Alligator is through the eventual royalty payments.

And just to add on that subject, it's also then paid once the study is completed. So it has nothing to do with top line or something. It's when they complete the study. So if the study will continue because the patients are still on treatment, then the payment of the master will be deferred.

Absolutely. Good. Then the third question from Philip is, are you considering divesting your interest in HLX22 to a royalty farmer or maybe Abclo? I would say that yes, we are. It is being discussed to a certain extent. I think we need to also realize that the value of these royalty streams is a is a is a function of of probability of success and not not only value so it's clear that that the closer we get to to read out the potential value of of of of monetization will be will increase and and for alligators management on board it's really about finding the right balance, not selling the future royalty too cheaply to solve a, what can we say, I wouldn't negligence, but a smaller here and now problem and foregoing a significant royalty upstream, a royalty cash flow from and thereby investor value going forward. So the balance has to be right. to do so. And so far, we have been discussing, we have seen a number of, not a number, we have seen a few offers where that balance has simply not been right and where I don't think any of you would praise your hand, me nor the board, if we had signed any of those agreements.

But that's an ongoing discussion.

Then we have a couple of questions here. One from Carlo. Finding a partner to launch at the phase three story of META is time consuming. What other opportunities do you see beyond collaborating with other biotech and pharmaceutical companies? I think that's an excellent question. And Alligator, me, Johan, the board, the rest of the company, We are responsible management and we are stewards of Mitosalumab. And even though the main focus is finding a partner, we are also developing and have developed and are maturing opportunities to maintain the momentum of Mitosalumab leveraging some of the tools that we have discussed earlier today. We are also all aware that we are a listed company, so I cannot go into detail with those plans, but we will inform you and the market promptly if either a deal, of course, but also if something else materializes. But we are developing alternatives to continue bringing Metasellum up forward.

Then we have a question here. Runways.

So this is for you, Johan. Runway is short, so obviously a game plan for runway think extension uh is clinical it's critical beyond uh co14 and uh and uh if we could elaborate a little bit on on that i don't know how much you can say your hand but but a few words would probably be yeah not so much uh on top of what i said before around the the second quarter of 2026 but also what sir just mentioned that we are looking into options and of course that might

include some kind of financing. So all of that is a package that we are currently reviewing and maturing. So let us come back once we have something to disclose.

And then we have

A last question here for now, at least. Are there any potential commercialization partners discussed related to metacelumab phase 3? That's a good question. Yes, there actually is. There is a lot of interest from commercialization partners. beyond your classical development partner. And Hannah and I are, of course, entertaining these discussions. It's maybe a little bit too early to really... materialized discussions or advanced discussions with this at the current stage. But yes, there is a significant interest from commercialization partners relating to metacetamol.

Good.

I think that ended the list of today's questions. Unless we had... We had one question more here. I saw that in the chat. Now it disappeared. Gretchen, maybe you can help us have it... Any sense? Yeah, so this... There's another one. Now they're coming in here in the 11th hour. Any sensitive goals of phase three completion targeted? Let's start with phase three initiation. We have a phase three study agreed with the regulators of around 550 patients. And we expect that is a study that can be, depending on partner and depending on investment level, can be recruited in 18 to 24 months. And then you can expect a first interim analysis around maybe a year later from that at a time point where there is a real probability of approval. So approximately two and a half to three years, more likely three years after the first patient is

is enrolled in the study?

Then we have a couple of questions here about progress with partners. Yes. One is even asking whether it isn't better to do a bad deal than no deal. That, of course, depends on on how bad it is and what the alternatives are. The only thing I can say is that we are doing the best we can as management and board and advisors to negotiate deals with interested parties. And at the same time, as I said, we are developing alternatives that will make it easier to partner Mr. Saddlemap and still lowers the investment level needed to bring the drug forward for a partner and also maintain building value into the program. Somebody asked here, you previously said that you have advanced negotiations, or advanced some of the negotiations compared to before. Can you say the same today? I can, for a number of partners. It's also evident that one or two discussion partners have chosen to do other deals since last time we had a queue call. But business development is a process that takes a long time. It's not only the day that you send out the press release. Often you have one, two, three years discussions and negotiations before that. And I would say we're still making progress in those discussions. good and now i can see the chat is running dry so i want to thank you for your participation and wish you a lovely afternoon or day wherever you are in the world thanks a lot thank you