ImmunoGen, Inc. (NASDAQ:IMGN)
Q2 2016 Earnings Conference Call
January 29, 2016 08:00 ET
Carol Hausner - Executive Director, Investor Relations and Corporate Communications
Dan Junius - Chief Executive Officer
Charlie Morris - Chief Development Officer
Dave Johnston - Chief Financial Officer
Jessica Fye - JPMorgan
Michelle Gilson - Oppenheimer
Matthew Harrison - Morgan Stanley
Simos Simeonidis - RBC Capital Markets
Mara Goldstein - Cantor Fitzgerald
Boris Peaker - Cowen and Company
Andrew Peters - UBS
Biren Amin - Jefferies
Michael Schmidt - Leerink Partners
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 have 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 will 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 U.S. 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 U.S., specialize in the treatment of gynecologic cancer such as ovarian cancer and are expected to play an important role in patient enrollment. As a result, we anticipate we will have the majority of our U.S. centers open for patient enrollment by June.
Patient dosing is underway in 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, advancing 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 1 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 2 trial assessing our IMGN529 product candidate in combination with rituximab for diffuse large B-cell lymphoma and later in the year, in our Phase 2 trial assessing our coltuximab ravtansine in a different combination for this cancer.
Finally, we are on track to start Phase 1 testing of 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, calculates DNA without cross-linking it. We are excited about the potential for this technology and we are 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 will briefly touch on some of the progress being made by our partners. On Tuesday, we announced that Bayer has initiated a global Phase 2 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 recall, highly encouraging Phase 1 data with anetumab and mesothelioma were presented at the World Conference on Lung Cancer last September. We are 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 to potential registration testing.
On the topic of Kadcyla, Roche expects data from their neoadjuvant trial, KRISTINE, to be reported this year, and if positive, to 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 early breast cancer testing and compares a Perjeta Kadcyla regimen to a Perjeta Herceptin regimen. Roche also has a Phase 2 trial underway with Kadcyla in HER2-positive lung cancer. Roche continues to expand 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 anti-tumor responses, early days of course, but exciting stuff.
I am 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 are 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 will 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 1 expansion cohort in this disease. Data reported that triple meeting included that 7 of these 20 patients or 35% had a confirmed objective response on treatment with mirvetuximab soravtansine unless 6 of these 7 patients run treatments 6 months or longer. As you recall, our target for advancing mirvetuximab as monotherapy was 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 have sized this first ovarian cancer Phase 1 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 a submission to ASCO. And when the data mature, we do [indiscernible] with regulators.
Last quarter, we completed enrollment in the Phase 1 ovarian cancer cohort designed to further enhance our understanding of biomarkers. One of the questions that will help answer is whether expression of folate receptor alpha from 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 we 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 are working towards having over 50 clinical sites in the U.S. and Western Europe and rolling patients into FORWARD I. Conducting this trial in partnership with the GOG Foundation leverages their knowledge experience in clinical site network facilitating the trials timely execution. Last quarter, we also completed enrollment in the Phase 1 cohort assessing mirvetuximab in the treatment of relapsed/refractory folate receptor alpha-positive endometrial cancer. The findings aren’t specifically mature for submission to ASCO by next Tuesday’s deadline, but should be ready for presentation at the later medical conference.
While I spent most of my time on mirvetuximab, I should note that we are also making meaningful progress with other pipeline programs. In December, we reported new preclinical data in 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 patient dosing is expected to begin in early 2016 in our Phase 2 clinical trial of this combination regimen. We also reported new data at ASH for our CD33 targeting ADC, IMGN779, which is on track to begin Phase 1 testing for acute myeloid leukemia in the next couple of months. As you know, IMGN779 is the first ADC utilized in our one of our new class of DNA alkylating payload agent scope IGNs, which in preclinical testing have shown marked tolerability advantages of DNA cross linkers.
