Clovis Oncology Inc (CLVS) 2013 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Clovis Oncology fourth quarter and year-end 2013 financial results conference call. My name is Celia, and I will be your operator for today.

(Operator Instructions)

As a reminder this conference is being recorded for replay purposes. I would now like to turn the conference over to your host for today Ms Anna Sussman, Senior Director, Investor Relations. Please proceed.

Thank you, Celia. Good afternoon, everyone, and welcome to the Clovis Oncology fourth quarter and year-end 2013 conference call. You should have received the news release announcing our 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 our website during the call and will be available on our archives for the next several weeks. The agenda for today's call is as follows. Pat Mahaffy, Clovis' President and CEO, will discuss the highlights of 2013 and provide an update on our clinical development programs. Then Erle Mast, Clovis' Chief Financial Officer, will cover the financial results of the quarter and year in more detail and comment on the Company's outlook for 2014.

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 will turn the call over to Pat Mahaffy.

All right. Thanks, Anna. Welcome, everybody. Thanks for joining us this afternoon.

2014 will no doubt prove to be an important year for advancing our clinical development programs which I will briefly review. We are also aware that there a lot of moving parts in our rapidly evolving global clinical development plan for 1686 as well as clear opportunities to potentially accelerate our NDA submission. 1686 is our targeted covalent inhibiter of the mutant forms of EGFR for the treatment non-small cell lung cancer.

1686 targets both the initial activating EGFR mutations as well as the dominant resistant mutation T790M. Now what do we know so far? 1686 is a very well tolerated drug.

We have shown that we are the only EGFR inhibitor that doesn't hit wild-type EGFR in clinical studies. We have seen no evidence of TKI related EGFR wild-type rash or diarrhea at any dose or formulation setting. We believe this represents a significant point of differentiation for 1686 compared to other TKIs approved or currently in development.

It is also a very active drug. In October of 2013 we announced most recent update of CO-1686 clinical data which included six RECIST partial responses observed at that time in nine evaluable T790M positive patients dosed at 900mg BID of the freebase formulation for a 67% objective response rate.

Eight of the nine evaluable patients, or 89%, experienced PRs tumor shrinkage greater than 10%. These patients were heavily pre-treated prior to receiving 1686. Eight of the nine patients had progressed on an EGFR TKI immediately prior to enrollment in the study. Six of the nine patients received two or more previous TKI lines. At that time 56 patients had been treated with 1686 across all dosing cohorts of the freebase with no evidence of dose related wild-type EGFR driven toxicity which remains true today as well.

Clearly we believe that 1686 is potentially a very important drug, and we are determined to identify the best possible way to get this drug approved rapidly and in the hands of physicians and patients who may benefit. This can now become our focus as we have completed dose escalation with the improved hydrobromide formulation of 1686. We have commenced enrollment of the Phase II expansion cohorts in patients with EGFR mutant non- small cell lung cancer and our two T790M+ cohorts are increasing from 80 patients to approximately 300 patients in total, or 150 patients in each.

These cohorts will test the efficacy of 1686 and two patient subsets in two dose cohort each. The first in approximately 150, perhaps up to 200 patients who are T790M+ directly after progression on their first and only TKI therapy similar to our TIGER2 study design. And the second in approximately 150 T790M+ later-line patients directly after progression on their second or later TKI therapy or subsequent chemotherapy subsequent to our TIGER3 study design. The FDA has made a number of public comments about the importance of fully exploring dose in development.

This is particularly important, we believe, for well-tolerated targeted therapeutics where MTD-based dosing may not be ideal or in certain cases, and maybe ours, not possible. This program is designed to rapidly and thoughtfully ensure that we have explored dose beyond our stated dose of 750mg BID in large groups of patients. Importantly, we have seen very encouraging activity in each of the HBr doses which makes it possible to fully explore dose in these expansion cohorts.

Of course it is particularly attractive to us since these data could also serve as the basis of an accelerated NDA submission. A maximum tolerated dose of 1686 has not been reached and will not be reached since we are planning to do no further dose escalation work. While a dose limiting toxicity of hyperglycemia has been observed in a minority of patients, most of these patients have been asymptomatic, and all cases have been easily managed.

