Q3 2019 Earnings Call

Good morning, and welcome to Immunogen first 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'connor Senior director of corporate Communications and Investor Relations. Please go ahead.

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'd like to turn the call over to Courtney Okonig, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

Good morning, and thank you for joining today's call earlier today, we issued a press release. It includes a summary of our recent progress and third quarter 2019 financial result.

Courtney Okonig: Good morning, and thank you for joining today's call. Earlier today, we issued a press release that included a summary of our recent progress and third quarter 2019 financial results.

Courtney Okonig: The recording of this call can be found in the Investors and Media section of our website.

Press, releasing a recording of this call can be found under the investors in media section of our web site at Immunogen Dotcom.

Courtney Okonig: All on the call today are Mark Enyedy, our President and CEO, and Anna Berkenblit, our Chief Medical Officer.

On the call today are more Kennedy, our president and CEO and an American, but our chief Medical officer treat the wingrove, our senior Vice President of regulatory affairs in quality and they foster our Chief Accounting Officer will also join us for today.

Courtney Okonig: Teresa Wingrove

Courtney Okonig: 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 and our third quarter financial results.

During today's call. We will review recent progress our third quarter financial results and highlight upcoming milestones.

Courtney Okonig: and highlight upcoming milestones. During the discussion, we will use forward-looking statements and our actual results.

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 of immune engine are included in our of TC filings and with that I'll turn the call over to Mark.

Courtney Okonig: Results may differ materially from those stated. 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 Joseph Enyedy: 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 Mervituximab to start the next phase three 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 Mervitoximab, we presented full data and exploratory analysis for Forward 1 and Esmo in September. These results provide valuable insights into the patients who benefit most from Mervitoximab and allow us to proceed with confidence to pursue a new Phase III study, which we call MIRASOL, to compare Mervitoximab head-to-head with single-agent chemotherapy in platinum-resistant ovarian cancer patients whose tumors express high levels of folate receptor alpha.

Thanks coordinate good morning, everyone and thank you for joining us today.

Following the restructuring we announced in late June we 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 position merger talks about the start the next phase three study by yearend advanced our early stage portfolio and significantly reduced our operating expense.

We will look to continue this momentum as we exit 29 team and deliver on a number of important milestones in the coming here.

Beginning with Mirvetuximab, we presented full data an exploratory analysis performed one 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 three study, which we call mirasol compare mirvetuximab head to head.

With single agent chemotherapy, and platinum resistant ovarian cancer patients, whose tumors express high levels of folate receptor Alpha we've met with FDIC to review the design of Marisol and anticipate enrolling our first patient body ended the year in parallel we will continue to advance our combination cohorts with encouraging initial.

Mark Joseph Enyedy: 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 to triplet cohort presented at ESMO in September. These data demonstrate that full-dose mervituximab can be combined safely with standard dosing for both avastin and carboplatin, with encouraging anti-tumor responses that compare favorably to those of other triplets.

Data from the phase one before two triplet cohort presented at ESMO in September . These data demonstrate that full does mirvetuximab can be combined safely with standard dosing for both the vast in and Carboplatin with encouraging anti tumor responses the compare favorably to those of other triplets.

Mark Joseph Enyedy: We also completed enrollment in our second Mervitoximab 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 IMGN-632, our anti-CD123-ADC, which we are developing in AML, BPD-CN, and now ALL under our collaboration with Jazz. In the last quarter, we continued enrollment in the Phase I expansion study of IMGN-632 as monotherapy in patients with relapsed AML and BPD-CN, and opened an expansion cohort now enrolling patients with We also initiated combination studies with IMGN-632, 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.

We also completed enrollment in our second Mirvetuximab, plus avastin cohort impatience read recurrent ovarian cancer, regardless of platinum status in September we will report longer term data from the triplet an initial data from the doublet during 2020.

Moving to our earlier stage portfolio, we've continued to make progress with I am Gen. Six three to our anti CD 123, 80 C, which we are developing an M.L.P.P.D.C.N. and now AOL under our collaboration with jazz over the last quarter. We've continued enrollment in the phase one expansion study of I MTN six.

Three two as monotherapy in patients with relapsed AML and B P. D C N and open in expansion cohort now enrolling patients with relapsed Ll. We also initiated combination studies with I MTN sixthree to either side of the Dean and we need to clocks and relapse refractory unfit AML patients as well as a model.

Therapy cohort in patients who have minimal residual disease. Following frontline induction therapy. Lastly, we are pleased to share that for Sixthree. Two presentations will be made at ash next month, including an oral presentation and updated clinical monotherapy data in AML and B P. D. C N a poster presentation of preclinical combination.

Mark Joseph Enyedy: 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 BPD-CN, a poster presentation of preclinical combination data, and two trials-in-progress posters. In addition to the positive momentum with 6.3.2, we advanced two additional assets that demonstrate our continued innovation in ADCs. First, in collaboration with Macrogenics, the IND for IMGC 9.3.6 is planned to be filed in the first half of 2020. And second, we expect our next generation anti-folate receptor alpha ADC, IMGN 1.5.1, to enter preclinical development in mid-2020.

Data and two trials in progress posters.

Addition to the positive momentum with Sixthree too we advance to additional assets. The demonstrate our continued innovation in 80 sees first in collaboration with Macrogenics. The I'd for I.M.D.C. 936 is planned to be filed in the first half were 2020 and second we expect our next generation anti folate receptor Alpha age.

Do you see I am just had 151 to enter preclinical development and mid 2020, So overall sound progress with the portfolio this quarter in a number of important milestones in the coming month.

