Exelixis Inc (EXEL) 2012 Q1 法說會逐字稿

Good day ladies and gentlemen and welcome to the first quarter 2012 Exelixis financial results conference call. My name is Keisha and I will be your operator for today.

At this time all participants are in listen-only mode. Later we will conduct a question and answer session. (Operator Instructions)

As a reminder, this conference is being recorded for replay purposes. I would now like to hand the conference over to Mr. Charles Butler, Vice President of Investor Relations. Please proceed.

Thank you for joining us for the Exelixis first quarter 2012 earnings call. Joining me on today's call as usual are Mike Morrissey, our President and CEO, Frank Karbe, our CFO, and Gisela Schwab, our CMO who will together review our corporate financial and development progress for the quarter ended March 31, 2012.

They also will discuss upcoming objectives and provide an update on cabozantinib, our lead clinical development program. As a reminder, we are reporting our financial results on a GAAP basis only and as usual, the complete press release with our results can be accessed through our website at Exelixis.com.

As a reminder, during the course of this presentation we will be making forward-looking statements regarding future events or the future performance of the Company. Actual events or results of course could differ materially. We refer you to the documents that Exelixis files from time to time with the Securities and Exchange Commission specifically the Company's most recent Form 10-Q filed today, May 3, 2012. These documents contain and identify under the heading Risk Factors important factors that could cause actual results to differ materially from those contained in any forward-looking statement including risk related to the future potential failure of cabozantinib to demonstrate safety and efficacy in clinical testing, Exelixis's ability to conduct clinical trials of cabozantinib sufficient to achieve a positive completion, the sufficiency of Exelixis' capital and other resources and the uncertainty of the FDA review and approval process.

With that, I'll turn the call over to Mike.

Okay, thank you Charles and thanks to everyone joining us on the call today. We continue to make strong progress advancing cabozantinib, or cabo for short, in the first quarter of 2012 and we are well positioned as we move forward towards the ASCO annual meeting in early June.

Before I pass the call over to Frank for the finance updates and to Gisela for an R&D update, I want to provide a few key points about how we're thinking about our Q1 performance and what our work to date in 2012 says about our plans for the rest of the year.

First and most importantly, we continued to advance our highest priority internal development programs in MTC and CRPC over the last quarter. Our progress on the MTC filing continues as planned and we expect to complete the NDA submission in the second quarter of 2012. Comet 2 is up and accruing subjects and we expect to initiate Comet 1 in the second quarter.

The first quarter was an important one in terms of cabozantinib's clinical progress. As we said previously, cabo is more than just a bone drug and it's more than just a prostate cancer drug. Our data presentations since the end of 2011 continued to support this perspective. We have presented encouraging interim data from both the metastatic liver and breast cancer cohorts of our Phase 2 randomized discontinuation trial as well as new interim data from both the renal cell carcinoma and differentiated thyroid cancer cohorts of our Phase 1b drug/drug interaction study to support the MTC filing.

In each study we saw a dramatic tumor regression in the majority of patients, encouraging rates of durable resis responses, high rates of disease control, and prolonged progression-free survival. It's important to note that these patient populations were heavily pretreated which potentially provides another important aspect of cabozantinib's differentiated product profile.

The depth and breadth of our clinical activity and tumor indications outside of MTC and prostate cancer was a critical component of our decision to establish a CRADA with the NCI's cancer therapy evaluation program or CTEP and also expand our own investigator sponsored trial or IST program.

These two initiatives will be critical in our efforts to maximize cabo's potential beyond MTC and CRPC and we have made significant progress in both initiatives in the first quarter.

From a high level perspective we have initiated five ISTs to date and recently approved 12 new trials with CTEP. In addition, we were notified today that a thirteenth new trial was approved for a Phase 2 trial in second line differentiated thyroid cancer.

Together we believe the ISTs and CTEP trials will help us better document cabo's unique activity profile and harness that knowledge as we prioritize additional late stage clinical development programs beyond MTC and CRPC.