We will continue to move forward with the TIGER program, which includes three global registration studies for 1686, all in EGFR mutant non-small cell lung cancer. These include TIGER2 and T790M+ second line patients directly after progression on the first and only TKI, TIGER3 in more advanced patients after progression on their second or later TKI therapy or subsequent chemotherapy. And of course TIGER1 in newly diagnose patients who have not had TKI therapy but who may have received one type of chemotherapy, this study randomized against erlotnib or torcedo.

Our next presentation of 1686 data will be at the European Lung Cancer conference in Geneva in late March. Doctor Heather Wakelee, one of our investigators, will present the 1686 data in an oral presentation during the advanced disease or targeted agent session scheduled from 9.00 am to 10.30 am Geneva time on March 27. It is our understanding this presentation will be webcast, and we will of course publish a news release with the details of the presentation.

This presentation of data will provide a first look at efficacy in patients dosed with the hydrobromide formulation. These data will include both patients who started on the freebase and transitioned to the hydrobromide as well as patients who started initially on the hydrobromide formulation.

The data presented at ELCC will also provide for the first time evidence of durability of benefit for the original group of 900mg BID freebase patients who transitioned to 500mg BID of the HBr formulation in the fall of 2013 as well as a full presentation on the tolerability and PK for all of the Phase I patients. As you know the timing of these conferences is never perfect relevant -- or relative to development time lines, and many of the hydrobromide patients will not yet have had a second scan. By ASCO we expect to have an even more robust update on both efficacy and durability.

As we mentioned at our R&D event in January, we are also beginning to explore combination studies that could ultimately improve long term disease control. Finally, we intend to initiate our Japanese Phase I study later this quarter.

Let me turn to rucaparib, our oral potent small molecule inhibitor of PARP1 and PARP2 which we are developing for the treatment of platinum sensitive relapsed ovarian cancer of BRCA patients as well as other DNA repair deficiencies. Rucaparib is now also being explored in pancreatic cancer patients with BRCA mutations. Currently we are enrolling patients in two studies in the ARIEL development program.

ARIEL2 is our global Phase II single arm open label study designed to identify molecular features that predict sensitivity to rucaparib using DNA sequencing to evaluate each patient's tumor. This study assesses and correlates rucaparib response with the genotype and phenotype of each patient. These data will inform the final definition of homologous recombination deficiency through the ARIEL3 registration study.

And ARIEL3 is our global randomized double-blind Phase III registration study that compares the effect of rucaparib versus placebo. This study will evaluate whether maintenance rucaparib therapy can extend the period of time for which disease is controlled after successful chemotherapy in platinum sensitive ovarian cancer patients. This study will utilize pre-specified step down efficacy analyses, first in BRCA patients and then in the broader HRD population as we'll have defined through the ARIEL2 study and then all comers, all comers meaning those who enrolled in the study who are of course sensitive to platinum -based therapy.

Let me comment briefly on the Phase II study of pancreatic cancer patients with BRCA mutations that we intend to initiate during the second quarter. While we realize it represents a small n, we have now observed striking partial responses in the two germline BRCA pancreatic cancer patients treated with rucaparib to date, each of whom have failed traditional chemotherapy.

As you know there is a significant unmet medical need for the treatment of pancreatic cancer particularly now in the second line stay. So, if successful, there is potential here for accelerated approval for rucaparib in this indication. Now to lucitanib. Lucitanib is our oral potent inhibitor of the tyrosine-kinaise activity of FGFR1 and FGFT2, VEGFR1-3 and PDGFR alpha and beta. We hold exclusive US and Japanese rights and have a collaboration agreement with Servier the holder of European and rest of world rights for the global clinical development of lucitanib.

We are initially targeting solid tumors with FGFR pathway activation including breast and squamous non-small cell lung cancer. We are enthusiastic about our newest compound which we acquired through the acquisition of EOS in 2013. It has demonstrated in studies thus far impressive response rates with manageable side effects in previous trials of heavily pre-treated patients. And the collaboration with Servier integrates well into our clinical development program through which Servier is responsible for the initial $110 million of investment in the lucitanib global development plan.

