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spk04: Good morning and welcome to the Unigine's first quarter of 2021 Financial and Operating Results Conference call. Today's conference is being recorded. At this time, I'd like to turn the call over to Courtney O'Connor, Senior Director of Corporate Communications and Investor Relations. Ma'am, please go ahead.
spk00: 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 in first quarter 2021 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.com. With me today are Mark Ennedy, our President and CEO, Anna Birkenblit, our Chief Medical Officer, and Susan Altshuler, our CFO. During today's call, we will review key accomplishments for the business over the last three months, our financial results, and anticipated upcoming events. During the discussion, we will use forward-looking statements, and our actual results may differ materially from such statements. Descriptions of the risks and uncertainties associated with an investment in immunogen are included in our SEC filings. And with that, I'll turn the call over to Mark.
spk02: Thanks, Courtney. Good morning, everyone, and thank you for joining us today. I'll begin with our lead program, Mervituximab. We recently completed enrollment in SREA, which is our pivotal single-arm study in platinum-resistant disease, which has shifted the anticipated timing of top-line data from the third into the fourth quarter of this year and the projected submission of the BLA into the first quarter of 2022. We've also experienced some COVID-related impact on accrual for our confirmatory Murasol trial and correspondingly now expect the readout on the primary endpoint to move from the second to the third quarter of 2022. Anna will provide some more color around the updated timelines in a moment. Importantly, with positive results from these studies, we continue to anticipate potential accelerated approval of Mervituximab in 2022 and full approval in 2023. Beyond platinum-resistant ovarian cancer, we've submitted a protocol for a single-arm study of Mervituximab monotherapy in recurrent platinum-sensitive disease and anticipate initiating patient enrollment for this cohort in the second half of this year. This study further expands our approach to displacing single-agent chemotherapy in later lines of treatment in ovarian cancer. Turning to Mervituximab in combinations, we were pleased to learn that mature data from our phase 1b forward 2 doublet of Mervituximab plus Avastin in patients with platinum agnostic disease were accepted for an oral presentation at ASCO this year. In addition, a 70-patient IST led by Dr. Rebecca Aaron at UAB is now underway evaluating Mervituximab in combination with carboplatin in the neoadjuvant setting. Finally, we're supporting a randomized study comparing Mervituximab combined with carboplatin to standard of care in patients with recurrent platinum-sensitive disease in a large IST led by Philip Harder in the AGO in Germany, with patient enrollment expected to start in the second half of this year. We continue to advance our second pivotal program, IMGN 632 and CD123 positive hematologic malignancies. Having established a path to full approval in BPDCN, we are progressing our phase one expansion cohort in frontline patients and expect to generate top line data in the first half of 2022 with potential approval next year. We are also advancing 632 in combination studies with azacitidine and venetoclax and relapsed and refractory and frontline AML patients and look forward to presenting data from these combinations at ASH in December. Moving to our earlier stage pipeline, we presented preclinical data at AACR for our first in class ADAM9 targeting ADC IMGC936, which we are co-developing with Macrogenics. We also continued IND enabling activities for our next generation folate receptor alpha targeting ADC IMGN151 and expect to submit an application by year end. 2021 and 2022 are critical years in Immunogen's evolution as we prepare to bring two products to the market and further our innovative portfolio of transformative ADCs for solid tumors and hematologic malignancies. We look forward to keeping you apprised of our progress as we generate clinical data and prepare for commercialization. And with that, I'll turn the call over to Anna to provide some additional color on our clinical programs. Anna?
