Good morning, and welcome to the ImmunoGen's SORAYA Top- Line Data Conference Call. Today's conference is being recorded. At this time, I'd like to turn the call over to Courtney O'Konek, Senior Director of Corporate Communications and Investor Relations. Please go ahead. Thanks, Courtney. Good morning, and thank you for joining. Today, we issued a press release that includes a summary of the top-line results from our pivotal SORAYA trial of mirvetuximab soravtansine in ovarian cancer. This press release and a recording of this call can be found under the Investors and Media section of our website at immunogen.com. With me today are Mark Enyedy, our President and CEO, Anna Berkenblit, our Chief Medical Officer, and our co-principal investigators, Robert Coleman, Chief Scientific Officer of US Oncology Research, and Dr. Ursula Matulonis, Chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute and Professor of Medicine at the Harvard Medical School. Susan Altschuller, our Chief Financial Officer, and Kristen Harrington-Smith, our Chief Commercial Officer, will also join us for Q&A. During the discussion, we will use forward-looking statements with respect to our business strategy, the development and benefits of our product candidates, the presentation of clinical data for our product candidates, the anticipated timing of regulatory submissions to the FDA for certain product candidates, and the anticipated commercial launch for certain product candidates. 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 issued this morning and in the Risk Factors section of our most recent annual report on Form 10-K and our other SEC filings available at sec.gov and on our website at immunogen.com. These forward-looking statements in this presentation speak only as of the original date of this presentation, and we undertake no obligation to update or revise any of these statements. With that, I'll turn it over to Mark. Thanks, Courtney. Good morning, everyone, and thank you for joining us. My comments to start will be brief so that Anna can get to the details of the SORAYA data. Today marks an important milestone in advancing the treatment of platinum-resistant ovarian cancer and is the culmination of many years of work at ImmunoGen dedicated to delivering the next generation of ADCs to improve outcomes for patients living with cancer. Our highest priority as an organization has been the development of mirvetuximab in ovarian cancer. The results from SORAYA are highly encouraging and represent a significant step forward in providing additional therapies to patients with folate receptor alpha-positive platinum-resistant disease. With a confirmed objective response rate of 32.4%, we have resoundingly met the primary endpoint of SORAYA. Together with a tolerability profile consistent with our experience in the more than 700 patients we've treated in our broader program, we believe the significant and durable responses reported in this trial demonstrate that mirvetuximab delivers clinically meaningful benefit to patients in the platinum-resistant setting. With these data in hand, we look forward to submitting the BLA for mirvetuximab next quarter and to an anticipated approval next year. With that, I'll turn the call over to Anna to review the top-line data. Anna? Thanks, Mark. We are extremely pleased with the results from SORAYA and are deeply thankful to the patients, investigators, and colleagues whose efforts brought us to today. Recall that SORAYA is a single-arm study of mirvetuximab in patients with platinum-resistant ovarian cancer, whose tumors express high- levels of folate receptor alpha and who have been treated with up to three prior lines of therapy, at least one of which must have included prior bevacizumab. The primary endpoint is confirmed objective response rate or ORR, as assessed by the investigator. ORR, as assessed by blinded independent central review, is a sensitivity analysis. Duration of response or DOR is a key secondary endpoint. As a reminder, this population has high unmet need. Despite advances in the platinum-sensitive setting, most patients with ovarian cancer eventually develop platinum-resistant disease, which is difficult to treat. In this setting, standard of care single-agent chemotherapies have low response rates, short durations of response, and are associated with significant toxicities. For purposes of the primary endpoint in SORAYA, we aligned with FDA that the benchmark for best available therapies would be the objective response rate demonstrated in the single-agent chemotherapy control arm of the AURELIA study in patients with platinum-resistant disease with just 1-2 prior lines of therapy. I'll note that less than 10% of patients in AURELIA had prior anti-angiogenic exposure, including prior bevacizumab. In that population, the objective response rate by investigator was 12%. Accordingly, we designed SORAYA to exclude 12% at the lower bound of the confidence interval for the primary endpoint ORR. The SORAYA study enrolled 106 patients with a median age of 62- years, including 51% of patients with 3 prior lines of therapy and 48% with 1-2 prior lines of therapy. All patients received prior bevacizumab, and 48% received a prior PARP inhibitor. The primary endpoint of confirmed objective response rate as assessed by investigator was 32.4%, with 5 complete responses noted. The lower bound of the 95% confidence interval was 23.6%, well above the 12% benchmark the study was designed to exclude. The sensitivity analysis by blinded independent central review was highly concordant with the investigator assessment, with an ORR of 31.6%. Five complete responses were also reported by blinded independent review. As of the data cutoff on November 16, 2021, the median follow-up time was 8.1 months. The median duration of response is currently 5.9 months, with a 95% confidence interval of 5.6-7.7 months. With nearly half of the responders still receiving mirvetuximab at the time of the data cutoff, the duration of response continues to evolve. With longer follow-up, median DOR could range from 5.7 to just above 7 months. We believe these data are quite remarkable, considering that over half of the patients were fourth line, all patients received prior bevacizumab, and almost half received a prior PARP inhibitor. Yet the overall response rate of 32.4% nearly tripled to 12% ORR in AURELIA, where patients had just 1-2 prior lines of therapy and were essentially bevacizumab. Similarly, the median duration of response in SORAYA was 5.9 months. That surpassed that demonstrated by single-agent