All right, good afternoon, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Goltz, one of the biotech analysts here, and it's my pleasure to introduce Mai-Britt Zocca, CEO, and Amy Sullivan, CFO, from IO Biotech. Just a reminder, the format for today is a fireside chat. So if anyone has any questions, please feel free to raise your hand and we'll address your question. And thanks to those who are sticking with us so late in the day. We really appreciate it. And I guess before we get started, I just need to read a quick disclaimer, "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, maybe I can turn it over to Mai-Britt, say, you know, appreciate your time today, and maybe we just dive right into the Q&A. Maybe just discuss, you know, high level, your approach with the cancer vaccine, and maybe historically, why that approach has been so challenging.
Yeah, so thank you. It's always good to be here at the conference here in New York, and we appreciate the time today as well for the fireside chat, so our approach is quite differentiated, so the science might be very complicated, but let me just make it simple because we also view it as such. We are targeting the cancer cell, as has been the normal route for the cancer vaccines during the last many years as a way to have an impact on the outcome for the patients. Beyond that, we are also targeting the immunosuppressive compartment. We know that that is a big player in why many drugs are not working as efficacious as they could do.
Because we are doing both, we are seeing a much better outcome with our way of developing cancer vaccines. What we have seen so far, what we published in the past from our pivotal and from our proof of concept trial, the phase I/II trial in first line metastatic melanoma, is still data that hasn't been surpassed as of today. We had great response rate. We also had a great PFS readout in that patient cohort, and that led us to the clinical programs that we have as of today.
Maybe you can just expand a little bit about the dual activity in terms of the targets, you know, and how you sort of promote that.
Yeah. So what we're using is really key immunosuppressive proteins that are expressed in multiple different cancer indications. And the first targets that we are working on are IDO, which is overexpressed in multiple different cancer indications, and as well as PD-L1. And what we have seen, not only in the clinical testing, but also in preclinical models, animal models, is that when you combine those two, you really get a much better response by having both of them in the vaccine. And when we then add it on top of anti-PD-1, then we are really seeing a great response and effect.
Maybe you can just touch on IDO and just, you know, there's been some history there, and obviously, you're seeing different results than in the past, but just maybe walk us through that a little bit.
Yeah. So of course, we have followed closely, as well, what has been going on with the IDO small molecule inhibitors. The epacadostat trial that failed in phase III was a big disappointment for the field, not only for the ones conducting the trial, but also for the rest of us. So the mechanism of action from IDO small molecule inhibitors is really to block the enzymatic pathway. We're not using that mechanism for our way of targeting IDO. We are really looking at the cells that are overexpressing IDO, which will lead to flags on the surface of the cells, that the T cells can then identify and thereby become a target for the T cells. So that's our different way of using-
Yeah
... IDO as a target.
Yeah. So basically, a targeting mechanism.
Yeah.
Makes sense.
Yeah.
You touched on this already, but just the very promising results you saw in the phase I, II melanoma study, and maybe just walk us through that in a little bit more detail, and why those results were so promising.
Yeah. So what we saw, we took IDO and PD-L1, as we have just talked about, and tested that in first line metastatic melanoma patient. It was a single center, single-arm trial, 30 patients enrolled, and we combined with anti-PD-1 inhibitor. The readout was really quite encouraging. We saw a response rate of 80%. We saw a median PFS readout of 25.5 months. So that taken together was really a doubling compared to standard of care, if we look at anti-PD-1 monotherapy. So together with the safety profile, that was really very favorable. We didn't see any tolerability issues on top of monotherapy. And based on those data, we got a breakthrough therapy designation granted from the FDA.
Long story short, now we have fully enrolled our phase III trial based on that work we did.
Yeah.
Yeah.
Yeah, so basically doubling of activity over what you'd expect for the standard of care, pretty promising there. I guess you also mentioned sort of a single-arm study and single-site study, just, you know, any risk there, or how do you think about that?
... So what we saw is, I mean, there is, of course, always a risk to move from a single center, single arm study, and then into a multi-country, multi-center phase III trial. But given the confidence we had and have in the data, is that the effect was really dramatic. And of course, fingers crossed, we are expecting to see that when we have a readout of the primary endpoint from our phase III trial.
Yep.
