Nov 2, 2023
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 Anabel Chan, Head of Investor Relations. Please go ahead.
Good morning, and thank you for joining today's call. 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 & Media section of our website at immunogen.com. With me today are Mark Enyedy, our President and CEO; and Isabel Kalofonos, our Chief Commercial Officer; Michael Vasconcelles, 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 Factors 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.
Thanks, Anabel. 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 ELAHERE in the U.S., progress made towards both geographic and label expansion for ELAHERE and the advancement of our portfolio. Starting with the commercial update.
We delivered a strong quarter with ELAHERE generating just over $105 million in net sales, resulting in over $210 million in revenue year-to-date, which puts us on track with 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 ELAHERE 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 ELAHERE driven by engagement by our medical affairs team the compelling data for 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 ELAHERE 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 ELAHERE 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 of Huadong received acceptance of the NDA in China.
In addition, we announced a collaboration with Takeda to develop and commercialize ELAHERE in Japan and submitted a supplemental BLA to FDA to support the conversion of the accelerated approval of ELAHERE to full approval here in the U.S. In step with our commercial efforts, we are advancing the broader ELAHERE development program to support low expansion into platinum-sensitive disease and to position ELAHERE as the combination agent of choice in ovarian cancer.
In this context, we are pleased to share that our PICCOLO Phase II trial evaluating ELAHERE monotherapy in platinum-sensitive ovarian cancer has met its primary endpoint of objective response rate. Noting that PICCOLO is ongoing and patients are continuing to receive ELAHERE, to date, we've observed no new safety signals in this patient population.
These data represent an important step towards expanding ELAHERE 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, PVEK, we look forward to reporting data from our PVEK triplet in 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, IMGC936 and IMGN151 are progressing, and 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 Hewett 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 ELAHERE 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?
Thank you, Mark. The commercial team build 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 ELAHERE as the standard of care portfolio receptor also 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 4 key factors, including: a strong adoption in an area of high unmet need; rapid access and reimbursement coverage; the solid execution of our commercial customer-facing teams; and increased physician experience and awareness or 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 insight into the dynamics observed while launching into an area of high unmet need.
Starting with the identification of patients, almost a year into our launch, we have seen the overall awareness for FR alpha testing increased and rapid adoption of the FORWARD I diagnostics 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 ELAHERE into the treatment decision, needless to say, testing has not been to adoption. Since launch, we have endeavored to provide the market with a number of tests conducted at our 3 largest centralized labs.
As of the end of the quarter, that number stood at 16,000 tests. However, with approximately 40 labs now certified to branded tests, our visibility into the number of tests performed has decreased and will discontinue reporting on the metrics on subsequent calls.
We will, however, continue to report the foliate receptor alpha positive rate which remains between 35% and 40%, in line with our expectations. Looking at patient adoption.
ELAHERE addresses a high unmet need among platinum-resistant ovarian cancer patients. As indicated by the initial strong uptake in later life with the need has been great.
In the first quarter, the vast majority of patients were from later lines of therapy. And as the launch has progressed, will shift to earlier lines.
This is low and steady trend, and we expect this to become a key driver of future growth. Moving to our second key factor, access and investment.
Driven by the effort of our alpha team, we secured coverage policies aligned to our level for over 95% of both Medicare and commercial lives within the first 7 months of launch, exceeding another benchmark, ADC. In addition, with the inclusion of ELAHERE NCCN guidelines, we have seen utilization in a broad population, including the use of monotherapy related lines and in combination with bevacizumab in low, medium and high FR alpha presentations.
Third, a strong execution by our commercial team driving adoption of ELAHERE. Our customer-facing team have been highly active since launch.
During the third quarter, they continues to engage priority targets to broaden our reach resulting in continued growth in both academic and community accounts. Complementing new account generation is a significant percentage of accounts with repeat orders.
While academic institutions continue to comprise our largest customers, roughly 70% awarded during the quarter came from nonacademic institutions and community-based oncology groups, consistent with the prior quarter. And lastly, increased 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 we over 120 physicians across the academic and community setting, over 80% of physicians are aware of ELAHERE.
This has nearly doubled since April, and we are especially pleased to see awareness increasing with medical oncology. Given 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 relate enthusiastic feedback from clinicians regarding their experience with ELAHERE. In summary, we are very pleased with our performance to date.
And based on the market research, I just referenced, we expect continuous growth due primarily by number one, increasing FR alpha testing. Awareness of FR alpha testing as a biomarker is already high, and physicians indicate a 30% growth with the convenience of an in-house testing and testing earlier in the patient journey.
Two, increasing awareness of the benefits ELAHERE 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. Third, we also expect to see increase in premium rates over historical benchmarks given the compelling efficacy of LIC and increased experience with the treatment, including the management of adverse events.
