Q4 2019 Earnings Call

Good morning, and welcome to managing fourth quarter and full year 2019 financial operating results Conference call. Today's conference is being recorded.

Operator: Good morning, and welcome to ImmunoGen's fourth quarter and full year 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 Okonik, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

I like to turn the call over to Port Neal Connie Senior director of corporate Communications and Investor Relations. Please go ahead.

Good morning, and thank you for joining today's call.

Courtney Okonik: 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 fourth quarter and full year 2019 financial results. This press release and a web stream of this call can be found in the Investors and Media section of our website at ImmunoGen.com. With me today are Mark Enyedy, our President and CEO, and Anna Berkenblit, our Chief Medical Officer. Theresa Wingrove, our Senior Vice President

Earlier today, we issued a press release. It includes a summary of our recent progress and fourth quarter and full year 2019 financial result.

This press release of the web stream of this call can be found under the investors and media section of our website at Immunogen Dotcom with me today are mark entity, our president and CEO and in a broken but our chief Medical officer treat the wingrove, our senior Vice President of regulatory affairs, and quality and Dave Foster our Chief Accounting Officer will also join us for two and aim there.

Courtney Okonik: Our Chief Accounting Officer will also join us for Q&A.

Courtney Okonik: We will review key accomplishments for the business over the last 12 months, our financial results, and 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.

On today's call will review key accomplishments for the business over the last 12 month, our financial adult an 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 S easy filings and with that I'll turn the call over to Mark. Thanks, Gordon and good morning, everyone and thank you for joining us today and our comments. This morning, and then I will recur.

Mark Joseph Enyedy: Thanks, Courtney. Good morning, everyone, and thank you for joining us today. In our comments this morning, Anna and I will recap our progress over the last 12 months and then highlight the milestones we anticipate for a productive year ahead. 2019 was a challenging year for us. As we reported in March, the phase three study for our lead program, Mervituximab, did not meet the primary endpoint. Since then, we have restructured the business to reduce our costs, prioritized our portfolio to focus on our most promising programs, and worked closely with FDA to define an accelerated path to approval for Mervituximab in ovarian cancer. With the benefit of these steps, we've emerged with strong prospects for ImmunoGen as we move into 2020. In particular, looking at the business today, the data we've generated from the phase three study of Mervituximab give us a clear view of which patients benefit most from Mervituximab and how best to identify those patients. This, in turn, gives us confidence that our next studies with Mervituximab will produce positive outcomes. To this end, we have aligned with FDA that a single-arm study in women with folate receptor alpha-high platinum-resistant ovarian cancer who've been previously treated with Avastin could support accelerated approval.

Cap our progress over the last 12 months and then highlight the milestones we anticipate for a productive year ahead.

2019 was a challenging year for us as we reported in March the phase three study for our lead program Mirvetuximab did not meet the primary endpoint. Since then we have restructured the business to reduce our cost prioritized our portfolio to focus on our most promising programs and work closely with F.D.A. that define an accelerated path.

[music] approval for Mirvetuximab in ovarian cancer with the benefit of these steps we've emerged with strong prospects for immunogen as we move into 2020 in particular looking at the business today. The data we've generated from the phase three study of Mirvetuximab give us a clear view of which patients benefit most from Mirvetuximab.

And how best of identify those patients. This in turn gives us confidence that our next studies with Mirvetuximab will produce positive outcomes to this end we have aligned with F.D.A. that a single arm study in women with folate receptor Alpha high platinum resistant ovarian cancer who've been previously treated with Avastin could support accelerated.

Approval, we call. This study survey and expect to enroll the first patient this quarter with top line data anticipated in mid 2021, followed by a B L. A submission in the second half of 2021, and a potential approval and 2022 beyond the first approval, we have ongoing studies to expand the potential indications from.

Mark Joseph Enyedy: We call this study SEREA and expect to enroll the first patient this quarter, with top-line data anticipated in mid-2021, followed by a BLA submission in the second half of 2021 and a potential approval in 2022. Beyond the first approval, we have ongoing studies to expand the potential indications for Mervituximab with additional data this year. Our portfolio also includes three additional programs targeting a range of tumor types in both hematological malignancies and solid tumors, each with important milestones this year, which I'll cover in a moment. From a financial perspective, we ended 2019 with just over $175 million in cash on the balance sheet. We recently completed an upsized follow-on offering that generated roughly $98 million in net proceeds. We will provide detailed guidance later in the call, so suffice it to say that this cash position will allow us to advance our portfolio through material inflection points, including the initial approval of Mervituximab.

Mirvetuximab with additional data this year. Our portfolio also includes three additional programs targeting a range of tumor types in both haematological malignancies in solid tumors, each with important milestones this year, which I'll cover in a moment from a financial perspective, we ended 2019 with just over 175.

Million in cash on the balance sheet. We recently completed an upsize follow on offering the generated roughly $98 million in net proceeds we will provide detailed guidance later in the call. So suffice it to say that this cash position will allow us to advance our portfolio through material inflection points, including the initial approval of Mirvetuximab.

Bob.

Mark Joseph Enyedy: With this combination of assets and an experienced management team, we are well positioned to execute on our strategy and generate significant value, both short and long term. As a reminder, we have set three strategic priorities for the business. First, obtain initial approval for mervituximab as monotherapy in platinum-resistant ovarian cancer and then look to expand into earlier lines of therapy. Next, accelerate our early-stage portfolio with an emphasis on our program in hematological malignancies. And finally, expand our reach, gain access to complementary capabilities, and strengthen our financials through partnering. We have made significant progress with each of these priorities and expect continued momentum as we head into 2020, with a number of important milestones this year. These include, for mervituximab, opening the SREA trial in the first quarter, continuing to enroll patients in our confirmatory phase III mirosol trial, and presenting data from our platinum-agnostic and platinum-sensitive combination studies.

With this combination of assets in an experienced management team, we are well positioned to execute on our strategy and generate significant value both short and long term as a reminder, we have set three strategic priorities for the business first obtained an initial approval for mirvetuximab as monotherapy in platinum resistant ovarian cancer.

And then look to expand into earlier lines of therapy next accelerate our early stage portfolio with an emphasis on our program in Hematological malignancies, and finally expand our reach gain access to complementary capabilities and strengthen our financials through partnering we've made significant progress with each of these price.

Ladies and expect continued momentum as we head into 2020 with a number of important milestones. This year. These include for Mirvetuximab opening this array of trial in the first quarter continuing to enroll patients in our confirmatory phase three marisol trial, and presenting data from our platinum agnostic and platinum sensitive combination.

In studies for our program in Hematological malignancies, we continued to advance I am Gn sixthree too in the clinic and expect to present monotherapy data and B P. D C N and MRT positive ammo along with combination data in M.L. at Ash later this year for a preclinical programs, we expect to file an I.M.D.

