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Edited Transcript of IMGN earnings conference call or presentation 1-Nov-19 12:00pm GMT

Q3 2019 ImmunoGen Inc Earnings Call

WALTHAM Nov 10, 2019 (Thomson StreetEvents) -- Edited Transcript of ImmunoGen Inc earnings conference call or presentation Friday, November 1, 2019 at 12:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Anna Berkenblit

ImmunoGen, Inc. - Senior VP & Chief Medical Officer

* Courtney O’Konek

ImmunoGen, Inc. - Senior Director of Corporate Communications & IR

* Mark J. Enyedy

ImmunoGen, Inc. - President, CEO, Interim Principal Financial Officer & Director

* Theresa G. Wingrove

ImmunoGen, Inc. - SVP of Regulatory Affairs & Quality

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Conference Call Participants

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* Biren N. Amin

Jefferies LLC, Research Division - MD and Senior Equity Research Analyst

* Boris Peaker

Cowen and Company, LLC, Research Division - MD & Senior Research Analyst

* Daniel G. Wolle

JP Morgan Chase & Co, Research Division - Analyst

* David Simms Ruch

SVB Leerink LLC, Research Division - Associate

* Joseph Michael Catanzaro

Piper Jaffray Companies, Research Division - VP & Senior Biotech Analyst

* Justin Reid Zelin

Canaccord Genuity Corp., Research Division - Associate

* Kennen B. MacKay

RBC Capital Markets, Research Division - Co-Head of Biotechnology Research

* Michael Werner Schmidt

Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD

* Tsan-Yu Hsieh

William Blair & Company L.L.C., Research Division - Senior Research Analyst

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Presentation

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Operator [1]

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Good morning, and welcome to the ImmunoGen's Third Quarter 2019 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 O'Konek, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

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Courtney O’Konek, ImmunoGen, Inc. - Senior Director of Corporate Communications & IR [2]

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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 third quarter 2019 financial results. The press release and recording of this call can be found under the Investors & Media section of our website at immunogen.com.

On the call today are Mark Enyedy, our President and CEO; and Anna Berkenblit, our Chief Medical Officer. Theresa Wingrove, our Senior Vice President of Regulatory Affairs and Quality; and David Foster, our Chief Accounting Officer, will also join us for Q&A. During today's call, we will review recent progress, our third quarter financial results and highlight upcoming milestones.

During the discussion, we will use forward-looking statements and our actual results may differ materially from such statements. Descriptions of the risks and uncertainties associated with an investment in ImmunoGen are included in our SEC filings.

And with that, I'll turn the call over to Mark.

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Mark J. Enyedy, ImmunoGen, Inc. - President, CEO, Interim Principal Financial Officer & Director [3]

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Thanks, Courtney. Good morning, everyone, and thank you for joining us today. Following the restructuring we announced in late June, we've moved forward to execute on the priorities we set for the business and build value for our shareholders.

In line with these objectives, during the third quarter, we positioned mirvetuximab to start the next Phase III study by year-end, advanced our early-stage portfolio and significantly reduced our operating expenses. We will look to continue this momentum as we exit 2019 and deliver on a number of important milestones in the coming year.

Beginning with mirvetuximab. We presented full data and exploratory analyses for FORWARD I at ESMO in September. These results provided valuable insights into the patients who benefit most from mirvetuximab and allow us to proceed with confidence to pursue a new Phase III study, which we call MIRASOL, to compare mirvetuximab head to head with single-agent chemotherapy in platinum-resistant ovarian cancer patients whose tumors express high levels of folate receptor alpha. We've met with FDA to review the design of MIRASOL and anticipate enrolling our first patient by the end of the year.

In parallel, we will continue to advance our combination cohorts with encouraging initial data from the Phase Ib FORWARD II triplet cohort presented at ESMO in September. These data demonstrate that full dose mirvetuximab can be combined safely with standard dosing for both Avastin and carboplatin with encouraging antitumor responses that compare favorably to those of other triplets.

We also completed enrollment in our second mirvetuximab plus Avastin cohort in patients with recurrent ovarian cancer regardless of platinum status in September. We will report longer-term data from the triplet and initial data from the doublet during 2020.

Moving to our earlier-stage portfolio. We've continued to make progress with IMGN632, our anti-CD123 ADC, which we are developing in AML, BPDCN and now ALL under our collaboration with Jazz. Over the last quarter, we've continued enrollment in the Phase I expansion study of IMGN632 as monotherapy in patients with relapsed AML and BPDCN and opened an expansion cohort now enrolling patients with relapsed ALL.

