ImmunoGen Inc (IMGN) 2016 Q2 法說會逐字稿

Good day and welcome, everyone, to the ImmunoGen second-quarter fiscal year 2016 fiscal results conference call. Today's call is being recorded. At this time, for opening remarks and introductions, I would like to turn the call over to Executive Director Investor Relations and Corporate Communications, Carol Hausner. Please go ahead.

Thank you and good morning. At 6:30 this morning, we issued a press release that summarizes our financial results for the quarter ended December 30, 2015, which is the second quarter of our 2016 fiscal year. I hope you've all had a chance to review it. If not, it's available on our website.

During today's call, we will make forward-looking statements. 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, which also can be accessed through our website.

In our call today, our Chief Executive Officer Dan Junius will provide an update on ImmunoGen; our Chief Development Officer, Dr. Charlie Morris, will discuss our wholly-owned compounds in greater depth; and our Chief Financial Officer, Dave Johnston, will discuss our financial results and guidance. We'll then open the call to questions. Dan?

Thank you, Carol, and good morning everybody. ImmunoGen is off to a strong start for 2016 with multiple clinical trial initiations underway as well as significant partner activity.

Of particular importance is our FORWARD I trial assessing mirvetuximab soravtansine as single agent therapy for pretreated, Folate Receptor Alpha positive ovarian cancer, which we believe is the fastest path to registration. This study is open for patient enrollment, and we are working to initiate sites in the US and have also made our first submissions to European authorities.

We are pleased to be conducting FORWARD I in partnership with the GOG Foundation. Members of the GOG, which is the Gynecologic Oncology Group, across the US specialize in the treatment of gynecologic cancers such as ovarian cancer and are expected to play an important role in patient enrollment. As a result, we anticipate we'll have the majority of our US centers opened for patient enrollment by June.

Patient dosing is underway and our FORWARD II trial, which assesses mirvetuximab soravtansine for ovarian cancer used in combination with different agents -- bevacizumab, Doxil, carboplatin -- with more cohorts expected.

As you know, we have a two-pronged development strategy for mirvetuximab soravtansine -- advance it to registration as quickly as possible through the FORWARD I study, and expand its potential to help patients through evaluation in additional settings. FORWARD II begins the assessment of mirvetuximab soravtansine in ovarian cancer patients who have received fewer prior therapies, including patients with platinum sensitive disease.

In the fourth quarter of 2015, we completed patient enrollment in two more Phase I expansion cohorts, the 20-patient ovarian cancer cohort requiring current biopsies and the 20-patient cohort assessing mirvetuximab for the treatment of endometrial cancer. To date, over 170 patients have been treated with this first-in-class ADC, including nearly 130 patients with ovarian cancer.

Patient enrollment is also expected to start early this year in our Phase II trial assessing our IMGN529 product candidate in combination with rituximab for diffuse large B-cell lymphoma and later in the year in our Phase II trial assessing our coltuximab ravtansine in a different combination for this cancer.

Finally, we are on track to start Phase I testing of our IMGN779 product candidate for acute myeloid leukemia in the next couple of months. As you recall, this ADC utilizes one of our IGNs, a new class of DNA acting payload agents which, unlike other approaches, alkylates DNA without cross-linking it.

We're excited about the potential for this technology and we're finding considerable interest in our IGNs from third parties due to the more favorable therapeutic window seen in preclinical assessments.

Before Charlie takes you through our programs in more detail, I'll briefly touch on some of the progress being made by our partners. On Tuesday, we announced that Bayer has initiated a global Phase II clinical trial in mesothelioma designed to support registration of their mesothelin targeting ADC anetumab ravtansine. This event triggers a $10 million milestone payment to ImmunoGen, which will be reflected in our third-quarter financial results.

As you'll recall, highly encouraging Phase I data with anetumab in mesothelioma were presented at the World Conference on Lung Cancer last September.

