Oncternal Therapeutics Inc (ONCT) 2012 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the fourth-quarter 2012 GTx earnings conference call. My name is Carissa and I will be your operator for today. At this time all participants are in a 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's call, 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 November 8, 2012 with the SEC, where we discuss the risks and uncertainties that affect our business.

I will begin with an update of our clinical program starting with enobosarm for the prevention and treatment of muscle wasting in patients who have advanced non-small cell lung cancer.

As we previously announced last quarter, we have completed enrollment of our two Phase III clinical studies of enobosarm, POWER 1 and POWER 2. We have enrolled into each clinical study approximately 325 subjects who have either Stage III or Stage IV non-small cell lung cancer in over 80 clinical sites located in the United States, Europe, Russia and South America.

The objective of these studies is to determine the potential of 3 milligrams of enobosarm versus placebo to prevent and treat muscle wasting in advanced non-small cell lung cancer patients when given at the same time they initiate standard first-line chemotherapy consisting of a platinum doublet.

More specifically, in POWER 1 subjects are receiving a platinum, which is cisplatin or carboplatin, plus a taxane, docetaxel, a Paclitaxel, and in POWER 2 subjects are receiving a platinum plus a non-taxane, gemcitabine, vinorelbine or pemetrexed.

Unlike Megace and other drugs which are currently used to increase appetite and have detrimental effects of muscle mass in cancer patients with cachexia, with the enobosarm in this indication clinical benefit is defined as maintaining or improving total lean body mass or muscle assessed by DEXA and improving physical function assessed by the Stair Climb Test a day before.

The co-primary endpoint for each of these studies consists of a responder analysis of clinical benefit. Durability of the drug is being evaluated as a secondary endpoint as five months of treatment in those patients who are determined to have responded at day 84.

This is not an appetite drug. Its agent is being evaluated to prevent or treat muscle wasting, a common and devastating cancer-related symptoms for which there are no current -- which there are currently no medical treatments.

With the last patient being enrolled at the end of December 2012 we expect all subjects to complete the two studies by the end of May 2013. And after taking into account the time required to finalize all patient documentation for both studies at sites in eight countries in order to prepare for data lock, which at this time is still somewhat dynamic, we currently anticipate that we will see top-line data for these studies in the third quarter of this year.

We intend to share the top-line data for both studies, POWER 1 and POWER 2, at the same time. The top-line data at a minimum will include the co-primary endpoints of lean body mass and physical function and safety as well as an update on the survival information at that time.

In January of this year we announced that FDA has designated enobosarm for the prevention and treatment of muscle wasting in patients with non-small cell lung cancer as a fast track development program. An IND for enobosarm is in the oncology division and this action is consistent with my previous points on the seriousness of muscle wasting as a cancer-related symptom.

Fast track status is a process designed by FDA to facilitate the development and expedite the review of new drug candidates that are intended to treat serious diseases that have the potential to fill an unmet medical need.

With a Fast-Track Designation there is an increased possibility for a priority review of a new drug application we filed for enobosarm and more opportunity for us to have frequent interactions with FDA both prior to and following the filing of the NDA. The FDA clearly recognizes muscle wasting in these cancer patients as a serious and unmet medical need.

The oncology field is also changing; clinicians are now finding in their treatment of cancer patients that addressing patient symptoms and quality of life can result in better clinical outcomes from the underlying cancer treatment. Over the past several years we have seen the development of new cytotoxic chemotherapies to treat advanced non-small cell lung cancer.

However, these chemotherapy agents have offered little or no survival advantage over standard therapy. These new therapies cannot make meaningful improvements in survival for non-small cell in cancer patients when treating their tumor. We believe enobosarm by treating the host, the patient, can at least improve their quality of life such as physical function while they fight their cancer and potentially better equip them to tolerate the chemotherapy treatments for longer periods of time and delay their need for specialized nursing services and hospice care.

The American Society of Clinical Oncology, or ASCO, recently published a provisional clinical opinion regarding the need to integrate palliative care early into standard oncology care in patients with non-small cell lung cancer. Early palliative care for the treatment of lung cancer patients is recognized as a critical component of a effective cancer comprehensive care.

Patient issues and concerns such as quality of life, muscle wasting resulting in a decline in physical function, fatigue, loss of independence and increased healthcare services utilization are important aspects in the care of patients undergoing cancer treatment.

GTx has designed its POWER 1 and POWER 2 Phase III clinical studies to assess many of the same outcomes suggested by ASCO as key endpoints in these studies including quality of life, healthcare resource utilization, ability to receive plan chemotherapy, dose intensity and overall survival.

