ImmunoGen, Inc. (IMGN) CEO Mark Enyedy on Q4 2018 Results - Earnings Call Transcript

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About: ImmunoGen, Inc. (IMGN)
by: SA Transcripts
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Earning Call Audio

ImmunoGen, Inc. (NASDAQ:IMGN) Q4 2018 Results Earnings Conference Call February 8, 2019 8:00 AM ET

Company Participants

Courtney O’Konek - Corporate Communications

Mark Enyedy - President and CEO

Anna Berkenblit - CMO

Rich Gregory - Chief Scientific Officer

Blaine Mckee - Chief Business Officer

Dave Foster - Chief Accounting Officer

Conference Call Participants

John Newman - Canaccord Genuity

Michael Schmidt - Guggenheim

Jessica Fye - JP Morgan

Biren Amin - Jefferies

Debjit Chattopadhyay - HC Wainwright & Co

Andy Hsieh - William Blair

Boris Peaker - Cowen

Jonathan Chang - Leerink

Kennan MacKay - RBC Capital Markets

Operator

Good day, and welcome to the ImmunoGen Fourth Quarter 2018 and Year-End Results Conference Call. Today's conference is being recorded.

At this time, I would like to turn the call over to Ms. Courtney O’Konek. Please go ahead.

Courtney O’Konek

Good morning and thank you for joining today's call. Earlier today, we issued a press release that includes a summary of our recent progress and fourth quarter and full year 2018 operating results. This press release and a recording of this call can be found under the Investors and Media section of our website at immunogen.com.

On the call today are Mark Enyedy, our President and CEO, and Anna Berkenblit; our Chief Medical Officer, Rich Gregory, our Chief Scientific Officer; Blaine Mckee, our Chief Business Officer and Dave Foster, our Chief Accounting Officer will join the team for the Q&A session. During today's call, we will highlight key recent accomplishments with the business over the last 12 months, review our fourth quarter and year-end financial results and discuss upcoming milestones.

During the discussion, we will use forward-looking statements, and our actual results may differ materially from such statements. Descriptions of the risks and uncertainties associated with an investment in ImmunoGen are included in our SEC filings.

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

Mark Enyedy

Thank you, Courtney. Good morning, everyone, and thank you for joining us today. 2018 was another year of rapid execution and significant progress for ImmunoGen, led by the completion of enrollment in FORWARD 1, our registration study for Mirvetuximab in platinum-resistant ovarian cancer, the presentation of combination data and over a 100 patients to support label expansion for this program and the advancement of our earlier-stage portfolio. With the benefit of this performance, we entered 2019 poised to deliver on a number of important catalyst including topline results from FORWARD I in the first half of the year; potential BLA and MAA submission for Mirvetuximab monotherapy in the second half of the year, additional data from combination studies with Mirvetuximab and from expansion studies in AML and BPDCN for our programs targeting hematological malignancies, and finally in IND for our next development program IMGC936 before the end of the year. We also completed the year with a strong balance sheet and a proven management team that brings deep experience in Oncology development and commercialization to deliver on the business. This combination of (inaudible) and capabilities positions us well to execute on our strategy and generate significant value in the coming year.

As a reminder, we’ve set four strategic priorities for the company; first, complete the development and launch Mirvetuximab in 2020 for the treatment of women with platinum-resistant ovarian cancer. Second, accelerate our IGN programs in hematological malignancies; next, build up on our leadership position in ADCs through continued platform innovation; and finally, expand the reach of that innovation and maintain financial strength through high value partnerships.

Over the last 12 months we’ve made significant progress towards each of these objectives. For Mirvetuximab, we successfully completed a pre-specified interim futility analysis for FORWARD I and finished patient enrollment in the study in April, well ahead of schedule. We believe this rapid accrual reflects the oncology communities’ interest in Mirvetuximab and underscores the need for a new treatment for this disease. In June, the FDA granted fast track designation for the program, and as the year progressed we advanced our pre-commercial and launch readiness activities for Mirvetuximab. To date, we’ve completed a thorough assessment of the market opportunity for Mirvetuximab and ovarian cancer with the goal and ability and preliminary go-to-market model.

