Good afternoon, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Ulz, one of the biotech analysts here. It's my pleasure to introduce Mai-Britt Zocca, CEO from IO Biotech. Just a reminder, the format for today is a fireside chat. Before we get started, I just need to read a quick disclosure. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, Mai, thanks for sharing your time with us today, and I thought we could start by some introductory comments, so I'll turn it over to you.
Thank you. And I'm really excited to be here today, so, thank you, and, yeah, let me just get started on, just being excited about the recent financing we did, $75 million in a pipe that we pulled through together during the summer here. So very excited about having now the ability to execute on our planned program, and getting ready to next level. Today, we had data coming out from our phase II basket trial at the World Lung, so also very excited about that, and I'm looking forward to potentially also discuss that in more detail.
Yeah, we're definitely going to discuss that.
A little bit later today. And really, what is exciting us here at IO Biotech is, as we saw when we came out of ASCO earlier this year, that the chapter two, two of the IO book is already being written. This was very elegantly described by our friends at Merck, and what we see is based on the strong foundation established in the chapter one of the IO book. So what we are here for is really to play a strong role in the chapter two. There is still a clear unmet need in the space, and IO Biotech is here with a vision, not only to play a strong part of the chapter two, but also really to make a change for people with cancer.
So let me just highlight some of the three reasons that, you should have that give you, the belief that we are able to execute on, on that vision. So we are working on the T-win technology platform. This is, called T-win, and you should really think about it as the winning T cell. So what we are generating are really T cells that are able to, come into the tumor microenvironment, and they eradicate not only cancer cells, but also really immune suppressive cells. When we took the concept into clinical testing, and this is really the proof of concept we have established with our lead program, we were able to announce a 100% increase on top of, standard of care.
So that was really remarkable data, and we got the breakthrough designation granted from the FDA based on those data. And third, but not least, we are enrolling quite fast in our global phase III trial. It's going well, and I'm very excited about that enrollment is giving us the opportunity to have a readout, which I'm sure we will also discuss in more details in a little bit, but during mid-2024. So let me just pause here.
Yeah, that's perfect. Thanks for that introduction. And maybe I thought we could start with a little bit of background on the platform, and maybe you can talk about sort of the chapter one of the current immunology treatments and kind of what are the issues there, and how do you sort of, you know, write chapter two with your T-win program-
Yeah
How's that specifically?
Yeah. So let's stay in the add-on logic and really speak to the current standard of care. So what we have seen is, of course, responses in approximately 50%-60% of the patients. There's still a need and some of the drugs that we have in the standard of care as of today give effect, but it really comes with a high cost. That's not good for patients. It's also not good for the payers that needs to bring in additional cost to manage the adverse events that comes with these treatments.
What we are seeing with the emerging standard of care that is coming into the picture right now, and really being a part, maybe, of the chapter two that we are discussing, is drugs that are having effect, but less than the current standard of care, but also with less toxicity. So where we see that we are able to play a strong role and come in and treat across first-line patients, is really to come in with similar or even better clinical benefit for the patients and no added toxicity. So I think this is the important picture that we wanna draw, and where we also have set our goals to succeed with our phase III trial.
And maybe just highlighting a few items, so high effect, then low toxicity. We have a treatment that goes across patients in the first-line settings. So regardless of PD-L1 expression, positive, negative, we see effect, and we also go across BRAF mutant versus wild type. And just the last point maybe I wanna draw here is that if you think about tumor indications, one thing is melanoma, where we have strong data, and we will speak about the basket trial, but our antigens are really expressed in multiple indications, so that also gives a clear link into other indications. So we are really excited.
Yep. Maybe, maybe one more question just on the platform in terms of how it's different from more traditional cancer vaccines?
Yeah. Yeah, that's a really interesting question. So of course, I could speak a lot of details on the biology, you know that. But, let me just try to keep it simple, because it's really very simple, in the sense that, traditional cancer vaccines targets cancer cells. We do as well, but in addition to this, we also target the immune suppressive cells. So what we have really figured out is to identify antigens that are expressed not only on cancer cells, but also on the immune suppressive cells, and that really gives and drives what seems to be a much better effect.
Gotcha. Maybe we just shift to the lead program, so the IO102-IO103, maybe just talk about the targets there.
Mm.