We believe the treatment of muscle wasting in non-small cell lung cancer patients is an attractive market for enobosarm. Approximately 1.6 million people worldwide will be diagnosed with lung cancer this year and the five-year survival rate for this diagnosis remains only approximately 15% notwithstanding the introduction of many new cancer treatments.

About 85% of all lung cancers are the non-small cell lung cancer type making this disease a leading cause of death for both men and women. Our market research suggests that our peak US sales from enobosarm should be approximately $700 million -- $750 million. And of course this estimate does not take into account sales outside of the United States and the potential for enobosarm to address muscle wasting in other disease states or to treat other indications.

We're already planning additional clinical studies for enobosarm to address indications where we believe there is a good opportunity to benefit patients and to expand the drug candidate's commercial potential.

Now to update you on Capesaris, also known as GTx-758, our other late stage clinical program where we are conducting our fifth Phase II clinical study of Capesaris, an oral selective estrogen receptor alpha agonist developed by GTx scientists for the treatment of advanced prostate cancer.

We believe Capesaris can offer a unique treatment option for men with advanced prostate cancer by reducing free or the unbound testosterone levels lower than can be typically achieved by LHRH agents or surgical castration.

Capesaris accomplishes this by causing the liver to increase production of a protein called sex hormone binding globulin, or SHBG, which binds very tightly to the unbound or free testosterone circulating in the blood and further reduces the levels of serum free testosterone in the castrate environment.

Treatment of prostate cancer with androgen deprivation therapy, or ADT, improves prostate cancer symptoms, but patients eventually develop castration resistant prostate cancer as their cancer adapts and uses the available free testosterone in the blood to grow.

Dr. Evan Yu, Associate Professor of Medicine at the Fred Hutchinson Cancer Research Center in Seattle, Washington presented last week four related abstracts at the 2013 ASCO Genitourinary Cancer Symposium in Orlando, Florida.

In two Phase II clinical studies in men with advanced prostate cancer patients receiving either the 1,000 milligram or 2,000 milligram daily doses of GTx 758 demonstrated significant reductions in their serum free testosterone levels with related increases in SHBG and reductions in their levels of serum PSA.

One of the trials, 705, compared the effects of 1,000 milligrams and 2,000 milligram doses of GTx-758 in newly diagnosed advanced prostate cancer patients with a cohort of patients receiving leuprolide in established primary androgen deprivation treatment. The primary endpoint of the trial was the proportion of men who achieved medical castration by day 60.

Though in hormone naive advanced prostate cancer patients in the study with lesser reductions in serum total testosterone observed in men receiving GTx-758 dose by 28 days, there were larger decreases in serum free testosterone that were observed in the same men as compared to leuprolide.

Reductions in serum PSA 28 days appears to be more strongly associated with the observed changes in free testosterone rather than total testosterone with PSA reductions of 84%, 73% and 56% from baseline for subjects treated with 1,000 milligram and 2,000 milligram doses of GTx-758 and leuprolide respectively. In men treated with GTx-758, SHBG levels increased approximately 400% and were associated with decreases in serum free testosterone and serum PSA.

In the other presentations Dr. Yu reviewed the data from our Phase II studies on the effects of GTx-758 leuprolide on the estrogen deficiency side effects where GTx-758 compared to leuprolide patients had fewer hot flashes, had improvement in bone markers and had less insulin resistance even in the background of having a lower free testosterone level.

In the current Phase II clinical trial, 712, to evaluate the safety and effectiveness of lower doses of GTx-758 to treat men with metastatic castration resistant prostate cancer, 75 men with metastatic castration resistant prostate cancer are being randomized into one of three cohorts to receive a 125 milligram, a 250 milligram or a 500 milligram daily dose of GTx-758.

Each arm will have 25 patients and the enrollment will be conducted sequentially with the 125 milligram cohort currently accruing patients. The enrollment into the next higher dose of GTx-758 will commence if an acceptable incidence of VTEs is observed among randomized patients for 30 days following enrollment of the last patient in the previous cohort.

The primary endpoint will be to lower serum PSA by greater than 50% -- greater or equal to 50% by day 90 and other key endpoints include free and total testosterone, SHBG levels and progression free survival in the study subjects. In addition, the study will evaluate the ability of GTx-758 to treat certain estrogen deficiency side effects associated with medical castration such as hot flashes, bone loss and insulin resistance.

