Greetings, and welcome to the Immunocore Holdings plc conference call and webcast. At this time, all participants are in a listen-only mode. The question and answer session will follow the formal presentation. If anyone should require operator assistance, please press star zero on your telephone keypad. As a reminder, this conference is being recorded.

It is now my pleasure to introduce Clayton Robertson, Head of Investor Relations. Thank you. You may begin..

Thank you. Good morning and good afternoon. Thank you for joining us on our 4Q and full year 2024 earnings call. During today's call, we will make some forward-looking statements which are qualified by our safe harbor provision under the Private Securities Litigation Reform Act of 1995.

Please note that actual results can vary materially from those indicated by these forward-looking statements, including those discussed in our filings with the SEC. On today's call, I am joined by Bahija Jallal, CEO of Immunocore Holdings plc, who will share a strategy update.

Then Ralph Torbay, Head of Commercial, will review our full year 2024 KymTrak sales and KymTrak's life cycle management plans. David Berman, our Head of R&D, will provide some pipeline updates highlighting near-term readouts in infectious diseases.

Travis Coy, our CFO and Head of Corporate Development, will also provide highlights about our financial results reported this morning..

Thank you, Clayton, and good morning, good afternoon, everyone. Our first order of business today is to welcome Travis Coy, our new CFO. This is Travis' first earnings call for Immunocore Holdings plc, and we are delighted to have him join us. He was on our board previously. Welcome, Travis.

Today, the team will share the details of our fourth quarter and full year 2024 performance, and the progress of our clinical portfolio. As always, we have been laser-focused on advancing our mission of bringing transformative medicine to patients.

I am very proud that 2024 was another year of strong execution, thanks to the fantastic work delivered by our teams. We delivered KymTrak to more patients around the world and achieved 5% growth in Q4 versus Q3, with 30% year-on-year revenue growth culminating in a total of $310 million in revenue for the year.

This continues our great track record of commercial execution. In 2024, we also progressed our deep and diverse clinical pipeline with exciting and promising molecules at all stages of development and across three therapeutic areas, which could bring new treatment options to patients.

We have advanced our three ongoing phase three trials, including the two phase three melanoma trials, TEBIAM and ATOM, as we execute on our contract lifecycle management. We also randomized the first patient in our third phase three trial, Plizumel.

We remain encouraged by the preliminary data in other tumors and will continue to expand to have the data we need to determine next steps. Our portfolio growth is fueled by an R&D engine that delivers a robust early pipeline. In 2024, we initiated two phase one trials with two novel molecules that David will talk to you about in a few minutes.

Expanding beyond oncology, in infectious diseases, we completed the HBV single ascending dose trial, and we will be presenting initial data from the multiple ascending dose portion of our HIV trials later this quarter. Our modular technology allowed us to expand into new therapeutic areas, tackling autoimmune diseases.

We advanced two autoimmune candidates, one targeting type 1 diabetes and the other atopic dermatitis. These efforts have been delivered by all our employees, guided by an excellent leadership team, and supported by a strong balance sheet and disciplined spending. I now ask the team to share additional details.

First, Ralph will discuss KymTrak's commercial performance.

Ralph?.

KymTrak monotherapy, KymTrak in combination with PEMBRO, and a control arm which includes options such as investigator choice of chemotherapy, retreatment with NTPD-1, or BRAF therapy or clinical trials. We have line of sight on data within the next eighteen months.

Enrollment is on track to finish in the first half of 2026, and data in the second half of 2026..

The ATOM trial is the only registrational phase three trial in the new uveal melanoma setting with the potential to prolong time to progression and survival. There remains a huge unmet need for patients at high risk of recurrence after definitive treatment, which is often radiation or removal of the eye.

Patients currently have no other option but to watch and worry. Yet we know for half of these patients, metastases will occur within three years. The ATOM trial, in collaboration with EORTC, aims to treat patients during this period with the goal of delaying or eliminating metastases.

EORTC enrolled the first patient in the fourth quarter of 2024, and the trial is currently recruiting patients globally. As we look to the future for KymTrak, we strongly believe in its potential to help up to six thousand patients with melanoma live longer.

