All right, let's go ahead and get started. My name is Ashleigh Acker, Biotech Analyst on Allison Bratzel's team here at Piper Sandler. Thank you for joining us at the Piper Sandler Healthcare Conference. It's my pleasure to introduce IO Biotech, joining us for a fireside chat today. We have CEO Mai-Britt Zocca and CFO Amy Sullivan. Thank you for joining us for this fireside. This is meant to be informal, so if anyone in the audience has a question, please feel free to raise your hand. Before we jump into the formal Q&A, just to level set for investors, Mai-Britt, could you just give a quick overview of IO Biotech, the story, the setup into year-end and 2026?
Yeah, thank you, and it's great to be here, and I always love this meeting here in New York at this time of the year, so where we are, and definitely 2025 has been kind of transformational for IO Biotech. We read out on our Phase III trial earlier this year, so in the third quarter, and what we saw was really very exciting, despite the narrowness we had on the p-value for our lead study, so let me just go through about the study and the data that we saw, and then also maybe just highlight some of the other exciting things that we have shared during 2025.
So the P hase III trial was testing our lead program, IO102-IO103 in combination with pembro in first-line metastatic melanoma patients, and was set as a trial where we were ready to file for a BLA here at the end of this year if we had hit on all parameters. But what we did see was really a clinically meaningful readout. We have a drug that's clear. Our trial was just probably a bit too small to really detect the p-value or the statistical significance of the outcome. We saw a hazard ratio in PFS of 0.77, and really the median PFS was 19.4 in the experimental arm versus 11 months in the control arm. So quite exciting data that comes hand in hand with a clear safety profile. So really the drug profile that everybody's looking for, where you're seeing effect and with no safety concerns.
So this is really also validating the platform that we are working on, the T-win technology platform, where we have the ability to drive antigens or generate peptides that we are using as therapeutic cancer vaccines off the shelf to target not only the tumor cells, but also the immune suppressive cells. And we do believe that this is what is driving the effect that we are seeing in the clinical trials where we are testing this concept. And I could go on, but I want to pause here and maybe go into the next questions.
Definitely. So let's take a closer look at the mechanism. Can you help us understand why this mechanism of action makes sense, given what we've seen with previous IDO inhibitors in a combo setting? I think what comes to mind is the epacadostat story. So that was a high-profile fall. So just help us make sense of this.
Yeah. And I've said it before, but I still remember the readout of the epacadostat trial back in 2018. I think it was in the spring of that year. And that was really a trial that everybody was waiting for the data. Everybody was very excited about it. And also because IDO, of course, is a very relevant and still very relevant target in oncology. It's expressed throughout many different cancer indications, and it's really a target that is, or it's an enzyme that is linked to poor prognosis as a poor prognostic marker in multiple indications. So the way we have approached IDO and the way that we are taking an approach to make this use as a drug is that we are targeting cells that are overexpressing IDO, and then we're killing them.
Or we are turning the tumor microenvironment into an environment where it cannot be used as a shield or a barrier to the tumor cells. And that is really what we are seeing is turning our ability to use IDO as a target into also being a relevant drug. So I'm happy that we have continued the developments of IDO despite the failure that we saw with epacadostat.
Great. So as a follow-up, can you just quickly walk us through the rationale for targeting PD-L1 with a cancer vaccine in a combo approach?
Yeah. So it's really very synergistic in combination with an anti-PD-1 antibody. So again, the way that we are using our targeting PD-L1 is to go after cells that are positive for PD-L1 and then using this as a target for T cells to target those cells. So this is a way where we are transforming the tumor microenvironment into becoming more tumor hostile. And because we are using different interactions than anti-PD-1 antibodies are using, it's working also very nicely in synergy with anti-PD-1.
Great. So let's talk a little bit about IO102-IO103 and frontline melanoma. You previously laid out how half of advanced melanoma patients progress within one year of treatment and how novel combos are needed to improve patient outcomes. Can you just quickly outline the patient journey and the potential TAM here?
