TESARO's (TSRO) CEO Lonnie Moulder on Q4 2016 Results - Earnings Call Transcript
Q4 2016 Earnings Conference Call
February 28, 2017 04:15 PM ET
Executives
Jennifer Davis - IR
Lonnie Moulder - CEO
Tim Pearson - CFO
Mary Lynne Hedley - COO
Analysts
Alethia Young - Crédit Suisse
Peter Lawson - SunTrust
Seamus Fernandez - Leerink
Adnan Butt - RBC
Chris Raymond - Raymond James
Robyn Karnauskas - Citigroup
Andrew Barron - Morgan Stanley
Jim Birchenough - Wells Fargo
Boris Peaker - Cowen
Operator
Good afternoon, and welcome to the TESARO Fourth Quarter 2016 Conference Call. [Operator Instructions] As a reminder, this call is being recorded and webcast.
I'll now turn the call over to Jennifer Davis, Vice President of Investor Relations and Corporate Affairs at TESARO. Please go ahead.
Jennifer Davis
Thank you, Crystal. Good afternoon, and thank you for joining us today to discuss our recent business progress and TESARO's fourth quarter 2016 operating results. With me here today are CEO, Lonnie Moulder; our President and COO, Dr. Mary Lynne Hedley; and our CFO, Tim Pearson.
Earlier this afternoon, we issued a news release detailing our Q4 results. Please note that this news release and the slide presentation that we'll refer to during this conference call are both available in the Investors section of our website, www.tesarobio.com.
Before we begin, I'd like to remind you that discussions during this conference call will include forward-looking statements. These statements are subject to a number of risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. We undertake no obligation to update or revise any forward-looking statements for any reason. The factors that could cause actual results to differ are discussed in the press release issued today; and in our SEC filings, including our annual report on Form 10-K for the year ended December 31, 2016, and quarterly report on Form 10-Q for the quarter ended September 30, 2016.
During today's call, we may refer to certain non-GAAP financial measures that involve adjustments to GAAP figures. These non-GAAP financial measures are not a substitute for GAAP financial measures and are unlikely to be comparable to non-GAAP information provided by other companies. We believe non-GAAP measures may be useful to investors as a supplement to but not as a substitute for the applicable GAAP number.
I'd now like to turn the call over to Lonnie Moulder, CEO of TESARO. Lonnie?
Lonnie Moulder
Thank you, Jen, and thank you, everyone, for joining us this afternoon. I'll make a few introductory remarks about our recent accomplishments, and we'll provide a brief update on VARUBI, niraparib prelaunch preparations and our international expansion. Tim will discuss our financial results. Mary Lynne will provide an update on our development programs and strategy and then we'll open up the call for questions.
2016 was an incredible year for TESARO, and during the fourth quarter, we continued to execute on our mission of responsibly developing and commercializing transformative therapies for patients with cancer. I'd like to start by highlighting several recent accomplishments. In the U.S., we have now completed the first full year of VARUBI oral launch, and we plan to expand our VARUBI franchise with the introduction of an IV formulation later this year. The launch of VARUBI in the U.S. enabled us to put the commercial infrastructure in place to support future product launches. Recently, we completed a targeted expansion of our field organization in order to launch niraparib. Our U.S. field-based team is now comprised of approximately 175 associates including territory managers, health systems managers, medical science liaisons, nurse educators and account managers, all with deep oncology experience that will enable TESARO to reach community and hospital-based health care providers. This team of associates is excited to bring niraparib to patients and we are prepared to launch this important product in the first half of 2017 in the U.S.
Our niraparib expanded access program initiated in the U.S. in January, so that women with recurrent ovarian cancer have access to niraparib during regulatory review. Work continues with European regulators so that patients in Europe can also potentially benefit from niraparib during the MAA review process and subsequent negotiations with health authorities. Our international organization continues to expand and by year-end should include approximately 130 associates, who are intent upon globalizing our mission. Currently, this team is enthusiastically preparing to launch VARUBI and niraparib in 17 European countries.
We recently received a positive CHMP opinion for VARUBI and subject to final approval and completion of pricing and reimbursement discussions; we plan to launch this product in Europe on a country-by-country basis beginning next quarter. Potential EMA approval of niraparib and the initial anticipated launch are planned for the end of 2017. We continue to make excellent progress across our development portfolio, highlighted by progress with our niraparib clinical development program and in advancing our immuno-oncology candidates in the clinic. Mary Lynne will speak in greater detail about these programs and our plans later on in the call.
In summary, 2017 is off to an excellent start. We are excited about the opportunities that lie ahead this year, and we look forward to four potential new product launches, VARUBI IV and niraparib in the U.S. and oral VARUBI and niraparib in Europe. Turning to VARUBI; we continue to hear positive feedback from clinicians regarding the benefits of VARUBI for the prevention of delayed chemotherapy-induced nausea and vomiting, in particular for patients with breast, lung and ovarian cancers, who receive emetogenic chemotherapy regimen. The launch of oral VARUBI was just the first step in our broader strategy to drive growth for this brand. The expected U.S. launch of VARUBI IV later this year will allow us to reach the vast majority of the U.S. market and over time, extend the use of NK-1 receptor antagonist to the majority of patients receiving emetogenic chemotherapy regimen as recommended by the NCCN Guidelines.
