Thank you once again for joining us for the 45th Annual TD Cowen Healthcare Conference. I'm Yaron Werber with the TD Cowen Biotech Team, and it's a great pleasure to introduce IO Biotech. With us today is Mai-Britt Zocca, the Chief Executive Officer and Founder of the company. Mai-Britt is going to do a presentation, and then if there's any time, we'll take some Q&A as well. The team is here. Thank you for coming. We appreciate it.
Thank you. Yeah, thank you. It's always a pleasure to be here in Boston at the Cowen Conference. Let me just start off here with the forward-looking statements and then move fast forward to introduce what we are really going to discuss today. I will share with you the power of our approach, where we are combining innovation with speed, accessibility, and scalability. Cylembio is the U.S. brand name for IO102-IO103 , our lead investigational off-the-shelf therapeutic cancer vaccine. We view this as not just a potential medical breakthrough; it also attempts to really redefine what is possible in oncology. The platform we are working on, the T-win, can be applied across patients and also across tumor types. We see this giving us an unlimited potential, and we are also well-positioned to really take or capture significant market shares in multiple cancer indications.
I trust you will appreciate this with me when I go through the presentation here today. Let me start off with what is most important for all of us that is working in this field, and that's the patients. Patients, when they come in and they present and they are diagnosed with a cancer, they, of course, get nervous. They are filled with anxiety and uncertainty, and they have a long journey in front of them going through the treatment options that are available. What we are focusing on with our lead product is the first- line unresectable metastatic melanoma. Here we have a huge patient number that are receiving standard of care in the first- line settings right now that is really not working that well.
We see that we have a great opportunity to come in here and capture a market share and offer treatment that works for these patients here. We are well-positioned, as I mentioned in the beginning. Our treatment is off-the-shelf , which means that patients can be treated fast. It is being applied as a subcutaneous administration. I will share more details on that as I go through my presentation. Some of the key features for the company as such are based on what I am sharing here in this slide. It is really highlighting what it is all about. We are about breaking boundaries and igniting changes. We say that with the minds on our very strong platform and the pipeline. Everything is built on the T-win platform that is delivering the immune modulatory off-the-shelf cancer vaccines. As of today, we have Cylembio as our lead asset, IO102-IO103.
We also have in the preclinical pipeline IO112 and IO170. Today, we are working in three indications: melanoma, head and neck, and lung. Actually, the newer targets in our preclinical pipeline give us the opportunity to also expand into other cancer types. Front and center is the opportunity we have in melanoma, and what this is built on is the clinical proof of concept that we established in our phase I/II trial that gave us the breakthrough therapy designation granted by the FDA. We got this when we shared with them the data: 80% overall response rate, 50% CR, and 25.5 months median PFS. This is really unprecedented data. When it comes hand in hand with also adding no systemic toxicity, it's really exciting not only for the patients and investigators, but of course also for the FDA.
We went through with launching our phase III trial, pivotal trial. We are now awaiting the data, and we have just updated our guidance on the expectations of the readout to Q3 2025. Based on this, we will still be able to submit our BLA at the end of this year, so there is no change to that. I am just excited again to share that we have taken on and calling our lead asset IO102-IO103 , Cylembio as the brand name here in the U.S. Let me just go into more details about the lead indication we are working in. There is a high unmet need in advanced melanoma, and we aim to address that.
It is the fifth most common cancer type in the U.S., and there is, and you can see the numbers here on the slide, there are many patients being diagnosed, and the five-year survival rate is only 23%. We also know that there is a growing market in the metastatic melanoma setting. If you look at the numbers here, it's growing with a 10% rate going from 2023- 2030, capturing all the way up to $13 billion in 2030. If we look at standard of care, only 50% of the patients benefit right now, and of this, only patients that, some of the patients, 50% of the patients that do respond are actually also not benefiting fully from the treatment. We also know that 50% of patients will develop adverse events based on the standard of care that they are receiving.
Is really a high unmet need in this indication. Our data that I shared already in my introductions are published in Nature Medicine back in December 2021. We gave an update in JITC in May 2023, and based on these data, we went directly into our pivotal phase III trial that is now fully recruited. I welcome that you go and read both the Nature Medicine and the JITC publication for more in-depth details around those data. The clinical trial, the pivotal phase III trial, was really a mirror of our phase I/II study. We plan to enroll 380 patients where we randomized IO102-IO103 in combination with pembro against pembro alone. We ended up fully recruiting 407 patients that we did ahead of time in December 2023, and we have had several IDMCs, and all of them have continuously recommended that the trial continues without any modifications.
