Clovis Oncology, Inc.
Q3 2019 Earnings Call Transcript

Published: 7 Nov 2019

[Operator:]

Ladies and gentlemen, thank you for standing by, and welcome to the Clovis Oncology Third Quarter 2019 Earnings Conference Call. At this time, all participants’ lines are in a listen-only mode. After the speakers’ presentation, there will be a question-and-answer session. [Operator Instructions]I would now like to hand the conference over to Ms. Breanna Burkart, Vice President, Investor Relations. Please go ahead.

[Breanna Burkart:]

Thank you, Simon. Good morning, and welcome to the Clovis Oncology third quarter 2019 conference call. Thank you for joining us.You have likely seen this morning's news release. If not, it is available on our website at www.clovisoncology.com. As a reminder, this conference call is being recorded and webcast. Remarks may be accessed live on our website during the call and will be available on our archive for the next several weeks.Today's agenda includes the following

[Patrick Mahaffy:]

Thanks, Breanna. Welcome, everybody. We appreciate you taking time.I'll begin with the commercial update for Rubraca. I'm pleased to report that our global revenue for this quarter was $37.6 million, up 14% over the last quarter and 65% over Q3 2018. This growth was driven by encouraging progress in new patient starts and in duration of use. We also continued to make slow progress in reducing the supply of free drugs. Our key near-term objectives remain the same

[Dan Muehl:]

Thanks, Pat, and good morning, everyone.The Q3 2019 financial results are included in today's press release. We reported net product revenue for Rubraca of $37.6 million for Q3 2019, which included U.S. net product revenue of $36.5 million and ex-U.S. net product revenue of $1.1 million, compared to the all U.S. net product revenue for Q3 2018 of $22.8 million. This represents a 14% increase over Q2 2019 and a 65% increase year-over-year.U.S. net product revenue increased 12% sequentially from Q2 2019 and 60% year-over-year. Ex-U.S. revenue increased sequentially from Q2 2019 to Q3 2019 as anticipated. The supply of free drug distributed to eligible patients through the Rubraca patient assistance program for Q3 2019 was lower at 20% of overall commercial supply compared to 22% in Q2 2019. This represented $9 million in commercial value for Q3 2019 compared to $9.3 million in Q2 2019.Gross to net adjustments were flat from Q2 2019 to Q3 2019 at 14.2% and 14.1%, respectively. Last quarter, we provided global net product revenue guidance for 2019 in the range of $137 million to $147 million for the full year. Today, we update that guidance to a range of $141 million to $147 million to reflect the potential for continued growth during the fourth quarter of 2019.Turning now to a discussion of cash. As of September 30th, we had $354.1 million in cash, cash equivalents, and available-for-sale securities. In August, we raised $255 million in net proceeds from a private placement sale of $263 million convertible notes due in 2024. A total of $171.8 million of those proceeds were used to repurchase $190.3 million of par value of convertible notes due in 2021, with the remaining $83.2 million available for general corporate purposes.In addition, as of September 30th, we still had upto $154 million remaining to draw under the TPG financing for the ATHENA clinical trial financing agreement to fund the expenses of ATHENA trial through Q3 2020.Based on the Company's anticipated revenues, spending, available financing sources and existing cash, cash equivalents and available-for-sale securities, we believe we have sufficient cash, cash equivalents and available-for-sale securities to fund our operating plan into the second half of 2021. This does not include any cash repayment that may be required to pay off, unless we refinance the remaining $97 million principal amount of convertible notes at their maturity in September 2021.Cash used in operating activities was $57 million for Q3 2019 and $253.5 million for the first nine months of 2019, compared to $72.5 million Q3 2018 and $283.3 million for the first nine months of 2018. It’s worth mentioning that on a sequential basis, Q3 operating cash used was 42% lower than Q2 2019.In addition to these decreases in cash used in operations, the TPG ATHENA financing provided $12.2 million in cash in Q3, resulting in a net cash reduction of $44.8 million during the quarter. We reported a net loss for Q3 2019 of $94.1 million or $1.72 per share and $300.9 million, or a net loss of $5.62 per share for the first nine months of 2019.Net loss for Q3 2018 was $89.9 million or $1.71 per share and $268.8 million or a net loss of $5.18 per share for the first nine months of 2018. Net loss for Q3 in the first nine months of 2019 included share-based compensation expense of $14 million and $41.7 million compared to $10.9 million and $37.7 million for the comparable periods of 2018.Research and development expenses totaled $77.9 million for Q3 2019 and $210.7 million for the first nine months of 2019, compared to $63.9 million and $160.1 million for the comparable periods in 2018. The increase is primarily due to higher research and development costs for rucaparib clinical trials.We expect research and development costs to trend lower for the full year starting in 2020 and in the following years, compared to 2019, as the largest of our sponsored clinical trials near completion and as the Company reduces spending related to clinical programs and other activities.Selling, general and administrative expenses totaled $41.8 million for Q3 2019 and $137.6 million for the first nine months of 2019, compared to $42.5 million and $126.6 million for the comparable periods in 2018. Selling, general and administrative expenses decreased year-over-year for Q3 2019 and also sequentially by 13%, from $48 million in Q2 2019 to $41.8 million in Q3 2019 based on cost reduction efforts by the Company.Now, I turn it back to Pat.

