Clovis Oncology, Inc.
Q1 2017 Earnings Call Transcript

Published: 4 May 2017

[Operator:]

Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Clovis Oncology Incorporated First Quarter 2017 Earnings Conference Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session and instructions will follow at that time. [Operator Instructions] I would now like to introduce your host for today's presentation Ms. Anna Sussman. Ma'am, please begin.

[Anna Sussman:]

Thank you, Robert. Good afternoon everyone. Welcome to the Clovis Oncology first quarter 2017 conference call. You should have received the news release of announcing our first quarter results. If not, it's 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 webcast during the call and will be available in our archives for the next several weeks. The agenda for today's call is as follows

[Patrick Mahaffy:]

Thanks, Anna. Welcome everybody for joining us. I’d like to start with an update on the launch of Rubraca. We were very pleased with our first full quarter sales for Rubraca, which as you know is improved on December 19, 2016 by the FDA's monotherapy for the treatment of patients for the deleterious BRCA mutations associated advanced ovarian cancer who have been treated with two or more chemotherapies. We had our first Rubraca prescription written the day after approval and then our first full launch quarter, we achieved 7 million in net sales with over 350 new patients on therapy and equally impressive, we have over 300 unique healthcare providers who prescribed Rubraca during the first quarter. Patients who have refilled their descriptions, the average time to refill is 29 days. These are another initial patient data suggest the high adherence for the recommended dose and limited dose reductions that we've seen today. In fact, 94% of the dispensed volumes in the quarter were 300 milligram tablets and less than 10% of refills for down dose from 300 milligram to 200 milligram dose. These metrics of course have been absorbed early in the launch and may move around a bit. As we know in fact, we will see some dose reductions as this is common for all oral oncolytics. We’re therefore pleased to announce today that the FDA is now approved the 250 milligram Rubraca tablet. As a result, we have three tablets approved in United States 200, 250 and 300 milligrams strength, each of which is priced equivalently and provide physicians with maximum flexibility and options to reduce the dose, if and as needed. Fair coverage has been quite positive, as with other oral oncolytics launches Rubraca generally requires prior authorization and to-date 96% of new prescriptions have been efficiently processed and filled. Let me review a selection of prescription and utilization pattern today. You may remember from our February call, the best time 70% of Rubraca prescriptions were written by clinicians and academic institutions and about 30% were generated from community-based practices. The shift to a majority of the community-based prescriptions is occurring and for the first quarter 45% of Rubraca prescriptions were from academic institutions and 55% through community-based practices. We anticipate that the percentage of prescriptions from community-based practices will continue to grow overtime. 80% of our prescribers to date are clinicians who have previously prescribed rucaparib but approximately 20% of clinicians who treat the advanced ovarian cancer, but had not used the PARP inhibitor prior to Rubraca's approval. We are pleased to have seen this degree of market expansion this early in our launch. Overall, we’ll happy with the initial quarter of the Rubraca launch and in particular the feedback we were seeing from the field. We look forward to providing further update each quarter. Let me provide a quick update on our European submission for rucaparib, which is under review by the EMA for the same ovarian cancer treatment indication we submitted to the FDA. The review is progressing as we expected thus far and we anticipate an opinion from CHMP in late 2017. Pending a favorable opinion, we would expect a formal approval on early 2018. Given this timing, we are actively building our European commercial and medical affairs infrastructure. Of course, we already have regulatory, clinical safety and supply chain teams in place at our Cambridge, UK office. Turning now to the rucaparib development program, I'll start with our two confirmatory trials with the focus of course on ARIEL3. As announced in our news release this afternoon, we were notified by the Independent Data Monitoring Committee or IDMC that the ARIEL3 target progression events were achieved in mid April. Having received a certification, we have initiated final activities in preparation for the database lock and the release of top line results for ARIEL3. As we have stated before and as just comment, we anticipate that it will take approximately two months to conduct these final activities and total active database. As a result, we anticipate ARIEL3 top line results to be released by the end of June. We are well aware of the significant interest in these results which we share, and we'll seek to release sufficient information to inform investors about the results from this trial when we released the top line data, while preserving enough information to ensure acceptance for presentation at a scientific meeting this fall, hopefully it is note at early September. I know you know this, but we all other involved in the study other than the IDMC remain completely blinded to these results and will remain blinded for this approximately two months period. Pending positive data, we intend to submit a supplement NDA for the second line or later maintenance treatment indication for advanced ovarian cancer patients within four months or less of the database lock. Given the evident focused on this trial, I'll briefly review the trial design the ARIEL3 again. The ARIEL3 pivotal study is a randomized, double-blind study comparing the effects of rucaparib against placebo to evaluate whether rucaparib given as a maintenance treatment to platinum-sensitive patients can extend the period of time for which the disease is controlled after a partial or complete response to platinum-based therapy. Patients with high-grade serous ovarian cancer and have received two or more prior lines of platinum-based chemotherapy or randomized 2