We are excited to look forward to the PFS readout here in Q3 2025 and, of course, to rapidly thereafter submit our BLA submission. We have been very excited about the discussions that we have had with U.S. KOLs and also other KOLs from other parts of the world. They are all really looking forward to use the treatment that we are potentially able to come forward with to the patients in need. You can see some of the points that they are coming back to us with when they have looked at our TPP and the opportunity we have in hand. Based on the filing of the BLA on the back of our data that comes out later this year, we are already working on our launch goals.
We will be able to launch in 2026, and this is, of course, setting the team already now in work on achieving these goals. We see that Cylembio is having a potential to be practice changing, and we would like to have this product out to the patients as soon as possible. What we are aiming now to ensure for the launch goals is to establish the belief in our treatment. We are well aware with that, with all the discussions we are having with the KOLs. We are also maximizing the value of the product by making sure that we will be having product available to all eligible patients that will have access to our therapy. All of this is based on a pragmatic launch model where we are targeting top melanoma treaters in the academic and the community settings.
Very excited about where we are also with this work, looking forward to the launch of our product in 2026. The lead product is not only targeting melanoma as an indication. What is really beautiful about Cylembio is that the targets we are using, IDO and PD-1, are expressed across indications. Lung and head and neck is already well-established in our pipeline. We have a phase II trial where we have enrolled patients in both indications, and we have already shared early data from both of these indications. We are also working on expanding the value of Cylembio into the perioperative settings, neoadjuvant, adjuvant settings in both melanoma and head and neck. T-win is a platform technology, and it actually already is generating the next targets that we are working on driving towards IND. First of all, IO112 targeting Arginase 1.
We have shared in multiple posters and in multiple journals data from this target where we are seeing very exciting opportunity for moving into other solid tumor forms than the ones we are already working on. Similarly, we are also moving forward with IO170 targeting TGF-beta, where we have just recently announced also data from this target, and we are seeing exciting data also in support of the mechanism of action that we are looking for with this target as well. When you pull all this together and you look at the addressable patient numbers that we can do with all these activities, it's really giving us a very exciting opportunity. We see that we have a potential to redefine the treatment of hard-to-treat solid tumors and really expand beyond the first- line advanced melanoma settings.
What we aim to do is to anchor our foundation in the first- line advanced melanoma settings. I already shared with you the numbers: 15,000 patients of an opportunity here. When we have anchored here, we are expanding into head and neck and lung, and you see the numbers here, adding 40,000 patients on top of the 15. If we go in and we look at the earlier settings, the perioperative settings with head and neck and melanoma, the numbers get even bigger and larger. This is really exciting times for us, and 2025 can be a potential transformative year for IO Biotech, and we are looking forward for that, of course. We have similar charts, as I shared with you, on melanoma, both for lung and for head and neck.
We all know that lung is a huge indication, the second largest cancer indication worldwide, and with only 28% of five-year survival rate for patients with Stage IV. Similar to what we shared with melanoma, there is an expected growth rate of 10% from 2023- 2030, and with a market looking towards $60 billion U.S. dollars. The unmet need remains based on the fact that 40%-60% of the patients are failing to respond to the first- line treatment options. When we look at head and neck, it's a smaller indication. It's the sixth most diagnosed cancer worldwide. Here, the five-year survival rate is a little bit different with 50%. The growth rate of the market opportunity here is 6% if we look at 2023 going towards 2030, going all the way up to $5 billion U.S. dollars here in 2030.
The unmet need is based on the fact that 60% of the patients are failing to respond to the available treatments, and we know that for head and neck, a lot of failures have happened during the last many years, but we are seeing promising other opportunities coming up in the pipeline for head and neck. If we look at the trial design for the work that we have done so far with both head and neck and lung, it was a phase II basket trial, which is now fully recruited. We took in 37 patients in lung with a PD-L1 TPS score above 50%. And in head and neck, we included 21 patients, with 18 of those being evaluable with a PD-L1 TPS score of above 20%. We treated the patients with Cylembio in combination with pembrolizumab, and we were looking for overall response rate as the primary readout.
We were excited to share at ESMO last year that we hit the primary endpoint in head and neck with a readout of 44.4%. Later on during SITC last year, we shared the promising activity that we saw in lung with an unconfirmed overall response rate of 55% and a confirmed overall response rate of 48% in the efficacy available patients. The next step for both cohorts will be that we are looking to further update on both the PFS and also the duration of response in both cohorts. The data we shared during SITC last year are shown here, and I welcome you again to go and look for our poster that we presented during the meeting. What I want to highlight in the slide here is the median PFS, which is 8.1 months, and the disease control rate of 81%.
