Theravance Biopharma, Inc.

Ladies and gentlemen, good afternoon. I'd like to welcome everyone to the Theravance Biopharma fourth quarter and full year 2024 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. To ask a question, press star 1-1 on your phone. Again, that's star 1-1 to ask a question. If listening via webcast, please mute audio on your webcast device before asking a question over the phone. I will repeat these instructions after management completes their prepared remarks. Also, today's conference call is being recorded. And now I'd like to turn the call over to Rick Winningham, Chief Executive Officer. Please go ahead, sir.

Yeah, good afternoon, and welcome to Theravance Biopharma's fourth quarter 2024 Earnings Results Conference Call. On slide two, you'll find our forward-looking statements disclaimer, which covers certain risk factors, which could cause actual results to differ materially from any forward-looking statements we might make in today's call, and which are further described in our filings with the SEC. Moving to slide three, I'm joined today by Rhonda Farnham, Chief Business Officer, Anya Miller, Head of Development, and Aziz Swaf, Chief Financial Officer. On slide four, I'll begin by highlighting our fourth quarter results, which represent a strong close to the year. Fourth quarter upelry net sales increased 10% over the fourth quarter of 2023, reaching 66.7 million, an all-time high. And our hospital performance was excellent, with doses up 49% year over year. With Amproloxatine, we achieved solid enrollment in Cyprus throughout the quarter and remain on track with our development timelines. In December, we had a positive exchange with the FDA, which reaffirmed our expectations around filing, should Cyprus be positive. We learned that two abstracts had been accepted for oral presentations at the upcoming American Academy of Neurology meeting in April. and we completed market research underscoring the potential for ampryloxetine to address significant unmet needs of patients with MSA and symptomatic NOH. Finally, based on 2024 Trilogy Net Sales reported by GSK, we've earned a $50 million milestone payment from Royalty Pharma. We continue to manage our expenses carefully and delivered full-year results, which fell within our guidance ranges. I'll cover our strategic priorities on slide five. For upelry, we continue to focus on growing revenue while increasing brand profitability. In addition, there's a potential for a near-term $25 million sales milestone in the U.S., as well as milestone in royalty income from China once approved. With Amproloxatine, we're moving towards completing enrollment in the open-label portion of the Cypress study while simultaneously preparing for an expedited NDA filing. We plan to request priority review in order to bring this much-needed potential treatment to patients as quickly as possible, and we'll continue to build awareness of NOH within the MSA community. Turning to Trilogy, where there's a potential of an additional $150 million of milestones in the coming 24 months, plus the considerable value of our retained interest in Trilogy Royalties. We remain dedicated to maximizing the value of Trilogy and are committed to returning excess capital to our shareholders. We'll continue to build on our recent track record of strong expense management and capital discipline to deliver sustainable value to our investors. I'll now turn the Presentation over to Rhonda to cover UPelry's performance in the quarter. Rhonda?

Thanks, Rick. Beginning on slide seven, I'm pleased to report that the Theravance-Viatris Commercial Partnership delivered a strong finish to 2024, having driven UPelry net sales growth of 10% in the quarter, reaching approximately $67 million and full-year sales of $239 million, with UPel re-recording its highest level of profitability since launch. The growth in Q4 was primarily driven by a 9% increase in demand. Additionally, pricing continued to be favorable compared to the first half of 2024, which is a reflection of Vietris' efforts in demonstrating effective pricing strategy execution as well as an improved channel mix, meaning stronger demand in the higher margin channels aligning with our brand objectives. While the record high net sales this quarter closely tracked with demand generation, I will remind you that we traditionally experience seasonal dips in reported net sales as we transition from the fourth quarter to the first quarter of the following year. Turning to slide eight, We continue to experience considerable momentum in the hospital setting, which exemplifies the strength and effectiveness of the TheraVans hospital selling capability. During the quarter, there were 285,000 ukulele doses pulled through to hospital customers, up 49% year over year. In addition, we continue to broaden our base of formulary wins and therapeutic interchange protocols. achieving the highest annual gain since pre-COVID, and resulting in an increased long-acting NIM market share of nearly 20% by the end of the fourth quarter. Strong hospital performance remains critical to our overall brand strategy, specifically in transitioning patients from the hospital to the community setting, where UPelRe's long-acting NIM market share maintained roughly 32% through the end of the year. To summarize on slide nine, UPAL rate delivered another strong year of net sales growth of 8% in 2024 and driven by an impressive full year 11% growth in demand. Additionally, we're encouraged by the potential sales milestones in the U.S. along with the extended IP protection to 2039 and the opportunity for future milestones in royalties in China. At this point, I'll turn things over to Aziz for an update on Trilogy. Aziz?