spk01: Thanks, Mark. I'll start with Soraya. While we have recently fully enrolled the study, accrual was more variable relative to our prior experience due to a combination of factors, including COVID-19, as well as screening activity in some trials tapering in recent weeks as they anticipated imminent completion of enrollment. These factors contributed to a roughly six-week delay, which, as Mark mentioned, has shifted the timing for reporting top-line data for Soraya into the fourth quarter. The net effect has also moved our planned submission of the BLA into the first quarter of 2022. Despite Mirasol having had an earlier start, COVID-19 has also affected site activation and patient accrual in this trial. While we initially expected top line data in the latter part of the first half of 2022, we now expect top line data in the third quarter of 2022 with the submission of the supplemental BLA for full approval planned by the end of 2022. Completing the Sirea and Mirasol studies are the highest priority for the business, and we look forward to the opportunity to offer a new therapeutic option to patients living with ovarian cancer. With the continued uptake of PARP inhibitors as maintenance in the frontline and recurrent platinum sensitive settings, there is an increasing population of ovarian cancer patients for whom a non-platinum based regimen is needed. The initial data we have for Mervituximab monotherapy in heavily pretreated platinum sensitive patients are encouraging and we have therefore submitted a protocol to the FDA for a single arm trial in this population. Operational activities are underway to enable initiation of the study in the second half of this year. To expand into earlier lines of ovarian cancer treatment, we are pursuing combination studies with carboplatin. An investigator-sponsored trial in the neoadjuvant setting is now underway at the University of Alabama with Dr. Rebecca Arendt. This is our first opportunity to assess Mervituximab in the upfront setting. Importantly, this trial will support our goal of incorporating folate receptor alpha testing at diagnosis as part of standard of care. In addition to this trial, we are also supporting a randomized study comparing Mervituximab in combination with Carboplatin to standard of care in recurrent platinum sensitive disease with Dr. Philip Harder in Germany. This trial is slated to start in the second half of the year. In addition to starting these new trials in combination with carboplatin, we are pleased to have mature data from our Mervituximab Plus Avastin cohort in recurrent ovarian cancer, regardless of platinum status, selected for a virtual oral presentation at ASCO in June. Dr. Dave O'Malley from The Ohio State University will present mature safety and efficacy data from our Phase 1b Forward 2 cohort of Mervituximab Plus Avastin. which we believe will bring us a step closer to achieving our goal of establishing Mervituximab as the combination agent of choice in ovarian cancer and supporting its use in earlier lines of therapy. In addition, two posters from our collaborators were accepted for presentation at ASCO. Data from an expansion cohort from the City of Hope trial evaluating Mervituximab in combination with gemcitabine in patients with folate receptor alpha-positive platinum-resistant ovarian cancer, and a trial-in-progress poster from Dana-Farber, evaluating Mervituximab in combination with Pembrolizumab in patients with advanced or recurrent microsatellite-stable endometrial cancer. Moving to IMGC 936, our ADAM9-targeted ADC. Our partners at Macrogenics identified ADAM9 a known member of the matrix metalloproteinase and disintegrant family, as an attractive target for ADC development because it is overexpressed in multiple solid tumors but minimally expressed in normal tissue, and anti-ATOM9 antibodies are efficiently internalized and degraded by tumor cell lines. At AACR in April, we presented data on ADAM9 expression in solid tumors and evaluated the activity of IMGC936, in clinically relevant patient-derived xenograft or PDX models with ADAM9 expression similar to that observed in human solid tumors. IMGC 936 demonstrated compelling activity against a broad panel of PDX models including non-small cell lung, triple negative breast, gastric, and pancreatic cancers. We are actively enrolling patients with solid tumors known to express ADAM9 in a phase one dose escalation study and collecting tumor tissue for retrospective ADAM9 expression assessment by immunohistochemistry. We're excited about the potential of this program, and we look forward to presenting data at a major medical meeting, likely in early 2022. With that, I'll turn the call over to Susan to cover our financials. Susan?
spk00: Thanks, Anna. For the first quarter of 2021, we generated $15.7 million in revenue, nearly all of which came from non-cash royalty revenue. Operating expenses were $44.6 million, comprised of $34.4 million of research and development expenses, compared with $27.4 million for the first quarter of 2020. This increase was due to greater year-over-year clinical development costs related to advancing our SREA, MIRASOL, and IMGC 936 studies. and greater external manufacturing costs. G&A expenses were $10.2 million compared to 8.9 million for the first quarter of 2020, primarily due to increased professional fees and personnel costs. We ended the first quarter with $283.1 million in cash. Our financial guidance for 2021 remains unchanged. We expect revenues to be between $65 and $75 million, operating expenses to be between $200 and $210 million, and cash and cash equivalents at your end to be between $140 and $150 million. We expect our current cash to fund operations into the second half of 2022. We look forward to what is ahead of us, and with that, I'll open the call to questions.