This vision is built upon robust clinical data, groundbreaking phase three trials, and a proven track record in the clinic. We are steadfast in our commitment to transforming patient outcomes, solidifying KymTrak's position as a leading therapy in the melanoma landscape. Now I would like to pass the baton to David to discuss our promising pipeline.

David?.

Thank you, Ralph. I am pleased to share an update on our clinical portfolio. 2024 was an execution-rich year for our R&D team. We started two phase three trials, Plizumel and ATOM, two phase one trials, Plizumel, the Prain HLA, the MAD phase of HIV, and we completed the SAD of our HPV trial.

Over the next twelve to eighteen months, we hope to have data readouts, including potentially for TEBIAM, that will guide next steps for these programs. Ralph has just presented the KymTrak clinical trial updates, and so I will provide brief updates on Frame, HIV, and our autoimmune programs. Let's talk about Frame.

We are actively randomizing patients into the phase three study in newly diagnosed metastatic cutaneous melanoma, studying branetafus plasma volume app versus a nivolumab regimen.

The goal for this year is for the independent data monitoring committee to review data on the first ninety randomized patients in order to select between the forty microgram and the hundred and sixty microgram as the go-forward dose. Beyond cutaneous melanoma, we are focused on three goals this year.

First, building on the initial signals of activity in ovarian carcinoma, we will study brinetefest in chemo combinations in platinum-resistant ovarian, and in early alliance in combinations in platinum-sensitive ovarian carcinoma. Second, we will continue signal detection in lung cancer with oxymertonib and docetaxel.

And third, we will continue dose escalation of our preem Pathlight extended impact. All three will be reviewed together over the next twelve to eighteen months to determine next steps. Frame and GP100 are both well-known targets for TCR therapies.

In contrast, People is a novel first-in-class target, and our ongoing phase one program here demonstrates the power of our discovery engine. Colorectal carcinoma has an increasing incidence and a high unmet need.

R117 is the first immunotherapy to target T cell a protein expressing colorectal carcinoma, which we know has historically been insensitive to checkpoints. KeyWell is an attractive target since it's not expressed in normal vital a negative prognostic marker and has broad expression in about a quarter of colorectal cancer patients.

We designed the phase one dose escalation started last year, based on all the insights from our earlier intact programs. We have learned which signals are markers of activity for our platform, and we hope to see these mature over the next twelve to eighteen months.

We know that our Impex platform is validated in cancer, and, therefore, we have been excited to test whether the same approach of redirecting T cells can be used for chronic viral diseases, such as HIV and HPV. While antiretroviral therapy for ART has turned HIV into a chronic disease, there remains a large unmet need for functional care.

We estimate over half a million people living with HIV across G7 could be eligible for an MTAB that could deliver a functional cure for HIV.

The challenge for people living with HIV is that while ART does control the virus, when ART is stopped or interrupted, the virus rapidly rebounds and is detectable in the blood at fifty copies per ml, the threshold for detection, on average within two weeks.

Furthermore, eight weeks after interruption, the vast majority of people will have over two hundred copies per ml. This is the level of virus associated with risk of transmission or infection.

However, the fact that some people can control the virus is reason to believe that the immune system may be able to recognize and target HIV-infected cells and supports the hypothesis of our intact immune therapy approach.

In the most recent meta-analysis, which was just published last month, one of the best predictors of HIV control was whether the person started ART early versus late in their infection. The population in our phase one trial generally started ART later after initial HIV infection.

And here, the historical rate of HIV control at week twelve is very rare. Our phase one trial is called STRIDE, and we are treating people living with HIV with M113 on the background of ART for twelve weeks, and then stopping both therapies.

The objectives are to determine whether we can reduce viral RNA reservoir during the treatment phase, and then whether we can alter the kinetics or delay viral rebound after treatment interruption. We will present the initial MAD data from sixteen people living with HIV at a conference next month.

Over the next twelve months, we will continue to assess escalation to be followed by expansion. We know that our tissue targeting platform works based on the KymTrak survival benefit. We came up with the idea of using our tissue targeting platform to turn down the immune system for the treatment of autoimmune disease.

