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spk04: Good morning and welcome to Imogen's second 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 Annabel Chan, head of investor relations. Please go ahead.
spk26: 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 second 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 Enneby, our President and CEO, Isabel Calafonos, our Chief Commercial Officer, Anna Birkenblit, our Chief Medical Officer, and Renee Lentini, our Interim CFO. Michael Vasconcells, our EVP of Research Development and Medical Affairs, will also join us for Q&A. 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 risk 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.
spk16: Thanks, Annabelle. Good morning, everyone, and thank you for joining us today. You will have seen this morning's press release announcing that Anna will be stepping down from her position as Immunogen's Chief Medical Officer to take a well-deserved professional hiatus prior to pursuing new opportunities. I would like to take a moment to personally acknowledge and thank her for the essential role she has played in the transformation of this company. We've encountered no small amount of adversity as we navigated the last four years at Immunogen. Through it all, Anna rose to the challenge with intellect, grit, and good humor. Of particular note, she led the design and execution of the pivotal development program for Elihir that culminated in an FDA accelerated approval late last year and the unprecedented survival data shared at ASCO in June that have transformed the treatment landscape for patients with FR-alpha positive ovarian cancer. In parallel, under her leadership, We've also advanced our broader clinical pipeline, including a second pivotal program, and built a highly talented development organization. Anna, I value you as a colleague and wish you the very best in your future endeavors. On behalf of Immunogen, our collaborators, and most importantly, patients in need of more good days, thank you. Moving to our second quarter results. Since our last call, we've made great progress on multiple fronts and achieved a significant milestone for patients in our organization with our confirmatory phase three Mirasol trial, meeting not only the primary endpoint of progression-free survival, but also objective response rate, and most importantly, overall survival. This is an unprecedented result in platinum-resistant ovarian cancer, making Elihir the first novel therapy to demonstrate an overall survival benefit versus chemotherapy in a Phase III trial. With these results now in hand, we anticipate submitting an MAA in Europe and the SBLA in the U.S., both in the fourth quarter of this year. Turning to our commercial performance, we delivered a strong quarter with Elihir generating over $75 million in net sales, more than doubling our Q1 result with increasing breadth and depth of adoption. Isabel will provide more detail on our progress with the launch in a moment. As an initial point, given that this is just our second full quarter on the market, coupled with recent developments with both Elihir and the broader ovarian cancer landscape, we've elected not to provide full year guidance for LE year revenue today. The basis for this decision is this. We simply have not yet accumulated sufficient data and experience to confidently project the trajectory for LE year over the back half of this year. The key variables underlying this decision include Evolution of treatment rates. Given the compelling efficacy of Elihir, we believe treatment rates may be increasing over historical benchmarks, particularly for later Lyme patients. Shifting from prevalent to incident populations, which may potentially affect the growth rate of new patient starts. Duration of therapy. The claims data, which lag the market by 90 days or more, are not mature enough for us to provide a reliable forecast of how long patients are remaining on therapy at this time. Mix of testing and initial diagnosis versus testing to initiate treatment. And finally, monotherapy versus combination use. We are tapping multiple data sources to assess the percentage of combination use, which have yielded somewhat disparate outputs up to this point. Our clinical data suggests that combination use tends to generate higher response rates and longer durations of response, so an accurate assessment of this use is important. You will appreciate that each of these variables can have a significant impact on adoption and adherence. To better assess the evolving market here, we have commissioned a demand study with the goal of increasing our confidence in assessing trends and the growth trajectory for the product. In addition, our existing vendors are updating their databases and we are evaluating additional sources to gather more insights into the market. We look forward to updating you on our progress on these activities during subsequent calls. In terms of ongoing development, we are advancing our efforts to move Elihir into broader patient populations and to position it as the combination of choice in ovarian cancer. We look forward to our next milestone for the Elihir program with ORR data from our PICOLO trial expected before the end of the year. Moving to our PVEC program. We've completed enrollment in the pivotal de novo patient cohort of the CADENZA trial and expect top-line data in 2024. In addition, we progressed our 802 trial of PVEC in combination with Veneza for newly diagnosed AML patients and look forward to reporting data from these frontline cohorts at ASH later this year. Looking at the rest of the pipeline, IMGC 936 and IMGN 151 are progressing. and we remain focused on reinvesting in our research capabilities and expanding our pipeline. Together with a strong balance sheet bolstered by our follow-on offering, our progress over the first six months of the year has positioned us well to create meaningful value for our patients and our shareholders in the second half of 2023 and well beyond.
spk11: With that, I'll turn the call over to Isabel to cover our commercial progress. Isabel?
spk28: Thank you, Mark. We continue to successfully execute across the four launch imperatives as we work to position ELAHIR as the standard of care for foliar receptor alpha-positive ovarian cancer. In the second quarter, we generated $77.4 million in net sales. We're very pleased with another strong quarter of performance and believe this is due to the combination of factors, including the solid execution of the commercial teams Provided engagement by our medical team, increased breadth and depth of adoption driven by recognition of the benefits this novel treatment brings to patients with advanced ovarian cancer, and the compelling Mirasol data increasing awareness and interest from both patients and physicians. Uptaking the quarter continues to be broad and deep, with a significant percentage of accounts with repeat orders complemented by consistent ordering from new accounts. While academic institutions comprise our largest customer, roughly 65% of orders during the quarter came from non-academic institutions and community-based oncology groups, versus 70% in the first quarter. We anticipate the need of orders to continue to shift with an increasing percentage coming from academic accounts as satellite centers of major academic institutions start infusions. Regarding testing in response to the continuous strong demand for the foliar receptor diagnostic test, additional labs are actively being certified to run the test. As of the end of the quarter, we had 33 labs comprised of 16 centralized labs and 18 in-house labs fully certified with 15 additional labs in the process of validation. Of note, as testing becomes more decentralized, will have decreased visibility into the number of tests performed. Based on the information visible to us, we estimate that roughly 11,800 tests have been performed long today through the end of June, with a significant percentage of these tests being for newly diagnosed patients. In addition, the foliar receptor alpha positive rate remains between 35 and 40% in line with our expectations. Moving on to access, we continue to be very pleased with how quickly payers have included ELA hearing coverage policies aligned with our label. We ended the quarter with roughly 95% of both Medicare and commercialized coverage. Lastly, our customer-facing field team remained highly active. As of the end of June, our commercial team has engaged roughly 90% of the priority targets, and our medical affairs team continues to provide a full suite of support to ensure positive physician and patient experiences. Proportions in the field consistently relate enthusiastically back from clinicians regarding their experience with ELAHIR, which is a testament to our customer and healthcare professional-facing organization. In summary, we are very pleased with our performance and look forward to carrying this momentum into the second half of the year. With that, I would like to turn the call over to Anna to provide additional color on the mirrors of data on our ongoing development program. Anna?
spk06: Thanks, Isabel. Before I get into my update, thank you, Mark, for your kind words at the top of today's call. It has been a pleasure and a privilege to serve this organization. I take immense pride in having been part of this leadership team and having built a clinical development team comprised of top talent that executed effectively during a global pandemic, leading to the accelerated approval of Elihir with a broader than anticipated initial label and the first ever overall survival benefit for a novel therapy in platinum-resistant ovarian cancer. What we have done together is remarkable. Thank you for the opportunities you have given me and for your leadership. Now moving on to our review of the clinical programs. We were thrilled that shortly after we press released the top line data on May 3rd, Dr. Kathleen Moore was able to present the key efficacy and safety results from the confirmatory Murasol trial in a late-breaker oral presentation at ASCO in early June. Since then, we have continued to engage with stakeholders across the ovarian cancer community, and the enthusiasm for these data and the broader Mervituximab program is high. As a reminder, Mirasol is the randomized confirmatory phase 3 trial of Mervituximab versus investigators' choice of chemotherapy, weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. In patients with platinum-resistant ovarian cancer whose tumors express high levels of folate receptor alpha and who have received up to three prior regimens. The trial was a resounding success, and we are pleased that our compelling efficacy data with an unprecedented overall survival advantage were complemented by a consistent safety profile aligned to our prior clinical trial experience. Starting with safety, the AE profile continues to consist of predominantly low-grade ocular and gastrointestinal events with no new safety signals identified. Notably, compared with chemotherapy, MERV was associated with lower rates of grade three or greater treatment emergent adverse events, serious adverse events, and importantly, a lower rate of treatment emergent adverse events leading to discontinuation of study drug. On the primary efficacy endpoint of progression-free survival by investigator, Mirasol achieved a hazard ratio of 0.65 and a p-value of less than 0.0001, representing a 35% reduction in the risk of progression or death for the Elihir-treated population compared with chemotherapy. The key secondary endpoint, objective response rate, was also highly statistically significant. On the MERV arm, ORR was nearly triple compared to chemotherapy at 42.3% with 12 complete responses compared with 15.9% and no complete responses on the chemotherapy control arm as reported by investigators. PFF and ORR results by blinded independent central review were concordant with investigator assessment. Turning to the most meaningful clinical endpoint, overall survival, With 204 events reported, Elahir demonstrated a statistically significant improvement in survival compared to chemotherapy with a hazard ratio of 0.67 and a p-value of 0.0046. This corresponds to a 33% reduction in the risk of death with Elahir compared to chemotherapy. The median overall survival with Elahir was 16.46 months compared with 12.75 months on the chemotherapy control arm. As Mark noted earlier, Elihir is the first drug to demonstrate an OF benefit in a Phase III trial in platinum-resistant ovarian cancer. Quite simply, these data are practice changing. Let me now turn to the broader Mervetuximab development program, which has the potential to meaningfully expand the Elihir label by moving into platinum-sensitive disease and positioning Merv as the combination agent of choice in ovarian cancer. Specifically, we are progressing three studies. The first is PICOLO, a single-arm Phase II trial evaluating MIRV monotherapy in folate receptor alpha-high platinum-sensitive ovarian cancer. Enrollment was completed in January, and we anticipate sharing ORR data by the end of this year, with duration of response data expected in 2024. The second is GLORIOSA, our Phase III trial evaluating MIRV plus bevacizumab maintenance versus standard-of-care Bevacizumab maintenance in the second-line platinum-sensitive setting. This study levers our robust MERV plus Bev data in the treatment setting, which led to NCCN compendium listing for MERV Bev in platinum-resistant ovarian cancer, into the platinum-sensitive maintenance setting, where patients may stand to benefit from even longer durations of therapy. And the third is trial 420. A single-arm phase 2 trial evaluating MIRV plus carboplatin, followed by MIRV continuation in platinum-sensitive ovarian cancer patients with low, medium, or high levels of folate receptor alpha expression. Both combination trials, Gloriosa and Trial 420, are enrolling in the U.S. and are getting going in Europe. Moving to our second pivotal program, we presented data from an interim analysis of the Phase II CADENZA trial of PVEC in patients with frontline and relapsed refractory BPD-CN at the EHA or EHA conference in June. PVEC demonstrated encouraging clinical activity and tolerability, especially in light of the toxicities of available therapies. In the frontline setting, we observed a composite CR rate of over 70% and a median duration of response of over 12 months. In the relapsed refractory setting, which included patients previously treated with Tigraxibus, we observed a CCR rate of 20% and a median duration of response of over seven months. Commensurate with the increasing awareness of the potential of PVEC in this ultra-rare indication, we are pleased to share that we have completed enrollment in the pivotal frontline de novo BTDCN cohort of Cadenza and anticipate top-line data in 2024. For our 802 trial of PVEC in combination with venetoclax and azacitidine in frontline AML, we have enrolled 25 patients in both the venetoclax 14-day plus and the 28-day minus triplet cohort. These data will help us optimize the duration of venetoclax for the triplet and guide pivotal development in frontline AML. We look forward to reporting data from these cohorts at ASH later this year. As for our earlier stage assets, on IMGC936, our first-in-class ADAM9 targeting ADC in co-development with macrogenics, enrollment progressed in 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 expect later this year. Lastly, we are progressing our phase one 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. In closing, I want to thank all my Immunogen colleagues for their ongoing commitment to delivering more good days for patients with cancer. I will cherish my time with this business, both professionally and personally. As to what's next, I look forward to spending time with my family, continuing my board work, and pursuing consulting in the coming months while I watch Immunogen's bright future unfold. With that, I'll turn the call over to Renee to cover our financials. Renee?