chemotherapy in the control arm of not just AURELIA back from 2014, which was 5.4 months, but also the larger, more recently published randomized CORAL study. The population in CORAL is a bit more relevant, with a quarter of patients having received 3 prior lines of therapy and nearly half previously treated with bevacizumab, but less than 5% having received a prior PARP inhibitor. In the CORAL study, the chemotherapy control arm had a median duration of response of just 3.7 months, both by investigator and blinded independent review. This emphasizes how meaningful the clinical benefit observed in SORAYA is, both in terms of ORR and DOR, given poor outcomes with single-agent chemotherapy in this population. Turning to safety results from SORAYA, the tolerability is favorable and consistent with the known safety profile of mirvetuximab, which has been studied in over 700 patients. Mirvetuximab has a differentiated safety profile characterized by low-grade gastrointestinal and ocular events, which are able to be medically managed or mitigated, as evidenced by the low 7% discontinuation rate due to treatment-related adverse events, along with dose delays in 32% and dose reductions in 19% of patients. As in prior studies, the most common treatment-related adverse events were mostly low-grade ocular and gastrointestinal events, including blurred vision, 41% all grade, 6% grade three, keratopathy, 35% all grade, 9% grade three plus, and nausea, 29% all grade, with no grade three or higher nausea. Only one patient discontinued mirvetuximab for an ocular adverse event. With improved management guidelines for gastrointestinal adverse events, gastrointestinal events were observed less frequently in SORAYA than in prior mirvetuximab studies. I'd now like to ask Dr. Robert Coleman, Chief Scientific Officer of US Oncology Research, and co-principal investigator of SORAYA, to expand a bit on the unmet need in platinum-resistant ovarian cancer and how mirvetuximab might meet that need. Yes. Thanks so much, Anna. You know, platinum-resistant ovarian cancer is a tough disease to treat, and it's frustrating for both clinicians and patients alike. You know, the last approval in this setting was over seven years ago when bevacizumab was added to chemotherapy in 2014, despite multiple phase III attempts since and actually before then. While testing for biomarkers like BRCA and homologous recombination deficiency, along with the introduction of targeted therapy such as PARP inhibitors, these have improved outcomes for patients in the front line in the platinum-sensitive setting. We have no biomarkers or targeted therapies that have been successfully developed to advance care for patients with platinum-resistant disease. This is where folate receptor alpha and mirvetuximab play an important role, in particular, as demonstrated by the ORR and DOR in this study in SORAYA, high folate receptor alpha appears to predict clinically meaningful benefit from mirvetuximab in patients with platinum-resistant disease. Given these outcomes, I can't tell you how excited I am about the prospect of mirvetuximab redefining the standard of care in ovarian cancer. Thanks, Rob. Now I'd like to turn it over to your co-principal investigator on SORAYA, Dr. Ursula Matulonis, Chief of the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute and Professor of Medicine at the Harvard Medical School, to comment on her experience with mirvetuximab thus far and the data from SORAYA. Anna, thank you. These data have the potential to be transformative for ovarian cancer patients and their physicians. In the platinum-resistant setting, and particularly in later line-treated patients, response rates with available therapy are in the single- digit, also with significant toxicities. To see an overall response rate above 30% with a median duration of response of around 6- months, with nearly half of the responders still on mirvetuximab, is extremely exciting. Throughout the development of mirvetuximab, we've treated 85 patients at the Dana-Farber/Harvard Cancer Center, and I've been impressed not just with the anti-cancer activity of this drug, but also the favorable tolerability profile. I'm looking forward to the continued development of mirvetuximab, including the completion of the ongoing randomized MIRASOL trial and the initiation of additional trials of mirvetuximab in combination. Thanks, Ursula. With these impressive results, we are now focused on incorporating SORAYA data into the BLA and are on track to submit the BLA in Q1 of next year. If granted accelerated approval by FDA, we expect mirvetuximab's initial indication would cover second- through fourth-line patients with folate receptor alpha positive platinum-resistant ovarian cancer who have been previously treated with bevacizumab. Beyond SORAYA, we look forward to generating top-line data from our confirmatory MIRASOL trial in Q3 of 2020 to support the potential full approval of mirvetuximab monotherapy. We are also enrolling PICCOLO, the single-arm study of mirvetuximab monotherapy that could expand its reach to the growing number of patients with recurrent platinum-sensitive ovarian cancer. As we seek to move mirvetuximab into earlier lines of treatment and become the combination agent of choice in ovarian cancer, we are finalizing our formal label expansion strategy for mirvetuximab in combination doublets with bevacizumab and carboplatin in both platinum-resistant and platinum-sensitive disease and plan to provide more details in early 2022. With that, I'll turn the call back over to Mark to discuss the ovarian cancer landscape and commercial plans. Thanks, Anna. Each year in the U.S., roughly 21,000 people are diagnosed with ovarian cancer, and 14,000 will die from the disease. With a 49% five-year survival rate, ovarian cancer is one of the deadliest cancers impacting patients today. Approximately 40% of ovarian tumors express high- levels of folate receptor alpha. As you've just heard, the vast majority of ovarian cancer patients relapse and develop resistance to platinum-based chemotherapy, with limited treatment options characterized by low response rates and significant toxicities. Against this discouraging landscape, the results of SORAYA mark an important advance for patients with platinum-resistant ovarian cancer, and the consistency of the data across the entire mirvetuximab program gives us further confidence in our ongoing confirmatory MIRASOL trial. Commercially, we estimate that the initial label covered by SORAYA and MIRASOL will encompass roughly 4,200 patients annually, in