Adaptive Biotechnologies Corporation (NYKD) Earnings Call Transcript & Summary

So good afternoon and good morning to our guests and listeners from the U.S. I'm Michael Engsig, CEO of Vaccibody, and I'm very much looking forward to take you through what we consider to be a very important next step in building the leading vaccine technology company. Before I introduce my co-presenters today, I just want to take you through a couple of housekeeping issues. First of all, the forward-looking statements, I assume you are all familiar with those. And on that basis, we'll quickly move forward. You are also very welcome to send in questions via the function on the link on the web page you're looking at right now, and we'll be addressing these towards the end of this presentation. If we go to Slide 3, I am very excited to have with me today Agnete Fredriksen, Co-Founder and Chief Innovation and Strategy Officer of Vaccibody; Mikkel Pedersen, Chief Scientific Officer of Vaccibody; Siri Torhaug, Chief Medical Officer of Vaccibody; and from Adaptive Biotechnologies, Harlan Robins, Co-Founder and Chief Scientific Officer. If we move to Slide 4. Today, we'll be talking about the announcement we announced this morning, the collaboration and license agreement with Adaptive Biotechnologies, and we'll take you through the technology platform of Adaptive. We'll be talking about Vaccibody's CoV-2 vaccine efforts, both preclinical data as well as early [ vision ] efforts on the clinical side. And we will finish off with a quick look at finances, outlook and an update on our NEO N-02 program. If we move to Slide 5. For those listeners that are new to Vaccibody, just a few words on Vaccibody, Vaccibody at a glance. Vaccibody is a clinical-stage immunotherapy company. We are entirely focused on developing our leading vaccine platform, taking advantage of our differentiated technology to address a broad range of diseases. Our claim to uniqueness with our technology is our ability to target the antigens to the antigen-presenting cells. So that's the take-home message we really would like you to walk away with in terms of understanding the point of differentiation for Vaccibody: our ability to bring the antigens to the antigen-presenting cells. We have a highly advanced oncology pipeline with 2 clinical assets, VB10.NEO, which is a fully individualized cancer vaccine; and VB10.16, which is an off-the-shelf vaccine against HPV-driven cancer type. And we announced a significant landmark collaboration with Genentech in October last year. In addition to that, we are rapidly progressing our infectious disease platform and last week announced some news on the clinical development aspect of this one. And today are announcing a very interesting collaboration with Adaptive Biotechnologies regarding the T cell-focused variant or candidate in our pipeline. So in essence, and in a few words, what we're announcing today is a very exciting collaboration and license agreement with Adaptive whereby Vaccibody in-license gain access to Adaptive's proprietary epitopes, T-cell epitopes. And Vaccibody will be responsible for further development, manufacture and commercialization of the vaccine products. And we have already announced that we are right now planning to take the product into clinic in the second half of 2021, and we'll get much more into details on these aspects later today. So with those words, I'm going to hand over to Agnete to take us through an introduction to the COVID-19. Agnete, on Slide 7, please.

