Clovis Oncology, Inc.
Q4 2018 Earnings Call Transcript

Published: 27 Feb 2019

[Operator:]

Good morning. My name is Mariama and I will be your conference operator today. At this time, I would like to welcome everyone to the Clovis Oncology Q4, Year-End 2018 Financial Results Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. [Operator Instructions] Thank you. I would now like to turn the call over to Anna Sussman. You may begin your conference.

[Anna Sussman:]

Thank you, Mariama. Good morning, everyone. And welcome to the Clovis Oncology fourth quarter and full year 2018 conference call. You should have received the news released announcing our financial results. If not, it is available on our website. As a reminder, this conference call is being recorded and webcast. Our remarks may be accessed live on our website during the call and will be available in our archive for the next several weeks. The agenda for today's call is as follows. Patrick Mahaffy, Clovis' CEO and President, will discuss the key components of our corporate update provided in today's news release; then Dan Muehl, Executive Vice President of Finance and Principal Financial and Accounting Officer, will cover the financial results for the fourth quarter and full year in greater detail; Patrick will make a few closing remarks; and then, we'll open the call for Q&A. Before we begin, please note that, during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. All of these statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Please refer to our recent filings with the SEC for a full review of the risks and uncertainties associated with our business. Forward-looking statements speak only as of the date on which they are made, and Clovis undertakes no obligation to update or revise any forward-looking statements. Now, I'll turn the call over to Patrick Mahaffy.

[Patrick Mahaffy:]

