ImmunoGen Inc. (IMGN) Q2 2021 Earnings Call Transcript

ImmunoGen Inc. (NASDAQ: IMGN) Q2 2021 earnings call dated Jul. 30, 2021

Corporate Participants:

Courtney O’Konek — Senior Director of Corporate Communications and Investor Relations

Mark Enyedy — President and Chief Executive Officer

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Susan Altschuller — Senior Vice President and Chief Financial Officer

Analysts:

John Newman — Canaccord Genuity — Analyst

Yige Guo — Guggenheim Securities — Analyst

Boris Peaker — Cowen and Company — Analyst

Swayampakula Ramakanth — H.C. Wainwright & Co. — Analyst

Andy Hsieh — William Blair & Company — Analyst

Sudan Loganathan — RBC Capital Markets — Analyst

Kelly Shi — Jefferies — Analyst

Joseph Catanzaro — Piper Sandler — Analyst

Daniel Wolle — J.P. Morgan — Analyst

Presentation:

Operator

Good morning, and welcome to the ImmunoGen Second Quarter 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’Konek, Senior Director of Corporate Communications and Investor Relations. Please go ahead.

Courtney O’Konek — Senior Director of Corporate Communications and Investor Relations

Good morning, and thank you for joining today’s call. Earlier today, we issued a press release that includes the summary of our recent progress and second quarter 2021 financial results. This press release and a recording of this call can be found under the Investors & Media section of our website at immunogen.com.

With me today are Mark Enyedy, our President and CEO; Anna Berkenblit, our Chief Medical Officer; and Susan Altschuller, our CFO.

During today’s call, we will review key accomplishments for the business over the last three months, our financial results and upcoming anticipated 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.

Mark Enyedy — President and Chief Executive Officer

Thanks, Courtney. Good morning, everyone, and thank you for joining us today. Over the past three months, we continued to advance our pipeline of novel ADC candidates and execute on our strategic objectives, as we prepare to transition to a fully integrated oncology Company with potential for two innovative products on the market next year. With top line data from our pivotal SORAYA study on track for release next quarter, we have accelerated preparations for the BLA submission and commercial launch of mirvetuximab. Given these near-term catalysts, we see this is an opportune moment to briefly review with you the US market opportunity and dynamics in ovarian cancer. Starting with growth, analyst reports and other industry data project that the ovarian cancer market in the US will increase from approximately $1.6 billion today to over $3 billion in 2026, driven largely by the launch of novel targeted agents like mirvetuximab and the continued uptake of PARP inhibitors.

Looking at epidemiology, each year in the US roughly 20,000 women are diagnosed with ovarian cancer and 14,000 will die from the disease. With just a 50% five-year survival rate, ovarian is one of the deadliest cancers impacting women today. Based on our clinical experience, having tested more than 2,000 patient samples, our data suggest that approximately 40% of ovarian tumors express high levels of folate receptor alpha, which is the target patient population for mirvetuximab. Despite advances in earlier line settings with PARP inhibitors as maintenance, the majority of ovarian cancer patients relapse and become resistant to platinum-based chemotherapy. Treatment options for these patients are limited with poor outcomes and diminished quality of life. Against this discouraging landscape, our goal is to establish mirvetuximab, as the standard of care for FR alpha high advanced ovarian cancer.

With positive data from SORAYA, we anticipate mirvetuximab’s initial indication will cover second through fourth line patients with FR alpha high, platinum resistant ovarian cancer, who have been previously treated with Avastin. We believe this represents more than 2,000 patients in the US with confirmatory data from MIRASOL, our label would expand to over 4,000, as Avastin-naive patients would also be eligible. Beyond the platinum resistant setting, we are initiating PICCOLO, a single-arm study of mirvetuximab monotherapy in FR alpha high later line recurrent platinum-sensitive ovarian cancer aligned with our strategy to generate data that support mirvetuximab displacing single agent chemotherapy. Anna will share more details on that trial in a minute.

