Immunocore Holdings plc Price & Performance (IMCR)

Alicia, Thank you, Clay, and good morning, good afternoon, everyone. Our first order of business today is to welcome Travis Poy, our new CFO. This is Travis' first earnings call for Aynur Immunocore. And we are delighted to have him join us. He was our board previously Welcome, Service Today, the team will share the details of our fourth quarter and full year 2024 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 2024 was another year of strong execution thanks to the fantastic work delivered by our teams. We delivered KIM track to more patients around the world. And achieved 5% growth in Q4 versus Q3 and 30% year on year revenue growth culminating in a total of R310 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 stage of development, and across three therapeutic areas, which could bring new treatment options We have advanced our three ongoing Phase three trials including the two Phase three melanoma trials TAVI AM as we execute on our ChemTrack lifecycle management, We also randomized the first patient in our third Phase three trial, Tizumel, 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 and 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 few minutes. Expanding beyond oncology, in Infectious Diseases, we completed the HBB single ascending dose trial And we will be presenting initial data from the multiple ascending dose [indiscernible] of our HIV trials later this quarter. Our modular technology allowed us to expand into new therapeutic area, tackling autoimmune diseases. We advanced two autoimmune candidates one targeting type one 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 Chemtrax commercial performance. Ralph, Keith, Thank you, Faheesha. And hello, everyone. Himtrak has had another year of exceptional growth. And I continue to be very proud of our team's dedication to reach more patients globally. Chemtra truly embodies our mission of bringing transformative immunotherapies to patients. We have raised the bar for survival in first line HLA-two zero one metastatic hubial melanoma with unprecedented three year overall survival of around twenty seven percent.

Patients who before chemtraq were given twelve months to live are now alive two years, even three years later With three Pre Galia Awards and two New England Journal of Medicine, publications, among other recognitions this is what transformational innovation looks like. We take the responsibility of commercializing this transformational medicine very seriously And last year alone, we launched ChemTrak in 14 countries, for a total of 24 countries launched. We have also established ChemTruc as center of care across most major markets, with over eighty percent share of HLA-two zero one positive patients. We're continuing our global expansion with ChemTrack, which has now been approved in 39 countries, including most recently in Brazil. We have delivered nearly three years of continuous net revenue growth with ChemTrak. For the full year 2024, KimTruck generated $310,000,000 in net revenues, which represents a 30% year on year growth. In the fourth quarter, we've reported $84,100,000 in net revenues representing a 5% increase from the prior quarter. The United States accounted for $2.26 $6,000,000 growing at an impressive 34% year on year.

In 2024, we successfully treated two out of three patients in the community with nearly half of all new chemtrac patients starting there. We estimate a market penetration of around 65% in The U. S. With a duration of therapy of approximately twelve months. These numbers speak to our efforts and as importantly, to KymTruc's safety and exceptional efficacy.

Looking ahead at 2025, we continue to expect KymeTrak incremental growth driven by three main factors. First, U. S. Community expansion, focused on less dense areas, leveraging the AI tools we launched last year. Second, duration of therapy which continues to increase beyond clinical trial experience, highlighting KimTrux benefit beyond typical resist progression. And third, new launches ex U. S. Including the recent launch in UK and Poland. Also excited to potentially expand the benefit of KimTruck to additional indications with our lifecycle management program, which I will take you through in the next Slide Neurotherapy has been proven to extend survival in second line metastatic melanoma post checkpoint inhibitors. Patient survival in the setting is poor and hovers at around fifty five one year. Heavy AM is the first Phase three trial aiming to show improved overall survival in this setting. There are strong reasons to believe in the potential of KymTruck in this patient population. Based on Phase one trial data that showed seventy five percent survival rate at one year as well as an acceptable safety profile. The TEBBIAM trial has three arms, chemtrax monotherapy, KIMTREC in combination with pembro, a control arm, which includes options such as investigator choice of chemotherapy, [indiscernible] 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 first half of twenty twenty six, and data in the second half of twenty twenty six. The ATOM trial is the only registrational Phase III trial in the adjuvant nevio myeloma 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. [indiscernible] Patients currently have no other option but to watch and worry.