Thanks, Anna. Welcome, everybody. Thank you for you joining us this morning. I'll begin with an update on the US launch of Rubraca in the recurring ovarian cancer maintenance treatment setting following its Q2 2018 FDA approval. We had a strong fourth quarter, reporting $30.4 million in US Rubraca sales compared to $17 million in Q4 2017. This does not include the $10.4 million in commercial value provided to eligible patients, primarily Medicare patients as free drug supply through our patient assistance program. For the full year 2018, we reported $95.4 million in US Rubraca sales, up from $55.5 million in 2017. This also does not include the $33.4 million in commercial value provided to eligible patients as free drugs through our patient assistance program. The supply of free drugs represents approximately 26% of overall commercial supply for both the fourth quarter and the full year. We're optimistic about Rubraca's potential in the second line maintenance indication. As we have discussed, PARP inhibitor penetration as a class still represents a minority of the patients eligible for second-line maintenance treatment. So, in addition to competing for market share, we also continue to compete against the ingrained habit of watch and wait as opposed to active maintenance treatment. To address this, we have a three-pronged strategy in place to continue to grow US sales of Rubraca in the maintenance setting. One, differentiate Rubraca clinically based on the strong data from the ARIEL3 study. Two, expand our use for current prescribers and add new prescribers. And three, and importantly, empower patients to ask for Rubraca and support them during their treatment. There's significant opportunity to grow Rubraca's US share by reaching the large number of patients as clinicians continue to utilize a watch and wait approach, as well as by addressing the perceived lack of differentiation among the marketed PARP inhibitors. The watch and wait approach continues to be the most widely followed practice, following second-line platinum therapy, despite numerous published data sets demonstrating that PARP inhibitors substantially better outcomes than placebo, the equivalent of watch and wait, in the platinum-sensitive second-line maintenance study. To provide additional support for active maintenance treatment therapy, we launched our Maintenhance messaging and direct promotional materials in the fourth quarter. This program highlights data from a prespecified exploratory analysis from the ARIEL3 study, demonstrating that not only can Rubraca maintain PFS, progression free survival, it may in some patients also further their response comes off platinum therapy, including converting some partial responses to complete responses. This message is resonating with physicians who see the opportunity for additional tumor shrinkage, while in the maintenance setting as both the tangible and meaningful benefit for their patients. In fact, in some respects, tumor response can be a more powerful message than what can be the more abstract concept of progression-free survival. This message is further supported by our regional account team, which educates key accounts about the significant gap in patient care and establishing the importance of second line maintenance therapy, as well as our nurse education group which counsels nurses and other practitioners on the importance of second line maintenance and the management of patients on Rubraca. We believe this two-part efficacy message, maintaining progression-free survival and the potential for further tumor shrinkage, will have a positive impact on our market share and on growing the market in general. We also recognize the importance of highlighting differentiation amongst the PARP inhibitors, especially at a time the players in the competitive landscape have changed. We actually have a great opportunity to reach prescribers with these messages right now and our team is motivated to do so. We're continuing to provide them with the tools they need, as well as to help ensure they are reaching appropriate audiences. As I mentioned earlier, the launch of the Maintenhance program is directed at physicians and designed to establish the importance of second line maintenance therapy and to distinguish our unique objective response rate data. To augment our physician-focused messaging, during the fourth quarter, we launched significant patient-focused resources into the marketplace. This includes an increased focus on digital and Internet-based activities. During the first quarter, we expanded this direct-to-consumer campaign to reach patients directly with the goal to drive awareness and, ultimately, utilization of Rubraca. This highly-targeted program now includes both television and social media. I'm not sure if any of you have seen this ad, but we've received good reviews from those who have. I'll turn now to discussing our recent EU approval for Rubraca in the maintenance and our upcoming German launch. I'm pleased that, in late January, the European Commission approved an expanded label for Rubraca which now includes second line or later maintenance treatment indication based on the ARIEL3 data. This will make Rubraca available to eligible patients regardless of their BRCA status. Rubraca was the first PARP inhibitor licensed for an ovarian cancer treatment indication in the EU and is now the first to be available for both treatment and maintenance treatment among eligible patients. Our initial launch of Rubraca will take place this Friday, March 1 in Germany, followed by other EU countries during the rest of 2019 and into 2020. The majority of additional hires, including sales reps in EU countries beyond Germany, will coincide with reimbursement approval in the individual countries and will occur in 2019 and into 2020, as will any meaningful revenues. We do maintain an early access program in a limited number of EU countries for Rucaparib for treatment and as maintenance therapy in recurrent ovarian cancer to allow access to Rucaparib for patients in need until the time the drug is commercially available. Let me turn now to clinical development. I'll begin with an update on our supplemental NDA submission for Rubraca as treatment for men with BRCA mutated advanced prostate cancer. Planned filing will be based on data from the TRITON2 study. We were pleased to present the initial and encouraging data from the TRITON2 study at ESMO and at the PCF Scientific Retreat last October, which were the data on which breakthrough therapy designation was granted in early October. I should note that the responses shown at ESMO were based on assessments made by enrolling physicians. We were pleased that, following ESMO, the response rate from an independent assessment of the TRITON2 patients were shown to be completely consistent with the investigator-assessed data presented at ESMO. We were targeting late 2019, pending data maturity, for our filing of the supplemental NDA for Rubraca for accelerated approval in men with BRCA-mutant metastatic castration resistant prostate cancer. Filing is based on RECIST responses. PSA responses will be included as supportive data. Following our meeting with the FDA at the end of January, we are encouraged that the FDA has agreed to maintain an active dialogue with us and will review data updates over the course of this year. This opportunity for a more informal and frequent interaction with the FDA is an advantage of breakthrough therapy designation. This could also facilitate a more rapid regulatory review since they will be familiar with the data. We expect that the next public data update will be the medical meeting in the fall, most likely at ESMO 2019 in Barcelona. It is important to note that the TRITON2 data we presented at ESMO 2018 still represents the largest reported population of advanced mutant BRCA metastatic castration-resistant prostate cancer patients using the endpoint of RECIST response, obviously, in patients with measurable disease. Based on recently reported data from a competitor running a similar trial, seeking a potential accelerated approval, and on the stated filing or acceptance data of another competitor, we remain confident that the timing of our sNDA filing will be highly competitive. Our second Clovis-sponsored prostate study is TRITON3, a randomized comparative Phase III study that includes patients who have a tumor germline or somatic BRCA or ATM mutation, who have progressed on AR-targeted therapy and not yet received chemotherapy in the metastatic castration-resistant setting. The study will compare Rubraca to physicians' choice of AR-targeted therapy or chemotherapy. The planned primary endpoint is radiologic, progression-free survival, and we anticipate the study would serve as a confirmatory study should the TRITON2 study data result in an accelerated approval. We continue to enroll patients into both TRITON2 and TRITON3. We are also very enthusiastic about our collaboration with Bristol-Myers Squibb with a study in prostate cancer as well as ovarian and bladder cancers. As part of that collaboration, a Phase II prostate cancer study initiated in late 2017 and is sponsored and conducted by BMS. The study will evaluate the safety and efficacy of Opdivo in combination with Rubraca in patients with metastatic castration-resistant prostate cancer and is being conducted as an arm in the BMS-sponsored CheckMate 9KD study. Importantly, the prostate study is enrolling BRCA, HRD and biomarker-negative patients and will generate preliminary data on the relative benefits of the combination in these distinct patient populations. Let me turn now to bladder cancer, another potential new indication for Rubraca. Our ATLAS study is a single-arm, Phase II, open-label study of Rubraca as monotherapy in recurrent metastatic bladder cancer. This is in an all-comers population with no selection based on BRCA or HRD status. Eligible patients are those who have failed one or two prior therapies. The study is currently enrolling patients and is designed to potentially support an accelerated approval. Given that bladder cancer is particularly responsive to platinum-based therapy and that we estimate approximately 60% of patients have tumors that are HRD, we're hopeful about the potential for Rubraca in this indication. The trial is enrolling quickly. And we anticipate completing enrollment in this study by Q3 2019 and plan to present an initial look at data at a fall 2019 medical meeting. We have also initiated the ARIES study, a Phase II open-label, multi-cohort study evaluating the combination of Rubraca and Opdivo in patients with locally advanced or metastatic bladder carcinoma, as well as separate cohorts of relapsed ovarian cancer patients. This is a Clovis-sponsored study and the most recent addition to our broad clinical collaboration with Bristol-Myers Squibb. Since ARIES includes both bladder and ovarian cohorts, it provides a good segue back to our ongoing clinical efforts in ovarian cancer. We are aware of the desire to see robust combination results for PARP inhibitors and I/O agents broadly and for Rubraca and Opdivo specifically. We are, therefore, pleased to get this study going and we're looking for an opportunity to provide initial data from ARIES during 2020. The ATHENA study is also part of our clinical collaboration with Bristol-Myers Squibb. This Clovis-sponsored study is a Phase III trial in advanced ovarian cancer in the frontline maintenance treatment setting and is currently enrolling patients. ATHENA will evaluate Rubraca plus Opdivo, Rubraca, Opdivo and placebo in newly diagnosed patients with stage III/IV high-grade ovarian, fallopian tube or primary peritoneal cancer who have completed platinum-based chemotherapy. The study in approximately 1,000 patients includes an all-comers population with a step-down statistical plan similar to ARIEL3. Additionally, the Clovis-sponsored ARIEL4, our confirmatory study versus chemotherapy in the mutant BRCA ovarian cancer treatment setting, continues to enroll. RUCA-J is our Clovis-sponsored Phase I Japanese study now enrolling patients. The study, with safety and PK as primary endpoints, has identified the recommended 600-milligram BID dose of Rucaparib in Japanese patients, which will enable development of a bridging strategy and inclusion of Japanese sites in planned or ongoing global studies. To wrap up our clinical development update for Rubraca, there are over 30 investigator-sponsored monotherapy or combination therapy studies in a variety of tumor types approved or underway. Let me spend just a few minutes describing lucitanib. Lucitanib is our oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3, platelet-derived growth factor receptors alpha and beta, and fibroblast growth factor receptors 1 through 3. We hold global rights, excluding China, for lucitanib. Recently, there have been very encouraging data in studies of a very similar drug to lucitanib that inhibits the same 3 VEGF, PDGF and FGF receptor pathways called LENVIMA or lenvatinib in combination with a PD-1 inhibitor – in this case, Keytruda. These data represent a validated and compelling hypothesis for the development of lucitanib in combination with a PD-1. We are pleased today to announce that we have agreed to furthering our clinical collaboration with Bristol-Myers Squibb, this time combining Opdivo with lucitanib. The Clovis-sponsored study of lucitanib, in combination with Opdivo, is planned in gynecological cancers initially and will begin enrolling in the first half of this year. We also intend to initiate a study of lucitanib in combination with Rucaparib in ovarian and other cancers based on encouraging data of VEGF inhibitors and PARP inhibitors in combination. This study is also expected to initiate in the first half of 2019. For a preclinical overview of lucitanib, please visit the Events and Presentations page on our website. And with that, I'll turn the call over to Dan to discuss fourth quarter and full-year 2018 financial results.