[Patrick Mahaffy:]

Thanks, Dan.We’re pleased with our progress in the third quarter. We demonstrated strong sales performance in the U.S. market with Rubraca, the second-line ovarian cancer maintenance setting, while we remained focused on growing our share of the ovarian cancer PARP space, as well as expanding the second-line maintenance PARP opportunity overall. We're seeing initial progress in the EU with Rubraca now reimbursed with the Cancer Drugs Fund in England, and we continue to focus on Germany and prepare to bring on additional EU countries later in 2019 and early 2020.In addition to our sales progress, we also showed a significant reduction in our net cash burn, which we reduced to $45 million in Q3. We presented updated data for Rubraca in advanced prostate cancer patients in September, and our Q4 2019 supplemental NDA filing in BRCA1/2-mutant advanced prostate cancer is planned before year-end with potential for U.S. revenues from the prostate indication beginning in mid-2020.Our clinical collaboration with BMS now includes the additional BMS-sponsored combination study of Opdivo and Yervoy with Rubraca in advanced gastric cancer as an arm of the FRACTION study, and we continue to have active discussions about other possible combination studies. We remain very enthusiastic about the potential for lucitanib with two combination studies now open for enrollment, one with Rubraca in advanced ovarian cancer as part of SEASTAR as well as one in combination with Opdivo with advanced gynecological cancers and other solid tumors. We also have initial data from these trials of medical meetings next year beginning as early as mid-2020. In addition to Phase 1/2 combination studies sponsored by BMS, we will evaluate lucitanib in combination with Opdivo in patients with stage IV non-small cell lung cancer that has spread or reoccurred after failure of chemotherapy and immunotherapy.And lastly, we're enthusiastic about the opportunity to develop FAP-2286 and potentially upto three additional preclinical ratings [ph] by therapies. 3B Pharmaceuticals is an expert in this emerging field, and through this collaboration, we believe we have the opportunity to become a leader in the development of an important modality for multiple tumor types.And with that, I'd be happy to answer any questions you may have.

[Operator:]

[Operator instructions] And your first question is from the line of Kennen MacKay with RBC Capital Markets. Please go ahead.

[Kennen MacKay:]

Hi. Thanks for taking my question. And congrats on the quarter and continued growth there. Dan, maybe just a quick question on your narrowed guidance and some of the commentary there. Last quarter, you provided some positive commentary that we could expect continued growth ahead. In Q3, we saw that. Just wondering if that's how we should be thinking about Q4? And again, whether the majority of the growth coming ahead in Q4 is coming from U.S. or Europe? And then, secondly, taking a very different strategy, bringing Rubraca to frontline ovarian versus some of the other competitive agents out there, as well as prostate, wondering maybe what the feedback from physicians has been on these combo therapy approaches in sort of broader patient populations, especially coming out of the ESMO conference where some of these I/O PARP combinations were really a focus?

