Q2 2020 ImmunoGen Inc Earnings Call

Good morning, and welcome to Immunogen second quarter 2020 financial and operating results Conference call. Today's conference is being recorded I'd like to turn the call over to Courtney Okay. Okay.

Operator: Good morning, and welcome to ImmunoGen's second quarter 2020 Financial and Operating Results conference call. Today's conference is being recorded. I'd like to turn the call over to Courtney Okonick, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

Senior director of corporate Communications and <unk> Investor Relations. Please go ahead.

Good morning, and thank you for joining today's call earlier today, we issued a press release settings with a summary of our recent progress.

Courtney Okonick: 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 second quarter 2020 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, Anna Berkenblit, our Chief Medical Officer, and Susan Altshuler, our Chief Financial Officer. During today's call, we will review key accomplishments for the business over the last three months, our financial results, and upcoming milestones. In the discussion, we will use forward-looking statements, and our actual results may differ materially from such statements.

First and second quarter 2020 financial result, this press release of the web stream of this call can be found under the investors in media section of our website at Immunogen dotcom.

With me today are mark entity, our president and CEO, and a Burke and what our Chief Medical Officer, and Susan Altshuler, Our Chief Financial Officer.

During today's call, we will review key accomplishment for the business over the last three months, our financial results and upcoming milestones during the discussion we will use forward looking statements that 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 FCC filings and with that I'll turn.

Courtney Okonick: 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. Thanks, Courtney.

All over to Mark.

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

Mark Joseph Enyedy: Good morning, everyone, and thank you for joining us today. Despite the challenges of operating in the COVID-19 environment, our performance in the second quarter was marked by sound execution, key data presentations, and important regulatory milestones. Our highest priority for the business is the completion of the pivotal studies for mervituximab, and we are actively enrolling patients in both SREA and Mirasol. However, like other companies, we experienced slower than anticipated site initiation for these studies during the second quarter. With conditions improving, particularly in Europe, we estimate a limited six- to eight-week delay in reporting top-line results for SREA and now expect the read out to be in Q3 2021 versus our previous guidance of mid-2021.

Despite the challenges of operating in the colder 19 environment. Our performance in the second quarter was marked by sound execution key data presentations and important regulatory milestones our highest priority for the business is the completion of the pivotal studies from Mirvetuximab, we are actively enrolling patients to both Saran mirasol.

Like other companies however, we experienced slower than anticipated site initiation for these studies during the second quarter was conditions, improving particularly in Europe, We estimate a limited six to eight week delay in reporting topline results for Serbia, and now expect to read out to be in Q3 2021 versus our previous.

The 2021 that said given that large portions of the P.L.A. are already complete we continue to anticipate filing for accelerated approval mirvetuximab and the second half of 2021.

Mark Joseph Enyedy: That said, given that large portions of the BLA are already complete, we continue to anticipate filing for accelerated approval of mervituximab in the second half of 2021. With an earlier start and longer lead time, Mirasol remains on track for both top-line data and submission of a supplemental BLA. Beyond the initial approval for mervituximab, we are considering multiple options for label expansion. To this end, we presented encouraging data from the Fuller-2 Avastin Expansion Cohort in a virtual oral presentation at ASCO. These data demonstrate the potential of mervituximab to serve as the combination agent of choice regardless of platinum status and thereby meet the needs of a broader patient population within recurrent ovarian cancer.

Within earlier start and longer lead time Marisol remains on track for both topline data and submission of a supplemental B.L.A.

Beyond the initial approval for Mirvetuximab, we're considering multiple options for label expansion.

That said, we presented encouraging data from the forward to a vast and expansion cohort in a virtual oral presentation at ASCO. These data demonstrates the potential ameritox map to service the combination agent of choice, regardless of platinum status and thereby meet the needs of a broader patient population within the current ovarian cancer.

Moving to our earlier stage programs. We're pleased to share with you. This morning that remains committee for orphan medicinal products has adopted a positive opinion to grant I MTN 632 orphan drug designation for the treatment of BPVC and then after FDA has accepted the I'd application for our first in class Adam nine Targa.

Mark Joseph Enyedy: Moving to our earlier stage programs, we are pleased to share with you this morning that EMA's Committee for Orphan Medicinal Products has adopted a positive opinion to grant IMGN 632, an Orphan Drug Designation, for the treatment of BPDCN, and that FDA has accepted the IND application for our first-in-class ADAM9 targeting ADC, IMGC 936, which we are co-developing with Macrogenics. I thank Scott Koenig and the entire Macrogenics team for their partnership in delivering this IND. This is a great example of what good looks like when it comes to 50-50 co-development programs. We look forward to enrolling the first patient in the Phase I study in the fourth quarter. In addition, IMGN 151, our next-generation antifolate receptor alpha ADC, has advanced into preclinical development.

Getting a b C. I am GC 936, which we are co developing with Macrogenics I think Scott, Kenya, getting entire macrogenics team for their partnership and delivering the I. Andy. This is a great example of what good looks like when it comes to 50 50 co development programs. We look forward to enrolling the first patient in the phase one study and before.

This quarter. In addition, our engineered 151, our next generation assay fully receptor Alpha AIDC advanced into preclinical development, we presented compelling preclinical data HCR that supports further exploration in various fr Alpha positive tumor types and I will cover this program in more detail number.

Mark Joseph Enyedy: We presented compelling preclinical data at AACR that support its further exploration in various FR-alpha positive tumor types, and I will cover this program in more detail in a moment. Finally, we are pleased to have welcomed Stacey Cohn to Immunogen as our Chief Business Officer and, most recently, Susan Altshuler as our Chief Financial Officer. In addition to their great energy, Stacey and Susan strengthen our management team with invaluable skills and experience to support our transition to a commercial business.

Uh huh.

Finally, we were pleased to welcome Stacy call into Immunogen, It's our Chief business Officer, and most recently, Susan all to where as our Chief Financial Officer. In addition, the great energy Stacy and Susan strengthen our management team that invaluable skills and experience to support our transition to commercial business.

As we looked at the back half of this year, we will be presenting mature data from our trip what cohort evaluating mirvetuximab and combination the carboplatin and avastin in platinum sensitive these at ESMO and data from the P.D.C.N. expansion cohort and progress on an hour monotherapy and combination cohorts for I.N. sixthree to it.

Mark Joseph Enyedy: As we discussed at the back half of this year, we will be presenting mature data from our triplet cohort evaluating mervituximab in combination with carboplatin and avastin in platinum sensitive disease at ESMO, data from the BPDCN expansion cohort, and progress on the AML monotherapy and combination cohorts for IMGN 632 at ASH. With that, I'd like to welcome Susan to her first earnings call with ImmunoGen and turn the discussion over to her to review our financials. Susan?

Josh.

I'd like to welcome Susan to her first earnings call with their religion and turn the discussion over to hurt to review our financials. Susan. Thank you Mark I'm excited to be joining immunogen at such an important time in the company's evolution.

Susan Altshuler: Thank you, Mark. I'm excited to be joining ImmunoGen at such an important time in the company's evolution. ImmunoGen is on the cusp of transitioning into a commercial-stage biotechnology company, and I look forward to working with Mark and the rest of the team as we continue to advance our novel portfolio of next-generation AEDs. Moving on to our second quarter financial results, the details of which were included in our press release issued this morning. For the second quarter of 2020, we generated $15 million in revenue, nearly all of which came from non-cash royalty revenue. Second quarter operating expenses were $33.4 million compared to $56.6 million in the prior year. Operating expenses for the second quarter of 2019 included a $19.3 million restructuring charge.

Region is on the cost of transitioning into a commercial stage biotechnology company I look forward to working with Mark and the rest of the team as we continue to advance our novel portfolio of next generation 80 feet.

Moving to our second quarter financial result details of which were included in our press release issued this morning.

The second quarter 2020, regenerated $15 million in revenue nearly all of which came from noncash royalty revenue.

Second quarter operating expenses were three $3.4 million compared to $56.6 million in the prior year.

Operating expenses for the second quarter of 2019 included a $19.3 million restructuring charge.

R&D expenses for the second quarter were $22.9 billion compared to $28.6 million.