Over the next twelve to eighteen months, we will bring our two lead autoimmune candidates, one for type 1 diabetes, the second for atopic dermatitis, into the clinic. Our vision for treating autoimmunity is unique in that it is tissue-specific down modulation of the immune system, which would avoid systemic immune suppression.

We accomplished this with our MTai molecule, which has three features. First, the targeting arm, which binds strongly or tethers being tied to the target tissue. This provides tissue specificity. Second, is a PD-1 agonist that turns off T cells by checkpoint agonism, which is the opposite of checkpoint blockade.

And third is an FC fusion to enable longer half-life for infrequent dosing. These three features are designed to realize our vision of tissue-specific immune suppression. The whole of our approach is that the MTai will only inhibit T cell activity when tethered, or bound to the target cell or target tissue.

For example, when the implant is not tethered, that is free floating in blood or other tissues, it is not brought into the T cell synapse and so does not inhibit T cell activation. This avoids systemic immune suppression.

However, when the MTai binds to the target cell, it is brought into the T cell synapse where the PD-1 agonist effector potently inhibits T cell activity. This will result in tissue-specific immune suppression. Pipeline diabetes is a terrible autoimmune disease that requires lifelong insulin replacement and carries risks and morbidities.

There remains a high unmet need for well-tolerated medicines to delay or prevent progression of T1D. This is the goal of our first program, S118. T1D is caused when autoreactive T cells kill the beta cell in the pancreas. These are the cells that normally secrete insulin.

S118 protects against autoreactive T cell killing, only when tethered to the beta cell. When not tethered, the MTai is unable to prevent the killing of the beta cell. We have recently generated exciting in vivo proof of confidence for S118 in pancreatic slices from a deceased donor who had recent onset of T1D prior to their death.

We demonstrated that S118 binds specifically to beta cells, and that it can have an inhibitory effect on the T cells within the pancreatic slice. S118 is on track for CPA later this year. I will now turn to our second autoimmune program, that uses the same PD-1 agonist but employs a different targeting domain and is intended for atopic dermatitis.

Langerhans cells and an HLA-like molecule called CD1A that is expressed on Langerhans cells both play key roles in triggering allergic inflammation in the skin. Langerhans cells are sentinels in the skin. They monitor and are the initial triggers to alert the immune system.

Two important ways they alert the immune system are by presenting lipids via CD1A and by presenting peptides via class one and class two.

Preventing Langerhans cells from initiating pathogenic inflammation by blocking both lipid and peptide presentation may have therapeutic benefit in several important inflammatory diseases, including atopic dermatitis. Our candidate, U120, is designed to achieve this goal of dual blockade.

The targeting domain recognizes and binds CD1A and thus tethers the MTai to Langerhans cells. When it does bind CD1A, it sterically blocks lipid presentation. And this prevents lipid-sensing T cells from being activated.

By now coating the Langerhans cell in thousands of PD-1 agonist spikes, which is the effector arm, U120 will turn off any T cell that approaches the Langerhans cells to be activated by peptides. In fact, in vitro, U120 is more efficacious than terasolumab, a PD-1 agonist that is not tethered and has lower potency for PD-1 agonism.

The next twelve to eighteen months is an exciting time for our R&D teams. As we look forward to the conclusion of the phase three TEBIAM trial, decisions on the next steps for Frame, HIV, and HPV, and beginning our journey into developing our platform for autoimmune disease. I would like to welcome and now hand over to Travis..

Thank you, David. Good morning, good afternoon, everyone. Earlier today, we released our financial results for the fourth quarter and year ended 2024. Please refer to the press release and our latest SEC filing on Form 10-K for our full financial results.

Let me share some of our key financial highlights for 2024, and then touch upon our expectations for 2025. As Ralph mentioned, 2024 was a strong year for KymTrak sales, with net sales growing to $84 million in Q4, a 5% increase versus Q3, primarily driven by volume growth in the US, and continued launches outside of the US.

For the first time, we exceeded full year sales of $300 million with total sales for the year of $310 million. This represents growth of 30% over 2023. It is worth noting that the reimbursement environment in Europe remains challenged, and we continue to make our best estimates for revenue recognition as we finalize price negotiations.