Yeah.
Makes sense. Maybe in terms of the phase III trial, if you can just, you know, remind us of the design there, and any notable differences, you know, from the phase I?
Yeah. So, based on the data that we had in the phase I, II trial, we set up the phase III trial to really actually mirror what we had done in the phase I, II trial. We did some few adjustments. One was that we went from nivolumab to combine our IDO and PD-L1 with pembrolizumab. And then also we are treating the patients all the way up to two years. So in the first trial we did, we treated the patients with the vaccine up to one year, and then with anti-PD-1 alone for the following year. Now we are taking the patients all the way up to two years, both with vaccine and anti -PD-1. So that are the two biggest changes compared-
Mm
... to the phase I, II study.
Yeah. So with the longer treatment, is the view there that results could improve with longer treatment? Is that how to think about it?
That's how we should think about it. Our investigator that ran the first phase I-II trial was kind of, you know, like, feeling, "Oh, I wish I could have kept some of the patients on the vaccine treatment," given the great responses that they were getting. We took that learning into the phase III-
Yep
... trial.
Yep.
Yeah.
And then the other change that you pointed out is just the difference in the PD-1. Does that make any difference or, or not?
We don't anticipate that-
Yep
... to be any difference, yeah.
Yep. Okay. And then, I guess, recently, you had an interim analysis that you shared, or the top line view from maybe just walk us through that in terms of, you know, the bar-
Yeah
... the bar there and how high it was.
Yeah, so we shared a press release Friday last week on the interim data readout that we had, so it all started when we had 225 patients enrolled in our phase III trial. That really started the clock for the interim analysis. Those 225 patients were the patients that we needed to have 12 months on the treatment, before we could then do all the work that it took to hand in the data to the IDMC. As we know, and as we have shared with you all in the press release, is that there was a high bar to reach in this interim analysis, and we did that for two reasons.
First of all, to preserve as much alpha as we could, for the primary endpoint, so the trial is fully powered and set up for PFS, which we anticipate coming out in H1 of next year, and of course, to file for accelerated approval, you need to also show a high statistical significance, on the response rate to get approved, here in the U.S., so those were the two points that we navigated, and then the P value, we have shared that many times.
Yeah.
We have discussed it many times.
Sure.
It was 0.005 , so it was indeed a high bar. And we announced that the IDMC shared with us that the trial continues until PFS, and we did not reach the bar for the interim-
Yep
... data point.
Got it. And maybe just following up there, in terms of any read-through from the interim to the final, sounds like no, just given the super high bar there?
Yeah, so to me, it's just game on, right? It's where we are. It's still very exciting. We are very enthusiastic, and no one has blinked with an eye when the data came out, because of the expectations we had set already for the high bar and given that, so for us, there is no read-through, and what we have seen for other drugs in the past, we can take Opdualag as an example. They would not have hit on the ORR, but they have hit on the PFS. They are a fantastic drug today. 30% of the first-line patients are getting Opdualag today, so we remain very optimistic and confident.
Yeah, makes sense, and, you know, we're looking forward to that data as well in the first half of next year. Can you maybe talk about the powering of the PFS, to the extent you sort of shared that publicly?
Yeah. So what we have shared, and, the phase III trial is fully powered for the primary endpoint, and it's set at 89% power, with a hazard ratio of 0.65. And we are looking to have 226 events, which will lead us to reach the primary endpoint of the trial.
And just in terms of the event rate, to the extent you can comment there, you know, how confident are you in that sort of timeframe?
Mm-hmm.
I know you, you sort of, you know, increased your confidence and, and sort of pulled it forward, so has anything changed there?
So far nothing has changed, and of course, it's event driven, so we hope our expectations through H1 of 2025 will stay as we have guided to.
Gotcha. And then, you know, assuming, you know, data is positive as expected, you know, maybe just talk about potential next steps, you know, in melanoma.
Yeah. Then we file as fast as we can, both in U.S. and in Europe. So I mean, the good outcome of us continuing just straight to the PFS without a filing first here in the U.S. is that we have the opportunity to file in both Europe and in the U.S. at the same time. So we will be ready to do that when the PFS is read out, and then of course ready to launch the product right away.