Mark Joseph Enyedy: For our program in hematological malignancies, we continue to advance IMGN 632 in the clinic and expect to present monotherapy data in BPD-CN and MRD-positive AML, along with combination data in AML, at ASH later this year. For our preclinical programs, we expect to file an IMD for IMGC 936, our novel ADAM9 targeting ADC, during the first half of the year, and to advance IMGN 151, our next generation FR-alpha targeting ADC, into preclinical development.

Before I am GC 936, our novel, Adam nine targeting AIDC during the first half of the year and to advance I am G.N. 151, our next generation fr Alpha targeting AIDC into preclinical development. So an exciting year ahead, turning to our financials. The details are covered in the press releases.

Mark Joseph Enyedy: So an exciting year ahead. Turning to our financials, the details are covered in the press release issued this morning, so just a few summary results. For the full year 2019, we generated $82.3 million in revenue, comprised of $47.4 million of non-cash royalty revenues and $34.8 million from license and milestone fees, of which $15.2 million in related cash will be received in 2020. Operating expenses were $174.4 million, comprised of $114.5 million in R&D expenses, compared to $174.5 million in 2018. This $60 million decrease was driven by lower expenses, resulting from the restructuring of the business at the end of the second quarter of 2019 and the closing of our manufacturing facility at the end of 2018. Lower external manufacturing costs due to the activity to support commercial validation of mervituximab in the prior year, and decreased clinical trial expenses driven by lower activity in the 4.1 Phase III clinical trial.

This morning, So just a few summary results for the full year 2019, we generated $82.3 million in revenue comprised of 47.4 million of noncash royalty revenues and 34.8 million from license and milestone fees of which 15.2 million in related cash will be.

Received in 2020.

Operating expenses were 174.4 million comprised of 114.5 million in R&D expenses compared to 174.5 million in 2018. This $60 million decrease was driven by lower expenses, resulting from the restructuring of the business at the end of the second quarter of.

2019, and the closing of our manufacturing facility at the end of 2018, lower external manufacturing costs do the activity to support commercial validation of Mirvetuximab in the prior year and decreased clinical trial expenses driven by lower activity in the forward one phase III clinical trial DNA expenses were.

38.5 million compared to 36.7 million in 2018, primarily due to higher allocation of facility related expenses for excess laboratory and office space, resulting from the restructuring. In addition, we incurred a $21.4 million restructuring charge in 2019.

Mark Joseph Enyedy: G&A expenses were $38.5 million, compared to $36.7 million in 2018, primarily due to higher allocation of facility-related expenses for excess laboratory and office space resulting from the restructuring. In addition, we incurred a $21.4 million restructuring charge in 2019. We ended the year with $176.2 million in cash on the balance sheet. As I mentioned earlier, we strengthened our cash position with an upside follow-on offering, which added approximately $98 million in net proceeds to our balance sheet. In terms of financial guidance for 2020, we expect revenues to be between $60 and $65 million, our operating expenses to be between $165 and $170 million, and our cash at year-end to be between $170 and $175 million. We expect that our current cash, inclusive of the proceeds of the follow-on offering and anticipated cash receipts from partners, will fund our operations into the second half of 2022. With that, I'll turn the call over to Anna to review our pipeline progress in more detail. Anna?

We ended the year with 176.2 million in cash on the balance sheet as I mentioned earlier, we strengthened our cash position with an upside follow on offering which added approximately $98 million a net proceeds to our balance sheet.

In terms of financial guidance for 2020, we expect revenues to be between 60, and 65 million our operating expenses to be between 165, and 170 million and our cash at year end to be between 170, and 175 million, we expect that our current cash inclusive of the proceeds of the fall.

Oh on offering and anticipated cash receipts from partners will fund our operations into the second half of 2022 with that I'll turn the call over to enter to review our pipeline progress in more detail Anna Thanks, Mark first I'll review, Syria, and Mirasol and will then provide details on our presentations at ash.

Threat and Mirasol as part of the productive dialogue last year ft advised us that a new single arm trial in patients with platinum resistant ovarian cancer could support accelerated approval for Mirvetuximab provided that overall response rate and duration of response surpass those of the best available therapy at the time of.

Anna Berkenblit: Thanks, Mark. First, I'll review Soraya and Mirasol, and we'll then provide details on our presentations at ASH. As part of a productive dialogue last year, FDA advised us that a new single-arm trial in patients with platinum-resistant ovarian cancer could support accelerated approval for mirvotoximab, provided that overall response rate and duration of response surpass those of the best available therapy at the time of regulatory action. As part of this guidance, FDA said that the relevant benchmark for currently available therapy is a 12% overall response rate. Based on this feedback, we will begin enrolling patients in SIREA this quarter.

Regulatory action.

As part of this guidance F.D.A. advised that the relevant benchmark for currently available therapy is a 12% overall response rate.

Based on this feedback we will begin enrolling patients in Serbia. This quarter, Syria is a pivotal single arm trial evaluating mirvetuximab monotherapy in approximately 110 women with platinum resistant ovarian primary personnel or fallopian tube cancer that is fr Alpha high as measured by.

Yes, two plus scoring who had been previously treated with bevacizumab.

We have reviewed the data generated from our previous trials with mirvetuximab, including a pooled post hoc analysis of our phase three forward one trial using a P.S. two plus we scoring method to assess tumor samples for fr Alpha expression, along with patients from phase one and have identified 70 patients, whom we build.

Anna Berkenblit: SIREA is a pivotal, single-arm trial evaluating myrvotoximab monotherapy in approximately 110 women with platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer that is FR-alpha high as measured by PS2 plus scoring and who have been previously treated with bevacizumab. We have reviewed the data generated from our previous trials with Mervituximab, including a pooled post-hoc analysis of our Phase 3 Forward 1 trial using a PS2 Plus rescoring method to assess tumor samples for FRAlpha expression, along with patients from Phase 1, and have identified 70 patients whom we believe would have met the key eligibility criteria for psoriasis. Each has platinum-resistant ovarian cancer with FR-alpha high expression and received one to three prior lines of therapy, including prior bevacizumab. Based on an analysis of these 70 patients, the overall response rate was 31.4%, with a median duration of response of 7.8 months.

Leave would have met the key eligibility criteria for Cerenia.

Each has platinum resistant ovarian cancer with Fr Alpha high expression and received one to three prior lines of therapy, including prior Bevacizumab.

Based on an analysis of these 70 patients. The overall response rate was 31.4% with a median duration of response, a 7.8 month.

We believe that these data compare favorably to the response rate seen with single agent chemotherapy in platinum resistant ovarian cancer, which was 11.8% in the or really a trial and 12.2% in the core rail trial, both of which included patients naive to and previously treated with Bevacizumab.

As Mark mentioned, we expect to report topline data from Syria in mid 2021, and if positive submitted an application for accelerated approval of Mirvetuximab based on these data during the second half of 2021.

