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Executives

Mike Aguiar - SVP and CFO

Rick Winningham - Chairman and CEO

Mathai Mammen - SVP, Research and Early Clinical Development

Analysts

Steve Byrne - Bank of America/Merrill Lynch

Ronny Gal - Sanford Bernstein

Ian Somaiya - Piper Jaffray

Daniel Brims - Brean Murray

Howard Liang - Leerink Swann

Anant Padmanabhan - Cowen and Company

Stephen Willey - Stifel Nicolaus

Theravance, Inc. (THRX) Positive Topline Results From TD-1211 Phase 2b Study 0084 for the Treatment of Opioid-Induced Constipation July 10, 2012 5:00 PM ET

Operator

Ladies and gentlemen good afternoon. At this time I’d like to welcome everyone to the Theravance Conference Call. During the presentation all participants will be in a listen-only mode. A question-and-answer session will follow the company’s formal remarks. (Operator Instructions) Today’s conference call is being recorded.

I’d now like to turn the call over to Mike Aguiar, Senior Vice President and Chief Financial Officer. Please go ahead sir.

Mike Aguiar

Good afternoon everyone. Thank you for joining us today as we discuss the positive topline Phase 2b study results for compound TD-1211 in the Peripheral Mu Opioid Receptor Antagonist program for opioid-induced constipation or OIC.

With me on the call today is Rick Winningham, Chief Executive Officer; and Mathai Mammen, Senior Vice President of Research and Early Clinical Development.

We prepared a few brief remarks for today’s call and then we will open up for questions. A copy of the press release and slide presentation can be downloaded from website or you can call Investor Relations to 650-808-4100 and we will be happy to assist you.

Before we get started we would like to remind you that this conference call contains forward-looking statements regarding future events and future performance of Theravance. Forward-looking statements include anticipated results and other statements regarding Theravance’s goals, expectations, strategies and beliefs. These statements are based upon the information available to the company to-date and Theravance assumes no obligation to update these statements as circumstances change. Future events and actual results could differ materially from those projected in the company’s forward-looking statements. Additional information concerning factors that could cause results to differ materially from our forward-looking statements are described in greater detail in the company’s Form 10-Q filed with the SEC.

I remind you that the slide presentation can be accessed from our website and the slide number referenced during the discussion can be located in the lower left corner of each slide.

I will now turn the call over to Rick Winningham, our Chief Executive Officer. Rick?

Rick Winningham

Good afternoon everyone and thanks for joining us. I’m very pleased to report the positive topline results with TD-1211 in study 0084; the key study in the Phase 2b program for the treatment of opioid-induced constipation or OIC. TD-1211 was discovered by Theravance as a part of a Peripheral Mu Opioid Receptor Antagonist program with the goal of developing a medicine that will restore normal bowel function in patients suffering from OIC without affecting analgesia.

As many of you know opioids are one of the largest and most affective classes of medicines used for managing serious chronic pain conditions. They primarily exert their analgesic affect by acting on regions of the brains spinal cord inside the central nervous system or CNS. However, opioids also circulate outside the CNS compartment which results in a variety of side effects including debilitating constipation. This can adversely affect and impact the quality of life for many patients and limit the ability to properly manage the dosing of pain medications. Unfortunately, currently there are no orally absorbed medicine improved in the U.S. to help elevate OIC and lacks if they are not affective for many patients.

The goal with this program is to develop a best-in-class medicine that normalizes bowel function in OIC patients without interfering with the opioids analgesic effect. Based upon our market research we believe that the efficacy and reliving the symptoms of OIC is the product attribute most highly valued by patients. I’m pleased to report the results of 84 particularly at the 10 milligram and 15 milligram doses. As they show the potential for best-in-class effectiveness. All doses of TD-1211 demonstrates statistically significant increases in average complete spontaneous bowel movements or CSBMs per week, which is one of the most stringent measures of efficacy. In addition, we saw a consistent durability of effect to the efficacy analysis period and no evidence of CNS penetration. TD-1211 was generally well tolerated in patients receiving the 10 and 15 milligram doses of TD-1211 or generally satisfied with their treatment.