the U.S., with a slightly larger market in Europe. We began preparing for the potential commercial launch of mirvetuximab earlier this year. With the recent hiring of our chief commercial officer, Kristen Harrington-Smith, we are focused on building an experienced and high-performing commercial organization and establishing enterprise-wide processes and infrastructure to ensure day-one readiness for the anticipated launch of mirvetuximab and the folate receptor alpha companion diagnostic that's being developed by Ventana. In addition, within medical affairs, we continue to advance our education and awareness efforts on the unmet need in platinum-resistant disease and the promise of folate receptor alpha as a novel biomarker in ovarian cancer. The treater base is relatively concentrated, and we are engaging with gynecologic oncologists, medical oncologists, pathologists, and patient advocacy groups as we move forward towards approval. We'll have more to say about our launch plans in coming months. In closing, I'd like to express our deep appreciation to the patients, families, caregivers, and investigators for their commitment to this trial. These results represent years of hard work from the entire ImmunoGen team who are committed to bringing mirvetuximab to patients as quickly as possible. We are dedicated to our mission of delivering more good days to people living with cancer. Before we open the line for questions, I'd like to remind everyone that while we've disclosed the key top-line results for SORAYA, including the primary endpoint, we cannot discuss the full results of the study today in order to preserve the opportunity to present the data at an upcoming medical meeting. You may have questions we are unable to answer, but we'll do our best to provide as much clarity as possible. With that, we're happy to take questions from our covering analysts with the help from Doctors Matulonis and Coleman. Operator? Thank you. To ask a question, you'll need to press star one on your telephone. To withdraw your question, press the pound key. Our first question comes from John Newman with Canaccord. Your line is open. Hi, guys. Good morning and, congrats on a really excellent data set here. I know a lot of people. Thanks, John. We're really pleased. I know you guys have been working hard for a long time on this. Just a few questions. Question number one, any sense as to when you would have the final data cut regarding the durability? Question number two, trying to recall if this study will follow patients longer term for PFS. If I could hear from the investigators, just curious if you could try to put this data in the context of the currently available treatments that you have for these types of patients that walk into the clinic today. Thanks. Great. I'm gonna turn that over to the doctors, starting with Dr. Berkenblit. Great. Thanks. I'll address your first two questions and then turn it over to Dr. Coleman and Dr. Matulonis to address your third question. Regarding duration of response, as you heard, nearly half of the responders are still on mirvetuximab at this point. We anticipate that we will have updated duration of response data at a major medical meeting Q1 next year. Turning to your second question, progression-free survival is a secondary endpoint of this study, as is overall survival, and we are following patients for both of those endpoints and again anticipate presenting those data at some major medical meeting next year. Turning to your third question regarding putting our data into context, I'd first like Dr. Coleman to comment and then Dr. Matulonis. Yeah, thanks, Anna, thanks for the question. I'd love to be able to have the opportunity to speak a lot about this topic because this is a very frustrating space for us, as I mentioned in my statement. Our available therapies, as was this trial was designed against, is what we would see typically in our clinics today. That's what patients have seen prior, for the most part in biomarker-annotated patients and for those that are not, and those that have with the use of bevacizumab. This trial was designed to be a real-world experiment of using a novel therapy in a patient population that is exposed to our best available therapies already. I feel very confident about where this lies. Our options in this setting are limited. In the rare patients that haven't received bevacizumab before, we have the options, if they fall within the label, to use bevacizumab in an earlier line of therapy. Other than that, we are looking at single-agent chemotherapy. It's just as we saw in this trial and just as what has been reported in multiple other trials that have tried to go into this space. We know what those response rates are. The excitement you're hearing from us, Ursula and myself, is that unmet need that we feel we have attained. Ursula, any- Yeah, Rob, thanks so much. Thoughts? I truly concur. I mean, I think in answer to the question, and as Rob has mentioned, the available therapies are single-agent non-platinum chemotherapy. You know, topotecan, and most patients will have received agents such as weekly Taxol, pegylated liposomal doxorubicin with bev. In the post-bev setting, platinum resistance setting, you know, we've got single-agent treatment, and these response rates are truly below 10%. Yeah. I think the other important fact is that if patients have responses which are very, very infrequent, they just last for a few weeks. Patients will get stable disease really just for a few weeks and then progress. They have significant toxicities as well because they've already been so heavily pretreated. Mm-hmm. These data are truly spectacular and I think, and I said in the press release, have the potential to be transformative for our patients and really represents an outstanding option for those patients who have folate receptor alpha-positive cancers. Great. Thank you. Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open. Hey, guys. Good morning, and congrats on the data from you as well. It's very nice to see the results essentially coming in consistent with your pooled analysis that was done previously post hoc. So it's nice to see that being very consistent. Just a quick question. I know you got it to BLA filing early next year. Could you just remind us of your plans for potentially you know including this and other data that you have in NCCN guidelines and what your plans were for that and for the physicians I guess should a comprehensive data set be included in guidelines later on? I guess how would the drug be used in clinical practice? Sure, Michael. One, thanks very much for the comments. We're really pleased again with the consistency of the data across the program as a whole. You know, obviously, going into FDA Q1, and then with the benefit of approval, we would approach the compendia to support the integration of these data into the treatment guidelines. Of course, we have a wealth of additional data for mirvetuximab, including the combination data we've previously published on, in particular with the bevacizumab and also the broader triplet cohort. First approach I think would be the bevacizumab combination data. You'll recall that study was in what we call the platinum-agnostic population. There were a group of patients who were platinum sensitive who were enrolled in that study, as well as a group of patients that had platinum-resistant disease. You may recall that the overall response rate in those patients was 64%, which is of course well above what one would expect in that setting. Our goal would be to have those data also integrated into the treatment guidelines. As you know, with the compendia listing, that could support reimbursement for both monotherapy mirvetuximab as well as these combinations. I think that was the gist of the question. Happy to go into more detail if you have a further question. Yes. Thanks. Maybe for the physicians, I guess, how would you use the drug in clinical practice relative to other options? Yeah. I'll ask Ursula Matulonis first to comment and then Robert Coleman. Yeah. I think, you know, we're gonna use the drug based upon how the trial's been designed, and that's for patients who have platinum-resistant ovarian cancer, who've received prior bevacizumab, and their cancers express folate receptor alpha. I mean, I think it's. I mean, the data is clear here, with you know a very impressive response rate and duration of response. I think speak for Rob on this, that both of us are very excited to use this drug in clinical practice. Great. Thank you. Yeah, I think what I would add to it is that, you know, our paradigm, we approach patients with the diagnosis is gonna change, 'cause now, just as we did with, you know, with PARP and the realization of a predictive biomarker associated with that drug, we'll do the same here. We have a predictive biomarker for this drug, and we will now incorporate it into our standard assessment as patients, you know, predominantly in this recurrent setting. But as this platform continues to grow, this will become a broader part of our portfolio and, you know, the availability of drug will, like I say, redefine how we approach platinum-resistant disease and hopefully move it into different settings. Thank you. Thank you. Our next question comes from Boris Peaker with Cowen. Your line is open. Good morning, and let me add my congratulations on the excellent data. My next question is, and maybe I think this is to the physicians, I wanna understand from the practical perspective, how do you see the prophylaxis working in the medical setting in terms of managing the vision tox or any other toxicities? Ursula. Yeah. I'll ask Ursula Matulonis to comment on that, given your experience with mirvetuximab throughout the program. Yeah, no, it's a great question. Certainly, you know, the ocular toxicity is an ADC toxicity, so it's associated with this type of a medication. You know, I've been working with this drug for many years now and, you know, we have a set group of ophthalmologists whom we refer patients to. Patients are given lubricating eye drops, steroid eye drops, and are really asked to report any visual changes to us and we'll make appropriate changes in management. It's really not that hard. I think, you know, compared to other toxicities that we deal with other types of therapies, this one is very straightforward to deal with. I think it's also important to point out that the ocular toxicities really did not result in very many patients dropping out of the study, and it's all reversible. That's really important. Yeah. The only thing I would add to that, Ursula, is that, you know, it's predictable. We know when to expect it. Like any toxicity for a new agent that comes on the market, you know, it's also expectation for the treatment team. Because we've had a fair amount of experience with this drug over the years, I think we've gotten pretty good at this. Knowing that you can reassure the patient to get through this process, knowing that it can resolve in most of these cases, when it's expected to occur makes this much easier. It's gotten much easier to do this, to administer the compound. Agreed. Great. My question just for management maybe, in terms of timing, I understand that you anticipate the randomized results in Q3 of next year, which overlaps roughly with the timing of the future PDUFA date. Have you had a discussion with the FDA if they would wait for the randomized data prior to approval if the timing is very close? Boris Peaker, this is Mark Enyedy. We have not had a specific conversation. Here's what we do know, though. We're filing under Subpart E for accelerated approval, and there are very specific standards that are applied with respect to applications under Subpart E. In particular, you know, does the agent in question, you know, surpass the outcomes with available therapy? The answer provided, you know, emphatically by these data is yes, it does. That's the basis on which this application would be reviewed. There is no alternative basis for the FDA to say, "No, no. We're gonna wait to approve this application," because it's not part of the regulatory standards here. Great. Thank you very much for taking my questions. Thank you. Our next question comes from Andy Hsieh with William Blair. Your line is open. Great. Thank you for taking my questions, and congratulations on the great data. Really happy for the entire ImmunoGen team. My question has to do with, you know, different components of the clinical data. In terms of the complete response rate, I'm just wondering if Dr. Matulonis and Coleman could educate us on kind of the significance of seeing CR, especially so late in the treatment lines. Mm-hmm. Any sort of differences that you saw from CRs from chemotherapy-treated patients and CRs seen from, you know, mirvetuximab soravtansine-treated patients. I'll ask Rob to comment first and then Ursula. The first point is, you know, talking about a CR in this patient population at any CR is groundbreaking. Remember, these are patients who have progressed through our best therapies multiple times, and they have actual visible tumor that went away. That's just not our