spk04: Thank you, presenters. To ask a question, you need to press star 1 on your telephone. To withdraw your question, press the pound key. Your first question comes from John Newman, Your line is now open.
spk07: Hi guys, good morning. Thanks for all the updates and thanks for taking my question. So Mark, I just wondered now that the top line data for SREA looks like it will surface in the fourth quarter of 21. Might that allow you to give us a little bit more detail regarding the durability of responses when you present the top line data? Thanks.
spk02: Yeah, and I'll ask Anna to comment any further, but the answer is yes.
spk01: Yeah, that's exactly right, John. Given the pace of enrollment over the entire course of the study, including the last few months, we anticipate that we'll have not only top-line ORR data for the primary endpoint, but we will also have a reasonable estimate of duration of response.
spk07: Okay, great. Thank you. I had just one follow-up question, sort of on a different topic. It's been a lot of activity recently with the FDA regarding accelerated approval. Our understanding is that the agency actually views studies, companies that have studies already running at the time of accelerated approval that would be confirmatory as a significant positive. I just wondered if you could comment on your thoughts there. It seems like if you've already got your confirmatory study up and running, the agency's more comfortable. Just curious as to how you think about that. Thanks.
spk02: Yeah, maybe just at a high level. I mean, that's, in fact, the regulatory guidance. So when you talk to the FDA about an accelerated approval study, the first thing they say to you is, great, but we want to make sure you've completed enrollment in your confirmatory study at the time of regulatory action. So that's formal guidance that they provide every applicant. What happens in practice is that not everybody achieves that objective. We expect to be right in that place. Then you saw the ODAC on some of the accelerated approvals, which Anna had the opportunity to sit through. I think we were very pleased with the overall disposition of the ODAC relative to some of these so-called hanging approvals. Excellent. Great. Thank you.
spk04: Your next question comes from Mr. Michael Smith of Guggenheim. Sorry, your line is now open.
spk09: Hey, guys. Good morning. Thanks for taking my questions. I had a question on both ongoing studies, Sarai and Durasol, And perhaps, you know, related to your comments about the increased use of PARP inhibitors in recent years, just wondering how you think Mervituximab might perform in a more heavily pretreated patient population with PARP inhibitors specifically?
spk01: Sure, Michael. So PARPs are being incorporated into frontline maintenance or recurrent platinum sensitive maintenance therapy. And we've absolutely seen with each trial that we have enrolled over the past six years an increasing percentage of patients receiving a prior PARP. And what I can tell you is we've looked across each study and Mervituximab really has nice activity regardless of prior PARP use or not. And, you know, that makes sense given that biologically there's no reason to expect any kind of cross resistance between our tubulin directed payload and a PARP inhibitor which impairs the ability to repair DNA damage.
spk09: Makes sense. And then a question on your new single arm study in recurrent platinum sensitive patients. Just wondering if you could help us maybe outline just sort of the size of the study, potential timelines, and also the size of the commercial opportunity perhaps relative to the psoriatic patient population.
spk01: Yeah, so we've designed this study of single-agent Mervituximab in patients with recurrent later-line platinum-sensitive disease to really address an increasing unmet need with a larger population of patients who technically are still platinum-sensitive by that rather arbitrary definition of recurring greater than six months after the last dose of platinum. but we know they're at high risk for allergic reactions or their bone marrow may be a little bit tired and they need other well-tolerated active therapies. So from our phase one study way back, we had a handful of patients, well more than that actually, we had patients enrolled in a couple of our cohorts. the biopsy cohort, and then the cohort with three to four prior lines of therapy, who indeed had platinum-sensitive disease. And when we look at those patients, the activity of Mervituximab looks quite nice. And so that has supported the study that we have just submitted the protocol to FDA. You can think of it basically as a two-stage design study. And so once we are ready to open the study, we'll share more details.