Fourth, of therapy. Improving perception relative to the standard of care will support moving into earlier lines of therapeutic 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 ELAHERE. With that, I would like to turn the call over to Mike to provide additional color on the ELAHERE development program and our broader pipeline.
Thanks, Isabel. We were pleased to present additional data from MIRASOL, our randomized Phase III trial of ELAHERE in platinum-resistant ovarian cancer at the 24th Annual European Society of Gynecologic Oncology Congress in September.
Dr. Bangor, Professor of Gynecologic/Oncology at the University of presented 2 subset analyses in an oral session, highlighting efficacy benefits with ELAHERE versus investigator choice or IC chemotherapy in progression-free survival, objective response rate and overall survival.
Dr. Bangor 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 and to ELAHERE's consistent clinical benefit compared to IC chemotherapy in both subsets. Turning now to the broader mirvetuximab clinical development program, we aim to expand the ELAHERE label into platinum-sensitive ovarian cancer and further position ELAHERE as the standard of care in fully receptor alpha-positive disease.
We are currently advancing 3 sponsored clinical trials in support of these objectives. Let's start with PICCOLO, our single-arm Phase II trial evaluating mirvetuximab monotherapy efficacy and safety in patients with FR alpha high platinum-sensitive ovarian cancer who have received at least 2 prior lines of platinum-containing therapy or have a documented platinum The unmet medical need in this patient population is noteworthy and growing, driven predominantly by 2 key factors.
First, even if a patient meets the clinical criteria of platinum-sensitive disease, each subsequent line of platinum cutaneous therapy is associated with both decreased efficacy as measured by a lower probability of achieving an objective response and meaningful response duration and decreased tolerability. But 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, the observations further reinforce the need for treatment alternatives.
No randomized Phase III data exist for the patient population enrolled and treated in PICCOLO. 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-containing regimens in similar patient populations.
These analyses drove the trial standard final 2-stage design and its statistical assumptions. Regarding the former objective response rate as the primary endpoint.
The key secondary endpoints for 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%. Because an observed objective response rate exceeding 28%, would set these data apart from the historic benchmark data I referenced above.
In other words, and positive trial results would require an observed or actual objective response rate that excluded 28% based upon 95% confidence intervals. In the fully enrolled PICCOLO 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 mirvetuximab. Based upon the prespecified 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 end point of the study has been achieved. The investigator-assessed objective response rate excludes 28%.
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 signal bevacizumab.
The insights I've shared today from the ongoing PICCOLO trial are meaningful as the numerically largest data set for mirvetuximab reported thus far in patients with platinum-sensitive disease, we believe these data reinforce earlier previously published data set of mirvetuximab in combination that demonstrate mirvetuximab's potential in FR-alpha expressing platinum-sensitive ovarian cancer or PSOC. Assuming the tolerability and safety profile in PSOC that remains consistent with that observed across the mirvetuximab development program, we've seen mirvetuximab 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 mirvetuximab monotherapy in PICCOLO, we are advancing 2 trials designed to establish mirvetuximab as the combination agent of choice in platinum-sensitive ovarian cancer. The first is our Phase III trial evaluating mirvetuximab plus bevacizumab maintenance versus standard of care, bevacizumab maintenance, in the second-line platinum-sensitive setting.
This study builds upon our robust mirvetuximab plus bevacizumab data in the platinum-resistant setting, which led to the NCCN compendia looking for this combination. This combination in the maintenance setting is designed to establish the opportunity for patients to benefit from even longer duration of therapy with mirvetuximab.
The second is Trial 420, a single-arm Phase II study evaluating mirvetuximab plus carboplatin with mirvetuximab continuation until disease progression in platinum-sensitive ovarian cancer patients with low, medium or high level of a 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 or PVEK, in patients with frontline 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 PVEK as a potential new option in this rare indication.
In our AML program with PVEK, we continue to advance enrollment in our A02 trial of PVEK in combination with venetoclax and azacitidine which we refer to as the PVEK 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 PVEK triplet, a first step to guide further clinical development, including planned pivotal development in frontline AML. As for our earlier stage programs, on IMGC936, our first-in-class ADAM9-targeting ADC in 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 to next year.
Lastly, we are progressing our Phase I trial of IMGN151, our next-generation antifolate 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?
Thanks, Mike. For the third quarter of 2023, we generated $113.4 million in revenue, including $105.2 million in net product sales of ELAHERE, with the remainder primarily from noncash 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 $0.10.
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 ELAHERE 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 ELAHERE revenue guidance for 2024 when we announce fourth quarter and full year 2023 financial results.
With that, we'll open the call for questions.
[Operator Instructions]. And our first question coming from the line of John Newman with Canaccord.
Great continued work, successful launch. Just had two questions.