expectation. We see rare occasions we will see a few of those occur on some of our other treatment trials, but it is much more the norm that we do not see any CRs at all. It was one of the things when I saw this top- line data, I was immediately drawn to. You know, it's great, and it speaks to the efficacy of the agent. In the clinic, that we're really looking for is the failure, the lack of progression. So to have these responses is, you know, just extra icing on the cake here. To see it go away and to show a patient and her CAT scan with the tumor being gone is a tearjerker. I mean, this is a huge difference than what we've seen before. You know, again, I just trying to contain my excitement about this, but this is important because, you know, going forward with patients who can achieve a lasting response when this occurs and the very unusual study to see a CR in a patient population as heavily pretreated with the types of agents that this patient population has been treated with is really remarkable. Yeah, no, Rob, I completely concur. I think, you know, this is really important for patients who, you know, they're heavily pretreated, but some of them will have symptoms related to their cancer, some of them will not. The patients, you know, who have symptoms related to their cancer, to have such extraordinary responses, both PRs and CRs, you know, you're gonna make patients feel better. They're gonna Mm-hmm. Have a diminution of their symptoms. It really just shows you that even in platinum-resistant ovarian cancer where, you know, typical chemotherapy has single-agent response rates, if you hit the right target with the right drug, this cancer can respond and respond really significantly for a significant amount of time. I agree with Rob. Again, this is, for me, really gratifying because I've been working with this drug for many years now. I've seen Mm-hmm. I've seen patients respond to this drug, their cancers respond to this drug. Mm-hmm. To see this data, you know, presented today, is just super exciting. Excellent. I'm also curious about the approval of Tivdak in an adjacent market, I would say, in cervical cancer, whether that could help in terms of the education effort in managing ocular toxicity, maybe not just you, but perhaps your community, colleagues as well. Yeah. I'll ask Robert Coleman to comment on that. Yeah. Thank you, Anna. Yeah. As you mentioned, tisotumab vedotin is, you know, another ADC that got, you know, recent approval. We're very excited about that as well. It has a slightly different ocular toxicity than this compound. As Ursula mentioned so nicely in her comments, you know, this is something that we are seeing across the class. To some extent, you know, this story started with MIRV, with initial exposure to this in the phase I. We started to get good at managing ocular toxicity, the expectations. I think you're right on. I mean, our educational component to the ADCs in general has already started. With a wider exposure across the different GYN platform, you know, the GYN cancers, a lot of the investigators and clinicians have gained experience with these class of drugs. They are slightly different, but they have a you know, predictable components to them. You're right, we're getting much better at it. Yeah. The only thing that I would add is that the vast majority of the ocular toxicities with mirvetuximab are low- grade. Yeah. As Rob mentioned, it's predictable and it's reversible. Yes, reversible. Got it. Very, very helpful. Maybe last question, if I may. You know, as we are anticipating the MIRASOL study, the randomized study, I'm just curious if you could educate us on the Avastin pretreated and Avastin naive population, any sort of particularities in terms of, you know, differences, baseline characteristics in those population and how translatable data from one population is to the other. Yeah, Andy. We know back from FORWARD I that about half of the patients in that study had prior bevacizumab and half didn't. We anticipate that will be similar in the MIRASOL study. Typically, bevacizumab in the U.S. is given generally a little bit later than in Europe. I don't think that we can make any blanket statement given regional differences in terms of when bevacizumab is used in the treatment algorithm, as well as different regions and their ability to access bevacizumab. What I would say is that as you can see in the SORAYA study, over half of the patients had three prior lines of therapy. There is a correlation with prior bevacizumab and more heavily pretreated patients. I would also point out that when bevacizumab is used in the front line, some physicians actually reserve it for the higher risk patients with stage four disease because that's where it's been shown to have an overall survival benefit. For some patients who've had prior bevacizumab, they actually have worse disease. I'm sharing that level of detail and complexity so that folks understand overall the SORAYA study is a more heavily pretreated population, and I would say potentially a worse population than what we will ultimately see in the MIRASOL study. That's very helpful. Thank you so much for answering all my questions. Sure. Thank you. Our next question comes from Kelly Shi with Jefferies. Your line is open. Thank you for taking my questions and congrats on a very impressive outcome. I actually wonder if you have details of folate receptor alpha expression profile collected and analyzed to find out if there's a correlation between the depth of response and the durability of response to the FRα expression level. Also for doctors, I'm just curious whether you see the potential of mirvetuximab to be expanded to like to the patients with a lower expression level of FRα, for example, the intermediate expressers. Thank you. As we've shown throughout the development of mirvetuximab, Kelly, the higher the folate receptor alpha expression, the deeper and more durable the tumor shrinkage is. We learned in FORWARD I that mirvetuximab is quite active in patients with medium levels of FR alpha expression, with similar response rates as you see with chemotherapy, actually similar PFS, frankly. It's really the high FR alpha patients who comprise about 40% of the ovarian cancer population who benefit the most from mirvetuximab in terms of ability to get a response and the depth and duration of that response. Mirvetuximab will be used in that 40% of patients with high FR alpha. In terms of extending mirvetuximab into a broader population, given our results from FORWARD I, as well as our combination studies, there is