Thank you all for coming today. My name's Keith Alexander, as he said, and I'm excited to present to you ExpreS2ion Biotechnologies. I'll start off with a quick overview of our company. I think many of you know who we are already. I see some familiar faces in the audience. Then I'll go into our pipeline and our platform and dive deeper with an update on our therapeutic breast cancer vaccine, ES2B-C001. Before we get started, I'd like to spend a few minutes on our disclaimer. Actually, I'd just encourage you to read it. Of course, there are important things here. What I present may include some forward-looking statements that can change over time based on things as they evolve. Of course, everything that we say is under this disclaimer. I'll start off with presenting a company overview.
Here's Max, our Senior Vice President of Research and Development. ExpreS2ion Biotech Holding AB is a First North listed company on the First North exchange in Stockholm, Sweden. Our ticker is EXPRS2, and the sole purpose of that entity is to own 100% ExpreS2ion Biotechnologies ApS. That's our operating entity. It's where we do all of our development and business. In the operating entity, we're around 20 people based in the DTU Science Park up in Hørsholm. All of our operations are there, and of course, we work virtually with a lot of other organizations as well, but we're 20 people up in Hørsholm. It's worth mentioning that we own 34% of AdaptVac ApS. AdaptVac is a joint venture that we started in 2017 with the University of Copenhagen, a group there called NextGen Vaccines ApS. It's a group of professors there.
They're important to us because they have a VLP technology, which is a virus-like particle technology, which can be a core building block for a vaccine. I'll mention later on that two of our vaccines are actually using their technology. Just briefly on the management team, we have over 100 years of combined experience that are relevant to developing drugs. Our CEO, Bent Frandsen, who I imagine many of you have met before or seen present before in this venue, has over 25 years of experience in Danish biopharma with some of the leading companies here. His background is in finance, business development, and management. Next is me. I'm the CFO. You can hear I'm American. I've been working in banking for over 20 years before I became the CFO of ExpreS2ion.
I worked at JP Morgan in New York City as a Research Analyst and also in asset management, advising the CEO and CFO of the asset management division. In 2013, I came to Denmark to work for Danske Bank, and there I was Head of North American Asset Management. So that's my brief background. Our CSO has over 35 years of experience. He's the most experienced of us. He's worked for many vaccine development companies, and he has a PhD in Virology. Our SVP of R&D and Technology, Dr. Max Søgaard, he's been with the company the longest, over 10 years, and his background is in molecular biology. Jumping into our platform, our platform is relevant and interesting because it enables two things. First of all, it enables the development of vaccines.
The way it can work is either that we develop vaccines using just the product of our platform, which is antigens, or we can mix them with various building blocks. I gave the example of a virus-like particle developed by AdaptVac. On the right-hand side of this page, you can see a depiction of what it might look like. In the middle, there is the VLP, the virus-like particle, which is an empty capsid with no DNA in it or anything, with antigens attached to hundreds of points on the outside of the capsid shell. This particular formulation is really interesting because it is safe. It looks like a virus to the body, but it has none of the harmful DNA. It is immunogenic or effective because it looks like a virus.
It can train the body to have an immune response against the virus, should it actually have the virus in the future. Finally, it is versatile. We can use this combination in a lot of different ways. We can develop vaccines for infectious diseases. We can develop vaccines for breast cancer. We could do it for other therapeutic areas as well, for example, cardiovascular disease. It is really a flexible platform. The second thing our platform enables is the production of hard-to-produce antigens or proteins. Here I am thinking more about our CRO business. We also have a business where we are making antigens for other companies, for biotechs and pharmaceutical companies, that they can use in their vaccines or in their diagnostic devices or for other purposes. There are a lot of advantages to our platform. It has a fast time to production.
It generates high yields for the amount of materials that you put in. It creates homogenous manufacturing batches, and that is important when you go into clinical production. Your product needs to be very pure and consistent. It is thermally stable. What we have seen in some of the vaccines that we have created in the past is that they could be transported at room temperature instead of requiring a cold chain, meaning transport at - 70 degrees Celsius or the like. Finally, with our antigens, there is the option for functional modification. We can alter them in some way, for example, by putting a sugar on the outside of the antigen to make them more immunogenic. We have some options there as well. Our platform has been validated in a lot of projects.