With that, I'll turn the call over to our CFO, Tim Pearson, for a review of our fourth quarter and full-year financial results. Tim?
Tim Pearson
Thank you, Lonnie. The fourth quarter saw a significant unit growth over the third quarter with over 9,100 commercial doses of VARUBI shift from specialty distributors and specialty pharmacies. VARUBI experienced increasing demand, new account orders and increased penetration at key large practices over the quarter.
We believe that approximately 20% of the fourth quarter unit volume relates to buying ahead of our anticipated year-end price increase. Absent the impact of these speculative purchases, our unit growth over Q3 was approximately 40%. As such, we expect sequential unit volume growth for the first quarter of 2017 to moderate, as this inventory is utilized.
TESARO reported total revenue of $4.2 million for the fourth quarter of 2016. Net product revenue recognized during the fourth quarter was $2.5 million and included shipments of VARUBI made during the quarter to patients through our specialty pharmacy and to providers through our network of specialty distributors.
License, collaboration and other revenue totaled $1.8 million for the fourth quarter and included amortization of upfront payments and shipments of clinical materials under our license agreements with Hengrui and Janssen.
Research and development expenses increased to $71.5 million for the fourth quarter of 2016 compared to $42.9 million for the fourth quarter of 2015. The increase was driven primarily by higher costs related to the ongoing registration trials of niraparib, manufacturing and other research and development costs related to niraparib, advancements of our immuno-oncology portfolio and increased headcount.
Selling, general and administrative expenses increased to $54.5 million for the fourth quarter of 2016 compared to $27.9 million for the comparable period of 2015, primarily due to commercial activities in support of the launch of VARUBI; prelaunch activities related to niraparib; expansion of European commercial organization; increased headcount; and higher professional service fees. Acquired in-process research and development expenses totaled $9 million for the fourth quarter of 2016 and included milestone payments related to niraparib.
For the fourth quarter of 2016, TESARO reported a net loss of $136.9 million compared to a net loss of $75.8 million for the fourth quarter of 2015. For the full year of 2016, TESARO reported revenue of $44.8 million. Net loss totaled $387.5 million for 2016 compared to a net loss of $251.4 million for 2015. The increase in net loss for the full year of 2016 was driven primarily by the same increases in cost as mentioned for Q4; commercial initiatives for VARUBI, expanded development program activities and growth in our workforce.
As of December 31, 2016, TESARO had approximately $786 million in cash and cash equivalents, which included approximately $224 million in net proceeds from a follow-on offering of common stock completed in November. For the first half of 2017, we expect that our cash and cash equivalents balance will decrease by approximately $110 million to $120 million per quarter on average, excluding one-time regulatory milestones, totaling $35 million that are expected to be paid at the time of the first commercial sale of VARUBI oral in Europe and approval of niraparib in the U.S. In anticipation of 4 potential new product launches in 2017, TESARO will invest in prelaunch inventory manufacturing and development of supply chain capabilities and capacity in addition to making milestone payments for regulatory submissions.
With that, I'll hand the call over to Mary Lynne.
Mary Lynne Hedley
Thank you, Tim. I'll now review each of our development programs, beginning with VARUBI. We have completed the review process with EMA and a few days ago, EMA's Committee for Medicinal Products for Human Use, or the CHMP, branded a positive opinion for VARUBI oral. Our first European approval represents an important milestone for TESARO and subject to final approval and completion of pricing and reimbursement discussions, we plan to launch this product in Europe on a country-by-country basis beginning next quarter.
In January, the FDA issued a complete response letter concerning the IV formulation of rolapitant. In the CRL, FDA requested additional information regarding the in vitro release method utilized to demonstrate comparability of drug product produced at the 2 proposed commercial manufacturers for rolapitant IV that were included in the NDA. We are working expeditiously to provide these data, and we continue to expect approval of rolapitant IV in the first half of this year.
Turning now to niraparib, our PARP inhibitor. In October of last year, we submitted the niraparib MAA and NDA. In December, the FDA accepted the NDA for niraparib and assigned it a priority review designation. The MAA also accepted the niraparib application for review, and both of these applications continue to advance through the process. As you know, these submissions are based upon the results from NOVA, which was the first data from a successful prospectively designed, randomized Phase III trial for a PARP inhibitor in any tumor type. NOVA was designed to evaluate a single daily oral dose of niraparib in patients with recurrent ovarian cancer and to definitively assess which patients could benefit from a PARP inhibitor.
As we announced last year, positive results were achieved and a statistical and clinically meaningful improvement in progression free survival, or PFS, was observed in patients regardless of BRAC mutation or HRD status. As such, our proposed indication for clinical use includes patients with recurrent ovarian cancer, regardless of biomarker status. Ovarian cancer is a dreadful disease, for which there have been few therapeutic advances made in the past decade. The effectiveness of platinum-based chemotherapy diminishes over time, and PFS and platinum-free intervals generally become shorter after each round of platinum therapy. As a result, women with recurrent ovarian cancer have limited treatment options and often experience considerable anxiety about future recurrences. We believe that extending the response to platinum provides a meaningful benefit for patients, who today have few treatment options.