The commercial opportunity for the treatment of OIC may be substantial, there are approximately 4 billion treatment days of non-injectable opioids in the U.S. every year. About 40% of the total patients on chronic opioid therapy suffer from OIC and self treat with laxatives. Approximately 45% of those patients still report insufficient relief of their OIC symptoms all in all there could be well over 500 million treatment days in the U.S. alone for a safe and effective peripherally restricted view opioid antagonists.

I will now turn the call over to Mathai Mammen who will take us through the design of the Phase 3 program and the positive topline data from study 84. Mathai?

Mathai Mammen

Thank you, Rick. I’m very excited to review the results from the key clinical study in the Phase 2b program with TD-1211. Let’s start with Slide 4.

TD-1211 was discovered in-house using our multivalent approach to drug design and demonstrated positive results in Phase 1 and proof of concept Phase 2a study. Based on these results we designed a robust Phase 2b program exploring different doses and dosing regimen to inform Phase 3 design with the goal of maximizing efficacy and tolerability.

This Phase 2b program consists of three individual studies that randomize approximately 380 patients in total. The key study the subject of this press release this afternoon is study 84. This Phase 2b randomized 217 patients and assessed 5, 10 and 15 milligram doses of TD-1211 versus placebo with a rigorous primary end point of a change from base line in average complete spontaneous bowel movements or CSBMs per week over the last four weeks of treatment.

Complete and spontaneous are two important elements of a normal healthy bowel function. Complete refers to the (inaudible) completeness after a bowel movement and spontaneous refers to a bowel movement that occurs naturally and specifically does not require (inaudible).

The second study in our 2b program is 74, which looked at a dose to affect the strategy in 69 randomized patients. Our third study, 76, is an open label study assessing different dose initiation regimen in approximately 95 patients. The preliminary results of 74 and 76 support further development. I’ll focus my discussion today on the Phase 2b study 84, the detailed results from all three studies were made available through upcoming medical meetings.

Let’s turn to Slide 5. Study 84 was a double blind randomized placebo controlled parallel group dose ranging study conducted in the U.S. Patients with non-cancer chronic pain and opioid-induced constipation were enrolled in this study. They were assessed during a run in period to ensure that they met the inclusion criteria with fewer than5 SBMs over a two week period. We randomized 217 patients following this two week base line period into one of four groups including placebo and TD-1211, 5, 10 and 15 milligrams and treated them for a total of five weeks.

All patients given TD-1211 received an initiation dose of 5 milligrams for four days and were then treated with 5, 10 or 15 milligram through the remainder of the five weeks. The primary end point in this study is changed from base line in the weekly average CSBMs per week over the last four weeks of treatment. The last four weeks of treatment were assessed in order to provide an indication of the treatment affect per patients on chronic therapy.

Now onto Slide 6. The baseline characteristics of the patients in study 84 are shown here. The overall characteristics are consistent across treatment groups. We study patients on a wide variety of opioids and the mean daily morphine equivalent units in this study with 145 with a range of 30 to 1,740.

Let’s now turn to Slide 7 to review the primary efficacy results. I’ll focus my discussion on the 10 and 15 milligram dose groups. Shown in the table on Slide 7 are the weekly average CSBMs at baseline and on treatment as well as least squares mean differences from placebo adjusted for baseline.

As you can see these patients were quite constipated at baseline having only 0.1 to 0.3 CSBMs per week on average. Many of these patients had no CSBMs during the two week baseline period. During the last four weeks of treatment patients reported average weekly CSBMs of 3.0 at 10 milligram, 2.7 at 15 milligram versus 1 per placebo. The respective p values for differences from placebo adjusted for baseline were 0.001 for 10 milligram and 0.0003 for 15 milligrams. All doses of TD-1211 achieve statistical significance for the primary efficacy endpoint.

I know that the slide also contains at the bottom the week one CSBM data which were higher than subsequent weeks as expected but not included in our primary endpoint analysis.

Next I’ll review key secondary endpoint starting with week five efficacy on Slide 8. The table shows the change from baseline of CSBM at baseline at week five the last week of treatment. This is a particularly important analysis as it shows the durability of response by the end of treatment. The 10 and 15 milligram doses performed very well but CSBM responses of 2.5 at 10 milligram and 2.9 at 15 milligram with p values of 0.01 and 0.0001, respectively. We are pleased with the durability of response with TD-1211 as the end of therapy week five CSBM response is similar to the CSBM response over weeks 2 to 5.