Anna Berkenblit: We believe that these data compare favorably to the response rate seen with single-agent chemotherapy in platinum-resistant ovarian cancer, which was 11.8% in the Aurelia trial and 12.2% in the Corail trial, both of which included patients naive to and previously treated with bevacizumab. As Mark mentioned, we expect to report top-line data from Soraya in mid-2021 and, if positive, submit an application for accelerated approval of mervituximab based on these data in the second half of 2021. Moving to Mirosol, you may recall following the results of our Phase 3 Forward 1 study, we conducted exploratory analyses to assess the factors that may have contributed to a negative statistical outcome in Forward 1. We identified what we believe to be the key factors and designed Mirasol accordingly to improve the probability of technical success, including reverting to the original PS2 plus scoring method to select those patients most likely to benefit from mirvotoximab.

Moving to Mirasol you may recall following the results of our phase three forward. One study we conducted exploratory analyses to assess the factors that may have contributed to a negative statistical outcome and forward one.

We identified what we believe to be the key factors and designed to Mirasol accordingly to improve the probability of technical success, including reverting to the original PS two plus scoring method to select those patients most likely to benefit from Mirvetuximab.

Myris all will enroll approximately 430 patients with folate receptor alpha high platinum resistant ovarian cancer, who have been treated with up to three prior regimens.

Patients will be randomized one to one to receive mirvetuximab or and investigators choice of chemotherapy Paclitaxel Pegylated, liposomal doxorubicin or tell but he can.

The primary endpoint is PFS by investigator and the secondary endpoints are overall response rate overall survival and patient reported outcomes.

If we receive accelerated approval for Mirvetuximab based on the results of Cerenia, we expect that Mirasol would serve as a confirmatory trial to support full approval of Mirvetuximab.

Anna Berkenblit: Mirasol will enroll approximately 430 patients with folate receptor alpha-high platinum-resistant ovarian cancer who have been treated with up to three prior regimens. Patients will be randomized one-to-one to receive mirvotoximab or an investigator's choice of chemotherapy, paclitaxel, pegylated liposomal doxorubicin, or topotecam. The primary endpoint is PFS by investigator, and the secondary endpoints are overall response rate, overall survival, and patient-reported outcomes. If we receive accelerated approval for Mervituximab based on the results of SOREA, we expect that Mirasol will serve as a confirmatory trial to support full approval of Mervituximab. We look forward to continuing enrollment in Mirasol this year and expect to report top-line data in the first half of 2022.

We look forward to continuing enrollment in Myris, all this year and expect to report topline data in the first half of Twentytwenty too.

In parallel we continue to advance our combination cohorts with Mirvetuximab as we look to move this drug into earlier lines of therapy.

We anticipate presenting updated data from our phase one the forward to platinum agnostic doublet cohort evaluating mirvetuximab in combination with Avastin ASKO this year and updated data from our platinum sensitive triplett cohort evaluating mirvetuximab in combination with Carboplatin and have asked.

In the fall.

Lastly, we plan to initiate in mid 2020, an additional study in platinum sensitive disease evaluating mirvetuximab in combination with Carboplatin. This will be an investigator sponsored trial in over 100 patients randomizing them to either the Mirvetuximab carbo, platen combination or and investigators choice.

Anna Berkenblit: In parallel, we continue to advance our combination cohorts with mervitoximab as we look to move this drug into earlier lines of therapy. We anticipate presenting updated data from our Phase 1b-2 Platinum Agnostic Doublet Cohort, evaluating Mervituximab in combination with Avastin at ASCO this year, and updated data from our Platinum Sensitive Triplet Cohort, evaluating Mervituximab in combination with Lastly, we plan to initiate, in mid-2020, an additional study in platinum-sensitive disease evaluating mervituximab in combination with carboplatin. This will be an investigator-sponsored trial in over 100 patients, randomizing them to either the mervituximab-carboplatin combination or an investigator's choice carboplatin-based regimen. I'll now briefly review our progress with our early stage portfolio.

Carbo platinum based regimen.

I'll now briefly review our progress with our early stage portfolio.

At Ash, we presented updated safety and efficacy findings from the dose escalation and expansion of our phase one study of I MGM 632 in patients with relapsed or refractory AML NBP DCN.

I am Gn Sixthree too is the CD 123 targeted AIDC that deploys, our most potent IDN payload and the updated findings demonstrated anti leukemia activity across all of those dose levels tested along with a well tolerated safety profile and activity at doses up to and including zero point.

Anna Berkenblit: At ASH, we presented updated safety and efficacy findings from the dose escalation and expansion of our Phase I study of IMGN632 in patients with relapsed or refractory AMLs and BPDCM. IMGN 632 is a CD123-targeted ADC that deploys our most potent IgN payload, and the updated findings demonstrated anti-leukemia activity across all those dose levels tested, along with a well-tolerated safety profile and activity at doses up to and including 0.09 mg per kilogram per cycle. We have selected a recommended dose and schedule for phase two and believe that the anti-tumor activity, favorable tolerability, and the convenience of a short infusion reinforce the ongoing expansion of IMGN-632 monotherapy in BPD-CN, AML, and ALL. Additionally, we initiated our IMGN-632 combination trial with azacitidine and venetoclax in relapsed and frontline AML, as well as IMGN-632 as a monotherapy in minimal residual disease positive AML patients. We look forward to continuing patient enrollment in 2020 and sharing data at ASH. With that, I'll turn the call back over to Mark for some closing remarks.

Zero nine milligrams per kilogram per cycle.

We have selected a recommended dose and schedule for phase two and believes that the anti tumor activity favorable tolerability and the convenience of a short infusion reinforce the ongoing expansion of I am GE and 632 monotherapy NBP DCN AML and AOL. Additionally, we initiated.

Our I MGM Sixthree, two combination trial with a society and Venetoclax in relapsed and frontline AML as well as I am Gn sixthree too as a monotherapy in minimal residual disease positive AML patients and look forward to continuing patient enrollment in twentytwenty and sharing data at ash.

With that I'll turn the call back over to Mark for some closing remarks.

Thanks, Anna just a few thoughts before we open the call for Q1 day after a challenging year, we've emerged with strong prospects for the business with important near term catalysts for our lead program. Our earlier stage portfolio accelerating a strong cash position to advance our portfolio to material inflection points and an experienced management team to.

Deliver on the business, we look forward to an exciting and productive next 12 months and with that we'll open the call for questions.

Thank you, ladies and gentlemen, SASSA question at this time. Please press Star then one on your touched on telephone switch on your question. Please press the pound <unk> I first question comes from John Newman of Canaccord. Your line is open.

Mark Joseph Enyedy: Thanks, Anna. Just a few thoughts before we open the call for Q&A. After a challenging year, we've emerged with strong prospects for the business, with important near-term catalysts for our lead program, our earlier stage portfolio accelerating, a strong cash position to advance our portfolio to material inflection points, and an experienced management team to deliver on the business. With that, we'll open the call to questions.

Hey, good morning, guys. Thanks for taking the question.

So I suffer Ana and Mark I'm, just curious if you could give us a rough sense as to the number of patients.

For the forward to platinum agnostic.

We might be a year and wondering if any of the patient.

