Good morning and welcome to this presentation here at the HC Wainwright conference, where I'm going to present an update from IO Biotech. Let me first share the forward-looking statements. We have them here, and then jump forward into what it's all about in today's presentation. SilentBio™, this is really showcasing the power of our approach, where we are combining innovation with speed, accessibility, and also scalability. We do see that SilentBio™, which is the US brand name for IO102 and IO103, our lead investigational off-the-shelf immune modulatory cancer vaccine, is not just a potential breakthrough in oncology. It's going to probably set a completely new stage for what is possible in oncology. I trust you will agree with me at the end of today's presentation. SilentBio™ is derived from our technology platform, the T-win® Technology Platform, that can be applied across patients and also tumor types.
We do see an unlimited potential from not only SilentBio™, but also our platform. We see ourselves as being well-positioned to capture a significant market share in the landscape where we are entering, first of all, into first-line advanced melanoma. With that, let me just take you through the key messages that we have coming out of IO Biotech today. Recently, we read out from our Phase 3. These were expected results from our pivotal Phase 3 trial in the first-line advanced melanoma setting, where we tested SilentBio™ in combination with pembrolizumab against pembrolizumab alone. What we saw was that we have clearly demonstrated clinical improvement. We came out with the data with a narrow miss on statistical significance, which we have shared across all the discussions we have had until now. The results really show a dramatic effect in terms of median progression-free survival (PFS).
We had a 19.4 median PFS in the experimental arm against 11.0 months in the control arm. PFS read out with a hazard ratio of 0.77, and it came out with a p-value of 0.056. I want to highlight here again that we needed to hit on a p-value of 0.045, so just a slight miss. We did see PFS improvement across all pre-specified subgroups and also across stratification factors. We have seen this improvement in clinical effect that is in all the patients that we have treated without adding any systemic toxicity versus pembrolizumab alone. The way that we are summing it up now is that we have the effect of a dual compound, but really the toxicity profile of a monotherapy. This is very exciting for us, and of course, also potentially for the patients and the investigators that are going to use our drug.
With this opportunity in hand, we are already setting ourselves ready for discussions with the FDA and potentially submit, as planned, a BLA towards the end of this year. Our discussions are based on a briefing package that we have already submitted to the FDA. We have the meeting scheduled here at the end of Q3, so everybody can expect that it's happening within the next couple of weeks. We'll be happy to share the outcome of that in a press release when we have the minutes from that meeting. The market for first-line advanced melanoma is still there. There is a clear unmet need. 50% of the patients that are treated with today's standard of care do not really benefit. You can see the numbers. They speak for themselves. 15,000 patients in the US alone are diagnosed with advanced melanoma, and the market is growing.
It's a huge market opportunity, growing 9% annually. Not only do we have great clinical data, but we also really have secured the supply chain, and also distribution is already in place. We are manufacturing at commercial scale, and we are doing so with well-established CDMOs that are ready now also to deliver the product together with us for the patients in need of better treatments. I mentioned in the beginning that we do have a platform technology here that has focused on being able to deliver products that can be used across indications. We are not looking to develop products for indications specifically, but already now we know that SilentBio™ has shown effect also in head and neck and lung as well. Let me just go forward here and maybe address a little bit what it's all about.
The patient is front and center for us, as for any company working with drug development. Of course, when patients are diagnosed with a cancer, they get nervous. They get filled with anxiety on securing the path in front of them. This is where we come in and look at the convenience that we can apply to the patients with treatments that are ready when you are at the time of diagnosis. We're working right now under bullet point number four. This is the market we are addressing, as I mentioned before. Some of our trials are also already now addressing the patients with resectable melanoma under bullet point number three. The data that came from this trial that we embarked on some years ago, where we opened more than 100 centers across the world: Europe, Australia, South Africa, Israel, and US, and 407 patients were enrolled.