[Dan Muehl:]

All right. Thanks, Patrick. And good morning, everyone. Our fourth quarter and full-year 2018 financial results are included in today's press release. I'll review the highlights of our financial results and provide some additional commentary. Product revenue was $30.4 million for Q4 2018 and $95.4 million for the year ended 2018. This compares to $17 million in Q4 2017 and $55.5 million for the year ended 2017. This is a 78% quarterly increase year-over-year and a 72% annual increase for the year ended 2018. The number of weeks of inventory at our distributors at the end of Q4 was flat to Q3. The supply of free drug provided through our patient assistance programs totaled $10.4 million in commercial value during the quarter and $33.4 million for the full-year 2018. This represents approximately 26% of overall commercial supply for the quarter and the year. This percentage appears to have stabilized. We ended the fourth quarter and year with $520.1 million in cash, cash equivalents and available for sale securities. Cash used in operating activities was $82.7 million for Q4 2018 compared with $65.6 million for Q4 2017. The $82.7 million in cash used in Q4 2018 is a sequential increase from the cash used in Q3 2018 of $72.5 million. This is due to higher drug purchase costs of $22.7 million in Q4 2018 versus no drug purchase costs in Q3 2018. We reported a net loss of $99.3 million or $1.88 per share for Q4 2018 compared with $51.9 million or $1.04 per share for Q4 2017. Our Q4 2018 R&D expenses totaled $71.2 million compared to $38 million in Q4 2017. We anticipate that R&D expenses will continue to increase in 2019 as our planned clinical studies and development activities progress. Selling, general and administrative expenses totaled $49.1 million for Q4 2018 compared to $38.5 million in Q4 2017. We expect that SG&A expenses will also continue to increase in 2019 in support of our commercial activities related to Rubraca in the United States and in the EU. Now, I'll provide some color on Rubraca from a finance perspective. Revenue was recorded net of estimated rebates, chargebacks, discounts and other deductions, as well as estimated product returns. These gross-to-net adjustments totaled approximately 10% of gross revenue for Q4 and the full year of 2018. Gross-to-net adjustments are expected to be in the low-double digits as a percentage of gross revenue for 2019, assuming the distribution and payer mix remain consistent. And lastly, cost of product sales for the fourth quarter and the year was 23% of product revenue. Now, I'll turn the call back over to Pat.