In addition to the improvement in median PFS, from our perspective, the NOVA results were compelling in other ways. The niraparib treatment effect was consistent and durable for each of the primary population studied. For example, 18 months following randomization, which is approximately 24 months post initiation of chemotherapy, the proportion of patients with or without a germline BRCA mutation, who are alive and without disease progression, was 50% and 30%, respectively, for patients on niraparib compared to only 16% and 12%, for patients receiving control. The hazard ratio for PFS represents a relative risk reduction of progression of death of 73% for patients with germline BRCA mutation and 55% for patients without a germline BRCA mutation.
Importantly, the effects are durable even at two years post initiation of chemotherapy. Patient reported outcome status showed that niraparib did not reduce the body of life in comparison to patients receiving a placebo control. For a patient population whose median disease progression is shorter than a year from the time they start IV-based chemotherapy, we believe this represents a significant improvement and offers hope to patients, who previously may have had none.
Although less than 20% of events had occurred at the time of the NOVA unblinding, and overall survival data were immature, the hazard ratio was 0.73 in favor of niraparib. Anticipating that the survival data would be immature at the time of database lock, we assessed other end points to address two relevant questions about the impact of niraparib treatment. First, the treatment with niraparib reduced the benefit of the subsequent therapy. And second, with a positive effect of niraparib prolonged. Both of these questions can be addressed by an examination of the PFS2 data. As a reminder, PFS is measured from the time of randomization to disease progression, and PFS2 is measured from the time of randomization all the way to the second disease progression, which, of course, occurs following progression on both niraparib and subsequent therapy.
So to address the first question, does niraparib reduce the benefit of subsequent therapy? For each patient, the PFS interval is subtracted from PFS2. The data for the niraparib in the control populations were then compared and the results for the two groups were found to be identical, clearly demonstrating that niraparib treatment does not resolve in a decreased benefit from subsequent therapy. Details associated with these analyses will be presented at an upcoming medical meeting.
Now the second question, is the benefit of niraparib treatment sustained? To address this question, we also look at PFS2. At the time of the NOVA unblinding, the PFS2 data were also immature given the relatively long PFS that patients experienced on niraparib. Only 30% to 50% of events have been captured for patients in the germline BRCA-mutant and non-germline BRCA-mutant cohorts, respectively. In other words, the events that had been captured at that time were from those patients, who had progressed relatively early on niraparib or controlled treatment. Nevertheless, data for this secondary endpoint were compelling with a hazard ratio of 0.48 for patients with germline BRCA mutation and 0.69 for patients without germline BRCA mutation.
In summary, niraparib treatment does not reduce the benefit of subsequent therapy and the benefits are sustained beyond disease progression. We believe the benefit of niraparib beyond those with BRCA mutations is in part due to the unique characteristics of the special molecule that are described by nonclinical and clinical data.
In nonclinical study, niraparib was shown to be highly permeable, allowing it to concentrate in the tumor relative to plasma and delivered selective near complete sustained PARP inhibition and a persistent anti-tumor effect. One dose of niraparib provides greater than 90% PARP inhibition for up to 24 hours in the tumor and produces tumor regressions, where other PARP inhibitors do not. The high permeability of niraparib enables it to concentrate in tumors despite efflux pump, such as P-gp, which can cause resistance to other PARP inhibitors. In clinical studies, niraparib was shown to be highly bio-available, broadly distributed and slowly cleared.
The combination of these effects may be most relevant to producing clinically meaningful outcomes in a broad patient population, where the majority of patients do not have tumors with a BRCA mutation. And those tumors are inherently more difficult to kill with a PARP inhibitor. We believe that based on clear differences in the clinical pharmacology and chemical properties between PARP inhibitors, the clinical activity of one PARP inhibitor cannot be extrapolated across the class, particularly into patients without BRCA mutations.
Looking ahead, given the NOVA data, we view niraparib as a potential franchise opportunity and are advancing this promising drug in a broad development program that includes different lines of therapy in ovarian cancer and other tumor type. We plan to assess the activity of niraparib as a monotherapy as well as in combination with other anticancer agents. First, in ovarian cancer, as you know, we have two ongoing registration trials; PRIMA and QUADRA. PRIMA is a global randomized controlled trial being conducted with our partners, ENGOT and GOG; in which 330 patients with ovarian cancer who have achieved a response to their first line of platinum-based chemotherapy are randomized two-to-one to receive niraparib or placebo. Hierarchical testing schema will be used to assess the primary endpoint of PFS. PFS in the HRD-positive patient population will be assessed first and if that achieves statistical significance, then PFS in the entire population will be assessed.
Moving now to QUADRA; this trial is also enrolling a broad population of patients, whose disease has progressed after receiving multiple lines of chemotherapy, including patients previously treated with PARP inhibitors. We intend to enroll approximately 125 patients, who are HRD positive and another 125, who are HRD negative. We anticipate approximately 50 to 60 patients in the HRD-positive population will have a tumor BRCA mutation.