We continued to execute from a financial perspective in Q1 as well. We demonstrated our fiscal discipline as we maintained our tight focus on cabo and we continued to apply our resources in an efficient and effective manner. Frank will review the specifics in a few minutes but our Q1 results largely reflect our successful transition to a Company focused on the cabozantinib development program and the dynamics that we forecasted at the end of last year.

We finished the quarter with a cash balance of over $230 million including the net proceeds of our public offering of common stock.

Our progress in the first quarter provides us with a good foundation as we approach ASCO where cabo will be the subject of nine separate data presentations. We expect that cabo will have good visibility at the meeting and we're looking at it as an important opportunity to further document cabo's broad clinical and commercial potential in MTC, in prostate cancer, and in a variety of other tumor indications where cabo has shown activity.

I'll share some more thoughts about our cabo lineup at ASCO towards the end of the call. We obviously can't say much at this stage. Our hope is that ASCO attendees will walk away from the meeting with an up to date picture of how cabo's differentiated clinical profile driven by dual inhibition of MET and VEG-F can translate into meaningful clinical activity in a variety of tumor indications that potentially improve the treatment experience for patients.

So with that, I'll turn the call over to Frank who will provide an overview of our first quarter financials. Frank?

Thanks Mike. As usual, I will focus my comments on the highlights of our financial performance and refer you to our press release and today's 10-Q filing for additional details.

In summary, our first quarter financial results reflect the dynamics that we forecasted toward the end of last year. Namely, compared to Q1 last year our revenues are lower as a result of having realized the majority of our deferred revenue in prior periods and our operating expenses are down mainly as a result of lower R&D expenses as well as having essentially completed our restructuring activities resulting in slightly lower net loss year over year.

We ended the quarter with over $330 million in cash up from last quarter predominately as a result of our equity offering in February of this year which brought in approximately $65 million in net proceeds.

Revenue decreased $17.4 million or 48% to $18.5 million year over year mainly due to the transfer of the development activities pertaining to the PF3K assets, XL147 and XL765 to Sanofi in April 2011, the wind down of the Sanofi discovery collaboration in 2011, as well as the termination of the Bristol-Myers Squibb 2008 cancer collaboration for XL281 in October 2011. This reduction was partially offset by the remaining and final revenue recognition of $10.7 million in connection with the upfront payment from the out-licensing of our PF3K delta program to Merck which we announced in December of last year.

R&D expenses decreased by $12.6 million or 28% to $33.1 million compared to the first quarter last year mainly due to lower clinical trial expenses, lower allocations of general corporate costs, and lower headcount expenses. The decrease in clinical trial expenses was predominately due to the transitioning of our PF3K assets and costs to Sanofi mentioned a moment ago as well as the gradual winding down of our exam pivotal study for cabozantinib in MTC. The remainder of the decrease in expenses primarily reflects the completion of restructuring activities.

G&A expenses decreased by $1.3 million or 14% to $7.9 million despite lower allocations of general corporate costs to R&D. Expenses have decreased across most cost categories but the biggest contributor are lower rent expenses as a result of having successfully subleased significant portions of our campus.

Operating expense overall decreased by $18.8 million or 32% to $40.8 million compared to the first quarter last year which, in addition to the aforementioned reductions in cost, also incorporates a reduction in restructuring charges year over year by approximately $5 million.

I would like to point out that the Q1 operating expenses levels are not necessarily representative for the remaining quarters of this year. In addition to Comet 2 we expect to soon also be actively enrolling Comet 1 and as these two pivotal studies ramp up we expect our quarterly operating expenses to increase. However, for the full year we expect operating expenses in line with our previously issued guidance of $190 million to $220 million which is in line with our 2011 expenses. Net loss has decreased slightly by $1.3 million or 5% to $26.2 million or $0.18 per share.

