Nykode Therapeutics As

Greetings and welcome to the NICODE Q4 2024 Financial Results Webcast. At this time, all participants are in listen-only mode. If anyone should require operator assistance, you may do so by pressing star zero on your telephone keypad. A question and answer session will follow the formal presentation. You may ask a question at any time by typing it into the Ask a Question feature on your screen. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to your CEO, Michael Ensig. Please go ahead.

Thank you very much, Kevin. And also from my side, a warm welcome to all the participants for this NICODE's fourth quarter webcast. Just a quick reminder of our forward statement. We assume you're all familiar with those. On that note, we'll move forward. I am very pleased to, as usual, have Agnes Frederiksen, Chief Scientific Officer, Head of Business Development and Co-Founder with me together with Harald Gurvin, Chief Financial Officer together. We'll take you through the key highlights of the fourth quarter, as well as, of course, the financial numbers. So it's been an eventful fourth quarter for us, although obviously there are parts of this we are not looking forward to. to see any time through. It has been a tough period with a number of layoffs and people leaving the organization. Because we have announced the strategic refocus to align our activities and our organization and our cash branch with our cash runway. And we are good through these processes right now. The intent is, of course, to align the activities with the cash runway and to extend the cash runway into 2030. We'll achieve that by reaching an annual cost base of approximately $20 million going forward. We are reporting today a strong cash position of more than $150 million, which is, I think, in these days in this industry, a uniquely strong position to be in. Also, on the very positive side, we did publish the final dataset from our phase 2 trial, the CO2 trial, in the peer-reviewed JITSI journal, once again confirming what we saw in the interim data, a prolonged benefit, a definitive vaccination effect in the patients with advanced cervical cancer. We regained ownership. including the IP rights to our VB10eo program from our partner Genentech and are now looking into the optimal path for that program going forward. We did announce a small set of data from the NO2 trial that does confirm what we've seen earlier in the N01 trial, a competitive immune response. I will take you a little bit through these data again later in this call here. But just to say that we remain very confident in the VB10neo program compared to the industry or other programs in the same field. Then we presented new data on both our cancer vaccine, the mRNA modality, and we'll spend a little bit of time for that later in this call here. And of course, on our very exciting APC target immune tolerance program, we'll also be spending some time on this later in this call here. We've been through this before but just want to recap for everybody the purpose of our refocused strategy is to create a company which is obviously lean and research focused. Focused on discovering novel assets which we in turn think will create very exciting investment opportunities through targeted development activities including also clinical trials. And everything we do will be geared and aimed towards generating early partnerships. We do believe that is the best way to create value for a company like Nyko with a very strong technology platform, but also with our strongest competences in the product discovery and early development area. So expect to see us continue to generate exciting new assets from our research engine. and in a very cost-conscious way also take decisions on targeted cost-efficient development activities to create shareholder value and pave the way for early partnerships. Our lead program, BB1016, is still in progress and also here reminding you that we are addressing a patient population with a huge unmet need And perhaps surprising to some, still remain with high and growing incidences. It's been a notion that some of the prophylactic vaccines would change the market opportunity for this patient population going forward. That does not seem to be the case. First of all, because of a lack of uptake of prophylactic vaccines around the world, which means there will be a continued use or need for therapeutic vaccines in the HPV16-driven cancer fields in the future. We have now reported very strong data for BV1016 combined with atezolizumab. in the CO2 trial together with also a favorable safety profile. We see an even stronger effect in the PD-L1 positive patients and again even stronger effect in the PD-L1 positive patients with only one prior line of systemic treatment. Again reminding you that we have also in our very first trial with VB1016 in a H-cell patient seen very encouraging effects with BB1016 as a monotherapy in an area that is also gaining increasing attentions from industry players around the world. We have an ongoing trial, CO3, where we are looking for the immune responses and safety in first-line patients with head and neck in combination with pembrolizumab. We did announce or publish the data from the CO2 trial, and we're