Within that wouldn't have received prior.

Therapy. Thanks.

So the Oh, yes, sorry, so the cohort is 60 patients and yes, a number of those patients will have received a prior a vast and I can't say right at the top my head how many that is.

Operator: Thank you. Ladies and gentlemen, to ask a question at this time, please press star then one on your touchtone telephone. To withdraw your question, please press the pound key. Our first question comes from John Newman of Canaccord. Your line is now open. Hey, good morning, guys. Thanks for taking the question. So, question for Anna and Mark, just curious if you could give us a rough sense as to the number of patients for the Forward 2 Platinum Agnostic Doublet that we might see mid-year, and wondering if any of the patients within that group would have received prior Avastin therapy. Thanks.

Okay, Great and then just a quick question on.

Yeah.

I'm, assuming that given in the U.S.

For more than one.

Line of a fast and.

And a little bit challenging until recently.

I'm wondering if the patient.

We'll have just one prior lines of therapy with the fasten or if you might have a few patients that would have.

Thanks, John So surez being enrolled in the U.S. as well as in Europe, and historically typically patients really only get one line of the vast and if they do have access to it at all and remember this is patients with platinum resistant disease with one to three priors. So.

Anna Berkenblit: So the cohort is 60 patients, and yes, a number of those patients will have received prior Avast, and I can't say right off the top of my head how many that is.

Anna Berkenblit: Okay, great. And then, just a quick question on SREA. I'm assuming that in the U.S., getting reimbursement for more than one line of Avastin has been a little bit challenging until recently. I'm wondering if the patients in SREA will have just one prior line of therapy with Avastin, or if you might have a few patients that would have more than one.

So the only data that I'm aware of really showing that vast and after a vast and works is from them I don't Mango study were on it was shown that after frontline treatment within a vast and containing regimen is still that benefit in the recurrent platinum sensitive setting.

With another a vast and regimen. So we anticipate that very few patients will have had more than one prior lines of have asked.

Anna Berkenblit: Thanks, John. So, SREA is being enrolled in the U.S. as well as in Europe, and historically, typically, patients really only get one line of Avastin if they do have access to it at all. And remember, these are patients with platinum-resistant disease with one to three priors. So, the only data that I'm aware of really showing that Avastin after Avastin works is from the Mitomango study, where it was shown that after frontline treatment with an Avastin-containing regimen, you still got benefit in the recurrent platinum-sensitive setting with another Avastin regimen. So, we anticipate that very few patients will have had more than one prior line of Avastin.

Okay, great. Thank you very much.

Sure.

Yeah, and then next question comes from.

Jefferies. Your line is that open.

Hi, guys. Thanks for taking my questions and on the forward to trial with the triplet can you just maybe give us what next steps are I think.

In 2019, you presented some data there in about 41 patients so pretty strong response rates and deal or how much additional data do you need to see before.

You move the triplet forward into a pivotal study.

Yes, so we will be presenting longer term data from the triplet likely at ESMO. This year, where we should have mature PFS data you may recall that the benchmark for other triplets so [noise].

Operator: Okay, great. Thank you very much. Thank you. And our next question comes from Byron Adman of Jeffries. Your line is now open. Yeah. Hi guys.

Carbo Jan.

Yes, and Carbo pack bad there the median PFS is somewhere around 12 to 14 months.

Operator: Thanks for taking my questions. Anna, on the 402 trial with the triplet, can you just maybe give us what the next steps are? You know, I think in 2019 you presented some data there in about 41 patients and saw pretty strong response rates in DOR. How much additional data do you need to see before you move the triplet forward into a pivotal study?

Carbo Doxil Bev also read out at ESMO last year the year before also looking similarly, so those are those are the benchmarks and so we'll see how our triplet stacks up in terms of PFS as well as a safety and Tolerability and then we'll take it from there.

The potential registration option for that triplett would be a large long trial.

Anna Berkenblit: Yeah, so we will be presenting longer-term data from the triplet, likely at ESMO this year, where we should have mature PFS data. You may recall that the benchmark for other triplets, so CarboGemBev and CarboPakBev, the median PFS is somewhere around 12 to 14 months. CarboDoxelBev also read out at ESMO last year or the year before also looking So those are the benchmarks, and so we'll see how our triplet stacks up in terms of PFS, as well as safety and tolerability, and then we'll take it from there. Any potential registration option for that triplet would be a large, long trial, so we'll be examining the data quite closely.

So where it will be examining the data quite closely.

Okay, and then on I MGC 936 of the Adam nine AIDC.

You had presented I think last year in a CR some preclinical data and given your moving as program into line. The are you going to be Stratifying based on Adam line expression and I guess, what tumor types are you looking and the phase will until.

Yes, so we will be assessing Adam nine levels, and we will be poised to have a companion diagnostic down the road if needed for patient selection. So early on will be gathering data are the for tumor types, where initially going to target include pancreatic gastric lung and triple negative breast.

Anna Berkenblit: Okay, and then on IMGC 936, the ADAM9 ADC, you had presented, I think, last year at AACR some preclinical data, and given you're moving this program into IND, are you going to be stratifying based on ADAM9 expression, and I guess what tumor types are you looking at in Phase I-II?

Cancer there are some other solid tumors that also express Adam nine but these are the for that we're going after first in the phase one study.

And you know based on what we see in dose escalation. We can then certainly do some expansion cohorts.

Great. Thank you.

Thank you and your next question comes from any have see of William Blair. Your line is now open.

Anna Berkenblit: Yeah, so we will be assessing ADAM9 levels, and we will be poised to have a companion diagnostic down the road if needed for patient selection, so early on, we'll be gathering data. The four tumor types we're initially going to target include pancreatic, gastric, lung, and triple negative breast cancer. There are some other solid tumors that also express ADAM9, but these are the four that we're going after first in the phase one study, and, you know, based on what we see in dose escalation, we can then certainly do some expansion cohorts.

Great. Thanks for taking my question, so one for Mark I think.

The company has to do something for the past.

Q3 quarters, just wondering if the accelerated approval pathway that was clarified a december change of course at that.

Yes.

They should question anybody the.

We took the you know the largest part of the restructuring took place in Q2 in early Q3.

Operator: And our next question comes from Annie Hesty of William Blair. Your line is now open. So one for Mark, I think, you know, the company has been restructuring for the past two or three quarters. Just wondering if the accelerated approval pathway that was clarified in December changed the course of that.

And we were targeting a head count number and narrower folks that were transitioning over the back half of the year and yeah, we sort of got too you know what I'll call a nader in terms of head count.

And with the benefit of the FDA guidance around survey, a we've actually begun to add a very modest number of heads.

Mark Joseph Enyedy: Yeah, so thanks for the question, Andy. We took the, you know, the largest part of the restructuring took place in Q2 and early Q3, and, you know, we were targeting a headcount number, and there were folks that were transitioning over the back half of the year, and, you know, we sort of got to, you know, what I'll call a nadir in terms of headcount. And with the benefit of the FDA guidance around SRAE, we've actually, you know, begun to add a very modest number of heads as we go forward, and so you'll see from the guidance that we gave, our operating expenses for 2020 are going to be in the same range as they were for 2019 on an aggregate basis.

