Categories Earnings Call Transcripts, Health Care

ImmunoGen, Inc. (IMGN) FY 2021 Earnings Call Transcript

IMGN Earnings Call - Final Transcript

ImmunoGen, Inc.  (NASDAQ: IMGN) FY 2021 earnings call dated Feb. 25, 2022

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

Kristen Harrington-Smith — Senior Vice President and Chief Commercial Officer

Analysts:

John Newman — Canaccord — Analyst

Yige Guo — Guggenheim Securities — Analyst

Etzer Darout — BMO Capital Markets — Analyst

Boris Peaker — Cowen — Analyst

Andy Hsieh — William Blair — Analyst

Han — Jefferies — Analyst

Kennen MacKay — RBC Capital — Analyst

Jessica Fye — JPMorgan — Analyst

Earl De — H.C. Wainwright — Analyst

Joe Catanzaro — Piper Sandler — Analyst

Jonathan Chang — SVB Leerink — Analyst

Presentation:

Operator

Good morning, ladies and gentlemen and welcome to ImmunoGen’s Fourth Quarter and Full-year 2021 Financial and Operating Results Conference Call. [Operator Instructions]

At this time, I’d like to turn the call over to Courtney O’Konek, Senior Director of Corporate Communications. 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 a summary of our recent progress and fourth quarter and full-year 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 Enyedy, our President and CEO; Anna Berkenblit, our Chief Medical Officer; and Susan Altschuller, our CFO; Kristen Harrington-Smith, our Chief Commercial Officer will also join us for Q&A.

During today’s call, we will review recent accomplishments for the business, our financial results and highlight upcoming anticipated events. We will use forward-looking statements with respect to our business strategy, the development and benefit of our product candidates, the design of our clinical trials, the presentation of clinical trial data for our product candidates, the anticipated timing of clinical trials and regulatory submissions to the FDA for certain product candidates, the anticipated commercial launch for certain product candidates, financial guidance and our cash runway.

Each forward-looking statement is subject to risks and uncertainties that could cause our actual results to differ materially from such statements. These risks and uncertainties include those described in our press release issued this morning and in the Risk Factor section of our most recent annual report on Form 10-K and our other SEC filings, which are available at sec.gov and on our website at immunogen.com. These forward-looking statements and this presentation speak only as of the original date of this call and we undertake no obligation to update or revise any of these statements.

With that, I’ll turn the call over to Mark.

Mark Enyedy — President and Chief Executive Officer

Good morning, everyone and thank you for joining us today. 2021 was a productive year for ImmunoGen, with significant progress across the business as we move towards our objective of becoming a fully integrated oncology company. In particular, we delivered resoundingly positive results in SORAYA, our pivotal study for mirvetuximab in ovarian cancer, generated compelling data with IMGN632 and AML, advanced our earlier-stage programs, established a plan to reignite our research engine, laid the groundwork to support our first commercial launch and executed the single largest financing in the history of the company.

With this progress, we’ve generated significant momentum in the business as we entered 2022. To expand on these points, starting with our lead program, Mirvetuximab Soravtansine in ovarian cancer. Our top priority this year is to gain accelerated approval for mirvetuximab as a monotherapy in patients with folate receptor alpha positive platinum-resistant disease. To this end, we believe the positive top line SORAYA data reported in late November position us for initial approval in this setting with significant unmet need.

We’re on track to submit the BLA for mirvetuximab by the end of this quarter and are preparing for a potential accelerated approval and launch in the second half of the year. We also expect to generate data from our confirmatory MIRASOL trial in the third quarter, which is intended to support full approval. As part of our comprehensive strategy to move mirvetuximab into broader patient populations and become the combination agent of choice in ovarian cancer, we’ve designed a number of additional company-sponsored studies and in parallel are supporting investigator-sponsored trials for mirvetuximab, which Anna will discuss in further detail shortly in the call.

In step with advancing the mirvetuximab program towards regulatory approval, we began building our commercial and medical affairs organizations now led by our Chief Commercial Officer, Kristen Harrington-Smith and our Head of Medical Affairs, Dr. Mimi Huizinga. Launch preparations for mirvetuximab are well underway and are focused on four key priorities, redefining expectations from positive outcomes with mirvetuximab in platinum-resistant ovarian cancer, supporting adoption of early folate receptor alpha testing and establishing standards for in-house and centralized testing, ensuring positive physician and patient experiences through tailored education and guidance for patient management and seeking broad payer access and reimbursement and delivering a seamless patient experience.

We’re off to a strong start building best-in-class sales, marketing and medical education teams and have most recently added our Head of Sales. Our second program, pivekimab sunirine formerly known as IMGN632 is progressing nicely. We’ve advanced our pivotal CADENZA study in BPDCN and expect top line data in the frontline cohort in the second half of this year. In addition to BPDCN, we were pleased to present data from the triple regimen evaluating PVAC in combination with azacitidine and Venclexta in relapsed/refractory AML during an oral session at ASH and are encouraged by the safety profile and efficacy observed, particularly in the higher intensity cohorts.

Based on these data, we’ve initiated an expansion cohort for the triplet relapsed patients and expect to move into frontline patients during the year. Regarding our earlier-stage portfolio, dose escalation continues in the Phase one trial of IMGC936, our first-in-class ADAM9 targeting ADC which we are co-developing with MacroGenics in multiple solid tumor types and anticipate sharing data from this program later this year. We also submitted the IND for IMGN151, our next-generation antifolate receptor alpha ADC. Due to a delay in drug product production at our vendor, FDA placed a hold on our IND application pending responses to some CMC-related information request.