Thanks, Rhonda. I'll start on slide 11, where I'll discuss our potential to earn milestones for Trilogy. In 2024, GSK reported full-year sales of $3.5 billion, up 26% year-over-year, which triggered a $50 million milestone payment to Theravance, with cash receipt received this month. Going forward, given the grant's continued growth trajectory, and consensus being well above the required threshold, we believe there is a high probability of achieving the higher end of milestones in both 2025 and 2026, totaling an additional 150 million. On slide 12, I'll comment on our royalty interest in Trilogy. In mid-2029, we will start to receive royalties based on ex-U.S. sales, and in January 2031, start to receive royalties based on U.S. sales. As a reminder, these royalties expire on a country-by-country basis the later of 15 years after commercial launch or until expiration of the longest-lived patent. To give you a sense of the potential financial implications for TheraVance, we've outlined consensus net sales on the right-hand side of the slide. Based on these projections, we expect to receive several hundred million of cumulative royalties starting in 2029 and lasting through the duration of the royalty terms. Combining these royalties with 150 million of probable milestones over the next two years represents a significant and durable source of value to the company. With that, I'll pass it to Anya to provide an ample oxygen update. Anya?

Thanks, Aziz. I'll begin the development update on the top of slide 14. We continue to focus on important academic institutions and affiliated MSA centers of excellence as we near the completion of enrollment in the Cypress study. We have observed a solid month-over-month enrollment rate over the last quarter. This progress keeps us on track to achieve our objective of enrolling the final patient in the open-label portion of Cypress by the middle of this year and disclosing top-line results of the study approximately six months later. We are very pleased to announce that we've had two abstracts accepted for oral presentations at the upcoming American Academy of Neurology annual meeting scheduled to take place this April in San Diego. Our first oral presentation will focus on the analysis of supine blood pressure measured in the home with a 24-hour ambulatory blood pressure monitor, the gold standard method for detecting supine hypertension, allowing us to assess the impact of amperlactetine on supine blood pressure in the double-blind randomized control study 169. The second oral presentation looks at orthostatic blood pressures and venous norepinephrine levels and allows for a detailed analysis of the mechanism of action of amperloxidine in the previous randomized withdrawal study 170. Turning now to the bottom of the slide, I also want to provide an update on where we stand with preparations for the amperloxidine NDA. We are very encouraged by a recent Type C interaction with the FDA in December of last year, where we reaffirmed alignment on key requirements for a full approval should the cipher study be positive. In this interaction, we covered important pre-NDA topics, including content of the NDA and our data analysis plan. This represents another important milestone on our journey to advance Amproloxidine as a new treatment option for NOH in patients with MSA. We are well positioned to complete key modules of the NDA in advance of the Cypress readout and then be poised for an expedited regulatory filing should Cypress be positive. We also intend to request a priority review at the time of filing. Now I'll turn the call back to Rhonda to highlight some of the work we've been doing in support of our launch preparedness. Rhonda? Thanks, Anya.