[Dan Muehl:]

Sure. We did up the lower end of the range in our guidance. On the last call, I said, we were beginning to see some green shoots in the United States in terms of both commercial new patient starts and in terms of duration. And I think that is seen now in the Q3 numbers. We're cautiously optimistic. You'll note that we didn't take the lower end of our guidance markedly higher than what we delivered in Q3. And we’ve cautioned everybody that this is a quarter-by-quarter effort where we're really pleased with our progress and the effort being made in the field. But, it remains an effort to convince many physicians to move beyond observation or watch and wait and to consider active PARP therapy. And the more progress we make in converting those physicians and their patients, and frankly the more progress our classmates make in making that same effort, we’re going to see continued growth for the class and continued growth hopefully for us.We do anticipate now, as we launched formally under reimbursement in the UK. You may recall, we were selling in the UK to the sort of 5% to 6% of patients who were private pay, but that is pretty limited. Now, with reimbursement in the UK, we formally launched in October. We anticipate a launch in Italy before the end of the year. We anticipate launches in Spain and France in the first quarter. So, we will begin to see contribution to our growth in sales from these European countries.As to the frontline strategy, I think, the enrollment in the trial speaks to the enthusiasm physicians have for the potential for this combination. The enrollment in this 1,000-patient study will take somewhere probably less than two years to fully enroll, which is a really rapid trial enrollment, especially in light of competing trials and commercially available product for limited populations in this class. And if there's anything that came out of the important data presentations and the reaction to those data presentations at ESMO, particularly in the HRD and biomarker negative population, there is a need for combinations that can deliver greater duration of benefit and potentially a curative regimen, at least in the population of those treated. And I will say that the enthusiasm for the trial remains as high as it’s been, and for looking not only at the monotherapy results, which we’ll see first for Rubraca, but also looking beyond that to a combination of Opdivo.

[Kennen MacKay:]

And Pat, I think that was referring to ovarian, maybe also seemingly for the strategy in prostate, moving up in terms of sort of post chemo into some of the earlier lines of therapy there as well, potentially in combination.

[Patrick Mahaffy:]

We didn't have ton of conversation at ESMO about the combination of for instance PD-1 with Rubraca in prostate. There was a lot of focus on the TRITON2 results with great enthusiasm by both the medical oncology community and not so much at ESMO but in other meetings, then one-on-ones with urology community here in United States.I think that it’s interesting, if approved, it will be one of, if not the first approved in a targeted population in prostate. And the community is excited about having a targeted therapy that may provide meaningfully greater benefit than chemo or other agents in an all-comers population. And I think the adoption, unlike we’ve seen in maintenance in ovarian, which kind of cap out at 35% or 40% and now we're slowly gradually improving that, I think, given that this is a treatment regimen and particularly for men with an advanced stage of disease, I think we're going to see a much more rapid adoption for the class in the treatment of prostate. The enthusiasm for it is very high.

[Operator:]

Your next question is from the line of Tazeen Ahmad with Bank of America. Please go ahead.

[Tazeen Ahmad:]

Pat, just your view about the European market. We've talked now for a while about some of the dynamics that have impacted the ability of Rubraca to have uptake in the U.S. I was just wondering if you can share with us some of your thoughts about certain dynamics that might be specific to the European market, and how you're thinking about the general ramp opportunity there versus how it ramps here in the U.S. And then, I have a follow-up. Thanks.

[Patrick Mahaffy:]

Yes. It's going to be both, very similar and have some of its own nuances, and some of those will differ by territory. In general, the adoption of maintenance thus far, second-line maintenance in ovarian appears to be kind of following the U.S. example, where there is a group of early adopters that take adoption to a kind of 35% rate, and it's going to take an effort by us and our competitor and peers to drive that higher.It looks to us as I interpret and do a currency change to the GSK number in Europe that they're doing on an annualized basis around 135 million. So, they've seen some success in Europe in penetrating, and they're still in launch mode in several territories. So, I think, it represents the fact that there is an opportunity for us as we gain approvals in these territories to come into a market with a differentiated offering and some degree of physician population who are committed to and interested in prescribing PARP inhibitor in the second-line maintenance setting.One difference compared to the United States is that in certain countries, only niraparib is reimbursed for patients beyond BRCA. So, olaparib is reimbursed in all second-line maintenance patients who are in mutant BRCA but in only about half the territories do they have an approval for use beyond the RAC population. So, while we will continue to -- or plan to compete for those BRCA patients, the competition for the BRCA wild-type patients, which represent 75% of the patient population, is going to be limited to us and niraparib. So, there will be a different dynamic territory-by-territory. But, I think the sales performance by ZEJULA represents the fact that there is an opportunity in Europe, even at the much lower prices that were reimbursed at compared to in United States. And so, we look forward to these launches.

[Tazeen Ahmad:]

And then, on the commercial opportunity for prostate, you talked about some of your early thoughts about what kind of commercial organization you would need. And I just wanted to get some more updated thoughts from you about whether or not you can leverage any of your current sales force to move into prostate. And if you did need to increase your sales organization, by how much do you think you would need to do that and what would be your areas of focus at the early part of the launch?

