Theravance Biopharma Inc (TBPH) 2017 Q1 法說會逐字稿

Ladies and gentlemen, good afternoon. At this time, I'd like to welcome everyone to the Theravance Biopharma Conference Call. (Operator Instructions) Today's conference call is being recorded.

And now, I would like to turn the call over to Alex Dobbin, Head of Investor Relations. Please go ahead.

Okay. Thank you very much, operator. Good afternoon, everyone. We were just informed by the NASDAQ before we begin that NASDAQ is having technical difficulties in their operation center. So we do hope this call proceeds uninterrupted. In the event that we do disconnect, I hope that you will try to reconnect.

With that, thank you for joining us for our first quarter 2017 financial results conference call and webcast. With me today, Rick Winningham, Chief Executive Officer; Renee Gala, Chief Financial Officer; and Brett Haumann, Chief Medical Officer. Following prepared remarks, we will open the call for questions. A copy of the press release and the slides accompanying this call can be downloaded from our web site or you can call Investor Relations, 650-808-4045, and we will be happy to assist.

We'd like to remind you this call will contain forward-looking statements which involve certain risks and uncertainties, including statements about our product pipeline, expected benefits of our products, the anticipated timing of trial results and regulatory filings, and expected financial results. Information concerning factors that could cause results to differ materially from our forward-looking statements are described further in the company's filings made with the Securities and Exchange Commission.

And with that, I'll hand the call over to Rick.

Thanks, Alex. Good afternoon, everyone, and thank you for joining us. 2017 is shaping up as an extraordinary year of progress for Theravance Biopharma. Building on our accomplishments in 2016, we are continuing to make important clinical gains across our key programs, with multiple clinical milestones anticipated through the remainder of 2017 and 2018. In our call today, we will provide an update on our key programs and near term milestones. First, I will give an overview, and then Brett will share more color, then Renee will review our financial performance, then we will open the call to questions.

First, our Phase 1b study of TD-1473 in patients with moderate to severe ulcerative colitis is progressing. We expect data in mid 2017. TD-1473 is designed to be selectively active, reducing inflammation in the intestinal wall, while sparing the body from systemic immune suppression. In the Phase 1b study, we are looking for a meaningful reduction in disease activity in ulcerative colitis patients, and we want to achieve this without systemic immune suppression, consistent with the findings in the Phase 1 healthy volunteer study. Data from the Phase 1b study will inform our broader clinical development plans for this compound, including potential assessments and immune checkpoint inhibitor colitis as well as Crohn's disease.

Second, we anticipate completing in the middle of the year, the Phase 3 long-term safety study for revefenacin, our nebulized once-daily long-acting muscarinic antagonist, or LAMA, for the treatment of COPD. This long-term safety study, combined with the two positive pivotal Phase 3 efficacy studies reported last October, is intended to support our NDA filing, which we expect to submit to the FDA in the fourth quarter of this year.

We recently initiated a Phase 3b study of revefenacin in COPD patients with low peak inspiratory flow rate or PIFR. These patients, who are not able to breathe in with sufficient force to effectively use handheld inhalers, and these patients exist at all levels of disease severity. Brett will elaborate shortly on a recent publication showing a relationship between low PIFR and reduced hospitalizations when these patients are discharged on nebulized therapy.

Our Phase 3b study is designed specifically to evaluate the effect of revefenacin in this population of patients. The study is intended to support commercialization of revefenacin, and is not required for the NDA submission later this year. We expect results from the PIFR study in the early part of 2018.

TD-9855, a dual norepinephrine and serotonin reuptake inhibitor or NSRI, is in a Phase 2a study in neurogenic orthostatic hypotension or NOH. As we reported in February, we have seen encouraging patient responses in a single ascending dose portion of the study. And as a result, we have extended the duration of the study, to allow for those patients who respond to continue dosing for up to 20 weeks to test the durability of response.

Sustained durable response is important because currently approved therapies have not demonstrated evidence of sustained long-term effect. Showing a durable response would represent a major therapeutic advance and a competitive advantage. We expect data from the extension study before the end of 2017. In parallel, we plan to seek regulatory support for an orphan drug designation and expedited development pathway based on the encouraging patient responses seen to-date in the Phase 2a study.