As we as we go forward and so.

You will see from the guidance that we gave you know our operating expenses for a 2020, you're going to be in the same range as they were for a 2019 on an aggregate basis.

And so what that reflects our you know sort of a leveling the head count was as I said, some modest additions, particularly a in the clinical and regulatory group from where we thought we were going to be and then you know a significant.

Ramped in external expenses.

Versus you know say, where we were in Q3 of a of 2019, reflecting the you know concurrent execution around both Serbia, and Mirasol and ultimately bringing online.

Mark Joseph Enyedy: And so, you know, what that reflects are, you know, sort of a leveling of the headcount with, as I said, some modest additions, particularly in the clinical and regulatory group from where we thought we were going to be, and then, you know, a significant, you know, ramp in external expenses, versus, you know, say, where we were in Q3 of 2019, reflecting the, you know, concurrent execution around both SEREA and Mirasol, and ultimately bringing online 936 later in the year.

936 later in the year.

Okay excellent. So in terms of from I guess ft, a dialogue perspective.

Very intrigued by the randomized investigator sponsored doublet.

Just curious about given kind of potentially.

Adding that high quality data in the regulatory packages.

Operator: Okay, excellent. Um, from a, I guess, FDA dialogue perspective, uh, very intrigued by the randomized, uh, investigator-sponsored, uh, doublet, just curious about, you know, potentially adding that high-quality data to the regulatory packages. I just want to know if there's any sort of mechanism by which you can include investigator-sponsored trials in a regulatory package.

Just want to know if there's any sort of mechanism by which you can include investigator sponsored trial in a regulatory package.

Oh, Hi, this is theresa.

Yes, there are certain opportunities to include iced teas.

You know the data has to be robustly collected but after you would consider that data. This is a combination trials, though however, so could not be used to support devaluation of efficacy from monotherapy.

Theresa Wingrove: Hi, this is Theresa.

Theresa Wingrove: Yes, there are certain opportunities to include ISTs, you know; the data has to be robustly collected, but FDA would consider that data. This is a combination trial, though, so it could not be used to support the evaluation of efficacy for monotherapy. Okay.

Okay got it and.

Lastly, I think because it for deanna.

So.

I guess immunotherapy hasn't really been biggies in that.

Roche is running a phase two trial that may read out this year. So just curious if in phase one be monotherapy combination or for Glenn.

Operator: And lastly, I think for Anna... [inaudible] I guess immunotherapy hasn't really been used in that, but Roche is running a phase two trial that may read out this year, so just curious if, you know, in phase one B monotherapy combination or forward one, did you guys look at any IO treated population and how they did with MIRV?

Did you guys look at any I O treated population and how they did with merger.

So.

Anna Berkenblit: So, you're right, Andy, that checkpoint inhibitors have not really moved the needle in ovarian cancer, and I think the large phase three that you're referring to is the IMAGINE study. In terms of

You're right Andy that checkpoint inhibitors have not really move the needle in ovarian cancer and I think the large phase three that you're referring to is the imagines study in terms of us yeah, and and that's in the frontline setting a incorporating a a tesla is a map.

Anna Berkenblit: Yeah, and that's in the frontline setting, incorporating TESLA as a map. You know, in terms of us looking at our data set, looking at patients who've had prior checkpoint inhibitors, honestly, there weren't enough of them given sort of when we enrolled Forward I. So I can't really speak to it, but given the modest activity, like single-digit response rates for checkpoint inhibitors by themselves, and given the lack of any potential cross-resistance, I don't think prior checkpoint inhibitor therapy would impact MIRV activity.

You know in terms of us looking at our dataset looking at patients who've had prior checkpoint inhibitors honestly, there hasn't been enough of them given sort of when we enrolled forward one.

So I can't really speak to it but I will say given the modest activity like single digit response rates for for checkpoint inhibitors by themselves and given the lack of any potential cross resistance I don't think prior checkpoint inhibitor therapy would impact or back tivity.

Got it.

Operator: Got it. Great, that's really helpful. Thank you very much. Sure. Thank you, and our next question comes from Boris Peaker of Cal, and your line is now open. Great. A couple of questions.

Great. That's really helpful. Thank you very much.

Sure.

Thank you.

Question comes from Boris Peaker of Cowen Your line is now open.

Right.

Couple of questions. So first on the combo trials I'm just curious whats the regulatory strategy in general is the goal to select the best combo and moved out forward or do you anticipate to advance several different combinations somehow in parallel.

Operator: A couple questions. First, on the combo trials, I'm just curious, what's the regulatory strategy in general? Is the goal to select the best combo and move that forward, or do you anticipate to advance several different combinations somehow in parallel? Yeah, so, the first step with the combinations is to ensure, at the time we have regulatory action on monotherapies around a positive outcome from psoriasis, that we would have sufficient publications to support a compendia listing for the combinations. And so that's our initial goal, so that to the extent there is discretionary use by physicians, they can obtain reimbursement for that use. Yes, longer term, you know, our goal is to have an expanded label, particularly to embrace platinum-sensitive patients. And so evaluating these combinations and also in this segment of what we're calling platinum agnostic patients, you know, trying to define a path forward there. So, you know, the opportunities here are one, looking at doublets with CARBO and comparing that to the investigator's choice. And that's what HARTR is doing for us with the AGO in Germany with this large IST.

Yeah. So.

The first the first step with the combinations is to ensure at the time, we have regulatory action on the monotherapy around you know a positive outcome from surface area that we would have sufficient publications to support a compendia listing for.

Combinations and so that's that's our initial goal so that to the extent there is discretionary used by physicians that they could obtain reimbursement for that use yes longer term you know the the.

Our goal is to have you know and expanded label, particularly to embrace platinum sensitive patients and so evaluating a these combinations and also in this segment of what we're calling platinum agnostic patients.

Trying to define of a path forward. There. So you know the opportunities here are one looking that doublet with with carbo and comparing that to investigators choice.

And that's what harder is doing for US a would the AG show a in a in Germany with this large I S. T. I think that would be a good guide for us the data that we will have.

Mark Joseph Enyedy: I think that would be a good guide for us. The data that we will have at ASCO in June with this platinum agnostic cohort equally provides us with a strong signal in terms of, you know, where we might go with the program. And, you know, as Anna mentioned earlier, as we think about the triplet, some of those, you know, some of those studies get to be very, very large. And I think, you know, we would likely look to cooperative groups to help with any of those broader studies. So, what I would say is, stay tuned.

ASCO in June with this platinum agnostic cohort equally provides us with a you know with a strong signal or in terms of where we might go with the with the program in their mentioned earlier on the is we think about the triplet.

Some of those you know some of those studies get to be very very large and I think you know we would likely look to cooperative groups to a to help with any of those those broader study so.

