Cassava Sciences Inc (SAVA) 2003 Q3 法說會逐字稿

Good morning, ladies and gentlemen, and welcome to the Pain Therapeutics conference call. At this time all participants are in a listen-only mode. Following today's presentation, instructions will be given for the question and answer session. Anyone needs assistance at any time during today's conference, please press the "star" followed by "zero" on your pushbutton telephone. As a reminder, this conference is being recorded today, Tuesday, October 21, 2003. Now, I would now like to turn over to Ms. Christi Waarich. Go ahead, ma'am.

Good morning and thank you for joining us today. The purpose of this call is to discuss Pain Therapeutics third quarter 2003 financial results and to our far more confidence in our clinical program. By now we hope you have had a chance to review the press release that was posted on our Web site earlier this morning. Before we start I'd like to discuss the mechanics of this call. You can hear this presentation on our Web site. If you would like to ask a question during the call please do so using the dial-in number provided in the press release.

I would like to now introduce today's participants. Pete Roddy, Chief Financial Officer, will open today's call with financial results and Remi Barbier, President and CEO, will discuss clinical programs and provide closing comments. We will then open a call to a q-and-a session.

Let me mention that during this conference call except for historical information and discussions contained herein, statements may constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. PTIE disclaims any intent to evaluation, updated forward-looking information and claims the protection of the safe harbor for forward looking information contained in the act.

An Example for such statements include that are not limited to you any statements relating to the company's cash usage in 2003 and through late-stage development of the drugs Canada and the timings though an expected out come of the upcoming milestones, Company's clinical development of the drugs Canada and the timings, scope and expected outcome of the clinical studies, the potential benefit of the Company's drug Canada, the sides of the potential market for the product and expected commercial potential or success of the company's drug Canada.

Such statements are based on management's current expectations the actual results may differ materially due to the various factors including but not limited to those risks and uncertainties relating to difficulties or delays in development. Such things, regulatory approval, production or marketing of the company's drug Canada unexpected other side effects were inadequate therapeutics efficacy of the Company's drug Canada that could prevent product approval. The risks that current and past results of clinical studies are not necessarily indicative of future results of clinical studies. Uncertainty of patent protection for the company's intellectual property or trade secrets and the company's ability to obtain additional financing if necessary.

For further information regarding these and other risks related to the company's business, investors should consult filings with the SEC, including the company's form S-3 as amended and filed September 22, 2003. With that, I'd like to turn over to Pete Roddy, Chief Financial Officer.

Thank you Christi. In the third quarter we had a net loss of just under $6 million. This is right in line with expectations. On a year-to-date basis, we had a net loss of $14.9 million. The increase in spending is part of the ongoing achievement of corporate and clinical milestones.

Now, let's talk about cash. We used cash for operations of about $14 million so far this year. We'll spend about $6 million more in the fourth quarter. So, we're reconfirming our prior guidance of total cash for operations for 2003 of approximately $20 million. The income statement includes traditional non-cash expense items for depreciation and amortization.

So, our P&L for the year will be closer to $21 million again as expected. We have $83.2 million of cash at the end of September, including the proceeds from our recently completed public follow-on offering. We announced on September 22nd, the pricing of the offering of $7.65 million shares of our common stock. That offering pro-lead by Citigroup and CIBC, along with participation by Think Equity Partners and Leerink Swann closed on September 25th. We received about $46.3 million at the closing on September 25th, after deducting the typical underwriter commission discount and cost associated with the offering.

In October, the underwriters exercised their over allotment option and purchased additional 80,500 shares of common stock, adding approximately $0.5 million. This amount reflects the demand for our stock during the over allotment period.

In sum, our completed offering resulted in approximately $47 million in net proceeds, combined with cash we had before the offering we believe we have enough cash to bring two of our drug candidates through late-stage clinical development while continuing to hold worldwide commercial rights. We've met our development goals so far this year and believe we'll meet the remainder of our goals. As a reminder, these goals are posted on our Web site.

