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spk04: Good morning, ladies and gentlemen, and welcome to Immunogen's fourth quarter and full year 2021 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 Okanek, Senior Director of Corporate Communications. Please go ahead.
spk05: 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 and fourth quarter and full year 2021 financial results. This press release and a recording of this call can be found under the Investors and Media section of our website at immuneengine.com. With me today are Mark Ennedy, our President and CEO, Anna Birkenblatt, our Chief Medical Officer, and Susan Eltshuler, our CFO. Kristen Harrington-Smith, our Chief Commercial Officer, will also join us for Q&A. During today's call, we'll review recent accomplishments for the business, our financial results, and highlight upcoming anticipated events. We will use forward-looking statements with respect to our business strategy, the development and benefit of our product candidates, the design of our clinical trials, the presentation of clinical trial data for our product candidates, the anticipated timing of clinical trials and regulatory submissions to the FDA for certain product candidates, the anticipated commercial launch for certain product candidates, financial guidance, and our cash runway. Each forward-looking statement is subject to risks and uncertainties that could cause our actual results to differ materially from such statements. These risks and uncertainties include those described in our press release issue this morning and in the risk factor section of our most recent annual report on Form 10-K and our other SEC filings, which are available at sec.gov and on our website at immuneengine.com. This forward-looking statement and this presentation speak only as of the original date of this call, and we undertake no obligation to update or revise any of these statements. With that, I'll turn the call over to Mark.
spk16: Good morning, everyone, and thank you for joining us today. 2021 was a productive year for Immunogen, with significant progress across the business as we moved towards our objective of becoming a fully integrated oncology company. In particular, we delivered resoundingly positive results in Sirea, our pivotal study for Mervituximab and ovarian cancer, generated compelling data with IMGN 632 and AML, advanced our earlier stage programs, established a plan to reignite our research engine, laid the groundwork to support our first commercial launch, and executed the single largest financing in the history of the company. With this progress, we've generated significant momentum in the business as we enter 2022. To expand on these points, starting with our lead program, Mervituximab, soroftanzine, and ovarian cancer, our top priority this year is to gain accelerated approval for Mervituximab as a monotherapy in patients with folate receptor alpha-positive platinum-resistant disease. To this end, we believe the positive top-line TREA data reported in late November position us for initial approval in this setting with significant unmet need. We're on track to submit the BLA for Mervituximab by the end of this quarter, and are preparing for potential accelerated approval and launch in the second half of the year. We also expect to generate data from our confirmatory Murasol trial in the third quarter, which is intended to support full approval. As part of our comprehensive strategy to move Mervituximab into broader patient populations and become the combination agent of choice in ovarian cancer, we've designed a number of additional company-sponsored studies and, in parallel, are supporting investigator-sponsored trials for Mervituximab which Anna will discuss in further detail shortly in the call. In step with advancing the Mervituximab program towards regulatory approval, we began building our commercial and medical affairs organizations, now led by our Chief Commercial Officer, Kristin Harrington-Smith, and our Head of Medical Affairs, Dr. Mimi Huizenga. Launch preparations for Mervituximab are well underway and are focused on four key priorities. redefining expectations for positive outcomes with Mervituximab and platinum-resistant ovarian cancer, supporting adoption of early folate receptor alpha testing and establishing standards for in-house and centralized testing, ensuring positive physician and patient experiences through tailored education and guidance for patient management, and seeking broad payer access and reimbursement in delivering a seamless patient experience. We're off to a strong start building best-in-class sales, marketing, and medical education teams, and have most recently added our head of sales. Our second program, Paveka Madison Nearing, formerly known as IMGN 632, is progressing nicely. We've advanced our pivotal cadenza study in BPDCN and expect top-line data in the front-line cohort in the second half of this year. In addition to BPDCN, we were pleased to present data from the triplet regimen evaluating PVEC in combination with azacitidine and venetoclax and relapsed refractory AML during an oral session at ASH and are encouraged by the safety profile and efficacy observed, particularly in the higher intensity cohorts. Based on these data, we've initiated an expansion cohort for the triplet and relapse patients and expect to move into frontline patients during the year. Regarding our earlier stage portfolio, dose escalation continues in the phase one trial of IMGC936, our first in class ADAM9 targeting ADC, which we are co-developing with macrogenics and multiple solid tumor types and anticipate sharing data from this program later this year. We also submitted the IND for IMGN151, our next generation antifoliate receptor alpha ADC. Due to a delay in drug product production at our vendor, FDA placed a hold on our IMD application pending responses to some CMC-related information requests. We are generating the data responsive to these requests and look forward to enrolling our first patient following submission of this information to the agency. Turning to business development, we were pleased to announce a multi-target global licensing deal with Eli Lilly earlier this month. This deal demonstrates the strength of our technology and leadership in ADCs and generates value from our intellectual property around our proprietary Camp to Thesis platform. Lastly, we completed an upsized follow-on offering that generated roughly $295 million in gross proceeds in the fourth quarter, and we ended the year with over $475 million in cash. These funds, together with product and collaboration revenues, will support the business through the initial launch of Mervituximab and other material inflection points and into 2024. With that, I'll turn the call over to Anna to provide some additional color on our clinical programs. Anna?