spk25: Thanks, Anna. For the second quarter of 2023, we generated $83.2 million in revenue, including $77.4 million in net product sales of Eliher and the remainder from non-cash royalty revenues. Operating expenses were $86.4 million, comprised of $50.1 million of R&D expenses and $36.4 million of SG&A expenses. In May, pursuant to an equity offering, we further strengthened our balance sheet generating approximately $351 million in net proceeds. We ended the second quarter with $572 million in cash on the balance sheet. Our financial guidance for 2023 has been updated, and we now expect operating expenses between $350 million and $365 million. This increase reflects greater spending in support of Elihir, including preparations for a launch in Europe. in addition to expanding our research capabilities and pipeline. Revenue guidance, excluding Elijer sales, remains unchanged at between $45 and $50 million. We expect that our existing cash and cash equivalents, together with anticipated future product and collaboration revenues, will fund operations for more than two years. With that, we'll open the call for questions.
spk04: As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. The first question comes from John Newman with Canaccord. Your line is open.
spk09: Hi, guys. Thanks a lot for taking my question. So, Anna, first, I just want to say congrats on all the great work at Immunogen. You'll certainly be missed. And they say the best companies in biotech are the ones that can execute their clinical studies near perfect, and Immunogen is certainly included in that bucket. Just had one question, which is, we know that Mervetuximab and Mirasol was tested in patients with FR-alpha high. confirmed by 3-plus expression level. Just curious if you can talk about whether you expect MERV, or I should say ELLA here now, will be used in patients with 2-plus expression levels, and perhaps if we're seeing that at the moment. Thanks.
spk06: Thanks, John. Thank you for your kind words. Just to clarify, the definition of FR-alpha high expression by our companion diagnostic is at least 75% of tumor cells, at least 2-plus positive by immunohistochemistry staining, so 2-plus and 3-plus. And that comprises between 35% and 40% of all ovarian cancer patients, and the commercial testing has performed as we've seen in clinical trials. We have previously explored Mervituximab in patients with lower levels of FR-alpha expression as monotherapy. You can recall from Forward One, And we know from that study that patients with medium levels of FR-alpha expression, which is at least 50% of cells, so medium is between 50 and 75% of cells with at least two plus expression by immunohistochemistry. And that encompasses about another 20% of ovarian cancer patients. We know that they do about as well with Mervituximab as with investigator choice chemotherapy based on a post-hoc exploratory analysis. And certainly, based on that data, as well as some preclinical data that we have showing synergy with various agents, we are exploring patients with lower levels of FR-alpha expression in our combination strategies. We also know that when we combine Mervituximab with Bevacizumab across a broad range of FR-alpha expression, so low, medium, and high, lows being at least 25% to 50% of cells with at least 2-plus expression, that we get very nice data that were published earlier this year in the DynOnc journal, and that led to compendia listing for MERV plus BEV for patients with low, medium, or high FR-alpha expression, and that encompasses about 80% of ovarian cancer patients. Looking to the future, we're also combining MERV with carboplatin in patients with low, medium, and high FR-alpha expression for in our 420 study. So, our initial approval in patients with high FR-alpha expression for MERV monotherapy is just the beginning.
spk09: Great. Thank you. If I could ask one quick additional question. On combination with abacizumab, just curious if you're seeing anything at the moment from your data with regard to perhaps the uptake there in combination with abacizumab. Thanks.
spk16: Yeah, the answer is yes. So, when we look at the claims data, and I'm sure we'll have lots of questions on that, it's early days, but we absolutely do see combination use as part of the claims set, and the feedback that we get anecdotally certainly supports that. Great. Thank you.
spk04: Please stand by for the next question. The next question comes from Michael Schmidt with Guggenheim. Your line is open.
spk15: Hey, guys. Thanks for taking my questions, and congrats on another very strong quarter. And let me just add my congratulations to Anna as well for all the success in your agenda. You will be missed, obviously, by many. I have a question on the evolving testing paradigm. So in our due diligence, we've heard that many of the large academic institutions prefer in-house testing over using the centralized labs that you have established. And I was wondering if you could confirm that and how many of the big centers are not yet certified for in-house testing in the U.S.?
spk28: Thank you. As you know, we had a very strong demand for testing so far. And in the second quarter, we surpassed 11,400 tests. And now we are over 13,000 tests. We can confirm that today. And when it comes to the labs, we have 33 labs that are operational, of which 15 are academic centers. And in those centers, we have less visibility about the data that we have. In process, we have another 15 labs that are in the process of being certified, so we continue to see very strong testing, as I just mentioned.
spk15: Okay, thank you. And regarding the Piccolo study, how should we think about the regulatory bar for response rate in that platinum-sensitive setting? Is the bar similar to that that was applied to the Soraya study, for example, or is it higher or lower?
spk06: I think the bar is to be determined, Michael, because, you know, the landscape has evolved with the incorporation of PARP inhibitor maintenance, particularly now in the frontline setting. And we know from multiple studies that, unfortunately, PARP maintenance therapy seems to induce resistance to subsequent DNA damaging agents, particularly things like platinum. as well as topotekin and doxil, which also are DNA damaging agents. But what that means is that patients who are technically platinum sensitive post a PARP inhibitor, in other words, they've recurred greater than six months after the last dose of their last platinum, may not be as sensitive to platinum as they were previously. So that coupled with the fact that there were not there are no robust randomized phase three level one evidence studies in later line platinum sensitive disease to begin with, even in the pre-PARP days. We don't really know what the benchmark is. That said, more studies are coming out, again, showing that more platinum for these post-PARP patients may not be in their best interest. So, you know, the way we're thinking about it is that the higher the response rate, the longer the duration of response in PICOLO, the easier the conversation will be with regulators about what an appropriate bar would be for us to beat. So at this point, we're really excited about the PICOLO study. We're on track for ORR data before the end of the year. We know these patients are doing well, and so we will anticipate having DOR data next year.
spk15: Okay, thank you. And then last question, just regarding the 802 study of PVEC in AML, could you just Remind us of the two cohorts that you're running in frontline and what you're looking for here in the ASH data that would support initiation of phase three trials. Is it a primary look at safety or certain efficacy measures are important as well for you?
spk06: So just as background, you know, Ven-Aza has become the new standard of care for unfit frontline AML patients, which is about half of AML patients, although even the definition of unfit is being evolved so that more patients do get Ven-Aza. That said, it's a tough regimen in and of itself at the labeled doses and schedules. Many compounds have tried to combine with Vaneza and have failed because of just excess toxicity of the triplet. Ours is not one of those. We are one of the few that has been able to combine successfully. And so we started out, I would say, in an appropriately conservative manner to protect patient safety with what's called a 14-day plus regimen of venetoclax in the relapsed refractory setting. We proved safety of that regimen and moved it up into the front lines setting where we had 10 patients' worth of data we presented at ASH last year with the 14-day-plus regimen. In conversation with FDA, FDA made it clear their expectation is that we combine with a standard or labeled dose and schedule of venetoclax, and venetoclax is generally given per label up to 28 days in a row. But the problem is many patients can't tolerate that extended duration of venetoclax because of profound myelosuppression. And so we have basically completed accrual now in 25 patients using what we call the 14-day plus and 25 patients in the 28-day minus regimen. So what happens is for each of these patients do get a bone marrow around 14 days in the 14-day plus or later in the 28-day minus regimen. And if patients have residual blasts, they continue with the venetoclax. If the bone marrow shows no blasts, then they stop the venetoclax, because at that point, venetoclax would just be adding toxicity. And so we're going to combine the data from those sets to understand the safety of the triplet, understand the efficacy, both in terms of CR rate as well as MRD, or measurable residual disease rate. And both safety and efficacy will guide how we're thinking about a frontline pivotal triplet AML registrational trial. So, stay tuned for ASH.
spk32: Great. Super. Thanks for all the detail, Anna.
spk04: Please stand by for the next question. Our next question comes from Peter Lawson with Barclays. Your line is open.
spk29: Great. Thank you so much. Just wanted to offer my congratulations and Also wanted to mention it was always been a pleasure talking to you, Anna, and best of luck with the next step. Just as we think about the duration of use, I wonder if you could kind of provide some kind of, it sounds like there's a range you're getting from your estimates, but if there's anything you can give around that range for the duration of use, kind of the line of therapy and whether you're mostly seeing it in combination with Bev.