Yeah. So it's really tough when you come in and you get diagnosed with metastatic cancer disease. And of course, if you are at a point where you can't be cured by surgery, as in the case of melanoma, there's very few options available for the patients. And of course, you are nervous and have anxiety about the journey in front of you. And many of the drugs that are being offered right now come also with a price in terms of toxicity. So the way that we approach it is really that we want to generate drugs that are effective without any toxicity. So that has been our goal from the beginning. And that's really where cancer vaccines come in very strong.
Why the interest has been going on for decades now, I think it's more than 30 years or so, that there has been an attempt to develop therapeutic cancer vaccines. It's really because it can potentially be a very safe way of generating effect for patients.
Excellent. So in your original remarks, you talked a little bit about the pivotal data. So that was disclosed back in August with that slight miss on the primary endpoint. But you also had more fulsome data at ESMO. So can you just walk us through some of the results, how they tie into the original top-line data, and help us understand their significance, and maybe how the ESMO presentation adds to the body of evidence that supports the combo's immune modulatory approach?
Yeah. We are very excited about the data, and that is being shared with everybody that were seeing the presentation during ESMO as a late-breaking abstract. What we saw was PFS that we read out. I said that in my introduction, hazard ratio 0.77 and median PFS of 19.4 versus the 11th month in the control arm. That was already a clear separation in the Kaplan-Meier curves, and of course, we're excited to see that mature now as well. What we are also excited about is that if we look in different subgroups, we see also clear effect in these subgroups. Basically, across all subgroups and stratification markers, we're seeing a clear drug effect. This is, of course, very exciting, and again, it comes hand in hand without adding any safety concern to the patients treated.
And then when we look at OS, and we know that OS is really a very important readout in oncology, we are already seeing an effect there as well. So very excited about those data.
Excellent, so speaking about overall survival, the last we heard, this is trending favorably with a hazard ratio of 0.79, with the combo being well tolerated, no significant added systemic toxicity. You previously mentioned that we could get more mature OS data next year. Is this still the thinking?
This is still our thinking. And of course, we are excited to share that next year. And fingers crossed that it's trending as we are expecting. So very excited about sharing that during next year.
Great. How has the pivotal data resonated with physicians and KOLs in the field?
So I do think that all the feedback we have gotten based on the data that read out, and despite the slight miss, everybody has been very excited about what we are seeing. This is the first time a cancer vaccine, therapeutic cancer vaccine, has shown a clear benefit in the metastatic disease setting. So not only is it clinically meaningful, it's also really just giving the relevance of this type of modalities as being effective in the metastatic settings. We have seen some great data in the adjuvant settings, but really, when you come and you go into the metastatic disease settings, there has just not been anyone that has been clear to show what we have been able to show in a randomized Phase III trial. So that is shared across the community of investigators. And we're just very proud to have these data in hand.
Great. So let's move on to some of the regulatory updates that we've gotten from you guys. So we know from following a pre-BLA meeting with FDA, the agency recommended that you not submit a BLA based on the data from the pivotal study in first-line advanced melanoma. How surprising was the outcome? And maybe walk us through the approach that FDA took when looking at the data and the rationale behind the recommendation.
Yeah. Of course, I mean, we were fighting our case to file our BLA. Everybody I trust would be doing the same thing. As I just mentioned, we do see a clear benefit in terms of efficacy readout. And with the tolerability profile we have, the risk-benefit ratio is really in favor of our drug. And with patients in need of better treatments, that was, for us, the strongest argument to go in front of the FDA and discuss the data. Of course, we know that the p-value is also equally important. Statistical significance is a bar that is clearly set by the FDA, and we respect that they are adhering to their guidance in terms of that. So we missed on the p-value, and that's basically the feedback that we have gotten.
