ExpreS2ion Biotech Holding AB (publ)

Welcome to today's event where we have the pleasure to present Expression Biotechnology. So that was through today's presentation. We are joined by Keith Alexander, CFO. Today's topic and very relevant with the CFO is of course the Fulia and Q4 results from you. So that will be the focus of the presentation today, but of course also a broad presentation to the company. As always, you can ask questions down in the box down below. Do it in Danish or in English. If in Danish, I will try and translate to the best of my ability. But for now, I think I will hand the call over to you, Keith.

Great. Thank you, Michael. Good to meet you all virtually for this presentation of our Q4 2024 results. As Michael mentioned, my name is Keith Alexander and I'm the CFO of Expression. Bent is unable to join today and I'm more than happy to provide you with an update. During this presentation, I will go through our company and pipeline with a focus on our lead asset, as well as our Q4 and Fulia 2024 results. Next slide. And we can just keep going. One more. For those who are new to Expression, Expression is listed on the NASDAQ first North growth market in Stockholm. The listed entity is our Swedish holding company, Expression Biotech Holding AB. Everything is done in the Danish entity located in the DTU Science Park, 20 kilometers north of Copenhagen. We are currently 18 full-time employees, predominantly employed in R&D. We own 34% of ADAPTVAC, a spin out from the University of Copenhagen. ADAPTVAC developed the VLP technology we employ in our breast cancer vaccine. Next slide. During Q4, we were able to deliver important news related to our pipeline partnerships and financing. In October, we announced the signing of a term sheet with SII, the world's largest vaccine manufacturer. The term sheet covers two of our four malaria vaccine projects, which the University of Oxford is developing in clinical phase one and two. We are still in the process of defining a final license agreement. We remain pleased that we have a foot in the door, as there seem to be several common interests in the vaccine field between our two companies. In November, a vaccine, our collaboration partner in the CMV Discovery Project, presented preliminary data from our cytomegalovirus vaccine discovery efforts. We entered December with the announcement of the CTA approval for our breast cancer vaccine development project, a major milestone. Shortly afterwards, we completed a 10 million SEC warrant subscription, which was 69% subscribed. Finally, also in December, we saw the publication of clinical phase 2b data for the RH5.1 malaria project in the Lancet Infectious Diseases Journal. This is one of the programs that SII takes an interest in. All in all, another exciting quarter for the company. Next slide, please. In this preliminary part of my presentation, the focus is on our cancer immunotherapy program, but I do want to mention that we have a broad pipeline of vaccines against infectious diseases. Most of these programs are carried out and funded in collaboration with leading academic and government institutions around the world. I do want to direct your attention to the bottom of the chart. We are part of a COVID-19 vaccine program that progressed into a large phase 3 trial a couple of years ago. As reported by our partner Bavaria Nordic, this COVID vaccine performed very well in phase 3. It was safe and highly immunogenic. However, the program was stopped because the pandemic was winding down and because the preference of that time was for vaccines which, although less immunogenic, were easier to adapt to the rapidly emerging new virus strains. This vaccine was based on the same expression and VLP technologies we now use in ES2b C001. Next slide, please. ES2b C001 is a novel -in-class immunotherapeutic vaccine to treat patients with metastatic breast cancer. What is unique about our product is that it combines, for the first time, one of the most validated cancer-expressing targets we know, the HER2 receptor, with two proprietary vaccine platforms, the EXPRESS2 expression platform and an in-licensed -in-class VLP platform, to target the entire extracellular domain of the HER2 receptor. This is unique and has not been done before. There are compelling immunological reasons to expect a broader and more powerful immune response from this approach than what has been seen before, and our preclinical data backs up this expectation. We are now recruiting for the phase 1 trial in breast cancer. The coming 9 to 18 months will be extremely exciting as the results start to come in and create additional value in our program. Additional cancer targets are also a possibility, for instance, gastric cancer and gynecological cancers like ovarian and cervical cancer. We have assembled an extremely experienced team around this program. Our ambition is to take it into phase 2 ourselves. We're currently exploring ways to fund this next step. So far, we have invested 30 million euros to date, including funding already allocated to clinical phase 1. Next slide, please. The chief feature of ES2B-C001 is that it's the world's first vaccine to incorporate all four extracellular domains of the HER2 molecule. Herceptin targets just one epitope, generally consisting of a few amino acid residues on a subdomain of the HER2 protein, the