spk08: Thanks, Mark. We are extremely pleased by the positive top-line results for our pivotal SORAYA trial. Recall that despite advances in the frontline and platinum-sensitive settings, most patients with ovarian cancer eventually relapse with platinum-resistant disease. Treatment options for platinum resistant ovarian cancer are limited consisting primarily of single agent chemotherapy which has limited activity with objective response rates ranging from 4 to 13% and considerable toxicities. Having aligned with FDA on the substantial unmet need in this population, Sirea was designed as a single arm study of Mervetuximab in patients with platinum resistant ovarian cancer whose tumors express high levels of folate receptor alpha and who have been treated with one to three prior lines of therapy, including prior Bevacizumab. The primary endpoint of confirmed objective response rate, or ORR, as assessed by investigator, was 32.4%, well over double the expected response with single agent chemotherapy. Five of the responses were complete responses, which doesn't happen very often with available therapy in platinum resistant disease. Median duration of response, or DOR, is a key secondary endpoint and was 5.9 months as of the data cutoff on November 16th, 2021. With nearly half of the responders still receiving Mervituximab at that time, the duration of response continues to evolve. These results are particularly encouraging in light of the heavily pretreated population in which 51% of patients had three prior lines of therapy. All patients received prior Bevacizumab, and 48% had received a prior PARP inhibitor. Turning to safety, the profile in Sirea is consistent with a known safety of Mervituximab, which has now been studied in over 800 patients. The most common adverse events were low-grade, reversible, ocular, and GI events, managed with supportive care and dose modifications if needed. The tolerability of Mervituximab is demonstrated by the low 7% discontinuation rate for treatment-related adverse events, including just one patient in Sirea discontinuing for an ocular adverse event. No corneal ulcers or perforations have been reported. As in prior studies, the ocular events were predictable, manageable, and reversible. Looking ahead, Dr. Ursula Matalonis will present the full SREA dataset at SGO during the plenary late-breaking abstract session on Saturday, March 19th. Data will include updated duration of response and key subgroup analyses, including patients with three prior lines of therapy and those who received a prior PARCC inhibitor. Progression-free survival data will also be presented. As mentioned, we are on track to submit the BLA for Mervituximab before the end of the first quarter in support of potential accelerated approval later this year. In support of full approval, the confirmatory Murasol study of Mervituximab is expected to read out in the third quarter of 2022. We also continue to enroll patients in Piccolo. a single-arm study of Mervituximab monotherapy in approximately 75 patients with folate receptor alpha-high recurrent platinum-sensitive ovarian cancer intended to support label expansion. PICOLO is designed to address the increasing unmet need for an effective non-platinum option in later lines of platinum-sensitive disease. With an overall response rate of 64%, our Phase I data show a potential for Mervituximab in this patient population. We have formalized our strategy to position Mervetuximab as the combination agent of choice. With compelling data from the Mervetuximab plus Bevacizumab doublet in patients with folate receptor alpha high recurrent ovarian cancer, we expect to gain compendia listing for this combination in close proximity to the initial monotherapy approval of Mervetuximab. These data also support our design of FLORIOSA, a potential label-enabling phase three study in the second-line platinum-sensitive maintenance setting. About a third of second-line platinum-sensitive patients receive a platinum doublet plus Bevacizumab, followed by Bevacizumab maintenance. The addition of Bevacizumab to a platinum doublet provides an overall modest improvement in PFS of approximately three to four months in this setting, highlighting the limitations of available therapy. Gloriosa is designed to evaluate the PFS benefit of Mervituximab plus Bevacizumab maintenance versus Bevacizumab maintenance alone in all patients who have not progressed following completion of their platinum doublet plus Bevacizumab. Approximately 440 patients will be randomized to either Mervituximab plus Bevacizumab or Bevacizumab alone for maintenance. The primary endpoint is progression-free survival. Secondary endpoints include overall survival and overall response rate. We anticipate initiating Gloriosa in the second quarter of this year. Given the promising activity we've seen with imervituximab plus carboplatin development in phase one dose escalation in recurrent platinum sensitive disease across a range of folate receptor alpha expression with an ORR of 80% and median duration of response of 24 months in FR-alpha medium and high patients, We recently announced the planned initiation of Trial 420. Trial 420 is a single arm phase two 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. The data from this study will inform our path to registration in this setting. Moving to pivecumab-sunarine, our CD123 targeting ADC. We presented initial safety and efficacy findings from the Phase 1-2 study of pivecumab in combination with azacitidine and venetoclax in patients with relapsed refractory AML in an oral session at ASH in December. Demonstrating an ORR of 48% in all relapsed refractory AML patients, these data are encouraging, particularly in higher-intensity cohorts where we observed higher response rates, including an ORR of 59% and a 38% composite complete remission rate. Importantly, the Pavecimab triplet demonstrated no tumor lysis syndrome, veno-occlusive disease, capillary leak, or cytokine release. These data reinforce the potential of Pavecimab as a new combination therapy for AML, which unfortunately is characterized by poor outcomes despite available therapies. We have opened an expansion cohort in relapsed AML patients and plan to initiate a frontline expansion cohort later this year. Also at ASH, we presented Pivecamab monotherapy data featuring vignettes from three frontline BPVCN patients in a poster session. All three patients achieved clinical complete remission and Pivecamab was associated with limited grade three or greater treatment-related adverse events and no capillary leak syndrome. We continue to enroll patients in the U.S. and Europe in CADENZA, our pivotal phase two study in frontline and relapsed refractory BPD-CN, anticipate top-line data during the second half of 2022, and believe Pivetamab has the potential to become a best-in-class monotherapy treatment option for BPD-CN patients.