Now let’s turn to Slide 9, where I’ll review the SBM endpoint. The patient at baseline had on average 1.1 to 1.2 SBMs per week. On treatment the patients reported 4.5 SBMs at 10 milligram and 4.9 at 15 milligrams versus 3.1 on placebo. The respective p values from least squares mean differences were 0.0038 for 10 milligram and 0.0003 at 15 milligram. We know that the SBM frequency was higher on week one than on week 2 to 5 with 6 and 6.6 SBMs at 10 and 15 milligrams, respectively.

Please now turn to Slide 10. Here we show the pre-specified SBM responder rate. A responder is defined here as a patient who on treatment has at least 3 SBMs per week with an increase of at least 1 SBM relative to baseline for at least 3 over the last four weeks of treatment. We found 61% at 10 milligrams and 70% at 15 milligrams were responders versus placebo at 39%. All of these responder rates on active treatment was statistically significantly higher than placebo.

That concludes the discussion of efficacy. In short we are excited by the robust and durable results in this study, in particular at the 10 and 15 milligram doses. Let’s now turn to safety and tolerability on Slide 11.

The overall incidence of adverse events or AEs was 44% on placebo and 39 to 55% on TD-1211. The most common AEs in this study were gastrointestinal typical of studies in OIC. The most common GI AE was abdominal pain which is typically described by the patient as cramping. These GI AEs were distributed across the TD-1211 treatment groups with 12.5, 11.3 and 15.4% of patients on 5, 10 and 15 milligram compared with 11.1% of patients on placebo. There were three early [terminations] related to GI adverse events for patients on TD-1211.

I’ll remind you that TD-1211 patients were on 5 milligrams for the first four days of treatment and to the large majority of GI AEs occurred during this period. So, it's not surprising to us that the GI AE event rates look similar for the different dose groups. From day 5 to onward when patients were at their target doses, GI AEs in all groups were infrequent and similar to placebo. There were four SAEs in study 84 and none of these were treatment related.

Let’s turn to Slide 12. TD-1211 was generally well tolerated at all doses. A majority of the treatment related GI AEs noted in the previous slide were associated with initiation of the treatment, resolves within a few days and were generally mild to moderate. There were no treatment related findings in any ECG assessment. Importantly, there was no evidence of CNS opioid withdrawal in any of the treatment arms. And finally, there was no significant treatment related findings in laboratory test results or vital sign assessment.

Now let’s turn to Slide 13 to sum up. Study 84 achieved its primary endpoint for all three doses study and achieved key secondary endpoints at the 10 and 15 milligram doses. One particularly important result I’d like to highlight is the global impression of changed scale ratings reported by patients. Patients were asked at the end of treatment whether their constipation was changed and asked to rate the change on a 7-point scale.

The top two choices were better and much better. 66% of the patients on 15 milligrams at TD-1211 reported that their constipation was better or much better after five weeks of therapy. In addition, when asked at the end of treatment of their likelihood to take the medication again if offered by a physician after [approve] for use, we were pleased that over 90% of the patients on 15 milligrams of TD-1211 stated that they were likely to take the medication again. The data we report here today on TD-1211 support progression in the Phase 3 development.

And with that I’ll turn the call back over to Rick. Rick?

Rick Winningham

Thanks Mathai. In summary, the positive results from study 84 show that TD-1211 as an opportunity to be a best-in-class medicine that makes a difference to patients suffering from OIC. All three doses of TD-1211 achieve the primary endpoint and key secondary end points were achieved with 10 and 15 milligram doses. Your next steps are to review the results of these studies with the potential partners and to meet with the FDA and discuss requirements for these three programs.

We remain very focused on advancing our pipeline, pursuing a best-in-class strategy to discover and develop medicines in a number of therapeutic areas. We recently reported positive topline results from our four Phase 3 studies and our LABA MABA program in collaboration with GSK. We remain on track for filing Relovair in the U.S. and Europe in the near future, and we’re driven by the opportunity to improve life per patients with serious medical conditions.

And now I’d like to turn the call over to the conference facilitator and open the call for questions.

Question-and-Answer Session

Operator

(Operator Instructions) Our first question comes from Steve Byrne of Bank of America. Your line is now open.

Steve Byrne - Bank of America/Merrill Lynch

Can you quickly define what is the EA population and what patients were excluded in that protocol?