Have you been doing any sort of launch prep, or is there anything you can do sort of before the data to sort of accelerate that in any way?
Yeah. So maybe, sure, we will.
So we've been doing a lot already to get ready for the BLA submission. Our CMC teams have been producing with our contract manufacturers, the PPQ batches to put up on validation to ensure that the BLA submission will be ready. So that is all ongoing. From the commercial side, we're also doing some prep work in terms of some initial market research, payer research, making sure we understand the landscape to get a full commercial plan that will be ready to really flip the switch on as soon as we have data.
Yep. Maybe you could just touch on sort of the market opportunity in melanoma in terms of maybe the patient numbers, where the unmet need is, you know, potentially where you could fit in?
Unfortunately, the market is still growing, and growing significantly. The five-year life expectancy is still less than 50%. You have a big need in this marketplace, a big need in patients' lives, to come out with a product and that delivers two benefits. One, efficacy, strong efficacy, but also with a very favorable safety profile. We think that with that profile, that we will be able to create a nice market opportunity for the product.
I guess beyond melanoma, assuming, you know, positive, positive data in melanoma, sort of can it de-risk opportunities in your other tumor types, like head and neck and non-small cell lung?
So I think we have ESMO coming up next week, right?
Yep.
And we have an abstract submitted from the O22 study from the head and neck cohort, and we are very excited to give an update on that cohort during the ESMO meeting next week in Barcelona. What we saw in the first data readout was based on only six patients. We saw a response in three out of those six patients. Now, we have a data update where we have fully enrolled the head and neck cohort in the O22 study. We have 21 patients enrolled. 18 of those patients are evaluable, and we will give an efficacy readout on those 18 patients, and of course, also patient characteristics as well.
We'll both have a swimmer plot and also a waterfall plot, and we will also have some early biomarker data, where we will have, like, the NanoString analysis. We will also have some data from the peripheral blood, where we are looking to see for T-cell responses based on, of course, the induction of T-cell specific both for IDO and PD-L1, so very excited about sharing this broader data package from the head and neck cohort, and of course, what we are looking for is a clinical signal that can validate that our drug is working not only in the melanoma cohort, but also in head and neck.
Yeah.
As we know, nothing has really been working in head and neck for many, many years. There's still only 23% overall response rate based on anti-PD-L1 monotherapy. It's few months in median PFS, so there's really a huge unmet need in that indication as well. Based on the early data we had last year, we are excited to share an update here as well.
Yeah. So based on the early data, looks like you're, you know, twice above the bar here of around 23%. I guess, what... You know, sometimes when you add more patients, you know, the data tightens up a bit, you know, given the bar of 23%, like what level above that would kind of be sort of a meaningful sort of improvement?
Yeah. So I think as you were saying yourself, you know, meaningful for us would be like a 20% on top of the pembro alone, so 23% to around the early 40s%-
Yep
...in response rates. So I think that would validate that we have something that is adding on top of anti-PD-L1 alone. And then, of course, we are always looking for the PFS readout as well, so we will also be happy to share that. Last mention, just, in the last comment, is that it's around the 3.5-month median PFS on pembro alone. So again, here we would be looking for something that is also doubling up on top of that.
You'll have PFS data at ESMO coming up here or-
Yes.
Is that later?
We would have a time point, PFS data as well, yeah.
On the full patient subset?
On those 18 patients that are-
Okay
... evaluable, yeah.
Got it.
Yeah.
I guess assuming you kind of hit the bars you're talking about, what's kind of the next steps there?
Yeah. So, of course, we will look at the totality of the data, to determine next step. It's important for us also to look into the safety profile-
Yep
... which so far has been very favorable. And that whole next step would be then randomized phase II, where we can fully validate the clinical signal in head and neck as well.
... how fast would you be able to move that forward? Or are there other considerations to think about, you know, moving that?
There's always other considerations. So, I mean, if we could do anything we wanted, then we would-
Yeah, right.
be moving fast forward. But we have a cash runway that we are, of course, looking to as well. So, right now, we don't have a phase II randomized study now. Yeah.
So then just maybe thinking that forward a little bit, would it be, you know, maybe you want to wait to see the melanoma data first and kind of determine, you know, how you-
I think we are so close to a data read-out that is coming up in H1 of 2025.