spk06: With that, I'll turn the call over to Susan to cover the financials. Susan? Thanks, Anna. Starting with our results for the full year 2021, We generated $69.9 million in revenue, $46.8 million of which came from non-cash royalty revenues. The remainder came from license and milestone fees, which include recognition of $14.6 million of the $40 million upfront fee previously received under the company's collaboration agreement with Huadong Medicine, and $7.4 million of revenue from partner milestones. Operating expenses were $194.9 million, comprised of $151.1 million of R&D expenses compared with $114.6 million in 2020, and $43.8 million of G&A expenses compared with $38.6 million in 2020. We ended 2021 with $478.8 million in cash on the balance sheet. Turning to our financial guidance for 2022. 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 the anticipated product and collaboration revenues, will fund operations comfortably into 2024. With that, I will turn the call over to Mark for closing comments.
spk16: Thanks, Susan. We entered this year with a motivated and strong team and exciting prospects for the business. Between now and the end of the year, we expect to launch our first product, report pivotal data for PVEC, advance our early stage programs, and further build our pipeline and research capabilities. We have the right strategy, leadership, and resources in place to generate significant value in the near and long term, and I look forward to more good days for our people, our business, and our patients. With that, we'll open the call for questions.
spk04: Ladies and gentlemen, if you'd like to ask a question at this time, you will need to press the star, then the one key on your touch-tone telephone. To withdraw your question, you may press the pound key. Please stand by while we compile the Q&A roster. Now, first question coming from the line of John Newman of Canaccord. Your line is now open.
spk17: Hi, guys. Good morning. Thanks for taking my question. Congrats on the continued progress. I have two quick questions. First one is, for the progression-free survival data from SREA at SGO, just curious if we'll see both investigator-assessed and independently-assessed. And then on Pevecumab or 632, Just curious as to what patient population and potential combinations you're considering for a future pivotal study. Thanks. Anna?
spk08: Hi, John. Yeah, so at SGO, we will have the full data set from SREA, which will include overall response rate, duration of response, subsets, and we will include PFS data as well. I would encourage folks to come to SGO to assess the PFS data, and we will have an investor event shortly thereafter. Moving on to the PVEC question, in terms of future pivotal trials, we are thinking about the triplet, PVECAMAB plus azacitidine plus venetoclax in relapsed refractory AML. based on the data that we have already generated in Phase I dose escalation and now we're exploring in an expansion cohort, that potentially could support a single-arm study in the relapsed setting. In addition, we plan to explore a frontline setting for this triplet, and should those data look promising, then we could consider a frontline randomized Phase III trial to support approval for that triplet in the frontline setting.
spk17: Great. Thank you.
spk04: Now, our next question coming from the line of Michael Schmidt from Guggenheim Securities. Your line is open.
spk15: Hi, good morning. This is Ige Alpha Michael. Congrats on the progress, and thanks for taking our questions. Two quick questions from us. Number one, for Mirasol, Anna, could you please help us understand the mix of the patients with and without prior bevacizumab how are the two groups different in baseline characteristics, and how might that impact the response to MERV? And the second question, can you talk about your Capital 1000 ADC platform that you're licensed to really? How is the payload different from other Type 1 topoisomerase-targeted ADC? Thank you. Diana?