We also continue to generate highly encouraging data supporting the potential of mirvetuximab to become the combination agent of choice for ovarian cancer. We were pleased to share final data from our mirvetuximab plus Avastin doublet in an oral presentation last month at ASCO. These data demonstrated compelling anti-tumor activity in patients with FR alpha high recurrent ovarian cancer, regardless of platinum status. We believe the publication of these data, together with the mirvetuximab plus Avastin cohort published in 2019, could support compendia listing in close proximity to the initial monotherapy approval for mirvetuximab ahead of formal label expansion for this combination.

Given this [Phonetic] potential, as I mentioned at the top of the call, we’ve accelerated our work in preparation for the BLA submission and commercial launch of mirvetuximab. To this end, we continue to engage with the ovarian cancer medical community to educate on the robust data sets already generated with mirvetuximab and to increase awareness of folate receptor alpha as a promising biomarker for patient selection for targeted therapy. In parallel, we are gearing up to submit the BLA in the first quarter of 2022 to support potential accelerated approval in the second half of the year, and with commercial inventory in place, we are finalizing plans for distribution. So we got a lot going on and look forward to keeping you updated on our progress, as we approach the potential launch of mirvetuximab next year.

The remainder of our innovative portfolios, ADCs is also progressing IMGN632, our CD123 targeting ADC also has the potential to launch in 2022 in BPDCN and is also being studied in combinations with AML, with data from our AML cohort expected at ASH next quarter. IMGC936 and ADAM9 targeting ADC that we’re co-developing with MacroGenics is advancing through dose escalation. And IMGN151, our next-generation anti-folate receptor alpha ADC is on track for an IND submission by year end.

So with that, I’ll turn the call over to Anna to provide some additional insight into our clinical programs and more on our medical education initiatives. Anna?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Thanks, Mark. Just a few more details on the final data from our FORWARD II study evaluating mirvetuximab in combination with Avastin in patients with medium and high FR alpha expressing recurrent ovarian cancer for whom a non-platinum-based combination regimen is appropriate. These data were presented during an oral session at ASCO in June. The combination demonstrated robust anti-tumor activity in patients with high FR alpha expression, including a confirmed overall response rate of 64%, a median duration of response of 11.8 month and a median progression-free survival of 10.6 month, with manageable adverse events that were consistent with the side effect profiles of each agent. We are highly encouraged by these findings as we believe they reinforce mirvetuximab’s potential to serve as a combination agent of choice in ovarian cancer and support of use in earlier lines of therapy.

Additionally, a randomized Phase 2 investigator-sponsored study with Dr. Phillip Harter in Germany is now under way, evaluating mirvetuximab plus carboplatin, compared to standard of care in approximately 140 recurrent platinum-sensitive ovarian cancer patients. These data, along with the outcomes from the ongoing 70 patient neoadjuvant IST, led by Dr. Rebecca Arend at UAB, will further inform our path forward, as we consider our label expansion options for mirvetuximab in combination with carboplatin.

Turning to mirvetuximab monotherapy beyond SORAYA and MIRASOL, this quarter, we plan to initiate patient enrollment in PICCOLO, our new single-arm study of mirvetuximab monotherapy in third line plus, FR alpha high recurrent platinum-sensitive ovarian cancer patients, with the primary endpoint of confirmed overall response rate and a secondary endpoint of duration of response. With the incorporation of PARP inhibitors, as maintenance in front line and in platinum-sensitive first relapse, where ovarian cancer patients are recurring with later line disease, but it’s still technically platinum-sensitive with the platinum-free interval of greater than six-month, but these patients may not be suitable for another platinum-based therapy. This is because of the cumulative risk of hypersensitivity reactions with repeated exposure to platinum, as well as other potential toxicities related to platinum.

In addition, patients who recur after their tumors have been under selected pressure from the maintenance PARP inhibitor, may not be as sensitive to additional platinum, as well as to recur [Phonetic] in the absence of maintenance therapy. The PICCOLO trial is designed to address this increasing unmet need for an effective non-platinum option in later lines platinum-sensitive disease.

As mirvetuximab moves closer to potential approval, we continue to educate the medical community on the importance of establishing folate receptor alpha as an important biomarker in ovarian cancer. These medical education efforts, include advisory boards of pathologists and oncologists, biomarker workshops and symposia at congresses and presentations at upcoming congresses. We’re working with Roche Tissue Diagnostics and Roche Diagnostics Corporation to develop and commercialize the companion diagnostic for folate receptor alpha. With the groundwork we are laying, we expect physicians to assess folate receptor alpha expression as part of their standard diagnosis and treatment decision process following approval of mirvetuximab and the companion diagnostic.

