ImmunoGen Inc (IMGN) 2021 Q3 法說會逐字稿

Good morning, and welcome to ImmunoGen's Third 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.

Good morning and thank for joining today's call. Today, we issued a press release that includes the summary of our recent progress and third quarter 2021 financial results. This press release and a recording of this call can be found in the Investors and Media Section of our website at immunogen.com.

With me today are Mark Enyedy, our President and CEO; Anna Berkenblit, our Chief Medical Officer; and Susan Altschuller, our CFO. During today's call we will review key recent accomplishments for the business, our financial results and anticipated upcoming evenings.

During the discussion, we will use forward looking statements with respect to our business strategy, the developments and benefits of our product candidates, the presentation of clinical data for our product candidates, and the anticipated timing of regulatory submissions to the FDA and the EMA for certain product candidates, our 2021 financial outlook and our projected cash runway.

This information is subject to risk and uncertainties. Our actual results may differ materially from such statements and include those described in the risk factors section of our most recent annual report on Form 10-K and our other SEC filings.

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

Thanks, Courtney. Good morning everyone and thank you for joining us today. In the third quarter, we advanced our pipeline and continued our pre-launch activities as we look to transform ImmunoGen into a fully-integrated oncology company in the coming year.

Starting with our lead program, mirvetuximab soravtansine and platinum-resistant ovarian cancer, I am pleased to say that we are on track to report top line data from our pivotal SORAYA study this quarter. For this release, we expect to include data on the primary endpoint of overall response rate as assessed by investigator, the sensitivity analysis of overall response rate as assessed by blinded independent central review, the key secondary endpoint of duration of response and the safety and tolerability profile of mirvetuximab.

We believe this data will provide a comprehensive picture of the results of the trial. We are planning for success with SORAYA, and to that end, our preparations for the BLA are well underway with the goal of submitting the application before the end of Q1, along with activities in support of the potential launch of mirvetuximab in the second half of next year.

In addition to SORAYA, we are pursuing a broad program to establish mirvetuximab as the new standard-of-care for patients with folate receptor alpha-positive ovarian cancer. Our confirmatory MIRASOL trial continues to enroll, and we expect top line data in the third quarter of next year. If positive, this data could enable full approval of mirvetuximab in the U.S. and importantly support an application for marketing authorization in the EU.

This past quarter we also initiated PICCOLO, a single-arm study of mirvetuximab monotherapy designed to address the increasing unmet need for an effective non-platinum option for FR alpha high recurrent platinum-sensitive ovarian cancer. Beyond mirvetuximab monotherapy, we have generated encouraging data with mirvetuximab in combination with bevacizumab and carboplatin. We believe mirvetuximab has the potential to become the combination agent of choice for ovarian cancer, and we look forward to sharing our label-enabling combination strategy next quarter.

As we continue to expand our team, we are very pleased to welcome Dr. Helen Thackray to our Board of Directors. Her deep development and regulatory expertise will be invaluable, both in the near term as we look to bring mirvetuximab to market and longer term for our full portfolio.

With that, I'll turn the call over to Anna to provide an update on the rest of our development pipeline. Anna?

Thanks, Mark. I'll start with IMGN632, our CD123-targeting ADC in clinical development for hematological malignancies. As a reminder, IMGN632 is being evaluated as a monotherapy for patients with frontline and relapsed refractory BPDCN and in minimal residual disease positive AML, as well as in combination with azacitidine and venetoclax for patients with relapsed/refractory AML.

IMGN632 uses our novel indolinobenzodiazepine dimer, or IGM payload, which is designed to alkylate DNA without crosslinking. Our IGMs are highly potent against leukemic blast, while demonstrating less toxicity to normal marrow progenitors.

We are excited to share initial combination data from the AML cohort at ASH in December. Previously, we reported data that demonstrated the monotherapy activity and favorable tolerability of IMGN632 in heavily-pretreated AML patients, including a 40% overall response rate in relapsed and refractory de novo AML patients treated at the recommended Phase II dose.

The combination data for IMGN632 with azacitidine and venetoclax, we plan to share at ASH, include safety and anti-leukemia activity from dose escalation to guide further development of the triplet. In a separate presentation, we plan to present vignettes of frontline BPDCN patients who received IMGN632 prior to us commencing the currently enrolling pivotal cohort. Abstracts will be released next Thursday, November 4.