spk08: Yeah, so for Mirasol, The patient population will include both patients with and without prior Bevacizumab. Similar to Forward 1, the prior Phase 3 study where we had a mixture of patients, in Forward 1 about half of the patients had prior Bevacizumab and half did not. We anticipate a similar patient mix in Mirasol. And when you think about which patients get Bevacizumab, They tend to be patients with worse prognosis and are more heavily pretreated. Let me start with the worst prognosis and then move to heavily pretreated. Bevacizumab is approved in several settings for ovarian cancer, the only one of which that has demonstrated an overall survival advantage is in the first-line setting for poor-risk patients. These are patients with stage 4 disease, suboptimally debulked, ascites, etc., So many physicians often reserve Bevacizumab for those worst patients, particularly in Europe. And we can see that, actually, in the Soraya study when you come to SGO in terms of the demographics of the patients enrolled in terms of their stage of disease. Moving to a number of prior lines of therapy also, Bevacizumab, it's hard for us in prior studies to tease apart bevacizumab versus number of prior therapies. And, you know, as a point of reference to support that, in the FORWARD-1 study, 65% of patients had one to two prior lines of therapy, and 35% had three priors. You may recall that in sirea, 51% of patients had three prior lines of therapies. So the sirea population is more heavily pretreated and potentially a worse population than what we anticipate seeing in the Mirasol study based on the prior FORWARD-1 study. Moving to the next question on camptothesins. So our camptothesin payloads are specifically designed to address potent anti-tumor activity and have basically unique properties from a chemical perspective that give broad IP coverage for us. I think that's what I can say at this point. I don't know, Mark, if you want to add any color to the camptothesin payloads.
spk16: Yeah, maybe just a little broader observation here. So, you know, we take some pride in having multiple classes of payloads to apply to ADC. So, you know, we've got at least three generations of metanzines. We have our indolino benzodiazepine DNA acting payloads, and we're looking for additional classes. And our team, you know, engineered – this, you know, this new version of the camp to seasons with a goal of broadening the therapeutic index versus what we see, um, with, uh, some of the other campus seasons that, um, have been deployed in the eight context. And we've got very good preclinical data, uh, supporting that we've been able to, you know, drive activity at least, uh, in that range, uh, with better tolerability. So we're excited about that. Lily was excited about that. And, uh, are moving forward with the tech transfer for them, for their targets, while at the same time advancing internal programs that will deploy that payload.
spk15: Thank you very much.
spk04: And our next question, coming from Delana Edzard with BMO Capital Markets. Delana is open.
spk02: Great. Thanks for taking the question. The first one for me, you know, with respect to PFS and Soraya, I guess, how meaningful is this update from your perspective in this late-line post-BEV, you know, setting, and will we see benchmarks for this specific population at SGO? And then secondly, on IMGM 151, given sort of the CMC submission update, Are you still on pace to start the phase one in the first half of this year? Thank you.
spk08: I'll take the PFS question, and then I'll turn it over to you, Mark, for the 151 question. Regarding SREA, you're absolutely right. The population is a late-line post-BEV setting. Frankly, This is one of the most heavily pretreated populations that has been studied in platinum-resistant ovarian cancer in a study this size, so there are no good benchmarks. But what I can tell you is there are multiple studies that have been published showing in ovarian cancer, as in other solid tumors, the law of diminishing returns, if you will, with each line of therapy, the expectations for response rate, duration of response, and progression-free survival diminishes. So when you get to these really later-line patients, physicians' expectations regarding efficacy are quite low, given their experience. And certainly, you know, the data that we've shared with the investigators on the SREA study, they're quite pleased with the totality of the efficacy data that we have shared with them in terms of ORR, duration of response, and PFS, because, as I said, the expectations that they have for these patients, later-line post-Bev setting is quite low. What I will tell you is that we will share data at SGO to put the PFS data from SREA into context based on what we've known from prior studies of Mervituximab. As you've seen, we've replicated the overall response rate data in SREA that we had previously gathered in that 70 patients of foundational data that basically created the hypothesis that we have tested in SREA and now confirmed. Again, we'll have the data and put it into context for you at SGO. Mark, over to you for 151.
spk16: Yeah, thanks. So just to reiterate the point that we made in the introductory comments, this is a CMC and not a clinical issue. So, you know, in order to issue a study may proceed letter for an IND, the FDA requires the sponsor to submit CMC data relating to the drug, including drug product stability. Most often, those data are included in the IMD submission, and in some cases, the sponsor will make the data available to the agency during the review period. In the case of 151, we plan to submit the required data during the review period. However, due to delays at our drug substance vendor, we were not able to secure a drug product production slot as we had planned, which meant that we weren't in a position to update the IMD during the review period, so the agency put us on hold. We've now secured our drug product slot for this quarter, and we will generate the required data and expect to come off clinical hold in due course. It's too early to give updated guidance in terms of we will be delayed, but it's too early to give updated guidance on the timeline for first patient, but we will update you when we've got a better sense following the DP run.
spk02: Got it. Thank you. Congrats on all the progress.
spk16: Thank you.
spk04: Our next question coming from the lineup. We're a speaker with Colin. Your line is open.
spk13: Great. Thanks. Maybe looking forward to the SGO, I think a lot of investors are going to be focused obviously on the PFS results and use that as a basis to estimate the probability of success of Mirasol So maybe you could help us try to understand how we should be thinking of translating the PFS from Soraya to Mirasol quantitatively.