We are generating the data responsive to these requests and look forward to enrolling our first patient following submission of this information to the agency. Turning to business development, we were pleased to announce a multi-target global licensing deal with Eli Lilly earlier this month. This deal demonstrates the strength of our technology and leadership in ADCs and generate value from our intellectual property around our proprietary Camptothecin platform.

Lastly, we completed an upsized follow-on offering that generated roughly $295 million in gross proceeds in the fourth quarter and we ended the year with over $475 million in cash. These funds together with product and collaboration revenues will support the business through the initial launch of mirvetuximab and other material inflection points into 2024.

With that, I’ll turn the call over to Anna to provide some additional color on our clinical programs. Anna?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Thanks, Mark. We are extremely pleased by the positive top line results from our pivotal SORAYA trial. Recall that despite advances in the frontline and platinum-sensitive setting, most patients with ovarian cancer eventually relapsed with platinum-resistant disease. Treatment option for platinum-resistant ovarian cancer are limited, consisting primarily of single-agent chemotherapy, which has limited activity with objective response rates ranging from 4% to 13% in considerable toxicities.

Having aligned with FDA on the substantial unmet need in this population, SORAYA was designed as a single-arm study of mirvetuximab in patients with platinum-resistant ovarian cancer, whose tumors express high levels of folate receptor alpha and who have been treated with one to three prior lines of therapy, including prior bevacizumab. The primary endpoint of confirmed objective response rate or ORR, as assessed by investigator, was 32.4%, well over double the expected response with single-agent chemotherapy.

Five of the responses were complete responses, which doesn’t happen very often with available therapy in platinum-resistant disease. Median duration of response or DOR is a key secondary endpoint and was 5.9 months as of the data cutoff on November 16th, 2021, with nearly half of the responders still receiving mirvetuximab at that time, the duration of response continues to evolve. These results are particularly encouraging in light of the heavily pretreated population, in which 51% of patients had three prior lines of therapy.

All patients received prior bevacizumab and 48% had received a prior PARP inhibitor. Turning to safety. The profile in SORAYA is consistent with the known safety of mirvetuximab, which has now been studied in over 800 patients. The most common adverse events were low grade, reversible ocular and GI events, managed with supportive care and dose modifications if needed. The tolerability of mirvetuximab is demonstrated by the low 7% discontinuation rate for treatment-related adverse events, including just one patient in SORAYA discontinuing for an ocular adverse event.

No corneal ulcers or perforation have been reported. As in prior studies, the ocular events were predictable, manageable and reversible. Looking ahead, Dr. Erso Amadalonas will present the full SORAYA data set at SGO during the plenary late-breaking abstract session on Saturday, March 19th. Data will include updated duration of response and key subgroup analyses, including patients with three prior lines of therapy and those who received a prior PARP inhibitor.

Progression-free survival data will also be presented. As mentioned, we are on track to submit the BLA for mirvetuximab before the end of the first quarter in support of potential accelerated approval later this year. In support of full approval, the confirmatory neurofil study of mirvetuximab is expected to readout in the third quarter of 2022. We also continue to enroll patients in PICCOLO, a single-arm study of mirvetuximab monotherapy in approximately 75 patients with folate receptor alpha high recurrent platinum-sensitive ovarian cancer intended to support label expansion.

PICCOLO was designed to address the increasing unmet need for an effective nonplatinum option in later lines of platinum-sensitive disease. With an overall response rate of 64%, our Phase one data show potential for mirvetuximab in this patient population. We have formalized our strategy to position mirvetuximab as the combination agent of choice with compelling data from the mirvetuximab plus bevacizumab doublet in patients with folate receptor alpha high recurrent ovarian cancer, we expect to gain compendia listing for this combination in close proximity to the initial monotherapy approval of mirvetuximab.

These data also support our design of GLORIOSA, a potential label-enabling Phase three study in the second-line platinum-sensitive maintenance setting. About a third of second-line platinum-sensitive patients receive a platinum doublet plus bevacizumab followed by bevacizumab maintenance. The addition of bevacizumab to a platinum doublet provides an overall modest improvement in PFS of approximately three to four months in this setting, highlighting the limitations of available therapy.

GLORIOSA is designed to evaluate the PFS benefit of mirvetuximab plus bepapizumab maintenance versus bevacizumab maintenance alone in all patients who have not progressed following completion of their platinum doublet plus bepapizumab. Approximately 440 patients will be randomized to either mirvetuximab plus bevacizumab or bevacizumab alone for maintenance. The primary endpoint is progression-free survival, secondary endpoints include overall survival and overall response rate. We anticipate initiating GLORIOSA in the second quarter of this year.

Given the promising activity we’ve seen with the mirvetuximab plus carboplatin development in Phase I dose escalation in recurrent platinum-sensitive disease across a range of folate receptor alpha expression with an ORR of 80% and median duration response of 24 months in FR-alpha medium and high patients, we recently announced the planned initiation of Trial 0420. Trial 0420 is a single-arm Phase two study of mirvetuximab plus carboplatin, followed by mirvetuximab continuation in approximately 110 patients with folate receptor alpha low, medium or high platinum-sensitive ovarian cancer.