And finally, we ended the quarter with approximately $332 million in cash which includes cash inflows of $95.7 million during the first quarter of 2012 of which $65.4 million related to the net proceeds from our equity phone offering in February and $27.3 million related to BD payments from Merck and Sanofi.

With that, I will turn the call back to Gisela who will review the cabozantinib development program in more detail.

Thank you Frank. As Mike described, the first quarter was a productive one for the Exelixis development team.

The cabozantinib development program is driven by three distinct areas of effort. First, as you know, our internal efforts are highly focused on the NDA filing in medullary thyroid cancer, the randomized discontinuation trial, and on the execution of our prostate cancer Phase 3 program. Second, our investigator sponsored trial program, or IST program, that is executed by numerous investigators. These trials are exploring potential new indications and combinations for cabozantinib.

And third, we have just announced the approval of the initial program of 13 clinical trials under our CRADA with CTEP. As you recall, we entered into a CRADA with CTEP late last year that covers a broad program including up to 20 active trials per year. These studies will be executed under the R&D held by CTEP and are supported by NCI funds.

Through both the IST and CTEP programs we believe that we will be able to greatly expand the development efforts and to support cabozantinib's development in a cost efficient manner. The result is a broad global development program for cabozantinib that builds on all of the activity we have seen to date including activity in 12 of 13 tumor types tested. It gives us the ability to generate the clinical data that will be integral to maximize the clinical and commercial value of the compound.

Now let me update you on the status of each of these work streams starting with our medullary thyroid cancer program. We are preparing to present results from exam the Phase 3 trial in medullary thyroid cancer at ASCO. Meanwhile, the work on the NDA filing is proceeding as a high priority. We are on track to complete the submission by the end of the second quarter and plan to request priority review for the filing. If the FDA accepts the filing for priority review we would expect and FDA decision on our application for cabozantinib in MTC before the end of the year.

We are also preparing a manuscript and exam for submission to a key medical journal.

Our Comet program in prostate cancer continues to advance as well. As you know, Comet 2, with a focus on pain palliation came online in December. We expect to initiate Comet 1, our overall survival trial in CRPC in the second quarter of 2012. If these trials are successful, cabozantinib will demonstrate an ability to control pain in patients with CRPC and prolong overall survival.

This will potentially result in a differentiated profile that could well position cabozantinib in the oncology marketplace.

The prostate cancer program is also benefiting from our CRADA and IST programs. First, regarding our ISTs, even as we implement the Comet trials, studies and other CRPC indications are underway. As we have previously reported data from Dr. Matthew Smith's IST evaluating cabozantinib at lower doses continued to demonstrate an activity profile that is consistent with that seen at higher doses but with a clearly improved tolerability profile.

We believe the profile of the low dose regimen could support the use of cabozantinib in earlier lines of therapy or in combination with other compounds in the treatment of CRPC. Updated data from this IST will be presented at ASCO later this year.

Recently, a new Phase 2 IST has been initiated in chemotherapy naive patients with CRPC and in addition, we look forward to the initiation of multiple combination studies with cabozantinib including the recently announced combination studies with docetaxel and with Abiraterone. We are also planning a Phase 1 trial of cabozantinib in combination with MDV3100.

Collectively, these studies could set the stage for further late stage evaluation of cabozantinib in the front line setting which, if successful, would considerably increase the potential size of the cabozantinib market in prostate cancer.

Ongoing non-CRPC ISTs include a Phase 2 trial in women with hormone receptor positive metastatic breast cancer and bone metastases and a trial in patients with advanced pancreatic neuroendocrine and carcinoid tumors.

Additional Phase 1 ISTs in relapsed or refractory multiple myeloma and in a Phase 2 trial in patients with solid tumors with bone metastases are also expected to initiate this year.

Now let me turn to the CRADA with CTEP. With regard to the program under the CRADA with CTEP itself we announced today that we have reached agreement with CTEP on an initial list of 13 proposed trials, several randomized Phase 2 trials with active comparative arms are part of these initial 13 approved trials.