We validated commercial drug product which is now in inventory, initiated the PMA submission for a folate receptor alpha companion diagnostic and began a staged approach to building out our commercial team. On the strength of this execution, we are on track to report topline data from FORWARD 1 in the first half of the year, with positive data we would expect to submit a BLA and an MAA for full approval of Mirvetuximab, as single agent therapy for the treatment of women with platinum-resistant ovarian cancer in the second half of the year.

In addition to the monotherapy indication, we continue to advance our FORWARD II study to expand the benefit of Mirvetuximab in to earlier treatment setting for ovarian cancer. Over the course of 2018, we presented data on more than a 100 patients from our FORWARD II study of Mirvetuximab in combination doublets with Keytruda, Avastin and Carboplatin and women with platinum-resistant or platinum-sensitive ovarian cancer. We also completed patient enrollment in the triple combination cohort evaluating Mirvetuximab plus carboplatin and Avastin.

(inaudible) Mirvetuximab, our novel IGN program 632 and 779 has demonstrated encouraging early results in hematological malignancies which were presented at ASH in December. Our early stage pipeline has also yielded our next promising development candidate IMGC936, a first-in-class ADAM9-targeting ADC which being developed in collaboration with MacroGenics. We plan to file the IND for the 936 before the end of the year. Together with our platform, each of these assets has the potential to create significant additional value for ImmunoGen.

We also achieved a number of operational milestones over the last year including an upsize and oversubscribed secondary that raised a $163 in net proceeds in June, and most recently the sale of our residual rights to receive royalties on commercial sales of Kadcyla for $65 million. Through these transactions, we started 2019 with approximately $325 million on our balance sheet. With respect to the remainder of our financial results, this mornings’ press release covered the details. So briefly we generated 54 million in revenue over the course of the year, operating expenses for the full year were approximately $214 million of which a 174 million was in R&D expenses driven by Mirvetuximab and 632 clinical trial cost and pre-commercial activities from Mirvetuximab mostly notably manufacturing.

For 2019 financial guidance, we expect cash and cash equivalents at December 31, 2019 to be between a 135 million and 140 million, revenues to be between 40 million and 45 million and operating expenses between 265 million and 270 million. We anticipate that current cash combined with the cash receipts expected from partners and collaborators will enable us to fund our operations at least a year beyond our release of topline results from the phase 3 401 trial, which as I mentioned is expected in the first half of 2019.

With that, I’ll turn the call over to Anna to review our pipeline progress. Anna?

Anna Berkenblit

Thanks Mark. As mentioned 2018 was another year of significant progress towards our highest priority objective, which is to bring Mirvetuximab to market as monotherapy for women with platinum-resistant ovarian cancer in 2020. Our FORWARD I study is progressing well; the pivotal phase 3 trial was designed to enroll 333 patients with folate receptor alpha positive platinum-resistant ovarian cancer who have received up to three prior treatment regimen. The study randomized patients two to one to receive Mirvetuximab or physicians choice of Liposomal doxorubicin, weekly paclitaxel or topotecan. The primary end point is progression free survival or PFS by blinded independent central review in the entire study population which includes both medium and high folate receptor alpha expressions, as well as in a subset of patients with high folate receptor alpha expressions.

Based on the encouraging and consistent safety and activity observed in clinical studies to date, we believe that Mirvetuximab has the potential to displace chemotherapy as a single agent treatment in the platinum resistant setting, and we look forward to assessing the topline data in the coming months with the plans to present the data at a medical meeting later this year.

In addition to Mirvetuximab monotherapy, we are advancing the combination expansion cohorts in the FORWARD II trial, looking at Mirvetuximab in combination with Avastin or Keytruda in patients with folate receptor alpha positive platinum-resistant ovarian cancer, as well as a triple combination cohort that is evaluating Mirvetuximab plus carboplatin and Avastin in patients with recurrent platinum sensitive disease.