We also initiated combination studies with IMGN632, azacitidine and venetoclax in relapsed/refractory unfit AML patients as well as a monotherapy cohort in patients who have minimal residual disease following frontline induction therapy. Lastly, we are pleased to share that 4 632 presentations will be made at ASH next month, including an oral presentation of updated clinical monotherapy data in AML and BPDCN, a poster presentation of preclinical combination data and 2 trials-in-progress posters.

In addition to the positive momentum with 632, we advanced 2 additional assets that demonstrate our continued innovation in ADCs. First, in collaboration with MacroGenics, the IND for IMGC936 is planned to be filed in the first half of 2020. And second, we expect our next generation anti-folate receptor alpha ADC IMGN151 to enter preclinical development in mid-2020. So overall, sound progress for the portfolio this quarter and a number of important milestones in the coming months.

Turning now to our financials. The details are covered in the press release issued this morning. So just a few summary results. During the third quarter, we generated $13.3 million in revenue, nearly all of which came from noncash royalty revenues. Operating expenses were approximately $31 million comprised of $21 million in R&D expenses compared with $47.2 million in the same quarter in 2018. This decrease was primarily due to lower personnel and third-party research expenses resulting from the restructuring of the business at the end of the second quarter of 2019, lower clinical trial costs in the current period driven by greater activity in the FORWARD I Phase III clinical trial during the prior year period and lower external manufacturing costs driven by activity to support commercial validation of mirvetuximab in the prior year period. In addition, we incurred a $1 million charge related primarily to retention costs resulting from the recent restructuring. And we had $9.2 million in G&A expenses compared to $8.3 million in the third quarter of 2018, primarily due to higher allocation of facility-related expenses for excess laboratory and office space resulting from the restructuring.

We ended the quarter with approximately $205 million in cash on the balance sheet. With the benefit of a full quarter following our restructuring, we are updating our financial guidance today. For the full year, we expect revenues to be between $65 million and $70 million, reflecting recognition of deferred revenue under our Jazz collaboration related to the discontinuation of IMGN779. We also expect our operating expenses to be between $170 million and $175 million and our cash at year-end to be between $170 million and $175 million.

With that I'll turn the call over to review our progress with mirvetuximab in more detail to Anna.

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [4]

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Thanks, Mark. First, I'll briefly review the FORWARD I data informing our decision to move forward with MIRASOL and then provide some additional details for the trial. While we are disappointed that FORWARD I did not achieve its primary endpoint at progression-free survival, we did observe consistent efficacy signals for mirvetuximab in the prespecified high folate receptor alpha subgroup with a hazard ratio of 0.69 for the primary PFS endpoint by blinded independent review.

Similarly, the confirmed overall response rate was higher for mirvetuximab at 24% than for chemotherapy at 10%. Overall survival at the time of the primary analysis was also longer in patients who received mirvetuximab compared with chemotherapy, with a hazard ratio of 0.62. While we cannot claim statistical significance for any of these, the consistency of the data and the nominal P values reinforce the strength of the efficacy data in the prespecified FR alpha high population.

While encouraging, the top line results did not achieve the efficacy outcomes we had previously observed with mirvetuximab in this setting. To better understand this data, we conducted a comprehensive assessment of the factors that may have contributed to the Outcome in FORWARD I. And from these analyses, gained important insights to inform our next steps with mirvetuximab.

Briefly, we learned that the use of a simplified scoring method to assess tumor samples for FR alpha expression inadvertently introduced a population of patients into the FORWARD I with lower levels of FR alpha expression than intended. We had since rescored the patient samples from FORWARD I using the method used in our Phase I and II trials which we call PS2+. And for those patients with high levels of FR alpha expression upon rescoring, we observed efficacy outcomes from mirvetuximab much more in line with our previous experience with improved activity, correlating with FR alpha expression and the strongest treatment effect for all efficacy endpoints in the intended FR alpha high patients.

To summarize the results from the exploratory analyses compared with chemotherapy, mirvetuximab was associated with longer progression-free survival with a median PFS of 5.6 months versus 3.2 months and a hazard ratio of 0.549. Similarly, mirvetuximab was associated with a higher overall response rate by blinded independent review, approximately 29% versus 6% with chemotherapy.