[Patrick Mahaffy:]

Yes. We’re going to leverage all of our commercial organization in the United States to launch into the prostate market. And our intent now is not to add field-based personnel to support the launch. We have around 140 people in the field right now. We may increase it slightly. But, this includes a mix of sales reps, regional account managers that allow us to have a dialogue at both the business and physician level within large important centers, nurse educators to provide support for the nursing and administrative staff at the clinics, and of course not a commercial group but the MSL group is also in the field able to answer any medical inquiries. We think, we are well situated to address at all the medical oncology centers that we address today for Rubraca. And the focus for us will be primarily to the medical oncology community, but we do believe that for these larger urology practices that at history of for instance prescribing abiraterone and enzalutamide that the organization we have will be able to call on these, which are almost always adjacent to these large medical -- primarily academic hospitals.

[Tazeen Ahmad:]

Okay. Thank you.

[Patrick Mahaffy:]

You bet.

[Operator:]

Your next question is from the line of Gena Wang with Barclays. Please go ahead.

[Gena Wang:]

Thank you for taking my questions. The first one was the commercial question, since this quarter has a strong quarter, Pat, just wondering if you can give a little more color regarding how much is driven by the new patients and how much is driven by the longer treatment or duration of treatment drug?

[Patrick Mahaffy:]

It’s pretty hard to give you a distinct quantitative view of what the primary driver is. We are pleased with the new patient starts we’re seeing, and particularly to be fair, the commercial new patient starts, given the modest reduction in the amount of patients, number of patients or percentage of patients who are getting access to free drug through the FAP [ph] program. The duration continues to improve in relatively modest increments. But, we now know that duration of use is somewhere between -- it’s definitely over seven months, it’s probably around seven and half months. So, we think it’s continuing to improve. So, we will see a benefit as that continues. It does speak to the general tolerability. Rubraca, one of the things we talked about a lot is that, in oncology in United States, only about 50% go off therapy because they have progressive disease, may go off therapy because of side effects or because they're just having difficulty just being on continuous treatment. The fact that we're seeing this increase in duration kind of flies in the face of that speaks to the general tolerability of Rubraca.

[Gena Wang:]

Okay. And then, second question I have is CHECKMATE 9KD in prostate cancer trial, just wondering, having that the trial started already in 4Q ‘17, wondering when should we see the data.

[Patrick Mahaffy:]

Don't really have an answer for that. We have a great clinical collaboration with Bristol-Myers and a close relation to them, but they are in charge of both, enrollment in that trial, management of that trial. And any predicted time for any reported data from that trial is going to be on them. We don't really have the ability to say.

[Gena Wang:]

Maybe I rephrase, like the trial is still enrolling patients, do you have a sense or can you share with us like how many patients already enrolled and that benefit enrollment?

[Patrick Mahaffy:]

No. We're pretty comfortable with our policy of letting Bristol-Myers speak to their trial activities. The trial does continue to enroll. And I would imagine that when they have completed enrollment, that will go up on ClinicalTrials.gov and we would certainly report that as and when it does.

[Operator:]

Your next question is from the line of Cory Kasimov with JPMorgan. Please go ahead.

[Unidentified Analyst:]

Hi. This is Gavin on for Cory. Thanks for taking our questions. We had one on prostate as well actually. How are you viewing the prostate market with Astra in a similar timeframe, but with FPS data in a randomized trial, just trying to get your thoughts kind of on the potential competitive landscape there. Does this make that look more challenging, or are you confident enough in the TRITON2 data that we've seen. Thank you?

[Patrick Mahaffy:]

Yes. So, you're right. There will likely be two of us in the market in 2020. And can't know for sure when they or for that matter when we will be approved. But, we are opining as if we're going to be approved on a relatively consistent timeframe.It is true that their approval will be based on PFS, based on a randomized trial. It will also be true that the number of patients treated in that trial in their package, their NDA package is going to be the same or slightly lower in terms of number of BRCA1/2 patients. So, I think that it isn't necessarily going to be an advantage to come in with what is still a fairly limited data set compared to the package that will be submitted by the end of the year.As to PFS versus response rate, the reality is, these are both important endpoints to treating physicians. Response rate is a little easier for patients to understand because it's evidence that tumor is going away, which is what they really want to see. So, I've never believed that a somewhat more abstract endpoint like PFS is more important than response, which is how our patient thinks about what's happening inside his body. And further, what we both will probably focus on and certainly the treating physicians and patients will focus on is in fact PSA response. Now, those will be in the publications. That will be a subject of discussion. We did not see PSA data for AstraZeneca in their presentation at ESMO. I'm confident it's good. But, I would imagine that this is how most advanced, and for that matter, even earlier stage prostate cancer patients and their physicians think mostly about the benefit or sadly, the progression they're seeing on any given treatment.

