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spk11: Good morning, and welcome to Immunogen's first quarter 2022 financial and operating results conference call. Today's conference is being recorded. At this time, I'd like to turn the call over to Courtney Okonik, Senior Director of Corporate Communications. Please go ahead.
spk09: Good morning, and thank you for joining today's call. Earlier today, we issued a press release that includes a summary of our recent progress in first quarter 2022 financial results. This press release and a recording of this call can be found under the Investors in Media section of our website at ImmuneEngine.com. With me today are Mark Ennedy, our President and CEO, Anna Birkenblatt, our Chief Medical Officer, Kristen Harrington-Smith, our Chief Commercial Officer, and Susan Altshuler, our CFO. During today's call, we will review recent accomplishments for the business, our Q1 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 in our other FCC filings, which are available at fcc.gov and immunogen.com. And with that, I'll turn the call over to Mark.
spk14: Good morning, and thank you for joining us today. Building on the strong SREA data and capital raised late last year, we've continued to make excellent progress in 2022. Our top priority is to gain approval for MIRV monotherapy in patients with folate receptor alpha-high platinum-resistant ovarian cancer, and we recently achieved two critical milestones to that end, the presentation of results from our positive pivotal SREA trial at SGO and the submission of the BLA to FDA for potential accelerated approval. As we progress towards our goal of becoming a global, fully integrated oncology company, Since the start of the year, we've also continued enrollment in the confirmatory Phase III Mirasol and Phase II Piccolo studies with MIRV monotherapy, expanded our commercial team and accelerated launch preparations in anticipation of a MIRV approval, further accrued patients in our pivotal Cadenza study of PVEC and BPDCN, initiated expansion cohorts in both relapsed and frontline AML patients combining PVEC with azacitidine and venetoclax, and progressed our earlier stage programs, IMGC 936 and IMGN 151. To expand on these points, starting with MIRV, enrollment in our confirmatory Mirasol trial accelerated following the release of top-line results from Sirea. This is an event-driven study, so enrollment is not the only factor in the timing of the top-line analysis. Based upon a re-forecast generated in conjunction with the recent pre-specified interim futility analysis for Mirasol, we now expect to reach the requisite number of PFS events in the fourth quarter of this year and report top-line data from Mirasol in early 2023. Anna will provide more color on this and our label expansion studies in a moment. Our second pivotal program, PVEC, is progressing nicely and we expect preliminary efficacy data from our pivotal cadenza study in frontline BPD-CN before year-end. In addition, patient enrollment is ongoing in our Phase 1B-2 expansion cohorts, evaluating PVEC, azacitidine, and venetoclax in both relapsed and frontline AML patients, which are accruing rapidly. We expect to share data from both cohorts at ASH later this year. Looking at the rest of our pipeline, we anticipate sharing initial data before year-end from the Phase I dose escalation trial of IMGC936, our first-in-class ADAM9 targeting ADC, which we are co-developing with Macrogenics. In addition, a manuscript describing the preclinical evaluation of IMGC936 was recently accepted for publication in Molecular Cancer Therapeutics and will soon be available online. We also made meaningful progress addressing the CMC information request from FDA regarding our Phase I study of IMGN151, and expect to initiate the clinical study by mid-year. With our progress to date and meaningful catalysts ahead, we believe we are well-positioned to create significant value as we move through the remainder of the year. With that, I'll turn the call over to Anna to provide additional color on the Mervituximab program. Anna?
