Afternoon, it's Michael Schmidt, Senior Biotech Analyst with Guggenheim. It is my great pleasure to welcome the ImmunoGen team. With us today we have Anna Berkenblit, the Chief Medical Officer. Anna, welcome, and thanks for joining us. Thanks, Michael. All right, Anna. I think given that most people presumably are very familiar with the ImmunoGen story at this point, we will jump right into questions. Starting out with talk about the ELAHERE commercial launch. I know Mark spoke about it recently publicly as well, but maybe just remind us of, you know, what your experience has been so far with the early launch of ELAHERE and how the product has been tracking relative to your expectations. Yeah, sure. What I would say is that out of the gate, the launch has exceeded our expectations. You may recall that ELAHERE was approved ahead of its PDUFA date in middle of November last year. We saw a very brisk uptake in terms of testing for folate receptor alpha with 1,500 tests performed by the end of 2022. With that, the first patient who received commercial ELAHERE was on December 1st. By the end of the year, we had sold $2.6 million, $2.4 million of which was in December. I would say off to a very, very strong start. What I can tell you now is that we're seeing repeat customers, so folks who are buying more ELAHERE, and that's presumably so that their patients can continue on the drug, as well as new starts. We are also seeing a very nice mix between community setting and academic setting. We were actually pleasantly surprised that about 70% of patients, 70% of orders were from community sites, 30% from academic, and that 75% of orders initially were from non-ELAHERE experienced physicians. That means the word has really gotten out. Well, that's great to hear. I know there's been some debate over, you know, drug launches in general that require biomarker testing. It sounds like, you know, that has been going well so far, but maybe just remind us of, you know, how you're implementing the folate alpha testing paradigm into the ovarian cancer, you know, physician practices, so to speak. Right. Over the past bunch of years now, physicians, both medical oncologists and gynecologic oncologists, have become used to testing ovarian tumor tissue for biomarkers including BRCA, which can be tested somatically, as well as HRD. Adding another test, you know, checking another box is easier in terms of physician adoption as opposed to really suddenly changing the paradigm. It's been a very small shift in their behavior. You may recall that the CDx has been developed by VENTANA Roche, and so you know, they are a leader in the field. It's a simple immunohistochemistry test. You know, to ensure we would have a successful launch, there were four labs, four centralized labs up and running at the time of launch. Now, we are seeing more and more requests from sites that have the BenchMark ULTRA machine to add the FOLR1 test to their panel. So we are really quite excited about it. Okay. What% of the market is initially targeted by a commercial infrastructure, be it commercial sales team, and, you know, how could that evolve over the rest of the year? Yeah. It's a relatively concentrated market with about 4,300 physicians in the U.S. taking care of over 80% of ovarian cancer patients. When you drill down a little bit further, there are 400 physicians we include in tier one who take care of about a third of ovarian cancer patients. We have been able to really cover our bases with about 44 sales reps. We also have, I would say a small but mighty medical affairs team, that have really been able to reach the majority of the tier one, if not all of them at this point. Okay. The drug, the ADC did get into NCCN guidelines pretty quickly out of the gate. Can you talk a bit about, you know, how important that has been or will be for the continued launch? Also, are you seeing it being used in combination with Avastin? Yeah. Just as a reminder, the SORAYA study that led to accelerated approval was limited to patients with prior Avastin. Yet, based on FDA's review of the ongoing confirmatory MIRASOL study, we got a broad label for platinum-resistant disease regardless of prior Avastin use. The NCCN compendia listing came out rather rapidly after we got our initial approval with a category two A listing for mirvetuximab monotherapy in platinum-resistant disease. I would note that it is not specific regarding number of lines of therapies or histologies. We also got concurrently a category two B listing for mirvetuximab plus Avastin for platinum-resistant ovarian cancer. That's based on data that we presented at IGCS in September in New York and is just out now in the Gynecologic Oncology Journal. What is really nice about the MIRV plus Avastin combination is that the NCCN listing is based on those data that were in patients with at least low levels of FRα expression, so low, medium, and high. So that's potentially appropriate for up to 80% of ovarian cancer patients, whereas the MIRV monotherapy indication is really appropriate for FRα high patients, which are about 35%-40% of the population. We are quite excited about it. We know just, you know, from our medical affairs colleagues engaging physicians, that physicians who use Avastin are using mirvetuximab plus Avastin, and that does lead to a very nice duration of response and long PFS. I know the test is not a we talked about it yesterday. I think the test is not a binary readout. Yeah. Physicians actually know the, you know, the degree of- Yeah overexpression. Do you see mirvetuximab or ELAHERE use in low or medium expressing patients as well? Certainly with the MIRV Avastin combination that's supported by the NCCN compendia listing, I think, you know, physicians have some discretion, because, high is defined as at least 75% of cells, at least 2+ positive. You know, if the readout