Slide 7, yes. Thanks, yes. So absolutely, we are pursuing our COVID-19 vaccine candidates and taking them forward into the clinic. And why is there still a cause for concern? We do see that these genetic variants of SARS-CoV-2 continue to emerge. As you're all aware of, we do observe that there is a decline in efficacy over time and a continued emergence of these variants are still expected. What we also see from these first-generation vaccines is that the variants do add increased transmissibility and/or infectivity and we see a reduced sensitivity to these antibody-based immunity over time. The current variants of concern includes the alpha, beta, gamma and delta where you see alpha was rapidly dominating from earlier this year, and then now we also have the delta that is increasing in numbers every day. So unfortunately, it seems to be just a matter of time before emerging variants do escape immunity from the current vaccines that are based on -- still based on the original Wuhan spike sequence. So if we go to the next slide, Slide 8. As of December last year, Vaccibody did publish data from the first-generation vaccine, which consisted of the receptor-binding domain, the RBD, from the spike protein from the original Wuhan strain. That showed very promising preclinical data with rapid onset of immunity, both antibody and T cell responses. And at that time point, we realized that these variants of concern were coming, and we needed to update the vaccines. We have focused on novel vaccines compared to those that are already on the market. So what we are moving into the clinic now is second-generation vaccine that's based on the same concept that we published back in December but with the receptor-binding domain that is matching the South African or beta variant that is currently circulating. We have some data today to show to you that, we think, is very encouraging. We see that it offers a rapid, strong levels of neutralizing antibody responses, but we also see that it's able to neutralize several variants of concern. Also, as it's very important today where we have our friends at Adaptive joining our call, we are developing what we can call a third-generation vaccine that is very different from the vaccines that are currently being used. And this is targeting universally broadly protective T cell vaccine. There is increasing evidence of the importance of a broad T-cell response against COVID-19. But also these T-cell responses are very important for offering long-term memory responses and very important as, if you are able to generate a broad T-cell response, this will be less sensitive to viral mutations, both the ones we are seeing now and in the future. So with this vaccine, we aim to boost and also broaden the most clinically relevant and conserved T cell responses against multiple SARS-CoV-2 epitopes. And these have been identified by Adaptive Biotechnologies with their unique technology that I will come back to. So we aim to use long-lasting protective immunity across all population groups and across current and future variants with this vaccine. Interestingly, also what we've seen with the technology, because we target the antigen-presenting cells, is that we do generally see a very rapid onset of immunity, which opens up for potential for safe, effective, easy-to-administer drugs in a therapeutic setting that can reduce severity and also clear infection. If we go to the next slide, we are, as you can see, very selective when it comes to the partners that we choose to work with and that it is truly a partner of choice for Vaccibody. When I mentioned the importance of the T cell responses, it has been a true technical difficulty to really map the specificity of T cell responses across the broad patient populations and which ones are immunodominant. Adaptive has really changed this over the last years, and they have now applied their immune medicine platform to identify and validate immunodominant T cell epitope hotspots across several different diseases. When it comes to COVID-19, as you'll see, they've used their sequence information sampling with samples from more than 6,500 patients that are impacted by COVID-19, more than 150,000 specific TCR-antigen pairs across the entire viral genome and not only the spike antigen. Their technology is also validated through their diagnostic tool for COVID. So they have launched the T-Detect, which is the first-in-class T cell-based clinical test for COVID-19 that has received its FDA Emergency Use Authorization. So this is really our partner of choice, and it has been a true pleasure so far to work with the entire Adaptive team to design this vaccine that we are now moving into the clinic and is the basis for the announcement today regarding our in-licensing deal with Adaptive. And it's my true pleasure today to introduce you to Harlan Robins, which is the Co-Founder and Chief Scientific Officer of Adaptive Biotechnologies and looking forward to hear you and your story, tell us more about Adaptive, Harlan.