We're excited about the potential of Bayer's product candidate to make a meaningful difference for patients with mesothelioma. Anetumab ravtansine is the third ADC with our technology, along with our own mirvetuximab soravtansine and Roche's Kadcyla, to show encouraging results in a difficult to treat solid tumor indication and advance the potential registration testing.

On the topic of Kadcyla, Roche expects data from their neoadjuvant trial KRISTINE to be reported this year and, if positive, will bring the findings to regulatory authorities for potential filing in 2016. As you recall, KRISTINE is one of several Roche trials assessing Kadcyla in an earlier breast cancer setting and compares a Perjeta Kadcyla regimen to a Perjeta Herceptin regimen. Roche also has a Phase II trial underway with Kadcyla in HER2 positive lung cancer.

Roche continues to extend their Kadcyla program and are initiating a breast cancer trial that includes evaluating Kadcyla in combination with their PD-L1 inhibitor atezolizumab. Recently published preclinical data suggests use of Kadcyla with checkpoint inhibition could potentially provide not only immediate anticancer effects but also longer-term ones as well. Related research conducted by ImmunoGen and academics indicate that use of maytansinoid cancer killing agents could play a central role in these findings due to the impact of the maytansinoid on the dendritic cells of the immune system that stimulate antitumor responses. Early days of course, but exciting stuff.

I'm also pleased to note that, in December, Takeda took their first license to use our technology to develop ADCs to an undisclosed target. Our partnership with Takeda was established less than a year ago, and we're impressed with the pace at which this program is progressing.

Let me now ask Charlie to discuss our programs in more detail.

Thanks, Dan, and good morning everyone. I'll start with our lead program, mirvetuximab soravtansine, a potential new treatment for ovarian cancer, endometrial cancer, and other Folate Receptor Alpha positive solid tumors.

Shortly after our last quarterly call, we reported updated findings at the AACR-NCI-EORTC, or triple meeting, on the initial 20 valuable patients with Folate Receptor Alpha positive, platinum-resistant ovarian cancer who have been enrolled in our first Phase I expansion cohort in this disease.

Data reported at the triple meeting included that seven of these 20 patients, or 35%, had a confirmed objective response on treatment with mirvetuximab soravtansine and that six of these seven patients were on treatment six months or longer. As you recall, our target for advancing mirvetuximab as monotherapy with a response rate of 30% with meaningful durability.

Additionally, there was evidence of a relationship between the amount of Folate Receptor Alpha present on patient tumor cells and response to treatment with all of the objective responses occurring among the patients with high or medium levels of mirvetuximab's target on their tumor cells, which were the majority of patients.

As you know, we upsized this first ovarian cancer Phase I cohort from 20 to 40 patients and are now gaining safety, efficacy, and durability information for the 40 plus patients enrolled. We are preparing an abstract with initial data for submission to ASCO and, when the data mature, we intend to discuss them with regulators.

Last quarter, we completed enrollment in a Phase I ovarian cancer cohort designed to further enhance our understanding of biomarkers. One of the questions it will help answer is whether expression Folate Receptor Alpha on patient tumor cells changes over time, which could help our understanding of the ability of archival specimens to predict Folate Receptor Alpha expression when starting mirvetuximab soravtansine treatment. We are in the process of analyzing the biomarker data and will also be submitting an abstract with initial findings to ASCO.

As Dan noted, FORWARD I is open for enrollment and we have begun patient dosing in FORWARD II. We're working towards having over 50 clinical sites in the US and Western Europe enrolling patients into FORWARD I. Conducting this trial in partnership with the GOG Foundation leverages their knowledge, experience and clinical site network, facilitating the trial's timely execution.

Last quarter, we also completed enrollment in the Phase I cohort assessing mirvetuximab in the treatment of relapsed refractory Folate Receptor Alpha positive endometrial cancer. The findings aren't sufficiently mature for submission to ASCO by next Tuesday's deadline, which should be ready for presentation at a later medical conference.

