Feb 9, 2018
Executives
Sarah Kiely - Director, IR Mark Enyedy - CEO Anna Berkenblit - Chief Medical Officer Dave Johnston - CFO Rich Gregory - Chief Scientific Officer
Analysts
Michael Schmidt - Leerink Debjit Chattopadhyay - H.C. Wainwright Kennen MacKay - RBC Boris Peaker - Cowen Jessica Fye - JPMorgan Andy Hsieh - William Blair Biren Amin - Jefferies
Operator
Good day and welcome everyone to the ImmunoGen Fourth Quarter 2017 and Yearend Results Conference Call. Today’s call is being recorded.
And at this time, for opening remarks and introductions, I would like to turn the call over to Sarah Kiely, Investor Relations and Corporate Communications. Please go ahead.
Sarah Kiely
Good morning. And thank you.
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 2017 operating results.
This press release and a recording of the call can be found under the Investors section of our website at immunogen.com. On the call today are our CEO, Mark Enyedy, our Chief Medical Officer, Anna Berkenblit; and our CFO, Dave Johnston.
Rich Gregory, our Chief Scientific Officer will join the team for the Q&A session. During today’s call, we will highlight key accomplishments from 2017, provide an update on our development programs, including our lead asset, mirvetuximab soravtansine, review key 2017 financial results and our guidance for 2018 and outline anticipated events for the year ahead.
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.
With that, I will now turn the call over to Mark.
Mark Enyedy
Thank you, Sarah. Good morning, everyone and thank you for joining us today.
We're pleased to be with you to review the progress we made with the business in 2017 and why we look forward to another productive year in 2018. Our efforts at ImmunoGen start with a focus commitment with four strategic priorities.
First, complete the development and launch mirvetuximab for the treatment of women with ovarian cancer by 2020. Second, accelerate our pipeline of novel IGN programs.
Third, build on our leadership position in ADCs through continued innovation. And fourth, expand the reach of our innovation and maintain financial strength through partnering.
Throughout 2017 we made significant progress towards each of these priorities with four consecutive quarters of strong execution across the company. Operationally, we advanced our FORWARD I Phase 3 study of mirvetuximab in platinum-resistant ovarian cancer.
Since enrolling the first patient at the end of January 2017, we've activated more than 100 sites in FORWARD I and are on track to complete enrollment before the end of June, which means we will have fully accrued 333 patients in roughly 17 months. At ASCO in 2017, we presented a pooled analysis of 113 patient supporting our registration strategy for mirvetuximab as monotherapy in platinum resistant disease.
In addition to support the expanded benefit of mirvetuximab in earlier lines of therapy, we also presented data from the dose escalation stage of our FORWARD 2 trial evaluating multiple combination regimen including mirvetuximab with Avastin, Keytruda and carboplatin. These data demonstrated that full doses of mirvetuximab could be combined with full doses of these agents with no new safety signals and encouraging efficacy outcomes.
Taken together, these data have generated a high degree of interest from investigators, which have supported the rapid accrual FORWARD 1 and enabled us to initiate expansion cohort IN FORWARD 2 with mirvetuximab plus Avastin and mirvetuximab plus Keytruda in platinum-resistant patients. In addition, this quarter we've started a triplet combination with mirvetuximab plus carboplatin and Avastin in the platinum sensitive setting.
Moving to our earlier stage portfolio, we accelerated the clinical development of two novel ADCs 779 and 632 that integrate our proprietary DNA alkylating payloads, which we call IGN. 779 and 632 are supported by our strategic collaboration with Jazz Pharmaceuticals, which we established in August.
This partnership generates substantial funding to advance these programs at scale, offers access to global development and commercial capabilities and for the first time, provides ImmunoGen with substantial commercialization rights for a partners program. With the progress made in both programs in 2017, the collaboration is off to a strong start.
As part of those efforts at ASH in December, we reported safety data and antileukemia activity from the dose escalation stage of our Phase 1 clinical trial 779 in patients with acute myeloid leukemia or AML. Last month, we began dosing patients in our first Phase 1 clinical trial 632 in patients with AML as well as patients with a rare and aggressive blood cancer referred to as BPDCN.
Anna will go into more detail on each of these studies in a moment. Financially, we added more than $235 million to the balance sheet in 2017, a $135 million came through business development activities and $100 million through our successful follow-on offering.
In addition, we converted almost $100 million of debt into equity reducing our outstanding debt to around $2 million. These efforts have significantly strengthened our financial position with almost $270 million in cash and very little debt on the balance sheet as of the end of the year.
With the momentum we generated in the last 12 months, we enter 2018 from a position of strength with a number of important catalysts expected during the year. We are on track to conduct the FORWARD 1 interim analysis in the first quarter, which as a reminder, for futility only.
