Nykode Therapeutics AS (NYKD) Earnings Call Transcript & Summary

Good afternoon, everyone. I'm [ Josh Bowers ] from the London health care banking team. And it's my pleasure today to introduce Michael and the team from Nykode. [ Quick ] brief presentation, you all know the drill, and then some Q&A afterwards. And with that, I hand over to Michael.

Thank you very much, Josh, and thanks for the invite to the entire JPMorgan team here. Always a pleasure. So today, we're going to go through an introduction to Nykode Therapeutics, give an insight into the technology and the lead programs as well as our growth strategy. So we assume you're all familiar with the forward-looking statements. So on that note, we'll skip forward to a very brief high-level introduction to Nykode. Nykode is a clinical-stage immunotherapy company. We are entirely focused on leveraging our unique proprietary immunotherapy platform, which in one sentence, targets the antigens to the antigen presenting cells. We use that to drive immune tailored -- immune response -- sorry, a tailor-made immune response, which we right now focus in the field of oncology and autoimmune diseases, but we also have applicability in the infectious disease settings. From the oncology point of view, our platform is validated and derisked through very strong clinical responses showing both a long durability of the immune sponsors as well as very convincing survival data. We have also announced a ambitious aspirational focused strategy to take our lead asset, VB10.16 forward towards the market in advanced cervical cancer as well as head and neck. And we see and have embarked also on reaping the further commercial potential that is in the early stage, adjuvant setting for the same cancer types. We've seen on the back of the interesting data that was shown from some of the mRNA companies also interesting data in the early setting. So we also want to check what we can do with our technology in the mRNA setting. And they also show that regardless of whether we use DNA or mRNA, we still see the same benefit of applying our technology to the cancer vaccine. We've embarked on exploring the same modality in the autoimmune disease setting. I'll show you the mechanism of actions for each of those settings in a couple of slides, which, of course, constitute a -- as significant commercial upside for us as the oncology field. We believe in partnerships and have entered 2 strategic partnerships, both transformational and sizable with top-tier biopharma companies from the U.S., Genentech in 2020 and Regeneron in 2021. The company is well capitalized with USD 159 million in cash at the end of third quarter. We did a private placement in -- or direct replacement, sorry, in October last year and listed at the OSLO Stock Exchange. So this cash gets us easily in the next couple of years into the future to really realize our growth strategy. As the company grows, we've also been focusing on building a leadership team, an organization with a solid track record in drug development, drug discovery. I'm happy to have with me here both the Co-Founder and Chief Business Officer, Agnete sitting here and behind her, the Chairman of the Board, Martin Nicklasson. So if there's time, they're also happy to take a few questions in the end. Just a quick look at our partnerships with Genentech and Regeneron. Back in 2020, we entered the partnership with Genentech centered around our individualized cancer vaccine. I'll tell you more about that program later, VB10.NEO. That deal gave us USD 200 million in upfront and additional access to potentially USD 515 million in downstream milestones plus, of course, royalties on sale. The year after, we entered a multiprogram deal with Regeneron, centered around 5 different programs, 3 on oncology, 2 in infectious diseases. That program gave us USD 50 million in upfront plus additional USD 875 million in potential downstream milestones and again, royalties on sales. So of course, these deals we are immensely proud of and also served to both validate and derisk the entire investment case. Quick look at the pipeline, which is really a testament to the diversity of our assets as well as our platform's ability to quickly and effectively generate new assets that we can take into development. So you'll see us spanning a nice range of different tumor types, both with our off-the-shelf vaccines as well as the fully individualized. You also see us present in the infectious disease with the 2 Regeneron programs as well as moving slowly into the autoimmune disease program. Look at it a little bit differently when we look at just in zooming in on our oncology programs. We really see our technology playing out both in the advanced recurrent metastatic setting as well as into the more early-stage settings where you will see most of the other cancer vaccine companies focusing. So we will be focusing on building a balanced portfolio of assets that spans both the advanced setting as well as early-stage cancer across a number of tumor types in the future. Quick look at the mechanism of action. The fellow you have on the left side of this slide here is really the core of our technology. We call it a Vaccibody. It's a fusion protein consisting of 3 different domains in the lower dark purple part. You have the antigens. That's the ones we want to create an immune response to all -- decrease an immune response to if we're talking about the autoimmune field. In the middle, we have a dimerization unit, which function is to make sure that the protein comes together as a homodimer that increases the strength of the signal. And in the