Development of velusetrag is continuing on target. Velusetrag is partnered with Alfa Wassermann in certain ex-U.S. geographies, and Alfa Wassermann has largely funded the Phase 2b program. We are completing a 200-patient Phase 2b study of velusetrag in both idiopathic and diabetic gastroparesis patients. Velusetrag has already shown a positive effect on gastric emptying in a Phase 2a study in gastroparesis and was granted a fast track designation last year. We anticipate results from the Phase 2b study in gastroparesis in mid-2017.

With regard to VIBATIV, the current basis for our acute care sales infrastructure, we are advancing our commercial and label expansion strategies. The branded antibiotic space remains challenging, particularly due to the introduction of multiple suppliers of generic daptomycin last year. We expect pressure in the outpatient setting to recede in the second half of 2017 after the outpatient reimbursement price for generic daptomycin resets. Our ongoing Phase 3 study in primary bacteremia is progressing, and we expect data in 2018. If positive, the study would enable us to file an SNDA in this indication.

Additionally, our recently completed patient registry study, or TOUR, is providing valuable information about the use of VIBATIV in real world clinical settings, including reports of positive clinical responses and patients with bacteremia, endocarditis, osteomyelitis, and skin and respiratory infections.

With a strong cash position and a robust business model, we are moving forward with momentum across our pipeline of proprietary and partnered assets. In addition, GSK's Closed Triple for COPD represents an important strategic asset and a promising source of income, potential source of income, for Theravance Biopharma. Looking ahead across an extensive set of milestones, we believe we are well positioned to improve the lives of patients and create long-term value for our shareholders.

I will now turn the call over to Brett for additional perspective. Brett?

Thanks, Rick. I will provide an overview of four of our key programs, all of which have clinical study readouts expected this year. Each program is the result of internal research and discovery, and we believe each could represent meaningfully differentiated therapeutic options for patients.

Firstly, in our JAK inhibitor program, the goal is to develop a highly differentiated treatment for inflammatory bowel diseases, including ulcerative colitis, Crohn's disease and colitis associated with the use of immune checkpoint inhibitors. We are developing JAK inhibitors that are designed to remain localized and only act within the gut wall, thereby maximizing local anti-inflammatory efficacy and minimizing the systemic exposure that would otherwise lead to immunosuppression.

Our approach has a potential to increase the therapeutic index by improving the safety profile seen with systemic JAK inhibitors and by increasing the potential to go to higher doses than can be achieved with systemic JAK inhibitors to achieve even greater efficacy. It's also worth noting, that our approach allows us to leverage the broad anti-inflammatory effect of a pan-JAK inhibitor by restricting its activity to the diseased organ in contrast to systemic JAK inhibitors that need to be more selective in order to reduce systemic toxicity.

As previously reported, we are conducting a small Phase 1b trial of TD-1473 in patients with active, moderate to severe ulcerative colitis. The study is designed to assess the safety and tolerability of TD-1473 and the effect of TD-1473 on a range of relevant markers of inflammation in the colon, cellular changes and measures of endoscopic improvement, and clinical benefits, including changes in partial mayo score.

We will also measure PK to assess whether the systemic levels of TD-1473 in patients match the very low level seen in healthy volunteers. The study has an adaptive design, which provides flexibility in dosing and yields a maximum amount of data for a study of this size. The collection of evidence from this novel Phase 1b study is intended to inform future developments of TD-1473, including the potential to advance to more definitive induction and maintenance study. We expect data from a Phase 1b trial in mid 2017.

Now, moving on to revefenacin; as Rick briefly summarized, we recently initiated the study in approximately 200 GOLD 2, 3, and 4, COPD patients with low PIFR. This study is not required for filing, but rather is being conducted to better understand the needs of these patients and to support commercialization of revefenacin, if approved. We believe that this patient group, many of whom only have moderate disease, may benefit particularly from the use of nebulized therapy, as opposed to handheld inhalers because these patients are not able to inhale with enough force to benefit fully from handheld inhalers.

In this respect, the paper that Rick mentioned earlier is noteworthy. This retrospective study, published in the Annals of ATS by Loh, et al., showed that more than half the patients who are hospitalized with an exacerbation of COPD had low PIFR, and that in this group, rates of all-cause readmission and COPD readmission were significantly lower for those patients who were discharged with nebulized therapy compared to inhaler therapy. In fact, the results were stark. Fifty percent of patients discharged on handheld inhaler therapy were readmitted within 30 days of discharge, compared to 0% for patients discharged on nebulized therapy. The average time to readmission for COPD in the handheld inhaler group was 27.5 days, less than a month, compared to 103 days, more than three months, for the nebulized group.