Investigator-assessed ORR was also higher for mirvetuximab, namely 38%, which is more in line with what we saw in Phase I based on investigator assessment. These trends continue when we look at overall survival in the PS2+ (inaudible) FR alpha high subset with longer median overall survival in patients who received mirvetuximab compared with chemotherapy, namely 16.4 months versus 11.4 months, with a hazard ratio of 0.678.

So in summary, these exploratory analyses demonstrate the strongest treatment effect for all efficacy endpoints in the PS2+designed FR alpha high patient population and this is how we will select patients for future mirvetuximab monotherapy trials.

The results of our exploratory analyses ultimately informs the design of our new trial called MIRASOL using PS2+ scoring in FR alpha high ovarian cancer patients. MIRASOL is a Phase III trial of mirvetuximab, in which 430 patients will be randomized one-to-one to receive either mirvetuximab soravtansine or investigator's choice of single-agent chemotherapy, weekly paclitaxel, pegylated liposomal doxorubicin or topotecan. Eligibility criteria include patients with platinum-resistant ovarian cancer with high levels of FR alpha using the PS2 scoring method who have been treated with up to 3 prior regimens. The primary endpoint of the study is progression-free survival by investigator assessment. The key secondary endpoints include overall response rate, overall survival and patient reported outcome.

We recently reviewed the design of MIRASOL with the FDA and we anticipate enrolling our first patient by the end of the year with the top line readout expected in the first half of 2022.

I'll briefly review now our progress with combination regimens in the FORWARD II trial. As mentioned, we presented encouraging initial data from the triplet cohort evaluating mirvetuximab in combination with carboplatin and Avastin in earlier-line patients at ESMO. In 41 patients with recurrent platinum-sensitive disease with medium or high FR alpha expression levels who have received up to 2 prior lines of therapy, the confirmed overall response rate for the triplet was 83% with a complete response rate of 17%. In the subset of 31 patients with only one prior line, the confirmed overall response rate was 90%, with a complete response rate of 19%. These are encouraging efficacy outcomes relative to those reported in similar patient populations for other carboplatin and bevacizumab-based triplets. Additionally, no new safety signals were identified and adverse events were as expected based on the side effect profiles of each agent.

Looking ahead to next year, additional platinum combinations in the platinum-sensitive setting will be initiated, and we will present initial data from the FORWARD II mirvetuximab plus bevacizumab platinum agnostic cohort as well as updated triplet combination data in mid-2020.

Turning to our combination strategy moving forward. We believe that we are well positioned with our triplet and doublet data in platinum-sensitive disease. We are interested in generating additional doublet data for carboplatin plus mirvetuximab as the landscape in platinum-sensitive settings continues to evolve and settles into a new treatment paradigm, incorporating PARP as maintenance in the frontline setting and then potentially bevacizumab in recurrent platinum-sensitive disease. We believe that patients will be living longer with platinum-sensitive disease, and therefore, will need additional platinum-based combinations that are well tolerated.

With that, we will open the call for questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from Boris Peaker of Cowen.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [2]

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Just on the combination comment you were just making, maybe want to get a sense of do you plan to start novel combo studies? Or is there a plan to maybe advance a specific combo into a pivotal development? And if so, what's the potential time line behind that?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [3]

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Thanks, Boris. So we've generated encouraging data for carboplatin plus mirvetuximab as well as the triplet carbo, mirv and bevacizumab, So these 2 combinations are quite important for us as we move up into the platinum-sensitive space, and we are working on the finalization of our plan to start a combination study next year. Right now, our primary focus is on getting MIRASOL up and running, and we view moving into the platinum-sensitive space as an important next step. But we have not planned the entire details of that quite yet.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [4]

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Got you. And maybe another question on FORWARD I. Just curious what fraction of patients in FORWARD I were pre-treated with PARPs or had PARPs prior to seeing your drug? How did the PARPs subgroup or pretreated subgroup do relative to the non-PARP and kind of how do you see the PARP use being in your new Phase III study?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [5]

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So in FORWARD I, about 10% of patients had a prior PARP. Remember, we enrolled FORWARD I when PARPs were approved in the treatment setting and were being studied as maintenance to the platinum-sensitive setting. So about 10% of patients had BRCA mutations and about 10% of patients had prior PARPs. We do expect that in MIRASOL, higher percentage of patients will have prior PARPs because of incorporation in the maintenance setting and platinum-sensitive disease. That being said when we looked at the subset of patients in FORWARD I who had prior PARPs, they benefited from mirvetuximab over chemotherapy as did the patients who did not have prior PARPs. So we believe mirvetuximab has very nice activity regardless of prior PARPs or not.

