Q4 2024 Immunocore Holdings PLC Earnings Call
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Thank you for watching.
Speaker Change: Greetings and welcome to the ImmunoCore conference call and webcast. At this time all participants are in a listen-only mode.
Speaker Change: 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.
Speaker Change: Thank you. Good morning and good afternoon. Thank you for joining us on our 4Q and full year 2024 earnings call.
Speaker Change: 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.
Speaker Change: Please note that actual results can vary materially from those indicated by these four looking statements, including those discussed in our filings with the SEC.
and many others. Thank you. Thank you.
Speaker Change: On today's call, I'm joined by Bahija Jallal, CEO of Immunocore, who will share a strategy update.
Speaker Change: Then, Ralph Torbay, head of commercial, will review our full-year 24 ChemTrac sales and ChemTrac's lifecycle management plans. David Berman, our head of R&D, will provide some pipeline updates highlighting near-term readouts in infectious diseases.
Bahija Jallal: Travis Coy, our CFO and head of corporate development, will also provide highlights on our financial results reported this morning. Bahija?
Thank you, Clay, and good morning, good afternoon, everyone.
Speaker Change: Our first order of business today is to welcome Travis Quay, our new CFO. This is Travis's first earnings call for Winnicore, and we are delighted to have him join us. He was on our board previously. Welcome, Travis.
Speaker Change: Today, the team will share the details of our fourth quarter and full year 2024 performance and the progress of our clinical portfolio.
Speaker Change: As always, we have been laser-focused on advancing our mission of bringing transformative medicine to patients.
Bahija Jallal: I am very proud that 2024 was another year of strong execution, thanks to the fantastic work delivered by our teams.
Speaker Change: We delivered ChemTracs 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 $310 million in revenue for the year.
This continues our great track records of commercial execution.
Speaker Change: 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.
Speaker Change: We have advanced our three ongoing Phase 3 trials, including the two Phase 3 melanoma trials, Tebi-AM and Atom, as we execute on our chemtrack life cycle management.
Speaker Change: We also randomized the first patient in our third phase 3 trial, Prism Mel. 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.
Speaker Change: Our portfolio growth is fueled by an R&D engine that delivers a robust early pipeline.
Speaker Change: In 2024, we initiated two Phase I trials with two novel molecules that David will talk to you about in a few minutes.
and many more. Thank you. Thank you.
Speaker Change: 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 portion of our HIV trial later this quarter.
Speaker Change: Our modular technology allowed us to expand into new therapeutic areas tackling autoimmune diseases.
Speaker Change: We advanced two autoimmune candidates, one targeting type 1 diabetes and the other atopic dermatitis.
Speaker Change: 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.
Speaker Change: I now ask the team to share additional details. First, Ralph will discuss Kim Trach's commercial performance. Ralph, please.
Thank you, Bahija, and hello, everyone.
Speaker Change: Chemtrail has had another year of exceptional growth, and I continue to be very proud of our team's dedication to reach more patients globally.
Speaker Change: Chemtrail truly embodies our mission of bringing transformative immunotherapies to patients.
Speaker Change: We have raised the bar for survival in first-line HLA-0201 metastatic uveal melanoma with unprecedented three-year overall survival of around 27%.
Speaker Change: Patients who before ChemTrac were given 12 months to live are now alive two years, even three years later, with ChemTrac.
Speaker Change: With three Prix Gallien awards and two New England Journal of Medicine publications, among other recognitions, this is what transformational innovation looks like.
Speaker Change: We take the responsibility of commercializing this transformational medicine very seriously and last year alone, we launched Chemtrack in 14 countries, for a total of 24 countries launched.
Speaker Change: We have also established CHIMTRAC as a center of care across most major markets with over 80% share of HLA-021 positive patients.
Speaker Change: We're continuing our global expansion with Chemtrack, which has now been approved in 39 countries, including most recently in Brazil.
Speaker Change: We have delivered nearly three years of continuous net revenue growth with Chemtrack.
Speaker Change: For the full year 2024, Chemtruck generated $310 million in net revenues, which represents a 30% year-on-year growth.
Speaker Change: In the fourth quarter, we've reported $84.1 million in net revenues, representing a 5% increase from the prior quarter.