As Mark mentioned earlier, over the course of 2018, we’ve reported data on more than a 100 ovarian cancer patients, treated with Mirvetuximab in combination with either Avastin or Keytruda. We have established that full dose Mirvetuximab can be combined safely with full doses of Avastin, Keytruda and carboplatin with no new safety signals. And we have reported encouraging initial anti-tumor activity across the doublet combination cohort.

In the first quarter, we completed enrollment of 41 patients in the triplet cohort ahead of schedule. In addition, based on the encouraging data reported to date with Mirvetuximab in combination with Avastin, we initiated a second of Mirvetuximab plus Avastin cohort in a patient population that we’re calling platinum agnostic. These are patients who may or may not meet the criteria of platinum-resistance that is recurring within six months of (inaudible) platinum, but they are nevertheless appropriate candidate for a non-platinum containing doublet such as Mirvetuximab plus Avastin.

We expect to enroll approximately 40 to 60 patients to generate additional data to guide label expansion for this combination doublet. As FORWARD II continues, our goal remains to establish Mirvetuximab as the combination agent of choice in ovarian cancer and to support its use in earlier lines of ovarian cancer therapy. To this end, we plan to present initial data from the triplet cohort as well as mature doublet expansion cohort data at medical meetings over the course of 2019.

Moving to our novel IGN programs, IMGN 632 and IMGN 779 are being investigated in hematological malignancies with a focus on AML and BPDCM. Despite several new treatment approval for AML in recent years, a significant need remains for these patients. Last year, both of these programs were granted orphan drug designation from the FDA for the treatment of AML. Our new IGN payload, which are DNA acting agents are designed to overcome the limitations of first-generation cross-linking agents of this class. Our IGN payload to find just one strand of DNA retaining potent anti-tumor activity while sparing normal healthy cells which we believe will facilitate repeat doses and provide (inaudible) treatment.

In December at ASH, we reported encouraging phase 1 data on both IGN programs in back-to-back oral presentation. IMGN 632 is a CD123 targeting ADC that deploys our most potent IGN payload. Initial data from the phase 1 study of 632 in patients with relapse or refractory AML and BPDCM showed us that IMGN 632 displays anti-leukemia activity across all dose level testing and the tolerable safety profile of doses up to 0.3 mg/ kg. Enrollment in expansion cohorts is ongoing to identify the recommended phase 2 dosing schedule so that we can move forward with IMGN 632 monotherapy development in BPDCM as well as additional combination studies in AML which we plan to initiate this year.

IMGN 779 is our CD33 targeting ADC, which again displayed quite favorable tolerability with repeat dosing across a range of doses in relapsed AML. Encouragingly in data presented at ASH we saw anti-leukemia activity in more than 40% of relapsed and refractory patients. This year we expect to establish the recommended phase 2 dosing schedule for IMGN 779 to move forward with in combination regimen in AML. As we look ahead, we have important clinical milestones in 2019 with most notably the topline FORWARD I data in the coming months.

Now I’ll turn the call back over to Mark.

Mark Enyedy

Thanks Anna. Coming back to the business to date, we generated significant momentum across ImmunoGen in 2018 and entered 2019 from a position of strength with important near-term catalyst with our lead program, our earlier stage portfolio accelerating and an experienced management team to deliver on our commitment to bring more good days to people living with cancer. We look forward to another exciting and productive year and will update you on our progress in the coming months.

With that we’ll open the lines for questions.

Question-and-Answer Session

Operator

[Operator Instructions] We’ll now take our first question from John Newman of Canaccord. Please go ahead. Your line is now open.

John Newman

Mark and Anna, back last year in October we saw some interesting data for Mirvetuximab in combination pembrolizumab (inaudible) and I’m wondering since that time have you seen any maturation of that data? I recall when those data were initially presented you had told us that the PFS data especially were a bit immature, so I’m just curious if maybe you’ve seen any signs since than that those data continued to show.

Anna Berkenblit

We continue to follow the patients on that cohort, but our attention really in terms of data cleaning and focus right now is on the FORWARD I phase 3 trial, so we are following patients on Mirvetuximab and Pembrolizumab as the data mature and look forward to presenting it later this year.