He also concluded that, and I quote, "Incorporating measurements of peak inspiratory flow in clinical practice is simple and beneficial," and they went on to recommend, again I quote, "checking peak inspiratory flow in both in- and outpatients to assess the need to switch from drypowder inhaler to other delivery devices or nebulized therapies."

Indeed, PIFR is very easy to measure, requiring an inexpensive and readily available device, which means PIFR has the potential to become a powerful and accessible factor for physicians to consider as they determine the proper prescription for patients. We and our partner Mylan are confident that there is a significant market need for a once-a-day nebulized LAMA. If approved, revefenacin represents the first such therapy. Further, pivotal Phase 3 efficacy studies we reported last year show the benefit for our once-a-day LAMA versus a standalone agent, and when added to existing COPD therapy, including LABA and LABA ICS.

Now, turning to TD-9855 in neurogenic orthostatic hypotension or nOH. nOH is a disorder of the autonomic nervous system, characterized by the inability to regulate blood pressure when moving from a lying to a sitting or standing position. It's an orphan condition, affecting fewer than 200,000 patients in the U.S. and includes patients with multiple system atrophy, Parkinson's disease, and pure autonomic failure. The condition is very debilitating and confines patients to their beds, severely impacting mobility and quality of life.

Our objective, with TD-9855 is to develop a treatment for nOH that can enhance blood pressure regulation, reduce patient symptoms, and offer the potential for a meaningful improvement in quality of life. There are only limited treatment options available, and these require multiple doses during the day, and carry the risk of rebound hypotension, when patients lie down. These agents, midodrine and droxidopa, improve vascular tone by increasing levels of norepinephrine in the body.

In contrast, TD-9855 is a reuptake inhibitor, prolonging the effect of the normal norepinephrine that is already present in the body. TD-9855 has a long half life, which supports the potential for once-daily dosing and has demonstrated favorable tolerability in over 500 subjects dosed in other clinical trials to-date.

Our Phase 2a proof-of-concept study in patients with nOH was initiated last year and was designed to evaluate postural changes in blood pressure, symptom reduction, and safety and tolerability following single ascending doses. Based on encouraging treatment responses in the majority of patients enrolled to date in a single ascending portion of the study, we chose to modify the study design to allow those patients who respond to continue dosing once-daily for up to 20 weeks. The study extension will allow us to assess the durability of the treatment effects of TD-9855, which could prove to be a meaningful point of differentiation, particularly when one considers that droxidopa has not been able to demonstrate clinical effect beyond two weeks, as reported in its label.

We expect to report data from the extended Phase 2a study before the end of 2017. In parallel, as Rick mentioned, we plan to seek an orphan drug designation for TD-9855 in nOH as well as an expedited development path

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and certain other geographies.

Our earlier Phase 2a crossover study confirmed that velusetrag reduces gastric emptying time for patients with diabetic or idiopathic gastroparesis. The current study builds on this data to assess the effects of velusetrag on both gastric emptying time and the symptoms of gastroparesis. We were very pleased to have the FDA grant fast track designation for velusetrag in gastroparesis, a testament to its potential importance in treating a clinically important condition with limited alternative therapy. We expect results from our Phase 2b study in mid-2017. And assuming a positive outcome, we'll confer with our partner the next steps that could lead to a pivotal Phase 3 registration program.

Lastly, I'd like to update you briefly on our NEP inhibitor program, where our goal is to develop a medicine that has broad potential to be combined with complementary mechanisms to treat heart failure as well as other serious cardiovascular and renal diseases.

We're evaluating both TD-714 and TD-1439 in Phase 1 program. Today, as reported in our press release, we are pleased to share that we completed the multiple ascending dose study of TD-1439 in healthy volunteers. And the results are in line with what we saw in a single ascending dose study, and supportive of our target product profile, specifically 24-hour target engagements, non-renal clearance and a favorable safety and tolerability profile. With these data, we now have two promising NEP inhibitors, each showing favorable results in Phase 1 studies in healthy volunteers, and we are currently evaluating next steps for these compounds in our NEP inhibitor programs.

I'll now pass the call over to Renee to provide our financial update.

Thank you, Brett.