Later in the year, we plan to initiate a Phase 2 trial assessing our coltuximab ravtansine therapy for B-cell malignancies and a combination regimen. We are projecting this study will start in the second half of 2016. In all we are making solid progress advancing our strong pipeline. On that note, I will 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 due to their taking of license in the period, while the prior year includes a $41.4 million in amortization of upfront fees from Novartis and Lilly due to their licensing activity in that period. The current period also includes $2 million of cash milestone earned from Sanofi in their advancement of SAR 428926 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 royalty revenue that is partially offset by non-cash interest expense resulting in non-cash net income. Operating expenses for our second quarter fiscal year 2016 were $46.3 million compared to $34.5 million in the second quarter of last year. These consisted a $38.2 million in R&D revenue expenses in the second quarter of 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. Revenue changed from prior fiscal year are increased third-party expenses – 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 the 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 prior – in this period of 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 on 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 will turn the call back over to Dan.
Thank you, Dave. I think you can tell by the comments here that there is 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 the presentation of the initial biomarker findings at ASCO. We will also have the 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 the Stage 1 of the FORWARD I study by year end.
We also expect to begin patient dosing in our Phase 2 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 2 trial later this year. We are very happy with the progress being made by Bayer with anetumab ravtansine and we anticipate that another of our partners will advance the program into registration enabling testing in 2016.
Roche expect data from their KRISTINE trial with the Kadcyla in the neoadjuvant setting to be reported this year and if positive, 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 are seeing a high level of interest in our ADC technology and are having discussion with a number of parties. Predicting outcomes and timing however, is always challenging. So executing our product plans and look forward to providing you updates as these programs progress.
With that, let me turn it back to Carol so that 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 questions per person until each analyst has had an opportunity to ask a question. We will now open the line to questions.
Thank you. [Operator Instructions] We will go to Jessica Fye with JPMorgan.
Hi guys. Thanks for taking my questions. 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 are going to get, are you expecting to breakdown between high, medium and low expression to be the same, i.e. should we expect sort of another 10ish high expressing patients that thus far seem to be showing investor sponsor it? And then second, just heading into this meeting with 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.
Yes. Thanks Jessica. So on the first one, I don’t actually know the split off hand of how things work 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 and what’s going to come through in the ASCO abstract. In terms of the FDA, I mean I think the key point is going to be kind of response rate support and approval. Does the proposed design enable us to show an adequate improvement in the response rate that the FDA would be sufficiently impressed to see that the space of an approval. And also talk 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 news I think that you can’t have this meeting before with the FDA before we actually go to ASCO, i.e. when we see the sub-data ASCO, will you have – not 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 mean, I don’t think we are 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 have previously described, you will know about it. Now, ASCO, it’s probably the earliest we were in a position to let you know that, but I think it’s soon to make promises on that.
Got it. Thank you.
We will go next to Chris Marai with Oppenheimer.
Hi, guys. 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 just wondering….
Michelle, you are very quiet.
Oh, I am sorry. Is this better?
That’s a lot better. Thank you.
Hi, this is Michelle. I was just wondering if or when we might see any data from FORWARD I since its open label? And then we also were just wondering maybe what you are seeing pre-clinically with the PD1 and mirvetuximab? And then maybe when you plan to initiate studies with that combo?
Just to say the FORWARD I question first. We – as we said on the call, we have said previously we certainly anticipate that we will 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 statistically – separately from Stage 2. So, there is no impact on the integrity of the overall study presenting Stage 1 as an intermediate point. So, I think we should be hoping for ASCO ‘17, but obviously we will update you as we get more. I certainly won’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 have 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 that 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, so something that we want to assess. I think there is 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 is 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.
Alright, great. Thanks, guys. And one more are you guys going to provide any enrollment updates for your FORWARD I and FORWARD II trials?
Well, I think we did a little bit to say that FORWARD I is open for enrollment and we are enrolling patients in FORWARD II. I don’t know that we will be providing quantitative updates as much as directional updates. We were quite encouraged with how enrollment proceeded certainly post-ASCO, with some of the additional cohorts that we had, biopsy for example, are also completing the endometrial cohort, the additional 20 patients 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 then getting down to specific numbers gets a little bit too detailed, but we will certainly try to give you some directional information.
