Oncternal Therapeutics Inc (ONCT) 2012 Q2 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the GTx Inc. corporate update and second-quarter 2012 financial results conference call. My name is Taheesha 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 turn the conference over to your host for today, Dr. Mitchell Steiner, CEO of GTx. Please proceed.

Thank you, Operator. I will be making forward-looking comments during today's call, and I direct you to the press release of our financial results we filed today and the Quarterly Report on Form 10-Q we filed May 10, 2012, with the SEC where we discussed the risks and uncertainties that affect our business.

GTx has made good progress in advancing our two late stage clinical programs, Enobosarm for the prevention and treatment of muscle wasting in patients who have advanced non-small cell lung cancer and Capesaris as a secondary hormonal therapy in men with castration resistant prostate cancer.

As for Enobosarm program, we are currently enrolling subjects into two international pivotal Phase III clinical trials called POWER 1 and POWER 2 in over 80 clinical sites located in the United States, Europe, and South America. Each clinical trial will enroll 300 subjects who have either stage III or stage IV non-small cell lung cancer. These subjects are being randomized to daily doses of either 3 mg of Enobosarm or placebo at the time they start first line platinum doublet chemotherapy. More specifically, the chemotherapy regimen for the POWER 1 trial is a platinum plus a taxane and for the POWER 2 trial is a platinum plus a non-taxane. The primary endpoint for each of these studies is a co-primary endpoint consisting of a responder analysis of clinical benefit defined as maintaining or improving total lean body mass assessed by [DEXA] and improving physical function assessed by the Stair Climb Test. Durability of the drug is being evaluated as a secondary endpoint at five months of treatment in those patients who are determined to have responded at three months. Enrollment is progressing steadily in both studies of randomizing subjects at essentially the same rate. Based on the current enrollment trajectory, we expect to complete enrollment of all 600 subjects during the fourth quarter of this year. We expect to release topline results from both studies during the second quarter of 2013.

Early palliative care for the treatment of lung cancer patients is increasingly recognized as a necessary component for effectively providing comprehensive care to address host issues like quality of life, muscle wasting leading to a decline in physical function, fatigue, loss of independence and healthcare services utilization. This past February, ASCO issued a provisional clinical opinion of the integration of palliative care into standard oncology care. Seven published randomized controlled clinical trials have demonstrated early palliative care given alongside of usual oncologic care in patients with advanced cancer maintains or improves survival and improves quality of life. Based on this strong evidence, patients with metastatic non-small cell lung cancer should be offered concurrent palliative and standard oncologic care at initial diagnosis. Early palliative care leads to better patient and caregiver outcomes, which include improvements in symptoms, quality of life, and patient satisfaction with reduced caregiver burden.

As the ASCO experts observed in their provisional clinical opinion, and I quote, therefore it is the panel's expert consensus that combines standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care with evaluation of its impact on important patient and caregiver outcomes -- for example, quality of life, survival, health care utilization, and costs and on society -- should be in an area of intense research, end quote.

The ASCO provisional clinical opinion is now emphasizing quality of life. Their point is if patients do not survive longer can they live better? For example, if patients with advanced lung cancer have only a median survival of eight to 12 months, will they spend most of their time at home being active or will they spend the majority of their remaining time requiring skilled nursing care and/or hospice care? Muscle wasting has been shown to correlate with decline in physical function, weakness, fatigue, mobility disability, less tumor response and a potential for higher adverse side effects with chemotherapy, more frequent hospitalizations and shorter survival. If the POWER 1 and POWER 2 clinical trials are successful and Enobosarm demonstrates that by preventing and treating muscle wasting, there is an improvement in physical function which allows lung cancer patients to maintain their independence longer with better quality of life, then the avoidance as expensive healthcare services could translate to significant savings for the health-care system.