Our intent is to analyze the response and the duration of response in each of these populations and assuming the results are positive; submit an application for niraparib label expansion. We expect to have data from this study in the second half of 2017. Beyond ovarian cancer, patients with germline BRCA-mutated breast cancer are enrolling in the Phase III BRAVO trial. We expect data from this study in the second half of the year and the NDA and MAA submissions to follow shortly thereafter. Niraparib is also being evaluated in 2 combination trials that include patients with ovarian cancer.
The TOPACIO combination trial of niraparib plus pembrolizumab, an anti-PD-1 antibody, continues to enroll patients, who have either recurrent platinum-resistant ovarian cancer or triple-negative breast cancer. Patients with these tumors have demonstrated low response rates to anti-PD-1 and PARP inhibitor monotherapies, and we hope to improve upon the clinical activity with this combination approach. The dose escalation phase of this study has been completed, and we have initiated cohort expansion, which includes approximately 48 patients in each cohort. Patients in this study are accruing rapidly and will be assessed for tumor response and the duration of response. Early data from the trial are encouraging, and we anticipate reporting these data at an upcoming medical meeting.
The AVANOVA study, which is being conducted by our ENGOT collaborators, is evaluating the combination of niraparib plus the VEGF receptor inhibitor bevacizumab in patients with recurrent ovarian cancer. The dose escalation phase of this study is complete, and patients are currently being enrolled and randomized to niraparib versus niraparib plus bevacizumab in the expansion phase of the study. The primary endpoint is PFS. Initial data reported at ASCO indicate that for the 12 patients enrolled in part 1 of the study, the median duration of treatment was 41.7 weeks. We anticipate that updated data from this study will be reported in the second half of the year.
Finally, regarding expansion of the niraparib franchise into other tumor types, the NOVA data suggests that a common denominator for niraparib activity is a genetic background that enables response to platinum. Such tumor types include non-small lung cancer, bladder and head and neck cancer. Recently, clinical data has led to the approval or pending approval of agents that target the PD-1 and PD-L1 axis in these indications. While these agents are effective, combination with niraparib, potentially immunoactive agents that induce this durable effect may increase the number of responders and potentially duration of benefit to these agents.
Our development strategies will incorporate recent shifts in the treatment paradigm for these tumors such that data from potential registration studies of niraparib will continue to be relevant upon their completion. We are finalizing the designs now and intend to initiate clinical studies in certain of these tumors this year.
And finally, turning to our immuno-oncology program. We expect that immuno-oncology products, including antibodies directed to PD-1, TIM-3 and LAG-3, will become a foundation of cancer therapy regimens across a variety of tumor types. Having all 3 of these antibodies in our pipeline provides a competitive advantage and allows TESARO to be well positioned to collaborate with others who may have complementary approaches. The foundation of our work in immuno-oncology is currently focused on the presence of checkpoints on exhausted T-cells and on the common belief that immuno-oncology approaches may be most effective when used in combination.
Clinical data for the currently available anti-PD-1 antibodies shows a relatively low response rate for most unselected tumor type on the order of 15% to 30%. Upregulation of checkpoint such as TIM-3 expression on PD-1-positive tumor-infiltrating T-cells inhibits proliferation and secretion of cytokines that are important for anti-tumor T-cell-mediated activity. TIM-3 expression on CD4-positive and CD8-positive tumor-infiltrating T-cell has been associated with the generation of an immunosuppressive tumor microenvironment and PD-1 resistant. Preexisting TIM-3 expression might contribute to the relatively low response rates for anti-PD-1 antibodies observed from multiple tumor types, including unselected non-small cell lung cancer. In vitro studies demonstrate that combination treatment of human T-cells with anti-PD-1 and anti-TIM-3 antibodies can reactivate the exhausted T-cells and increase production of immune promoting cytokines.
Phase I trials of TSR-042, our anti-PD-1 antibody; and TSR-022, our anti-TIM-3 antibody, are ongoing. For TSR-042, we have identified a dose and a schedule and are now enrolling expansion cohorts. And in the coming months, we plan to initiate a registration trial for this antibody.
Our TSR-022 anti-TIM-3 antibody is in the final dose escalation cohort and by midyear, we plan to identify a dose and schedule for TSR-022 and initiate combination studies with TSR-042 shortly thereafter.
Our anti-LAG-3 clinical candidate, TSR-033 is being evaluated in IND-enabling studies, and an IND is intended for the second quarter of this year. We've also selected an anti-LAG-3 PD-1 bio-specific antibody candidate and are on target to select our first clinical candidate as part of our small molecule, IO collaboration with MD Anderson in the first half of 2017. We are very excited about the potential for our pipeline, and we look forward to keeping you apprised of our progress.
I'll now turn the call over back over to Lonnie. Lonnie?
Lonnie Moulder
Thank you, Mary Lynne. In summary, TESARO is well positioned to continue to create value for patients and shareholders, and to execute on the launch of 4 new products this year. I'll wrap up with a brief summary of our goals for a very exciting 2017.