Moving to our second pivotal program, we continue to enroll front line and relapsed/refractory BPDCN patients in our Phase 2 study of IMGN632 and expect top line data in the first half of next year. Recall that 632 is also advancing in the Phase 1b/2 dose escalation study in combination with azacitidine and venetoclax in patients with relapsed/refractory AML and as a monotherapy in patients with MRD positive AML. We look forward to presenting initial AML combination data for IMGN632 with venetoclax and azacitidine at ASH in December. As Mark mentioned, we are also excited about the advancement of IMGC936 and IMGN151 and look forward to updating you on our progress with both of these ADCs.

With that, I’ll turn the call over to Susan to cover the financials. Susan?

Susan Altschuller — Senior Vice President and Chief Financial Officer

Thanks, Anna. Starting with our results for the second quarter of 2021, we generated $16.9 million in revenue, which consisted primarily of non-cash royalty revenues. Operating expenses were $44.3 million, comprised of $34.6 million of R&D expenses, compared with $22.9 million in 2020; $9.7 million of G&A expenses, compared to $9.8 million in 2020. We ended the second quarter with $239.5 million in cash and cash equivalents on the balance sheet.

Our financial guidance for 2021 remains unchanged. We expect revenues to be between $65 million and $75 million, operating expenses between $200 million and $210 million, and cash and cash equivalents at year-end to be between $140 million and $150 million. Our current cash runway continues to be sufficient to fund operations into the second half of 2022.

With that, we’ll open the call for questions. Operator?

Questions and Answers:

Operator

Thank you. [Operator Instructions] And our first question comes from John Newman with Canaccord. Your line is open.

John Newman — Canaccord Genuity — Analyst

Hi, guys. Thanks for taking my question. Just wondering if you could talk a bit more about the rationale behind the PICCOLO study. Also, curious if you could talk about how that will mesh with your strategy for expanding mirvetuximab in other lines of therapy going forward after approval. Thank you.

Mark Enyedy — President and Chief Executive Officer

Yeah. So, maybe I’ll ask Anna to talk about the medical rationale and what we’re seeing in terms of an increasing population of these patients and why that might be the case. And then, I can talk a little bit more about the broader strategy.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So, we know that platinum historically has been the most active agent in ovarian cancer, and therefore, when patients recur after platinum-based therapy, if their platinum-free interval is greater than six months, they typically get another line of platinum. And unfortunately for patients with each line of platinum, there is a law of diminishing returns, if you will, and their disease-free or progression-free survival gets shorter and shorter, and at some point, they develop platinum-resistant disease. However, as more and more patients are being treated with PARP inhibitors in maintenance after achieving a CR or PR from platinum-based therapy, this is extending their platinum-free interval. And so, patients may now have — still have technically platinum-sensitive recurrent disease, but their platinum-free interval, if you will, has been artificially extended by PARP inhibitor maintenance and the selective pressure that that has been putting on the tumors. So, this emerging population of patients may not be the same as patients in the olden days, if you will, who had a platinum-free interval of six to 12 months, but their tumors saw nothing in the interim.

And so, we anticipate that there will be more data out there, as more patients are becoming part of this category that will guide further understanding of what the benchmark in this population is. But what I can tell you right now is based on anecdotal data from earlier in the mirvetuximab program, where patients with recurrent platinum-sensitive disease did receive mirvetuximab monotherapy, mirvetuximab is quite active. And so, that’s why we’re beginning the PICCOLO study this quarter and that will help us further understand the efficacy profile for mirvetuximab in this later line recurrent platinum-sensitive population that is growing with an increasing unmet need.