spk02: Michael, just in terms of the market opportunity, our DRG data tell us that third-line platinum-sensitive patients are about 2,000 patients. Obviously, we're targeting only a subset of those folks, but it's an evolving segment of the marketplace, so we won't get all 2,000 of those patients, and it will depend on to a large degree on the efficacy that we generate relative to what you see with platinum-based combinations in that setting. And the data there are actually a little bit scarce. But based on what we've seen preliminarily, we think motor monotherapy can compete quite effectively there, both in terms of efficacy but equally important tolerability and to some degree convenience as well. Okay, great.
spk09: And then I know you did speak about a few new investigator-sponsored studies. I was just wondering if you could perhaps speak to evolving thinking about potentially supporting company-sponsored studies in earlier stage patients.
spk02: Sure. So as Anna mentioned, we're really excited about this neoadjuvant study being conducted by Dr. Aaron, led out of UAB for the reasons that she described. One, being in the frontline setting, you know, having access to, you know, essentially fresh tumor tissue and being able to assess fully receptor alpha levels in those patients. So I think we're excited about that. And then, you know, the study we're doing with Philip Harder and the AGO is, you know, a randomized controlled study of upwards of 140 patients. So we expect to have a pretty strong signal there in terms of, you know, direct comparison against the standard of care. And so we are evaluating a company-sponsored effort in that setting and working through the details of the design as we speak.
spk09: Great, thanks so much.
spk04: Your next question comes from Boris, Boris, speaker of COVID. Sir, your line's now open.
spk11: Good morning. Good morning. I just wanted to probe maybe initially in terms of the delay in the Soraya study. How is COVID impacting ovarian cancer? I'm just trying to understand since you aren't relying on new patients' diagnosis, So shouldn't all the patients for the SEREA trial already be kind of diagnosed and in the system?
spk02: Yeah, I'll let Anna give you a little more color. But to start with, we're working with IQVIA as our CRO. And what they tell us is that in more than 70% of their studies, which include other ovarian cancer studies, they saw a decline in accrual rates in the first quarter of this year in comparison to Q4 of last year. So there was a COVID impact. Part of what we see as well is, you know, there's some variability. So we're normally, we're accustomed to seeing, you know, sort of a direct correlation between the number of sites that we have active and are cruel throughout the study. And what we've seen in particular was acute during the early spring with some variability in accrual, which, you know, we in the CRO attribute to COVID.
spk11: That's interesting. I guess my second question is on BPDCN. Remind us again what you need to show in that study for it to be considered successful.
spk01: Yeah, so the BPDCN frontline cohort to support full approval, is enrolling, and we've aligned with FDA that it will include up to 20 frontline patients. These are patients who may have had local therapy, surgery or radiation, but have not had any systemic therapy. And so the study is designed to rule out a CR slash CRC or clinical CR rate of 10%. Great.
spk11: Thank you very much for taking my question.
spk10: Hello. Can you guys hear me? Sounds like that's Andy. No, sorry. Sorry. This is, this is, uh, Luke Brennan on for Jess.
spk09: Oh, great.
spk10: Okay. Hey Luke. Good.
spk09: Yeah.
spk10: Thanks. Thanks for your question this morning. Um, so with the FDA feedback that you guys, uh, expect, um, on the, on the protocol is the goal for the FDA to sign off on that single arm trial and later line platinum sensitive patients as the basis for approval.
spk01: No. So basically when we are getting ready to start a study, we submit the protocol to FDA. There's a 30-day waiting period. And so, you know, there's a good chance actually that we may not hear anything back from FDA. We, of course, are waiting so that if they do have feedback, we'll have the opportunity to incorporate it before we enroll the first patient in the study.
spk10: Okay. So I guess could you guys just give a little bit more color on the dynamic between starting you know, both the combo therapy and the monotherapy trials in the same setting?
spk01: So the monotherapy study is in patients with two or more prior lines for platinum, so with at least two, so two to three prior lines of platinum therapy. And that really is a population that, again, is still technically platinum sensitive but needs something else. We are also planning to allow patients who've had one prior line of platinum-based therapy but who had a hypersensitivity reaction that would make them inappropriate for further platinum. So that is a setting, again, we think will be increasing in frequency just because there are more patients with later line platinum-sensitive disease. Our carboplatin combinations, one is the neoadjuvant setting, so that's up front. And so those are patients who have not had any therapy before. We're very excited about that because that'll be our first opportunity to study Mervituximab in untreated patients. And then the randomized phase two study, the IST that Mark mentioned being done in Germany, that's going to be a randomized study of Mervituximab plus carboplatin versus standard, basically platinum-based doublets with standard of care maintenance therapy as appropriate for each patient.
