Immunogen Inc (NASDAQ:IMGN) Q3 2019 Earnings Call Transcript

Immunogen Inc (IMGN) Q3 2019 earnings call dated Nov 1, 2019

Corporate Participants:

Courtney O’Konek — Senior Director of Corporate Communications and Investor Relations

Mark J. Enyedy — President and Chief Executive Officer

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Analysts:

Boris Peaker — Cowen and Company — Analyst

Justin Zelin — Canaccord Genuity — Analyst

Kennen MacKay — RBC Capital Markets — Analyst

Andy Hsieh — William Blair — Analyst

Biren Amin — Jefferies — Analyst

Daniel Wolle — JP Morgan — Analyst

David Ruch — SVB Leerink — Analyst

Michael Schmidt — Guggenhiem Securities — Analyst

Joe Catanzaro — Piper Jaffray — Analyst

Presentation:

Operator

Good morning, and welcome to ImmunoGen’s Third Quarter 2019 Financial and Operating Results Conference Call. Today’s conference is being recorded.

At this time, I like to turn the call over to Courtney O’Konek, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

Courtney O’Konek — Senior Director of Corporate Communications and Investor Relations

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. This press release and a 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 Dave 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.

Mark J. Enyedy — President and Chief Executive Officer

Thanks, Courtney. Good morning, everyone, and thank you for joining us today. Following the restructuring we announced in late June, we’ve move 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 analysis for FORWARD I and 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 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 1B 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 Venclexta in relapsed-refractory unfit AML patients, as well as a monotherapy cohort in patients who have minimal residual disease following front line induction therapy.

Lastly, we are pleased to share that four 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 two trials and progress posters. In addition to the positive momentum with 632, we advanced two 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 pre-clinical development in mid 2020. So overall, sound progress with 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 non-cash 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 3 clinical trial during the prior-year period and lower external manufacturing cost 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.

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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 of progression-free survival, we did observe consistent efficacy signals for Mirvetuximab in the pre-specified 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% then 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 pre-specified 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 these 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 FORWARD I with lower levels of FR alpha expression then intended.

We have since rescored the patient samples from FORWARD I using the methods used in our Phase I and Phase II trials, which we call PS2+. And for those patients with high levels of FR alpha expression upon rescoring, we observed efficacy outcomes for 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 the 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+ [Technical Issue] 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+ defined 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 Mirvetuximabsoravtansine 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 methods, who have been treated with up to three prior regimens. The primary endpoint of this study is progression free survival by investigator assessment. The key secondary endpoints include overall response rate, overall survival and patient reported outcomes. We recently reviewed the design of Mirasol with FDA and 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 two 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 cohorts, 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 settled into a new treatment paradigm, incorporating PARP as maintenance in the front line setting and then potentially bevacizumab in recurrent platinum sensitive disease.

We believe that patients will be living longer with platinum sensitive disease and therefore we will need additional platinum based combinations that are well tolerated.

With that, we’ll open the call for questions.

Questions and Answers:

Operator

[Operator Instructions] And our first question comes from Boris Peaker of Cowen. Your line is now open.

Boris Peaker — Cowen and Company — Analyst

Great. Just on the combination comments you were just making, maybe we 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 timeline behind that?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Thanks, Boris. So we’ve generated encouraging data for carboplatin plus Mirvetuximab, as well as the triplet carbo, mirv and bevacizumab. So these two 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 review moving into the platinum sensitive space as an important next step, but we have not planned the entire details of that quite yet.

Boris Peaker — Cowen and Company — Analyst

Got you.And maybe another question on FORWARD I. I’m just curious what fraction of patients in FORWARD I were pretreated with PARPs or had PARP prior to receiving your drug. How did the PARP subgroup — 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?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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 we’re being studied as maintenance in the platinum sensitive setting. So about 10% of patients had BRCA mutations and about 10% of patients had prior PARP. We do expect that in MIRASOL higher percentage of patients will have prior PARPs because of incorporation in the maintenance setting in platinum sensitive disease.

That being said, when we looked at the subset of patients in FORWARD I who had prior PARP, 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 PARP or not.

Boris Peaker — Cowen and Company — Analyst

Great. Thanks for taking my questions.

Operator

Thank you. And our next question comes from John Newman of Canaccord. Your line is now open.

Justin Zelin — Canaccord Genuity — Analyst

Hi, good morning, 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?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

So we presented updated data at ESMO from an August data cut, which was about six to seven months after the initial primary analysis. And as you saw at ESMO, the overall survival trend for FORWARD I continue 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.

Mark J. Enyedy — President and Chief Executive Officer

I would say, at some point we will submit this to Journal and at that point we would have the updated survival data in that …

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Right.

Justin Zelin — Canaccord Genuity — Analyst

Got it. And just on the diagnostic, will you — you’re working on a new companion diagnostic that will utilize the PS2 method of scoring from MIRASOL?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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 1 and Phase 2 studies used 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.