Mathai Mammen

The EA population, the efficacy analysis population needed to complete the trial and have two weeks minimum of adequate diary reporting. And the number of dropouts we were pleased were very minimal in this study, so those that initiated treatment and dropped out were a couple per arm.

Rick Winningham

I’d also just add Steve to get to the heart of your question, the analysis of the study and the results of the study don’t change whether you are analyzing the ITT population or the EA population.

Steve Byrne - Bank of America/Merrill Lynch

And if I recall correctly, back in your Phase 2a data on this drug, your 10 milligram dose had a much higher level of abdominal pain I think in the 30% range. Was one of the things different about the design of this was that, that four day (inaudible) at the 5 milligram is that different and do you see that as affecting a reduction in the abdominal pain?

Rick Winningham

Yes, we did lot of work to try to understand the GI symptoms from study 67 our proof of concept study; and yes, you are right the GI adverse event rate was higher in that study. So, the key difference what we attribute here as making the big difference is that four day initiation period. So, as a reminder vast majority of GI related AEs that occurred in this study occurred during the dose initiation period when the patients were on 5 milligrams. And we got them to particularly affect the doses of 10 and 15 with the AE profile of 5.

Steve Byrne - Bank of America/Merrill Lynch

And then just lastly Mathai, you mentioned in your remarks about this molecule being a multivalent molecule, what about it is multivalent and how is that strategy helped here?

Mathai Mammen

Yes, so with couple of protein receptors generally, we have employed a multivalent strategy meaning that we bind to a piece of the receptor where the endogenous neurotransmitter in this case opioids might actually bind. And then we also reach out and touch a separate region on the receptor. What we have done is that, that’s gotten us two attributes, one is we make a compound that’s specific for opioid receptors, very specific for opioid receptors and two, we use that secondary binding element to build in the physical property such that the compound can be orally available and excluded from the CNS compartment.

Operator

Thank you. Our next question comes from Ronny Gal of Bernstein. Your line is now open.

Ronny Gal - Sanford Bernstein

Three questions; the first one on efficacy and then safety and then on partnership. The efficacy piece element guys, if I look at the comparable data across you and (inaudible) spontaneous bowel movement or responder analysis. The data seems to be relatively similar, I know some of your competitors simply they now present the complete spontaneous bowel movement, but across the secondary endpoints, there seem to be some more of a similar numbers. May be I’m reading the data wrong but what gives you guys the confidence that you actually have a best-in-class efficacy here?

Rick Winningham

Ronny you have to all of the studies are that have been done by different people that are pursuing at improved therapy for this condition are slightly different. I think one of the highlights that is a different of our study is that we chose to do the efficacy analysis on weeks two through five, and excluded week one because in doing the study what we were attempting to do was to get an evaluation of durable efficacy, efficacy that we could expect if we were going to do a Phase 3 study. As you can see as noted, and as Mathai pointed out on the slides the efficacy, whether you are looking at SBMs or CSBMs is higher in week one and it's higher because the antagonist is initially blocking the effect of the opioid in the bowels are effectively being cleared in that first week. And then post the first week you really get evidence of the molecule itself and the ability of the drug to create a durable response. And so while I can’t, I don’t want to get into a comparison between other drugs, I do think that that’s the design of our study is important to keep in mind. The other point I’d make is that we are once a day and many of these patients are faced with substantial pill burden and the use of their opioids to control their pain and anything that we can do to help by developing this drug in a once a day fashion to lower their pill burden. We believe we will increase its overall effectiveness and treatment. Mathai?

Mathai Mammen

Yes, the other point I think I made during the slide review was the patient experience. We ask them what they felt about the change in their constipation and all related symptoms and the majority really thought that they benefited from being on TD-1211. And like we said particularly at the high dose.

Ronny Gal - Sanford Bernstein

Is there similar there for some of the other drugs from this category that I could pull out to compare or that you are aware of?

Mathai Mammen

You’d have to look and ask the other companies that are developing products in this space.

Rick Winningham

We are not aware of them.

Ronny Gal - Sanford Bernstein

You are not aware of them. Okay, fine. I appreciate that. Second on safety, I mean you have done a very nice job you have taken away the abdominal pain. The question I have primarily was around the nausea and vomiting data point, there seems to be still a much smaller but still a signal there. I was wondering if that is something that you have seen across the compound o is there something that you think might be more specific to this particular compound?