The data from this study will inform our path to registration in this setting. Moving to pivekimab sunirine, our CD123 targeting ADC. We presented initial safety and efficacy findings from the Phase 1/2 study of pivekimab in combination with azacitidine and venetoclax in patients with relapsed refractory AML in an oral session at ASH in December. Demonstrating an ORR of 48% in all relapsed/refractory AML patients, these data are encouraging, particularly in higher intensity cohort, where we observed higher response rates, including an ORR of 59% and a 38% composite complete remission rate.

Importantly, the pivekimab triplet demonstrated no tumor lysis syndrome, veno-occlusive disease, capillary leak or cytokine release. These data reinforce the potential of pivekimab as a new combination therapy for AML, which unfortunately is characterized by core outcomes despite available therapies. We have opened an expansion cohort in relapsed AML patients and plan to initiate a frontline expansion cohort later this year. Also at ASH, we presented pivekimab monotherapy data featuring [Indecipherable] from three frontline BPDCN patients in a poster session.

All three patients achieved clinical complete remission and pivekimab was associated with limited grade three or greater treatment-related adverse events and no capillary leak syndrome. We continue to enroll patients in the US and Europe in CADENZA, our pivotal Phase II study in frontline and relapsed/refractory BPDCN, anticipate top line data during the second half of 2022 and believe Tisotumab has the potential to become a best-in-class monotherapy treatment option for BPDCN patients.

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 full-year 2021. We generated $69.9 million in revenue, $46.8 million of which came from noncash royalty revenues. The remainder came from license and milestone fees, which include recognition of $14.6 million of the $40 million upfront fee, previously received under the company’s collaboration agreement with Huadong Medicine and $7.4 million of revenue from partner milestones. Operating expenses were $194.9 million, comprised of $151.1 million of R&D expenses compared with $114.6 million in 2020 and $43.8 million of G&A expenses compared with $38.6 million in 2020.

We ended 2021 with $478.8 million in cash on the balance sheet. Turning to our financial guidance for 2022. We expect revenues to be between USD75 million and USD85 million, operating expenses between USD285 million and USD295 million and cash and cash equivalents at year-end between USD245 million and USD255 million. Given the range and timing for potential approval of mirvetuximab, revenue guidance does not yet include potential product sales from mirvetuximab. We expect that our current cash, combined with the anticipated product and collaboration revenues will fund operations comfortably into 2024.

With that, I will turn the call over to Mark for closing comments.

Mark Enyedy — President and Chief Executive Officer

Thanks, Susan. We entered this year with a motivated and strong team and exciting prospects for the business. Between now and the end of the year, we expect to launch our first product, report pivotal data for PVAC, advance our early-stage programs and further build our pipeline and research capabilities. We have the right strategy, leadership and resources in place to generate significant value in the near and long-term and I look forward to more good days for our people, our business and our patients.

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

Questions and Answers:

Operator

[Operator Instructions] And our first question coming from the line of John Newman of Canaccord. Your line is now open.

John Newman — Canaccord — Analyst

Hi, guys. Good morning. Thanks for taking my question. Congrats on the continued progress. Just have two quick questions. First one is for the progression-free survival data from SORAYA at SGO, just curious if we’ll see both investigator-assessed and independently assessed. And then on pivekimab or 632, just curious as to what patient population and potential combinations you’re considering for a future pivotal study? Thanks.

Mark Enyedy — President and Chief Executive Officer

Anna?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Hi, John. Yeah. So at SGO, we will have the full data set from SORAYA which will include overall response rate, duration of response, subsets and we will include PFS data as well. I would encourage folks to come to SGO to assess the PFS data and we will have an investor event shortly thereafter. Moving on to the PVAC question, in terms of future pivotal trial, we are thinking about the triplet pivekimab, plus azacitidine plus venetoclax in relapsed/refractory AML based on the data that we have already generated in Phase one dose escalation and now we’re exploring in an expansion cohort that potentially could support a single-arm study in the relapsed setting. In addition, we plan to explore a frontline setting for this triplet and should those data look promising, then we could consider a frontline randomized Phase three trial to support approval for that triplet in the frontline setting.

John Newman — Canaccord — Analyst

Great, thank you.

Operator

And our next question coming from the line of Michael Schmidt from Guggenheim Securities. Your line is open.

Yige Guo — Guggenheim Securities — Analyst

Hi, good morning. This is Yige Guo for Michael. Congrats on the progress and thanks for taking our questions. Two quick questions from us. Number one, for MIRASOL, Anna, could you please help us understand the mix of the patients with and without prior bevacizumab. How are the two groups different in baseline characteristics? And how might that impact the response to mirv? And the second question, can you talk about your Camptothecin ADC platform that you licensed to Eli Lilly, how is the payload different from other type one Topoisomerases targeted ADC? Thank you.

Mark Enyedy — President and Chief Executive Officer

Anna?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah, so for MIRASOL, the patient population will include both patients with and without prior bevacizumab similar to FORWARD I, the prior Phase three study, where we had a mixture of patients. In FORWARD 1, about half of the patients had prior bevacizumab and half did not. We anticipate a similar patient mix in MIRASOL. And when you think about which patients get bevacizumab, they tend to be patients with worse prognosis and are more heavily pretreated. Let me start with the worse prognosis and then move to heavily pretreated.