spk08: Thanks, Boris. You know, I think we have actually much better data to guide PFS from Forward 1 to Mirasol. What I mean by that is that PFS in a single-arm study like Sirea is really not interpretable. You don't have a control arm to tease apart the anti-tumor activity from the underlying tempo of disease. And so that's why FDA does not use PFS when they are looking at anti-tumor activity to support accelerated approval. It's about ORR and DOR. If people want to assess the probability of technical success for Mirasol, I would encourage them to review the data that we've already generated in FORWARD-1. Recall that FORWARD-1 was the randomized Phase III study of Mervituximab versus investigator-choice chemotherapy. And in the FR-alpha-high subset, identified by the PS2 scoring method, that is the population that we're basically replicating in Mirasol. And in Forward 1, we demonstrated a median PFS in that population of 5.6 months. The hazard ratio in Forward 1, based on either investigator or blinded independent review, was around 0.6. And you may recall that in Mirasol, we designed the study to target a hazard ratio of 0.7, much more conservatively. So we've already run the experiment in Forward 1. The population in Mirasol will be essentially the same in terms of platinum resistance, one to three priors, FR-alpha high, about half of them having prior Bevacizumab. The one difference is that we'll have a higher percentage of patients with PARP inhibitors now, and we've already demonstrated in Sirea, and you'll see the full data at FGO, that Mervituximab has very nice activity regardless of prior PARP use or not. So from our perspective, the Sirea data increased the probability of technical success for Marisol because we now have that answer about what about prior PARP inhibitors. Thanks, Boris.
spk13: Got it. And my second question is on the Cadenza study and BPTCN. Could you set expectation what you need to show in the study for approval?
spk08: Yeah. So the statistical design for Cadenza is really allowing us to enroll a cohort of up to 20 patients in this ultra-rare indication. There's somewhere between 500 and 1,000 new patients a year in the U.S. and similarly in Europe. And so looking at the efficacy data for the one approved agent in BPD-CN, we know that the CR-CRC rate is in the 40% to 50% range. And so we would need to demonstrate a CR, CRC rate in that range with nice efficacy. And from a statistical perspective, based on the sample size that we're using, that rules out this 10% CRC rate that FDA guided us to.
spk13: Got it. Thank you for taking my question. Sure.
spk04: Our next question coming from the line of Andy with William Blair. Your line is open.
spk14: Great. Thanks for taking my questions. And congratulations on all the progress last year. So first question has to do with the new trials. So Anna, I'm just curious if you have decided on the trial design for Gloriosa in terms of treatment duration. in the maintenance phase? And also maybe a step back, can you use this trial as a confirmatory study for Piccolo? I know that sometimes FDA allows you to confirm using kind of a different patient population. And the second question is for Kristen. I'm just curious, as you prepare to launch Merv, have you decided on how the drug will be distributed? So specifically, I'm curious about the ordering and delivery system. Is that mostly on demand? And if that's the case, how should we think about the gross demand? Thank you.
spk08: Sure. So we're really excited about the Gloriosa study, which is a study of adding Mervituximab to maintenance Bevacizumab versus maintenance Bevacizumab in the recurrent platinum-sensitive settings. Why are we excited about this? Because we've already generated beautiful data in the treatment setting for the MERV, BEV, doublet showing response rates of 59% in platinum-resistant disease, 69% in platinum-sensitive disease that are above the benchmarks. And so we want to move that active, well-tolerated doublet into the maintenance setting. We know that patients, once they have recurrent platinum-sensitive disease, more and more of them will have already had a PARP inhibitor in the frontline setting, and so using a triplet in the recurrent platinum-sensitive setting makes a whole lot of sense. So with that, we will take all patients who have completed their triplet in terms of the carboplatin doublet portion of it, and as long as they haven't progressed, so they have a CR, a PR, or stable disease, they will be randomized to MIRV-BEV versus BEV alone. And you may recall that in this setting, that entire treatment path for Bevacizumab, Bev only adds about three to four months of progression-free survival. So adding Mervituximab, you know, a non-cross-resistant targeted cytotoxic, we anticipate that we will have responses on the Merv Bev arm, and there will be a long treatment duration on the Merv Bev arm, really benefiting patients. The primary endpoint is progression-free survival. The study also has sufficient power for us to demonstrate an overall survival advantage, and that could really transform the treatment paradigm for these patients. Regarding your question about confirming whether or not Gloriosa could stand in as a confirmatory trial for Piccolo, it's a little too soon for us to work that through. Piccolo is enrolling now. And we need to engage with FDA on the exact criteria for a path toward accelerated approval. So I would stay tuned for that. And let me turn it over to Kristen now.
spk09: Thanks, Anna. So to respond to your question, we do plan on using a 3PL. So like you said, an on-demand or drop-ship model. And this is to help us with our growth to net. But at this time, that's all... That's all we would like to comment on gross to net. Does that help?
spk14: Yeah, okay. So I guess the question is really how would the gross to net differ from other drugs or more traditional distribution? So that's kind of where I am curious about.