Susan Altshuler: R&D expenses for the second quarter were $22.9 million compared to $28.6 million. This $5.7 million decrease was driven by lower expenses resulting from the restructuring of the business at the end of the second quarter of 2019. This was partially offset by greater clinical trial costs related to advancing our Murasol, SIREA, and 632 studies. General and administrative expenses for the second quarter of 2020 increased to $9.8 million compared to $8.7 million for the second quarter of 2019 due to increased professional fees and a higher allocation of facility-related expenses for excess laboratory and office space, partially offset by lower personnel expenses. After the second quarter, we will have $219.5 million in cash.

It's $5.7 million decrease was driven by lower expenses, resulting from the restructuring of the business at the end of the second quarter of 29 team.

This was partially offset by greater clinical trial costs related to advancing on yourself to rare and 62 study.

General and administrative expenses for the second quarter of 2020 increased to $9.8 million compared to $8.7 million for the second quarter of 2019 due to increased professional fees and a higher allocation facility related expenses for access laboratory enormously, partially offset by lower personnel expenses.

After the second quarter, we have $219.5 million in cash.

Our 2020 financial guidance remains unchanged, we continue to expect revenues to be between 60 and $65 million operating expenses to be between 165 and $170 million and our cash at year end to be between 170 and $175 million.

Susan Altshuler: Our 2020 financial guidance remains unchanged. We continue to 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. ImmunoGen is preparing for potential accelerated approval for Mervituximab in platinum-resistant ovarian cancer and is planning for increased investment in 2021 related to manufacturing in support of the potential commercial launch. With the addition of these investments, the company expects that its current cash and anticipated cash received from partners will fund operations into the second quarter of 2022. With that, I'll turn the call over to Anna to review our clinical progress in more detail. Anna?

Neogen is preparing for potential accelerated approval from Mirvetuximab and platinum resistant ovarian cancer and planning for increased investments in 2021 related to manufacturing support the potential commercial launch.

The addition of these investments the company expects that its current cash and anticipated cash received from partner will fund operations into the second quarter of 2022.

With that I'll turn the call over to add on to review our clinical progress in more detail Ana.

Thanks, Susan.

I'll begin by mentioning that we have maintained a nimble approach to clinical trial execution consistent with the latest regulatory guidances and are continuing to activate sites and enroll patients in our registration trials for Mirvetuximab and in our I M. P. S 632 program.

Regarding mirvetuximab, you'll recall that in late 2019, we aligned with the F.D.A. on an accelerated pathway for approval of Mirvetuximab bias array of our pivotal single arm study evaluating mirvetuximab monotherapy and approximately 110 women with platinum resistant ovarian cancer.

Anna Berkenblit: Thanks, Susan. I'll begin by mentioning that we have maintained a nimble approach to clinical trial execution, consistent with the latest regulatory guidance, and are continuing to activate sites and enroll patients in our registration trials for mirvotoximab and in our IMDN 632 program. Regarding Mervituximab, you recall that in late 2019, we aligned with FDA on an accelerated pathway for approval of Mervituximab via SREA, our pivotal single-arm study evaluating Mervituximab monotherapy in approximately 110 women with platinum-resistant ovarian cancer whose tumors are folate receptor alpha-high, as measured by the PS2-plus scoring method, and who have previously received a VAS As Mark mentioned, the COVID-19-related site activation delays are anticipated to result in a six- to eight-week enrollment delay.

Tumors are full late receptor alpha high as measured by the P.S., two plus scoring method and who have previously received of Aston.

As Mark mentioned, the Cobot 19 related site activation delays are anticipated to result in a six to eight week enrollment delay. However, we're confident that we will gain sufficient momentum in both the U.S. and Europe this quarter to support topline data in Q3, 2021 and potential approval in 20.

22.

We're continuing to enroll patients and open additional sites in Mirasol, our confirmatory phase three study of Mirvetuximab, which launched in December last year.

As a reminder, 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.

Anna Berkenblit: However, we are confident that we will gain sufficient momentum in both the U.S. and Europe this quarter to support top-line data in Q3 2021 and potential approval in 2022. We are continuing to enroll patients and open additional sites in Mirasol, our confirmatory Phase III study of Mervituximab, which launched in December last year. As a reminder, 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 mirvetuximab or and investigators choices chemotherapy, namely Paclitaxel Pegylated, liposomal doxorubicin or Towboats weekend.

The primary endpoint is progression free survival and the secondary endpoints are overall response rate overall survival and patient reported outcomes.

We continue to anticipate topline data for this study in the first half of 2022 to support full approval in 2023.

Turning to our forward to combination studies with Mirvetuximab, we are pursuing doublet and triplett cohorts with Bevacizumab and Carboplatin in order to expand into earlier lines of therapy provide longer durations of treatment and serve as the combination of choice in ovarian cancer.

Anna Berkenblit: Patients will be randomized one-to-one to receive mirvotoximab or an investigator's choice of chemotherapy, namely paclitaxel, pegylated liposomal doxorubicin, or topotecam. The primary endpoint is progression-free survival, and the secondary endpoints are overall response rate, overall survival, and patient-reported outcome. We continue to anticipate top-line data for this study in the first half of 2022 to support full approval in 2023. Turning to our Forward II combination studies with mervituximab, we are pursuing doublet and triplet cohorts with bevacizumab and carboplatin in order to expand into earlier lines of therapy, provide longer durations of treatment, and serve as the combination of choice in ovarian cancer. At the virtual ASCO meeting in May, initial efficacy and safety data evaluating mirvotoximab in combination with bevacizumab in recurrent ovarian cancer were highlighted in an oral presentation demonstrating an encouraging overall response rate of 64% in patients with high folate receptor alpha expression, regardless of platinum status.

At the virtual ASCO meeting in May initial efficacy and safety data evaluating mirvetuximab in combination with Bevacizumab in recurrent ovarian cancer were highlighted in an oral presentation, demonstrating an encouraging overall response rate of 64% in patients with high folate receptor alpha expression rugs.

Cardless of platinum status.

The data generated to date could support Compendia listing and given the observed responses and favorable Tolerability profile. We're currently evaluating formal label expansion opportunities for this combination.

Looking ahead to the fall we plan to present mature data from the forward to platinum sensitive triplett cohort evaluating mirvetuximab in combination with Carboplatin and Bevacizumab at ESMO in September and look forward to supporting initiation of a randomized phase two investigator sponsored trial evaluating both.

<unk> in combination with carbo platinum in platinum sensitive disease in the second half of the year.

Anna Berkenblit: The data generated to date could support compendia listing, and given the observed responses and favorable tolerability profile, we are currently evaluating formal label expansion opportunities for this combination. Looking ahead to the fall, we plan to present mature data from the Forward 2 Platinum Sensitive Triplet Cohort evaluating mervitoximab in combination with carboplatin and bevacizumab at ESMO in September, and look forward to supporting the initiation of a randomized Phase 2 investigator-sponsored trial evaluating mervitoximab in combination with carboplatin in platinum-sensitive disease in the second half of Moving to our earlier stage portfolio, we continued to advance programs that target a range of tumor types in both hematological malignancies and solid tumors. We continue to progress multiple cohorts with IMGN 632, including monotherapy expansion in BPD-CN and minimal residual disease positive AML following frontline induction therapy, and combinations with azacitidine and venetoclax in relapsed refractory AML patients.

Moving to our earlier stage portfolio, we continued to advance programs that target a range of tumor types in both hematological malignancies and solid tumors.

We continue to progress multiple cohorts with I am GE and six three to including monotherapy expansion in B P. D C N and minimal residual disease positive AML following frontline induction therapy and combinations with visa siding and the need to KLAX in relapsed refractory AML patients.

We look forward to presenting data from the I.M. GE and six three to monotherapy B P. D. C N expansion cohort and progress on the A.M.L. monotherapy and combination cohorts at Ash in December.

We also moved I am G.N. 151, our next generation E.D.C. designed to target tumors with a broad range of full late receptor alpha expression into preclinical development.

As a reminder, I M. G.N. 151 comprises an asymmetric by vaillant by para topic antibody targeting two independent epitopes of Fr Alpha linked to a highly potent maytansinoid derivative damn 21 via cleavable peptide linker with enhanced stability longer half life.

Anna Berkenblit: We look forward to presenting data from the IMGN 632 Monotherapy BPD-CN Expansion Cohort and progress on the AML Monotherapy and Combination Cohorts at ASH in December. We have also moved IMGN151, our next generation ADC designed to target tumors with a broad range of folate receptor alpha expression into preclinical development. As a reminder, IMGN151 comprises an asymmetric, bivalent, biparatopic antibody targeting two independent epitopes of FR-alpha, linked to a highly potent metansinoid derivative, DM21, via a cleavable peptide linker, with enhanced stability, longer half-life, and increased bystander activity.

