Immunocore Q2 2024 Earnings Call Transcript

Quartr
Provided by Quartr
August 8, 2024

There are 21 speakers on the call.

Operator

At this time, all participants are in a listen only mode. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. I would now like to turn the call over to Clayton Robertson, Head of Investor Relations.

Operator

Thank you. You may begin.

Speaker 1

Good morning and good afternoon. Thank you for joining us on our Q2 and first half twenty twenty four earnings call today. 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'm joined by Bahija Doolal, CEO of Immunacor and Brian De Donato, CFO and Head of Strategy, who will share a strategy update.

Speaker 1

Ralph Torbay, Head of Commercial, will review our first half KimTrak sales and additional growth opportunities for KimTrak. David Bourbon, ImmunoCORE's Head of R and D, will provide some pipeline updates, including near term readouts in oncology and infectious diseases. Brian will also provide highlights on our financial results reported this morning. Khadija?

Speaker 2

Thank you, Clay. As you may be able to hear, I'm losing my voice and I have pharyngitis. So to be able to answer your questions at the end, I will ask Brian to pinch hit for me. Brian, please.

Speaker 3

Thank you, Bahija.

Speaker 4

We hope you feel better.

Speaker 5

We are

Speaker 6

pleased to share

Speaker 4

with you an update on ImmunoCore through the first half of twenty twenty four. We've achieved excellent commercial results while advancing our T cell engager platform in 3 therapeutic areas. We appreciate your continued support in advancing our mission of delivering innovative and life changing medicines to patients. Earlier this year, we outlined our 3 strategic pillars and our areas of focus for the next 18 months to 24 months. Today, we will provide updates on the first two of these pillars.

Speaker 4

1st, we continue to maximize KimTrak performance. Completely report continued sequential revenue growth for the quarter and significant year over year growth for the first half of twenty twenty four. This growth is driven by strong U. S. Performance.

Speaker 4

We expanded our customer base and increased market penetration and reported longer duration of therapy. We also continue to increase our global footprint with additional country launches, allowing us to bring KimTrak to more patients around the world. To achieve our longer term growth objectives for KimTrak, we are simultaneously pursuing label expansion in both late line cutaneous melanoma with the ongoing TebI AM trial and also an adjuvant uveal melanoma with the soon to start ADAM trial.

Speaker 5

If successful,

Speaker 4

these two expansions may allow up to 6,000 patients to benefit from the survival benefit of Kymtrex. Moving to the 2nd strategic pillar, our aim is to progress our 9 clinical programs, all first in class leading bispecific TCR therapies, our innovative research engine to identify additional novel targets and therapeutics. At ASCO, we presented Phase 1 data of bradentefuss, our PRAME targeted therapy. In previously treated cutaneous melanoma patients, which drove the decision to start the Phase 3 registrational trial in first line cutaneous melanoma patients.

Speaker 3

Next month in ESMO,

Speaker 4

we will present late line ovarian cancer data. And in Q4, we are planning to present late line data in lung cancer at a medical conference.

Speaker 3

We're also

Speaker 4

excited about the potential of our platform to treat infectious diseases. As you recall, our objective is to deliver a functional cure for people living with HIV We expect to present the MAD data from our HIV trial early next year. I'll now ask the team to share additional details. First, Ralph will discuss Chemtrack's commercial performance. Ralph?

Speaker 3

Thank you, Brian, and hello, everyone. We've had a strong first half in twenty twenty four delivering $146,000,000 in net sales, which represents a 34% increase compared to the same period last year. I'm proud of our cross functional team's achievements and commitment as we expanded our reach to more patients. We've now launched chemtrak in 19 countries including 9 new launches since the beginning of the year. In the context of a challenging reimbursement environment in Europe, we have made good progress with AXIS, signing 2 additional reimbursement agreements in Poland and Sweden, which are expected to launch in the Q4.

Speaker 3

In Q2, we also announced the acceleration of our Phase 3 trial, the PEBI AM study in advanced cutaneous melanoma. This is an important part of our growth strategy beyond MUM and we are very pleased with this progress. I will now take you through the figures and financial performance in more detail. We delivered 75 point $3,000,000 in net revenues with KimTrak in the 2nd quarter, which is an increase of 7% compared to the Q1. Net revenue growth was driven primarily by the U.

Speaker 3

S. Where we saw an 11% growth compared to the Q1. This growth comes from our continued focus on the community and increasing duration of therapy. We estimate we now have around 65% market share in the U. S.

Speaker 3

And believe there continues to be opportunity for further growth. In terms of penetration since launch, over 500 unique sites in the U. S. Have treated patients with KimTrak, most in the community. To continue expanding our reach, we're constantly innovating and recently rolled out our AI enabled patient finding tool.

Speaker 3

This has allowed us to find more patients in lower density community centers, while keeping our field force footprint unchanged. Our goal is to continue growing the U. S. Through further market penetration and appropriately supporting duration of therapy, currently trending to 11 plus months. This is exceptional and speaks to a different mechanism of action with the benefit of chemtraq extending beyond the typical RECIST response.