certainly the potential for us to broaden usage of mirvetuximab in a combination strategy in patients with lower levels of FRα expression, particularly the 20% with medium levels of expression. What I would really remind folks about is that our next generation FRα-targeted ADC, IMGN151, has been specifically engineered to address a broader population of patients with FRα-positive tumors. Not just the rest of the ovarian cancer population, but also endometrial cancer, triple-negative breast, and lung cancer. We're on track to file the IND for that agent before the end of the year. Great. Thank you very much. Thank you. Our next question comes from Kennen MacKay with RBC Capital Markets. Your line is open. Hi, let me offer a big congratulations to the whole team this morning, and thanks for taking the question. I had a question on duration. I was wondering if you could remind us of your conversations with the FDA towards a duration of therapy expected from single-agent chemo or a duration that would be sufficient for an accelerated filing. That chemo control arm of AURELIA was about 5.4 months DOR, but less heavily pretreated patients. Anna, previously, we talked about a DOR of about 6 months being clinically meaningful. Does this need to mature to above 6 months, or is 5.9 sufficient here? Yes. Thanks, Kennen. That's right. The data that you've cited from the AURELIA study show a DOR of 5.4 months in a less heavily pretreated population. Our conversation with FDA, they were very clear about that 12% overall response rate that we needed to rule out. Similarly, they said that the duration of response should surpass that with available therapies but did not give us a hard number. This 5.9 months is essentially 6 months. I think the difference is 3.5 days, to be perfectly honest. Looking at our data, you know, we've done some very, I would say, sophisticated modeling to take a look at those patients, nearly half of the responders who are still on study drug and looking when they're due for their next scan. We've modeled scenarios including everything from the worst-case scenario, where every single one of them progresses at their next scan, in which case, the worst our DOR could be is 5.7 months, which is still above that 5.4 months in a less heavily pretreated population. We run simulations, anticipating realistic scenarios that are based from our FORWARD I study in terms of a percentage of responders progressing at their next scan, simulating it 1,000 times, and we've gotten a range anywhere from 5.7 to over 7 months. With longer follow-up, we will have mature DOR. I think the estimate that we have right now of 5.9 months is absolutely clinically meaningful, and we look forward to sharing updated data at a major medical meeting Q1 next year. Maybe just a follow-up question on that, Anna, as well as for the KOLs. I was wondering if there's anything from this dataset or prior datasets, FORWARD I dataset, that you could talk to around the kinetics of response and the majority of these patients responding on their first or second scan. Similarly, the patients who don't immediately respond, who might have stable disease, is there any incidence of longer stable disease? Thank you. Yeah. We have great data from the prior studies showing that about half of patients will respond at their first scan. Of course, you need another scan six weeks later to confirm that response. You know, at each time point, about half more patients will respond. Again, about half of the responses occur quite early, and then over time, we still have patients who have later responses. There's still patients on with stable disease who haven't met the formal criteria for a response by RECIST, but they're clearly benefiting because they had platinum-resistant disease. They started mirvetuximab a long time ago, and they're still on it. Hopefully that gives you a sense of the kinetics of response, Kennen. Yeah. No, thank you. I'm just thinking about PFS here. It seems like maybe it could be longer than that duration of response. Maybe just one final housekeeping question here. Just wanted to confirm from your conversations with Ventana, would they be filing that companion diagnostic in Q1 as well, or do you understand sort of timelines associated with that? Thanks, and congrats again to the whole team. Yeah. Thanks, Ken. Really appreciate the kind words. Yeah, actually the first module of the PMA has actually already been submitted by Ventana, and then the expectation is that the remaining modules, which would include the clinical data that we're sharing with you today, would be submitted relatively contemporaneous with the BLA submission and then CDRH and our review division coordinate on the timing so that the CDX is approved contemporaneous with the drug itself. Thank you. Our next question comes from Jessica Fye with J.P. Morgan. Your line is open. Hey, guys. Good morning. Thanks for taking my questions. A couple for management and maybe one for the physicians. First, for the ImmunoGen team. You guys mentioned that the SORAYA data makes you even more confident in the success of MIRASOL. Can you just remind us of the powering assumptions for that trial, what you've assumed for PFS for the active and control arms, and the delta you need to show to separate? You're just talking about time to response with Kennen, and can you talk about the depth of response in patients who responded? If given the consistency of investigator and the BICR results, does it seem to assume that there weren't a bunch of sort of cuspy responses here? Lastly, for the investigators, to the extent you directly cared for any of those patients with the CRs, I'm curious whether they received full courses of treatment without dose reduction or interruption. Thanks. Okay, Jess. Starting with MIRASOL. MIRASOL is designed as a randomized trial with progression-free survival as the primary endpoint. We are using a hazard ratio of 0.7, and we are assuming on the control arm a median PFS of 3.5 months. That's actually very data-driven based on the results from our FORWARD I study where we actually already showed in FRα-high patients a hazard ratio much less than that. I think we have a high probability of technical success in MIRASOL. Turning to your next question about time to response and depth of response and investigator and BICR, what I would say is our responses you know per RECIST you need to have a 30% decrease in the sum of the longest diameters from baseline to have a response. Some of our responses are, you know, just over that, and some of them are complete responses, with 