not going to take you through all the data. The publication is available also through a link on the homepage. We just want to remind you what gives us a very high level of confidence and conviction in VB1016. What you show here is the key data from the patient population with high PD-L1 expression. And we shown you here the overall response rate, the PFS, and the median overall survival compared to three different historical trials that were assessing checkpoint inhibitor. Monotherapy in a very similar patient population, also PL1 positive. And you see that the CO2 trial basically observed an ORR of 29 compared to from 16 to 18% seen with checkpoint inhibitor monotherapy. We saw PFS of 6.3 months compared to 1.9 to 3 months for the checkpoint inhibitor monotherapies. And very impressively, we saw the medium role survival land at 24.7 months. compared to overall survivals ranging from approximately 10.6 to 13.9 months observed with checkpoint-inhibited immunotherapy. These data obviously gives us, as I said before, a very high level of conviction and confidence in the effect of VB1016 and give us every reason to continue developing VB1016 and look for partners. Next slide just shows you what we've seen in the patient population that are PD-L1 positive and have only received one prior line of systemic therapy. If you go to the far right of this graph or table here, you see the OR climbing from 29% up to 40%, the PFS from 6.3% to 15.8%. month and for this patient population we did not reach the medium overall survival. So this also gives us conviction that the earlier stage we go into the higher the efficacy we will observe for VB1016. With those words, I'm going to hand over to Auneide, our Chief Scientific Officer, Head of Business Development, to take us through the updates on VB10neo and our immune tolerance program. So please, Auneide.

Thank you, Michael. So moving into VB10neo, that's our fully individualized new antigen-based cancer vaccine. This has really the potential to address a broad set of indications as we do make one vaccine per patient that could be applicable for basically all tumor types. We do see a strategic focus on large investments these days in individualized cancer vaccines in late-stage trials by our peers, focusing then importantly on the adjuvant setting. and expecting data readout from these trials from our peers in N25 and in 26, 27. So as you may all be aware of, there has been limited transactions in the field of cancer vaccines since Michael was very active in this space in 2020 and 2021. We now see that that is changing in the landscape, being very aware of what's happening in the field of cancer vaccines in early stage. So that's positive for NICODE and also regaining the rights from VB10E. We do have, as you all should be aware of, proven to generate broad and long-lasting T cell responses. across two clinical trials. And importantly, this has not been in adjuvant setting. This has been in heavily pretreated patients with recurrent metastatic solid tumors. We have successfully established in-house proprietary neoantigen selection algorithm that we call NeoSelect. And we work with plasmid DNAs that for individualized cancer vaccines do have a very competitive turnaround time and cost of goods reaching the market. Strong patent protection. You do remember we got a patent approved earlier this year for VB10-Neo. And as we reported in Q3, preliminary immunogenicity data from the NO2 trial aligns and confirms the final positive data from the NO1 trial, even though these patients are with even a broader set of indications and later stage patients. A final analysis is currently ongoing as we are regaining also all the rights from Genentech for this program. Looking forward to finalize all the analysis. As we also showed in Q3, preclinical data supports the opportunity for strong and durable responses using our technology across modalities, importantly here with mRNA. I'll show you the next slide. So just to remind you, we have done some preliminary analysis from VBNO2 that we reported in Q3, where we see comparing to what was presented in NO1 that we generate the same amount or even slightly higher percentage of immunogenic neoantigen patients with at least one immunogenic or de novo induced vaccine response. and those that do have a response to any new epitope. Additionally, where we haven't shown you really the data yet, we are looking forward to do that in the future. We do see a persistent expansion of T cell clones in the majority of valuable patients measured also by the alternative method TCR sequencing. We see persistently expanded clones emerging already as early as after two to four vaccinations and also durable in frequencies. And the adduction of this persistent de novo T cell response has been confirmed by IBS Alicebot, which means we can identify that some of these clones are truly generated by the vaccine. So we continue to be very confident in Vibitinib's potential and happy to see that there is an increased interest in cancer vaccines by the environment. Go to the next slide. These are data that we've generated to also investigate our technology across modalities. So this is generated by mRNA LNP and we looked into durability. As Michael