We increased our R&D spending to meet clinical and operational goals. R&D spending increased to $5.3 million for the third quarter. In particular, our R&D spending increased in the third quarter for our first Phase III study of Oxytrek, as well as to prepare for the second fades three study. We announced in June that we had initiated enrollment in first Phase III clinical study of Oxytrek.

This first Phase III study is enrolling patients with severe chronic low back pain. In the first quarter of 2004 we plan to initiate a second Phase III study of Oxytrek. This second Phase III study will enroll patient severe and chronic osteoarthritic pain. We would like to reiterate our estimates for the cost of our studies. Each of these two Phase III clinical studies for Oxytrex is expected to cost up to $10 million.

As previously announced, we also plan to initiate a Phase III clinical program with PTI-901 by year-end. PTI-901 is a proprietary new drug we're developing to treat men or women with Irritable Bowel Syndrome or IBS. We are still finalizing the details of this program. Naturally with all this clinical activity we expect to see an increase in our spending for R&D in 2004.

However, we don't expect to see significant increases in head count, facilities, equipment and other G&A spending in 2004. With that in mind we will give specific guidance for R&D spending and total spending for 2004 later in the fourth quarter. With that, I'd like to turn over to Remi to comment on clinical programs.

Thank you, Pete. I'd like to start of by stating the obvious, namely there has been an incredible amount of noise and confusion about the Oxytrex clinical data in the last few trading days. This noise has really led to quite a widespread sell-off causing a lot of pain and suffering to our investors. Personally, I'm shocked by what the stock has done.

I believe that the positive news has been completely drowned out by the negative. For those shareholders caught up in the vortex of confusion, I need to offer my apologies as CEO I'm here to create clarity, not confusion.

And as a large shareholder, I want to remind you I have suffered as you have. Recently I got a very interesting phone call from a large investor saying, Remi, on a scale of one to 100, what is your confidence level? Instantly, my answer was 110. And so in the next few minutes I would like to reaffirm our enthusiasm for Oxytrex and the entire pipeline.

Let's review what is going on here. Very broad level what we're doing is we have a visionary opportunity to recreate a billion dollar drug market for better painkillers. At a tactical level, we have three things going on. We have two Phase III programs by the end of the year, both of which we believe have blockbuster status and we own all rights to these drugs.

So, you might ask what is our enthusiasm driven by? That's an easy one. Our enthusiasm is driven entirely by the clinical data, while the interpretation of the data is subject to just that, interpretation, we think the data speaks for itself. In particular, I'd like to reaffirm the three things that we saw in our Oxytrex study. Namely we saw twice a day dosing is better than four times per day dosing. We saw that Oxytrex provides more pain relief and we saw that Oxytrex clears up symptoms of Osteoarthritis.

I'd like to say here that we think the -- high diversity of opinion is important to a company. In fact, I can't think of any great company that was ever built on unity of opinion. I happen to believe that as a drug reaches late-stage clinical trial, divergence of opinion is the rule rather than exception. We respect and we encourage all divergent opinions as long as these are built on material facts.

I'd like to now go over the specifics of our trial design and based on some of the feedback we have heard. Let me break it down into three components. First of all, if we thought our drug provided simply nothing more than pain relief, the protocol, the clinical study for better pain relief is straightforward. Basically we would compare the same daily dose of our drug to the standard of care and we would measure patients' pain scales in the same way across the board.

That is a straightforward almost an easy study. The second component is if we simply had longer pain relief that too would be a relatively easy study. We would simply compare total daily dose of our drug versus total daily dose of another drug, standard of care, we would simply offset the frequency of dosing. However, when you put together more pain relief and longer pain relief that's when you get into fairly subtle and complex trial design.

I believe that the confusion and perhaps the complexity of the past few days has to do really with the complexity of the incredible benefits of - incredible bounty of clinical benefits offered by Oxytrex. Let's review the specifics. Number one, why is twice a day better than four times a day dosing? Well, I think that is an obvious question. Our real competition is twice a day dosing. I want to repeat twice a day dosing was not a random design.