And increased bystander activity.

At the virtual a CR meeting in June we presented data on I am G.N. 151, demonstrating enhanced anti tumor activity in both in vitro and in vivo preclinical models with complete regression of human tumor xenograft models induced in those with high medium and low levels of fr Alpha expression.

Based on these data we look forward to exploring I am G.N. 151 in the clinic in multiple fr Alpha positive at the field malignancies, including ovarian endometrial triple negative breast and non small cell lung cancer and expect to finally I N D for I am G.N. 151 in the second half of 2021.

Yeah.

With that I'll turn the call back to Mark.

Hi, fan and with that we'll open the call for questions operator.

Thank you.

Anna Berkenblit: At the virtual AACR meeting in June, we presented data on IMGN151 demonstrating enhanced antitumor activity in both in vitro and in vivo preclinical models, with complete regression of human tumor xenograft models induced in those with high, medium, and low levels of FR-alpha expression. Based on these data, we look forward to exploring IMGN151 in the clinic for multiple FR-alpha-positive epithelial malignancies, including ovarian, endometrial, triple negative breast, and non-small cell lung cancer, and expect to file the IND for IMGN151 in the second half of 2021. With that, I'll turn the call back to Mark. Thanks, Anna. And with that, we'll open the call for questions. Operator?

Ask a question you'll need to press star one on your telephone to withdraw your question press the pound key again, that's star one to ask a question.

And our first question comes from John Newman with Canaccord. Your line is open.

Hi, Good morning, guys. Thanks, very much for taking my question.

Sure Mark and Anna maybe first question just curious if the FDA has allowed any accommodations or in the service studied due to cold. It we know that they've issued some guidance in the past several months for example.

Just curious if perhaps you might be able to enroll them an additional patient to it. If you have to have someone dropout for Covidien, then step and additional question, which is in terms of the triple combination for Mirvetuximab.

Operator: Thank you. To ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key. Again, that's star 1 to ask a question. And our first question comes from John Newman with Ken Accord. Your line is open. Hi, good morning, guys. Thanks very much for taking my question. Mark and Anna, maybe for this question, I was just curious if the FDA has allowed any accommodations in the SREA study due to COVID. We know that they've issued some guidance in the past several months. For example, I was just curious if perhaps you might be able to enroll an additional patient or two if you have to have someone drop out for COVID.

Should we think about that ultimately as a frontline regimen or would it be more likely that you would explore mirvetuximab and carbon flattening in the frontline beforehand. Thanks.

Thanks, John.

That's the a and potential accommodation for coated.

The way the trial design right.

We need to have approximately 110, a valuable patients and typically we define availability based on you know ensuring patients have baseline in follow scan.

If it turns out that there are some patients who are quite building because of kobin. It's not comply with a protocol related procedures wouldn't anticipate potentially with amending the protocol and we're discussing with Sta, but we will have 100 incentive eligible patients.

Anna Berkenblit: And then an additional question, which is in terms of the triple combination for mervituximab. Should we think about that ultimately as a frontline regimen, or would it be more likely that you would explore Mervituximab and carboplatin in the frontline beforehand? Thanks, John.

The primary efficacy analysis.

To your separately.

Regarding myrna talking down, but this isn't that combination this isn't really exciting combination be because we saw activity in both recurrent platinum sensitive.

Anna Berkenblit: So in terms of FDA and potential accommodations for COVID, the way the trial is designed, Saraya, is that we need to have approximately 110 evaluable patients. And, you know, typically we define evaluability based on ensuring patients have baseline and then follow-up scans. If it turns out that there are some patients who are quite ill because of COVID and cannot comply with protocol-related procedures, we would anticipate potentially amending the protocol and or discussing it with FDA, but we will have 110 evaluable patients for the primary efficacy analysis. To your second point regarding the myrmetoxin-ambevacizumab combination, this is a really exciting combination because we saw activity in both recurrent platinum- So thinking about the development of this doublet, it certainly could be in platinum-resistant disease, also in platinum-sensitive disease, even in the frontline setting as an outback maintenance doublet. So it really has a lot of potential, and this is why we're working hard now to figure out the formal label expansion strategy for that doublet.

Ovarian cancer and platinum resistant ovarian cancer, so thinking about development of this Dublin.

Certainly could be in platinum resistant disease also in platinum sensitive to be even in the frontline setting as an outback, making in Dublin. So.

As a lot of central and this is why we're working hard now on to figure out the form of label expansion strategy for that Dublin.

Additionally, our gathering more data for her toxin have thought cobbled platinum based on the really encouraging data from phase one dose escalation and that certainly could be an upfront doublets work again is appropriate for recurrent platinum sensitive.

Our focus right now for that doublet, <unk> T a up and running a with our colleagues in Germany.

Sure.

John maybe just to follow up on your question about the triplet.

I will hop in data at a ESMO and.

Well be looking at that I think principally in the recurring.

Setting.

And evaluating different approaches to think about where we would go up front and potentially even in neoadjuvant setting. So those are discussions that are ongoing with our with our key advisors and as I say, we'll have a mature data at a at ESMO somebody from the initial tripling cohort.

Okay, great. Thank you very much.

Mark Joseph Enyedy: In addition, we are gathering more data for Mervituxinab plus Carboclatin, based on the really encouraging data from phase one dose escalation, and that certainly could be an up-front doublet, or again, appropriate for recurrent platinum-sensitive patients. Our focus right now for that doublet is to get the IST up and running with our colleagues in Germany later this year. John, maybe just to follow up on your question about the triplet, we'll have the data at ESMO and we'll be looking at that principally in the recurrent setting and evaluating different approaches to think about where we would go up front and potentially even in the neoadjuvant setting. So those are discussions that are ongoing with our key advisors, and as I say, we'll have the mature data at ESMO from Great, great. Thank you very much. Thank you. And as a reminder, once you ask your question, please mute your line. Our next question comes from Kenan McKay with RBC Capital Markets. Your line is open.

Thank you. That's a reminder, once you ask your question. Please mute your line. Our next question comes from Kennen Mackay with RBC capital markets. Your line is open.

Hi, Thanks, so much for taking my questions, giving opens up opportunities either working closely here or maybe just on hold on an enrollment obviously, what's your through was really an unprecedented hardwood really didnt Gordon's accompanied shut down for a a little while but.

Okay and was probably much induced entered a standard wondering.

You are sort of building in a vote mountains or geography into the new.

On trial enrollment timelines or what you're hearing.

Now that technically the problem is open to all told you all the people are still being impacted thanks much.

Yeah. Thanks, Karen you know at a high level.

We started strong in part because a lot of the filings and you know initial approaches to the sites to place and before the heavy onset and mid to late March and so little bit of how does occur, but what we observed during the quarter was a slowdown in terms of the responsiveness.

Mark Joseph Enyedy: Hi, thanks so much for taking the question and giving us the opportunity to work on questions here. Maybe just on the slowdown in enrollment, obviously Q2 was really an unprecedented time, with really the majority of the country shut down for at least a little while. But it does seem like COVID-19 is here to stay. I'm wondering if you are sort of building in slowdowns in various geographies to the new guidance on trial enrollment timelines, or what you're hearing now that technically, the country has opened back up, but several geographies are still being impacted. Thanks so much.

Particularly at the site level as they were closing insights to to access the people other than Epicentral personnel and the like and so that's really what we see what we saw a over the course of the second quarter correspondingly what we see on a go forward basis is that the sites.

Are we opening in terms of access people onsite, particularly administrators.

Mark Joseph Enyedy: Yeah, thanks, Karen, you know, at a high level. We started strong, in part because a lot of the filings and initial approaches to the sites took place before the heavy onset in mid to late March. So we were a little bit ahead of the curve, but what we observed during the quarter was a slowdown in terms of responsiveness, particularly at the site level as they were closing sites to access to people other than essential personnel and the like.

Turning around the paperwork and the like Weve implemented some innovative approaches around patient screening all all of which I'm, particularly in Europe and keep in mind that you know, we expect to enroll at least as many patients and these studies in Europe as we do in a in the U.S. and so what we what we see.

King of late.

It's you know a resurgence an acceleration of activity, particularly in Europe as it relates to the study and that's what we have factored in as we've looked at.