part known as domain 4, whereas progeta targets domain 2. So immediately, we understand why a combination of herceptin and progeta is more efficient than either molecule alone. But constructing all four extracellular domains is not enough. We need a vehicle to break tolerance. BLPs are virus-like particles. They are spherical structures that look exactly like virus particles to the immune system, but they are not viruses. They are completely artificial and inert in themselves. They contain no infectious materials, so they're completely safe. We tag our HER2 protein on these VLP particles. The platform is unique because it achieves this coupling of the HER2 protein on the surface of the VLP in a uniform and directed manner. It presents the same epitopes repeatedly in a tight array in the same orientation. This achieves two very important things. First, this is exactly how a virus looks like, which makes the immune system's reaction all the stronger. Second, this uniform expression of the HER2 protein on the surface of the VLP increases the chance of cross-linking B cell receptors, triggering a cascade of cellular responses that lead to B cell activation and ultimately to the generation of an adaptive immune response. In short, what we achieve is a polyclinol antibody response with numerous anti-HER2 antibodies direct against all four extracellular domains of HER2. Importantly, this vaccine is easy to combine with other treatment approaches, and it is reasonably simple to produce. Lastly, the concept of presenting antigens to the immune system via VLPs is already applied in approved vaccines such as Gardasil and Cerverix, which are HPV vaccines against cervical cancer. Our concept is in a very competitive, advanced vaccine technology. Next slide, please. It is always more difficult to treat cancer once it has been established. In this well-known therapeutic model, we administer tumor cells to mice and let them establish over the course of 10 days. Left untreated, these tumors at first grow slowly, but around four to five weeks they accelerate quickly to become significant tumor masses. We subjected these mice to the same treatment schedule we expect to employ in humans and found that we could completely prevent this tumor growth. In the control group, all 10 mice developed massive tumors by day 50 and had to be euthanized, whereas the 10 mice treated were still alive by day 600. We effectively cured them of the cancer. We saw that even without an adjuvant, ESGB C001 was highly protective. Next slide, please. There are industry-accepted algorithms that allow you to translate animal data like these into human years equivalents. If these algorithms are correct, our vaccine would lead to a progression free survival benefit of more than seven years. We don't dare to set our hopes at high. Nevertheless, we carried out an extensive literature search to find previously reported clinical data from some of the approved treatments that ESGB C001 will be compared to and are combined with. The best progression free survival data right now belongs to the well-known Herceptin-Perjeta combination, shown here as Pertussumab-Trestussumab. That combination's PFS is around 18 months. Trestussumab-Directstekin, branded as Inertu, might eventually turn out to be better. In this patient group, a PFS benefit of more than five years would be nothing short of a miracle. Next slide, please. The phase one clinical trial is a dose escalation trial, where we start with 50 micrograms with adjuvant and move up to 450 micrograms with adjuvant. Patients will receive one intramuscular injection every third week, in total five injections. The primary endpoints are related to safety. Secondary endpoints are immune responses and signs of clinical efficacy. The dose escalation will be carried out in three cohorts of three patients with advanced metastatic breast cancer, whose cancer is expressed for two. Subsequently, additional patients will be dosed to confirm the recommended phase two dose, whereafter we will have evaluated up to 27 patients in the 18 months, which we expect the trial to last. Next slide, please. Breast cancer is a significant market opportunity, with several anti-Hertu products selling more than one billion U.S. dollars per year. Inertu had sales of $2.6 billion in 2024, whereas Projeta had sales of more than four billion. Trends in this market include moving these treatments into earlier lines of treatment, patients with less Hertu expression, other cancers also expressing Hertu, and not least, international expansion. This is a very attractive market, with most of the major pharmaceutical companies, such as Roche, Pfizer, Novartis, AstraZeneca, and Amgen, heavily engaged. Next slide, please. We have developed a comprehensive bottom-up model of the market opportunity based on the number of breast and gastric cancer patients in different geographies. This graph provides a simple sales forecast if we receive approval in 2033 for Hertu expressing breast and gastroesophageal cancers. We assess peak sales of more than five million U.S. dollars. We believe there is much more, sorry, five billion U.S. dollars, and we believe there is much more room for business case improvement if we are able to price ES2B-C001 to the same level as Projeta and Hertu, both of which command significantly higher prices in the