Twice a day dosing for Oxytrex was driven by pre-clinical, as well as clinical data, namely pharmacokinetic and pharmacodynamic. We happen to think there is a huge benefit from twice a day dosing from four times a day dosing. And there are really three different reasons why we designed a study for twice a day, namely it was data driven, as I mentioned, driven by specifically pharmacokinetic data.

Second, the design of the study was reviewed by the FDA so, that brings us to the highest level of confidence about the design. Third, and perhaps more importantly, this is how pain relief drugs are often approved. If you look for example at the summary basis of approval for sustained relief Oxycodone, it was approved by comparing twice a day dosing versus four times per day dosing.

We feel very comfortable in fact would change nothing about the dosing frequency of our drug. The second point that we've heard a lot about is why are we doing a second Phase III study? Well, I have to believe that some analysts and our investors, certain investors, are surprised by this. I personally again and surprised by their surprise.

If you look for anyone in the audience who attended our road show or read our 10-K or more recent S-3, we stated in black and white in all these documents that we have always believed we would need to conduct two Phase III clinical trials. Why two? By conducting two different clinical trials and two models of pain, the FDA has given us written guidance that we would be eligible to receive broad level approval. That is a very big thing for a company to have. In fact, as far as I am aware we are the only company in the pain stage to get written guidance from the FDA saying show us clinical data and two models of pain and we can provide you a broad-level approval.

The other point that I'd like to address is Oxytrex II versus Oxytrex I. First of all what is Oxytrex II? Oxytrex II is basically has the same dose of Oxycodone as Oxytrex I. The only difference is that Oxytrex II has twice the dose of low-dose antagonist. A number of investors have noted that in their opinion Oxytrex II did not work as well as Oxytrex I. We agree.

In fact, that was the whole point of including Oxytrex II, to show we can optimize one of two parameters, either increased pain relief and same side effects or decrease side effects and same pain relief. Because we believe patients with chronic care preferred to have much higher doses of pain relief, that is what we optimized for and that's why we had the Oxytrex I dose come out ahead.

The other point we've heard quite a bit about is safety. We repeat the obvious, Oxytrex was extremely well tolerated. There were no serious adverses in and the adverse events that we did see are those commonly observed with opioid related chronic dosing.

Finally, the number of investors and constituents have asked about what about tolerance, anti-addiction and physical dependence. Again, this is part of the clinical benefits that have been drown out. In all of our pre-clinical data, we have seen a clear trend towards lack of tolerance, lack of addiction, lack of physical dependence. Let's think about this.

For 150 years, Manton has been using opioid and it's been suffering from tolerance, addiction, physical dependence and so forth. For the first time ever, we have an opioid that provides strong pain relief and minimizes tolerance, addiction and physical dependence. One must not overlook these qualities. However, I do want to point out that these are difficult metrics -- it is very difficult benefits to measure and as far as we can tell, there are no acceptable metric to measure tolerance, addiction or physical dependence.

Therefore, we have relied on (inaudible) clinical data and we will not make any intent to get clinical claims for anti-addiction or tolerance or physical dependence. However, we expect to attract these effects in large phase IV type studies.

You know, in some ways let me summarize by saying that our again, if all we wanted to show is increased pain relief, it would be a fairly easy study. If all we wanted to show a longer pain relief, that, too would be fairly easy study.

But, because we have one drug provides multiple clinical benefits, the trial design itself has appeared to be more complex than many anticipated. I assure you that we remain incredibly enthusiastic about those complex trial design and the product and the entire pipeline.

Now, let's review our timeline. We maintained that we announced in June of this year that we initiated our first Phase III clinical trial and enrollment for that trial going well. In Q1 of next year we will be initiating our second Phase III clinical trial for Oxytrex. In 2004, will basically be a year of patient enrollment for us.

During 2004 we expect to complete patient enrollment for both Oxytrex Phase III clinical studies as well as completing patient enrollment for the IBS drug, PTI-901. I want to state upfront that none has this has changed from any of our previous guidance. Furthermore, in 2005, we expect to release clinical data from these studies as well as file an NDA. To sum up, our timelines have never changed.