Yet we know for half of these patients metastasis will occur within three years. The ATOM trial in collaboration with DRTC aims to treat patients during this period with the goal of delaying or eliminating metastases. ERTC enrolled the first patient the fourth quarter of twenty twenty four and the trial is currently recruiting patients globally. As we look to the future for ChemTrack, 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 improvement track record in the clinic. We're steadfast on our commitment to transforming patient outcomes and solidifying KymTrux position as a leading therapy in the melanoma landscape.

Now I'd like to pass the baton to David to discuss our promising pipeline. [indiscernible] Thank you, Ralph.

I am pleased to share an update on our clinical portfolio. 2024 was an execution rich year for our R and D team. We started two Phase three trials, Prisomell and ADAM, [indiscernible] MAD phase of HIV and we completed the SAD of our HBV trial. Over the next twelve to eighteen months, we hope to have data readouts including potentially for TEVI AM, that will guide next steps for these programs. RELFA has just presented the KEYTRAC clinical trial updates and so I will provide brief updates on PRAME, if you will, 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 branetifast, plus nivolumab versus a nivolumab reg of The goal for this year is for the independent data monitoring committee to review data on the first 90 randomized patients in order to select between the forty microgram and the one 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 we will study brnetifast in chemo combinations in platinum resistant ovarian and in early alliance in combinations and platform sensitive ovarian carcinoma. Second, we will continue signal detection in lung cancer with osimertinib and docetaxel. And third, we will continue dose escalation of our PREM Pathlight extended impact. All three will be reviewed together over the next twelve to eighteen months to determine Raymond GP100 are both well known targets for TCR therapies.

In contrast, SPEAKER one:] In contrast, SPEAKER two:] .is a novel first in class target our ongoing Phase one program here demonstrates the power of our discovery engine. Golorectal carcinoma has an increasing incidence and a high unmet need.

R117 is the first immunotherapy to target T wall.

A protein expressing colorectal carcinoma, which we know has historically been insensitive to checkpoints.

KeyWell is an attractive target since it's not a expressed in normal vital tissues is 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 or markers of activity for our 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 HVAD. While antiretroviral therapy for arts, has turned HIV into a chronic disease there remains a large unmet need for functional care. We estimate over zero point five 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 50 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 200 copies per ml This is the level of virus associated with risk of transmission or infection.

However, the fact that some people can't 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 predictives of HIV control 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 12 is very rare.

Our Phase trial strives and we are treating people living with HIV with M113 on the background of ARC for twelve weeks and then stopping both therapies.

The objectives are to determine when whether we can reduce the 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 16 people living with HIV at a conference Over the next twelve months, we will continue dose escalation be followed by expansion.

We know that our tissue targeting platform works based on the KEYTRAC 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 one diabetes the second for atopic dermatitis Our vision for treating autoimmunity is unique.

And that is tissue specific down modulation of the immune system, which would avoid systemic Immunocore suppression. We accomplished this with our Immtai molecule, which has three features. [indiscernible] the targeting arm. Which binds strongly or Tethers the implied to the target tissue. This provides tissue specificity Second is a PD-one 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 hallmark of our approach is that the M type will only inhibit T cell activity when tethered or bound to the target cell or target tissue. For example, when the Imtai 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 M type binds to the target cell, it is brought into the T cell synapse [indiscernible] effector potently inhibits T cell activity this will result in tissue specific immune suppression. Type one 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 anti is unable to prevent the killing of the beta cell. We have recently generated exciting ex vivo proof of confidence for S-one 18 in pancreatic slices from a deceased donor who had recent onset of T1D prior [indiscernible] 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 CTA later this year. I will now turn to our second autoimmune program, that uses the same PD-one 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 longer term cells, Both play key roles in triggering allergic inflammation in the skin. Long arm 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 by presenting peptides, by a Class one and Class two.

