Q1 2022 ImmunoGen Inc Earnings Call
Good morning.
First quarter 2022 financial ones.
This conference call today's conference is being recorded at this time I'd like to turn the call over to Neil.
Senior director of corporate Communications. Please go ahead.
Good morning, and thank you for joining today's call earlier today, we issued a press release that includes a summary of our recent progress and first quarter 2022 financial results. This press release and a recording of this call can be found under the investors and media section of our website at Immunogen Dotcom with me.
Mark Enyedy: This is an event-driven study, so enrollment is not the only factor in the timing of the top-line analysis. Based upon a re-forecast generated in conjunction with the recent pre-specified interim futility analysis for Mirasol, we now expect to reach the requisite number of PFS events in the fourth quarter of this year and report top-line data from Mirasol in early 2023. Anna will provide more color on this and our label expansion studies in a moment.
Today are mark <unk>, our president and CEO and a broken black our Chief Medical Officer, Kristin Harrington Smith, our Chief commercial officer, and Susan Altshuler, our CFO during today's call. We will review our recent accomplishments for the business, our Q1 financial results and highlight upcoming anticipated or that we.
Mark Enyedy: Our second pivotal program, PVEC, is progressing nicely, and we expect preliminary efficacy data from our pivotal Cadenza study in frontline BPD-CN before year-end. In addition, patient enrollment is ongoing in our Phase 1b slash 2 expansion cohorts, evaluating PVEC, azacitidine, and venetoclax in both relapsed and frontline AML patients, which are accruing rapidly. We expect to share data from both cohorts at ASH later this year. Looking at the rest of our pipeline, we anticipate sharing initial data before year end from the phase one dose escalation trial of IMGC936, our first-in-class ADAM9 targeting ADC, which we are co-developing with Macrogenics.
We will be making forward looking statements based on our current expectations and beliefs. These statements are subject to risks and uncertainties and our actual results may differ materially. Please consult the risks outlined in our press release issued this morning, and the risk factors section of our most recent annual report on Form 10-K and in our other SEC filings, which are available at SEC Gov.
An immunogen dotcom and with that I'll turn the call over to Mark Good morning, and thank you for joining US today building on the strong survey data and capital raise late last year. We've continued to make excellent progress in 2022, our top priority is to gain approval for mirv monotherapy in patients with folate receptor Alpha high platinum resistant.
Mark Enyedy: In addition, a manuscript describing the preclinical evaluation of IMGC936 was recently accepted for publication in Molecular Cancer Therapeutics and will soon be available online. We also made meaningful progress addressing the CMC information request from FDA regarding our Phase I study of IMGN151 and expect to initiate the clinical study by mid-year. With our progress to date and meaningful catalyst ahead, we believe we are well positioned to create significant value as we move through the remainder of the year. With that, I'll turn the call over to Anna to provide additional color on the Merva Talks map program. Anna
In ovarian cancer, and we recently achieved two critical milestones to that in the presentation of results for our positive pivotal <unk> trial. It S. G O and the submission of the BLA to FDA for potential accelerated approval.
As we progress towards our goal of becoming a global fully integrated oncology company since the start of the year. We've also continued enrollment in the confirmatory phase III Mirasol and phase two Piccolo studies with Mirv monotherapy expanded our commercial team and accelerated launch preparations in anticipation of a merv approval further.
Other accrued patients in our pivotal cadenza study of <unk> N V. P. D. C N initiated expansion cohorts in both relapsed and frontline AML patients combining P back with as decided in and we need the clocks and progressed our earlier stage programs I M. G. C 936, and I M. G N 151 to expand on these.
Anna Birkenblatt: Thanks, Mark. We were thrilled to have Dr. Matalonis present the results from the Pivotal SEREA trial in a plenary session at the SGO annual meeting in March. Since then, we have continued to engage with stakeholders across the ovarian cancer community, and the enthusiasm for these data and the broader MRFA-TUXOMAB program is high. As a reminder, SIREA is a single-arm Phase III study evaluating mervitoximab in patients with folate receptor alpha-high, platinum-resistant ovarian cancer.
Points, starting with mirv enrolment in our confirmatory Mirasol trial accelerated following the release of top line results from Surya. This is an event driven study. So enrollment is not the only factor in the timing of the topline analysis.
Anna Birkenblatt: Soraya enrolled a heavily pre-treated population of 106 patients, all of whom had received prior bevacizumab. 38% had stage four disease, 51% had three prior therapies, and 48% had received a prior PARP inhibitor. Treatment options for platinum-resistant ovarian cancer consist of single-agent chemotherapy, which produces low response rates and limited duration of response.
Based upon our re forecast generated in conjunction with the recent pre specified interim futility analysis for Mirasol. We now expect to reach the requisite number of PFS events in the fourth quarter of this year and report top line data for Mirasol in early 2023, and al will provide more color on this in our label expansion studies in a moment.
Our second pivotal program P. Vac is progressing nicely and we expect preliminary efficacy data from our pivotal cadenza study in frontline V. P. D. C N before year end. In addition patient enrollment is ongoing in our phase one b slash two expansion cohorts evaluating P back as decided in if you need a class in both relapsed in front.
Anna Birkenblatt: The primary endpoint of SIREA was an overall response rate of 32.4% and included 5 complete responses, which rarely occur in this population. Importantly, as we updated at SGO, the median duration of response, the key secondary endpoint, was 6.9 months by investigator, and the median progression-free survival, or PFS, in this heavily pretreated population was 4.3 months. These efficacy and durability data are consistent regardless of the number of prior lines of therapy or prior PARP inhibitor use.
Line AML patients, which are accruing rapidly we expect to share data from both cohorts at Ash later this year.
Looking at the rest of our pipeline, we anticipate sharing initial data before year end from the phase one dose escalation trial of I M. G. C 936, our first in class Adam nine targeting ADC, which we are co developing with Macrogenics. In addition, a manuscript describing the preclinical evaluation of I M. G. C 936 was.
Anna Birkenblatt: The safety profile observed in Soraya is consistent with that seen in the broader Mervituximab program and is characterized by predominantly low-grade, reversible ocular and GI events, which were generally managed with supportive measures and dose modifications if needed. The most common adverse events were blurred vision, keratopathy, nausea, dry eye, and fatigue.
Recently accepted for publication and molecular cancer Therapeutics and will soon be available online.
We also made meaningful progress addressing the CMC information requests from FDA regarding our phase one study of I M. G. N 151, and expect to initiate the clinical study by mid year.
Anna Birkenblatt: At ASCO, we look forward to presenting integrated safety data from over 450 patients treated with Mervituximab in SIREA Forward I and our Phase I study, and we plan to provide more color on SIREA efficacy data, including the PFS curve, CA-125 response rate, and impact of dose modifications. At SGO, we also disclosed that the foundational 70 psoraea-like patients, all FR-alpha high by PF2+, all platinum-resistant with one to three priors, and all with prior bevacizumab, showed a similar median PFS with MIRV as what we saw in psoraea.
With our progress to date and meaningful catalysts ahead, we believe we are well positioned to create significant value as we move through the remainder of the year.
With that I'll turn the call over to Anna to provide additional color on the mirv. It talks map program Anna.
Thanks Mark.
We're thrilled to have Dr. Matt alone is present the results from the pivotal Soraya trial in a plenary session at the S. G O annual meeting in March.