Bevacizumab is approved in several setting for ovarian cancer. The only one of which that has demonstrated an overall survival advantage is in the first-line setting for poor risk patients. These are patients with stage four disease, sub-optimally debulked, ascites, etc. So many physicians often reserve bevacizumab for those worse patients, particularly in Europe. And we can see that actually in the SORAYA study when you come to SGO in terms of the demographics of the patients enrolled in terms of their stage of disease. Moving to number of prior lines of therapy also bevacizumab, it’s hard for us in prior studies to tease apart bevacizumab versus number of prior therapies.

And as a point of reference to support that, in the FORWARD I study, 65% of patients had one to two prior lines of therapy and 35% had three priors. You may recall that in SORAYA, 51% of patients had three prior lines of therapy. So the SORAYA population is more heavily pretreated and potentially a worse population than what we anticipate seeing in the MIRASOL study based on the prior FORWARD I study.

Moving to the next question on Camptothecin, so our Camptothecin payloads are specifically designed to address antitumor — potent antitumor activity and have basically unique properties from a chemical perspective that give broad IP coverage for us. I think that’s what I can say at this point. I don’t know, Mark, if you want to add any color to the Camptothecin payloads?

Mark Enyedy — President and Chief Executive Officer

Yeah, maybe just a little broader observation here. So we take some pride in having multiple classes of payloads to apply to ADC. So we’ve got at least three generations of maytansine. We have our indolinobenzodiazepine DNA-acting payloads and we were looking for additional classes. And our team engineered this new version of the Camptothecin with the goal of broadening the therapeutic index versus what we see with some of the other Camptothecin that have been deployed in the AP context and we’ve got very good preclinical data supporting that we’ve been able to drive activity at least in that range with better tolerability. So we’re excited about that, Lilly was excited about that and are moving forward with tech transfer for them for their targets, while at the same time advancing internal programs that will deploy that payload.

Yige Guo — Guggenheim Securities — Analyst

Thank you very much.

Mark Enyedy — President and Chief Executive Officer

Sure.

Operator

And our next question coming from the line of Etzer Darout with BMO Capital Markets. Your line is open.

Etzer Darout — BMO Capital Markets — Analyst

Great. Thanks for taking the question. First one for me, with respect to PFS and SORAYA, I guess how meaningful is this update from your perspective in this late line post bev setting? And will we see benchmarks for this specific population at SGO? And then secondly, on IMGN151, given sort of the CMC submission update, are you still on pace to start the Phase one in the first half of this year? Thank you.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah, I’ll take the PFS question and then we can — I’ll turn it over to you, Mark for the 151 question. So regarding SORAYA, you’re absolutely right. The population is a late line post bev setting. And frankly, this is one of the most heavily pretreated population that has been studied in platinum-resistant ovarian cancer in a study of this size. So there are no good benchmarks.

But what I can tell you is there are multiple studies that have been published showing in ovarian cancer as in other solid tumors, the law of diminishing returns, if you will, with each line of therapy, the expectation for response rate, duration of response and progression-free survival diminishes. So when you get to these really later-line patients, physicians expectations regarding efficacy are quite low given their experience.

And certainly the data that we’ve shared with the investigators on the SORAYA study, they’re quite pleased with totality of the efficacy data that we have shared with them in terms of ORR, duration of response and PFS because as I said, the expectations that they have for these patients later line post-bev setting is quite low.

What I will tell you is that we will share data at SGO to put the PFS data from SORAYA into context based on what we’ve known from prior studies of mirvetuximab. As you’ve seen, we’ve replicated the overall response rate data in SORAYA that we had previously gathered in that 70 patients of foundational data that basically created the hypothesis that we have tested in SORAYA and now confirmed. So again, we’ll have the data and put it into context for you at SGO. Mark, over to you for 151.

Mark Enyedy — President and Chief Executive Officer

Yeah, thanks. So just to reiterate the point that we made in the introductory comment, this is a CMC not a clinical issue. So in order to issue a study may proceed letter for an IND, the FDA requires the sponsor to submit CMC data relating to the drug, including drug product stability. Most often those data are included in the IND submission. And in some cases, the sponsor will make the data available to the agency during the review period. In the case of 151, we plan to submit the required data during the review period.

However, due to delays at our drug substance vendor, we were not able to secure a drug product production slot as we had planned, which meant that we weren’t in a position to update the IND during the review period, so the agency put us on hold. We’ve now secured our drug product slot for this quarter and we will generate the required data and expect to come off clinical hold in due course. It’s too early to give updated guidance in terms of — we will be delayed, but it’s too early to give updated guidance on the time line for first patient in, but we will update you when we’ve got a better sense following the DP run.

Etzer Darout — BMO Capital Markets — Analyst

Got it. Thank you and congrats on all the progress.

Mark Enyedy — President and Chief Executive Officer

Thank you.

Operator

And our next question coming from the line of Boris Peaker with Cowen. Your line is open.