I believe we have a few more minutes here to open up for questions. Again, I'd like to reiterate that we believe this is a visionary opportunity to win over a billion-dollar market. We have two Phase III clinical programs. We will have two phase III by year-end, both products we believe have the blockbuster status and we own all rights to this pipeline. For those of you -for those investors who have written to us and have bothered to e-mail us, I want to thank them for taking time. I want to remind people that in the life sciences we are at the bottom of the first inning. We have lots of game time left for us to win with that, I'd like to open up for questions.

Thank you, sir. Ladies and gentlemen, at this time we will begin the question-and-answer session. If you have a question, please press "star" followed by "one" on your pushbutton phone. If you would like to decline from the pooling process, please press the "star" followed by "two". You will hear a free tone prompt acknowledging your selection. Your questions will be pulled in the order they are received. If you are using speaker equipment, you won't need to lift the handset before pressing the numbers. One moment for the first question. First question comes from Mara Goldstein. Please go ahead. Mara Goldstein

Can you hear me? Can you talk more about the dependency factor or lack of? You mentioned -- can you tell us what exactly Phase II and what you will see looking for or have design the trial for in the Phase III to be able to show that?

Sure. There is a fair amount of background noise. Let me repeat the question. The question has to do with tolerance and perhaps the accompanying of other clinical things such as addiction and physical dependence.

And do we plan to measure these things in our clinical Phase III clinical trials? We do not plan to measure tolerance, addiction or dependence in Phase III clinical trials. In fact, RSAV our scientific advisory board, medical advisors and even our consultations with the FDA, all of these constituents have suggested that there really are no validated clinical model of tolerance addiction physical dependence and so forth. There are good preclinical models.

In several preclinical models, both us and our constituents have noted the lack of tolerance and so forth with our drug. The long and short is no, we do not plan to measure tolerance in the Phase III trials. What we do plan to measure, however are the same things that we've been measuring in our Phase II trials, which is more pain relief, sustained pain relief and WOMAC scores proves physical functionality as measured by the WOMAC osteoarthritic index with our OA studies.

Perhaps let me add that one of our questions we've had quite a number of times was how our pain scores are measured? Well, let me say pain scores are measured with what's called a visual 8 scale, which is the validated way to measure these patients' pain. And every night before the bedtime dose of their drug, patients note in their diary how much pain they are in. I want to repeat patients note in their daily diary how much pain they are in immediately before their bedtime dose. We did this by design so that at the time patients note how much pain there is. They are at the lowest blood levels of pain relief or pain opioid, I should say.

Thank you. Our next question comes from Alan Goldberg with Goldberg and Company. Please go ahead.

Thank you for taking my call Mr. Barbier and I appreciate the clarity on the broad label approval strategy. Oxycodone is the drug I read about every day in the New York Times. My question is does that have broad label approval?

Thank you, Dr. Goldberg for that question. Obviously we are not and cannot be spoke first, people for another company's product or drug. Oxyconton has been quite a tremendously successful drug both in terms of clinical success and marketing success for its owners. We admire a lot of what is the Oxyconton owners have done to educate the pain community about painkillers and the need to treat it. Having said that, there is a dark side, unfortunately to Oxyconton abuse.

This is well documented in the late press as well as in the peer review journals. We understand from reading the summary basis of approval that Oxycodon was approved on the basis of better dosing frequency. In other words, once again, twice a day dosing is better than four times to day dosing. If you read the PDR, you will see that Oxycodone is approved for pain relief of moderate to severe pain where opioid use is appropriate.

Does that answer your question, sir?

To your knowledge, does Oxycodone have the broad label approval? I'm not a doctor.

Oxyconton is another company's drug. I would like to focus on what we have. The approval for Oxyconton as we read it, is approved for the release of moderate to severe pain where opiate-use is indicated. This does the most people would represent broad-label use.

Thank you.

Thank you. Our next question comes from Steven Shapiro with Intrepid Capital Management. Please go ahead.

I was hoping you could update us -- I notice on clinical milestone calendar in November you've indicated a new product announcement. Just a question, is that new product announcement still on track? B, have you specified a date for that? Then, C, you mentioned that your cash balance, $83 million was enough to finance the two drugs in the pipeline now. Is the $83 million also sufficient to finance this new drug candidate? Thanks.

