This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk00: Good morning, ladies and gentlemen, and welcome to Immunogen's third quarter 2023 financial and operating results conference call. Today's conference is being recorded. At this time, I'd like to turn the call over to Annabelle Chen, head of investor relations.
spk15: Please go ahead. Good morning, and thank you for joining today's call.
spk04: Earlier today, we issued a press release that includes a summary of our recent operating progress and third quarter financial results. This press release, a recording of this call, and an updated corporate deck can be found under the Investors and Media section of our website at Immunogen.com. With me today are Mark Ennedy, our President and CEO, Isabel Califonos, our Chief Commercial Officer, Michael Vasconcellos, our EVP of Research, Development, and Medical Affairs, and Lauren White, our CFO. During today's call, we will review recent progress for the business, our financial results, and highlight upcoming anticipated events. We will be making forward-looking statements based on our current expectations and beliefs. These statements are subject to risks and uncertainties, and our actual results may differ materially. Please consult the risks outlined in our press release issued this morning, in the risk factor section of our most recent annual report on Form 10-K, and quarterly report on Form 10-Q, and in our other SEC filings, which are available at sec.gov and immunogen.com. With that, I'll turn the call over to Mark.
spk07: Thanks, Annabelle. Good morning, everyone, and thank you for joining us today. This has been another productive quarter for Immunogen, highlighted by the ongoing exemplary execution of the commercial launch for Elihir in the U.S., progress made towards both geographic and label expansion for Elihir, and the advancement of our portfolio. Starting with a commercial update, we delivered a strong quarter, with Elihir generating just over $105 million in net sales resulting in over $210 million in revenue year to date, which puts us on track for one of the most successful oncology launches in a decade. This performance is driven by a combination of factors, including strong adoption of FR-alpha testing and corresponding product ordering in a population with high unmet need, with robust uptake in our labeled indication across both academic and community settings, as well as discretionary use in a broader patient population based on NCCN guidelines, including use of Elihir monotherapy in later lines and in combination with Bevacizumab. Rapid achievement of broad access and reimbursement, increased breadth and depth of prescribing driven in part by penetration into priority accounts, and increased awareness of Elihir driven by engagement by our medical affairs team, the compelling data from Mirasol, and positive physician and patient experiences. Looking forward, we expect continued growth, albeit at a moderating pace, supported by continued focus on execution with respect to our launch imperatives, a strong and growing prescriber base, and Elihir becoming the medicine of choice for patients with FR-alpha positive disease. Isabel will have more to say about our current and future business in a moment. As we aim to expand the geographic footprint for Elihir and look to bring this novel ADC to patients globally, we are pleased to share that the EMA has accepted our marketing application to support potential European approval, and our partner, Wadong, received acceptance of the NDA in China. In addition, we announced a collaboration with Takeda to develop and commercialize Elihir in Japan. and submitted a supplemental BLA to FDA to support the conversion of the accelerated approval of Elihir to full approval here in the U.S. In step with our commercial efforts, we are advancing the broader Elihir development program to support label expansion into platinum sensitive disease and to position Elihir as the combination agent of choice in ovarian cancer. In this context, we are pleased to share that our PICOLO phase two trial evaluating Elihir monotherapy in platinum-sensitive ovarian cancer has met its primary endpoint of objective response rate. Noting that PICOLO is ongoing and patients are continuing to receive Elihir, to date we've observed no new safety signals in this patient population. These data represent an important step towards expanding Elihir into the platinum-sensitive setting And Mike will discuss these data in more detail shortly. Turning briefly to the rest of the pipeline, in our second pivotal program, PVEC, we look forward to reporting data from our PVEC triplet and frontline AML later this year at ASH. And we are on track with top line data from the pivotal frontline de novo cohort in BPDCN expected in 2024. In addition, IMGC 936 and IMGN 151 are progressing. We remain focused on reinvesting in our research capabilities and expanding our pipeline. Lastly, I'm pleased to report that we strengthened our leadership team with the recent appointment of Lauren White as Chief Financial Officer, and commensurate with our expanding commitment to continued innovation of our ADC platform, we welcome Heather Hewitt as Chief Scientific Officer. With an experienced management team in place and a strong balance sheet, We are well positioned to expand the commercial opportunity for ELA here, and in parallel, continuing to advance and invest in our pipeline. With that, I'll turn the call over to Isabel to cover our commercial progress. Isabel?