spk16: So, you know, it starts with the claims data, right? And so it trickles in. So, you know, as we gather those data, so, for example, if you look at, you know, the last claims data I saw was earlier this month, you know, we had four patients reported, right? And so it's a little hard to, you know, think about extrapolating that over the back half of the year when you sort of have to back up then 90 days and try and accumulate the totality of the experience and then project that forward. And so duration of therapy falls exactly into that bucket, which is it's difficult to ascertain at this point when we look at the accounts versus the claims data to assess what's happening commercially. with the brand at this point. And so, you know, our experience that we've related is with the Saraya data where it's complete, where we saw, you know, a mean number of cycles of seven in that population. That population certainly was the most heavily pretreated that we've observed in our clinical experience. And so, you know, I think that's a baseline for duration of therapy. What we can say, Peter, generally is that in the initial stages of the launch, the claims data indicate that we were starting in later Lyme patients. Particularly with the Marisol data, what we see is movement into earlier Lyme patients, which we think will correspond with longer durations of therapy generally. In addition to that, what we see are combination use. The results from that, as we shared in the prepared remarks for today, are disparate across the databases. So, we're making a concerted effort to try and reconcile those databases and supplement that with a demand study in order to get a better assessment of what's going on. As we think about this, the commercial team here has put together essentially a matrix, and on one axis is the impact that it has on revenue, and on the other is our confidence level. So when we look at things that have high impact and high confidence, We include there our FR-alpha positivity rate because we've run the experiment on over 13,000 tests and have a pretty high degree of confidence in terms of the positivity rate. In terms of duration of therapy, we simply have an incomplete data set when we look over the claims data. And similarly, we just see an evolving picture in terms of lines of therapy. So Again, it's something that we are, you know, working on aggressively in order to have, you know, a very clear view of the market that we could articulate to the investment community.
spk29: Gotcha. Your conversations with physicians, does that point into most of the combination use or is it, again, kind of a broad range?
spk16: We see a significant percentage or, you know, we have... physicians report to us in their practices that a significant percentage of the use is in combination.
spk29: Thank you so much. I'll jump back into the queue.
spk04: Please stand by for the next question. The next question comes from Itzer Darrow with BMO Capital Markets. Your line is open.
spk13: Great. Thank you. And congrats on the quarter. And I also would like to echo my colleague's sentiment on the contribution, Anna, that you've had to Imogen's story. First question for me is I just wondered if you can maybe talk a little bit about some of the major differences in ovarian cancer treatment or practice, I guess, in the U.S. versus some of the major countries in the EU. And, you know, what impact maybe those differences could have on sort of the launch trajectory or maybe your overall strategy in Europe versus what we've seen early on here in the U.S.? And then I have a follow-up. Thanks.
spk06: So I'll start with practice pattern differences and then turn it over to my colleagues to discuss how that influences our launch strategy in Europe. The one real difference, Esther, is how and when physicians use bevacizumab or Avastin. And we've known that. It was approved in 2014, 2015. It has three approvals in the U.S. and Europe. It's approved in combination with chemotherapy and platinum-resistant disease. It's approved in combination with chemotherapy in recurrent platinum-sensitive disease and then continued as maintenance and in the frontline setting in combination with chemotherapy and as continued as maintenance. The problem with Bev is that it's never shown an overall survival advantage in any of these settings except in a poor prognosis, high risk subset in the frontline setting. So these are patients who present with stage four disease or parenchymal metastasis. They have ascites. They're suboptimally debulked. In that subset, the addition of Bevacizumab does improve overall survival. So particularly in Europe, oftentimes Bevacizumab is only reimbursed or patients only have access to Bevacizumab in that frontline poor risk setting. And in fact, that kind of bore out in our SREA study where, you know, the majority of patients were enrolled in the U.S., excuse me, in Europe. And that study had a higher percentage of stage four patients than is typically seen in a relapsed or recurrent, you know, ovarian cancer study. So because of that, in Europe, a higher percentage of patients in the platinum resistance setting get single-agent chemotherapy, and that's important for how we're thinking about ELAHIR when we get it approved.
spk28: Yes, and the way this translates for the launch is that the admin need there is even higher, and the number of patients that will be eligible for ELAHIR is also higher. Our goal, therefore, is to, as mentioned by Mark, is to file by the end of this year, and we are making significant progress towards the launch. First, we're working on our global values here and pricing. And payers in Europe tend to value overall survival data. So we feel very confident that that will give us a strong initial position there. Second, we are really pleased that we have a very solid engagement with KOLs there. As you remember, over 70% of our patients in the clinical studies were enrolled in SUS. So those very strong relationships, we are leveraging that. We will be having two other presentations at ESCO in Istanbul at the end of September, and we also will have a present at ESMO. So we continue to have this one-on-one engagement, and we are also partnering with the community in preparation for the launch. Finally, we are ramping up the team towards preparing for execution, and we feel very confident that we have a successful launch in Europe as in the U.S.
spk16: Maybe the only other thing to add there, Ed, sir, is that it's just a very highly concentrated market. So when we do the market research across both the five largest markets and expanding that into 16 markets, we see a relatively consistent pattern, which is a small number of centers treat a high percentage of the patients. So, when we look at the five key markets, for example, 60-odd centers treating 80% of the market. So, this is something that we can address with a modest incremental commercial investment, and particularly given the data that we have, and as Isabel mentioned, the relationships that we have, we expect a very robust launch there.
spk13: Great. Thank you. And then the follow-up was on IMGC 936. Sort of the market here is paying a lot of attention to sort of another ADC mechanism, the TROP2 and non-small cell lung cancer. And for sort of the interim analysis that you have maybe in the back half of this year, how you're thinking about what the go-no-go is. Is it going to be on response rate, duration of response? Is it maybe PFS? If you could maybe provide a little bit of color on how you're thinking about sort of to go forward strategy on that asset. Thank you.
spk06: Sure. So IMGC936 is our ADAM9 targeting ADC that, you know, ADAM9 is expressed across a broad array of solid tumors, and we've prioritized non-small cell lung cancer based on what we saw early in development. And so we have expanded the first stage of a two-stage design, if you will, to understand the activity of IMGC936 in non-small cell lung cancer. And I think the initial hurdle at SIR would be just overall response rate or objective response rate in the initial cohort of patients. And at that point, that data would guide further expansion into the second stage. at which point we would have a larger data set where we would look at ORR and DOR to assess, you know, how we're thinking about further development. Just in terms of single arm studies and PFS data, typically it's hard to make robust decisions based on PFS, so it's typically ORR and DOR data that will guide further decision making.
spk37: Great. Thank you.
spk04: Please stand by for the next question. The next question comes from Boris Peeker with Cowan. Your line is open.
spk08: Thank you. And I'd like to add my congratulations to Anna specifically and the entire MUNIGEN team for the excellent progress. So maybe my first question is on the testing centers. You've obviously mentioned that there's been an increasing in testing centers being brought online, but how much do you estimate maybe the current revenue being potentially limited based on the existing testing infrastructure in the second quarter?
spk16: Yeah, not at all. I mean, we just testing is simply not a barrier to entry. You know, we do know that the institutions at present have a preference for in-house testing, but that didn't prevent them from sending tests out to, you know, so before their centers were open, we could see, you know, ordering from accounts and testing from accounts that didn't have in-house testing. And, you know, as we've mentioned, you know, as time progresses, a number of those institutions are taking it in-house What I will also say, Boris, is we've actually had some interesting conversations about this phenomenon as it related to PD-1, PD-L1 testing. And what we hear is that initially there was great enthusiasm among the academic institutions to take that testing in-house. However, over time, that enthusiasm waned to some degree, and they began sending their tests back out to centralized labs. So, as we've discussed, we see the migration in-house. over time, whether that's a sustainable phenomenon, I think, is an open question at this point. But just to be very clear, you know, we've done over 13,000 tests launched to date. It has simply not been a barrier to entry.
spk08: Great. And my second question is, in terms of the NCCN guidelines, do you anticipate any future updates incorporating maybe Mirasol or any other data in the near future?
spk06: Yeah, so we anticipate with Mirasol being the only study to show an overall survival advantage in a randomized Phase III setting for a novel agent, we anticipate Mirasol could move our Elihir compendia listing from 2A to Category 1, and it would be the only medication in the NCCN platinum-resistant treatment guideline that would have that level of evidence. We also are anticipating that the PICOLO data could support NCCM compendia for later line platinum-sensitive ovarian cancer for MERV monotherapy. And also, we are generating three data sets at this point for Mervituximab plus carboplatin. The 420 study that is our sponsored study in low, medium, and high FR-alpha expressing patients. as well as we are supporting two investigator-sponsored trials, a neoadjuvant study and a randomized phase two study in Germany led by Philip Harder. And those data could absolutely support compendia listing as well.
spk28: Yeah, we also hope that we can move, sorry, the compendia listing of the combination from 2B to 2A. From IRF-BEV, yes.
spk08: Do you have a sense of timing for that?
spk28: Oh, well, we are aiming to make some changes for the listing of Elagir monotherapy in October, and similarly for the combination of MedVap from 2B to 2A.
spk06: Yeah, we will work with NCC and around their scheduled meetings.
spk08: Great. Thanks for taking my questions, and congratulations once again.
spk04: Thanks. Please stand by for the next question. The next question comes from Andy Shea with William Blair. Your line is open.
spk14: Congratulations on another blowout quarter, and it's been a pleasure working with you, Anna. I wish you the best of luck. So I have a question about kind of the strength of the community and non-academic centers. So I'm curious if you have a view on that or any sort of market dynamics you're seeing there. And I also have a follow-up in terms of the R&D and your P&L. Obviously, you know, strength from Ella here could fuel your R&D. I'm just curious about maybe the near and mid-term vision about R&D, what's in store, what do you expect the R&D to look like in the next three years? In terms of P&L, obviously, you're pretty close to break even this quarter. I'm just curious if that's the goal. How do you think about, you know, your income statement as ELL here continues to ramp at this just incredible pace? Thank you.
spk16: Sure. Thanks, Andy. So, I'm going to ask Isabelle to start and then Mike to talk about R&D and then some combination of Renee and I can tackle the P&L. Sure.
spk28: So we are very pleased with the strong adoption in both the community and academic centers. And if you remember early in the launch, we thought that the academic centers would start first and community would follow. What we had seen is a very strong adoption in community, and that's testament to the unmet need and the target profile of the drug. We also see that academics have to follow the normal process. They have to wait for the committee, they have to wait for In some centers, they have the testing in-house, but they have now started to test, and we are very pleased that pretty much all the major institutions are already ordered ELA here. We have additional events that will create additional growth in both. We have the JCODS July 1st. We have been included in Pathways. And we think that that's going to continue driving the growth in both academic and non-academic institutions. In terms of the mix, we think it will remain relatively similar with more, 65 to 35%, with more growth maybe coming from academic institutions in the second quarter.