Thank you. So I'll first introduce Adaptive for those of you who are not quite so familiar, and then I'll describe the technology more broadly and then get into the specifics on how we're applying it in COVID and the specifics about the relationship with Vaccibody and how excited we are about helping them develop a vaccine that we think might have a much broader and lasting efficacy. So if we could turn to Slide 11, please. Okay, so Adaptive was actually founded in 2009. I was a professor at -- a faculty member at Fred Hutchinson Cancer Center in Seattle. And my colleagues and I created a technology that I ended up spinning out with my brother actually to form Adaptive Biotechnologies in 2009. A few years ago, we went public on the NASDAQ, and we now have nearly 700 employees. We're headquartered in Seattle but have offices in San Francisco and New York and recently, an entity in Amsterdam in Europe. And we've prided ourselves on validating our technology in the public sphere. So we have 600-plus publications to date related on the technology. And we've developed quite a massive database, which is sort of the heart and soul of our barrier and our technology. And I'll go through that as we go through this -- after this. Okay, so the primary pieces of our technology that -- of our company that create value and create a moat around the platform is the technology itself, which is, one, for sequencing T cell and B cell receptors, which I'll tell you more about in a minute; as well as connecting T cell and B cell receptors to the antigens they actually bind to and induce immune response against. We have a strong computational biology and machine learning component to our work and a really nice partnership with Microsoft who's also headquartered in Seattle area and contributed 40 FTEs that are machine learning experts to our program. And then we have this large database, which I just told you about. And all of this together leads to many different applications, mostly because the adaptive immune system is involved in so many different disease states whether it's helping prevent or clear a disease or, in the case of autoimmune disease, causing a disease. And in fact, I think we're seeing that in COVID, too. That's the immune system's response that often causes some of the symptoms. But so either way, because the adaptive immune system is involved in so many different disease states and our expertise is really understanding what the adaptive immune response is doing at a specific scale, a really small scale, we're able to create applications across the board. And I'll go through what those are in a minute. Next slide, Slide 13, please. Okay, so the adaptive immune system is made up of 2 different types of cells: T cells and B cells. And these cells are unique in the human body in that all the -- every other cell in your body has the same DNA. If you have a heart cell, a lung cell, a kidney cell, the DNA, except for some minor mutations, are genetically identical. This is not true for T and B cells where they actually make unique genes by rearranging one particular little piece of their DNA to create new receptors. And the idea is that you want to create so many different receptors with so many different shapes that no matter what foreign entity comes into your system, at least one or more of those is bound by a T cell or a B cell receptor, which then causes a cascade and creates the adaptive immune response. And this is the human body's way of protecting itself against foreign entities. But what that means is that the vast majority of the unique genes in your whole body are these T and B cell receptors. You have 30,000 genes in your genome, hard-coded, and you have tens of millions of different T cell and B cell receptors. So what Adaptive does is specifically focus sequencing. We apply high throughput sequencing specifically to these T and B cell receptors in a quantitative way, and that creates this huge database of genetic information from these T and B cell receptors. And then we have a separate technology for actually mapping these receptors to exactly what they bind to, to what the antigen is, the piece of the disease; in the case of COVID, the piece of the SARS-CoV-2 virus that these particular receptors bind to. And we use that for that data that we get out for research purposes, for diagnostics and for drug discovery. And I'll just take you through what our pipeline is in a second. Can you turn to Slide 14, please? So in the upper left corner, what we originally started with is using the technology for a variety of research applications. And right now, we have a set of products that groups use sort of all over the world whether they send us samples we run in our lab or we send out kits that works for companies and/or academics to use in their own lab. On the upper right side is our diagnostic. We have 2 different diagnostics platforms: ones with B cell receptors and ones with T cell receptors. The B cell receptors are sort of applied specifically to measure residual disease in blood cancers. And those top 3, for ALL, multiple myeloma and CLL, are all FDA approved and commercialized. And for NHL, the rest of the non-Hodgkin's lymphoma bucket, is also available in our lab for [ clinical use ]. So these are all used regularly for commercial use, for people, for monitoring and treating leukemias and lymphomas. On the bottom right, we're developing another set of diagnostics based on our T cell platform, which is more related to what we're working with Vaccibody on. And in this case, our first product was a COVID diagnostics. So we have the first T cell-based diagnostic for any infectious disease, and that's on market now and being commercialized. So we have a pipeline of many more, a couple coming later this year. And then in the coming years, we'll have more and more diagnostics built off the same platform. On the drug discovery side, we have a large cell therapy collaboration with Genentech, which as you probably -- it's not coincidence. I think that Vaccibody's largest partner on the personalized side is Genentech as is ours. And that was -- the main introduction between Adaptive and Vaccibody was through Genentech. So they've been great partners to us and to Vaccibody. So now hopefully, independent of them, we're going to form a great partnership with Vaccibody directly. And so on the vaccine side, you can imagine that the same technology, if we can understand and use T cells for diagnostics and therapeutics, what they bind to, really understanding what it is that's driving this immune response, is really the key to how vaccines work. So we just basically let the T cells tell us the answer to that. We ask the T cells what they're binding to in a real immune response, and then we know for sure and can confirm that that's really what's driving the immune response in the first place. So those are what you'd want to use for a T cell-based vaccine. Okay, so how does this work? If you go to Slide 15. We have 3 main sources of data. One is a way of mapping T cells to antigens. And I have a little schematic of this on the right-hand side. I won't go through how the technology works exactly. But this is a proprietary technology that we don't actually sell at all. We just use internally. And what we do is we map T cells to antigens at scale. So we'll take thousands of antigens and cross them against tens of millions of different T cell receptors in each experiment and just run experiments over and over again to create this massive mapping between T cells and antigens. Then we employ Microsoft's and our computational team as a collaboration to elucidate more of the mapping than we're able to come up with explicitly from the experiments. We basically learn from these experiments about other mapping, the rest of the mappings between other T cell receptors and