Enrollment in the trial is brisk and we should complete accrual by midyear, positioning us for a topline readout on the primary endpoint in the first half 2019. In addition, over the course of this year, we will report combination data for more than 100 patients from our FORWARD 2 study.
These readouts will begin with efficacy data from the dose escalation cohort in combination with Keytruda in March at SGL, followed by the Avastin expansion cohort for which we will submit an abstract for ASCO and the Keytruda expansion cohort expected as ASMO in October. Finally, we are advancing our 779 and 632 programs in the clinical with data from both Phase 1 studies anticipated for ASH.
Consistent with our strategic objectives, we regularly review our operations to improve efficiency and focus resources on our highest priority program. Through this end, we recently conducted an in-depth analysis of our manufacturing and quality functions with the goal of developing a model that could support our long-term development and commercialization needs.
Based upon this assessment, we determined that immunogen will benefit from moving to an operating model that transitions manufacturing and quality testing of both drug substance and drug product to external partners. These benefits include gaining access to external expertise, levering advances in contract manufacturing capacity and building in-house capabilities that can effectively oversee our CMO network to ensure timely, high-quality production and delivery of our early and late stage pipeline materials.
With these considerations in mind, we will be closing our Norwood Massachusetts facility in early 2019 and eliminating approximately 20 positions from the functions currently located there. Over the next year, we will continue to support manufacturing and testing for 779 and 632 as well as our partner programs from this facility and this decision will not affect the development timelines for any of these programs.
Combined, the decommissioning of the facility and revisions to manufacturing and quality operating model are expected and generate over $20 million in savings during the next five years. I should also add that consistent with the guidance we will provide later in the call, growth in other areas of the business is anticipated to result in a slight net increase in staffing by the end of the year.
Norwood has been a long-standing staple of ImmunoGen's business, delivering high-quality products to patients and partners without interruption for more than 25 years. We are grateful for the contributions that all of our Norwood-based employees have made to the growth and evolution of ImmunoGen.
We will provide comprehensive retention and severance benefits in line with industry norms to support the employees affected by this decision. With multiple catalysts in the next 12 months, we look forward to another productive year in 2018 as we advance our pipeline to bring new therapies to patients and create more value for shareholders.
With those goals in mind, Anna will now review the progress in our clinical stage program and the upcoming data events in more detail.
Anna Berkenblit
Thanks Mark. I am going to start off by reviewing updates related to mirvetuximab and our FORWARD 1 Phase 3 registration study, which is designed to support full approval of mirvetuximab for women with platinum resistant ovarian cancer.
As Mark mentioned, we now have more than 100 sites opened across the U.S., Canada and Europe and we are on track to complete enrollment by midyear. We continue to be very pleased with how FORWARD 1 is progressing.
As a reminder, the primary endpoint in FORWARD 1 is progression-free survival of PFS in both the intent to treat population that includes both medium and high FR-alpha expressers and in the subset of patients with high levels of folate receptor alpha expression. With the encouraging and consistent safety and activity profile observed so far, we believe mirvetuximab has the potential to displace chemotherapy as a single agent in the platinum resistant setting.
This quarter, we expect to reach 80 PFS events required for the pre-specified interim analysis, which as a reminder is for futility only. If the hazard ratio for the intent to treat population is greater than one and the hazard ratio for the high folate receptor alpha subset is greater than one, then the trial would stop.
Otherwise the trial continues. Once the analysis is complete and we the recommendation of the independent data monitoring committee, we will update you.
Beyond FORWARD 1, we are conducting the FORWARD 2 combination trial to expand the potential of mirvetuximab positioning it as an earlier line therapy and expanding into platinum-sensitive disease. To date, we have shown that full dose mirvetuximab can be combined safely with full doses of Avastin, carboplatin and Keytruda.
Expansion cohorts are ongoing in both the Avastin and Keytruda combination, with three data readouts expected throughout the year. We will have a featured poster presentation at SGOs Annual Meeting on Women's Cancer in March, reporting on the 14 patients from the Keytruda dose escalation cohort, followed by plans to provide an update on 35 patients from the expansion cohort at ASMO in October.
We're also submitting an abstract on the combination with Avastin for ASCO in June, which includes data from the 55 patient expansion cohort. In addition, we have expanded the FORWARD 2 study to evaluate a triplet combination of mirvetuximab plus carboplatin and Avastin in recurrent platinum-sensitive ovarian cancer.
I am pleased to announce that we enrolled our first patient this week and look forward to sharing more details in due course. Beyond the internally sponsored mirvetuximab studies there are also several investigator-sponsored trials that are evaluating mirvetuximab in other tumor types expressing folate receptor alpha and in other combination.
This includes three studies with the NCCN, the National Comprehensive Cancer Network to our investigating mirvetuximab as monotherapy in patients with triple negative breast cancer and the third is looking at mirvetuximab in combination with gemcitabine in gynecologic malignancies. We are also co-sponsoring a study with Clovis, which will evaluate mirvetuximab in combination with Rubraca in ovarian cancer.