[Dan Muehl:]

Thanks, Patrick, and good afternoon everyone. Our first quarter 2017 financial results are included in this afternoon press release. I'll review the highlights of our financial results and provide some additional commentary. Net product revenue was 7 million for our first four quarters sales. We ended the first quarter with 408.8 million in cash, cash equivalents and available for sales securities including net proceeds of $221.2 million from an operating of 5.75 million shares of common stock in January 2017. Cash used in operating activities was 80.4 million for the first quarter of 2017, 3.3 million lower than the prior year quarter. We reported a net loss of 58.5 million or $1.33 per share for the first quarter of 2017, this compares to 83.4 million or $2.17 per share for the comparable period in 2016. The reduction in net loss year-over-year was primarily due to lower R&D spending including balance sheet classification of rucaparib API or drug substance payments and prepaid deposits on future production, which we previously expense prior to product approval in December 2016, and higher net product revenues for the same quarter in 2016. Our first quarter 2017 R&D expenses totaled 32.4 million. This compares to 74.6 million for the comparable periods in 2016. The decrease year-over-year is primarily due to lower spending on rucaparib and rociletinib development activities and classifying as selling, general and administrative certain expenses related to commercialization of Rubraca that has been classified as Research & Development prior to FDA approval. Selling, general number administrative expenses totaled 29.2 million for the first quarter of 2017. This compares to 9.8 million for the comparable periods in 2016. The increase year-over-year is primarily due to classifying as selling, general and administrative certain expenses related to commercialization of Rubraca that has been classified as research and development prior to FDA approval. Operating expenses for the first quarter of 2017 includes share-based compensation totaling 8.9 million, compared to 11 million in the comparable period of 2016. Now I’ll provide some further color on Rubraca from a finance perspective. We distribute our product principally through a limited number of specialty distributor and specialty pharmacy providers. These customers subsequently resell products to patients and healthcare providers. Separately, we have arrangements with certain payers and other third parties that provide for government mandated and privately negotiated rebates, charge backs, and discounts. As previously net product revenue is 7 million for the quarter, revenue is recorded net of estimated rebates, charge backs, discounts and other deductions as well as estimated product returns known as gross to net, GTN adjustments, which total approximately 11% to gross revenue for the quarter. As revenue rise the growth to net adjustments are expected to decrease to high-single-digits as a percentage of growth revenue as the year progresses, assuming that the distribution and payer mix remain constant. We only recognize revenue on product sales, once the product is resold to the patient or healthcare provider by the specialty distributor especially pharmacy provider. Our distribution mix for the quarter was approximately 75% specialty pharmacy and 25% specialty distributor consistent with our expectations. And our payer mix is approximately 66% Commercial, 30% Medicare and 4% Medicaid in other also consistent with our expectations. Cost of sales for the quarter ended March 31, 2017 was 1.5 million or approximately 22% of net revenue and consist of costs associated with sale of Rubraca mainly freight, royalties, and amortization of capitalized acquired intangible license rate and milestone payments related to Rubraca. Based on our policy to expense costs associated with the manufacturer of our products prior to regulatory approval, certain of the costs Rubraca recognizes revenue during the year ended December 31, 2016 were expensed prior to the December 19, 2016 FDA approval. And therefore are not included in the cost of sales during the current period. We expect cost of sales to remain generally consistent in relation to product revenues as we deplete these inventories and amortize, capitalized, acquired, intangible license rights and milestone payments related to Rubraca. We expect to use the remaining pre-commercialization inventory for product sales through the third quarter of 2017. With the FDA approval of Rubraca all sales and marketing expenses associated with Rubraca are included in selling, general, and administrative expenses and no longer in R&D. This will have the impact of lowering R&D expenses on a comparable basis from 2016 to 2017. Clinical trial expenses were shift in composition in 2017 as well with the completion of all rociletinib trials and the winding down of ARIEL2, ARIEL3 Study 10 for rucaparib. The initiation of TRITON2 and TRITON3 and ARIEL4 and other company sponsored and investigator initiated trials Pat mentioned earlier, we begin to add the high levels of spending as 2017 progresses. Now, I'll turn the call back to Patrick for some closing remarks and we'll open it up for Q&A.