Boris Peaker — Cowen — Analyst

Great, thanks. Maybe looking forward to the SGO, I think lot of investors are going to be focused, obviously, on the PFS result and you said us invasive to estimate the probability of success of MIRASOL. So maybe you could help us try to understand how we should be thinking of translating the PFS from SORAYA to MIRASOL quantitatively?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Thanks, Boris. I think we have actually much better data to guide PFS from FORWARD I to MIRASOL. What I mean by that is that PFS in a single-arm study like SORAYA is really not interpretable. You don’t have a control arm to tease apart the antitumor activity from the underlying tempo of disease. And so that’s why FDA does not use PFS when they are looking at antitumor activity to support accelerated approval, it’s about ORR and DOR. If people want to assess the probability of technical success for MIRASOL, I would encourage them to review the data that we’ve already generated in FORWARD I.

Recall that FORWARD I was the randomized Phase three study of mirvetuximab versus investigator choice chemotherapy. And in the FRa-high subset identified by the PS2 scoring method, that is the population that we’re basically replicating in MIRASOL. And in FORWARD I, we demonstrated a median PFS in that population of 5.6 months. The hazard ratio in FORWARD I based on either investigator or independent blinded independent review was around 0.6. And you may recall that in MIRASOL, we’ve designed the study to target a hazard ratio of 0.7 much more conservatively.

So we’ve already run the experiment in FORWARD I. The population in MIRASOL will be essentially the same in terms of platinum resistance one to three priors, FR-alpha high, about half of them having prior bevacizumab. The one difference is that we’ll have a higher percentage of patients with PARP inhibitors now. And we’ve already demonstrated in SORAYA and you’ll see the full data at SGO that mirvetuximab has very nice activity regardless of prior PARP use or not. So from our perspective, the SORAYA data increased the probability of technical success for MIRASOL because we now have that answer about what about prior PARP inhibitors. Thanks, Boris.

Boris Peaker — Cowen — Analyst

Got it. And my second question is on the CADENZA study in BPDCN. Could you just set expectation what you need to show in the study for approval?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah, so the statistical design for Cadenza is really allowing us to enroll a cohort of up to 20 patients in this ultra rare indication. There’s somewhere between 500 and 1,000 new patients a year in the US and similarly in Europe. And so looking at the efficacy data for the one approved agent in BPDCN, we know that the CR/CRC rate is in the 40% to 50% range. And so we would need to demonstrate a CR/CRC rate in that range with nice efficacy. And from a statistical perspective that based on the sample size that we’re using, that rules out this 10% CRC rate that FDA guided us to.

Boris Peaker — Cowen — Analyst

Got it. Thank you for taking my question.

Mark Enyedy — President and Chief Executive Officer

Sure.

Operator

Our next question coming from the line of Andy Hsieh with William Blair. Your line is open.

Andy Hsieh — William Blair — Analyst

Great. Thanks for taking my questions and congratulations on all the progress last year. So first question has to do with all the new trials. So Anna, I’m just curious if you have kind of decided on the trial design for GLORIOSA in terms of treatment duration in the maintenance space? And also maybe a step back, can you use this trial as a confirmatory study for PICCOLO? I know that sometimes FDA allows you to confirm using kind of a different patient population? And the second question is for Kristen. I’m just curious, as you prepare to launch MIR, have you decided on how the drug will be distributed? So specifically, I’m curious about the ordering and delivery system. Is that mostly on demand? And if that’s the case, how should we think about the gross to net? Thank you.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Sure. So we’re really excited about the GLORIOSA study, which is a study of adding mirvetuximab to maintenance bevacizumab versus maintenance bevacizumab in the recurrent platinum-sensitive setting. Why are we excited about this? Because we’ve already generated beautiful data in the treatment setting for the mirv, bev doublet showing response rates of 59% in platinum-resistant disease, 69% in platinum-sensitive disease that are above the benchmarks.

And so we want to move that active, well-tolerated doublet into the maintenance setting. We know that patients once they have recurrent platinum-sensitive disease, more and more of them will have already had a PARP inhibitor in the frontline setting. And so using a triplet in the recurrent platinum-sensitive setting makes a whole lot of sense. So with that, we will take all patients who have completed their triplet in terms of the carboplatin doublet portion of it.

And as long as they haven’t progressed, so they have a CR, a PR or a stable disease, they will be randomized to mirv bev versus bev alone. And you may recall that in this setting, that entire treatment path for bevacizumab only — bev only adds about three to four months of progression-free survival. So adding mirvetuximab, a non-cross-resistant targeted cytotoxic, we anticipate that we will have responses on the mirv-bev arm and there will be a long treatment duration on the mirv-bev arm really benefiting patients. The primary endpoint is progression-free survival.

The study also has sufficient power for us to demonstrate an overall survival advantage and that could really transform the treatment paradigm for these patients. Regarding your question about confirming whether or not GLORIOSA could stand in as a confirmatory trial for PICCOLO, it’s a little too soon for us to work that through. PICCOLO is enrolling now and we need to engage with FDA on the exact criteria for a path toward accelerated approval. So I would stay tuned for that. And let me turn it over to Kristen now.

Kristen Harrington-Smith — Senior Vice President and Chief Commercial Officer

Thanks, Anna. So to respond to your question, we do plan on using a 3PL. So like you said a on-demand or a drop-ship model. And this is to help us with our growth to net. But at this time, that’s all we would like to comment on gross to net. Does that help?

Andy Hsieh — William Blair — Analyst

Yes. Okay. So I guess the question is really how would the kind of gross net differ from other drugs or more traditional distribution. So that’s kind of where I am curious about?

Kristen Harrington-Smith — Senior Vice President and Chief Commercial Officer

Yeah, so our goal is to avoid many of the wholesaler fees.