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Operator [6]

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And our next question comes from John Newman of Canaccord.

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Justin Reid Zelin, Canaccord Genuity Corp., Research Division - Associate [7]

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This is Justin Zelin on for John Newman. I was just curious on FORWARD I. Are you still planning on presenting overall -- updated overall survival data in 2020 for the population?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [8]

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So we presented updated data at ESMO from an August data cut, which was about 6 to 7 months after the initial primary analysis. And as you saw at ESMO, the overall survival trend for FORWARD I continued to hold up over time. We don't expect that to change. We have not really decided yet whether or not additional presentations for the FORWARD I data will be made next year because our focus now is on getting MIRASOL up and running.

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Mark J. Enyedy, ImmunoGen, Inc. - President, CEO, Interim Principal Financial Officer & Director [9]

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I would say at some point we will submit this to a journal. And at that point, we would have the updated survival data in -- yes.

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [10]

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Right.

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Justin Reid Zelin, Canaccord Genuity Corp., Research Division - Associate [11]

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Got it. And then just on the diagnostic, will you be working on a new companion diagnostic that will utilize the PS2 method of scoring for MIRASOL?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [12]

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Yes. We continue to work with Ventana regarding the development of the CDx. And Ventana has been with us the entire way. The scoring earlier in the program in the Phase I and Phase II studies use the PS2 scoring that we developed with Ventana. And we are now working with them to make sure that the assay that will become the CDx assay is the one we're implementing in MIRASOL.

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Operator [13]

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And our next question comes from Kennen MacKay of RBC Capital Markets.

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Kennen B. MacKay, RBC Capital Markets, Research Division - Co-Head of Biotechnology Research [14]

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Maybe I was wondering if you could just help us understand the time lines of MIRASOL enrollment and the time lines you're thinking around generation of the data around the primary endpoint that support that expectation for data in sort of, gosh, 2.5 years or so. And I was wondering if there's any feedback from some of the clinical trial sites that you previously had opened in FORWARD I that helped with that decision making. Then I just had a quick follow-up on trial design.

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [15]

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Sure. So we are on track to start enrollment by the end of the year. Remember, this is a 430-patient trial and so we anticipate completing enrollment in 18 months. So that gets us into the middle of 2021 and then we need to follow patients for progression-free survival, which is the primary endpoint, and that gets us into top line data readout first half of 2022.

In terms of enrollment and trial sites, recall that we enrolled 360 patients in under 15 months in the initial trial. And based on that, we believe that now that folks largely understand the activity of mirvetuximab, we will be able to enroll the next trial at a faster rate. We are also working with the sites that have enrolled the best in FORWARD I so we know the sites that are most engaged and have the patient population.

One factor to offset that, however, remember, is that we're focusing on FR alpha high patients, which are about 40% of the population and we are no longer enrolling medium patients which are about 20% of the population. I will say that every site that we've discussed the next Phase III trial with that participated in FORWARD I, every single one of them is looking forward to and is excited to participate in MIRASOL. So we look forward to getting a quick start off the ground.

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Kennen B. MacKay, RBC Capital Markets, Research Division - Co-Head of Biotechnology Research [16]

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Got you. And maybe just revisiting some of the conversations that came out of ESMO. Is there any other commentary you can make around the powering of MIRASOL? And in the design and thinking around that powering, how are you handicapping the fact that this new diagnostic or biomarker is using a retrospective look at the FORWARD I data? Looking forward to the data at ASH.

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [17]

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Sure. So we have designed MIRASOL to target a hazard ratio of 0.7. And you may recall that FORWARD I was targeting a hazard ratio of 0.58. Now when we look at the FORWARD I prespecified FR alpha high subgroup, we saw a PFS improvement with a hazard ratio of 0.69, okay? When we went back and looked at it, as you say, retrospectively with the PS2+ methodology, we saw a hazard ratio of about 0.58. Well, actually, 0.543, which was much more in line with how we had designed the trial. So what I would say is we've taken a conservative approach for MIRASOL, targeting a hazard ratio of 0.7 given the consistency of the data that we're seeing when we use the PS2 methodology for patient selection which is what we will be using in the MIRASOL trial. That -- I hope that was clear because it is rather complex.