Justin Zelin — Canaccord Genuity — Analyst

Got it.Great. Well, thanks for taking my questions.

Operator

Thank you. And our next question comes from Kennen MacKay of RBC Capital Markets. Your line is now open.

Kennen MacKay — RBC Capital Markets — Analyst

Hi. Thanks for taking the question. Maybe, I was wondering, if you could just help us understand the timelines of MIRASOL enrollment and the timeline that you are thinking around generation of the data around the primary endpoint that support that expectation for data in sort of, gosh, half years or so. And I was wondering if there is any feedback from some of the clinical trial sites that you previously had opened in FORWARD I that help with that decision making? Then I just had a quick follow-up on trial design.

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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 in 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 the 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 in the next Phase III trial would then participate 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.

Kennen MacKay — RBC Capital Markets — Analyst

Got it. Thank you very much for that. 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 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? Thank you very much for taking the question. I’m looking forward about that at ASH.

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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 pre-specified 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 — actually 0.543 which was much more in line with how we had design the trial.

So what I would say is, we’ve taken a conservative approach from 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.

I hope that was clear, because it is rather complex.

Kennen MacKay — RBC Capital Markets — Analyst

That is helpful. Thank you very much. Maybe just a subsequent 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 biomarkers, can you help us understand sort of how many different metrics you — by how many different other means you retrospectively examine the FORWARD I data was this, the only other sort of biomarker cut you examined, because this is what you used in the earlier trial of Mirvetuximab. Or were there others that maybe didn’t factor into our Phase III design. But what it means of looking at the FORWARD I data.

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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.

Kennen MacKay — RBC Capital Markets — Analyst

Got it. Thank you very much for the color. I’m looking forward to the at ASH.

Operator

Thank you. And our next question comes from Andy Hsieh of William Blair. Your line is now open.

Andy Hsieh — William Blair — Analyst

Great. Thanks for taking my questions. 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?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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 did not have to have platinum-resistant disease. In other words, they could have recurred greater than six 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 six to nine months, nine to twelve months and some with a slightly longer platinum free interval. But these are not patients with platinum free intervals of two years. I mean,

that would not have been appropriate for physicians to enroll those patients typically to get another platinum based doublet. But these are patients who physicians feel are 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 are these — there is a growing population of patients who are still technically platinum sensitive and physician 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.

Andy Hsieh — William Blair — Analyst

Got it. And going back to the MIRASOL design, I noticed that the randomization before FORWARD was two to one, now it’s one to one. Is there a rationale behind that?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yes. So the rationale for FORWARD I having a two to one randomization is that it was much earlier in the development of Mirvetuximab and we actually need it 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 one to one randomization which is actually more efficient from a statistical design perspective.

Andy Hsieh — William Blair — Analyst

Right. Okay. That makes perfect sense. Okay. Thanks for taking all my questions.

Operator

Thank you. And our next question comes from Biren Amin of Jefferies. Your line is now open.

Biren Amin — Jefferies — Analyst

Yeah. Hi. Thanks for taking my questions. Just on IMGN151. How does that differentiate to Mirvetuximab?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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’re 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.

Biren Amin — Jefferies — Analyst

Got it. And then, I think at ASH you’re going to have some data on IMGN632. I think you’ve done oral presentation potentially in AML and BPDCN expansion cohorts. 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 four doses. Are those four doses still being tested, did you narrow the dose range in the expansion phase further after the ASH update?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yeah. 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 0.45 mix per kg, an after 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.

Biren Amin — Jefferies — Analyst

Great. Thank you.

Operator

Thank you. And our next question comes from Jessica Fye of JP Morgan. Your line is now open.

Daniel Wolle — JP Morgan — Analyst

Hi. This is Daniel. Thanks for taking our question. Following on Biren’s question, should we expect any new data with the ASH abstract for IMGN632?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yes, we will have over twice as many patients worth of data this year compared with last year.

Daniel Wolle — JP Morgan — Analyst

All right. So maybe I was more specifically asking, in the abstract should we expect new data or should we just expect the new data to be presented at the presentations?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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.

Daniel Wolle — JP Morgan — Analyst

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

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Sure. So BPDCN is a very rare — very aggressive hematologic malignancy for which until recently there were no approved therapies, physicians used aggressive AML regimens, ALL regimens and nothing worked particularly well. Since then, however, stem line has gotten SL-401 approved specifically for BPDCN. It targets our 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 front line 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-Alzheimer’s and also in the upfront setting. Our agent has demonstrated activity already at ASH last year in the post-Alzheimer’s settings 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 bar would be, but we think it will be a potential option for accelerated approval for us based on single-arm data, and potentially waiting for approval.

Daniel Wolle — JP Morgan — Analyst

Great. Thank you very much.

Operator

Thank you. And our next question comes from Jonathan Chang of SVB Leerink. Your line is now open.