Data from these studies will help guide how we further develop mirvetuximab to reach as many patients as possible who may benefit from treatment. In 2017, we made significant progress with our earlier stage IGN programs in hematologic malignancies.
Both IMGN779 and IMGN632 use our novel and highly potent IGN payloads, which were designed by ImmunoGen as DNA acting agents that alkylates one strand of DNA instead of causing double-stranded DNA damage, retaining potent anti-tumor activity with relative sparing of healthy cells. IMGN779 is a novel CD33 targeted ADC that we are evaluating in patients with relapsed refractory CD33 positive AML.
We have an ongoing Phase 1 study in patients with AML looking at both biweekly and weekly dosing schedule from which we presented updated data at ASH in December. Data from the dose escalation portion of the study demonstrates that 779 has been well tolerated with no dose limiting toxicities.
Pharmacokinetic exposure and pharmacodynamic CD33 saturation increased with dose and anti-leukemia activity has been observed in patients including those with poor prognostic features. We are continuing to dose escalate with both the biweekly and weekly schedule.
This year we expect to establish the recommended Phase 2 dose for 779 and submit additional data from the Phase 1 study for presentation at ASH in the fourth quarter. As we continue to evaluate 779's safety and efficacy and dose escalation, we look forward toward combining it with standard therapy as well as novel agents, which may include additional cytotoxic hypomethylating agents as well as flip three NbCl2 inhibitors.
At ASH in December, we presented preclinical data for 779 in combination with cytarabine, a commonly used chemotherapeutic in AML. These data showed increase CD33 levels, enhanced DNA damage, growth arrest and apoptosis in in-vitro models, as well as prolonged survival and increased numbers of complete remissions with no tolerability issues in the combination using in vivo human AML preclinical models.
Moving on to our second IGN program IMGN632 is a CD123 targeting ADC that has demonstrated potent and selective activity in preclinical models of AML and acute lymphoblastic leukemia or ALL. At ASH in December, we presented preclinical data with our collaborators at MD Anderson, which demonstrated promising activity and safety of 632 in preclinical models of B-cell ALL.
We reported that CD123 expression is prevalent across ALL subtypes including 90% of BALL and nearly half of T-cell ALL. IMGN632 demonstrated promising activity in both BALL cell lines and patient samples in vitro, including the elimination of more than 90% of blasts in six out of eight patient samples.
Importantly normal cells were not affected by 632 at 100-fold higher concentrations, suggesting the potential for an increased therapeutic window. We're very encouraged by the preclinical results we have reported to-date and believe there is strong potential for 632 across a range of hematologic malignancies.
To that end, we recently announced dosing the first patient in our Phase 1 study evaluating IMGN632 in patients with CD123 positive malignancies, including AML and BPDCN or blastic plasmacytoid dendritic cell neoplasm. The study followed the once every three-week dosing schedule while in its dose finding stage.
The selective dose will then be used in expansion cohorts in patients with BPDCN, AML, ALL and other CD123 positive hematologic malignancies. We expect to present initial data from this study at ASH in the fourth quarter.
As you heard, we are extremely encouraged by the potential of our leading pipeline and have a robust set of milestones in the year ahead. We look forward to sharing updates throughout the year.
Now I'll turn the call over to Dave.
Dave Johnston
Thanks Anna. Our financial results were detailed in this morning's press release, so I'll just review the highlights and our updated guidance for 2018.
Throughout 2017, we operated with financial discipline and this is reflected in our full year operating expenses of approximately $174 million driven by approximately $140 million of research and development spending, heavily focused on advancing our mirvetuximab clinical trials. In 2017, we recorded approximately $115 million in revenue, largely due to the breadth of business development activities executed last year.
Revenues included a $30 million paid-up license fee related to an amendment to our collaboration and license agreement with Sanofi, $29.5 million related to the sale and transfer of IMGN5292 Debiopharm, $7 million in partner milestone payments, $12.7 million in amortization of a non-cash fee related to our license agreement with CytomX and lastly, $28.1 million and non-cash royalty revenues on [indiscernible] sales. As you heard from Mark earlier, over the course of 2017, we substantially cleaned up and strengthened our balance sheet.
This was done in part through the conversion of roughly $98 million of debt into 26.2 million shares of common stock, reducing our outstanding debt to just about $2 million today. In October of 2017, we successfully closed a public offering of 16.7 million shares that raised net proceeds of about $102 million.
So, added over $235 million to the balance sheet throughout the year, enabling us to end 2017 with approximately $267 million in cash and cash equivalents. Looking ahead we expect 2018 revenues of between $60 million and $65 million and operating expenses between $185 million and $190 million.
We anticipate ending 2018 with between $115 million and $120 million of cash and cash equivalents. We expect that our current cash, combined with the expected cash revenues from partners and collaborators will fund our operations into the fourth quarter of 2019, which will take us through a number of important milestones including topline FORWARD 1 results.