Speaker Change: The United States accounted for $226 million, growing at an impressive 34% year-on-year.
Speaker Change: In 2024, we successfully treated two out of three patients in the community with nearly half of all new Kim track patients starting there.
Speaker Change: We estimate a market penetration of around 65% in the U.S. with a duration of therapy of approximately 12 months.
Thank you for watching. See you next time.
Speaker Change: These numbers speak to our efforts and, as importantly, to ChemTrac's safety and exceptional efficacy.
Speaker Change: Looking ahead at 2025, we continue to expect KimTrack incremental growth, driven by three main factors.
Speaker Change: First, U.S. community expansion, focused on less dense areas, leveraging the AI tools we launched last year.
Speaker Change: Second, duration of therapy, which continues to increase beyond clinical trial experience, highlighting ChemTrac's benefit beyond typical resist progression.
Speaker Change: And third, new launches ex-US, including the recent launch in UK and Poland.
Thank you for watching. See you next time.
Speaker Change: We're also excited to potentially expand the benefit of KimTrack to additional indications with our Lifecycle Management Program, which I will take you through in the next slide.
and David Berman. Thank you. Thank you.
and many more. Thank you. Thank you.
Speaker Change: No therapy has been proven to extend survival in second-line metastatic cutaneous melanoma post-checkpoint inhibitors.
Speaker Change: Patient survival in this setting is poor and hovers at around 55% at one year.
Speaker Change: TEPI-AM is the first Phase III trial aiming to show improved overall survival in this setting.
Speaker Change: There are strong reasons to believe in the potential of chemtrails in this patient population based on Phase I trial data that showed 75% survival rate at one year as well as an acceptable safety profile.
For more information, visit www.fema.gov
Speaker Change: The TEBI-AM trial has three arms, ChemTrac monotherapy, ChemTrac in combination with Pembro, and a control arm which includes options such as investigator choice of chemotherapy, re-treatment with NTPD1, or BRAF therapy, or clinical trials.
Speaker Change: We have line-of-sight on data within the next 18 months. Enrollment is on track to finish in the first half of 2026 and data in the second half of 2026.
Thank you for watching.
Speaker Change: The ATOM trial is the only registrational phase 3 trial in the adjuvant uveal melanoma setting with the potential to prolong time to progression and survival.
Speaker Change: 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.
Speaker Change: Patients currently have no other option but to watch and worry.
Yet we know for half of these patients
Speaker Change: Metastases will occur within three years. The ATOM trial in collaboration with URTC aims to treat patients during this period with the goal of delaying or eliminating metastases.
Speaker Change: ERTC enrolled the first patient in the fourth quarter of 2024, and the trial is currently recruiting patients globally.
and many more. Thank you. Thank you.
Speaker Change: As we look to the future for ChemTrack, we strongly believe in its potential to help up to 6,000 patients with melanoma live longer.
Speaker Change: This vision is built upon robust clinical data, groundbreaking phase three trials, and a proven track record in the clinic.
Speaker Change: We're steadfast on our commitment to transforming patient outcomes and solidifying Chemtrails position as a leading therapy in the melanoma landscape.
Speaker Change: Now, I'd 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.
David Berman: 2024 was an execution-rich year for our R&D team. We started two phase 3 trials, Prismel and Adam, two phase 1 trials, P-Well and Prane HLE, the MAD phase of HIV, and we completed the SAD of our HPV trial.
Speaker Change: Over the next 12 to 18 months, we hope to have data readouts, including potentially for Tebby AM, that will guide next steps for these programs.
Speaker Change: Ralph has just presented the ChemTrac clinical trial updates and so I will provide brief updates on CRAME, HEWL, HIV and our autoimmune programs.
Let's talk about training.
Speaker Change: We are actively randomizing patients into the phase 3 study in newly diagnosed metastatic cutaneous melanoma, studying brinatophas plus nivolumab versus a nivolumab regimen.
Speaker Change: 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 40 microgram and the 160 microgram as the go-forward dose.
Speaker Change: 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 brinetifus in chemo combinations in platinum-resistant ovarian and in earlier lines in combinations in platinum-sensitive ovarian carcinoma.