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were $20.8 million as compared to $23.6 million for the same period in 2016. The decrease in expense is due to a reduction in external costs and a decrease in non-cash share-based compensation expense. First quarter SG&A expense includes $5.2 million in non-cash share-based compensation.

Following our financing activities in 2016, we remain in a well capitalized position with $540.7 million in cash, cash equivalents, and marketable securities at the end of the first quarter. Completing our fundraising activities in 2016 enables the company to fund multiple potential pipeline advancements in both 2017 and 2018 as we enter an incredibly catalyst rich period for the company.

Now turning to guidance. Our 2017 financial guidance remains unchanged from the guidance we provided in February of this year. For the full year of 2017, we expect our operating loss, excluding non-cash share-based compensation to be in the range of $195 million to $205 million. As a reminder, our guidance does not include the impact of any potential new business development transactions. And we do not expect to receive milestones in 2017 related to existing collaboration.

Finally, I will summarize our economic interest related to the GSK respiratory program as they represent an important potential source of income for Theravance Biopharma in the near and long term. At the end of 2016, GSK submitted regulatory filings for the Closed Triple for COPD in both the U.S. and the EU. Based on timelines provided publicly by GSK, we could expect approvals in both regions before the end of the year and could begin receiving cash flows related to this program as soon as early

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which is expected to read out later this year. This study in 10,000 patients with COPD is designed to assess the impact of the closed triple on COPD exacerbation.

In late 2016, GSK initiated the Phase 3 CAPTAIN study in asthma. This study is expected to read out in 2018, and if positive, would be followed by regulatory filings also in 2018. In addition, GSK recently released data from the Salford Lung Study of RELVAR, which contains two of the active ingredients of the Closed Triple. The findings in this study reinforce the value of once-daily therapy in patients suffering from asthma, which should have a positive impact on the future potential value of the Closed Triple for Theravance Biopharma.

Now, I will turn the call back over to Rick.

Thanks, Renee. As we progress into mid-2017, we're on track to deliver clinical results at every stage of development in our pipeline throughout the remainder of the year. From a personal perspective, very rarely in my career have I ever entered a year, where I have Phase 1a, Phase 1b, Phase 2a, Phase 2b, Phase 3a, Phase 3b studies, with a potential NDA approval and an NDA filing all anticipated to occur over a 12 month period of time. But that's the opportunity that 2017 presents for Theravance Biopharma. This is an unprecedented period for the company, and underscores the depth and breadth of our portfolio, the productivity of our internal R&D engine, and a robust business model.

In summary, and if you reference the slide accompanying today's call, in 2017, we expect to achieve the following milestones: data from our Phase 1b study in TD-1473 in ulcerative colitis; data from our Phase 2b study of velusetrag in gastroparesis; data from the Phase 3 12-month safety study of revefenacin, followed by a planned NDA filing; data from the Phase 2a study of TD-9855 in neurogenic orthostatic hypotension; final data from the TOUR patient registry study with VIBATIV; data from the Phase 3b IMPACT study with a Closed Triple; and potential regulatory approval of the product in the U.S. and the EU for COPD.

And in 2018, we expect to achieve the following milestones: data from the Phase 3b study of revefenacin in patients with low peak inspiratory flow rate, intended to support commercialization; data from the Phase 3 registrational study of VIBATIV in bacteremia followed by a planned SNDA submission in the U.S.; the potential regulatory approval of revefenacin in the U.S. for COPD; the potential to start earning income from the Closed Triple; and finally, data from the Phase 3a CAPTAIN study of the Closed Triple in asthma patients followed by a potential regulatory submissions for asthma.

In closing, we're very proud of our entire team at Theravance Biopharma. All of them continue to drive our business forward. We believe that our programs represent valuable and differentiated product opportunities with the potential to have a meaningful impact on patients lives, change how serious diseases are treated, and create long-term value for our shareholders.

And now, I'd like to turn the call over the operator for questions.

Thank you, sir. I would like to apologize for the technical difficulties. We appreciate your patience. (Operator Instructions) We will have our first question from Geoffrey Porges of Leerink Partners.

Thanks very much and a few questions if I may. Looking forward to all of those readouts in the remainder of the year. So, Rick, first, on TD-9855, could you explain the protocol change and the extension a little bit more clearly, and whether you have seen the data? And if not, what made you to make the change?