100% tumor shrinkage and disappearance. Again, given that these are all high FRα patients, we are seeing again, you know, deep and durable responses. I don't think I can share more than that at this point, but look forward to sharing, you know, additional data at a major medical meeting Q1 next year. In terms of investigator and blinded independent central review, we were very gratified by the concordance that we saw, across the study for investigator and blinded independent central review. From my perspective, that just emphasizes the high quality of the data and the excellent conduct of our study at the sites. you know, the investigators were GCP compliant, and there was no evidence of bias in their assessments. If I could cue Ursula Matulonis and Robert Coleman to speak to any CRs that they may have had on the study. I have to sort of look back, but certainly I have had CRs with mirvetuximab. It's you know, again, extremely gratifying because that essentially never happens with single-agent chemotherapy. Yeah. To have a CR with mirvetuximab is fantastic. Yeah, I mean, no more to say, but it's great, and I think it just speaks to the real efficacy of this drug in folate receptor alpha, you know, positive ovarian cancer. Yeah. I mean, I didn't have a patient with a CR, but the way that we handle CRs and PR is actually the way we handle patients who have nothing more than PR and don't have progression is pretty much the same. You know, as Ursula mentioned, for the patients that are symptomatic, a response, if the tumor is actually producing the symptom, pain, heaviness, pressure, those types of things, then a response can actually lead to not only, you know, a favorable benefit with respect to the cancer progression component, but also can reduce their symptoms, and that's important. For those that are asymptomatic, which many of these patients are, you know, we are just continuing to treat until we see signs that it's stopped working. Our patients obviously that go into a CR will have a longer time for regrowth to actually meet a criteria for progression. At the clinic, with the patient in front of you're basically, you know, trying to keep them alive as long as possible with available therapies, and this is a measurable difference than what we have available to us. Yeah, it's very exciting to see responses. Thank you, Rob and Ursula. I just wanna answer, Jess, your last question around dose reductions and dose delays. We only had less than 20% of patients with treatment-related dose reductions and 32% with dose delays. Recall that mirvetuximab is dosed once every three weeks, so a dose delay would be a one-week delay. We have no evidence that dose reductions or dose delays reduce efficacy. In fact, across the program with over 700 patients, we've had many patients on dose-reduced mirvetuximab, even up to several years. I hope that addresses your question. Great. Thank you. Thank you. Our next question comes from R.K. Ramakanth with H.C. Wainwright. Your line is open. Thank you. Congratulations, folks. I'm sure you folks have been waiting for this day for quite a bit of time. Great news for patients and investors. Yes. As well. A lot of my questions have been answered. But just couple of quick ones. Just trying to look beyond SORAYA. How should we think about or what is there a read through to patients who did not receive a PARP inhibitor, and also to think about how this data could read through to platinum-sensitive patients? I think your question, R.K., was for patients who've not received a PARP inhibitor. Yes. How these data might be relevant for platinum-sensitive. Okay. About PARP inhibitors. About half of our patients on SORAYA had a prior PARP inhibitor. As you'll see at a major medical meeting next year, mirvetuximab is active regardless of prior PARP use or not. That's a really important point. You know, the data from SORAYA has been consistent with what we've seen previously, that prior PARP use does not at all diminish mirvetuximab's activity. In terms of the relevance of these data for platinum-sensitive disease, I think in the short term, as you heard from Mark Enyedy, the mirvetuximab plus bevacizumab cohort in platinum-agnostic patients is quite strong, not just in platinum-resistant, but also the platinum-sensitive space. For patients who have platinum sensitive disease for whom a non-platinum combination is appropriate, MIRV plus bev is really a nice option. You know, we will be engaging the compendia to have that listed so that physicians and patients will have two choices around the time of the initial approval. Either MIRV monotherapy on label or mirvetuximab plus bevacizumab in combination. In the longer term, in terms of platinum sensitive disease, we know that later-line platinum sensitive disease is a growing population of patients with the introduction of PARP inhibitors. PARP inhibitors have been fantastic as maintenance in the front line setting and recurrent platinum sensitive setting, essentially artificially extending the platinum-free interval for months of selective pressure from a PARP inhibitor, which is potentially cross-resistant with a platinum. We know that there will be more patients with later-line platinum sensitive disease who actually won't respond as well to another round of platinum as they may have in the olden days prior to introduction of PARP maintenance. For that reason, mirvetuximab is being studied in the PICCOLO study in later-line platinum sensitive disease because we believe these patients will need more options. Great, thank you. Couple more quick ones. In real life, how often is folate receptor expression detected? Also, how do you, for the physicians, how do you think about this data when you think of going upstream from where you are now or from the current clinical, you know, data that you have on hand? In terms of real-life data for folate receptor alpha, we have tested thousands of tumor samples at this point, and we know that FRα is expressed in the majority of ovarian cancer patients, and FRα high is in approximately 40% of patients. I think the data that we have are relevant and reflective of real-life distribution of FRα in the ovarian cancer population. In terms of moving mirvetuximab upstream, certainly we've discussed our combination strategies. You know, when we have the formal label expansion laid out, we'll discuss that next year. I'd be curious to have Robert and Ursula talk about their thoughts about how to move mirvetuximab up into earlier lines of therapy. Ursula, go ahead, if you wanna start. I think, you know, the trials will