Enrollment for the study is progressing; we continue to add sites to the study including sites outside the United States and we anticipate we will have data from this open label study sometime in the summer. We believe the lower doses now being studied will be effective in substantially raising SHBG and thereby lowering free testosterone while minimizing concerns associated with VTEs seen in our studies of Capesaris at higher doses.

If this proves to be true then GTx will assess the potential treatment options available to Capesaris including using the drug product as a first secondary hormonal therapy or as a primary therapy used in combination with ADT in the treatment of advanced hormone naive prostate cancer.

This morning we also released our financial results for the fourth quarter and full year of 2012. While I will not review the financial results in detail, let me point out that we reported $56.1 million in cash at the end of the year and we have no debt or warrants outstanding. 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). Eric Schmidt, Cowen and Company.

First on enobosarm, Mitch, you mentioned or reiterated the primary endpoint of studies at three months. But it sounds like, if I followed you correctly, that you are only going to unlock the data after the five-month secondary endpoint, is that the intention? And why wouldn't you unlock the database just after the three-month primary endpoint?

Okay. So to make sure I understand the question. So the question, the primary endpoint is going to be a day before three months and you are going to continue to follow the patients for another two months to have five months on study. And the question that you are asking is, well, if all the patients are done with the primary endpoint at month -- day 84 then why not just look at the data at day 84? Is that the question?

That is right, correct.

Okay. Well, the answer is -- we have had a lot of discussions about this. The FDA also takes very, very seriously a key secondary endpoint which is durability. And so, the concern would be that if you unlock the data at day 84 and present that data without -- and the patients that are still on the study find out that we have positive results, then how is that going to affect the day 147 or the five month data?

And the protocol that we have written clearly says that the protocol is not over until -- the conduct of the study is not over until the patients have crossed day 147. So it is just -- we are just following protocol. So it is not really one reason or not. So that is the reason why we have to wait for the last patient to come out in May.

Okay, so, do you think you kind of need to see the durability effect at five months? Do you need the five-month data to be positive as well as the three-month in order to file the drug?

Well, as you know, the answer doesn't have to be positive and I will tell you -- let me say it a different way. Because of the fact it's a five-month endpoint and because of the fact that we are not powered to show a positive effect at five months from the standpoint of durability, it is purely [descriptive].

The FDA sees this as a key secondary endpoint and so it is not like you have to have, quote, statistical significance. But the FDA is interested in seeing what happens to those patients that responded day 84, did they continue to respond at month five. So that is really what it is as opposed to, oh my gosh, now you have got another endpoint you have to hit. It is descriptive in nature.

So you might want to see a trend in other words?

That's right. Or at least understand what the durability is, it's not necessarily (multiple speakers).

Okay. And I think is the first time you have given your peak US market expectation of $750 million. Could you talk about the details behind that assumption maybe -- any kind of a pricing range that you are thinking about and whether that deep projection assumes that you have disease modifying profile or impact on overall survival?

Yes. So let me see if I can summarize it. What we did is we hired an outside independent group to do the market research for us because one of the big issues we wanted to make sure that we understood -- we wanted to make sure that we understood what the market would be because folks like yourself and others have been saying, well, there are a lot of alternatives, we just don't know what the marketplace is going to -- other alternatives.

Will GTx be able to get their price? Will people use the drug? And quite frankly, we have a fiduciary responsibility to make sure that we understand what the market is especially now that we are in Phase III. So we spent the money, got an independent market research both in US quantitative -- qualitative in US, qualitative ex US and quantitative in US which means they do even more extensive interviews with payors, with oncologists, with primary care physicians.

And what we ask them to do, Eric, it's not -- it's not to address the issue of overall survival, because most of our key opinion leaders are saying if we can't hit overall survival with our chemotoxic agents how are we going to expect to see an improvement in survival with our agent that is treating the host?

Now they all believe we should see a trend, but that is not the issue. The issue is when you are trying to pick your target product profile, which is an agent that will improve physical function and maintain lean body mass in these patients that are being hit with first-line chemotherapy and the safety being a safe drug, which I can say at this point now everything points in the direction that there are no surprises that we know of.

So therefore that was the product target, product profile that was put to the oncologists. The oncologists get it; there is a big move now to treat muscle wasting and at least have something to treat muscle wasting. If you talk to the typical oncologist they will tell you that Megace will increase appetite but actually be a detriment to muscle. And so, this is not a substitute or an alternative for a drug like this.