spk08: Thanks, Mark. We were thrilled to have Dr. Matalonis present the results from the Pivotal Thorea trial in a plenary session at the SGO annual meeting in March. 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, SREA is a single-arm Phase III study evaluating Mervituximab in patients with folate receptor alpha-high platinum-resistant ovarian cancer. SREA enrolled a heavily pretreated population of 106 patients, all of whom had received prior Bevacizumab. 38% had stage 4 disease, 51% had three prior therapies, and 48% had received a prior PARP inhibitor. Treatment options for platinum-resistant ovarian cancer consist of single-agent chemotherapy, which produces low response rates and limited duration of response. The primary endpoint of psoriasis was an overall response rate of 32.4% and included five complete responses, which rarely occur in this population. Importantly, as we updated at SGO, the median duration of response, the key secondary endpoint, was 6.9 months by investigator, and the median progression-free survival, or PFS, in this heavily pretreated population was 4.3 months. These efficacy and durability data are consistent regardless of the number of prior lines of therapy or prior PARP inhibitor use. The safety profile observed in SREA is consistent with that seen in the broader Mervituximab program and is characterized by predominantly low-grade reversible ocular and GI events, which were generally managed with supportive measures and dose modifications if needed. The most common adverse events were blurred vision, keratopathy, nausea, dry eye, and fatigue. At ASCO, We look forward to presenting integrated safety data from over 450 patients treated with Mervituximab in SREA, Forward 1, and our Phase 1 study. And we plan to provide more color on SREA efficacy data, including the PFS curve, CA125 response rate, and impact of dose modifications. At SGO, we also disclosed that the foundational 70 SREA-like patients all FR-alpha high by PS2+, all platinum resistant with 1 to 3 priors, and all with prior bevacizumab, showed a similar median PFS with MIRV as to what we saw in Sirea. One frequent question that arose was how these patients in the chemotherapy control arm of forward 1 performed. Reviewing these data, the equivalent chemotherapy control population showed a median PFS of under 2.8 months, Remember that this is based on post hoc analyses with small patient numbers, especially in the control arm of forward one due to the two-to-one randomization. But nevertheless, this is consistent with BEV pretreated patients representing a worse population with higher unmet need and underscores the clinical meaningfulness of the median progression-free survival of 4.3 months in psoriasis. In addition, it supports our belief that Mervituximab will show a clinically meaningful improvement in PFS over chemotherapy with a longer median PFS in a less heavily pretreated population in Mirasol. Moving to Mirasol, and as Mark mentioned, we have recently completed an interim analysis, and we are pleased to report the IDMC recommended the study continue without modification. Following the disclosure of SREA top-line results, Mirasol enrollment increased significantly. Considering the continued acceleration of enrollment and now having assessed the PFS event rate in conjunction with the interim analysis, we are updating our Mirasol guidance to include a projected primary completion date in the fourth quarter and top-line data in early 2023. While the timeline for Mirasol's top-line data has been adjusted, we continue to expect potential accelerated approval for Mervituximab monotherapy this year based on the SREA data. Turning to the rest of the Mervituximab program, we're continuing to enroll Piccolo, our single-arm study of Mervituximab monotherapy in patients with folate receptor alpha-high recurrent platinum-sensitive ovarian cancer intended to support label expansion. There is an increasing need for an effective non-platinum option in later lines of platinum-sensitive disease, and we believe our Phase I antitumor activity in this population are quite promising. Our strategy to position Mervituximab as the combination agent of choice is also advancing. We expect to gain compendia listings for the Mervituximab plus Bevacizumab doublet in patients with folate receptor alpha-high recurrent ovarian cancer in close proximity to the initial monotherapy approval of Mervituximab. Furthermore, work to initiate the Phase III Gloriosa study is underway, and we expect to enroll the first patient by mid-year. Gloriosa will evaluate the benefit of Mervituximab plus Bevacizumab maintenance versus Bevacizumab maintenance alone in the second-line platinum-sensitive maintenance settings. The addition of Bevacizumab to a platinum doublet provides a modest improvement of PFS of just three to four months in this setting. So we are excited by Mervituximab's potential to improve upon this based on the data we have generated for Mervituximab plus Bevacizumab in the treatment setting. Rounding out the Mervituximab program is Trial 420. Based on promising activity observed in phase 1 dose escalation for Mervituximab plus carboplatin in recurrent platinum-sensitive disease, we plan to initiate trial 420 this quarter to inform our path to registration in this setting. This is a single-arm phase 2 study of Mervituximab plus carboplatin, followed by Mervituximab continuation in approximately 110 patients with folate receptor alpha low, medium, or high platinum-sensitive ovarian cancer. And with that, I'll turn the call now over to Kristen to cover our commercial preparations.