You can see here that we have projects at every stage of the development process, including up to phase III clinical validation. Right now I would say that, actually, I have updated this today or yesterday. With the malaria projects, we now have six partner-driven projects at the University of Oxford that are in phase I, and one that is in phase II. That is a lot of projects that are using our platform. On top of everything that you see here, the antigens that we have produced are in use by many biopharma companies for other projects that we cannot disclose here, either because we have not been disclosed them or because we do not have the ability to say it. Moving to our own proprietary pipeline. Our lead asset is a therapeutic HER2-positive breast cancer vaccine called ES2B-C001, and I will go into much more detail on this in a moment.
It's currently in the CTA enabling phase. We're very close to being able to file the CTA, which is what goes to the regulators for approval so we can start a phase I clinical trial. The next project we have is a cytomegalovirus vaccine that we're developing in partnership with another Danish company called Evaxion. They have an AI platform. They're also based up in Hørsholm at the DTU Tech Park. That one's in a very early stage of development. We hope to have a candidate by the end of next year. On top of that, we have two non-disclosed projects that we're working on, and we hope to be able to present to you guys in the near future. They're very exciting to us. The final thing I would say is that all of these are in very large markets.
The breast cancer vaccine is in a EUR 10+ billion market, depending on how you measure it. The other ones are in EUR 2 billion and greater markets. There's a lot on this page. I don't intend you to read this, but maybe if you download the presentation after this, you might be curious to look through it. What I'll do is summarize on the rows under general and fundraising over the last four years, which is the timeframe we've been a pipeline-driven company. We have raised over EUR 40 million, either through fundraising or through grant-driven projects. Our breast cancer vaccine started off as just an agreement on paper, and we developed it almost into the clinic. Our cytomegalovirus vaccine started off as a signature back in December of 2022, and right now is going through AI-driven candidate selection. It's going very rapidly right now.
Finally, I'd say that you probably know us from the COVID-19 vaccine. That was developed extremely rapidly for a vaccine. In our view, it's still superior to the ones that are on the market for a lot of reasons, but we won't go into that here today. Now I'd like to transition to our lead candidate, which is ES2B-C001, our therapeutic HER2 positive breast cancer vaccine. Just to talk about the unmet medical need. It's the most common cancer. One in eight women in her lifetime will have invasive breast cancer. Of the cases of breast cancer, 25% of them will have HER2 overexpressed, and this is more dangerous because you can have a more aggressive disease, more recurrence, and a higher mortality rate. Speaking of mortality, there's 685,000 deaths worldwide in 2020 associated with breast cancer. It's a terrible disease.
The competitive landscape, there are a lot of therapies on the market. The dominant ones in the standard of care are monoclonal antibodies, including Herceptin, which is trastuzumab and Perjeta, pertuzumab. The other novel form of therapy that's come to the market recently are antibody drug conjugates, and there the leading one is ENHERTU. The monoclonal antibodies work by targeting HER2 receptor on the tumors to decrease the spread and ultimately kill the tumor. The antibody drug conjugates, what they do is they deliver a toxin agent to the HER2 receptor to destroy the tumor. As I mentioned, there are a lot of therapies here. These are sometimes used together. They're sometimes used sequentially. When you get into the metastatic setting, you want to try everything. But even with these options, there are serious drawbacks. The first one mentioned here is that resistance can develop.
In a lot of cases, people develop ultimately a resistance to trastuzumab, Herceptin, and that's one thing we're going to talk about in a second. Next, it's a very arduous process to be treated with this. You have chemotherapy. You have intravenous injections that are made on a regular basis. It has a huge impact on the body, and furthermore, it's also hard for hospitals to do this because there is a lot involved in that. Then finally, these therapies can have the potential to be toxic. They can lead to heart failure and other toxicity events. The other thing not mentioned here is cost. They're very expensive. The average cost in the metastatic setting is EUR 150,000 a year per patient. This is quite high. In the early breast cancer setting, it's about half that, EUR 75,000 a year.