spk18: Thank you, Mark. The commercial team built upon the strong momentum established in the first half of the year and delivered another strong quarter as we continue to make progress towards positioning ELA here as the standard of care for foliar receptor alpha-positive ovarian cancer. In the third quarter, we saw a 35% sequential growth versus the prior quarter. We are pleased with our performance since launch and believe it is due to a combination of four key factors, including a strong adoption in an area of high-end med needs, rapid access and reimbursement coverage, the solid execution of our commercial customer-facing team, and increase physician experience and awareness of the benefits this novel treatment brings to patients with advanced ovarian cancer. Let me take some time to address each of these key factors in more detail. First, let me share some insights into Dynamics Observe while launching into an area of high amendment. Starting with the identification of eligible patients, almost a year into our launch, We have seen the overall awareness for FR-alpha testing increase and rapid adoption of the foliate 1 diagnostic being incorporated as a standard component of the initial panel conducted on newly diagnosed patients and for patients moving to the next line of therapy. Our market research indicates that over 80% of physicians are familiar with FR-alpha testing, up from a baseline of under 50% at the time of approval. It is becoming the standard of care that will enable oncologists to rapidly incorporate ELLA here into their treatment decision. Needless to say, testing has not been a barrier to adoption. Since launch, we have endeavored to provide the market with the number of tests conducted at our three largest centralized labs. As of the end of the quarter, that number stood at roughly 16,000 tests. However, with approximately 40 labs now certified to run the test, our visibility into the number of tests performed has decreased, and we will continue reporting on this metric on subsequent calls. We will, however, continue to report the foliar receptor alpha positive rate, which remains between 35 and 40% in line with our expectations. Looking at patient adoption. Ella here addresses a high unmet need among platinum-resistant ovarian cancer patients, as indicated by the initial strong uptake in later lines where the need has been greatest. In the first quarter, the vast majority of patients were from later lines of therapy, and as the launch has progressed, we'll see a shift to earlier lines. This is a slow and steady trend, and we expect this to become a key driver of future growth. Moving to our second key factor, access and reimbursement. Given by the effort of our access team, we secured coverage policies aligned to our label for over 95% of both Medicare and commercial life within the first seven months of launch, exceeding another benchmark, ADCs. In addition, with the inclusion of LIHEAP and NCCN guidelines, we have seen utilization in a broad population including the use of monotherapy in later lines and in combination with an assistive map in low, medium, and high FR-alpha presentations. Third, a strong execution by our commercial team driving adoption of ELLA here. Our customer-facing field team has been highly active since launch. During the third quarter, they continue to engage priority targets to broaden our reach, resulting in continued growth in both academic and community accounts. Complementing the account generation is a significant percentage of accounts with repeat orders. While academic institutions continue to comprise our largest customers, roughly 70% of orders during the quarter came from non-academic institutions and community-based oncology groups. consistent with the prior course. And lastly, increase physician experience and awareness. We place a high priority on increasing awareness and cultivating a positive physician and patient experience. Based on our market research, in August, with over 120 physicians across the academic and community setting, over 80% of physicians are aware of ELAHIR. This has nearly doubled since April, and we are especially pleased to see awareness increasing with medical oncology. We attribute this to the compelling data from Mirasol and to the robust engagement by our medical affairs team, who has continued to provide a full suite of support to ensure positive physician and patient experience. As a testament to their efforts, Reports from the field consistently relay enthusiastic feedback from clinicians regarding their experience with Elaheer. In summary, we are very pleased with our performance today, and based on the market research I just referenced, we expect continuous growth due primarily by, number one, increasing alpha testing. Awareness of FR-alpha testing as a biomarker is already high, and physicians indicate a 30% growth with the convenience of in-house testing and testing earlier in the patient journey. Two, increasing awareness of the benefits ELLA here brings to patients with advanced ovarian cancer. As physicians gain experience and our medical affairs team continues to educate on our clinical data in both monotherapy and in combination Our research shows that physician education translates into increased depth and breadth of prescribing, with current prescribers projecting higher rates of utilization in both monotherapy and combination. Also, we anticipate physicians previously unaware becoming new adopters. We also expect to see increasing treatment rates over historical benchmarks, given the compelling efficacy of LIHEAP and increased experience with the treatment, including the management of adverse events. Four, signs of therapy. Improving perceptions relative to the standard of care will support moving into earlier lines of therapy or treatment in the platinum-resistant setting. Finally, we are also currently fielding a demand study, and we expect to gain additional insight into the current and future utilization of ELLA-HEAR. With that, I would like to turn the call over to Mike to provide additional color on the ELLA-HEAR development program and our broader pipeline. Mike?