They were hoping that [EPO] would do this with fatigue by increasing red blood cells, but that is not -- I mean this seems to be more related to the lack of muscle. So when we did our market research the first thing we found out was that if this drug was available most medical oncologists would use this drug and on a scale of 7 the rating that we got was like 5.8 to 6.2.

So it is a highly rated drug that would be used especially if it was in the NCCN Guidelines, which would make sense it would be since this is a first-in-class compound.

Then the next question would be, well, remember now all we are going to do is maintain lean body mass and improve physical function and what would that be worth? And so, after going through the pricing of other cancer-related symptom type drugs like Zometa, Xgeva, neulasta and things that you give the host, i.e. the patient, to make them feel stronger.

The price range -- lower end of the elasticity, in other words I'm not going to go to the hind because the high end is always great. The lower end was they felt that we could get $1,500 a month for the patient and if you did $1,500 a month plus on average patients would be on drug for five months and you take the number of lung cancer patients in the United States, which they independently confirmed was in the range of 170,000 patients a year, we end up with a peak of about 750 million in US alone.

Payors did say they would pay for this with minimal pre-authorization and would be considered a -- I believe, Marc, it was at Tier 3? And then the other thing we know is that the payors also recognized that it could potentially be used in other cancer types. Of course we would never promote for that, but there is a willingness to reimburse for that. And we would do Phase IV's and make sure we properly -- Phase IV's or additional Phase III's to make sure that we have the data there to expand our label in cancer.

And that was -- so we were very pleased with the quantitative and qualitative data that we were able to go back to our Board and tell them that in the US only we would have $750 million in sales, they reviewed that. And again, that is US only, only in non-small cell lung cancer, it doesn't take into account ex-US or as we expand into other indications.

Great, those are very helpful details. One last question moving over to Capesaris. Could you disclose the acceptable incidence of VTEs in the first 25 patient cohorts that would allow you to move on to the next cohort?

There are really two -- there are two answers to that. The first one is what do we think should be an acceptable VTE rate to go forward with the program, forgetting going to the next cohort. And the answer is we are going to look for something less than 5%. But the stopping rules are more lenient than that.

But if we want to go into early prostate cancer, which means hormone naive prostate cancer, we'll be the first hormonal -- secondary hormonal therapy for example at non-metastatic castrate resistant prostate cancer patients. Then we really, regardless -- I mean regardless of the stopping rules we really need to see a VTE rate less than 5%.

Okay and the stopping rule is then how high?

It is higher than that, but it doesn't matter because we are not going to go -- we are not going to move forward if we don't have a product.

Okay, so you would -- even if you had, I don't know, a 6% (multiple speakers) a 6% rate of VTEs you would move forward?

I don't know -- the number is higher than that, but we still [wouldn't] move forward.

Okay, thank you.

Biren Amin, Jefferies.

Yes, thanks for taking my questions. I wanted to ask you, Mitch, on the POWER 1, POWER 2 study, I know you mentioned that you are going to provide an update on overall survival when the study reads out. And since the overall program has I think about 450 events that you have built into the program, what are the number of OS events that you expect when the study does read out in Q3?

Okay, so, just to be clear, overall survival is a key secondary safety endpoint and we have agreement with FDA that we will pull the data from both the POWER 1 and POWER 2 studies in order to make an assessment. The assessment is, as I said, descriptive. And although we have -- will provide in our SAP statistical analyses in the event that survival trend is strong enough that we can hit statistical significance.

With that said, at the time we pull the trigger and look at our top-line data we will not be at 450 events, as you mentioned, we will be somewhere in between. And consequently what we will do is we will tell you the number of deaths in POWER 1 and we will tell you the number of deaths in POWER 2 so that at least you will have an understanding of what the deaths look like. And when I say it deaths, it's deaths in the treated and deaths in the placebo.

Right now we are tracking appropriately to see the number of deaths of 450 pretty darn close to the time that we file the NDA. And also, as you know, given the additional 120 days for a safety update after we file the NDA. So at the time of the top-line data -- and I'm just guessing at this point -- we should be well beyond half the deaths at that point -- half the expected deaths.

And as part of your analysis what do you expect on OS? Are there any assumptions that you would -- as far as how the OS would perform in the placebo group versus the active arm?

Well, the good news is we can go back -- you mean like a point estimate kind of thing?

Right.

So we can go back and look at the -- it's very interesting. We went back and looked at the actual overall survival rates in patients on first-line chemotherapy, for all of the different chemotherapies that we are giving we can go back to the label and actually find the point estimates for these patients. And the point estimates for these patients almost in every single one of these chemotherapy agents are about 0.8.