John Newman

And as a follow-up question for you Anna, I think you previously said it seems to be that the proportion of patients for each choice in the control arm of paclitaxel led some of us (inaudible); I think you agree when you said that that is pretty reflective of what you see in the real world, is that the case?

Anna Berkenblit

Yes, that’s the case. So we buy data from with real world use and typically what we see is the majority of patients with platinum resistant ovarian cancer receive Pegylated Liposomal Doxorubicin. Primarily because is a pretty convenient schedule and its given once a month. The next most common is weekly paclitaxel, physicians typically give that for patients you had a good response to every three week paclitaxel and they’ve recovered from neuropathy, and then topotecan is also approved and used.

Operator

We will now take our next question from Michael Schmidt of Guggenheim. Please go ahead.

Michael Schmidt

I had another one regarding the FORWARD I trial and I know you’ve done a lot of work previously in terms of dosing and then ocular prophylaxis and we’ve heard from docs that Mirvetuximab is considered very well tolerated so far. And so I was just wondering in this context maybe what assumption you have incorporated in the FORWARD I trial with respect to potential dropouts or [sensing] rate?

Anna Berkenblit

There were two factors that we took in to consideration when we made assumptions about the dropout rate. One is as you point out Michael, the potential for patients if not well managed to drop out because of ocular adverse events on Mirvetuximab and the other was potentially for patients on the control arm to drop out once they realized that they were randomized to the control arm because it is an open label study. And so we put a lot of effort in to educating investigators and making sure we had patients facing materials for the ocular profile to minimize the dropout rate and the drop out that we’ve seen across this study is consistent with our expectations.

Michael Schmidt

And just to play devil’s advocate, should the FORWARD I study fail, to what degree might or might not affect your new plans to study Mirvetuximab combination as you mentioned drugs including Avastin and carboplatin cohort?

Anna Berkenblit

It really would depend on why the study failed, Michael. There are many scenarios that one could contemplate where the study is not statistically significantly positive for the primary endpoint and so we would really need to understand the monotherapy data that would really drive our next step for development for Mirvetuximab from a registration perspective. Either its monotherapy or it’s a combination.

Michael Schmidt

And then the last question, more housekeeping question around your operating expenses guidance. I was just wondering if that is a cash figure or if that includes non-cash comp and then what are the assumptions that you are staying in to that guidance with regards to Mirvetuximab commercialization activity.

Mark Enyedy

That guidance includes both cash and non-cash operating expenses, that’s directly from the expected P&L for next year. Those stock comp would be in there.

Michael Schmidt

And does that include an initial buildout of the commercial infrastructure or maybe a more substantial buildout or is that still pending on the data itself?

Mark Enyedy

So it does include the buildout of the commercial organization. So we’re assuming success with respect to that guidance, and it’s a staged approach Michael. So right now we’re managing all of our pre-commercial planning with existing headcounts, but the goal would be with the benefit of a positive readout to begin building with a significant amount of that expense coming in the back half of the year.

Operator

We will now take our next quarter from Jessica Fye of JP Morgan.

Jessica Fye

A couple on FORWARD I, if we think about the enrollment of that trial, can you ballpark how much of that enrollment occurred towards the end of the study; say in the last three months that you’re enrolling patients? Second can you confirm if you have hit the targeted number key (inaudible) yet, I think in response to the first quarter and then you might have said your focus is now cleaning data for FORWARD I. Does that imply that the full number of events has been hit? And third, can you remind if OS is relevant from a regulatory standpoint with all here i.e. if OS data search mature while the filing is under view. Has the FDA provided feedback on how they would interpret that information?

Anna Berkenblit

So, you may recall last year that we completed enrollment ahead of schedule, nearly two months ahead of schedule and so enrollment was brisk over the last three months of the trial. I can’t quote you exactly what percent of patients were enrolled then, but again towards the end enrollment was quite brisk. Regarding your second question, we are focused on data cleaning as we have been for many months now, so that we can get the trial over the finished line so to speak, but my statements were not intended to imply anything regarding whether or not we have hit the targeted number over there. And then as to your third question, regarding overall survival, it is a key secondary endpoint. The study is not powered to show us statistically significant improvement in overall survival, however, we would expect that all of the end points are consistent and so would expect to see a trend in overall survival in the right direction and typically we would anticipate providing updated overall survival data to FDA with the day 120 [bid].