Mark Enyedy — President and Chief Executive Officer

So, John, maybe just to frame this in the broader — in the context of the broader development plan and expected lables for the product. So, our initial label comes in platinum-resistant disease and there, we’re looking to displace single agent chemotherapy. Single agent chemo is about half the market in platinum-resistant disease today. So, the goal is to supplant that. The remainder of the platinum-resistant space is treated with generally a range of combinations, specifically Avastin-based chemo combinations. And so, the data that we published at ASCO in June really speaks to the opportunity there. And we think we’ve got compelling data to support a compendia listing for that indication.

When you look at the platinum-sensitive space, as Anna was talking about, patients as their first line therapy are treated with CarboPac [Phonetic] or CarboGem [Phonetic] combinations often as a triplet with Avastin followed by PARP maintenance. Although, the share of patients getting maintenance is might be smaller than one would imagine.

When you get to third line platinum, however, or third line therapy, what you see is only about 30% of patients are receiving platinum-based chemo. And so, there is a big gap. The remainder of that population that we could target either with the MIRV-BEV combo. And again, some of the data that we had at ASCO, we had a 69% response rate with the MIRV-BEV combo in platinum-sensitive patients. But this is really a gap where we think a monotherapy could fit in. The data, in terms of patient numbers is a little sketchy, in terms of third line platinum-sensitive. Our best estimate, based on DRG and some physician surveys is, there are about 2,000 patients in third line. And as I just said about 30% of those patients get a platinum-based chemo regimen, so that leaves us the remainder of that population to go after.

John Newman — Canaccord Genuity — Analyst

Okay. Excellent. Thank you.

Operator

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

Yige Guo — Guggenheim Securities — Analyst

Hey. Good morning, guys. This is Yige on for Michael. Thanks for taking our questions. I think I have a quick one on mirvetuximab. Do you think retreatment with MIRV is possible with some of other backbones of combo therapies? And if so, with various combo regimens currently being evaluated, how could each MIRV combo recommend this sequence?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So, there certainly is precedent for retreatment even with non-targeted cytotoxic in ovarian cancer. So, obviously, we just talked about retreatment with platinum in a lot of detail. Retreatment with tubulin-directed inhibitors, it’s like paclitaxel actually also is beneficial in ovarian cancer. There is very nice data showing that patients who received prior Q3 week paclitaxel may benefit from subsequent weekly paclitaxel. And as you know, the payload for mirvetuximab is a tubulin-directed inhibitor. So there certainly is the potential for repeated treatment with mirvetuximab based on the mechanism of action of the payload.

Switching to the target, we did show in our biopsy cohort several years ago now that patients who received mirvetuximab and then have a subsequent biopsy after a couple of cycles of mirvetuximab still express folate receptor alpha. So it’s not quickly down-regulated that would suggest resistance.

Yige Guo — Guggenheim Securities — Analyst

Got it. That’s fair. Very helpful. Thank you.

Operator

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

Boris Peaker — Cowen and Company — Analyst

Good morning. Maybe one question on mirvetuximab, but another on 632. On mirvetuximab, can you just comment on the PICCOLO study time frame? And when we would be getting any kind of updates from it? How the [Phonetic] overlaps with some of the other clinical studies ongoing?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So PICCOLO is on track to start this quarter. And I think it’s a little too early to say, Boris, certainly — once the trial is up and running at future calls we can certainly provide some guidance regarding timing. Right now, our key focus is the SORAYA BLA and MIRASOL and we’re getting PICCOLO up and running and we look forward to the data from that study because we think it’s really increasing population with unmet need.

Boris Peaker — Cowen and Company — Analyst

Got it. On 632, so can you maybe shed some data expectation at ASH? And also just want to understand from the regulatory perspective, as monotherapy and MRD positive disease, what’s the FDA’s view on MRD positive to MRD negative conversion as the regulatory endpoint?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So at ASH, we anticipate presenting all the data that we have for the triplet of 632 with azacitidine and venetoclax. You may recall, we started out with doublet combining with azacitidine and with venetoclax and then we moved into the triplet dose escalation. So we will have, I would say, a robust data set at ASH, dose escalating, exploring 632 with azacitidine and venetoclax, that will give a good sense of the safety profile of the triplet, the tolerability of the triplet, as well as the anti-leukemia activity that we’re seeing at this point that supports further development in the relapsed/refractory setting and ultimately perhaps in the front line setting.