top, you have what we were often referred to as the secret sauce. That's the targeting unit. The targeting unit will always be a ligand that binds to a receptor or surface molecule on the antigen presenting cells. That's the core of our technology. In all our cancer vaccines, we use the CCL3L1 molecule or the [ MIP1-alpha ] that binds to the receptor on the antigen presenting cells and it has 2 very interesting features. First, it's a chemoattractant for APCs. So when it's injected into the environment, you'll find an influx of the APCs coming to the site of the injection. Once it binds to the surface of the APCs and internalized because it is internalized via the CCL3L1 molecule, it activates not only the classical pathway, which leads to CD4 activation, but also the cross-presentation pathway, which leads to a very strong and broad CD8 T cell response, which, of course, is exactly what you want in a cancer vaccine. Now we don't administer the product as a protein. We could. Our technology and our IP platform is agnostic. But for various different reasons, we'll also come into later, we administer it as a DNA plasmid and we inject it into the muscle. We are a needle-free injector. It enters the muscle cells, gets expressed and secreted into environment and then we have the whole immune response starting from there. We could also do this as an mRNA. We've shown that in preclinical models. It gives the same added benefit. We could do it via a viral vector or we could do it as a purified protein. If we take a deep dive into our lead asset VB10.16, it's a therapeutic cancer vaccine candidate, [ directed towards ] the HPV16-driven cancer types, so mainly head and neck and cervical cancer plus a host of additional cancer types that are driven by the virus. We include in the antigen part, the E6 and E7 protein from the HPV16 virus, same targeting unit as we use in all our cancer programs, CCL3L1. And this program is currently in Phase II. Wholly owned by Nykode. We're not giving away any commercial rights to this program at this time point. Now HPV16 driven cancer type does represent a huge commercial opportunity with a high medical need. We are focusing on cervical and head and neck to begin with. Cervical is the lead indication for us. And as you see on this slide here, we see more than 130,000 new cases of HPV16-driven cancer types alone in the U.S. and Europe each year. Approximately 1/3 of these are cervical cancer. Very poor prognosis, so less than 5% of the women that presents with recurring metastatic cervical cancer are alive after 5 years. We also see, and that's perhaps a little bit surprising, increasing incidence of the HPV16-driven cancer types. We get this question very often whether the prophylactic vaccines and the rollout of those are not slowly undermining the market for this kind of therapeutic vaccines and I'm inclined to say, unfortunately not. We do look at still increasing incidences, partly due to the fact that the rollout of the vaccine is not as good as we had hoped for, but also because of changes of lifestyle. So for the next 10 years, we will continue to see an increasing addressable patient population for this vaccine. We did back in 2023 release the data from our C-02 trial, Phase II trial, where we assessed VB10.16 in combination with Roche's checkpoint atezolizumab in patients that were second line or more with advanced cervical cancer. What you see on the left is the key data, objective response rate, PFS and overall survival for the arm that had vaccine plus atezolizumab compared to the published data for checkpoint inhibitors in a comparable patient population. On the right, you see the data from TIVDAK, which we contemplate will be the competitor for us when we reach the market. So you see with an objective response rate of 29% in the PD-L1 positive patient population, which is the one we focus on here versus for all the checkpoint inhibitors between 16%, 17%, 18% and a medium overall survival not reached at the time point of the reporting here. So estimated to be more than 25 months versus what you see with the checkpoint inhibitor in monotherapy 10 to 13.9 months, we see a near doubling of the numbers that you expect to see with a checkpoint inhibitor monotherapy. Compared to TIVDAK, as I said, which will be our competitors, also here, we see a very strong competitive profile, which makes, of course, very comfortable we have a competitive as we move forward. We have on the back of these positive data, devised a growth strategy for our lead asset, where we will continue on a fast path to market in the advanced cervical cancer setting. So the next trial that we are starting now is C-04. Here, we will test checkpoint -- sorry, VB10.16 on top of atezolizumab in patients that are refractory to the first-line treatment in advanced cervical cancer, so checkpoint -- so plus -- chemo plus/minus atezolizumab. This trial has been discussed with the FDA. We have approved from the IND and the FDA knows our plans for this program here also. And the first patient will be enrolled imminently. This, of course, represents for us a faster market strategy. So a shorter goal for getting to the market and the patients as fast as possible. But we are not stopping here. We've also initiated the first step into head and neck with the C-03 trial. So it's going to be a VB10.16 in combination with checkpoint inhibitor in first-line patients, head and neck, testing 2 different doses. And on the back, of course, we'll decide how to move forward in that program also. And we've announced the start of C-05, or at least the planning of C-05 trial, which is our