That's the plan.
Yeah.
Yep.
Yeah.
Gotcha. I guess maybe flipping around this question to a prior question I asked, if there's success in melanoma, maybe you get read through to other indications, but what about the reverse here? If you're seeing, like, more success here, like, how does that read through to melanoma? Does that give you more confidence?
I think it should give everyone, beyond me, confidence in the drug, right?
Yep.
I mean, there's only so much luck you can have in clinical development. And if you see a clinical effect beyond your primary indication, then I think we are in a good place with our development. Yeah.
Okay. Maybe just switching to non-small cell lung as well. I think you're planning to have another update sort of later this year. Maybe you can, you know, talk about that.
Yes, we have submitted an abstract, and it's been accepted at a medical meeting this fall. We aren't able yet to disclose which one. But in that cohort, we've enrolled 31 patients, and we'll have 31 patients' worth of data. Last year at ESMO, we presented 18 patients' worth of data, so it's almost a doubling up of the patient numbers. The longer term follow-up, PFS data on that patient cohort and OR.
It's a way to think about it, sort of similar to what we'll get in head and neck, you know.
Very similar.
OR, PFS.
Also some biomarker data.
Okay, and then, can you remind us the last time you presented the lung data and kind of what you were seeing in terms of response?
Yeah, I'll let you do that one.
Yeah. Yeah, so last time we presented, the lung data was at World Lung last year, and the data were very exciting already at that point in time. Of course, it was a smaller patient group. We had only 15 patients-
Mm.
At that point in time. Now, we have 30 patients, so we have longer time now to evaluate the responses that we saw already at that point in time, and then also to, of course, substantiate the data, as Amy just said, also with biomarker data as well. So very excited to share what we have from lung as well later on this year. And I want to say similar to what I said on head and neck, you know, if we see a signal also in lung, I mean, then we will have a totality of a clinical signal and three indications, very different patient populations where yeah, we potentially have a good effect.
Yep. Can you talk about the bar in lung? You know, in head and neck, it seems to be pretty low. What's kind of the equivalent in lung?
Yeah. So in lung, you know, one would be looking at the data that is in the KEYNOTE-024 study, where we are around 39% overall response rate. So-
It's a little bit higher.
Yeah, it's a little bit higher than what we are seeing in head and neck. Of course, we have also other studies coming out with TROP2 and other agents that are newer data that are coming in, but seen from just a benchmark towards pembro alone, this is what we are looking for. And again, clinically meaningful would be similar in the ballpark area that what as we talked about under the head and neck data.
Okay. Maybe just the market opportunities for just head and neck, and lung, and just maybe in the context of what the opportunity in melanoma looks like, roughly?
The market opportunities, unfortunately, for all three indications are quite large.
Yep.
So if you look at head and neck, it's a fast-growing market. Many patients and very few treatment options when you look. So the response rates that we're seeing today with pembro alone, 23%, is just really not hitting it, right?
Yep.
These patients are really in need. So when we can add on and show a clinical benefit, and again, do so with no additional systemic toxicity, makes a big difference in patients' lives. So we're seeing a real big opportunity there. Also, if you look at development costs for a program, that could actually get us to the market, because it's a smaller patient population.
Yeah.
It's not quite as capital intense.
Mm-hmm.
Which is helpful.
Yep. No, that's interesting.
Lung, obviously a huge market, unfortunately. And there are lots of competitions, lots of things moving, but still nothing that's really solving the problem for patients.
Yeah. And, if we just think big picture and, you know, melanoma works out, there's some promise in these other indications, you know, for, when you think about, you know, commercializing, maybe just talk a little bit about that, and is there leverage there, and, and, and how does that sort of look?
There's leverage, but melanoma, the first one, is a very big market.
Yep.
We will be ready, and we will invest, and we'll do everything that we need to do to make sure that we are ready to launch.
Yep.
When we think about going up against a big behemoth like BMS-
Mm-hmm
-it's something that, it might be better if we could do it with a partner.
Yep.
So we'll take all of that into consideration.
... Is the trigger for the sort of partnering discussions, obviously phase III data, is that how to think about it?
We talk to everybody all the time.
Okay, okay.
So we make sure that we kick people along for this journey with us.