IMGC936, our ADAM9-targeting ADC is advancing through Phase I dose escalation in multiple solid tumor types. And IMGN151, our next-generation antifolate receptor alpha ADC, is on track for IND submission by year-end.

With that, I'll turn the call over to Susan to review our financials. Susan?

Thanks Anna, starting with our results for the third quarter of 2021. We generated $9.2 million in revenue, which consisted primarily of non-cash royalty revenues and a $2.5 million anticipated partner development milestone fee. Recall, there was a reduction in non-cash royalty revenues starting in the third quarter and continuing forward due to the completion of the first tranche of payments under the 2015 transaction covering the sale of Kadcyla royalties.

Operating expenses were $43.4 million, comprised of $33.1 million of R&D expenses compared with $24.7 million in the third quarter of 2020 and $10.3 million of G&A expenses compared to $10.2 million in the third quarter of 2020. We ended the third quarter with $245.8 million in cash and cash equivalents on the balance sheet.

Moving to our updated financial guidance for 2021. Revenue guidance is unchanged at $65 million to $75 million. Operating expenses are now expected to be slightly lower at $190 million to $200 million. And cash and cash equivalents have increased, we expect to have between $190 million to $200 million at year-end. With the addition of approximately $43 million through our ATM facility and the sale of a pre-funded warrants to an investor during the quarter, we believe our current cash runway will be sufficient to fund operations into the fourth quarter of 2022.

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

(Operator Instructions) Our first question comes from John Newman with Canaccord.

Just one question on SORAYA, which is after the data readout, is there any need for you to meet with the agency prior to the BLA submission in the first quarter?

Need is an interesting choice of words. What I would say is, any sponsor is very well advised to meet with the Agency ahead of the filing. It's called the pre-BLA meeting. Virtually, all sponsors do that. So yes, we will be talking to the Agency between the top line and the filing.

Our next question comes from Michael Schmidt with Guggenheim.

Just quick 3 for me. The primary endpoint of the study is, obviously, overall response rate per investigator assessment. Can you just talk about how important the independently assessed response rate is in the approval process? And -- so that's question number one.

And then the second question was just on the regulatory hurdle for duration of response. I think you've spoken about 6 months before. Some of your peers in ovarian cancer have spoken about a potential 4 months DOR hurdle. Just wondering what your updated thoughts are on that?

Sure, Michael. So as you know, our primary endpoint is overall response rate by investigator. And in the protocol, we have overall response rate by blinded independent central review as a sensitivity analysis, consisted with prior approvals in ovarian cancer. FDA will have both datasets available to them to inform the overall benefit risk.

Regarding duration of response for this population, there's not a lot of great data out there, but the study that has associated the 12% response rate is AURELIA. And in AURELIA, the control arm of single-agent chemotherapy that had a 12% response rate, that was associated with immediate duration of response of 5.4 months.

That being said, I can certainly understand other folks describing a meaningful duration of response of 4 months, because as you may recall, in AURELIA, these are patients with platinum-resistant disease with just one to 2 prior lines of therapy. It's essentially at best naive population. And we're going after, frankly, a higher unmet need group, including patients with 3 prior lines of therapy, and they have all received bevacizumab.

That being said, you may recall that in our foundational 70 patients worth of data, we had a median duration of response of 7.8 months. And we believe that based on the 5.4 months from the AURELIA study, anything around 6 months or greater would certainly be clinically meaningful.

Our next question comes from Andy Hsieh with William Blair.

Mark, I think you mentioned something after the comments about Avastin and carboplatin combination that labeling - label-enabling combination strategies will be disclosed next quarter. Can you give us a little more color on that comment?

Sure. So as you know, we have pursued a number of early-stage studies looking at various mirvetuximab combinations and been very pleased with both the activity and the tolerability of those combinations. So what we've typically seen is response rates and measures of progression-free survival and duration of response that exceed the relevant benchmarks for the combination partner. So for example, if you look at our early data with carbo and mirv, what we saw was response rate of 70% to 80%. 80% in the FR alpha high patients and progression-free survival of about 15 months. And that contrasted nicely with other carbo doublets that have been reported, where you see response rates in the mid-50s and progression-free survival in the range of 8.5 months to 10.5 months.

So with the benefit of those data, along with what we've seen with mirv-bev, we are working through, as we speak, a comprehensive strategy that will include studies that will support formal label expansion with respect to these combinations. Some of that requires conversations with the agencies, with our investigators and so on, and we are taking the fourth quarter to work through those points with them and look forward to talking to you in the first quarter about where we come out and the studies that we're initiating.