Indications for these randomized Phase 2 trials are renal cell cancer, hepatocellular cancer, non-small cell lung cancer and ovarian cancer. Briefly, the study designs are as follows -- first, a randomized Phase 2 trial comparing cabozantinib versus Sunitinib in patients with previously untreated metastatic renal cell cancer, second, a randomized Phase 2 trial comparing cabozantinib versus placebo in patients with hepatocellular cancer who have previously been treated with Sorafenib, third, a randomized Phase 2 trial comparing cabozantinib versus Erlotinib and versus the combination of cabozantinib plus Erlotinib in patients with EGFR mild type non-small cell lung cancer and fourth, a randomized Phase 2 trial comparing cabozantinib versus weekly Paclitaxel in women with platinum resistant or refractory ovarian cancer.

Other Phase 2 trials approved in the initial program under the CRADA will evaluate cabozantinib in the second line setting of differentiated thyroid cancer, in ocular melanoma and in easier form mutant non-small cell lung patients progressing on Erlotinib. These are indications in which we have previously seen activity with cabozantinib.

Further Phase 2 trials will evaluate cabozantinib's activity in additional tumor types consisting of trials in advanced endometrial cancer, bladder cancer, and sarcoma.

Phase 1 trials are also included in the program consisting of a trial evaluating cabozantinib in combination with docetaxel in CRPC patients, a trial exploring the utility of combining cabozantinib with Vemurafenib, a BRAF inhibitor, in patients with BRAF mutated melanoma and a trial to evaluate the safety and pharmacokinetics of cabozantinib in pediatric malignancies.

With all of our ongoing clinical development activities we expect to have multiple opportunities to present data over the rest of 2012. We will have a significant presence at the upcoming ASCO meeting and I will now turn the call back to Mike for a discussion of planned ASCO events.

Thank you Gisela. I'll close today with a few final words about ASCO. Obviously, with nine cabo presentations on tap for this year's meeting ASCO will be both an important and busy time for us at Exelixis. Cabo will be featured in four oral presentations for data from first the MTC exam trial, in addition the prostate cancer non-randomized extension cohort, the liver cancer cohort, and the RCC cohort. We'll also have four poster discussions for breast cancer, the low dose prostate cancer IST that Gisela just mentioned, melanoma, and non-small cell lung cancer and then finally, a poster presentation for differentiated thyroid cancer.

These presentations should provide additional support for cabo's unique activity profile across a wide variety of tumor indications and we believe that they will help to drive further interest in cabo as an important new cancer therapy.

As we have in past years we'll also host an investor briefing at ASCO. This briefing will be an opportunity for some of our clinical investigators and members of the Exelixis clinical team to provide context around the data presented at the conference and discuss our plans for cabo going forward.

30 pm and will be available via webcast at Exelixis.com.

I'd like to end today by thanking all of our employees for another very productive quarter. The progress that we've made to date in 2012 is a direct reflection of your individual and collective talents, efforts, and commitment to advancing cabo for the potential benefit of patients and to help build value for shareholders.

So with that, we'll stop here and be happy to take questions now. Operator?

(Operator Instructions)

Your first question will come from the line of Eric Schmidt with Cowen and Company. Please proceed.

First just on Comet 1, assuming Gisela, that you're able to kick off the enrollment this quarter what is your best guess on timelines for completing the enrollment?

We are hoping to complete the enrollment in about one year and that is a timeframe that has previously been achieved for other Phase 3 studies in the setting of CRPC. We are intending to go out to a large number of sites, up to 250 sites in various different parts of the world including Europe, the U.S., Asia-Pacific.

And then a question on the NCI CTEP. It sounds like you're putting a lot of resources behind these now approved 13 or so trials. You didn't provide the number of patients that might be included in those trials. I'd be curious if you could and maybe financially a question for Frank, if he's got an estimate for what kind of spending they're committing to this program.