As for our Capesaris program for advanced prostate cancer, we have clinical sites that are now beginning to screen for patients who have metastatic castration resistant prostate cancer. Approximately 25 clinical sites in the United States will participate in our Phase II 712 clinical study of Capesaris as a secondary hormonal therapy for metastatic castration resistant prostate cancer. The Phase II 712 clinical study will build on our previous clinical experience with approximately 500 subjects who have participated in our earlier Phase Is and four Phase II clinical trials. The Phase II 712 clinical trial will test doses lower than those studied in our previous Capesaris Phase II clinical trials for advanced prostate cancer. 75 men with metastatic castration resistant prostate cancer will be randomized into one of three cohorts of 120 mg, 250 mg, and 500 mg daily dose of Capesaris. Each arm will have 25 patients and the enrollment will be conducted sequentially such that the 125 mg group will be enrolled first followed by the 250 mg group and then the 500 mg dose group of Capesaris. The enrollment into the next higher dose cohort of Capesaris will occur if an acceptable incidence of VTEs is observed for 30 days following the enrollment of the last patient in the previous cohort.

The primary endpoint is the proportion of men who have achieved a serum PSA response by 90 days. In addition we will be evaluating serum PSA progression, time to progression and progression free survival.

Phase II 712 clinical study will further confirm the mechanism of action for Capesaris, which is to increase SHBG and reduce free testosterone, thereby resulting in suppression of prostate cancer progression. We have observed this mechanism of action in the four previous Phase II clinical trials.

The safety signal we will be monitoring is the rate of venous thromboembolic events, a safety finding that has been previously reported with the estrogen class of drugs as well as other hormonal therapies. We believe that a more acceptable rate of VTEs will be observed in this new study than what was seen in our earlier Phase II clinical studies of Capesaris for the following reasons.

One, we will be evaluating lower doses of Capesaris. Two, the study is designed to include patients with a history of VTEs or who screen positive for blood clotting factors, mutations and deficiencies. Three, we will provide a daily 81 mg aspirin to subjects who are not already taking aspirin. And four, we plan to monitor patients with a development of new VTE risk factors while on study and, where appropriate, consider the administration of [BTE] prophylaxis. With these additional requirements added to the protocol, we believe the rate of VTEs will be shown to be similar to what has been reported in men with prostate cancer who are being treated with primary ADT achieved by LHRH agonists, LHRH antagonists or surgical orchiectomy.

Data from the previous Phase II clinical studies that were stopped earlier this year, as well as from the earlier Phase I and Phase II clinical studies, give us comfort that Capesaris will continue to be effective at the lower doses we are now testing in men with metastatic castration resistant prostate cancer. One important observation from our previous study is that SHBG levels appear to become saturated at higher doses. That is, SHBG levels do not elevate to greater levels with higher doses of Capesaris. Since the mechanism of action of Capesaris involves increasing SHBG to lower [free T], we will be trying to determine the optimal increase in the level of SHBG required to lower serum PSA in men with castration resistant prostate cancer who already have achieved castration and are maintained at castrate levels while on primary ADT.

In the Phase II 707 clinical study in men with castration resistant prostate cancer at the 2000 mg a day dose of Capesaris, we reported that the mean increase in SHBG was only 399 plus or minus 85% for men that had a serum PSA response. And we now have evidence from our previous Phase Is and Phase II clinical studies that we can achieve similar increases in levels of SHBG at lower Capesaris doses. In fact, we have data that suggests even lower levels of SHBG could also lower free testosterone and serum PSA.

Another unique characteristic of Capesaris is that not only does it have the potential to reduce [free] testosterone in men who have already achieved castration, but also as an estrogen-based therapy we have observed that Capesaris improves the estrogen deficiency side effects associated with ADT such as hot flashes, bone loss and insulin resistance. We expect to release our clinical data from these previous Phase 2 studies in several upcoming scientific meetings.

In summary, Capesaris offers a unique secondary hormone therapy to treat castration resistant prostate cancer by increasing SHBG and further lowering free T while potentially avoiding the estrogen deficiency side effects of ADT. It is now clear that advanced prostate cancer can continue to be suppressed by different hormonal therapies and the prostate cancer field is evolving to be more like the breast cancer field where several secondary hormonal therapies will be used sequentially and in combination before cytotoxic chemotherapy is attempted.