Okay, great. Thanks, guys.
We will go to Matthew Harrison with Morgan Stanley.
Great. Good morning. Thanks for taking the question. I just want 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 maybe reflected? So for example, it sounded like what you said earlier was if you upsized 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 layout a couple of what you see is the potential outcomes from that meeting and how we might interpret that? Thanks.
I mean, I think when we have the meeting, if we make changes to program, I think as we tend to be, we open about what the considerations there are. The good case scenario that I already described they like the design, they would accept the response as an endpoint as they have already in this disease. Obviously, they may say they are not going to accept it. 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. And then of course the other one would be that, yes, they see this support, but it maybe based on other thoughts we would prefer to use something else as a confirmatory study. 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 generally, obviously, we are optimistic because we are very encouraged by our data. We don’t see any downside to going and laying these plans out to the 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.
And we will go to Simos Simeonidis with RBC Capital Markets.
Good morning, guys. 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 stage of FORWARD I?
I will go to the second part of question first, if I may, Simos, which is absolutely not. We will not be waiting for the first stage in FORWARD I, because that would then put the FDA consultation on the critical path at 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 1 and 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 layout the best possible stories that it makes sense when the FDA reviews it. So, it’s really about having the right level of maturity of those data, 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 it’s 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 have been seeing. So, I think all of that together is why we have been pointing towards this meeting being in the first half of this calendar year. It’s because I believe that is the appropriate timing and clearly that would not require anything else of FORWARD I together.
Okay. And the second question is in terms of the ocular AE that you witnessed so far, either 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?
I mean, 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 or FORWARD I, there is not prophylactic use of corticosteroid eye drops. You may remember, we are exploring that in an additional cohort of patients in the Phase 1, so that – and that is actively – we are actively accruing patients into that particular cohort now. Now, again, more information that can feed into Stage 2 of the study so that by the time we get to Stage 2 and are enrolling on Stage 2, we will have more information about the right cook point for folate receptor alpha expression. We will have more information about the best way to manage the ocular events and we have the FDA import. So I think by the time we are at that point, we have got everything that we need to execute very successfully.
Yes. And to add to that we 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 patients. So there will 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.
We will go to Mara Goldstein with Cantor Fitzgerald.
Thanks very much for taking the question. Two things, can you just remind us on the – I believe its Ventana relationship on the development of the IHC 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 am 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?
So from the Ventana perspective, yes we – Ventana is using one of our antibodies in the development of an IHC-based companion diagnostic. We are taking that to all of the appropriate stages. We will be having the appropriate consults with CDR8 – 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 is using, as I said, one of our antibodies we have licensed to Ventana. And that’s the successful relationship. And we are pleased on how that’s being executed. Commercial elements and all of that will kick in at later point. But as of right now, that’s progressing very nicely. In terms of the GOG Foundation, we have worked closely since the beginning of this with some of the senior investigators of the GOG. I think working with them is the sign that they are 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 are working at those sites, the expectation is that those sites, if they have completing 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 what is 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 not only for FORWARD I, FORWARD II we believe that we can do getting that specifically into GOG Foundation, we will be working with absolutely same centers, but not under the umbrella of the GOG Foundation.
We will go to Boris Peaker with Cowen and Company.
Great. Thank you for taking my questions. I guess I just wanted to confirm in terms of data, at the triple meeting recently, we had 10 responses and out of 20 patients, 50% response rate, three of those weren’t confirmed and it looks based on today’s data update that the unconfirmed were not confirmed in the future scan. And as a 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?
Well, I think those – some of that first 20, those that you rightly point to being confirmed, essentially cannot be confirmed. To progress before they were able to have a confirmatory scan or have progressed with the next scan and another one got 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 that have occurred very, very late, it should be have had time to being confirmed. Not at the time of the abstract, they won’t all have time to being 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 provided at that time.
Great. And just on the abstract, since you are going to be submitting it pretty soon, can you give us any sense of how many actually patients worth of data there is going to be in the abstract itself?