Moving to your question regarding MRD positive to negative conversion, clearly, that is not yet precedent for approval in the AML setting. There is a precedent in the ALL setting, but that was a bit different because there was a prior Phase 3 data with overall survival benefit for the drug, where it then allowed for subsequent consideration of approval in terms of MRD conversion. I think it’s a little premature to assume that it would be an appropriate endpoint for FDA.

I would also note that ONUREG did get their approval, that’s the oral azacitidine in a broader population in maintenance, so not just MRD positive patients. And when you look at the subset data for ONUREG, the MRD positive subset in their study doesn’t do so well. And so, there is certainly, I would say, a remaining unmet need there. Hope that clarifies, Boris.

Boris Peaker — Cowen and Company — Analyst

Great. Thanks very much for taking my question.

Operator

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

Swayampakula Ramakanth — H.C. Wainwright & Co. — Analyst

Thank you. This is RK from H.C. Wainwright. Couple of quick questions. On the press release you have a note saying that IMGC936 is being looked at in multiple solid tumors. Is it possible for you to enumerate at least some of the major tumors that you are looking at?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Sure. So IMGC936 targets ADAM9, which is a member of the matrix metalloproteinase disintegrin family. It is in — expressed highly across multiple solid tumors, including pancreatic cancer, gastroesophageal cancer, triple-negative breast cancer and lung cancer. It’s also expressed in other tumor types as well. And so, we’ve already generated very nice preclinical data showing the distribution of expression across those solid tumors supporting their inclusion in the Phase 1 dose escalation study. We are enrolling all-comers given the anticipated ADAM9 expression in these tumor types. We’re collecting tumor tissue on all patients, so that retrospectively we can look at ADAM9 by immunohistochemistry, and then we’ll be well positioned to develop a companion diagnostic for patient selection should we need it.

Swayampakula Ramakanth — H.C. Wainwright & Co. — Analyst

And just a follow-up on that, any timing at all in terms of data? And then also, regarding 151, what work needs to be done before we can launch it into the clinic?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So timing for IMGC936, we’re in dose escalation, and we anticipate data early next year, at which point we’ll have recommended Phase 2 dosing safety and a sense of the tumor types that are of greatest interest.

Moving to 151, we’re on track to file the IND before the end of the year. We’re doing the last bits and bobs of what we need to from a tox perspective and a CMC perspective.

Swayampakula Ramakanth — H.C. Wainwright & Co. — Analyst

Thank you very much, Anna. Thanks for taking all my questions.

Mark Enyedy — President and Chief Executive Officer

Sure.

Operator

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

Andy Hsieh — William Blair & Company — Analyst

Great. Thanks for taking my questions, and congratulations on all the progress. So…

Mark Enyedy — President and Chief Executive Officer

Thank you.

Andy Hsieh — William Blair & Company — Analyst

Regarding the PICCOLO study that you’re planning to start this quarter. I am just wondering, how much enrollment optimization can you achieve with the study, just given your existing network of clinical trial sites for SORAYA and MIRASOL.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

I think the short answer is, a lot, given that we studied mirvetuximab now in well over 100 sites, closer to around 200 sites throughout the globe. So, we’re — again, like we did with SORAYA and MIRASOL, we’re picking the best of the best sites who have high patient volumes, participate in clinical trials with high data quality, following GCP and have the patient population that’s appropriate here.

Mark Enyedy — President and Chief Executive Officer

And experience with our drug.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah.

Mark Enyedy — President and Chief Executive Officer

Yes.

Andy Hsieh — William Blair & Company — Analyst

Right. That’s helpful. Thank you. And also, maybe picking a macro view on the folate receptor ADC space. Maybe Mark or Anna, perhaps you can opine on the Bristol Myers and Eisai collaboration that was announced earlier this month? And also kind of looking at the pipeline, you have four assets right now. In the event of a successful SORAYA trial, how should we think about future R&D investment going forward?