spk07: And Andy, this is Mike, regarding your question about continued investment in R&D. Just to remind you, as Anne has nicely summarized, we have a broad ongoing life cycle management program with Mervituximab. It's important for us to think about every woman with ovarian cancer that expresses folate receptor alpha to have the right medicine at the right time. That will include investigation of alahir and platinum-sensitive ovarian cancer. You've already heard about that, but I wanted to also remind you about IMGN 151, which we continue to move through phase one development and has the potential to broadly impact FR-alpha expressing cancers, not only in ovarian cancer, but beyond in cancers such as endometrial, non-small-field lung cancer, and others. You've also heard about the continued investment of PVEC in frontline AML, and we look forward to those data informing continued clinical development there. And then importantly, as a reminder, we have three broad classes of payloads with associated linkers that form the basis of our portfolio, the metansenoids, the IGN, and importantly, a campathesin group of compounds that have yet to be formally tested in clinical development. So we look forward to work that's already ongoing with collaborators to bring forward novel antibodies, linkers, and test those payloads in a broad swath of cancers. So, we're really very committed across the spectrum and look forward to sharing this earlier progress of molecules and research as we move forward closer to IND.
spk16: So, Andy, as Mike just articulated and we've also talked about the expansion globally of Ella here with the labeled indications, we do expect to invest heavily in the business in the coming years. So, you know, we've given cash guidance. to say that we've got more than two years worth of cash. And that is a reflection of both the existing balance sheet as well as the strength of the ELLA here launch. But we aspire to be a fully integrated oncology company. We're fortunate to have one marketed product and three additional clinical candidates, but our goal is, again, to expand our preclinical capabilities. We've done so incrementally with a number of partnerships, and we look to continue that activity and also rebuild some in-house capabilities as it relates to our core areas of expertise, as Mike has outlined. The focus is, again, you know, international expansion for the business, supporting the launch, lifecycle management and rebuilding our preclinical pipeline. So, again, you know, areas of investment on a go-forward basis.
spk17: Great. That's very helpful. Thank you so much. Sure.
spk04: Please stand by for the next question. The next question comes from Kelly Sher with Jefferies. Your line is open.
spk24: Congrats for another great quarter. And also, please allow me to add my congrats to Anna. My first question is for PICOVA trial, what kind of a treatment duration could we expect? And also, in this platinum sensitive setting, is the proportion of FRR for high patient same as in the platinum resistance settings around 35 to 40%.
spk06: Thanks, Kelly. So, let me address your second question first. The vast majority of patients who have participated in Mervituximab trials and who are receiving commercial Elihir do so based on archival tumor tissue testing. So, patients generally have debulking surgery at the time of diagnosis, and that's when they're FR-alpha. That's when they have tumor taken for FR-alpha testing. So, the 35% to 40% is true regardless of what setting the patient is in. Going back to your first question about treatment duration for Piccolo, you know, these are later line platinum-sensitive patients, but we know that platinum-sensitive patients in general do better than platinum-resistant patients, you know, regardless of therapy, although, again, that does seem to be possibly changing for the subset of platinum-sensitive patients post-PARP who get more platinum. That said, you know, we anticipate the treatment duration for the PICOLO study is going to be appreciably longer than, for example, in Mirasol or Soraya. So, stay tuned.
spk24: Okay, great. Thanks. And also, for 936 in non-small cell lung cancer cohort, Just curious, is this pre-specified interim analysis applied to a post-PD-1 setting?
spk06: So it's not specifically in the post-PD-1 setting, but this is a phase one study where patients with non-smell cell lung cancer have had the appropriate prior therapies, and the vast majority, if not all of them, have had a checkpoint inhibitor.
spk03: Okay, great. Thank you.
spk04: Please stand by for the next question. The next question comes from RK with HC Wainwright. Your line is open.
spk21: Thank you. Congratulations. And, Anna, congratulations and nothing like signing off on a high note. I will certainly miss you, especially on all the helpful conversations that we have had in the last few years. And additionally, both my dog and I are going to miss you on our Zoom calls, you know, future Zoom calls with immunogen. So in terms of expectations at the ESGO, you know, what additional analysis, you know, could we see at that conference?
spk06: Yeah, ESGO is in Istanbul this fall. I think it's the end of September. And we have two abstracts that have been accepted for oral presentation in terms of additional subset analyses from Mirasol. The ones that will be focused on in this initial array of data are the subsets based on number of prior lines of therapy. as well as patients who have or have not had a prior PARP inhibitor. So those are the key subsets because, you know, physicians are quite interested to understand where to position Elihir in the treatment paradigm. And I think these subset data will be very informative for them.
spk21: Thanks, Anna. Also, as you plan to file the MAA in Europe during the next six months, How should we think about the commercialization there? Would this be directly by yourselves, or are you seeking for a commercial partner there? I'm just trying to understand the commercial structure that could be set up in it all.
spk16: Sure. Okay. So, we plan to go direct in the five largest markets. There's a pretty leveraged approach that one can take by clustering. So we can add 11 additional markets. So we expect to be direct in 16 markets in Europe. Of course, that takes place over time, just given the cadence of reimbursement in those markets. And then we would use distributors outside of what we call the EU 16. Thanks, Mark.
spk22: Thanks for taking my question. Sure. Sure.
spk04: Please stand by for the next question. The next question comes from Astaka Goonwarden with Truist. Your line is open.
spk15: Hey, guys. Good morning. Astaka from Truist here. Thanks for taking my questions. Also, my congratulations on a very elegant execution to the team. And on a personal note, Joanna, we only launched coverage nine months ago, but in our limited time, it's been a pleasure to get to know you and appreciate your discipline. We wish you the best for your next adventure. Just a couple of quick mock-up questions for us here. You're clearly getting a nice boost from what one might call off-label use in the U.S., but in general, in oncology, do you think off-label use in Europe can be as strong as you do get seen in the U.S., or do you think the docs over there in Europe are going to stick to the script a bit more? Second question is I'd like to test and see if we can get any sort of color on timelines for Gloriosa. I know that's one of the next things that people are going to be looking at as well here after Piccolo. And then lastly, Mark, when do you feel confident that you'll get enough of a sample from the claims data to give us a, to give us some guidance on a product level basis failure? Thanks, guys.
spk16: Sure. So, as to the first question, it's not so much the physicians that make the decisions with respect to the use outside the label in Europe as just a reimbursement there, and it's very stringent. There are very limited instances where you can see off-label coverage there, and that's distinct from what we see in the U.S. market, particularly where drugs are listed in the compendia, as we've seen with Ella here, both in terms of no restriction on Prior lines of therapy and the combination with Avastin. So they're fundamentally different markets as it relates to reimbursement, and that's what drives it. So the expectation should be that use there will be within the label approved by the EMA. In terms of Glorio, it's early days, so we haven't given any guidance there. And then, sorry, your third question was? I think it needs to be driven by two things. The two key factors that are most opaque at this point are duration of therapy and, really importantly, discontinuations, which of course are related to duration of therapy. And I think it's going to be, you know, some time before we get to that. I certainly would expect us by, you know, the beginning of next year when we all get together at J.P. Morgan or in conjunction with our year-end earnings call to have, you know, a reasonably clear-eyed view on that. You know, and as I say, we've got this demand study going, and, you know, we'll see what that tells us as well.
spk15: Great. Thanks for taking my questions, guys.
spk04: please stand by for the next question. The next question comes from Joe Cottanzaro with Piper Sandler. Your line is open.
spk35: Hey, guys. Thanks for squeezing me in. Congrats on the nice quarter, and congrats to you on a nice tenure here. Maybe just two for me. I'm wondering if you had a sense around the cadence of new patient starts in 2Q and whether it was evenly distributed or not, and relatedly, whether you saw an uptick in usage in June and July following the Mirasol presentation at ASCO. And then my second question, Mark, you mentioned sort of the difficulty in modeling prevalent incidents. I'm wondering sort of where you think you are in that curve and what metrics you're looking at that will give you an indication that, you know, you're shifting to majority usage in the incident population. Thanks.
spk28: Okay, so when it comes to the incidence versus prevalence population and how we are looking at the patient data, we have longitudinal data and claims, and the issue with that, frankly, is that it's lagging 90 days, so we have very few patient data at this point. We get it from DRG by lines of therapy, and we are tracking that, and we think we need additional time before we can tell you what is happening there. We have seen, though, that the MIRASOL data does have an impact in terms of uptake of more patients, as you saw in the second quarter. And we also can see early signs from the claims that patients are moving to treat in earlier lines of therapy, pretty much as a sign of first resistance.
spk18: Okay, thank you.
spk04: Please stand by for the next question. The next question is from Jonathan Chang with Lyric Partners. Your line is open.
spk36: Thanks for taking my question. Congrats on the quarter and best wishes on our next steps. Just one question for me. How are you guys thinking about potential business development opportunities for Ella here and strategic interest broadly? Thank you.
spk16: Yeah, so, you know, what we've done with Ella here is we've decided to go direct in the largest markets where we can with, you know, modest investment, support a robust launch. So starting here in the U.S. as we talked, you know, a bit on this call, going to Europe, In markets where that's not feasible, for example, in China, we've elected to go with partners. We're exploring partnerships for Japan in a similar vein. And outside of that, I think we plan to use distributors because we think that with a time-limited distribution agreement, we can call back those when we're ready to move to a direct model. You know, in terms of, you know, more broadly, business development, you know, as we've talked, we want to rebuild the front end of the pipeline and, you know, some of the deals that we've done, OBT, and more recently, a very small deal with ImmunoBioChem, again, to build the front end of the pipeline. So we're very excited about this business. We love the momentum that's been generated this quarter in the marketplace, and that's paired very nicely with with data, progress with the pipeline. So we're excited about our long-term prospects here.
spk19: Got it.
spk04: Thank you. I show no further questions at this time. I would now like to turn the call back to Mark for closing remarks.
spk16: Great. Well, thank you all very much for joining us today. We had a very strong first half. We do expect to carry this momentum for the remainder of the year, you know, as we look to deliver more good days for our patients and, importantly, create value for our shareholders. So we look forward to keeping you updated on our progress as we move through the second half. So thanks again for your time today.
spk04: This concludes today's conference call. Thank you for participating. You may now disconnect. Hello. music music Thank you. Thank you. Good morning and welcome to Immugent's second 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 Chan, head of investor relations. Please go ahead.