[Operator:]

Your next question is from the line of Paul Choi with Goldman Sachs.

[Paul Choi:]

I had two pipeline questions on lucitanib. First, Pat, I think, I heard you say earlier that the initial data with Rubraca could potentially be seen mid next year but from the SEASTAR study. But, I was also wondering, what would the potential timing be for the combination arm with the sacituzumab govitecan ADC? Is that something we could see in 2020 as well? And if not, what is sort of a gating factor there?

[Patrick Mahaffy:]

I think, I said that we would expect to see -- hope to see data for -- just to be clear, for both, lucitanib plus Rubraca, and lucitanib plus Opdivo by middle of 2020. So, to be clear, there were two populations or regimens for which we hope to have data. We have to go and discuss with the team when we think we would have data for the combination with Immunomedics and I don't know to what extent the team has had much dialogue with Immunomedics. So, I'm not going to give you a date. I'm not going to give you a date for that combination. But, I would hope we would see initial data before the end of next year.

[Paul Choi:]

Okay, great. Thank you for that. And then, with regard to the combination with nivolumab, I think clin trials indicates that your initial starting dose for the lucitanib portion would be 6 mgs QD to start. And I guess, since in prior trials you down dosed it from 15 mgs down to 10 mgs, I guess, you should potentially have visibility on the go-forward dose for the Phase 2 dose expansion portion relatively quickly. Is that the right way to think about it? And when would you I think be in a position to sort of talk about the go forward Phase 2 dose for the nivolumab lucitanib combination? Thank you very much for taking our questions.

[Patrick Mahaffy:]

You bet. You're right. Starting dose was 6 mgs. And we purposely chose the dose. It was lower than what ultimately was the monotherapy dose of 10 mgs, with the belief that we would at least go up one dose level. By the end of this year, we’ll have treated patients at both 6 mgs and 8 mgs. My expectation is that around the end of the year, early next year, we will choose between the 6-mg and 8-mgs dose as our go forward dose. And that would be the time when we would initiate the expansion cohorts in gynecological and other solid tumors.At the time, we do initiate dose-expansion cohorts, we would, at [indiscernible] or at our February call make sure everyone is aware of the dose we chose, and the fact that we would at that time be beginning those expansion cohorts. But, that's kind of a general pipeline and the general does, but I would guesstimate are going to be one of the two doses we would choose to move forward.

[Operator:]

[Operator Instructions] Your next question is from the line of Andrew Berens with SVB Leerink. Please go ahead.

[Andrew Berens:]

Thanks. Hi, Pat. I just wanted to go a little deeper into the prostate opportunity and Lynparza. What are your expectations for their potential label in regards to ATM and what are the commercial applications, if they actually get ATM on their label?

[Patrick Mahaffy:]

So, I don't think they’re going to have any impact on the opportunity of mutant-BRCA if they have ATM or if they don't have ATM. These are going to be distinct populations, and physicians will make the choice about how they treat ATM patients in the same way they're going to make choice about how they treat BRCA patients.Obviously for them, and not just for them, potentially for us from TRITON3, the ATM population would nearly double the number of patients that would be eligible for PARP inhibitor therapy from 12% to 15% for mutant-BRCA to a total of something like 25%. So, as a commercial opportunity, it’s important. Its impact on the BRCA population I think will be limited.As to whether they get it in their label or not, it’s hard for us to interpret the data as they represented at ESMO. And it's important to us because it has implications for how we think about what may happen with TRITON3. So, we're obviously kind of conflicted. We never wish them well, because we're competitors. But, in this case, I kind of hope they get ATM because I think that would be good for us in the context of filing for approval based on TRITON3.So, the big issue is, what is the benefit in ATM patients and does it matter? So they definitely hit their primary end point of the combination population of BRCA in ATM population. So, that’s they hit it. The ATM data at the median, we didn't see hazard ratios or we didn't see the Kaplan-Meier curve, so we can't really dissect it, but at the median, showed pretty similar results in terms of median PFS. It's going to be up to FDA to decide how they're going to interpret that, and whether to go with the fact that they hit it for all-comers or -- all-comers being BRCA and ATM, or whether they're going to look at the distinct populations individually and determine for those subset populations, in this case BRCA and ATM what the benefit is. The benefit in BRCA2 was superb as one would expect, ATM not so much. And it's consistent with data we've reported and others have reported for olaparib. When you look at responses for patients on ATM, the one thing that would be really helpful to see in those curves is if there were a reasonable number of dropouts that were censored because of the PSA spike but didn't count as progressive disease because they never got to the point of radiological progression. So, if that number is a reasonably high number, that's going to impact on the FDA’s view of benefit in the ATM population. But, we weren't able to interpret those data; they didn't show them at ESMO