first expansion into the locally advanced, so the adjuvant setting of cervical cancer, which, of course, represents an even larger commercial opportunity for VB10.16. Out there in the future, we also see opportunities in the locally advanced head and neck setting and the other hosts of cancer types that are driven by HPV16 plus also the PD-L1 negative patient population. But we have not disclosed any plans for those patient populations yet. So together right now, our portfolio of trials includes 4 different trials for VB10.16. C-02 is the one we reported data from in 2023. Next milestone from that one is we will be updating on the overall survival data in the first quarter, so imminently. C-03 first step into head and neck. We have started that trial. So we contemplate to have enrolled and reached the stage where we can decide which dose to move forward in Part 2 by the end of this year. C-04, we'll be dosing the first patient imminently. We do expect to have finalized enrollment of that trial in 2024 and be able to report data in the mid of 2025 for that program from the interim for the first part. So that's 30-plus -- 30 patients in a randomized setting. C-05, we are in the planning of that one [ currently ]. That will also be a combination trial on top of a checkpoint inhibitor and we'll be updating the market on both design and choice of checkpoint inhibitor during this year. Moving from our lead asset VB10.16 into our individualized cancer vaccine VB10.NEO, which we run in collaboration with Genentech. So this is the concept for those of you who follow Moderna, you will be familiar with, this is where we take a biopsy from a patient who presents with a solid tumor. We do a whole genome sequencing. We determine some mutations specific for that patient and then we use our proprietary algorithm for selecting the best epitope to target with our vaccines. We then incorporate that into our vaccine technology, which we know drives a long, strong and broad CD8 T cell response, manufacture it, and of course, then give it back to the patient. We also think that because we use DNA as the modality here, we will have advantages towards the mRNA companies, both in terms of fast production as well as the cost of goods when we get closer to the market. Here, we have been engaging 2 trials. N-01 that we have reported the immune response data from and the N-02 trial is the one we're running together with Genentech where we're testing 2 different doses of VB10.NEO on top of Genentech/Roche checkpoint inhibitor atezolizumab. We did earlier report immune data from the N-01 trial. Here is just a highlight. On the left graph here, you will see a very consistent broad response to the epitopes that we include. So we include 20 epitopes into each vaccine or up to 20. And you see the percentages of epitopes that are shown to be immunogenic in the patients afterwards with an average of 53% of the epitopes showing immune responses in the patients. We are far beyond what we've seen reported from the other individualized cancer vaccines. On the right, you see the immune response over time. And 2 things worth noticing here, a very consistent slow buildup of a long sustained immune response while on treatment but as importantly, also post treatment, a very strong and durable immune response with a very slight decline over time which, of course, tells us we have a technology that is very applicable not only in the recurrent metastatic setting, but also as we think of moving into the early-stage locally advanced setting across the tumor types. Latest, we reported the expansion of the pipeline by -- including also the NYK011, a preclinical program in the colonic -- colon cancer setting here. Here, we are really using our technology to address, again, a huge unmet need as you know, but also play across various disease settings here. So we see this cancer vaccine potentially being used both in the setting of high-risk polyp patients, which have a very high likelihood of risk of developing colon cancer but also in the actual or advanced colon cancer setting. This program here takes advantage of some of our latest technology developments, what we call the 4th module or second-generation vaccine. So it's the first time we would be taking the second-generation vaccines into the development. We have earlier shown and as you see here, you would see the fusion protein, the Vaccibody fellow in the middle with the 3 different domains in the protein. We can in the DNA plasmid add additional cytokines in that, which will be released in conjunction with the vaccines or not together, not attached to, but in the vicinity where we also release the Vaccibody that then attracts the antigen presenting cells. And we've shown this to drive a stronger immune response preclinically, and we've also shown this to turn into better protection in the challenge models with tumor. So here, we're very excited to be taking this technology, the second-generation technology into development for the first time, potentially with this NYK011 program. Skipping to our technology application in the autoimmune disease fields. So you recognize this figure from the start of the presentation where we're talking about oncology. When we look at the autoimmune disease setting, it's basically the same concept we use here. We are focusing on the core of our technology, the Vaccibody protein, which is again a fusion protein of 3 different domains. We changed the targeting unit here. So we are not addressing the traditional APCs that we would be addressing with the cancer vaccines, where we instead target the tolerogenic dendritic cells. And