spk10: Okay. Thank you very much.
spk04: Thank you. Your next question comes from Andy Shy of William Blair. Sir, your line is now open.
spk05: Oh, great. Thanks for taking my question. Sorry about the technical difficulty. And congratulations on the SORA enrollment completion. I have two questions regarding kind of the label expansion opportunities. It might be a little bit complicated. early to answer this question, but the new kind of platinum agnostic study that you're proposing, do you foresee Marisol potentially serving as a confirmatory trial for that opportunity? And also, Mark, I'm just wondering if you can educators on the Compendia listing process. I'm just curious about how much interaction that you might have back and forth kind of relative to the regular FDA review process.
spk01: Yeah, so I'll start. So the new study that we are getting ready to start later this year of MERV monotherapy and recurrent platinum sensitive disease. It's not exactly platinum agnostic, Andy. These are patients who've technically are still platinum sensitive, having recurred greater than six months from the last dose of platinum. Again, these patients need other non-platinum-based options. So that study is slated to get going later this year. I think it's unlikely that Mirasol would serve as a confirmatory study for that. Mirasol will likely read out prior to us completing the study that we're planning to start later this year. Moving to compendia listing, typically you need two separate studies to support compendia listing. And I think the best example for us right now is our combination data with Mervituximab plus Bevacizumab. You may recall we have one cohort specifically in platinum-resistant disease that was presented at ASCO a couple years ago now, twice. And then we have our second cohort in platinum agnostic, so a broader population of patients with recurrent ovarian cancer That is another cohort, 60 patients, and again, we anticipate that the safety and efficacy data from those two separate cohorts will support compendia listing. It may very well be the case that with Mervituximab plus carboplatin, based on the data we're planning to generate for that doublet, we could also gain compendia listing in advance of a formal label expansion from a registration trial.
spk05: Got it. That's very helpful. And then last question, Anna, I'm just curious about your thoughts on investigators' learning curve in using MERV in the context of a clinical trial. So specifically, I'm just wondering if you expect to see some sort of safety or efficacy benefit from clinical sites that had participated in Forward One and are concurrently recruiting patients for Soraya and Marisol?
spk01: Yeah, so we have a wealth of data from the FORWARD-1 study, Andy, and it gives me a lot of comfort because you may recall with FORWARD-1, we went from, you know, 10 or 15 Phase 1 sites to over 100 sites for the Phase 3 study. And the safety profile of Mervituximab in FORWARD-1 in 243 patients who were dosed with Mervituximab looked quite good. For me, the bellwether there is that only one of those 243 patients discontinued due to blurred vision. And that tells you that new sites, new investigators were very well informed and educated. We really did focus on that in ForwardOne like we are in Sirea and Mirasol to manage patients appropriately on Mervituximab. And I would expect no different in the Sirea and Mirasol studies. I will say you're absolutely right. We picked the best sites. from ForwardOne to be included in SREA. And I think that was a really important strategy for us, both in terms of getting accrual completed and ensuring that we have optimal data integrity.
spk05: I see. That makes total sense. Thank you very much.
spk04: Thank you. Your next question comes from Sayamakula Ramanath. from H.C. Wainwright. Your line is now open.
spk08: Thank you. This is R.K. from H.C. Wainwright. A couple of quick questions. Mark, as you embarked the regulatory strategy with the two studies, Soraya for accelerated approval and Mirosol for full approval, you're also trying to evergreen Mervituximab with various combination regimens being tested in the FORWARD program. So what gives you the confidence and comfort to put a lot of resources behind this molecule when some could think this is a big, bold step with no approval yet in any indication?