Focusing on slide 15, as part of our launch preparation efforts supporting disease education and awareness and our work developing product positioning, we have been actively engaged with the MSA community. Today, I'd like to share with you some of the early results of our market research, which supports the high unmet need for an improved NOH therapy. In Q4, we conducted a blinded survey of 200 board certified neurologists and cardiologists who are treating patients with MSA and are familiar with NOH symptoms. As you see on the left-hand side of slide 15, the vast majority of those we surveyed agreed that there is a significant need for better NOH therapies, with over 70% of neurologists indicating that they strongly agreed. On the right, We asked these physicians to rank different attributes that they consider to be most important in selecting a new treatment for NOH. Effectiveness in improving NOH symptoms ranked highest, followed closely by the ability to improve a patient's quality of life and durability in maintaining symptom improvements. Finally, safety and tolerability including avoiding worsening of supine hypertension also ranked amongst the top five most important attributes. Next, we turn to slide 16, which highlights amproloxetine's target product profile. This profile is based on the results in the MSA subpopulation from the previous phase three study and closely matches the market research respondents' ranked desired attributes. Based on this assumption and if FDA approved, Amproloxetine could provide a differentiated new treatment option with a meaningful improvement in OHSA composite scores, positive impact on patients' daily activities of living, and durable effectiveness. Market research also suggests that Amproloxetine small once daily pill without the need for dose titration is another point of differentiation, as this could provide a better experience, especially for patients with MSA who often have difficulty swallowing. Lastly, as shown in the graph on the right, amproloxetine's target product profile has the potential to address the high NMET need in the NOH population if FDA approved. The majority of physicians had a favorable view of amproloxetine's blinded target product profile with 90% of neurologists and 80% of cardiologists signaling they are likely to prescribe such a product if available. The results from our initial market research coupled with discussions with neurologists and advocacy organizations have reinforced our belief in the significant impact amproloxetine could have on the estimated 40,000 patients with MSA in the U.S. suffering with NOH symptoms. Now, I will turn the presentation back to Aziz to cover the financials. Aziz?

Thanks, Rhonda. Let's begin with the quarterly results. Slides 18 and 19 cover the detailed financials. On slide 20, I'll highlight our quarterly performance where we generally exceeded expectations and stayed within all financial guidance ranges for the full year. In the fourth quarter, collaboration revenue grew by 8% to approximately $19 million, and Upelri brand-level cash profitability reached its highest level to date. Operating expenses, excluding share-based comp, increased to $22 million this quarter. This was due to incremental commercial and medical affairs spend on ampriloxetine pre-launch activities and increased R&D expenses due to an uptick in Cypress patient enrollment. As mentioned, for the year, R&D, SG&A, and share-based comp expense were all within our full-year financial guidance ranges. We utilized $3 million of cash this quarter and $14 million for the full year, aligning with our goal of maintaining a strong balance sheet while progressing towards the completion of the CIPRS study. We ended the year with $88 million of cash, which excludes the $50 million Trilogy Milestone cash receipt. On slide 21, I'll provide our 2025 financial guidance. First, we're guiding to R&D expense, excluding share-based comp of between $32 and $38 million. This reflects the completion of the CYPR study with clinical trial costs decreasing in the second half of the year, offset by one-time incremental spend to facilitate the majority, to facilitate the completion of a majority of the NDA prior to data readout. Second, we expect slight growth to our SG&A expense driven by measured investments for ampryloxetine in areas such as market research, market access, and medical affairs in preparation for potential NDA filing. For the year, we expect total SG&A expense, excluding share-based comp, to be between 50 and 60 million. Third, we expect share-based comp to decrease year over year to a range of 18 to 20 million, driven by continued cost-cutting initiatives. And finally, we expect non-GAAP losses and cash burn to be similar to 2024 levels, where we had non-GAAP losses of 16 million and cash burn of 14 million. For both metrics, we anticipate higher levels in the first half of the year with improvements coming in the second half. And as Rhonda has mentioned, Q1 collaboration revenue will be impacted by typical upelry seasonality we've experienced over the past several years. Lastly, our accounting treatment for the Trilogy milestones has been updated to reflect recent changes to accounting guidelines. We will now only recognize other income if cumulative milestones exceed 194 million. For example, achieving the remaining $150 million of milestones would result in only $6 million of other income recognized in 2026, with no other income recognized in 2024 and 2025. As a reminder, this accounting treatment has no impact on cash receipt, which we expect in Q1 of each year. With that, I'll pass it back to Rick to conclude.