Or the mechanism of action to support tumor killing, but also T-reg killing, I guess.
Yeah. So, yeah, our lead program, IO102, IO103, is targeting cells expressing IDO, IO102, and cells expressing PD-L1, IO103. And what these two proteins, immune suppressive proteins, are really two interlinked, but still separate immune suppressive pathways that are known to be expressed in multiple cancer indications and really drive the tumor escape that we know that tumor cells are so clever to establish. We are also aware that these proteins are expressed by different cell types in the tumor microenvironment. So by actually using both in the same vaccine, we are driving a much better response, and we see synergy when we are using these two together.
In addition to this, we also have seen in our models and also in patients tested, that we also get synergy when we combine it with anti-PD-1.
Mm-hmm. And, maybe we can, we can move to the phase I/II melanoma data. Obviously, that was pretty exciting data. So maybe you can just walk us through that and, and sort of why that data was so powerful.
Yeah. So what was really funny, I saw it in a paper yesterday that just came out here. I think it was this week in Nature or Science, with a quote from our principal investigator that ran that trial, was that she just couldn't keep calm. That she-- This one of the quotes that she gave in this recent paper. And that's really true. We also couldn't keep calm, what we saw with the data coming in. So first of all, we have a response rate of 80%, with a 50% CR, and then a median PFS of 25.5 months. So across those data, it's really a doubling of, compared to standard of care.
No one has been able to really come even close to those data in this indication, so we still have the best data out there. This is also based on these data that we are currently executing on our phase III. So again, I want to highlight and allude to also the safety profile that we saw in that study, which was no added safety event on top of standard of care. So it's really also the study that drove the breakthrough designation. When we brought the data to the FDA, they were very excited to see those data.
Yep.
Yeah.
Maybe you can just talk, maybe remind us the size of that study in terms of the patient numbers, and then just given it's a single-arm study, just-
Mm.
What drives your confidence? I know a doubling, it's-- that's a good reason to be confident, but just-
Yeah. So it is a single center, single-arm study. 30 patients were taking in, in first line metastatic melanoma. What we saw was the response rate that I just mentioned, 80% and 50% CR rate. So what really drives confidence from that study, and also what we have discussed, of course, with the authorities, is really that the responses are deep and durable. This is what you want to see when you treat patients in the IO space, and this is what we are seeing in this study as well.
Yep.
Yeah.
Gotcha. Maybe moving to the ongoing p hase III study, and maybe you could just start telling us about the design of that study, and are there any notable differences-
Yeah
... relative to the phase I/II?
Yeah. So when we set up the study and, and still being very excited about, the data that we saw in, in the phase I/II, trial, was really to completely mirror, the trial that we, that we had just, received these great, data from. So the phase III trial is completely similar to the phase I/II trial, besides the, fact that we are combining with , which, was a strategic decision we made. It really expands our, knowledge about, not only have data based on nivolumab, but also now, getting data, with pembro. In addition to this, we also made a decision to continue treating the patients with, also the vaccine up to two years, which follows the pembro label.
In the phase I/II trial, the vaccine was terminated or stopped after one year, and then, the patients were treated up to the two year with, nivolumab, as per the nivo label. And you can imagine that the investigator at that time really regretted not having a protocol that would allow further treatment and, and really, maybe drive even better responses. So that are the two, main, protocol, changes.... you know, changes that we have made.
What do you think the effect of pembro versus nivo? I know they're fairly similar, but they're not completely similar. Does that have any impact on the outcome of the study?
Yeah.
Or does that add any risk, I guess?
We, we don't see this as adding any risk and, yeah.
No, makes sense. Maybe we can go back to the phase III. You gave some updates earlier this year, decided to sort of upsize the study. Maybe talk about what drove that decision, what impact the timelines it had or didn't have.
Yeah. So earlier this year, we hit a very critical milestone for our phase III study and also for the team, and that was the enrollment of 225 patients coming into the trial. And that was important because that really started the clock for the interim readout that we have coming up here in mid-2024 then. So very excited about that part, and that was a part of the announcement we gave there back in in June. Together with that, we also announced that we are upsizing the trial, going from the originally planned 300 patients to 380 patients. And that was really driven by the enthusiasm that we are seeing from the sites, fast enrollment into the trial, and the momentum that we have.
