Immunocore Holdings plc (IMCR) Earnings Call Transcript & Summary

Good day, ladies and gentlemen. Thank you for standing by. Welcome to Immunocore's FDA approval of KIMMTRAK webinar. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Brian Di Donato, CFO and Head of Strategy from Immunocore. Please go ahead, sir.

Thank you, Kevin. Good morning, and good afternoon, everyone, and thank you for joining us today to discuss the FDA approval of KIMMTRAK. Before we begin, I'd like to remind you that this call will contain forward-looking statements concerning Immunocore's future expectations, clinical development and clinical trials, regulatory approval processes, plans, prospects, corporate strategy and performance, which constitute forward-looking statements for the purpose of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our filings with the SEC. We're very pleased you can join us on this special day as we announce the approval of tebentafusp, trade name KIMMTRAK; the first and only FDA-approved therapy for metastatic or unresectable uveal melanoma. On our call today, we will hear an introduction from our CEO, Dr. Bahija Jallal; a review of our randomized Phase III clinical trial results from our CMO, Dr. Mohammed Dar; and an overview of our commercial and launch strategy from myself; and our Head of Commercial, Ralph Torbay. After that, we'll have concluding remarks from Bahija and then we'll open the call for questions. I'll now turn the call over to Bahija.

Thank you, Brian, and thank you for joining us today. To say that we are thrilled is an understatement. This is a tremendous day for patients and for Immunocore, every patient with uveal melanoma in the U.S. We just announced that the FDA has approved tebentafusp, now known as KIMMTRAK, for the treatment of HLA-02, unresectable or metastatic uveal melanoma. This new treatment was granted orphan drug designation, priority review and breakthrough therapy designation. It was also reviewed under the Real-Time Oncology Review pilot program. We are thrilled that the approval came 1 month before our PDUFA date of the 23rd of February 2022, and only 5 months after BLA acceptance, I am so proud of the team and their hard work. Uveal melanoma is a devastating aggressive disease, which until now has had no FDA-approved treatment. In fact, by NCCI guidelines, the standards of care for these patients was a clinical trial. But today, this will change. KIMMTRAK is bringing hope to these patients. Evidence from our Phase III clinical trial showed that KIMMTRAK provides a highly significant and clinically meaningful improvement in overall survival over checkpoint inhibitors and chemotherapy. We were very proud that the totality of the data was published in New England Journal of Medicine. But for us, it's even more important because it also brings a very strong validation of the science at Immunocore and our new platform. This is a real bench to bedside story that has been in the making for 15 years. We are truly pioneering a new class of therapeutics. It's not a lot of time where you can say that in your career. So I'm going to say it again. We are truly pioneering a new class of therapeutics. KIMMTRAK represents a number of firsts for us and for patients. KIMMTRAK is the first approved TCR therapeutic, first and only approved treatment for metastatic uveal melanoma and unresectable, the first TCR engager to show overall survival in solid tumors. This also opens the way for more innovative science and exciting molecules that we have in the pipeline and then have the potential to help even more patients. In fact, after the trial was stopped early for efficacy and before approval, we launched our global early access program to bring this medicine to patients around the world. We have made KIMMTRAK available to more than 200 patients in 13 countries. Now today, with this approval, the Immunocore team, the Board and myself are extremely confident that our commercial, medical affairs and value access program teams are ready to ensure that every patient in the U.S. that needs -- who needs KIMMTRAK is treated by KIMMTRAK. We intend to launch immediately, and the medicine will be available in the coming weeks. Our profound gratitude is extended to patients, their families, the uveal melanoma community, our clinical trial investigators, their caregivers, investors and our employees. So now I'll pass it on to Mohammed, our CMO, who is delighted to talk about the data behind the approval. Mohammed?