[Patrick Mahaffy:]

Thanks, Dan. It’s a very exciting time here with our initial launch of BRCA underway, ARIEL3 ARIEL3 data on the near term horizon and an anticipated CHMP opinion late this year followed by a potential EU approval and launch early next year. And it's hard enough to reflect to upon the fact that after many of these calls, turns out the next sign we will likely all be on the phone together will be to discuss ARIEL3 top line results. With that, I'll be happy to answer any questions you may have.

[Operator:]

[Operator Instructions] Our first question or comment comes from the line of Cory Kasimov of JPMorgan. Your line is open.

[Cory Kasimov:]

Hi, good afternoon Pat and thanks for taking the questions. I have two of them for you. First one is, do you plan to disclose the results specifically for the biomarker negative patients in addition the three primary analysis in that top line release in June?

[Patrick Mahaffy:]

We haven't fully landed on what all we’re going to provide. But, I would imagine that in addition to the three groups that we have already pre-specified in this statistical analysis plan. I am aware that there would be an interest including by us in activity in the biomarker negative population uniquely. And I would expect that we would provide those data.

[Cory Kasimov:]

Okay. And then my follow-up question is obviously the PARP market has just evolve very, very rapidly. I'm curious how you think this kind of continued evaluation or the impact to continue evaluation that we get once you get the results from first line maintenance later this year from studies like SOLO1?

[Patrick Mahaffy:]

So, again, SOLO1 is going to be limited to germline BRCA, but it also going to tell us story about whether that the pronounced activity other that have seen in the maintenance setting in more advance patients. So, we have fairly seen in the treatment study by even more impressive in patients with less advanced in their disease progression. So, we look forward to seeing those results. I can tell you that we and collaborators are incredibly excited about the combination studies we’re running and our European study with Avastin and in our plan PD1, PDL1 study. And one of the things that has happened and lot of the desire driven, but some of them is well rucaparib or PARP inhibitor driven is that there is a greater expectations that these combination at least in some patients could be curative. And this includes patients who have really no thought of curative regimens only two, three, four, five years ago. And so I think the evolution is going to be first in earlier line patients at ovarian then to include early line patient including PD1 or PDL1 and the enthusiasm for that is hard to describe. And then obviously we and others are seeking pretty substantially advanced PARP inhibitor therapy into other indication either is immunotherapy or increasing in our time studies in combination with the PD1 or PDL1. I would say that in my career obviously the most exciting thing that is happened has been IO. But right now, at least at this moment in time the second most talked about plasma compound is PARP inhibitor and the enthusiasm we see, the interest we see is incredibly high.

[Operator:]

Thank you. Our next question comes from the line of Alethia Young from Credit Suisse. Your line is open.

[Alethia Young:]

Hey guys thanks for taking my question. Two from me, just on the launch, I'm curious if you're seeing kind of any differences in like use between academic and the community positions. And then second, I was just curious if you can run through with us kind of your thoughts again on LOH versus HRD and are they more similar than different and have been had any incremental point kind of evidence on your side to kind of make you feel more comfortable or have greater confidence within confidence there? Thanks.