There are currently three Phase II monotherapy trials of lucitanib planned our underway. The first is underway, the Servier sponsored European Phase II study in advanced breast cancer patients, known as FINESSE, which began late in 2013. We are planning a Clovis sponsored US Phase II study in treatment refractory FGFR1 or 11Q amplified patients with advanced breast cancer and a Clovis sponsored global Phase II of advanced squamous lung cell cancer patients with FGFR1 amplifications. Most of the Clovis sponsored studies are expected to initiate during the second quarter of 2014.

Now let me turn the call over to Erle to discuss fourth-quarter and year-end 2013 financial results and reiterate our guidance for 2014.

Good afternoon, everyone. Our full financial results are included in this afternoon's press release, so I will direct my comments to highlights through the quarter and provide some additional analysis and commentary.

We reported a net loss of $29.2 million or $0.92 per share for the fourth quarter of 2013 and $84.5 million or $2.95 per share for the full year of 2013. Our research and development expenses totaled $22.5 million for the fourth quarter and $66.5 million for the full year 2013. R&D expense for the full year increased by $7.6 million compared to last year. This is the net effect of two factors, expanded clinical development activities for CO-1686 and rucaparib partially offset by the termination of CO-101 program beginning late 2012.

As expected, research and development expenses in the fourth quarter of 2013 increased over the third quarter of 2013 by $6.5 million. This growth is due primarily to the initiation of the ARIEL2 and ARIEL3 studies in the second half of the year as well as the manufacturing of additional clinical supplies for both the 1686 and the rucaparib programs.

General and administrative expenses totaled $5.5 million for the fourth quarter 2013 and $16.6 million for the full year. G&A expenses for both the fourth quarter and the full year were impacted by transaction costs and fees associated with our acquisition of EOS this past November. Those cost totaled $1.6 million for the fourth quarter and $2.2 million for the full year 2013.

Our operating results for the fourth quarter were also impacted by non-cash expenses relating to the accounting for the EOS acquisition. We incurred non-cash charges totaling approximately $1 million in the fourth quarter relating to the currency translation of euro denominated contingent payment obligations as well as the accretion of these future contingent payments.

Finally, our operating expenses for the fourth quarter and the full year of 2013 included $2.8 million and $9.5 million of stock compensation expense respectively. We ended 2013 when cash totaling $323 million, with no outstanding debt and with 33.9 million shares of common stock outstanding. As we previously stated, we expect cash burn of approximately $120 million for 2014, however, we will continually evaluate this estimate as we see how enrollment in our clinical trials progress.

With that I will turn the call back over to Pat for some closing remarks, and then we will open it up for Q&A.

Great. Thanks, Erle. Let me zip through our anticipated milestones for 2014.

For 1686, we have now initiated the expansion cohorts for the Phase I-II study, to swiftly build a larger data set for out T790M+ cohorts and expanded them to include approximately 300 patients in two dose cohorts each. These include approximately 150 to 200 T790M+ patients in two dose cohorts directly after progression on first and only TKI as well as approximately 150 T790M+ later line patients in two dose cohorts directly after progression on their second or later TKI therapy our subsequent chemo.

We intend to initiate the Phase I study in Japan this quarter and to initiate the first three studies in the TIGER program all in non-small cell lung cancer, which include the following. The TIGER2 registration study in T790M+ patients directly after progression on first and only TKI. TIGER3 three registration study in later-line patients directly after progression on second or later TKI or subsequent chemo. And the Phase II portion of the TIGER1 registration study in first-line EGFR positive patients.

Rucaparib will continue enrollment of the ARIEL2 treatment study and ARIEL3 maintenance study in platinum sensitive ovarian cancer patients with BRCA mutations and other DNA repair deficiencies. And during the second quarter we intend to initiate the Phase II study of rucaparib in pancreatic cancer patients with BRCA mutations.

