Theravance Biopharma, Inc.

Hello ladies and gentlemen. Good afternoon. I'd like to welcome everyone to the TheraVans BioFarmer First Quarter 2025 Conference Call. During the presentation, all participants will be in a listen-only mode. A question in this session will follow a company's formal remarks. To ask a question, press the star key followed by the digit one on your phone. Again, that is star one 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 is being recorded. And now, I would like to turn the call over to Rick Wenningham, Chief Executive Officer. Please go ahead,

sir. Good afternoon, and

welcome to TheraVans BioFarmer's First Quarter 2025 Earnings Results Conference Call. On slide two, you will 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 described further in our filings with the SEC. Moving to slide three, I'm joined today by Rhonda Fardham, Chief Business Officer, Anya Miller, Head of Development, and Aziz Salaf, Chief Financial Officer. Moving to slide four, and beginning on the left-hand side, you've already delivered solid results in the first quarter with net sales increasing 6% to just over $58 million. This performance was driven by a similar increase in demand, as well as favorable pricing and channel mix. Building on the strong momentum we experienced in 2024, hospital doses increased 48% year on year. We are steadily advancing the Cypress trial, consistent with our objective of enrolling the right patients at high-performing sites, and are pleased to be nearing the completion of the planned enrollment into the open-label portion of the study. Shifting to the randomized withdrawal portion of the study, we are laser-focused on ensuring that we optimize those factors that are within our control, including study power and patient experience. Based on our current projections, we anticipate enrolling the final patient into the open-label portion of the study by late summer with top-line data available approximately six months later. Our overarching objective remains to deliver the highest quality result possible in order to bring this once-daily selected norepinephrine reuptake inhibitor to a rare disease population of roughly 40,000 U.S. patients with MSA who desperately need new options to address their symptoms of NOH, as well as thousands more around the world. And finally, our positive outlook for Trilogy and our strong financial position remain unchanged. On April 30th, GSK reported another strong quarter for Trilogy with global net sales at 14%, placing us comfortably on pace to achieve the higher $50 million milestone from Royalty Pharma in 2025. We ended the quarter with $131 million in cash and remain committed to returning excess capital to shareholders. I'll now turn the presentation over to Rhonda to cover UPelry's performance in the quarter. Rhonda?

Thanks, Rick.

If you turn to slide six, you'll see that the Theravans and Beatrice commercial partnership turned in another strong quarter of UPelry performance. Overall net sales increased 6%, which was driven primarily by demand growth, as well as pricing and channel mix improvements since the first half of 2024. As we've communicated, the first quarter has historically been impacted by seasonality, not only for UPelry, but across other maintenance COPD products, demand and overall net sales to continue to improve throughout the year. On slide seven, in addition to the importance of the community channel efforts and volume, our hospital performance continues to be a key strategic differentiator and contributor to UPelry's growth. We achieved record high volume in the quarter with approximately 316,000 units pulled through the hospital channel, which was up 48% year over year. This was our strongest quarter launched to date in the hospital setting and demonstrates the impact of our focus and continued success in securing formulary wins and therapeutic interchange protocols. The strong hospital performance remains critical to the overall brand strategy, specifically in transitioning our growing number of UPelry hospital patients to community maintenance care. Moving to slide eight, there continues to be significant future potential with UPelry. Recent market research conducted with Beatrice supports additional demand growth, along with the sizable remaining addressable patient population. Our joint brand strategies continue to increase both the adoption of concomitant use with llama lava therapies, as well as switches to UPelry from handheld only regimens, where patients may have difficulty receiving the full benefit of those medications and could be better served with once daily nebulization. We're also encouraged by our success in improving fulfillment and are confident that we can expect continued progress across adherence, persistency and overall claim approvals. UPelry remains a foundational, durable and highly profitable asset. It continues to demonstrate strong brand momentum across both the hospital and community channels, with sales up 6% in the most recent quarter in expanding margins. With the potential for a $25 million near term milestone, extended IP protection through 2039 in the US and future royalties and milestones from China, we believe UPelry is well positioned to deliver long term sustainable value to TheraVance and our shareholders. At this point, I'll turn things over to Aziz for a quick update on trilogy. Aziz.