While I spent most of my time on mirvetuximab, I should note that we're also making meaningful progress with our other pipeline programs. In December, we reported new preclinical data at the ASH meeting on the pronounced activity seen with our IMGN529 product candidate when used in combination with rituximab in models in non-Hodgkin lymphoma, and patients dosing is expected to begin in early 2016 in our Phase II clinical trial of this combination regimen.

We also reported new data at ASH for our CD33 targeting ADC, IMGN779, which is on track to be in Phase I testing for acute myeloid leukemia in the next couple of months. As you know, IMGN779 is the first ADC utilizing one of our new class of DNA alkylating payload agents called IGNs, which, in preclinical testing have shown marked tolerability advantages over DNA cross sectors.

Later in the year, we plan to initiate the Phase II trial assessing our coltuximab ravtansine therapy for B-cell malignancies in a combination regimen. We are projecting this study will start in the second half of 2016.

In all, we're making solid progress advancing our strong pipeline. On that note, I'll turn the call over to Dave to discuss our financials.

Thanks, Charlie. As Carol noted, we issued a press release this morning with our second-quarter fiscal year 2016 financial results. I will review the highlights and then our guidance for the fiscal year.

Revenues in the second quarter of our fiscal year 2016 were $18 million as compared to $48.3 million in the same quarter of last year. Recall that our revenues are largely made up of amortization of upfront fees and cash milestones and therefore tend to be a bit lumpy.

For example, the current period includes $8.6 million from the amortization of the upfront fee previously received from Takeda do to their taking of license in the period, while the prior-year includes $41.4 million in amortization of upfront fees from Novartis and Lilly due to their license activity in that period. The current period also includes $2 million of cash milestones earned from Sanofi in their advancement of SAR428926 into the clinic testing.

Our revenue in the current period includes $6.3 million of non-cash revenue royalty on the sales of Kadcyla for the three months ending September 30, 2015. As a reminder, the royalty is passed to the purchaser of the royalty stream and we report non-cash Kadcyla growth to revenue that is partially offset by a non-cash interest expense, resulting in non-cash net income.

Operating expenses for our second quarter of fiscal year 2016 were $46.3 million compared to $34.5 million in the second quarter of last year. These consisted of $38.2 million in R&D revenue expenses in the second quarter this fiscal year compared to $27.6 million in the same period last year.

$8.1 million in G&A expense this year compared to $6.9 million in the same quarter of last year. Driving the change from prior fiscal year are increased third-party expenses of our third-party costs related to the advancement of our product candidates, primarily mirvetuximab soravtansine, and higher personnel related expenses principally due to recent hiring.

For the quarter, we reported a net loss of $33.2 million, or $0.38 per share, compared to a net income of $13.6 million, or $0.16 per share, for the same quarter of last year, again, tied to non-cash revenue recognition in this period last year.

Our cash used in operations was $63.0 million in the first six months of this fiscal year compared with $34.4 million in the same period of last year. And our capital expenditures were $7.6 million in the first six months of FY 2016 compared with $2.6 million in the same period last year.

Lastly, we ended the quarter with $212.3 million of cash and cash equivalents compared with $278.1 million at June 30, 2015 and we continue to have no debt.

Our fiscal year 2016 guidance remains unchanged from what we issued previously. Revenues are expected to be between $70 million and $80 million, operating expenses between $175 million and $180 million, net loss between $120 million and $125 million, cash used in operations between $100 million and $105 million, and capital expenditures to total between $13 million and $15 million. And we expect to end our fiscal year with between $165 million and $170 million in cash. Our cash position is strong, allowing us to aggressively invest in advancing our portfolio of product candidates led by mirvetuximab soravtansine.

So, with that, I'll turn the call back over to Dan.

Thank you, Dave. I think you can tell by the comments here that there's a lot going on and we look forward to continued strong progress and a steady news flow. Let me walk through some of that.

Our anticipated events for mirvetuximab soravtansine include meeting with regulators in the first half of 2016 on the development program, including the design of the second stage of FORWARD I. It also includes presentation of mature data from the 40-patient ovarian cancer cohort at ASCO as well as presentation of the initial biomarker finding at ASCO. We'll also have a presentation of data from the endometrial cohort at a later medical conference and continued progress with the FORWARD I and FORWARD II studies with an objective of completing patient enrollment in Stage 1 of the FORWARD I study by year-end.