Thanks, Aziz. To summarize on slide 22, we entered 2025 in a strong financial position with a compelling outlook for shareholders. We ended the year with $88 million in cash, excluding the $50 million we just received from Royalty Pharma, no debt, and up to another $150 million in trilogy-related potential milestones in the near term. We're also increasingly optimistic regarding the value that the trilogy royalties may bring to the company and remain committed to ensuring our shareholders benefit directly from our financial success. Thanks to the hard work of our employees and our partner, Vietris, we're well-positioned to continue driving upelry growth for the foreseeable future with strong demand generation and a winning patient-centered strategy. We're optimistic regarding the growing contributions to TheraVance which not only include our share of U.S. profits, but meaningful royalties in China and potential near-term milestones in both territories. Finally, I'd highlight the transformation. Continue to complete, continue to expect to complete enrollment in the open-label portion of Cyprus by mid-2025, with top-line data expected approximately six months later. Based on the results we've generated today, as well as feedback from the community and market research, we believe ampryloxetine has the potential to deliver meaningful clinical benefits to many patients with MSA who suffer debilitating symptoms of NOH. We thank you for your continued support and ready to take your questions. Operator?

Thank you, sir. Once again, if you would like to ask a question, you may do so by pressing the star key followed by the digit 1-1 on your touchtone phone. If listening via webcast, please mute audio on your webcast device before asking a question over the phone. If you're using a speakerphone or on today's call, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, that's star 1 if you'd like to ask a question. And we'll pause for a moment to assemble our roster. And our first question comes from the line of Douglas Tau from HC Wainwright. Your question, please.

Hi. Good afternoon. Thanks for taking the questions and congrats on the progress. Maybe as a starting point, I guess I would like to hear a little bit more from Rhonda about about what really drove so much of the success of the hospital channel this particular quarter. I mean, was it just sort of a follow through on some of the execution or sort of some of the initiatives you've had ongoing or was there anything in particular that led to this real sort of step up in performance?

Thanks, Doug. Really always appreciate your questions. On the hospital front, the team is executing the strategy very clearly. And to see the wins in larger systems and that these systems are now more frequently, not always, but more frequently coming with therapeutic interchange as part of the initial formulary approval, that brings additional volume, as I think you already appreciate. you will see a doubling of market share in those accounts that have a therapeutic interchange versus a conventional formulary approval. So the team is executing. They know where to go. They have a strategy of not only ensuring that concomitant use becomes adopted in protocols and then following on with that to ensure if there's opportunity for converting short-acting nebulized use to long acting, that certainly follows through. So we're just very, very pleased with what our small team of 14 have been able to accomplish, particularly this last quarter.

And Rhonda, I guess on the therapeutic interchange side, I'm just curious, I mean, how long, when did those wins occur? And did you sort of anticipate seeing this improvement or just maybe not quite as early? You know, just because sort of the magnitude or sort of the sort of inflection is quite impressive.

It starts with knowing who to focus on, and then it takes a full team effort with starting with national accounts and having C-suite discussions. with ensuring that when requested that the medical team can provide the clinical information that's necessary for completing the dossier submission for formulary review. And then once approved, that's when the sales team is certainly there to ensure the pull through or recognizing the clinicians, whether they're hospitalists, radiation therapy, or the pulmonologist specialist And the discharge team understand the access, meaning formulary is approved, so product is available, and that everyone involved knows how to use it. And then ensuring that these patients are leaving the hospital with what they were exposed to in the hospital with their upelri script in hand so that they continue their maintenance care post. So it's the execution again. It's knowing where to prioritize the efforts.

And then one final one for me, if I can. I know you talked a lot about sort of improvement and a focus on the channel mix to improve the growth to that. And I think some of that improvement seems to have happened maybe faster than you expected. And I guess I'm just curious, sort of the trajectory we should expect to see on that front into 2025.