Finally, for lucitanib, during the second quarter we intend to initiate our Phase II study of lucitanib in selected patients in addition to the FINESSE breast cancer study currently underway by our partner Servier. These include the US Phase II study in patients with treatment refractory FGFR aberrant breast cancer and the global Phase II study with patients with metastatic squamous non- small cell lung cancer with FGFR1 amplification.

In summary, we expect to enroll more than 1000 patients in the Clover sponsored studies around the world in 2014. I am very proud of what our team has achieved in 2013 and look forward to an even more important year as we continue to advance -- and aggressively advance our clinical development programs.

All right. Thanks for joining us today. And we're now happy to answer any questions you may have.

(Operator Instructions)

The first question comes from the line of Cory Kasimov with JPMorgan. Please proceed.

Good afternoon, guys, and thank you for taking the questions. I have a lot of them, but I will narrow it down to just a few here.

So I guess first things first on this Phase II expansion strategy you are announcing today, what led to the change in the path forward from just one month ago a your R&D Day? Was this based off of interactions with the FDA or push from investigators, or what was it?

I think we landed on it for a variety of reasons. First I want to say did not involve interaction with FDA or any regulatory agencies, so just put that aside.

We landed on it as a what's not to like about this? We have a lot of pressure from investigators who have a number of slots and patients waiting to get into this trial and were already worried that at 80 they were going to run out of slots. So pressure from investigators is real for us right now.

Two, we have a really active drug that has shown really good evidence of activity across multiple doses. And we know that FDA is increasingly telling sponsors they like to see a full exploration of dose in the context of their development programs. Given that we didn't hit an MTD, this is a perfect example of where we can provide FDA with what they requested, a much more complete exploration of dose.

And, finally, we've known all along that it was in the realm of the possible to consider a more accelerated timeline for NDA submission. That was of course dependent on generating data that would have met what we believe to be appropriate requirements. We think we're doing that.

So for us, all of that adds up to a really clear path to increase the size of the expansion cohorts, to consider them for accelerated approval and to explore dose in that context all the while keeping our investigators happy with what we're doing.

Okay. And are you able to say what two does you are taking forward?

I think we're going save that -- we're going to discuss that more fully in Geneva.

Okay. And then on Geneva, are you able --

Including telling you what the are. I didn't mean to sound like a --

I understand. (multiple speakers) On Geneva, can you tell us at least roughly speaking how many patients we might see data on at ELCC?

Yes, we could. No we won't. We don't exactly know the date of the cut off. We will have a reasonably robust patient population for you at Geneva.

Okay. And one for Erle, and then I can hop back in the queue with the others. On the financial side of things, this decision to substantially increase and accelerate development of 1686 not really sure how this doesn't impact the burn guidance for this year something else slowing down?

No, it's not slowing down, Cory. It's a good question, and so much of our burn and cash is just driven about how our clinical trials enroll. And I think given we are at the beginning of the year, what I'd like to do is we're still have not changed our guidance.

As we get to reporting for Q1 and we have a better sense on the timing and on the enrollment pace then we will update that. So it's nothing more than we are at the beginning of the year, and I'd like to see how the first few months play out before we revise that guidance.

That's completely true, and it's a bit of a moving target. The other thing you should know is we are evaluating given a breadth of this substantial cohort now, whether we may dial back the number of patients we enroll in each TIGER2 and TIGER3. So we'll evaluate that over the course of the next couple of months.

At this point, though, TIGER2 is smaller in sample size it seems like than your expansion cohort in Phase II? Is that correct.

The TIGER2 thing -- TIGER2 is a single dose, and so they're highly complementary program to say the least.

Okay. All right. Thank you for taking the questions.

Sure.

The next question comes from the line of Brian Klein with Stifel. Please proceed.

Thank you for taking my questions. Just a few here.

First, on the dose limiting toxicity of hyperglycemia. What exactly was the threshold that led you to call that the DLT. And secondly were you seeing that only at the highest dose tested, or did you see it at other doses as well?

The threshold -- this is Andrew Allen, the Chief Medical Officer. The threshold for grade 3 toxicity, which was the definition for DLT is fasting plasma glucose of 250 milligrams per deciliter or greater. So that's the threshold, and we will give you the toxicity by third stage in Geneva.