spk01: Kristen? Thanks, Anna. In anticipation of bringing Mervituximab to market later this year, following potential accelerated approval by FDA, we have built our commercial leadership team with some key hires, including our head of market access, strategy and operations, and sales. In addition to attracting best-in-class talent, we also have made progress on our launch imperatives, And as a reminder, those are focused on redefining expectations for positive outcomes with Mervituximab in platinum-resistant ovarian cancer, supporting adoption of early folate receptor alpha testing, and establishing standards for in-house and centralized testing upon approval, ensuring positive physician and patient experiences through tailored education and guidance for patient management, and seeking broad payer access and reimbursement to deliver a seamless patient experience. The start of 2022 has been both intense and purposeful for the commercial team. Not only have we selected and onboarded our agency of record, we have also moved quickly to identify and address the key requirements for a successful launch while limiting potential barriers to treatment for patients. That means we are and will continue to be focused on educational efforts supporting awareness of Mervituximab and the importance of testing for folate receptor alpha expression, and we are working in close partnership with our colleagues in medical affairs. In addition, we've initiated a go-to-market assessment to determine the commercial field roles necessary to drive demand, identify and prioritize relevant accounts and providers, and optimize our customer-facing teams. On the market access front, we've initiated setup of our patient support services platform, and we are actively working with our distribution channel partners to have Mervituximab ready for shipment to customers shortly after approval. So with a focus on high-priority, high-impact initiatives, and an agile, experienced team in place, we believe we are well-positioned for a successful launch, and we look forward to bringing Mervituximab-Soraptanzine to patients in need. With that, I will turn the call over to Susan to cover our financials.
spk00: Susan? Thanks, Kristen. For the first quarter of 2022, we generated $38.1 million in revenue, $6.4 million of which came from non-cash royalty revenues. The remainder came substantially from license and milestone fees, which include recognition of $21.6 million of fees previously received under the company's collaboration agreement with Huadong Medicine, and $9.2 million of a $13 million upfront fee received in the first quarter under the company's license agreement with Lilly. Operating expenses were $60.9 million, compared with $44.6 million in the first quarter of 2021, and comprised of $44.3 million of R&D expenses, compared with $34.4 million in the first quarter of 2021, and $16.6 million of selling general and administrative expenses compared with $10.2 million in the first quarter of 2021. We ended the first quarter with $437.7 million in cash on the balance sheet. Our financial guidance for 2022 remains unchanged. We expect revenues to be between $75 and $85 million, operating expenses between $285 and $295 million, and cash and cash equivalents at year-end between $245 and $255 million. Given the range in timing for potential approval of Mervituximab, revenue guidance does not yet include potential product sales from Mervituximab. We expect that our current cash, combined with anticipated product and collaboration revenues, will fund operations comfortably into 2024. With that, we'll open the call for questions.
spk11: Thank you. To ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question is from John Newman with Canaccord. Your line is open.
spk06: Hi, guys. Good morning, and thanks for taking my question. So you mentioned that enrollment for Mirasol picked up following presentation of the SREA data this year. Just wanted to confirm that the planned enrollment target for Mirasol remains the same. You also mentioned that you anticipate compendia listing for the combination of Mervituximab plus Avastin shortly after the initial Mervituximab approval. What I'm wondering is if this were the case and doctors were to use this combination, where in the treatment paradigm do you think that combination might be used? Thanks.
spk08: Thanks, John. So our enrollment target for Mirasol remains the same at 430 patients Enrollment did increase after we presented top-line data from Soraya late last year, and so we have kept the target for Mirasol at 430 patients. For the Mervituximab plus Avastin combination, we anticipate receiving Compendia listing in close proximity to our initial approval, and so I'll turn it over to Kristen Harrington-Smith to discuss where that combination might be used.
spk01: Sure. So when we look at the platinum-resistant ovarian cancer market dynamics, we see that well over more than 25% of patients in any line, second, third, fourth, fourth plus, receive a Vastin plus chemotherapy regimen or any kind of combo with Fevacizumab. So we anticipate that it will be used where it's already used, in combination across those lines.
spk04: Thank you.
spk11: Our next question comes from Michael Schmidt with Guggenheim. Your line is open.
spk05: Hey, guys. Good morning. Thanks for taking my question. And I was just wondering if you have any additional information on this Verasol interim analysis. I don't know if you could share you know, what, you know, how many patients perhaps triggered this and what the parameters were that were assessed at that analysis. And then, you know, a second question on Murasol, just wondering around the enrollment dynamics of the trial. I'm just curious if you had overlapping trial sites with Soraya, which obviously focused on the Avastin pre-treated patients that, you know, in Soraya and whether perhaps that may skew, you know, enrollment early in the neuropath study towards Avastin naive patients and whether that perhaps, you know, may play a role in the overall cadence of the PSS event.