spk14: Thanks, Isabel. We were pleased to present additional data from MIRA-SAW. our randomized phase three trial of Elhir in platinum-resistant ovarian cancer at the 24th Annual European Society of Gynecologic Oncology Congress in September. Dr. Van Gorp, professor of gynecologic oncology at the University of Louvain, presented two subset analyses in an oral session, highlighting efficacy benefits with Elhir versus investigator choice or IC chemotherapy in progression-free survival, objective response rate, and overall survival. Dr. Van Gorp reported on subsets defined by the number of prior lines of therapy or prior PARP inhibitor exposure. With no new safety signals arising from these analyses, these findings provide valuable insights for physicians into Eliher's consistent clinical benefits compared to IC chemotherapy in both subsets. Turning now to the broader Mervituximab clinical development program, we aim to expand the ALAHIR label into platinum-sensitive ovarian cancer and further position ALAHIR as the standard of care in fully receptor alpha-positive disease. We are currently advancing three sponsored clinical trials in support of these objectives. Let's start with PICOLO, our single-arm phase two trial evaluating Mervituximab monotherapy efficacy and safety in patients with FR-alpha high platinum sensitive ovarian cancer who have received at least two prior lines of platinum containing therapy or have a documented platinum allergy. The unmet medical need in this patient population is noteworthy and growing, driven predominantly by two key factors. First, even if a patient meets the clinical criteria of platinum sensitive disease, each subsequent line of platinum containing therapy It's associated with both decreased efficacy, as measured by a lower probability of achieving an objective response and meaningful response duration, and decreased tolerability. With this reality, available therapy for these patients today is limited. Second, emerging clinical data indicate that treatment with a PARP inhibitor may negatively impact the efficacy of subsequent platinum-containing therapy. Given the importance of PARP inhibitors in the maintenance setting in the first line treatment regimen for many patients, these observations further reinforce the need for treatment alternatives. No randomized phase three data exists for the patient population enrolled and treated in PICOLO. No level one evidence, if you will. As such, there is no agreed upon established standard of care for patients with later line platinum sensitive disease. Therefore, to design this trial, we synthesized historic data of both non-platinum monotherapy and platinum-continuing regimens in similar patient populations. These analyses drove the trial's standard Simon two-stage design and its statistical assumptions. Regarding the former, we defined objective response rate as the primary endpoint. The key secondary endpoint was duration of response. Safety and tolerability were important additional study objectives. Based upon the assumed or hypothesized objective response rate, we established the trial size to rule out a confirmed objective response rate by investigators of 28 percent because an observed objective response rate exceeding 28 percent would set these data apart from the historic benchmark data I referenced above. In other words, a positive trial result would require an observed or actual objective response rate that excluded 28 percent based upon 95% confidence intervals. In the fully enrolled PICOLO trial, a total of 79 patients have been treated, most of whom have received prior PARP inhibitor therapy. As of today, a number of those patients remain on treatment, continuing to receive merpitexamab. Based upon the pre-specified trial design, until the response duration for the entire study population is mature, the trial remains ongoing. However, We are able to share today that, based on an interim assessment of response and safety, the primary endpoint of the study has been achieved. The investigator-assessed objective response rate excludes 28%, and we anticipate an overall objective response rate of at least 48% when we report the full data in 2024. Also of note, to date we have detected no new safety signals with Mervituximab. The insights I've shared today from the ongoing PICOLA trial are meaningful. As the numerically largest data sets for Mervituximab reported thus far in patients with platinum-sensitive disease, we believe these data reinforced earlier previously published data sets of Mervituximab in combination that demonstrate Mervituximab's potential in FR-alpha-expressing platinum-sensitive ovarian cancer, or PSOC. Assuming a tolerability and safety profile in PSOC that remains consistent with that observed across the Mervituximab development program, we see Mervituximab eventually becoming a new standard of care in PSOC, assuming a trajectory similar to that already underway in platinum-resistant disease. In addition to evaluating Mervituximab monotherapy in TICLO, we are advancing two trials designed to establish Mervituximab as the combination agent of choice in platinum-sensitive ovarian cancer. The first is Gloriosa, our phase three trial evaluating Mervituximab plus Bevacizumab maintenance versus standard of care Bevacizumab maintenance in a second-line platinum-sensitive setting. This study builds upon our robust Mervituximab plus Bevacizumab data in the platinum-resistant setting, which led to the NCCN compendium listing for this combination. This combination in the maintenance setting is designed to establish the opportunity for patients to benefit from even longer durations of therapy with Mervituximab. The second is trial 420, a single arm phase two study evaluating Mervituximab plus carboplatin with Mervituximab continuation until disease progression in platinum sensitive ovarian cancer patients with low, medium, or high levels of folate receptor alpha expression. Both Gloriosa and Trial 420 are enrolling in the U.S. and advancing in Europe. Moving to our second pivotal program, we continue to anticipate top-line data from the Phase II Cadenza Trial of Pevecamab Steneurin, or PVEC, in patients with front-line and relapsed refractory blastic plasmacytoid dendritic cell neoplasm, or BPDCN, in 2024. Given the encouraging efficacy and tolerability data we have observed, as presented at the European Hematology Association Annual Meeting earlier this year, we are excited about PVEC as a potential new option in this rare indication. In our AML program with PVEC, we continue to advance enrollment in our 802 trial of PVEC in combination with venetoclax and azacitidine, which we refer to as the PVEC triplet. We expect to report data from this study at ASH in December. Two cohorts enrolled patients with newly diagnosed acute myeloid leukemia, and each were designed to inform the optimal schedule of venetoclax in the PVEC triplet, a critical first step to guide further clinical development, including planned pivotal development in frontline AML. As for our earlier stage programs, on IMGC 936, our first-in-class ADAM9 targeting ADC and co-development with macrogenics, We continue to progress our non-small cell lung cancer expansion cohort, and we plan to provide an update after the protocol-specified interim analysis is completed, which we now expect next year. Lastly, we are progressing our phase one trial of IMGN151, our next generation antifoly receptor alpha targeting ADC, to address a broader range of folate receptor alpha-expressing tumors. Initial exploration is in ovarian and endometrial cancers, and dose escalation is proceeding as anticipated. With that, I will turn the call over to Lauren to cover our financials. Lauren?