So with that, we could see that we could recruit additional 80 patients in the same time frame as we had already planned for the 300 patients, so we didn't need to change timelines. Another great benefit was we also didn't need to change the financial guidance, so we stayed on those two factors, which was very important for the team. And the upside of really doing this was came in when we understood that we might have the possibility to pull in the PFS readout by adding those additional 80 patients. And now, maybe the next question would be: So how could you actually calculate that, or how could you see that?
So if we look at patients treated with PD-L1 positive expression versus negative in the RELATIVITY-047 study, we learned that PD-L1 positive patients stay longer on treatment, and therefore it takes longer time before they add to the events. So we wanted to secure that we get the events in as early as possible. And that is really driven by the fact that PFS is the primary readout from the trial. So we will need that for the full approval here in the U.S. And also in Europe, to get approval, we need the PFS endpoint.
Yep.
We are interested in getting it as early as possible.
Yep.
Yeah.
Just the ORR update you're going to provide-
Mm-hmm
- sort of next year, maybe, maybe talk about the bar there or, you know, how to think about that. And is there a particular delta that you need to show to sort of be, I don't know, to think it's a meaningful benefit, I guess?
Yeah. So I think we have discussed before that, for us here at IO Biotech, I mean, for benefit is between 15%-20% as a delta. And what we have in this trial is actually an 80% bar compared to the pembro arm.
Mm.
What we know from the KEYNOTE-006 study is that pembro comes in at 46%. So then you can look at the delta there. But for us, that's really the bar. It's around 18%, yeah.
There's plenty of room there.
Yeah.
I guess in terms of the PFS, what's the reasonable expectation for pembro and PFS? And I guess I'm asking it to get a sense of when we might see the PFS data.
Yeah. So we do anticipate, based on the enrollment we have done here in the trial, that the PFS readout will come in the second half of 2025. And again, based on what we know, the trial is also set so we have a meaningful readout around the PFS as well.
And then just, I know you spoke about this already, but just remind me the regulatory path in the U.S. versus Europe and how it's different or not different?
Yeah. So, we have the breakthrough designation in hand. That really gives us the opportunity to file based on the overall response rate readout that we have mid-2024. That gives us accelerated approval, and in order to get full approval, we need to convert that to full approval based on the PFS readout. So that covers the regulatory strategy that we have here in the U.S. In Europe, as I mentioned earlier, it's different, so we need to go for the full PFS readout and have those data in hand before we can submit the MAA.
Maybe you could just touch a little bit on the competitive landscape and sort of, you know, frontline melanoma.
Yeah. So it is, as you were saying, it's very competitive. There is a lot of activities going on in frontline melanoma. It's still an indication where there is a huge unmet need, but it's also an indication where there is really a huge market. So without discussing the anticipated label that we expect to get, I can share that the market is huge.
Yeah.
That's what we are going after. If you look here in 2023, there is an expectation of $5 billion, and that is growing into 2028 all the way up to $8 billion. Of course, the growth is driven both by incidence and also newer drugs coming in.
And maybe just for melanoma again, just going forward, the next sort of catalyst would be ORR mid-next year? Okay.
Yeah.
And maybe we can shift to just the basket study. You shared some data at World Lung earlier today, for obviously your lung cohort. So maybe you could-
Yeah
- sort of talk about that.
Yeah. So, the second study we have in our pipeline is the IOB-022 study. It's a phase II basket trial, where we have enrollment into two cohorts. The trial was originally set up with three cohorts, also bladder as an indication, which we have decided to close down earlier this year. Basically, based on changes in the landscape and lack of belief that we were able to recruit patients into this cohort in an interesting time frame. So we are focusing now on lung and head and neck, and I was very excited about the announcement that came this morning by our principal investigator, Jonathan Riess, who did a mini oral presentation in Singapore this morning.
What we have shown is really an effect, encouraging effect that we are seeing in the first 15 evaluable patients. The way that the evaluable patients are defined and included in this data cut is based on at least two treatments with our experimental drug, the combination, and then two scans post treatment or discontinuation. What we had as a readout based on that was eight patients that achieved a partial response out of those 15, and that gives a response rate of 53.3%. Knowing that standard of care, so pembro alone is around the 39%, that we do see that as a very encouraging readout from the trial.