Thank you, Bahija. It's my distinct pleasure to be here with you today and to provide an overview of the data supporting KIMMTRAK approval. By way of background, around 1,700 people every year in the U.S. are diagnosed with uveal melanoma, an ultra-rare and aggressive tumor of the eye. Not only does this diagnosis mean loss of vision in the affected eye, but it also begins an anxiety-filled watch-and-worry period to see if the uveal melanoma will come back. Unfortunately, in about 50% of cases, the disease does come back. And when it does, it metastasizes usually to the liver. Until today, these patients were then told by their physician that there were no FDA-approved therapy specific for this dreadful disease, and that the median survival was only about a year. Today, KIMMTRAK offers a new option for eligible patients and represents the first real innovation in the treatment of metastatic uveal melanoma in decades. Approximately 400 patients with metastatic uveal melanoma will be eligible for KIMMTRAK annually. This is based on the fact that about half of the 1,700 diagnosed each year with primary uveal melanoma will eventually develop metastatic disease, and about half of those are expected to be HLA-02:01-positive. With this background, I want to now introduce KIMMTRAK and walk you through the Phase III data that supported its approval. KIMMTRAK is a novel off-the-shelf bispecific T-cell engager designed to target gp100-expressing tumor cells. The target of KIMMTRAK gp100 is a protein normally expressed by pigment cells, melanocytes, in the skin, as you see on the left, and is strongly over expressed in tumors such as cutaneous and uveal melanoma. KIMMTRAK's mechanism of action is based on its bispecific design. It has a targeting end, which is the end that uses the TCR to bind gp100 peptide HLA complex on tumors, and it has an effector end, which uses a CD3 domain to bind and redirect polyclonal T cells to kill tumor cells. The Phase III trial supporting KIMMTRAK approval was the largest such trial ever conducted in patients with metastatic uveal melanoma. 378 patients who are HLA-02:01-positive, and had newly diagnosed metastatic uveal melanoma and had yet to receive prior therapy were randomized 2:1 to receive either KIMMTRAK or investigator choice. Most patients in the investigator choice arm, 82%, received pembrolizumab. The primary endpoint for the trial was overall survival, which is the gold standard in oncology. This study met its primary endpoint with a very strong survival benefit in favor of KIMMTRAK. There was an almost 50% lower risk in death noted among patients who received KIMMTRAK and median overall survival was 21.7 months. As you see on the right, the Kaplan-Meier survival curve separated early and remain separated throughout the entire study, highlighting the early treatment effect and durability of benefit. The safety profile was consistent with the proposed mechanism of action and fell into 2 major classes, rash and cytokine release syndrome. The overall safety profile was predictable with most adverse reactions occurring during the first 3 weeks and was also manageable with a very low rate of treatment-related discontinuation and no treatment-related death. Cytokine release syndrome results from rapid T cell activation. All immune therapies, including KIMMTRAK, that induce CRS have a box warning, in part because of the potential risk for CRS rapidly becoming serious or life threatening. In our Phase III trial, the CRS profile was predictable and manageable. Most episodes occurred after the first 3 doses and decreasing frequency and severity with repeat dosing. The majority of patients experienced mild to moderate CRS, while we observed a low rate of Grade 3 CRS and there were no Grade 4 or fatal CRS events. The following is a summary of the prescribing information. In addition to dosing and safety, the prescribing information also provides a summary about how the clinical studies were conducted, including a treatment beyond progression in patients who continue to derive benefit. Before I pass it on to my colleague, Ralph Torbay, I really want to reflect on this tremendous day and the amazing journey that my team and I have been on to deliver this innovative medicine, KIMMTRAK, to patients who have been waiting for years for a medicine that can truly offer a promise for extended survival. Ralph?