So if you have an 80% probability of survival certainly at the four- to five-month time point. And so it gives you sort of a stake in the ground in terms of you don't want your survival to be worse than chemo alone. But it also tells you that if we come in better than that, that that is what chemo alone can do.

Great, thanks for taking my questions.

David Nierengarten, Wedbush Securities. Ryan Martins, Lazard Capital Markets.

Mitch, I was wondering if you could maybe speak about how the activity of enobosarm could vary, if at all, when combined with the different non-taxanes in one of the Phase IIIs.

Okay, so the question is, are there any potential drug-drug interactions with enobosarm with taxanes or non-taxanes -- or quite frankly even with the platinum, is that the question?

Yes, actually more on the lines of how the activity of enobosarm could vary depending on what the non-taxane is that is used.

Yes, so our belief is it should not vary. We do not think we will have an effect on any of the chemotherapies. Enobosarm is metabolized by glucuronidation. And so consequently -- and the body has a huge capacity for glucuronidation. So we are not expecting, whether it is a taxane or in non-taxane or a platinum, that we will have any appreciable drug-drug interaction. So we are not concerned about that.

Okay and just to confirm, we will see the durability data at five months when you have your top-line press release?

No, I think what we are going to be presenting is -- at least at this point, that is why if you heard my prepared comments I said at minimum, because that is what everybody wants to know, what will they see in the top-line.

And so, at minimum we are going to do the primary -- co-primary endpoint, the safety update or safety at top-line and then the deaths at the time, survival at the time and of course we will update the survival. And we just haven't made a determination on durability, but just talking out loud; if we have it there is no reason why we can't share it.

And another one around the DSMB, aren't they supposed to be meeting again before you get the top-line? Will we just get some update on the safety at that point too?

Yes. So the DSMB meets again in April. And so, at that point after the DSMB meets we will make a comment as to the outcome of that meeting.

Perfect. And just on Capesaris finally. Are we going to have data from all three cohorts when you report it in the summer or is it going to be a couple cohorts at that point?

It's a good question. Since we are doing dose escalation pretty much it will be -- we will give you data as we have it and hopefully be conclusive enough that you can understand where we are going in the next steps. And so I would rather leave it open because it is open label and we are accessing each one not only for safety but also for efficacy.

And so, if you are seeing the efficacy that you need at the lower doses we may elect not to go higher. And so, it is not like you have to fill the trial to get every cohort filled, that is why it is open label. So we will make some decisions along the way, we are hoping by summer we could make a decision.

And have you said where you are in enrollment currently?

What we set enrollment on.

No, no not really. We just -- not really. I mean all we want to do is make sure by summer we can make a conclusion.

Okay, thanks.

Mike King, JMP Securities.

Thanks for taking my call. I had a question on enobosarm and a question on Capesaris. Just first on enobosarm, Mitch, I don't know if you'd be willing to tell us, but I'm just wondering -- can you speak to sort of proportionally the sites and their geographic location? In other words, are you expecting 10%, 20% to be in the US, less or more, and how that's splaying out right now?

Yes, so the study is done and we have -- we have the majority of the sites are outside the US as expected with clinical trials these days. What was more important to us than the actual location was making sure that we didn't introduce geographic variability because of -- like for example if we had sites in China and sites in India and sites in strange places where we did not have experience.

What we did is we took a different approach. Our Phase IIb was done in South America and US and most of the patients of European descent and extraction. And so we focused primarily in making sure that we filled the trial with similar patients that we did in the Phase IIb.

Because if you do that then you don't get into the confounding problems of, like for example, in India where patients may show up very, very late in their disease and consequently you are dealing with a very advanced stage as opposed to what you see in the US, Europe or in South America or Russia, for that matter.

So that was more important to us than making sure that we balanced the homogeneity, if you will, of the patients and the type of standard of care they would get and try to minimize that. We can always go into special populations later.

Okay, yes, I think really more concerned with things like protocol adherence and (multiple speakers) appropriate enrollment. Sorry?

Yes, no, we have -- I will tell you that from a GCP standpoint we have done our audits, it looks good and on top of that we have not had to -- we have stuck very, very hard on our protocol. So once the study started there were basically no additional amendments.

I mean I am proud of that. Sometimes studies have amendment after amendment, we did not. And then I personally visited sites all through Europe, almost all of them quite frankly in Europe, almost all of them in South America, (multiple speakers) all of them in the US and these are top sites.