What I'd say stay tuned you know we gathered a lot of data.

Mark Joseph Enyedy: You know, we've gathered a lot of data. The key points to date are first that we can combine full doses of mervitoximab with full doses of everything we've tried at this point without, you know, generating new safety signals. So the drug is well tolerated in combination, and the efficacy benchmarks that we've hit with mervitoximab have exceeded the comparable. So you know, if you look at our Avastin combination data relative to what was reported in Aurelia, we compare very favorably there. The triplet compared favorably to, you know, these are high benchmarks too. I mean, some of the studies with triplets are in the low 80s, and when we look at apples to apples, we get to a 90% response rate in those patients.

The key points to date, our first that we can combine full doses of Bourbon talks mab with full doses of everything we've tried at this point without.

Generating new safety signals, so the drug as well tolerated in combination the efficacy benchmarks that we've hit with Mirvetuximab have exceeded the comparable so you know if you look at our a vast in a combination data relative to what was reported in a really a we compare.

Very favorably or there the triplet compared favorably.

To Oh no. These are high benchmarks to I mean, some of the studies with triplets or in the in the low Eightys and when we look at apples to apples, we got to a 90%.

Response rate in those patients. So are you aren't we're encouraged in I think the you know the question will be what can we do on our own what could we rely on the cooperative groups and along the way ensuring that to the extent that ER physicians are encouraged by the early data and want to use the drug that they can obtain reimbursement here in the.

Mark Joseph Enyedy: So you know, we're encouraged, and I think the question will be, what can we do on our own? What can we rely on the cooperative groups? And along the way, ensuring that to the extent that physicians are encouraged by the early data and want to use the drug, that they can obtain reimbursement here in the U.S. Gotcha. My second question is on 632.

The U.S.

Gotcha.

Question is on six three to just curious what indications do you see is having the shortest path to approval.

Mark Joseph Enyedy: I'm just curious, what indications do you see as having the shortest path to approval?

Yes, BPVC end so.

Mark Joseph Enyedy: Yeah, BPD-CN. So, you know, we reported data on a small cohort of nine patients at ASH, and we had three responders in that group, all of whom, or all of whom, had previously received Alzheimer's. And so the goal for us, Boris, is to collect sufficient data in this relapsed BPD-CN population to see whether we can, you know, create a dossier sufficient to approach FDA for a breakthrough therapy designation in this patient population and, as part of that discussion, define how many additional patients they would like to see in order to support an accelerated approval for that indication. And so you may remember that I think the number of patients supporting the Alzheimer's approval was around 50, between 50 and 60, and so those numbers could be reasonably modest.

You know we reported data on a small cohort of nine patients at a at Ash and we had three responders in that group all of which are all of whom had previously received elds on resin. So the goal for us for us is to collect a sufficient data in this.

Relapsed Bbds Yan population to see whether we can create a dossier sufficient to approach F.D.A. for a breakthrough therapy designation in this patient population and as part of that discussion define how many additional patients they would like to see a in order to support an accelerated.

Approval for that for that indication and so you may remember that I think the number of patients supporting the Alzheimer's approval was around 50 between 50 and 60 and so those numbers could be reasonably modest and what we've done with 62 is go to Europe and open sites and.

Mark Joseph Enyedy: And what we've done with 632 is go to Europe and open sites, and the, you know, investigator and patient response there has been quite encouraging from an accrual standpoint. You may remember that Stemline did not go to Europe with that drug, and so we've been able to take advantage of that from a patient accrual perspective, which I think will allow us to, you know, accumulate the data we need to have the conversations with FDA.

You know investigator in patient response, there has been quite encouraging from an accrual standpoint are you remember may remember that Stemline did not go to Europe with with that drug and so.

Well the to take advantage of that from a patient accrual perspective, a which I think will allow us to.

Accumulate the data we need to go have the conversations with FBR.

Gotcha and maybe just last question on I am Jan 151, how does a different from Mirvetuximab.

Mark Joseph Enyedy: Gotcha. Maybe just the last question on IMGen 151. How does it differ from Rituximab?

Yeah. So we have a new linger and payload for that program and then we've also done some antibody a engineering to improve the the PK and so we will have data at a CR in April where we can talk in more detail.

Mark Joseph Enyedy: Yeah, so we have a new linker and payload for that program, and we've also done some antibody engineering to improve the PK, and so we will have data at AACR in April where we can talk in more detail about the improvements that are reflected or embodied in that molecule.

So about a improvements that are reflected in body done that molecule.

Operator: Great, thank you very much for taking my questions. Thank you. And again, ladies and gentlemen, if you have a question at this time, please press star then 1 on your touchtone telephone. And our next question comes from Jessica 5, JPMorgan. Your line is now open. Hey guys, good morning. Thanks for taking my questions. If you have SIREA data in mid-21 and file that in the back half of 21, what are the potential implications for that review if Mirasol fails to meet its end point while that BLA is under review with the FDA? Well...

Great. Thank you very much for taking my questions sure.

Yeah, and again, ladies and gentlemen, if you have a question at this time. Please press Star then one on your touched on telephone and next question comes from Treska five JP Morgan Your line is that open.

Hey, guys. Good morning, Thanks for taking my questions or if you have sort of red data in mid 21 and filed I in the back half of 21.

What are the potential implications to that review if myris fall.

Fails to meet at some point wall that feel a is under review with the FDA.

Well [laughter].

Mark Joseph Enyedy: So... Soraya is based on a surrogate endpoint. I think we would be challenged, candidly. Given the accelerated approval based on overall response and DOR as a surrogate, if we then came out with data in Mirosol that showed no statistically significant difference on a full approval endpoint, I think that would be a challenging surrogate. That would be a challenging circumstance for their agency.

So.

So rare.

Based on a surrogate endpoint I think if you know I think we would be challenged candidly if ah if the.

Given the accelerated approval based on overall respond to de or as a surrogate. If we then you know came out with data in a and mirror saw that showed no statistically significant difference on a full approval endpoint I think that would be a challenging circumstance.

For for the agency.

And just thinking about the timelines here I think clinical trials that dovish pointing to June 2022 for me I saw so yeah first half, but conceivably could read out after that decision as a possible that that.

Mark Joseph Enyedy: And just thinking about the timelines here, I think clinicaltrials.gov is pointing to June of 2022 for Mirasol. So, yeah, first half, but conceivably could read out after that decision. Is it possible that the timelines kind of play out that way where you... Get the Accelerated Approval for Marisol reads out after FDA's kind of made a call on it? Yeah, I think that's probably the more likely scenario here, and I get there in the following way. So, we think...

The timelines kind of play out that way where are you.

Got the accelerated approval and Marisol reads out after after he is kind of made a call on.

Yeah, Yeah, I think that's probably the more likely scenario here and get there in the following way so we.

Previously have drafted substantial segments of the B.L.A. for Mirvetuximab and you know those things are not going to change as it relates to you know preclinical and so on so essentially what we're looking for a as a clinical component to a two the B.L.A. So our view is.