The main question in prostate cancer today is how these are hormonal therapies will be used, not whether that will be used prior to chemotherapy. They all will be used prior to chemotherapy. The use and order of the secondary hormonal therapies will be based on their respective efficacy and safety profiles.

We are excited about the potential of Capesaris to offer a novel treatment to men with advanced prostate cancer. We look forward to sharing the efficacy and safety data from this study by the summer of 2013.

This morning, we also released our financial results for the second quarter of 2012. While I won't review the financial results in detail, let me point out that we ended the quarter with $55.9 million in cash in short-term investments. Marc Hanover and I will be happy to answer any questions you may have about our financial results during the Q&A.

Operator, we are now ready for our first question.

(Operator Instructions). Joel Sendek, Stifel.

I have a question on each of the programs. First of all, on Enobosarm, so you have two endpoints. I am just wondering if you need both of the two for the trial to be successful. In other words do you need the responder analysis and the durability to be met? And also can you go over the difference as to what happens in three months and five months with durability? And then I have a follow-up on Capesaris after that. Thanks.

So, first of all to be clear, the end point is a co-primary point which means that the study -- the study, not the patient, but the study -- needs to achieve, one, to consider the responder maintain or improve your lean body mass, that is one endpoint. And the other endpoint is a 10% improvement in physical function measured by Stair Climb. So, a single patient and the endpoint happens at three months.

The single patient doesn't have to hit both, although we know that if you have an increase in lean body mass and maintain it, you are more likely to hit both but for the study to be successful, you need to hit physical function improvement and you need to hit an improvement or maintain the lean body mass. We have a P value of less than 0.05 for each, and so again the study at three months needs to hit both of those, okay?

Now with that said the durability is a secondary endpoint. And so that is a little different. In the secondary endpoint the patients who responded at three months will then be looked at again to see if they continue to respond by five months. At two months later are they still responding. That is really almost a descriptional statistics as opposed to a hard statistical endpoint. So that is why it is a secondary endpoint.

The other important point about the primary endpoint is it is a responder's analysis so there is no missing data. That means that the base -- the patient is not going to be really compared to the placebo. The patient is being compared to themselves. So if a patient maintains a lean body mass compared to their baseline, then they win. That is a yes. If a patient has a 10% improvement in their physical function, then that is a yes. And the goal is to see whether we have more yesses with our drug compared to placebo. And so that is out little different than typically when you look at continuous variable data where it is the mean or the median of the placebo versus the mean or the median of the treated. It is actually from baseline. And we know that our patients do best when you compare them to their baseline.

Got it. Okay. Thanks. And then quickly on Capesaris, I guess my concern would be given the fact that you are making these provisions to reduce the potential for VTEs, does it -- is it no longer a real world study and might the FDA have some issues with you being able to -- this drug still being safe in a generalizable population -- or a general population that might not take all those measures?

Right. So let me see if I can answer that question. We do think it represents real world and the reason it represents real world is as a hormonal based therapy especially in estrogen, go read the labels for hormone replacement therapy with estrogen and postmenopausal women, and also go read the labels for oral contraceptives or any contraception in women. And you'll see that the language that they have will be pretty much the language that we will have. Because at the end of the day this is what this class does. So we are not going to get away from that.

And all we are saying in our inclusion-exclusion criteria is to make sure that people that have a history of VTEs shouldn't be taking one of these drugs. And that is real life with any of these drugs today. So we are not really changing the positioning of a hormone-based therapy. So that is number one.

Number two, the only thing that would be different in the real world would be screening patients. In other words, it may be that the label says screen -- if you have Factor V Leiden mutation, you shouldn't be taking the drug. Well, that is personalized medicine and that is moving into the realm that the FDA likes and then, quite frankly, it is using testing that we currently have. So what is the rate? And we will find out more from the study of patients that have Factor V Leiden mutations and other ones like that. It is going to be less than 5% to 10% of your population.