We started 2018 in a very strong financial position and we will continue to evaluate all mechanisms to maintain the strength to execute on our programs and bring those to market. So, with that, we'll open the lineup for any questions.
Operator
Thank you, Sir. [Operator instructions] And we'll go first to Michael Schmidt with Leerink.
Michael Schmidt
Hey guys. Congrats on terrific 2017 and on all the progress made.
I had one question regarding the mirvetuximab-Avastin combination study. The update that you said you'll probably provide at the ASCO conference and just wondering if you could remind us of the patient characteristics in this study, for example what line are these patients in?
How many of those have received Avastin before? What about folate receptor alpha biomarkers and can you help us maybe get a sense of how to benchmark the efficacy data that we might get in the middle of the year, thanks?
Anna Berkenblit
Hi Michael, thank you for your question. So, at ASCO, we plan to present data from the mirvetuximab-Avastin combination and you may remember that we presented initial data from heavily pretreated patients in dose escalation at ASCO last year.
Subsequently, we've expanded and we have two expansion cohorts; one is patients who are Avastin naïve, who had one to two prior lines of therapy and the intent when we designed that cohort what to benchmark our data against the same population as in the AURELIA trial. The second expansion cohort is an Avastin pretreated group and there the idea is to enroll patients who have received prior Avastin and are more heavily pretreated.
So, we are allowing up to five prior lines of therapy. So, we will be presenting data from all of the patients that we've enrolled in these expansion cohorts at ASCO and will be providing the appropriate subset analyses with the caution that there are of course small subsets.
I do want to observe however, that the AURELIA study, while that has been critical for the approval of Avastin in platinum-resistant disease, since we designed that cohort of Avastin naïve patients, Avastin has gotten approved in the recurrent platinum-sensitive setting in the U.S. as it had already been in Europe.
And so, we believe that Avastin is going to be used more in earlier lines of therapy and that's one of the reasons we started the triplet. The last question that you had was folate receptor alpha and we have included patients with FR alpha low, medium and high.
And again, we'll be presenting subset data in detail at the ASCO presentation.
Michael Schmidt
Great. Thanks for the added information.
And should the efficacy signal be compelling enough, I was wondering I guess, how do you think about next steps i.e. do you think you’re in a position to potentially start another Phase 3 retrial this year or is it something that should maybe be considered in 2019?
Thank you.
Anna Berkenblit
Yeah. So, I consider the data with Avastin very supportive of expanded use in the platinum-resistant setting down the road if the data continue to hold up.
And really, it provides confidence in our strategy to move up into earlier lines of therapy specifically with the triplet of carboplatin, Avastin and mirvetuximab in the recurrent platinum settings. We do not expect to start another Phase 3 trial this year that will be down the road.
Michael Schmidt
Great. Thank you very much.
Operator
And we’ll go next to Debjit Chattopadhyay with H.C. Wainwright.
Debjit Chattopadhyay
Hey, good morning. Can you hear me?
Mark Enyedy
Yeah. Very well.
Thanks.
Debjit Chattopadhyay
Thanks. Actually, Michael kind have asked what I was heading at.
But when I take a more 40,000-foot deal questions here. So, as you survey the oncology landscape, I think the mine share is largely immune-oncology.
Where do you see opportunities for ADCs broadly?
Mark Enyedy
Sure. So, if you think about in particular, let’s start with the management of solid tumors then we can move to hematologic malignancies.
Most patients present with later-stage disease, they undergo surgery and then have adjuvant chemotherapy. And most of them ultimately will progress, which I think reflects a little bit unmet need in the space.
And so, what we see is an opportunity given the profile of ADCs with the benefit of targeting highly potent anti-tumor agent and particularly when we look at mirvetuximab for example, a very favorable tolerability profile, the ability to combine with multiple agents in addition to having compelling single agent efficacy. And so classically in clinical development, we find ourselves in a relapsed population typically in the case of ovarian cancer platinum-resistant patients, that is patients who progressed after receiving initial platinum therapy, which enables us to pursue a rapid to market strategy head-to-head against single agents therapy with a relevant endpoint in this case progression free survival.
So, and then the question is how do you move up into earlier lines of therapy, and typically that will involve chemotherapy. And so, as we look at the oncology landscape moving forward, we of course observe that immuno-oncology agents are taking an increasingly important role.
As part of our strategy, we are collaborating with Merck, with Keytruda and see interesting results which we will share again in March at SGO from a dose escalation cohort and platinum-resistant disease. On the basis of those early results, we've moved into an expansion cohort.
So, as we think about ADCs in the broader landscape, we see an increasing role four of those agents again both as single agents and as preferred combination partners. And we think for example with the profile that we see with mirvetuximab, we have the potential to displace for example chemotherapy in the treatment paradigm again as a single agent and also as a preferred combination partner.