The you know the impact to the study timeline here and so what were what we see really there's about a six to eight week delay at this point.

Mark Joseph Enyedy: Correspondingly, what we see on a go-forward basis is that the sites are reopening in terms of access, people onsite, particularly the administrators to turn around the paperwork and the like. We've implemented some innovative approaches around patient screening, all of which are particularly in Europe. And keep in mind that we expect to enroll at least as many patients in these studies in Europe as we do in the U.S. And so what we've seen of late is a resurgence and acceleration of activity, particularly in Europe, as it relates to this study. And that's what we have factored in as we've looked at the impact on the study timelines here. And so what we see really is about a six- to eight-week delay at this point.

<unk>.

Got it thank you for a second question.

Sure.

Thank you. Our next question comes from Andy High with William Blair. Your line is open.

Oh excellent. Thanks for taking my question I hope everybody is doing well and congratulations on your new roles Susan in Stacy So the more deposit is.

Opportunity a mel opportunities Gotta interesting, but just wanted to check my understanding in terms of where 632 fits into treatment paradigm. So you basically have patients getting induction following induction it.

On this particular patient has MRV positivity then you get 32, followed by oral he decided he made to then I'm thinking that we can improve is that how you kind of speak about where it.

Anna Berkenblit: Thank you for taking the questions. Thank you. Our next question comes from Andy High with William Blair. Your line is open.

So Andy we are exploring I am GM sixthree too in MRV positive disease as a maintenance option and we're excited that orally society has paved the way.

Anna Berkenblit: Oh, excellent. Thanks for taking my question. I hope everybody's doing well. And congratulations on your new roles, Susan and Stacey.

Anna Berkenblit: So the MRD positive, AAML opportunity is kind of interesting. So just want to check my understanding in terms of where 632 fits into the treatment paradigm. So you basically have patients getting induction, following induction, if this particular patient has MRD positivity, then you get 632, followed by oral azacitidin maintenance based on the recent approval. Is that how you kind of think about where it is?

You know from a clinical trial for affected and and potentially regulatory perspective here as well, although their design with a bit different than ours.

It's too early to tell but given the tolerability that we've seen for our monotherapy and the convenience of you know short Ivy infusion. Once every three weeks as an outpatient we think it really has the potential to be the best on maintenance option for patients with and now it's early days I'm certainly we're also combining it with either.

Anna Berkenblit: So, Andy, we are exploring IMGM632 in MRD-positive disease as a maintenance option. And we're excited that oral azacitabine has paved the way, you know, from a clinical trial perspective and potentially a regulatory perspective here as well, although their design was a bit different than ours. You know, it's too early to tell, but given the tolerability that we've seen for our monotherapy and the convenience of, you know, a short IV infusion once every three weeks as an outpatient, we think it really has the potential to be the best maintenance option for patients with AML. It's early days.

I didn't mean and that could be another option not just for treatment, but also a a maintenance regimen as well so early days handy, but the way you're thinking about it you know there or is it one of the options and there certainly others.

Oh got it thanks to the clarification and back to merge.

Yeah, there's a lot of moving parts, including.

No the potential as a vast input harp or as a maintenance option a in the second half of this year. So just curious about how that could change some computer trial design and also kind of related to that.

You know very excited about the as no triple a data but going forward.

Anna Berkenblit: Certainly, we are also combining it with azacitabine, and that could be another option, not just for treatment but also as a maintenance regimen as well. So, early days, Andy, but the way you're thinking about it, you know, that is one of the options, and there are certainly others.

Do you have to kind of think about incorporating a harp is an option for patients in the maintenance part of the trial.

And just to make sure that captures kind of the current treatment paradigm as well.

Mark Joseph Enyedy: Thanks for the clarification. And, you know, back to MERV, there are a lot of moving parts, including, you know, the potential of BASTON plus PARP as a maintenance option in the second half of this year. So just curious about how, you know, that could change some future trial designs. And also kind of related to that, you know; very excited about the ESMO triplet data. But going forward, do you have to kind of think about incorporating PARP as an option for patients in the maintenance part of the trial, just to make sure that captures kind of the current treatment paradigm as well? Yeah, so let me unpack some of the concepts that you just laid out there, Andy, and tell you how we're thinking about it.

Yeah, So let me and some of the concepts that you just laid out there Andy and tell you how we're thinking about it. So yeah hearts are being combined with the Boston and the data look quite good there as a potential maintenance option certainly we had very nice data showing that we combine well with UBS.

Often there's also a on an I.S.T. that is being performed for mirvetuximab with recapture it didnt heavily pre treated patients.

So we do look forward to gathering more data for Mirvetuximab.

Peter I.

I think you know that field is evolving quite rapidly in terms of trying to understand which patients benefit the most some PARP inhibitors and how to sequence therapies.

Yeah mutation patients either germline or somatic certainly benefit the most from PARP inhibitor. Then when you think about the broader HIV positive group those patients benefit as well, but then once you get to the HRG negative patients on.

Anna Berkenblit: So, yes, PARPs is being combined with Avastin, and the data look quite good there as a potential maintenance option. Certainly, we have very nice data showing that we work well with Avastin. There's also an IST that is being performed for Mervitopsinab with Rutaparib in heavily pretreated patients, so we do look forward to gathering more data for Mervitopsinab with the PARP inhibitor. I think, you know, the field is evolving quite rapidly in terms of trying to understand which patients benefit the most from PARP inhibitors and how to sequence therapies. BRCA mutation patients, either germline or somatic, certainly benefit the most from PARP inhibitors.

You know they really don't benefit that much from PARP inhibitor. So the unmet need in that group remains high as well. So I think we're still trying to figure out you know how best to integrate mirvetuximab in combination in earlier lines of therapy because of the dynamic landscape I'm optimistic that merger talks and that will be.

On the combination partner of choice because of the Tolerability profile, we've generated a thus far the other point to know what is that there are no data showing that PARP inhibitors work. After PARP inhibitor. So you know our sense is that part will be upfront in the maintenance setting and then after that patients aren't going to need additional.

Active therapies and Mirvetuximab will play a larger so well for patients with ovarian cancer.

Okay, Yeah, right, that's totally makes sense, so or for as no. After we got a quinsa you know what's the column you know Super High response rates in the city.

Anna Berkenblit: Then, when you think about the broader HRD-positive group, those patients benefit as well, but then once you get to the HRD-negative patients, you know, they really don't benefit that much from PARP inhibitors. So, the unmet need in that group remains high as well. So, I think we're still trying to figure out how best to integrate mervituximab in combination in earlier lines of therapy because of the dynamic landscape. But I'm optimistic that mervituximab will become the combination partner of choice because of the tolerability profile we've generated thus far. The other point to note is that there are no data showing that PARP inhibitors work after PARP inhibitors. So, you know, our sense is that PARPs will be used up front in the maintenance setting, and then after that, patients are going to need additional effective therapies, and mervituximab will play a large role for patients with ovarian cancer. Okay, yeah, right. That totally makes sense. So for ESMO, you know, last year, we got a glimpse of what's to come, you know, super high response rates in the 80s, you know, 90% percent range, depending on which segment you're looking at. So what are some things that, you know, you're kind of mostly excited about?

80% percent range, depending on which segment you're looking at so what are some things that.

That you know you're kind of mostly excited by what are the things to watch out for as we approach the ESMO conference.

Yes, so the treatment of American talks about harmful side.

And the Boston is quite asking based on the spot freight as you saw last year and this year, we're going to show you longer duration follow up and you'll see progression free survival in duration of response data no doubt that triplet is active.

And no doubt that it is feasible I think you know there are other analysts out there and there's really three of them. They do get you to tackle cargo adopted carbo, John of Aston and Carbo, Doxil adapted and so thinking about how our triplet could be integrated and where it was that for patients will require.

You know work also you know typically he's triplets are you in the frontline setting and so that will be a large long trial, a big commitments for immunogens. So as we speak about lifecycle management the triplet could play an important role, but right now our near term focus is werent label expansion strategies that will yield.

Benefit for patients, who nerf from a regulatory perspective.

Anna Berkenblit: What are the things to watch out for as we approach the ESMO conference? Yeah, so the triplet of mirvotoximab, carboclatin, and avastin is quite active based on response rates, as you saw last year. And this year we're going to show you longer duration follow-up, so you'll see progression-free survival and duration of response data. No doubt this triplet is active, and no doubt that it is feasible.