Thank you, Mohammed. I'm thrilled to be here today to discuss the commercial plans for KIMMTRAK. I have made it my mission and the mission of my team to deliver life-saving medicines to patients. I have been fortunate to have personally delivered 3 such launches in the last 4 years. Now it is my greatest privilege to launch KIMMTRAK as it establishes important firsts for industry and medicine. KIMMTRAK is the first approved TCR therapeutic. It is also the first T cell engager to show an overall survival benefit in a solid tumor. And most importantly, as of today, it is the first and only FDA-approved treatment for metastatic uveal melanoma. We are excited by the opportunity to deliver this groundbreaking new therapy to patients. Every patient matters, and our ambition is to help as many patients with metastatic uveal melanoma as possible. To do so, we have established a lean, fit-for-purpose global commercial footprint that is launch-ready in the U.S. and soon to be launch-ready in Europe. In addition, we are complementing our direct Immunocore footprint with a network of commercial partners with oncology and rare disease experience to expand our reach to more patients globally. We are launch-ready. The U.S. team is ready to change the practice of medicine to establish KIMMTRAK as the first line standard of care for eligible patients with metastatic uveal melanoma. We have built our U.S. commercial capabilities by hiring and deploying a dedicated and highly experienced team with an average of 11 years of oncology, melanoma and rare disease expertise. Our team of medical sales and market access representatives are prepared for launch. I'm very proud of the work this team has done over the past several months. They have profiled 300 accounts that we believe capture 75% of all potential U.S. patients with uveal melanoma. In the next 48 hours, this highly capable team will be trained and ready to promote KIMMTRAK. This field team is complemented with an omnichannel approach that will be in field within the first week of launch. Ultimately, we look forward to meeting our 2 launch objectives of establishing KIMMTRAK as a standard of care in first-line mUM and to support patients throughout their treatment journey to achieve an optimal outcome with KIMMTRAK. For us to help patients, we must ensure that they have access to KIMMTRAK as rapidly as possible. To achieve this, we have profiled and engaged with our top payer accounts and decision makers covering over 90% of eligible patients with metastatic uveal melanoma. Along with rapid access, we plan to make KIMMTRAK commercially available within weeks of launch. I am grateful to our highly capable and dedicated regulatory supply and market access teams who have validated our global supply chain, have contracted with a network of specialty distributors covering 100% of our customer base and have ensured that our launch supply is already in the U.S. to avoid any potential delays due to COVID. We are determined to ensure that all patients in our early access program are supported and that there are no treatment interruptions in the transition to commercial supply. We have taken an inclusive approach to determining the value of KIMMTRAK based on consultations with patients, patient advocates, payers and health care professionals. I am pleased to say that all stakeholders recognize the compelling value proposition KIMMTRAK brings to patients and society. This value is anchored on our unprecedented overall survival and supports our pricing approach. The wholesale acquisition cost of 100-microgram vial of KIMMTRAK is $18,760. Based on a median duration of treatment of 5.3 months as observed in our Phase III clinical trial, we expect a median total cost of KIMMTRAK to be around $400,000. This price does not include mandatory discounts, and of course, patient out-of-pocket costs will vary based on their insurance. To support patients throughout their treatment journey, we have established KIMMTRAK Connect. This is our comprehensive patient assistance program designed to help patients with personalized and proactive support. KIMMTRAK Connect offers 2 core pillars of assistance to patients. First its personalized education and support delivered through a dedicated nursing staff as well as financial assistance aimed at ensuring patients have access to KIMMTRAK regardless of their personal or financial situation. Every patient matters, and KIMMTRAK Connect is another way we show our support to patients. Today is a historic day for all of us at Immunocore and most especially for our patients. Perhaps best captures what KIMMTRAK's approval means for the metastatic uveal community. I cannot possibly do it justice. So I'll pause and give you a moment to take it in for yourselves. As you might imagine, the Immunocore team and I are more determined than ever to support this community and to give hope to patients who until now have had no approved treatment options. Thank you. And I will now invite back Brian to discuss our 2021 achievements and 2022 milestones.

Thank you, Ralph. 2021 was a transformational year for Immunocore, and I am proud to be part of the team that is bringing life-changing medicines to patients. As you heard from Ralph and Mohammed, our teams have accelerated our global regulatory applications for KIMMTRAK, received a priority review in the United States and an accelerated review in Europe. We have opened a global early access program for metastatic uveal melanoma patients and we have now dosed over 200 in 13 countries at no cost to them. The teams are prepared for the global launch of KIMMTRAK. In addition, we continue to advance our oncology portfolio. With new KIMMTRAK efficacy data in cutaneous melanoma presented at SITC in November and our initial MAGE-A4 Phase I data that included responses in ovarian and head and neck cancers presented at ESMO IO in December, we have now validated our ImmTAC platform in multiple solid tumors, with both low and high tumor mutational burden and both low and high protein expression. Importantly, with our February initial public offering, we have improved Immunocore's capital position to invest in our growing development portfolio. As we began 2022, our team's plan is to, number one, continue to ensure as many patients as possible globally have access to KIMMTRAK; two, expand KIMMTRAK into other melanoma indications, including cutaneous melanoma; and three, accelerate the development of our ImmTAC's targeting PRAME and MAGE-A4 in multiple solid tumors. I would now like to turn the call back to Bahija for concluding remarks before we open for questions.

Thank you, Brian. So where do we go from here? The team is working really hard to bring KIMMTRAK to patients outside the U.S. In fact, we have had our application accepted by the MHRA and the EMA. We had also our marketing authorization applications accepted in Canada and Australia under priority review. But before I open the call for questions, I would like to take a few moments to reflect that this team joined the company 3 years ago for the exciting science and the platform, but to really what attracted us is that potential that KIMMTRAK has. We saw that potential. So I am delighted that we have achieved our goal of bringing this medicine to patients today. So once again, I offer my sincere thanks to everyone who believed in Immunocore, to our employees past and present, patients and their families and to the FDA for a very collaborative interaction. Thank you. And now operator, back to you.

[Operator Instructions] Our first question today is coming from Michael Yee from Jefferies.