Similarly, here is the data that we shared during ESMO last year, where we were very happy to announce that the primary endpoint was met. Again, I want to just stress the median PFS, where we had 6.6 months and a disease control rate of 12%. The data that we are looking at here in head and neck are really exciting. What we are seeing here is actually doubling up compared to standard of care. When we take all this together and we look at everything that we have achieved so far from a clinical data point of view, we are excited. It's very compelling to have not only data that are giving us a clear indication of a drug in melanoma, but also in head and neck and as well in lung.
There's only so much luck you can have, and I do believe that it's a drug and not luck when you see a clear signal in three indications, and therefore we remain very confident for our readout of our phase III trial here later this year. I shared with you in the overview that we are also expanding into the perioperative setting. This is a trial where we have enrolled in three cohorts. Cohort A was a single-arm melanoma enrollment of 15 patients, and we enrolled similar in head and neck in a single-arm setting, 15 patients. We saw huge interest for the trial, really a rapid enrollment of these first two cohorts. Therefore, we expanded the trial to also include Cohort C, where we are in a randomized session. We have enrolled patients being treated with IO102-IO103 in combination with pembro against pembro alone.
You can see the treatment scheme here in the overview, where we are giving two to three cycles of the treatment prior to surgery, and then post-surgery, we are treating the patients all the way up to 15 cycles. We are excited to share the first data from this trial later on this year, and of course, as I mentioned already, to build on the clinical data that we have so far on Cylembio. Last but not least, I would like to share just a little bit more details on the preclinical pipeline. We have IO112 that is moving forward with IND planned here in 2025. The role of Arginase is really well- established in multiple cancer indications, and it's linked to a high presence of myeloid-derived suppressor cells in the tumor microenvironment.
This can, for example, be found in ovarian cancer, which is known to be a difficult-to-treat cancer indication, and as well in multiple other of this similar type of cancer indications. We are excited about moving forward with IO112 with an IND planned this year. IO170 targeting TGF-beta. A lot of work has been done already in the past around TGF-beta, but with a lot of safety concerns around this target. We see an opportunity for our MOA to come in and really treat towards this target with a safe modality. The data that we have seen so far in our preclinical models are giving us hope that we actually are able to do something around this target as well.
Looking further out to the future, and this is really future future, we are also seeing that the T-win application can be used outside immuno-oncology. Here we are thinking about opportunities, for example, investigating infectious diseases as well. Very excited about not only Cylembio, but also the opportunity we have around the T-win technology platform with the newer targets and also with the opportunities outside of immuno-oncology. Before we go in and look at the key milestones that I also want to use the opportunity to share with you today, let me just highlight the mechanism of action that we are working on with the T-win technology. It is therapeutic cancer vaccines that are activating the immune system and targeting both tumor and immune suppressive cells. This is key.
This is really a key differentiator that makes us excited about our platform compared to any other cancer vaccine developed right now. We are using a subcutaneous injection treatment path for our vaccine strategy, which will activate T cells with a dual mechanism of action. That will enable the T cell to target both tumor cells and immune suppressive cells, which then will lead further to the tumor microenvironment becoming modulated and inflamed, and thereby also becoming immune permissive, and thereby further tumor cell killing can be allowed by other T cells. This is really a circle that is kicked off with the initiation of the T cells based on our targets. One of the things that has really been keen to us is not only the fast treatment of patients out at the clinics.
It's also really how we manufacture, store, and procure our product until the patients are being able to receive the treatment. We have checked all these boxes going from now the GMP manufacturer, which was at clinical scale, and now we are at commercial scale. We are also indeed getting ready on that front, and I'm very proud of what the team has achieved in a record time around this. This has not been an easy task to lift, and I'm very excited about us being ready for really having the product available to patients eligible for our therapy. The vaccine is also easily stored at 2- 8 degrees Celsius and is easily ordered by the clinic.
Time to treatment, side of the care, and convenience for patients is something that has been high on our list, and I'm proud to say that we have checked those boxes as well. I see that the time is running, so let me just also go into the outlook and going through the milestones that we have in front of us. We have just updated our guidance. We are looking for the primary endpoint now expected here in the Q3 of 2025, still enabling us to submit the BLA at the end of this year. We haven't made any changes to the guidance in that regard, and also keeping our guidance on when we are expecting the U.S. approval. As I have shared, we are already working on our launch as well here in the U.S.
We will have additional data coming out from several of the other trials that we have. These are really important clinical milestones that are coming out in support of the value of Cylembio in additional indications and in earlier clinical stages as well. We are excited also about filing the IND for IO112 later on in this year, and then also, of course, to start enrolling in this phase I study already here in 2025. We are working on IO170 on the IND enabling studies, and we are also looking forward to give update around all the work that we are doing here as well. I want to end up my presentation just again sharing our opportunity that we see here with Cylembio. We are seeing ourselves as the front runner, the driver of the next frontier of immunotherapy.