Mark Joseph Enyedy: 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 revenue. Operating expenses were approximately $31 million, comprised of $21 million in R&D expenses, compared with $47.2 million in the same quarter of 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 Mervituximab in the prior year period.

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 dollars in R&D expenses, compared with 47.2 million in the same quarter in 2018.

The 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 a greater activity in the forward one phase three clinical trial during the prior year period, and lower external manufacturing cost.

Driven by activity to support commercial validation of Mirvetuximab and the prior year period. In addition, we incurred a $1 million charges related primarily to retention costs, resulting from the recent restructuring and we had 9.2 million in gionee expenses compared to 8.3 million in the third quarter of 2018.

Mark Joseph Enyedy: 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 and $70 million, reflecting recognition of deferred revenue under our Jazz collaboration related to the discontinuation of IMGN-779. We also expect our operating expenses to be between $170 and $175 million, and cash at year-end to be between $170 and $175 million. With that, I'll turn the call over to Anna to review our progress with Mervituximab in more detail.

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 and $70 million, reflecting recognition of deferred revenue under our jazz collaboration related to the discontinuation of I am GE and 779 or.

Checked our operating expenses to be between 170, and 175 million and our cash at year end to be between 170, and 175 million with that I'll turn the call over to review our progress with Mirvetuximab in more detail to Ana.

Thanks, Mark first I'll briefly review the forward one data informing our decision to move forward with Mirasol and then provide some additional details for the trial.

Well, we are disappointed that forward one did not achieve its primary endpoint of progression free survival. We did observed consistent efficacy signals for mirvetuximab in the pre specified hi, folate receptor alpha subgroup with a hazard ratio of 0.69 for the primary PFS endpoint by blinded Independent review.

Anna Berkenblit: Thanks, Mark. First, I'll briefly review the Forward One data informing our decision to move forward with Mirasol and then provide some additional details about the trial. While we are disappointed that Forward1 did not achieve its primary endpoint of progression-free survival, we did observe consistent efficacy signals for Mervitoximab 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 myrvotoximab at 24% than for chemotherapy Overall survival at the time of the primary analysis was also longer in patients who received myrvotoximab 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.

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 the 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 topline 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 one and from these analyses gained important insights to inform our next steps with Mirvetuximab.

Briefly we learned that they use of a simplified scoring method to assess tumor samples for fr Alpha expression inadvertently introduced a population of patients into forward one with lower levels of Fr Alpha expression then intended.

Anna Berkenblit: While encouraging, the top-line results did not achieve the efficacy outcomes we had previously observed with mervituximab 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, we gained important insights to inform our next steps with mirvotoximab. 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 than intended. We have since rescored the patient samples from Forward1 using the method used in our phase one and two trials, which we call PS2+.

We have since we scored the patient samples from forward one using the method used in our phase one and two trial, which we call P.S., two plus and for those patients with high levels of Fr Alpha expression. Upon re scoring 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 month versus 3.2 months and a hazard ratio of 0.549.

Anna Berkenblit: And for those patients with high levels of FR-alpha expression upon rescoring, we observed efficacy outcomes for mervituximab 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 patient. To summarize the results from the exploratory analyses, compared with chemotherapy, mirvotuximab 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, Mervituximab was associated with a higher overall response rate by blinded independent review, approximately 29% versus 6% with chemotherapy. The investigator-assessed ORR was also higher for Mervituximab, namely 38%, which is more in line with what we saw in Phase 1 based on investigator-assessed ORR.

Similarly, Mirvetuximab was associated with a higher overall response rate by blinded independent review, approximately 29% versus 6% with chemotherapy.

Investigator assessed our our was also higher for Mirvetuximab, namely, 38%, which is more in line with what we saw in phase one based on investigator assessments.

These trends continue when we look at overall survival in the P.S., two plus defined fr Alpha high subset with longer median overall survival in patients who received mirvetuximab compared with chemotherapy, namely 16.4 month versus 11.4 month with a hazard ratio to 0.678.

So in summary, these exploratory analyses demonstrate the strongest treatment effect for all efficacy endpoints in the P.S. two plus 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 informed the design of our new trial called Mirasol using P.S., two plus scoring in fr Alpha high ovarian cancer patients.

Anna Berkenblit: These trends continue when we look at overall survival in the PF2 plus defined FR-alpha high subset, where the median overall survival was 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 plus defined FR-alpha high patient population. And this is how we will select patients for future myrvatoximab monotherapy trials. The results of our exploratory analyses ultimately informed the design of our new trial called MIRASOL, using PS2-plus scoring in FR-alpha high ovarian cancer patients. MIRASOL is a Phase III trial of mervituximab in which 430 patients will be randomized one-to-one to receive either mervituximab-sorabtansine or investigator's choice of single-agent chemotherapy, weakly paclitaxel, pegylated liposomal doxorubicin, or topotecan.

Mirasol is a phase three trial of Mirvetuximab in which 430 patients will be randomized one to one to receive either mirvetuximab soravtansine or investigators choice of single agent chemotherapy weekly Paclitaxel, Pegylated lysosomal doxorubicin or tell but he can.

Eligibility criteria include patients with platinum resistant ovarian cancer with high levels of Fr Alpha using the P.S. to scoring method, who had 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 New York, all with FDA and anticipate enrolling our first patients by the end of the year with a top line read out expected in the first half of 2020 too.

I'll briefly review now our progress with combination regimens in the forward to trial as mentioned, we presented encouraging initial data from the triplett cohort evaluating mirvetuximab in combination with Carboplatin and investing in earlier line patients at ESMO.

In 41 patients with recurrent platinum sensitive disease with medium or high fr Alpha expression level whoever teed up to two prior lines of therapy. The confirmed overall response rate for the triplet was 83% with a complete response rate of 17%.