Preventing lignin 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 U-one 20 is designed to achieve this goal of dual blockade. The targeting domain recognizes and buying CD1a and must tethers the Imtai to Langerhan cells. When it does find CD1a, it sturically blocks lipid presentation. And this prevents lipid sensing T cells from being activated. By now coating the lignin cell, in thousands of PD-one agonist spikes, which is the effector arm, U-one 20 will turn off any T cell that approaches the lung on cells. To be activated by [indiscernible] In fact, in vitro, U-one 20 is more efficacious than terasolimab, a PD-one agonist that is not tethered and has lower potency for PD-one agonism. Next twelve to eighteen months, is an exciting time for our R and D teams as we look forward to the conclusion of the Phase three Heavy AMFA decisions on the next steps for PRAME, 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 filings on Form 10 ks, which Let me share some of our key financial highlights for 2024 then touch upon our expectations for 2025.

As Ralph mentioned, 2024 was a strong year for Kim sales. With net sales growing to $84,000,000 in Q4. A 5% increase versus Q3. Primarily driven by volume growth in The U. S. And continued launches outside of The U. S. For the first time, we exceeded full year sales of $300,000,000 with total sales for the year of $310,000,000 which represents growth of 30% over 2023.

It is worth noting that the reimbursement environment in Europe remains Challenging.

And we continue to make our best estimates forever revenue recognition as we finalize price negotiations. As we continue to invest in our portfolio, SG and A and R and D expenses have increased versus 2023. R and D expenses increased primarily due to investments in our three Phase three trials.

The Phase III cord expansions in ovarian and lung for vermetafus also contributed to the increase. Our SG and 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 ChemTrex sales growth expectations and our SG and A SG and A and R and D expenses for this year. For Chemtraq, we expect revenue to grow incrementally in 2025 led primarily by growth in The U. S. 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 and D expenses will increase relative to 2024 as we further advance our clinical and preclinical pipeline candidates. And shifting to SG and A expenses, expect those investments to be mostly consistent with Q4 twenty twenty four levels over the course of 2025. While anticipating typical quarterly Turning briefly to our cash position. Am pleased to report that we had $820,000,000 in cash and marketable securities securities at the end of the year. As a reminder, we repaid our $50,000,000 loan with Pharma Con 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 patient across all three of our therapeutic areas. And I'll pass the call back to Majid. Thank you, Travis.

Starting with the HIV MAD data this quarter. This year, we expect incremental growth of ChemTRAC, will continue enrolling patients in our three Phase three melanoma trials pursue additional opportunities in our Prem franchise 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. 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. We wanted to understand in the sixteen patients would they all have twelve weeks or so off therapy, off all the therapy And so 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, do you want to 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. 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 we need to get to top dose and then expand. But in terms of TPP, Michael, I would point you to recent 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 200 copies per ml for two years in about twenty percent to thirty percent of people. That's minimum commercially successful PPP. Ralph, you want to address the Europe?

Happy to. So as Travis mentioned, Michael, Europe is having a challenging reimbursement environment. And as you know, we are negotiating prices with Germany and [indiscernible] We had 14 successes worldwide, which speaks to sort of how well we're doing. And 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 going to help you determine a go forward dose and how you would think about next steps once dose escalate something like that look like? [indiscernible] Yes. Jeff, thank you for the question. So in terms of the factors we would use to select the go forward dose, of course, safety. This is 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. There might need 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. 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 anymore because of control is actually quite low.

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

Yes. 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 Cowen. Please proceed with your question.

Hey, guys. Good morning. Thanks very much. I'll ask another one on HIV just for additional clarity. 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 controlled 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, in the clinic or what level of follow-up is required as well. Tyler, so the twelve weeks is toll booths of interruption is historically being used in these one trials to get 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 it's extremely low. When you're conducting these trials, you don't want to keep the people off of therapy for too long, especially 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 rely [indiscernible] So this is a new area that there is no precedence to bake it on I would really refer you to that white paper that published what a commercially successful PPP what the minimum case is and 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 Brenny and the PRISMMEL study, the dose selection that's going to 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 going to make a decision on early disease control. Is that feasible given the follow-up? I'm also kind of curious as to whether we'll see updated Phase one data on brining in second line melanoma this year?