Eric, it's Mike. Let me take a crack at that first. The trials that we discussed today will cover a potential range of approximately 500 to 900 patients. I would look at this as a high level early estimate in that the protocols have to get written and finalized so those numbers could change over time as those protocols get locked down but you can do the math yourself to a certain degree but even using, take a very conservative dollar per subject metric, I think this tactic is extremely cost efficient for us to expand the scope of the cabo development plan and really move forward outside of MTC and CRPC.

And I would add maybe -- Eric, it's Frank -- that our financial obligation in connection with these trials is limited to $20,000 per trial per year plus we are providing the drug substance.

Okay, so certainly very conservative estimates for the expense to you guys.

Absolutely. I think it's a highly advantageous arrangement for us.

Your next question will come from the line of Joel Sendek with Stifel Nicolaus. Please proceed.

A couple questions here, first, Mike, you went through all the orals at ASCO really quickly. Was there one for CRPC or not?

Yes, the NRE cohort will have an oral presentation as well.

Okay, I missed that. Alright, and then with regard to that or the randomized discontinuation trial is there -- I know you said you can't give us much detail on what's going to be presented but will you have, can you tell us whether you'll have duration of response in CRPC, an update there?

It's a little bit premature I think to think about detailed data points. I think it's fair to say that we're planning a very well rounded presentation of the non-randomized extension of data. As you know, the study is set up on the basis and the background of the learnings from the RDT study and the value I think of the non-randomized extension cohort is one that allows us to evaluate cabozantinib in a very homogeneous patient population all of whom had received prior chemotherapy with docetaxel. Some could have had the Cabazitaxel in addition. Some have Abiraterone as well so a pretreated patient population and really, we are evaluating the end points of pain and bone scan response prospectively having learned from the RDT study if we are evaluating them prospectively in the same way as we are evaluating them for the Phase 3 studies and therefore, I think it will be very informative in view of the Phase 3 studies.

Okay and with regard to those new studies that you're doing under your CTEP collaboration especially the signal search ones, is there any basis for expectation that they'll work in those indications or is it clearly a search mission? And then maybe a corollary to that is what dose are you going to use in those studies?

That's a good question, Joel. We spent a lot of time with the NCI and our team going through the biology there. Peter Lamb is here today. Maybe he could take a few moments and just opine upon some of those different trials and the biology that is associated with both the rolled up MET and VEG-F play in those. Peter?

Sure, thanks Mike. I'd be happy to, Joel. Just in terms of some of the, my goal of the signal search trials, the basic rationale behind their selection basically follows some similar themes. In all cases there is data from clinical biopsy samples that MET and in most cases, (inaudible) MET is up-regulated in those tumors versus the corresponding normal tissue so there is a signal of MET activation in those tumor types. In some cases, that's also accompanied by up-regulation of VEG-F so the VEG-F pathway is also up-regulated so there are good indications essentially to test the impact of dual inhibition of MET and VEG-FR and a good example there for example would be the bladder carcinoma Phase 2 trial that is part of the agreement. There are some really nice data showing up-regulation of activated MET the degree to which correlates quite well with the invasiveness and aggressiveness of the cancer. It's a negative prognostic factor for overall survival. VEG-F is also highly up-regulated in that particular setting so although there is no clinical signal right now it's a very good indication to take a look in.

Some of the other trials that we're contemplating as well really start to address the question of how MET activation mediates or might mediate resistance to various current approved therapies and I think a really exciting one right now is Zelboraf in melanoma. There was some very interesting data discussed at ACR this year basically showing that MET activation via HTF produced by tumor stromal tissue can mediate primary resistance to Zelboraf in BRAF-mutant melanoma. As you're aware, not all BRAF-mutant melanomas completely respond to Zelboraf. There is range of responses and there are some patients whose tumors just grow right through it even though they have the mutation. So there is some thinking that MET activation may play a role in that so a kind of combination trial of (inaudible) and Zelboraf is aimed at addressing that.