In addition to those, there are also other vaccines that are under development, but what I'd say there is that there are very few that have advanced into the clinical setting, and none of them are phase III validated. There's nothing that's approaching the market from a vaccine perspective. On top of that, all of these approaches have limitations. They either focus on a very select subset of the tumor group. They can also develop resistance, toxicities, there are some concerns with safety, the cost could be high, and we believe that our vaccine will actually address all of these problems and be better, and that's based on our preclinical data that we have. Now I'm going to talk briefly about what our vaccine is and how it works. Briefly put, again, we're focused on HER2 positive breast cancer.
The way we administer it is with a vaccine intramuscularly, just a shot like you would get with any normal vaccine, and the stage is preclinical. In the middle on the bottom, I show a diagram here that references back to our kind of illustrative vaccine. It works in this case because if you look at the call-out where we expand, you start with the VLP in the bottom, the AP205, that's the name of our VLP. There's a catcher and tag system connecting it to four antigens. These antigens represent the HER2 extracellular domain. There's a lot of science here that I cannot explain. I'd have to have our CSO go into more detail on it. But it's important that you understand that we're targeting all four epitopes of the extracellular domain.
The reason why that's important is if we look at the standard of care, here on the right-hand side, Perjeta and Herceptin, they're focused on two of the four epitopes. Because we're focused on all four, it makes sense that we would generate a broader immune response. We think that we're going to have a better response from our vaccine when it's put into a human body. In the next three slides, I'm going to show a bit about our data. The first one will be focused on proof of concept against trastuzumab resistance. The second is proof of concept in a preventative setting, and the third is in a therapeutic setting. Starting with overcoming Herceptin resistance, here what we have is basically a Petri dish where human HER2 cancer cells have been injected, and there are three Petri dishes.
The first one is left untreated, there you can see that the cells grow. The second is treated with Herceptin, there the growth is inhibited. The third is treated with our vaccine, also the growth is inhibited. Now the problem is over time, a lot of people with this cancer will develop resistance to Herceptin. We do it again against cells that have developed the resistance. We inject again these three Petri dishes with these cells. In the control and Herceptin, the tumors expand and grow. But then when introduced with our vaccine, they do not grow, or at least they don't grow as much. It has an impact on reducing the proliferation of these cells. This is early in vitro evidence. This is in a preventative setting. We have a type of mice called HER2 transgenic Delta 16 mice.
These mice will naturally grow a cancer cell that is effectively the human form of HER2 breast cancer. What we've done now is we've done three sets. We've done a control where they just age over time. The second will be injected with our vaccine, and the third will be injected with our vaccine with adjuvant. In the control, you can see that after about 24 weeks, very few of these mice are tumor-free. This is as expected. That's what they should do. When injected with our vaccine, less than half of them have a tumor. When injected with our vaccine with an adjuvant, none of them have a tumor. It's very common to use an adjuvant. Adjuvants are added to a lot of vaccine. All the HPV vaccines have adjuvant added.
This shows that our vaccine is effective in preventing the tumor growth. Of course, now we need to test it in humans. Now shown in a therapeutic setting. Now we have a different kind of mice. These are called FVB mice. They've been injected with the cells on day zero. After that, what we've done is we've injected them with the vaccine on all the points that are red, then we've done what's called a bleeding, where we remove a sample on the days that are black. What you can see in the black, that's the control. After about 75 days, the average volume of tumor is 2.5 cu cm in the control group. With our vaccine, it's about 0.5 cu cm. With our vaccine with adjuvant, there's no tumor growth.
In this case, we prevented tumor growth even when introduced with a tumor. I'm going to show on the right-hand side the same mice over a much longer period of time, 600 days. We wanted to see what the survivability was. You can see within, I guess it's around 60 days, all the control group have tumors. When they've been introduced with our vaccine, it's less than half that have tumors. When they get the vaccine and adjuvant, none of them have tumors. Therapeutically, our vaccine has worked in mice, and we need to test it in human. Where are we now? As I mentioned before, we're almost ready for the clinic. We've completed our safety study. The draft report is almost fully complete. In terms of manufacturing the drug, we're producing the drug right now for the clinical trial.