spk09: Yeah. So our goal is to avoid many of the wholesaler fees.
spk16: Andy, is that the one? Yeah, no, no. So, I mean, when you look at the patient numbers and volumes here, there's no need to have, you know, a massive amount of inventory sitting at wholesalers, you know, awaiting to be distributed. So, it's much more efficient from our perspective. And most of the ADCs use this model. of setting up a 3PL and then having the orders come in and fulfilling those using the dropship model. In doing that and setting up a very streamlined approach here, we're avoiding a lot of the fees that are intended to having inventory sitting at a wholesaler. We can't tell you right now what exactly the gross to net would be, and that probably wouldn't be a good idea in the first instance.
spk14: Right, okay, that's really helpful. Thank you so much. So, Anna, I'm curious, is there like a fixed duration for the maintenance phase for Gloriosa? Is there like one year, you know, 18 months or two years? I'm just curious if that's been set.
spk08: Yeah, so in the frontline setting, when you do maintenance trials, there is a fixed duration because there's a chance that some of your patients are going to be cured. Once you have recurrent platinum-sensitive disease, the expectation is that you're not cured. So patients will be treated until progression and intolerable toxicity or, you know, intolerable toxicity. But I have to say, I mean, across the MIRV program, we've had patients on Mervituximab for one year, two years, three years, even up to four years and still going. So, you know, in terms of the tolerability of Mervituximab as a monotherapy, we know that it's quite well tolerated. And with the MervBev, we've had patients on that doublet for a good long time as well, both in the platinum-resistant and the platinum-sensitive settings. So, you know, I can't tell you an estimated duration in maintenance in the recurrent platinum-sensitive setting, but it's going to be long because we're, you know, we know that the PFS of these patients is going to be quite long.
spk14: Great. Thank you so much for answering all my questions.
spk16: Thanks, Andy.
spk04: Our next question coming from the line of Kelly Hsu with Jeffrey.
spk11: Good morning. This is Hao calling in for Kelly Hsu. First, congratulations on the great quarter. So my question is really for the MIRASO trial, given the assumption for the medium PFS, the chemo arm is about 3.5 months. Do you see any risk that the control arm might outperform given that more option of chemotherapy is available for the control arm? And then my second is regarding to the ECOG01 performance status. Do you see that may also influence the patient outcome in the control and treatment arm and how the patient, in terms of the consistent weight of the zero-one status, if it's consistent from the forward one trial to Soraya and the Mirasol trials?
spk08: Okay. So your question about the progression-free survival estimate on the control arm of Mirasol, we have designed it for 3.5 months, because that's pretty much what every study in platinum-resistant ovarian cancer has shown. I would remind you that in Forward 1, for the FR-alpha high subset, we actually had a median PFS of 3.2 months. You know, there are some studies out there suggesting that FR-alpha is a poor prognostic factor, so it may be with single-agent chemotherapies, patients with high FR-alpha do worse than the overall population. If anything, I think the control arm on Mirasol might underperform, not outperform. I didn't understand your comment about it might outperform because more options are available. The options on the Mirasol control arm are topotecan, paclitaxel, and doxil, just like they were in the Forward One study. These are all drugs that have been approved 20 years ago. So it's not like now there's more better therapies. Unfortunately, we're using the same old single-agent chemotherapies that have been around for a couple of decades. So if anything, I think the control armor and mirror cell might underperform, but we certainly didn't design it assuming that it needed to, you know, for success of the study. Moving to ECOG performance status 0 or 1, you know, the ECOG performance status of 0 means people feel perfectly well. ECOG status of 1 means they're a little tired, and the lower the performance status, certainly the worse patients do. And that's why we've excluded patients with poor performance status, 2, 3, or 4, because that's when you know that the risks of whatever you're studying begin to potentially outweigh the benefits because the patients just aren't fit enough. So given the population that we've enrolled across the Mervituximab program, ECOG status is 0 or 1. We typically have a similar distribution across all the studies, and we do not anticipate any difference from an efficacy or a tolerability perspective for either subset of patients.
spk11: Great. Thank you so much. That's very helpful.
spk04: Our next question, coming from the line of Kenan McKay with RBC Capital. Your line is open.
spk10: Hey, good morning, and thanks for taking the question. Just one on the Sariah filing plans. Is the data from Sariah sufficient for the Ventana full R1 companion diagnostic and accelerated approval of the diagnostic as well, or is there additional data from Mirasol or other trials in the future that's also needed or, again, just in a confirmatory sense? And then on the Mirova trial, Can you maybe talk about the rationale for that trial and that carboplatin plus MERV doublet and potentially what the next steps there could be? Thanks.
spk16: Sure. I'll take the CDX question, and then, Anna, you can talk about the IST with harder. So the answer is yes. The data from SREA are sufficient to support the approval of the of the companion diagnostics. I think as we've discussed previously on these calls, we're working with Ventana, which is Roche Tissue Diagnostics. They've actually submitted the PMA is in four modules. They've already submitted the first module. They have our clinical data, which is being integrated into the subsequent modules, and they will file in close proximity to our BLA submission, which would put them on track to have the CDX approved at the same time as the drug.