spk26: 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 second 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 Kalofonos, our Chief Commercial Officer, Anna Birkenblit, our Chief Medical Officer, and Renee Lentini, our Interim CFO. Michael Vasconcells, our EVP of Research Development and Medical Affairs, will also join us for Q&A. 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 then our other FCC filings, which are available at scc.gov and immunogen.com. With that, I'll turn the call over to Mark.
spk16: Thanks, Annabelle. Good morning, everyone, and thank you for joining us today. You will have seen this morning's press release announcing that Anna will be stepping down from her position as Immunogen's Chief Medical Officer to take a well-deserved professional hiatus prior to pursuing new opportunities. I would like to take a moment to personally acknowledge and thank her for the essential role she has played in the transformation of this company. We've encountered no small amount of adversity as we navigated the last four years at Immunogen. Through it all, Anna rose to the challenge with intellect, grit, and good humor. Of particular note, she led the design and execution of the pivotal development program for Elihir that culminated in an FDA accelerated approval late last year and the unprecedented survival data shared at ASCO in June that have transformed the treatment landscape for patients with FR-alpha positive ovarian cancer. In parallel, under her leadership, we've also advanced our broader clinical pipeline, including a second pivotal program and built a highly talented development organization. Anna, I value you as a colleague and wish you the very best in your future endeavors. On behalf of Immunogen, our collaborators, and most importantly, patients in need of more good days. Thank you. So, moving to our second quarter results. Since our last call, we've made great progress on multiple fronts and achieved a significant milestone for patients in our organization with our confirmatory phase three Mirasol trial, meeting not only the primary endpoint of progression-free survival, but also objective response rate, and most importantly, overall survival. This is an unprecedented result in platinum-resistant ovarian cancer, making Elihir the first novel therapy to demonstrate an overall survival benefit versus chemotherapy in a Phase III trial. With these results now in hand, we anticipate submitting an MAA in Europe and the SBLA in the U.S., both in the fourth quarter of this year. Turning to our commercial performance, we delivered a strong quarter with Elihir generating over $75 million in net sales, more than doubling our Q1 result with increasing breadth and depth of adoption. Isabel will provide more detail on our progress with the launch in a moment. As an initial point, given that this is just our second full quarter on the market, coupled with recent developments with both Elihir and the broader ovarian cancer landscape, we've elected not to provide full year guidance for LE year revenue today. The basis for this decision is this. We simply have not yet accumulated sufficient data and experience to confidently project the trajectory for LE year over the back half of this year. The key variables underlying this decision include Evolution of treatment rates. Given the compelling efficacy of Elihir, we believe treatment rates may be increasing over historical benchmarks, particularly for later Lyme patients. Shifting from prevalent to incident populations, which may potentially affect the growth rate of new patient starts. Duration of therapy. The claims data, which lag the market by 90 days or more, are not mature enough for us to provide a reliable forecast of how long patients are remaining on therapy at this time. Mix of testing and initial diagnosis versus testing to initiate treatment. And finally, monotherapy versus combination use. We are tapping multiple data sources to assess the percentage of combination use, which have yielded somewhat disparate outputs up to this point. Our clinical data suggests that combination use tends to generate higher response rates and longer durations of response, so an accurate assessment of this use is important. You will appreciate that each of these variables can have a significant impact on adoption and adherence. To better assess the evolving market here, we have commissioned a demand study with the goal of increasing our confidence in assessing trends and the growth trajectory for the product. In addition, our existing vendors are updating their databases and we are evaluating additional sources to gather more insights into the market. We look forward to updating you on our progress on these activities during subsequent calls. In terms of ongoing development, we are advancing our efforts to move Elihir into broader patient populations and to position it as the combination of choice in ovarian cancer. We look forward to our next milestone for the Elihir program with ORR data from our PICOLO trial expected before the end of the year. Moving to our PVEC program, We've completed enrollment in the pivotal de novo patient cohort of the CADENZA trial and expect top-line data in 2024. In addition, we progressed our 802 trial of PVEC in combination with Veneza for newly diagnosed AML patients and look forward to reporting data from these frontline cohorts at ASH later this year. Looking at the rest of the pipeline, IMGC 936 and IMGN 151 are progressing. and we remain focused on reinvesting in our research capabilities and expanding our pipeline. Together with a strong balance sheet bolstered by our follow-on offering, our progress over the first six months of the year has positioned us well to create meaningful value for our patients and our shareholders in the second half of 2023 and well beyond.
spk11: With that, I'll turn the call over to Isabel to cover our commercial progress. Isabel?
spk28: Thank you, Mark. We continue to successfully execute across the four launch imperatives as we work to position ELAHIR as the standard of care for foliar receptor alpha-positive ovarian cancer. In the second quarter, we generated $77.4 million in net sales. We're very pleased with another strong quarter of performance and believe this is due to the combination of factors, including the solid execution of the commercial teams Provided engagement by our medical team, increased breadth and depth of adoption driven by recognition of the benefits this novel treatment brings to patients with advanced ovarian cancer, and the compelling Mirasol data increasing awareness and interest from both patients and physicians. Uptaking the quarter continues to be broad and deep, with a significant percentage of accounts with repeat orders complemented by consistent ordering from new accounts. While academic institutions comprise our largest customer, roughly 65% of orders during the quarter came from non-academic institutions and community-based oncology groups, versus 70% in the first quarter. We anticipate the need of orders to continue to shift with an increasing percentage coming from academic accounts as satellite centers of major academic institutions start infusions. Regarding testing in response to the continuous strong demand for the foliar receptor diagnostic test, additional labs are actively being certified to run the test. As of the end of the quarter, we had 33 labs comprised of 16 centralized labs and 18 in-house labs fully certified with 15 additional labs in the process of validation. Of note, as testing becomes more decentralized, will have decreased visibility into the number of tests performed. Based on the information visible to us, we estimate that roughly 11,800 tests have been performed long today through the end of June, with a significant percentage of these tests being for newly diagnosed patients. In addition, the foliar receptor alpha positive rate remains between 35 and 40% in line with our expectations. Moving on to access, we continue to be very pleased with how quickly payers have included ELA hearing coverage policies aligned with our label. We ended the quarter with roughly 95% of both Medicare and commercialized coverage. Lastly, our customer-facing field team remained highly active. As of the end of June, our commercial team has engaged roughly 90% of the priority targets, and our medical affairs team continues to provide a full suite of support to ensure positive physician and patient experiences. Proportions in the field consistently relate enthusiastically back from clinicians regarding their experience with ELAHIR, which is a testament to our customer and healthcare professional-facing organization. In summary, we are very pleased with our performance and look forward to carrying this momentum into the second half of the year. With that, I would like to turn the call over to Anna to provide additional color on the mirrors of data on our ongoing development program. Anna?
spk06: Thanks, Isabel. Before I get into my update, thank you, Mark, for your kind words at the top of today's call. It has been a pleasure and a privilege to serve this organization. I take immense pride in having been part of this leadership team and having built a clinical development team comprised of top talent that executed effectively during a global pandemic, leading to the accelerated approval of Elihir with a broader than anticipated initial label and the first ever overall survival benefit for a novel therapy in platinum-resistant ovarian cancer. What we have done together is remarkable. Thank you for the opportunities you have given me and for your leadership. Now moving on to our review of the clinical programs. We were thrilled that shortly after we press released the top line data on May 3rd, Dr. Kathleen Moore was able to present the key efficacy and safety results from the confirmatory Murasol trial in a late-breaker oral presentation at ASCO in early June. Since then, we have continued to engage with stakeholders across the ovarian cancer community, and the enthusiasm for these data and the broader Mervituximab program is high. As a reminder, Mirasol is the randomized confirmatory phase 3 trial of Mervituximab versus investigators' choice of chemotherapy, weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. In patients with platinum-resistant ovarian cancer whose tumors express high levels of folate receptor alpha and who have received up to three prior regimens. The trial was a resounding success, and we are pleased that our compelling efficacy data with an unprecedented overall survival advantage were complemented by a consistent safety profile aligned to our prior clinical trial experience. Starting with safety, the AE profile continues to consist of predominantly low-grade ocular and gastrointestinal events with no new safety signals identified. Notably, compared with chemotherapy, MERV was associated with lower rates of grade 3 or greater treatment emergent adverse events, serious adverse events, and importantly, a lower rate of treatment emergent adverse events leading to discontinuation of study drug. On the primary efficacy endpoint of progression-free survival by investigator, Mirasol achieved a hazard ratio of 0.65 and a p-value of less than 0.0001, representing a 35% reduction in the risk of progression or death for the Elihir-treated population compared with chemotherapy. The key secondary endpoint, objective response rate, was also highly statistically significant. On the MERV arm, ORR was nearly triple compared to chemotherapy at 42.3% with 12 complete responses compared with 15.9% and no complete responses on the chemotherapy control arm as reported by investigators. PFS and ORR results by blinded independent central review were concordant with investigator assessment. Turning to the most meaningful clinical endpoint, overall survival, With 204 events reported, Elahir demonstrated a statistically significant improvement in survival compared to chemotherapy with a hazard ratio of 0.67 and a p-value of 0.0046. This corresponds to a 33% reduction in the risk of death with Elahir compared to chemotherapy. The median overall survival with Elahir was 16.46 months compared with 12.75 months on the chemotherapy control arm. As Mark noted earlier, Elihir is the first drug to demonstrate an OF benefit in a Phase III trial in platinum-resistant ovarian cancer. Quite simply, these data are practice changing. Let me now turn to the broader Mervetuximab development program, which has the potential to meaningfully expand the Elihir label by moving into platinum-sensitive disease and positioning Merv as the combination agent of choice in ovarian cancer. Specifically, we are progressing three studies. The first is PICOLO, a single-arm Phase II trial evaluating MIRV monotherapy in folate receptor alpha-high platinum-sensitive ovarian cancer. Enrollment was completed in January, and we anticipate sharing ORR data by the end of this year, with duration of response data expected in 2024. The second is GLORIOSA, our Phase III trial evaluating MIRV plus bevacizumab maintenance versus standard-of-care Bevacizumab maintenance in the second-line platinum-sensitive setting. This study levers our robust MERV plus Bev data in the treatment setting, which led to NCCN compendium listing for MERV Bev in platinum-resistant ovarian cancer, into the platinum-sensitive maintenance setting, where patients may stand to benefit from even longer durations of therapy. And the third is trial 420. A single-arm Phase II trial evaluating MIRV plus carboplatin, followed by MIRV continuation in platinum-sensitive ovarian cancer patients with low, medium, or high levels of folate receptor alpha expression. Both combination trials, Gloriosa and Trial 420, are enrolling in the U.S. and are getting going in Europe. Moving to our second pivotal program, we presented data from an interim analysis of the Phase 2 CADENZA trial of PVEC in patients with frontline and relapsed refractory BPD-CN at the EHA or EHA conference in June. PVEC demonstrated encouraging clinical activity and tolerability, especially in light of the toxicities of available therapies. In the frontline setting, we observed a composite CR rate of over 70% and a median duration of response of over 12 months. In the relapsed refractory setting, which included patients previously treated with Tegraxifus, we observed a CCR rate of 20% and a median duration of response of over seven months. Commensurate with the increasing awareness of the potential of PVEC in this ultra-rare indication, we are pleased to share that we have completed enrollment in the pivotal frontline de novo BTDCN cohort of Cadenza and anticipate top-line data in 2024. For our 802 trial of PVEC in combination with venetoclax and azacitidine in frontline AML, we have enrolled 25 patients in both the venetoclax 14-day plus and the 28-day minus triplet cohort. These data will help us optimize the duration of venetoclax for the triplet and guide pivotal development in frontline AML. We look forward to reporting data from these cohorts at ASH later this year. As for our earlier stage assets, on IMGC936, our first-in-class ADAM9 targeting ADC in co-development with macrogenics, enrollment progressed in 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 expect later this year. Lastly, we are progressing our phase one trial of IMGN151, our next generation antifolate receptor alpha targeting ABC, 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. In closing, I want to thank all my Immunogen colleagues for their ongoing commitment to delivering more good days for patients with cancer. I will cherish my time with this business, both professionally and personally. As to what's next, I look forward to spending time with my family, continuing my board work, and pursuing consulting in the coming months while I watch Immunogen's bright future unfold. With that, I'll turn the call over to Renee to cover our financials. Renee?