Speaker 3

Many patients with the best response of stable disease do well and remain on chemtraq years later, contributing to the growing duration of therapy we observe. Shifting gears to Europe, demand flattened in Q2 and revenues declined net of $6,700,000 increase in rebate reserves. The access environment remains very challenging across Europe and we expect incremental demand growth in the second half of the year to come from the launches in Poland and Sweden. I'm pleased with our team's effort to reach more patients globally with MUM, driving near term growth. CIMTRAC has the potential to benefit patients beyond MUM and drive mid term growth through label expansion with the TEDA AM study.

Speaker 3

Following a consultation with the FDA, we converted and accelerated our TebA AM study into a Phase 3 registrational trial in second line plus advanced cutaneous melanoma. This is exciting and helps us in 2 ways. First, to robustly test the PD-one combination and chemtrax monotherapy arms. And second, by rolling the 120 patients already enrolled into the Phase 2, we accelerate the time to final analysis of the Phase 3 by up to 12 months. We now expect to complete the enrollment in the first half of twenty twenty six and potentially see data in the second half, noting of course the event driven nature of the endpoint.

Speaker 3

Today, we're only at the beginning of the chemtra journey. In MUM, we're growing chemtra double digit year over year as we increase our penetration in the U. S, support duration of therapy around the world and launch new markets. Our 2 ongoing Phase 3 registrational clinical trials position us for continued growth in the mid to long term. With the TEDDAM trial, we see the potential to extend the benefit of chemtrak to up to 4,000 additional patients with second line plus metastatic cutaneous myeloma.

Speaker 3

With the ATOM trial, we see this benefit expanded into the adjuvant duveal myeloma setting where all the evidence with KimTrak points to our platform being potentially transformative. If successful, we could help up to 6,000 patients across all three indications live longer and better lives. I'm very excited about our future and to tell you more, I'll hand over to David.

Speaker 5

Thank you, Ralph. I'm really pleased to update you on the strong progress we've made on our pipeline. I'm proud of our R and D team. We've hit all our development milestones and progressing 9 clinical programs, including 3 Phase III trials, starting 3 new Phase I and expanding to 3 therapeutic areas. Today, I'm going to focus on the 2 clinical stage programs with beta readouts over the next 18 months, brinidafusp and HIV.

Speaker 5

Let's recall our strategy in cutaneous melanoma and the data supporting the Phase 3 trial. The most common therapies used globally are anti PD-one either as monotherapy or in checkpoint combination and BRAF therapy for BRAF mutation positive patients. Once patients progress on these available therapies, the only options are clinical trials and pills for select patients. Our strategy is to demonstrate in the Phase 1 trial in third line patients that bonetifast is active and well tolerated and that this activity would support a PFS endpoint in a Phase 3 trial in first line. Here's a summary of the key data from the Phase 1 trial we presented at ASCO.

Speaker 5

1st, BRENI has monotherapy activity, something not commonly seen for other biologics in heavily pretreated melanoma. 2nd, the disease control rate, which is a surrogate of progression free survival is higher for brinidipus monotherapy than the combination of nivolumab plus ralapolumab in a similar setting. 3rd, we see higher activity in PRAME positive versus PRAME negative. This provides biological plausibility as the PRAME negative subset behaves as an internal negative control. And finally, the systemic T cell fitness data indicates we expect an even higher disease control rate and longer PFS in first line.

Speaker 5

These data supported our decision to move to Phase 3 in first line. In our Phase 3 first line trial, we will combine 2 biologics, pernidaFusp and nivolumab, each with monotherapy activity and with complementary mechanisms of action. Based on the Phase 1 cross trial comparison I just shared with you, we fully expect that brinidafus plus nivolumab in the first line setting will be superior to both nivolumab alone and nivolumab plus relatable. We are pleased to announce that the Phase 3 PRISM MEL-three zero one study has started and we are focused on activating more sites globally. With the PRISM MEL-three zero one in first line I just shared and with the TebVie AM in second line that Ralph shared, we are really proud to be one of the few companies to have multiple Phase 3 investments in cutaneous melanoma, both backed by strong data.

Speaker 5

I will now turn to brinetofest in ovarian cancer. Women with ovarian carcinoma are cycled through platinum regiments shown in the blue until they become resistant or refractory shown in the green, at which point they received non platinum chemotherapies or the folate alpha receptor positive tumors antibody drug conjugate. Unlike melanoma, ovarian cancer has historically not been sensitive to immunotherapy. In heavily pretreated platinum resistant, which is the population in our Phase 1 trial, the outlook is poor with non platinum chemotherapies having response rates less than 10% and disease control rates between 40% to 50%. In our Phase 1 trial, we aim to demonstrate in the platinum resistance setting that brinetafus is clinically active and can be combined with non platinum chemo.

Speaker 5

This will be the subject of our ESMO poster next month. We have learned for our platform that clinical benefit manifests as disease control, that activity is even higher in earlier lines and that combinability with standards of care may enable at least additive activity. In addition, unlike melanoma, ovarian cancer is more complex with 2 distinct disease segments that are treated very differently, which requires us to study more combinations. Therefore, our next step in ovarian is twofold. 1st, in the heavily pretreated platinum resistant disease, we will expand our patient data set of combinations with non platinum chemotherapy.

Speaker 5

And second, in the earlier line platinum sensitive disease setting, we will test the combinations with bevacizumab and with platinum chemotherapy. Let's now turn to lung cancer. Lately lung cancer is a heterogeneous disease with patients generally having rapid progression. With lung, we're still in the signal detection phase. Later this year, we plan to share monotherapy in heavily pretreated lung cancer selected for PRAME expression and combinations with the late line chemotherapies enrolled without regard to selection for PRAME expression.