[Patrick Mahaffy:]

Very good. Thanks, Dan. To close, we are pleased with our progress, having recently achieved several key milestones and with additional milestones anticipated in 2019. Our quarter-over-quarter sales growth was strong and we believe we're making inroads in both expanding the PARP market and increasing our share of the PARP inhibitor market through our marketing efforts and initiatives to date. With our EU maintenance approval in hand and our European infrastructure established, we will launch in Germany this Friday, March 1, and other EU countries will be added over the rest of 2019 and 2020 as we achieve reimbursement. Our robust prostate cancer development program continues to enroll patients in both TRITON2 and TRITON3. And based on the very encouraging initial data presented at ESMO and PCF for BRCA-mutant patients with advanced metastatic castration-resistant prostate cancer from TRITON2, we are targeting late 2019 for potential supplemental NDA filing pending data maturity. We're also planning to provide a data update from TRITON2 at a fall 2019 medical meeting, hopefully at ESMO. Our ATLAS bladder cancer study is enrolling patients quickly and we anticipate completion of enrollment by Q3 2019, with a first look at initial data at a fall 2019 medical meeting. Our combination studies of Rubraca and Opdivo through our clinical collaboration with Bristol-Myers Squibb are initiating or underway, including the ATHENA Phase III study in ovarian cancer, the CheckMate 9KD Phase II study in advanced prostate cancer, and the ARIES Phase II in bladder and ovarian cancers. I'm very pleased that we're furthering our clinical collaboration to include not only a combination study of lucitanib and Opdivo, but that we are also in active discussion of other tumor types for Rubraca and Opdivo combination studies. We are also very enthusiastic about our clinical development program for lucitanib that includes 2 combinations, one with Opdivo in gynecological cancers and one with Rubraca in ovarian cancer, both of which are expected to begin in the next several months. With that, I'll be happy to answer any questions you may have.

[Operator:]

[Operator Instructions]. Your first question comes from Tazeen Ahmad with Bank of America Merrill Lynch.

[Tazeen Ahmad:]

Hi, guys. Good morning. Thanks for taking my questions. I wanted to get some color from you on your thoughts on the prostate cancer space in general. So, all three companies that have PARPs in the space have advanced studies underway. And, Pat, I'm just hoping to get some color on how you think – I guess, number one, how you thought of the GALAHAD data that was recently presented and how you are thinking about potentially what everyone's timeline to filing might be?

[Patrick Mahaffy:]

Well, there's going to be an element of conjecture here, but here's what I think. We know that FDA is still looking for around 100 patients. And that drives our time line. We also know FDA is going to treat all sponsors exactly the same in terms of that requirement. So, when we saw the GALAHAD data, we saw their 37%, 38% response rate in mutant BRCA patients that compares to our 45%. So, let's even just say they are kind of similar. Certainly, it's not better. A side effect profile that was consistent with what we are used to seeing for niraparib. So, a constant theme of slightly higher incidence of grade 3 and grade 4 hematological tox. So, it's the same drug. It's niraparib. But I think what's most interesting is the data they presented with the November 10 cutoff date included 16 patients, BRCA patients, eligible for a RECIST response. And you'll recall that our cutoff for our ESMO presentation was in middle of April. So, eight months, seven months, whatever that is, earlier, with the 25 patients eligible at that time. So, it's clear. We are ahead in the enrollment. And I think it's important to note that the entire enrollment of that population, of 16 patients, seems to have occurred from using the new diagnostic they have over the course of when they reinitiated their study, GALAHAD, in December of 2017. They got to 16 eligible patients by November of '2018. Now, that's a look in the rearview mirror. I don't have any idea how you can use that to predict exactly where they're going to be. But I think that anybody would say that with 16 patients in February and a requirement of somewhere between 80 and 100, which they acknowledged in their presentation, they're not going to file in 2019. And at this present enrollment rate, it would be almost heroic for them to file in 2020. So, I feel really optimistic about what we've learned over the course of the last couple of months about our time relative to theirs. The second study that is profound, which is the AstraZeneca comparative study to either enzalutamide or abiraterone, the one you haven't already failed, and it's an interesting study. They have announced that they will have data at the end of this year and that they will file or be accepted for filing in the first half of 2020. It's worth spending a minute on the design of the study because I think it probably isn't one that's well understood. So, the study is designed with a 2