Anna Berkenblit: Eligibility criteria include patients with platinum-resistant ovarian cancer with high levels of FR-alpha using the PS-2 scoring method 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 Miracle with FDA and anticipate enrolling our first patient by the end of the year, with a top-line readout expected in the first half of 2022. I'll briefly review now our progress with combination regimens in the FORWARD-2 trial. As mentioned, we presented encouraging initial data from the triplet cohort evaluating mirvotoximab 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 outcome relative to those reported in similar patient populations for other carboplatin and Bevacizumab based triplet.

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 to 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 Douglas data in platinum sensitive disease. We are interested in generating additional doublet data for carbo platinum plus mirvetuximab as the landscape in platinum sensitive settings continues to evolve and settles into a new.

New treatment paradigm, incorporating parks as maintenance in the frontline setting and then potentially that this is an NAV 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.

Anna Berkenblit: 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.

With that we'll open the call for questions.

Thank you as a reminder to ask the question do you want me to press Star one on your telephone switch all your question press the pound Keith Please standby, while we compile the came in a roster.

And our first question comes from Boris Peaker of Cowen Your line is that open.

Anna Berkenblit: 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 Mervitoximab plus Bevacizumab platinum agnostic cohort, as well as updated triplet combination data in mid-2020. Moving 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 mervituximab as the landscape in platinum-sensitive settings continues to evolve and settles into a new treatment paradigm, incorporating PARPS 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- With that, we'll open the call for questions.

Great just on the combination common she was just making.

Maybe you want to get a sense of do you plan to start novel Combo studies or is there plan to maybe advance the specific combo into a pivotal development and if so what's the potential timeline behind that.

Thanks for so we've generated encouraging data for Carboplatin, plus mirvetuximab as well as the triplet carbo Merv and Bevacizumab. So these two combinations are quite important for us as we move up into the platinum sensitive face.

And we are working on a the finalization of our plan to start a combination study next year right now our primary focus is on getting the Russell up and running a 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.

Operator: Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. And our first question comes from Boris Peaker of Cowen. The line is now open.

True maybe another question on poll and forward one just curious what fraction of patients of forward, one where pretreated with Parps will have parps prior to see or drugs or how did the PARP subgroup pretreated subgroup do relative to the non park and kind of how do you see the PARP use.

Mark Joseph Enyedy: Great, just on the combination comments you were just making, maybe you want to get a sense of whether 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?

Being in your new Phase three study.

So in forward won about 10% of patients had a prior harp remember we enrolled a forward one when parts where.

Mark Joseph Enyedy: Thanks Boris. So we've generated encouraging data for carboplatin plus mervituximab as well as the triplet carbomerv 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.

Approved in the treatment setting and we're being studied a as maintenance and the platinum sensitive setting.

How about 10% of patients had BRC, a mutations and about 10% of patients had prior PARP. We do expect that in Mirasol, a higher percentage of patients will have prior parts because of incorporation in the maintenance setting and platinum sensitive disease that being said when we looked at the subset of pay.

Operator: Thank you very much.

Anna Berkenblit: Gotcha. And maybe another question on Forward 1. I'm just curious, what fraction of patients in Forward 1 were pre-treated with PARPs or had PARPs prior to seeing your drug? How did the PARP subgroup, the pre-treated subgroup, do relative to the non-PARP group? And kind of how do you see the use of PARPs in your new Phase 3 study?

And in forward, one who had prior apart.

They benefited from Mirvetuximab over chemotherapy as did the patients who did not have prior part. So we believe mirvetuximab has a very nice activity, regardless of prior park or not.

Anna Berkenblit: 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 in 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 Mirosol, a 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 PARPs, they benefited from Mervituximab over chemotherapy, as did the patients who did not have prior PARPs. So, we believe Mervituximab has very nice activity regardless of whether you have prior PARPs or not.

Thanks for taking my questions.

Thing Yeah, and then next question comes from John Newman at Canaccord. Your line is now open.

Hi, Good morning. This is Stephens Allen on for John Newman.

I was just curious on forward one are you still planning on presenting overall updated overall survival data.

In 2020 for the population.

So we presented updated data at ESMO from an August data cut which was about six to seven months. After the initial a primary analysis.

And as you saw at ESMO. The overall survival trend for forward one continue to hold up overtime. We don't expect that to change Oh, we have not really decided yet whether or not additional presentations off for the forward. One data will be made next year because our focus now is on getting mirasol up and running well would say you know.

Operator: Thank you for taking my questions.

Anna Berkenblit: Thank you. And our next question comes from John Newman of Canicleworks. Your line is now open.

Anna Berkenblit: Hi, good morning. This is Justin Zelen on behalf of John Newman. I was just curious about Ford One; are you still planning on presenting updated overall survival data in 2020 for the population?

At some point, we'll submit this to a journal and a and at that point, we would have the updated survival data in that I am I right yeah.

Anna Berkenblit: 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 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.

Got it and I'm just I'm a diagnostic will you be working on a new companion diagnostic that will utilize the appeals to method of scoring from Airseal.

Yes, we continue to work with Ventana regarding the development of a cdx and Ventana has been with us the entire way the scoring earlier in the program on the phase one in phase two studies use the P.S. two scoring.

That we developed with Ventana and we're now working with them to make sure that the assay that will become the Cdx assay is the one we're implementing in there so.

Anna Berkenblit: I would say, you know, at some point, we'll submit this to a journal, and at that point, we will have the updated survival data in that.

Anna Berkenblit: Right, yeah. Got it. And just on the diagnostic, will you be working on a new companion diagnostic that will utilize the PS2 method of scoring from aerosol?