Another way of saying it is 90% of your population are going to do just fine and why would you want to put them on a therapy if you know that the therapy may put them at risk? So that would probably be the only thing. And if that is the case it will knock our market by 90%.

The other side of the equation is efficacy. This -- DES, diethylstilbestrol, is a sloppy nonspecific estrogen that is being used today in patients with prostate cancer. And it is being used today because it works. It has been used for 60 years. It works for primary castration. It works when somebody fails primary castration. It works when somebody fails abiraterone or any of those drugs, it fails ketoconazole, it works after somebody fails in AR blocker. It works after chemotherapy and it works even after you stop the drug and reintroduce it.

So, there is a place for this compound and the question is, if all our label shows is that we have basically an estrogen base type therapy with those caveats and we have to screen patients with new science that could get into trouble, then you are really still dealing with 90% of the population that can have a tremendous benefit. It is worth pursuing a drug that is a souped-up, better and selective and [safe route] DES.

Okay. Thank you.

David Nierengarten, Wedbush Securities.

Thanks for taking the question. I was just wondering if you could define what you thought or if you had any guidance on what the acceptable rate of VTEs would be in your Capesaris study?

Yes. So, if you go back and look at the -- I will give you two endpoints. If you look at DES diethylstilbestrol, that VTE rate can be as high as 24%. That is a pretty high VTE rate.

If you look at Lupron -- and there's some great studies showing that people that just start Lupron for the first time, and then you follow those patients, the VTE rate is about 3.8%. 3.8%. So what we observed in our studies when you look at the 709, 710 and 705 studies, the maintenance part, we saw a VTE rate that was 5.86% -- 5.8% to 6%. Roughly 6%. So what we are asking is with these new provisions can we move that VTE rate down towards the 3.8%? Can we get it less than 4%? If we can get it less than 4%, then we will be in the realm of what you would expect with primary hormone therapy and certainly a lot lower than the estrogens that are being used today.

And then a quick follow-up. Thanks for that. In terms of how we are evolving to be essentially what I would call super hormones with [ensoludomide] and abiraterone, do you -- how do you see -- or do you think an interesting niche or an interesting positioning of the compounds since we don't know yet really how patients respond, if they respond, if they take ensoludomide and then abiraterone, it is kind of like will you -- you will have a place because you have a different mechanism of action in your product positioning, so a physician would feel comfortable prescribing that, knowing he would have the option to use ensoludomide post Capesaris, for example?

Yes. So the way I look at it is I look at it the following way. First of all, would you consider a hormone therapy or would you consider a chemotherapy? And I see chemotherapy has been pushed way out as these hormonal therapies whether it is abiraterone, prednisone, ensoludomide or Capesaris. They would all most likely be used before you attempt cytotoxic chemotherapy. Okay, that is point one.

Point two. I see that the angin receptor blockers and drugs like abiraterone with prednisone will make the -- will further castrate the patient and making the rest of the deficiency side effects worse. So the bone loss, the hot flashes, fractures, all of that stuff will get worse only because you are squeezing the T even more. The advantage of Capesaris in that setting is that in addition to squeezing the T more, we also -- because it is estrogen-based, or replacing the estrogen that is deficient so that the hot -- the potential or avoid the potential for hot flashes, bone loss, insulin resistance, some of these other things. So what I see happening is the following.

One is that the sequencing of these drugs, whether it is abiraterone with prednisone, ensoludomide by itself or our compound is going to be based on the profile, efficacy profile and the safety profile. Then again because of all hormonal therapies they are going to be better to the evidence side of toxic chemotherapy.

Then the next thing that is going to happen is how do you sequence it? In other words which one should you go first? And I would say it is going to be based on efficacy and safety. And the second thing is and we know that this is true that when you are using these drugs in combination there should be even more activity.

In the breast cancer field for example tamoxifen was I guess introduced approximately 30 to 40 years ago and the New England Journal of Medicine just reported on a combination hormone therapy study using drugs that have been in this space for a long time. So, I think the question of combination and sequencing is going to be a long one. I mean this is going to be five, 10 years. And so the monotherapies are now getting their seat at the table and to have monotherapy, you need to show that you work as monotherapy. And because we have a different mechanism and it is not a me too and the drugs of this class have shown activity, then we need to move forward with evidence-based science to show that we have a place.