Congratulations. A great achievement for you guys. Congrats. We had a question around how you're thinking about the commercial launch as you get underway here. On one hand, while you don't have specific guidance, could you just maybe talk about how many patients do you think you could get on by the end of the year and the visibility you have on that? And then maybe the dynamics at play, for example, the sickest patients might be getting on early. Maybe just talk about the present pressure with the launch and how many patients do you think you could have in the first year?

Great. Thank you, Michael. And I'm really very, very thrilled. We are ready. The team is ready. And I'm pretty sure, Brian and Ralph will talk about what we intend to do. Very briefly, we're not guiding just because we are really getting into a new territory, if you will. This is -- there was no analogs before, but we can give some colors from Ralph and from Brian.

Thank you, Bahija. So from a launch perspective, the team is, in fact, ready. What they've been doing really is profiling 300 accounts that based on claims data, we believe really capture 75% of the patient population, and we've made it a priority for the field. Now we plan to reach 100% of patients through what we call the omnichannel approach, which is a set of different tactics that we're putting in place week 1. So our goal is 100% of patients in the U.S. Of course, that's going to take some time for us to get there. Brian?

Yes. As you heard, Michael, the EAP is open to currently dosing over 200 patients. The majority of those are in Europe and slightly less in the United States. So within weeks, we'll be transitioning those patients to commercial. Commercial medicine is our #1 objective that we are aware of patients ready and waiting for the approval that aren't on the EAP because the EAP was individual IND and a very labor-intensive process. So we recognize that. So there will be new patients early. And the overall 2022 projections will really be driven by the timing of the European accelerated approval. So right now, we're targeting a Q2 launch in Europe, Germany first. We -- as you know, we are already receiving revenue in France. France has a program where they pay for the EAP patients, and we started receiving that revenue in August. And on March 3, on our earnings, we'll announce what those numbers are, but that's only a fraction of the market opportunity, we believe, in France once we get approval. The other thing I'll say is in our second quarter earnings in early August, we'll have a better sense of the European launch trajectory, and we'll give you more guidance on what the full year 2022 will look like.

Okay. So let me be clear. You have 200 people in EAP, most of them are in Europe, but those could start transitioning to paying drug after approval in the U.S. Of that 200, perhaps dozens are in the U.S. And so those could transition pretty quickly? Is that a fair statement?

That's a fair statement. About 1/3 are in the U.S., a little over 1/3. Yes.

Our next question today is coming from Jessica Fye from JPMorgan.

Congrats on the approval. Maybe similar to Michael's question. When we think about those greater than 100 patients on EAP in Europe, I'm trying to think about how fast they could transition to revenue-generating patients, obviously, excluding those in France where you're already getting revenue.

Thank you, Jess. I'm pretty sure, Ralph, you can address that.

Thank you, Bahija. So first, Jess, I think we're very proud of the commitment that the team has made to accelerate patient access through the EAP. And we plan to support every patient throughout the transition. As you know, in Europe, the different countries launch at different times because they reimburse at different times. So as Brian mentioned, we will be focused initially on Germany and France. And then eventually on the remaining countries that are the wave 1 where Immunocore is supporting these patients in the commercial transition.

Great. And do you see any potential for off-label use? I recognize you have a frontline approval here, but what about other patients who might benefit from therapy?

Yes, definitely. We can't comment on that, but pretty sure, David...

Yes. I mean, I'll just comment on the excitement we have about the cutaneous data. That was a Phase I and a small Phase II data. And so we plan to follow up on that this year with the start of a randomized trial in cutaneous melanoma.

Your next question today is coming from Justin Kim from Oppenheimer.

Congrats on the very impressive news this morning. Maybe just on sort of the measurement of response and clinical benefit. Could you discuss how the EAP and other sort of data may help inform how you sort of guide physicians to measuring clinical benefit for patients and potentially keeping patients on drug when they could still benefit?

Thank you, Justin. Thank you very much. We're very thrilled. Yes, definitely, I think we -- that's the real world, if you will, that we will learn a lot from there. But David, do you want to comment?

Yes, I'm going to start and then I'll ask Mohammed. This is a new mechanism that we're pioneering here. So we're also continuing to learn. You do have the traditional RECIST criteria, but we found that underestimated the benefit. We published some data showing ctDNA reductions correlated to survival, but that is still exploratory in nature, and we have to validate that. Mohammed, do you want to comment on how patients were treated in the clinical trials with regard to assessments and benefit?

Sure. Absolutely. So the trial actually prespecified the possibility of treatment beyond progression. And our investigators are actually quite experienced from immunotherapy perspective. So the trial allowed if patients had radiographic progression that they could be treated beyond progression as long as they were continuing to derive clinical benefit. And around 43% of patients were treated beyond progression based on the protocol guidance.