other antigens that we haven't seen before. So together, we're making this quite massive map. And then we then do case control studies where we sequence thousands of patients with a disease and we have many, many tens of thousands of healthy controls. And we can look and see which T cell receptors are enhanced in the subset of patients versus the controls, and that confirms that these really were part of an immune response. And when we do that correctly, those enhanced sequences form the basis of a diagnostic, which I'll show you in a second. And then that's what also creates this massive database as we go. So can you go to Slide 16? So how do we apply this then to SARS-CoV-2? Well, as you can see, this is a map of the SARS-CoV-2 genome. And the red parts highlight the spike protein. All prior vaccines are targeted on spike and spike alone. And the reason for that is that the spike is what this RBD -- the tip of the spike protein is what actually binds to the human cells, the ACE2 receptor on lung epithelial cells. And this is what allows the virus entry. And so you can imagine that the way you block with antibodies' viral entry is by having these antibodies stick on the top of the spike, and that's how you neutralize the virus with antibodies. And since that has been the primary effort of how vaccines have worked up until now, that was the entire focus of the vaccine technology. However, if you go to Slide 17, we're hitting a moving target. And in particular, because the same spot where the spike protein binds to the ACE2 receptor is the spot where the neutralizing antibodies bind, it's also the spot that allows the virus -- any new changes in that virus at that spot can allow the virus to get into the cell faster to be a more effective virus effectively and increase its efficacy, its fitness. And so because of that, that's the spot that keeps mutating and causing these variants of concern, as you can see. And that's a very dangerous thing for the present set of vaccines. And if you go to the next slide, on Slide 18, you can see by many different studies, the gray bars are across the -- these are all the different variants of concern on the bottom here. And the gray bars are the amount of neutralization that you get from the standard vaccine against the different variants of concern. You can see that it drops massively. So the variant from -- the delta variant, for instance, for most of these different vaccines, you have less than 20% of the efficacy you would get against the initial strain. The T cell response, so far, hasn't changed at all, and it's still just as efficacious, which is likely why these vaccines are still performing reasonably well even though you lost a lot of your neutralization. But the scary thing is that we've so far only seen -- we probably haven't yet seen much evolution of this virus due to selection pressure from the immune system because it had -- now it's just increasing its own fitness and coincidentally, that happens to knock out a lot of the neutralization. But as more of the world gets vaccinated and more of the world gets infected, we're going to start to see significant changes where the vaccines -- the real pressure of this vaccine is going to be applied by the immune system. And that's a scary place to be because that should knock out the efficacy of some of these vaccines. And that's why we're so excited about this partnership with Vaccibody where we can perhaps overcome that and have a vaccine that has much broader and long-term appeal. So if you go to Slide 19. We've mapped out the immune response at the epitope level across thousands of different people, specifically to all the different pieces of the SARS-CoV-2 genome. If you look in the upper right corner, the blue lines are all the spots that we've seen T cell responses, both Class I and Class II responses, to the virus. And we can determine exactly the relative amount of immune response to each of these different spots and elucidate them directly. If you go to Slide 20. As I said a minute ago, we've used this information to create diagnostics. And here, we've trained our model on thousands of different patients and controls. And then we've applied it also to many, many thousands, now tens of thousands, of patients and controls as well. And as you can imagine, these T cell receptors that are specific to SARS-CoV-2 are found in much, much higher levels in people with SARS-CoV-2 than not and, therefore, make a really good diagnostic for assessing whether or not someone's had a past infection of SARS-CoV-2. Okay. But the same technology can be used, as we were saying, to explicitly determine what the antigen is, what it is that the immune system is binding to. And how do you take advantage of that information? Well, this is what was so exciting to us about Vaccibody, which is that they're able to actually target the T cell response by having their vaccine directly be targeted towards antigen-presenting cells that can present the T cell response and not just the epitopes to generate a B cell response. So the adaptive immune system has 2 pieces, and vaccine makers have sort of systematically ignored the half of it, right? They focus only on this top part here, which is the -- sorry, this is Slide 21 now -- the antibody response, which is obviously a massively important part of protection against future infection and ability to reduce harms from actually getting infected. And Vaccibody is able to do this as well. But it's this bottom channel that they have a unique ability to do, which is actually target it to cells that present and generate a T cell response. So the combination there is what's going to be needed, I think, to create a much broader immune response against these different variants. You're creating -- instead of being focused only on the spike protein and only on a very small subset of potential epitopes where you can get -- reasonably expect there'll be immune escape from the different variants in the future, we can, combined with Vaccibody, target epitopes from all over the virus in a much broader sense to create basically a set of immune response that can't be escaped because there's too many different places that you'd have to modify the virus. You'd have to have too many variants to escape from this. And that, of course, is also exciting is their ability to -- the actual component and delivery mechanism, which is hopefully much, much cheaper and easier and more stable. This can be used at room temperature. It should get around a lot of logistical concerns of some of these RNA viruses at present. So we're also excited about that aspect. And then just finally, just on Slide 22, and I'll end it and pass it back to the team at Vaccibody. Just to give an explanation of what we're doing with them, we're picking and validating the T cell epitopes that we see that are actually generated by the human immune response to SARS-CoV-2 within each different HLA context. We're only including ones that are naturally processed, presented and immunogenic, so true epitopes that are seen by the immune system. And then we focus specifically on the immunodominant T cells. There's lots of potential T cell epitopes, but we're able to pick out the ones that are specific here. And then this informs the design of Vaccibody's second-generation COVID-19 vaccine. So anyways, as you can probably tell, we're super excited about this collaboration and very excited to work with Vaccibody. We've known them for a decent amount of time now and already started working with the group. And I think both on the science side as well as on the personal side, this has been a fantastic collaboration. We're really excited about moving forward and think we have a chance to really help the world as this virus continues to evolve and be a plague. So I'll pass it back. Thanks to Vaccibody.