Mark Enyedy — President and Chief Executive Officer

Sure. So I’m going to let Anna tackle the competitive landscape, and then we can talk about where we’re going as the business.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So, we considered to be asset-light [Phonetic] deal really validating in terms of them recognizing as we do that folate receptor alpha is an important target in the treatment of cancer. What I would say is that, the publicly available data for their compound MORAb-202 are, at this point, limited to a single site in Japan. As you may recall, they have linked up their failed farletuzumab naked FR alpha antibody with eribulin, which is their cytotoxic that is approved for later line breast cancer. And so, based on the data from dose escalation in that one site, in Japan, they have certainly seen activity in tumor types that are known to express folate receptor alpha. And so, certainly, I think that form the foundation for their agreement. They are currently in a US study, open at a handful of sites. On their dose escalating, they don’t yet have a recommended Phase 2 dosing schedule, but we will follow them.

And I think from our perspective, not only is it validating for FR alpha, but it makes us that much more excited to get IMGN151 in the clinic as soon as possible because we really know from our preclinical data that it’s designed to address the broader population of FR alpha positive tumors and really has the chance to really move the field even further than mirvetuximab will.

Mark Enyedy — President and Chief Executive Officer

So — and Andy, in terms of the future direction for the business, so you may recall when we restructured back in 2019, we chose four programs to move forward and given the progress over the last two years, I’d say, we chose well. But at that time, we had programs that we shelved and in particular, we have a new class of camptothecin payloads that have been internally developed. And so, as we look ahead and with some success in SORAYA, the objective will be to move those programs off the shelf, and in particular, pursue additional development of this camptothecin payload. We have a fair amount of inbound interest with respect to the ImmunoGen platform broadly in terms of linkers and payloads and specific interest in this new class.

In addition to that, akin to the relationship that we have with MacroGenics, we continue to have folks approach us about co-development collaborations where they’ve identified an antibody that they think would be a good candidate for an ADC. And so, those discussions are ongoing as well. And so, we do expect following a positive outcome in SORAYA to begin to expand the portfolio levering our existing technology and our ability to combine with antibodies to generate a novel ADC. So, it’s absolutely the direction that we’re headed.

Andy Hsieh — William Blair & Company — Analyst

That’s very helpful. Thanks for answering my questions, Mark and Anna.

Mark Enyedy — President and Chief Executive Officer

Sure.

Operator

Thank you. Our next question comes from Kennen MacKay with RBC Capital Markets. Your line is open.

Sudan Loganathan — RBC Capital Markets — Analyst

Hi. This is Sudan Loganathan [Phonetic] on from Kennen’s team. Thanks for taking the question. So, first, I wanted to ask kind of what the benchmark is kind of discussed amongst the physician population for the single-arm PICCOLO study for mirvetuximab as a monotherapy? So, kind of, what would kind of give the confidence to the physicians to use that as a monotherapy class? And then, kind of where the conviction comes from you guys on the FR alpha target for ovarian cancer? And then, how that could grow into a monotherapy for other indications?

And then secondly, just kind of a large picture question just on any headwinds that you see from the COVID-19, a bit kind of macro environment to enrollment for some of the other pipeline studies that’s already been kind of determined or could there be some headwinds there going forward? So –. Thanks.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So, the benchmark question regarding PICCOLO is an important one. So, we’re targeting later line platinum-sensitive disease and these are patients who didn’t really exist in the past, or if they did at very small numbers. And actually, frankly, they were mostly BRCA mutant patients because those patients, whose tumors have BRCA mutations are exquisitely sensitive to platinum, and they’re the ones who can get multiple lines of platinum and continue to get benefit, again, each with a diminishing return.

So now that PARP maintenance is being incorporated not just for BRCA mutations, but also for HRD and even in an untargeted fashion, where admittedly the benefit is less. There are still — there are more patients with this later line platinum-sensitive disease. And there are, to our knowledge no, I would say, Level 1 evidence papers to support a firm benchmark. I’m very personally interested in the data that will be coming out over the next year or so that will shed light on what the appropriate benchmark is. Guardrails wise, the data that are out there admittedly from older populations that are less relevant, now include response rates in second and third line platinum-sensitive disease for non-platinum single agents, as 10% to 12%. And in the later line, three to four priors, who are platinum-sensitive and have a BRCA mutation, the response rate is about 30%.