Mathai Mammen

Let’s take them may be piece by piece, the vomiting, so we are focused on the 10 and 15 milligram doses. So, at 10 there was one patient and at 15 there was zero, [because there was one]. And on nausea there were 8 and 3 patients on 10 and 15 versus 2 on placebo, so there may or may not be something there but again we want to emphasize that all of this occurred during that dose initiation period. And if one looks beyond that there is very little going on, and that we feel is going to be representative of what the patient experience is in a long run, post initiation period for the remainder of time that they are on therapy.

Ronny Gal - Sanford Bernstein

That was just a very small number set and should not be over extrapolated.

Rick Winningham

I think Ronny just to emphasize the very small numbers the AE of the GI AEs occurred primarily right around the initiation therapy.

Ronny Gal - Sanford Bernstein

And last but not least, I mean this is more to the management, okay guys I mean you got a compound you can work with, where do you stand in terms of the timeline to getting this partnered and do you think if the question of if or is it the question of when you will be able to find this compound [at home].

Rick Winningham

I think our objective here is to engage or continue discussions with the partners that with that we have sort of put a little bit on hold as this data as the study close and we are close to unblinding. Our objective here is to partner the program, I think while we are working through these discussions we will be continuing our discussions with the global regulatory authorities on what the design of the Phase 3 program looks like and be preparing to go into Phase 3. But our objective here is to partner the program.

Ronny Gal - Sanford Bernstein

And your assessment obviously you are not committing to anything here, but your assessment you will be able to find some that will take you to Phase 3.

Rick Winningham

I think we are pretty optimistic about that today and when we have the deal done you can rest assured we will announce that.

Operator

Thank you. Our next question comes from Ian Somaiya of Piper Jaffray. Your line is now open.

Ian Somaiya - Piper Jaffray

One question on the efficacy, since looking, Mathai, the (inaudible) period week two through five, is it possible to break down what the efficacy was on a weekly basis. Now you spoke to it in terms of week one efficacy, if you could just give us a sense of how these patients benefitted each of the individual weeks, from two to week five?

Mathai Mammen

What we tried to do is give you sense of that by looking at weeks two to five to those four weeks and comparing it to week five. And what you see is that the values of weeks two to five are pretty similar to what we get at week five. So, it gives you dose by dose essence for the shape of that curve. What we want to do is put all of that data out there at upcoming medical conferences, but you get a pretty good sense from just those two slides. Yes, week one of course we just want to emphasize is different. Week one tends to be a pretty active week and there are higher number of bowel movements SBMs and CSBMs then on consequent weeks.

Rick Winningham

I think when people view the data at a medical meeting and they look at weeks two through five at the 10 and 15 milligram doses they will see that these durable responses.

Ian Somaiya - Piper Jaffray

And question on safety, I guess the titration strategy did work doesn’t make sense to further titrate may be [shut off] even at a lower dose or key patients with a 5 milligram for a longer period of time as we think about potential discussions with FDA on the Phase 3 design.

Rick Winningham

I think what we found here with a four day dosing of 5 milligrams as a good schedule and that if you look at the patient overall satisfaction scores through the [PGIC] analysis, you see that patients are satisfied with treatments. So, I think we got a pretty good schedule here and I’m not sure that further work is going to be necessary. Now with that in mind with 74 and 76 the two smaller studies we looked at different doses and the effect of different doses and different regimens in those studies, and I think again what we know thus far about the analysis of data from those studies is that they support the 5 milligrams is a good initiation dose. Mathai?

Mathai Mammen

That’s exactly right, we asked ourselves this question after study 67 our proof of concept study and designs of 74 and 76 were in part to try to run experiment using data that was coming in from those studies helped us with 84. And we feel looking at all of that right now, the 5 milligrams for four days is pretty good, and the GI event rates as you saw in the safety slide were quite comparable to placebo.

Ian Somaiya - Piper Jaffray

One last question on the drop on for patients who were part of the efficacy analysis population where [one part] efficacy announced population , can you give us a sense of what led to what drove either a lot of compliance or dropping out of the study, what were some of the issues you will be facing so as to complain about?