Great. So let's talk about some more recent news that we got from you guys. You recently outlined a proposed global adaptive Phase II/III clinical trial evaluating IO102-IO103 in combination with Opdualag in first-line advanced melanoma. You previously discussed how the design of the study is based on FDA discussions, but also an investigator-initiated Phase II trial at Memorial Sloan Kettering. So can you just provide a quick overview of the Phase II trial and the results that supported moving into a pivotal study in this combination?
Yeah. Yeah. So again, I mean, we remain very excited about what our drug is able to do. So this is a two years ago, Memorial Sloan Kettering-initiated and investigator-initiated trial in first-line advanced melanoma setting where they are testing IO102-IO103 in combination with Opdualag. And this is, of course, based on the recent approval at that time of Opdualag and the interest to see how that combination then would pan out in the patient settings that we have tested now, IO102-IO103 in combination with pembrolizumab. So these data are just not mature yet, but what we know is that they are actually seeing an effect in the combination with Opdualag of IO102-IO103.
So that is exciting for us, and especially because while we have been executing on the Phase III that recently read out, the standard of care has changed here in the US, especially with Opdualag approval, and now taking at least 30%-35% of the market share. So in the discussions with the FDA, knowing how the market has changed, now the new trial design that we are proposing is a combination with Opdualag to kind of adhere to where standard of care today. So the combination of those data from the MSK trial, the new standard of care, our discussions with the FDA all together have given input to the trial design that we are now working on.
Can you walk us through the trial design and some of the outcomes that you aim to demonstrate based on the design?
We are still working our way through the clinical trial design, but it will be a classic randomized study one-to-one with the experimental arm testing IO102-IO103 in combination with Opdualag versus Opdualag alone. We will go and we will have a readout of PFS, and then, of course, also follow the trial for an OS readout as well.
Great. So looking beyond FDA engagement, you guys are planning to discuss the data from the pivotal study with EU regulators to determine a path to MAA submission, which is currently being guided to 2026. Any additional color you might be able to provide on the timing and potential disclosure of EU engagement, and maybe talk a little bit about the viability of the data in the EU given the regulatory precedence of Opdualag?
Yeah. So I mean, we are eager to share as soon as possible the feedback from the interactions with the EU. It's moving a little bit slow. They are overwhelmed with work and delayed in the processes. But hopefully, we will be having some feedback within the next couple of months. So there is a difference in the guidelines in the EU compared to the guidelines here in the US. And some of the guidelines are actually giving us a reason to believe that we can have a good discussion with EMA around filing potentially in some of the subgroups where we are seeing benefit in the trial. So this is what we will set up to discuss with the regulators in the EU.
Excellent. So let's talk about IO102-IO103 in the neoadjuvant and adjuvant setting. So you guys have a phase two solid tumor basket study evaluating IO102-IO103 and pembro in the neoadjuvant adjuvant setting in patients with resectable melanoma or SCCHN, and it's underway. And initial data is being guided to, I guess at this point, by the end of the year, and presentation will follow in 2026. So how are you level-setting investor expectations heading into this readout? And help us understand the outcomes that you're hoping to see that would support continued development in this setting.
Yeah. So of course, we are following the landscape as it's evolving both in head and neck and in melanoma. And more and more patients are treated in the adjuvant settings and potentially also in the neoadjuvant setting. And of course, we also see with the clear tolerability profile that we have of our drug that we have an opportunity to have benefit for patients in that clinical settings as well. So what we are looking for is, of course, to push the time to recurrence in these patients. And it's the secondary endpoint in that trial. So what one would like to see is that we can prolong the time before the patients move into a more later stage of their disease.
Excellent. So maybe just to touch on one more point here. We had some recent KOL feedback that use in the adjuvant setting might be difficult, at least in melanoma, given the theory that combination immunotherapies have largely failed due to the lack of macroscopic tumor available. But the KOL does see more promise in the neoadjuvant setting. Anything you'd like to add to this discussion and your perspective on the use?
Yeah. I think there's still time for us to learn about the outcome in those two different settings. Our trial is being conducted both in the neoadjuvant and adjuvant settings, so we are treating patients prior to surgery and then again after surgery, and we'll be very excited to see how patients fare after those treatments.