is negative and yet 70% of the cells are 2+ positive, you know, physicians certainly understand that there's a potential for mirvetuximab to benefit their patients there. Right. The December sales obviously impressive, out of the gate. You know, it'd be interesting to see how the launch trajectory evolves, throughout this year. You know, can you comment if there is been any, you know, patient warehousing or if there are any, you know, channel stocking dynamics as we think about sort of the next few months? The answer to both of those questions is no. Platinum and platinum-resistant ovarian cancer patients are not patients who can wait. You know, while certainly physicians are testing e-frontline patients, so some of the FRα positive tests that we're seeing are in frontline patients who are not yet ready for ELAHERE. Patients with platinum-resistant disease, you know, they cannot wait around. We are not seeing this warehouse of patients who suddenly are getting on drug and then it'll peter off. I don't think that's gonna happen. I think actually the converse of that is gonna happen. And then in terms of shipment, we use a drop ship model so you know, when they need drug, they order it, and they get it. I would say that, you know, what we are seeing, not surprisingly, is although the majority of orders are coming from the community, the academic sites, have larger orders just 'cause they're treating larger numbers of patients. What I can tell you now with more conviction than Mark shared at JP Morgan is we are seeing repeat orders and that tells me that patients are continuing on drug and they're starting additional patients on therapy. Well, great. Well, thanks. Maybe switching to some of the label expansion, opportunities and other ongoing trials, maybe starting with MIRASOL, which is obviously the confirmatory phase 3 in similar perhaps slightly earlier stage patients than the SORAYA study that supported FDA approval. So you know, I think you guided to reporting the data early this year. Just remind us perhaps how inventories are tracking relative to your expectations and whether we are still on track to see the data. Yeah. Sure. The primary endpoint for MIRASOL is progression-free survival, by investigator. It's an event-driven study. We had initially guided that we thought we would reach the requisite 330 PFS events before the end of December. At JP Morgan, we shared that that's bled into 2023. That being said, we are still on track for top-line data early this year. Great. You know, assuming success or, if the study is successful, you know, to what degree, you know, might that provide an additional, you know, an additional tool to commercialize the drug or, you know, will it drive additional demand, I suppose, given that it's a randomized study? And you know, secondly, you know, will we perhaps see overall survival as well in addition to PFS, which is the primary endpoint of the study? We already have a broad label for ELAHERE in the U.S. that is consistent with the MIRASOL population. That's double the population than would have been if we were niched into the SORAYA post Avastin population.So I think the full approval in the U.S. is gonna do a few things for us. While it's not gonna broaden the label, it will secure a full approval for us, and it will make us the new standard of available therapy for folate receptor alpha positive tumors. I think the other folks who are behind us developing FRα-targeted therapies, they would need to beat us. I think that's gonna be interesting to see how that plays out. I think importantly, what Mirasol will give us is approval in Europe, and so we're really prioritizing the MAA, and we anticipate getting approval in Europe, latter half of 2024, again, assuming Mirasol reads out positively. To your point, given that there is nothing else out there for platinum-resistant ovarian cancer, while there may be some physicians who are holding out for randomized data, I think, you know, just consistent with the brisk uptake it from launch that we are seeing, physicians are clamoring for something. They haven't had anything new to talk about or to offer their platinum-resistant ovarian cancer patients since Avastin in 2014. The unmet need is quite high. Right. As we think about, you know, we've obviously seen a lot of data for ELAHERE in prior clinical trials. The chemotherapy mix that is sort of has been used in the past in platinum-resistant ovarian cancer has been pretty consistent in terms of performance, have there been any changes, I guess in your opinion in recent time that could have- Yeah ... affected the sort of the performance of the chemotherapy arm? Right. There's nothing been approved in the platinum-resistant space, since again, since 2014. That being said, since we completed FORWARD I, there's been more data that has come out with for Doxil, in combination with carboplatin and Avastin in the recurrent platinum-sensitive setting. So previously the only two, and still the only two approved triplet regimens for recurrent platinum-sensitive disease are carbogem Avastin and carbotaxol Avastin. Now more recently, a phase 3 study came out showing that carbodoxil Avastin is another good regimen, and Doxil is often preferred by patients. If there are physicians who are using Doxil more now in the recurrent platinum-sensitive setting, either as a doublet with carbo or as a triplet with Avastin, they may not be able to use it again in the platinum-resistant setting because there's a risk of cumulative cardiotoxicity. There may be a little bit of shifting in terms of the distribution of the 3 chemos, Taxol, Doxil, and topotecan. I would describe MIRASOL as still having a healthy mix, and we stratify for choice of chemotherapy. Got it. All right. Great. Looking forward to the data, soon- Yes ... I I suppose. And then you know, as we think about, you