Speaker 5

The next steps are additional combinations with acimertinib in EGFR mutant patients and with docetaxel. This will then be followed by first line platinum combinations. PRAME is a promising target across multiple tumors and brinetofus is a 1st in class frame Impek. When you pioneer a novel platform, you have to be ready to look, to learn and to adjust. And in fact, frankly, this is the exciting part of drug development.

Speaker 5

We did this for venetafest in melanoma and we'll follow the same thoughtful approach for venetafest in ovarian and lung. I will now close by updating on HIV. HIV is currently managed by antiretroviral therapy, but when ART has stopped the virus rebounds on average within 2 weeks. By week 8 after treatment interruption, 98% of people will have a viral load of at least 200 copies per ml. This is the threshold commonly used to denote risk for viral transmission.

Speaker 5

The next frontier in HIV treatment is functional care, where the goal is to reduce or eliminate the viral reservoir, which would then delay or prevent viral rebound. To date, no therapy has convincingly demonstrated either of these endpoints. This is the goal of our 113B program called STR1VE. Demand portion of the STR1VE study is ongoing. We are treating with 113B plus ART for 12 weeks and then stopping both therapies.

Speaker 5

The objectives of the study are 2 fold. 1st, determine whether we can reduce the viral RNA reservoir during the treatment phase. And second, whether we can delay viral rebound or alter the kinetics of viral rebound after treatment interruption. As of June, we have enrolled 15 people living with HIV across 3 cohorts, the highest at 300 micrograms. The 300 microgram dose is biologically active.

Speaker 5

The next step is to enroll more people living with HIV to better characterize the activity and to explore higher doses. This will move the data release into the Q1 of 2025. I'm very proud of our R and D team. We pioneered the world's 1st TCR therapeutic. We saw the value of Kimtrac early in Phase 1 and we followed that vision to bring a fantastic new medicine to metastatic uveal melanoma patients.

Speaker 5

We saw that value for Kimtrac and cutaneous melanoma and the potential in adjuvant uveal and these programs are underway. We see that value in Vernetoclusp and we are excited to follow through on that vision as well. Brian, I'm going to hand back to you now.

Speaker 4

Thank you, David. Earlier today, we released our financial results for the Q2 ended June 30, 2024. Please refer to the press release and our latest SEC filing on Form 10 Q for our full financial results. I'll now share some of the key highlights. In Q2, global Kymntrack unit sales and net sales have both continued to grow sequentially, even with the challenging reimbursement environment in Europe.

Speaker 4

Net revenue grew to $75,300,000 in Q2 from $70,300,000 in Q1, a 7% increase driven primarily by the 11% growth in the United States. The U. S. Has consistently contributed over 70% of global net sales. In Q2, we increased rebate reserves by $6,700,000 in Europe as we continue to make best estimate revenue recognition assumptions and associated accruals.

Speaker 4

For the remainder of 2024, we anticipate global unit sales will continue to grow on a sequential basis as we continue to expect solid demand in the U. S. Market and new country contributions from non U. S. Markets.

Speaker 4

While both SG and A and R and D expenses declined sequentially this quarter, they have increased 31% in the first half over the same period in 2023. We expect R and D expenses to marginally increase in the second half compared to the first half as clinical development for late stage PRAME and KymTrak Phase 3 programs continue to accelerate. In aggregate, our net loss for the first half of $36,100,000 or $0.72 a share was roughly unchanged from 2023 given our increase in sales revenue. As you can see on this slide, our net cash and marketable securities position increased to $860,000,000 as of June 30 or $770,000,000 net of the planned $50,000,000 loan repayment and an expected $40,000,000 in European sales rebate payments, both expected in the second half of twenty twenty four. I'd like to congratulate the teams on continued KymTrak sales growth as we reach progressively more patients globally.

Speaker 4

This cash flow enables us to accelerate the broader portfolio while delivering transformative outcomes to patients. For the remainder of 2024, we will be presenting the Bridentafus Phase 1 late line ovarian data at ESMO then in Q4 the initial Phase 1 lung data at a medical conference. Looking over the next 4 years, we expect numerous data readouts, including additional data from bernantafoss, our HIV Phase 1 study, data from our 3 Phase 3 trials with KimTrak and bernantafoss and data from several new trial starts across our 3 therapeutic areas. With a strong balance sheet, a robust and diversified portfolio, our talented and dedicated teams and a clear and compelling vision for the future, we are confident we can continue to deliver significantly for patients and shareholders. Thank you.

Speaker 4

We will now take questions.

Operator

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 questions.

Speaker 7

Hey guys, thanks. Good morning. Congrats on great progress. We have two questions. On KimTrak, I know you made a few comments about the challenges about reimbursement in Europe.

Speaker 7

Can you just help us understand in the Q2 there what the reserve was for? Was that a specific country? And what does that mean for the go forward 3rd 4th quarters? Do we go back to adjusting for that? And was that a one time reserve?

Speaker 7

So help us understand the second quarter and then 3rd and 4th quarter adjustments. And then on the pipeline, I thought you made a very, very interesting comment about HIV. Can you just expand on that a little bit? You're saying you're enrolling more patients at a higher dose and it's biologically active. Have you been looking at the prior doses?