They were randomized against pembrolizumab alone, and we were using the combination of IO102 and IO103 together with pembrolizumab in the experimental arm. We can see the primary endpoint was PFS read out by central review. These are the top-line results that we shared just recently. Very proud of what we saw in the intent to treat analysis of the experimental arm coming out at 19.4 months median PFS versus the 11 months in the patients treated with pembrolizumab alone. I mentioned in my introduction the p-value with a slight miss coming out at 0.056 and a hazard ratio of 0.77. We started looking at the data, understanding a little bit more how our drug is working also in different subgroups of the cohort that were treated and enrolled in the trial.
When we excluded patients with prior anti-PD-1 exposure, and those patients were not a part of our phase one to initial trial that laid the foundation for this phase 3 trial, we really saw something that excited us as well. Median PFS came at 24.8 months versus, again, the 11 months in the control arm, hazard ratio now at 0.74, and now a nominal p-value at 0.037. Going further and looking at the PD-L1 negative group, the group where we know that there is a highest need in this population because the anti-PD-1 alone does not really work well there, we saw a dramatic effect. 16.6 months of median PFS in the patients treated in the control arm versus three months in the patients treated with pembrolizumab alone. Now the nominal value sitting at 0.006 and a hazard ratio of 0.54.
Not only are we excited about the results, we are also hearing a lot of good input from KOLs and other groups, stakeholders across the society that have seen and are learning about these data. It all comes with an OS that is already trending favorable towards the combination arm. The hazard ratio is at 0.79. It's not yet matured, we are keeping on following that, but it's already showing that the curves are widening post nine months. I want to emphasize that what we are excited about is not only the effect, but also the lack of added systemic toxicity. This is really what you're looking for when you're developing a new drug. We are pleased to see the readout from the trial here. Just showing you the curves here, it's always great to have a good Kaplan-Meier curve in front of you.
Here we are seeing the clear separation of the two arms, showcasing the median PFS here, the blue curve, the experimental arm versus the red curve, the pembrolizumab arm: 19.4 and 11 months median PFS. When we look at the curve, the Kaplan-Meier curve showing the trend in overall survival, you can see that the curve starts separating at the nine months and really widening out. We are very excited to follow the OS as it matures into 2026. I already mentioned it. The safety profiles are really clean. We are not seeing anything that is concerning. On top of pembrolizumab alone, it's only injection site reactions that we have in the experimental arm. This is expected. This is a vaccine that we are injecting subcutaneously, and therefore, it's nothing that is of a surprise to us. I mentioned this in the introduction.
This is really a market that is growing, and there is a huge need. 50% of the patients are still in lack of better treatment in the first-line advanced melanoma setting. The market is growing 9%, and we have a billion-dollar opportunity here for our profile that we have come out with. We expect also to be able to take a significant market share of this first-line advanced melanoma indication. How are we doing that? We are already preparing for launch of SilentBio™. If approved, we will be ready to bring the product to the market and also be ready to set a new standard for the treatment of advanced melanoma patients. We do see that our product is very differentiated compared to any of the other products that are available for this patient group right now. The opportunity is large and growing.
As I mentioned already, we are seeing that there is a growing awareness from all constituents with an awareness of our data as being very excited and also very promising. Of course, the team here at IO Biotech is ready and already geared up to go out and do the job in terms of making sure that we hit the market in the right way. With that, let me just spend a little bit of time going through some of the other programs that we have in our pipeline. SilentBio™ is not only a product that is meant to be used for melanoma. It's really a product where we are using antigens IO PD-L1 that is expressed across multiple different tumor indications across all the patients coming in with those tumors that we are working with.
We have set up also two other Phase 2 trials to expand the value of SilentBio™ and understand also how we feel in other indications such as lung and head and neck with the IO BO22 trial. First-line solid tumors, we have already shown data from those indications, and we are seeing a signal in both indications as well. We have further also moved ahead and testing SilentBio™ in earlier clinical stages. We are testing it in neoadjuvant adjuvant setting, also a Phase 2 basket trial where melanoma and head and neck are our indications. Data from both of these trials will be shared at upcoming conferences, and we are ready already to share this initial data in the end of 2025 to be presented in 2026 from the O32 study. We are also working with other targets that are coming out of our platform.