Andy Hsieh — William Blair — Analyst

Okay. That’s [Indecipherable]

Mark Enyedy — President and Chief Executive Officer

Yeah, no, no, so I mean when you look at the patient numbers and volumes here, there’s no need to have a massive amount of inventory sitting at wholesalers waiting to be distributed. So it’s much more efficient from our perspective. And most of the ADCs use this model of setting up a 3PL and then having the orders come in and filling those using the drop ship model. In doing that and setting up a very streamlined approach here, we’re avoiding a lot of the fees that are attended to having inventory sitting at a wholesaler. We can’t tell you right now what exactly the gross to net would be and that probably wouldn’t be a good idea in the first instance.

Andy Hsieh — William Blair — Analyst

Right. Okay. That’s really helpful. Thank you so much. So Anna, I’m curious the — so the — is there like a fixed duration for the maintenance Phase for GLORIOSA, is it like one year, 18 months or two years. I’m just curious if that’s been set?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Yeah, so in the frontline setting, when you do maintenance trials, there is a fixed duration because there’s a chance that some of your patients are going to be cured. Once you have recurrent platinum-sensitive disease, the expectation is that you’re not cured. So patients will be treated until progression and intolerable toxicity or intolerable toxicity. But I have to say, I mean, across the mirv program, we’ve had patients on mirvetuximab for one year, two years, three years, even up to four years and still going.

So in terms of the tolerability of mirvetuximab as a monotherapy, we know that it’s quite well tolerated. And with the mirv-bev, we’ve had patients on that doublet for a good long time as well, both in the platinum-resistant and the platinum-sensitive setting. So I can’t tell you an estimated duration in maintenance in the recurrent platinum-sensitive setting, but it’s going to be long because we know that the PFS of these patients is going to be quite long.

Andy Hsieh — William Blair — Analyst

Great. Thank you so much for answering all my questions.

Mark Enyedy — President and Chief Executive Officer

Thanks, Andy.

Operator

And our next question coming from the line of Kelly Shi with Jefferies. Your line is open.

Han — Jefferies — Analyst

Good morning. This is Han [Phonetic] calling in for Kelly Shi. First, thanks, first, congratulation on the great quarter. So my question is really for the MIRASOL trial. Given the assumption for the median PFS, the chemo arm is about 3.5 months. Do you see any risk that the control arm might outperform given that more optional chemo therapy is available for the control arm? And then my second is regarding to the ECOG 01 performance status. Do you see that may also influence the patient outcome in the control and treatment arm and how the patient in term of the consistent weight of the 01 status — it’s consistent from the FORWARD I trial to SORAYA and MIRASOL trials.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Okay. So your question about the progression-free survival estimate on the control arm of MIRASOL, we have designed it for 3.5 months because that’s pretty much what every study in platinum-resistant ovarian cancer has shown. I would remind you that in FORWARD I, for the FR-alpha high subset, we actually had a median PFS of 3.2 months. There are some studies out there suggesting that FR-alpha is a poor prognostic factor.

So it may be with single-agent chemotherapy, patients with high FR-alpha do worse than the overall population. So if anything, I think the control arm on MIRASOL might underperform, not outperform. I didn’t understand your comment about it might outperform because more options are available. The options on the MIRASOL control arm are topotecan, paclitaxel and Doxil, just like they were in the FORWARD I study. These are all drugs that have been approved 20 years ago. So it’s not like now there’s more better therapies, unfortunately we’re using the same old single-agent chemotherapies that have been around for a couple of decades.

So if anything, I think the control arm and MIRASOL might underperform, but we certainly didn’t design it, assuming that it needed to for success of the study. Moving to ECOG performance status 0 or 1. The ECOG performance status is 0 means people feel perfectly well. ECOG status of one means they’re a little tired and the lower the performance status, certainly the worse patients do.

And that’s why we’ve excluded patients with poor performance status two, three or four because that’s when you know that the risks of the — whatever you’re studying begin to potentially outweigh the benefit because the patients just aren’t fit enough. So given the population that we’ve enrolled across the mirvetuximab program, ECOG status is 0 or 1, we typically have a similar distribution across all the studies and we do not anticipate any difference from an efficacy or a tolerability perspective for either subset of patients.

Han — Jefferies — Analyst

Great, thank you so much. That’s very helpful.

Operator

Our next question coming from the line of Kennen MacKay with RBC Capital. Your line is open.

Kennen MacKay — RBC Capital — Analyst

Hey, good morning and thanks for taking the question. Just one on the SORAYA filing point. Is the data from SORAYA sufficient for the Ventana 4R1 companion diagnostic and accelerated approval of the diagnostic as well? Or is there additional data from MIRASOL or other trials in the future that’s also needed or again just in a confirmatory sense? And then on the MIROVA trial, can you maybe talk about the rationale for that trial and that carboplatin plus mirv doublet and potentially what the next steps there could be? Thanks.