Well, as we've commented in the past, in partnership with Vietris, this not only starts with effective execution, but also ensuring there's contracting discipline along the way and effective pricing strategy. So, we certainly did comment that it would take probably more into 2025 before you would see more right-siding of that, but I think that strategy of pricing coupled with that improvement in channel mix meaning getting to those higher margin volumes pushing through or being pulled through that's what's driving the improvement and we're very pleased about it obviously okay great thank you thank you and our next question comes to the line of julian harrison from ptig your question please

Hi, good afternoon. Congrats on a very strong end to 2024 and for taking my questions. Thank you for taking my questions. It looked like 4Q was really a standout quarter on the hospital side. Kind of related to the last questions asked, I'm wondering if you could comment on any follow through of that trajectory or trend you saw in 4Q into the first two months of 2025.

Well, Rhonda, you want to take that? Yes. Julian, not to get ahead of ourselves, as I've commented, Q1 can typically be a softer quarter. I think everyone's quite aware of what's happening, particularly on the hospital front, relative to RSV, flu, and census being high in the hospital. So I think the demonstrated need of ensuring that having product access to upelri is paying off and that's also, whether I would probably classify that as unfortunate giving patients are having difficulties, there's a need. So I do think that is a tail end for us.

Okay, great, thank you. And then can you remind us of the next steps for upelri in China? Just waiting for a regulatory decision there with your partner, Beatrice. Do you have an approximate sense of the timing of next steps, too?

Definitely, it's the waiting for the regulatory commentary back to the Beatrice team and for planning assumptions, as we've stated in the past. you know, that two-year window is what we typically would expect from time of submission to approval. So that's still what we're operating under.

And as a reminder that in June of 2024, so last year, so two years from then would be, you know, middle of next year is kind of the baseline assumption for that. That obviously triggers a seven and a half million milestone and then you know, very high, 14% to 20% royalties on any potential sales in the market.

Excellent. That's helpful. And then finally, I'm just curious if you could talk more about your recent feedback from the FDA on ampryloxetine. I'm wondering if you could share specifically what spurred that interaction, and can you talk in any more detail about what you received clarity on?

Andy, you want to take that?

I don't know, we can't hear Anya, but this was a type C meeting. We just wanted to make sure that we understood what the content of the filing should be, make sure that we had everything documented in terms of FDA expectations for the filing. And that was really just good regulatory practice so that, as we said, we can invest the money in 2025, you know, really developing and writing the NDA such that it would provide for an expedited filing once we had Cypress results, hopefully, that are positive.

Got it. Thank you. That makes sense.

Thank you. And our next question comes from the line of David Reisinger from Lee Ring Partners. Your question, please.

Yes, thanks very much, and thanks for all of the detail today, and congrats on the fourth quarter performance. So I just had some basic sort of financial questions. So first, was there any channel stocking or any other anomalies that benefited the fourth quarter net revenue? Second, what percentage of UPEL resales are non-hospital sales dollars? Just wanted to understand, you know, if hospital is like 90% of net sales of UPelri or 60% of net sales of UPelri. Just wanted to understand that. And then third, could you just explain why the non-hospital sales dollars are trending down year over year? Thanks very much.

Just in terms of the, and I'll turn this over to, turn this over to Rhonda, but just in terms of, you know, sort of year-end levels, I think based on what we understand, year-end inventory levels were about the same as they are, you know, every year for, you know, for Vietris. So, I don't think there was anything unusual there. Rhonda?

That's correct, Rick. David, your second question, if I understand correctly, the percent of UPelry that runs through?

Yes, just trying to understand what percentage of UPelry sales dollars come from the non-hospital category, however you categorize it, and then why is that trending down year over year?

The hospital business accounts for, pure volume within the inpatient setting is roughly 10% of the total brand. So you can see it's a smaller proportion, leaving 90% to the larger channels of the community setting, which includes long-term care. So you'll have to orient me to what your question or where you're finding data of what the decline is because that's, you know, not in line with what we're seeing relative to the demand increase, which was 11% full year for last year.