Speaker Change: Second, we will continue signal detection in lung cancer with osimertinib and docetaxel. And third, we will continue dose escalation of our PREEM path-like extended IMTAP.
Speaker Change: All three will be reviewed together over the next 12 to 18 months to determine next steps.
Speaker Change: Frame and GP100 are both well-known targets for TCR therapies. In contrast, T-WILL is a novel first-in-class target and our ongoing phase one program here demonstrates the power of our discovery engine.
Speaker Change: Colorectal carcinoma has an increasing incidence and a high unmet need. R117 is the first immunotherapy to target P-wall, a protein expressed in colorectal carcinoma which we know has historically been insensitive to checkpoints.
Speaker Change: PEEWL is an attractive target since it's not expressed in normal vital tissues, is a negative prognostic marker, and has broad expression in about a quarter of colorectal cancer patients.
Speaker Change: We designed the phase one dose escalation, which started last year, based on all the insights from our earlier in-tech programs.
Speaker Change: We have learned which signals are markers of activity for our platform, and we hope to see these mature in the next 12 to 18 months.
Speaker Change: We know that our IMTAX 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.
Speaker Change: While antiretroviral therapy, or ART, has turned HIV into a chronic disease, there remains a large unmet need for functional care.
Speaker Change: 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.
and many more. Thank you. Thank you.
Speaker Change: 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.
Speaker Change: 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.
Speaker Change: 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 MTAB immune therapy approach.
Speaker Change: 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.
Speaker Change: And here, the historical rate of HIV control at week 12 is very rare.
Speaker Change: Our Phase 1 trial is called STRIVE, and we are treating people living with HIV with M113 on the background of ARC for 12 weeks, and then stopping both therapies.
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Speaker Change: The objectives are to determine whether we can reduce the viral RNA reservoir during the treatment phase.
Speaker Change: and then whether we can alter the kinetics or delay viral rebound after treatment interruption.
Speaker Change: We will present the initial MADD data from 16 people living with HIV at a conference next month.
Speaker Change: Over the next 12 months, we will continue dose escalation to be followed by expansion.
Speaker Change: We know that our tissue targeting platform works based on the ChemTrac survival benefit.
Speaker Change: We came up with the idea of using our tissue targeting platform to turn down the immune system.
for the treatment of autoimmune disease.
Speaker Change: Over the next 12 to 18 months, we will bring our two lead autoimmune candidates, one for type 1 diabetes, the second for atopic dermatitis, into the clinic.
Speaker Change: Our vision for treating autoimmunity is unique, and that is tissue-specific down-modulation of the immune system, which would avoid systemic immune suppression.
Speaker Change: We accomplish this with our MTI molecule which has three features. First, the targeting arm which binds strongly or tethers the MTI to the target tissue.
This provides tissue specificity.
Speaker Change: Second, is a TD1 agonist that turns off T-cells by checkpoint agonism, which is the opposite of checkpoint blockade.
Speaker Change: and third is an FC fusion to enable longer half-life for infrequent dosing.
Speaker Change: These three features are designed to realize our vision of tissue-specific immune suppression.
Speaker Change: The hallmark of our approach is that the MTI will only inhibit T-cell activity when tethered or bound to the target cell or target tissue.
Speaker Change: For example, when the MTI 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,
Speaker Change: When the M-type 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.
and others. Thank you. Thank you.
Speaker Change: Type 1 diabetes is a terrible autoimmune disease that requires lifeline insulin replacement and carries risks and morbidities.
Speaker Change: 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.
Speaker Change: T1D is caused when autoreactive T cells kill the beta cell in the pancreas. These are the cells that normally secrete insulin.
Speaker Change: S118 protects against autoreactive T-cell killing only when tethered to the beta cell.
Speaker Change: When not tethered, the M-type is unable to prevent the killing of the beta cell.
Speaker Change: We have recently generated exciting ex vivo proof of confidence for S118 in pancreatic slices from a deceased donor who had recent onset of T1D prior to their death.
Speaker Change: 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.
Speaker Change: 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.
Speaker Change: Langehans cells and an HLA-like molecule called CD1A that is expressed on Langehans cells both play key roles in triggering allergic inflammation in the skin.