spk08: Yeah, thank you, Michael. So for Mirasol, we had a pre-specified interim analysis for futility, just like we had done in Forward One. It's really to allow a dry run, if you will, from an operational perspective so that we know we're in good shape for when we're ready to do the final protocol-specified analysis for the primary endpoint. So it was triggered at the time we had 110 PFS events. And so as long as the efficacy data in terms of PFS is trending in the right direction, the study was to continue as planned, and that's exactly what IDMC recommended to us, to continue the study without modification. Turning to your second question regarding enrollment dynamics, you are correct that we do have sites that have participated both in SREA and are participating in Mirasol. And so Sirea was limited to the Avastin pretreated patients, and Mirasol allows both Avastin pretreated and Avastin naive. Given the extent of patients, or rather the extent of sites around the globe that are participating in Mirasol, what I can tell you looking, you know, tracking the demographics of the patients enrolled in Mirasol, the percent of patients with prior Avastin is Basically behaving as expected. And so we look forward to data from Mirasol sharing the data early next year.
spk05: Okay, great. Thanks. Then I have an unrelated follow-up just on the cadenza study where you noted the top-line data is on track for later this year in BPDCN. And I was just wondering if you could remind us of the efficacy hurdle in the study and the number of patients that will be part of that filing.
spk08: Yeah, so you may recall that we received breakthrough therapy designation from the data we generated in the relapsed refractory BPD-CN setting. And FDA guided us toward a study designed for a pivotal frontline cohort in up to 20 patients. and the efficacy hurdle is really around what's feasible in an ultra-rare indication, and it's to rule out a CRCRC rate of 10%. And so we do have the opportunity to stop the trial early for efficacy with less than 20 patients, and so we're on track to have data later this year.
spk05: Okay, super. Thanks for taking my questions.
spk11: Our next question comes from Edgar Rout with BMO Capital Markets. Your line is open.
spk04: Hi. Thank you for taking the question. A couple for me. The first one, I guess, back to sort of the Mirasol trial. And I guess if you could help us understand, I guess, the pushes and pulls to the re-forecast of the PFS events. does it imply any differences in sort of, you know, in underlying PFS assumptions, or is it maybe more a factor of the recent acceleration in enrollment? And the second question, just if you could go back to the analysis you mentioned in the introductory remarks on the 2.8-month PFS for chemo in Avastin pretreated patients and whether or not this is something that you've presented or would be sort of submitting to the FDA. Thank you.
spk08: Thanks, Esther. So your first question regarding the pushes and pulls involved in the reforecasting for Mirasol, PFS is an event-driven endpoint, and the timing of that is a factor of both the enrollment rate and the rate of having progression-free survival events, and it's really not possible to disentangle those two. But, you know, based on how the study is performing, you know, we have not changed our thinking regarding PFS assumptions when we designed this study. And in terms of accelerated enrollment, yes, we certainly did see an uptick in enrollment after we shared the SREA data. I will say it has been offset a bit based on what's been going on in Ukraine and Russia in terms of geopolitical events and also in terms of China's and the COVID surges with lockdowns in Beijing and Shanghai. So it is multifactorial, and we look forward to sharing top-line data early next year. Turning to your second question regarding the 2.8-month progression-free survival on the chemotherapy control arm of Forward One in the SREA-eligible subset, if you will, those are not data that we have published yet. in a peer-reviewed manner, and certainly the data sets are available to FDA. But really, from our perspective, it just highlights the unmet need in these patients. You know, as we look through all of the studies that have, you know, the large studies in platinum-resistant ovarian cancer, none of them prior to psoriasis had a uniformly pretreated population, all of whom received prior Avastin. And we know that these patients have an extremely high unmet need. You know, the PFF for the chemotherapy patients is 2.8 months or just under 2.8 months, highlighting the unmet need. You know, I do need to caution folks that this is an exploratory analysis that we performed after Forward One read out. It's using the PS2 plus analysis. And once we rescored with the PS2 plus, the stratification factors were blown. And so, you know, all I would say is it's entirely consistent from a biological perspective that chemotherapy does not work well in these patients. They need better options. And the SREA data have demonstrated that.
spk04: Great. Thank you.
spk11: Our next question comes from Borger with Callen. Your line is open. Boris, your line is open. Please check your mute button.
spk02: Sorry. Can you guys hear me?
spk14: Can now.
spk02: Awesome. So just I wanted to follow up a little more on the Mirasol interim analysis that recently completed. I'm just curious. Can you comment on what was the specific stopping rules that there were, maybe some kind of a PFS threshold or any kind of a hazard ratio?