Since then we have continued to engage with stakeholders across the ovarian cancer community and the enthusiasm for these data and the broader MRF attacks and that program is high.
As a reminder, Surya is a single arm phase III study evaluating <unk> in patients with folate receptor Alpha high platinum resistant ovarian cancer.
Anna Birkenblatt: One frequent question that arose was how these patients in the chemotherapy control arm of Forward I performed. Reviewing these data, the equivalent chemotherapy control population showed a median PFS of under 2.8 months. Remember that this is based on post-hoc analyses with small patient numbers, especially in the control arm of Forward 1 due to the 2-to-1 randomization. But nevertheless, this is consistent with BEV-pretreated patients representing a worse population with higher unmet need and underscores the clinical meaningfulness of the median progression-free survival of 4.3 months in psoriasis.
So ray it enrolled a heavily pretreated population of 106 patients all of whom had received prior bevacizumab.
38% had stage four disease, 51% had three prior therapies and 48% had received a prior PARP inhibitor.
Treatment options for platinum resistant ovarian cancer consist of single agent chemotherapy, which produces low response rates and limited duration of response.
The primary endpoint of threat with an overall response rate of 32, 4% and included five complete responses, which rarely occur in this population.
Anna Birkenblatt: In addition, it supports our belief that Mervitoximab will show a clinically meaningful improvement in PFS over chemotherapy with a longer median PFS in a less heavily pretreated population in Mirasol. Moving to Murosol, and as Mark mentioned, we have recently completed an interim analysis, and we are pleased to report the IDMC recommended the study continue without modification. Following the disclosure of Soraya top-line results, Mirosol enrollment increased significantly
Importantly, as we updated at S. G. L. The median duration of response the key secondary endpoint was $6 nine months by investigator and the median progression free survival or PFS in this heavily pretreated population was for three months.
These efficacy and durability data are consistent regardless of the number of prior lines of therapy or prior PARP inhibitor use.
The safety profile observed in Syria is consistent with that seen in the broader merv attacks on that program and is characterized by predominantly low grade reversible ocular M. Gi events, which were generally managed with supportive measures and dose modifications if needed.
Anna Birkenblatt: Considering the continued acceleration of enrollment and now having assessed the PFS event rate in conjunction with the interim analysis, we are updating our Mirosol guidance to include a projected primary completion date in the fourth quarter and top-line data in early 2023. While the timeline for Mirasol's top-line data has been adjusted, we continue to expect potential accelerated approval for Mervitoximab monotherapy this year based on the SREA data. Turning to the rest of the Mervituximab program, we're continuing to enroll piccolo, our single-arm study of Mervituximab monotherapy in patients with folate receptor alpha-high, recurrent platinum-sensitive ovarian cancer intended to support label expansion. There is an increasing need for an effective non-platinum option in later lines of platinum-sensitive disease, and we believe our phase one anti-tumor activity in this population is quite promising.
The most common adverse events were blurred vision, keratopathy nausea, dry eye and fatigue.
At <unk>, we look forward to presenting integrated safety data from over 450 patients treated with <unk> in Korea forward, one and our phase one study.
And we plan to provide more color on survey of efficacy data, including the PFS curve CA 125 response rate and impact of dose modifications.
At F. G O. We also disclosed that the foundational 70, so ray of like patients all fr Alpha high by P. S. Two Clos all platinum resistant with one to three priors and all with prior Bevacizumab showed a similar median PFS with Merck as to what we saw in Syria.
Anna Birkenblatt: Our strategy to position Mervituximab as the combination agent of choice is also advancing. We expect to gain compendia listings for the Mervituximab plus Bevacizumab doublet in patients with folate receptor alpha high recurrent ovarian cancer in close proximity to the initial monotherapy approval of Mervituximab. Furthermore, work to initiate the Phase III Gloriosa study is underway, and we expect to enroll the first patient by mid-year. Gloriosa will evaluate the benefit of Mervatuximab plus Bevisusimab maintenance versus Bevisusimab maintenance alone in the second line platinum sensitive maintenance setting.
One frequent question that arose with how these patients in the chemotherapy control arm a forward one performed well.
Reviewing these data the equivalent chemotherapy control population showed a median PFS of under 2.8 months.
Remember that this is based on post hoc analyses with small patient numbers, especially in the control arm of forward one due to the two to one randomization, but nevertheless, this is consistent with Bev pretreated patients representing a worst population with higher unmet need and underscores the clinical meaningfulness of the median progression.
Ration free survival of four three months in Syria.
Kristen Harrington-Smith: The addition of bevacizumab to a platinum doublet provides a modest improvement in PFS of just three to four months in this setting, so we are excited by Mervitoximab's potential to improve upon this based on the data we have generated for Mervitoximab plus bevacizumab in the treatment setting. Rounding out the Mervituximab program is Trial 420. Based on promising activity observed in phase 1 dose escalation for Mervituximab plus carboplatin in recurrent platinum-sensitive disease, we plan to initiate Trial 420 this quarter to inform our path to registration in this setting.
In addition, it supports our belief that Merv Rituximab will show a clinically meaningful improvement in PFS over chemotherapy with a longer median PFS and a less heavily pretreated population in mirasol.
Moving to Mirasol and as Mark mentioned, we have recently completed an interim analysis and we are pleased to report the IBM see recommended the study continue without modification.
Following the disclosure of Soraya topline result, mirasol enrollment increased significantly.
Considering the continued acceleration of enrollment and now having assessed the PFS event rate in conjunction with the interim analysis. We are updating our mirasol guidance to include a projected primary completion date in the fourth quarter and top line data in early 'twenty 'twenty three.
Kristen Harrington-Smith: This is a single-arm phase 2 study of Mervituximab plus carboplatin followed by Mervituximab continuation in approximately 110 patients with folate receptor alpha low, medium, or high platinum-sensitive ovarian cancer. And with that, I'll turn the call now over to Kristen to cover our commercial preparations. Okay?
While the timeline for Mirasol topline data has been adjusted we continue to expect potential accelerated approval for Murdo toxin that mono therapy. This year based on this array of data.
Kristen Harrington-Smith: Thanks, Anna. In anticipation of bringing mirabatexamab to market later this year, following potential accelerated approval by FDA, we have built our commercial leadership team with some key hires, including our head of market access, strategy, and operations, and sales. In addition to attracting best-in-class talent, we also have made progress on our launch imperatives. And as a reminder, those are focused on redefining expectations for positive outcomes with mirvotuximab in platinum-resistant ovarian cancer, supporting adoption of early folate receptor alpha testing, and establishing standards for in-house and centralized testing upon approval.
Turning to the rest of the mirv attacks, a mab program, we're continuing to enroll piccolo, our single arm study of murder toxin that monotherapy in patients with folate receptor Alpha high recurrent platinum sensitive ovarian cancer intended to support label expansion. There is an increasing need for an effective non.
Latin am option and later lines of platinum sensitive disease, and we believe our phase one the antitumor activity in this population are quite promising.
Our strategy to position Merv attached to them as the combination agent of choice is also advancing.
Kristen Harrington-Smith: Ensuring positive physician and patient experiences through tailored education and guidance for patient management and seeking broad payer access and reimbursement to deliver a seamless patient experience. The start of 2022 has been both intense and purposeful for the commercial team.
We expect to gain compendium listing for the murder tucks in Nab plus bevacizumab doublet in patients with folate receptor Alpha high recurrent ovarian cancer in close proximity to the initial monotherapy approval of Mirv Rituxan App.