On ELAHERE, I'm curious, if you're seeing ELAHERE use in combination with Avastin continue to grow as a share of total ELAHERE use? And also if you are expecting to see increased duration of therapy here?
And then second, just a quick question on what we should be looking for in terms of the data at ASH this year?
I'll ask Isabel to answer those questions?
John, yes, well, we continue -- we are very pleased with the performance in the third quarter, as we said, over $100 million in sales. We continue to drive the utilization both in monotherapy in combination.
So we have preliminary data on that, we could say, yes, there is growth involved, 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 on PVEK?
I think, John, it's Mike. Yes, with respect to our upcoming data at ASH, as I mentioned in the prepared comments, we're going to have as much data as we -- essentially, as we have on the 2 cohorts that have solidified the dose and schedule of the triplet as we move forward in year 2.
So 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.
Our next question coming from the line of Michael Schmidt with Guggenheim.
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 reeks through to other trials you have ongoing in a platinum-sensitive ovarian cancer setting?
Mike, I'll start and then ask Isabel and Mike to address the additional points here. 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 this 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 products growing as well.
And so -- but to sort of stand back at this point and give you a specific share number, just not in a position to do that. Isabel, I don't know if you want to add anything to that?
No, I just would like to say that this is an area of high unmet need and what we are pleased is to see a steady adoption across all the accounts, significant depth and breadth in both academic and community savings. So we expect this will continue to increase in terms of market share.
We are not in a position to comment at this time.
Thanks, Mike, for the question. In terms of the PICCOLO data.
I can't imagine a better foundation on which to build in platinum-sensitive ovarian cancer than interim assessment that we've been able to share with respect to PICCOLO. 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 to low double digits, and we see a 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 48% objective response rate. So this sets a really nice foundation for the continued work of mirvetuximab sensitive disease.
And our next question coming from the line of Etzer Darout with BMO Capital Markets.
Congrats on continued ELAHERE 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 ADAM9 as well.
Just thinking about sort of some of the recent data we got at ESMO from the TROP2 mechanism. In terms of the response dynamics potentially and sort of a squamous versus 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 first preference for a particular sort of non-squamous histology.
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 -- if there's any signal that we see that is distinguishable based on histology, when we have that expansion data, we'll obviously be looking forward to sharing that.
But at this point, given the broad expression across epithelial cancers, we're continuing to look broadly in that cohort. With respect to the first question, I just want to reinforce that we're really looking forward next year, sharing the full data from PICCOLO.
And it's -- your questions are really going to be relevant in the context of the specific demographics, even more detail 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 rate 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 next year.
Next question our next question coming from the line of Boris Peaker with TD Cowen.
Congratulations on the progress. Two questions for me.
So first, on ELAHERE, I'm just curious what 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 the competitive products, DS-6000 from Daiichi that's in early stage development?
Yes. Boris, the claims data that we have at this point are not sufficient to allow us to project duration of therapy among the patients that have been treated.
As a general rule, what we observe is that patients in earlier lines tend to have higher response rates and stay on drug longer. We reserve that same phenomenon with the use in combination.
Boris, it's Mike. And with respect to your second question, Yes.
Clearly, the data you referenced that were presented, I think, last week are interesting. It's the Phase I 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 in which those data progress, but we're years ahead in terms of the platinum-resistance space, and candidly, the platinum-sensitive space in terms of where we're at with ELAHERE.
Our next question coming from the line of Brian Chan [ph] with JPMorgan.
Congrats on the quarter. Mark, how should we think about the sales trajectory next year from the dynamics of patients on combo of and the use in early line versus discontinuation just due to natural progression.
How should we think about the trajectory moving forward? And then two on PICCOLO.
How should we think about the regulatory path look like post your PICCOLO final analysis? And do you think the final analysis will give you an efficient leverage for conversation for label expansion next year?
Thanks, Brian. I'll start.
Look, we expect to see continued growth. We will give guidance in conjunction with our earnings call in February of next year when we report our full year results.
But for the reasons that Isabel articulated in her opening comments. What we see from our market research is increased testing, and that trend should continue, increasing awareness.
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, we'll be able to go to the market with that. And what we observed from the market research at this point is with increased education, we also see increase the 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 a new therapy and an area of unmet need.
We've pointed out earlier that 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 increase.
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 observed again in the research is an inclination to use the drug earlier in the treatment cascade.
And so we do anticipate these questions over the course of the call and today. And so -- 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 of quarters.
And this is Mike. Regarding -- yes.
This is Mike. Regarding your -- yes, your second question -- so first of all, let's just keep in mind where we're at, right?
This is a 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 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 compendia listing eventually when we see the full data. And I'd like to reserve judgment on dialogue with regulatory authorities until we have that full data because there's just no way to put an overall objective of response rate into context with that the durability of response.