Mark Joseph Enyedy: I previously drafted substantial segments of the BLA for Myrvotoximab, and those things are not going to change as it relates to preclinical and so on. So essentially, what we're looking for is a clinical component to the BLA. So our view is that we can move very quickly from the readout of the top-line data to the submission for, you know, supported by SREA. You know, we've got a priority review for this.

We can move very quickly from the read out of the topline data to the submission for Oh, you know supported by psoriasis.

Yeah, We've got priority review for this side effect of the Michigan to state Yeah, sorry. Thank you.

Mark Joseph Enyedy: Yes. Yes.

And so you know my sense is that you know the F.D.A., particularly in these patient populations, where there is significant unmet need and you know that was one point of very clear alignment between us and the agency around these you know a platinum resistant patients previously treated with a vast and so our expectation is there going to move.

Mark Joseph Enyedy: And so, you know, my sense is that, you know, the FDA, particularly in these patient populations where there is significant unmet need, and, you know, that was one point of very clear alignment between us and the agency around these, you know, platinum-resistant patients previously treated with Avastin. So, you know, our expectation is they're going to move quite quickly on this application. And so, we're saying 2022 because that's, you know, that is a reasonable timeline for them to act on this application, but, you know, in cases where they have, you know, where data are good and the need is high, they've acted in shorter time frames, you know, in three or four months in some cases. And so, you know, we'll see, but, you know, I do think that the likely scenario is regulatory action on SREA followed by readout of Mirasol.

Quite quickly on this application and so we're saying 2022, because that's a you know that is a reasonable timeline for them to act on this application.

But you know in cases, where they have you know.

Where data are good and the need is hard they they've acted in you know in shorter timeframe zone, three or four months in some cases and so.

We'll see but you know I do think that the likely scenario is regulatory action on so ray a followed by a read out of Marisol.

Okay got it and when we think about the 70 patients.

Mark Joseph Enyedy: Okay, got it. And when we think about the 70 patients Swayampakula Ramakanth, Dingding Shi, Boris Peaker, Etzer Darout, Anna Berkenblit, Renee, You know, a number of priors and background therapies those folks have had. I'm wondering if those patients, given kind of the mix of trials they came from, might end up being a little bit thicker on the margin than the ones who are going to end up being enrolled in SHREA.

Kinda group, who look like they would meet the enrollment criteria for ceramic.

I'm just trying to think about art or you can present that that analysis. So so we can kind of take a look at at and T. more nuance around the.

You know number of prior some background therapy as those folks have had I'm wondering if those patients might.

You know given kind of the mix of trials. They came from my end up being a little bit sick or on the margin than the ones, who are going to end up being enrolled in Serbia.

Anna Berkenblit: So, we don't have any plans to formally present additional details on those 70 patients, Jess. We, you know, we did a lot of detective work looking through our program to really understand who the patients are who've already been treated with mervituximab to give us confidence that psoriasis will have a high probability of technical success. So, at a very high level, these are all patients with platinum-resistant ovarian cancer. They've all had one to three prior lines of therapy. They're all FR-alpha high by PS2+, and they've all had bevacizumab at some point prior to receiving mervituximab. The vast majority of them came from the phase three trial, and somewhere around 14 or 15 of them came from the phase one trial.

HM.

So we don't have any plans to formally present additional details on those 70 patients. Jeff. We you know we did a lot of Spadework looking through our program to really understand.

Who the patients are who have already been treated with mirvetuximab to give us confidence that Serbia will have a high probability of technical success. So at a very high level. These are all patients with platinum resistant ovarian cancer, they've all had one to three prior lines of therapy, there all fr Alpha high by PS two plus.

And they have all had bevacizumab at some point prior to receiving Mirvetuximab. The vast majority of them came from the phase three trial on about somewhere around 14 or 15 of them came from the phase one trial. So you know we've we've looked through out and we're confident that we will be able to.

Anna Berkenblit: Replicate these data in terms of ruling out a 12% response rate. The very minor nuance that may be informative for you is that when we enrolled, when we designed Forward One, we excluded primary platinum refractory patients, and those were patients who progressed within four weeks of their last dose of their first line platinum. Subsequently, talking with key opinion leaders, they have suggested that primary platinum refractory disease should really be those patients who progress within three months of the prior platinum, so we are not enrolling those patients in Forward One, nor, I'm sorry, are we enrolling them in SEREA and Mirasol moving forward. You know, in the randomized trial setting, that would probably have a similar impact on both arms, not so much on SEREA, but the benchmarking we've done for SEREA takes that into consideration as well.

Replicate these data in terms of ruling out a 12% response rate the one.

Very minor nuance that may be a informative for you is that when we enrolled a when we designed forward one we excluded primary platinum refractory patients and there those where patients who progressed within four weeks of.

Platinum of their last dose of their first line of platinum subsequently talking with key opinion leaders a they have suggested that the primary platinum refractory disease should really be those patients who progressed within three months of the prior platinum. So we are not enrolling those patients and forward one nor.

Sorry, we're not in rolling them in Serbia, and Mirasol moving forward on you know in the randomized trial setting that would have you know similar impact probably on on both arms are not too much on ceria that the benchmark and we've done for ceramic takes that into consideration as well.

Got it thank you.

Anna Berkenblit: Got it. Thank you. Thank you, and our next question comes from Jonathan Chang of SCV Laryngoland. Hey guys, this is David Rue, Sean on behalf of Jonathan. Thanks for taking our questions. You guys have mentioned in the past the neoadjuvant opportunity for MRF plus chemo, and it seems like a setting where KOLs would be receptive to using an ADC. Could you just elaborate a little bit on how you're thinking about potential combinations and design of these studies down the road?

Thank you.

No.

Hi, guys. This is David we've shown for Jonathan Thanks for taking my questions.

You guys mentioned in the past.

Roger been opportunity for Murph, plus chemo and it seems like a setting where cana wells would be receptive to using an 80 see could you just elaborate a little bit on how you're thinking about potential combinations and design of these studies on the road.

You're absolutely right.

Anna Berkenblit: You're absolutely right. A neoadjuvant trial is a high priority for our investigator-sponsored trial strategy, and all I can say is we're having active discussions, and we're really excited to be in a position to have those discussions and get a trial up and going with our investigators.

I had you been trial is a high priority for our investigator sponsored trial strategy.

And all I can say as we're having active discussions and we're really excited to be in a position to have those discussions and get a trial, a up and going with our investigators.

Alright, great end to clarify that would be an ice tea or yeah. Okay. Okay great.

Anna Berkenblit: All right, great. And to clarify, that would be an IST or not? Yes. OK. OK, great. Thank you. And next, now that the Forward One data are a little bit more mature, have you considered presenting any type of retrospective biomarker analysis that maybe looks at the longitudinal expression of Foley receptor alpha in these patients over time?