Thanks.

Biren Amin, Jefferies.

Thanks for taking my questions. It seems the POWER enrollment timelines are slightly delayed since previously the Company was guiding for finishing enrollment at the end of summer versus current guidance of the Q4 completion. So can you maybe discuss the reasons for the delay? And also can you give us the enrollment split across the US versus ex-US in each of the two trials?

Right. So the question is, is it delayed. We have been guiding everybody that we were planning to complete the study at the end of summer which is the September timeframe. The good news is that we now have enough data and trajectory in our enrollment that we are quite pleased with our enrollment. Our enrollment is, as I said in my comments, enrolling steadily. It is enrolling equally in both studies. At one point I was concerned that maybe one we enrolled more than the other. And that's -- we are feeling pretty good that this thing is going to be fully enrolled in fourth quarter which, compared to end of third quarter is not much of a delay, given the complexity of a trial of this nature where you are dealing with newly diagnosed advanced lung cancer, stage III, stage IV, catching them right when they are starting their chemotherapy. So I am proud of our team and I don't think the delay will be material.

With that said, in terms of the mix of patients, I have to -- I don't know the exact statistics, but the United States has roughly 30 sites and we have about 80 to -- 80 sites worldwide and so I am not sure on the split. We are shooting for having good US representation. But the truth of the matter is, that we are also running all through Europe and all through South America. So we will just have to see how it shakes out.

And with regards to the consistency of the site's ex-US, in your opinion do the South American sites, are they consistent as far as measuring for star client power, for example, or DEXA scans versus the US site?

Yes very consistent. We have -- they get extensive training. First of all the DEXAs are all centrally read by [Synarc]. And before any site whether it is US, Europe or South America and began to test patients they have to go through complete training and sign off in qualification and validation through Synarc who centrally reads the information.

In terms of Stair Climb power we have, again, extensive training. The monitors are constantly going back and making sure that everything is done correctly and what we've seen so far it has been very consistent across continents. And of course, during -- when the study is complete, FDA requires that you also show where there is any geographical variation. But at this point now, those are pretty hard endpoints. I mean, for DEXA, that having that done by [Central Read] is important and Stair Climb, the only thing that the sites are measuring, quite frankly, is the height of the stair -- staircase which is eight steps and the computer does the rest of it. The patient touches the pads and the pads are all identical and the equipment is all identical across the world.

And moving on I saw on clintrials.gov recently that GTx is about to initiate a Phase II trial with Ostarine in 89 patients with metastatic breast cancer who have failed prior hormonal model therapy. It doesn't seem that it is being studied as palliative, given the primary endpoint as response rates. So can you maybe discuss the rationale for evaluating [this arm] in this study?

Yes. So where are with that is we have not pulled the trigger on that trial because we are focusing primarily on Enobosarm and getting back to the finish line and Capesaris doing the Phase II study and making sure that we are getting data. We did file that trial which has not started and the reason we filed it is because we are thinking about it. But we certainly are not going to execute it without money.

With that said, the trial design is exciting from a standpoint that it is well known that in addition to estrogen, androgen receptors are very, very important in breast cancer. In fact it has been used for again approximately 50 to 60 years. People have used [how Testim] and other testosterone like products to treat breast cancer. And a new hormonal therapy has not been introduced into breast cancer in over 20 years.

It turns out that if the patient is estrogen receptor-positive and antigen receptor-positive that the androgen receptor is anti-proliferative. And this has again been shown with these dirtier off target compounds, while our sarm is a clean AR positive binding agent that doesn't cause a viralization location in women. We now know this with -- if you count the number of patients an hour -- that will be done in our current study plus the other studies we've done, I mean, we -- 600 to 1,000 patients. We know pretty much that this is not a viralizing drug at this point.

And so, that is based on those eight clinical studies that we have done in 600 patients. Not referring to the study that we are doing at this point now because I don't have any data. But with the past studies it doesn't viralize.