Yeah, let me take the three questions one by one. First of all, we remain incredibly enthusiastic about the new drug candidate that we will be announcing in New York during an analysts' day on November 5th. I urge all of you to attend. One of the analyst -- we did read an analyst report suggesting that this is nothing more than a sustained release version of Oxycodone, in other words, twice a day dosing. It is a lot more than simply another sustained relief Oxycodone. With that, unfortunately I can't reveal anymore, but I do urge you to attend.

I do want to say that the clinical development plan will be a lot simpler, a lot less complex and less subtle for the new product than for Oxytrex. The second question had to do with cash and whether or not we have enough cash to develop all three products. Very consistently we've been saying that the cash on hand is sufficient to develop two products all the way through -- we believe all the way through Phase III really NDA filing. The third product, undisclosed product, we are still in negotiations with the FDA on what the final clinical development plan might look like. Until we get better guidance from the FDA, let's -- I don't want to make any commitments yet.

Thanks very much.

Thank you. Our next question comes from Patrick Singleberg (ph). Please go ahead.

Thanks for taking the call. Two quick questions. One, on your second phase III in osteoarthritis for Oxytrex, can you talk little bit more about the design of that study as you anticipate it or not?

Yeah, again we have not provided broad guidance on the design of that study. So, I will avoid talking about details. However, I will provide you with the same guidance we provided our investors in the past which is that this will be a large clinical study, probably about 6 to 700 patients. All patients will suffer from moderate to severe advanced forms of osteoarthritic pain. We will be testing our drug, Oxytrex against both placebo, as well as immediate-relief Oxycodone. The primary end point in the secondary end-point and functional analysis scores will be very similar to those scores that you just saw with our data-release last week.

OK

Again, the point of conducting a large study on osteoarthritis is to get clinical result from two different models of pain so that we can get the broad-level approval that we seek.

which brings me to my next question. The broad label, there was a discussion earlier with respect to broad label for competitive drug. You pursuing two different indications is it fair to say that you are going for broad-label, yet with a specific indication rather than broadly to suppress I guess non-manageable pain which is not correct language I am using. I guess I am trying to say, differentiate your drug obviously based on clinical and efficacy features and safety features from others, but also by being able to go to the doctor with a cleaner marketing message and say this is broadly usable, specifically with two very broad indications?

I think you are on the right track. The wording is a little bit different.

OK.

Indication refers to where the drug is approved.

Right.

OK. We are looking to receive broad-label approval from the FDA. That will be our label indication. We know that in order to win in the marketplace, we need twice a day dosing. It turns out that even in the absence of any sustained relief mechanism, Oxytrex has a built-in, sustained effect. So, we know that we can compete right off the bat with the twice a day version of Oxycodone. But, that is not enough.

Sooner or later, twice a day Oxycodone will go off patent and a number of different companies will pile into the space. So, our game plan is to show not only the equivalent dosing, I mean twice a day dosing but better pain relief and better relief of the symptoms of osteoarthritis. It's really improving therapeutic index and providing more pain relief with no increase and the incidents of side effects compared to the approved drugs. Does that help?

That helps. OK. One last question on your 901 Phase III trial you I assume we will look for guidance further or later on in the year with respect to design and things like that or?

Correct. We have one more discussion with the FDA that will occur shortly in the next definitely within this quarter. As soon as we get feedback from the FDA on the protocol design and so forth, we will provide full relief and details on what the Phase III clinical trials will look like for IBS.

Thank you.

I may also add that the discussion there has to do with whether or not we want to conduct one mega trial consisting of men and women or whether it is preferable to conduct one trial consisting of men only and one trial consisting of women only.

Thank you. Our next question comes from Paul Morango. Please go ahead.

Thank you. One, good job on dispelling the confusion around the current trial I think you did it very clearly and certainly was help to me. Regarding the broad level approval of Oxytrex, wouldn't another strategy be to file the NDA on the narrow usage and get the broad-label approval from Phase IV study, which would enable you to get to a revenue-generating situation earlier? Had you thought about that or?