mentioned, we have very strong convincing durability of VB1016 in the CO2 trial leading to prolonged medium overall survival. We wanted to see if that holds through when we also use the mRNA format. Here we have vaccinated in preclinical models two times early and looked that we can actually still identify neoantigen-specific T cell responses at day 133 after two initial vaccinations. But also importantly, when we boost this with a third vaccination at day 132, we are able to really boost the T cell response to see up to 35,000 spots there in this particular experiment, which can mimic either that you do see the antigen coming naturally by the disease or with a third vaccination. So very promising data. We also see very strong increase in the number of new epitopes that are boosted after this long-term, in this long-term assay. If you go to the next, we also looked whether these T cell responses were able to come for tumor protection at this later time point. So here, vaccinating either at day zero or two times, day zero and day 21, and doing a tumor trial in as late as day 90, we see that with one vaccination, we generate 75% tumor protection, but with two vaccinations, we've been able to fully protect the mice at this time. late to time point of tumor challenge. So able to prove that the T cell responses that's generated are efficacious also long term. And then, as Michael mentioned, the immune tolerance field is a very interesting field these days in the industry. We see a lot of activities in immune tolerance. We also see a lot of activities and interest into this field that we are working with, which is truly antigen-specific immune tolerance. The field as such has huge opportunities, both within a range of autoimmune diseases, but also allergies and organ transplant rejection. So basically those indications where we see an unwanted antigen-specific immune response that we can then modulate with the treatment. The antigen-specific immune tolerance field is unique and still new with a few players, but a lot of activities. Also, we see transactions in the field. There's a lot of unmet medical need, and we know that up to 1 in 10 people are actually affected by autoimmune disorders, and then you can add allergies, organ transplant rejection. This has a huge focus for NICO these days. That is obviously supported by the preclinical proof of concept data that we've generated in the most common autoimmune disease models that is being used by the field. We show potent therapeutic advantage of our APC targeting technology that is significantly better than other technologies operating in the space that do not have our APC targeting technology. platform patents obviously submitted and we are moving very rapidly forward now establishing several tolerance relevant methods and assay that will be extremely important in order to both identify the most optimal version of the NICODE tolerance vaccine but also to really understand our opportunity to specifically modulate the immune system in different directions also within autoimmune diseases. These are data shown in Q4 with the comparison of two different versions of our technology where we have kept everything identical except the two targeting units. So we have a range of different targeting units that we can use that we believe can turn the immune response into tolerance. You see they are both very effective in preventing disease in this EIE model, which is the model that most of the players in our field are using really to understand the efficacy and the mode of action of antigen-specific tolerance. If you go to the next, when we look into that in particular with different dose levels as well as comparing with constructs that do not have any relevant targeting units of the non-targeted vaccine, which is then shown in black in the figures, you really see that adding a functional targeting unit provides a very strong increase in the ability to alleviate disease in this model. And this was done with the first targeting unit that we did show earlier this year. And then if you go to the next, we mimic this with the second targeting unit and confirm that this also works and potentially works as good or even slightly better with this targeting unit here. And then if you go to the next version, we have also now successfully set up a very interesting alternative model, which is a relapsing-remitting EAE model, which means that We have generated data with another construct that holds the different relevant antigen PLP compared to MOG antigen that we used before. We also see that this provides efficacy in a relapsing-remitting model. And all of these data now allows us to move more rapidly forward from where we stand today to really dig into the variety of our different constructs, which ones provides the optimal activity and modulates which arms of the immune system. Should we go to the next? We are currently in Boston and looking forward to present new data from our antigen-specific immune tolerance efforts at this highly relevant conference, Antigen-Specific Immune Tolerance Summit. going on this week. We will present a lot of interesting data tomorrow. Then, by those words, I will transfer to you, Harald, for going through the financial results.