spk08: And for the Mirova study, this is a randomized Phase II investigator-sponsored trial in Germany led by Dr. Philip Harder. It's approximately 140 patients who will be randomized one-to-one to Mervituximab plus Carboplatin followed by Mervituximab continuation versus Carboplatin doublet of choice, followed by maintenance of choice. And the idea here is, you know, when you talk to physicians about Mervituximab, they want to be able to replace Paclitaxel with our drug because patients don't lose their hair, we have less neuropathy, and so this is the first opportunity for us to really combine Merv plus Carbo in a larger study for Dr. Harder to do so and compare it directly to standard carboplatin doublets, which include carbopaclitaxel, carbodoxyl, and carbogemcitabine. And so this study will help us get a better sense of the tolerability profile of the doublet because at this point our database is limited, but also the antitumor activity efficacy in the recurrent platinum-sensitive setting head-to-head against available therapies. So this data set from Mirova will help guide further development of mervituximab plus carboplatin as a doublet. I should point out that it is one of three prongs that we are taking to understand the potential of mervituximab plus carboplatin. The second prong is a neoadjuvant study, IST, here in the U.S., led out of Ohio State. and that study is in the neoadjuvant setting, the first time we can get Mervituximab in untreated patients up front with tumor tissue available at the time of their debulking surgery. And then the third is trial 420 that you heard about earlier, which is Mervituximab plus carboplatin in a broader population of FR-alpha positive tumors. So among those three data sets, we will then have sufficient data to support the registration path for the Mervituximab plus carboplatin doublet.
spk10: Got it. Thanks, Anna. Maybe just one follow-up. You'd mentioned that there's certainly some evidence and some publications out there to support the fact that patients with folate receptor positive disease or folate receptor high positive disease potentially have worse outcomes, is there any other data that the team is working on or that might become available that could be used to sort of further support that factor or be added to the SRIA accelerated approval submission? Or if not, what data set do you see as the most supportive for that? Thank you.
spk08: We do not need any data regarding FR-alpha as a prognostic factor to support our SREA study and our path toward accelerated approval. We know that FR-alpha is predictive of benefit from Mervituximab. We have a biomarker-identified population in SREA, FR-alpha high patients, who clearly benefit from Mervituximab with a near tripling of the response rate clinically meaningful duration of response, and very nice tolerability. And so FR-alpha is clearly predictive of benefit from Mervituximab. The one data set that we can point to now that is more robust in terms of answering this prognostic question, the one data set that we can point to really is the FORWARD-1 data set where we did the post hoc analysis looking at Merv versus chemotherapy because, again, you need this control arm, right, because that's where you're assessing how patients do with available therapies, where we inadvertently enrolled the low, medium, and high patients. And you can see with the higher the FR-alpha expression, the worse patients do with investigator-choice chemotherapy, be it response rate or progression-free survival. And I think, frankly, that's the only data set that we're going to have for a while, Kenan, because Now that we know, we're focused on the FR-alpha high patients, approximately 40% of all of the ovarian cancer patients who benefit the most from Mervituximab. Down the road, maybe with Mervituximab plus carboplatin when we demonstrate very nice activity across a broader spectrum of FR-alpha patients and we do a randomized trial there, maybe then we'll have a mix of patients where we can circle back on this question of it being a prognostic factor. But really, From a development perspective and for physicians to understand who benefits the best from Mervituximab, it's FR-alpha high patients, and that's what matters the most.
spk10: Got it. Thanks again, and looking forward to seeing you at SGO. Thanks.
spk04: Our next question coming from the line of Jessica Fai with J.P. Morgan. Your line is open.
spk07: Hey, guys. Good morning. Thanks for taking my question. I need one more specific one on SGO. Should we expect to see a swim plot, a spider plot, a waterfall at SGO? And also, will we see a PFS Kaplan-Meier curve or just the median PFS number?
spk08: Come to SGO, Jess. We will have visualizations of the data for you to understand the data.
spk07: OK. Great. And on the platinum-sensitive setting, can you talk about what you see at the bars, either for approval or for further development for the Phase III evaluating MervitexNAG plus Bev maintenance in the fluid receptor high platinum-sensitive setting, as well as for that Merv-Cargo combo? with mortuximab continuation in the kind of broader folate receptor alpha expressing population?