know, a number of label expansion opportunities that you're pursuing, in combinations as well as monotherapy, you know, can you talk about perhaps sort of the magnitude of the opportunity beyond monotherapy? Which are the biggest label expansion opportunities? Maybe just highlight so some of the trials that are underway. Sure. Let me build through them. I will start so with monotherapy, though, for mirvetuximab in later-line platinum-sensitive disease. This is a growing population of patients who, that because the PARP inhibitors, I would say, artificially extend their platinum-free interval, there are patients who have more later-line platinum-sensitive disease who may not be as sensitive to platinum as they used to be and need better options. The PICCOLO study of MIRV monotherapy can really potentially help these patients. We should have ORR data before the end of the year. DOR data, probably not because patients do well that have recurrent platinum-sensitive disease. That could support compendia listing and potentially label expansion. We would need to align with FDA on what the benchmark would be to beat there if we did a single-arm study, or we could do a randomized study. Moving to combinations. We're most excited about our MIRV Avastin combination data in the treatment setting. We've levered that by bringing it into the recurrent platinum sensitive setting, for patients who are getting a triplet of carbo, whatever, Avastin, as long as they haven't progressed. In the GLORIOSA study, they are randomized to either MIRV plus Avastin or continuation of Avastin. I think this has a chance to really be practice-changing because I think given how strong the benefit for MIRV plus Avastin is, I wouldn't be surprised if we had not just a PFS benefit, but an OS benefit, and that could increase the usage in that setting and drive the population. And lastly, mirvetuximab plus carboplatin, which is arguably quite a valuable combination to go up front. We're gathering data in 3 trials to really understand the benefit of MIRV plus carbo. The Study-420, which is our sponsored trial, that's up and running now for low, medium, and high FRα-expressing patients, so approximately 80% of ovarian cancer patients. We're supporting 2 ISTs, a neoadjuvant study and a randomized Phase II of MIRV carbo in the recurrent platinum-sensitive setting. Maybe just following up on the GLORIOSA study, which is, you know, the first randomized, the next randomized study to sort of kick off. How should we think about the magnitude of that opportunity and perhaps when you consider sort of the treatment duration that you could see there? Right. If you look at the numbers, of patients who get a triplet in the recurrent platinum-sensitive setting, it is not a huge number to be perfectly, you know, blunt. However, the long treatment duration in the maintenance setting is really quite appealing. Like I said, I personally think that study has a high probability of technical success, not just for PFS, but OS, in which case that could, again, be landscape changing, if you will. Right. For PICCOLO, that's the study in sort of late-line platinum-sensitive patients. You know, what have you seen so far in terms of data in that setting? I guess, what is your expectation for, you know, response rate? You said the bar, the regulatory bar is sort of an FDA discussion, I mean, how should we think about sort of the magnitude of benefit in that context? When we say later-line platinum-sensitive disease, we mean patients who've had at least 2 prior lines of therapy. You know, it's hard to benchmark that. Patients with 1 prior line of therapy, when they get another platinum-based doublet, you know, the response rate is in the mid-50s. There's 1 study, the CALYPSO study, that shows a response rate for patients with 2 prior lines that's in the 40s. You know, my expectation would be with available therapies, the response rate would be probably in the 30s in this later line setting. You know, we certainly had very nice, I would call it anecdotal data from a couple handfuls of patients in phase I for mirvetuximab in this population that spawned the PICCOLO study. Again, that's why, we're looking forward to sharing ORR data before the end of the year. Okay To guide further decision-making. Okay. Great. Looking forward to that. Then maybe switching gears over to pivekimab, which is your CD123 ADC in a hematology setting. We have seen some data recently, again, at ASH in AML, and I know you've been running a number of Phase I and II studies to sort of, you know, support next development steps. Maybe just remind us where you are with the AML program and, you know, what your latest thinking is in terms of possible registration opportunities. Yeah. Sure. Let me start, though, with BPDCN because CD123 is a validated target in BPDCN based on the ELZONRIS approval. ELZONRIS is active but quite challenging for patients. And so, you know, our drug is a short IV outpatient infusion once every three weeks. You don't need to be hospitalized like you do with ELZONRIS. We don't have potentially fatal capillary leak syndrome. You know, FDA really guided us after we received Breakthrough Therapy designation for BPDCN in the relapse setting toward a frontline pivotal study. And we shared data in August last year showing very nice initial data for that frontline pivotal cohort that's led us in consultation with FDA to really focus on the de novo patients. Now that that data are out there, investigators are quite excited about it. And that could be our first approval. Again, we could get first full approval, rather, based on a 20-patient frontline cohort. That's our fast-to-market strategy. Really the ultimate value is in AML, which is where you started. We shared data at ASH. It was our fourth oral presentation in a row yearly at ASH, showing that we can combine safely