Debjit Chattopadhyay
Great. And then, ADC is obviously, it’s a multi-component system you've got literally three things, actually four things, but three that you can full around with linkers, payloads and drug to antibody ratios, given your platform versus what's evolving on from a competitive viewpoint, where do you think ImmunoGen really needs to move forward to say drive more partnerships in the space?
Thanks so much.
Mark Enyedy
So, I'm going to ask Rich to tackle that question. I mean, I think overall, we think we’ve got the most comprehensive platform in the industry and I think that positions as well.
But I’ll ask Rich to address some of the questions you're asking around immunological responses.
Rich Gregory
Yeah. So first of all, I have to say the advancements generally in the field over the last five years to six years have been remarkable.
And if you look at the number of ADCs that have moved into the clinic, not just from us, but from our competitors as well, it's a burgeoning area for sure, which I think reflects a lot of optimism that the technology does have a pretty strong place in the future of oncology. And I tend to look at it as sort of Venn diagrams that certainly patients who will respond to IO and then there is patients who will respond to targeted therapies such as ADC's.
And they'll be some overlap in this patient populations where hopefully we'll see synergy, which some of the preclinical data suggests. So, where are we positioned?
We have, I think as Mark discussed the most comprehensive toolbox in terms of our ability to think about targeting agents and those could be antibodies, small scaffolds such as you might see from companies like Ablynx or Pieris or other companies in that space. We have, I think a very diverse set of payloads that allow us to think about how we adapt our payload science to the particular needs of any specific tumor type.
So, we are extremely well-positioned going forward to, I think participate in this field in a really meaningful way. Now, you asked about how that plays into partnerships and I think that's more of a strategic question for us about how we want to approach partnerships.
We have, I think modified our approach to this thinking more about collaborative co-development as opposed to simply out-licensing our technology, which is I think of limited value and we think we can gain the most value by working with people, who have, for example, great targets or great drugs that might work in the complementary way with our drugs and that would be the way we’ll be pursuing our partnership strategy going forward.
Mark Enyedy
As part of that looking to gain access to complementary technology. So, for example the technology swap that we did with CytomX is a good example where we thought that the probody masking technology would be helpful in terms of addressing a wider array of targets.
And so, we’ve look to deploy that and have a program moving forward against the target Abcam and CytomX has an antibody or a probody that they put in the clinical development deploying our link or payload technology.
Debjit Chattopadhyay
Thanks for the added color. Good luck.
Mark Enyedy
Thanks.
Operator
We'll go to Kennen MacKay with RBC.
Kennen MacKay
Hey, good morning and thanks for taking the question. Maybe just real quick housekeeping question for David, first.
In the revenue guidance of $60 million to $65 million for 2018, can you help us with sort of what milestones that implies and when those could come?
Rich Gregory
Good morning, Kennen. It implies that if you compare it to 2017 where the license and milestone revenue reflected the extraordinary amount of business development activity that we had.
We don’t anticipate matching that in 2018, at least that’s not in our guidance right now because those are the things that happen or don’t happen and it’s kind of hard to predict. So, it reflects a relatively modest amount of license and milestone revenue.
And about half of business development is actually going to be non-cash revenue related to Kadcyla royalties. So, we generally don’t provide updates on when we expect milestones because first of all it’s out of our control and secondly, it’s relatively minor in the whole scheme of things.
Kennen MacKay
Okay. Got you.
And okay. And then maybe one for Mark, can you just help us understand the manufacturing decision you announced last night and a little bit more sort of specifically what spurred these conversations at the board level and with this in response to sort of GMP checks within the facility or relating to mERV or FDA interactions or just help us understand, I guess how this idea came up at the board level?
Thank you.
Mark Enyedy
Yeah, so let me just start with the last part of that question. So, there was no GMP issues with the plant whatsoever, we are continuing to produce material there and we'll do so throughout the remainder of 2018.
And as it relates to mirvetuximab, all of the production from mirvetuximab currently sits with contract manufacturers at this time. So, but let me pull the aperture back now and talk about what's going on here.
So, look sound management requires that we regularly review all of our operations. Our business has evolved with the changes in strategy that we put in place, back in the fall of 2016 in particular to emphasize our proprietary portfolio.
And as Rich just mentioned really a shift away from these broad-based partnerships that we had with Roche and Novartis and others to focus on developing our own programs and so the net effect of that was that the capacity requirements for our Norwood facility were declining over time, particularly as we did some mapping in our long-range planning. In addition to that, we do quality testing there and we were moving the quality testing for a pivotal programs out to the contract manufacturers, who were going to produce both the pivotal and the commercial material.
And then finally, there was a need to put in-place a more comprehensive approach to managing and expanding network of contract manufacturers. And so, given those developments, we conducted a comprehensive assessment of our manufacturing and quality operations with the goal of developing a model that would support our long-term growth aspirations.