we've shown and reported that at the -- last year that we can by using this approach have an upregulation of antigen-specific regulatory T cells. Recently at our Capital Market Day in New York last year in September, we also reported that that upregulation of antigen specific regulatory T cells translates into benefits in our preclinical model. The first one we show here is the NOD model, which is a model for type 1 diabetes, where we included the preproinsulin as the antigen targeting units that are not yet disclosed but attaches or addresses the tolerogenic dendritic cells. And then also included in this setting here up to 3 different of our 4th module technology, the same that we also use, as I mentioned before, in our NYK011 program here. And what you see on the yellow curve is the NOD mice spontaneously developing type 1 diabetes similar symptoms. On the triangular graph in the middle is when we include our vaccine without any fourth molecule, you see a significant delay and reduction of the risk of developing the type 1 diabetes symptoms. And on the lower one, which is parallel with the X graph, you see where we have included the 3 fourth molecule programs. And there you see absolutely no development of type 1 diabetes symptoms in these mice. We then subsequently -- so this is the first time we show this data, we stopped the vaccination after 16 weeks. And so even after stopping the vaccination, there is a persistent protection against developing the type 1 diabetes symptoms in these mice, which, of course, gives us a lot of enthusiasm for this asset going forward as a potential medication for type 1 diabetes in the very early stages. We also tested the technology in a model for multiple sclerosis, the EAE model, where it's induced, not spontaneous developing here. And again, we do the same thing. We include the antigen -- [ and the antigen part ] there. We test different targeting units in this case. See the same effect across the range of targeting units here. And again, you see a strong protection and reduced risk of developing the MS symptoms in this model here. So the top one is the untreated mice, the middle graph, that light purple, the ones treated with the antigen alone, which in this case here is known to give a certain protection and the lower graph with almost no development of symptoms is oral vaccine. We also did the same experiment with -- here. And here we looked at the release of cytokines. So again, similar protection, not shown here, but shown at an earlier stage. And what I really wanted to focus on here is the kinetics or the dose-dependent effect on the release of the inflammatory cytokines. In this case here, we see an almost complete elimination of the inflammatory cytokines by increasing the dose of our vaccines gives a lot of enthusiasm for this protein. And remember, if we were using our traditional targeting unit and including the same antigen here, we would actually see a dose-dependent increase of these inflammatory cytokines. So a very strong indication of the proof of concept. As we said, we are also encouraged by the results that are emerging by other cancer vaccines with the mRNA modality. So we set out to say to explore what kind of benefit we add to that modality. As I said, the IP for our vaccine or our technology is agnostic, so it also covers MI and viral vectors. And here -- just go forward to this one, here we tested 20 different epitopes in a vaccine giving as mRNA alone. So naked antigens, very similar to what you see with the mRNA cancer vaccine companies on the right and our vaccine. So mRNA encoding our targeted vaccines or with a targeting unit in the middle column. And you see here, both on the prime and the boost results a stronger result, but as interestingly and probably more important for cancer vaccine, a broader response. So you see more different epitopes when we use our targeting vaccine, generating a strong immune response compared to what you see with the antigen alone mRNA molecule. So it gives us actually some enthusiasm that this -- our technology will also add benefit for the mRNA technologies. Quick look at the financials. So I said we're strong capitalized with USD 159 million at the end of the third quarter. Gives us sufficient years into the future to realize our growth strategy, which we've been through here. We've also publicly indicated that we are heading towards the U.S. by announcing we have initiated a process to explore a potential listing on the U.S. NASDAQ. We're not giving any indications on the timing for such an event. Finally, a quick look at the catalysts. So we had a busy year last year and fortunately continue to be busy in 2024. So within the lead asset program, we will be starting up the C-04 imminently, as I said. The IND is in place, and we're just waiting for the first site to start enrolling and dosing probably over the next couple of weeks. For VB10.16 also, we look forward to report the updated survival data from the C-02 trial in the first quarter. And of course, we also are pursuing the neck indication and hope to be able to have patients enrolled to allow to pick the dose at the end of the year. For C-04, we are planning to have patient enrolled for the part 1 of that trial, so that's 60 patients at the end of the year, then we'll be on track to report the data by mid-2025. And then, of course, we will continue to give you updates on our autoimmune program development as well as our partnered programs with Regeneron and Genentech, although it is inherently more difficult to provide guidance on those. With those words, I think we are open for questions, Josh.