Okay, great. Appreciate that. You are working on your 1 million mile club.

It's actually more than that, but I'm embarrassed to say, but, yes.

And then on Capesaris, do you have the unblinded PSA and SHBG levels? And I don't know if there is any hint or suggestions that you might be able to provide us with that the trends are what you expected as far as the overall data set is concerned?

Yes, so the question you're asking is, are we getting any early indications that the doses that we are testing is showing some activity?

Yes.

And if you want a more complete review on that, we did mention -- we had an -- and you were on the call, I believe. We had an Analyst Day or an Analyst Hour at GU ASCO. And if you go to our website and look under GTx Analyst Day you will be able to get more complete information not only on the study but also based on what three key opinion leaders think about our drug and how it fits in the field and some data, like for example, Dr. Evan Yu.

But for the purposes of this call, yes, we are seeing very small numbers, but nonetheless when you're dealing with blood levels small numbers are pretty tight. And we are seeing substantial increases in SHBG reductions and free T reductions in PSA. But it's still too early to say much more than that.

So I'm excited because one of the concerns that we raised is that, yes, you can lower the dose by tenfold from your lowest other dose and twentyfold from the dose you did in 707. And we are going to feel comfortable that you are going to hit your safety but you are not going to have your efficacy. Well, I am comfortable now that we are fine and we just have to prove it out.

Okay. I will get back in queue. Thank you.

Howard Liang, Leerink Swann.

Just on the -- for your enobosarm Phase III study, do you have an understanding of what FDA is looking for in overall survival data? Does it have to show a positive trend or does it have to just not to show an inferior signal?

Yes, so it is the inferior signal. So the FDA -- the FDA made it very -- it's funny because we had three face-to-face meetings with FDA and one of the -- in the second meeting -- the first meeting, actually, they said that overall survival would be a key secondary endpoint, a secondary safety endpoint.

So we didn't know what that meant, so we went back and had a full statistical evaluation plan and the FDA reviewed it and said, no, no, no, you don't understand. You are not going to have the power to show that kind of stuff. He said all we care about is that the trend doesn't go negative and it can be purely descriptive. So that is all the FDA is looking for.

Okay, great. Then just regarding the test, the functional test, for example. When are they are performed -- are they performed periodically or only at three months or five months?

They are being performed at -- they are being performed at baseline, day 42, day 84, day 147.

Okay, great. Thanks very much.

Mike King, JMP Securities.

I just wanted to ask a question about the requirement or the interest in durability for enobosarm. And I guess I am a little bit baffled by it because why would that be important after drug cessation? It just seems like if you are treating the patient with chemotherapy that could induce sarcopenia that you would keep the patient on the drug. There is no incentive to take the drug away. So what is the thought process there?

The thought process here is almost like the pulmonary artery hypertension drugs in which the FDA is -- all they are asking is can we make some statement about what happens to a patient if they stay on drug. They are not -- so the durability is if you take the patients that responded at day 84 month three and now you go back and look at five months how many of those patients continue to have the same durability?

Not -- [I'm not saying] same durability is they have to show a 10% improvement in physical function and they have to maintain their lean body mass. It is descriptive, it is not statistical. So this is more in terms of just understanding what you could tell the patient, it is not -- this is not the primary endpoint.

No, I understand. I'm just -- again, it seems like it is a thought experiment but it doesn't seem like it has got clinical relevance.

Right, that is fair. Because the clinical relevance is that you are going to start the patient on the drug right when they start chemotherapy, right when they are going to have the onslaught of the toxicity related to the drug and the toxicity related to the tumor.

And since prevention and treatment it is not only treating the patients that are already in trouble but to prevent patients from getting into trouble. And those by definition are two different populations and they will be assessed in this.

And so the way we look at it is that we are going to get good information about what happens in patients that take our drug the entire time, not just the ones that respond to -- at day 84. Because you could argue that if you have a patient at day 84 that didn't respond as well as they need to to hit the responder's analysis definition, but if they stay on the drug up to five month and now they start responding, well that is good information too.

I see. Okay, great. Mitch, thanks.

At this time I would like to turn the call back over to Dr. Steiner for closing remarks.

I would like to thank everybody for joining us on today's call and I would like to thank you all for your interest in GTx. I look forward to updating you on the progress of our studies in the future. Thank you.

Thank you very much. This concludes today's conference. Thank you for your participation. You may now disconnect. Have a wonderful day.