with venetoclax and azacitidine in the relapsed AML setting and in the frontline setting. Admittedly, we are behind magrolimab. Magrolimab is also one of the few drugs that can combine safely with ven/aza, and they are ahead of us. What I would say is neither triplet overcomes resistance to ven/aza. You know, at this point, we have a two-pronged approach. We are continuing to gather data in the frontline setting to figure out the optimal dosing of venetoclax as a triplet with PVEK and azacitidine. You know, we will have enough data from a safety and an efficacy perspective to decide whether or not it makes sense to launch into randomized phase III trial in the frontline setting head-to-head against ven/aza. We also announced, around the time of ASH, collaboration with Gilead to combine PVEK with magrolimab. There are some preclinical data supporting targeting CD123 and CD47. It just makes sense also from a clinical development strategy perspective because regardless if you have relapsed AML, if you had frontline intensive therapy and you relapse, or if you had ven/aza and you relapse, you're going to need something else. Two novel non-cross resistant agents are exciting. You know, while we're starting with magrolimab, from a proof of concept perspective, there are certainly other CD47s that are out there, that we could consider working with down the road. We have options. In order to, you know, and launch a Phase III in first-line AML, just, you know, I guess what type of data would you wanna see that gives you confidence that it's truly superior? Yeah. So you know, at the end of the day, OS is really what matters. event-free survival is important. you know, what we are thinking about is when we look at an expansion cohort for our triplet, it's not just about CR rate, I think it's also gonna be about the depth of CR. I think if we can show really nice MRD negativity, that should translate into prolonged better outcomes for patients, potentially overall survival. I think CR rate and MRD negativity are gonna be the things that will factor into our decision-making. All right. looking forward to that, presumably at ASH on these types- Yeah. Yeah. Then, you know, ADAM9, ADCs, IMGC936 is one where, we'll get some data soon from the phase I study as well. Maybe just remind us of, you know, how that target, perhaps is positioned relative to some other solid tumor targets out there where ADCs are being developed against, and also what we should expect to see in the phase I. Sure. MacroGenics came to us with the target, and the antibody. ADAM9 is highly expressed on a variety of solid tumors. It is not particularly expressed on normal tissue, and it internalizes well. So those are all necessary components for a good ADC target. We brought our linker payload technology know-how to it, to create the construct IMGC936. That has been in dose escalation in all the tumor types that we know express ADAM9. We have a lot of in vitro and in vivo xenograft, and PDX models really showing nice activity for the drug, kind of regardless of ADAM9 expression. We may not even need a companion diagnostic for cutoff, but we're certainly doing all the spade work so that if we do need a CDX, we'll have the data to support it. All of the patients are sending in tumor tissue, and we're assessing ADAM9 levels retrospectively. You know, the cohort of dose escalation patients was heavily weighted toward colorectal cancer, which we don't think is really gonna respond to a tubulin-directed payload like we have, and also pancreatic cancer. So what we did once we got a recommended Phase II dosing schedule is we went seamlessly right into some expansion cohorts in triple-negative breast cancer and lung cancer 'cause that's where we really expect to see a signal first. They are enrolling now and, you know, we've recently updated our guidance that we should have initial data from those expansion cohorts in Q2. Great. Last but not least, you know, you have obviously IMGN151 now in the clinic as well. Yes. Which is your next gen, folate receptor alpha ADC. Yep. You know, again, just help us think through how that might be positioned relative to ELAHERE longer term. Yeah. Our chemists and biologists really were looking at mirvetuximab and saw, you know, it's wonderful for for tumors that have high levels of FRα expression. What they've done with IMGN151 is really innovated on each of the 3 components of the ADC. Number 1, the antibody itself binds 2 separate epitopes on folate receptor alpha, twice as many binding events, twice as much internalization, twice as much cell killing. Excuse me. The linker is a little more stable in circulation than the linker in mirvetuximab, and that could lead potentially to longer half-life, and again, you know, better activity. The payload is our next generation maytansinoid payload, a little more potent, a little more hydrophobic than the DM4 payload in ELAHERE. We've shown more bystander killing activity, which is important when there Is heterogeneity of FRα expression. It's really designed to address a broader population of FRα tumors. What we've shown pre-clinically is we have similar activity at lower levels of exposure for IMGN151 in these high FRα models where ELAHERE works. 151 has activity in models with lower levels of expression where mirvetuximab really probably isn't the best option. We are really excited about the potential for 151. We're exploring it in dose escalation right now in ovarian and endometrial cancer 'cause that's where we expect to see the signal the fastest. Once we have proof of concept there, and are, you know, proceeding with a fast to approval strategy, we'll expand into other tumor types, triple negative breast, lung cancer, maybe even cervical cancer. Great. Well, thank you, Anna. With that, I think it's time to wrap up. I really appreciate it. Great. Thanks, Michael.