Speaker Change: Long-on cells are sentinels in the skin. They monitor and are the initial triggers to alert the immune system.
Speaker Change: Two important ways they alert the immune system are by presenting lipids via CD1A and by presenting peptides via class 1 and class 2.
Speaker Change: Preventing long-run cells from initiating pathogenic inflammation by blocking both lipid and peptide presentation may have therapeutic benefit in several important inflammatory diseases including atopic dermatitis.
and others. Thank you. Thank you.
Speaker Change: Our candidate U-120 is designed to achieve this goal of dual blockade.
The targeting domain
Speaker Change: recognizes and binds CD1A, and thus tethers the MTI to Langerhans cells.
Speaker Change: When it does find CD1A, it sterically blocks lipid presentation, and this prevents lipid-sensing T cells from being activated.
Speaker Change: By now coating the long-neuron cell in thousands of PD-1 agonist spikes, which is the effector arm,
Speaker Change: U120 will turn off any T-cell that approaches the long-run cells to be activated by peptides.
Speaker Change: In fact, in vitro, U120 is more efficacious than Parasolamide, a PD-1 agonist that is not tethered and has lower potency for PD-1 agonism.
Speaker Change: The next 12 to 18 months is an exciting time for our R&D teams as we look forward to the conclusion of the Phase 3 TEBI-AM trial.
Speaker Change: Decisions on the next steps for PREEM, EWO, HIV, and HPV.
Speaker Change: and beginning our journey into developing a platform for autoimmune disease.
Travis: I would like to welcome and now hand over to Travis.
Travis: Thank you David. Good morning, good afternoon everyone. Earlier today we released our financial results for the fourth quarter and year ended 2024.
Speaker Change: Please refer to the press release and our latest SEC filing on Form 10-K for our full financial results.
Speaker Change: Let me share some of our key financial highlights for 2024 and then touch upon our expectations for 2025.
Speaker Change: As Ralph mentioned, 2024 was a strong year for Chemtrax sales, with net sales growing to $84 million in Q4.
a 5% increase versus Q3.
primarily driven by volume growth in the U.S.
and continued launches outside of the U.S.
Speaker Change: For the first time, we exceeded full year sales of $300 million, with total sales for the year of $310 million, which represents growth of 30% over 2023.
Speaker Change: It is worth noting that the reimbursement environment in Europe remains challenging.
Speaker Change: and we continue to make our best estimates for revenue recognition as we finalize price negotiations.
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Speaker Change: As we continue to invest in our portfolio, SG&A and R&D expenses have increased versus 2023.
Speaker Change: R&D expenses increased primarily due to investments in our three phase 3 trials.
Speaker Change: The Phase I-II chord expansions in ovarian and lung for Bermuda Fusp also contributed to the increase.
and others. Thank you. Thank you.
Travis: Our SG&A expenses increased slightly, primarily due to an increase in general business functions needed to support our operations.
Travis: Moving to 2025, let me provide some comments on how to think about Chemtrax sales growth expectations and our SG&A and R&D expenses for this year.
Travis: For Chemtrack, 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.
Travis: We anticipate that R&D expenses will increase relative to 2024 as we further advance our clinical and preclinical pipeline candidates.
Travis: And shifting to SG&A expenses, we expect those investments to be mostly consistent with Q4 2024 levels over the course of 2025.
while anticipating typical quarterly variability.
Travis: Turning briefly to our cash position, I am pleased to report that we had $820 million in cash in marketable securities at the end of the year.
Travis: As a reminder, we repaid our $50 million loan with Pharmacon in November.
Travis: 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.
I now pass the call back to Bahija.
Thank you, Travis. Thank you, David and Ralph.
Speaker Change: We enter 2025 with an eye toward delivering significant results in the next 12 to 18 months, starting with the HIV Mad Data this quarter.
Travis: This year, we expect incremental growth of ChemTrac. We'll continue enrolling patients in our three Phase III melanoma trials.
Travis: pursue additional opportunities in our PRAME franchise and continue to develop the next generation of transformative immunomodulating therapies.
Travis: 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.
Travis: Thank you, and we will now open the floor for questions.
Speaker Change: Thank you for watching. This is a production of the Center for Contemporary Politics. No part of this recording may be reproduced without the support of the Center for Contemporary
Speaker Change: Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 to remove yourself from the queue.