Okay, great. Thanks for taking my question.

Thank you. Our next question comes from Debjit Chattopadhyay with H.C. Wainwright. Your line is open.

Hi, guys good morning.

That's good.

<unk>.

So once patients are enrolled.

He's completion of follow ups scans, becoming difficult.

Anna Berkenblit: I think, you know, there are other triplets out there, and there are really three of them that do get used, taxylcarboavastin, carbogenavastin, and carbodoxalavastin. And so thinking about how our triplet could be integrated and where it would best serve patients will require additional work. Also, you know, typically, these triplets are used in the frontline setting.

Because the inability to.

Got to the clinic sites.

And should be.

Correct.

Yeah.

Yeah.

Uh huh.

You know either at the.

All studies.

Hi, Mike deal with that.

So.

Evaluation.

Yeah. So as Mark mentioned, we're seeing a site regaining momentum in one when things are open and there are enrolling patients. We don't anticipate that you know they will suddenly not be able to get their scan done a you know if they are opening up to the point that they can screening patients for eligibility.

Anna Berkenblit: And so that will be a large, long trial, a big commitment for ImmunoGen. So as we think about life cycle management, the triplet could play an important role. But right now, our near-term focus is on label expansion strategies that will yield benefits for patients sooner from a regulatory approach. Okay, great. Thanks for taking all my questions.

Do the dosing every three weeks a for the Mirvetuximab iron ore on the control arm from yourself, a we anticipate that patients will be able to get all of the protocol required assessments for them to be a valuable and I mentioned earlier in the call. If it turns out but there are some patients who are not a valuable we certainly have.

Anna Berkenblit: Thank you. Our next question comes from Debjit Saropata with HC Wainwright. Your line is open.

Options to adjust the protocol would roll additional patients to ensure that we have to sufficient number of a valuable patients were the primary efficacy analysis.

Anna Berkenblit: Hi guys, good morning. This is Aaron from DevJet. Thanks for taking the questions. So once patients are enrolled, how is completion of follow-up because of the inability to get to the clinic site? And should we...

Okay great.

Okay.

Perfect spot.

<unk>.

Study.

Anna Berkenblit: Expecting any missing data. Top line readouts, you know, either of the ongoing pivotal studies. How might you deal with that and the effects?

Hello.

At this point or.

Yeah, I'm going to be clear. We don't report on confirmed response is all of our responses are confirmed responses. So there's there's nothing to update there.

Anna Berkenblit: Yeah, so as Mark mentioned, we're seeing sites regaining momentum, and when sites are open and they're enrolling patients, we don't anticipate that, you know, they will suddenly not be able to get their scan done. If they're open enough to the point that they can screen patients for eligibility and do the dosing every three weeks for the Myrvotuximab arm or on the control arm for Murisol, we As I mentioned earlier in the call, if it turns out that there are some patients who are not evaluable, we certainly have options to adjust the protocol to enroll additional patients to ensure that we have a sufficient number of evaluable patients for the primary efficacy analysis. Okay, great.

Data were.

Rock solid supposedly unimportant, but I mean, that's this is how we approach all of our a publication.

Okay great.

[music].

And then a lot.

So are there.

Or are there any steps being taken to mitigate the.

Toxicity issues, and Oh, I'm going to handle.

But you got that that administration.

Scott there right.

It really good job.

Lowering the great wanted to.

So are those.

Given prophylactically or is there any sort of evaluation patients to see if they have any.

For the four.

Issues anything any update there.

Anna Berkenblit: So, the unconfirmed responses that were reported at ASCO in the 4.2 study... Unknown Executive, Swayampakula Ramakanth, Dingding Shi, Boris Peaker, Etzer Darout, Anna Berkenblit, Renee Lentini, Anabel Kalofonos, Lauren White, ImmunoGen Inc. Yeah, just to be clear, we don't report unconfirmed responses.

So not to talk to that had been studied in over 700 occasion, we have a very good understanding of the okcular profile for murder toxin that in fact to even did a separate macular cohort early in the development of the drugs to demonstrate a the benefit of corticosteroid eye drops given.

That's all patients and therefore in our initial phase III trial for would want all patients got lubricating and narrowing eye drops a friend and start and with that we saw that it was the minority of patients who had any ocular adverse event and those that did it was almost entirely low grade the discontinuation.

Anna Berkenblit: So there's nothing to update there. Those data were already published. This is how we approach all of our publications. Okay, great. That's good to know. And then, last, could you tell me are there... Are there any steps being taken to mitigate the ocular damage? I mean, I know that you guys had that administration of lubricating drops of steroids.

Great for ocular adverse event is extremely low we only had one patients in the phase three trial, a discontinued due to bring to blurred vision. So based on the really nice data we generated thus far we are continuing with the same management a these okcular adverse events the lubricating eyedrops.

Anna Berkenblit: Lowering the Grade 1 and Grade 2 Events. So are those being given prophylactically, or is there any sort of evaluation of patients to see if they have any? and any updates there. So far, Mervitoximab has been studied in over 700 patients. We have a very good understanding of the ocular profile for Mervitoximab. In fact, we even did a separate ocular cohort early in the development of the drug to demonstrate the benefit of corticosteroid eye drops given to all patients. And therefore, in our initial phase 3 trial, Forward 1, all patients got lubricating and steroid eye drops from the start, and with that, we saw that it was the minority of patients who had any ocular adverse event. And those that did, it was almost entirely low grade.

Narrowed I dropped for everyone and anticipation is having blurred vision a that requires some adjustment you can have a dose modification and again with that we basically had only a handful of patients. These 700 discontinued due to blurred vision.

Okay, great. Thanks for that.

Right.

Thank you.

Our next question comes from Byron Admin.

With Jefferies. Your line is open.

Yeah, Hi, guys. Thanks for taking my questions, maybe if I could just start on line three six you announced I think the idea it's been accepted by U.S. left the a.

What are the next plans in terms of just phase one two trial, which tumor types would you look I'm going to some of this is a three plus three design.

Anna Berkenblit: The discontinuation rate for ocular adverse events is extremely low. We only had one patient in the phase 3 trial discontinue due to grade 2 blurred vision. So, based on the really nice data we've generated thus far, we are continuing with the same management of these ocular adverse events. So, lubricating eye drops, steroid eye drops for everyone, and then if a patient is having blurred vision that requires some adjustment, you can have a dose modification. And again, with that, we basically had only a handful of patients out of these 700 discontinue due to blurred vision. Okay, great. Thanks for the context.

Are you also going to be incorporating the eight score and the trial.

Yes, so Adam kind as a novel matrix metallic how do you need a target for antibody drug conjugates ours is the first addressing this target and yes, we are planning to get it into the clinic. Later this year, we will do a standard dose escalation three plus three in a handful of different.

All in tumors that we know expressed high levels of Adam nine this includes non small cell lung cancer.

After a triple negative breast cancer, and pancreatic cancer and yes, we will be assessing Adam nine by Immunohistochemistry and a you know based on our deep experience in the development now Ah Ah Biomarkers for patient selection based on our folate receptor Alpha experience Oh, we will apply those lessons learned to nine free.

Mark Joseph Enyedy: All right. Thank you. Our next question comes from Byron Abman with Jeffreys. Your line is open. Yeah, hi, guys. Thanks for taking my questions. Maybe if I could just start on 936.

Anna Berkenblit: You announced, I think, the IND has been accepted by USFDA. What are the next plans in terms of just the Phase 1, 2 trial? Which tumor types would you look at? I'm going to assume this is a 3 plus 3 design. Are you also going to be incorporating the ACE score in the trial? Yeah, so ADAM9 is a novel matrix metalloproteinase target for antibody drug conjugates. Ours is the first addressing this target. And, yes, we are planning to get it into the clinic later this year. We will do a standard dose escalation, 3 plus 3, in a handful of different solid tumors that we know express high levels of ADAM9. This includes non-small cell lung cancer, gastric, triple negative breast cancer, and pancreatic cancer.

On to ensure that we selected patients that will most benefit from this antibody drug conjugate anticipating it will have expansion cohorts in one or more of these solid tumor type based on preliminary efficacy that we see in dose escalation.

And then just on I guess I'm chance exposure to I think you announced that you're going to have some data at ash.

And yeah, Okay, we'll announce I guess data in both the monotherapy.