spk25: Thanks, Anna. For the second quarter of 2023, we generated $83.2 million in revenue, including $77.4 million in net product sales of Eliher and the remainder from non-cash royalty revenues. Operating expenses were $86.4 million, comprised of $50.1 million of R&D expenses and $36.4 million of SG&A expenses. In May, pursuant to an equity offering, we further strengthened our balance sheet generating approximately $351 million in net proceeds. We ended the second quarter with $572 million in cash on the balance sheet. Our financial guidance for 2023 has been updated, and we now expect operating expenses between $350 million and $365 million. This increase reflects greater spending in support of Eliher, including preparations for a launch in Europe. in addition to expanding our research capabilities and pipeline. Revenue guidance, excluding Eliher sales, remains unchanged at between $45 and $50 million. We expect that our existing cash and cash equivalents, together with anticipated future product and collaboration revenues, will fund operations for more than two years. With that, we'll open the call for questions.
spk04: As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. The first question comes from John Newman with Canaccord. Your line is open.
spk09: Hi, guys. Thanks a lot for taking my question. So, Anna, first, I just want to say congrats on all the great work at Immunogen. You'll certainly be missed. And the best companies in biotech are the ones that can execute their clinical studies near perfect, and Immunogen is certainly included in that bucket. Just had one question, which is, we know that Mervetuximab and Mirasol was tested in patients with FR-alpha high. confirmed by 3-plus expression level. Just curious if you can talk about whether you expect MERV, or I should say ELLA here now, will be used in patients with 2-plus expression levels, and perhaps if we're seeing that at the moment. Thanks.
spk06: Thanks, John. Thank you for your kind words. Just to clarify, the definition of FR-alpha high expression by our companion diagnostic is at least 75% of tumor cells, at least 2-plus positive by immunohistochemistry staining, so 2-plus and 3-plus. And that comprises between 35% and 40% of all ovarian cancer patients, and the commercial testing has performed as we've seen in clinical trials. We have previously explored Mervituximab in patients with lower levels of FR-alpha expression as monotherapy. You can recall from Forward One, And we know from that study that patients with medium levels of FR-alpha expression, which is at least 50% of cells, so medium is between 50 and 75% of cells with at least 2 plus expression by immunohistochemistry. And that encompasses about another 20% of ovarian cancer patients. We know that they do about as well with Mervituximab as with investigator choice chemotherapy based on a post-hoc exploratory analysis. And certainly, based on that data, as well as some preclinical data that we have showing synergy with various agents, we are exploring patients with lower levels of FR-alpha expression in our combination strategies. We also know that when we combine Mervituximab with Bevacizumab across a broad range of FR-alpha expression, so low, medium, and high, lows being at least 25% to 50% of cells with at least 2-plus expression, that we get very nice data that were published earlier this year in the DynOnc journal, and that led to compendia listing for MERV plus BEV for patients with low, medium, or high FR-alpha expression, and that encompasses about 80% of ovarian cancer patients. Looking to the future, we're also combining MERV with carboplatin in patients with low, medium, and high FR-alpha expression for in our 420 study. So, our initial approval in patients with high FR-alpha expression for MERV monotherapy is just the beginning.
spk09: Great. Thank you. If I could ask one quick additional question. On combination with abacizumab, just curious if you're seeing anything at the moment from your data with regard to perhaps the uptake there in combination with abacizumab. Thanks.
spk16: Yeah, the answer is yes. So, when we look at the claims data, and I'm sure we'll have lots of questions on that, it's early days, but we absolutely do see combination use as part of the claims set, and the feedback that we get anecdotally certainly supports that. Great. Thank you.
spk04: Please stand by for the next question. The next question comes from Michael Schmidt with Guggenheim. Your line is open.
spk15: Hey, guys. Thanks for taking my questions, and congrats on another very strong quarter. And let me just add my congratulations to Anna as well for all the success in your agenda. You will be missed, obviously, by many. I have a question on the evolving testing paradigm. So in our diligence, we've heard that many of the large academic institutions prefer in-house testing over using the centralized labs that you have established. And I was wondering if you could confirm that and how many of the big centers are not yet certified for in-house testing in the U.S.?
spk28: Thank you. As you know, we had a very strong demand for testing so far. And in the second quarter, we surpassed 11,400 tests. And now we are over 13,000 tests. We can confirm that today. And when it comes to the labs, we have 33 labs that are operational, of which 15 are academic centers. And in those centers, we have less visibility about the data that we have. In process, we have another 15 labs that are in the process of being certified, so we continue to see very strong testing, as I just mentioned.
spk15: Okay, thank you. And regarding the Piccolo study, how should we think about the regulatory bar for response rate in that platinum-sensitive setting? Is the bar similar to that that was applied to the Soraya study, for example, or is it higher or lower?
spk06: I think the bar is to be determined, Michael, because, you know, the landscape has evolved with the incorporation of PARP inhibitor maintenance, particularly now in the frontline setting. And we know from multiple studies that, unfortunately, PARP maintenance therapy seems to induce resistance to subsequent DNA damaging agents, particularly things like platinum. as well as topotekin and doxil, which also are DNA damaging agents. But what that means is that patients who are technically platinum sensitive post a PARP inhibitor, in other words, they've recurred greater than six months after the last dose of their last platinum, may not be as sensitive to platinum as they were previously. So that coupled with the fact that there were not there are no robust randomized phase three level one evidence studies in later line platinum sensitive disease to begin with, even in the pre-PARP days. We don't really know what the benchmark is. That said, more studies are coming out, again, showing that more platinum for these post-PARP patients may not be in their best interest. So, you know, the way we're thinking about it is that the higher the response rate, the longer the duration of response in piccolo, the easier the conversation will be with regulators about what an appropriate bar would be for us to beat. So at this point, we're really excited about the PICOLO study. We're on track for ORR data before the end of the year. We know these patients are doing well, and so we will anticipate having DOR data next year.
spk15: Okay, thank you. And then last question, just regarding the 802 study of PVEC in AML, could you just Remind us of the two cohorts that you're running in frontline and what you're looking for here in the ASH data that would support initiation of phase three trials. Is it a primary look at safety or certain efficacy measures are important as well for you?
spk06: So just as background, you know, Ven-Aza has become the new standard of care for unfit frontline AML patients, which is about half of AML patients, although even the definition of unfit is being evolved so that more patients do get Ven-Aza. That said, it's a tough regimen in and of itself at the labeled doses and schedules. Many compounds have tried to combine with Vaneza and have failed because of just excess toxicity of the triplet. Ours is not one of those. We are one of the few that has been able to combine successfully. And so we started out, I would say, in an appropriately conservative manner to protect patient safety with what's called a 14-day plus regimen of venetoclax in the relapsed refractory setting. We proved safety of that regimen and moved it up into the front lines setting, where we had 10 patients' worth of data we presented at ASH last year with the 14-day plus regimen. In conversation with FDA, FDA made it clear their expectation is that we combine with a standard or labeled dose and schedule of Venetoclax, and Venetoclax is generally given per label up to 28 days in a row. But the problem is many patients can't tolerate Venetoclax that extended duration of venetoclax because of profound myelosuppression. And so we have basically completed accrual now in 25 patients using what we call the 14-day plus and 25 patients in the 28-day minus regimen. So what happens is for each of these patients do get a bone marrow around 14 days in the 14-day plus or later in the 28-day minus regimen. And if patients have residual blast, they continue with the venetoclax. If the bone marrow shows no blasts, then they stop the venetoclax, because at that point, venetoclax would just be adding toxicity. And so we're going to combine the data from those sets to understand the safety of the triplet, understand the efficacy, both in terms of CR rate as well as MRD, or measurable residual disease rate. And both safety and efficacy will guide how we're thinking about a frontline pivotal triplet AML registrational trial. So, stay tuned for ASH.
spk32: Great. Super. Thanks for all the detail, Anna.
spk04: Please stand by for the next question. Our next question comes from Peter Lawson with Barclays. Your line is open.
spk29: Great. Thank you so much. Just wanted to offer my congratulations and Also wanted to mention it was always been a pleasure talking to you, Anna, and best of luck with the next step. Just as we think about the duration of use, I wonder if you could kind of provide some kind of, it sounds like there's a range you're getting from your estimates, but if there's anything you can give around that range for the duration of use, kind of the line of therapy and whether you're mostly seeing it in combination with BEV.