That's a very good point. The short answer is yes, we have thought about pursuing initially a narrow indication and going after broad-label approval. But, here is the reality is that the FDA, they are people, too. And know these drugs are used in the clinic very broadly. So, the FDA's concern we feel might be even with a narrow-label indication, physicians might go out and use the drugs broadly by themselves. So, rather than -- we just think there is a better clarity and it makes the FDA's job easier, we think, if we give them what they want, which is clinical data in two models of pain to achieve approve the drug on broad label approval.

Thank you very much.

It is something we thought of, but feel it is non optimal.

Ladies and gentlemen, if you have additional questions press the "*" followed by "1". And if you like to decline from the polling process, please press the "*" followed by 2.

Next question comes from William Crane as a private investor. Please go ahead.

Good afternoon. My question involves the trials that you referred to earlier that Purdue conducted concerning Oxycodone and how they relates to Oxytrex study, especially Oxytrex I. In looking at Purdue studies I wonder if we can agree that the study showed two times a day dosing worked, but didn't show greater pain relief for pays sustained relief Oxycodone?

The question is little confusing. Let me repeat the question to make sure I understood correctly our drug twice a day offer the pain relief of Oxycodone four times a day? The answer is no, it doesn't. Our drug twice a day provides more pain relief. So, this was not an equivalency test. This was a test of superiority.

I understand that. I'm asking you not about the Oxytrex studies, which we agree on, but the studies that (inaudible) ran on Oxycodone back in the early '90s. As I read those studies, it appears they show twice a day dosing, but with the equivalent pain relief. Is that your understanding of the studies?

We read it the way you read it.

OK. Also, since the FDA approved Oxycodone based on those two times a day sustained relief studies versus four times per day immediate release Oxycodone, either fair to assume the FDA felt that that method of comparison was appropriate and scientifically valid?

We absolutely agree with you. We absolutely agree. In fact, a number of -- you know, it's a very interesting point. Remember, I started by saying if you feel your drug offers longer clinical benefits whether pain relief or anything, you basically -- it is relatively straightforward clinical design. You compare the same daily dose of your drug versus the competitor you simply change the dosing frequency twice a day versus four times per day. And a number of different products offer sustained relief affects whether it is Claritin or Oxytrex or others have adopt way of showing the benefits. Indeed, to your point that's what we show.

Now, just shifting to Oxytrex for a moment. Am I correct that at PTI, your scientists realize that by combining a low dose now tracks on with Oxycodone, but you could offer let's say a built-in sustained relief mechanism without getting involved with capsules?

You are correct. The thinking is correct, but the words are a little different. It is really not sustained-release effect. It is sustained effect period.

Fair enough.

There is no addition of another material that would create slow release.

OK. Staying with the same example, let's say we're talking about two doses of 20 milligrams sustained release versus four doses of 10 milligrams immediate release. Now, using that example, is it my understanding that simply by combining the Naloxone with Oxycodone that PTI was able to allow the blood levels of pain relief to be sufficient for 12 hours?

You are correct.

Now, the question then that I can't quite come to grips with and I was hoping you could give me guidance. Given this information, the fact that we had more pain relief with two times a day application with Oxytrex, what I'm wondering is whether our longer-acting mechanism, which is now Naloxone, versus Oxycodone's mechanism of using a capsule mechanism, whether our formulation is in a tablet form or is in some kind of capsule form. When I say our, I mean Oxytrex.

So the question is whether it is tablet or capsule?

Correct.

It's a Tablet.

Now, As I've read the news recently, the problem with Oxycodone is that it is capsules contain granules or other type of design so that when the capsule is broken as it is not supposed to be, it is subject to a different experience and therefore has led to abuse. Is that your understanding of the problem?

Once again, we understand that the way you do.

OK. Does Oxytrex in the longer-acting version you've described, have this potential abuse problem of being somehow broken up or crumbled up or in some way misused by the user to for any reason get a different kind of -- let's call it a high?