So if that's the case, then we do think there is a role for at least showing in a Phase II setting that we can affect breast cancer progression. So that is why it is in there. It is exciting. I know other companies are going after AR blocker's, the problem with AR blockers and this has been done with bicalutamide. That is a much smaller group of patients. But the majority of patients are going to be those that are ER positive, AR positive, that want to avoid chemotherapy and will be happy to have another hormonal therapy that again taking advantage of a sarmal receptor, be anti-proliferative and also help bone. Because remember Ostarine was the old name for the compound because it increases BMD.

Great. Thank you.

Ryan Martins, Lazard.

Thanks for taking the questions. The first one is just a question on Enobosarm. Does the regulatory strategy, let's say one of the trials is successful, the other is not. I mean how do you think about regulatory strategy there? And secondly, have you done any pricing reimbursement to work on Enobosarm given as you mentioned ASCO's put out this guidance on early palliative treatment? And also wanted to find out what kind of educational effort you think may be needed once you think about launching this drug?

Great. So the first question, sort of a regulatory strategy and that is in the event that one trial comes in positive and the second trial does not, again there's all what ifs. But I would argue that if either one of the studies come in positive the only difference between the two studies is the chemotherapy that is being used. So for POWER 1 it is ataxane with a platinum and POWER 2 is ataxane with a non-platinum.

It is well known that platinum ataxanes could have their own set of issues independent and that is the reason why we ran it separately. So that at least from a safety standpoint we will be comparing apples to apples.

In the event that one study is positive and the other one is not positive or at least supportive, we still think there is a way forward. Because then you will have information that you can go to FDA. It is a cancer patient population and you are treating a cancer related symptom and as you know the FDA, especially in a patient group that has poor survival, this would be important.

We -- so our position would be to still move forward and have a discussion with the FDA and see what paths to take forward.

In terms of your second question which is, have we done any work to understand how doctors and payers feel, we have. And then to answer your question about education, we have. And I am going to turn both of those questions over to Marc Hanover since he has been responsible for the independent research that is being conducted on the half of GTx. Marc?

We have gathered independent market research and, as Mitch mentioned, the market research includes interviews with doctors, patients and managed care organizations. A few of the takeaways that I think are important to mention -- and again we are still gathering this. But the target product profile for Enobosarm is seen by the doctors and the managed-care folks that we interviewed as being of benefit to patients. They view the target product profile as potentially being an important component to the treatment armamentarium for these patients.

I think what is most important to us that we saw throughout this market research was the acceptance of and the importance of seeing that this drug is potentially very valuable and should be given at the earliest point that the patients are diagnosed. And I think that in and of itself is, to us, was important from a market perspective in that A, they see the value of what the drug can bring to the table. But B, it also brings into the equation a benefit to the patient which ultimately gives us flexibility on pricing. So I think that was very important for us to see.

And the other key takeaway was that in doing the market research, it was very clear that this drug has the opportunity to be a $750 million drug in the US alone. That doesn't take into account anything ex-US. So we feel that Enobosarm continues to be a very valuable asset and one that we are excited about.

From the educational standpoint, clearly there is if there's one thing we saw in this independent market research is it does require education, it will require education and that is something that we are currently working on right now. Our team is doing that currently but we also know that we have to do more. And that is something that we will do, continue to do and then of course look to do as well post data. So, right.

Right, and just to add a couple more points on the payer side, the payers did make the point that if there is a patient benefit in spite of survival, just showing the benefit in physical function that even the payers are stepping in and realizing that this is a an important product for the patient. Because just because sometimes a physician thinks so doesn't mean the payers will and that is not what we learned from our independent research.

The second thing is, there was great awareness about a product of this type by the medical oncologists and it, quite frankly, rated pretty high in terms of whether they would adopt and use it both in prevention and treatment. But Marc is absolutely correct. In order to take advantage of that high rating, we need to make sure we educate them on the efficacy and safety of our products once we have the data.

Thanks and one final one. In Capesaris, what kind of mutations are you screening for? Can you go through some of the detail on that?