Great. So let's talk maybe just a little bit on your other phase two basket study. So this is evaluating IO102-IO103 in combination with Pembro in front-line PD-L1 high, NSCLC, and SCCHN. Longer-term data from these cohorts was shared at this year's ESMO meeting. So can you just quickly walk us through their meaningfulness and maybe talk a little bit about the early analysis looking at the immune modulatory signature?
Yeah. So I mean, this is really fantastic. But because what we are seeing is that IO102-IO103 is having effect beyond melanoma alone. And this is what we anticipated from the beginning. We wanted to develop not only an off-the-shelf product, but also a product that can be used across different indications. And this is really what we are seeing also in this trial where we are seeing we hit on the primary endpoint in head and neck, and we had very encouraging data in lung as well. And what we start seeing now is also that some of the patients that are reacting or having effect of the treatment, we can identify certain profiles in those patients and maybe use that to guide and enrich, of course, patients that are being treated when we better understand if this is actually linked to the effect.
So very excited about this data as well. Yeah.
Wonderful. So maybe just to close out this conversation on the Phase II basket study. So we understand that you guys are open to partnering, and you've been discussing opportunities for collaboration. What might this look like going forward, or is the focus largely on melanoma at this point?
I mean, we are focusing on reaching the finishing line in melanoma. We expected it to be relatively soon. That's not maybe the case here in the US, but hopefully, we can get something going in the EU. But I mean, we want to execute on the program with IO102-IO103 in melanoma, and then we'll get back to the other indications when that is back on track.
Great. So why don't we spend the last couple of minutes talking about your earlier pipeline? So you have IO112, which is your second immune modulatory therapeutic cancer vaccine. It's targeting Arginase 1. It's designed to activate and expand Arginase 1-specific T cells. So there's also an earlier pipeline candidate, which is IO170, and that is a targeted TGF-beta peptide vaccine. Have these assets been gaining any traction in the last couple of months, or again, has the focus largely been on IO102-IO103?
Yeah. So I mean, we had two posters, one with each one of those targets at SITC. And there was really a huge interest during those poster presentations for both targets. So IO170 is TGF-beta, and that's really also a target that has been attempted to be drugged for many, many years, but without any luck because there have been safety concerns. And what we are seeing is that we have an ability to really target TGF-beta without any safety concerns. And we are seeing some very exciting data in different models that are really giving us hope for moving forward with this target into the clinic as well. Similar for IO112, which is Arginase 1. And it has a similar story as IDO, where it has been attempted to be developed as a small molecule inhibitor without any luck.
Now we are using our technology to move forward targeting Arginase 1 with T cells. It's really also shown fantastic data. IO 112 is getting IND ready. Hopefully soon we can start moving those into the clinic as well when we are, yeah, as I mentioned before, ready with IO102-IO103 in melanoma.
Excellent. So now I have a question on cash position. So Amy, so can you remind us of your cash position and burn and expectations on cash runway?
Yep. Thank you, Ashleigh. So we ended the third quarter with just over $30 million, almost $31 million in cash. That takes us through the first quarter of 2026. So we will be looking over the next few months to raise capital to support us as we get ready for the Phase III trial next year.
Excellent. And maybe kind of zooming out and thinking more broadly, where is the biggest disconnect between your current valuation and investors? What are people missing or not grasping?
So I think the biggest thing is the opportunity first in melanoma, but also the pan-tumor effect that IO102-IO103 and our other assets could have. So there's a lot of value to be created there, I think, Ashleigh. And I think that's probably what's being missing.
Yeah. I fully agree with Amy on that one.
Is there anything else that we didn't touch on that you guys would like to share?
Just very enthusiastic for 2026.
Excellent.
It's going to be a big year for us.
I think that's all that I had. Yeah, we really appreciate you guys joining us today.
Thank you.
Thank you.