As we continue to invest in our portfolio, SG&A and R&D expenses have increased versus 2023. R&D expenses increased primarily due to investments in our three phase three trials. The phase one/two cohort expansions in ovarian and lung per vermetabas also contributed to the increase.

Our SG&A expenses increased slightly, primarily due to an increase in general business functions needed to support our operations. Moving to 2025, let me provide some comments on how to think about KymTrak sales growth expectations and our SG&A and R&D expenses for this year.

For KymTrak, expect revenue to grow incrementally in 2025, led primarily by growth in the US by further penetration into the community setting, and by growth, to a lesser extent, from launches in the EU and international markets.

We anticipate that R&D expenses will increase relative to 2024 as we further advance our clinical and preclinical pipeline candidates. And shifting to SG&A expenses, expect those investments to be mostly consistent with Q4 2024 levels over the course of 2025, while anticipating typical quarterly variability.

Turning briefly to our cash position, I am pleased to report that we had $820 million in cash and marketable securities at the end of the year. As a reminder, we repaid our $50 million loan with PharmaCon in November.

We believe our robust financial position, coupled with prudent expense discipline and data-driven investments, enables us to advance our portfolio to deliver transformative medicines to patients across all three of our therapeutic areas. And I'll pass the call back to Bahija..

Thank you, Travis. Thank you, David and Ralph. We entered 2025 with an eye towards delivering significant results in the next twelve to eighteen months, starting with the HIV MAD data this quarter.

This year, we expect incremental growth of KymTrak, will continue enrolling patients in our three phase three melanoma trials, pursue additional opportunities in our Frame franchise, and continue to develop the next generation of transformative immunomodulating therapies.

With our strong financial position, a deep differentiated portfolio, our dedicated teams, and a clear line of sight for the future, we are confident in our ability to continue delivering significant value to both patients and shareholders. Thank you, and we'll now open the floor for questions..

Thank you. We will now be conducting a question and answer session. You may press star two to remove yourself from the queue. As a reminder, we ask that you please limit yourself to one question. One moment please while we poll for your questions. Our first question comes from the line of Michael Yee with Jefferies. Please proceed with your question..

Hey. Good morning. We had a question on the upcoming HIV results, which David made a bunch of comments on coming up.

And we wanted to understand in the sixteen patients, would they all have twelve weeks or so off therapy, off all the therapy, and show you would have a clear picture of whether there would be viral rebound over an extended period of time. And what you would deem to be a good rate of patients not rebounding.

And then a follow-up question is a quick housekeeping question. Maybe, the company could comment on the European sales, which appeared to be down sequentially Q4 to Q1.

Was there some one-time adjustment on price or lumpy ordering patterns? What was going on there?.

Great. Thank you.

David, you wanna take the first one?.

Michael, thank you very much. Yes. All patients will have been off of therapy and entered the ATI, and all will have been available to see whether there is antiviral activity and, of course, whether there is a viral reservoir reduction during the treatment phase.

In terms of your question of what rate is good, I would just remind you that this is a phase one dose escalation with five to six people per cohort. So I wouldn't focus necessarily on rates at this point. I think they need to get to a top dose and then expand.

But in terms of a TPP, Michael, I would point you to a recent publication a few years ago in terms of what they would like to see in terms of rates and in terms of what good looks like.

And essentially, it is copies they would like to see suppression of viral copies to less than two hundred copies per ml for two years in about the twenty to thirty percent of people. That's the minimum commercially successful TPP..

Ralph, you wanna address the Europe?.

Happy to. So as Travis mentioned, Michael, this Europe has is having a challenging reimbursement environment. And as you know, we are negotiating prices with Germany and France. We have line of sight on those negotiations. You know, we had fourteen successes worldwide, which speaks to sort of how well we're doing.

And, you know, we have some incremental growth as we've been guiding basically in Europe, which is what is reflected in our numbers..

Thank you. Our next question comes from the line of Jessica Fye with JPMorgan. Please proceed with your question..

Hey, guys. Good morning. Thanks for taking my question.

So maybe following up on Mike's question, for HIV, can you elaborate on what factors are gonna help you to determine a go-forward dose and how you would think about next steps once dose escalation is complete? Would you move directly to a registrational trial? What could something like that look like? Thank you..