[Patrick Mahaffy:]

Sure. So first, I don't think we've seen much difference in the use between academics and the community setting. It's pretty early days it's three months or so, but I don't have any evidence that there is markedly different prescribing patterns in the community versus academic setting. So, the quick answer to that I think is no more to come as the launch evolves. As through LOH versus HRD, I probably have 15 answers to that, but I'll try to make it quick. So, we do not believe that there is going to be a meaningful difference in the patients identified as HRD from the Myriad test versus LOH from the Foundation test with the one exception that patients with somatic mutations of BRCA are included in our definition of BRCA in the tissue BRCA test that is conducted by Foundation. And those patients are in included in the definition of HRD and in the definition by Myriad and used by Tesaro in the Noble study. But broken out, so you can see the pure HRD which was helpful interestingly enough given the label it appears that while we clearly will describe to you HRD outcomes or LOH outcomes. And as I think Cory was noting, there is probably going to be more entrant to what the outcomes are in the non-BRCA patients versus the BRCA patients because that's the way the label for Tesaro is delineated. So, I don't anticipate much of the difference. I think the greater interest is going to be on the all comers, the all comers non-BRCA population.

[Operator:]

Thank you. Our next question comes from the line of Peter Lawson from SunTrust Robinson. Your line is open.

[Peter Lawson:]

Wonder if you could give us any details about how BRCA is being used with the recent whether you think also in the maintenance setting being used in treatment of second line versus later lines will be great?

[Patrick Mahaffy:]

We don't capture perfect data and we tend to leave off more anecdote than we do perfect data. We do get a lot of questions about given that it's two prior chemotherapies that can be used in patients who may only have had some combination of carbo and taxel or maybe with bev. We certainly have physicians who don't really believe that there is a well delineated in the real world population of maintenance versus treatment. And we get physicians who are quite open to using it when they feel the patient is going to benefit having to follow a platinum-based regimen and benefited from a platinum-based regimen, which could be pretty early, which I guess would classified more in the maintenance, but we know it's been used in that setting or patients who fairly are progressing where it would be absolutely defined as treatment. I do think this is a well delineated zone for the purposes of regulators and clinical trials but a much less well delineated zone in the world of treatment especially women who now have been through two rounds of chemotherapy and who are clearly inevitably sadly likely to progress.

[Peter Lawson:]

Got you. Thank you. And then just, are you seeing physicians switching from positive use?

[Patrick Mahaffy:]

We have heard that patient have switched and again I don’t have data, I have anecdotes. But clearly some of our sites -- I tend to go out and meet with our local commercial teams who are in New York or L.A or Boston and whatever. And clearly there are patients who switched from olaparib to rucaparib, I think that’s driven by two things. One is as you know at this moment in time and this will change when they have approval for their tablets. But at this moment in time, the pill burden or capsule burden to olaparib is fairly difficult for any women to tolerate. So, they can drive a decision to change. We are still going to see patients who are beginning to progress on a PARP inhibitor consider on alternative PARP inhibitor. And the data suggest expectations should be relatively low for a meaningful effect in those patients, but obviously at that moment physicians and patients are desired or trying whatever they can.

[Operator:]

Thank you. Our next question or comment comes from the line of [indiscernible]. Your line is open.

[Unidentified Participant:]

So first of all, there is subgroup analysis in patients with low residual disease burden, which and many of this could be similar to the Nova population. Would you be putting that out initially or that kind of being benchmark for the ASMO meeting?

[Patrick Mahaffy:]

Yes. I’m determine that what comfortable that to tell everybody, what we plan to putting that flexibly, because partly, because we don’t really know, what we put that press release. But having very clear that we think, that could be important in the event. It is important. We will likely have it in the press release. If the results are largely similar to intend to pre-population, we would probably say that, we would say so and save that for scientific presentation.

[Unidentified Participant:]

Great. And then any thoughts on because obviously it’s slightly different tests in terms of the loss of heterozygosity 16% in the Phase 2 versus 14% here, do you think companion diagnostic comes to play or do you expect the label to be very Tesaro without a companion diagnostic burden?