David Ruch — SVB Leerink — Analyst

Hi, good morning guys. This is David Ruch on for Jonathan. Just to go back to 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?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yes. We do, so — I don’t know about the predominance part.

Mark J. Enyedy — President and Chief Executive Officer

Right. So, I mean if you think about segmentation here for a second, when you look at the data that’s 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 though when you add that — the totality of that patient population now, 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 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 used 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?

David Ruch — SVB Leerink — Analyst

Yeah. That’s really helpful. I appreciate that. And is that something we could expect to see stratified in the MIRASOL study?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

So 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 HID for that matter. We’ve consulted a lot of our KOLs, both in the US and Europe, and ultimately we decided not to stratify. As Mark mentioned, we expect 50%, maybe 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 pre-specified to look at.

David Ruch — SVB Leerink — Analyst

Great. Thank you for all the color there. 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 essentially red 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?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yes, we have 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 and sensitivity analysis as well.

David Ruch — SVB Leerink — Analyst

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

Anna Berkenblit — Senior Vice President and Chief Medical Officer

So we talked a little bit already about Alzheimer’s 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 toward 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 is 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 has some real advantages. So that gives you a sense of the color of the different agents out there.

David Ruch — SVB Leerink — Analyst

Great. Thank you so much. And I look forward to seeing you at ASH.

Mark J. Enyedy — President and Chief Executive Officer

Great.

Operator

Thank you. [Operator Instructions] Our next question comes from Michael Schmidt of Guggenheim Securities. Your line is now open.

Michael Schmidt — Guggenhiem Securities — Analyst

Hey, good morning. And thanks for taking my questions. 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, how many patients worth of data would be required, for example, for BPDCN submission?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

No, we have not discussed this with FDA yet.

Michael Schmidt — Guggenhiem Securities — Analyst

Okay. And would you initially go into one of the frac free patients on newly diagnosed BPDCN. I think the Stemline product may have a label for both, but I’m not 100% sure.

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yes, Stemline has a label for both, and in one of those subsets it was two out of 13 patients in the relapsed-refractory setting had what they considered a response to 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 therapies. So you raised a really good point, and we’re looking forward on gathering proof of concept data that will able — enable us to engage with FDA to have a discussion about what it would take for approval.

Michael Schmidt — Guggenhiem Securities — Analyst

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

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Over twice as many as last year, and last year there were three.

Michael Schmidt — Guggenhiem Securities — Analyst

Okay. All right. The other question I had, just maybe talk a little bit about the irrational to combine 632 with Vidaza and Venclexta in relapsed-refractory AML patients, as opposed to frontline? And how should we think about activity of these agents after they’ve potentially been used already previously in patients, in combination?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Sure. So the dose escalation part of the study, when we’re just beginning we 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’ve established basic safety, we will then move to the triplet. And so the patients that physicians will choose for each of those doublet 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.

Michael Schmidt — Guggenhiem Securities — Analyst

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?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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 the study that we’re just opening with the combinations. So this MRD positive AML cohort are patients who had induction therapy and now are NCR, but they have minimal residual disease presence. 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.

Michael Schmidt — Guggenhiem Securities — Analyst

And would this MRD positive patient population, would there be an alternative to relapsed-refractory — labeling had indication or…

Anna Berkenblit — Senior Vice President and Chief Medical Officer

It’s another option. That’s right.

Michael Schmidt — Guggenhiem Securities — Analyst

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

Anna Berkenblit — Senior Vice President and Chief Medical Officer

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.

Michael Schmidt — Guggenhiem Securities — Analyst

Okay. Thank you. Now that’s very helpful. I really appreciate it. Looking forward to the ASH abstract then next week.

Operator

Thank you. And our next question comes from Joe Catanzaro of Piper Jaffray. Your line is now open.

Joe Catanzaro — Piper Jaffray — Analyst

Great. Thanks for taking the question. 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 two investigator, the hazard ratio ticks up ever so slightly. So just wondering what were your considerations to use investigator assessment for MIRASOL? Is it simply the turnaround time is quicker? Or are there other things that are being considered there?

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yeah. So there is 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, etc.

I would say the difference in hazard ratio that you’re pointing out, it’s like 0.549 versus 0.61. Remember that these are post talk smaller sample sizes because about a third 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.

Joe Catanzaro — Piper Jaffray — Analyst

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

Anna Berkenblit — Senior Vice President and Chief Medical Officer

Yeah. So there is an IST ongoing combining mirvetuximab with rucaparib in, I would say, heavily pretreated patients. From a biological mechanistic point of view, there is 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 regimens are quite active. So those are the ones that we’re focusing on and have prioritized for further development in the platinum sensitive space.

Joe Catanzaro — Piper Jaffray — Analyst

Okay. Great. Thanks for taking my questions.

Operator

Thank you. 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.

Mark J. Enyedy — President and Chief Executive Officer

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

Operator

[Operator Closing Remarks]