Yes. In the clinical trials that we completed are 350 safe two trials, we did not have any measures of abusability in this age, we are convinced that every NDA that is being filed for a strong opioid will contain a quite-detailed risk management plan, including characterization of the abuse potential. That is something that we will address in our NDA, but not now.

All right. But just from your point of view of pharmacological design typically, well let's take Perkaset drugs that has been around in immediate release for years. Does just crumbling up a normal capsule -- excuse me, crumbling up a normal tablet have any historic basis for concern of the crumbling effect leading to abuse?

Yes, Sure. I mean, again, we cannot be spokes people for other companies' drugs, but it is well known that if you take any formulation of opiate (ph) agonist, Oxycodone or Moxyn Hydrocodone and you crush it and ingest it or inhale it snored it, patients, people, who want to abuse these drugs can and do get hard. But we feel that this is something that will have to be addressed at the NDA stages. And it's not something really that we want to talk about during this Phase II problem to phase II or phase. But I do assure you that we are thinking along the lines that you are and will have additional news later on.

OK. One last question, remain appreciate your time. Assuming the Phase III studies of Oxytrex I confirm the results of Phase II study and Oxytrex wanted to approve by the FDA, physicians would have a choice of two different forms of twice a day 12-hour sustained release Oxycodone to prescribe? Given the fact that-- you have shown increased pain relief in this 12-hour formulation, can you think of any circumstance were a physician would have any reason to prescribe sustained-release Oxycodone, which is branded as OxyContin, as Oxytrex?

I am sorry, bill You can't lock me in this question

Can you think of any circumstance where a physician would have any reason to prescribe OxyContin rather than Oxytrex assuming Phase III confirms Phase II?

Again, if the Phase III data confirms Phase II data and if the preclinical data holds up showing lack of tolerance, anti-addiction and cyst or in lack of physical dependence in preclinical models, personally if I were a physician, I would have a tough time prescribing twice a day generic Oxycodone instead of prescribing an drug opio drug that provided for lack of tolerance and addiction and fist dependence.

Let me back up and let's leave out for a moment because we don't know the answer on addiction and tolerance in human trap we have that in the preclinical course. But Assuming Phase III shows as Phase II did, that twice a day Oxytrex I provides more pain relief relative to Oxycodone, whereas OxyContin only provided the same pain relief, just on the issue of more pain relief, same dosing, same side effects, can you think of any circumstance leaving aside the bonus of addiction issues where a physician would have any reason to prescribe OxyContin rather than Oxytrex?

I can't think of any reason why a patient would want to take the lesser drug, that the drug with the poorer therapeutic index. In fact, you know in clinical practice today drugs that offer better therapeutic index almost always win the date. Whether in a category of anti-depressants or pain or antihistamines or starting to you name it, I can offer concrete evidence that drugs that have better therapeutic index that offer more clinical benefits with no increase in ill-effects of the drug, those drugs almost always win to date.

OK. For Just , you know and I appreciate you clarifying these issues. To sum it up in own mind, it seems Oxytrex used identical protocolin in testing Oxytrex I twice a day -- sustained relief as Purdue used for Oxycontin FDI Purdue Accrue Purdue in Oxycontin and the technique that they used? Also, Oxytrex showed greater pain relief, Oxycontin showed the same pain relief. The only thing that seems to remain is whether there is bonus of no addiction no tolerance as preclinical suggest and whether Phase III confirms Phase II? Other than that, seems like a pretty simple decision.

We think so.

Thank you very much.

Thank you.

Thank you. We have no further questions at this time. I would like to turn the call back over for any concluding comments.

Thank you to the audience for hanging in and you know what is a rather noisy and confusing time. I want to reaffirm we are incredibly enthusiastic about the clinical data we think there is a lot of value to twice the date of twice a day dosing versus four times a day we have seen a more pain relief and we have seen clearance of the symptoms of osteoarthritic pain with Oxytrex and we will build on the clinical findings all the way through an NDA. Thank you.

Ladies and gentlemen, this concludes today's Pain Therapeutics conference call. Thank you for participating in today's conference. You may now disconnect.