Oh, got it. Yeah, to orient you, so the slide only discusses the hospital growth and volume of something like 49%. And the company never discusses non-hospital volume or non-hospital sales dollars. So that's what drove the question. I was wondering, you know, what is happening in non-hospitals since, you know, the slide this quarter and historical quarters only relate to hospital. So that's what was driving the question, but I misperceived. I thought that hospital was a larger percentage of the sales dollars, but obviously since you just, you know, disclosed that the hospital volume is only 10% of total upillary volume. Now I have better context and I understand that non-hospital is growing.

That's right. Thank you, David. And I think a point of differentiation there, it's unit dose in the hospital. And an average stay is roughly three and a half days. for exacerbating patients, whereas obviously I think you appreciate in the community setting, it's a 30-day script. So that's a volume differentiator right there.

Got it. Thank you. The other, you want to just touch on demand growth as well, just so that David's got that. Rhonda?

Yes. I offered that up at the beginning, 11% full years.

And so, yeah, David, the strategy here for us and Beatrice is, you know, we're in the hospital driving, you know, driving use of the hospital such that the patient can have a good experience with the product. Obviously, we're talking about the ability to breathe better, good experience, and therefore healthy. get a prescription as they leave the hospital for outpatient use. And we get about 80%, between 80 and 90, depending on the quarter of patients leaving the hospital with the script. And I think for the future, another source of growth for us and Beatrice is just simply converting a higher and higher percentage of those scripts to really true chronic therapy in the outpatient setting. Got it. Thanks again.

Thank you. And as a reminder, ladies and gentlemen, if you do have a question at this time, please press star one, one on your telephone. And our next question comes from the line of Mark from TD Cowan. Your question, please.

Hi, this is Alex. I'm for Mark. Congrats on the quarter. And thanks for taking my question. Uh, so just a couple on ampouloxatine, uh, First, what do you ultimately see as the bar for success for the Cypress readout? And then, you know, assuming Cypress is positive, what would kind of be the scale of the commercial organization you need to kind of assemble to market the drug? And, you know, will any of that build occur ahead of the data or is the potential OPEX increase entirely a 2026 story? Thanks.

Yeah, just I think that we've touched on this before, but, you know, a one-point change in the OHSA composite score is a clinically meaningful change. So seeing a one-point move in the OHSA composite and evaluating patients in the randomized withdrawal and that being statistically significant, that would constitute success both from a statistical as well as a clinical meaningfulness I'll let Rhonda touch on the other point, but really just on the spend, you know, we will hold off on increasing the size of the organization until after we have Cypress data. But Rhonda, just you want to qualitatively talk about the size of the organization?

Yes. Alex, it's an important question and work that we have underway for determining what is the optimal size when it relates to specific in-person promotion. But what I will say, given what we understand about the market today and having a very close evaluation of claims to particularly understand what's being prescribed and where and by who, we believe we can be very efficient. with how we assemble and deploy the sales effort. And when I say the sales effort, that would be any personnel, whether that's in person or we have virtual reach, and then that's complemented by digital surround sound with omni-channel reach. So appreciating that, the script view that we have today, it helps us to appreciate the concentration of the potential targets. but that being roughly 3,000 prescribers, and then that being concentrated across, I believe, 250 centers and clinics that we want to ensure we're highly focused on. So that concentration really allows us to be very efficient, which I think we've set the example of how efficiently we can operate with our current sales team.

And Alex, just to clarify the cost question. So, yeah, as you mentioned, the SG&A is going up, but not by much, right? The midpoint of guidance is 55 million relative to actuals of 53 in 2024. So, you're going up a couple million bucks. Very measured investment in medical affairs, market access, et cetera, market research, et cetera. This is all external spend and basically no incremental FTEs prior to the Cypress data readout. So, no incremental FTEs baked into the guidance in 2025 for SG&A.

Got it. Thanks again.

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

I'd just like to thank everyone for joining us today and thank you for the questions. We look forward to an exciting 2025 and being able to deliver on the strategic priorities that we outlined in today's call. Have a great day.

Thank you. Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.