spk08: Sure. So in terms of the bar, we have designed Gloriosa, the randomized phase three study, to support full approval. The primary endpoint is progression-free survival. It's about 440 patients, and the hazard ratio we're aiming for is around 0.7. or that's what it's designed for. And so this study is designed in a robust manner to demonstrate superior efficacy for Mervituximab plus Bevacizumab versus Bevacizumab alone. In terms of the bar for Mervituximab plus carboplatin, that doublet, we would anticipate needing a randomized Phase III study for that doublet. So again, we would need an adequately powered randomized Phase III study with a control arm of standard available platinum-based doublets. That should answer your question, Jeff, because the strategies would be randomized trials. I think where the bar is less clear, to be honest, and the unmet need is increasing, is in the later line platinum-sensitive patients that we are studying in the PICOLO study. That's a population where I think the unmet need is increasing, and the bar there is not clear. We've already generated a handful of data going forward with the PICOLO study, and we look forward with engaging FDA on what the bar would be in that setting to support approval from a single-arm trial for an accelerated approval. Got it. Thank you.
spk04: And our next question coming from the lineup are today with HC win, right? Your line is open.
spk03: Hey, good morning, everyone. Thanks for taking my question. Most of our questions have been answered it. I just wonder, could you guys give us more color on the advantage for the kept toasting platform? And if possible, Could you guys give us more color on the partnership with Eli Lilly?
spk16: Sure. I mean, we covered most of what we have said publicly about this program. So, you know, our chemists were looking for an additional payload. We noted that Daiichi was enjoying with their camp decisions, and so the question was, as a medicinal chemistry exercise, could we design, uh, you know, a, you know, a, a better topo, uh, one inhibitor that, um, of the campathesin class, uh, that, you know, would expand the therapeutic index, uh, for the, for the payload, either by better tolerability, better efficacy, or both. Um, what we think we have is, is a molecule with at least equivalent efficacy with, um, with, um, Better tolerability, and we think potentially better bystander killing with this molecule. So, you know, that's the basis. And then I can't really comment on the financials of the deal beyond what's included in the press release that we issued last week or the week before.
spk03: Thank you for the addition of color, and congrats on the progress this quarter. Thank you.
spk04: Our next question coming from the line of Zoe Cantanzaro with Piper Sandler. Your line is open.
spk12: Hey, guys. Thanks so much for taking my question here. Maybe one just quick one from me. If I think back to Forward One, I think it took about 10 months or so from enrollment completion to readout. So just wondering why there will be a shorter window for Mirasol. I know it's not maybe – apples to apples, but maybe you could help us better understand that dynamic, whether it be enrollment kinetics, event rate, or other things, and if there's risk that the readout could be pushed beyond 3Q. Thanks.
spk08: You're spot on. Enrollment kinetics influence the timing of the readout. Progression-free survival is the primary endpoint. It's an event-driven study, right? So we will trigger the analysis for the primary endpoint when we reach the requisite number of events. And that is a function of both the enrollment as well as the timing of the events. The event rate in Mirasol is and should be similar to the event rate in ForwardOne. given that we're enrolling very similar populations. The enrollment rate in Mirasol has been different from Forward One. With Forward One, we had a very, very brisk enrollment the last three months. Like, it just shot up like crazy. So a whole bunch of patients were enrolled right at the very end. So we had to wait a good long time to get to the requisite number of progression-free survival events. Here, with Mirasol being a larger study and with the pandemic, you know, we don't anticipate that super-duper sharp tail in enrollment, like the curve right up. And so that accounts for the differences in the timing. And so we're on track for top-line data in Q3.
spk12: Okay, got it. That's really helpful. Thanks for taking my question. Sure.
spk04: Now, our next question coming from the line of Jonathan Chang with SVB Learing. Gilan is open.
spk01: Hi, guys. Thanks for taking my questions. A couple non-MIRV questions for me. First question, can you provide any color on your revenue guidance of $75 to $85 million? You noted that this doesn't include potential product sales from Mervituximab. So if you could provide any color as to what's reflected in this guidance, that'd be helpful. And then the second question is, can you provide any additional color on how the IMGC936 dose escalation is going and any additional granularity on when initial data could be disclosed this year? Thank you. Great. Susan?
spk06: Yes. So on the revenue guidance, we include our non-cash royalty revenues and the license and milestone fees to to an inclusive of the 75 to 85 million so we don't include the more product revenues because you don't have a producer date yet of course and so they're just the timing of potential revenues would make we have a factor in that so that that's that's what's inclusive in the revenue guidance and turning to IMGC 936 we are in dose escalation for this novel ADC with a novel atom 9 directed antibody
spk08: and the first DM21 linker payload. So we are in dose escalation, and we look forward to presenting data later this year once we've identified the recommended Phase II dose and schedule, and then we'll be able to also share plans for further development in ADAM9-positive tumors.
spk01: Got it. Thank you.
spk04: And that's all the time we have for our Q&A session. I would now like to turn the call back over to Mr. Mark Ennity for any closing remarks.
spk16: Great. Thanks, everybody, for joining us today. We're excited about the year ahead. We have a number of important events upcoming, starting with SGO in a couple of weeks, and we look forward to talking to all of you then. So thanks very much, and we'll keep you updated on our progress.
spk04: Ladies and gentlemen, that was the conference for today. Thank you for your participation. You may now disconnect.
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