Operator

We will now take our next question from Biren Amin of Jefferies. Please go ahead.

Biren Amin

Just to clarify on the prior question in response to Anna. What would trigger cleaning of the trial, would it not be triggered by achievement over the final event or are there other parameters that you would consider?

Anna Berkenblit

We clean data throughout the course of the trial and again there was no trigger to start data cleaning. Data cleaning started as soon as we started enrolling patients in the trial, but again as one reaches towards the end of the trial there is an increased focus on that and all I can say is for the past many months now we have been focused on cleaning the data.

Mark Enyedy

This is Mark. Just keep in mind, the minute you have your first screen failure you start to collect data and try and lock down those patients, and then as the study moves forward, patients comes off studies, the goal is to clean and lock down as many of those patients as you can before you get to your final event. So as Anna was saying, obviously the more patients we accrued, the higher the volume of that activity. So that’s all was implied by that statement.

Biren Amin

And then given the FORWARD I trial design on PFS end point on both the overall cohort and the high FR expressers, let’s just say if the overall cohort misses, what type of a PFS benefit would you need to see in the high FR expressers to hit a P value of 0.025 or less?

Anna Berkenblit

There are different scenarios for that variance, so I don’t think I can give you an exact answer, because there are different scenarios, but overall what I can tell you is, we have designed a study looking for PFS improvement from 3.5 months in the control arm to six months in the experimental arm which translates in to a healthy ratio of 0.58 and we’re going to be looking for that delta, if you will, both in the ITT and the high subset. And if we miss on the ITT, we can still claim success in the high subset.

Biren Amin

And then maybe just one more question on FORWARD I, given the chemotherapy arm that allows for investigators choice of three chemo agents, how should we think about the distribution of each of those three agents in the trial, and do you expect any geographic difference between US versus Ex-US sites in terms of choice of chemo agent?

Anna Berkenblit

So as I mentioned, we anticipated that the distribution of investigator choice chemo in the trial would reflect real world usage, and in the real world as we discussed Doxil tends to be used most often followed by weekly paclitaxel and topotecan, and given what we know about usage in the US and Europe, we do not anticipate differences in those two geographic regions regarding preferences for each of these single agent chemotherapies. The practice is pretty similar with regard to choice of single agent chemotherapy.

Operator

We will now take our next question from Debjit Chattopadhyay. Please go ahead.

Debjit Chattopadhyay

I’m going to stay away from FORWARD I, but may be a two part question on the Keytruda combo. So first maybe the platinum resistant setting, would you pursue the keytruda combo or stick with agents with established activity in the platinum resistant setting. And then secondly in the platinum sensitive patients, would you not think that if Keytruda carboplatin (inaudible) would make the more sense, given the lessons from non-small cell?

Anna Berkenblit

So platinum resistant ovarian cancer, which is where we initially explored Mirvetuximab plus pembrolizumab and are still following patients, it’s going to really depend on how the data when we do look at it in terms of maturity. And so we haven’t made a decision yet there. Regarding platinum sensitive ovarian cancer, I agree with you that the data that pembrolizumab had generated was platinum based therapy for non-small cell lung cancer is really quite nice and could potentially be relevant in the ovarian cancer settings. And at the moment, however, we’re focused on following patients on our triplet with carboplatin, Mirvetuximab and Avastin. But I agree with you that pembrolizumab based triple is something we could consider in the future.

Debjit Chattopadhyay

And then the three chemos that are being used, obviously there is kind of a spread of outcomes for the individual chemos, but more recently weekly paclitaxel seems to be doing better in terms of outcomes. But Doxil is most commonly used, at talks on that dichotomy there or people are yet to catch up for that weekly versus what was previously approved.