Yes, I'm happy to take that. So the way the ninety patient dose selection analysis is set up is that those patients will be followed up for between eight and twelve weeks So really it's looking at a high level for both safety response rate and it's really set up to look for big differences because we know that both doses are Thank you. Our next question comes from the line of Justin Zelen 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 you expect the safety and tolerability profile of IMtech outside of the oncology settings such as in the infectious disease or autoimmune disease settings to shake out? And what would be the minimum commercially successful TBP that would be in these settings in regards to adverse events such as CRS Thank you. [indiscernible] take that. It's a 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 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 don't that aren't in in the body. So 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 HBV where the people are generally healthy. In terms of autoimmune, actually, we don't expect to have any Right now, don't expect to have 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. Any Immunocore 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 the autoimmune and in IV, we're looking for very infrequent dosing.

That is very well tolerated.

Yes. 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 this the safety profile is very good.

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

Hi. This is Sam on for Greg. Thank you for taking our question. Maybe going back to Brenny, 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?

I'm happy to take that, Sam. So with ovarian, we're building up the initial signals. It was clear that Brenny had monotherapy activity in late line [indiscernible] we needed to see a path forward and that path forward is in earlier lines and in combinations. Saw an interesting signal for chemo combinations in the platinum resistant. So we need to expand platinum resistant chemo combo then we need to study platinum sensitive hepatozoimab those are ongoing now. In the lung setting, we're more in the signal detection phase here. And so here we're looking [indiscernible] combinations with osimertinib and docetaxel, which are generally early aligned than the lateline HERA. And so we hope to see signals there In terms of when we're going to share the data, going to share the data when there's 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 [indiscernible] Hi, guys. Thanks for taking the question. How are you guys thinking about business development opportunities for 2025?

Thank you. [indiscernible] 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 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 our question. This is Paul on for Michael.

For Chemtrax, just on the commercial performance, I believe you've been at or around 65% U. S. 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 Where do you see that share in The U. S. Market plateauing?

And then on treatment duration, you mentioned trending over twelve months. What's your best estimate of where that could land on the term?

Great. Ralph, I think it's 65%, but go ahead.

Well, thank you for the question. And as you said, we are at 65% penetrated, which is good news because we've been growing significantly 34% growth last year in The U. S. And look, we're continuing our work into the community where the good news is that half of our prescriptions are coming of our new start. 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 is still a lot of patients there and saw unmet needs, so we're going to continue that work. In terms of the duration of therapy, this is 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 we'll see it hopefully grow together.

Yes, which is really unusual actually. It speaks highly of the treatment [indiscernible] Second half of twenty twenty five, it seems like eight to ten weeks minimum follow-up is expected with 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, ctDNA or PFS? And to what extent the interim data be communicated in the company? And finally, can you comment as to whether there will be a there is a futility analysis included as part of the dose selection decision? And thanks. So I can start. So we are not intending to to release the data just for the integrity of the of the trial that's going to be the IDMC looking at the they're the only ones looking at the trial. But David, do you want to comment? Thank you. Cladnam?

There will not be a futility analysis. The net analysis is strictly to choose a dose. That will be done by the IDMC in terms of what will be used at the IDMC will use both efficacy and safety. I would just remind you that in the Phase one trial, [indiscernible] both doses were active and well tolerated, forty and one hundred and sixty, and we didn't really see a dose response. So are going to be looking for large differences. And if they don't see large differences, then we're going to be using they'll 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.

Hi. Thanks for taking our question.

This is Ethan on for Gil. So you mentioned some reimbursements challenges in Europe for Chemtrax. Which isn't very surprising, but I know it's early on, but do you anticipate similar challenges for Berenetifest in Europe? Or are these challenges more product indication specific to Chemtrax? Thank you.

Yes. I think I'll start in the Ralf please comment. I think we are actually, I'll look at the cup half full. We had so far good negotiations and 14 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 get now we're launching in The UK. That's one of the toughest markets. But, Raf, you want to comment?