Got it great wall, Thanks for taking my questions.

Thank you Yeah and then next question comes from Kennen Mackay of RBC capital markets. Your line open.

Operator: Yes, we continue to work with Ventana regarding the development of a CDX, and Ventana has been with us the entire way. The scoring earlier in the program, in the Phase I and Phase II studies, used the PS-2 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.

Hi, Thanks for taking my question, maybe I was wondering if you could just help us understand the timeline to mirror Sol enrollment and tomorrow just thinking around.

Generation of be.

Stayed around the primary endpoint that our support that's expectation for.

Anna Berkenblit: Got it. Great. Well, thanks for taking my questions.

Got it and sort of.

Josh tuner tough years for sports for so I was wondering if there's any feedback from some of the clinical trial sites. That's a you'd previously had open in forward one.

Anna Berkenblit: Thank you, and our next question comes from Kenna McKay of RBC Capital Markets, and the line is now open.

Anna Berkenblit: And I was wondering if there's any feedback from some of the clinical trial sites that you previously had open in Ford One that could help with that decision-making. And then I just had a quick follow-up on trial design.

To help with that decision, making that I just had a quick follow up on jobs aren't.

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.

Anna Berkenblit: 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 in the first half of 2022. Recall that we enrolled 360 patients in under 15 months in the initial trial, and based on that, we believe that now that people largely understand the activity of mervituximab, we will be able to enroll the next trial at a faster rate. We are also working with the sites that enrolled the best in Forward I, so we know the sites that are most engaged and have the patient population.

Progression free survival, which is the primary endpoint and that gets us into topline data read out first half of 2022.

In terms of enrollment and trial sites.

Recall that we enrolled a 360 patients in under 15 months in the initial trial and based on that we believe that now that folks are largely understand the activity of mirvetuximab.

We will be able to enroll the next trial at a faster rate. We're also working with the sites that have enrolled a the best in the four would ones. So we know the sites that are most engaged in half the patient population.

Anna Berkenblit: One factor to offset that, however, to remember, is that we're focusing on FR-alpha high patients, which are about 40 percent of the population, and we are no longer enrolling medium patients, which are about 20 percent 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 on the ground.

One factor to offset that however, remember is that we're focusing on fr Alpha high patients, which are about 40% to 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 three trial with that participated in four would one every single one of them is looking forward to and is excited to participate in marisol. So we look forward to getting a quick start off the ground.

Okay. Thank you very much about maybe just revisiting some of the conversations.

Anna Berkenblit: Thank you very much for that. And maybe we should just revisit 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 the thinking around that powering? How are you handicapping the fact that this new diagnostic or biomarker is using a retrospective look at the 4.1 data? Thank you very much for taking the question. I'm looking forward to the Data Dash.

Came out of Kosmos or any other commentary you can make around the power in the middle falling into design and thinking around that.

Powering how are you handicapping, the five new diagnostics or Biomarkers using a retrospective look before one better. Thank you very much.

[laughter] better gosh.

Sure. So we have designed mirasol to target a hazard ratio of 0.7.

Anna Berkenblit: Sure, so we have designed Mirasol to target a hazard ratio of 0.7. And you may recall that Forward 1 was targeting a hazard ratio of 0.58. Now, when we looked at the Forward 1 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 PF2 plus methodology, we saw a hazard ratio of about 0.58, 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 Mirosol, targeting a hazard ratio of 0.7, given the consistency of the data that we're seeing when we use the PF2 methodology for patient selection, which is what we will be using in the Mirosol trial. I hope that was clear, because it is rather complex.

And you may recall that forward, one was targeting a hazard ratio of 0.58.

Now when we looked at the forward one 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 P.S. two plus methodology, we saw a hazard ratio of about.

Five eight <unk> 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 marisol targeting a hazard ratio of 0.7, given the consistency of the data that we're seeing a when we use the P.S. to methodology for patients.

Collection, which is what we will be using in the Marisol trial.

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

No that is.

Helpful. Thank you very much maybe just a subsequent follow ups about just as we think about this and get a retrospective <unk> looking at data and how much confidence we reached an outage in the new a bar Mark can you help us understand sort of how many different metrics you you.

Anna Berkenblit: Just as we think about this and sort of retrospectively look 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 sort of, or by how many different other means you retrospectively examined the Forward 1 data? Was this the only other sort of biomarker cut you examined because this was what you'd used in the earlier trial of Roboteximab? Or were there others that maybe didn't factor into a Phase 3 design but were a means of looking at Forward 1 data?

How many different or other means.

Retrospective examined the forward one data was this the only other.

Our marker college.

Hammond because this is what.

Earlier.

<unk>.

Remember, where there are others.

Dr. Andrew.

But.

It means of looking forward one another.

So when the forward one data read out and they were not as strong as we anticipated. That's really the first thing. We did was to take a hard look at the patient selection methodology, and we went back and.

Anna Berkenblit: So when the ForwardOne data came 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 ForwardOne, and those data are interesting. None of them rose to the level of us needing to come up with an entirely new biomarker, so Frankly, we're going back to the one that we knew previously worked.

They use the PS two again, we re scored with the PS two plus and I would not call. It a new biomarker now I would say we went back to the way we had done. It previously you know of course, we had exploratory biomarker endpoints put in for would one.

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.

Dr. Thank you very much for current and looking forward to gather gosh.

Operator: Gotcha. Thank you very much for the call. I'm looking forward to the da-da-dash.

Thank you know at our next question comes from any to see of William Blair. Your line open.