[Patrick Mahaffy:]

Well, that’s an important question that is an answerable today. So in the event that we have shown similar outcome in both the HRD population, but also that has dated in the all comers population. I would expect that we were follow a very similar path as they get did and their interactions with the regulators. So it's highly dependent on the data but if our data are equally robust and the all comers non-BRCA population then I think it will probably follow a similar path.

[Unidentified Analyst:]

And okay in terms of the checkpoint inhibitor combos, this might be a weird question, but does any feedback from KOLs regarding the somatic mutation burden has? Does that increase with your number of chemo regimens that patients have had before? We've seen some of that in prostate cancer, does that also happens here in ovarian cancer? And in which case, what makes more sense? And both with PD1s early on or later down the road?

[Patrick Mahaffy:]

Well, it clearly works for in early on in the maintenance setting. We uniquely I think or maybe not uniquely because I know uniquely had fairly good data where because in ARIEL2 we mandated that not only would begin archival tissue, but we would also get tissue at the time of enrollment in the trial. We were concerned or curious or some word about whether or not there will be a large increase in the number of somatic mutations or even in the definition of HRD in relationship to disease progression and to the effect of rounds of chemotherapy. And we did not see very much at all in the way of differences between those mutations and archival tissue, which would have been initial diagnosis and following several rounds of therapy. So, we don't think in ovarian they're likely to be a meaningful number of differences. It maybe that it is pronounced in prostate and you're right, both the percentage of germline and somatic patients in prostate cancer increases pretty significantly by round of therapy. But what physicians believe is that is less likely to be in response to therapy, but those somatic and germline mutations of BRCA in prostate cancer patients are a really poor prognostic factor. And so you've seen enrichment in later line and progressing patients for those who have that poor prognostic factor. And so because of it may not be exactly what you think, it makes us bigger than enrichment for these patients who unfortunately or more likely to progress and progress into metastatic disease.

[Unidentified Analyst:]

Great. Thank you so much. And one last question in terms of timing of data and powering of the bev plus chemo plus BRCA study? Thank you for taking my questions.

[Patrick Mahaffy:]

Okay.

[Operator:]

Go ahead sir.

[Patrick Mahaffy:]

I think that was a question to me. I can't say for sure when the timing of that study will be and I don't have full knowledge on the powering that. I'm pretty sure it was 80% powered to show hazard ratio of at least 0.5. But we'll figure out a way to make that to review in the next couple of days. We don’t control enrollment or timing of that trial because it's a cooperative group in Italy that is running it. But we know and I think I just met with the investigator with the PI in the last month or so that there is a tremendous amount of enthusiasm for enrollment in that trial, participation in that trial. And I know that I can do that because this will then happens to be the highest individual enroller in the ARIEL3 study. So they are good enrollers.

[Operator:]

Thank you. Our next question or comment comes from the line of Steven Breazzano from Piper Jaffray. Your line is open.

[Steven Breazzano:]

Hi thanks guys. From me, how long from the data release would be expect for publication in the scientific general incorporation into NCCN Guidelines? And could this be concurrent with presentation on a scientific conference like ASMO?

[Patrick Mahaffy:]

Well, we have an impressive presence. We were impressed that Tesaro was able get the New England Journal publication and exactly the same time as our ASMO presentation. And it goes without saying that we here are challenged to deliver similar outcomes. So, we are going to do our best. I mean I can't predict this. I suspect the robustness of the data will drive the enthusiasm for publication, but we clearly are going to try to be in the similar zone as to the timing of potential NCCN Guidelines. I’m sure you’re aware that NCCN Guidelines do require publications or highly incentive to have that publication is rapidly as we can and I would hope that within the matter of relatively small number of months, smaller in publication. Again, if the data is robust as we all hope that it would make it into NCCN Guidelines.

[Operator:]

Thank you. Our next question or comment comes from the line of Terence Flynn from Goldman Sachs. Your line is open.

[Terence Flynn:]

Hi. Thanks for taking the question. Maybe two from me. First just wondering Patrick, if you can remind us on just where your confidence in the prostate cancer opportunity comes from, give us a sense of what data is out there that drive that? And then the second question I might have missed at the beginning was the breadth of prescribing for rucaparib. What have you seen so far with respect to your target population in the U.S.? Thanks.