Our next question coming from the line of Alexandra Ramsey [ph] with William Blair.
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 presented the full data.
I just want to confirm that, that's a confirmed 48% response rate? And then, looking at the MIRASOL data presented earlier at ESCO, it appears 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?
Yes. So this is Mike.
Regarding your second question, it's important in that subset analysis to look at the demographics of the patient population when the MIRASOL data set 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 short of it is, there are some differences that are more apparent in the PARP-naive 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 the molecular profiling for PARP inhibitors.
And with respect to the first question, yes, 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.
And so 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 caveat that when the full data are presented mid next year that in the process of providing those full data, there could be 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. No, that makes sense.
And so you are seeing kind of durability increase over time. It sounds like you're based on how long people have been on treatment but just confirming that.
Yes. I mean 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 2024.
Our next question coming from the line of Peter Lawson with Barclays.
Just going back to your comments around CDH 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 molecule and your molecule?
And then on PICCOLO, if I could just go back to that. Does the 48% mean there's kind of unconfirmed there and should get to above 48% or are at 48%.
So any details around that kind of find a detailed commentary you made, would be great.
Yes. Well, I'll say to the second point, which kind of relates to the prior question is that we do see late responses in our data sets generally.
And as I mentioned, there are a number of patients that remain on mirvetuximab. 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 day to be higher Yes, it could be higher. With respect to your first question, it's so conjectural.
I mean, like you said, we've got a Phase I molecule that has a really interesting early signal. Like I said earlier, looks like to me, we're trying to figure out dose that I think there were some grade 5 interstitial lung disease-related deaths.
So gosh, I hope for patients that were 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.
Perfect additional detail. What's the overlap between FR alpha and CDH?
Yes. 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.
Our next question coming from the line of Dingding Shi with Jefferies.
Congrats on another great quarter. I have two.
Firstly, on the regulatory approval, would you be able to share your launch of strategy in Europe at the moment? And also, how should we consider the cost associated with the launch?
And another question regarding the Adam9 program. So for the upcoming update in non-small cell lung cancer, could you share what interim analysis?
Is it based on is -- is it a response rate or the durability of response?
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.
And so 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 therapies it's prudent to wait for that to mature and we look forward to sharing those data next year.
Great. And so in terms of Europe, I'll start and then ask Isabel to comment further.
But we were very pleased 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 events, we're on the ground already in Europe with established headquarters in Switzerland and a small stack 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.
Yes, Mark, thank you. Well, as we have shared previously, the market in Europe is highly concentrated, and really the majority of the 65 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 show, we presented at ASCO and ESMO, and we have very strong relationships with KOLs in Europe that are really excited to have this therapy available to them in a of course, our very much supporting our efforts in this. In addition to that, we are going up our team in in Germany, in all 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.
And 1 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, 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.
And our next question coming from the line of Asthika Goonewardene from Truist.
First off, congrats on another robust quarter for especially coming in line with the aggressive buy side expectation. That's good to see.
I 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 trending at, but what about duration of response?
As you've given us what the statistical are, 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 have mentioned that suggested that this could be also an area where PICCOLO 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 PICCOLO in order to discuss it with the NCCN?
Or can you share that with the NCCN ahead of a public presentation?
So let me start with the market question. And 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 1 to 3 prior lines of therapy who are FR alpha positive. So -- 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 3 prior therapies, and that continues as we speak. We then observed that there are patients who might not be -- 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 2 readouts.
One is positive or negative based on whether it meets that cut point of 2-plus intensity staining. But also, there's a numerical score with respect to the expression level.
So it's stated in 5 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 a 70% level of expression with monotherapy use at this point, the data -- we're not able to from a data perspective to match those 2 things.
And then we do see 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 I think a number of you on the call have produced your own sort of market research studies that show both existing and anticipated increasing use of combination therapy.
I don't know if you want to add anything to that?
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 has silence around high medium or low monotherapy in addition to lifting 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 combination.
And this is Mike. With respect to your second, third and fourth questions.
Let me make a point about this patient population that perhaps haven't been quite explicit 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 the clinical trial like mirvetuximab that when we see the final data, I would expect that we'd have a substantial proportion of patients that have a short -- 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 needs 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.
We have time for one more question.
Certainly. Our last question are coming from the line of Lee Chen with HC
Can you hear me okay?
Yes. So just upon the conversion from accelerated approval ELAHERE to full approval, I believe that Takeda -- under the license agreement with Takeda, there's additional payment.
Can you provide more details on that?
So I can comment on the Huadong license, and that does call for additional milestone payments upon full approval. I won't comment on the exact amount of those.
I would have to get back to you on the Takeda license. 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. So again, I look forward to keeping you updated, and we'll see many of you at ASH.
Ladies and gentlemen, that does end our conference for today. Thank you for your participation.
You may now disconnect.