And the conclusion of that analysis was that we would benefit from a move to a model that we’d rely on external sources for our both the manufacturing and the testing. And so, the CMO and the centralized testing world is evolving rapidly and so we wanted to make sure that we had increased access to that expertise to take advantages in capacity and technology, and at the same time building our own in-house capability with respect to an oversight capabilities.
And finally, to increase our focus and resources on the things that we do best, which is development and ultimately commercialization of our own portfolio. So, based on those considerations, we've taken the decision to de-commission our Norwood facility in early 2019.
As I mentioned at the top, that means we're going to continue to produce product and in this case it’s IMGN779 and IMGN632, as well as a couple of our partner programs. This decision will have no impact on the timelines of these programs.
I think it's important to stress that. This does have an impact on our employees.
This will result in a net reduction of about 20 FTEs. This facility has been a long-term staple of our business.
And we thank those employees, we're accounting on them through the course of 2018, but they've been a highly productive part of the organization. We're grateful for their efforts.
And as a result of that, we will be providing a comprehensive retention in severance packages. And then looking longer term with the decommissioning of the facility, we expect to save about $20 million over the next five years.
Kennen MacKay
Got it. Thank you, Mark.
I really appreciate the added color and clarity. That makes a lot of strategic sense.
And then, I guess just one final question thinking about some of the combinations and sort of the changing standard of caring in ovarian cancer, this has turned I think from a setting that was off the radar that many investors given that the standard of care hadn't changed in this last 30 plus years outside of Avastin. But I had one or two, I guess take your temperate on, how you saw PARP inhibitors sort of altering that market as they go into the earlier lines of maintenance therapy potentially with AstraZeneca, so one getting them into sort of potentially frontline maintenance?
And what that meant for later line therapies and whether with mirvetuximab -- mirve, even sort of outside of their collaboration with Clovis whether there was any early data suggesting activity post PARP inhibitors and if we knew anything about how that changed the activity there whether sensitized patients more or potentially even you know or potentially it could make them a little bit more resistant to PARP treatment any comment that would be helpful? Thank you.
Mark Enyedy
Sure, I'm going to ask Anna to touch on the points that you raised there.
Anna Berkenblit
Thanks, Kennen. So PARP inhibitors have transformed the landscape for platinum sensitive disease.
There's no doubt about that. In platinum resistant disease PARP have basically negligible activity single digit response rates.
And so, physicians will use them in the platinum sensitive setting, but not once patients have become platinum resistant and so that's where our initial indication is with mirvetuximab. That's point number one.
Point number two is that PARP, because of their safety profile at least the ones that are currently approved are indicated as monotherapy maintenance, because they cannot be combined with cytotoxic chemotherapy. And cytotoxic chemotherapy at least in the near future will certainly remain an integral part of frontline therapy, so platinum-based doublet therapy.
And then in the recurrent platinum sensitive setting as well to de-bulk patients before our maintenance strategy is undertaken. And because of the tolerability profile of mirvetuximab, you know it targets tubulin like paclitaxel does, but it does not have the associated hair loss and seems to have a less neuropathy.
There is the potential for mirvetuximab to become the preferred combination agent in platinum-based regimens and that's why we're so excited about it having started the triplet regimen this quarter with carboplatin, mirvetuximab and Avastin, so that’s the second point. The third point is that there are currently two maintenance strategies that have demonstrated significant benefit for patients with platinum-sensitive disease in the recurrent setting, which is Avastin and PARP.
So, it would not surprise me if one of them is used frontline if you will out back after initial chemotherapy and then patients will do better than they currently do with standard of care frontline therapy. But at some point, most of them will still relapse and when they relapse, many of them will have recurrent platinum-sensitive disease, and they'll get another round of combination chemotherapy with the other maintenance therapy.
So, you know PARP first, Avastin second or flip-flop the other way around. And certainly, our hope is that at least in the frontline setting, some patients – more patients will be cured currently are because right now the majority of patients are not cured, most of them do relapse.
But then at some point, there will still be patients with platinum-resistant disease who may benefit from our initial indication. And again, I think this is why mirvetuximab has the potential to benefit patients in the platinum-resistant setting initially, but moving up as the preferred combination chemotherapy agents in the platinum-sensitive space.
That answer your question, Kennen?
Kennen MacKay
Yeah. Sure, it does.
Anna Berkenblit
Okay. Great Mark, reminded me your other question was what about MERV activity after part.
So, in the puled analysis that we presented at ASCO last year, we demonstrated, we showed in the demographic table a significant percentage of patients have higher PARP inhibitors about 20%, 25%. And that's exactly what you would expect based on the frequency of BRCA mutations and the indications for PARPs at the time that we were enrolling the monotherapy study.