spk02: The first thing is we are looking at a relatively accelerated approval timeline for Mervituximab with the BLA submission in the first quarter of 2022. We have fast-track designation for this product, and I think we could reasonably expect priority review, which gives us a relatively short window for review and approval. Our objective then is to ensure that Mervituximab can be used as widely as the data warrant. This is why we place some emphasis on the compendia listings that could be available to us at the time of initial approval. The goal here is really to accelerate the penetration of MERV both within its label and then as physicians decide in their own discretion to use the products consistent with compendia listing that's available to them so that reimbursement would not be a barrier to that. So we don't view that as a high-risk strategy, particularly in light of the data that we've already generated. you know, there's no further work really needed other than generating the actual publications from Merv in combination with Avasta. And then, you know, when we look at the data that we've generated to date, and particularly in some of these earlier Lyme patients from some of our, you know, phase one work, you know, the data looked quite compelling in terms of the response rates that we've generated relative to current benchmarks. And so you may remember from, you know, it's a small end, but our initial CARBO data in patients with high levels of expression was an 80% response rate and progression-free survival was 15 months. If you look at our triplets that were published at ESMO, similarly, very high response rates. Our goals here are really to lever that. We have a lot of conviction that this drug should be the combination agent of choice for both Avastin and Carbo. And, you know, I think it's our responsibility to accelerate that work. And part of that's just driven by, you know, our overall conviction about an initial approval and the availability of this drug in 2022.
spk08: Perfect. Thank you. On IMGN 632, you know, while certainly this drug also could target multiple liquid tumors, you know, your initial focus is on BPTCN followed by AML. So do you or should we expect, you know, following what you're trying to do with broadening the profile of 632 in additional liquid tumors, you know, what would be your plans on that?
spk02: Right. So, I mean, high level with our portfolio, our ethos in terms of pursuing development is fast-to-market strategies where we can use single-arm studies to support accelerated approval in the case of Mervituximab. In the case of 632 and BPDCA, we'll have full approval. But you may recall that we got breakthrough therapy designation for that program in relapsed refractory and aligned with FDA around an additional cohort in frontline patients, which we are pursuing as we speak. But yes, our goal is to, CD123 is expressed across a range of hematologic malignancies, and our principal foray there has been in acute myeloid leukemia. Initially as monotherapy, where we saw some interesting activity, But clearly the benchmark has been set in that disease with the combination of azacitidine and venetoclax. And so the goal was to integrate 632 into that doublet to create, you know, looking at both doublets and most importantly, I think, a triplet to see whether we can generate response rates and duration of response that would make that regimen competitive. We're working through that as we speak, and we expect to have data at ASH at the end of the year with the triplet. But yes, that represents a significant potential expansion beyond the BPDCN label.
spk08: Thank you, Mark. Thanks for taking my questions. Sure.
spk04: Your next question comes from Kenan McKay of RBC Capital Markets. Your line is now open.
spk07: Hey, Kenan. Kenan, you're breaking up substantially.
spk05: I only could make out about every third word.
spk07: I did not get that kind of apology. So maybe we can follow up offline. Sorry, yep.
spk02: Operator, can you do the next question? Okay.
spk04: Next question comes from Joe Catanzaro of Pfeiffer Sandler. Your line is now open.
spk06: Hey guys, thanks so much for taking my questions. Maybe just one quick one from me to follow up on the single arm monotherapy trial in platinum sensitive patients. So Anna, you had mentioned that way back in the phase one experience, you actually had enrolled platinum sensitive patients. I'm wondering if maybe you could elaborate a little bit more on what exactly you saw in those patients and specifically how it relates to folate receptor expression levels and the various cut-offs that you utilized back in that phase one trial. Thanks.
spk01: Yeah, sure, Joe. So, as I mentioned, we had the biopsy cohort, which was silent on platinum status, and we also had what we affectionately called the eyedrop cohort in patients with three to four prior lines of therapy, regardless of platinum status. You know, that was back in the day when Olaparib got its accelerated approval initially. as treatment in patients with three to four priors. So we were sort of following that model. As a result, even though our intent at the time was really not to focus on platinum-sensitive disease, we did enroll enough patients across those two cohorts with later-line disease. I mean, these were patients with three prior lines of therapy. And they had a very nice, the FR-alpha-high patients had a very nice response. So, you know, these are internal data that we're using to support the design of the single-arm study that is on track to get open later this year. And, you know, we're very pleased with the data that we have from that Phase I experience. And so, again, we're going to have a—it's basically a two-stage design. And, you know, once the study's up and running, we can sort of talk more about the actual design statistics and timeline.