Furthermore, work to initiate the phase III Glorioso studies underway and we expect to enroll the first patient by mid year.
Kristen Harrington-Smith: Not only have we selected and onboarded our agency of record, but we have also moved quickly to identify and address the key requirements for a successful launch while limiting potential barriers to treatment for patients. That means we are and will continue to be focused on educational efforts supporting awareness of myrtidioxamab and the importance of testing for folate receptor alpha expression, and we are working in close partnership with our colleagues in medical affairs. In addition, we've initiated a go-to-market assessment to determine the commercial field roles necessary to drive demand, identify and prioritize relevant accounts and providers, and optimize our customer-facing team.
Glorioso, we'll evaluate the benefit of <unk>, plus bevacizumab maintenance versus Bevacizumab maintenance alone in the second line platinum sensitive maintenance setting.
The addition of Bevacizumab to a platinum doublet provides a modest improvement of PFS of just three to four months in this setting. So we are excited by <unk> potential to improve upon this based on the data we have generated for <unk> plus bevacizumab in the treatment setting.
Rounding out the murder toxin that program is trial for 'twenty.
Based on promising activity observed in phase one dose escalation for <unk> plus carboplatin in recurrent platinum sensitive disease, we plan to initiate trial for 'twenty this quarter to inform our path to registration in this setting.
Susan Altshuler: On the market access front, we've initiated the setting up of our patient support services platform, and we are actively working with our distribution channel partners to have Mervituximab ready for shipment to customers shortly after approval. So, with a focus on high priority, high impact initiatives and an agile, experienced team in place, we believe we are well positioned for a successful launch, and we look forward to bringing Mervituximab, SORAbtanz With that, I will turn the call over to Susan to cover our financials. Susan?
This is a single arm phase two study of <unk>, plus Carboplatin, followed by Margaret toxin that continuation and approximately 110 patients with folate receptor alpha low medium or high platinum sensitive ovarian cancer.
And with that I'll turn the call now over to Kristin to cover our commercial preparations Kristen.
Thanks, Anna in anticipation of bringing <unk> to market later this year following potential accelerated approval by FDA, we have built our commercial leadership team with some key hires including our head of market access.
Susan Altshuler: Thanks, Kristen. For the first quarter of 2022, we generated $38.1 million in revenue, $6.4 million of which came from non-cash royalty revenues. The remainder came substantially from license and milestone fees, which included recognition of $21.6 million of fees previously received under the company's collaboration agreement with Huadong Medicine and $9.2 million of a $13 million upfront fee received in the first quarter under the company's license agreement with Lilly. Operating expenses were $60.9 million, compared with $44.6 million in the first quarter of 2021, and comprised of $44.3 million of R&D expenses, compared with We ended the first quarter with $437.7 million in cash on the balance.
Strategy in operations and sales.
In addition to attracting best in class talent. We also have made progress on our launch imperatives and as a reminder, those are focussed on redefining expectations for positive outcomes with Merck Rituximab in platinum resistant ovarian cancer supporting adoption of early folate receptor alpha testing and establishing <unk>.
Standards for in house and centralized testing upon approval.
Ensuring positive physician and patient experiences through tailored education and guidance for patient management App.
And seeking broad payer access and reimbursement to deliver a seamless patient experience.
The start of 2022 has been both intense and purposeful for the commercial team not only have we selected and on boarded our agency of record. We've also moved quickly to identify and address the key requirements for a successful launch will eliminate potential barriers to treatment for patients.
Operator: Our financial guidance for 2022 remains unchanged. We expect revenues to be between $75 and $85 million, operating expenses between $285 and $295 million, and cash and cash equivalents at year end between $245 and $255 million. Given the range and timing for potential approval of mervituximab, revenue guidance does not yet include potential product sales from mervituximab. However, we expect that our current cash, combined with anticipated product and collaboration revenues, will fund operations comfortably into 2024. With that, we'll open the call for questions. Thank you. To ask a question, you will need to press star 1 on your telephone.
That means we are and will continue to be focused on educational effort supporting awareness of them or protect the man and the importance of testing for folate receptor Alpha expression and we are working in close partnership with our colleagues in medical Affairs.
In addition, we've initiated a go to market assessment to determine the commercial field roles necessary to drive demand identify and prioritize relevant accounts and providers and optimize our customer facing team.
On the market access front, we've initiated setup of our patient support services platform and we are actively working with our distribution channel partners to have mirv texoma ready for shipment to customers shortly after approval.
Operator: To withdraw your question, press the pound. Please stand by while we compile the Q&A roster. Our first question is from John. Hi guys. Good morning.
With a focus on high priority high impact initiatives and an agile experienced team in place. We believe we are well positioned for a successful launch and we look forward to bringing merv attack them absorb tanzania to patients in need.
John Newman: Thanks for taking my question. You mentioned that enrollment for Mirosol picked up following, I just wanted to confirm that the planned enrollment target remains the same. You also mentioned that you anticipate a compendia listing, with a combination of Rituximab plus Avastin, shortly after the initial Mervituximab approval. What I'm wondering is if this were the case and doctors were to use this combination.
With that I will turn the call over to Susan to cover our financials Susan.
Thanks, Kristen for the first quarter of 2022 we generated $38 $1 million in revenue $6 4 million of which came from noncash royalty revenues.
Remainder came substantially from license and milestone fees, which include recognition of 21 6 million of fees previously received under the company's collaboration agreement with what on Medicine, and $9 2 million of a 13 million upfront fee received in the first quarter under the company's license agreement with Lilly.
Anna Birkenblatt: Where in the treatment paradigm do you think that combination might work? Thanks, John. So our enrollment target for Mirasol remains the same at 430 patients. Enrollment did increase after we presented top-line data from Suraya late last year. And so we have kept the enrollment target for Mirasol at 430 patients.
Operating expenses were $69 million compared with 44 6 million in the first quarter of 2021 and comprised of $44.3 million of R&D expenses compared with $34 4 million in the first quarter of 2021, and $16 $6 million of selling general and administrative expenses.
Kristen Harrington-Smith: For the Mervituximab plus Avastin combination, we anticipate receiving compendia lifting in close proximity to our initial approval, and so I'll turn it over to Kristen Harrington-Smith to discuss where that combination might be used. Sure.
As compared with $10 2 million in the first quarter of 2021, we.
We ended the first quarter with $437.7 million in cash on the balance sheet.
Kristen Harrington-Smith: So when we look at the platinum-resistant ovarian cancer market dynamics, we see that well more than 25% of patients in any line, second, third, fourth, fourth plus, receive Avastin plus chemotherapy regimen or any kind of combo with fevicizumab. So we anticipate that it will be used where it's already used in combination across those lines. Thank you. Our next question comes from Michael. Hey guys, good morning.
Our financial guidance for 2022 remains unchanged, we expect revenues to be between 75 and $85 million operating expenses between 285 and $295 million in cash and cash equivalents at year end between 245 and $255 million.
Given the range and timing for potential approval Martha toxin that revenue guidance does not yet include potential product sales from more of a toxin that we.
We expect that our current cash combined with anticipated product and collaboration revenues will fund operations comfortably into 'twenty 'twenty four with.