Anna Berkenblit: Thank you. And our next question comes from Andy Garcia, William Blair. Your line is now open. Great, thanks for taking my question. 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, you know, all that, all that kind of, you know, baseline properties.

Great. Thanks for taking my questions. So once the enrollment completed so I'm kind of talking about the platinum agnostic cohort.

How should we think about baseline patient characteristics.

In terms of treatment experience prior therapy.

No.

Right.

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

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 on in terms of the patients that we enrolled unlike a the prior bevacizumab combination cohort these or what.

Anna Berkenblit: 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 treatment. When we look at who actually enrolled in the trial, you know, there was a good distribution of patients with a platinum-free interval of six to nine months, nine to 12 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 get another platinum-based doublet, but these are patients for whom physicians feel a non-platinum regimen is the appropriate next step.

We call platinum agnostic. So they did not have to have platinum resistant disease in other words, they could have rickard greater than six month. After their last platinum when we look at who actually enrolled on the trial. A you know there was a good distribution to patients a with a platinum free interval of fish.

Nine months nine to 12 month, then some with a slightly longer platinum free interval, but these are not patients you know with platinum pre intervals of two years I mean that would not have been appropriate for physicians with all 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 a in the treatment landscape is evolving with more patients get impart maintenance and bad maintenance patients are doing better and there are these but there's a growing population of patients who are still technically platinum sensitive and fish physicians feel that they really need something aside from platinum because.

Anna Berkenblit: 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'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 Mervituximab plus Bevacizumab really makes a lot of sense.

Their bone marrow is getting tired and so a regimen like margetuximab plus that as isn't that really makes a lot of sense.

Got it and going back to the Airseal to sign.

Anna Berkenblit: Got it. And going back to the maricel design, I noticed that the randomization before 4-1 was 2-1, and now it's 1-1. Is there a rationale behind that?

I notice that the randomization before for one was to do one now it's one to one is there.

You know behind that.

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

Yes, so the rationale for forward one having a two to one 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 more of a tough.

And that 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.

Right, Okay that makes perfect sense okay.

Operator: Right, okay, that makes perfect sense. Okay, thanks for taking all my questions. Thank you. And our next question comes from Byron Ammon of Jeffreys. Your line is now open.

Thanks for taking my questions.

Thank you Yeah and then next question comes from Byron Ammon of Jefferies. Your line is now open.

Anna Berkenblit: Hi, thanks for taking my questions. Just on IMGN151, how does that differ from marvotuximab?

Yeah.

Hi, Thanks for taking my questions just fun I am Gen 151, how does that differentiate tomorrow, we're talking them up.

So we look forward to sharing data from our next generation folate receptor Alpha agent.

Anna Berkenblit: 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 mervitoximab, 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, you know, 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 mervitoxima Specifically, those with lower FR-alpha expression, and so we're excited about that next year.

Next year early next year and given what we know about Mirvetuximab. Our basic scientists are 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 a dress in terms of.

You know ability to bind to the target ability to dose ability to have bystander activity. So there are many features a and I would say we've done a really nice comprehensive assessment of all of the things that can be tweaked a 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.

Anna Berkenblit: Got it. And then I think at ASH you're going to have some data on IMGN 632. I think you've got an oral presentation potentially on AML and BPD-CN expansion cohorts.

Got it and then I think at Ash, you're going to have some data on I am Jan Sixthree too I think you've done all presentation.

Potentially in AML and BBCN expansion cohorts, so and I, maybe can you just talk a little bit of outside because I think that last year's ash storing the oral on it was highlighted that 60 to one into an expansion phase across four doses are those four doses still being passed it did you narrow.

Anna Berkenblit: Anna Berkenblit, Renee Lentini, Anabel Kalofonos, and Lauren White, ImmunoGen Inc

Anna Berkenblit: At last year's ASH oral, it was highlighted that 6.3.2 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?

The dose range and the expansion phase further after the actual update.

Yeah. So.

Anna Berkenblit: Yeah, so at ASH this year, we will have over twice as many patients' worth of data, both in terms of AML and BPD-CN, so we have been working very hard this year to understand the optimal dose and schedule. You may recall last year we 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 dose and schedule we would move into combination, and that's 0.045 mg per kg, and that's the dose of IMGN-632 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.

Actually this year, we will have over twice as many patients worth of data both in terms of AML and B P. D. C. N. A so we had been working very hard this year to understand the optimal dose and schedule. You may recall last year, we had presented data from a Q3 weeks schedule, a as well as a weekly schedule.

And since then we've generated additional data that allowed us to choose the dose and schedule, we would move into combination and that's 0.4 or five minutes per keurig announced the dose of I MTN 62 that we're combining with Venetoclax in Asia, citing in the trial, that's up and running now on we are.

Also exploring a one additional dose level of the Q3 weeks schedule to get additional data and we look forward to sharing all the data that we have at ash.

Operator: And our next question comes from Jessica Five, JPMorgan. Your line is now open. Hi, this is Daniel. Following on Barry's question, should we expect any new data with the ASH abstracts for IMGN 632?

Great. Thank you.

Thank you and then next question comes from Jessica Five JP Morgan Your line is that open.

Hi, This is Daniel Thanks for taking my question. Following on bearings question actually we expect any new data with the ash abstracts for GE and 62.

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

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

So maybe yet.

Anna Berkenblit: Alright, so maybe I was more specifically asking in the abstract: do we expect new data, or should we just expect new data to be presented in the presentations?

I was more specifically asking the abstract we expect you data or should we just expect than you do not to be presented.

'cause patients.

Anna Berkenblit: 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'll have the most recent data.

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 we'll have additional patients worth of data and then at Ash will have the most recent data.