Mark Enyedy — President and Chief Executive Officer

Sure. I’ll take the CDX question and then Anna you can talk about IST with harder. So the answer is yes. The data from SORAYA are sufficient to support the approval of the companion diagnostic. I think as we’ve discussed previously on these calls, we’re working with Ventana, which is Roche Tissue Diagnostics, they’ve actually submitted the PMAs in four modules. They’ve already submitted the first module. They have our clinical, which is being integrated into the subsequent modules enabled file and close proximity to our BLA submission, which would put them on track to have the CDx approved at the same time as the drug.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

And for the MIROVA study, this is a randomized Phase two investigator-sponsored trial in Germany led by Dr. Philip Harder. It’s approximately 140 patients who will be randomized 1:1 to mirvetuximab plus carboplatin, followed by mirvetuximab continuation versus carboplatin doublet of choice followed by maintenance of choice. And the idea here is, when you talk to physicians about mirvetuximab, they want to be able to replace paclitaxel with our drug because patients don’t lose their hair. We have less neuropathy.

And so this is the first opportunity for us to really combine mirv plus CARBO in a larger study for Dr. Harder to do so and compare it directly to standard carboplatin doublet, which include carbo paclitaxel, carbo doxil and carbo gemcitabine. And so this study will help us get a better sense of the tolerability profile of the doublet because at this point our database is limited, but also the antitumor activity efficacy in the recurrent platinum-sensitive setting head-to-head against available therapies.

So this data set from MIROVA will help guide further development of mirvetuximab plus carboplatin as a doublet. I should point out it’s that it is one of the three prongs that we are taking to understand the potential of mirvetuximab plus carboplatin. The second prong is a neo-adjuvant study, IST here in the US, led out of Ohio State. And that study is in the neo-adjuvant setting, the first time we can get mirvetuximab in untreated patients upfront with tumor tissue available at the time of their debulking study — surgery.

And then the third is Trial 0420 that you heard about earlier, which is mirvetuximab plus carboplatin in a broader population of FR-alpha positive tumors. So between those three — among those three data sets, we will then have sufficient data to support the registration path for the mirvetuximab plus carboplatin doublet.

Kennen MacKay — RBC Capital — Analyst

Got it. Thanks. And then maybe just one follow-up. You’ve mentioned that there’s certainly some evidence and some publications out there to support the fact that patients with FORWARD receptor-positive disease or boy receptor high positive disease, potentially have worse outcomes. Is there any other data that the team is working on or that might become available that could be used to sort of further support that factor or be added to the SORAYA Accelerated Approval submission? Or if not, what dataset do you see as the most supportive for that? Thank you.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

So we do not need any data regarding FR-alpha as a prognostic factor to support our SORAYA study and our path toward accelerated approval. We know that FR-alpha is predictive of benefit from mirvetuximab. We have a biomarker identified population in SORAYA, FR- alpha high patients who clearly benefit from mirvetuximab with a near tripling of the response rate, clinically meaningful duration of response and very nice tolerability.

And so FR-alpha is clearly predictive of benefit from mirvetuximab. The one data set that we can point to now that is more robust in terms of answering this prognostic question, the one data set that we can point to really is the FORWARD I data set where we did the post hoc analysis looking at mirv versus chemotherapy because, again, you need this control arm, right, because that’s where you’re assessing how patients do with available therapies, where we inadvertently enroll the low, medium and high patients.

And you can see with the higher the FR-alpha expression, the worse patients do with investigator choice chemotherapy, be it response rate or progression-free survival. And I think, frankly, that’s the only data set that we’re going to have for a while, Kennen, because now that we know we’re focused on the FR-alpha high patients approximately 40% of all of the ovarian cancer patients who benefit the most from mirvetuximab.

I mean, down the road, maybe with mirvetuximab plus carboplatin when we demonstrate very nice activity across a broader spectrum of FR-alpha patients and we do a randomized trial there, maybe then we’ll have a mix of patients where we can circle back on this question of it being a prognostic factor. But really, from a development perspective and from — for physicians to understand who benefits the best from mirvetuximab, it’s FR-alpha high patients and that’s what matters the most.

Kennen MacKay — RBC Capital — Analyst

Got it. Thanks again and looking forward to seeing you in your next review.

Mark Enyedy — President and Chief Executive Officer

Thanks.

Operator

And our next question coming from the line of Jessica Fye with JPMorgan. Your line is open.

Jessica Fye — JPMorgan — Analyst

Hey, guys. Good morning. Thanks for taking my question. Maybe one more specific one on SGO. Should we expect to see a swim plot, spider plot, a waterfall at SGO? And also will we see a PFS Kaplan-Meier curve or just the median PFS number?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Come to SGO, Jess. We will have visualizations of the data for you to understand the data.

Jessica Fye — JPMorgan — Analyst

Okay. Great. And on the platinum-sensitive setting, can you talk about what you see as the bars either for approval or for further development for the Phase three evaluating mirvetuximab plus bev maintenance and the float receptor high platinum sensitive setting, as well as for that mirv combo with mirvetuximab continuation in the kind of broader folate receptor expressing population?

Anna Berkenblit — Senior Vice President, Chief Medical Officer

Sure. So in terms of the bar, we have designed GLORIOSA, the randomized Phase three study to support full approval. The primary endpoint is progression-free survival, it’s about 440 patients and the hazard ratio we’re aiming for is around 0.7 or that’s what it’s designed for. And so this study is designed in a robust manner to demonstrate superior efficacy for mirvetuximab plus bevacizumab versus bevacizumab alone. In terms of the bar for mirvetuximab plus carboplatin that doublet, we would anticipate needing a randomized Phase three study for that doublet.