Cohort and BP DCN as well as a combo cohorts in animal can you just maybe talk about how many patients what type of follow up should we expect.

Anna Berkenblit: And, yes, we will be assessing ADAM9 by immunohistochemistry. And, you know, based on our deep experience in the development of biomarkers for patient selection based on our folate receptor alpha experience, we will apply those lessons learned to 936 to ensure that we select the patients that will most benefit from this antibody drug conjugate. I anticipate that we'll have expansion cohorts in one or more of these solid tumor types based on the preliminary efficacy that we see in dose escalation. And then just on IMGN 632, I think you announced that you're gonna have some data at ASH and, you know, we'll announce data in both the monotherapy cohort and BPD-CN as well as the combo cohorts in AML.

And.

Do you expect that we would see you know a signal where are you would have I guess.

You would have identified a phase two dose to move forward with.

Yeah. So for Q3 two out we're really excited about the monotherapy B P. D. C. N data on that enrollment has continued to go quite well and so we'll share all the data that we have at ash.

The combination says you know, we're combining 62 when he decided even we're combining with the need to class and we're combining as a tripling and those combinations are progressing I think ashes, probably premature for us to say that we declared a random recommended phase two dose, but we certainly will show the progress that.

We've made a at that point.

Great. Thanks for taking my questions.

Thank you. Our next question comes from Boris Peaker with Cowen Your line is open.

Hi, Good morning, Ah first I just want to ask about the Marisol answering your trial just curious how do they differ in terms of patient follow up requirements or any other patient burdens kind of in the corporate environment is one more appealing to patients than another.

Anna Berkenblit: Can you just maybe talk about how many patients, what type of follow-up we should expect, and do you expect that we would see a signal where you would have, I guess, you would have identified a phase two dose to move forward with? Yeah, so for 6.3.2, we're really excited about the monotherapy BPD-CN data and that enrollment has continued to go quite well, and so we'll share all the data that we have at ASH. The combinations, as you know, we're combining 6.3.2 with azacitidine, we're combining with venetoclax, and we're combining as a triplet. And those combinations are progressing.

So in terms of patient follow up and burden of clinical trial procedures. The trials are identical the only difference between Iran and Mirasol. Some intelligibility perspective is that the ramifications must have had prior avastin so that.

They are appropriate for single agent such as Mirvetuximab.

In Mirasol patients may or May not has had prior of after the other key difference is that threat is a single arm study. So when a patient enrolled on saran. They know they're going to get Mirvetuximab Mirasol is the randomized trial one to one so patients will have a 50 50 chance of getting mirvetuximab.

Anna Berkenblit: I think ASH is probably too early for us to say that we've declared a recommended phase 2 dose, but we certainly will share the progress that we've made at that point. Great, thanks for taking my question. Thank you. Our next question comes from Boris Peaker with Cowen. Your line is open.

Oh for investigator choice chemotherapy.

That's true.

Anna Berkenblit: Good morning. First, I just want to ask about the Mirosol and SIREA trials. I'm just curious, how do they differ in terms of patient follow-up requirements or any other patient burden? Kind of, in the COVID environment, is one more appealing to patients than another? So, in terms of patient follow-up and burden of clinical trial procedures, the trials are identical. The only difference between SIREA and Mirasol from an eligibility perspective is that SIREA patients must have had prior Avastin so that they are appropriate for single-agent treatments such as myrmitoximab.

Our friends on the combination from Mirvetuximab combination I mean, you talked about several triplets options and certainly a lot of moving pieces I just want to kind of get incentive timeline. When do you think you kind of a boil down the leading combination for pivotal study in and what that pivotal study might look like.

Oh, we're working through the label extension options for murder talks amount plus Bevacizumab right. Now you know we've generated data in a 120 patients for that combination based on the two cohorts. So that really is I would call the lead prospect for label expansion with the triplet as you know we have Uh huh.

Anna Berkenblit: In Mirasol, patients may or may not have had prior Avastin. The other key difference is that SIREA is a single-arm study, so when a patient enrolls in SIREA, they know they're going to get myrmitoximab. Mirasol is a randomized trial, one-to-one, so patients will have a 50-50 chance of getting myrmitoximab or investigator-choice chemotherapy. My next question is about the combination of myrtotoxin with doxazosin.

The 30 or 40 patient cohort and it will present the updated data at ASMO for that and I would imagine we would consider generating additional data for our triplet before we you know put her stick in the ground for label expansion strategy for that again in part because a large size and long duration of any type of randomized trial.

Anna Berkenblit: We talked about several triplet options and certainly a lot of moving pieces. I just want to kind of get a sense of when you think you'll kind of boil down the leading combination for a pivotal study and what that pivotal study might look like. We're working through the label expansion options for Mervituximab plus Bevacizumab right now. You know, we've generated data in 120 patients for that combination based on the two cohorts. So that really is, I would call, the lead prospect for label expansion.

What's triplet therapy with such a high response rate and long progression free survival catcher and lastly on the BP DCM study you mentioned shaygan presenting at Ash could you comment just what kind of response rate do you think you need to show you need to advance patients in a single arm study for to be acceptable for approval.

Anna Berkenblit: With the triplet, as you know, we have a 30 or 40 patient cohort, and we'll present the updated data at ASMO for that. And I would imagine we would consider generating additional data for our triplet before we, you know, put our stick in the ground for a label expansion strategy for that. Again, in part because of the large size and long duration of any type of randomized trial with triplet therapy with such a high response rate and long progression-free survival. And lastly, on the BPD-CN study, you mentioned, obviously, that you're going to be presenting it at ASH. Could you comment just what kind of response rate do you think you need to show in these advanced patients in a single-arm study for it to be acceptable for approval? So we look forward to discussing that very question with FDA, essentially later this year. But what I can tell you is that in the Alzheimer's label in relapsed refractory disease, there were two CRs, CR, and CRC, out of, I think it was 13 patients. So I think the bar is pretty low.

So we look forward to discussing that very questions with F.D.A. essentially later this year, but what I can tell you is that in the Alzheimer's label in relapsed refractory disease, there were to see our CRC or the.

Out of I think it was 13 patients so I think the bars pretty low.

Great. Thank you very much for taking my questions.

Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open.

Hi, guys. Good morning, Thanks for taking my questions.

I had one on Gee I had one 510, it's interesting to see that reach and a CR.

Comparison, I guess pre clinical comparison to more of a tuck smile I'm just curious if how you think about a.

Contribution to the sort of improved efficacy you know just curious how much of that maybe due to the different talks and that that is being used versus the a buy up her a topic anti body and maybe maybe some additional information on that deal 21 talks and then how that compares to the more legacy type.

Toxins Houston Mirvetuximab.

Anna Berkenblit: Thank you very much for taking my question. Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open. Hey guys.

Yeah.

I think it's a little bit hard at this point to tease out the individual components I think what were most proud of is that you were able to integrate multiple improvements into that molecule. So you know the.

Mark Joseph Enyedy: Good morning. Thanks for taking my questions. I had one on INGN151.

Later or payload complex is a more stable so we got more drugs.

Mark Joseph Enyedy: It was interesting to see the recent AACR comparison, I guess, preclinical comparison to Mervitaximab. I was just curious how you think about the contribution to the sort of improved efficacy. You know, I was curious how much of that may be due to the different toxin that is being used versus the paratopic antibody and maybe some additional information on the DM21 toxin and how that compares to the more legacy-type toxins used in Mervitaximab. Michael, I think it's a little bit hard at this point to tease out the individual components.

The team or the first instance, we have.

True binding internalization, which improves advocacy and then as you mentioned designed around me I'm 21.

Cleaves off active metabolite, which also improves the bystander effect. So it's really all other things working together as a I'm not sure we'd get isolated individual elements, it's sort of say what what's the impact is but you know what we clearly see from those data is a you know significantly improved African C.

Particularly and in those all lines have been models with lower levels of folate receptor Alpha expression, which was the key design criteria here based on the clinical experience with it was merger talks about and so that's how we're thinking about it and so you know as we look at the Big picture here, obviously is gives us.

Mark Joseph Enyedy: I think what we're most proud of is that we were able to integrate multiple improvements into that molecule. So, you know, the linker payload complex is more stable, so we get more drug to the tumor in the first instance. We have improved binding and internalization, which improves efficacy. And then, as you mentioned, the design around DM21 Cleaves Off, and Active Metabolite, which also improves the bystander effect

The chance to within ovarian cancer or too.