We plan to launch VARUBI IV and niraparib in the U.S. and VARUBI oral and niraparib in Europe, we anticipate multiple data readouts, including TOPACIO data at an upcoming medical meeting and QUADRA, BRAVO and AVANOVA data in the second half of the year. We will introduce our lung cancer plans for niraparib in the first half of the year and discuss the potential registration strategy for niraparib plus TSR-042 in combination in the second half of the year.
Turning to our IO, we expect to submit the IND for TSR-033 in the second quarter of 2017 and initiate a registration program for TSR-042 in the first half.
Finally, we plan to identify a dose and schedule for TSR-022, our anti-TIM-3 antibody in mid-2017 and initiate a Phase I clinical trial in combination with an anti-PD-1 antibody shortly thereafter.
Operator, at this point could you please open up the call for questions?
Question-and-Answer Session
Operator
Thank you. [Operator Instructions] And our first question comes from Olivier Young from Crédit Suisse. Your line is now open.
Alethia Young
This is Ale Young for Olivier, thank for taking my question. So just on the SOLO-2 trial, just wanted to get your thoughts on this. If the results were similar to get us in germline BRCA, how would you look at positioning yourself in the commercial landscape?
Lonnie Moulder
Well, clearly, if the Niraparib label is expanded to include the results for SOLO-2 data that would continue to be focused just in patients who have tumors for the BRCA mutation, which from our experience with the NOVA trial and looking at the Phase II elaborate trial in a similar population, is somewhere around 30%, whereas, we anticipate the broad label for Niraparib to cover the full recurrent population of patients who are following a response would receive Niraparib response from platinum. So I think having a label and a data set that covers about 3 times the population positions us extremely well. And it's not just the data, it's actually having a label, and then not having the cumbersome aspect of a biomarker test upfront. And, although NCCN guidelines suggested these women should all receive a BRCA test for genetic counseling and personal purposes is not always the case. And even if that does occur, it requires -- when prescription is written for product, before there is adjudication, there is prior authorizations, to ensure the biomarker had been assessed and the status of that biomarker, so we'd like the position that will have a potentially with a broad label, not encumbered with some of the points I just made and obviously, a much broader population and quite powerful data as Mary Lynne reviewed.
Operator
Thank you. Our next question comes from Peter Lawson from SunTrust.
Peter Lawson
Hey Lonnie, just a follow-up on the SOLO-2 question. Due to the formulations of the passage, do you think any way you get close to Niraparib?
Mary Lynne Hedley
Yes, Peter, this is Mary Lynne. I mean, with a 50% increase in exposure I think and, again, in a BRCA2 patient population, where we expect PARP inhibitors to be most effective. There's certainly reason to believe you will see an increase in activity over Study 19. So again, I think we have to wait and to see the data and to Lonnie's point, even if the data are as good as the NOVA data, the fact that we don't have a biomarker test if we don't anticipate having a biomarker test, and the fact that we have a much broader patent population that can gain accessed to niraparib, I think that I'd rather have that doing anything.
Peter Lawson
And then just given the evolution of the lung cancer treatment landscape, how do you think about position yourself in lung cancer?
Mary Lynne Hedley
Yes, so our original thought related to lung cancer were to focus primarily on the fact that lung cancer patients were -- and other tumor types were platinum sensitive. And if you look at the HRD data, so just basically, looking at how does the genetic makeup of those patients appears using an HRD test compared to let's say, ovarian and breast cancer. We see a reasonable amount of HRD. We see platinum responsiveness. And that suggests to us the genetic background is amenable to potentially treatment with niraparib. But we knew this space is moving rapidly towards combination therapy with PD-1. So we started the TOPACIO trial, many -- eventually before we have the NOVA data in part because we were thinking, where did we need to be in a couple of years, when we have NOVA data, as we were positive having data that would speak to the niraparib PD-1 combination potential will be very helpful to solidify our thinking related to moving into these other tumor types such as lung. So I would say, we've expanded beyond our -- simply on monotherapy type of approach in terms of our thinking and moved into a combination.
Operator
Thank you. Our next question comes from Seamus Fernandez from Leerink. Your line is open.
Seamus Fernandez
So, just a couple of questions; Lonnie, can you give us a general sense of how the VARUBI launch is progressing relative to your expectations with the oral, particularly, the comment that you made on the third quarter conference call that you guys expected at least in the oral space, to be the market leader, just wondering how that's tracking? And then on the IV VARUBI opportunity, how are you guys thinking about driving that conversion? The second question is for Mary Lynne. Can you just give us a general sense for the -- have you already filed an abstract with ASCO on TOPACIO, and did you already have data at the time of the February submissions? If you can't comment on that, can you just give as a general sense of what the thresholds investors should be thinking about for the sort of potential comparators in TOPACIO so the platinum-resistant patient population response rate there, and then response rates that one perhaps might anticipate in the triple-negative patient population.