spk16: So, it starts with the claims data, right? And so, it trickles in. So, as we gather those data, so, for example, if you look at the last claims data I saw was earlier this month, we had four patients reported, right? And so, it's a little hard to think about extrapolating that over the back half of the year when you sort of have to back up then 90 days and try and accumulate the totality of the experience and then project that forward. And so duration of therapy falls exactly into that bucket, which is it's difficult to ascertain at this point when we look at the accounts versus the claims data to assess what's happening commercially. with the brand at this point. And so, you know, our experience that we've related is with the Saraya data where it's complete, where we saw, you know, a mean number of cycles of seven in that population. That population certainly was the most heavily pretreated that we've observed in our clinical experience. And so, you know, I think that's a baseline for duration of therapy. What we can say, Peter, generally is that in the initial stages of the launch, the claims data indicate that we were starting in later Lyme patients. Particularly with the Marisol data, what we see is movement into earlier Lyme patients, which we think will correspond with longer durations of therapy generally. In addition to that, what we see are combination use. The results from that, as we shared in the prepared remarks for today, are disparate across the databases. So, we're making a concerted effort to try and reconcile those databases and supplement that with a demand study in order to get a better assessment of what's going on. As we think about this, the commercial team here has put together essentially a matrix, and on one axis is the impact that it has on revenue, and on the other is our confidence level. So when we look at things that have high impact and high confidence, We include there our FR-alpha positivity rate because we've run the experiment on over 13,000 tests and have a pretty high degree of confidence in terms of the positivity rate. In terms of duration of therapy, we simply have an incomplete data set when we look over the claims data. And similarly, we just see an evolving picture in terms of lines of therapy. So Again, it's something that we are, you know, working on aggressively in order to have, you know, a very clear view of the market that we could articulate to the investment community.
spk29: Gotcha. Your conversations with physicians, does that point into most of the combination use or is it, again, kind of a broad range?
spk16: We see a significant percentage or, you know, we have... Physicians report to us in their practices that a significant percentage of the use is in combination.
spk29: Thank you so much. I'll jump back into the queue.
spk04: Please stand by for the next question. The next question comes from Itzer Darrow with BMO Capital Markets. Your line is open.
spk13: Great. Thank you, and congrats on the quarter, and also would like to echo my colleague's sentiment on the contribution, Anna, that you've had to Imogen's story. First question for me is, I just wondered if you can maybe talk a little bit about some of the major differences in ovarian cancer treatment or practice, I guess, in the U.S. versus some of the major countries in the EU, and, you know, what impact maybe those differences could have on sort of the launch trajectory or maybe your overall strategy in Europe versus what we've seen early on here in the U.S.? And then I have a follow-up. Thanks.
spk06: Sure. So, I'll start with practice pattern differences and then turn it over to my colleagues to discuss how that influences our launch strategy in Europe. The one real difference, Esther, is how and when physicians use Bevacizumab or Avastin. And we've known that. You know, it was approved in 2014, 2015. It has three approvals in the U.S. and Europe. It's approved in combination with chemotherapy and platinum-resistant disease. It's approved in combination with chemotherapy in recurrent platinum-sensitive disease and then continued as maintenance and in the frontline settings. in combination with chemotherapy, and as continued as maintenance. The problem with Bev is that it's never shown an overall survival advantage in any of these settings except in a core prognosis high-risk subset in the frontline setting. So these are patients who present with stage 4 disease or parenchymal metastasis. They have ascites. They're suboptimally debulked. In that subset, the addition of Bevacizumab does improve overall survival. So particularly in Europe, oftentimes Bevacizumab is only reimbursed or patients only have access to Bevacizumab in that frontline poor risk setting. And in fact, that kind of bore out in our SREA study where, you know, the majority of patients were enrolled in the U.S., excuse me, in Europe. And that study had a higher percentage of stage four patients than is typically seen in a relapsed or recurrent ovarian cancer study. So because of that, in Europe, a higher percentage of patients in the platinum-resistant setting get single-agent chemotherapy. And that's important for how we're thinking about ELA here when we get it approved.
spk28: Yes, and the way this translates for the launch is that the admin need there is even higher. and the number of patients that will be eligible for ELA here is also higher. Our goal, therefore, is to, as mentioned by Mark, is to file by the end of this year, and we are making significant progress towards the launch. First, we are working on our global values here and pricing, and payers in Europe tend to value overall survival data, so we feel very confident that that will give us a strong initial position there. Second, we are Really pleased that we have a very solid engagement with KOLs there. As you remember, over 70% of our patients in the clinical trials were enrolled in SUS. So those very strong relationships, we are leveraging that. We will be having two other presentations at ESCO in Istanbul at the end of September, and we also will have a presentation at ESMO. So we continue to have this one-on-one engagement, and we are also partnering with the community in preparation for the launch. Finally, we are ramping up the team towards preparing for execution, and we feel very confident that we have a successful launch in the U.S.
spk16: Maybe the only other thing to add there, Ed, sir, is that it's just a very highly concentrated market. So when we do the market research across both the five largest markets and expanding that into 16 markets, we see a relatively consistent pattern, which is a small number of centers treat a high percentage of the patients. So when we look at the five key markets, for example, 60-odd centers treating 80% of the market. So this is something that we can address with a modest incremental commercial investment, and particularly given the data that that we have. And as Isabel mentioned, the relationships that we have, we expect a very robust launch there.
spk13: Great. Thank you. And then the follow-up was on IMGC 936. Sort of the market here is paying a lot of attention to sort of another ADC mechanism, the TROP2 and non-small cell lung cancer. And for sort of the interim analysis that you have maybe in the back half of this year, how you're thinking about What the go-no-go is, is it going to be on response rate, duration of response? Is it maybe PFS, if you could maybe provide a little bit of color on how you're thinking about sort of the go-forward strategy on that asset? Thank you.
spk06: Sure. So IMGC936 is our ADAM9 targeting ADC that, you know, ADAM9 is expressed across a broad array of solid tumors, and we've prioritized non-small cell lung cancer based on what we saw early in development. And so, we have expanded the first stage of a two-stage design, if you will, to understand the activity of IMGC936 in non-small cell lung cancer. And I think the initial hurdle would be just overall response rate or objective response rate in the initial cohort of patients. And at that point, that data would guide further expansion into the second stage. at which point we would have a larger data set where we would look at ORR and DOR to assess, you know, how we're thinking about further development. Just in terms of single arm studies and PFS data, typically it's hard to make robust decisions based on PFS, so it's typically ORR and DOR data that will guide further decision making.
spk37: Great. Thank you.
spk04: Please stand by for the next question. The next question comes from Boris Peeker with Cowan. Your line is open.
spk08: Thank you. And I'd like to add my congratulations to Anna specifically and the entire MUNIGEN team for the excellent progress. So maybe my first question is on the testing centers. You've obviously mentioned that there's been an increasing in testing centers being brought online, but how much do you estimate maybe the current revenue being potentially limited based on the existing testing infrastructure in the second quarter?
spk16: Not at all. Testing is simply not a barrier to entry. You know, we do know that the institutions at present have a preference for in-house testing, but that didn't prevent them from sending tests out to, you know, so before their centers were open, we could see, you know, ordering from accounts and testing from accounts that didn't have in-house testing. And, you know, as we mentioned, you know, as time progresses, a number of those institutions are taking it in-house. What I will also say, Boris, is, you know, we've actually, you know, had some interesting conversations about this phenomenon as it related to PD-1, PD-L1 testing. And what we hear is that, you know, initially there was great enthusiasm among the academic institutions to take that testing in-house. However, over time, that enthusiasm waned to some degree, and they began sending their tests back out to centralized labs. So, as we've discussed, we see the migration in-house over time, whether that's a sustainable phenomenon, I think, is an open question at this point. But just to be very clear, you know, we've done over 13,000 tests launched to date. It has simply not been a barrier to entry.
spk08: Great. And my second question is, in terms of the NCCN guidelines, do you anticipate any future updates incorporating maybe Mirasol or any other data in the near future?
spk06: Yeah, so we anticipate with Mirasol being the only study to show an overall survival advantage in a randomized Phase III setting for a novel agent, we anticipate Mirasol could move our Elihir compendia listing from 2A to Category 1, and it would be the only medication in the NCCN platinum-resistant treatment guideline that would have that level of evidence. We also are anticipating that the PICOLO data could support NCCN compendia for later line platinum-sensitive ovarian cancer for MERV monotherapy. And also, we are generating three data sets at this point for Mervituximab plus carboplatin. The 420 study that is our sponsored study in low, medium, and high FR-alpha expressing patients. as well as we are supporting two investigator-sponsored trials, a neoadjuvant study and a randomized phase two study in Germany led by Philip Harder. And those data could absolutely support compendia listing as well.
spk28: Yeah, we also hope that we can move, sorry, the compendia listing of the combination from 2B to 2A. From IRF-BEV, yes.
spk08: Do you have a sense of timing for that?
spk28: Oh, well, we are aiming to make some changes for the listing of Elagir monotherapy in October, and similarly for the combination of MedVap from 2B to 2A.
spk06: Yeah, we will work with NCC and around their scheduled meetings.
spk08: Great. Thanks for taking my questions, and congratulations once again.
spk04: Thanks. Please stand by for the next question. The next question comes from Andy Shea with William Blair. Your line is open.
spk14: Congratulations on another blowout quarter. And it's been a pleasure working with you, Anna. I wish you the best of luck. So I have a question about kind of the strength of the community and non-academic centers. So I'm curious if you have a view on that or any sort of market dynamics you're seeing there. And I also have a follow-up in terms of the R&D and your P&L. Obviously, you know, strengths from Ella here could fuel your R&D. I'm just curious about maybe the near and mid-term vision about R&D, what's in store, what do you expect the R&D to look like in the next three years? In terms of P&L, obviously, you're pretty close to break even this quarter. I'm just curious if that's the goal. How do you think about, you know, your income statement as ELL here continues to ramp at this just incredible pace? Thank you.
spk16: Sure. Thanks, Andy. So, I'm going to ask Isabelle to start and then Mike to talk about R&D and then some combination of Renee and I can tackle the P&L. Sure.
spk28: So we are very pleased with the strong adoption in both the community and academic centers. And if you remember early in the launch, we thought that the academic centers would start first and community would follow. What we had seen is a very strong adoption in community, and that's testament to the unmet need and the target profile of the drug. We also see that academics have to follow the normal process. They have to wait for the committee, they have to wait for In some centers, they have the testing in-house, but they have now started to test, and we are very pleased that pretty much all the major institutions are already ordered ELA here. We have additional events that will create additional growth in both. We have the JCODAS July 1st. We have been included in Pathways. And we think that that's going to continue driving the growth in both academic and non-academic institutions. In terms of the mix, we think it will remain relatively similar with more 65 to 35% with more growth maybe coming from academic institutions in the second quarter.