Michael Vasconcelles: Thanks for taking my question. And I'm just wondering if you have any additional information on this MIRASOL interim analysis. I don't know if you could share, you know, how many patients perhaps triggered this and what the parameters were that were assessed in that analysis. And then, you know, a second question on MIRASOL is just wondering around about the enrollment dynamics of the trial. I'm just curious if you had overlapping trial sites with Soraya, which obviously focused on the Avastin pre-treated patients in Soraya, and whether perhaps that may have skew enrollment early in the research study towards Avastin naive patients and whether that perhaps may play a role in the overall cadence of the PSR. Yeah, thank you, Michael.
That will open the call for questions.
Yeah.
Thank you to ask a question you will need to press star one on your telephone to withdraw your question press the pound key.
Please stand by while we compile the Q&A roster.
Our first question is from John Newman.
Your line is open.
Hi, guys. Good morning, Thanks for taking my question.
So you mentioned that enrollment for Mirasol picked up following.
Presentation of the data this year.
Just wanted to confirm that the planned enrollment target from here.
So it remains the same.
You also mentioned that you anticipate compendium listing.
The combination of Rituxan plus avastin.
Shortly after the initial mirv rituxan approval.
I'm wondering is if this were the case and doctors where to use this combination.
Where in the treatment paradigm do you think that commonly combination Mike.
Thanks.
Thanks, John So our enrollment target for Mirasol remains the same at 430 patients.
Anna Birkenblatt: So, for Mirosol, we had a pre-specified interim analysis for futility, just like we had done in Forward One. It's really to allow a dry run, if you will, from an operational perspective so that we know we're in good shape for when we're ready to do the final protocol-specified analysis for the primary endpoint. So, it was triggered at the time we had 110 PFS events. And so, as long as the efficacy data in terms of PFS were trending in the right direction, the study was to continue as planned, and that's exactly what IDMC recommended to us, to continue the study without modification.
Enrollment did increase after we presented top line data from Syria late last year and so we have kept the target for Mirasol up 430 patients for the <unk> plus Avastin combination we anticipate receiving.
Receiving compendium lifting in close proximity to our initial approval and so I'll turn it over to Christian Harrington Smith to discuss where that combination might be used sure. So when we look at the platinum resistant ovarian cancer.
Market dynamics, we see that well over more than 25% of patients in any lines second third fourth fourth plus receive a a vast and plus chemotherapy regimen or any kind of a combo with bevacizumab. So we anticipate that it will be.
Anna Birkenblatt: Turning to your second question regarding enrollment dynamics, you are correct that we do have sites that have participated both in SOREA and are participating in Mirasol. And so SOREA was limited to Avastin pretreated patients, and Mirasol allows both Avastin pretreated patients and Avastin naive patients.
Anna Birkenblatt: Given the extent of patients, or rather the extent of sites around the globe that are participating in Mirasol, what I can tell you looking, you know, tracking the demographics of the patients enrolled in Mirasol, the percent of patients with prior Avastin is basically behaving as expected. And so we look forward to data from Mirasol sharing the data early next year. Okay, great. Thanks.
Used.
Where it's already used in combination across those lines.
Thank you.
Our next question comes from Michael Schmidt with Guggenheim. Your line is open.
Hey, guys. Good morning, Thanks for taking my questions.
And I keep wondering if you have any additional information on the.
Susan Altshuler: Then I have an unrelated follow-up just on the Cadenza study where you noted the top line data is on track for later this year in the PDCN. And I was just wondering if you could remind us of the, you know, the efficacy hurdle in the study and the number of patients that will be part of that. Yeah, so you may recall that we received breakthrough therapy designation from the data we generated in the relapsed refractory BPD-CN setting, and FDA guided us toward a study designed for a pivotal frontline cohort in up to 20 patients.
Interim analysis I don't know if you could share.
What you know.
Many patients perhaps triggered triggered this and what's the Caribbean, Florida and websites at that analysis.
And then you know a second question in Europe . So I was just wondering around.
The enrollment dynamics of the trial I'm just curious if you had overlapping.
Trial sites with Suraj.
Susan Altshuler: And the efficacy hurdle is really around what's feasible in an ultra-rare indication, and it's to rule out a CR-CRC rate of 10%. And so we do have the opportunity to stop the trial early for efficacy with less than 20 patients, and so we're on track to have data later this year. Okay, super. Thank you.
Obviously, he's focused on the.
Pre treated patients.
You know in Soraya, I'd, whether perhaps that may skew.
You know enrollment early in the neuro close sorry towards them.
Patients.
No may play a role in the overall cadence of the PFS event.
Yeah. Thank you Michael so for Mirasol, we had a pre specified interim analysis for futility just like we had done in forward. One it's really to allow a dry run if you will from an operational perspective. So that we know we're in good shape for when we're ready to do the final protocol.
Operator: Our next question comes from... Hi. Thanks for taking the question. A couple for me.
<unk> analysis for the primary endpoint. So it was triggered at the time, we had 110 PFS events.
Etzer Darout: The first one, I guess, back to sort of the MIRASOL trial, and I guess if you could help us understand the pushes and pulls to the re-forecast of the TFS events. Does it imply any differences in underlying TFS assumptions, or is it maybe more a factor of the recent acceleration in enrollment? And the second question, just if you could go back to the analysis you mentioned in the introductory remarks on the 2.8-month PFS for chemo-innovative pre-treated patients and whether or not this is something that you presented or would be sort of submitting to the FDA. Thank you. Thanks, Etzer.
And so as long as the efficacy data in terms of PFS is trending in the right direction. This study was to continue as planned and that's exactly what I DMC recommended to us to continue the study without modification.
Turning to your second question regarding enrollment dynamics you are correct that we do have sites that have participated both in Syria and are participating in mirasol and so soraya was limited to the Avastin pretreated patients and Mirasol allows both the vast and pretreated and avast and naive.
Given the extent of patients or rather the extent of sites around the globe that are participating in mirasol.
What I can tell you looking you know tracking the demographics of the patients enrolled in Mirasol the percent of patients with prior Avastin is.
Anna Birkenblatt: So your first question regarding the pushes and pulls involved in the reforecasting for Mirosol. PFS is an event-driven endpoint, and the timing of that is a factor of both the enrollment rate and the rate of having progression-free survival events. And it's really not possible to disentangle those two.
Basically behaving as expected and so we look forward to data from Mirasol sharing the data early next year.
Okay, great. Thanks, and then I had an unrelated follow up just on the.
Study, where you you noted the the top line did I sort of on track for later this year and I was just wondering if you could remind us.
The hurdle in the study and the number of patients.
Anna Birkenblatt: But, you know, based on how the study is performing, we have not changed our thinking regarding the PFS assessment. And we certainly did see an uptick in enrollment after we shared the SEREA data. I would say it has been offset a bit based on what's been going on in Ukraine and Russia in terms of geopolitical events and also in terms of China and the COVID surges with lockdowns in Beijing and Shanghai.
Part of that.
Yeah. So you may recall that we received breakthrough therapy designation from the data we generated in the relapsed refractory B P. D C at in setting and F. D. A guided us toward a study design for a pivotal frontline cohort in up to 20 patients.
And the efficacy hurdle is.
Really around what's feasible in an ultra rare indication and it's to rule out a CR CRC rate of 10%.
Anna Birkenblatt: So it is multifactorial, and we look forward to sharing top-line data early next year. Turning to your second question regarding the 2.8-month progression pre-survival on the chemotherapy control arm of Forward I in the SREA-eligible subset, if you will. Those are not data that we have published in a peer-reviewed manner, and certainly, the data sets are available to FDA. But really, from our perspective, it just highlights the unmet need in these patients.