What we also shared this morning with the audience in Singapore was early biomarker data from the trial. We are seeing that we are getting an immune response based on the treatment from the vaccine. And we are also seeing that we have a dramatic drop in ctDNA in the patients that we shared this morning. It was only two patients, but we had a complete clearance in one patient and a dramatic drop in another patient. So that is also indicating that the treatment works in these patients. So I'm very excited about it, and I'm looking forward. We have another presentation that comes up at ESMO, where we will share maybe more biomarker data.
We will see from the lung cohort, but what we will also share at that meeting is data from the head and neck portion of that trial as well. So, hopefully as encouraging as what we have seen with the lung indication.
But maybe for the head and neck update, how many, roughly how many patients do you think you'll have? And then also, what's, what's the bar in that -
Yeah
- group?
So that surely is a different indication with a completely different bar.
Yep.
What we know is, the pembro is only giving 23%. So, yeah, we will see what the readout will be, but nothing is really working well in that indication. There will not be 15 patients in the update. The head and neck cohort started slower, not slower. It started later, after the lung already started enrolling, so it's just having a little bit of a lag time.
Yeah.
Yeah.
Maybe talk a little bit about, maybe next steps for the basket study. Obviously, you'll give us this update, but as we think past that, is it continue to follow patients longer? Could you move into, you know, specific, like, lung study, for example, or what's your thinking there?
Yeah. So, so we continue enrolling patients in both arms, and we will continue until we have hit the patients that are specified by the protocol, which is up to 30 patients in the lung cohort. And we'll give data during 2024 on both the patients we have now, and of course, also the patients that will come into the trial. And post that enrollment of those patients, we will also decide if we go further with a, for example, randomized-
Sure
- phase II trial, which will be the natural-
Yeah
Next step, based on the data that we have.
Okay. I think you also have a neoadjuvant investigator-sponsored study, you know, ongoing in solid tumors. Maybe tell us a little bit about that.
Yeah. So it is set up to start recruiting. It's not recruiting yet, but it will start recruiting this year. We have another study also in neoadjuvant adjuvant. That is an IO Biotech-sponsored trial, the IOB-032 trial, that will start enrolling patients later this year. So this is again focusing on our lead program, IO102-IO103, then looking at both melanoma and head and neck as indications. And we do anticipate having the first patient coming in here at the end of this year.
Okay. Maybe we can just touch on another pipeline program quickly, the 112, I believe it's called. Maybe tell us about that target, you know, where you are in development.
Yeah. We're still early getting ready for IND filing. So, arginase 1 is really interesting because it's linked to a huge presence of myeloid-derived suppressor cells in the tumor microenvironment, and therefore mediating a completely different escape mechanism than what we are seeing with IDO and PD-L1. So it really gives us a different opportunity in different cancer indications than the lead program is giving us. What we have seen so far is that we are able, in preclinical models, to drive both a modulation of the tumor microenvironment as well as an impact on tumor growth as well. So, very excited about this new program. The other program is TGF-beta.
It's still much earlier than arginase 1, and we're excited about what we are seeing, but moving towards maybe a more IND-enabling studies.
Yep.
Yeah.
Gotcha. Maybe we can just. You mentioned earlier, the financing earlier this year, but maybe remind us current cash position, and the run rate there.
Yeah. So right now, we have a cash runway that takes us all the way into the fourth quarter of 2025. And this is really important because that secures the critical milestones that we have in our programs. And here I'm especially focusing on the phase III program, where we will reach the interim readout mid-next year. And then, as I mentioned to you a little bit earlier, we also have the PFS readout in 2025. So we have cash that takes us all the way through to the PFS readout. So I'm very happy about the cash position that we have, and we're able to execute on those milestones.
Yep. Maybe I could ask about your thoughts on partnering. You've got a phase III readout, assuming positive data-
Mm.
Would you consider partnering to commercialize, or just what are your general thoughts there?
Yeah. So, I think, as anyone else in biotech, we are considering all our-
Yep
- options, and that's maybe the standard answer, so.
That's okay.
Yeah.
That works.
So yeah, but this is where we are as well, in that.
Okay.
Yeah.
Sounds good. We're just about out of time, so why don't we wrap it up there, Mai? Thanks for your time, and we're looking forward to the data next year.
Thank you. So are we. Thank you.