U.S. Pricing very much depends on the clinical benefits our vaccine is able to demonstrate in pivotal trials. The anti-Hertu market is intensely competitive with many big pharma players involved, so we have assumed a modest market share even in our upside case of up to 10% penetration. Nevertheless, the size of the opportunity is substantial. Next slide, please. The Hertu target has been the object of several substantial deals over the last 10 years. In 2019, AstraZeneca paid $1.3 billion upfront to InLicense and Codevelop and Hertu, which at that time had showed very promising results in Hertu and Hertu, and obviously Genentech's portfolio of anti-Hertu antibodies was a major reason, perhaps the main reason, why Roche acquired the company in 2009. Next slide, please. Now we're going to move to the financial results. On the next slide, in the fourth quarter of 2024, Expression generated operating income of 2.2 million Swedish crowns, a decrease of 5% compared with the prior year quarter. Our net loss in the quarter was 16 million crowns compared with a net loss of 13 million in the third quarter of 2023 and drove a loss of 7.03 sec per share or 5 sec on a fully diluted basis. At the end of December, Expression had 82 million sec in cash. I'll dive into the key drivers of these figures and others in more detail on the coming slides. Next slide. Starting with operating income, we experienced a 5% decrease year over year in the fourth quarter to approximately 2.2 million Swedish crowns due to the progression of client and grant projects. In the middle chart, we focus on net sales, which reflects revenue from projects, licenses, and our webshop. They were well below the long-term average in the quarter, reflecting the transition to a pipeline strategy, as well as an increase in emphasis on grant-driven projects. In the chart on the right, we show other operating income, that is grant-related income, which remained at a high level, driven primarily by the Ndigo and Mukavax grants, with a significant contribution from Vichy as well. On the next slide, moving to the cost side, operating costs in Q4 amounted to approximately 22 million Swedish crowns, a decrease of 4% compared with the fourth quarter of 2023. As a reminder, we announced a restructuring in the quarter of 2023, which has been a driver of cost reduction since then. In the middle and right charts, we illustrate the two largest components of operating costs. Starting on the left side with external R&D costs, these peaked in the fourth quarter of 2022 due to preclinical development costs for the breast cancer vaccine and have decreased since then. Compared with a year ago quarter, these costs were 26% lower in Q4 2024. Costs in this category are large, volatile, and primarily driven by our pipeline activities. Moving to the chart on the right, we have removed the cost of share-based compensation from personnel costs to calculate the underlying personnel costs. The underlying figure is approximately the cash cost of personnel. It peaked in Q1 of 2023 and was essentially flat compared to the year ago quarter. Note that personnel cost is sensitive to wage inflation and foreign exchange since we report in SEC and pay wages in DKK. On the next slide, moving to the net loss for the period after financial expenses and taxes, we had a net loss of approximately 16 million SEC in the fourth quarter compared with a net loss of 13 million in the year ago quarter. Note that the year ago quarter benefited from a 4.5 million SEC reversal, a prior year impairment of investment in associated companies. Excluding that, the Q4 2024 loss was less. We show the full year comparison on the right. For 2024, the net loss was 36 million SEC, a 60% decrease from the 91 million SEC loss in 2023. Our next slide shows how our cash balance developed in 2024. At the start of the year, the company had a cash balance of 58 million SEC. Cash burned from operating activities has approximately 34 million SEC. The net cash inflow from investing activities was 21 million, primarily reflecting the dividend paid by ADAPTBEC in April. Financing increased cash by just over 35 million driven by the rights issue completed in early July and the TO10 warrant subscription completed in Q4. Finally, FX increased cash by approximately 2 million. Putting this all together, at the end of the year, the company had a cash balance of 82 million Swedish crowns, an increase of 24 million year to date. On the next slide, we show the trend in our cash balance, which ended the quarter at 82 million, an increase of 6 million in the quarter. Looking forward, we have a warrant subscription period in the third quarter of 2025 for the TO11 warrants. On the next slide, which is the last, as we move into 2025, we have several important milestones ahead. We're focused on progressing the ES2B CW1 phase one trial, including generating the clinical data on safety, tolerability, and immune response. We're working to finalize a definitive agreement with the Serum Institute of India for malaria vaccines and continue advancing our discovery pipeline programs. Alongside this, we're strengthening our IP and validating our platform technologies through grant-funded projects. It's a busy year, and while the work isn't easy, we're committed to making real progress. Thank you for being part of the journey. And with that, I'll