Lonnie Moulder
Seamus regarding VARUBI, the oral launch. As Tim described, we've had a really nice growth fourth quarter-over-third quarter although there was some price speculation. So as people look at the IMS data, you could just take some of the data, about 20% of out of the fourth quarter and think about what that would have meant for the first quarter. So you'll have IMS data from January this week. But we -- our December shipments put us in a number one market share position of the oral NK-1 receptor antagonist category. That category continued to shrink quite a bit up until the time we launched. So it's actually less than 10%. It's high single-digits. So the vast majority of the market opportunity is in IV. We focused on community oncology clinics that had in-office dispensing operations, and I think that's been an effective strategy. Now with IV, we'll be able to broaden our efforts with our expanded commercial organization to many more community clinics that did not have an office dispensing, about half; and the hospital segment, now that we have health systems managers in place. So the opportunity for VARUBI IV, of course is substantially greater; the IV market is about 90% of the market opportunity. So having the share penetration of one year that I just described and [technical difficulty] tells us that clinicians like the drug, the drugs delivering the benefit, and they're using as much as they can in that limited segment of the market, and that goes well for the same molecule, but in a formulation that clearly people preferred in many of the clinics because they can't dispense to enroll drug and hospitals. So that sets up us well for the IV launch. Mary Lynne?
Mary Lynne Hedley
Yes, to answer to your questions, yes, 11% to 15% and 10% to 18%. But your questions, and more specifically just probably already [indiscernible] you might not remember, yes, we do submit an abstract to ASCO, yes, we did have data although data were preliminary. And the response rate that you can expect to see or has been reported actually previously, for anti-PD-1 antibodies and with this platinum-resistant ovarian cancer 11% to 15%, and then the triple-negative breast cancer residing is 10% to 18%.
Lonnie Moulder
And of course, it is something better than that for the combination.
Operator
Thank you. Our next question comes from Adnan Butt from RBC. Your line is open.
Adnan Butt
First, sort of procedural one on niraparib. Have you actually inspected the manufacturing facilities yet or something scheduled? And then secondly, in terms of the QUADRA study, would you be able to estimate how many patients in that study would be PARP inhibitor experience?
Mary Lynne Hedley
Sure. So I mean, just to start, we don't comment on the process the FDA is going through during the NDA review. As you can imagine, we try to keep those conversations with them confidential. I would just say that, things are progressing positively, and we're happy with where we are at this point. Related to QUADRA, we would estimate, at this point that and this is still early, but let's just say 10% or so of the patients have previously seen PARP inhibitor. There is a better than underestimate and that's the whole population when you look at the BRCA immune patients, obviously with patients who had a PARP inhibitor or BRCA immune patient population so it's a drop, it's a bigger number of the BRCA immune patient population.
Operator
Our next question comes from Chris Raymond from Raymond James.
Chris Raymond
Just a couple of questions on niraparib and the process in Europe. So just noticing on, it looks like a week or 2 ago, CHMP published that you've gotten your 120-day questions. And just wanted to clarify, did you get you guys have standard assessment in Europe, if you can just confirm that, is that correct? And then also, can you maybe describe, I know, you probably don’t want talk too much about the discussions there, but maybe, maybe generally talk about their attitude towards the necessity of the HRD test. Is it more similar to FDA stands? Or more similar to how I think how you think the FDA might view that? Or is it different?
Mary Lynne Hedley
So Chris, we do receive the 120 questions and as you noted, and that we do have a standard assessment, and we don't generally comment on how conversations are going with regulators is either FDA or EMA.
Operator
Thank you. Our next question comes from Robyn Karnauskas from Citigroup. Your line is open.
Robyn Karnauskas
Thank you and you just asking a little bit about your TIM-3 and PD-1. So can you give us a little bit more color about how we learn about the registration strategy for your PD-1 and when we can get initial data? And then for TIM-3, through a combination with another checkpoint, how do you think about that as a collaboration? Or would you just be paying for drugs? And when should we get data from data for the combination?
Mary Lynne Hedley
So, Robyn, as our registration study, we actually already have started that in mind, but we are trying not to be particularly vocal about that from our competitive advantage perspective. I mean, the way you can, I guess, I can give you some guidance and I know the way to think about it. So we think about it, we think about trying to come up with a study design which looks a little bit like NOVA in the sense that identify a patient population, a sub group within the population that you think might have a strong benefit, protect that population, and in the study design but go for the greater population where you might have a broader win in a more meaningful market opportunity. I know that's not probably not particularly satisfying but and the best I can do just at this point, I think for the lot of us is to just let you know that we have a strategy in mind. We've initiated work to just get sites up and running that would be able to contribute patients to that study, and we're well on our way, related to how we think will that 042 registered.
Related to things really TIM-3, we intend to develop with 042 as I indicated, we are planning to start those combination studies in the middle of this year and the way that we think about it is with this entire on one of the data sites that we showed you during this presentation. We have extensive amount of data looking at first tumor isolate across many tumor types and with many samples within the given tumor types to phenotype those samples and understand, A do they have T cells, B, what is the phenotype of those T cells, C what is the general immuno status of those tumor samples. And one of the sizes that you saw was the expression on lung setting out PD-1 TIM-3 and likely CD8 infiltrating T cells.
So to start out if there are no T cells for a PD-1 TIM-3 approach has been useless. If the T cells are there and a substantial number of the patients have expression of TIM-3 and PD-1 on their sub surface that might be a place where you can go into that tumor type unless PD-1 antibodies is already approved, compare PD-1 to a PD-1 plus TIM-3 approach and the goal there would be to hypothesis is that, of course, you don’t have higher response rates because the patients who already have TIM-3 on as a facilitator can't respond.