Travis: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. As a reminder, we ask that you please limit yourself to one question. One moment, please, while we poll for your questions.
Speaker Change: Our first question comes from the line of Michael Yee with Jeffries. Please proceed with your question.
Speaker Change: Good morning. Thanks for the question. We had a question on upcoming HIV results which David made a bunch of comments on coming up and we wanted to understand in the 16 patients would they all have
Speaker Change: 12 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.
Speaker Change: 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? Thank you.
Travis: Thank you for joining us. We hope you have a great day. And we'll see you next time.
David Berman: 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.
Speaker Change: 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 1 dose escalation with five to six
Speaker Change: people per cohort. So I wouldn't focus necessarily on rates at this point. I think we need to get to the...
Speaker Change: top those and then expand. But in terms of a TPP, Michael, I would point you to a recent
Speaker Change: 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 200.
Speaker Change: copies per ml for two years in about 20 to 30 percent of people. That's the minimum commercially successful TPP.
Ralph, do you want to address the Europe?
Speaker Change: And as you know, we are negotiating prices with Germany and France. We actually have blind sight on those negotiations.
Speaker Change: We had 14 successes worldwide, which speaks to how well we're doing. And we have some incremental growth as we've been guiding in Europe, which is what is reflected in our numbers.
Speaker Change: Thank you. Our next question comes from the line of Jessica Thigh with J.P. Morgan. Please proceed with your question.
Jessica Thigh: 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 escalation is complete? Would you move directly to a registrational trial? What could something like that look like? Thank you.
and Clayton Robertson.
Speaker Change: Yeah, Jess, thank you for the question. So, in terms of the factors we would use to select the go-for-goes, of course, safety. This is a relatively healthy population, so it needs to be a well-tolerated regimen. And then we need to be, we need to see that
Speaker Change: We have evidence of antiviral activity that, you know, gives us reason to believe that we can achieve a functional cure. Right now we've selected 12 weeks of dosing. We're focused on the dose. There might need to be to optimize
Speaker Change: that would then lead to a phase three trial. Now, interestingly, the meta-analysis that was just published.
Speaker Change: 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 2 anymore because the historical rates.
Speaker Change: 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 that.
Speaker Change: And we definitely will talk to the regulatory authorities before we do anything.
Speaker Change: Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Please proceed with your question.
Speaker Change: Hey guys, good morning, thanks very much. I'll ask another one on HIV, just...
Speaker Change: for additional clarity. It's been very helpful what you've said already, but just the 12-week time point of patients being controlled following ART interruption
Speaker Change: 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?
Speaker Change: And I would add that no one, no therapy or company or anyone has been able to demonstrate viral control reliably.
Speaker Change: So, this is a new area that, you know, 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.
Speaker Change: Thank you. Our next question comes from the line of Eric Schmidt with Cantor Fitzgerald. Please proceed with your question.
Eric Schmidt: Thanks for taking my question. Maybe I'll mix it up a little bit and ask a question on Brenny and the Prism Mel study, the dose selection that's going to happen, I guess, later this year. On those first 90 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.
Eric Schmidt: feasible given the follow-up. I'm also kind of curious as to whether we'll see updated phase one data ready in second line melanoma this year. Thank you.
Yeah, I'm happy to take that.
Eric Schmidt: analysis is set up is that those patients will be followed up for between 8 and 12 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.
Speaker Change: Thank you. Our next question comes from the line of Justin Zelen with BTIG. Please proceed with your question.
Speaker Change: 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 MTACs 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.
Speaker Change: Justin, yeah, Justin, happy to take that. It's a very good question. In terms of infectious disease,
Speaker Change: What we would expect to see of course is cytokine release syndrome because that's the mechanism T cell activation leads to cytokine
Speaker Change: But in contrast to oncology, we can't really have moderate or severe CRFs, so we really need to only have mild CRFs, and we think that's really achievable. We don't expect to have any on-target, off-viral activity, because...
Speaker Change: We don't expect to see any other toxicity aside from mild cytokine release syndrome. And I think that's...
Speaker Change: what would be needed in HIV and HPV where the people are generally healthy.