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Kennen B. MacKay, RBC Capital Markets, Research Division - Co-Head of Biotechnology Research [18]

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Yes -- no. That is helpful. Thank you very much. Maybe just a follow-up to that. Just as we think about this and sort of retrospectively looking at data and how much confidence we can have in the new biomarker, can you help us understand sort of how many different metrics you -- by how many different other means do you retrospectively examine the FORWARD I data? Was this the only other sort of biomarker cut you examined because this is what you'd used in the earlier trial of mirvetuximab? Or were there others that maybe didn't factor into a Phase III design but were means of looking at FORWARD I data?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [19]

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So when the FORWARD I data read out and they were not as strong as we anticipated, really, the first thing we did was to take a hard look at the patient selection methodology. And we went back and used the PS2. Again, we rescored with the PS2+. And I would not call it a new biomarker now. I would say we went back to the way we had done it previously. Of course, we had exploratory biomarker endpoints put in FORWARD I and those data are interesting. None of them rose to the level of us needing to come up with an entirely new biomarker. Frankly, we're going back to the one that we knew previously worked.

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Kennen B. MacKay, RBC Capital Markets, Research Division - Co-Head of Biotechnology Research [20]

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I'm looking forward to the data at ASH.

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Operator [21]

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And our next question comes from Andy Yu Hsieh, William Blair.

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Tsan-Yu Hsieh, William Blair & Company L.L.C., Research Division - Senior Research Analyst [22]

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So with the enrollment completed, so I'm kind of talking about the platinum-agnostic cohort, how should we think about the baseline patient characteristics in terms of treatment experience, prior therapies, all that kind of baseline properties?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [23]

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Right. So we look forward to presenting initial data from the platinum-agnostic cohort middle of next year. You may recall we completed enrollment in that 60-patient cohort in September. So the data are maturing.

In terms of the patients that we enrolled, unlike the prior bevacizumab combination cohort, these are what we call platinum agnostic. So they do not have to have platinum-resistant disease. In other words, they could have recurred greater than 6 months after their last platinum.

When we look at who actually enrolled on the trial, there was a good distribution of patients with a platinum-free interval of 6 to 9 months, 9 to 12 months and then some of the slightly longer platinum-free interval. But these are not patients with platinum-free intervals of 2 years. I mean that would not have been appropriate for physicians to enroll those patients typically. Get another platinum-based doublet. But these are patients who physicians feel a non-platinum regimen is the appropriate next step. And I will say, as the market is evolving and the treatment landscape is evolving with more patients getting PARP maintenance and bev maintenance, patients are doing better and there's a growing population of patients who are still technically platinum-sensitive and physicians feel that they really need something aside from platinum because their bone marrow is getting tired. And so a regimen like mirvetuximab plus bevacizumab really makes a lot of sense.

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Tsan-Yu Hsieh, William Blair & Company L.L.C., Research Division - Senior Research Analyst [24]

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Got it. And going back to the MIRASOL design, I noticed that the randomization before FORWARD I was 2:1, now it's 1:1. Is there a rationale behind that?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [25]

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Yes. So the rationale for FORWARD I having a 2:1 randomization is that it was much earlier in the development of mirvetuximab and we actually needed to treat a whole bunch more patients with mirvetuximab to increase the size of our safety database. Now we have many hundreds of patients treated with mirvetuximab so we have a robust safety database. And therefore, we've moved to a 1:1 randomization, which is actually more efficient from a statistical design perspective.

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Operator [26]

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And our next question comes from Biren Amin of Jefferies.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [27]

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Just on IMGN151. How does that differentiate to mirvetuximab?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [28]

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So we look forward to sharing data from our next-generation folate receptor alpha agent next year, early next year. And given what we know about mirvetuximab, our basic scientists, our researchers have really focused on things that we can do to make the next FR alpha targeted agent even better. There are features that we can address in terms of ability to bind the target, ability to dose, ability to have bystander activity. So there are many features. And I would say we've done a really nice comprehensive assessment of all of the things that can be tweaked and we are excited about the next-generation FR alpha targeted agent because we think it may benefit patients that mirvetuximab currently does not benefit, specifically those with lower FR alpha expression. And so we're excited about that next year.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [29]

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Got it. And then I think at ASH, you're going to have some data on IMGN632. I think you've done an oral presentation potentially in AML and BPDCN expansion cohort. So Anna, maybe can you just talk a little bit about that? Because I think at last year's ASH during the oral, it was highlighted that 632 went into an expansion phase across 4 doses. Are those 4 doses still being tested? Did you narrow the dose range in the expansion phase further after the ASH update?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [30]

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Yes. So at ASH this year, we will have over twice as many patients' worth of data, both in terms of AML and BPDCN. So we have been working very hard this year to understand the optimal dosing schedule. You may recall last year, we had presented data from a Q3 week schedule as well as a weekly schedule. And since then, we've generated additional data that allowed us to choose the dosing schedule we would move into combination and that's 0.045 mg per kg and that's the dose of IMGN632 that we're combining with venetoclax and azacitidine in the trial that's up and running now. We are also exploring one additional dose level of the Q3 week schedule to get additional data, and we look forward to sharing all the data that we have at ASH.