It just needs to be put into vials. Stability studies are underway. Those continue for many years as we do the trial. It is just to understand how long it lasts. The clinical phase I trial design is underway. Finally, what I would say is that we have been talking with various potential pharmaceutical partners to see if somebody wants to co-sponsor the clinical development with us. Finally, I want to talk about the market. We estimate the obtainable market for this vaccine is EUR 2.8 billion. How do we get there? We start with the total number of breast cancer patients per year, which is 1.4 million. That is estimated at a $32 billion market by 2026, I believe it is. We then filter it down to the top eight countries focused on advanced and early breast cancer. That is 1.1 million patients per year.
We are very selective about the serviceable addressable market. Here we are just doing EU and the top five countries in the U.S. We then go through each HER2 breast cancer type, and we say what percent can we actually address with the therapy? We are down to 114,000 patients per year. Finally, we assume a penetration rate. There is an uptake curve for every drug as it approaches or enters the market. It is very standard. We start with 4% and we assume a peak penetration of 20% after four years. At that peak penetration, it is about 26,000 patients per year. Based on the prices in the market, that comes out to about EUR 2.8 billion. That is how we think of the market, and this is down the road when it is in the market.
Finally, I want to say that we are backed by a very experienced oncology scientific advisory board. They have been advising us through the whole process. These are the foremost experts, primarily in the U.S. and in Europe, in oncology and specifically breast cancer. You will see a few names here from Denmark, but also in Tennessee, in Vienna, and in Spain. From around the U.S. and Europe. Just to summarize at the end, as I mentioned before, we are targeting a huge unmet medical need of breast cancer, the most common cancer. The market size is EUR 2.8 billion. Our platform is technically validated in phase III clinical trials, and we have an experienced team of management, our Board, and our oncology scientific advisory Board. I hope you enjoyed the presentation. With that, I will take any questions.
Thank you.
Two questions.
Okay.
Wasn't there something about malaria vaccine at some point in Africa?
Yes.
Also, what are your competitors in the breast cancer study?
Sure. Starting with malaria, yes. Actually, I think I show it briefly here as proof of concept. Yes.
Oh, sorry. Yes.
No, it's okay. I know we presented our pipeline differently before. I think, because it's actually the University of Oxford who's running these projects, and it's using our antigens as the active ingredient, it makes sense to show it as proof of concept for our platform. But we don't own those projects. It's University of Oxford that owns those projects. Then the competitors in the breast cancer space. There are competitors out there, and actually Perjeta and Herceptin, they're both owned by Roche. I forget who owns ENHERTU. That could also be Roche from what I understand. But there are some large companies there. Roche, Merck, I believe, has some products there. There is activity in the space, but there's still room for an improvement. As I mentioned before, a lot of people will develop tolerance to those medications.
What we're looking at is maybe a cure, but first and foremost, what we want to do is extend and improve the quality of life of people who have breast cancer.
Thank you for the presentation. I was thinking about, you're now going to start this breast cancer study, right? The financing, you don't have that much cash now. You have the possibility that you get part of the royalties paid from Bavarian Nordic to the other company. What's it called? It was-
AdaptVac.
Yeah, exactly.
Yeah.
Are you going to? You need some funding right now
Yeah
to finance this study.
We're a public company. There's only so much I can say about that, but yes, AdaptVac has actually received money from Bavarian Nordic for the phase III clinical trial milestone. They've put out a press release saying, and actually we have too, that at some point they will dividend a portion of it to ExpreS2ion. They haven't stated how much. They said they're going to conserve some for operating needs. Keep in mind, a portion will also go to NextGen. We only own 34% of ExpreS2ion, so we get a share of it. Beyond that, we're pursuing other things as well, grant applications. We mentioned the Nipah grant back in December, which is quite a large grant. Of course, fundraising is also something that is on the table. We're pursuing everything concurrently.
We would prefer not to do a fundraising, but of course that's a luxury if we cannot.