Thanks Rhonda. I'll begin on slide 10 where I'll discuss our potential to earn milestones for trilogy. In Q1, which is typically the lowest quarter of the year, GSK reported 854 million in sales, up 14% year over year. This puts us on track to achieve the 50 million milestone this year, which is tied to achieving 3.4 billion in annual sales. The brand continues to experience strong growth as evidenced by the quarter and recent all time highs in script volume. As a result, we remain confident in achieving the higher end milestones, totalling 150 million in 2025 and 2026 with consensus estimates materially exceeding the sales thresholds to achieve these milestones. Of note, consensus estimates for both 2025 and 2026 have increased by approximately 100 million since our last earnings call in February, reflecting continued confidence in the brand's growth trajectory. Turning briefly to slide 11, where we continue to see substantial long-term value in the trilogy royalties. As a reminder, these royalties returned us in 2029. While still several years away, that date is steadily approaching now just four years out. The combination of a shortened time horizon and continued strong brand performance gives us greater clarity and confidence in the future value of these royalties. With that, I'll pass it to Anya to provide an AmpliLoxTeen update.

Anya? Thanks, Aviv. I'll begin by covering our phase three Cypher study on slide 13. We continue to focus on quality as we advance towards completion of enrolment in the Cypher study. Our efforts remain centred on ensuring the right patients are enrolled at the right sites with close collaboration across our network of leading academic institutions and MSA centres of excellence, recognised for their high touch approach to patient engagement. This disciplined, data-driven approach supports our overarching goal of generating high quality data to maximise the likelihood of a successful outcome and one that reflects the therapeutic potential of AmpliLoxTeen. We are now nearing the end of the open-label period of the study and expect to enrol the last patient by late summer. Based on our expectations around achieving database lock and finalising our initial analysis, we expect to share top-line results approximately six months after we complete enrolment. Drawing your attention to the bottom of the slide, the Cypher study is comprised of two phases, a 12-week open-label period followed by an eight-week randomised withdrawal period. We have included an enrichment strategy during the open-label period in order to identify patients benefiting from AmpliLoxTeen and to optimise the population enrolled in the randomised withdrawal portion of the study. This randomised withdrawal phase is critical. It's the component that evaluates the sustained efficacy of AmpliLoxTeen and will deliver the data needed for regulatory submission. We believe our thoughtful and rigorous execution intended to deliver a sufficient number of patients through the randomised withdrawal period positions as well to advance a robust data package that, if positive, would ultimately support a new treatment option for patients with MSA, a community urgently in need of effective therapies. On slide 14, I'll provide a quick update on our activities at recent and upcoming medical conferences. First, we had a highly productive American Academy of Neurology meeting last month where we presented important new analysis of our prior Phase III programme. Findings from these analyses supported AmpliLoxTeen's highly selective mechanism of action and its pharma-dynamic effects over time, resulting in durable target engagement and a physiological effect on standing blood pressure. In addition, in-office and 24-hour ambulatory blood pressure findings show that AmpliLoxTeen did not exacerbate supine hypertension in study 169, potentially a meaningful differentiator in this population. At this weekend, we are also excited to participate in the International MSA Congress in Boston. At this conference, we are presenting analysis based on a pre-specified MSA subpopulation from study 170, as well as an analysis highlighting the high symptoms and quality of life burden NOH places on these patients. Finally, turning now to the bottom of the slide, I want to highlight that we are making excellent progress on key modules of the NGA in parallel with the ongoing study. We already have a substantial body of work completed, which enables us to compile and order significant portions of the NGA ahead of the Cypress readout. This proactive approach positions us to move quickly and efficiently towards an expedited regulatory submission should Cypress be positive. At the time of filing, we also intend to request a priority review to accelerate the potential path to approval. Now I'd like to turn the call back to Aziz to cover our financial performance and outlook. Aziz?