Speaker Change: In terms of autoimmune, actually, we don't expect to have any right now. We don't expect to have cytokine relief syndrome because we're turning off the immune system. We're not turning it on.
Speaker Change: 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.
Speaker Change: In autoimmune and in IV, we're looking for very infrequent dosing.
Speaker Change: that is very well tolerated. Yeah, I just want to add to that. I think you see in HIV, we did actually share that...
Speaker Change: We are escalating beyond 300 micrograms, just to give you an idea, so I think the safety profile is very good.
Speaker Change: Thank you. Our next question comes from the line of Craig Savinovich with Mizuho Securities. Please proceed with your question.
Speaker Change: Hi, this is Sam Wong for Gregg. Thank you for taking our questions. I'm going to be 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 recruitment in those indications and when might you be able to share next data? Thank you.
I'm happy to take that, Sam.
Speaker Change: Brenny 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-resistant chemo combo, and then we need to study platinum-sensitive betasizumab, and those are ongoing now. In the lung setting, we're more in the signal detection phase here, and so here we're looking at
Speaker Change: at combinations with Asi-Martineb and Dosi-Taxel, which are generally earlier lines than the late-lane C-rod.
Speaker Change: and so we 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 12 to 18 months.
Speaker Change: Thank you. Our next question comes from the line of Jonathan Chang with Lear Inc. Partners. Please proceed with your question.
Speaker Change: Hi guys, thanks for taking the question. How are you guys thinking about business development opportunities for 2025? Thank you.
Thank you.
Speaker Change: Great, thank you. Travis? Yeah, thanks for the question. First of all, we're obviously very excited about the opportunities we have in the pipeline currently.
Speaker Change: At the same time, we do continuously look for opportunities to enhance the value of the portfolio.
Speaker Change: 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.
and many more. Thank you. Thank you.
Speaker Change: Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim Partners. Please proceed with your question.
Speaker Change: Hi. Thanks for taking our question. This is Paul. I'm from Michael. For Chemtrack, just on the commercial performance, I believe you've been at or around 65% U.S. penetration for the past couple 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 U.S. market plateauing? And then on treatment duration, you mentioned training over 12 months. What's your best estimate of where that could land longer term? Thank you.
I think it's 65%, but go ahead.
Speaker Change: 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.
Speaker Change: and look we're continuing our work into the community where the good news is that you know 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 out there and you know so on unmet need so we're going to continue that work
Speaker Change: In terms of the duration of therapy, 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. Yeah, which is really unusual, actually. It speaks highly of the treatment.
the impact of Chemtrail.
Speaker Change: Thank you. Our next question comes from the line of Jack Allen with Baird. Please proceed with your question.
Nikon: Hey, this is Nikon for DAG. Thanks for taking my question. Surrounding the Pivotal First Line Prism Mel Study of Radiant and Melanoma, it appears you're now specifying timeline for...
Speaker Change: This election decision, second half of 2025, it seems like 8-10 weeks minimum follow-up is expected to be reviewed by the IDMC.
Speaker Change: 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 de-selection decision? And thanks.
Speaker Change: So I can start, you know, 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 at the trial, but David you want to comment?
Thank you
Speaker Change: 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 will just remind you that in the Phase I trial,
Speaker Change: Both doses were active and well-tolerated, 40 and 160, and we didn't really see a dose response. So they're gonna be looking for large differences. And if they don't see large differences, then they'll be using modeling. We'll be providing support by modeling to help select the dose.
and others. Thank you. Thank you. Thank you.
Speaker Change: Thank you. Our next question comes from the line of Gil Blum with Needham & Company. Please proceed with your question.
Speaker Change: Yeah, hi, thanks for taking our questions. This is Ethan on for Gill. So you mentioned some reimbursement challenges in Europe for KimTrack, which isn't very surprising, but I know it's early on, but do you anticipate similar challenges for Burnetifest in Europe, or are these challenges more product indication specific to KimTrack? Thank you.
Speaker Change: 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.
Speaker Change: 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 Ralph, you want to comment?
Speaker Change: So, as Bahija said, yes, we've had a lot of successes with Chemtrail, and that speaks to the value proposition of Chemtrail.