Yep. No, maybe.
That obviously would be a big trigger point.
Okay. Gotcha. You know, you also have some, you know, phase, neoadjuvant and adjuvant studies ongoing.
Mm.
Maybe you can, you know, talk about that, you know, and kind of maybe the next data update there.
Yeah. We haven't really guided to a precise update for those data, but we are very excited about the trial and the way that it's being conducted. So we see a lot of excitement from the participating physicians to enroll patients into the trial. It always gives you a confidence where they are interested to put patients on your study. So we went from a small study. We started out with 30-patient study, where we had 15 patients in melanoma and 15 patients in head and neck, where we treat with three cycles prior to surgery, and then 15 cycles after surgery of the combination of pembro and vaccine.
When we saw the interest to join the trial and almost fully recruited a cohort in melanoma, we actually decided to expand the trial already there given the huge interest, and we have now a randomized arm in the trial as well, which is cohort C, where we are having 30 patients being treated with a experimental treatment, pembro plus vaccine versus 30 patients that are being treated with pembro alone, so when we get data read out somewhere in 2025 , we will be able to also give data that is also based on a randomized setting in that trial. I think that is really s-
Mm-hmm
... incredibly strong, already, given the early, you know, stage-
I see
of our development
Yeah
In those clinical settings.
Yeah. Data would be much more meaningful-
Yeah
Randomized, right? Yeah.
Yeah. And as we know, there is a huge interest from the field in these earlier settings. We know the Moderna, Merck study that is being conducted in the adjuvant settings. We see a strong from our opportunity to come in and start the treatment already in the neoadjuvant phase with our opportunity. So that's-
Yep
We are looking very much forward for those data.
Maybe just talk about opportunity to even expand further, assuming you sort of get the positive results.
Yeah
... you know, beyond head and neck, lung, melanoma, like, what, where else could you potentially go?
Yeah. So the opportunities are many, and if we do see a clear signal from those three indications, of course, it's a matter of choosing the next indication carefully and then move forward. But we also have other targets in our pipeline that we are moving forward. So we have Arginase 1, IO112. That is also going to share data from this target later on this year at one of the scientific conferences. What we are very excited about is that we are seeing that this target is being expressed by a different immunosuppressive cell type than the two other targets we are working on, IDO and PD-L1.
Mm.
So it's giving us a great opportunity to move into potential other indications as well. And then, of course, there is the opportunity to combine internally with either IO102 or IO103 or both, of course, as well. So we are seeing great opportunities for future indications, not only from IO102 and IO103, but also from IO112.
Can you maybe just talk about the current status of development there and next steps?
Yeah. So we are pretty far already and getting ready actually for BLA filing, and hopefully that is happening in Q1 of next year.
And I think, you also have another sort of asset, preclinical-
Yeah
-that's in development. I think it's the IO170.
Yeah.
I got that right?
Yeah.
Maybe you can just talk quickly about that.
Yeah. So that's our TGF-beta program. And what we have seen, and again, it's a vaccine where we are developing T-cells that are targeting TGF-beta positive cells. And what we have seen is really a confirmation of that mechanism of action as well. It's very early days, but some of the animal models have read out in a very exciting way.
Okay.
Yeah.
When could that move forward, or when?
I will say that we will need more data before we can give firm date on that.
Yep. Makes sense.
Yeah.
Maybe just talk about current cash runway at the moment.
Yeah.
You know, how you think about that?
So we ended Q2 with just over $100 million, and that takes us well into Q4 of 2025. So through some significant data inflection points.
Gotcha. And maybe in the last, you know, couple minutes here, you know, we've covered a lot. There's lots of opportunity here. Maybe just talk about, you know, what you think is most underappreciated by investors, in your view.
Okay. I think the fact that we have now shown, and will continue to show this fall, clinical efficacy and a signal in now three indications, not just melanoma, but lung and head and neck, these are very difficult-to-treat patient populations. When we look at that, I think it really validates the platform, validates the program, and in our minds, says we very likely have a drug on our hands. So the upside, we think, is really strong.
Yep, makes sense. We're almost out of time, so why don't we end it there? Thanks so much, Mai-Britt and Amy. Appreciate your time today.
Thank you, Mike.
Thank you.
Thank you.