And then I guess, looking back at ESMO, I think HER2 is one of the conference winners in terms of compelling datasets. I'm just curious about your take on the optimizations done there and kind of any read-through to IMGN151, the next-generation asset.

So Andy, if you could clarify what you're thinking -- so you're talking about in HER2. Daiichi's HER2 ADC with a camptothecin and you're thinking about how that's built upon the success of Kadcyla, and you're asking an analog for how might IMGN151 build on the success of mirvetuximab, is that what you're driving at?

Yes. That and also, I guess, for -- and HER2 is basically 2 sites of optimization, right? So basically, the linker and the payload. And I believe 151, all different components were optimized. So just curious about kind of that lead through the clinical benefit derived from 2 optimization versus theoretically 3 for 151?

Yes, sure. So we're always innovating. And so the innovations that we've built into 151 includes the antibody is a biparatopic, so it binds 2 separate epitopes on folate receptor alpha, which we've shown leads to more internalization events and more cell killing. And that translates into being able to target tumors with broader expression of FR alpha, so that we see activity -- very nice activity for IMGN151 in low and medium levels of FR alpha expression in vitro and in vivo. And so IMGN151 is really designed to address a broad range of FR alpha positive tumors, including essentially almost all of ovarian cancer as well as then moving into endometrial cancer, triple-negative breast and lung cancer.

And you're right, the linker-payload has also been innovated on in terms of having a more stable linker-payload that's even more stable in circulation than mirvetuximab. The payload itself is a bit more hydrophobic, a bit more potent and has a bit more bystander killing. So we're really excited to be on track to file the IND before the end of year for 151 and get that into the clinic early next year.

Our next question comes from Kennen MacKay with RBC Capital Markets.

Looking forward to the SORAYA data. Maybe with the SORAYA data, really looming ahead here, just wanted to get your current perspective on sort of the bar for accelerated approval again as it relates to our overall response rates as well as the confidence intervals associated with the overall response rate. Whether that overall response rate itself is more important or nonoverlapping confidence intervals there with standard of care.

And then secondarily, I just wanted to -- housekeeping question here, just wanted to see if the folate receptor alpha diagnostic would be ready to be filed alongside mirv if SORAYA is successful in Q1 there.

Sure, Kennen. So the guidance that we got from FDA is that we need to exclude 12%. So what that means is the lower bound of the 95% confidence in durable needs to be above 12% to be considered statistically positive study. And certainly, the larger the sample size, the narrower the confidence interval. And so as a reminder, we had 70 patients where we demonstrated a confirmed overall response rate of 31.4%. The lower bound of that confidence interval was 20.9%. And the SORAYA study is actually a bit bigger, right? It was designed to be about a 100, 105 patients. So again, the confidence interval will be appropriate for that sized study. So again, that interprets statistical significance. In terms of what's clinically meaningful to physicians and patients would be a doubling of response rate from what you get expected with standard of care single agent chemotherapy, which, again, is 12%.

Turning to your second question regarding the companion diagnostic. We've been working with Ventana since the inception of the mirvetuximab program, and we anticipate that the CDx will be available contemporaneously with the drug. We've already -- the Ventana has already filed some of the components of the PMA, so we're on track there.

And next question comes from Kelly Shi with Jefferies.

So for the SORAYA trial, the product allows tubulin inhibitor treatments. I wonder like you could estimate what percentage of that patients that actually had an inhibitor treatment? And also a follow-up question is, given the difference of prior treatment on Avastin and Erbitux, SORAYA compared to FORWARD I, what do you think the impact of both this agents in the background on mirv treatment efficacy.

So over the past several years, PARPs have been adopted and incorporated into the treatment of ovarian cancer. In the FORWARD I study, which was performed at the time that the initial approvals in the treatment setting were being done and the maintenance trials were ongoing, about 10% of patients had, had a prior PARP inhibitor.

With each subsequent cohort that we have enrolled since then with all of our combination studies, the percent of patients who have had a prior PARP inhibitor has increased to about 35% to 40% over time with the most recent publicly reported cohort. And what we've seen is a consistent and continued efficacy of mirvetuximab regardless of prior PARP use or not.

And you may recall that the mechanism of action for PARP inhibitors, they interfere with the tumor cell's ability to repair DNA damage. And our drug is a tubulin directed inhibitor, so there's no reason on [priority] to anticipate cross resistance between these mechanisms.