spk08: Yeah, Boris, the hazard ratio just needed to demonstrate PFS trending in the right direction for Mervituximab over chemotherapy.
spk02: Got it. And I just want to also, on the platinum-sensitive patients in the trial 420, you're enrolling fully receptor alpha or low, medium, and high patients. I'm just curious, what's the objective of including some of these lower-expressing patients? And are you exploring some of these lower-expressing patients in any other of your studies?
spk08: So early in development, Boris, when we did our combination study combining Mervituximab with Carboplatin with Avastin, we did include a broad range of patients with folate receptor alpha expression. We now know that it's really the high patients who benefit most from Mervituximab monotherapy. We also know that patients with lower levels of FR-alpha expression really benefit nicely from combinations, including Mervituximab plus Bevacizumab, and also, in particular, Mervituximab plus carboplatin. and we have published those data from dose escalation for Mervituximab plus carboplatin, showing really that both the mediums and the highs do extremely well with this doublet, and also we saw very nice responses in the mediums. It was a small phase one data set with just 18 patients, and so we look forward to expanding our understanding of this doublet in a larger population in trial 420. The hypothesis here, Boris, is that the patients with higher levels of FR-alpha expression will lean a little more on the Mervituximab activity, and the patients with lower levels of FR-alpha expression will lean a little more on the carboplatins activity, and that the combination really should benefit a broad range of patients with FR-alpha expression.
spk02: Got it. Great. Thank you very much for taking my questions.
spk11: Our next question comes from Andy Tsai with William Blair. Your line is open.
spk03: Great. Thanks for taking my question. So in terms of MERV, appreciate the 101 PFS events additional information there. I'm just wondering if you could remind us how many events are required to trigger the primary analysis of PFS out of the 430 targeted enrollment? And also on the regulatory front, I'm just curious in your previous discussions with the FDA, has the subject of having an outcome ever came up during that discussion? And moving on to the Vectormab, we're just curious, you know, housekeeping, you know, you mentioned about the forward dosing. Is that the 45 micrograms per kilogram that you'll be examining? And then lastly for CMC, I'm just curious about the process there with the FDA. Is there like a back and forth after you submit the data, or should we kind of think about it as kind of an IND where after a certain period of time, you know, it becomes active? Thanks for taking all my questions.
spk08: Great. All right, Andy, I'll take all four. So the first one is that for Mirasol, the primary endpoint is progression-free survival, and the analysis will be triggered when we have 330 PFS events. For your second question regarding an ADCOM, you may recall that we submitted the BLA for SREA at the end of March, and we are actively engaged with FDA, responding to information requests. and certainly we expect in the coming months to understand whether or not an ADCOM would be needed. Given the safety profile of our drug and the activity that we've seen, you know, I can't speculate on what FDA will say, but I can tell you that we will be prepared should FDA require an ADCOM. Going to your third question for PVEC, yes, the recommended Phase II dose and schedule in combination is, with azacitidine and venetoclax for PVAC is 0.045 milligrams per kilogram or 45 micrograms per kilogram. And we have already opened expansion cohorts for the triplet in both relapsed refractory AML as well as actually relapsed AML and then in the frontline cohort. And I must say enrollment is going quite briskly for both of those. And to your last question, I'll make an initial comment and turn it over to Mark. From the process to interacting with the CMC, with FDA, we're providing data to them when we have it, and then we anticipate the clinical hold will be lifted, and then we'll start enrolling patients later this year.
spk03: Nothing to add. Great. Thanks so much.
spk11: Our next question comes from Kelly Shee with Jefferies. Your line is open. Thank you.
spk10: Thank you for taking my questions. First, regarding the RASO enrollment, could you share more color regarding the timing to complete the enrollment? And also, will the ECOG performance status influence patient outcome in both chemo and the MERV treatment arm, in your view, in RASO trial? And do you think the RASO trial has consistent ECOG split at the zero versus one with the previous forward one in the MIRACIL trial. And lastly, for MGC936, item 986, what would be the efficacy bar to select a certain tumor type for the next phase of the study? And how many inpatient data could we expect for the first data readout? Thank you.