So as Beijia said, yes, we've heard a lot of successes with ChemTruck and that speaks to the value proposition of ChemTruck. Look, I Think The Market Is Challenging Or The Reimbursement Landscape Is Challenging For For All Companies And You've Seen This Communicated By Everybody. So All We Can Do Is Expect Good Data And Keep Working To Freight Access For Patients Across Europe. And hopefully we'll have the same successes of the data with preventive hospital business like the Kintra data. [indiscernible] expect the same thing. I think if we are lucky and have an OS endpoint that facility thinks in Europe. That's exactly what happened with ChemTrack.

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 the call late, but I'd just love to know around the HIV data that's coming up, how should we should be thinking about the buzz for success whether it's around SPARRA reservoir reduction or the delay in viral rebound? And if you can say around that and kind of doses we should expect to see and 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 data is just not ready for the data cut for the presentation. In terms of what success would look like, this is a setting both viral reservoir reduction during treatment phase and then demonstrating viral control at interruption, it's never been reliably shown. For any therapy. So for us, what we're looking for in a Phase one dose aspiration is do we have signals of activity? Can we reliably reduce the reservoir and can we alter the kinetics? Me, that would be a huge success to 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 percentage of patients who would have antiviral control is there enough strength to move forward to 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 the HIV program.

Was just curious if based on the data that's generated in this MAD portion, of the STRIDE trial, if there you might see a potential for a combination strategy for MO and 3b 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 priority review or other regulatory incentives for potential accelerated development path? [indiscernible] Patrick, thank you for that question. And it's a good one because it reminds me to that pretty much our entire platform oncology, ID and potentially autoimmune is combinable. In fact, the Phase one trial that we'll share data with in the next few weeks is on the background of ART. And And certainly, this could be combined with LRAs It could be combined with anything. Essentially. But the goal for here is not to have chronic long term treatment, it's for to have 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. 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 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 app 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.

Yes.

In terms again, 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 lung around cells play in skin inflammation. Our initial entry point will be in patients who have 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 [indiscernible] commercially acceptable PPP is. In terms of the HIV data, which is next month and then the HPV, I think you asked about that. SAD data. I actually look 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 first time and off the shelf TCR therapy in HBV. And so I think although the HBV is SAD data, the question there is we're going to 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 ImmTav can work in chronic viral diseases.

Yes, just to add, I think on CD1, there are multiple indications and I think that's the attractiveness about the mechanism. And both HIV, HPV gives 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 Yay with UBS. Please proceed with your question.

Great.

Hey, thanks for taking my questions. Just one from me. So regarding HEI B program, just want to dig into the mechanism of action. Could you maybe 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 this the impacts can bridge a T cell to an infected CD4 T cell so a CD8 killer cell to infected CD4 T cell, we've shown that this can work even when you don't stimulate the when you don't kick in 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 body of evidence we've already published.

Yes. And I think the one reason for this platform and for the HIV, we know that the reservoir has very low expression, if you will, of the target. And we know that our technology can go can kill down to five to 10 targets or copies per cell. So that's another another reasons to believe Thank you. Our next question comes from the line of Jeff Jones with Oppenheimer.

Hi guys and thanks for taking the question.

Just one from us. And in terms of the autoimmune program and AD being your first universal program, how are you thinking about a applicability of that to the oncology programs? Thanks.

Yes, I would say that it's what they have in common is tissue targeting part that we can show a 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 In the autoimmune, we're turning T cells off. And so they differ in that regard, but they both have in common the TCR targeting. And fact, our preclinical toxicology derisking program that we're going to use for autoimmune does incorporate many of the aspects we use for oncology.

Yes.

The way I think about it is the yin and yang. If you 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 Bahish Jalal for any closing remarks.

Yes. Thank you, operator. I just wanted thank you again for dialing in for have a great day.

Thank you. This does conclude today's teleconference. We appreciate your participation. May disconnect your lines at this time. Enjoy the rest of your day.