spk05: Thanks, Mike. For the third quarter of 2023, we generated $113.4 million in revenue, including $105.2 million in net product sales of Elihir, with the remainder primarily from non-cash royalty revenues. Operating expenses were $85.3 million, comprised of $47.6 million of R&D expenses and $37.7 million of SG&A expenses. We recorded net income of $30.7 million and EPS of 10 cents. We ended the quarter with $605.5 million in cash on the balance sheet. Our financial guidance for 2023 remains unchanged. We continue to expect revenues, excluding ELAHIR sales, between $45 million and $50 million, and operating expenses between $350 million and $365 million. Lastly, since we are quickly approaching the end of 2023, I'd like to share that we anticipate providing full-year ELAHIR revenue guidance for 2024 when we announce fourth quarter and full-year 2023 financial results. With that, we'll open the call for questions.
spk00: Thank you. Ladies and gentlemen, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, you may press star one one again. Please stand by while we compile the Q&A roster. And our first question coming from the line of John Newman with Canaccord, your line is open.
spk06: Hi there. Good morning. Thanks for taking my question, and great continued work, successful launch. Just had two questions. On Elihir, curious... Sure. On Elihir, curious if you're seeing Elihir use in combination with Avastin continue to grow as a share of total Elihir use, and also if you are expecting to see increased duration of therapy here, and then second, There's a quick question on what we should be looking for in terms of the PUVECAMAB data at ASH this year.
spk07: Thanks. I'll ask Isabella to answer those questions.
spk18: Hey, John. Yes. Well, we continue. We are very pleased with the performance in the third quarter, as you said, over 100 million in cells. We continue to track the utilization both in monotherm and combination. While we have preliminary data on that, we could say, yes, there is growth in both, and we continue to see that. And our market research indicates that that will continue to grow in the next few months. Can you please repeat your question, Vivek?
spk14: Sure. I think, John, hi, it's Mike. Yeah, hi, John, it's Mike. Yeah, with respect to our upcoming data at ASHE, As I mentioned in the prepared comments, we're going to have as much data essentially as we have on the two cohorts that have solidified the dose and schedule of the triplet as we move forward in 802. So, you know, efficacy data, safety data, obviously it's an ongoing study, and so sort of the maturation of those data with respect to response duration. is something that's going to take more time. But I think we'll be able to expand a fair bit on what I just shared.
spk16: Great. Thank you.
spk00: Thank you. One moment for our next question. And our next question coming from the line of Michael Schmidt with Guggenheim. The line is open.
spk12: Hey, guys. Good morning. Thanks for taking my questions. And congrats on reaching cash flow positivity this quarter. amazing job on the launch so far. Mark or Isabel, could you comment a bit more what you think your treatment share is at this point in time in the platinum resistant ovarian cancer setting as opposed to other patient subsets in this market? It's been a very strong launch, obviously. And then secondly, could you comment on how the Piccolo trial result potentially reads through to other trials you have ongoing in a platinum-sensitive ovarian cancer setting. Thank you so much.