perfect. Let's jump into that, Keith. The first question, with the current share price used in the TO11 program, how long is your current expected runway?

Well, I'm not going to answer that quite specifically. What I would say is that we're monitoring our financial position on an ongoing basis and very carefully managing our resources to align with our strategic priorities. As we are, we're very disciplined in our financial planning and management, and we're going to assess future funding needs in line with our progress and strategic opportunities. And as always, any material decisions about financing will be communicated to the market in due course.

In general, there's, of course, some questions about the breast cancer study. What is the status? And whether the timeline earlier announced is still holding up, or have you seen any delays? And also, has the trial started? And has the first person got any treatment? And if it has started, how long until you are able to trace any effects of this? So in general, a little bit about the breast cancer, whether the timeline is still holding up, and whether you have initiated the first patient already.

Sure. I'll try to unpack that in a bit. It sounds like a lot of questions. Yeah. What I would say is that we have initiated the trial, meaning that we've started recruitment. We will provide an update to the public once we have dosed the first patient. We're targeting metastatic, her two positive breast cancer patients, which naturally take time to recruit. I would say that so far, the timeline aligns with our prior expectations and planning. If we wanted to accelerate recruitment, we have the option of opening a second site that's within our budget as well. But it's important to recognize that these are very sick individuals, and they're going to make their own decisions about participating. So we want to be respectful of that. And we appreciate the patients or investors. And right now, we're just very much focused on executing the trial with high standards of care and scientific rigor.

Perfect. So I think the answer is that no first patients, I understood that. But we should look out for, you will announce when you start the first patient on the phones. That will be announced to the public through an announcement. Was that correctly understood?

That's our plan right now. Yes. Perfect.

Then there's a, could you please update us on the cooperation with the Serum Institute? And maybe there's also a question on when could we expect you to have finalized? Right now it's a term sheet. So a little bit, I know you can't give us an exact date or anything, but maybe an estimate on when do you expect to have finalized this deal?

Sure. Well, the discussions are still ongoing. It's taking perhaps a little bit longer than we initially anticipated, but we still remain very optimistic about reaching a definitive agreement. It's a complex agreement. So we're focused on making sure we get the best outcome for all parties involved. We're not going to set a specific timeline at this time, but we'll provide an update when there are material developments to report.

Perfect. And then there's also a question, and maybe you also touched a little bit upon it. Other potential collaboration with this cell, I know you can't give any details out if you're talking to it, but maybe just give your feel that there could be other potential candidate that this company could be looking at also in your pipeline.

I mean, sure. That's also something that we're exploring. And as I mentioned, my prepared remarks that there are certain things that we're both interested in, but I can't give anything specific at this time. We'll come to that later if there's something to announce.

Perfect. Then there's a question. There's not much news from ADAPTVAC. Can you give us an update on the ownership here and whether there'll be a dividend again this year?

Sure. I mean, there's no change to the ownership. We still own 34% of ADAPTVAC. Regarding updates from them, I'd actually encourage you to reach out to them directly or look at their news flow and see what they've reported. The dividend that we reported last year was definitely a one-time dividend related to a payout that they received from Bavarian Nordic for completing the phase three clinical trial of the breast cancer vaccine. So given that nature, we don't expect that to repeat itself.

And then a very specific question. I don't know whether you give out such details. How much do you expect R&D costs to rise in 25 with the phase one on the ES2B CO11 breast cancer vaccine starting?

Yeah, we're not providing forward guidance on our cost burn. So yeah, I think I have to just revert back to the prepared remarks that we had stating what we have used historically. And yeah, I think that covers what we can say here.

But if I understood you correctly, you say you have it fully funded. You have a cost overview and an expectation on what this should cost. Is that correct, Keet?

Well, I think we have funded the dose escalation part of the trial and that we the funding status later.

Good. I think that was the last question from the outside. So thank you to you, Keet, for presenting the results and taking the questions. And thank you for the audience for listening in. May everybody have a nice day.

Thank you, Michael.