Anna Berkenblit

I think typically ovarian cancer patients wind up getting more multiple lines of therapy, and the sequencing of single agent chemotherapy in the platinum resistant setting is really based on physician patient conversation around what is important to the patient in terms of the adverse event profile, the schedule etcetera. I will remind everyone that we are stratifying patients in our trial on several characteristics including selection of single agent chemotherapy. So that is one of the stratification factor Doxil, topotecan or a paclitaxel and now the stratification factor is one to two versus three prior therapies. So, whatever factors physicians take in to consideration when they assign the investigator choice chemotherapy, we’ll make sure that its stratified so there’s balance across the arm.

Mark Enyedy

I mean part of this is, typically a platinum sensitive patient is going to get a platinum based doublet that usually has Taxane as its partner, and so once you got in to a platinum resistant patient rather than reintroduce a Taxane with peripheral neuropathy and the other things the fall is more likely to be like with Doxorubicin and that’s in fact what we see in the market place today, both here in the US and in Europe and in fact single agent chemotherapy has a higher percentage of usage in the platinum resistant setting about 80% of patients in the EU versus about 60 here.

Operator

We will take our next question from Andy Hsieh of William Blair. Please go ahead.

Andy Hsieh

Curious to hear Anna’s take on this recent negative trial Javelin ovarian 200, is it triple arm study avelumab plus Doxil versus avelumab versus Doxil. I think the Doxil arm actually underperforms versus historical norms and just curious your view on that and its potential relevance to your control arm assumptions for FORWARD I?

Anna Berkenblit

I am aware that they have press released a topline data from Javelin 200 where they described response rate and hazard ratios, but I don’t believe that I have seen the absolute value for progression free survival for any of the arms so I really can’t comment on that. But I guess what I would say for that study is, it has not achieved proof of concept for checkpoint inhibitors in platinum resistant ovarian cancer and I would also point out that the Javelin, I think it’s 100 of the ovarian trial and the frontline setting was also stopped early at interim analysis for futility.

Operator

We will now take our next question from Boris Peaker of Cowen. Please go ahead.

Boris Peaker

Maybe on FORWARD I, we talked about a lot of the incremental details as you’re working to finish the study, but I’m just curious, do you think that that is going to come in 1Q or 2Q?

Mark Enyedy

We haven’t narrowed the guidance. So what we’ve said previously and where we are today is that we expect the study to readout in the first half of the year.

Boris Peaker

And maybe on the combos, obviously you’ve done a lot of work on the combos and a lot of data keeps maturing, but what is the strategic plans on actually starting a pivotal study for any of the Mirvetuximab combos?

Anna Berkenblit

We have two options at the moment for combination studies that we’re thinking about moving in to the next registration study; one is Mirvetuximab plus Avastin and one is the triplet of carboplatin, Mirvetuximab plus Avastin, and we continue to gather data for both of those regimen to help inform our next decision regarding our next registration trial. So for Mirvetuximab plus Avastin, we are actively enrolling our second cohort which we call the platinum agnostic cohort and we plan to enroll between 40 and 60 patients there to see the consistency of data we hope with the initial cohort that we have published and also the triplet which we have completed enrollment ahead of schedule in December last year and we look forward to initial safety data from that this year and then subsequently efficacy data. Now remember the triplet cohort, these are platinum sensitive patients and so it will take a while before we have mature data from not just in the oral but PSF perspective for decision making.

Boris Peaker

And my last question on 779, I’m just curious what the development strategy there is and would you have to deal head-to-head against minor target endpoints or can you avoid doing that?

Anna Berkenblit

So for 779 you may recall that we’ve demonstrated quite nice favorability and definitely anti-leukemia activity. And in discussions with investigators there is interest in continuing development of IMGN 779 as a combination therapy. So, the first thing would be for us to figure out really what the recommended phase 2 dosing schedule is for 779 to proceed in combination. At this point, we do not have plans to do a head-to-head monotherapy versus (inaudible).

Operator

We will now take our next question from Jonathan Chang from Leerink. Please go ahead.

Jonathan Chang

A couples of questions, one on FORWARD I, can you talk about the reasons confidence now that the control arm is expected to perform, and then second question can you talk about your expectations for how many of the patients on FORWARD I would be FR alpha high?