Cylembio is a potential first-in-class immune modulating off-the-shelf therapeutic cancer vaccine candidate that we see as an opportunity to transform the IO treatment paradigm. I'm building on that based on what I have already shared with you on the several successful milestones that we have achieved with really the compelling data in our phase I/II metastatic melanoma trial, and also the promising data that we have already seen in our lung and head and neck indications. We have already fully enrolled our phase III trial, which I also think was a great achievement by the team, and looking towards the readout of this trial in Q3 here this year. We are preparing, getting ready for our BLA filing end of year and potentially launch Cylembio during 2026. With that, I would like to say thank you to you all for listening in and hearing our update.
I have a question you can repeat. Thank you so much. Maybe a couple of questions. I guess the first one on the primary endpoint of PFS. I think you've said that the data was kind of mid-year, now it's Q3. The event rates slowed down a little bit. Can you share any information with us at all? Secondly, do you need to build inventory to support the launch? How does that work?
Yeah. Allow me to repeat the question so it's clear for everybody. First of all, there is a question about the updated guidance on the PFS events, and then of course around launch as well. Qasim, our Chief Medical Officer, is here with me today and can take the first question.
Thank you, Mai-Britt. Regarding PFS, we're just trying to be as close to accurate as we can be. It's a slight shift from what we were saying previously with first half now to Q3. We are still blinded to the analysis, so we cannot share more, but this is as accurate as we can get.
Have the events been? This is just something you've noticed and you got that from the DSMBs to whether they're going to trigger? This is the final analysis, right, on PFS?
This is the final PFS analysis.
In any sense, did the event rates slow recently? How did this typically work?
I would say it's just a natural process of how you would expect them to happen.
It's hard to know kind of what's driving that.
They could be several factors.
Remind us maybe just a little of what you touched on and how you powered the study and what you expected to see in control.
Yeah, the study is fully powered with 89% of power, and we are expecting a 0.65 hazard ratio, showing 35% benefit.
Just remind us, based on what was the expectation from the placebo from the control line?
Pembrolizumab, we just look at if you think of the pembrolizumab historical data, it's ranged between 4.9 months of median PFS to about eight months. The best we have from pembrolizumab is 11.6 months that was from KEYNOTE-006 . We took all of those as benchmarks.
Why is there such a wide range? First-time pembro, right?
It depends on a number of factors. I think one of them, especially if you look at KEYNOTE-006, it had a high proportion of PD-L1 positive patients. It was about 80% PD-L1 positive. There could be many other factors as well that you can list.
In your study, are you selecting based on [audio distortion]?
We do have a stratification. The patients are not stratified in the trial as such, but we do have PD-L1 status.
They're not stratified by your following?
Yes.
You're not enriching for either one of them?
No.
Do you have any sense what percent of the patients saw IO previously in the adjuvant setting?
I would say there would be very few of them. We're not expecting too many because the standard of care still was evolving as we enrolled the study.
You're allowing?
Yeah. They have a six-month window.
They could as long as they can.
They could have, yes. Then a six-month window.
It didn't matter why they were relapsing at that point?
Yeah, it did not.
Okay. Got it. It is an 89% based on the hazard ratio. That hazard ratio of 0.65, was it based on the 11.6 from 006, or how did you, which PFS did you model it based on?
I think you can, well, we took an average of that, and that is eight months.
Based on average of eight months.
Yeah.
Got it. As long as you're eight going to, let's say, 11 or 12.
12.
12, 11, 12. BioNTech recently ran a first-line study also with a vaccine. That study, they've stopped talking about that study. That study has been taking too long. They're de-emphasizing it. Obviously, with very different kinds of vaccines completely. It's unclear what happened there. Reading between the lines, it looks like they probably didn't get the separation they wanted. Any sense? Is there any cross-reads to here? I mean, it almost seems like pembro did extremely well in that study for bizarre reasons.
I cannot comment on the BioNTech study, so we don't know yet.
Are you seeing in the community that pembro might be doing better than expected for whatever reason? Maybe that's why the events are just not happening as fast?
We just look at the benchmark data, and then from a benchmark, we know what pembro has done best in any of the studies versus where we are today. We had our last patient recruited in the trial in December of 2023, and we're almost 15 months from that time period.
Just remind us, where were the sites? Kind of how many?
It's a global study. The majority of our sites are in Europe, but we do have sites in the U.S., in Israel, Turkey, and South Africa.
Got it. Okay. Terrific. It sounds like the events that will happen in Q3, or you will announce it in Q3.