[Andrew Berens:]

Okay. Thanks for that color. Do you get a sense from physicians that if they do get the ATM and label, there could be the perception that Lynparza is a more active drug in prostate or is it going to be like ovarian cancer where most of the physicians feel like these drugs are basically the same on efficacy, or there may be some differences on safety tolerability?

[Patrick Mahaffy:]

I for sure [indiscernible] these are not, it’s going to be the latter. I don't think that evidence of a modest PFS benefit, and almost indistinguishable PFS benefit versus an unapproved agent in this indication, second-line abiraterone and enzalutamide is going to sway anybody's belief that PARP inhibitors as a class for all that active and ATM patients. I think, they're going to be seen as generally similar.

[Andrew Berens:]

Okay. And then, just one last one on prostate. Do you think set the bar at FDA could change based on the availability of a drug from a randomized trial with a PFS endpoint?

[Patrick Mahaffy:]

I don't have a lot to say about that. We're confident, based on the pre-sNDA meeting that we have a very good and encouraging dialogue with FDA and it is highly related to the data sets that we've presented them? So, I think that -- for instance if you're asking about an accelerated approval versus a full approval, you may note that on QUADRA data set, which was exceptionally limited data set, they actually achieved the full approval for that. So, FDA has a lot of discretion.

[Andrew Berens:]

Okay. And then, just one last question and I’ll jump back in the queue. Could you just give us some color on the free drug decrease in the patient assistance program? Is that an overall trend that we should see in the market in other drugs, and is it sustainable going forward?

[Patrick Mahaffy:]

If there is a trend, you see it’s a modest reduction in the use of path from 22% to 20%. So, it’s not dramatic. For us, what's important, it isn't the 26% we saw on average last year. I think, we are going to continue to see it slowly go down for two reasons, specific to second line ovarian and in our case Rubraca, one is, we've worked really closely with our third-party provider of this assistance program to ensure they are actively looking at multiple options for reimbursement for the patients. And so, I think we've done a better job of ensuring those who are not really eligible for the program don't benefit from the program. So, some of that is on us through efforts to make sure, those who truly needed, get the free drug, but those who don't, do not. And then, the second fact is, last year, after a little bit of funding in Q1 of the foundations that do provide co-pay assistance to patients in ovarian, that funding dried up and it was not existent for the majority of it, if not all of post January 2018. This most recent quarter and this year, it isn't every day and our providers check every day at the foundation, but there has been intermittent funding at the foundation. So, some additional support has been available to patients with Medicare in ovarian cancer.

[Andrew Berens:]

Okay. And I do just have one more question, if you allow me. You mentioned the program with Immunomedics and sacituzumab as being something in 2021 or beyond. What type of dosing protocol are you guys thinking about to limit some of the overlapping tox at…

[Patrick Mahaffy:]

First, I’ll say, I said I hope we had data by the end of next year. I just don’t want to commit you. But that's what I said is the end of '20 -- before the end of 2020. Lindsey is on the phone. And it might be better, Lindsey, if you answer the dosing strategy question?

[Dr. Lindsey Rolfe:]

Yes. You’re welcome, Pat. Thanks for the question, Andy. You're right. There are potential overlapping toxicities, and that means that we start with lower doses of both rucaparib and sacituzumab in the clinical trial. And, I would not anticipate that this would be a very straight forward path. But, we will make our way forward, adjusting the dose of one of both drugs, as necessary.

[Andrew Berens:]

Okay. Could it be like a maintenance-type setting, line in ovarian cancer?