Okay Gisela, do you want to comment on the dose?

Yes, the dose generally speaking unless it's in a Phase 1 combination study in which case we would start even lower but generally the Phase 2 dose is going forward with 60 milligrams daily dosing. And maybe just to add to the tumor types, various tumor types that I mentioned included renal cell cancer, hepatocellular cancer, ovarian cancer, differentiated thyroid cancer, we have already seen very encouraging signals of activity so these studies expound on that experience and the expectations are that we will see further activity certainly with cabozantinib. The attraction is that we are now going forward with randomized Phase 2 studies in various indications and some of them with active comparatives.

Your next question comes from the line of Cory Kasimov with JPMorgan. Please proceed.

Hi there, it's actually Matt Lowe in for Cory today. Just a couple of quick questions, I was wondering if you could comment on the early accrual or enrollment of patients in the Comet 2 study and then with all the presentations of the RDT study at ASCO is there one or two in particular you would direct our attention to which you think will capture a lot of attention at the meeting? Thank you.

Regarding the Comet 2 question, as we said we initiated the study late last year and we are in the process. As you know, it takes a little while getting all the sites up very actively. The study is enrolling and that is going per the plan I would say at this point.

Regarding your question on ASCO I think certainly there is a broad array of presentations. I would think certainly all the oral presentations are of high interest but I think the data from all the RDT cohorts is of interest.

Your next question comes from the line of David Miller with Biotech Stock Research. Please proceed.

Can you describe in more detail the pre-chemotherapy prostate cancer trial including when we might see data from that?

This is an investigator sponsored trial that David Smith at the University of Michigan is conducting and it is a study that evaluates patients who have not been pretreated with chemotherapy so chemotherapy naive patients and the main objectives in this study are evaluation of bone scan response but also other markers of activity including biomarkers, the usual response assessments, and certainly a prolonged follow up of the patient as well. Circulating tumor cells are part of the evaluation as well.

Is this a randomized study or --?

I'm sorry, this is a single arm study. It's not a randomized study.

When would you expect that we would start seeing the first data generated from your randomized Phase 2s off of the CRADA that you just announced?

I think it really depends on the time of initiation and then the speed of accruals so it's a little bit difficult to predict. Just to say in terms of the time to initiation from approval to first patient in CTEP is certainly thriving to shorten the timelines and expect a timeframe in the order of six to 12 months time to initiation. It depends on the individual trials, how large they are and how quickly they accrue.

And then finally, you had mentioned a cabo and MDB3100 trial. Can you give us some details on that, particularly when it might start, patient size, and what indication, what kind of patient?

That study is in the planning phase so we'll defer that probably better to another call.

Your next question comes from the line of Ryan Martins with Lazard Capital Market. Please proceed.

Just wanted to ask something around Comet 2. OncoGeneX recently stopped their trial, their version of the pain trial due to they said what was for them difficulty in recruiting patients due to their requirement for stable baseline pain analgesic use. I just wanted to find out how your requirements may compare to what they were doing and if you have been seeing any kinds of problems in terms of recruiting patients initially at least in Comet 2.

Thanks for the question. Our study is different obviously in design from the OncoGeneX study and I will try to describe the key features that are different. I think the first key feature is the patient population. We are allowing patients into the study who have been pretreated with prior docetaxel and Abiraterone or MDV3100 and we're not limiting other prior therapies so that difference obviously from the set of the OncoGeneX study where there was a combination with docetaxel, the treatment regimen, and that was the patient population was one that had been exposed to prior docetaxel and I think that presented some issues that possibly investigators didn't want to retreat patients with docetaxel necessarily. I think that is not an issue in our study since we are using a single agent cabozantinib approach versus midostaurin and prednisone so that requirement is basically very different.