[Tazeen Ahmad:]

Okay. Thanks for all of that color, Pat. And then, just wanted to get your thoughts. We've talked in the past about the importance of being first to market. And based on what you said, it seems like you are still comfortable that based on what you know – you can't know everything about what everyone else's studies are – but based on what you know now, it seems like you still feel confident that that would still be a possibility here. Is that right?

[Patrick Mahaffy:]

Yeah, with the important caveat based on what we know. But based on the public statements by AstraZeneca and based on the data we saw and the totality of the data in 16 patients, yes, I'm still optimistic that we'll be first to market.

[Tazeen Ahmad:]

Okay, thank you.

[Patrick Mahaffy:]

Thank you.

[Operator:]

Your next question comes from Gena Wang with Barclays. Your line is open.

[Gena Wang:]

Thank you for taking my questions. The first one is regarding with BRCA revenue in 4Q. Pat, you also mentioned the strong quarter, mainly driven by better adherence. So, just wondering, what was the average time period patient on drug and how much improvement they had over time?

[Patrick Mahaffy:]

Yeah. It's a rolling number. And so, we won't get to a mature number until we've had a year or more from the launch of the maintenance indication. But at this time last year, we were a little over five months average duration. So, that was primarily, of course, with the treatment setting in a largely more advanced population. We're now a little over six and a half months average duration. So, I like the trend. And I think our team is optimistic that we'll be at seven months or better by the end of the year.

[Gena Wang:]

Okay. And then, another question regarding the EU launch expectation. So, how many EAP patients in the EU and how many in Germany? And how should we compare initial launch to Zejula European launch?

[Patrick Mahaffy:]

Well, I don't know exactly how to answer your question in terms of comparing our launch to the Zejula launch. Zejula did have a good launch in Germany. I think their last quarter where we saw their independent numbers – because now, of course, they are subsumed by GSK – I think they did somewhere between $12 million and $15 million in Q3 in EU, in predominantly German sales. So, that was a good launch for them. They did have a very active prelaunch program that enrolled about 200-some patients in a compassionate use program. And then, in Germany, you can convert those patients to commercial patients once you're approved. So, they seeded that launch very effectively. It was a little harder for us to do, given that they had already done that in Germany. Patient population in Germany, the incidence is about 6,000 to 8,000 patients every year. It's an important market. It's a market that is dominated by active intervention. And it's somewhat guideline-driven, but we're really enthusiastic about our potential in Germany. We have a good relationship now with the KOL community. Although we are formally launching on March 1, our launch symposium and a press conference to support that is on April 2 and 3. And I can't give a forecast for German sales, but we certainly are benchmarking ourselves against what was achieved by niraparib, given, of course, that they had a first in the market advantage.

[Gena Wang:]

Great. I'm just wondering, so if you can share with us how many EAP patient in Germany if you can share with us that number.

[Patrick Mahaffy:]

We haven't disclosed that. I will just say it's not very close to 200. It's substantially less than that.

[Gena Wang:]

Okay. And the last quick question, will you give 2019 guidance at some point?

[Patrick Mahaffy:]

There are a lot of moving parts in 2019. With the European launch, the impact of SOLO-1, the transition from TESARO to GSK. So, we clearly are not giving it today and we have not made a formal decision about whether we will or won't over the course of this year.

[Gena Wang:]

Okay. Thank you very much.

[Patrick Mahaffy:]

You bet.

[Operator:]

Your next question comes from Kennen MacKay with RBC Capital Markets. Your line is open.

[Kennen MacKay:]

Hi. Thanks for taking the question. I have a quick commercial question and then a couple of follow-ups on ATHENA and lucitanib. On the commercial perspective, I guess, from a regulatory and sort of US guideline perspective, I didn't see anything change in the ovarian cancer space as it relates to PARP inhibitors. So, could you maybe help us understand a little bit more what happened commercially between Q2 and Q3, which was slightly down versus Q4 which saw really impressive growth. And then, additionally, how much of the Q4 growth came from off-label use in prostate cancer after that very impressive ESMO data?