And so we do have the opportunity to stop the trial early for efficacy with a less than 20 patients.
And so we're on track to have data later this year.
Okay Super Thanks for taking my question.
Okay.
Yes.
Our next question comes from with.
BMO capital markets. Your line is open.
Alright, thank you.
Anna Birkenblatt: As we look through all of the studies that have large studies in platinum-resistant ovarian cancer, none of them, prior to SREA, had a uniformly pre-treated population, all of whom received prior Avastin. We know that these patients have an extremely high unmet need.
Particularly the question a couple for me the first one I guess, but some sort of the liver so.
Trial, and I guess, if you could help us.
Understand I guess, the pushes and pulls to the forecast of the PFS events.
Does it imply any differences in sort of an email in underlying assumptions or is it maybe more of a factor of the recent acceleration.
Anna Birkenblatt: The PFS for the chemotherapy patients is 2.8 months or just under 2.8 months, highlighting the unmet need. I do need to caution folks that this is an exploratory analysis that we performed after Forward I read out. It's using the PS2-plus analysis.
And enrollment and the second question.
If you could go back to the analysis you mentioned in the introductory remarks on the 2.8 months PFS for chemo in Avastin pretreated pace.
Anna Birkenblatt: Once we rescored with the PS2-plus, the stratification factors were blown. All I would say is it's entirely consistent, from a biological perspective, that chemotherapy does not work well in these patients. They need better options, and the SREA data have demonstrated that. Great, thank you. Your line is open, please check your... Sorry, can you guys hear me?
Patients.
Whether or not this is something that you.
You presented or would be sort of submitting to the FDA. Thank you.
Yes.
So your first question regarding the pushes and pulls are involved in the re forecasting for Mirasol.
S. S. A is an event driven endpoint and the timing of that is a factor of both the enrollment rate and the rate of having progression free survival events, and it's really not possible to disentangle those too, but you know based on how the study is performing.
Operator: Ken now. Awesome. Um, so I wanted to follow up a little more on the Marisol interim analysis that was recently completed. I'm just curious.
We have not changed our thinking regarding PFS assumptions when we designed the study.
And in terms of accelerated enrollment, yes, we certainly did see an uptick in enrollment. After we shared this array of data I will say it has been offset a bit based on what's been going on in Ukraine, and Russia in terms of geopolitical events and also in terms of China.
Boris Peaker: Please comment on what the specific stopping rules that there were, maybe some kind of a PFS threshold or any kind of a hazard ratio. Yeah, Boris, the hazard ratio just needed to demonstrate PFS trending in the right direction for mirvotuximab over chemotherapy. Got it. And I just want to also point out that in the platinum sensitive patients in trial 420, you're enrolling folic receptor alpha, low, medium, and high. I'm just curious, what's the objective of including some of these lower-expressing patients, and are you exploring some of these lower-expressing patients in any other of your studies?
And COVID-19 searches with Lockdowns and in Beijing, and Shanghai. So it is multifactorial and we look forward to sharing top line data early next year.
Turning to your second question regarding the 2.8 month progression free survival on the chemotherapy control arm of forward one in the.
Our survey of eligible subset. If you will those are not data that we have published in a peer reviewed manner and certainly the datasets are available to F. D. A.
Anna Birkenblatt: So early in development, Boris, when we did our combination study combining mirvotuximab with carboplatin and avastin, we did include a broad range of patients with folate receptor alpha expression. But we now know that it's really the high-expression patients who benefit most from mirvotuximab monotherapy. We also know that patients with lower levels of FR alpha expression really benefit nicely from combinations including mirvotuximab plus bevacizumab and also, in particular, mirvotuximab plus carboplatin. And we have published data from dose escalation for mirvotuximab plus carboplatin showing that both the mediums and the highs do extremely well with this doublet. And we also saw very nice responses in the media.
But really from our perspective, it just highlights the unmet need in these patients you know as we look through all of the studies that have you know the large studies in platinum resistant ovarian cancer, none of them prior to Syria had a uniformly pretreated population all of whom received prior avastin.
And we know that these patients have an extremely high unmet need you know the PFS for the chemotherapy patients is 2.8 months.
Or just under 2.8 months, highlighting the unmet need.
Do need to caution folks that this is an exploratory analysis that we performed after forward one read out its using the P. S. Two plus analysis.
Anna Birkenblatt: It was a small phase one data set with just 18 patients, and so we look forward to expanding our understanding of this doublet in a larger population in trial 420. The hypothesis here, Boris, is that the patients with higher levels of FR alpha expression will lean a little more on the mirvotuximab activity, and the patients with lower levels of FR alpha expression will lean a little more on the carboplatin activity, and that the combination really should benefit a broad range of patients with FR alpha expression. Great. Our next question comes from Andy Tsai with William Blair.
And once we re scored with the P. S. Two plus the stratification factors were.
We're blown and so you know.
All I would say is it's entirely consistent from a biological perspective that chemotherapy does not work well in these patients they need better options and this is already a data have demonstrated that.
Great. Thank you.
Our next question comes from Volcker with Cowen Your line is open.
Boris Your line is open please check your mute button.
Sorry can you guys hear me.
Ken now awesome. So just I wanted to follow up a little more in the Mirasol interim analysis of the recently completed I'm. Just curious can you comment on what was the specific stopping rules. If there were maybe some kind of a PFS threshold or any kind of a hazard ratio.
Andy Tsai: Great. Thanks for taking my question. So in terms of MERV, I appreciate the 101 PFS events and the additional information there. I'm just wondering if you could remind us how many events are required to trigger the primary analysis of PFS out of the 430 targeted enrollments. And also on the regulatory front, I'm just curious if, in your previous discussions with the FDA, the subject of having an outcome ever came up during that discussion? And moving on to VECR-MAB, we're just curious about housekeeping, you know, you mentioned forward dosing. Is that the 45 micrograms per kilogram that you'll be examining?
Yeah, Boris the hazard ratio just needed to demonstrate PFS trending in the right direction, former botox a map over chemotherapy.
Got it and I just wanted to also on the platinum sensitive patients and the trial for 'twenty that you're enrolling fully receptor alpha low medium and high patients.
Curious, what's the objective of including some of these lower expressing patients in our U S.
Exploring some of these lower expressing patients in any other of your study.
So early in development Boris when we did our combination study combining merv rituxan Nab with Carboplatin with Avastin.
Anna Birkenblatt: And then lastly for CMC, I'm just curious about the process there with the FDA. Is there like a back and forth after you submit the data, or should we kind of think of it as kind of an IND where after a certain period of time, it, you know, it becomes active? Thanks for taking all my questions. Great. All right, Andy, I'll take all four.
We did include a broad range of patients with folate receptor Alpha expression. We now know that it's really the high patients who benefit most from Murdo toxin that monotherapy, we also know that pace.
Patients with lower levels of Fr Alpha expression really benefit nicely from combinations, including <unk> plus Bevacizumab and also in particular, Merv rituxan that plus carboplatin and.
Anna Birkenblatt: So the first one is that for Mirosol, the primary endpoint is progression-free survival, and the analysis will be triggered when we have 330 PFS events. For your second question regarding an ADCOM, you may recall that we submitted the BLA for SORAYA at the end of March, and we are actively engaged with FDA, responding to information requests, and certainly we expect in the coming months to understand whether or not an ADCOM would be needed.