Speaker 7

Is the study all blinded? What are you seeing there? And what gives you that confidence to enroll more patients? Thank you.

Speaker 2

Thank you, Michael. Ryan or Ralf for the first question and David for the HIV, please.

Speaker 4

Great. Ralf, why don't you take the European question?

Speaker 3

Sounds good. Thank you. Thank you, Michael, for the question. So, look, we've had successes with reimbursement as proven by the 9 launches that we've had so far in this first half of the year. We increased the estimated reserves by $6,600,000 This should be a one time thing based on the latest assumptions that we have on the negotiations.

Speaker 3

Now in terms of looking forward, I would caution you against just adding the $6,700,000 because the erosion is both backward looking and forward looking and it's mainly on our negotiations with France and Germany.

Speaker 2

David?

Speaker 5

Michael, so with the HIV program, we're in the dose escalation phase of the multiple ascending dose. And as mentioned, we've gotten up to 300 micrograms and we'll continue to dose higher. There's a couple of important firsts here that we're looking at. This is the first time we've taken our platform into a setting with such a low peptide target density and where we have such a low infect cell target density. And so it was an important question for us to ask, can we actually see anything?

Speaker 5

And then of course, there's never been a functional care. There's never been a therapy that can reduce the reservoir or delay the rebound. So these are all really important first. And we do see evidence of biological activity during the MAD portion, but it's still early and there are only a few patients per cohort. And so we think it's prudent to get some more patients in that cohort and also to continue to go higher.

Speaker 5

We will discuss more of what biological activity means as we approach the full data release, which will be in the Q1 of Nexner.

Speaker 7

Analyzing. Thank you.

Operator

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

Speaker 8

Hey, this is Nick on for Jess. Thanks for taking our questions. First, on the brine ovarian update we should expect at ESMO. Can you just help set the stage for how many patients with the data we should expect kind of the split between mono and combo that I believe you stated should be more combo? And maybe add some more detail around what you see as promising data that sports continues evaluation here in the setting based on some of those benchmarks you provided?

Speaker 2

David, go ahead.

Speaker 5

Yes, happy to. So in terms of size, it's going to be roughly the same number as the cutaneous melanoma dataset at ASCO. It will be mostly monotherapy, but in contrast to the ASCO melanoma, we will have more combinations because there's more chemotherapy options to test here. So we'll be mostly mono with combination as well. In terms of the questions that we're going to be asking, so number 1 is, and these are the standard questions I've been asking throughout my drug development career in the States.

Speaker 5

Is there monotherapy activity? Can you combine with the intended registrational partner if you plan to do a combination? And can you have confidence that the drug activity can meet whatever registrational endpoint? So those are the types of questions we're asking in order to progress. In terms of the metrics or the benchmarks, I think you were asking, yes.

Speaker 5

So there aren't a lot of good benchmarks in this heavily pretreated platinum resistant setting. There are a few published chemotherapy trials. And so the chemotherapy benchmarks there, the response rates are in the single digits and the disease control rates is about 40% to 50%.

Speaker 8

Great. And then in addition to evaluating the platinum resistant ovarian cancer patients, you noted some evaluation in the platinum sensitive setting as well. So can you provide a little bit more detail the progress there and when we kind of expect an update from that data set?

Speaker 2

Mohan, do you want to take that?

Speaker 6

Sure. Happy to do that. So as David mentioned, obviously, ovarian is more heterogeneous and complex than melanoma. So we've been exploring mostly in the platinum resistant setting. But now the study does allow us to move to earlier lines and combined with therapies that are used in sensitive and those include bev and also will include platinum doublet.

Speaker 8

Great. Thank you.

Operator

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

Speaker 9

Hey, guys. Good morning. Thanks very much for the presentation.

Speaker 4

I have a couple of

Speaker 9

follow ups on the ovarian update at ESMO. So I understand that the bar for beating non platinum chemo and platinum resistant patients is low. But for the Breni combo chemo combo specifically, isn't elahir or mirvetuximab data the bar? And then the second question is if you can combine with non platinum chemo with good safety, do you believe that the likelihood of combining with platinum chemo

Speaker 3

in the frontline with platinum sensitive patients is high?

Speaker 2

David and Mohamad? Yes.

Speaker 5

So I'll address the first one and then Mohamad, you can talk about the fact. So Tyler, the MIRVA, it's good to see that there's a new medicine for these patients and it's not this MIRVA is a targeted chemotherapy. We know chemotherapies do work there. So, the key differences, I would say Tyler for us is that the MRV strategy is in the PRoC setting is to replace chemotherapy. Our strategy is to add on to chemotherapy, not to replace chemotherapy.

Speaker 5

And so our approach is going to be an add on to chemotherapy. And of course, eventually, there also could be an add on to mirvetuximab as well. And do you want to comment on the platinum sensitivity?

Speaker 6

Sure. Happy to do that. So I would say Tyler, this is early days. This is the first time we're actually combining our platform with chemotherapy and we're learning. But so far, the expectation is that we should be able to combine and the plan is to then move from the non platinum based chemotherapies to the platinum based chemotherapies over the coming months and into next year.

Speaker 4

Thank you.

Operator

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

Speaker 10

Thanks for taking my question. Maybe back to, KimTrak for a moment. It sounds like you've crossed the $300,000,000 annualized run rate for the first time. You've grown now, for several quarters at 30% or more year on year. You've spoken to more patients out there than you thought previously and longer duration, of course, than you would assume.