Anna Berkenblit: And then just one more, given the recent advances in the standard of care for BPDCM, could you elaborate on the developmental pathway that you guys are thinking of for 632 in that indication?

Got it and then just one more given the recent advances in the standard of care for PPPC and could you elaborate on the developmental pathway that you guys are thinking all 460 commitment that indication.

Sure. So bpd CNN is a very rare a very aggressive hematologic malignancy for which until recently there were no approved therapies ER physicians used aggressive they ml regimens Ll regimens and nothing works, particularly well since then however stemline.

Anna Berkenblit: Sure, so BPD-CN is a very rare, very aggressive hematologic malignancy for which until recently there were no approved therapies. Physicians used aggressive AML regimens, and ALL regimens, and nothing worked particularly well.

Anna Berkenblit: Since then, however, Stemline has gotten SL-401 or L-zonerase approved specifically for BPD-CN. 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-L-zonerase and also in the upfront setting.

And has gotten SL for a one where else nonres approved us specifically for BP DCN its targets CD 123, with a diphtheria toxin conjugate on did theory toxins I have some challenges, particularly in terms of Ah our bodies, making antibodies against the did theory a toxin condo.

We get 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 Syria toxin physicians are not entirely satisfied with its ability to meet the unmet need in this population. So they're there remains an unmet need both in the relapse refractory setting postal's Andreas and also a in the upfront setting.

Anna Berkenblit: Our agent demonstrated activity already at ASH last year in the post-L-zonerase setting for BPD-CN 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'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 full approval.

Our agent has demonstrated activity already at Ash last year in the post sales on resetting for BP DCM 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 you know we're working on what the bargains, but we think it will be a potential option for accelerated approval for us based on single arm data.

And potentially nickel approval.

Operator: Great, thank you very much. Thank you, and our next question comes from Jonathan Chang of SCB Laring. Your line is now open.

Great. Thank you very much.

Thanks, Yeah, and then next question comes from Jonathan Chang of I see Sep Larry signs that open.

Anna Berkenblit: Hi, good morning, guys. This is David Rouche on for Jonathan. Just to go back to the first question on PARP use and its impact on mirosol patients. Specifically, given that only 10% of 401 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?

Hi, Good morning, guys. This is David room, Sean for Jonathan.

To go back to the first question on par abuse and its impact on Marisol patient.

Specifically given that only 10% of forward on patients had a PARP do you think that earlier line use of parts could result in a predominant for patients and either earlier or later lines of therapy.

Anna Berkenblit: Yes, we do!

Yeah.

We do so I don't know about the predominance part right I mean, if you think about segmentation here for a second we look at the data that just a were published at ESMO. What you see is profound activity from the PARP inhibitors in the maintenance setting, particularly those patients.

Anna Berkenblit: Right. So, I mean...

Anna Berkenblit: If you think about it...

Anna Berkenblit: 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 to the totality of that patient population, you get to about half of the patient population. The benefits of the PARP inhibitors in BRCA wild-type patients or HRD-negative patients are, you know, I think the clinicians there are going to be balancing risk-benefit using PARP inhibitors there. So, you know, I do think that you're going to see, you know, half of the early-line patients using PARP inhibitors. And you know, 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 inhibitors, 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?

Braca mutations.

And those with homologous recombination deficiency, and though when you add that the totality that patient population that you got to about half of the of the patient population the benefits of the PARP inhibitors, and Braca wild type patients or HR de negative patients.

It is you know I think the conditions there are going to be balancing risk benefit using PARP inhibitors. There. So I do think that you're going to see you know half of the early line patients using a PARP inhibitors.

You know as I say when we look at the data that we have not only from four three but some of our combination studies to we now see PARP inhibitor or pay prior apart using those patients and we don't see it having an impact on the activity or the safety of murph.

Prior apart treated patients.

So helpful.

Anna Berkenblit: Yeah, that's really helpful. I appreciate that.

Yeah, that's really helpful. I appreciate that and is that something we could expect to see stratified and a and b.

Anna Berkenblit: And is that something we can expect to see stratified in the Marist Health Study?

Anna Berkenblit: So, we do have stratification factors in the mirosol study, specifically lines of therapy and choice of chemotherapy. But I can assure you that there was a lot of discussion around whether or not we should stratify for prior PARP use or BRC 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%, 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've pre-specified to look at.

Yeah.

So there we do have stratification factor is in the Mirasol study specifically lines of therapy in choice of chemotherapy or I can assure you that would there was a lot of discussion.

Around.

Whether or not we should stratified for prior part views or BRC mutations or age I'd for that matter on we've consulted a lot of our okay well both in the U.S. and Europe .

And ultimately we decided not to stratify as Mark mentioned, we expect 50% maybe 40% of patients on to have a prior part 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.

Operator: Great. Thank you for all the colors.

Great. Thank you for for all the color there.

Second question really quick could you just provide any additional color on the discussions with.

Anna Berkenblit: 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. 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, although assuming that we collect and hold the scans for the blinded independent review for any necessary

Specifically around the use of investigator assessed versus the centrally red criteria.

I think this was asked about on the last call, but you had met with them yet so.

Just wanted to come from kind of what there what the responsible for that.

Yeah, we had the opportunity to discuss the key design elements with half the a and they did agree that PSS by investigator assessment is an acceptable primary endpoints from aerosol.

Assuming that we collect and hold the scans for the blinded independent review for any necessary on it.

Anna Berkenblit: Sensitivity analysis as well.

Statistical analysis heavy analysis as well.

Anna Berkenblit: 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?

Okay awesome, great and.

Last one from me.

How do you view 62 as differentiated from some of the other CD went 23 players in the space.