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Operator [31]

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And our next question comes from Jessica Fye of JPMorgan.

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Daniel G. Wolle, JP Morgan Chase & Co, Research Division - Analyst [32]

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This is Daniel. Following on Biren's question, should we expect any new data with the ASH abstract for IMGN632?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [33]

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Yes. We will have over twice as many patients' worth of data this year compared with next -- last year.

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Daniel G. Wolle, JP Morgan Chase & Co, Research Division - Analyst [34]

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Right. So sorry, I was more specifically asking the abstract. Should we expect new data or should we just expect the new data to be presented at the presentation?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [35]

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So the abstract was submitted, I think, in August and we used all the data that we had and we were enrolling quite well earlier this year. So the abstract will have additional patients' worth of data, and then at ASH, we will have the most recent data.

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Daniel G. Wolle, JP Morgan Chase & Co, Research Division - Analyst [36]

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Got it. And then just one more. Given the recent advances in the standard of care for BPDCN, could you elaborate on the developmental pathway that you guys are thinking of for 632 in that indication?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [37]

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Sure. So BPDCN is a very rare, very aggressive hematologic malignancy for which until recently there were no approved therapies. Physicians use aggressive AML regimens, ALL regiments and nothing works particularly well. Since then, however, Stemline has gotten SL-401 or ELZONRIS approved specifically for BPDCN. It targets CD123 with a diphtheria toxin conjugate. Diphtheria toxins have some challenges, particularly in terms of our bodies making antibodies against the diphtheria toxin conjugate, making long-term administration a challenge.

That being said, they did get approval based on a small study of patients in the relapsed/refractory setting as well as a handful of patients in the frontline setting. What we are hearing is that despite its approval, because of some of its liabilities with capillary leak syndrome from the diphtheria toxin, physicians are not entirely satisfied with its ability to meet the unmet need in this population. So there remains an unmet need both in the relapsed/refractory setting post-ELZONRIS and also in the upfront setting. Our agent had demonstrated activity already at ASH last year in the post-ELZONRIS setting for BPDCN patients. So we believe we have an opportunity here to really become best-in-class. And given the rare nature of this disease, the regulatory precedent, we have -- we're working on what the borrower would be but we think it will be a potential option for accelerated approval for us based on single arm data and potentially even for approval.

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Operator [38]

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And our next question comes from Jonathan Chang of SVB Leerink.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [39]

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This is David Ruch on for Jonathan. Just to go back on the first question on PARP use and its impact on MIRASOL patients. Specifically, given that only 10% of FORWARD I patients had a PARP, do you think that earlier line use of PARPs could result in a predominance of patients in either earlier or later lines of therapy?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [40]

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Yes, we do. So I don't know about the predominance part.

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Mark J. Enyedy, ImmunoGen, Inc. - President, CEO, Interim Principal Financial Officer & Director [41]

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Right. So I mean, if you think about segmentation here for a second, when you look at the data that just were published at ESMO, what you see is profound activity from the PARP inhibitors in the maintenance setting, particularly those patients with BRCA mutations and those with homologous recombination deficiency. And when you add that, the totality of that patient population up, you get to about half of the patient population. The benefits of the PARP inhibitors and BRCA wild-type patients or HRD-negative patients is, I think, the clinicians there are going to be balancing risk-benefit using PARP inhibitors there. So I do think that you're going to see half of the early-line patients using PARP inhibitors. And as I say, when we look at the data that we have, not only from 403 but some of our combination studies too, we now see PARP inhibitor -- prior PARP use in those patients and we don't see it having an impact on the activity or the safety of mirv in prior PARP-treated patients. Is that helpful?