spk07: Mike, I'll start and then ask Isabelle and Mike to address the additional points here. You know, so we aren't in a position to quote you a specific share at this point. The way we are looking at the business is we see some important trends. I think we've characterized it as slow but steady growth as we look at the utilization of the product as monotherapy. So when we started out, the majority of the patients were fourth and later line. As time has gone by, what we see in the claims data is movement into earlier lines of therapy. And in parallel with that, we see combination use of the product growing as well. And so, but to sort of stand back at this point and give you a specific share number, I'm just not in a position to do that. Isabella, I don't know if you want to add anything to that.
spk18: No, I just would like to say that this is an area of high-end needs and what we are pleased is to see a steady adoption across all the accounts. Significant depth and breadth in both academic and community So, we expect this will continue to increase in terms of market share. We are not in a position to comment at this time.
spk14: Thanks, Mike, for the question in terms of the PICOLO data. You know, I can't imagine a better foundation on which to build in platinum-sensitive ovarian cancer than the interim assessment that we've been able to share with respect to PICOLO. This is a, just to remind you, this is a heavily pretreated population of patients with platinum-sensitive disease, and when we look across the available therapy, which is very heterogeneous because there are so few options, we see single-agent monotherapy objective response rates in the high single digits low double digits. And we see platinum-based doublet objective response rates anywhere between the high 20s and high 30s. And here we are with an interim assessment of an ongoing study where we expect at least a 48% objective response rate. So this sets a really nice foundation for the continued work of Mervituximab and platinum-sensitive disease.
spk08: And thank you. As a reminder.
spk00: Thank you. One moment for our next question. And our next question coming from the line of Ed Serderup with BMO Capital Markets. Your line is open.
spk08: Great. Thanks for taking my questions, and congrats on continued execution here. Maybe on Piccolo, and thanks for the additional color on the study. Just wanted to know if you could comment at all on sort of the standard of care, duration of response, and sort of just sort of level setting expectations from sort of a standard of care perspective for that study. And I had a question on ADAM-9 as well, just thinking about sort of some of the recent data we got at ESMO from the TROP2 mechanism. In terms of the, you know, response dynamics potentially in sort of a squamous versus a non-squamous non-small cell cancer population, if you could comment at all on sort of the ADAM9 mechanism and whether or not there's sort of a preference or confers preference for a particular sort of non-squamous histology. Thank you.
spk14: Sure. This is Mike. Let me respond to the second question first. I think the long and the short of it is that ADAM9 is broadly expressed, and we look forward if there's any signal that we see that is distinguishable based on histology when we have that expansion data. Obviously, Steve looking forward to sharing that, but at this point, given the broad expression across epithelial cancers, you know, we're continuing to, you know, to look broadly in that cohort. With respect to the first question, you know, I just want to reinforce that we're really looking forward mid-next year, sharing the full data from PICOLO. And your questions are really going to be relevant in the context of the specific demographics, even more detailed than what we're able to share today with respect to, for example, more detail around the platinum-free interval in this patient population to be able to better interpret not just the interim assessment objective response rates that we're seeing, but also the durability of response and other factors that are going to be important to essentially round out this interim assessment with the full data. So we're really looking forward to that. And like I said, I think we've shared that we expect that in the next year.
spk16: Thank you.
spk00: Thank you. One moment for our next question. And our next question coming from the line of Boris Peeker with TD County. Line is open.
spk11: Great. Congratulations on the progress. Two questions for me. So first on Ella here, I'm just curious, what is the current duration of therapy and how do you expect, I guess, to increase in piccolo patients? And the second is maybe kind of get your general thoughts on on the competitive products DS6000 from Daiichi that's in early stage development?
spk07: Yeah, Boris, the claims data that we have at this point are not sufficient to allow us to project a duration of therapy among the patients that have been treated. As a general rule, what we'd observe is that patients in earlier lines tend to have higher response rates and stay on drug longer. We observed that same phenomenon with the use in combination.
spk14: Hi Boris, it's Mike. And with respect to your second question, Yeah, clearly the data you referenced that were presented, I think, last week are interesting. It's a phase one experience. It looks to me, at least from the data, there's some work to do with respect to identifying the appropriate dose. It's going to be something that we're going to want to keep an eye on and think about ways progress, but, you know, we're years ahead in terms of the platinum-resistant space and, candidly, the platinum-sensitive space in terms of where we're at with ELA here.
spk11: Great. Thanks for taking my question.
spk00: Thank you. And our next question coming from the line of Brian Cheng with JPMorgan. Your line is open.
spk13: Hey, guys. Congrats on the quarter, and thanks for taking my question this morning. Mark, how should we think about the sales trajectory next year, you know, from the dynamics of patients on combo with Bev and the use in early line versus discontinuation just due to natural progression? How should we think about the trajectory moving forward? And then, you know, too, on Piccolo, how should we think about the regulatory path look like you know, post your PICOLO final analysis. And do you think the final analysis will give you sufficient leverage for conversation for label expansion next year? Thank you.