If you look at platinum doublet in patients who just had one prior line, the response rate is about 40%, 45%. So, imagine it dropping with each line of therapy. And this is why we really believe there is a high unmet need for these patients. And again, based on the anecdotal data that we have, we’re quite excited about the potential for mirvetuximab in this population. That was your first question.

Your second question was other indications. So for mirvetuximab, we are supporting a couple of investigator-sponsored trials in endometrial cancer, one is a monotherapy in high-grade serous endometrial cancer and one in combination with pembrolizumab. We have some data for mirvetuximab monotherapy in endometrial cancer already that suggests that would be an interesting additional target. I think we’re saving lung cancer and triple-negative breast cancer for IMGN151.

And then, your last question was regarding COVID-19 headwinds. Yes, there are COVID-19 headwinds. I mean, with the Delta variant emerging now and the recent CDC guidance around masking, it will be interesting to see, frankly, how hospitals and clinical sites may be changing their working policies. I don’t think it’s going to necessarily impact patient care, because patients with recurrent ovarian cancer need treatment. But I wouldn’t be surprised if there are like we’ve already experienced some delays in contracts turnover, IRB meetings, the paperwork aspect of clinical trials as people are working from home. But what I hope to say is during COVID over this past year, we’ve gotten really good at managing through those with our contingencies.

Sudan Loganathan — RBC Capital Markets — Analyst

Great. Thank you so much for all the color on those questions. Appreciate it.

Mark Enyedy — President and Chief Executive Officer

Okay.

Operator

Thank you. Our next question comes from Kelly Shi with Jefferies. Your line is open.

Kelly Shi — Jefferies — Analyst

Thanks for taking my questions. I also have a question for PICCOLO trial. What drive — what — at this stage, what drives the differential only include FR alpha high patients given that you mentioned that there are large unmet need in the third line platinum-sensitive patients? And also based on the previous experience, MIRV achieved in the FR alpha intermediated patients? Thank you.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. We know now having studied mirvetuximab in well over 800 patients, the higher the FR alpha expression the deeper and more durable the tumor shrinkage. So you are absolutely right that mirvetuximab is active in patients with medium FR alpha expression, which is about 20% of the population. We know from the FORWARD I study that it’s probably about the same in terms of its activity with single agent chemotherapy. But we’re really trying to move the field forward and have the potential to be the agent of choice and we want to go where we can benefit patients the most and that’s really the 40% with high FR alpha expression, and that’s based on archival tumor tissue with — irrespective of platinum-sensitivity or resistance.

Kelly Shi — Jefferies — Analyst

Thank you for the color.

Operator

Thank you. Our next question comes from Joe Catanzaro with Piper Sandler. Your line is open.

Joseph Catanzaro — Piper Sandler — Analyst

Hey, guys. Thanks so much for taking my questions here. Anna, you mentioned the Phase 1 experience with mirvetuximab in platinum-sensitive patients. Just wondering the extent of prior PARP exposure in that population and whether there is any reason to think that extended PARP maintenance could potentially impact subsequent sensitivity to mirvetuximab.

And then, just with regards to the cash guidance and it being sufficient into the second half of 2022, what is that inclusive of? And, I guess, specifically around the potential commercial launches of both mirvetuximab and 632? Thanks.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So, the anecdotal data that we have, Joe, is I would say, limited, but quite encouraging. And there are certainly patients in our experience who had a prior PARP inhibitor and have recurrent platinum-sensitive disease and do very nicely with mirvetuximab. Throughout our program, when we’ve looked at patients who had a prior PARP inhibitor, whatever trial we look at, we see very nice activity for mirvetuximab. And that’s not surprising because there is no reason to believe this cross-resistance mechanism. PARP inhibitors interfere with the ability to repair DNA damage were tubulin-directed agents. And so, again, prior PARP use really doesn’t seem to impact the efficacy of MIRV.

Susan Altschuller — Senior Vice President and Chief Financial Officer

Great. And on the guidance that goes into the second half of 2022 that includes spend for pre-launch prep and BLA filing commercialization work for both mirvetuximab and 632. We feel that we’re in a strong place. We’ve been adding additional capital from our ATM facility. That said, we’re — I focus on the year-end cash now. We’re looking for ways to supplement that between now and then. But with a positive readout, we don’t think capital formation will be an issue.