And we have publish those data from dose escalation for <unk>, plus carboplatin, showing really that both the mediums and the highs do extremely well with this doublet and also we saw very nice responses in the mediums. It was a small phase one dataset with just 18 patients.
And so we look forward to expanding our understanding of this doublet in a larger.
Population in trial for 'twenty that hypothesis here Boris is that the patients with higher levels of fr Alpha expression will lean a little more on the <unk> activity and the patients with lower levels of Fr Alpha expression will lean a little more on the carboplatin activity and that the combi.
Anna Birkenblatt: Given the safety profile of our drug and the activity that we've seen, you know, I can't speculate on what FDA will say, but I can tell you that we will be prepared should FDA require an ADCOM. Going to your third question about PVAC, yes, the recommended phase two dose and schedule in combination with azacitidine and venetoclax for PVAC is 0.045 milligrams per kilogram or 45 micrograms per kilogram.
Nation really should benefit a broad range of patients with fr Alpha expression.
Got it great. Thanks for taking my questions.
Yeah.
Our next question comes from Andrew Tsai with William Blair. Your line is open.
Anna Birkenblatt: And we have already opened expansion cohorts for the triplet in both relapsed refractory AML as well as relapsed AML and then in the frontline cohort, and I must say enrollment is going quite briskly for both of those. And to your last question, I'll make an initial comment and turn it over to Mark. From the process to interacting with the CMC with FDA, we're providing data to them when we have it, and then we anticipate the clinical hold will be lifted, and then we'll start enrolling patients later this year. I have nothing to add.
Yeah.
Thanks for taking my question so.
In terms of mirv.
Appreciate the 101 PFS at that Additionally.
Additional information there.
I'm just wondering if you could remind us how many events or are required to trigger the primary analysis of PFS out of the 430 target enrollment.
And also on the regulatory front I'm just curious in your previous discussions with the FDA has the subject of having an AD comm ever.
K must during the discussion.
And moving on to does that get Mad, We're just curious housekeeping.
Anna Birkenblatt: Great, thanks so much. Our next question comes from Kelly Sheehan. Thank you for taking my questions. First, regarding Murazzo enrollment, could you share more color regarding the timing to complete the enrollment? And also, will the ECOG performance status influence patient outcome in both chemo and the MIRV treatment arm, in your view, in the NIRASO trial? And do you see NIRASO trial has a consistent e-coslet split at the 0 versus 1 with the previous forward 1 in the NIRASO trial?
Mentioned about the board dosing is that the 45 micrograms per kilogram that youll be examining.
And then lastly for the M C.
I'm just curious about the private process there with the F. D. A is there like a back and forth. After you submit the data or should we kind of think about it as kind of an eye and be where after a certain period of time.
It becomes active.
Thanks for taking all my questions.
Operator: And lastly, for MGC936, item 986, what would be the efficacy bar to select a certain tumor type for the next phase of the study? And how many inpatient data points could we expect for the first data readout? Thank you.
Great Alright, Andy I'll take all four so the first one is that for Mirasol are the primary endpoint is progression free survival and the analysis will be triggered when we have 330 PFS events.
For your second question regarding an AD com.
Recall that we submitted the BLA for Soraya at the end of March and we are actively engaged with FDA responding to information requests.
Anna Birkenblatt: Sure, so we anticipate Mirosol being fully enrolled this summer. Moving on to your second question regarding ECOG performance status. You know, ECOG performance status is an important predictor of how patients will do, how they'll tolerate therapy, and we focus on enrolling patients with an ECOG performance status of 0 or 1. So either patients feel perfectly well, or they may be a little bit tired, but certainly able to work and perform all of their activities of daily living.
And certainly.
We expect in the coming months to understand whether or not an AD com would be needed.
Given the safety profile of our drug and the activity that we've seen.
You know I can't speculate on what FDA will say, but I can tell you that we will be prepared should FDA require an outcome.
Going to your third question for P back, yes, the recommended phase two dose and schedule in combination.
With a decided in and they need a class four P back is 0.045.
Anna Birkenblatt: And so both of these subsets of ECOG patients we anticipate will be able to tolerate the therapies on both arms. And, you know, the patients that we've been enrolling in Mirasol are consistent with what we expect for this population and similar to what has been seen in Forward I. And then lastly, your question around 9.3.6, this is our ADAM9 targeted ADC. ADAM9 is expressed in a variety of solid tumors, including pancreatic, gastroesophageal, lung, triple negative breast cancer, and even colorectal cancer.
<unk> milligrams per kilogram or 45 micrograms per kilogram and we have already opened expansion cohorts for the triplet in both relapsed refractory AML as well as actually relapsed AML and then in the frontline cohort and I must say enrollment is going quite briskly for both of those and to your last question I'll make an initial comment and turn it off.
And apart from the process to interacting with the CMC with F. D. A we're providing data to them. When we have it and then we anticipate the clinical hold will be lifted and then we'll start enrolling patients later this year.
Anna Birkenblatt: And so in phase one dose escalation, the data will guide us regarding which tumor type or tumor types we will pursue initially in mini-expansion cohorts and then in formal expansion cohorts to support potentially accelerated approval. At this point, we're focused on identifying the recommended dose and schedule, and we look forward to sharing data this year once we have a sufficient data package that we can all interpret and share. Thank you; very helpful. This question comes from Jessica Fy.
Nothing to add.
Yes.
Yes.
Great. Thanks, so much.
Our next question comes from Kelly, She with Jefferies. Your line is open.
Thank you for taking my question sorry.
Regarding the lifestyle of enrollment could you share more color regarding the timing to complete the enrollment.
And also where that E com to performing status influence patient.
Patients all come in both chemo and the more between them into our view in the optic trial and do you seen there I saw the trial has consistent that you called out late.
Jessica Fy: Hey guys, good morning. Thanks for taking my questions. First, can you remind me when you expect to hear if you've received priority review on the SREA submission? Second, can you walk through the label you hope to achieve for mervitoximab based on the SREA data you submitted, particularly around it being silent with respect to prior avastin? Given that you're running Mirasol, that sort of seems like it would answer that question. How do you handicap the probability of getting that?
At zero versus wildly the previous fall or widen the murano trial.
And the lastly, fall and GC ninth Street six.
I'm not a D C. What would it be the advocacy of bar to see lack of certain tumor types for the next phase of the study and how many patients data could we expect for the first data readout. Thank you.
Sure. So we anticipate mirasol being fully enrolled this summer.
Anna Birkenblatt: Broad Label, and then lastly, with Gloriosa, expected to initiate enrollment in the middle of this year. When should we think about potentially seeing data from that trial? Yeah, so we anticipate hearing back from FDA by the end of this month regarding their acceptance of the filing and granting of priority review. Regarding the label, you know, given the strength of the data from SREA, we have gone into this with a broad label.
Moving to your second question regarding E. Com performance status, you know E. Com performance status is an important predictor for how patients will do how they'll tolerate therapy and we focus on enrolling patients with an <unk> performance status of zero or one so either patients feel perfectly well or they may be a little bit Ty.
But certainly able to work and perform all of their activities of daily living.
And so both of these subsets of the Cod patients, we anticipate we will be able to tolerate the therapies on both arms.