Okay. The abstract is going to include 40 plus. Got it.
Well, thank you very much for taking my questions.
We will go to Andrew Peters with UBS.
Thanks guys for taking my questions. A couple here, 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 set at ASH, as it helps to inform kind of your Phase 1 trial. 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 35% confirm that we have seen right now, would you be able to show a statistical difference if the physician’s choice say is at the higher end of the historic controls? Thanks.
Thanks Andrew. If you don’t mind I will take the second question first, because it relates to everything else that we have been discussing. So as you know, we have always thought in terms of patients having a roughly 15% to 20% response rate and with current standard chemotherapy agents. We have also always believe 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 are looking for. I will 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 rates obviously goes up from that particular point. So the response rate which is 44%, Carl is reminding me, in the medium and high patients for the confirmed and obviously we will 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 will continue to follow on that.
Coming back to the IGN piece, we don’t have direct comparisons with PVDs. When we first started looking at DNA targeting agents, we also have looked at cross-linking agent, which will be a similar class of drugs to be pyrrolobenzodiazepine. We also started with the benzodiazepine backbone. We saw some late onset toxicity using the – which sort of manifested in mice the 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 will certainly able to get 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 comparative 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 those patients. So as we learn more, we will find out whether those assumptions hold. Certainly pre-clinically, we found alkylation versus cross-linking that alkylating looked better for us.
We will go to Biren Amin with Jefferies.
Yes, thanks for taking my questions. Maybe on the rituximab 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 a far 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 I guess lastly on that biopsy data, how might it impact the use of archival tissue in the FORWARD I studies?
So, I think that cohort as you know completes the recruitment relatively recently, so a relatively limited amount of information at this particular point. But we should certainly – and I will remind you that what happens is we have taken patients there. Obviously, all have their archival specimen. We would biopsy them before treatment and then we biopsy them during treatment with mirvetuximab. So, I certainly think that by the time with 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 follow-up of the patients and perhaps see the impact of folate receptor alpha expression during treatment with mirvetuximab soravtansine as well. Those data are unlikely to be a major part in what we discussed with the agency though I think they do help us support our plans from the diagnostic point of view. That’s potentially having the ability to support that to be the diagnostic we are using, select the patients who are ready to benefit now, not just based on their archival specimens. And it may theoretically you could say could support, for example, looking at patients who were previously low and saying 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 will 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 have said based on the consistency of expression between archival specimens and the current status from biopsies.
Great, thank you.
We will go to Michael Schmidt with Leerink Partners.
Hey, good morning. Thanks for taking my questions. I just wanted to touch on your plans in lymphoma. And so question number one is you are going to value both of your ADCs 529 and the CD19 ADC. Can you just remind us on – and I believe you said you moved 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 1 studies, in neutropenia was one of the key side effects here. My understanding is that this has also been seen to mirvetuximab. 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.
I don’t think we have specified a specific bar for advancing. I think to have a differentiated look in relapsed/refractory DLBCL, so this is where currently patients maybe treated with, for example, bendamustine, rituximab or I think some patients will get gemcitabine or gemcitabine, oxaliplatin, rituximab in these settings. I think if you are not seeing a greater than 50% response rate and probably a 9 month 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 are being unsuccessful. So, I think if you start thinking towards those types of numbers to have the confidence to go forward that will probably be about the right place to be.
In terms of both rituximab is described as having some neutropenia and early neutropenia, but it’s rarely with rituximab is it something that would cause significant problems from the perspective of, for example, prolonged neutropenia or infections. So, I think we are reasonably comfortable particularly with the steps that we have previously taken in terms of pre-medicating patients with corticosteroids, but the neutropenia will be manageable. Most important thing is going to be to get the 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 have managed – we have learned how to manage the neutropenia with 529 rituximab, but our investigators don’t see it as a significant issue. I suspect it will be well-tolerated, but we will need to wait on data.
And do you think some of the 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...
I think we need to look at how recruitment goes and get started in a competitive field. We need to get an understanding of just how quickly we can get the patients on to 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 would 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.
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