[Patrick Mahaffy:]

Sure. Well, for prostate I’d say couple of things. We have as others do pretty impressive anecdotes of efficacy in our Phase 1 study as well in certain patients who under compassionate use availability of rucaparib where it used to treat prostate cancer patients. And in fact this is clearly an anecdote Terence, but it was a really great moment when a physician forwarded me a letter that a patient wrote where he called himself the comeback kid and he wanted to send to me for sharing with me and my colleagues here where he was a PS2 -- effectively a PS3, he was on oxygen, he was in a wheelchair and he was sending, he was about to be sent to hospice. And after six weeks have been with prostate cancer and after about four of five weeks of therapy, he walked into the clinic, no oxygen, fully mobile and had dramatically lower PSA response. Because of that thing that that impressed the physician to the point that he was our European PI now in the TRITON2 and TRITON3 study. More importantly, the De Bono paper that was published in December ’15, which looked at the lack of outcomes with somewhat complicated definition of response including PSA response and CTC response, but also and a small number of pay to do this for with fixed response to really pronounce affect on and that was in the New England Journal. It clearly has activated the prostate cancer community to the point where in interest and enthusiasm to participate in this trial is incredibly exciting. And I know that the Prostate Cancer Foundation, which we hold enormous influence in this setting has prioritized the importance of both BRCA testing and the possibly use of PARP inhibitors in the treatment of prostate cancer. So this is a well regarded opportunity and classic compound in the treatment of at least BRCA mutated, ATM mutated and potentially other HR related mutations in prostate cancer. And I will say one last thing about that, I think that the relationship of a PARP inhibitor to activity in BRCA mutated patients now is really well established at least for this group of very active PARP inhibitors of course rucaparib amongst those. With regard to the breadth of the prescribers, I think that I may have mentioned that in the script, I was really happy we have 350 independent per unique prescribers of rucaparib just in the first quarter alone. So, I think our reach is impressive than I anticipated that will be of course higher as we continue on our launch.

[Operator:]

Thank you. Our next question or comment comes from the line of Tom Shrader from Stifel. Your line is open.

[Tom Shrader:]

Good afternoon, let me add my congratulations. I couldn't tell if you answered this question earlier, so I want to try again. Is line of treatment driving a lot of your use and I guess what I'm really asking is, are you treating a lot of mostly early patients because they can get the drug on label earlier or it is that kind of relevant to physicians and they just like the drug?

[Patrick Mahaffy:]

I think they like the drug, I think that we don't have perfect information about -- we get questions from physicians. We don't know with profession or with detail whether the patient would have had two prior chemotherapies or two prior lines of therapy. We know what our label says. I think overtime, we'll follow a pattern that is pretty common in the launch of new drugs where frankly early in the launch you tend to get more later line patients or the physicians really challenge the drug and patients who've been through multiple rounds of therapy and where they may think they have alternatives in earlier line. And if they like what they see, they tend to move it up into earlier line even on label patients. So, I think that transition may occur overtime, it doesn't necessarily happen three months in the launch.

[Tom Shrader:]

And can you just remind us in your clinical trials with the drug. Would you have seen most of dose reductions at the first retail? Is that the major point that happen early?

[Patrick Mahaffy:]

In our experience, no, it can happen at any time. In our experience, most the dose reductions would occur I wouldn't necessarily say just after the first cycle but certainly after the first one or two cycles. But remembering there were three months number of our patients who may have been dosed in March have even have the refill yet. So while I'm pleased thus far with inherence as I pointed out in the script, it's a little early to make we must acknowledge that that's going to move around some over the course of the launch.

[Operator:]

Thank you. Our next question or comment comes from the line of Tazeen Ahmad from Bank of America Merrill Lynch. Your line is open.

[Tazeen Ahmad:]

Hi, thanks for taking my questions. Pat, I just joined the call few minutes and so forgive me if I'm asking you something already talked about. But you have talked about getting some used in earlier lines of therapy that, are you also seeing any used by doctors in the maintenance setting per se? And then my second question would be on the studies that are being conducted in combination with PD1 or PDL1. I guess just given the idea about costs here that would be potentially expensive combo. What kind of efficacy would you ideally like to see? You justify advancing into more advanced trials just stay so what you think would be an early clinically meaningful but commercial viable? Thanks.