So by doing a combination approach, our goal will be to increase the number of patients, the percentage of patients who can respond and then, of course, the plans since we know TIM-3 is one mechanism of PD-1 resistant potentially in with the various in that response. This updates on this phenotypic-type analysis that we're getting from our deep understanding of this going on immune profiling in many tumor samples.
Operator
Thank you. Our next question comes from Tony Butler from Guggenheim. Your line is open.
Unidentified Analyst
Hi this is Katelyn [ph] on the line for Tony. So we've heard from previous comments you made regarding the difference in patient population between the solar and PRIMA trials. I was just wondering if you could refresh us on this a bit more? And then secondly, when do you expect the updated more mature PFS2 data from NOVA? And then lastly, moving beyond lung, how are you thinking of -- you had mentioned niraparib and PD-1 in bladder and head and neck cancer settings, and now are you thinking about right now, is that something kind of in the distant future?
Mary Lynne Hedley
Sure. So Katelyn for those SOLO-1 and PRIMA trials, one of the biggest -- the big difference is that SOLO-1 is done only in the germline BRCA -- in BRCA mutant patient population, and PRIMA given the results of NOVA, we decided to expand to the entire patient population of first-line patients in response to platinum. But we're stratifying so we're riding everybody in, but we're stratifying based on HRD and then the primary analysis is on the HRD proposition again, to sort of protect the patient population is most likely to benefit. And if those patients are positively do step down analysis to include the whole patient population. So it gives you so much better opportunity than simply the germline BRCA mutant patient population in Solar1. The other difference in the study that we think could be meaningful is the fact that we're not letting patients into the study if there is no visible evidence of disease so those would be the R0 patients for the oncologists. And the reason for that is because, in previous studies, of first line ovarian trials, it's the R0 patients with patients with no visible evidence of disease that don't have even 15% of patients with the ovarian cancer are cured for the surgery and outline chemotherapy. So we want to eliminate those patients from the study, which will do two things: one, we think increase the likelihood velocity to be able to demonstrate the difference and two, we'll be able to demonstrate that difference in a reasonable period of time. It's all about getting -- enriching the patient population that's most likely to benefit, but secondly and lastly, I guess, we think the risk benefit profile is slightly different in the first line than the recurrent, so the reason I said, because some patients are, in fact, cured. So we want to focus solely on the patients that we think the risk benefit profile is most appropriate and that would be the patient who cannot be cured. So those are primary differences. And the next question is related to, I believe, the PFS2 data and to see more mature PFS2 data. You know, we'll have to see how long it takes events to progress. So there were 50% to 70% of the advance in the PFS2 were actually censored. You could see it's a relatively immature data set and that was when we blinded the NOVA trial back in end of May last year. So I imagine, some point this year or early into next year, we'll be able to provide update data on both the PFS2 and survival. And then your last question was related to moving beyond lung into potentially other tumor types such as bladder and head and neck and I would look forward to that towards the end of this year, early next year. I think I got them all.
Operator
Thank you. Our next question comes from Andrew Barron from Morgan Stanley. Your line is open.
Andrew Barron
Sounds like you've been very busy obviously and lot of time I wonder if you sleep there at all.
Lonnie Moulder
Just in deed Andrew.
Mary Lynne Hedley
Contraindicated.
Andrew Barron
Just wanted to get some color on the breast cancer patients their role in TOPACIO, and I don't know if I'm pronouncing correctly, but did they receive platinum chemo ahead of time most of them? And were there any adjuvant patients?
Mary Lynne Hedley
Well, that's a great question, actually. So we did allow patients into the study, so first of all, we only have 13 patients at the very beginning and now expanding into the 48 patients per cohort. So the data set we have is obviously smaller initially but, yes, we do a lot of patients with previous platinum, that they could not have progressed on platinum, and I guess six -- I'm getting the number wrong, within six months or something like that of receiving platinum. So we allow it, but no, they can't just blow through the platinum, to put it more clearly, I guess. Related to whether we allow adjuvant patients and we do, so patients can have received up to two prior lines of therapy.
Andrew Barron
So there could be some adjuvant patients in there, but there also could be some patients that did not have platinum-based chemo ahead of us?
Mary Lynne Hedley
Correct.
Andrew Barron
Now that you're expanding it, are you going to limit that expansion to triple-negative patients? Or are you going to have patients that could be HER2-negative, but not triple negative?
Mary Lynne Hedley
It's just triple negative at this point. We're going to maintain some level of homogeneity in the patient population, get back data and [technical difficulty] they inform us how to expand beyond triple negative.
Andrew Barron
And just wanted to ask a follow-up question on the NOVA PFS question. Are the scans still ongoing for the patients in NOVA for progression?
Mary Lynne Hedley
No. So we don't do any additional PFS analysis, but the PFS2 analysis, that Katelyn asked about that's analysis that comes after progression on NOVA, so after PFS and then they get another round of chemotherapy whatever they're going to get and then we collect the data. So those data we can continue to collect.