Mathai Mammen

There were a wide variety of things, some people were just did not show up, others had a wide variety of reasons for discontinuing. The three that we are interested in and focused on are the ones that discontinued because of a treatment related GI adverse event and there were several of those. And those ones right now are mixed at the different GI AEs including the crampening and diarrhea.

Ian Somaiya - Piper Jaffray

Or they have any given dose?

Mathai Mammen

So, they all occurred during the initiation periods as they were all on 5 milligrams. And so they were all within several days of initiating dose. They were in different dose groups ultimately but the dose they were on at the time was 5 milligrams.

Operator

Thank you. Our next question comes from Brian Skorney of Brean Murray. Your line is now open.

Daniel Brims - Brean Murray

This is Daniel Brims calling in for Brian. First off I guess what is the time for the first bowel movement and did that pretty much happened during the lead in dose?

Mathai Mammen

We are not going to comment on time to first bowel movement, we are still looking at all of the data as we just recently unblinded and they are reporting primary efficacy point in key secondary right now.

Rick Winningham

So, I’d say time to first bowel movement would be somewhat important if we were focused on developing just as a laxative. That’s not what our objective is, our objective here is to develop a medicine that can restore patients with opioid-induced constipation to normal bowel function. And therefore, that’s why we spent time on the call discussing really durability of response and because that’s really what our objective is, our objective is to get to a treatment regimen that provides a durable response and moves the patients towards normal bowel function.

Daniel Brims - Brean Murray

I’m just trying to get an idea if that lead in period is long enough or if they are not or whether or not extending it could aid in things. And my other question is with the partnering, would there be a situation where you would do the Phase 3 studies yourself or do you see as definitely being partnered before that?

Rick Winningham

Well, I don’t want to comment on that other than to say our objective is to partner the program. So, that’s what we are working on and we will certainly as I said reengage the partnership discussion we have put on a short hold and I think we are optimistic given the results of the study we are going to be able to pull something through.

Operator

Thank you. (Operator Instructions) Our next question comes from Howard Liang of Leerink Swann. Your line is now open.

Howard Liang - Leerink Swann

Regarding pain, is pain measured on study?

Mathai Mammen

Yes, it is, pain is measured on baseline and throughout the five week dose treatment.

Howard Liang - Leerink Swann

Conclusion is that there is no interference with pain?

Mathai Mammen

There is absolutely no interference with pain.

Howard Liang - Leerink Swann

On your highlighted data on global impression and also the 90% of patients likely to use the drug when offered again. What are the corresponding numbers for placebo and also for the other doses?

Mathai Mammen

So, for both of those numbers, placebo is a lot lower. So, we will report full range of data across the doses at a medical conference, but these numbers are statistically significantly better than placebo.

Howard Liang - Leerink Swann

Okay, what about the other doses also that are in placebo?

Mathai Mammen

So, they are better but we want to comment that we are particularly excited by the 15 milligram dose on those metrics.

Howard Liang - Leerink Swann

And then you said there is no apparent to CNS penetration, is that based on the pain measurement or what (inaudible).

Mathai Mammen

We have two ways of assessing that, one is very direct and we do these COWS basically that allow us to asses central withdrawal and the second is looking at their pain scores and their analgesia regimens. And on neither was there any evidence of CNS penetration. That’s consistent with the CNS penetration of study we did in Phase 1 where we looked at the drug and looked at the changes in people diameter to assess likelihood of CNS adverse events.

Howard Liang - Leerink Swann

You used the terms called COWS, do you want to define that?

Mathai Mammen

Central opioid withdrawal scale.

Howard Liang - Leerink Swann

Can I just ask a last question about partnership in terms of what you are looking for or you thinking about a royalty type of a structure or where you have continued participation in the program?

Rick Winningham

No Howard, I’m not going to, I won’t comment on that at this particular point in time. I think right now we are just excited about the results we believe today we have got important medicine that can potentially that go into a Phase 3 program and potentially benefit a number of patients. So, that’s I think partnerships terms there is a whole range of then and we will evaluate them based on what’s best for Theravance.

Operator

Thank you. Our next question comes from Anant P [Anant Padmanabhan] of Cowen. Your line is now open.

