Nykode Therapeutics As

Greetings and welcome to the NICO Therapeutics Q4 webcast. At this time, participants are in a listen-only mode. A question and answer session will follow the presentation. You can submit your questions at any time by typing them in the Ask a Question field on your screen. If you need any technical support during this conference, click the question mark icon on the upper right-hand corner of your screen. Please note, this conference is being recorded. I will now turn the conference over to our host, Michael Engsig, CEO. Thank you. Please begin.

Thank you very much, operator, and also from my side, a very warm welcome to all the participants for this quarterly webcast here on our financial results and update on the company highlights. Just to begin with, a quick look at our forward look statements. We assume you're all familiar with those. On that note, we'll move forward. Together with me, I'm pleased to have Alnita Frederiksen, our chief business officer and co-founder, as well as Harald Gurwin, our chief financial officer. Quick introduction to Nycode Therapeutics for those of you who are new to the story. Nycode is a clinical stage immunotherapy company. We are entirely focused on exploring our unique and proprietary immunotherapy platform which uniquely targets the antigens to the antigen-presenting cells and in turn generates a strong CD8 T cell response which has been shown to be correlated with clinical responses in solid tumors. Our technology is modular in its build-up which also provides a high degree of versatility that allows us to easily incorporate new antigens and adapt the products to new diseases across the oncology, infectious diseases, and autoimmune space. We are dedicated to advancing our wholly owned and lead assets, VB1016, an immunotherapy developed for HPV16-driven cancer types, And we're very happy to have been reporting both positive clinical data from that program back in May and followed up with additional positive data in November last year. And we are very much looking forward to be reporting the final data from the CO2 trial in the first half of 2023. We've also announced an expanded development program, an ambitious one at that, which includes a potential registrational study in advanced cervical cancer to be initiated towards the later part of 2023, as well as an expansion into head and neck with a dose escalation study that we're doing in combination with Keytruda to be initiated in the first half of 2023. We believe in partnerships. and have been signing a number of transformative partnerships for the company, including two large out-licensing deals with Genentech and Regeneron, as well as other partnerships with top-tier partners. We were capitalized with a cash position of $26 million as per 31st of December, and we'll come into further details on the financial reporting towards the end of this call. So both fourth quarter and 2022, its entirety has been a transformative year for NICODE, and we've been announcing a string of positive results across our programs, including our wholly owned and lead asset, BB1060, as well as our individualized cancer vaccine, BB10NEO, which we developed in combination with Genentech. We've also announced a collaboration with MST on the combination of VB1016 with Keytruda in the VBC03 trial. We'll tell you more about this trial in a few minutes, as well as a strategic manufacturing partnership with Richter Helm Biologics that will give us certain securities on supply chain flexibility. We are, as I mentioned, also very much looking forward to the major event, which is the final reporting from the BB1016 CO2 trial, which has been enrolled in patients with advanced cervical cancer. And this final analysis will cover the entire treatment phase for all the patients in this trial here. We've also, post the Q4, announced a collaboration with GOG Foundation, which will help us both design the optimal CO4 trial and also help the execution of the CO4 trial. We'll tell you more about that in a few slides. With those words, I'm going to hand over to our leader to take us through the key highlights from the positive data we reported in the fourth quarter.