Speaker 10

So I guess the question is, what's the ceiling for this drug in the current uveal melanoma indication? Do you think it's a $500,000,000 $600,000,000 $700,000,000 a drug? Where is this going to end?

Speaker 2

Thank you, Eric. Ralph, you want to take that and maybe Brian, you can comment also at the end.

Speaker 3

Happy to. Thank you, Erik for the question. So look, we're very proud of the growth that we've had. A lot of it has been driven as we've stated by the U. S.

Speaker 3

Growth where we're 65% penetrated. It's important to keep in mind 2 aspects. One is the reimbursement landscape in Europe is such and the challenges are such that we expect really minor to very incremental growth coming from Europe moving forward. So a lot of the growth will be driven by the U. S, a lot of the incremental growth will be driven by the U.

Speaker 3

S. That's for MUM. But really I think where we get very much excited is when we think about the label expansions that are possible with the TEB AAM study, which is expect which expects data in 2026 as I mentioned. And from the ATOM study a little bit further down the line and that also would bring us into the adjuvant setting, bring the platform to the adjuvant setting. So I think there is still significant growth for chemtrak up to 6,000 patients potentially benefiting from it.

Speaker 1

Ralph, do you want to add anything?

Speaker 4

Yes. The only thing I would add, Eric, is that, we're really pleased that given the survival benefit of chemtraq that the duration of therapy continues to extend. The mean duration of therapy is now over 11 months, approaching 12 months, maybe plus. And as patients stay on longer and the tail is pronounced as we see in the 3 year survival follow-up, it's still unclear how long the duration of therapy can extend. So that's one of the upside potentials in KymTraq.

Speaker 4

And as Ralph said, 73 percent of net sales are coming from the United States. We'd expect that to continue going forward.

Speaker 11

Thank you.

Operator

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

Speaker 12

Hey, guys. Thanks for taking my questions. I had another one for David, just on the PRAME program again. Could you just provide us maybe updated views on the opportunity in the lung cancer indication? Are there any particular patient substance and focus for the development strategy?

Speaker 12

Are you enriching certain patients into this cohort? Any particular genotypes perhaps that might benefit most from PRAME in lung cancer? And what should expectations be for the scope of that data readout later this year? Thanks so much.

Speaker 5

Yes. Thanks, Michael. So with Lyme, of course, it's a lot more heterogeneous disease on multiple levels than ovarian and melanoma. And so we have been very interested in looking at those key subsets in order to first see the initial signal before we expand. So one example of the key subset, of course, are actionable gene mutation positive patients because those are insensitive to checkpoints.

Speaker 5

And so that would make an interesting place for us to look, but there are other potential subsets as well. We have initially for the monotherapy, as I talked about in the presentation, we focused on enrolling PRAME positive because about half of the adenocarcinoma patients are PRAME negative, half are positive and for the initial signal, of course, we want to make sure that the patients are premed positive. And so we have been doing this double screening, looking for the right patients. And so, the monotherapy data later this year will be smaller probably than what we're seeing for ovarian and for melanoma, but it's a little too soon to guide to the numbers of that. The combinations, of course, is where we're also interested because that's where we believe our platform is going to work best in terms of, combination.

Speaker 5

So it will be a monotherapy and it will be a mostly chemotherapy combination initially. As I talked about, Michael, going into next year weeks, expect to move into earlier lines with the docetaxel combination and with the ocimertinib combination. Mohammad, anything you want to add?

Speaker 6

No. I guess we also will have chemo platinum based chemotherapy option that will come a little bit later after ocimartinib.

Speaker 12

Great. Thank you.

Operator

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

Speaker 13

All right. Thanks so much for taking the question and congratulations on the progress. I wanted to ask a little bit about the earlier stage pipeline. I know the PillWell program recently cleared CTA and is expected to enter

Speaker 5

the clinic in the second half of

Speaker 13

this year. And you also submitted the CTA for the half life extended PRAME and have plans to submit the CTA for the PRAME-eight twenty four program. I guess my question here is, when can we start to see the pipeline kind of build out and see clinical data from some of these earlier assets?

Speaker 2

Great. Thank you, Jack. Amit and Mohammad?

Speaker 6

Yes. Thanks for the question, Jack. So you're absolutely right. We're quite excited about the progress we're making with the early stage pipeline. So for PWIL, following submission, we're now in the stage of activating sites.

Speaker 6

And then hopefully, we'll be able to meet our target of enrolling the 1st station before the end of the year. With HLE, we've made the submission. So it's we're waiting for health authority feedback. And with A24, we remain on track for making the Health30 submissions by the end of the year. In terms of data, I mean, this is these are first in human trials, right?

Speaker 6

So we need to get the trials open and start accruing. I'm sorry, it's too early to guide to when we would expect data from these trials.

Speaker 5

If I could just add one other point, Jack, is Mohamad's team has really baked in important learnings that we've made from our entire platform, from ChemTraq and from Vernetifest. So the P WOL study is now designed in colorectal cancer with all the best knowledge we have about where this platform is going to work. Likewise, with the PRAME half life extension, which is essentially the same molecule as parenatoprost but with an Fc half life extended. All of the wall of data we're building in terms of combinations and translational insights are directly applicable to the trained half life extension. So we see acceleration in our Phase 1 trials based on these learnings.