And what I can tell you is having looked at subset analyses, mirvetuximab does have activity regardless of whether or not patients got a prior PARP inhibitor. The same holds true for whether or not they had a prior Avastin.
Kennen MacKay
Got you. Thank you very much for the follow up there and I was an incredibly thorough and looking forward to some additional conversations on this at SGO.
Anna Berkenblit
Great.
Operator
And we'll move next to Boris Peaker with Cowen.
Boris Peaker
Good morning. So, my first question is probably for Anna and FORWARD 1, so you're separately analyzing all comers as well as high folate expressers.
I'm just curious are there plans to stop enrollment in one group if that group happens to have a hazard ratio or close or even above one. And it seems to me that from a safety and efficacy standpoint kind of wouldn't make sense to keep enrolling particularly if the hazard ratio happens to be above 1 for that specific group?
Anna Berkenblit
Thanks, Boris. So, the way the interim analysis is currently designed is that if the hazard ratio is greater than one in both, we will stop.
We do not have a pre-specified adaptive design what you're describing, for example, is let's just say in the ITT population the hazard ratio is greater than one. But in hives, the hazard ratio is less than one.
That's probably the most likely of the unlikely scenarios if you will. And the reason, I say that is because our monotherapy data demonstrated significant tumor shrinkage in medium patients as well as you remember.
But be that as it may, in that case, we would continue the study and certainly, this is why we have an independent data monitoring committee because it's all about benefit risk. So, they will look at the efficacy, but they will also be looking at the safety and we will review their recommendations and then make a decision accordingly.
I do find it hard to imagine though that we would have benefit in the hives, which are two-thirds of the population approximately, and then somehow have such a negative impact on the minority patients who are mediums that it would swing the hazard ratio in the other direction.
Boris Peaker
Got you. And my second question is on IMGN632 and specifically in BPDCN.
I'm just curious how many BPDCN patients have you enrolled so far? Are you finding it difficult to actually find these patients?
And are they primarily frontline or second line? So, could you generally describe the BPDCN patients?
Anna Berkenblit
So, we just opened the study in January and so, we are enrolling AML and BPDCN patients as they come. And as you can imagine since there are more AML patients, the patients we've enrolled thus far in dose escalation are AML patients.
However, the investigators who are participating in the trial are those who have experienced with other agents for BPDCN they have patients in their clinic. And certainly, they would be given priority for enrollment when they come, but we will not hold up dose escalation for them
Boris Peaker
So, have you enrolled at least a single BPDCN patient or not?
Anna Berkenblit
No.
Boris Peaker
Got you. Okay.
Thank you.
Mark Enyedy
Yeah. So, keep in mind Boris, this is a standard 3+3 dose escalation.
So, we’ve enrolled the first cohort of three patients who will have a safety review sometime soon, and then open it up for the next three patients. So, it’s going to you know, it’s not surprising that we’ve got three AML patients to start.
Boris Peaker
Got you. Thank you very much for taking my questions.
Operator
We’ll go next to Jessica Fye with JPMorgan.
Jessica Fye
Great. Thanks for taking my question.
I just have on IMGN779 I guess, given that it seems like you are likely to go forward with the weekly dosing, and you are able to start dose escalation there higher than you did with the every other week, when within a year, should we expect to hear that a go forward dose has been identified?
Anna Berkenblit
So, at this point, Jessica we are still escalating every other week and the weekly schedule. Our goal for this year is to identify, excuse me, the recommended Phase 2 dose.
We will have data at ASH. I really can't predict when we would be able to put our stick in the ground and say we have a recommended Phase 2 dose because that would require dose limiting toxicity and we haven’t see any yet.
Jessica Fye
Okay. Thank you.
Operator
We'll go to Andy Hsieh with William Blair.
Andy Hsieh
Hi. Thanks for taking my question and congratulations again on a very productive 2017.
So, I have two questions and it's a little bit related to Jessica's question earlier. So, I believe Anna said during the last quarterly call that for IMGN779, you were at dose cohort 9, potentially maybe you can give us an update on the progress with that or have you guys progressed to other higher cohorts?
And secondly, this is about the powering assumptions for the FORWARD I, I believe you have disclosed publicly that the – for the intent to treat population the benefit, sorry you can detect a benefit of 6 months over 3.5 months, could you remind us if the assumption for the folate receptor high population has been disclosed? Thank you.
Anna Berkenblit
Your first question Andy was around the dose level for IMGN779. So, we are still escalating the every other week schedule.
So, I think, we disclosed up to dose level 9 at ASH and we’re continuing to escalate as quickly as we can. Remember there's a lot of enthusiasm for the trial and the cohort due to fill rather quickly.
For your second question regarding the powering, we're actually testing the same statistical assumptions so hazard ratio of 0.58, which corresponds to a progression free survival improvement from 3.5 months in the control arm to six months in the experimental arm. We would be testing that in the IGT population as well as in the high subset.
We don't have different statistical assumptions for the two.