spk07: Thanks, Brian. I'll start. We expect to see continued growth. We will give guidance in conjunction with our earnings call in February of next year when we report out full year results. But, you know, for the reasons that Isabel articulated in her opening comments. You know, what we see from our market research is increased testing and that trend should continue. Increasing awareness, you know, right now the survival data are not currently in the label and so we can't directly promote that information with the submission of the SBLA and subsequent approval will be able to go to the market with that. And what we observe from the market research at this point is with increased education, we also see increased breadth and depth of prescribing, both as it relates to the monotherapy as well as in combination. We think there are rising treatment rates. So this is, you know, a new therapy and an area of unmet need. You know, we've pointed out earlier that, you know, this is the first drug approved specifically in ovarian cancer in almost the last decade. And so the expectation here is that treatment rates will And then, in particular, with the Mirasol data, we have the ability to compare and contrast against the standard of care. And when we do that, what we observe again in the research is an inclination to use the drug earlier in the treatment cascade. You know, we do anticipate these questions over the course of the call and today, and so, you know, what I would say, again, is that we do expect continued growth, but I think it's also fair to say that coming off of $100-plus million base, the slope of the curve will not be as steep as it was in the past couple quarters.
spk14: And Mike, regarding, yeah, this is Mike. Regarding your, yeah, your second question, So, first of all, let's just keep in mind where we're at, right? This is foundational data that will unequivocally be clinically meaningful in this patient population. And the reason that the full data set won't be available until mid-2024 is because of the importance of presenting mature durability of response data. And just to keep in mind, the last patient was enrolled in this study early this year. So, it gives you a sense of the importance of what that mature response durability data will be. I fully expect, given what we know today, that these data will support compendial listening eventually when we see the full data. And I'd like to reserve judgment on the dialogue with regulatory authorities until we have that full data, because there's just no way to put an overall objective response rate into context with that durability of response.
spk13: Great. This is very helpful. Thank you.
spk00: Thank you. And our next question, coming from the lineup, Alexandra Ramsey with William Blair. Your line is open.
spk03: Hi, everyone. Thanks so much for taking my questions, and congrats on all the progress this quarter. So two quick questions. I guess first on Piccolo, that 48 response rate that you mentioned that you'll present, potentially present at the full data, I just wanted to confirm that that's a confirmed 48% response rate. And then looking at the mirror cell data presented earlier at ESCO, it appeared that the PARP-treated patients actually responded better than the PARP-naive patients. So I was just wondering if you could provide some color on why that might be the case. Thanks so much.
spk14: Yeah. So this is Mike. Regarding your second question, it's important in that subset analysis to look at the demographics of the patient populations when the Mirasol dataset is parsed by prior exposure to PARP inhibitor or not. We tried to point that out in the presentation, and I'd encourage you to go back and look at that. But the long and the short of it is, there are some differences that are more apparent in the population. And generally, in terms of outcomes, it's not surprising necessarily that we see slightly better outcomes in patients that are appropriate based on their molecular profiling for PARP inhibitors. And with respect to the first question, Yeah, so this is an interim assessment. It was a planned interim assessment following full enrollment. And these data are confirmed. The one caveat I'll say, and I think Mark mentioned this as well, is that this is an ongoing trial, right, with patients, a number of patients that are still receiving therapy. you know, in the parlance of a clinical researcher, we confirm the data when we share something like this, but of course, we need to reserve the, you know, the caveat that when the full data are presented mid-next year, that they're, you know, that in the process of providing those full data, there could be, you know, minor, you know, you know, minor shifts in the data, and that's why we're really clear to talk about an objective response rate of at least 48%. Okay.
spk03: No, that makes sense. And so you are seeing a durability increase over time. It sounds like it's based on how long people have been on treatment, but just confirming that.
spk14: Yeah. I mean, that's the issue of the maturity of the duration of response is exactly why. We're providing some guidance today that we would expect the full data in mid-2024.
spk00: Perfect. Thanks so much. Thank you. And our next question coming from the line of Peter Lawson with Barclays. Elon is open.
spk01: Thanks for taking my questions. Just going back to your comments around DH's CDH-SICH ADC, just curious on what you thought of the data and if kind of that response rate and durability kind of holds up, kind of how you think physicians will make a pick between Diage's molecule and your molecule. And then on pig life, I'll just go back to that. Does the 48% mean there's kind of unconfirmed there and it should get to above 48% or at 48%? So any details around that kind of? find a detailed commentary you made would be great.