Thank you, Michael. We will start off with some focus on the individualized cancer antigen-based vaccine program that that we are currently running then in tight collaboration with Genentech. So this is where we work with the individualized neoantigen-specific vaccines. And these are custom-designed and manufactured as one vaccine per patient, really based on mapping each patient's cancer-specific mutations. If you have followed the field recently, there has been multiple positive data, and Moderna and Merck announced at the end of last year interesting clinical benefit for their individualized neoadjuvant-specific cancer vaccine. This was in an adjuvant setting, but we really see that this has generated new enthusiasm for the promise of cancer vaccines, particularly in early-stage disease. It's important for us to highlight that Nygaard is a key player in this field. We were one of the first companies in the clinic with an individualized cancer vaccine, and that's our VB-N01 trial where we had the first patient, first dose already in 2018. Nygaard has also, last year, after entering a partnership with Genentech in 2020, We were presenting positive data in multiple indications. This is then in the trial setting with checkpoint inhibitor experience and advanced metastatic setting in multiple different indications. So it's a bit different setting from the data that we've seen from Moderna and Merck. So we presented updated positive immunogenicity data from this trial. which shows us and confirm this broad and strong CD8 skewed immune response. You've seen before that in preclinical studies, we are able to show a broader and stronger and more CD8 skewed immune response than multiple other vaccine technologies that focus on the antigen alone when we incorporate our APC-targeted technology. We also said that we have 100% manufacturing success rate with this. Importantly, this is on the DNA plasmid backbone and is also safe and well-tolerated across the studies we reported so far. So briefly, VB-N01 is the study where we reported this positive data. This is the trial that we initiated before entering the partnership with Russian Genentech And then after signing the agreement with Russian Genentech, we started at the end of 2021, the NO2 study, which is ongoing then in more than 10 indications. And this is where we're doing also a dose escalation. Recently, we have also revealed that we are increasing the dose up to nine mgs. in this trial, which will be the first trial where we look first obviously into safety over a three-time higher dose than what we tested before. And then subsequently, if this is safe, we will be able to investigate whether we have even further increased efficacy by increasing the dose. And this trial is really just highlighting this data that we presented in the fourth quarter. Based on what we've seen here, the breadth of the response is really confirming what we've seen in preclinical studies. We generate the response to a high number of neoepitopes also across, in this case, all patients. We see a neoantigen-specific response after predicting and selecting epitopes based on each patient's tumor and manufacturing one vaccine per patient. Now we also see that these are primarily de novo responses, which is important that they are new to the patients after starting vaccination, but also the inability to amplify these responses that were already pre-existing in the patients. And importantly, we continue to see this strong CD8-dominated T cell responses in this trial. So these data are not just important for us for the individualized cancer vaccine program, but it's really giving us comfort on the translatability of our vaccine platform's unique abilities compared to other vaccine technologies that goes across the platform and not just per product. Then for VB1016, this is all a wholly-owned asset. And you've seen in 2022 throughout that we are focusing on rapidly advancing this asset now in multiple different indications. It has the potential to treat patients with an HPV16 positive cancer across both cervical, head, and neck, and other diseases that are caused by HPV. and we have a pretty broad program ongoing with VB1016. Importantly here, we are now very much looking forward to report final data from the CO2 trial in cervical cancer. We reported interim data from that trial back in May last year, and now we are getting ready to do the final analysis and then report the data about how these patients will do after a whole year of treatment or more. Based on interim data, we have also decided to expand into head and neck and cervical cancer, as well as other potential trials. I'll go a bit more into the rationale for this in the subsequent slides. So importantly here, as a reminder for the interim data that we announced last year in anticipation of the future updated data set that will come out for CO2, remembering that this trial was in heavily pretreated advanced cervical cancer patients. We have said before it's fully enrolled, so 52 patients. This was then treated with a 3-mig dose of EB1016. We have highlighted that this patient population includes a high number of patients with multiple prior systemic treatment lines, so they have failed multiple lines of systemic cancer treatments, as well as we have also a quite high percentage of PD-L1 negative patients, knowing that these patient populations with later stage as well as PD-L1 negatives are, in general, the patient populations that respond less optimal to checkpoint inhibitors. And the last interim analysis was a preset where we had 18 patients that had reached the 18-week scan. As you can see here in the spider plot, but there were multiple patients that had been followed for a shorter period than 18 weeks and only a few patients that had gone through the entire first year of treatment. So this is really what we are then expecting to report within the next few months. Then all patients, all 52 patients, would have had the possibility to have been followed for the entire first treatment year, as well as some patients we will have longer-term follow-up when it comes to overall survival and durability of responses. And we have highlighted before that these very long-lasting clinical responses that we see in those patients that were followed for a year last time is what we are most excited about looking into for the final data analysis to see if we can repeat that pattern in more patients. That will be very important and meaningful for the promise of EB1016 in the future. We have also looked into previously this includes PD-L1 positive as well as negative patients And we see a very high objective response rate in the PD-L1 positive, higher in PD-L1 positive than negative, taking into account that the checkpoint inhibitor monotherapy in this indication has published around 14 to 16% objective response rate in PD-L1 positive. and then in general 0% in PD-L1 negative patients. So it will be important for us to look into these subpopulations also in the subsequent readout. I think for the key inflection points that we are now seeing ahead of us for VB1016 is this long-term follow-up from the CO2 trial. Importantly, we will look into patients that have had a minimum of 12 months, it's PD-L1 positive as well as PD-L1 negative patients that we will see how respond to treatment and it will be patients with both one or more prior systemic treatment lines based on the data that we've also released earlier that there is a higher likelihood of seeing strong responses in patients with with one or two prior systemic treatment lines than those that have failed more than three prior systemic treatment lines. So this will be both an update on our objective response rate and disease control rate. Importantly, also, new parameters that we haven't looked into before will be duration of response and overall survival. Then for the CO3 trial, that's actually a trial that we are expecting to have the first patient, first dose, also in the first half of this year. And in addition to the dose escalation trial that we have mentioned for the NO2 trial, this is also a trial where we will be able to look into how the higher 9-mig dose will perform in comparison with the 3-mig dose. It will be in PD-L1 positive patients, where we've seen also in CO2 trials that we have the highest efficacy, and it will be in first-line patients where we also have seen before that we have the highest efficacy. And we will be in combination with pembrolizumab after we announced that we signed a collaboration supply agreement with Merck in December last year. But for VB1016 in addition, we have an important program ongoing and we're preparing for the first patient first dose also in the CO4 trial, which is a potential registrational trial. And this is a trial that we now recently announced that we will do in tight collaboration with GOG. It is to be initiated in Q4. We are currently on track to do that. It will be then also in recurrent or metastatic cervical cancer setting. These will be refractory to first-line treatment, then including the checkpoint inhibitors performed in U.S. This is really a patient population with a high unmet medical need where we have a potential for fast-to-market. And WeBe 1016 will then be given in combination with a selected checkpoint inhibitor that will inform you on the decision of which one before we start the trial. And as mentioned, we are extremely fortunate to have been able to attract the collaboration with the Gynecological Oncology Group Foundation. This is a US-based expert group that is really focused on gynecological cancers, and it has a 50-year history of designing and executing clinical trials in cervical cancer, and they've really been involved in most all the treatment that has had approval in these gynecological settings. Then the last from the operational point of view is importantly our strategic partnership with Vistu Helm. As Michael mentioned, this is something that's important for us to secure and optimize manufacturing moving forward as a company with multiple programs running in parallel. This is a highly reputable plasmid DNA manufacturer with a proven track record. This will give us highly comparable cost of goods, and maybe most important, a flexible forecasting model that will secure capacity for our entire portfolio, both with our own programs, but also then for delivery to our partner programs. And the ability for us to do potential tech transfer to partners is also something that will be supported by Richter Helm, and that includes our own Nycode IP. So this has been an important collaboration for us moving forward. Thank you very much, Anita.