Speaker 4

Got it. Thank you.

Operator

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

Speaker 14

Thanks for taking the question and congrats on the progress. I think I'll ask a question about the autoimmune disease programs. It looks like you're kicking off CMC manufacturing care for candidates. Any thoughts on a timeline for entering the clinic on these programs?

Speaker 2

Thank you, Justin. We're hoping by next year. So the CMC is going well and we take it from there. But yes, we're excited about that program as well.

Speaker 14

Great. Thanks for taking my question.

Operator

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

Speaker 11

Hi, guys. Thanks for taking my questions. First question, how do you see the uveal melanoma competitive landscape potentially evolving in the future? What gives you confidence and the ability to continue and potentially expand the successful commercial story in the event of potential new entrants? And second question, I guess just out of curiosity for the lower tech people like myself, can you provide more color on the AI enabled patient finder?

Speaker 11

And how is this facilitating the commercial story? Thank you.

Speaker 2

Great. Thank you so much for the great questions. So I'll I'll start with David and maybe then Naval so you can comment more.

Speaker 5

Yes. Jonathan, in terms of the landscape, I think there are 2 ways to look at it. First in the metastatic setting, we in the HLA A2 positive, of course, we now have the 3 year survival benefit. It's a global standard of care. And so we're continuing to build on that.

Speaker 5

We know that in the HLA-two negative, there are studies going on. And by the way, it's great to see options that those that registrational study is in the HLA A2 negative setting. In terms of the adjuvant, we have the ADAM trial, which is a well designed standard relapse free survival endpoint. It's the standard endpoint used globally for full approval. So this is a trial that we believe will give us a full approval label with high confidence in the adjuvant setting.

Speaker 5

We are aware that there's competition in the neoadjuvant setting and I think it's too early for us to comment in terms of that. Ralph, do you want to talk about the AI?

Speaker 3

Sure. Thank you, David. So we're very excited about this tool actually because when you recall we were discussing initially how our approach to addressing the market, particularly in the U. S, we talked about the fact that there's a higher density at academic accounts and then after that it tails off with very low density in the community. And one of the challenges is how do you address that low density, those patients that pop up once a year or once every other year.

Speaker 3

And really now that AI has gotten to the place where some of the predictive models have become very good, we're leveraging that ability to predict based on historical data, where the patients and when the patients might pop in and some of the different practices. And that's enabled us to find patients and send reps on a just in time basis, which allowed us to basically keep our rep footprint the same.

Speaker 11

Understood.

Operator

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

Speaker 15

Hey, good morning. This is Alex on for Peter. Thank you for taking our questions. Just had 2 on the ovarian update. So assuming data supported, would you pursue a monotherapy or chemo combination approval in the platinum resistant setting?

Speaker 15

Or would the goal be to maybe try to go sort of directly into earlier lines of therapy in combination with chemo?

Speaker 2

Thank you, Alex. David?

Speaker 5

Yes. So, Alex, I guess it's important to understand to remind about our what insights we've made. First of all, our platform works really well with disease control. It works very well. It increases activity in earlier lines and we think it works best in combinations.

Speaker 5

In ovarian cancer, which is different from cutaneous, there's these 2 major disease segments and of course multiple different combinations. So we have to generate the data before we decide on what the next step is. So the immediate next steps are more chemotherapy combinations in the platinum resistant setting. And then as we talked about more platinum combinations and dinosizumab combinations in the platinum sensitive. This is the data set that we think will enable us to make the best decision on what the next study is, PRoC or PSA.

Speaker 15

Okay, great. And do we actually see any bev combination patients in the 3Q update?

Speaker 5

No, there won't be any bevacizumab combinations in this update.

Operator

Okay. Thank you. Thank you. Our next question comes from the line of Ahu Demir with Ladenburg Thalmann. Please proceed with your questions.

Speaker 16

Good morning. Thank you for taking my questions. Two questions from us. First one is on the lung cancer program. When you present data, disclose data from

Speaker 2

You cut off. If you could repeat your first question, please.

Speaker 16

I was asking how many patients' disclosure that you would have from the lung cancer and what percentage would have monotherapy versus combination? And I have another one.

Speaker 2

Okay. Thank you, Ashina. Thank you, I would say it's too early to say, but I'll give it to Mohammed to tell you.

Speaker 6

Sure. Thanks for the question. In terms of lung cancer, as David mentioned, it is obviously a more it's a more heterogeneous setting compared to melanoma and we are still in the initial signal detection mode. But in terms of patients, it will be likely a smaller data set than melanoma and ovarian, and we will likely have more combo patients than mono patients for the reason David mentioned that for monotherapy we have to select for PRAME and with combo we are allowing regardless of PRAME status.

Speaker 16

Okay, Soma. That's helpful. My second question is on the HIV program. You touched on the viral load and also the rebound rates. What would give you confidence to move forward from the

Speaker 5

David? Yes. It's a really good question, Tahoe, because of course, we're pioneering this area here. No one's generated the data thresholds for what surprised move forward. I would say at this stage, any evidence of activity that is definitely related to antiviral would be really intriguing to us because no one's been able to show that.