Great. Great. And maybe just to follow up on another sort of line of questioning. With the recent approval, do you think that sort of an available product could help facilitate or accelerate some of the ongoing clinical activities with tebe? And just curious whether you talked about investigator-sponsored trials or other sort of avenues as well?

Yes, Justin, I think I missed -- I didn't hear very well if that would accelerate. That's where I could not hear what you said. If you could repeat that, that would be great.

Just to sort of expanded and sort of development of tebe and sort of potential for investigator-sponsored trials, et cetera?

So yes, absolutely. I think we have our -- like David said, like this is a new mechanism. So the more we learn, the better. And I think that gives us an opportunity now through the medical affairs for ESRs and which we already started talking about and started on the ESRs. That also, more importantly, is what David said, we will be going into cutaneous melanoma, the data that we showed ourselves. So I think we have the opportunity now to explore a lot more and learn a lot more, which is also going to benefit the rest of the platform.

Our next question today is coming from Keyur Parekh from Goldman Sachs.

Hopefully you guys can hear me okay? And many congratulations on the approval. Just wondering if you guys have had a feedback from any of the kind of key payers from a U.S. perspective on kind of the patient's need here? And how do you think about the ramp from a U.S. perspective in the near term? And then secondly, as we think about the next kind of the further progression for the company, kind of can you just remind us of kind of what is -- what data we're going to see for both kind of the PRAME and the MAGE-A4 programs later this year?

Thank you for your question, Keyur. And yes, we'll address first the -- what you're going to see in the data, and then we'll go back and Ralph will address the first part. So we are -- as you know, for MAGE-A4, we have shown that there is activity, and we also showed that we have an expansion arm that we started. So we are basically intending to bring updates on that trial by the end of the year. On PRAME, as we have shared, we have 39 patients dosed when we shared the -- yes, on the Q1. And then we are on track actually to present data either somewhere between June and September, either for ASCO or ESMO. That's what we said. So we're on track there. You want to address the beginning. I think we hear something on the line, if somebody can mute their line. Okay?

Thank you, Bahija. So we have profiled and engaged with our top payer accounts and decision makers that cover over 90% of what we believe will be eligible patients with metastatic uveal melanoma. Based on those conversations, I can tell you that they have recognized their value proposition and it's ultrarare and devastating disease. And it's really seen the unprecedented OS as transformational for patients. And that's really where we based our value proposition on.

And your next question today is coming from Matt Phipps from William Blair.

And obviously, congratulations on the big approval. Just curious if, following up to Justin's question, will you try to actively educate physicians on using ctDNA as a better way to assess those patients that are receiving benefit? And then can you just maybe walk us through that 16 hours of initial monitoring for the first 3 doses? Is that -- do you see that as being kind of a limit to initial patient update?

Yes. Great. Thank you, first of all, and great question. So I'll address the ctDNA and then Mohammed will address the 16 hours. So the ctDNA data that's very encouraging that we published was in a conference was on the Phase II. We were -- we want to validate that first in the Phase III trial. So we were waiting to do the data to do basically until we have the approval. And so if validated, then we can go from there. So that's -- I think it's an exciting area, but it's also early, and we need to validate this data in Phase III, which we will do hopefully and share with everybody this year. Mohammed, do you want to talk about the 16 hours?

Sure. So we've actually now dosed over 700 patients with KIMMTRAK and have really found that the safety profile is quite predictable and manageable. Patients do need to be monitored for 16 hours after the first 3 doses, and this is really based on our experience in Phase II where we developed the algorithm, and then we subsequently validated it in Phase III. And we've shown that this is quite feasible and it's effective approach for monitoring the expected safety profile. In the U.S., we expect that most patients will be able to be -- this monitoring can take place in the outpatient setting. And then ultimately, this is really a new class of therapy. And so we're going to continue to learn over time based on the emerging data, what's the best way to monitor and continue to improve on the algorithms we develop. We're confident in terms of the guidance that's incorporated into the label.

And then, Mohammed, I think just to add, if the CRS will happen, it will happen at the beginning of the treatment. So that's, hence, the 16 hours.

Thank you. We've reached the end of our question-and-answer session. I would like to turn the floor back over to management for any further or closing comments.

Well, thank you, operator, and thank you, everyone. Really, again, we are thrilled. This is a huge day for patients and for Immunocore as a whole. But make no mistakes, we're going back to work right away because there are more patients still waiting for KIMMTRAK. So thank you so much for your support. We don't take it lightly, and we just, again, hopefully, we'll come with more medicines for more patients as we progress. Thank you so much.

Thank you. That does conclude today's teleconference webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.