We also expect to begin patient dosing in our Phase II trial assessing IMGN529 in combination with rituximab early this year. We also expect to begin patient dosing with our novel IMGN779 agent for acute myeloid leukemia in the next couple of months and to disclose our coltuximab ravtansine combination plans and begin that Phase II trial later this year.

We're very happy with the progress being made by Bayer with anetumab ravtansine and we anticipate that another of our partners will advance a program into registration enabling testing in 2016.

Roche expects data from their KRISTINE trial with Kadcyla in the neoadjuvant setting to be reported this year and, if positive, to bring these regulatory -- to bring these to regulatory authorities for potential filing in 2016. We also expect development events in earlier stage partner programs, including advancement of an additional ADC to the clinic in 2016.

We're seeing a high level of interest in our ADC technology and are having discussions with a number of parties. Predicting outcomes and timing, however, is always challenging. So we're executing on our product plans and look forward to providing you updates as these programs progress.

With that, let me turn it back to Carol so we can take questions.

Great, thanks, Dan. We are about to open the call to questions. We ask that these be limited to one to two per person until each analyst has had an opportunity to ask a question. We'll now open the line to questions.

(Operator Instructions). Jessica Fye, JPMorgan.

A couple. First, as we think about the full ovarian cohort coming at ASCO and kind of the incremental 20 or so patients worth of data that we're going to get, are you expecting the breakdown between high, medium and low expression to be the same, i.e. should we expect sort of another 10-ish high expressing patients that the stars seem to be showing the best response rate?

And then second, just heading into this meeting with the FDA, can you remind us what you think of as the most important points that you want to clarify with the agency about the design of the FORWARD program going forward? Thank you.

Thanks Jessica. So, on the first one, I don't actually know the split offhand of how things worked out, but, yes, I would anticipate that, based on the screening information that we know and the split of the patients that went into the first half, that you should expect approximately the same proportion of patients in the high, medium, low groups in what's going to come through in the ASCO abstract.

In terms of the FDA, I think a key point is going to be can response rates support an approval? Does the supposed design enable us to show an adequate improvement in the response rate that the FDA would be sufficiently impressed to see that as the basis of an approval?

I also talked about if that was to lead to an accelerated approval, what would the plan for a confirmatory study look like or even, in a best case scenario, whether we could upsize FORWARD I a little to use it for both accelerated and confirmatory purposes with more mature data.

Got it. And maybe just a follow-up to that. From a timing standpoint, is there any reason to think that you can't have this meeting before, with the FDA before we actually go ASCO? I.e. when we see this update at ASCO, will you have met with the FDA and have a little more kind of information for us? Or should we think about that FDA feedback maybe coming sometime after we get the ASCO data?

I don't think we're going to come out and go. We are going to the FDA next week or we were down at the FDA last week. I think what you should anticipate is that if we make adjustments to the structure of the protocol or any of the key features that we've previously described, you will know about it.

Now, ASCO is probably the earliest we will be in a position to let you know that, but I think it's too soon to make promises on that.

Got it. Thank you.

Chris Marai, Oppenheimer.

This is actually Michelle on for Chris. Congratulations on the quarter. You guys have an exciting year ahead. And I just have a few quick ones. I was wondering --

Michelle, you're very quiet.

Oh, I'm sorry. This is Michelle. I was just wondering if or when we might see any data from FORWARD I since it's open label? And then we also were just wondering maybe what you're seeing pre-clinically with the PD-1 and mirvetuximab, and then maybe when you plan to initiate studies with that combo?

So to take the FORWARD I question first, as we said on the call, or I hope we have said previously, we certainly anticipate that we would recruit Stage 1 fairly rapidly and have those patients accrued this year. So, our provisional intent would be to try to have some data in time for ASCO 2017.