Yes. So, essentially what we are screening for is a Factor V Leiden mutation because just take a step back. We were very fortunate that we can go back to the hormone replacement therapy data in postmenopausal women, which is estrogen-based, and as well as an oral contraceptive, again in women. And when you go back and look at those studies and ask the question, which women got into trouble with VTEs, 85% of those women if you screen -- I guess screen at that point is not the right term. If you measure some of these clotting factor disorders, you will find that 85% of these women you could have screened them out of the study if you knew ahead of time. That is a big comment.

So with that said, the ones that we are screening is going to be Factor V Leiden mutation which is probably the most common one. The other one is measuring protein C and protein S deficiency. Because those patients could get into trouble. We are going to look at a prothrombin mutation, and then some of the esoteric stuff that we are going to look at just mostly for education we will be looking at, for example, some of these antibodies like against cardiolipin and phospholipids. And these are small ones. We don't expect much.

But I would say the bulk of what we are doing will be again Factor V Leiden, protein S and protein C deficiency, and the prothrombin mutation. My bet is that the Factor V Leiden will be the most revealing and that is all because of what we've seen both in prostate cancer patients that were taking estromustine or DES and also in the hormone replacement therapy in contraception data all points to -- these are easily measurable things that we could limit a patient's exposure to drug; they should not be on drug.

(Operator Instructions). [Amir Bavar], Cowan.

Thanks for taking my questions. Actually most of them have already been asked. But I just wanted to ask could you talk all bit about -- you talked about the positioning of Capesaris and I was wondering if you could expand a little bit more on that. I know it's a bit early, but just in terms of your false going forward with potential combinations or sequencing trials in the future.

Yes. So, I mean the way -- to answer that question you have to think of your compound as achieving its target product profile. And our target product profile is of course we are going to be efficacious. But, in addition to being efficacious being a different mechanism that we will have the ability to treat bone because we won't see the bone loss. The hot flashes, which is an important quality of life issue, we will be able to avoid hot flashes. And just those two things alone and being an oral agent raises the question of where in this sequencing of events should we be used.

So if a patient has been on Lupron for five to 10 years and they begin to have a rise in PSA and they develop metastatic castration resistance prostate cancer, do you want to put them on an agent that will further reduce their testosterone and further increase -- or say definitely worsen their quality of life as it results in hot flashes and bone loss and having to take additional bone drugs. Or can we limit the polypharmacy and just add, for example, Capesaris? In which case, Capesaris is then added, patient gets the treatment for the cancer and, in addition to that, gets a benefit by treating the estrogen deficiency of side effects. This is also assuming that our VTE rates less than 4%.

Then what I would imagine would happen at that point the patient will progress. Always unfortunately all hormonal therapies eventually the patient will progress, and then, the next therapy decision would have to be what is the next drug that will be efficacious and safe. And then I would argue that the next one probably should be ensoludomide because ensoludomide has an excellent profile and you're not adding, for example, prednisone which is going to make the bones worse and metabolic syndrome, and maybe that is the next one. And then after that I would think abiraterone prednisone would make sense.

And again this is all in the pre-chemo setting, because in the future I just don't think that this will all be given post-chemo, will all be given free chemo. So in that setting I then envision abiraterone prednisone being important and again you can see the beauty of the first secondary hormonal therapy, the second secondary hormonal therapy, the third secondary hormonal therapy and patients that respond to hormones tend to continue to respond to hormones. And then you move into chemotherapy and post chemotherapy.

But then, how do you use them in combination which they will be? How do you use them sequentially in terms of how you compare them and stuff like that? That is going to be years and so I think, initially, if a monotherapy if you come in with a new mechanism that's not a duplication of an old -- of the mechanisms that are already on the market, and you are not cytotoxic chemotherapy then I think you have a place at the table.

Great. Thank you so much. My last question is about the cash on in terms of how far you think it will take? If I remember correctly before you had said something like mid 2013. I am wondering if that is still the case and just what your situation is on that.