Addressed patients with lower levels of expression, but also what we see when we look at other tumor types is those are characterized in general with lower levels of folate receptor Alpha expression. So this gives us an opportunity to more effectively address.

Mark Joseph Enyedy: So it's really all of those things working together. I'm not sure we could isolate an individual element to sort of say what the impact is, but what we clearly see from those data is significantly improved efficacy, particularly in those cell lines and models with lower levels of folate receptor alpha expression, which was the key design criterion here based on the clinical experience with myrmituximab. And so that's how we're thinking about it. And so, you know, as we look at the big picture here, obviously, this gives us a chance to address patients with lower levels of expression within ovarian cancer. But also, what we see when we look at other tumor types is that those are characterized, in general, with lower levels of folate receptor alpha expression.

The separate indications.

Okay, great. Thanks, and then just one question on ovarian cancer on the competitive landscape.

Just wondering.

If it's no and to what degree full it off our receptor expression overlaps with other anti chance such as and not be to be for example.

Yeah, I'm I'm not aware of any published data that answers that question, Michael but you know I'm fully receptor alpha is expressed in over 80% of ovarian cancer and Nappy. TV is also over expressed is about 80, 85% of ovarian cancer and I think you know Ah we also now.

Mark Joseph Enyedy: So this gives us an opportunity to more effectively address those separate indications. Okay, great, thanks. And then just one question on ovarian cancer in the competitive landscape. Just wondering if it's known to what degree folate alpha receptor expression overlaps with other antigens, such as NAPI2B, for example.

That is really the patients with high folate receptor alpha expression, the 40% of ovarian cancer patients who benefit the most from Marvin talked to now nappy QB certainly the generic attack a c. that has was stopped in development for nappy to be they did not use the patient selection strategy and they didn't really see sufficient access.

Anna Berkenblit: Yeah, I'm not aware of any published data that answers that question, Michael, but you know, folate receptor alpha is expressed in over 80% of ovarian cancer, and NAPI 2B is also overexpressed in about 80-85% of ovarian cancer. And I think, you know, we also know that it's really the patients with high folate receptor alpha expression, the 40% of ovarian cancer patients who benefit the most from my NAPI 2B, certainly the Genentech ADC that was stopped in development for NAPI 2B; they did not use a patient selection strategy, and they didn't really see sufficient activity to continue developing that molecule. Now with Mirsana's NAPI 2B, you know, they may need a patient selection strategy, and then it's not clear to me at this point whether or not those patients would overlap with high FR alpha.

70 to continue progressing that molecule now with Mersana snappy TV you know they may need a patient selection strategy and then.

It's not clear to me at this point, whether or not those patients would overlap with with high fr Alpha patient.

Very helpful. Thanks, and then last one I don't know that came up earlier, but just on the you know regulatory pathway and B P. D. C. N I'm just wondering you.

No I guess, if if there if you've had any sort of interactions with the F.D.A. on requirements. There and you know how are you thinking about timelines towards filing and B P. D C and specifically, which is a very Ah you know fast to market type that opportunity.

Anna Berkenblit: And then last one, I don't know if that came up earlier, but just on the, you know, regulatory pathway in BPD-CN, wondering, You know, I guess if there if you've had any sort of interactions with the FDA on requirements there and, you know, how do you think about timelines towards filing in BPD-CN specifically, which is a very, you know, fast to market type opportunity. Yeah, we see it in those terms, and so our goal for this year has been to generate sufficient data in this population to discuss a reasonably coherent profile for 632 and BPDCN in terms of efficacy, safety, and tolerability, and so our goal is to get with the agency before the end of this year with those data in hand to define a path forward, which, as you say, the goal there would be to emphasize a speed-to-market strategy for this rare indication. Okay, great. Thanks, and I appreciate the update. Great.

Yeah, we've seen in those terms and so our goal for this year or has that generate sufficient data in this population to discuss you know a reasonably coherent profile.

Were 62 wouldn't be PD, yeah in terms of.

Efficacy safety and Tolerability and so our goal is to get with the agency before the ended this year with those data in hand, too fine a path forward, which as you say the goal there would be to emphasize the speed to market strategy for this rare indication.

Okay, great. Thanks, and appreciate the update.

Great. Thanks, Michael.

Mark Joseph Enyedy: Thanks, Mark. Thank you. As a reminder, if you would like to ask a question, press the star then the one key on your touchtone telephone.

Thank you as a reminder, if he would like to ask a question press. The Star then one key on your Touchtone telephone.

Our next question comes from Jonathan Chang with FCB Leerink. Your line is open.

Mark Joseph Enyedy: Our next question comes from Jonathan Chang with SCB Lyrinc. Your line is open. Good morning, and thanks for taking my questions. First question, what are your latest thoughts on potential business development opportunities for Merpitec's MAP? As we've discussed previously, Jonathan, we've had inbound interest in terms of the rights to murmatoximab in China, and so we're pursuing those opportunities. And beyond that, you know, our focus is first and foremost the U.S. market. We see that as the largest and most profitable market, and so the expectation is that we would be in a position to launch in the U.S.

Hi, good morning, and thanks for taking my questions. My first question what are your latest thoughts on potential business development opportunities for Mirvetuximab.

As we've discussed previously Jonathan we try to inbound interest or in terms of the rights to Barbara talks a map in China. So.

We're pursuing.

Those opportunities and beyond that Youre, our focus is first and foremost the U.S. market, we see that as the largest and most profitable market and so the expectation is that a weakening in a position to launch and the U.S. This is a highly concentrated market limited.

Mark Joseph Enyedy: This is a highly concentrated market with a limited number of physician targets. In the initial label indication for the product, there's no active competition, so, I mean, what we're doing here is, you know, demonstrating superiority to single-agent chemotherapy, particularly in the Mirasol study design, and, you know, all of the drugs that are used there are generic drugs. And, you know, I can't speak directly to what Roche Genentech is doing in terms of vast amounts of information, but it's So that's the U.S., and I think we will be evaluating opportunities for Europe as we go forward. But again, the market there is actually slightly more concentrated than the U.S. market. However, the need to have national-level commercial infrastructure offsets that incremental increase in concentration.

Number of physician targets.

In the initial labeled indication for the product there's no active competition. So I mean, what we're doing here is you know demonstrating.

Superiority the single agent chemotherapy, particularly in the Mirasol study design and you know all day drugs that are you there are generic drugs and.

I can't speak directly to what Roche Genentech dealing in terms of a rapid promotion, but it's limited and so we think that you know a commercial investment here would be modest and something well within the and that of a company with our experience. So that's the that's the.

You asked and I think Oh, we will be evaluating opportunities.

For Europe as we go forward, but again the market there is actually slightly more concentrated a then the U.S. marcon however, the need to have national level.

Commercial infrastructure offsets that a incremental increasing concentration, but again you know focused investment could support a very effective launch a particularly in the the key five in a in a limited or additional set of clusters. For example, the Nordics and then I'll walk so I want to value.

Mark Joseph Enyedy: But again, you know, a focused investment could support a very effective launch, particularly in the key five in a limited additional set of clusters, for example, the Nordics and Benelux. So we're evaluating that as we speak. So the principal focus at the moment is around the opportunity in China. Got it, thank you. And another question on IMGC 936.

Leading that as a as we speak so the principal focus at the moment is around opportunity in China.

Got it thank you.

And second question on I am GC 936.

The Macrogenics team also found it really excited about this program on their call yesterday I can you talk about the promise of Adam nine as an 80 see target and reasons for excitement that this program.

Anna Berkenblit: The MacroGenics team also sounded really excited about this program on their call yesterday. Can you talk about the promise of ADAM9 as an ADC target and the reasons for your excitement about this program? Sure, so ADAM9 is a novel target. It's a matrix metalloproteinase expressed on the cell surface of multiple solid tumors. It is not expressed particularly in normal tissue. So that window, that difference between tumor expression and normal tissue expression makes it an ideal target for an antibody drug conjugate. We can target the tumor and spare normal tissues of the toxicities associated with non-targeted, if you will, cytotoxic therapies like standard chemotherapy. It is also internalized well. That is another key feature of any target that makes it a good target for an antibody drug conjugate.

Sure. So added nine is a novel targets and matrix and that's how pervasive across on cell surface of multiple solid tumor is not expressed particularly on new holiday issue. So that window that difference between tumor regression in normal tissues crushing makes it an ideal.