As you rightly say, that will be open label and it's, if you like, it's staged and it's physically set up separately from Stage 2. So there's no impact on the integrity of the overall study presenting stage I as an intermediate point. So I think we should be hoping for ASCO 2017 but obviously we'll update you as we get more. I certainly wouldn't expect it sooner than that, but I think that's a reasonable target.

Michelle on the second question regarding preclinical data, I think you specifically asked about a Checkpoint inhibitor plus mirvetuximab. That's an area that we are very interested in. We have discussed some preclinical work that we've done in the B-cell area. And you heard me reference the study that Roche announced that would include looking at Kadcyla in combination with their PD-L1. We haven't disclosed any preclinical work there.

I think the larger point is that given the preclinical work that's been done looking at maytansine as a class in combination with checkpoint inhibitors carries potential across both our and our partner product lines. It's something that we want to assess. I think there's the opportunity to assess that clinically without doing extensive preclinical work once safety has been proven with a maytansine-based ADC. So I think that, as you are seeing with others, there's the opportunity to move directly into the clinic to look at some of those without necessarily even having a lot of preclinical work done. So, it's something that we are quite interested in, both for our own pipeline as well as our partner pipelines.

Great, thanks guys. Oh, one more. Are you guys going to provide any enrollment updates for your FORWARD I and FORWARD II trials?

I think we did a little bit to say that we are -- that FORWARD I is open for enrollment and we are enrolling patients in FORWARD II. I don't know that we'll be providing quantitative updates as much as directional updates. We were quite encouraged at how enrollment proceeded, certainly post ASCO, with some of the additional cohorts that we had biopsied for example, also completing the endometrial cohort, the additional 20 patients that we brought into the expansion cohort.

So, the pace of enrollment, as additional cohorts have been available, has been encouraging. But again, I think it's -- and getting down to specific numbers gets a little bit too detailed, but we'll certainly try to give you some directional information.

Okay, great. Thanks guys.

Matthew Harrison, Morgan Stanley.

I just wanted to go back to the upcoming FDA meeting. Can you just help us think about -- and you talked about this a little bit already -- but help us think about what the potential outcomes of that meeting are and how they may be reflected?

So, for example, it sounded like what you said earlier was, if you upsize the trial, you would view that positively because potentially that means that you could use that as a registration study in addition to an accelerated study. So maybe if you could just lay out a couple of the what you see as the potential outcomes from that meeting and how we might interpret that. Thanks.

I think, when we have the meeting, if we make changes to the program, I think we, as we tend to be, be open about what the considerations there are. There's the good case scenario that I already described. If they like the design, they would accept response as an endpoint, as they have already in this disease. Obviously, they may say they're not going to accept it would be the flipside, but I think the outcome ultimately becomes the same, which is you upsize the study for progression free survival rather than for overall response rate.

So, and then of course the other one would be that, yes, they see the support, but it may be that, based on other thoughts, we would prefer to use something else as a confirmatory study. You know, getting into a combination study in an earlier setting of the disease may actually turn out to be strategically a more appropriate way to go and a better use of funds rather than doing more in the exact same indication.

So, but generally, we are obviously optimistic because we're very encouraged by our data. We don't see any downside to going and laying these plans out in a very open way with the agency, getting their feedback and hoping to have that feedback to share at least the consequences of any feedback with you in good time.

Simos Simeonidis, RBC Capital Markets.

Sorry, one more question on the FDA. Can you tell us what is the rate limiting step, so to speak, in terms of scheduling the meeting? Are you waiting to get the expansion cohort data, or would you have to have data from the first days of FORWARD I?

I'll go to the second part of the question first, which is absolutely not. We will not be waiting for the first data in FORWARD I because that would then put the FDA consultation on the critical path for the beginning of Stage 2.