Sure. It is the case, it will actually go a little bit beyond that. I want to make it clear though that we have said all along that both data points, both Enobosarm and Capesaris data points, subject to enrollment ought to be we ought to have both of those data cards before we run out of money. So just to remind you that we mentioned that earlier.

Howard Liang, Leerink Swann.

Thanks very much for taking the questions. First, on Capesaris. What will be the path to registration as a secondary hormonal therapy? I think the other secondary hormonal agent so far have done overall survival studies. Would testosterone suppression be (multiple speakers) in that study?

Right. So I view this next study that we are doing is sort of a Trojan horse from the standpoint that we are going to get efficacy data lower doses, understand our target product profile and then mostly again show that we can achieve a VTE rate in a selected population of less than 4%. If we do that, we do know that the compound if we decide to pursue a primary ADT population we do know that our compound will castrate and maintain castration, but the FDA will require that you maintain castra -- you castrate by day 28 and you maintain castration from day 28 to 360. So that setting what we would envision is very much like I said in the other conference calls is that we would probably start out by castrating the patient with Lupron, but maintaining that castration and having all the benefits of estrogen replacement and never having to give the patient another shot of Lupron after they start our drug.

So that is one path forward in which case you'd meet the need of reducing testosterone to castrate less than 50 nanograms per deciliter by day 28 and maintaining from day 28 to day 360.

The other path to take is that we are a unique mechanism and expect to show just like we have already shown in our Phase II 707 study activity in castration resistant prostrate cancer. If that is the case, the path to market, the path to registration will include progression-free survival and the question on the table is whether or not overall survival will be required, given that the field is expanding and overall survival is going to be difficult to show in a pre-chemo setting. If that is -- our position though is we will have discussions with the FDA after we complete this Phase II and we will be able to comment more more solidly on what that path forward will be.

But our position at this point is that progression-free survival which is now being validated by the -- and has been validated by the abiraterone, Zytiga and also by ensoludomide, and be further validated with the pre-chemo studies that will come out so that GTx can come in and say, well, look now you have got your link between progression-free survival and overall survival. At some point cancer therapy moves to progression-free survival only. And that is for example it happened in breast and lung cancer and renal cell and so on.

So that is kind of how we are thinking about it right now. But it is still very early.

For the Phase III trials of Enobosarm, is the treatment continuous as long as the patient can tolerate it or is it for a fixed duration? Or what is the guideline in the protocol treatment discontinuation? And the second part of the question is, I think FDA wants to see overall survival data from this trial. How mature would be overall data have to be before you can file?

Right. So the first question has to do with dosing and in a five-month study, how long are they being dosed. So in a five-month study the patients are being dosed every day with 3 kilograms of Enobosarm or they are getting a placebo. If the patient -- now, the drug as you know from our previous studies we have not seen -- let's say it a different way. The drug appears to be well-tolerated.

In this setting, however, these patients are getting cytotoxic chemotherapy and we do expect the dropout rate. And the dropout rate that we've built into the trial is 30% for each trial. And I am happy to report that we are lower than that dropout rate, so the assumption is still in place. Patients that drop out statistically are handled as a non-responder. So if they drop out that is typical for any cancer trial. So that is already built into the study.

If a patient discontinues -- excuse me Enobosarm, but they can still come in for an assessment, they would be still counted in the assessment. And then after five months, the patients will continue to be followed for survival. And so we expect by the time we get our data and we file the NDA, at 120 days after we filed the NDA, we expect to have 450 deaths in the 600 patients. And we do think that is going to be enough to certainly show safety.

And if we show a benefit that's certainly enough numbers to do that. The FDA's only requiring overall survival as a safety endpoint and if it is a key secondary endpoint and really descriptive only.

Great. Thanks very much.

That concludes the Q&A. I would now like to turn the conference back over to Dr. Steiner for any closing remarks.

Great. Thank you, Operator. I would like to thank everybody for your interest in GTx and I look forward to updating you in the future. Bye-bye.

That concludes today's conference. Ladies and gentlemen, you may now disconnect. Have a great day.