Anna Berkenblit: So, we talked a little bit already about Alzheimer's, it being a diphtheria toxin conjugate with some liabilities, including capillary leak and antibodies generated against it. So that's one.

[laughter] so.

We talk a little bit already battles andras, it being a dip Syria toxin conjugate with some liabilities, including capillary leak and antibodies a generated against it so.

So that's one the other compounds that are in development includes some bi specifics toward CD 123 for example, a macrogenics flooded tusa Mab you know these bi specifics they have activity for sure a and they have some challenges in terms of the need for a long infusion durations and cytokine release.

Anna Berkenblit: The other compounds that are in development include some bispecifics towards CD123, for example, macrogenic flotatuzumab. You know, these bispecifics 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 BioCAR-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. But 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 colors of the different agents out there.

<unk>.

Then there's the car T targeting PD 123, like other Mustang Bio party and as you know cartoons when they work worked beautifully and they're not for every patient a and there are some reimbursement challenges there I think our C. D. A 123 directed 80 see that's given intravenously as it.

Brief Ivy infusion in the clinic had some real advantages. So that gives you a a sense of the color of the different agents out there.

Operator: Great, thank you so much, and I look forward to seeing you at ASTRO.

Great. Thanks, so much and I look forward to see your dash.

Great.

Operator: Thank you. And again, ladies and gentlemen, if you do have a question at this time, please press star then 1 on your touchtone telephone. Our next question comes from Michael Schmidt of Guggenheim Securities. Your line is now...

Thank you, yeah, and again, ladies and gentlemen, if you do you have a question at this time. Please press Star then one I touched on telephone. Our next question comes from Michael Schmidt of Guggenheim Securities. Your line is that open.

Michael Werner Schmidt: Hey, good morning, and thanks for taking my questions. I had a couple on IMGN-632.

Hey, good morning, and thanks for taking my questions I had a couple on I am Gen six three too.

Maybe first regarding be PBC and I was wondering if I know it's so early in the program, but I was just wondering if you already had any kind of ask interactions with respect to the.

Anna Berkenblit: Maybe first regarding BPD-CN. I was wondering if, I know it's still early in the program, but I was just wondering if you had 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. I know we have not discussed this with FDA yet. Okay, and would you initially go into root-of-the-fractory patients or newly diagnosed BPD-CN? I think the Stemline product may have a label for both, but I'm not 100% sure.

Pivotal trial requirements for example, what what how many patients worth of data would be required for example up for a beep DCN.

Yes.

I now we have not discussed this with 58 yet.

Okay and would you initially go into it up to Frac fleet patients on newly diagnosed BPC, yet I think the Stemline product may have a labor for both but I'm not sure.

Anna Berkenblit: Yes. StemLine has a label for both, and in one of those subsets, two out of 13 patients in the relapsed refractory setting had what they considered a response, a 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 raise a really good point, and we're looking forward to gathering proof-of-concept data that will enable us to engage with FDA to have a discussion about what it would take for approval.

Yes, Donlin has a label for both and in one of those subsets. It was two out of 13 patients in the relapse refractory setting had a what they considered a response to see our CRC. So I think the bar is quite low in the relapsed refractory setting in the frontline setting their CRC our fee rate was higher but again it was a small.

Oh, a group of patients. So we actually are in the process of a amending our study to allow frontline patients who are unfit for standard of care available therapy. So you raise 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.

Anna Berkenblit: Okay, and how many patients with BPD-CN will be included in the ASH update?

Okay, and how many patients with BP DCN will be included in the Ash update.

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

Over twice as many as last year.

After there were three.

Anna Berkenblit: Okay. All right. The other question I had was about the irrationality of combined 632 with VDASA and Venplexa in relapsed refractory AML patients as opposed to frontline, and how should we think about the activity of these agents after they've potentially been used already in patients? [inaudible]

Okay, [laughter] [laughter] alright.

The other question I had just maybe talk a little bit about the irrationality combined 632 with me days sign Venclexta in that we'd have to frac three AML patients as opposed to frontline and how should we think about activity of these agents after they've potentially being used already.

The previously in patients.

Combination.

Anna Berkenblit: Sure, so the dose escalation part of the study, you know, when we're just beginning, will be in the relapsed refractory unfit population. And we're starting off somewhat cautiously, I would say, because Venasa is not necessarily an easy regimen for patients.

Sure. So the dose escalation a part of the study a you know when we're just beginning a will be in the relapsed refractory unfit population and we're starting off a somewhat cautiously I would say because then the Asia is not necessarily an easy regimen for patients. So we will be.

Anna Berkenblit: So we will be doing doublets of 6-3-2 plus venetoclax and doublets of 6-3-2 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 doublets initially will be based on, you know, treatments that they have 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.

Doing doublet.

Sixthree, two plus the need to clocks and doublet of 632, plus eight deciding and once we've established basic safety. We will then move to the triplet and so the patients that physicians will choose a for each of those doublets. Initially will be based on you know therapies that they had previously but ultimately certainly we'd be interested in movie.

This triplett up into the frontline setting, but we have to start first generating safety data and then appropriate population.

Anna Berkenblit: And then, you know, potentially having a quite substantial phase one data set for 632 by year end, I guess, how should we think about the efficacy bar to move this into pivotal studies, potentially?

Understood and then.

Just looking at you potentially having up quite substantial phase one data set for 62 by by year end I guess, how should we think about the efficacy bar.

To to move this into pivotal studies potentially.

So the dataset will be sharing at ash is a monotherapy and you know in the relapse refractory ore relapse setting the bar for CR rate is really around 30% I would say you know sixthree to has nice activity as a monotherapy in what we're doing based on the data we've seen thus far is.