Anna Birkenblatt: You know, I could point out that the data for mervituximab monotherapy in terms of the response rate actually is a bit higher than what you see with Avastin plus chemo in a less heavily pretreated Avastin naive population. And so we're really excited about these data, and we know that mervituximab, based on the impressive activity in this heavily pretreated BEV pretreated population, it's going to look even better in a BEV naive population. So that is why we have gone in with a broad label. I would be hesitant to put any odds on how this would go.
And you know the patients that we've been enrolling in Mirasol are consistent with what we expect for this population and similar to what has been seen in forward one.
And then lastly, your question around 93 six.
This is our atom nine targeted ADC Adam nine is expressed in a variety of solid tumors, including pancreatic gastroesophageal lung triple negative breast cancer and colorectal cancer and so in phase one dose escalation of the data will guide us regarding which tumor type or tumor.
Anna Birkenblatt: And then thirdly, in terms of Gloriosa, you know, we're really, really excited about this study, and we look forward to getting it up and running mid-year. I think it's a little bit early, Jess, to share when we think we'll have data from this study, but once we are up and running, you know, we've got sites activated, and we get a sense of how things are going, then, of course, we will update our guidance. Great, thank you. Thank you. As a reminder, to ask a question at this time, please press STAR, then star-1.
Hypes, we will pursue in initially in many expansion cohorts and then in a formal expansion cohorts to support potentially accelerated approval at this point, we're focused on identifying the recommended dose and schedule and we look forward to sharing data. This year once we have a sufficient data package.
Is that are we all kind of interpret and share.
Okay. Thank you very helpful.
And our next question comes from Jessica Fye with Jpmorgan. Your line is open.
Hey, guys. Good morning, Thanks for taking my questions.
Operator: Hey guys, thanks for taking my question. So, first one, on your last call back in February, I think you said you were right on track for a Murosol 3Q readout despite enrollment having not been completed because the enrollment dynamics were maybe more evenly distributed than forward once. So just want to understand a little better why the enrollment pace is having an impact on timelines.
Can you remind me by when you expect to hear if you've received priority review on the threat submission.
Second can you walk through the label you hope to achieve from Rituxan on based on the theory of data you submitted particularly around it being filing with respect to prior avastin.
Given that you're running mirasol it sort of seems like it would answer that question, how do you handicap the probability of getting it.
Anna Birkenblatt: Thanks, and I have a follow-up. Yeah, sure. Well, you may recall February was really before we understood the extent of the geopolitical events in Ukraine and Russia, and it was also prior to the surge in COVID resulting in lockdowns in Beijing and Shanghai.
Broadly ball and then lastly, with glorious are expected to initiate enrollment.
In the middle of this year when should we think about potentially seeing data from that trial.
Yeah. So we anticipate hearing back from FDA by the end of this month regarding.
Anna Birkenblatt: And, you know, all three of those countries, we had anticipated they would enroll in, you know, a portion of the trial. And so that, unfortunately, is not quite panning out as we had anticipated. So that's one of the drivers that is more clear now than it was in February. But the other driver is that we now have the data from the interim analysis that allows us to reproject the event rate. So it's really multifactorial.
Their acceptance of the filing and granting of priority review.
Regarding the label.
Given the strength of the data from Soraya, we have gone into this with a broad label.
Point out that the data for mirv it took them a monotherapy in terms of the response rate actually is a bit higher than what you see with Avastin plus chemo in a less heavily pretreated avastin naive population and so we're really excited about these data and we know that Murphy tux, a mab base.
Based on the impressive activity in this heavily pretreated Bev pretreated population, it's gonna look even better in a bev naive population. So that is why we have gone in with the broad label I would be hesitant to put any odds on.
Operator: Okay, thanks. That's very helpful. And I guess understanding that it's multifactorial, if I could just ask, you know, if we consider MIRV's experience in Soraya, it seemed to behave pretty much exactly how you guys expected it to based on ForwardOne and other prior data. So is there any reason why Mirosol could in any way be different from Soraya and MIRV maybe, in fact, could be outperforming your expectations? I know that's pure speculation, but I was wondering if you have any thoughts there.
You know how this would go.
And then thirdly in terms of Glory Oh, sorry.
We're really really excited about this study.
And we look forward to getting it up and running mid year I think it's a little bit early Jeff to to share. When we think we will have data from this study.
Anna Birkenblatt: I agree with you, that's pure speculation, and I think we're really excited to see the data from Mirosol because that's certainly a possibility. Okay, great, thanks for taking my questions. Hi, guys. Thanks for taking my questions. First question: what impact, if any, would you anticipate prior PARP use would have on the chemo arm performance in Miracel? Jonathan, thank you for that question.
But once we are up and running.
We've got sites activated and we get a sense of how things are going then of course, we will update our guidance.
Great. Thank you.
Yes.
Thank you as a reminder to ask a question at this time. Please press Star then one our next question comes from Joe Kansas.
With Piper Sandler your line is open.
Hey, guys. Thanks, Thanks for taking my question. So first one on your last call back in February I think you said you were right on track for Mirasol <unk> readout, despite enrollment having not been completed because the enrollment dynamics, where maybe more evenly distributed.
Jonathan: You know, the reason that you're asking this is that was an outstanding question for Mervituximab that we have really solidly answered with the SREA data set showing that Mervituximab has very nice activity regardless of prior PARP use or not. Your point is that in the Mirosol study, there will be a higher percentage of patients with prior PARP inhibitors than there were in 4.1, and how is that going to impact chemotherapy? I have speculated myself that of the three chemotherapies, weekly paclitaxel, topotecan, and doxil, prior PARP inhibitors may decrease the activity seen with patients randomized to or assigned to the doxil arm. And the reason I say that is that doxil, like carboplatin, is a DNA damaging agent. PARP inhibitors interfere with the repair of DNA damage.
Once it so just want to understand a little better why now enrollment cases, having an impact on on timelines. Thanks.
Follow up.
Yeah sure well you May recall February was really before we understood the extent of the geopolitical events in Ukraine, and Russia and it was also prior to the surge in Covid.
Elting in and Lockdowns are in Beijing and Shanghai.
And you know all three of those countries.
We had anticipated they would enroll you know a portion of the trial and so that unfortunately is not quite panning out as we had anticipated. So that's one of the drivers.
Anna Birkenblatt: I don't have any data to support that, but I think mechanistically there is the potential for the doxil stratum to perform worse. The other little data kernel, I would say, is that one of the early randomized studies of a PARP inhibitor head-to-head against chemotherapy was versus doxil, and that study was negative. But this is me just speculating.
That is clear clear it more clear now than it was in February but the other driver is that we now have the data from the interim analysis are that allowed us to re project. The event right. So it's really multifactorial.
Yes.
Okay. Thanks.
And I guess understanding that it's multifactorial.
I can just add if we consider mirv experienced in survey it seem to behave pretty much exactly how you guys expected it to based on forward one and other prior data sets or is there any reason why you know mirasol could in any way it would be different from Saran mirv, maybe in fact could be outperforming your expectations I know that's pure speculation.
Anna Birkenblatt: I certainly don't think a prior PARP inhibitor is gonna increase activity for chemotherapy, so I think either the chemotherapy control arm will do as anticipated or potentially worse.
Anna Birkenblatt: And the second question, ahead of the PIVA-ChemAb combination data at ASH, what do you see as the appropriate benchmarks for success in frontline and relapsed refractory AML? So, in frontline AML, the bar, admittedly, is high, and, you know, I think the VEN-ASA doublet has set the bar there. And we're also tracking closely the megrolimab triplet data. So, I think those are the bars that we're looking at.