So can I -- Agnete, you're on mute. I'll just jump in here to the operator. I'm getting feedback that the slide number is slightly delayed versus what we are trying to present here. So apparently, we have a 1 to 2 slide delay. Can I ask you to look at that to make sure we are showing the right slides? I'll hand it back to you, Agnete.

Yes. Okay. Thank you. And thank you, Harlan. It would be good to have the correct slides up at the same time point as we're speaking to. I hope you all got a very good background on Adaptive and their technologies and understand the uniqueness of what they bring to the table and the synergy between Vaccibody's technology and Adaptive's technology. I would like to give the word further on to Mikkel, our new CSO, that will show you some of the exciting preclinical data that we generated with both the candidates, both our RBD candidate as well as the T cell epitope candidate, that we're working on together with Adaptive.

Thanks a lot, Agnete. So let's move to Slide #24. So in the next few slides, I will share an overview of the design of our vaccine candidates and then give you some highlights of the preclinical data that we have generated. So first of all, as Harlan and Agnete also alluded to, our rationale for developing 2 vaccine candidates is that we want to exploit the protective role of both the humoral, which is the antibody mediated response; and also the cellular immune system, which is the T cell response. So both of our vaccine candidates are built on our targeted modular platform. So they both contain targeting units, a dimerization unit and then an antigen unit which, of course, is different from the 2 candidates. So if we turn first to the VB2129, which is our RBD candidate. So RBD is the receptor-binding domain of the spike protein. So it's a smaller part of the spike protein compared that we're using, which specifically is the domain that is involved in binding to H2 on the human cells. So for our RBD candidate, we have decided to use the beta variant of concern, the RBD sequence for the antigenic unit. So this is, can I say, different from the original Wuhan sequence that is used in many of the first-generation vaccines. In particular, what has been a concern of the South African variant, or the beta variant, is that it has been proven to be really resistant to neutralizing antibody responses, both in vaccinated people but also in people that have recovered from the COVID disease with the original strain. In particular, the immunoassay residue E484K has proven to be critical for driving this resistance to first-generation vaccines. So we believe it's important to include this immunoassay residue in particular in our RBD vaccine candidate. Then we have our second candidate, which is the VB2210, which is our T cell candidate. And the antigenic unit here, as Harlan and Agnete described, is the range of validated T cell epitopes that are identified by Adaptive Biotechnologies. So on the next slide, 25, I will show some data on our RBD candidate, VB2129. Let's jump to Slide 26. I'll just give the time for the slide to load for those on. So what we did here was that we vaccinated mice with VB2129, the RBD candidate, at day 0 and at day 21. We used different doses, as you can see, of 1 microgram, 6.25 microgram, 12.5 microgram and 25 microgram and then measured the antibody titers in the mice at day 7, day 14, day 28, day 35 and day 42. What you can really see here is that we see very rapid induction of antibody responses even at the lowest dose. And we also see a very strong response because at day 14, we get antibody titers that are almost as high as after our boost. But still, we get an increase in the antibody titers after the boost. So we are very, very encouraged by these data and which also confirms the results that we obtained with our previously published Vaccibody RBD vaccine candidate, which used the original Wuhan RBD sequence. So let's move to the next slide, Slide 27. So of course, does these antibodies that we raised using the RBD vaccine candidate leads to neutralization of the virus? So what we did is that we tested the sera from these mice in a pseudovirus neutralization assay. So to the left here, we have the pseudovirus neutralization assay using the South African variant of concern. And as you remember, that was the RBD sequence that we used in the vaccine candidate. So here, we expect to have a high neutralizing capability. And then indeed, we see that even after 1 dose with the lowest dose, we get very effective neutralization of the South African variant of concern. But still, we see an increase after the second vaccination. Importantly, what we also see is that these sera are able to cross-neutralize other variants of concern. So here we have tested the gamma variant, which was first described in Brazil; the alpha variant, which we all know was the one described in U.K. and rapidly took over in Europe; and then the original Wuhan strain. And again, you can see that both the 1 dose and after 2 doses, we have very effective neutralization of these virus variants of concern in our pseudo neutralization assays. Let's move on to the next slide, 28, and focus on our T-cell candidate, VB2210. Next slide, 29. So again, here, we investigated the ability of our T cell candidate to induce immunogenicity in 3 different mouse models. The first one to the left here is a transgenic human HLA model. And to the right, we have 2 wild types: BALB/c and C57 black in mice models. If we start to the left, we see an induction of a strong immunity response after just 1 vaccination against HLA-specific epitopes in these mice. The strong T cell response observed in the 2 other mice models show that we have really a breadth of the T cell response independent of MHC selection. Slide 30. So to summarize our preclinical study, VB2129, the RBD candidate; and VB2210, the T cell candidate, are 2 DNA vaccines designed using Vaccibody's modular antigen-presenting cell targeted technology. VB2210 contains T cell epitopes validated by Adaptive Biotechnologies. And our promising preclinical data really confirms that we induce a strong T cell response against multiple SARS-CoV-2 antigens in several mouse models. Our RBD candidate, using the South African variant of concern, B1.351, also has really promising preclinical data, demonstrating an induction of rapid, strong and persistent neutralizing antibody response in animal models. And importantly, we also saw cross-neutralizations of various variants of concern. So let's switch gear and move into manufacturing on Slide 13 -- 31, sorry. So we are using an already established manufacturing process to ensure a rapid supply of clinical trial material for our first-in-human trial. The manufacturing is progressing as planned for both our candidates. And the initial stability data indicates long-term thermal stability of our candidates: so at 4 weeks at 37 degrees, which is really stress conditioned; 10 weeks at 25 degrees; and more than a year at 2 to 8 degrees. To the right is just some data, which is looking at one of the stability indicating parameters, which is monomeric supercoiled topology. And you can see that in the course of 4 weeks at 37 degrees, we have really a very good stability of the candidate. So with this, let's move to clinical trial preparation, and I will give the word over to Siri.