spk08: Sure. So we anticipate Mirasol being fully enrolled this summer. Moving to your second question regarding ECOG performance status. You know, ECOG performance status is an important predictor for how patients will do, how they'll tolerate therapy. And we focus on enrolling patients with an ECOG performance status of 0 or 1. So either patients feel perfectly well or they may be a little bit tired. but certainly able to work and perform all of their activities of daily living. And so both of these subsets of ECOG patients we anticipate will be able to tolerate the therapies on both arms. And, you know, the patients that we've been enrolling in Mirasol are consistent with what we expect for this population and similar to what has been seen in Forward One. And then lastly, your question around 936, This is our ADAM9-targeted ADC. ADAM9 is expressed in a variety of solid tumors, including pancreatic, gastroesophageal, lung, triple negative breast cancer, and even colorectal cancer. And so in phase one dose escalation, the data will guide us regarding which tumor type or tumor types we will pursue initially in mini-expansion cohorts and then in formal expansion cohorts to support potentially accelerated approval. At this point, we're focused on identifying the recommended dose and schedule, and we look forward to sharing data this year once we have a sufficient data package that we all can interpret and share.
spk10: Thank you. Very helpful.
spk11: Our next question comes from Jessica Phi with J.P. Morgan. Your line is open.
spk07: Hey, guys. Good morning. Thanks for taking the questions. First, can you remind me by when you expect to hear if you've received priority review on the SUREA submission? Second, can you walk through the label you hope to achieve for Mervituximab based on the SUREA data you submitted, particularly around it being silent with respect to prior Avastin? Given that you're running Mirasol, that sort of seems like it would answer that question. How do you handicap the probability of getting that broad label? And then lastly, with Gloriosa expected to initiate enrollment in the middle of this year, when should we think about potentially seeing data from that trial?
spk08: Yeah, so we anticipate hearing back from FDA by the end of this month regarding their acceptance of the filing and granting of priority review. Regarding the label, given the strength of the data from SREA, we have gone into this with a broad label. I could point out that the data for Mervituximab monotherapy in terms of the response rates actually is a bit higher than what you see with Avastin plus chemo in a less heavily pretreated Avastin-naive population. And so we're really excited about these data, and we know that Mervituximab, based on the impressive activity in this heavily pretreated, Bev-pretreated population, it's going to look even better in a Bev-naive population. So that is why we have gone in with the broad label. I would be hesitant to put any odds on you know, how this would go. And then thirdly, in terms of Gloriosa, you know, we're really, really excited about this study and we look forward to getting it up and running mid-year. I think it's a little bit early, Jess, to share, you know, when we think we'll have data from this study. But once we are up and running, you know, we've got sites activated and we get a sense of how things are going, then of course we will update our guidance. Great. Thank you.
spk11: Thank you. As a reminder, to ask a question at this time, please press star then 1. Our next question comes from Joe Cantazzaro with Piper Sandler. Your line is open.
spk13: Hey, guys. Thanks for taking my question. So first one, on your last call back in February, I think you said you were right on track for Murasol's 3Q readout, I think despite enrollment having not been completed because the enrollment dynamics were maybe more evenly distributed. So I just want to understand a little better why now enrollment pace is having an impact on timelines. Thanks, and I have a follow-up.
spk08: Yeah, sure. Well, you may recall February was really before we understood the extent of the geopolitical events in Ukraine and Russia. And it was also prior to the surge in COVID resulting in lockdowns in Beijing and Shanghai. And, you know, all three of those countries, we had anticipated they would enroll, you And so that, unfortunately, is not quite panning out as we had anticipated. So that's one of the drivers that is more clear now than it was in February. But the other driver is that we now have the data from the interim analysis that allowed us to reproject the event rate. So it's really multifactorial.
spk13: Okay, thanks. That's helpful. And I guess understanding that it's multifactorial – If I could just ask, you know, if we consider MERV's experience in Soraya, it seemed to behave pretty much exactly how you guys expected it to based on ForwardOne and other prior data. So is there any reason why, you know, Mirasol could in any way be different from Soraya and MERV maybe in fact could be outperforming your expectations? I know that's pure speculation, but wondering if you have any thoughts there.
spk08: I agree with you that's pure speculation, and I think we're really excited to see the data from Mirasol because that's certainly a possibility.
spk13: Okay, great. Thanks for taking my questions.
spk11: Our next question comes from Jonathan Chang with SV Securities. Your line is open.
spk12: Hi, guys. Thanks for taking my questions. First question, what impact, if any, would you anticipate prior PARP use would have on the chemo arm performance in Miracel?