So it's really about great maturity of the data that we have from the existing data, the expansion cohort from the Phase I, and you know, being sure that we have enough information to say that the assumptions that we have made within the statistical assumptions of the protocol are supported by the data that we have. And really being able to lay out the best possible story so that it makes sense when the FDA reviews it. So, it's really about having the right level of maturity of those data and then -- of the ongoing data remembering, that in the background, we are also treating patients for example in the cohort of patients who have had biopsies. Now, they are allowed to be more heavily pretreated than the patients who will be going into FORWARD I, but nonetheless it's another collection of safety data. And although those data are relatively immature at this point, another source of response information so that we can confirm that we continue to see what we've been seeing.

So, I think all of that together is why we've been pointing toward this meeting being in the first half of this calendar year, is because we believe that is the appropriate timing. And clearly that would not require anything out of FORWARD I to get there.

Okay. And the second question is in terms of the ocular AEs that you witnessed so far, is there a plan to use eye drops of any or anything else prophylactically in FORWARD I in the first stage, or are you going to just treat patients if that arises as they come?

At the moment, we have a number of eye exams that we do before we start treatment. We encourage the use of lubricating eye drops. At this point in the Stage 1 of FORWARD I, there is not a prophylactic use of corticosteroid eye drops. You may remember we are exploring that in an additional cohort of patients in the Phase I so that -- and that is -- we're actively accruing patients into that particular cohort now.

Now, again, that's more information that can feed into Stage 2 of the study so that, by the time we get to Stage 2 and enrolling on stage 2, we'll have more information about the right cook point for Folate Receptor Alpha expression, we'll have more information about the best way to manage the ocular events, and we'll have the FDA input. So I think, by the time we're at that point, we've got everything that we need to execute very successfully.

Yes, I'd add to that will also have the information out of the biopsy cohort to the extent that sheds any light on any manifestation of the target from the archival tissue to the time when we are treating the patient. So, they'll be a lot of information to incorporate to let us do the best job we can of making sure the right patients are receiving treatment.

Great. Thank you.

Mara Goldstein, Cantor Fitzgerald.

Two things. Can you just remind us on the I believe it's the Ventana relationship on the development of the IAT assay to support the selection of the ovarian patients based on Folate Receptor Alpha expression. Where does that stand from the perspective of having it validated as a commercial tool?

And just secondarily, I'm curious about the GOG involvement in FORWARD I and how that might have affected the protocol, if at all, and how it also affects enrollment of patients and specifically if you can possibly quantify what you think might be the advantage from a time to enrollment and whether or not GOG will be involved in FORWARD II?

From the Ventana perspective, yes, Ventana is using one of our antibodies in the development of an IHC-based companion diagnostic. We are taking through all of the appropriate stages. We'll be having the appropriate consulted CDR rates at the FDA. And we are using that in FORWARD I and that also -- and FORWARD I Stage 1/Stage 2 will be set to be the validation that would enable it to be approved as a companion diagnostic. So this, it's using, as I said, one of our antibodies we've licensed to Ventana and that is a successful relationship and we're pleased with how that's being executed. Commercial elements and all of that will kick in at a later point, but as of right now, that's progressing very nicely.

In terms of the GOG Foundation, we've worked closely since the beginning of this week with some of the senior investigators at the GOG. I think working with them is a sign that they're very interested in the program. Obviously, it gives us access to a large number of sites in the United States of investigators who are very much committed to gynecologic oncology, including of course ovarian cancer. And it also means that, when you're working at those sites, they -- the expectation is that those sites, if they have competing trials, to remain sort of enrolled, if you like, with the GOG, you have to put patients on the GOG or GOG Foundation studies first. So that's really the advantage. It gives us lots of sites. It gives us lots of ability and we think lots of pace and with a lot of support.

In terms of -- but that's only for FORWARD I.

FORWARD II, you know, we believe that we can do that without getting that specifically into GOG Foundation. We will be working with perhaps not the same centers, but not under the umbrella of the GOG Foundation.

Boris Peaker, Cowen and Company.

I just wanted to confirm in terms of data. At the triple meeting recently, we had 10 responses and out of 20 patients a 50% response rate and three of those were unconfirmed. And it looks, based on today's data update, that the unconfirmed were not confirmed in the future scan.