Anna Berkenblit

In terms of our confidence in the control arm, all I can say is that it has increased since when we started the study and we designed it. We designed it really benchmarking the control arm on the AURELIA study, where the control arm which included the same drugs that we’re including had a medium progression free survival of 3.4 months. So that was our foundational assumption. And then in the fall last year the CORAIL study read out and that was over 400 patients study in platinum resistant disease not just with one to two prior like Aurelia but one to three priors like ours. So I think it’s the best benchmark out there and the most recent benchmark out there, and they are the control arm in two of the three drugs that were included in our phase 3 trial and again the median PFS there was 3.6 months. So we’re confident in the performance of the control arm.

In terms of your second question regarding how many patients will be folate receptor alpha high, what we have typically seen throughout the development program instead of our 40% of ovarian – of epithelial ovarian cancer is about high, 20% medium, 20% low and 20% negative and so we anticipate that the majority of patients will be eligible for Mirvetuximab based on medium or high expression, and again we anticipate that the majority of the patients in the trial will be high based on the distribution that we’ve seen thus far.

Operator

[Operator Instructions] We will now take our next question from Kennan MacKay of RBC Capital Markets. Please go ahead.

Kennan MacKay

I have another one for you, it’s actually a four parter here. First I just wanted to confirm in FORWARD I there are no platinum refractory patient, and then I just wanted to double check on how the chemotherapy protocols are sought defined – the options are defined in FORWARD I, whether this is actually restricted to per label usage or site protocol usage or NCCN guideline usage or anything along those lines.

Third, I just wanted to double check the definition of number of prior therapies in FORWARD I and see if this referred to total lines of therapy including combo therapies or whether this referred to the number of prior therapies, for instance with carboplatin plus paclitaxel plus Avastin, be considered a single line or three products? And then lastly just wanted to see if the arms would it all balance the platinum free interval or prior response to therapy or duration of this line?

Anna Berkenblit

So the first one, we have excluded primary platinum refractory disease. That is a small subset of ovarian cancer patients who just basically blow through their initial therapy and progress on their initial platinum based doublet. The typically do poorly no matter what. However, we are allowing patients with secondary platinum refractory disease. So what I mean by that is that they – after their second line of therapy, they may have progressed on that. But again we’ve excluded primary platinum refractory only.

Regarding your second question, the dose and schedule of the chemotherapies that we use in our study are those that investigators actually used, they are not necessarily the labelled dose. So a good example of that would be Doxil, the labelled dose is 50 mg/meter square and that’s tough for patients to tolerate due to mucositis and foot syndrome. So we’re using the more commonly used regimen of 40 mg/ meter square and similarly for topotecan, we’re allowing 1.25 mg/meter square daily times 5 which is a bit less than the approved dose of 1.5 and we’re allowing a weekly regimen for topotecan given some studies showing similar activity and essentially better tolerability. So we’re using the doses that investigators typically use in the clinic.

Regarding your third question, we are referring, when we say a number of prior, we really mean lines of therapy. So Taxil, carbo, Avastin, with Avastin out back as maintenance would be considered one line of therapy. And then regarding your last question, whether or not the arms are balanced for platinum-free interval or response to prior therapy that is not a specific stratification factor. We already had plenty of stratification factors with folate receptor alpha, number of priors and choices in investigator chemotherapy. But given the size of the study, we hope that random [chem] flow allowed for balance for that factor as well as whatever other factors are maybe important.

Kennan MacKay

And then may be just one quick follow-up on the lines of therapy, does that include neoadjuvant and adjuvant or is that just for metastatic disease?

Anna Berkenblit

Neoadjuvant and adjuvant are considered one line of therapy.

Operator

It appears at this time there are no further questions. I would like to turn the conference back to Mr. Mark Enyedy.

Mark Enyedy

Thank you, Operator. We apologize for the audio challenges, but we had to start the call this morning. Appreciate your patience and we look forward to keeping you updated on our progress as we move through the remainder of the first half of the year. Thanks very much.

Operator

This concludes today’s call. Thank you for your participation. You may now disconnect.