Mark Enyedy — President and Chief Executive Officer

Yeah. Maybe just to put a little finer point on some of what Susan was saying in terms of what we’re doing from an operational perspective. So those numbers include sales force build, it includes production of additional launch inventory for the business, build out of the medical affairs function. So, baked into that number is a fully formed organization ready to launch the drug in the second half of the year.

Joseph Catanzaro — Piper Sandler — Analyst

Okay. Thanks. That’s helpful.

Mark Enyedy — President and Chief Executive Officer

Yeah.

Operator

Thank you. Our next question comes from Jessica Fye with J.P. Morgan. Your line is open.

Daniel Wolle — J.P. Morgan — Analyst

Hi. Good morning. This is Daniel for Jessica Fye. Thanks for taking our question. Maybe a question for Anna. Targeting CD123 and AML hasn’t been as effective as the anti-tumor benefits we have observed in BPDCN. Could you maybe frame for us what could be driving a differentiated outcome in this — on those two settings? And how 632 can be differentiated here in AML?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah. So I think what you’re referring to is the activity of Elzonris or tagraxofusp or SL-401, which is approved for BPDCN. It’s a CD123 fusion protein with a diphtheria toxin. And BPDCN has the highest levels of CD123 expression. So if it’s going to work anywhere, it’s going to work there. And I think there monotherapy experience in AML was quite disappointing. They really didn’t have appreciable monotherapy activity in AML. That contrasts with our experience with IMGN632. You may recall at ASH, we’ve had a couple of oral presentations now showing actually quite reasonable monotherapy activity for IMGN632 in relapsed/refractory AML with very nice CRs — CRIs [Phonetic], didn’t quite meet our bar for a single-arm fast to approval strategy in the relapsed/refractory setting. But certainly, highly active — our drug is highly active as a monotherapy in AML, and I think it’s just because we have a better drug, frankly.

Daniel Wolle — J.P. Morgan — Analyst

Got it. Thank you.

Operator

Thank you. Our next question comes from John Newman with Canaccord. Your line is open.

John Newman — Canaccord Genuity — Analyst

Hi, guys. Perhaps it’s little noisy. Thanks for taking the follow-up. It’s a question for Mark and Anna. This is probably a difficult question to answer. But there is still a lot of conversation on prior calls about the accelerated approval pathway to mirvetuximab. But given the current timing for the program, BLA submission in early 2022, and then top line for MIRASOL, I believe in this third quarter of 2022. Isn’t it reasonable to assume that the FDA will be able to get a look at the top line data for MIRASOL, which could give them more confidence in the accelerated approval based on SORAYA? Thanks.

Mark Enyedy — President and Chief Executive Officer

Yeah. So, I think you have to deconstruct this and ask the question, what is the regulatory environment here and what — and then ask the question about practical considerations that overlay that. But from a regulatory perspective, we file under sub-party looking for accelerated approval. The standard there is to demonstrate a substantial improvement over available therapy. The FDA gave us the benchmark in terms of overall response rate, which is the primary endpoint for our study. And then secondarily, looking at duration of response. And so, if we meet those criteria under sub-party with the data that we generate from SORAYA, there is no basis for the FDA to delay regulatory action on the filing. So, I think that’s the first point.

Yes. If MIRASOL data are available at the time of the regulatory decision, and those data are positive, we think they will be positive. Yes, that would certainly bolster their ability to make a decision on mirvetuximab. But again, I think the base criteria here is, what are the applicable regulatory standards for accelerated approval, and we think we’re going to meet those with SORAYA and that will be the basis for regulatory action.

John Newman — Canaccord Genuity — Analyst

Okay. Great. Thank you.

Operator

Thank you. And I’m showing no other questions in the queue. I’d like to turn the call back to Mark Enyedy for any closing remarks.

Mark Enyedy — President and Chief Executive Officer

Great. Well, thanks very much for your time today, and we look forward to keeping you updated on our progress and to the fourth quarter with the SORAYA readout and also data on 632 at ASH. Thanks very much, and have a nice weekend.

Operator

[Operator Closing Remarks]