Great thanks. And then in terms of the expansion cohort versus the TIGER program do you expect enrolling patients in the expansion cohorts will impact your timelines for enrollment in TIGER2 and TIGER3?

No. I don't. We've got sites all over the world, and the expansion cohorts are predominantly in the United States. The TIGER2 and TIGER3 involve a number of Asian and European sites, and so there's not very much overlap at all.

And finally, we have the ability in the United States to involve the community as well -- would like to -- will involve the community setting for TIGER2, because the vast majority of TIGER2 appropriate patients are [pregetting the community] setting. So I think our timelines will not be affected at all.

Great. Thanks for taking my questions.

A question from the line of Marko Kozul with Leerink. Please proceed.

Hey guys good afternoon. And congrats on the progress.

Thank you.

On your expanded expansion strategy, many of your channels have been advocating either consider backfilling the ongoing 1686 trial given significant patient interest beyond capacity. So just to follow-up to some of the other questions, how quickly do you think you can enroll these expanded patients to the expanded cohort -- to the expanded portion of the study -- studies?

I think what we want to do it either at the time of Geneva provide you an early forecast, and if not by Geneva then certainly by ASCO provide your timeline. Let's get enrolling now, and I'd prefer to provide that timeline when we have a little better clarity.

Terrific.

Given everything we know, because there's a lot of patients out there. There's a lot of demand by our investigators. And we have clearly told you we believe that if the data are encouraging this will accelerate the timeline for our NDA submission in the United States.

Terrific. My second question has to do with duration of response data for the hydrobromide salt formulation that will be seeing soon at the ELCC. If the emerging duration of responses trend you well beyond six months say to six, seven, eight, nine months, how should we think about that in terms of de-risking to the frontline market opportunity?

Well, I think that -- I think it's pretty simple. You can do math if you want and assume we are going to get to a similar PFS as to torcedor or afatanib, 10.5 or 11 months. And then you can try to add the math to what we see in the T790M population. That's one metric you could use.

It' not a complete story about the drug and patients for one period of time. But I know if we've seen a very limited duration of benefit it would be worrying, and so my rule is usually if 'd be worried about it if it was bad, I am going to be kind of optimistic about it if it's good. Andrew, would you?

I think Increasingly, the community believes that the multiple clones of cancer are present at the outset of disease. And one clone will dominate Darwinian competitive system depending upon the drug that's in the environment. Obviously if there's no drug in the environment, in this disease it starts activating mutations that clearly are the fittest clones, that replicate the fastest and therefore dominate the clinical tumor that the patient presents with.

But the belief is that those resistant clothes including of course T790M are probably present in all of these patients pretty much from the beginning. And they grow quietly and they are frankly unaffected by the use of erlotinib, because it's a minority clone its growth is invisible clinically. Now when you then introduce a TKI, which kills off the [don19] clones now of course you've created a situation in which that resistant clone will slowly become the dominant clone. As we know it takes about 10 months or so on average for that resistant clone to grow through and terminate the apparent benefit s of erlotinib in the frontline setting.

Then you come in with our drug and obviously if we are suppressing that resisting clone we are now presumably creating an opportunity for the third 1686 resistant clone to grow through whatever that might be. So if you believe all of this is happening in parallel, and these clothes are growing independently of each other, then it's reasonable to simply add the PFS that you're seeing in the second line setting on top of what you see in the frontline setting. And obviously that -- the longer the second line PFS becomes, therefore the greater the expected hazard ratio when we compare ourselves against erlotinib in the frontline setting.

So I think that's where you're going, Marko, and that's a very reasonable set of assumptions, and obviously we'll test those in the TIGER1 trial.

That's a very helpful answer. Thank you.

And just one last one here on rucaparib. Can you give us some details on the two pancreatic patients treated so far? How should we interpret your comment about a striking response that we've observed, and how long have these patients been in the study? Thanks.

The first patient we presented at the R&D day, this is a patient with the germline BRCA mutation who received folfirinox front-line therapy which is now the likely standard of care in this disease. It's a full drug regimen. It carries pretty substantial toxicity, but has shown the greatest overall survival benefit when used in the frontline setting.