I think another point of differentiation is that we are in the phase of screening of the patients requiring for the patients to have a moderate to severe pain and BPI of greater than or equal to four, BPI being the Brief Pain Inventory, and that their narcotic medication is optimized and not stabilized as it was for the OncoGeneX trial. I'll explain that in a second.

Optimization basically means that the best dose regimen of narcotics is identified in this run-in phase and patients receive one long acting and then as needed short acting narcotic medication. That doesn't have to be exactly the same day to day. It is dosed to the patient's needs whereas in the stabilization requires, as the word indicates, a complete stabilization of the narcotics which is difficult because patients obviously have breakthrough pain and need, on occasion, additional short acting narcotics.

So I think those are two really important key features that differentiate the two approaches.

I appreciate the color and just on the ASCO presentation for DTC, is that going to be an update to what has been presented previously?

On differentiated thyroid cancer there will be more follow up, yes. There will be an update.

Your next question comes from the line of Amin Biren with Jefferies. Please proceed.

I wanted to ask when we should expect maybe a little survival data from the RDT trial in CRPC patients?

The follow up is ongoing for the patient and we will, once the data are a little bit more mature, certainly share the data and overall survival but right now there are lots of patients still being followed up.

Your next question comes from the line of Echo He with Maxim Group. Please proceed.

I just have a couple questions on previous trial results. In the Phase 2 trials and just cross compares and those potential competitors of cabo, I collected this bone scan data was also reported on Abiraterone and also MDV31 and I got impression that cabo in comparison to those two drugs, cabo probably has lower rate on stable disease but higher rate on partial response. Is that correct from what you concluded?

I think our results as have been presented on many occasions now indicate that the majority of patients actually achieve what we determine as a bone scan response so the complete resolution of the bone scan or marked improvement of the bone scan and that, in the view of many of our key opinion leaders as well as our own is, if you will, unprecedented in that it hasn't really been described with any other drug and so maybe that addresses your question?

So insignificant is better, I mean, in the eyes of oncologists, right?

That is what we are hearing, yes.

Okay, and another one is one the pain palliation data, I think at least docetaxel and Abiraterone also reported some pain palliation actually to a significant degree in their Phase 3 trials. What is your comparison to cabo's pain palliation effect?

That is a very good question and I think here the devil is in the detail because it really depends on how the pain information is collected and we have a very rigorous, we are pursuing a very rigorous approach to that using a validated tool, the Brief Pain Inventory, that is utilized by the patient and the patient basically provides the feedback every day, seven days in a row, every three weeks and types it in basically into a cellphone and so the patient reported outcome is directly collected and then we are comparing really the assessments at week six and week 12 back to baseline and patients who have a 30% decrease in the average of the pain score on these seven subsequent evaluations who have an average decrease of 30% or greater are termed responders and we require for a responder to be confirmed so a responder has to have a response at week six and at week 12 so it is a pretty demanding threshold.

In other trials that you mentioned, a different instrument has been utilized and the pain assessment has occurred either less frequently in some cases and also less rigorously if you will when you dig into the assessment reports of the approvals of these compounds and into the label of these compounds that you mentioned, pain palliation has not found its way into the label, the regulatory label for Abiraterone or other compounds that you mentioned and that really is a function of, largely of missing data oftentimes which is a really big issue for patient reported outcomes. Our focus for Comet 2 is to have as complete as humanly possible data collection and a very rigorous assessment of the pain which differs from the other studies that were mentioned.

Okay, I understand. So the stringency and also the high rate of collection would differentiate your --

Yes.

Right, I understand. Okay, that's it. Thank you so much.

There are no further questions in queue at this time. I would now like to hand the conference back over to Mr. Mike Morrissey for any closing remarks.

Okay, thanks again for joining us today on the call. I appreciate your time and interest and will look forward to seeing you out on the road or during the next call in the quarter. Thanks again.

Thank you for your participation in today's conference. This concludes the presentation. You may now disconnect your lines. Good day.