Yes. It would probably be a little bit difficult, you could say, to get money because you're very early stage now.
That's, I would say-
Stockholm syndrome.
What I'd say is that the market conditions last year were pretty terrible for early-stage biotechs to raise capital. We're in regular dialogues with our bankers, and as somebody who's worked in the market for a long time, I'm constantly looking for improvement there. What I would say is that we've seen improvement in the U.S. this year in terms of fundraising, but I haven't seen it fully hit the Nordics yet. There is a bit of improvement happening, but it's from a very low base in Sweden. I'm always hoping for the best, but we have to be realistic also.
Then, a little more, or a question on your breast cancer vaccine. Is it going to be a therapeutic vaccine or preventive vaccine or combination maybe?
That is a good question. We have to start therapeutic. That is just how it works. When we put this on the market, the regulators will want to focus on the people who are furthest along first, and then we have to back up and show safety to people who are least affected. Over the long term, it could be theoretically a preventative vaccine, but that is pretty far out. That is going to take some time to get there.
Okay, thank you.
Sure.
Any more questions? D o we have, yes.
Thank you. The milestone from Bavarian, is that the end of the COVID money flowing in?
I've got a simple answer for that. Yes.
No investors talk about COVID anymore when you meet them?
Not so much. I think that just given how much we talked about it from 2020 to 2022, 2023, I think we'd all like to put it behind us. Of course, we still think it's a great vaccine and there is potential for developing it into something that can work for the future. But it's not something that investors or I'm talking about much.
Okay. Is there any way to capitalize on the malaria projects or some of the other partner projects?
Yeah. I think that anything that is using our technology has the potential for some kind of commercial licensing arrangement, should it make it to the market. I think we have to wait and see how those develop before we can start saying anything definitive about them. There's time there. But there could be a potential commercial licensing agreement in the future. I wouldn't say that's in the near future.
If or when they go from phase II to phase III, there'll still be no milestones to you or anything?
No, not at this point.
You don't sell any product to them or to your-
You mean from our-
Your technology, the, your technology is in that, in their vaccine.
Yes. They're using our technology under the agreement that we already have with them. I don't believe that they would need to pay more to use it in the phase III clinical setting. But to get it into the market, I believe they would have to sign a commercial licensing agreement with us.
Yes. Yeah. That's all for me.
Okay.
Do we have more questions? Maybe just one more. Yes, of course.
Sure.
I don't recall whether you were focusing on the news flow in the coming time. As an investor, to invest in this stock now-
this year now, what should we expect regarding the news flow? The most important news flow will probably be regarding your breast cancer vaccine, right?
That would be the start of the study, but most important would be the data from the study, right?
Yes, I agree, but there is also the clinical trial application process, the approval, the first in human dosing, and then the data. There could be interim data points along the way. I haven't seen the final study design yet, so until we see that, we do not know exactly when that is going to happen. Another factor is the speed, depending on the number of sites that are used. Basically, the phase I duration is highly dependent on how fast we can find patients. Basically, by adding two sites, you double the speed at which you can find patients because you are going to two different areas. So if we have more money, we can do more sites, which means we can deliver the data faster. Did that answer your question?
Yes. But you do not have the money now for the study, right?
That is correct.
Yeah. Okay.
Yeah.
Just a last question.
Which is very common for biotech companies.
Yeah.
Just a
The last question, we haven't seen any breast cancer vaccines on the market. How come? There must be some challenges in developing this kind of vaccine, right? There must be a reason why we haven't seen any vaccines on, breast cancer vaccine, products on the market.
I'm not a virologist.
No.
I'm not a vaccine development PhD, but-
You're CFO of a-
Exactly. But what I do understand is, I showed you the competitors here, and in terms of vaccine development, people are trying. Maybe it is just too early, or maybe they have had the wrong technology. But from what we have seen our technology do in the COVID-19 vaccine, we are very optimistic about what it can do in the breast cancer vaccine.
Great.
Yep.
Was that the last question? No hands. Thank you very much to Keith Alexander.
Yeah. Thank you.