Thank you and ER next for me now that the forward one data are a little bit more mature have you considered presenting any type of retrospective biomarker analysis that maybe looks at the longitudinal expression of folate receptor alpha in these patients overtime.

So that would require serial biopsies, a which were not mandated as part of the protocol. So patients were enrolled primarily based on archival tumor tissue from their initial diagnosis.

Anna Berkenblit: That would require serial biopsies, which were not mandated as part of the protocol. Instead, patients were enrolled primarily on archival tumor tissue from their initial diagnosis. If, for whatever reason, archival tissue was not available, they could have had a fresh biopsy. But we were not subjecting these patients to sequential biopsies during their participation in the Phase III trial. So, unfortunately, we would not have the data available that you're requesting.

If for whatever reason archival tissue was not available they could have had a fresh biopsy, but we were not subjecting these patients to sequential biopsies during their participation in the phase three trial. So unfortunately, we would not have the data available that you're requesting.

Okay. Okay. Do you think that this might be something you do and sort out would you have pre and post study biopsies or.

Anna Berkenblit: Okay, okay. Do you think that this might be something you do in psoriasis? Would you have pre- and post-study biopsies?

Anna Berkenblit: So we did have a biomarker expansion cohort in our phase one that we presented at SGO several years ago now. And really, it was that study that showed that, you know, there was reasonable concordance between archival tissue and fresh tissue, and then we did biopsies after two cycles. I should note that there were a bunch of patients who had such tumor shrinkage on that arm that they couldn't actually get a biopsy after two cycles, so we had to over-enroll the cohort. That cohort also allowed for biopsies at progression, and you can imagine that that's a pretty hard conversation for an investigator to have with a patient saying, I'm sorry, the drug is no longer working. We'd like to subject you to a biopsy to see what's going on. At that point, patients typically prefer to engage in conversations around what's next from a treatment perspective.

So we did have a biomarker a expansion cohort in our phase one that we presented at S.G.O. several years ago now.

And really it was that study that showed that you know there was reasonable concordance between archival tissue and fresh tissue and then we did biopsies a after two cycles or I should note that there were a bunch of patients who had such tumor shrinkage on that arm that they couldn't actually get a biopsy. After two cycle. So we had to overenrolled a cohort.

On that cohort also allowed for biopsies at progression and you can imagine that it that's a pretty hard conversation for an investor theater to have with a patient say I'm sorry, the drug is no longer working we'd like to subjected to a biopsy to see what's going on I'm at that point patients typically prefer to engage in conversations.

And whats next from a treatment perspective.

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Alright, Thank you very much.

Anna Berkenblit: All right, thank you very much. Thank you. And our next question comes from Kenneth McKay of RBC Capital Markets. Your line is now open. Hi, thanks for taking the question. Just wondering, in BP-BCN, if you could help us understand where the efficacy bar is behind the L-zone risks, and if that is sort of the area of highest medical need, or as you're looking at potentially going through a breakthrough designation process here, or a potential Regulatory Trial Design if you could go potentially in front of that or if it had to be behind. Thank you.

Sure.

Thank you and our next question comes from Kennen Mackay with RBC capital markets. Your line is now open.

Hi, Thanks for taking my question just wondering in PBGC and if you could help us understand sort of where that see bar is.

Behind Elds, Andreas and if that is sort of the area of high unmet medical need or has your.

Looking at potentially going through a breakthrough designation process here for the.

Central regulatory trial design if you.

You could go a potentially in front us out or.

If it had to be fine. Thank you.

Yes, so as Mark mentioned Dell's honors was approved based on somewhere around 50 or 60 patients worth of data for P.P.D.C.N. larger safety database, but the responses in the label for Els honors in the relapse setting our I think it was two out of 13 patients on certainly if you look at their new England.

Anna Berkenblit: Yeah, so as Mark mentioned, Alzheimer's was approved based on somewhere around 50 or 60 patients' worth of data for BPD-CN, a larger safety database, but the responses in the label for Alzheimer's in the relapse setting are, I think it was 2 out of 13 patients. Certainly, if you look at their New England Journal article, they had additional partial responses, but those were not considered by FDA. And then if you look in the frontline setting, the Alzheimer's response rate was certainly higher. So we think there is a high unmet need for patients who've already had Alzheimer's, and I think the 3 out of 9 responders that we've had, certainly from a proof-of-concept perspective, although small numbers, you know, are quite encouraging. We're also hearing that, you know, not every patient is appropriate for L-zone risk.

Journal article they had additional partial responses, but those were not considered by F.D.A.

And then if you look in the frontline setting Osama says response rate was certainly higher on so we think there is a high unmet need for patients who've already had els on resin I think the three out of nine responders that we've had certainly from a proof of concept perspective, while small numbers.

You know is quite encouraging.

We're also hearing that a you know not every patient is appropriate for Els Andreas certainly you know if you look at the label a with the potential for capillary leak their patients a with low albumin are not appropriate for else on us in patients with cardiovascular or renal co morbidities, who.

Anna Berkenblit: Certainly, you know, if you look at the label with the potential for capillary leakage there, patients with low albumin are not appropriate for the L-zone risk, and patients with cardiovascular or renal comorbidities who perhaps couldn't handle the cardiovascular challenge that a capillary leak would pose for them. That might be another area where we might be able to demonstrate both activity as well as safety that could be supportive of going up front in frontline BPDACN patients who have not been previously treated with L-zone risk. And, you know, at this point, our heads are down, we're enrolling patients, and we're gathering data so that we have an informative data set with which to engage the regulators.

Perhaps couldn't handle the cardiovascular challenge that capillary leak would pose for them that might be another area, where we might be able to demonstrate a both activity as well as safety that could be supportive of going a upfront in frontline BP DCM patients who have not been previously treated.

Sales on a and you know this point or had their downward we're enrolling patients were gathering the data so that we haven't informative dataset with which to engage the regulators.

Interesting okay. Thank you I mean could we see an uptake from.

Anna Berkenblit: Interesting. Thank you. Could we see an update on an expansion of that at EHA, or would that be ASH for them to see?

Expansion about it at the home.

But the Ashley they did you.

Oh, I wouldn't I would suspect that ash would have a bigger dataset.

Anna Berkenblit: I would suspect that ASH will have a bigger data set with a longer duration, which will be important.

With longer duration, which will be important.

Anna Berkenblit: Thank you very much. Thank you. And ladies and gentlemen, this does conclude our question and answer session. I would now like to turn the call back over to Mark Enyedy for any closing remarks.

Thank you very much.

Thanks, Yeah, and ladies and gentlemen, this does conclude our question answer session I would now like to turn the call back over to Mark entity for any closing remarks.

Mark Joseph Enyedy: Great. Thanks, Sonia. We very much appreciate your participation and good questions today, and we look forward to keeping you updated on our progress throughout the remainder of the year. Thank you very much.

Great. Thank Sonia are very much appreciate the participation in good questions today, and we look forward to keeping you updated on our progress.

Throughout the remainder of the year, thanks very much.

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

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. Thank you for watching!

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