Thank you, Mikkel. So yes, as previously -- sorry, so we should move then to Slide 33. So as previously announced last week, Vaccibody is planning to initiate a Phase I/II trial to evaluate our second- and third-generation SARS-CoV-2 DNA vaccine candidates to address the emerging variants of concern. This is a 2-armed trial to evaluate the 2 candidates: the RBD as well as the T cell candidate in an open-label dose escalation manner, followed by a dose expansion phase. The objectives of the trial is to evaluate safety and immunogenicity of the 2 candidates. The clinical trial will be conducted in Norway, in Oslo as well as in Bergen. And the CTA submission is planned for Q3 of this year. We have had a frequent regulatory as well as scientific advice consultation with the Norwegian Medicines Agency and expect to initiate the trial early as of Q4 this year. The plan is to enroll up to 200 patients into this trial, and the trial is named VB D-01. So let's move into the next slide, please, Slide 34. So the VB-D-01 trial will investigate both our candidates as mentioned, so the VB2129, the RBD candidate; and the T cell candidate, VB2210, just presented by Mikkel. The trial will include both vaccine-naive patients or subjects as well as previously vaccinated healthy volunteers into 5 different cohorts. So candidate 1 will be initiated first with the cohort 1 and 2, which is the cohorts for the RBD candidate where we will be testing both naive as well as pre-vaccinated patients. After these 2 cohorts, it will be followed by cohort 4, which is the T cell candidate that will be tested for different dose levels. In addition to testing different dose levels in this dose escalation phase, we will also be testing both a single and a 2-dose regimen. So this part, in total, encompasses the dose escalation part of the trial. The 2 last cohorts, so the cohort 3 as well as the cohort 5, as you can see on the slide, which the cohort 3 is for the candidate 1, the RBD candidate; and the Cohort 5 is for the T cell candidates, these are the cohorts for the dose expansion part of the trial where we will add additional patients to be treated with a selected dose for further development. So next slide, 35, and then I will hand the word back to you, Michael.

Thanks a lot, Siri. And for just a few minutes, we're going to leave our COVID-19 vaccine, just to add a few words on our outlook, finance and also give an update on our N-02 trial. If I can ask you to move to Slide 36, which is just a visual representation of our pipeline which, in addition to the CoV-2 vaccine that we've talked about today, which we're excited now to move into the clinical phase, also includes 2 clinical-stage cancer vaccines, the VB10.NEO fully individualized, and we'll come back to that in a few seconds; and the VB10.16, which is our HPV-focused cancer vaccines. Slide 37. Vaccibody still has a very strong financial position. We reported a cash position exiting first quarter of USD 180 million, which obviously puts us in a very good position to realize our vision of building the leading vaccine technology company. Still, we have announced earlier in the year that we have initiated a process to explore a potential listing on the U.S. NASDAQ. If I can ask you to move to Slide 38, and we'll just provide you with a short update on the N-02 trial. So N-02 trial is the next trial run with our VB10.NEO program. And just to recap, VB10.NEO is our fully individualized cancer vaccine with which we entered the partnership with Genentech in October last year. So Slide 39. VB10.NEO is targeting antigen -- sorry, is targeting neoantigen on the patients on an individualized approach. So basically, we are determining the neoantigen patient by patient and developing the vaccine patient by patient. We have earlier reported very encouraging immunogenicity data and clinical data, starting back in SITC in 2019, across several cancer types. We also still continue to enjoy a 100% manufacturing success rate, which is unique for this kind of individualized cancer vaccine approaches, and we continue to see that our vaccine, for this program as well our VB10.16 program, is very well tolerated. And I'm going to hand back to you, Siri, on Slide 40 to provide a brief update on the efforts to initiate the VB N-02 trial.