(Operator Instructions) Our next question comes from Jessica Fye with JPMorgan.

This is Daniel for Jessica Fye. For SORAYA, and the reason that you rule out the 12% overall response rate with chemo and the analysis using the blinded independent central review, but it comes in below the doubling of chemo you've just suggested will be clinically meaningful. Maybe can you talk about what that scenario would mean for approval and for the commercial opportunity for mirvetuximab?

So again, we believe that the doubling of response rate would be considered clinically meaningful. And that 12% benchmark is based on investigator assessment from AURELIA. So we will have both data sets. FDA will review both data sets. And it's really about the overall benefit risk. So one is the benefit. So what is the response rate and what's the duration of those responses compared to available therapy.

And also, turning to risk, you may recall from the FORWARD I study, mirvetuximab has a very nice tolerability profile with fewer dose reductions due to drug-related adverse events and fewer discontinuations. So again, FDA will have both data sets to assess the overall benefit risk. But from a study perspective, it's about ruling out a 12% overall response rate for the primary endpoint.

As it relates to the commercial opportunity. As Anna has said, something clinically meaningful here would be to double the response rate versus standard of care and have somewhat longer duration of response than what we see reported. And then I think when you look at the real world evidence in these patients, 12% actually is an optimistic response rate as we think about additional studies that have been done here.

So we think with this profile that mirvetuximab will displace single agent chemotherapy, and as you think about the market opportunity here. When we look at second through fourth line platinum-resistant disease here in the U.S., each year, there are roughly 22,000 patients who are available for treatment. And -- but just under 50% of those patients get single-agent chemotherapy. So that will be our target indication, of course, with the cut for patients who express folate receptor alpha at high levels, which is about 40% of the patient population. So we think that between SORAYA and MIRASOL, we're looking at about 4,200 patients per year.

And then maybe a quick follow-up. I know it might be a little bit early, but in terms of the overall response rate that will be shown in the label, is it -- will it be based on investigator or -- assessment or will it be based on the [beaker] assessment?

So investigator assessment is the primary endpoint for our study. If you look at labels for other drugs that are approved in ovarian cancer, some of them have investigator assessment, some of them have independent assessment and some labels have both. So we look forward to discussing with the FDA during label negotiations.

Next question comes from Jonathan Chang with SVB Leerink.

First question, can you discuss your views regarding mirvetuximab into earlier line ovarian treatment settings? Specifically, what are your thoughts on the maintenance setting?

Yes. So maintenance has certainly become a part of ovarian cancer treatment, and it's really changed the paradigm for patients now as PARP inhibitors are being adopted, as well as with bevacizumab, that has been around a little bit longer both in the recurrent platinum-sensitive setting and the frontline setting. And then most recently with the PAOLA study, where the combination of olaparib plus bevacizumab is really quite helpful for patients, particularly the HRD patients.

So we're really excited about the potential for mirvetuximab as a maintenance option, knowing the safety profile of mirvetuximab monotherapy. We have had some patients on for well over a year, 2 years, even 3. And also, the combination for mirvetuximab plus bevacizumab. You may recall our really nice data in over 120 patients now with very nice progression-free survival, duration of response data and having patients on for many, many cycles.

So we believe that mirvetuximab absolutely has potential to be incorporated into the maintenance treatment paradigm. And as you heard from Mark, we look forward to sharing our label expansion strategies for combinations next quarter.

Yes. Maybe just to add one point there is -- I mean, there's 2 elements to this. The first is continuation of therapy. So for example, when we think about carboplatin, the first patients we enrolled got their normal 6 to 8 cycles on carbo, and then they simply continued on mirvetuximab therapy. And as we said, we reported out small numbers, but progression-free survival of about 15 months.

Separately, you could imagine combining mirvetuximab with Avastin in a maintenance protocol. So having received something else as an induction therapy to generate a response and then adding mirvetuximab to that. So we're working through those points as we speak and will be part of the discussion that we have next quarter.

And second question, can you provide any color on how the IMGC936 dose escalation has progressed, and should we expect data in the early part of next year?

Yes. So IMGC936 is our ADAM9-targeting ADC, and it has our next-generation maytansinoid payload DM21. ADAM9 is widely expressed across a variety of solid tumors. And so we're doing a dose escalation study, 3 plus 3 in those tumors that we know express ADAM9, including triple-negative breast cancer, colorectal, lung cancer, pancreatic and gastroesophageal. So I would say that, that Phase I dose escalation is going as anticipated and we look forward to sharing data in 2022. I don't think I can give more timing at the moment, but we'll update it certainly as we get closer.