guide us there. I mean, I think where we are right now with SORAYA, and as Rob mentioned, prior, you know, there hasn't been a drug approved in the platinum-resistant setting in seven years, which is pretty remarkable in itself. And the fact that this data has so clearly, you know, gone and surpassed what was expected of it, as you know, as discussed with the FDA, is super exciting. I think that there are combination studies afoot. We've certainly tested mirvetuximab with bevacizumab. seen, you know, very exciting results. It's been tested with other chemotherapy agents. I think it's only natural as drugs are tested in the later line setting and shown to be efficacious, just like PARP inhibitors, that they're gonna be slowly moved up front. We'll do those trials and see what the results show us. Yeah. This is Rob. I would agree. I would kind of agree. The issue is, you know, right now, if you look at this against available therapies, this is beating what we would normally give in the same drugs that were already in earlier lines of therapy. It makes perfect sense to be able to migrate this forward, as was already mentioned about PICCOLO. These are incredibly important trials to help guide that, to make a strategic decision to move it up earlier line of therapy. It's efficacious, it's active. We have a biomarker. I think this is, you know, it's a no-brainer. It will move forward. Great. Thank you all for taking all my questions. You're welcome. Thank you. Our next question comes from Joe Catanzaro with Piper Sandler. Your line is open. Hey, guys. Thanks so much for squeezing me in here, and let me add my congrats on the nice data. Maybe just following up on actually that last line of discussion. Wondering if you have a sense of how response rate and DOR broke out between patients with at least three prior lines of therapy versus those with one to two prior lines. Relatedly, for the KOLs, you know, what considerations would go into offering MIRV monotherapy as a second-line therapy versus, say, a fourth line therapy? Last question, just wondering if eye exams were mandated before each dose. Thanks. Yeah. When we look at the data across the SORAYA study, that response rate of north of 30% is quite robust. Looking at 1-2 versus 3 prior lines of therapy, what I can tell you is the patients with 3 prior lines of therapy do quite well with mirvetuximab, and we look forward to sharing the data on those subsets at a major medical meeting. I would highlight that there's really nothing approved for platinum-resistant disease with 3 prior lines of therapy. I think when you see that subset data, you'll be as impressed as we are. I'll leave it at that for now. Turning to ocular exams, we took really a patient-focused approach, doing eye exams in all of our trials at baseline to understand, you know, patients' ocular health at baseline. We took a symptom-driven approach. If patients have blurred vision, and about 40% do, they are referred to an ophthalmologist. For the 60% who do not develop blurred vision, they do not need to see an ophthalmologist. Your last question in terms of how our physicians thinking about using mirvetuximab in this, I would say broad population of second to fourth line. I'd ask Rob and Ursula to comment on that based on the data where and when you would use mirvetuximab in platinum-resistant disease. This is Robert. I'll start. You know, there's a lot of it comes with the predicting history of the patient. You know, many of these patients have received at least in my practice bevacizumab in the frontline setting, so they've had a prior exposure to bev. You know, I will be getting testing done much earlier, and I will be evaluating it against what we saw in this trial as to you know what would be the best for the patient and give them the options. 'Cause we do have a broad portfolio of responses in this study to compare against. You know, the single agent, it's very palatable to have a high response rate with that level of prior drug exposure. You know, half the patients in this trial had three lines of therapy, but that means that half of them had less. We'll look at that data in totality and look at the biomarker and I'll have a discussion with the patient. It's active, and I wanna move it up as soon as I can to the appropriate patient. We've got great guidance from this trial to help us with those decisions. Yeah. It's Ursula. I would completely agree. I think as long as we get to see the caveats of this trial, you know, the eligibility met, you know, receipt of prior bev platinum resistance, which as Anna mentioned at the beginning, you know, most of our patients do become platinum resistant, and that's unfortunately how they succumb to this cancer. Having the folate receptor alpha expression. The data really shows the excellent responses regardless of how many prior lines the patients have received. I mean, I really see this drug being used ubiquitously in patients as long as they have that FRα positivity expressed within their cancer. Mm-hmm. Great. Thanks for taking my question. You bet. Our next question comes from Jonathan Chang with SVB Leerink. Your line is open. Hi, guys. Congrats on the data, and thanks for taking my questions. A couple questions. First question, what% of patients screened positive for folate receptor alpha-high in SORAYA? Second question, is the 5.9 months duration investigator or centrally reviewed? If it's investigator assessed, can you provide the centrally reviewed number? Thank you. Yeah, sure. About 40% of patients screened positively for FRα high. You know, that's consistent with all the data that we have generated previously. Regarding duration of response data, the median of 5.9 months and then that range that I described earlier is based on investigator assessment, and all I can say at this point is that the blinded independent review of median duration of response is longer. Got it. Thanks for taking the questions. Thank you. I'm showing no other questions in the queue. I'd like to turn the call back to Mark Enyedy for any closing remarks. Great. Well, we thank everyone for joining us this morning, in particular Rob and Ursula, for your commentary and more importantly, your participation in SORAYA and MIRASOL. We look forward to publishing these results in a formal medical meeting in the early part of next year and to continue keeping you updated on both our preparations for FDA submission and launch of the product. We look forward to staying in touch. Thank you. This concludes today's Conference Call. Thank you for participating. You may now disconnect.