[Patrick Mahaffy:]

Yes. So, a couple of things about Q2 to Q3. To remind everybody, our sales were flat – marginally down actually in Q3 versus Q2. About $2.5 million, $2 million of that was a drawdown of inventory. Inventory levels have gone up in the launch quarter and there was kind of a drawdown from four weeks to three weeks from Q2 to Q3. That number was exactly flat three weeks and three weeks Q3 to Q4. So, there was no inventory impact on Q4. So, I'll just say that the Q3 looked a little worse than it really was in terms of demand, so just to contextualize it a little bit. We, obviously, are seeing some impact of our efforts to gain new patient starts and to gain share. And you saw some of that in Q4. But a lot of what you saw in Q4 was this improvement we have in duration. And I don't have any way to completely benchmark our duration in this setting versus either olaparib or niraparib. But I will say, we are seeing two things that are really encouraging. We're seeing very little in the way of dose interruptions or dose reductions. So, our average dose remains really close to the prescribed 600 milligrams. And so, that's encouraging in terms of keeping people on drug and managing them through any tox they may have. And related to that, we are seeing good duration. And so, I think that was the primary driver of our benefit in Q4. But it's encouraging in terms of the benefit physicians and patients are seeing on this drug.

[Kennen MacKay:]

Got you. And then, was there any off-label prostate use in Q4 after the ESMO trial? I would assume so, but just wondering if there is any color there that you can help us with?

[Patrick Mahaffy:]

Interestingly enough, I don't know when I should know, but I haven't asked. So, we're going to have to figure out a way to get back on that, but I don't have an actual number on prostate.

[Kennen MacKay:]

Got you. And maybe then, just a follow-up on ATHENA. Pat, you had mentioned the frontline maintenance trial has a statistical step-down plan like ARIEL3. Can you maybe elaborate on that just a little bit to help us understand sort of the powering at each level there?

[Patrick Mahaffy:]

Man, I haven't answered this question a long time. Lindsey, if you want to bail me out, I'd be happy to have you bail me out.

[Lindsey Rolfe:]

Sure. Hi, Kennen. I'll give you a top-level overview. So, basically, ATHENA is designed to answer two sets of questions. First set is around rucaparib compared with placebo in frontline switch maintenance. And the second set is around rucaparib plus nivo versus rucaparib in frontline switch maintenance. And those two concepts are tested separately and independently. So, the output is split between the two. In terms of the powering, clearly, the rucaparib versus placebo is loosely based and extrapolated from what we've seen in the recurrent part versus placebo comparison. And then, the doublet versus rucaparib is a bit different because there's an actual comparator, another placebo comparator. And we have really high expectations regarding the performance of the doublet. So, broadly, that's how it's set up. Does that answer your question?

[Kennen MacKay:]

Yeah, it does. That's really helpful. And maybe just one final question, if I may. Again, back to Pat. Since you are not issuing guidance at this time, maybe can I just ask sort of your level of comfort of around current consensus estimates for Rubraca in 2019, which are around $140 million to $150 million depending on which source you go from?

[Patrick Mahaffy:]

Well, I'm not going to answer that directly because we haven't given guidance. I would say that anybody who felt that they had no prayer of achieving a consensus would have to issue guidance to recognize that.

[Kennen MacKay:]

Fair enough. All right. I'll hop back in the queue with a final question on the VEGF please. But I'm going to let others ask their questions first. Thank you.

[Patrick Mahaffy:]

Thank you.

[Operator:]

Your next question comes from Cory Kasimov with JPMorgan. Your line is open.

[Cory Kasimov:]

Hey, good morning, Pat. Thanks for taking the questions. I wanted to go back to the frontline maintenance setting in ovarian. I know we've discussed this before, but can you talk about kind of your latest thoughts on how you see the recent approval of Lynparza there potentially impacting the downstream market. You alluded to this as one of the obvious moving parts for 2019. And then, as a continuation of that – I recognize this is probably a bit early, but do you have any sense of timelines yet for ATHENA? And I have one follow-up.

[Patrick Mahaffy:]

I'll do SOLO in a second. On ATHENA, we are tightening our timelines right now based on enrollment patterns and our analysis plan. And we intend to provide an update on the Q1 earnings call. So, stay tuned for a clarification of the timeline for that. With regard to SOLO-1, obviously, it's been well-received by the KOL and prescribing community, and it should be well received. In terms of its impact, a couple of things to remember. One is, it's directed at somewhere between 15% and 24% of the patients depending on physicians who will only use it in germline, others who will use it as it's indicated in germline and somatic. So, the impact does not carry over at all into the HRD or biomarker-negative population. Two, the downstream effects of it, I think will, one, be primarily to delay the initiation of second-line maintenance in patients who have benefited from olaparib in the frontline maintenance setting, but I don't think it will prevent second-line maintenance. And I don't think it's going to have a near-term effect because a woman who's already been through chemo and is three, four, five, six, seven months, whatever the timeline is, into her remission period is not likely to initiate therapy on olaparib in the maintenance setting. I think a large number of women who are presently getting platinum-based chemo and are mutant BRCA will get olaparib in the frontline maintenance setting, but the downstream flow, the kind of patient flow won't be very impactful for somewhere between 18 and 24 months. So, I don't think it's going to have a meaningful impact, but I want to validate that over the course of this year. One of the reasons I don't want to give guidance.