And then secondly, sort of related to TD-9855 and TD-5108, should we be assuming that both of those programs, if they are successful in the current Phase 2 trials, would be Phase 3 candidates for next year? And then related to that, are they partnering candidates or are they Theravance sort of owned full development and commercialization programs? And what, in addition to those, might be business development priorities? Sorry for the long list.

No, thanks, Geoff. I will turn over our thinking on TD-9855 to Brett because it's been a very exciting program for us. And I will just touch before Brett starts on sort of how we view velusetrag and TD-9855 from a partnering perspective. And clearly, TD-9855 is a program we can take all the way to the finish line ourselves. And given the relatively small target audience that treats neurogenic orthostatic hypotension in fact commercialize ourselves. So that's not one where we would require a partner.

In velusetrag, we have a partner today in Europe and number of other -- few other countries, Alfa Wassermann. So we have rights in the United States and Japan and a number of other countries. Whether we partner velusetrag or not, with regard to those regions that we currently own, will sort of depend on a number of factors going forward, including what is happening with other programs.

But I think right now, we see a pretty significant opportunity, if the Phase 2b study is positive for Velusetrag, a fairly significant opportunity for the program in the United States and Japan, in terms of making a difference with patients and then commercial opportunity because I think the data from the Phase 2b are such, that with good data on symptoms in the Phase 2b, we could be pretty confident on success in a Phase 3 study.

So TD-9855, we will keep ourselves. We got the ability to take that all the way ourselves. Velusetrag, we will have to see. We certainly, if things fall the right way, we could certainly develop velusetrag ourselves. And, of course, that's primarily diagnosed both in the emergency room as well as with gastroenterologists in terms of gastroparesis.

So, with that, I will turn it over to Brett.

Perfect.

Thanks, Rick. And, Geoff, you had asked about the sort of Phase 3 readiness for those two assets because with velusetrag, the intent with the current Phase 2b study was exactly that, to inform a pivotal registrational program as the next step for the classic Phase 3.

With TD-9855, of course, it's an orphan condition. And so, what we deem to be Phase 3 may look quite different. The pivotal registrational program for an orphan designation may look quite different from velusetrag. It is our intent, though, to use the current study to inform the next steps and interactions with agencies, particularly in the setting of an orphan designation.

You had asked about the protocol changes with TD-9855, and I think without going into too much of the specifics, I wanted to reassure you and others that, it's on the basis of encouraging positive data, as opposed to concerns about the single ascending dose. So we have seen evidence of effect in some patients who were exposed to the single doses. And so, on that basis, we'd like to explore the durability, the sustained treatment effect in those patients for longer durations of therapy. We touched on it in the script, but we do acknowledge that existing therapies really have no evidence to support their long-term use, and it's our intent to see whether this current therapy, TD-9855, could demonstrate efficacy over the longer term. So it is a value added dimension to the protocol, and that was the basis of extending it.

And just to add to that and the words that Brett used in his section, describing TD-9855 was -- we saw responses in a majority of patients. So that's really what gave us the energy and the motivation to take the product from single ascending dose and extend the dosing out to as long as 20 weeks.

Our next question comes from Brian Skorney of Robert W. Baird.

Hi. This is Neena on for Brian. Thanks for taking the question. I just had a question about the NEP inhibitors. I know you said that you're currently kind of looking at different options for how to take those two forward. Could you just talk a little bit more about what options you are looking at, whether or not you'd consider partnering, and what kinds of studies you might consider moving them into? Thanks.

Yes. Brett, do you want to address that?

Sure. So I think one of the elements of we being really preoccupied with on our NEP inhibitor program was the focus on drugs that were not renally cleared, and that's a distinct advantage over, even in Entresto, the only other NEP inhibitor in the class at the moment, that one approved, in combination with an ARB.

But sacubitril, which is a NEP inhibitor in that product, had 60% of elimination, dependent on kidney functions; so 60% excreted through the kidney. Although that may be favorable in a healthy person, people with heart failure often have secondary kidney dysfunction and failure because you need a good heart and a good profusion in order to make the kidney optimally performing.

So we have been focused on drugs that are not renally cleared, accepting that that maybe better suited to patients either with heart failure. So chronic heart failure is still an opportunity we are considering. But we also recognize a broader spectrum of disease opportunities, including patients who may have underlying renal dysfunction. So either it's primary heart failure with secondary kidney failure, with the possibility of considering a chronic kidney disease as well. Diabetic nephropathy, for example, has a considerable unmet need.