Anant Padmanabhan - Cowen and Company

Just a couple of questions, first on the endpoint itself, the CSBMs versus SBM, has the FDA given you any guidance on what is the preferred endpoint. It seems like the endpoints are fairly mixed and some of the competitors trial. So, just trying to get a sense of the agency does prefer CSBM over SBM? Thank you.

Mathai Mammen

So, I think the CSBM measure is a measure that potentially can be used to control placebo response a little bit better than SBMs but as I said our next step is really to go to finish the analyzing all of the data and to schedule and prepare for meetings with the global regulatory authorities, so, we can design the Phase 3 program. What’s important to us again about to reemphasize is that we are developing this product in order to restore normal bowel function to patients. And that’s really the set of endpoints that we will want to see in a Phase 3 program and to be able to demonstrate that in fact that the physician and the patient can have a level of confidence in response when taking this medicine.

Anant Padmanabhan - Cowen and Company

Okay, and then just one more on the dose response. Looking at the 10 versus the 15 how confident are you that you said you were excited about the 15. Would that be the dose that you will move into Phase 3, it seems like if you just look at the data and the side effects as well, there is a bit of inverse dose response to 15 dose look good but on the efficacy side the 10 looks pretty good as well.

Mathai Mammen

What we can say right now is that first off, where these data refreshed us and we are looking at it for the last few days only we will spend the next probably weeks or months looking at the rich data set that’s just collected across the three studies. The 5 milligrams clearly is a little different from the 10 and 15 and between the 10 and 15 frankly we need to think about it, because on the straight bowel frequency measures where there might be a similarity to them. There is the potential for differences on important secondary measurements including the patient experience. So, we need to look at all of that together and we will decide here on the most appropriate dose for Phase 3.

Operator

Thank you. Our next question comes from Stephen Willey of Stifel Nicolaus. Your line is now open.

Stephen Willey - Stifel Nicolaus

Could you maybe just provide some color with respect to where you guys are in terms of [tox work] for this compound and also what if any work needs to be done on the manufacturing front to scale up [material] for Phase 3.

Rick Winningham

We are in a great position with regard to manufacturing, the process chemistry group has been very successful driving down the cost of materials here. We are ahead of probably where we would where a lot of people might normally be when taking out Phase 2b data and the [tox] program. So, I think we are in very good position with regard to both CMC as well as preclinical toxicology.

Stephen Willey - Stifel Nicolaus

And then in terms you mentioned about initiating conversations with the regulatory agencies around Phase 3 design. I guess how seem do you look to start those conversations and then how do you balance that against a collaborative situation we are generally the big brother wants to have some kind of input into the process?

Rick Winningham

Well, I think that’s certainly something that we will take into consideration but I think we are moving with an eye of finishing the analysis of the existing studies, getting a couple of small Phase 1 and Phase 3 enabling studies finished getting the package into regulatory authorities and meeting with them and if we can get the partnership done in the mean time that’s great, but we are certainly not going to wait for that relative to scheduling and preparing for the meeting with the global regulatory authorities. And we have a bit of ongoing discussion with regulatory authorities over the course of the development of this program. So, it's not going to come, I don’t think it will come and something that’s completely new in a Phase 3 study, but really we do want to confirm what we need to do for both for major markets in the world.

Stephen Willey - Stifel Nicolaus

Can you just provide any color as to whether or not you have already provided any companies without their access or CDA to some of the clinical pharmacology data?

Rick Winningham

No, we can’t comment on that.

Operator

Thank you. And our next question is from Ian Somaiya of Piper Jaffray. Your line is now open.

Ian Somaiya - Piper Jaffray

I have a follow-up. Again I don’t know if you will answer this question but I thought ask anyway. Is Glaxo still [entered] the field or they have completely got away from it?

Rick Winningham

I think you would have to ask Glaxo that question, I don’t know they at one point in time had an option on the program that they turned down, but whether they are or not interested I wouldn’t make any comment. You would have to ask Glaxo on that.

Operator

Thank you. It appears we have no further questions on the phone. I’d like to turn the conference back to Mr. Winningham. Please go ahead sir.

Rick Winningham

Alright. Thank you very much operator and thanks everyone for participating. We appreciate you joining us again for a piece of good news that we had at the company and we look forward to providing you further updates on our programs in the near future. Have a great day.

Operator

This does conclude today’s conference call. We thank you for your participation. You may now disconnect.

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