This patient progressed after four cycles of full dose folfirinox, so he progressed on therapy. And then developed a very nice partial response rucaparib monotherapy. The duration of the actual response was around six months. He was on drug with very high quality of life for nearly a year.

So that was the first case which obviously captured our attention. And then we have the more recent case of the patient progressed on gemcytabine monotherapy also given a frontline treatment for pancreatic cancer. And that patient is now -- has entered her partial remission, and she is still in it. So we have the duration yet.

But again we're very compelled by this monotherapy very well tolerated drug leading to clear clinical benefit in patients who progressed on aggressive cytotoxic chemotherapy. That's obviously a striking that we're choosing not to ignore.

Appreciate you taking the questions. Thanks.

A question from the line of Peter Lawson with Mizuho Securities USA. Please proceed.

Just following up on the rucaparib second patient, how long have they been in partial remission?

We will update probably at ASCO this year. Obviously we don't give clinical information on the fly for individual cases.

Got you. And then just to be clear, the difference between the expansion and the TIGER2 and TIGER3 expansions for both of those are very similar to those. The differences are given larger different dosing and sounds like they've got different geographical mix as well.

That's fair, all of that is accurate.

Okay and we find out that dosing in Geneva?

You will.

Okay. And then on the data timeline -- Phase II data for CO-1686 when do you think you should see some of that?

From say the expansion cohorts?

Yes.

Most realistic at ESMO. There will be an update at ASCO on the dose cohorts that we explored in the Phase I portion, so you'll see data for those dose cohorts at -- in Europe at ASCO. I think the earliest date at which you can see data from the expansion cohorts is one of the fall meetings. I guess it would probably be ESMO at the end of September, but obviously the F-track deadline hasn't even occurred yet, so it will be one of the fall meetings.

Got you. Okay. Thank you so much.

(Operator Instructions)

The next question comes from the line of Charles Duncan with Piper Jaffray. Please proceed.

Hi, guys. It's Roy in for Charles. Thanks for taking the questions. Most have been answered.

I had a question about the recent patent issue in Europe between Puma and Boehringer. If you guys could comment on if that has any implications for 1686 in Europe and possibly the US?

Well, I could give you the answer I want to give you. My colleagues are telling me not to. It involves nasty, nasty words so I won't go there. Annie, you're welcome. Those of you modeling potential royalties for Puma should install this number for every year going forward, zero.

Okay.

There's a moment in time for that patent. What they did not tell you is that of all the claims VI aggressively sought to have thrown out, the first 22 were thrown out. They didn't tell you this could be the subject of a new appeal that would look at a small number of remaining claims. They didn't get around to telling you that in the United States you could look at file records publicly available that the only claim related to T790M is specific to neurontin.

It is the only drug by the way, not the only, but one of the many, who have proven itself to have exactly zero responses in the T790M+ lung cancer. This is silly and embarrassing. It will have no impact on our organization.

Okay, great. Thank you. A question broad one on the I guess the cap rate the foundation assay not super familiar with it. Is there a failure rate I'm guessing there is, and what is that?

There obviously will be a technical failure rate, but it's low single digits. The key obviously for the failure of any diagnostic test is the quality and quantity of tissue that is submitted.

And the good news about ovarian cancer if there is good news about this disease, is that women typically the first line of treatment undergo extensive so-called debulking surgery. Where all of the evident disease inside the pelvic and peritoneal cavity is removed. And therefore there is abundant tissue from that tumor available in the laboratory of the hospital where that patient receives their treatment.

Therefore for us to request some of that tissue firm and fixed paraffin embedded and send it to foundation is actually very straightforward. So for the ARIEL3 trial there's no requirement for further biopsy or needed for tissue that almost inevitably will be sitting in the path lab. So that's obviously very good news from the patients point of view, because which means we should be able to get high quality data on just about all of them. Obviously everything has a failure rate so it's not 100% success, but again low single digits is our expectation.