[Patrick Mahaffy:]

Yes. Good question. With regard -- first one, we’re getting some use in maintenance, I did address this earlier in the answer is yes. And answer is yes because the definitions of maintenance and the definition treatment grey area for women who already progress now or been treated with two prior line of therapy or a little less. The definitions are little less robust than there for regulatory or clinical development purposes. And we're well aware physicians who had used it and what might formally be called maintenance setting and then reimburse. And I can’t quantify that but I certainly have heard it. With regard to the potential financial toxicity, the PD1, PDL1, plus rucaparib, all of us and oncology or focus on developing combinations products, and in fact, there are number of PD1, PDL1 products that are already used in combination with [indiscernible] combination immunotherapy agents that already to combine two relatively sensitive drugs. I have been predicting for about 15 years that there is going to be more issue with pricing and I have been wrong for about 15 years. Ultimately, there will be more focus on this. I do think that given the pronounced effect seeing with some of these combinations and given that as I said earlier, what the expectation is from this trial or hope I should say from this maintenance study at least in the frontline set in the PDL1 is we see market increase in the number of patients who would be described as having been cured. I think that meaningful results of that nature including a meaningful increase in the PFS versus what’s available today would be reimbursable.

[Tazeen Ahmad:]

Okay. And then maybe just one question about the importance of being able to get a full label without the need for gene casting scenario would be positive. Some other feeds that we'll be getting from business churns about necessary launch of at least from the KOL front stay with license to gene status testing for patient. And I don’t know, if you’re hearing the same thing in general from physicians, but does it any way in your mind change the importance of having a label without needs to gene testing?

[Patrick Mahaffy:]

It’s a good dialogue to have and a dialogue it is currently occurring in community. The academic community for sure is very focused on ensuring data to be availability of testing both for BRCA patients and four HRD. And in addition to the ongoing debate about maintenance versus frequent and when best to use of PARP inhibitor because that debate continues both in the academic and community setting. They remain as well conversation about the relative Myriad in a patient who was neither defined as HRD or Rubraca and we all know from the ASMO data that there was a descending benefit first pronounced in BRA very good and HRD less. So, the biomarker negative and I would anticipate ours would follow the same path. I’m not saying it would be any difference. And I think it's extremely important that we as a community ensure that patients and physicians know their options for testing and important that they consider testing to determine which are the classifications they are. And I think it's important that as a marketer, we don't try to say assuming either we have a great data and the biomarker negative the testing is an important, testing is important because they're varying results here and varying alternatives. And most important, anything we do that would take away from testing from mutant BRCA has pronounced effects on the availability of that information, not just to a patient, but to her family. And in fact, we're embarking on a program now the increased testing and other tumor types which turned out it is just as relevant, prostate being a very good example. So yes, we hear that dialogue, yes, we participate in that dialogue. And I will say that there will be a delineation of those who may prefer to use in all comers that certainly going to be a population, but a population who limited to either BRCA or HRD.

[Operator:]

Thank you. We have time for one more question. Our final question comes from the line of Andrew Berens from Morgan Stanley. Your line is open.

[Andrew Berens:]

Maybe a question on commercial and then on ARIEL3 also. In terms of the usage, I know AstraZenica saw some usage out of ovarian cancer even without a formal label. And are you guys seeing that or kind of usage also just outside just the BRCA patients?

[Patrick Mahaffy:]

The data we have and again this is unrelated to promotional activities which are very focused on our label, but today that we had suggest that we're 10% of our scripts would be formally described as off label primarily another tumor types.

[Andrew Berens:]

Okay thanks. And what about outside of BRCA patients?

[Patrick Mahaffy:]

Well, I think for less of that. I think for now the majority of our usage is going to be in somatic or germline BRCA patients. We do know some patients who have been treated and reimbursed, I guess I should add this for defined as HRD that we do now. Primarily, in the academic setting.