Yeah. Just.

thank you for the question. So in terms of the factors we would use to select the go-forward dose, we need to see that the dose is well tolerated in a relatively healthy population, so it needs to be a well-tolerated regimen.

And then we need to see that we have evidence of antiviral activity that gives us reason to believe that we can achieve a functional cure. Right now, we selected twelve weeks of dosing. We're focused on the dose. They might need to be to optimize frequency, there might need to be duration. I will also look, of course, at biological activity.

So we'll use all of those, and there might, by the way, be two doses that we take forward into an expansion. In terms of the next steps after an expansion, once we've confirmed a signal, typically, there's a randomized phase two with the placebo. And that would then lead to a phase three trial.

Now interestingly, the meta-analysis that was just published, and I refer everyone to that last month, they're trying to argue that you don't need to do a placebo-controlled randomized phase two anymore because the historical rate of control is actually quite low.

So that meta-analysis argued for doing single-arm trials, but that's something we'll consider as we approach them..

Yeah. And we definitely will talk to the regulatory authorities before we do anything..

Thank you. Our next question comes from the line of Tyler Van Buren with TD. Please proceed with your question..

Hey, guys. Good morning. Thanks very much. I'll ask another one on HIV just for additional clarity. It's been very helpful what you've said already.

But just the twelve-week time point of patients being controlled following ART interruption, is that enough to have confidence that they would maintain control over the longer term, or do you need to follow them longer? And at which point would you have confidence based upon KOL feedback? And I guess related to that, have strategics told you what profile they would like to see demonstrated in the clinic or what level of follow-up is required as well?.

Tyler, so the twelve weeks of interruption is historically being used in these initial phase one trials to get a sense of whether you have any activity because based on the meta-analysis that I mentioned, the percentage of people who will have viral control at twelve weeks is about one percent.

So when you're conducting these trials, you don't want to keep the people off of therapy for too long, especially in the initial phases. So you first want to look for twelve weeks to see if you have evidence of antiviral control. You then move to expand those twelve weeks.

In terms of what is commercially acceptable, our target product profile, and I would add that no one, no therapy or company or anyone has been able to demonstrate viral control reliably. This is a new area that, you know, there is no precedence to bake it out.

I would really refer you to that white paper that published what a commercially successful TPP, what the minimum case is, what the base case is..

Thank you. Our next question comes from the line of Eric Schmidt with Cantor Fitzgerald. Please proceed with your question..

Thanks for taking my question. Maybe I'll mix it up a little bit and ask a question on branetafus and the PRISM BLA study, the dose selection that's gonna happen, I guess, later this year. On those first ninety patients, what kind of follow-up will you have in terms of duration, and I assume you're gonna make a decision on early disease control.

Is that feasible given the follow-up? I'm also kinda curious as whether we'll see updated phase one data on branetafus in second-line melanoma this year. Thank you..

Yeah. I'm happy to take that. So the way the ninety patient dose selection analysis is set up, it's said those patients will be followed up for between eight and twelve weeks. So, really, it's looking at a high level for both safety as well as initial response rate.

And it's really set up to look for big differences because we know that both doses are active and well tolerated..

Thank you. Our next question comes from the line of Justin Zelin with BTIG. Please proceed with your question..

Good morning, and thanks for taking our question, and congrats on all the progress. So it's great to see the progress in the pipeline outside of oncology. I want to ask, how you expect the safety and tolerability profile of mTACTS outside of the oncology setting, such as in the infectious disease or autoimmune disease settings, to shake out.

And what would be the minimum commercially successful TPP that would be in these settings in regards to adverse events such as CRS? Thank you..

Justin, happy to take that. Very good question. In terms of infectious disease, what we would expect to see, of course, is cytokine release syndrome because that's the mechanism, T cell activation leads to cytokine. But in contrast to oncology, we can't really have moderate or severe CRS. So we really need to only have mild CRS.

And we think that's really achievable. Don't expect to have any on-target off-viral activity because these are viral peptides that aren't in the body. So, you know, in contrast to GP100, we see rash. We don't expect to see any other toxicity aside from mild cytokine release syndrome.