And next question comes from RK Ramakanth with H.C. Wainwright.

And so let me add my question on mirvetuximab as well. In terms of MIRASOL enrollment, can you give us any color as to where it is at this point?

So MIRASOL is enrolling and we're on track to have data Q3 next year.

And then on 632, what sort of data expectations should we have for the combination in terms of -- like what sort of efficacy endpoints or safety that you would be putting out?

Thank you for asking, RK. We're quite excited about ASH, IMGN632 is our CD123 targeted ADC that we are in combination with azacitidine and venetoclax and we're looking forward to our presentation where we will share initial safety and antileukemia activity for the triplets. So stay tuned. I the ASH has been announced November 4, yes.

Yes, yes. I'm aware of that. And then on CADENZA, again, Mark, I know you have it in your slides as to when the data is expected. But how should we think about that data on top of what we're going to see at ASH, how are you planning to build that up so that we can try to understand how this drug is working not only as a monotherapy but also as a combination therapy.

So IMGN632 is being studied in BPDCN, both relapsed/refractory BPDCN and in an enrolling pivotal frontline BPDCN cohort after we've received Breakthrough Therapy designation from FDA in the relapsed/refractory setting. We're also exploring 632 as monotherapy in an MRD-positive cohort. That cohort is open to any AML patient who is MRD-positive after their prior therapy. So it could be after frontline induction or it could be later line.

And so we look forward to sharing data at ASH for BPDCN for, I would say, a handful of patients who are frontline. We've talked about them in the past. There are 3 frontline patients who received IMGN632 prior to us commencing the official pivotal cohort in the frontline setting. And we've shared in the past that each of those patients has had a CRC, and we look forward to sharing additional details around those 3 patients.

Our next question comes from Joe Catanzaro with Piper Sandler.

Maybe one quick one for me, just following up on MIRASOL. Just wondering how we should think about how the SORAYA response rate and DOR translates to MIRASOL? And maybe just sort of directionally where you think it would head in MIRASOL based on the SORAYA data. Thanks.

So SORAYA and MIRASOL are quite similar patient populations, Joe. The difference is that in MIRASOL, patients may or may not have had prior bevacizumab. Whereas in SORAYA, every patient has had prior bevacizumab. However, it's the same number of lines of therapy, one to 3 prior lines of therapy.

And you may recall in the FORWARD I study about half of the patients had prior bevacizumab. We anticipate a similar percent of patients in MIRASOL having prior bevacizumab. But remember, in MIRASOL, the primary endpoint is progression-free survival. Of course, we will be looking at overall response rate in the MIRASOL study as well. So I think that gives you a sense of the patient populations. And I think you will be able to think about how MIRASOL may play out, taking into consideration both the SORAYA data that we will share this quarter as well as the prior FORWARD I data set.

Our next question comes from Boris Peaker with Cowen.

But for the AML data update later at ASH, what do you consider successful data and considering the competitive dynamics in the AML space?

Yes. So CR/CRi rates are really important in AML -- in relapsed/refractory AML. And for a combination, we think CR/CRi rate, something in the rate of 30% to 40% would be quite clinically meaningful and would support further development.

And so my last question is for 632, if the data achieves that threshold, what is the time line for future development? And would you have to do a randomized study? And if so how long would something like that take?

Well, given the high unmet need in relapsed/refractory AML, many combinations and single agents are used and none of them are really outstanding. There is a potential for a single-arm study to support accelerated approval. And ultimately, there's also a potential for a frontline randomized study.

But I think it's a little early for us to really start getting into timing of what the pivotal registration trial or trials would be for the combination. We really are looking forward, however, to sharing the initial combination data for the triplet at ASH.

There are no further questions at this time. I'd like to turn the call back over to the team for any closing remarks.

Great. Thanks very much. I very much appreciate you joining us this morning. Obviously, we have a big quarter yet ahead of us. So like you, we await the SORAYA data with great anticipation and we're on track to deliver that data this quarter. And then separately, with 632 important data and ASH. And then finally, 151, we expect to file the IND for that program before the end of the year.

So stay tuned, and we will look forward to sharing this data with you over the course of the quarter. Thanks.

This does conclude the conference. You may now disconnect. Everyone, have a great day.