I noticed on the R&D slides that there was a failure rate -- it's not your data -- but 23% for FTS assays and that seemed a bit high. I wonder so --

Again, the context matter so a lot of the assays right now are being done in lung cancer. And in lung cancer you're in a very different universe where you're relying because of the difficulty of obtaining lung cancer biopsies you typically rely on very small fragments of tissue obtained bronchoscopically as the source material.

And obviously that has a much higher failure rate because sometimes you just don't have either any tumor tissue or enough tumor tissue to do the next gen sequencing work. Again as I explained in ovarian cancer we don't have that problem, I'm happy to say.

Okay and then the foundation -- last question the foundation assay just looking at in addition to the BRCA mutations loss of [parazacgosy]?

Yes, what foundation does is sequencing, and they sequence several hundred genes as well as a series of snips, single nucleotide polymorphisms which are evenly spaced throughout the genome. And it's the snips sequencing that tells you whether a patient has developed substantial amounts of LOH or loss of heterozygosity. So it's that LOH analysis plus the BRCA sequencing analysis that are central to our test and our classification.

Great. That's all. Thank you.

A question from the line of Yaron Werber, Citi. Please proceed.

Great. Thanks for taking the question. This is Chris in for Yaron. I have two questions.

First, in your press release you mentioned filing an NDA in 2015, but you don't specify what drug. I assume you're referring to 1686, but can you please clarify that? (multiple speakers).

It would be 1686, yes. Sorry about that.

Thank you. My second question is for Andrew regarding lucitanib. Can you comment a little bit on the profile of the drug and how you think it may differ from other similar drugs in development? It looks like the pre-clinical data especially the IC50s don't translate into clinical activity. What are your thoughts on that?

It's a great question, and I think what we learned as a community is the IC50s for this class of drugs do not tell you exactly what the drug will do in the clinic. And the obvious example is that there are several molecules which have VEGFRs up to two as one their high-profile targets where in vitro the IC50 is single digit [mananillo] against that receptor. But when these drugs are administered to patients, you see no hypertension or trivial amounts of hypertension.

And it's widely accepted that hypertension is a very good [thermanodynamic] of VEGFR2 marker of inhibition. So devita is a good example of a drug that has in vitro high potency against VEGFR2, but hypertension rate is single digit. So I think you have to judge each drug on its clinical data.

And what we've learned is that if you take pure -- relatively pure VEGFR inhibitors and you put them into women with breast cancer, you really don't see a great deal of activity. You ensure -- know -- several drugs have been tested in Phase II settings and one or two or in Phase III and have really not shown any meaningful response rate nothing beyond single digit or even 0% response rates.

Similarly pure or relatively pure FGF receptor inhibitors also even in FGF selected breast cancer patients also as far as we can tell have no objective responses. They data are not fully public, but they have been presented at scientific meetings over the last couple of years. And we don't know the exact denominator, but we know that those AstraZeneca and Novartis, they have included FGFR1 amplified breast cancer women in their critical trials and have not seen any objective responses.

The pure drugs don't seem to be working in the setting, and what's distinctive about lucitanib is that the toxicity tells your hits the VEGF receptor 2, and the efficacy is clearly different from pure VEGFR2 inhibitors and strongly suggests we are hitting VEGFR1 at least in women with breast cancer where we've seen a 50% rejected response rate. So that's the distinctive nature of lucitanib, and that' why we are so excited to be able to buy it last year and very excited to take it forward in breast cancer. Now where FGF receptor amplification appears to be present both from the get-go un a subset of women but also appears to be emerging as a very important driver of acquired resistance to many different types of therapy in breast cancer.

We're really excited to be pushing forward with this drug.

With no further questions we'll turn the call back over to Ms Anna Sussman for closing remarks.

Okay. Thank you very much, and thank you for your interest in Clovis today.

If you have any follow-up questions, please call me at (303)625-5022. This copy can be accessed during a replay of our -- via a replay of our webcast at www.clovisoncology.com beginning in about an hour, and it will be available for 30 days.

We appreciate your interest and time. Thank you. Have a good evening.

Ladies and gentlemen, that concludes today's conference. Thank you for your participation. You may now disconnect. Have a nice day.