And I think that's what would be needed in HIV and HPV where the people are generally healthy. In terms of autoimmune, actually, we don't expect to have any cytokine release syndrome because we're turning off the immune system. We're not turning it on. And the other nice feature of our platform is it's intended to be tissue-specific.

So any immune suppression we see will be localized in the target tissue. We shouldn't expect to see broad systemic immune suppression. In fact, that's one of the differentiating features. So we're looking in autoimmune and in HIV, we're looking for very infrequent dosing that is very well tolerated..

Yeah. I just want to add to this. I think you see in HIV, we did actually share that we are escalating beyond three hundred micrograms just to give you an idea. So I think the safety profile is very good..

Thank you. Our next question comes from the line of Graig Suvannavejh with Mizuho Securities. Please proceed with your question..

This is Sam on for Graig. Thank you for taking our questions. Maybe going back to branetafus, can you provide an update on the current efforts to generate data in ovarian and lung cancers? What were the changes that have been made in patient in those indications? And when might you be able to share the next data? Thank you..

I'm happy to take that, Sam. So with ovarian, we're building up the initial signals. You know, it was clear that branetafus had monotherapy activity in late-line platinum resistance, but we needed to see a path forward, and that path forward is in earlier lines and in combinations.

We saw an interesting signal for chemo combinations in the platinum resistance. So we need to expand platinum resistance chemo combo. Then we need to study platinum-sensitive capatasumab. Those are ongoing now. In the lung setting, we're more in the signal detection phase here.

And so here, we're looking at combinations with oxymartinib and docetaxel, which are generally early aligned than the late-line PRAC. And so we hope to see signals there. In terms of when we're going to share the data, we're going to share the data when there's a complete understanding of what's going on and we have a story that we can put together.

So I don't want to nail it down. Presumably, in the next twelve to eighteen months..

Thank you. Our next question comes from the line of Jonathan Chang with Leerink Partners. Please proceed with your question..

Hi, guys. Thanks for taking the question. How are you guys thinking about business development opportunities for 2025? Thank you..

Thank you. And thanks for the question. So first of all, we're obviously very excited about the opportunities we have in the pipeline currently. At the same time, we do continuously look for opportunities to enhance the value of the portfolio.

Those opportunities need to be, you know, need to be a good strategic fit that leverage our expertise and our capabilities. But we're in a strong position with what we have today, and having that optionality to pursue partnerships at the same time is a great benefit..

Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim Partners. Please proceed with your question..

Hi. Thanks for taking my question. This is Paul on for Michael. For KymTrak, just on the commercial performance, I believe you've been at or around 55% US penetration for the past couple of quarters.

How much additional headroom do you see there in terms of share of that market with your push into the community setting? Where do you see that share in the US market plateauing? And then on treatment duration, you mentioned trending over twelve months.

What's your best estimate of where that could land long term?.

Thank you for the question. And, you know, as you said, we are at 65% penetrated, which is, you know, good news because we've been growing significantly, 34% growth last year in the US. And look, we're continuing our work into the community where the good news is that, you know, half of our prescriptions are coming from the community.

In fact, two-thirds of our prescriptions are coming from the community. So we just have to continue that work. There are still a lot of patients out there and, you know, a lot of unmet need, so we're going to continue that work.

In terms of the duration of therapy, you know, the duration of therapy is performing better than we've seen in clinical trials. So it's difficult for me to predict where this is going to land, and, you know, we'll see it hopefully grow together..

Yeah. Which is really unusual, actually. It speaks highly of the treatment and the impacts of KymTrak..

Thank you. Our next question comes from the line of Jack Allen with Baird. Proceed with your question..

Hey. This is Nick on for Jack. Thanks for taking my question. Surrounding the pivotal first-line PRISMMEL study, abbreviated in melanoma, it appears you're now specifying a timeline for the selection decision that can happen in 2025. It seems like ten weeks minimum follow-up is expected to be reviewed by the IDMC.

What metrics do you expect the IDMC will use to make a dose selection decision, whether that's OR, c c DNA, or PFS? And to what extent will the interim data be communicated to the company? And finally, can you comment as to whether there is a futility analysis included as part of the dose selection decision? Thanks..