spk14: Yeah. Yeah, what I'll say to the second point, which kind of relates to the prior question, is that we do see, you know, we do see late, you know, responses, you know, in our data sets generally. And as I mentioned, there are a number of patients that remain on marbituximab. So, at this interim assessment, we can confidently say that we see an objective response rate of 48%, but we just need to be cognizant of those number of patients that remain on therapy. So, could the objective response rate at the final data be higher? Yes, it could be higher. With respect to your first question, it's so conjectural. I mean, like I said, we've got a phase one molecule that has a really interesting early signal. Like I said earlier, looks like to me we're trying to figure out dose. I think there were some grade five interstitial lung disease related deaths. Gosh, I hope for patients that we're able to work through that and it becomes potentially someday a meaningful therapy in ovarian cancer. But I think it's a little premature from where I sit to try to hypothesize about how physicians are going to make treatment choices compared to a medicine that has demonstrated survival benefit in platinum-resistant ovarian cancer.
spk01: Perfect. Thanks for the additional detail. What's the overlap between FR-alpha and CDHCs?
spk14: Yeah, you know, we're looking hard to understand that. I can't give you any numbers today, but when we have a better understanding of that, of course, we'll be able to share that. Brilliant.
spk01: Thank you so much. Congrats on the quarter. Thank you.
spk00: Thank you. And our next question coming from the line of Kelly Shee with Jefferies. Your line is now open.
spk17: Congrats on another great quarter, and thank you for taking my questions. I have two. Firstly, on the regulatory approval, will you be able to share your launch strategy in Europe at the moment? And also, how should we consider the cost associated with the launch? And another question regarding the Item 9 program. So for the upcoming update in non-fossil lung cancer, could you share what interim analysis is based on? Is it a response rate or the durability of response? Thank you.
spk14: I'll just briefly respond to the second question, and I think Mark or Isabel may tackle your question about Europe. So, this is a cohort expansion of a Phase I study. It's essentially, think about it as sort of fully enrolling that cohort and having the sufficient data to be able to share that in totality. It's nothing really more complicated than that. And if patients remain in the cohort, it's just prudent to, on therapy, it's prudent to wait for that to mature. And we look forward to sharing those data next year.
spk07: Great, thanks. And so in terms of Europe, I'll start and then ask Isabel to comment further. But we were very pleased to announce last week that the EMA had validated our marketing authorization application. And we think that sets us up very nicely for an approval late next year. In terms of the launch sequence, we're on the ground already in Europe with established headquarters in Switzerland and a small staff to support the key functions around market access regulatory and the like, and are starting to build a team to support initial sales in Germany, and then there'll be subsequent countries added on as we go forward. And then I'll let Isabel talk a little bit about the market. And overall, the comment here is that we can address this market with a modest incremental investment for the business. But maybe just talk a little bit about the dynamics there.
spk18: Yes, Mark. Thank you. Well, as we have shared previously, the market in Europe is highly concentrated and really the majority of the 55 centers account for about 80% of the patients there. So as Mark alluded to, with a small investment, we are able to reach these customers. We also have started already our engagement, and as you saw, we presented at ESCO and ESNO, and we have very strong relationships with KOLC in Europe that are really excited to have this therapy available to them in any time soon. And of course, our very much supporting our efforts in this. In addition to that, we are giving up our team in Germany, in other countries, and we are very excited to start our market research, our preparations to basically replicate the success of the launch that we have seen in the U.S.
spk07: One other point to add to that, which is, Kelly, our physician base there has tremendous experience with the drug already. So when we look at Mirasol, when we look at Soraya, more than 70% of the patients were enrolled outside of the United States, and the vast majority of those were enrolled in Europe. And so this is a group of physicians that has already significant experience with the drug. So we're excited about our prospects there.
spk00: Terrific. Thanks. Thank you. And our next question, coming from the line of I'll take a good warning from Truist. Yolanda's open.
spk09: Hi, guys. Good morning. Thanks for taking my questions. First off, congrats on another robust quote of growth, guys, especially coming in line with the aggressive buy-side expectation. That's great to see. Totally understand that you can't be too specific on off-label use here, but can you at least give us some sort of a bit of color here on what off-label population is the largest in what you're seeing so far and what is growing the most rapidly. I think that could just be a little helpful here for us as we're tweaking our models here. And then on Piccolo, good to hear about what the ORR is changing at. But what about duration of response? As you've given us what the statistical bar is for ORR, can you tell us what you need to beat for DOR? And I'll also add in previous calls, I think Anna and some of you guys had mentioned that suggested that this could be also an area where PICOLO could look good. So I just want to see if you feel confident about that as well, now that you're seeing more of the data in-house. And then lastly, do you need to publicly present PICOLO in order to discuss it with the NCCN, or can you share that with the NCCN ahead of a public presentation? Thanks.