But wondering if you have any thoughts there.
I agree with you that's pure speculation.
And you know I think we're really excited to see the data for Mirasol, because that's certainly a possibility.
Okay, great. Thanks for taking my questions.
Yeah.
Our next question comes from Jonathan Chang with SB Securities. Your line is open.
Hey, guys. Thanks for taking my questions.
Anna Birkenblatt: In the relapse setting, it's a little less clear, you know, especially in the post-VEN setting where nothing else works. But, you know, we would be thinking that a CR, and CRI rate of 40% in the relapse refractory setting would really be something exciting that could translate into meaningful benefit for patients.
First question what impact if any would you anticipate prior PARP use would have on the chemo arm performance in Mirasol.
Jonathan. Thank you for that question you know the reason that you're asking it is that was an outstanding question for Mirv Rituxan App that we have really solidly answered with the survey of dataset showing that mirv toxin AB has very nice activity, regardless of prior PARP use or not.
Anna Birkenblatt: Thanks again. Our next question is followed by... Hi guys, thanks a lot for joining in with the follow up. So, you know, I think investors overall are skeptical of retrospective analysis, probably rightly so, but... I just wondered if you could comment on the agreement between the actual data in Soraya and the retrospective analysis that you did ahead of that study, because I think... may help inform interpretation of the 2.8 months PFS from the Forward One subset that overlapped. I just don't know if you have those numbers in front of you, but I was just curious if you could talk.
Your point is that in the Mirasol study there will be a higher percentage of patients with prior PARP inhibitor than there were in forward, one and how is that going to impact chemotherapy.
I have.
Speculated myself that of the three Chemotherapies weekly Paclitaxel towboat he can indoxyl.
Prior PARP inhibitors may decrease the activity seen with patients randomized to <unk> were assigned to the docs will arm and the reason I say that is Doc so like carboplatin as a DNA damaging agent PARP inhibitors interfere with repair of DNA damage.
I don't have any data to support that but I think mechanistically. There is the potential for the doctoral stratum to perform worse.
John Newman: Yeah, so I think, John, what you're referring to is the remarkable consistency of efficacy for Mervituximab throughout development. And so, you know, that foundational 70 patients who are SREA-like, we had a response rate above 30%. We had a median duration of response of 7.8 months. We had a median PFS of 4.4 months.
The other like little data kernel I would say is one of the early randomized studies of our PARP inhibitor head to head against chemotherapy was versus docile.
And that study was negative but this is me just speculating I certainly don't think a prior PARP inhibitor is going to increase activity for chemotherapy. So I think either that chemotherapy control arm will do as anticipated or potentially worse.
Anna Birkenblatt: And we basically replicated that in the SREA study really quite accurately. And so, similarly, we anticipate that data from the Forward One study for the Mirosol-like population should replicate in the Mirosol study. You know, I would point folks to the 2019 ESMO presentation where Dr. Moore did show the post hoc exploratory analysis for Forward One looking at F-alpha high patients for Mervituximab versus chemotherapy. And we saw a very nice treatment effect for Mervituximab over chemotherapy, both by investigator and by blinded independent review with a hazard ratio of around 0.6.
Got it thank you.
And then just second question ahead of the pivot to map combination data at Ash, what do you see as appropriate benchmarks for success in frontline and relapsed refractory AML.
So.
In frontline AML the bar admittedly is high and.
And you know I think the ven as a doublet has set the bar there and then we're also tracking closely the Meg roller mab triplet data.
So I think those are the bars that were looking at in the relapsed setting, it's a little less clear.
Anna Birkenblatt: And so, we designed Mirosol with around a hazard ratio of 0.7, so it is more conservative. And so, we already knew that Mirosol was de-risked with a high probability of technical success. And from my perspective, given that SREA has replicated prior data from an exploratory post hoc analysis, I'm even more confident that Mirosol will also replicate the results. And especially knowing that prior PARP inhibitor use does not impact Mervituximab's activity, we remain quite confident about Mirosol and look forward to sharing data early next year.
You know, especially in the post <unk> setting where nothing else works.
But you know we would be thinking that a CR cri rate of 40% in the relapsed refractory setting would really be something exciting that could translate into a meaningful benefit for patients.
Yeah.
Got it thanks for taking the questions.
Our next question is a follow up from John Newman with Canaccord. Your line is open.
Hi, guys. Thanks, a lot for fitting me in with a follow up so I.
I think investors overall, sometimes are skeptical of retrospective analysis, which is probably rightly so but.
Anna Birkenblatt: Great, thank you. Thank you. I would now like to hand the conference back.
Just wondering if you could comment on the agreement between the actual data.
Mark Enyedy: Great. As we mentioned in the opening remarks, we're off to a strong start to the year, and we're moving fast and with purpose. And so, as we look ahead, we are looking forward to our first potential product launch, generating top-line data from the PVAC Pivotal Study, and advancing the remainder of our pipeline. We're very well positioned at this point to execute on our transition to a fully integrated company, and we're excited to offer more good days to our people, our business, and our patients.
Uh huh.
And the retrospective analysis that you did a hesitant study because I think.
It would help inform interpretation of the $2 eight months PFS from the forward one subset that overlap there just I don't know if you have those numbers in front of you, but just curious if you could talk about that thanks.
Yeah. So I think I think John what you're referring to is the remarkable consistency of efficacy or mirv. It talks a mab throughout development and so you know that foundational 70 patients who our survey of like you know we had a response rate above 30%. We had a median duration of response of seven.
Mark Enyedy: So, thanks for your time today, and we will look forward to seeing you all later this month at ASCO, where we'll have some additional data from our programs. Thanks. This concludes today's conference call. Thank you for participating. You may now disconnect.
Eight months, we had a median PFS of 4.4 months and we basically replicated that.
In the survey of study really are quite accurately and so similarly, we anticipate that.
Data from the forward one study for the Mirasol like population should replicate in the Mirasol study.
You know I would point folks to the 2019 ESMO.
Presentation, where Doctor Moore did show the post hoc exploratory analysis for forward one looking at Fr Alpha high patients.
For <unk> versus chemotherapy, and we saw very nice treatment effect for mirv Rituxan mab over chemotherapy, both by investigator and by blinded Independent review with a hazard ratio of our endpoint six.
And so we've designed mirasol to around a hazard ratio of <unk>, seven or more conservatively and so.
We already knew that Mirasol was derisked with a high probability of technical success and from my perspective, given that Syria has replicated prior data from that from an exploratory post hoc analysis I'm, even more confident that mirasol will also replicate the results and especially knowing that prior PARP.
Inhibitor used does not impact Merv Rituxan abbs activity, we remain quite confident about mirasol and look forward to sharing data early next year.
Okay, great. Thank you.
Thank you I would now like to hand, the conference back over to the team for closing remarks.
Great. So as so we mentioned in the opening remarks, we're off to a strong start to the year and we're moving fast and with purpose and so as we look ahead. We are looking forward to our first potential product launch generating topline data from the <unk> pivotal study and advancing.
The remainder of our pipeline, we're very well positioned at this point to execute on our transition to a fully integrated company and we're excited to offer more good days through our people our business and our patients. So thanks for your time today and we will look forward to seeing you. All later this month at <unk>, where we will have.
Some additional data.
From our programs.
Thanks.
This concludes today's conference call. Thank you for participating you may now disconnect.
Yeah.
Yes.
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