Speaker 5

So we're looking at can you reduce the viral reservoir and can you delay or alter the rebound kinetics. Anything I think here would be interesting for us to continue. Of course, at the end of the day, it's going to have to be an antiviral delay and rebound that is going to be the endpoint. But I think any insights we make here are going to be important for us. So immediate next steps are for us to generate more data and to get to higher doses because we only have a few patients per cohort.

Speaker 2

Yes. And I would just add one thing. I think you talked about combination. Just remind you that we do it the first part is on top of the anti retroviral.

Speaker 16

Okay. Thanks so much.

Operator

Thank you. Our next question comes from the line of Abantik Joshi with Mizuho. Please proceed with your question.

Speaker 17

Hi. This is Ivanka on

Speaker 18

for Greg. I just had a question. Are you still looking at BERNATOFAST in tumors beyond melanoma, ovarian and non small

Speaker 5

cell? Yes. We certainly are, and there's strong scientific rationale. But as a team, I've asked them to focus, right? We're launching a global Phase III cutaneous melanoma.

Speaker 5

We are committed to following up on the signals in ovarian and to look for signals in line. And we've certainly had the sites focused on those as well. We do have ongoing Phase I exploration in other tumors, but we've had to focus. And so we are certainly interested and continue to be interested in other tumors like endometrial.

Speaker 18

And one more question was for the earlier stage assets for P115C and P119C, Are you initially running basket studies? Are you focusing on specific tumors? Thank you.

Speaker 2

Go ahead, Mohammed. I have to admit that I'm not I want to retain the numbers, but go ahead.

Speaker 6

Are those numbers referring to the half life extended and the A24?

Speaker 18

Yes, the half life extended and the A24.

Speaker 2

We would have to simplify the

Speaker 16

Sorry about that. Sorry about

Speaker 3

that. It's not

Speaker 1

an issue.

Speaker 6

As David mentioned earlier, we are certainly applying all of the learnings from our F1 to succeed, PRAME program to those two programs. We know where PRAME is expressed. So yes, those trials are developed aggressively, so we have multiple options in terms of the types of patients that we can enroll.

Speaker 18

Okay. Thank you.

Operator

Thank you. Our next question comes from the line of Jeffrey Hung with Morgan Stanley. Please proceed with your question.

Speaker 17

Hello. This is Selena on for Jeff. Two questions here on PRAME. For the melanoma data, ctDNA responders were defined as 0.5 log reduction. Do you expect the threshold for meaningful correlation to longer survival to be similar across indications, like in ovarian in lung?

Speaker 17

And the second question was, when might we expect an update from the endometrial cohort? Thank you.

Speaker 5

Yes, I'm happy to take both of those. So, ctDNA response criteria are still in their early stages. Externally, companies have looked in lung cancer, for example, at a 0.5 log reduction. So there's precedence of that called the molecular response. In our cutaneous melanoma data that 0.5 log reduction did seem to sorry, in iuvial melanoma data that 0.5 log reduction did seem to be a good threshold cutoff for correlating with survival.

Speaker 5

We saw the same correlation in cutaneous melanoma and we'll share that data on CPD at on the ovarian data at ESMO. But it does look like that 0.5 log reduction I think is a good log reduction is a good threshold for us based on the data we have today. In terms of the endometrial timeline, I think it's a little too soon to guide because as I mentioned, we've asked the team to focus on ovarian line and continuous melanoma. We've asked the sites to focus on that as well.

Speaker 16

Thank you.

Operator

Thank you. Our next question comes from the line of Naureen Kibria with Capital One Securities. Please proceed with your question.

Speaker 17

Hi, good morning. Congrats on all the progress. I guess my first question sort of follows up on the last one. In terms of the premium results that you'll be presenting at ESMO, you've observed benefit with KimTrak outside of Rhesus response, right? So can you remind us how you're tracking response rates underestimates?

Speaker 17

Should we just focus on the disease control rates or you mentioned that there'll be ctDNA, is there anything else?

Speaker 5

Yes, it's a good question. I mean, we certainly saw this with uveal melanoma. This even patients with radiographic increase in size had benefit the survival benefit, long term survival. We saw a few patients of those with brinetifust in the cutaneous melanoma. We will, I think, continue to see that in the ovarian and the line as well.

Speaker 5

I think the way that we're looking at how do you measure benefit, of course, is CpDNA, which is a way to measure independence of radiographic, but also looking at treatment beyond progression because this is where the investigator sees the patient having a radiographic increase in size, but they feel the patient's benefiting. So if we saw this early, this treatment beyond progression was a good initial indicator. Now although we do see this PD benefit, we see it very strikingly for KimTrak, we feel that with prunetifrost disease control rate is an equally is a very good metric, to predict PFS. And in fact, my sense of the data is that although vinitivelyst does have benefit in the TB, it is more of a disease it has more disease control than contracted. But I think at the end of the day, of course, survival will be the ultimate endpoint.

Speaker 5

I do feel PFS is still a good endpoint for prunatifrost. Mohammad, anything to add on that? No.

Speaker 17

Okay. That's helpful. And I guess sort of sticking to the ovarian cancer topic, what's the distribution of PRAME compared to folate receptor? Is there like an overlap there? I guess I'm just trying to gauge if you expect to see any patients coming off of the Euler hair into this.

Speaker 17

Would there be any of those types of patients in the combo?