[Cory Kasimov:]

Okay.

[Patrick Mahaffy:]

And I think the general sense I get from all of – some of the market research we've done, but first the interactions with KOLs is that you're going to see a paradigm shift over time, which I think is actually really good in the second line maintenance market too, as people begin to adopt PARP inhibitor maintenance more broadly, is treatment with a platinum-based therapy, then PARP maintenance. Then if you do recur, platinum again, and then second-line maintenance. The enthusiasm and willingness to use PARP inhibitors sequentially is very high in this community. And I think it draws a little bit on their experience of using platinum-based therapy sequentially.

[Cory Kasimov:]

Okay. That's helpful. And then, the follow-up question I had is on the financial side of things. I just wanted to ask about the expected burn in 2019. It's, obviously, going to be highly dependent on Rubraca sales levels. But with both R&D and SG&A expected to continue to rise, any color you can provide on kind of thoughts around the company's cash runway?

[Dan Muehl:]

Yeah, Cory. So, similar to what we talked about last quarter where we guided that we had approximately two years' worth of cash. Again, depending on what revenues are over the next year or so, we do think that we have adequate cash get into the second half of 2020. And again, depending on revenue, whether that's – how far through 2020 it gets will depend on the revenue ramp.

[Cory Kasimov:]

Okay. Thanks, guys.

[Operator:]

Your next question comes from Asthika Goonewardene with Bloomberg Intelligence. Your line is open.

[Asthika Goonewardene:]

Hi. Good morning, guys. And thanks for taking my questions. I wanted to dig in a little bit on to lucitanib, please. So, given the similarities in targets that it has with lenvatinib, I wanted to just get your idea as to how you plan on differentiating this asset versus that, which is also being pursued in PD-1 combo studies. Specifically, what gynecological cancers are you targeting? I think that Merck already has a basket study underway, which includes ovarian cancer as well as a Phase III endometrial. And then related, what's the patent life on this asset? Thanks.

[Patrick Mahaffy:]

Yeah. I'll do the patent life really quickly first. So, the patent expires in the United States in 2030. And with Hatch-Waxman extensions will go to 2033 or 2034. So, it has a good, healthy life ahead of it. And that's the composition of matter. It has a similar – the patent expires a little bit earlier in Europe, but it has a longer extension period. So, we think that the timeline for patent protection will be similar in Europe, 2033, 2034. We are still finalizing our longer-term development plan. Maybe I'll turn it over to Lindsey for kind of a quick overview of initial thoughts and I may follow-up a little bit too. But, Lindsey, you want to address the first approaches?

[Lindsey Rolfe:]

Sure. So, Asthika, as you highlighted, this is a molecule and a program with a lot of potential. Of course, we are working hard to have a differentiated strategy. But it's worth noting, historically, with TKIs, that they often self-differentiate based on on-and-off target inhibition profiles. Our first trial indeed will focus on gynecological cancers. The first hurdle is to get a good dose of lucitanib plus nivo combined. I wouldn't anticipate that. That will be too difficult. But we need to test that first to establish a dose. And then, we'll be doing some single-arm expansion cohort in a spectrum of gynecological cancers, including endometrial and ovarian, but also adding cervical cancer and clear cell ovarian cancer. But that's just the beginning. As Pat highlighted, we're in a dynamic situation here. We are absolutely focused on differentiating a molecule. And we will plan to move beyond the gynecological setting into other cancer types where there's a good scientific rationale and where we believe we can offer clearly differentiated product.

[Asthika Goonewardene:]

Thanks, guys.

[Patrick Mahaffy:]

You bet.

[Operator:]

Your next question comes from Michael Schmidt with Guggenheim Partners. Your line is open.

[Yige Guo:]

Hi. Good morning. This is Yige Guo on for Michael. Thanks for taking our questions. We have two questions on bladder cancer. The first one is, according to the ESMO poster last year, ATLAS study has two interim analysis planned after 60 and 120 patients. So, should we assume data to be presented this year to include 60 patients? And are these patients previously treated with platinum? Are all the patients previously treated with platinum? Or are some of them are platinum naïve or ineligible? And I have a follow-up question after this.

[Patrick Mahaffy:]

Lindsey?