spk06: Okay, got it. Thanks for taking my question.
spk01: Sure.
spk04: Next question comes from Kelly Shy of Jefferies. Your line is now open.
spk03: Thank you for taking my questions. I have one question from one of your early phase trials. So the 936, I'm targeting ADC. You recently showed a nice proof of concept data at ASAR. I'm wondering, do you think ADAM9 is predictive for the treatment efficacy based on its biology? And also, are you going to screen patients after those escalation phase? Is there any companion diagnostic development ongoing at immunogen? And also, lastly, what has been learning from previous ADAM-targeting antibodies, if there are any? Thank you.
spk01: Sure. So ADAM9 is a member of the matrix metalloproteinase and desintegrin family. And I certainly remember the days that we were targeting MMPs, matrix metalloproteinases, to try to prevent metastasis and invasion. And those mechanistically oriented approaches really didn't turn out so well for cancer patients. However, ADAM9 is really, we're using it as a zip code to target our very potent next generation mecanizinoid toxic payload to tumor cells and to spare normal tissue. So it's really not, I wouldn't think of it as a biological mechanistic rationale, but really more targeting our toxic payload to the tumor cells. In terms of your next question around screening, we are generating data now in phase one dose escalation to inform whether or not we will need to select patients for ADAM9 expression or not. As you saw in our AACR poster, ADAM9 is actually reasonably highly expressed across a broad range of tumors. But we will be poised to select patients by ADAM9 expression and develop a CDX with a cutoff, a validated cutoff if needed. And, you know, right now we're doing all of the state work to get us to that point if needed. And then your last question around learnings from prior ADAM9 targeted antibodies. I really can't speak to that, because this is a novel target. Macrogenics brought the target and their antibody to us, and collaboratively we've developed this ADC. So we're really excited. The phase one dose escalation trial is enrolling, and we look forward to sharing data in early 2022. Thank you very much.
spk03: It's very informative. I also have another quick question. regarding the upcoming ASCO update for the MERV Avastin combo in the platinum agnostic patients. I just wonder what is the estimated ORR and the PFS achieved by standard of care in this folate receptor alpha high subpopulation? Or in another way, I should ask, what should be the benchmark for this selective patient population? Thank you.
spk01: Yeah, so there's two separate populations, if you will, platinum-resistant and recurrent platinum-sensitive. In unselected patients, platinum-resistant disease, I would point you to the Aurelia study that looked at Avastin plus chemotherapy, which had a 27% or 28% confirmed response rate and a medium TFS of 6.7 months. They did not assess for folate receptor alpha in Aurelia, so I don't know how the upper alpha high patients did, but what I can tell you is there are studies that have been published, mostly retrospective, looking at FR-alpha as potentially a poor prognostic factor. And if you look at our exploratory analyses from Forward One at ESMO in 2019, you'll see there may be something to that, but certainly not anything that I would use to design a study assuming high FR-alpha patients would do worse than the overall population with standard of care. Moving to recurrent platinum-sensitive disease, I would point you to the GOG213 study and the OCEANS study. looking at patients with one prior line of therapy, and there the response rate is in the mid-50s, and the PFS for platinum-based doublets is somewhere between 8 1⁄2 and 10 1⁄2 months. So keep that in the back of your mind when you see our data from our mature MIRV-BEV cohort that Dr. O'Malley will be presenting at an oral presentation at ASCO.
spk03: Okay, thank you.
spk04: Now I would like to hand the call over back to our presenters. for their final comments. Presenters, please go ahead.
spk02: Thank you. Well, we appreciate your time this morning. We look forward to keeping you apprised of our product and progress in the year, and in particular, seeing you at, or at least on Zoom anyway, for ASCO and the data updates there. Thanks.
spk04: This concludes today's conference call. Thank you all for joining. You may now disconnect.
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