So I can start. You know? So we are not intending to release the data just for the integrity of the trial. That's gonna be the IDMC looking at the they're the only ones looking at the trial.

But, David, do you wanna comment?.

Thank you, Nick. There will not be a futility analysis. The analysis is strictly to choose a dose, and that will be done by the IDMC. In terms of what will be used, the IDMC will use both efficacy and safety.

I would just remind you that in the phase one trial, both doses were active and well tolerated, forty and one hundred and sixty, and we didn't really see a dose response. So they're going to be looking for large differences. And if they don't see large differences, then we're going to be using modeling.

We'll be providing support by modeling to help select the dose..

Thank you. Our next question comes from the line of Gil Blum with Needham and Company. Please proceed with your question..

Yeah. Hi. Thanks for taking my question. This is Ethan on for Gil. So you mentioned some reimbursement challenges in Europe for KymTrak, which isn't very surprising, but I know it's early on, but do you anticipate similar challenges for branetafus in Europe? Or are these challenges more product indication specific to KymTrak? Thank you..

Yeah. I think I'll start, and then Ralph, please comment. You know, I think we are actually I'll look at the cup half full. You know, we had so far, you know, good negotiations and fourteen approvals for the drug. But as you know, Europe in general is country by country, and that's what you have to do, and it's more challenging right now.

But I want to point out to the fact that we actually overturned the NICE decision and we are now launching in the UK. That's one of the toughest markets.

But, Ralph, you wanna comment?.

So as Bahija said, yes. We've had a lot of successes with KymTrak, and that speaks to the value proposition of KymTrak. Look, I think the market is challenging or the reimbursement landscape is challenging for all companies, and you've seen this communicated by everybody.

So, you know, all we can do is expect good data and keep working to create access for patients across Europe, and, you know, hopefully, we'll have the same successes with branetafus like with KymTrak..

And for branetafus, we expect the same thing. You know, I think if we are lucky and have an OS endpoint, that facilitates things in Europe. That's exactly what happened with KymTrak..

Thank you. Our next question comes from the line of Peter Lawson with Barclays. Please proceed with your question..

Great. Thank you so much. I apologize. I joined the call late, but I'd just love to know around that HIV data that's coming up.

How should we be thinking about the bar for success, whether it's around spark or reservoir reduction, or the delay in viral rebound? And if you can see around that, and the doses we should expect to see and the number of patients in each dose. Thank you..

Peter, we expect we will show three doses, five to six people per dose. We are, by the way, continuing to dose escalate now that that data is just not ready for the data cut for the presentation.

In terms of what success would look like, you know, this is a setting, both viral reservoir reduction during the treatment phase, and then demonstrating viral control after interruption, it's never been reliably shown for any therapy.

So for us, what we're looking for in a phase one dose escalation is do we have signals of activity? Can we reliably reduce the reservoir, and can we alter the kinetics? To me, that would be a huge success for the field, actually, because no one's been able to show this.

Once we complete dose escalation, we then move to expansion, and there we want to get a better sense on the percentage of patients who would have antiviral control. Is there enough strength to move forward to a randomized phase two trial? So that information will come later this year..

Thank you. Our next question comes from the line of Patrick Trucchio with H.C. Wainwright. Please proceed with your question..

Thanks. Good morning. My question is also on HIV. I was just curious if, you know, based on the data that's generated in this MAD portion of the STRIDE trial, if there might be potential for a combination strategy for M113B, such as pairing it with LRAs.

And separately, just based on the outcome of this MAD portion, is there a possibility that M113B could qualify for a priority review or other regulatory incentives for potential accelerated development?.

Patrick, thank you for that question. And it's a good one because it reminds me to say that pretty much our entire platform, oncology, ID, and potentially autoimmune, is combinable. In fact, the phase one trial that we'll share data in the next few weeks is on the background of ART. And certainly, this could be combined with LRAs.

It could be combined with anything, essentially. But the goal here is not to have chronic long-term treatment. It's to have a finite dosing regimen so that we can stop treatment and the patients can be off all therapies for two to three years. I think that would be kind of our eventual goal.

