Theravance Biopharma, Inc.

phone for today's call, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, that's star one if you'd like to ask a question. And we'll pause for a moment to assemble our roster.

We'll have our first question from Eva Privateria from Cohen.

Congrats on all of the progress. So I had a question about ampryloxetine and the onset of the mechanism of action. When are you seeing the norepinephrine become elevated and how quickly is that translating to the blood pressure response?

That's a great question, Eva. Rick, you want to take that?

Yeah. So, Eva, because it was a phase three trial, we were measuring norepinephrine relatively sporadically, so we're not measuring it day one, two, three, and four. But early on, within a couple of weeks' time point, we do see norepinephrine levels change. That's expected because that's sort of a direct effect of the drug action on the transporter. We also see a relatively quick effect on blood pressure as well. Where there's a little bit of a gap is with regard to symptoms, and as we speak to our KOLs and the physicians and understand what these patients are dealing with, it does make sense that there can be a little bit of a lag between a change in norepinephrine, a change in blood pressure, which are direct effects, and then the symptom response, because it takes patients a little bit of time to understand the effectiveness that they're seeing on symptoms.

Great that's that's very helpful and my second question is on you power, so the growth in the hospital setting is very impressive, how do you expect that performance to translate to overall sales and is the trajectory you're seeing so far kind of lining up with your expectations.

Rhonda.

So I'll start with the latter component.

Is it in line with our expectations? Yes. And given how we have organized around the potential and really see the role of UPelry having the ability to support the very sizable niche of the COPD market, we do anticipate continued growth in the hospital setting. And I think the other important piece of this to understand, which I think you do quite well already, is we consider this hospital volume channel growth as a leading indicator for the community volume. So seeing that contribution over time, recognizing there is a difference in duration of therapy in the inpatient setting, approximately three and a half days, versus what is treatment in the outpatient setting, we do anticipate that that growth to continue.

How long is that lag between the hospital growth and the community growth?

I still think that's hard to be that precise, Eva, just because I still think of the performance of this brand as in launch mode. We basically had our launch halted with the pandemic in Q1 of 2020 and getting back to that trajectory and seeing that uptake, it's a little hard to be able to transcribe that to a very precise time contribution of the hospital business to the outpatient side.

What we do see in recent market research is that 50% of the hospital visits and discharges are accompanied by a prescription. The other key point is that we've just now, you know, in the past quarter, gotten back to the, you know, pre-pandemic levels with regard to patient visits in the pulmonologist sort of normalized for seeing respiratory-oriented care. The hospital was hit harder than the community in the pandemic. Both were hit, but the hospital's hit a little bit harder. So the growth rates that you're seeing in the hospital are higher than the growth rates currently that you're seeing in the community. But you do have this element of a leading indicator, as Rhonda said. And it's really up to the Beatrice and the and the TheraVets biopharma teams to maximize the opportunity that we're seeing with the terrific hospital growth that we have and the ongoing momentum that we see in the community.

Great.

Thank you so much for taking my questions. Our next question comes from Vikram from Morgan Stanley.

This is Gospel on for Vikram. We have one question. So for Amproloxotin, assuming the Phase III study you are planning in MSA is positive, what are all the data sets and studies that you would include in the NDA filing? And how large of a study do you expect the Phase III program to be in terms of patient enrolled and sites activated?

Thank you. Rick, you want to take that?

Yeah, sure. Thanks for the question. So the first question, if the phase three study is positive, what data sets would be included in the filing? With our recent type C meeting with FDA, we had several important agreements that were reached. One was we would do one new study in patients with MSA, and that would be supplemented by the MSA results from study 170. The other agreement was we agreed on the primary endpoint for that new study, which is the OHSA composites. That's the endpoint for which we saw a statistically significant effect in the Phase 3 study of 170. And then we also agreed on general study design elements, namely that it will be a similar study to 170 with a randomized withdrawal design. The data sets, therefore, would be the new study, study 170, safety data from our phase two study, our 169 study, and then our clinical pharmacology program as well, which we've previously had conversations with FDA and aligned on that approach. With regard to the second question, it's too early to comment on the number of patients that we're gonna include and site selection. We just recently came out of this important meeting with the FDA, so now that we have an alignment, we'll be working on finalizing the protocol. We'll be doing site feasibility We have tremendous experience already from running a large global phase three program, and we're going to take the learnings from that and conduct a very efficient study in this new study. I'd also just, in the meantime, refer you to what we had put out, I think it was around, it was in April, what we had put out on our slides, that in the 170 study, we saw a statistically significant effect on OHSA composite with 38 patients.

Awesome. Thank you very much.

Our next question comes from Joseph Stringer from Neatham and Company.

Hi. This is Ben. Thanks. On for Joey. Thanks for taking our questions. Just one question, kind of similar related to, just to clarify, for the planned phase 3 MSA trial, what type of MSA patients are you considering including in terms of inclusion criteria? Will this be similar or different to the previous MSA patients enrolled in the PH3 trial? Thanks.

Yeah, Rick, go ahead.

Yeah. Hi, Ben. Thanks for the question. You know, based on what we saw in study 170 with MSA patients, and we're very excited about the totality of data. Everything that we look at holds up and makes good scientific sense. We're going to try to keep things as consistent as possible to study 170. We don't want to change any variables because we believe there's a good effect in these patients that we had selected. You might remember we did things like included an enrollment steering committee to make sure that we're able to decrease signal from noise and enroll the right patients. We'll have certain other criteria at baseline, making sure that these are patients that have MSA and that may respond, and really just trying to find the best ways to minimize signal from noise, which we did a pretty good job of in study 170. The team has taken an extremely careful data-driven approach, though, to look at those elements perhaps in the 170 study that we might want to make some modifications to, and we're really threading the needle on that new study design. So largely similar to 170 with regard to patient selection, but taking a data-driven approach to optimize this next study.

Great. Thanks very much.

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.

Thank you, operator. I'd like to thank everyone for joining us on this call today. We're extremely proud of the accomplishments of the TheraVance Biopharma team in the second quarter and everyone who's participated in, in fact, achieving the transformative goals that we've achieved in the second quarter. And we look forward to bringing news of continued progress against the company's objectives in the third quarter and the fourth quarter this year. Please have a great day. And again, thank you for joining us.

This concludes today's conference call. We thank you for your participation. You may now disconnect.