So again, we would need an adequately powered randomized Phase three study with a control arm of standard available platinum-based doublets that should answer your question, Jess, because these are both — the strategies would be randomized trials. I think where the bar is less clear to be honest and the unmet need is increasing is in the later line platinum-sensitive patients that we are studying in the PICCOLO study.

That’s a population where I think the unmet need is increasing and the bar there is not clear. We’ve already generated a handful of data supporting that — going forward with the PICCOLO study and we look forward with engaging FDA on what the bar would be in that setting to support approval from a single-arm trial for an accelerated approval.

Jessica Fye — JPMorgan — Analyst

Got it. Thank you.

Operator

And our next question coming from the line of Earl De with H.C. Wainwright. Your line is open.

Earl De — H.C. Wainwright — Analyst

Hey, good morning, everyone. Thanks for taking my question. Most of my questions have been answered. I just wondered, could you guys give us more color on the advantage for the Camptothecin platform? And if possible, could you guys give us more color on the partnership with Eli Lilly?

Mark Enyedy — President and Chief Executive Officer

Sure, I mean we covered most of what we have said publicly about this program. So our chemists were looking for an additional payload. We noted the that Daiichi was enjoying with their Camptothecin. So the question was, as a medicinal chemistry exercise, could we design a better topo1 inhibitor that some of the camptothecin class that would expand the therapeutic index for the payload either by better tolerability, better efficacy in both. What we think we have is a molecule with at least equivalent efficacy with better tolerability and we think potentially better bystander killing with this molecule. So that’s the basis. And then I can’t really comment on the financials of the deal beyond what’s included in the press release that we issued last week or the week before.

Earl De — H.C. Wainwright — Analyst

Thank you for the additional color. And congrats on the progress this quarter.

Mark Enyedy — President and Chief Executive Officer

Thank you.

Operator

And our next question coming from the line of Joe Catanzaro with Piper Sandler. Your line is open.

Joe Catanzaro — Piper Sandler — Analyst

Hey, guys. Thanks so much for taking my question here. Maybe one just quick one for me. If I think back to FORWARD I, I think it took about 10 months or so from enrollment completion to readout. So just wondering, why there will be a shorter window for MIRASOL. I know it’s not maybe apples-to-apples, but maybe you could help us better understand that dynamic, whether it be enrollment kinetics, event rate or other things? And if there’s risk that the readout could be pushed beyond 3Q. Thanks.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

You’re spot on enrollment kinetics influence the timing of the readout. So progression-free survival is the primary endpoint, it’s an event-driven study, right? So we will trigger the analysis for the primary endpoint when we reach the requisite number of events. And that is a function of both the enrollment, as well as the timing of the events. The event rate in MIRASOL is and should be similar to the event rate in FORWARD I, given that we’re enrolling very similar populations.

The enrollment rate in MIRASOL has been different from FORWARD I. With FORWARD I, we had a very, very brisk enrollment the last three months, like it just shot up like crazy. So a whole bunch of patients were enrolled right at the very end. So we had to wait a good long time to get to the requisite number of progression-free survival events. Here with MIRASOL being a larger study and with the pandemic, we don’t anticipate that super duper sharp tail in enrollment like the curve right up and so that accounts for the differences in the timing. And so we’re on track for top line data in Q3.

Joe Catanzaro — Piper Sandler — Analyst

Okay. Got it. That’s really helpful. Thanks for taking my question.

Mark Enyedy — President and Chief Executive Officer

Sure.

Operator

And our next question coming from the line of Jonathan Chang with SVB Leerink. Your line is open.

Jonathan Chang — SVB Leerink — Analyst

Hi, guys. Thanks for taking my questions, couple of non-mirv questions for me. First question, can you provide any color on your revenue guidance of USD75 million to USD85 million, you noted that this doesn’t include potential product sales from mirvetuximab. So if you could provide any color as to what’s reflected in this guidance, that would be helpful. And then the second question is, can you provide any additional color on how the IMGC936 dose escalation is going? And any additional granularity on when initial data could be disclosed this year. Thank you.

Mark Enyedy — President and Chief Executive Officer

Great. Susan?

Susan Altschuller — Senior Vice President and Chief Financial Officer

Yeah, so on the revenue guidance, we include our noncash royalty revenues and the license and milestone fees to inclusive of the USD75 million to USD85 million. So we don’t include the Merck product revenues because we don’t have a PDUFA date yet, of course. And so that the timing of potential revenues would make a factor in that. So that’s what’s inclusive in the revenue guidance.

Anna Berkenblit — Senior Vice President, Chief Medical Officer

And turning to IMGC936, we are in dose escalation for this novel ADC with a novel ADAM9 directed antibody and the first DM21 linker payload. So we are in dose escalation and we look forward to presenting data later this year once we’ve identified the recommended Phase two dosing schedule and then we’ll be able to also share plans for further development in ADAM9 positive tumors.

Jonathan Chang — SVB Leerink — Analyst

Got it. Thank you.

Operator

And that’s all the time we have for our Q&A session. I would now like to turn the call back over to Mr. Mark Enyedy for any closing remarks.

Mark Enyedy — President and Chief Executive Officer

Great. Thanks, everybody for joining us today. We’re excited about the year ahead. We have a number of important events upcoming, starting with SGO in a couple of weeks and we look forward to talking to all of you then. So thanks very much and we’ll keep you updated on our progress.

Operator

[Operator Closing Remarks]

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