Target affording study drug conjugate, we can parse it can mertens their normal tissues of the toxicities associated with non Harvey then if you will cytotoxic therapy like standard chemotherapy. It is also in Taiwan.

Another key feature of any target that makes a good target for antibody drug conjugate and then it is expressed on the multiple solid tumors that really how high unmet need pancreatic cancer gastric cancer and even non small cell lung cancer, while there have been amazing developments in non small.

Anna Berkenblit: And then it is expressed on multiple solid tumors that really have high unmet need, pancreatic cancer, gastric cancer, and even non-small cell lung cancer. While there have been amazing developments in non-small cell lung cancer, the unmet need remains high there. And then triple negative breast cancer, that's a smaller portion of breast cancer, but these patients don't have any targeted therapies available to them, so that is another opportunity as well. These are really the top solid tumors that express ADAM9. And certainly, there are others that we could explore once we have achieved proof of concept with one of these tumors that I have just described.

Well in lung cancer, the unmet need remain high there a and then triple negative breast cancer, that's a smaller a portion of breast cancer, but these patients don't have any targeted therapies available to them. So that is another opportunity as well. These are really that the top solid tumors that express out a nine oh and certainly there are.

Or others that we could explore once we have achieved proof of concept a with one of the tumors that I just mentioned.

Anna Berkenblit: Got it. Thanks for taking the question. Sure. Thanks, John.

Oh.

Got it thanks for taking the questions.

Sure I think some instances.

Mark Joseph Enyedy: And just as an addendum there, I mean, we really do thank the team at Macrogenics. They've been great collaborators, worked hard to get the IND in, and so we're now in a position to move forward with this and are expecting our first patient in the fourth quarter. And we're really excited about this because this program integrates the DM21 payload.

And on there I mean really do you think the team at Macrogenics they've been great collaborators worked hard to get a the IDN and so we're now in a position to move forward with us and our to start being our first patient and in the fourth quarter. We're really excited about this because this this program integrates the do you have 21 payload.

So I specific conjugation made some improvements to the antibody and so I'm I'm, we're very much looking forward to seeing how this product performs in the clinic.

Mark Joseph Enyedy: We use site-specific conjugation, and we've made some improvements to the antibody, and so we're very much looking forward to seeing how this product performs in the clinic. Thank you. And we have a question from Joe Catanzaro with Piper Sandler. Your line is open. Hey guys, thanks so much for taking my questions here. Maybe one first on 632.

Thank you and we have a question from Joe CAD 10 zero with Piper Sandler Your line is open.

Hey, guys. Thanks, so much for taking my questions here, maybe one first on the Sixthree too. So I know you mentioned dell's on us we've gotten about five quarters worth of insight into the BP DCM market via that product just wondering how that influences your thinking around that opportunity and what learnings maybe that provide stuff to how you approach.

Mark Joseph Enyedy: So Anna, you mentioned Alzheimer's. We've gotten about five quarters' worth of insight into the BPD-CM market via that product. Just wondering how that influences your thinking around that opportunity and what learnings maybe that provides for how you approach it. Yeah, this is Mark, Joe. What we hear is that the clinical profile of Alzheimer's is quite challenging for physicians. And so, first and foremost, community physicians have generally not wanted to manage patients in their offices and so refer patients into larger centers.

[music].

Yeah. This is more Joe.

What we here is that the clinical profile of those aren't quite challenging for physicians and so first and foremost the community physicians have generally not wanting to manage patients and that office and so.

<unk> patients into the larger centers that drug requires hospitalization or for the first course, so patients have to go into the hospital for a minimum of six day and then you know there are significant other toxicities in metro carries a black box.

Mark Joseph Enyedy: That drug requires hospitalization for the first course, so patients have to go into the hospital for a minimum of six days. And then there are significant other toxicities, and that drug carries a black box warning for capillary leak syndrome. So there are a number of challenges with respect to the profile of that drug, and when we look at 6.3.2, what we see is compelling efficacy, really a very benign safety profile in terms of the adverse events, and this drug can be administered in 30 minutes in the outpatient setting. And so there is a profound difference in the profiles of those two drugs, which I think presents us with a very different opportunity from a development perspective.

Morning for capillary leak syndrome. So there are number of challenges with respect to the profile of that drug and when we look at.

Six three to what we see is compelling advocacy really a very benign safety profile in terms of the adverse events and Ms drugs can be administered in 30 minutes and the outpatient setting and so what we can see there's a profound difference and.

Profiles of of those two drugs, which I think presents us with a very different opportunity or someone development perspective, you know our initial focus is in the relapse refractory setting what we're seeing a is that patients who've been previously treated with elds onrad as well as previously treated with intensive chemotherapy.

Mark Joseph Enyedy: Our initial focus is in the relapsed refractory setting, and what we've seen is that patients who've been previously treated with Alzheimer's, as well as previously treated with intensive chemotherapy regimens, respond to IMGN 6.3.2. And so we think that, you know, we are focused, as we mentioned in some of the earlier comments with Michael and Boris, on the On Up Speed to Market strategy. We think the relapsed refractory patients position us best to affect that strategy. And with this profile, we think that it would allow us to get to an initial label, and then we could think through what expansion would look like in frontline patients. So this is a rare indication, but the goal here is to get a product on the market and then look for further expansion opportunities, which is why all of the groundwork we have ongoing in AML is important to the longer-term value of the program. Okay, I got it.

Regimens respond to a I am G.N. sixthree too and so.

We think that you know we are focused and as we mentioned in sort of the earlier comments.

It was like one borsellino speed to market strategy, and we think the relapsed refractory patients.

Positions as best to affect that a that strategy and with this profile, we think that that would allow us to get an initial day one that we could think through what expansion will look like into a into frontline patients. So this is a rare indication, but you know the goal here is to get a product on the market and.

And look for further expansion opportunities, which is why all the speed working dialog going in and now it's important to the longer term value the program.

Okay got it. Thanks, maybe just one quick follow up if I, if I may so you're still guiding towards the second half 21 late filing I think Mark you noted that large chunks of the B.L.A. already complete I'm, just wondering what parts of it needs to be completed beyond data from psoriasis and all those things that you could get started before the topline read out from that try.

Mark Joseph Enyedy: Thanks. Maybe just one quick follow-up, if I may. So you're still guiding towards the second half 21 BLA filing. I think, Mark, you noted that large chunks of the BLA are already complete. Just wondering what parts would need to be completed beyond data from Soraya and are those things that you could get started before the top-line readout from that trial, or do you need to wait? Yeah, so, I mean, one of the big elements of any DLA filing is the CMC section, and so, you know, we're in good order there in terms of all of our vendors lined up and the related processes, and so much of that work has already The preclinical sections are well underway, so it really would be the clinical supplement that we're looking at here.

I will do you need to wait.

Yeah. So I mean, one of the big elements of any of the L.A. by the CMC section and so you know we're in good order there in terms of all of our vendors like often.

Hey, good processes and so much of that work is already been completed so we'll look to do that are the preclinical a sections are well underway. So really wouldn't be the clinical supplement that we're looking out here.

Okay got it thanks, so much for taking my questions.

Mark Joseph Enyedy: Okay, got it. Thanks so much for taking my questions. Thank you, and there are no other questions in the queue. I'd like to turn the call back to Mark Enyedy for closing remarks. Great, thanks very much. We appreciate your time today. You know, it was a challenging quarter in terms of operating in the context of a pandemic.

Sure.

Thank you and there are no other questions in the two I'd like to turn the call back to Mark entity for closing remarks.

Great. Thanks, very much appreciate your time today, you know is a challenging quarter in terms of operating a in the context of a pandemic I'm very proud of the team here in terms of the work that we've been able to do to maintain momentum across the portfolio and keep us.

Mark Joseph Enyedy: I'm very proud of the team here in terms of the work that we've been able to maintain momentum across the portfolio and keep us generally on track with the timelines that we previously articulated. And we look forward to continuing to update you with additional milestones as we work through the back half of the year, in particular starting with ESMA. So, thanks very much, and stay safe. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.

Generally on track with the timelines that we previously articulated and we look forward to continuing to update you with a additional milestones as we work through the back half of the year, a particular, starting with a with as well. So thanks very much in the Stacey.

Ladies and gentlemen, this concludes todays conference call. Thank you for participating you may now disconnect everyone have a great day.

[music].