Thank you, Michael. Yes, so in collaboration with Genentech, Vaccibody will now initiate a second trial with our individualized vaccine, VB10.NEO. So from the first trial, the VB N-01, as Michael alluded to, we have shown some preliminary data that shows specific CD8-positive dominating T cell responses correlating with encouraging clinical response data. This trial is still running, and we have initiated first dose for the last patient as of February this year. Now we are excited to move into the next phase of this program in collaboration with Genentech where we will initiate the VB N-02 trial, where the plan is to combine VB10.NEO with the PD-L1 inhibitor, atezolizumab, as the combined treatment in the treatment for general solid tumors. So next slide, please, Slide 41. So in this trial, as mentioned, we are combining VB10.NEO with atezolizumab, and we will evaluate this treatment in various solid tumor indications. The trial will run in the U.S. as well as in Europe, more specifically in Germany and Spain in Europe. And we have planned a total of 10 sites evenly distributed across the 2 continents. The VB N-02 trial is in start-up phase, and we have an open IND in the U.S. as well as our first site activated. So the trial is officially now open for recruitment. Details about the trial will be available at ClinicalTrials.gov during this week. Next slide, please, Slide 42. The trial's primary objective is to look at safety, tolerability as well as the antigen-specific immune response of the combined treatment of VB10.NEO and atezolizumab. This will be explored in a dose escalation manner with 2 different doses of VB10.NEO, looking at the immunogenicity by number and magnitude of antigen-specific T cell responses. Based on this outcome, we expect to have a recommended dose to move forward with when it comes to VB10.NEO. A preliminary activity assessment of the combined treatment will be done, looking at both specific efficacy parameters, in addition to the already mentioned objectives, but so specific efficacy parameters like overall response rates, duration of response, progression-free survival as well as overall survival. The trial design has a 3-phase setup with a screening period where screen 1, the patient-specific neoantigens will be selected based on patients' specific biopsies, and the individualized vaccine will be manufactured. At the second screen, the patients will be assigned to one of the 2 cohorts with different VB10.NEO dosing, either 3 or 6 milligrams. Moving into the treatment phase, the patient will undergo an induction period with dosing every third week, with both products before moving into a maintenance phase where we will be dosing NEO every 6 weeks together with atezolizumab continuing on a Q3 weekly dosing schedule. The last phase of this trial will be safety as well as survival follow-up. And then I think I will hand back to you again, Michael.

Thank you very much, Siri. And just the final slide before we move to the question-and-answer session. With today's and last week's announcement on the CoV-2 efforts as well as the update on starting off the N-02 trial, we are proud to announce that we continue to deliver on our promises. We are looking into a continued exciting year 2021 that will very much be in the name of VB10.16 as well as, of course, the progress on the CoV-2 program. So with those words, we will end the presentation and open up for Q&A. [Operator Instructions]

I see that we already have a couple of questions here. I'll start off with questions from [ Rhonda ]. Thank you very much, [ Rhonda ]. I think the first question is for you, Agnete. What is the competitive situation for T cell-based vaccines? Who else is in development for these? And how do you rate yourself against these in terms of timing?

Yes, good question. And as maybe understood today, mapping the relevant T cell epitopes that are able to induce an immunodominant response across the broad patient population is not a trivial case. So there are not that many players in the field. And there are a couple of companies moving into Phase I these days with T cell-based candidates that we are aware of but with a much more limited set of T cell epitopes than what we are able to do in collaboration with Adaptive. And this is one of the key reasons for the collaboration that we have with Adaptive Biotechnologies is to really access the broad set of T cell epitopes across several SARS-CoV-2 antigens that have already been confirmed to be immunodominant across the broad patient population with Adaptive Biotechnologies, taking those thousands of samples that they have evaluated into account. So we definitely think that we have a huge, now, competitive advantage with the synergies that we see with Vaccibody's ability to generate strong and broad T cell responses and with these specific T cell epitopes that's been already confirmed to be immunodominant by Adaptive's technologies. So the competitive landscape looks promising for this candidate. We’re taking Vaccibody’s [ eyes ].

Thanks, Agnete. We'll just take one more question from [ Rhonda ] here. How does your 2129 data, so the one we just showed here, compare to similar mice studies for the MRA technology such as BioNTech's and Moderna's?