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [42]

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Yes, that's really helpful. I appreciate that. And is that something we can expect to see stratified in the MIRASOL study?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [43]

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So there -- we do have stratification factors in the MIRASOL study, specifically lines of therapy and choice of chemotherapy. I can assure you that there was a lot of discussion around whether or not we should stratify for prior PARP use or BRCA mutations or HRD for that matter. We've consulted a lot of our KOLs, both in the U.S. and Europe. And ultimately, we decided not to stratify. As Mark mentioned, we expect 50%, may be 40% of patients to have a prior PARP. So we think that statistically speaking, they will be balanced and we will be able to do an analysis appropriately. And of course, in our statistical analysis plan, that will be an important subset that we prespecified to look at.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [44]

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Great. Second question really quick, could you just provide any additional color on the discussions with the FDA specifically around the use of investigator assessed versus the centrally read criteria? I think this was asked about on the last call but you hadn't met with them yet. So just wanted to confirm kind of what their response was to that?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [45]

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Yes, we had the opportunity to discuss the key design elements with FDA and they did agree that PFS by investigator assessment is an acceptable primary endpoint for MIRASOL, assuming that we collect and hold the scans for the blinded independent review for any necessary audit.

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Theresa G. Wingrove, ImmunoGen, Inc. - SVP of Regulatory Affairs & Quality [46]

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Or sensitivity analysis.

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [47]

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Sensitivity analysis as well.

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David Simms Ruch, SVB Leerink LLC, Research Division - Associate [48]

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Okay. Awesome. Great. And last one for me. How do you view 632 as differentiated from some of the other CD123 players in the space?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [49]

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So we talked a little bit already about ELZONRIS, it being a diphtheria toxin conjugate with some liabilities including capillary leak and antibodies generated against it. So that's one. The other compounds that are in development include some bispecifics towards CD123. For example, MacroGenics' Flotetuzumab. These bispecifics, they have activity for sure and they have some challenges in terms of the need for long infusion durations and cytokine release. Then there's the CAR Ts targeting CD123 like the Mustang Bio CAR T. And as you know, CAR Ts, when they work, work beautifully and they're not for every patient and there are some reimbursement challenges there. I think our CD123-directed ADC that's given intravenously as a brief IV infusion in the clinic had some real advantages. So that gives you a sense of the color of the different agents out there.

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Operator [50]

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(Operator Instructions) Our next question comes from Michael Schmidt of Guggenheim Securities.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [51]

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I had a couple on IMGN632. Maybe first, regarding BPDCN, I was wondering if -- I know it's still early in the program, but I was just wondering if you already had any kind of FDA interactions with respect to the pivotal trial requirements. For example, what -- how many patients' worth of data would be required, for example, for BPDCN submission?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [52]

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No, we have not discussed this with FDA yet.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [53]

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Okay. And would you initially go into relapsed/refractory patients or newly diagnosed BPDCN? I think the Stemline product may have a label for both, but I'm not 100% sure.

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [54]

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Yes, Stemline has a label for both. And in one of those subsets, it was 2 out of 13 patients in the relapsed/refractory setting had what they considered a response in CR CRc. So I think the bar is quite low in the relapsed/refractory setting. In the frontline setting, their CR CRc rate was higher but again it was a small group of patients. So we actually are in the process of amending our study to allow frontline patients who are unfit for standard of care available therapy. So you raised a really good point and we're looking forward on gathering proof of concept data that will enable us to engage with FDA to have a discussion about what it would take for approval.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [55]

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Okay. And how many patients with BPDCN will be included in the ASH update?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [56]

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Over twice as many as last year. And last year, there were 3.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [57]

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Okay. All right. The other question I had, just maybe talk a little bit about the -- your rationale to combine 632 with Vidaza and Venclexta in relapsed/refractory AML patients as opposed to front line and how should we think about activity of these agents after they have potentially been used already previously in patients in combination then.

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [58]

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Sure. So the dose escalation part of the study, when we're just beginning, will be in the relapsed/refractory unfit population. And we're starting off somewhat cautiously, I would say, because Vidaza is not necessarily an easy regimen for patients. So we will be doing doublet of 632 plus venetoclax and doublet of 632 plus azacitidine. And once we have established basic safety, we will then move to the triplet. And so the patients that physicians will choose for each of those doublets initially will be based on therapies that they had previously. But ultimately, certainly, we'd be interested in moving this triplet up into the frontline setting but we have to start first generating safety data in an appropriate population.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [59]

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Understood. And then just looking at you potentially having a quite substantial Phase I data set for 632 by year-end, I guess, how should we think about the efficacy bar to move this into pivotal studies potentially?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [60]