Speaker Change: Look, I think the market is challenging, or the reimbursement landscape is challenging for all companies, and you've seen this communicated by everybody.
Speaker Change: 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 as the data with prenatal hospitals like the Kindred data.
Speaker Change: And for Brenny we expect the same thing. You know I think if we if we are lucky and have an OS endpoint that that facilitates things in Europe. That's exactly what happened with ChemTrack.
Speaker Change: Thank you. Our next question comes from the line of Peter Lawson with Barclays. Please proceed with your question.
and many more. Thank you for watching. I'm Ralph Torbay.
Speaker Change: Great, thank you so much. I apologize, I joined the call late, but I'd just love to know around the HIV data that's coming up, how we should be thinking about
Speaker Change: The buzz for success, whether it's around spiral 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 the number of patients in each dose. Thank you.
Hmm.
Speaker Change: 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.
Speaker Change: setting both viral reservoir reduction during the treatment phase and then demonstrating viral control after interruption. It's never been reliably shown.
Speaker Change: 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? To me, that would be a huge success for the field, actually, because no one's been able to show this. Once we complete...
Speaker Change: 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, and is there enough strength to move forward to a randomized phase 2 trial. So that information will come later this year.
and Clayton Robertson. Thank you. Thank you.
Speaker Change: Thank you. Our next question comes from the line of Patrick Truccio with HC Wainwright. Please proceed with your question.
Speaker Change: 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 a potential accelerated development path?
Speaker Change: Yeah, 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.
Certainly, this could be combined with LRAs.
Speaker Change: 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 a finite dosing regimen so that we can stop treatment and the patients can be on all therapies for two to three years. I think that would be kind of our eventual. In terms of.
Speaker Change: 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.
and many more. Thank you. Thank you.
and David Berman. Thank you. Thank you.
Speaker Change: Thank you. Our next question comes from the line of Rajan Sharma with Goldman Sachs. Please proceed with your question.
Speaker Change: that you'd be looking to to maybe increase confidence in the platform more broadly and if there's any crossroad to HPV there. Thank you.
Speaker Change: Yeah in terms again 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
Speaker Change: that CD1A and Langerhans 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 better sense to understand what a commercial acceptable TPP is.
Speaker Change: In terms of the HIV data, which is next month, and then the HPV, I think you asked about that.
Speaker Change: I actually look at them as a package, and I think they do...
Speaker Change: They are both important because they are the first time that TCR therapy has been used in HIV.
Speaker Change: about the mechanism. And both HIV, HPV gives us a higher confidence for the platform to work in infectious disease and a lot of learning there.
Speaker Change: Thank you. Our next question comes from the line of David Dye with UBS. Please proceed with your question.
David Dye: Great. Hey, thanks for taking my questions. Just one from me. So regarding the HIV program, I just want to dig into the mechanism of action. Could you highlight some of the preclinical data that gives you confidence of potential viral control for the phase one trial? Thanks.
Thank you.
Speaker Change: T-cells to kill HIV-infected CD4 T-cells. So we've shown that in vitro.
Speaker Change: We've actually shown imaging, microscopy showing that the mTAFs can bridge a T-cell to an infected CD4 T-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
Speaker Change: stimulate the, when you don't kick with the HDAC inhibitor, you don't have to activate the T cell to induce.
Speaker Change: Yeah, and I think the one reason, you know, 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
Speaker Change: our technology can go, can kill cells down to 5 to 10 targets or copies per cell. So that's another, another reasons to believe.
Speaker Change: Thank you. Our next question comes from the line of Jeff Jones with Oppenheimer. Please proceed with your question.
Hi guys, and thanks for taking the question.
Speaker Change: One from us, in terms of the autoimmune program and AD being your first universal program, how are you thinking about applicability of that to the oncology programs?
Thanks.
Speaker Change: 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.
Speaker Change: 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 in fact, our preclinical toxicology to risking program that we're gonna use for autoimmune does incorporate many of the aspects we use for oncology.
Speaker Change: 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.
and many more. Thank you. Thank you.
Speaker Change: 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.
Speaker Change: Yes, thank you operators. I just want to thank you again for dialing in for excellent questions and for your support and have a great day.
Speaker Change: Thank you. This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time.