Andrew Barron
So the 21.5 median number is going to be the final number in that trial, there'll be no updates?
Mary Lynne Hedley
Correct.
Operator
Thank you. Our next question comes from Jim Birchenough from Wells Fargo. Your line is open.
James Birchenough
So a couple on expected labeling for niraparib. What it reopen the possibility for repeat maintenance use? And either way, are you planning to study and is QUADRA sufficient to answer that question in patients who have received prior parts. And then just on the IO side, wondering if you can give us any sense of where the expansion cohorts are occurring, are they in patients, who've failed PD-1 or in populations that typically don't respond to PD-1? And then a final question, just on the bispecific approach. I didn't hear about the PD-1 TIM-3 bispecific but is that in the works as well?
Mary Lynne Hedley
So, Jim, related to the label specific indication wording, we're obviously not in a position to discuss at this point. And more to your real question, is QUADRA really the right price to assess parts after parts? It's one place. I mean another place that we are interested in better understanding and, in particular, in the maintenance side, how do you move from one maintenance. So chemo part, chemo part, chemo part, is that really doable. And so the concept would be to take the patients coming out of first line study -- first line maintenance study like PRIMA, and have them rolling to once they progress, roll into more than observational-like study to get that and provide niraparib to them to get that additional data. And then your last question, I believe is related to the PD-1 extension cohorts and now we are enrolling on PD-1 naïve as well as PD-1 experience patients. And actually, in the case of our 042 trials, those are PD-1 naive patients in extension cohorts in the case of our 022, 042 trials. We're actually thinking of enrolling both and the reason as you've acutely not set but are implying is that there are really 2 hypotheses to test and the first one is the one that I mentioned, which is the fact that if you have an inherent resistance because you expressed PD-1 anti-TIM-3 on the surface of infiltrating T cells, then providing that TIM-3 PD-1 combo upfront, is what we're trying to do to increase the response rate and duration. But we do know that patients generate resistance and one of the mechanisms as TIM-3, so can you take a PD-1 patient, who is progressed and there are a lot of lung and normal patients, in particular, who've progressed. And give them a PD-1 TIM-3 or just a TIM-3 and see what happens. We know in vitro, that a TIM-3 antibody can trump PD-1 meaning that we can just provide a TIM-3 antibody, and we can reactivate those cells. You don't need the PD-1. A question would be if that's true in the clinic and we don't know that yet. But will be able to with those extension cohorts to test both of those hypothesis. And your last question PD-1 lactate and those with PD-1 TIM-3, right now, we only had a PD-1 like to say biospecific.
James William Birchenough
Okay. Any reason for that, Mary Lynne?
Mary Lynne Hedley
This is technically we are not able to generate a PD-1 TIM-3 biospecific. It's not due to lack of interest that we weren't able to see all of our stating efforts to come up with one.
Operator
Thank you. And we will take our last question from Boris Peaker from Cowen. Your line is open.
Boris Peaker
I just had a question on subsequent therapy from the NOVA study, specifically if you look at the time to start-up subsequent therapy in the NOVA study in the BRCA positive patients. It was 21 months, which is the same as the PFS in the niraparib patients, which patients suggested that patients were started on subsequent therapy immediately after niraparib progression. However, if we look at the placebo patients, the medium PFS was 5.5 months while the time to subsequent therapy was 8.4. So there is about a 3 months gap from progression to start-up subsequent therapy. So can you first can you first confirm that we're interpreting the data correctly? And if so, why is there gap in placebo patients, while no gap in the niraparib patients?
Mary Lynne Hedley
Yes, we can't interpret it hesitate as shown in the chart. It's very difficult to rely on the medians because a few patients one way or another have really an impact. So we're trying to focus more on the overall picture and look at the hazard ratio, but even that as I said, there is immature at this point. So I think we just have to wait for some additional data. But there was no difference in terms of just operationally, starting patients up from niraparib to their next therapy versus starting patients from placebo to their next therapy. That was all the same from internal conductance perspective.
Boris Peaker
Thanks for clarifying that. And when we would get an updated result of this? Would it be publication or you think just would be a presentation at major medical meeting?
Mary Lynne Hedley
I suspect we would do both.
Boris Peaker
Got you. And the timing for that?
Mary Lynne Hedley
As I mentioned earlier, I think, that was towards the end of this year into next year. It's not, it's something that we'd like to do based on achieving a number of events. And then in particular, with the survival analysis because we don't want, every time we do the analysis, we find ourselves to rather wait longer in patient, but we rather wait longer for the purpose of preserving the data, the integrity of the data. So at this point, we still don't have a very large number of events, not many more than we had in a year ago, almost a year ago. So I guess, that’s a good sign, but.
Boris Peaker
You could provide an update maybe in HRD-negative, which I would imagine probably on lot more events since they progressed a lot faster? Or are you waiting for the entire population to progress?
Mary Lynne Hedley
At this time we have to make that specific decision, but we still don’t have enough events in either.
Operator
Thank you. And that does conclude our question-and-answer session. I would now like to turn the conference over Lonnie Moulder for any closing remarks.
Lonnie Moulder
Thank you, everyone. We appreciate your interest, and have a good evening.
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