spk08: Jonathan, thank you for that question. You know, the reason that you're asking it is that was an outstanding question for Mervituximab that we have really solidly answered with the SEREA data set showing that Mervituximab has very nice activity regardless of prior PARP use or not. Your point is that in the Mirasol study, there will be a higher percentage of patients with prior PARP inhibitor than there were in forward one, and how is that going to impact chemotherapy? I have speculated myself that of the three chemotherapies, weekly paclitaxel, topotecan, and doxil, prior PARP inhibitors may decrease the activity seen in with patients randomized to or assigned to the doxil arm. And the reason I say that is doxil, like carboplatin, is a DNA-damaging agent. PARP inhibitors interfere with repair of DNA damage. I don't have any data to support that, but I think mechanistically there is the potential for the doxil stratum to perform worse. The other little data kernel, I would say, is one of the early randomized studies of a PARP inhibitor head-to-head against chemotherapy was versus doxil, and that study was negative. But this is me just speculating. I certainly don't think a prior PARP inhibitor is going to increase activity for chemotherapy. So I think either the chemotherapy control arm will do as anticipated or potentially worse.
spk12: Got it. Thank you. And the second question, ahead of the PIVA-ChemAb combination data ASH, what do you see as the appropriate benchmarks for success in frontline and relapsed refractory AML?
spk08: So in frontline AML, the bar admittedly is high. And, you know, I think the VenAza doublet has set the bar there. And we're also tracking closely the Megrolimab triplet data. So I think those are the bars that we're looking at. In the relapse setting, it's a little less clear, you know, especially in the post-VEN setting where nothing else works. But, you know, we would be thinking that a CR, CRI rate of 40% in the relapse refractory setting would really be something exciting that could translate into meaningful benefit for patients.
spk12: Got it. Thanks for taking the questions.
spk11: Our next question is a follow-up from John Newman with Canaccord. Your line is open.
spk06: Hi, guys. Thanks a lot for fitting me in with the follow-up. So, you know, I think investors overall sometimes are skeptical of retrospective analyses, which is probably rightly so. But I just wondered if you could comment on the agreement between the actual data in Soraya and the retrospective analysis that you did ahead of that study, because I think it's may help inform interpretation of the 2.8 months PFS from the forward one subset that overlapped. I just don't know if you have those numbers in front of you, but just curious if you could talk about that. Thanks.
spk08: Yeah, so I think, John, what you're referring to is the remarkable consistency of efficacy for Mervituximab throughout development. And so, you know, that foundational 70 patients who are SREA-like You know, we had a response rate above 30 percent. We had a median duration of response of 7.8 months. We had a median PFS of 4.4 months. And we basically replicated that in the Soraya study really quite accurately. And so, similarly, we anticipate that data from the FORWARD-1 study for the Murasol-like population should replicate in the Murasol study. You know, I would point folks to the 2019 ESMO presentation where Dr. Moore did show the post hoc exploratory analysis for forward one, looking at FR-alpha high patients for Mervituximab versus chemotherapy. And we saw a very nice treatment effect for Mervituximab over chemotherapy and both by investigator and by blinded independent review with a hazard ratio of around 0.6. And so we've designed Mirasol to around a hazard ratio of 0.7, so more conservatively. And so we already knew that Mirasol was de-risked with a high probability of technical success. And from my perspective, given that SREA has replicated prior data from an exploratory post hoc analysis, I'm even more confident that that Mirasol will also replicate the results, and especially knowing that prior PARP inhibitor use does not impact merpetuximab's activity. We remain quite confident about Mirasol and look forward to sharing data early next year.
spk06: Great. Thank you.
spk11: Thank you. I would now like to hand the conference back over to the team for closing remarks.
spk14: Great. So as we mentioned in the opening remarks, we're off to a strong start to the year, and we're moving fast and with purpose. And so as we look ahead, we are looking forward to our first potential product launch, generating top-line data from the PVAC Pivotal Study and advancing the remainder of our pipeline. We're very well positioned at this point to execute on our transition plan, to a fully integrated company, and we're excited to offer more good days to our people, our business, and our patients. So thanks for your time today, and we will look forward to seeing you all later this month at ASCO where we'll have some additional data from our programs. Thanks.
spk11: This concludes today's conference call. Thank you for participating. You may now disconnect.
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