spk07: And Andy, this is Mike, regarding your question about continued investment in R&D. Just to remind you, as Anne has nicely summarized, we have a broad ongoing life cycle management program with Mervituximab. It's important for us to think about every woman with ovarian cancer that expresses folate receptor alpha to have the right medicine at the right time. That will include investigation of alahir and platinum-sensitive ovarian cancer. You've already heard about that, but I wanted to also remind you about IMGN 151, which we continue to move through phase one development and has the potential to broadly impact FR-alpha expressing cancers, not only in ovarian cancer, but beyond in cancers such as endometrial, non-small-field lung cancer, and others. You've also heard about the continued investment of PVEC in frontline AML, and we look forward to those data informing continued clinical development there. And then importantly, as a reminder, we have three broad classes of payloads with associated linkers that form the basis of our portfolio, the metansenoids, the IGN, and importantly, a campathesin group of compounds that have yet to be formally tested in clinical development. So we look forward to work that's already ongoing with collaborators to bring forward novel antibodies, linkers, and test those payloads in a broad swath of cancers. So we're really very committed across the spectrum and look forward to sharing this earlier progress of molecules and research as we move forward closer to IND.
spk16: So, Andy, as Mike just articulated and we've also talked about the expansion globally of Ella here with the labeled indications, we do expect to invest heavily in the business in the coming years. So, you know, we've given cash guidance. to say that we've got more than two years worth of cash. And that is a reflection of both the existing balance sheet as well as the strength of the ELLA here launch. But we aspire to be a fully integrated oncology company. We're fortunate to have one marketed product and three additional clinical candidates, but our goal is, again, to expand our preclinical capabilities. We've done so incrementally with a number of partnerships, and we look to continue that activity and also rebuild some in-house capabilities as it relates to our core areas of expertise, as Mike has outlined. The focus is, again, you know, international expansion for the business, supporting the launch, lifecycle management, and rebuilding our preclinical pipeline. So, again, you know, areas of investment on a go-forward basis.
spk17: Great. That's very helpful. Thank you so much. Sure.
spk04: Please stand by for the next question. The next question comes from Kelly Sher with Jefferies. Your line is open.
spk24: Congrats for another great quarter. And also, please allow me to add my congrats to Anna. My first question is for PICOVA trial, what kind of a treatment duration could we expect? And also, in this platinum sensitive setting, is the proportion of FRR for high patient same as in the platinum-resistant settings, around 35% to 40%.
spk06: Thanks, Kelly. So let me address your second question first. The vast majority of patients who have participated in Mervituximab trials and who are receiving commercial Elihir do so based on archival tumor tissue testing. So patients generally have debulking surgery at the time of diagnosis, and that's when they're FR-alpha. That's when they have tumor taken for FR-alpha testing. So, the 35% to 40% is true regardless of what setting the patient is in. Going back to your first question about treatment duration for Piccolo, you know, these are later line platinum-sensitive patients, but we know that platinum-sensitive patients in general do better than platinum-resistant patients, you know, regardless of therapy, although, again, that does seem to be possibly changing for the subset of platinum-sensitive patients post-PARP who get more platinum. That said, you know, we anticipate the treatment duration for the PICOLO study is going to be appreciably longer than, for example, in Mirasol or Soraya. So, stay tuned.
spk24: Okay, great. Thanks. And also, for 936 in non-small cell lung cancer cohort, Just curious, is this pre-specified interim analysis applied to a post-PD-1 setting?
spk06: So it's not specifically in the post-PD-1 setting, but this is a phase one study where patients with non-smell cell lung cancer have had the appropriate prior therapies, and the vast majority, if not all of them, have had a checkpoint inhibitor.
spk03: Okay, great. Thank you.
spk04: Please stand by for the next question. The next question comes from RK with HC Wainwright. Your line is open.
spk21: Thank you. Congratulations. And, Anna, congratulations and nothing like signing off on a high note. I will certainly miss you, especially on all the helpful conversations that we have had in the last few years. And additionally, both my dog and I are going to miss you on our Zoom calls, you know, future Zoom calls with immunogen. So in terms of expectations at the ESGO, you know, what additional analysis, you know, could we see at that conference?
spk06: Yeah, ESGO is in Istanbul this fall. I think it's the end of September. And we have two abstracts that have been accepted for oral presentation in terms of additional subset analyses from Mirasol. The ones that will be focused on in this initial array of data are the subsets based on number of prior lines of therapy. as well as patients who have or have not had a prior PARP inhibitor. So those are the key subsets because, you know, physicians are quite interested to understand where to position Elihir in the treatment paradigm. And I think these subset data will be very informative for them.
spk21: Thanks, Anna. Also, as you plan to file the MAA in Europe during the next six months, How should we think about the commercialization there? Would this be directly by yourselves, or are you seeking for a commercial partner there? I'm just trying to understand the commercial structure that could be set up in it all.
spk16: Sure. Okay. So, we plan to go direct in the five largest markets. There's a pretty leveraged approach that one can take by clustering. So we can add 11 additional markets. So we expect to be direct in 16 markets in Europe. Of course, that takes place over time, just given the cadence of reimbursement in those markets. And then we would use distributors outside of what we call the EU 16.
spk22: Thanks, Mark. Thanks for taking my question. Sure. Sure.
spk04: Please stand by for the next question. The next question comes from Astaka Goonwarden with Truist. Your line is open.
spk15: Hey, guys. Good morning. Astaka from Truist here. Thanks for taking my questions. Also, my congratulations on a very elegant execution to the team. And on a personal note, Joanna, we only launched coverage nine months ago, but in our limited time, it's been a pleasure to get to know you and appreciate your discipline. We wish you the best for your next adventure. Just a couple of quick mock-up questions for us here. You're clearly getting a nice boost from what one might call off-label use in the U.S., but in general, in oncology, do you think off-label use in Europe can be as strong as you do get seen in the U.S., or do you think the docs over there in Europe are going to stick to the script a bit more? Second question is I'd like to test and see if we can get any sort of color on timelines for Gloriosa. I know that's one of the next things that people are going to be looking at as well here after Piccolo. And then lastly, Mark, when do you feel confident that you'll get enough of a sample from the claims data to give us some guidance on a product level basis failure? Thanks, guys.
spk16: Sure. So, as to the first question, it's not so much the physicians that make the decisions with respect to the use outside the label in Europe as just a reimbursement there, and it's very stringent. There are very limited instances where you can see off-label coverage there, and that's distinct from what we see in the U.S. market, particularly where drugs are listed in the compendia, as we've seen with Ella here, both in terms of no restriction on Prior lines of therapy and the combination with Avastin. So they're fundamentally different markets as it relates to reimbursement, and that's what drives it. So the expectation should be that use there will be within the label approved by the EMA. In terms of Glorio, it's early days, so we haven't given any guidance there. And then, sorry, your third question was? I think it needs to be driven by two things. The two key factors that are most opaque at this point are duration of therapy and, really importantly, discontinuations, which of course are related to duration of therapy. And I think it's going to be, you know, some time before we get to that. I certainly would expect us by, you know, the beginning of next year when we all get together at J.P. Morgan or in conjunction with our year-end earnings call to have, you know, a reasonably clear-eyed view on that. You know, and as I say, we've got this demand study going, and, you know, we'll see what that tells us as well. Great. Thanks for taking my questions, guys.
spk04: please stand by for the next question. The next question comes from Joe Cottanzaro with Piper Sandler. Your line is open.
spk35: Hey, guys. Thanks for squeezing me in. Congrats on the nice quarter and congrats to you and a nice tenure here. Maybe just two for me. I'm wondering if you had a sense around the cadence of new patient starts in 2Q and whether it was evenly distributed or not, and relatedly, whether you saw an uptick in usage in June and July following the Mirasol presentation at ASCO. And then my second question, Mark, you mentioned sort of the difficulty in modeling prevalent to incidence. I'm wondering sort of where you think you are in that curve and what metrics you're looking at that will give you an indication that, you know, you're shifting to majority usage in the incident population. Thanks.
spk28: Okay, so when it comes to the incidence versus prevalence population and how we are looking at the patient data, we have longitudinal data and claims, and the issue with that, frankly, is that it's lagging 90 days, so we have very few patient data at this point. We get it from DRG by lines of therapy, and we are tracking that, and we think we need additional time before we can tell you what is happening there. We have seen, though, that the MIRASOL data does have an impact in terms of uptake of more patients, as you saw in the second quarter. And we also can see early signs from the claims that patients are moving to treat in earlier lines of therapy, pretty much as a sign of first resistance.
spk18: Okay, thank you.
spk04: Please stand by for the next question. The next question is from Jonathan Chang with Lyric Partners. Your line is open.
spk36: Thanks for taking my question. Congrats on the quarter and best wishes on our next steps. Just one question for me. How are you guys thinking about potential business development opportunities for Ella here and strategic interest broadly? Thank you.
spk16: Yeah, so, you know, what we've done with Ella here is we've decided to go direct in the largest markets where we can with, you know, modest investment, support a robust launch. So starting here in the U.S., as we talked, you know, a bit on this call, going to Europe, In markets where that's not feasible, for example, in China, we've elected to go with partners. We're exploring partnerships for Japan in a similar vein. And outside of that, I think we plan to use distributors because we think that with a time-limited distribution agreement, we can call back those when we're ready to move to a direct model. You know, in terms of, you know, more broadly, business development, you know, as we've talked, we want to rebuild the front end of the pipeline. And, you know, some of the deals that we've done, OBT, and more recently, a very small deal with Immunobiocam, again, to build the front end of the pipeline. So we're very excited about this business. We love the momentum that's been generated this quarter in the marketplace, and that's paired very nicely with with data, progress with the pipeline. So we're excited about our long-term prospects here.
spk19: Got it.
spk04: Thank you. I show no further questions at this time. I would now like to turn the call back to Mark for closing remarks.
spk16: Great. Well, thank you all very much for joining us today. We had a very strong first half. We do expect to carry this momentum for the remainder of the year, you know, as we look to deliver more good days for our patients and, importantly, create value for our shareholders. So we look forward to keeping you updated on our progress as we move through the second half. So thanks again for your time today.
spk04: This concludes today's conference call. Thank you for participating. You may now disconnect.
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