So a number of companies...

Here is the mic for you.

I have a few questions. So a number of companies have noted that their algorithm selects truncal mutations. And that's how they argue that even though they're sampling the primary tumor that's enabling them to also target metastases because in the adjuvant setting, new adjuvant setting, obviously, the surgeon is removing the primary and your objective is to hit the adjuvant. Can you comment on sort of the ability to actually do that?

Yes. So the element of clonality, right?

Well, the issue of where is the mutation. Is it truncular, is it a branch?

So I think we're all -- and when we talk to our colleagues out there, I think we are all more or less on the same path in terms of the algorithm. First of all, I think we realized pretty early that the algorithm needs to be tailored to the technology modality underneath. So we would be using different algorithms compared to what you'd be doing if you had a peptide based or if you had an mRNA. So that's the first one. We're all focused on finding epitopes that are present not only in the primary tumor but actually as a clonal one all over the body, also in the metastasis. I think we've been focusing on that from the start off by mainly 2 things. We are looking at -- we're sampling from as many places as we can when we take the biopsies -- that gives us a good indication of whether a mutation is clonal or not. And second one is we also take the ctDNA expression level into consideration. That was one of the first cancer vaccines that started taking ctDNA into the decision algorithm. That also gives us a feeling for whether the mutations are actually expressed clonally across metastases also.

So if you don't mind, that a follow-on question though to that would be the algorithm essentially is a tool. And so as you look at your clinical pathway, if you make any adjustments to the algorithm, do you have to start from the beginning as far as your clinical pathway?

That's a very good question that I think is inherent for the whole concept of individualized cancer vaccines. So I think even the authorities, the FDA, are still -- the juries are still out on how that works. What is very clear is we need to have a very well-controlled and confined environment where we have actually [ string ] control of what we are doing in terms of the algorithm. And I think there will be, as you say, a need to document the effect of any major changes we include there. It's not necessarily the intention to keep on mutating the algorithm. The algorithm is intended to be fairly solid over time. So the algorithm we use now was finalized and validated before we started the clinical trial. We're not changing the algorithm between the patients as we enroll right now. So I agree with you, there will be a need to document control changes for the algorithms as we go forward.