Yes. Good question. It's always difficult to compare across. But I think what we see is very high levels of both binding antibodies and neutralizing antibody levels, both as we published with the first candidate, VB2060, and which is now also confirmed with VB2129. I think one of the things that may be encourages Vaccibody the most is the rapid onset of not only antibody binding responses that bind to these receptor binding domains but the ability that we actually also do see a neutralizing activity already early on, as Mikkel showed, already after 1 dose and 1 low dose. And then recently, with the cross-neutralization data that Mikkel showed, that does not show any reduced neutralization titer towards the different variants of concern. I think both those parameters are differentiating with Vaccibody. So the rapid onset first dose and the cross-neutralization data gives us a lot of comfort moving this candidate into the clinic, has been different, in addition that it actually does include these mutations, consisting the most relevant variants of concern, that affects the neutralizing ability for the others to a great extent.

Very good. Thanks, Agnete. And a question for you, Siri, on the patient population. Are subjects in the vaccine trial -- both the vaccinated and the [ nonvaccinated ], allowed to have previously confirmed COVID-19 disease?

Yes, that's a good question. So we have decided for the initial phase not to enroll patients that have previously had an infection with SARS-CoV-2. So the patients will need to be either naive to the virus and also to vaccination and/or have been fully vaccinated before moving into the trial.

Very good. Thanks. A quick question to you, Siri, also about time lines. And this is an area where we are a little bit cautious given the uncertainty surrounding this field here. So can you maybe just repeat what we already did say and what we put into the press releases in terms of time lines for starting up this trial here?

Yes, sure. So as I mentioned, I think we've had dialogues with the health authorities in Norway with scientific advice consultation, which gives us confidence that we will be able to initiate the trial fairly rapidly. So as we have stated earlier, we are planning to submit the CTA in Q3 of this year and to initiate and having the first patient enrolled early in Q4.

Very good. And that's actually to the extent we dare come with guidance at this time point here. Harlan, I think a question to you. I think you already touched upon it a little bit. But certainly, I wouldn't mind having it repeated again. What are the key aspects, in your eyes, of Adaptive choosing Vaccibody as your partner?

Sure. The primary reason is the unique ability for Vaccibody to be able to induce an immune response against T cell epitopes. So to specifically engage a part of the immune system. I would say, half of the immune response is just sort of [ systemmarily ] ignored by the rest of the vaccine community. It's normally done, I would say, not in a targeted way. People obviously -- you can't get an antibody response without a T cell response. So obviously, every vaccine does induce a T cell response. But it just sort of comes along for the ride, it's never done in an orchestrated targeted manner. No one tries to optimize it in any way. They just hope that it works well enough to induce the antibody response they were hoping for. But we think if you could actually use that, target specifically the T cell response, you can create a much broader and longer lasting and efficacious vaccine. And Vaccibody has the unique ability to do this, and that was what was appealing to us.

Thanks, Harlan. One maybe for you, Agnete, regarding the data that we see on the cross-protection and do you speculate on sort of underlying mechanisms why we see this persistent cross-protection across the variants.

Yes. So our hypothesis is that we do display this receptor-binding domain differently than other vaccines due to our antigen-presenting cell targeting mechanisms where the targeting unit binds the surface receptors on antigen-presenting cells and then the C-terminal antigenic unit, which consist then of the entire receptor-binding domain, in this format, allows the immune system to recognize epitopes on receptor-binding domains that are more conserved than when the other companies are using the entire spike protein displayed in different manners. And that also generates very strong affinity antibodies, which is one of the reasons why we think we see this interesting antibody response that are not sensitive to the permutations that we see in the current variants of concern. We will continue to explore the breadth of this to other variants and other variants that we will see in the future. These are the ones we've tested so far. So that will be very interesting to follow. And as Harlan mentioned, I mean most companies have focused on antibody responses for a long period of time. They are important, but T cell responses are also important. They have just been much more difficult to really map out, which parts of that viral genome are actually responsible for inducing the best T cell epitope antigens to include into any vaccine. So now we have both parts of the picture that the adaptive immune system consist of, both the humoral and cellular immune responses. And now we can help the immune system in both angles with these 2 different candidates. So that's very interesting.

Excellent. Thanks a lot. I see that we are at the top of the hour. So although we still do have a couple of questions, I think we need to round it off here. With those words, just once again, I would like to thank, of course, my colleagues from Vaccibody but also, indeed, Harlan, for joining in on this call here. It's a very early time in Seattle today. So really appreciate you getting up this early and joining us for this exciting announcement here. And thanks to everybody listening in and posting questions on the system. So we wish you a very good day. Goodbye.