Anna Berkenblit: So the data set we'll be sharing at ASH is monotherapy. And, you know, in the relapsed refractory or relapsed setting, the bar for CR rate is really around 30%. I would say, you know, 632 has nice activity as monotherapy.

Anna Berkenblit: 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 combinations. So these MRD-positive AML patients are patients who've had induction therapy and now are in CR, but they have minimal residual disease present. And we know those 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 IMGN 632 to convert patients from MRD-positive to MRD-negative with the idea that that could ultimately really benefit patients. So that is another option for advancing monotherapy from a registration perspective.

We have opened up an m. R&D positive monotherapy cohort in the study that were just opening with the combinations. So this MRT positive AML cohort are patients who had induction therapy.

And now our NCR, but they have minimal residual disease present on and we know the patients do not do very well so.

So we have a cohort again it just opened up and is is enrolling that we we'll be looking.

At the ability as monotherapy I am G.N. sixthree two to convert patients from MRT positive to NRG negative.

The idea that that ultimately could really benefit patients. So that is another option for for advancing monotherapy.

From a registration perspective potentially.

Anna Berkenblit: And would this MRD-positive patient population, would there be an alternative to relapsed refractory, you know, a label for that indication, or not?

What this MRV positive patient population would that be an alternative to relapse refractory.

Labeling out indication or a it's another option that's right.

Anna Berkenblit: It's another option; that's right.

Anna Berkenblit: Understandable. Thank you. And, right, I guess, and what is the size of that patient population, potentially, the MRD positive AML subset? (inaudible)

Just a.

And.

Right I guess and what is the size of the that patient population potentially the MRT positive ammo subset.

[noise] and.

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

Anna Berkenblit: I will have to get back to you on that, but it is about 50 percent of the patients who go into CR. Again, it depends a little bit on what the molecular subtype of AML is.

Anna Berkenblit: Okay. Okay. Thank you. That's very helpful. I really appreciate it. I'm looking forward to the ASH abstract then.

Huh.

Okay. Okay.

Okay. Thank you know that's very helpful. I really appreciate it out looking forward to the ash abstract that next week.

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

Thanks, Yeah.

Question comes from Joe Cousins era of Piper Jaffray. Your line is open.

Anna Berkenblit: Great. Thanks for taking the time to answer 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 to investigator, the hazard ratio kicks up ever so slightly. So just wondering what your considerations were to use investigator assessment for Mirasol? Is it simply that the turnaround time is quicker, or are there other things that you think?

Great. Thanks for taking the question I just wanted to follow up quickly on the on the blinded centre of universe investigator assessed and so if we look at the P. has to re scoring 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 use investigator assessments for near Saul is it simply the turnaround time is quick or are there other things that are being considered there.

Yeah. So there's there's a few things that are being considered.

Anna Berkenblit: Yeah, so there's a few things that are being considered. Investigator assessment is what investigators typically use, you know, 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 that, in fact, is required for study entry. The blinded independent review may not necessarily see that, and so that makes it challenging then to look at the overall response rate, et cetera.

Investigator assessment is what investigators typically use you know in their day to day real life treatment of patients.

I would say there there was a shift previously toward on 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 I'm one of the issues with blinded independent review is that.

The investigator may see a measurable disease on the baseline scan that in fact is required for study entry blinded independent review may not necessarily see that and so that that makes it challenging then to look at an overall response rate et cetera, I would say you know the difference in hazard ratio that you're pointing out it's like 0.5.

Anna Berkenblit: I would say, you know, 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 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 this study for.

I have four nine versus 0.61 remember that these are post hoc 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 bobl a in the or some noise in the dataset, but remember both of these hazard.

Ratios are well below the 0.7 that we have designed the study for.

Anna Berkenblit: Okay, great. That's helpful. And then just one last one. So you mentioned you were thinking about other platinum-sensitive combinations to explore. If we think about the combinations that you've explored thus far, it seems like the only Unknown Executive, Swayampakula Ramakanth, Dingding Shi, Boris Peaker, Etzer Darout, Disclosure at this time.

Okay, Great. That's helpful. And then just one last one so you mentioned you're thinking about other platinum sensitive combinations to explore it.

If we think about the combination that you explore thus far it seems like the only.

Obvious one at this PARP inhibitors is that a combination approach you're you're considering are there other combinations that you can you disclose at this time.

Yes, so we there's an I.S.T. ongoing combining mirvetuximab went through a cap read in I would say heavily pretreated patients.

Anna Berkenblit: Yeah, so there's an ongoing study combining Mervitoximab with Rucaparib in, I would say, heavily pretreated patients. But 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 generated from a preclinical proof-of-concept perspective were for Mervitoximab 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.

From a biological on 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 a from a preclinical proof of concept perspective, a was four mirvetuximab with carboplatin and with Bevacizumab. Those data are published and we now have you know 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.

Okay, great. Thanks for taking my question.

Operator: Okay, great. Thanks for taking my questions.

Mark Joseph Enyedy: 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.

Thank you know and ladies and gentleman I stuff in your question answer session I'd now like to turn the conference back over to Mark and then de for any closing remarks.

Mark Joseph Enyedy: Thank you very much. I appreciate your time this morning.

Thank you very much appreciate your time. This morning, you know after a difficult moment in June restructuring the business, we've really puts immunogen on a path forward. We've built momentum in a in the business and are looking forward to a strong finish to the year and a productive 2020 and so we.

Operator: You know, 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.

I look forward as many of you mentioned the scene you all at a at Ash in December Thanks again.

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

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

Operator: BF-WATCH TV 2021