spk07: So, let me start with the market question, and then you can talk about Piccolo and CCN. So, in terms of discretionary use of this product outside the label, the first thing to keep in mind is that our label is platinum-resistant ovarian cancer in patients who've received one to three prior lines of therapy who are FR-alpha positive. What we observed very early on was that consistent with the NCCN guidelines, that physicians were using the product in later line patients, so beyond a patient who had three prior therapies. And that continues as we speak. We then observed that There are patients who might not be, that might not qualify as FR-alpha high who nonetheless are getting therapy as monotherapy where the FR-alpha expression is close to what would be considered FR-alpha high. Just as a reminder to folks, FR-alpha high is defined as 75% of the patient's tumor sample expressing FR alpha at 2 plus intensity staining. And so, when a pathology report comes back from our labs, it has two readouts. One is positive and negative based on whether it meets that cut point of 75 at 2 plus intensity staining. But also, there's a numerical score with respect to the expression level. So, it's stated in five percentage point increments, so 75, 80, 85, up to 100, and then downwards for 70, 65, and so on. What we hear anecdotally through market research in our advisory boards is that many physicians with a 70% reading will initiate monotherapy. As the FR-alpha expression levels go down, there's the opportunity to engage around combination use. And again, the NCCN guidelines are supportive here where they include use of the product for patients with medium and low levels of expression. And so we, as I said, we see use in later lines. It's a little hard to, we can't sort of match a patient who had, you know, a 70% level of expression with monotherapy use at this point. The data aren't, we're not able to, from a data perspective, to match those two things. And then we do see, you know, an increasing use of combination, and it comes through most prominently in our market research relative to the claims data, which lag a little bit. And, you know, I think a number of you on the call have produced your own sort of market research studies that show, you know, both existing and anticipated increasing use of combination therapy. I don't know if you want to add anything to that.
spk18: Yes, I just want to say awareness of NCCN guidelines has increased, and it has been included in some of the pathways to some of the centers. And NCCN guidelines are silenced around high, medium, low, and monotherapy, in addition to listing the value of the combination. So in addition to being used in later lines of therapy, yes, we see use on mediums and lows, particularly in combinations.
spk14: And this is Mike with respect to your second, third, and fourth questions. Let me make a point about this patient population that perhaps I haven't been quite explicit enough about. But when a patient with natural history who has still platinum-sensitive disease in third or subsequent lines, there's an important dichotomization around the relative platinum sensitivity that a clinician is thinking about when they think about appropriate therapy at this stage. And that's important as we think about the full data when we see those data next year, because the durability of response, just like the objective response rate, are going to be influenced whether the patient population has a platinum-free interval that's relatively short versus a platinum-free interval that's relatively long. And you can imagine or hypothesize that if the clinician is even considering a monotherapy non-platinum agent in a clinical trial like Mervituximab, that when we see the final data, I would expect that we'd have a substantial proportion of patients that have a relatively short platinum-free interval. And that's really important to help interpret the full data set, along with the proportion of patients that have prior exposure to PARP inhibitors and bevacizumab. So it's all of those clinical factors and demographics that need to be incorporated into the interpretation of the data to be able to put the data into context with respect to the objective response rate and durability of response. And with respect to your question around NCCN, I think a working assumption should be that the NCCN is looking for published data sets to review in the context of updating their guidelines.
spk09: Awesome. Thanks for taking all my questions, guys. Appreciate it.
spk07: I think we have time for one more question.
spk00: Certainly. Our last question are coming from the line of Lee Chen with HC Renright. Your line is open.
spk02: Hi. This is Lee Chen for RK. Can you hear me okay?
spk16: Yep.
spk02: So just upon the conversion from accelerated approval of ELA here to full approval, I believe that Takeda, under the license agreement with Takeda, there's additional payment. Can you provide more details on that?
spk07: So I can comment on the Hua Deng license, and that does call for additional, milestone payments upon full approval, won't comment on the exact amount of those. I would have to get back to you on the Takeda license.
spk16: Okay. Great.
spk07: Okay, well, thank you all for joining us today. Obviously, we are very pleased with the progress in the business. We've got an important and growing product. We look forward to continued progress there. So we look to expand geographically and also moving this drug into earlier lines of therapy. We've got an important second pivotal program ongoing as we speak, an exciting portfolio. And you'll hear more from us as we go forward about reinvesting in the pipeline and our research capabilities. We think that ADCs are an important and growing class of therapeutics. We've got a highly differentiated skill set as it relates to that class of therapy. Again, look forward to keeping you updated, and we'll see many of you at ASH. Thanks.
spk00: Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.
Disclaimer