We have seen really great data coming out from IO112. This is an arginase and it's expressed in a different set of tumors than the ones we are already working on. It's giving us an opportunity to broaden up our indications. The data that we have seen so far have led us to now making ourselves ready to submit an IND during next year. Similar, we are seeing a great trend of data coming out from IO170. This is targeting TGF-beta. We are seeing really good control of tumor growth as well as inhibition of fibrosis. I will touch on that a little bit later on in the presentation. First of all, I want to make sure that you all understand that we are laser-focused on making sure that we anchor in first-line advanced melanoma. This is front and center for the team and how we are working right now.
We are having the discussions with the FDA. We are making ourselves ready to submit a BLA towards the end of this year and then move forward. Of course, also with a submission, as I will mention, when we look at the milestones for 2026, a submission in Europe as well, where we also see a great opportunity for a first launch of our SilentBio™. As you saw in the pipeline, we are also moving further on. When we have anchored in melanoma, we will start moving forward and going into head and neck and lung, and then we will expand further into the earlier stages. The numbers speak for themselves in terms of total addressable patients, and these are numbers just in the U.S. alone. I touched on arginase and also TGF-beta when I went through the pipeline overview.
These two programs are really showing that we have an opportunity to expand from the T-win® Technology Platform, from going beyond what we have seen of exciting data from our lead program, SilentBio™, IO PD-L1, now also showcasing great data from arginase-1 and also TGF-beta. Especially TGF-beta is also showing some very interesting data in terms of fibrotic diseases. Very excited to share also data from these two programs as we move on. There is an opportunity for the T-win® Platform to also be used outside of immuno-oncology. This is a future potential that we are seeing for the platform, but I don't want to touch too much on that now. Just mentioned that this is also something that is laying in the future plans. Since I've now talked a lot about the platform and also the pipeline, let me just also share with you the mechanism of action.
This is novel biology, and we are very proud to be frontrunners executing on this biology. We are seeing others taking on and starting developing similar programs. We are still excited about being the first one that really has initiated this work. We are using a subcutaneous injection of peptides that are derived from immune suppressive proteins, which will lead to an activation of T cells with a dual mechanism of action. The antigens we are working with are expressed not only on immune suppressive cells, but also on tumor cells. It will lead to a T cell attack on both types of cells, which, of course, will lead not only to a killing of those cells, but also to a modulation and inflammation of the tumor microenvironment. It becomes more immune permissive. This is what we have seen across all the preclinical models we have used.
This is also what is now beautifully being played out in our randomized Phase 3 trial, where we are seeing a clear clinical benefit from the patients that have been treated with our lead product. I said in the beginning, we are focused on being convenient for the patients as well. They don't need to think too much about coming in and having our treatment, as it's off the shelf and it's a subcutaneous injection. It's really very convenient for the patients, fast access, and directly available. Also, it's convenient storage. We have a storage of two to eight degrees Celsius, and it can be a rapid administration, which I think is really also something that you look for when you come in and you have a cancer diagnosis. Let me just wrap up, and I'm glad that I'm doing it in time.
I'm seeing that the time is running out. This is my last slide I want to share with you today. I just want to mention in this last slide here that we have cash into the first quarter of 2026 with a Q2 cash balance of $28 million. We took in a second tranche from the European Investment Bank loan that came in the 4th of July, 2025. Of all these milestones that we have in this slide, let me just end the presentation here today with highlighting the most important ones that are the discussions with the FDA here in the fall with a potential BLA submission thereafter. I also want to highlight that we have a potential for an EU MAA submission early in 2026.
I can just finish up mentioning that last week we got an agreement on our pediatric development plan from the FDA that we are very happy about because it's been a huge task to develop the plan. We are glad and happy to share now that we have an agreed plan with the FDA. Thank you all for attending our presentation today and listening in. Thank you.