[Andrew Berens:]

Okay. And then in terms of ARIEL3, is there a marker for clinical progression like CA-125 in the trial? And was that used by the independent review the data monitoring board to assess the trigger, the 70% trigger?

[Patrick Mahaffy:]

No. So, the trigger is entirely given by progressive events as determined by [Indiscernible]. It's a local clinic the physicians of course would monitor CA-125 and in the event that they were monitoring CA-125 and saw a meaningful rise. They have the ability to call for a scan earlier. So that was a role of CA-125. But the independent data monitoring committee had no visibility to CA-125 response, not that I'm aware of, if they did and nothing to do with the timing of the goal.

[Andrew Berens:]

Okay. And progression events for the trigger were driven by the central review?

[Anna Sussman:]

No, the progression events for the trigger were driven by local review.

[Andrew Berens:]

Okay. And then just one last question I know you try to wrap up the call, but can you help us understand I know people have been trying to benchmark the enrollment and the last patient into the trigger with some of the other trials that have read out previously. Can you help us put that in context?

[Anna Sussman:]

Well, I could take an hour on this or I could try to do it in a little further period of time. So, I’ll try to do in a shorter period of time. First, I’m highly sympathetic to the desire investors have, to try to rank order. Where we are compare to the AstraZeneca data from SOLO2 and to SOLO data for Nova. So first I’m sympathetic. Second is turned out, it’s really hard to do. Each of these trials now it turns out and we’re going to have a complete time from patient in to release some data of just around three years. So, that is true. So these are all I think three new confidence an enrollment. It's going to be three years. In our case, it's going to be three year plus two months that’s exactly the timeline. The difficulty is that. One, in the Tesaro study because they added the HRD patients later than they did the original trial, which did include a focus patient group of HRD. Our understanding is that they delay the results until they had appropriately hit the number of events in HRD population. So, that historically is a benchmark because we don’t know what that timing would have been, if they had like us, it's going to rule everybody at the same time. For AstraZeneca, it turns out and I only recently learned this that they included enrollment in the first part of the trial at the end of ’14. In early ’15 there we open the trial to add a Japanese cohort of around 30 to 40 patients. And then, I think delay in our since that trial, until they have achieve some trigger or progression events and at Japanese cohort, it would become a full of join enrollment, but that user and the analysis particularly because, it’s hard not to believe, the decisions will roll them with driven by regulatory dialogue about how many Japanese basically like to see in that trial. So in both cases, there was not kind of the linear environment as both companies in their put around there were earlier than they did, if they had not elected to add additional patients in the one case Japanese patients, in the one case HRD patients. So, it just turns out as much as we all and how we like to do it too. We like to add some clarity and how deal at this moment like we compare. You cannot make this apples-to-apples comparison because it’s an apple to pear to an orange. Further, the enrollment in our trial was completely linear. As I mentioned earlier in the script, I am not sure if you've heard this, but we had a really interesting trial. We, half of our patients did enroll in the first year, half in the second year of the trial, and after a first few months where we were getting our FDA approvals and new sites. Our monthly enrollment was almost exactly the same month-to-month-to-month truly interesting to see that. You don’t see it quite that linear in these trials like we did, but it was really interesting. However, we don’t know the biomarkers status for those patients. So, since our trigger is driven by a subpopulation, BRCA, we have no idea, if our last BRCA patient enrolled in February of 15 or March of 15 or January of 15 or April of 15, we just don't know. And so make it even harder to make these comparisons. So, it's again I give not the other long one, but I got close. But it's just I get the people want to do it, I will tell you it is impossible to do it.

[Operator:]

Thank you. And I'd now like to turn the conference back over to Ms. Anna Sussman for any closing remarks.

[Anna Sussman:]

Thanks, Howard. I thank everyone for your interest in Clovis today. If you have any follow up questions, you can call me at 303-625-5022, for Breanna at 303-625-5023. This call can be accessed via replay at clovisoncology.com beginning in about an hour and it will be available for 30 days. We appreciate your interest and time. Thank you and have a good evening.

[Operator:]

Ladies and gentlemen, thank you for participating in today's conference. This concludes the program. You may now disconnect. Everyone have a wonderful day.