[Dr. Lindsey Rolfe:]

Ultimately, we could consider that. But, the trial that we're doing at the moment is a practical Phase 1b portion that looks the treatment in patients who have exhausted standard therapies.

[Andrew Berens:]

Okay. Thanks for all the questions, guys, and congrats on growing the top-line and shrinking the expenses.

[Patrick Mahaffy:]

Thank you.

[Operator:]

Your next question is from the line of Joe Catanzaro with Piper Jaffray. Please go ahead.

[Joe Catanzaro:]

Hey, guys. Thanks for taking the question, and congrats on the nice quarter here. Just a quick one here on ATHENA. So, we’ve seen some other competitive frontline maintenance combination trials incorporate adaptive design that allows them to sort of adjust how they randomize patients, based on how standard of care evolves. And I'm talking about BRCA patients receiving PARP maintenance. And I'm just curious whether you're seeing any evidence from physicians with ATHENA and in terms of enrolling BRCA patients and potentially enrolling them on to non-PARP arms or has BRCA enrollment sort of preceded in line with your expectations?

[Patrick Mahaffy:]

Lindsey?

[Dr. Lindsey Rolfe:]

So, ATHENA is enrolling in very many countries. In some countries, PARP inhibitor is available as standard of care for frontline maintenance of patients with disease, and in many other countries, it’s not. So, generally speaking, in the countries where there is no standard PARP inhibitor therapy available, we're seeing rapid enrollments at or above the expected level. And then, in countries where is available correspondingly we’re seeing BRCA enrollment less frequently. But overall, the trial is designed to minimize any risks associated with that. And I'm confident with the statistical analysis that Pat described from HRP to ITP, and based on the strong results in frontline maintenance studies of other PARP inhibitors, not only in BRCA but also in BRCA wild-type HRD positive patients that we’re well-positioned for success.

[Joe Catanzaro:]

And then, maybe just one quick one for Dan on cash utilization. So, should we expect net cash in operations to continue along in line with what we saw this quarter or were there some onetime items that will go away?

[Dan Muehl:]

No one time items necessarily. But, we tried to give the end range -- into second half of ‘21 to address some of the volatility by quarter. But, we've guided previously to a lower cash burn on our last call. And so, it won’t be necessarily exactly the same. But, it's at a lower rate compared to what it was before.

[Operator:]

And today's final question will come from the line of Michael Schmidt with Guggenheim Securities. Please go ahead.

[UnidentifiedAnalyst:]

Hey. Good morning. This is CZ [ph] on for Michael. Thanks for taking our questions. Maybe two quick questions on TRITON2. You previously said FDA would want to run 100 RECIST evaluable BRCA patients for the sNDA. Just wondering, based on your latest interaction with the FDA in October, are you still targeting 100 patients to be included in the NDA package? And then, we also noticed there are some European clinical sites enrolling patients for TRITON2. Just wondering what's your -- if you can help us understand your EU strategy for prostate cancer. Are you -- more specifically, are you going to submit TRITON2 to EMA as well or do they require confirmatory Phase 3…

[Patrick Mahaffy:]

Yes. For the number of patients, I think, beginning in our May call, we said it's going to be in the range of 100. So, we haven't given a precise number. But you should assume that the number that we have available for the sNDA is acceptable to FDA, given our successful pre-sNDA meeting and.As for the European site, yes, we are enrolling patients in Europe in TRITON2, and for that matter in TRITON3. We are not optimistic that TRITON2 will be on something that we can use for a submission in the EU as we are assuming an approval in the U.S. We may approach the EMA for discussion. But you’re profoundly aware that EMA is not involved with single arm studies as the basis of an approval, and also TRITON3 is going to be near-term enough for us and it’s going to be a much more robust data set a large number of patients that we’ll likely to use TRITON3 as the basis, and the supporting from TRITON2. But TRITON3 is the basis of an ultimate EMA submission.

[Operator:]

And at this time, there are no further questions. Do you have any closing comments?

[Breanna Burkart:]

Thanks, Simon. So, we thank all of you for your interest in Clovis. If you have any follow-up questions, please call me at 303-625-5023 or Anna at 303-625-5022. The call will be available via replay on our webcast at the website, clovisoncology.com, beginning in about an hour. Thank you and have a good day.

[Operator:]

Ladies and gentlemen, that concludes the Clovis Oncology third quarter 2019 earnings conference call. Thank you for joining. You may now disconnect.