And as kind of a follow-up to that, for the 40 patients at ASCO, will we have enough time to confirm every scan, or do you expect some of their patients to still be unconfirmed at that meeting?

I think those -- from that first 20, those that you rightly point to, three unconfirmed essentially cannot be confirmed. Two progressed before they were able to have a confirmatory scan or had progressed at the next scans. And another one dropped out of the study before she had her confirmatory scan.

By the time we get to ASCO, I think any response that you see, unless the responses have occurred very, very late, should be -- have had time to have been confirmed. Not at the time of the abstract they won't all have had time to be confirmed, but by the time we get to ASCO, I will be surprised if we are waiting for confirmatory scans on any of the new information that we provide at that time.

Great. And so just on the abstract, since you're going to be submitting it pretty soon, can you give us a sense of how many actually patients worth of data there's going to be in the abstract itself?

About 40 plus.

Okay. The abstract is going to include 40 plus. Got you.

Yes.

Okay. Well, thank you very much for taking my questions.

Andrew Peters, UBS.

First, just regarding the 779, in terms of the IGN payload, can you just compare/contrast versus some of the other CD33 targeting programs out there, notably the PVD program with Seattle? What are the advantages of the IGN approach? And related, what can you learn from the data sets at ASH as it helps inform kind of your Phase I trials?

And then just a follow-up on the last question. As it relates to Stage 2 of FORWARD I, how do you think about kind of powering assumptions on response? If the response rate indeed is closer to the 35% confirm that we've seen right now, would you be able to show a statistical difference if the physician's choice at ASH stays at the higher end of historic controls? Thanks.

Thanks, Andrew. If you don't mind, I'll take the second question first as it relates to everything else that we've been discussing. So as you know, we have always thought in terms of patients having a roughly 15% to 20% response rate with current standard chemotherapy agents. We've also always believed that we need to be somewhere around 35% or higher based on the approval of olaparib to get there. So, I think that gives a sense of what we're looking for.

I'll remind you though that between -- the 35% relates to the overall population included in the study. We are no longer including the low expressing patients, so the response rate obviously goes up from that particular point.

So the response rate, which is 44%, Carol is reminding me, in the medium and high patients for the confirmed, and obviously we'll have more information on those patients as we go forward.

So as it stands, our assumptions would hold, and that would be positive, and we'll continue to follow on that.

Going back to the IGN piece, we don't have direct comparisons with PP&Es. When we first started looking at DNA targeting agents, we also looked at cross-linking agents, which would be a similar class of drugs to the benzodiazepines. We also started with a benzodiazepine backbone.

We saw some late onset toxicity using the -- which sort of manifest in mice as weight loss, and felt that the therapeutic window that we were seeing was less than we wanted to using a cross-linking approach, which is how we came to the alkylating approach.

And with the alkylating approach, we were certainly able to get a much wider therapeutic index pre-clinically than we saw with the cross-linking agents. So our cross-linking agent clearly we have thought of at least as a comparator for PVDs, but it would be inaccurate to say that we have direct comparison to PVD. But it becomes a different class of agent. We are using something different.

Clearly, the PVDs are active, the CD33 targeting agent with PVD is an active agent. It also seems to have some marrow toxicity, which is important. And obviously, we think that maybe the opportunity for differentiation may come in the wide therapeutic window, enabling us to have better marrow recovery.

But it's early to say given that we haven't yet dosed patients. So as we learn more, we'll find out whether those assumptions hold. But certainly, pre-clinically, we found (technical difficulty) alkylation versus cross-linking that alkylating looked better for us.

Biren Amin, Jefferies.

Thanks for taking my questions. Maybe onmirvetuximab and the 20-patient biopsy data, I may have missed this. But are we expecting data at ASCO? And should we expect on that data split of FR expression and patient population as far as prior therapies to be similar to the 40-patient cohort? And also will those data support your FDA discussion?

And then I guess lastly, on the biopsy data, how might it impact the use of archival tissue in the FORWARD I studies?