Andy Hsieh
Got it. Thank you very much.
Operator
[Operator Instructions] We'll go to Biren Amin with Jefferies.
Biren Amin
Yeah. Thanks for taking my questions.
Just on the Keytruda combo at SGO. What should we expect in terms of how many patients will you have at SGO.
And I guess what was did you have a hurdle in terms of going from dose escalation to dose expansion in terms of efficacy that you needed ahead before you went into dose expansion for that trial? Thanks.
Anna Berkenblit
Hi, Biren. At SGO, we will present the data from the 14 patients who were enrolled in escalation for mirvetuximab plus Keytruda.
You may remember at ASCO we presented only safety data and it was from 13 patients. So, we hadn't quite finished dose escalation.
So Keytruda will have all 14 patients from dose escalation and we'll have safety and efficacy data. We did not wait for efficacy data to trigger opening of expansion.
The expansion cohort was triggered just based on safety. And we're in the midst of enrolling the expansion cohort and we'll present data from that later this year.
Biren Amin
Got it. And then on FORWARD 1, you’re expecting to complete enrollment by midyear.
Can you just tell us what the split is in terms of the geographic distribution in that trial and whether you expect patients to behave differently between U.S. versus Europe?
Anna Berkenblit
So, we are enrolling patients in North America and Europe. I would say that enrollment in both regions is brisk at this point and we are certainly monitoring the baseline characteristics of patients and we do not see any dramatic differences.
The stratification factors include one to two versus three priors and we’re also looking at the choice of comparator agents you know paclitaxel, Doxil, etcetera. So, you know I don’t anticipate that the patients will look very different in different regions.
Biren Amin
Great. Thank you.
Operator
And we’ll take the next question from Michael Schmidt with Leerink.
Michael Schmidt
Hey guys, thanks for taking the follow up. I just had a question regarding our prior discussions on next steps and I understand the desire to move into early lines in ovarian cancer as fast as possible including platinum-sensitive patients, I’m just wondering what internally at ImmunoGen what the decision-making process looks like to make that next step.
Is that something that you will consider once you have data and from all of the expansion cohorts in FORWARD 2 or is that something you could do early or should data look very compelling. And do you think you're in a position to do that on your own or is it something you would need to do with a partner to launch global program in the frontline setting or something along those lines?
Thanks.
Mark Enyedy
Sure. So, as you alluded, these are data driven decisions.
We review the programs regularly and take a look at the data as they're available, particularly with respect Forward 2 and the combinations and so we are prepared to turn quickly if we see compelling data. You'll see those data reviewed in increments over the course of the year starting with SGO and then a more substantial bolus of data, which we expect at ASCO and then ultimately at ESMO with the two you know leading candidates in terms of Keytruda and Avastin and our experience there.
Obviously, we're interested in the carboplatin combination and in particular the triplet and the ability to raise the efficacy bar. Their preliminary results with carboplatin alone in platinum-sensitive patients as a combination with mirvetuximab were quite interesting to us with response rates in the mid-60s and progression free survival north of the year in patients with a median of three prior therapies.
And so, that certainly caught our attention, which is what's driving the move to triplet combination, which you know we enrolled the first patient. Obviously, undertaking a large company sponsored study is a significant undertaking for a company at our stage, that said I think with the benefit of positive data over the course of this year, we should be in a position to finance those activities and certainly with the benefit of a positive readouts from FORWARD I, which you know we're expecting in the first-half of 2019.
I think, at that juncture, we could anticipate a company-sponsored study. We do have in down interest in mirvetuximab, as we’ve talked in other four, the predicate for entering into a relationship there and this would be outside of the United States, would be that the partner would have to enable us to substantially expand the program beyond the way in which we are currently thinking about it.
So, stay tuned there, these are business development conversations and they have their own course. So, this is a long way of saying that it's early at this moment to commit to a particular path in terms of label expansion for this program, but we've got some very interesting data, which is pointing us in a couple of directions here.
One of the things that we're going to be doing is evaluating data that comes from these – for a potential for breakthrough therapy designation with this program. And so, it's those kinds of considerations that will guide us.
But to answer your question fundamentally, the company we believe with the benefit of additional data, we'll be able to finance the needed studies to support label expansion for the product, but that said we are -- we do have inbound interest and we constructively engage around that interest.
Michael Schmidt
Great. Thank you so much.
Operator
With no additional questions, I'd like to turn the call back over to management for closing remarks.
Mark Enyedy
Great. Well, thanks for your time today.
We generated significant momentum with this business in 2017 and we entered 2018 from a position of strength. We've got a number of catalysts over the course of the year 2018 from a position of strength, we’ve we got a number of catalysts over the course of the year and so we look forward to keeping you updated as the business progresses.
Thanks very much.
Operator
Thank you, sir. That does conclude our call today.
Thank you for participating. You may disconnect at this time.