[Lindsey Rolfe:]

Well, I can't give you a breakdown of actual baseline data. But according to the protocol, patients have to have the current disease and they have to have had one or two previous lines of therapy. So, there certainly will be some checkpoint inhibitor naïve patients in there. I can't remember right now – and we can follow-up on this – if we mandate at least one line of platinum. But, definitely, they'll be checkpoint naïve, checkpoint both and we'll follow up on the platinum point.

[Yige Guo:]

Got you. Thank you. And I have a follow-up question on this. We've seen great efficacy of rucaparib in ovarian cancer patient who are sensitive to platinum, irrespective of BRCA or HRD mutation. However, in the second, third line urothelial cancer patients, many of them progressed after platinum treatment. So, that is to say they are resistant or refractory to platinum. And in ovarian cancer, PARP hasn't shown sensitivity in the platinum-resistant setting. So, maybe it's not a fair comparison where we're missing something here, but can you maybe help us understand the rationale of treating these urothelial cancer patients with rucaparib?

[Lindsey Rolfe:]

Well, as far as I know, this is the first study of any decent size. Indeed, the first study that's fully devoted to bladder cancer and monotherapy PARP inhibition. So, in that respect, it's a proof-of-concept study. It's a quite large study with 200 patients. And once we get the proof-of-concept data, we fully intend to mine it to really understand which of the patients and according to the molecular characteristics of the tumor and their response to previous therapy might benefit most from PARP inhibitor therapy. So, I don't have going into this study –because of the novel nature of the trial and the target, I haven't got a fixed set of assumptions, but for sure the study is robust enough and large enough to help us answer those important questions once we view the data.

[Yige Guo:]

Great. That's very helpful. Thank you.

[Anna Sussman:]

Operator, we have time for one more question.

[Operator:]

Thank you. Your next question comes from Kennen MacKay with RBC Capital Markets. Your line is open.

[Kennen MacKay:]

Hey, thanks for taking the follow-up here. This is just a quick one for Dan actually. The 23% COGS that you mentioned, this is a little bit high for a small molecule. Can you just remind us on the split between the royalty paid that's baked into the COGS and the actual cost of Rubraca manufacturing and production?

[Dan Muehl:]

Yes. The royalty is 15%.

[Kennen MacKay:]

Got you. Okay. Thank you. And then, the quick follow-up for Pat on lucitanib. When you had talked about sort of reviving this molecule, you're right, there had been a little bit of sort of a renaissance within the VEGF space. And you're comparing this quite a bit to LENVIMA. But we've also seen some setbacks, like with tivozanib and some of the challenges that that molecule has seen and the FDA recently advising them not to submit an NDA there. Can you maybe sort of talk about how this lucitanib is going to be sort of differentiated versus, for example, what happened with tivozanib?

[Patrick Mahaffy:]

I'll give a quick answer and then Lindsey should add or subtract from what I say. What I think is unique about lucitanib and related to lenvatinib is that it's – I'm the only one that calls it this, but it's a pangiogenic inhibitor – no one here likes that phrase, but I like it – because of its inhibition of VEGF, PDGF and FGF. And I don't know the details of the drug you've described, but what's further unique about the LENVIMA dataset is just how well it appears to deliver synergy in combination with a PD-1. So, we don't have any plans to develop lucitanib as a single agent. We're developing it solely in combination with either Opdivo now, where we're pleased to have extended our relationship with Bristol-Myers or with Rubraca, given the activity seen in an earlier trial with olaparib and a drug called cediranib, but where cediranib has a number of off-target effects, as Lindsey was kind of alluding to, that make it very difficult to take. So, I think we can use precedent combination studies and examples to guide us and hopefully avoid some of the pitfalls that may have faced other VEGF inhibitors. Lindsey, anything you'd say beyond that?

[Lindsey Rolfe:]

No. Obviously, I agree with you. I think that the key points are that this is a combination strategy; that as TKIs go, lucitanib has a relatively clean profile with relatively limited off-target effects. And we anticipate that that will set us up very well for a differentiated, well-tolerated, active regimen once we get the clinical program underway.

[Kennen MacKay:]

Got you. Thanks for taking the additional question. Congrats on the quarter.

[Patrick Mahaffy:]

Thanks, Kennen.

[Operator:]

There are no further questions at this time. I will now turn the call back over to Anna for closing remarks.

[Anna Sussman:]

Thanks, Mariama. We thank everyone today for your interest in Clovis. If you have any follow-up questions, please call me at 303-625-5022 or Breanna at 303-625-5023. Our call can be accessed via replay of our webcast at our website beginning in about an hour and it will be available for 30 days. Again, we appreciate your interest and time. Thank you and have a good day.

[Operator:]

This concludes today's conference call. You may now disconnect.