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So the data set we'll be sharing at ASH is monotherapy. And in the relapsed/refractory or relapsed setting, the bar for CR rate is really around 30%. I would say 632 has nice activity as a monotherapy and what we're doing based on the data we've seen thus far is we have opened up an MRD-positive monotherapy cohort in this study that we are just opening with the combinations. So this MRD-positive AML cohort are patients who've had induction therapy and now are in CR but they have minimal residual disease present. And we know that patients do not do very well. So we have a cohort. Again, it just opened up and is enrolling that we will be looking at the ability of monotherapy IMGN632 to convert patients from MRD-positive to MRD-negative with the idea that, that ultimately could really benefit patients. So that is another option for advancing monotherapy from a registration perspective potentially.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [61]

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And with this MRD-positive patient population, will that be an alternative to relapsed/refractory labeling [anatomication] or...

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [62]

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Yes, yes. It's another option. That's right.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [63]

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Understood. And right -- I guess what is the size of that patient population potentially, the MRD-positive AML subset?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [64]

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I would have to get back to you on that. But it is about 50% of the patients who go into CR. Again, it depends a little bit on what the molecular subtype of AML is.

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Michael Werner Schmidt, Guggenheim Securities, LLC, Research Division - Senior Analyst & Senior MD [65]

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Okay. That's really helpful. Really appreciate it. Looking forward to the ASH abstract then next week.

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Operator [66]

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And our next question comes from Joseph Catanzaro with Piper Jaffray.

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Joseph Michael Catanzaro, Piper Jaffray Companies, Research Division - VP & Senior Biotech Analyst [67]

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I just wanted to follow up quickly on the blinded central review versus investigator assessment. So if we look at the PS2 rescoring and when you go from blinded central review for PFS to investigator, the hazard ratio ticks up ever so slightly. So just wondering what were your considerations to using investigator assessment for MIRASOL? Is it simply the turnaround time is quicker? Or are there other things that are being considered there?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [68]

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Yes. So there's a few things that are being considered. Investigator assessment is what investigators typically use in their day-to-day real-life treatment of patients. I would say there was a shift previously toward having the blinded independent review be the gold standard. But now there is an understanding that it has its own set of biases. And so there is a move away from having that be required to be the primary endpoint. One of the issues with blinded independent review is that the investigator may see measurable disease on the baseline scan. In fact, it's required for study entry. The blinded independent review may not necessarily see that. And so that makes it challenging then to look at overall response rate, et cetera. I would say the difference in hazard ratio that you're pointing out is like 0.549 versus 0.61. Remember that these are post hoc smaller sample sizes because about 1/3 of the patients we had to exclude because of lower than expected FR alpha expression. So I would say there is some bobble or some noise in the data set. But remember, both of these hazard ratios are well below the 0.7 that we have designed the study for.

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Joseph Michael Catanzaro, Piper Jaffray Companies, Research Division - VP & Senior Biotech Analyst [69]

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Okay. Great. That's helpful. And then just one last one. So you mentioned that you're thinking about other platinum-sensitive combinations to explore. If we think about the combination that you've explored thus far, it seems like the only obvious one is this PARP inhibitors. Is that a combination approach you're considering? Are there other combinations that you can disclose at this time?

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Anna Berkenblit, ImmunoGen, Inc. - Senior VP & Chief Medical Officer [70]

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Yes. So we -- there's an IST ongoing combining mirvetuximab with rucaparib in, I would say, heavily pre-treated patients. From a biological mechanistic point of view, there's no strong rationale to combine a folate receptor alpha targeted therapy with a PARP inhibitor. The data that we have generated from a preclinical proof of concept perspective was for mirvetuximab with carboplatin and with bevacizumab. Those data are published and we now have initial clinical data for the doublet and the triplet suggesting that these regiments are quite active. So those are the ones that we're focusing on and have prioritized for further development in the platinum-sensitive space.

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Operator [71]

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And ladies and gentlemen, this does conclude our question-and-answer session. I would now like to turn the conference back over to Mark Enyedy for any closing remarks.

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Mark J. Enyedy, ImmunoGen, Inc. - President, CEO, Interim Principal Financial Officer & Director [72]

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Thank you. Very much appreciate your time this morning. After a difficult moment in June restructuring the business, we've really put ImmunoGen on a path forward. We've built momentum in the business and are looking forward to a strong finish to the year and a productive 2020. And so we look forward, as many of you mentioned, to seeing you all at ASH in December. Thanks again.

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Operator [73]

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Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.