So, I think that cohort, as you know, completed recruitment relatively recently. So, there's a relatively limited amount of information at this particular point.

We should certainly be -- and I'll remind you that what happens is we've taken patients. They obviously all have their archival specimen. We biopsy them before treatment and then we biopsy them during treatment with mirvetuximab.

So, I certainly think that, by the time we are at ASCO, you should expect to be able to see the consistency of expression of the Folate Receptor alpha Target as measured by the diagnostic that we are developing with Ventana. Those data and potentially some additional biomarker data based on the further follow-up with the patients and perhaps see the impacts of Folate Receptor Alpha expression during treatment with mirvetuximab soravtansine as well.

Those data are unlikely to be a major part of what we discuss with the agency, but I think they do help us support our plans from a diagnostic point of view. That's potentially having the ability to support that, the diagnostic we are using, select for patients who are ready to benefit now not just based on their archival specimens. And it may -- theoretically you could say it could support, for example, looking at patients who were previously low and seeing if they -- some patients may choose to re-biopsy to see if they have high expression at the time of treatment. But that's a little bit speculative at this point.

So what information we have we'll certainly have in our back pockets when we go to FDA. It's not a major part of informing the FDA discussion though, and we will be submitting an abstract, as we've said, based on the consistency of expression between archival specimens and the current status from biopsies.

Michael Schmidt, Leerink Partners.

I just wanted to touch on your plans in lymphoma. And so question number one is are you going to evaluate both of your ADCs, 529 and CD19 ADC?

Can you just remind us on -- and I believe you said you'll move one of the two agents forward depending on the next combination studies. If you could just remind us of the bar to the hurdle here internally to advance one of those or both potentially?

And then secondly, a question on 529. So in earlier Phase I studies, neutropenia was one of the key side effects here. My understanding is this has also been seen through rituximab. And my question is if we need to be worried about additive toxicities here for the combination study and what sort of protocol you have in place to manage this potentially. Thank you.

Well, I don't think we've specified a specific bar for advancing. I think to have a differentiated look in relapsed refractory DLBCLs, so this is where currently patients may be treated with, for example, vendamustatine (inaudible) rituximab. Also, I think some patients will get gemcitabine or gemcitabine, oxaliplatin, rituximab in these settings.

I think if you're not seeing a greater than 50% response rate in probably a nine months duration of response, it's going to be very difficult to differentiate yourself in a very busy field. So, we think we need to see clearly differentiated activity rather than minor increments to really want to take the risk of investing in an area where many drugs have been unsuccessful.

So, if I think, if you start thinking towards those types of numbers to have the confidence to go forward, that would probably be about the right place to be.

In terms of both -- rituximab, it is described as having some neutropenia and an early neutropenia, but rarely with rituximab is it something that would cause any significant problems from the perspective of, for example, prolonged neutropenia or infections.

So, I think we're reasonably comfortable, particularly with the steps that we have previously taken in terms of pre-medicating patients with corticosteroids that the neutropenia will be manageable. The most important thing is going to be to get this study started and to look at that and see as we go.

And it will be an important question for us.

But we think we've managed -- we've learned how to manage the neutropenia with 529, rituximab. Our investigators don't see it as a significant issue. I suspect it will be well tolerated, but we'll need to wait on data.

And do you think some of that data will be available already at ASH this year, or will this be more 2017 data point for the combination?

I think we need to get into dosing and see.

I think we need to look at how recruitment goes and get started. In a competitive field, you know, we need to get an understanding of just how quickly we can get the patients onto the study. So ASH isn't out of the question, but I think it's more likely a 2017 data point.

Okay, great. Thank you.

That concludes today's question-and-answer session. At this time, I'd like to turn the conference back over to Carol Hausner for any additional or closing remarks.

Thank you and thanks, everyone, for your attention and interest in ImmunoGen. And of course, if you have any subsequent questions, please don't hesitate to call. Have a great day.

And this does conclude today's conference. Thank you for your participation.