Speaker 6

Sure. Noreen, happy to address that. So for PRAME per se, it's very similar to in ovarian, it's very similar to melanoma, it's around 80% to 90%. With the rest of the folate receptor alpha, for ala heart, it's like between 35% 40%. The exact overlap, I don't think we have that data, but there's probably some overlap, but you can derive sort of 30% to 40% for folate receptor and 80% to 90% is the prevalence for premium ovarian.

Speaker 5

I'll just add that what we've seen continually we saw in melanoma BRAF mutant wild type in the and with the EGFR, because we've looked at that, mutation of that is in line that we see brain expression independent of whether there's a mutation or not. And so although as Mohammad said, we don't have the exact overlap with folate receptor alpha, I suspect 90% of folate receptor alpha positive are going to be positive for PRAME and I suspect 90% of folate receptor alpha negative are going to be. I suspect that, but we just don't have that data right now.

Speaker 17

Okay. Thanks so much. Thanks for taking my question.

Operator

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

Speaker 19

Hi, thanks for taking my question. So, just coming back to KimTrak dynamics and I just wanted to get your thoughts on how you see pricing evolving in the long term. So I think it was Slide 10 where you laid out the increased patient opportunity with the additional indications. But just given the extent of that potential volume uplift, do you expect there to be some pressure on price both in the U. S.

Speaker 19

And in Europe? And I guess related to your comments on Europe, if there is kind of downward pressure on price with these additional indications, do you think that the European launch would be viable for those? And then just to follow-up, and sorry if I missed it, but in ovarian cancer, do you expect to include frolate receptor alpha positive patients in that trial as well? And then just one follow-up on HIV, if I could. Where do you think dose could go?

Speaker 19

So I think at the minute you said 300 is the upper level. Related to that, how high do you think you can dose? Thank

Speaker 2

you. Great. Thank you, Roger. And I think several questions. Maybe we'll start with the HIV and then we'll go from there to commercial.

Speaker 5

Yes. So with the HIV, I mean, if you remember, we showed at 15 micrograms, we're already seeing target engagement because we saw IL-six. With our platform, you don't need to give a lot. With Kimtrac, it was in the 60 4, 68 microgram dose we see a survival benefit. So, we don't know how high we can go.

Speaker 5

We're going to go as high as needed, but we certainly know that you don't need to go up to milligram doses with our platform. In terms of the folate receptor alpha, we don't exclude prior folate receptor alpha. In fact, we have had a few patients who were who had prior ADC enroll on for our trial. Our approach once again is not to replace the MRR VA. It's not to go head to head, which is why it's to add on to chemotherapy.

Speaker 5

And so it's independent of the market data.

Speaker 2

And, Ross, can you comment on the reimbursement just to reiterate here? I don't think we have any issues in the U. S, but it's mostly the EU. Go ahead, Ralph, please.

Speaker 3

Sure. Happy to. So first of all, our pricing strategy really depends on the benefit that we see from the data, right? So if it brings benefit, significant benefit to patients and society, that's how we price our further indication. To your question on the U.

Speaker 3

S. And to Basijo's point, we have not seen any downward pressure in the U. S. So far. In fact, I expect that if the data is good and cutaneous, given that these are settings of high unmet need and with small patient populations that we would not have to erode the price significantly in the U.

Speaker 3

S. The other hand in Europe, you have a good question in terms of price erosion. And I think it's too soon to tell. We need data for us to decide whether we'll be launching in Europe or not. Although it is a very tough market access environment, frankly, one of the toughest I've seen through all my years working with Europe.

Operator

Thank you. Our next question comes from the line of Ethan Markowski with Needham and Company. Please proceed with your questions.

Speaker 20

Yes. Hi, this is Ethan on for Gil. Thank you for taking our questions. I think most of them have been answered thus far, but just wondering, so I know endometrial is not one of the focus indications for PRAME, but wondering if you plan on going into a similar strategy there where moving maybe combination in earlier lines like you're planning to do a non small cell lung cancer and ovarian? And then for KimTrak, you talked about the difficult reimbursement in Europe.

Speaker 20

Will growth there really be mostly driven by just adding additional countries? Or do you think that those dynamics are likely to change over time? Thank you.

Speaker 2

Thank you, Ethan. Mohamad, you can take the first one and Dovals maybe on Europe.

Speaker 6

Thanks Ethan for the question. I think as David mentioned, the focus has been on ovarian melanoma and lung for now. So the endometrial data that we're generating is really in monotherapy with some of the chemotherapies that are used in late line. And right now, we don't have current plans to explore endometrial in early lines until we actually generate data in the late lines to guide.

Speaker 3

Rob? Sure. So there is in fact a very tough environment in Europe as we've been discussing. However, we've had a lot of successes when it comes to reimbursement. So we've had 9 launches in the first half of the year.

Speaker 3

And we expect some of that marginal growth will come from further additional launches because we're currently in negotiations with several countries. In addition to that, I mean, obviously, we're very well penetrated. The team has been doing a great job in Europe. So really, it's the launch that's driving the next level of growth.

Operator

Thank you. There are no further questions at this time. I'd like to hand the call back over to Bahija Jallal for closing comments.

Speaker 2

All right. Thank you, operator. So once again, I just want to thank you for your patience, first of all, and continued trust and commitment, and we'll now close the call. Thank you.

Operator

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

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Earnings Conference Call
Immunocore Q2 2024
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