In terms of health authority interactions and priority reviews, I think that is certainly something we would consider once we need to, but we need to generate the data. And so that would come with, you know, it's still too early, I think, to comment on that..

Thank you. Our next question comes from the line of Rajan Sharma with Goldman Sachs. Please proceed with your question..

Hi. Thanks for taking the question. Just a couple left from my side. Atopic dermatitis, I know that it's a way out until we see the initial data.

But just at this point in kind of thinking about your planning for the asset, how are you thinking about potential benchmarks longer term? And then secondly, just on HBV, conscious that we obviously have the HIV update coming relatively imminently.

Is there anything from the HIV data set that you'd be looking to maybe increase confidence in the platform more broadly and if there's any crossover to HBV there? Thank you..

Yeah. In terms of the atopic dermatitis, I think right now, we have a lot of excitement about the mechanism in atopic dermatitis because of the role that CD1A and Langerhans cells play in skin inflammation. Our initial entry point will be in patients who are refractory to all therapy because we're going to be looking for a signal.

And I think after that, at that point, we'll probably be in a commercially acceptable TPP. In terms of the HIV data, which is next month, and then the HBV, I think, yes, about that. SAD data.

I actually looked at them as a package, and I think they do, they are both important because they are the first time TCR therapy has been used in HIV and the first time an off-the-shelf TCR therapy in HBV.

And so I think although the HBV is SAD data, you know, the question there is we're gonna be asking, can we see anything? Right? After a single dose, I think it's a hard hurdle, but can we see anything? So I think those two data pieces this year will be important to understand whether our Impex can work in chronic viral diseases..

Yeah. Just to add, I think on CD1, there are multiple indications, and I think that's the attractiveness about the mechanism. And both HIV and HBV give us higher confidence for the platform to work in infectious disease and a lot of learning there..

Thank you. Our next question comes from the line of David Dye with UBS. Please proceed with your question..

Great. Hey, thanks for taking my questions. Just one from me. So regarding the HIV program, just one digging into the mechanism of action. Could you just highlight some of the preclinical data that gives you confidence of potential viral control for the phase one trial? Thanks..

David, sure. So we've actually published several papers on the preclinical data. It's actually quite fascinating. So we've shown that this molecule can redirect T cells to kill HIV-infected CD4 T cells. So we've shown that in vitro. We've actually shown imaging microscopy showing that the Impex can bridge a T cell to an infected CD4 cell.

So a CD8 killer cell to an infected CD4 T cell. And we've shown that this can work even when you don't stimulate the, when you don't kick, and when you don't kick with the HSTACK inhibitor, you don't have to activate the T cell to induce transcription of the HIV expression. So we do have some interesting preclinical data.

We're happy to share those publications, but there is a body of evidence we've already published..

Yeah. And I think one reason, you know, for this platform and for the HIV, we know that the reservoir has a very low expression, if you will, of the target, and we know that our technology can go, can kill down to five to ten targets or copies per cell. So that's another reason to believe..

Thank you. Our next question comes from the line of Jeff Hung with Oppenheimer. Please proceed with your question..

Hi, guys. And thanks for taking the question. Just one from us. In terms of the autoimmune program and AD being your first universal program, how are you thinking about the applicability of that to the oncology programs? Thanks..

Yeah. I would say that it's, you know, what they have in common is the tissue targeting part, that we can show exquisite tissue targeting with our cancer program. And we believe we'll get exquisite tissue targeting with our autoimmune program. Where they differ, of course, is in the effector side.

In oncology, we are activating T cells, and in autoimmune, we're turning T cells off. And so they differ in that regard, but they both have in common the TCR targeting. And, in fact, our preclinical toxicology derisking program that we're gonna use for autoimmune does incorporate many of the aspects we use for oncology..

Yeah. The way I think about it is the yin and yang, if you will, of the oncology and autoimmune, and that's another reason why we are in both areas, therapeutic areas..

Thank you. There are no further questions at this time. I would now like to turn the floor back over to Bahija Jallal for any closing remarks..

Yes. Thank you, operator. I just wanted to thank you again for dialing in, for excellent questions, and for your support. And have a great day..

Thank you. This does conclude today's teleconference. We appreciate your participation..