And we do recognize that for those, those are sizable development commitments, and really, I think it would be fair to say, and we are fairly overt about this, but those are likely to require partnership discussions. We do recognize that there are also opportunities for narrower spectrum of development opportunities, and we are considering those. So I think there is a spectrum that we are considering. Our purpose was really to get the assets to this point, to be able to characterize each of them, and then consider differential development programs for each.

Our next question comes from Umer Raffat of Evercore ISI.

Rick, I have three on the JAK inhibitor perhaps. So first one, maybe to start off, can you update us on the recruitment? Is it fully enrolled? I think clin trials implies it's still in rolling, just wanting to check in on that, number one. Number two, the study site, so how many sites are in this trial, because clin trials implies it's only one center, but the site that's implied by clin trials isn't exactly -- it reads like a market research terms. I wasn't sure how many sites are participating and where they are. And then third, do you still expect close to XELJANZ-like efficacy on partial mayo scores? Thank you.

So, Umer, hi, this is Brett. You were fading in and out. So I just want to confirm, you were asking about the TD-1473 study, is that correct? These three questions?

Yes. So, yes, that's right.

No, that's fine. We don't go into the specifics of current numbers. Obviously, with an ongoing study, recruitment is something we don't disclose. I can confirm it's not a single center. There are a number of centers, and in fact we are participating in a number of countries on this program. Again, for the purposes of clinicaltrials.gov, often a single seminal site is listed, but there are several in this program.

You asked about clinical endpoints, and I think as you will have heard us perhaps referenced previously, although partial mayo is an endpoint in the study, it isn't the only one, and in fact, the study is not powered to be able to detect differences for a single endpoint. Our purpose here is to look at consistency in a number of different markers, including but the clinical improvements, the histological improvements, changes on endoscopy, and of course, the absence of any systemic risk, including looking at the usual suspects, white cells and so on, and the amount of drugs in the systemic circulation. So it is our purpose here to amalgamate all of that information and to provide what we hope to be a consistent story in order to support the localized effect of TD-1473. Rick?

Yes. I think relative to expectations versus tofa, what we are trying to do is affect both the numerator and the denominator in the therapeutic index. I mean, clearly, the data with tofacitinib, both some limited data in Phase 3 of the higher dose, and then the data that you -- that's in the Phase 2 program for tofa indicate that there is more efficacy available with higher concentrations. You just can't get there with the systemically delivered drug because of toxicity. So we think that there is more efficacy to be had via the pan-JAK mechanism, and we hope that because our focus is on intestinal restriction with a very limited amount of drug getting into the systemic circulation, that the safety concerns will in fact be much lower than other JAK inhibitors, be they JAK selective or pan-JAK inhibitor; simply keeping the drug, by and large, for all practical purposes out of the blood stream, and having it focused into the tissue, where the inflammation occurs, and again, trying to squeeze as much efficacy as we can out of the mechanism, but in fact keeping the drug out of the systemic circulation and because of that, creating a safer, better tolerated medicine.

Got it. So Rick, perhaps said another way, and maybe just to build on what you just said, would the trial enable -- since it's a Phase 1 trial, are you able to simply add more arms or higher doses if you had to, if you weren't satisfied with what you guys were seeing so far?

So, Umer, it is an adaptive design. And I think as you may have seen before, there is the ability to be informed from the results of one cohort to move up or down in the dose. So I think that flexibility does exist and certainly would allow for characterization at different points.

Bear in mind, this is not a conventional approach. Very few, in fact, we are not aware of any other companies that have taken this approach this early in development. But our purpose here really is to inform a narrower dose selection, to be able to move forward into the next round of development. So that flexibility is an intrinsic part of the value that we believe is created with this study.

Got it. Thank you very much.

Yes, Brett, you just may want to expand a little bit, with regard to how we're treating this 1b study, with regard to central evaluation given it is a multiple site.

Thanks, Rick. So a good point, and actually even for, what seems to be a fairly early and possibly a very small study, we have still applied the same rigor that would be assigned to a pivotal registrational study. So all of our endoscopy reads, for example, the images that are taken during the colonoscopy are centrally overread. They are not assessed by each individual investigator. And the purpose is to try and reduce bias. Of course, the other important point is that these patients are being scoped at the beginning and the end of therapy. So every patient serves as their own control, which increases our ability to detect effects over the course of treatment.

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

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