Thanks, Anya. Beginning with the quarterly results, slide 16 and 17 cover the detailed financials. On slide 18, I'll highlight our quarterly performance, which was generally in line with expectations. Starting with collaboration revenue, we reported 15.4 million up 6% year over year. Importantly, UPELRI brand level cash profitability grew at a faster rate than collaboration revenue, reflecting our disciplined approach to investment and focus on margin expansion. Operating expenses, excluding share-based comp, increased to 25 million this quarter. On the R&D side, growth was driven by increased Cypress patient enrollment and incremental NDA and regulatory activities. SG&A growth was primarily due to incremental pre-launch commercial and medical affairs related initiatives for Ampryloxetine. These increases were as expected as we near full enrollment for the Cypress study and move closer to the data readout and NDA filing next year. As a reminder, the NDA and regulatory activities reflect one-time incremental spending to facilitate the completion of a majority of the NDA prior to data readout. Share-based comp expense decreased 7% year over year, driven by ongoing cost-cutting initiatives. Lastly, we ended the quarter with 131 million in cash and no debt. The increase to cash in the quarter reflects the receipt of the 50 million trilogy milestone payment from Royalty Pharma, which was received in February. On slide 19, I'll cover our 2025 financial guidance. Following a detailed review of potential tariff measures announced by the current administration, we do not anticipate any material impact to our ongoing operations at this time. Accordingly, we are reaffirming all financial guidance metrics. Looking ahead to the remainder of the year, for R&D, we anticipate a decline in clinical trial costs in the second half as the study moves to completion, partially offset by continued incremental spending to complete the majority of the NDA ahead of the Cypress data readout. For SG&A, we're anticipating relatively flat or slightly lower expenses for the remainder of the year, with continued spending on pre-launch commercial and medical affairs activities for Ampulloxetine. For recurring non-GAAP loss and cash burn, excluding the impact of any potential milestones, we expect both metrics to improve throughout the year, especially in the second half, given primarily by continued growth in upelrinet sales and slightly lower costs. However, we do expect a one-time tax payment in Q2 related to the receipt of the 50 million trilogy milestone, which will reflect a one-time increase to cash burn in Q2 relative to Q1. Excluding this payment, we expect cash burn to improve sequentially throughout the year. Note that this one-time tax payment in Q2 will not affect the P&L, given that we have already accrued for this expense in prior periods. Finally, and more broadly regarding potential tariff implications, at this time, we do not expect any material impact to our value drivers. Trilogy milestones and royalties are based on net sales rather than COGs, which is where tariffs would apply from an accounting perspective. So our trilogy economics would be unaffected. Upelri also remains well-positioned with US-based manufacturing and an efficient cost structure. As for Ampriloxetine, given that the product is not yet approved, we have time to respond to any future policy or trade developments. That said, the broader situation remains fluid. Our assessment reflects what we know today and could change if there are material shifts in policy or action from the administration. Given the lack of formal guidance in the evolving policy landscape, we won't be providing additional specifics until there's more clarity. With that, I'll pass it back to Rick to conclude. Rick? Thanks,

Aziz. To wrap up on slide 20, we continue to execute our strategy with focus and remain well-positioned to deliver value across the portfolio. As Aziz indicated, we entered the quarter in a strong financial position with $131 million in cash and no debt. We have the opportunity to earn up to $150 million in additional trilogy milestones in 2025 and 2026, as well as significant royalties, which return in 2029 and extend through the mid-30s. UPELRI remains a core growth driver, and we're focused on improving its financial contribution to Theravans while advancing towards key economic milestones. We're on track to achieve one-time $25 million US milestone. Good sales reach $250 million in the calendar year, as well as a $7.5 million milestone should UPELRI receive approval in China. Finally, Ampriloxetine presents a truly transformational opportunity for our company. The Cyprus Phase III study is now entering its final stretch. We expect complete enrollment in the open-label portion by late summer and to deliver top-line data from the randomized withdrawal portion about six months later. Guided by our clinical results to date and constructive ongoing dialogue with the MSA community, our confidence in Ampriloxetine's commercial prospects continue to grow. Meanwhile, we continue to lay the groundwork for an expedited NDA submission and broaden awareness through disease state education and targeted stakeholder engagement. We look forward to sharing the Cyprus results soon and are now

ready to take your questions. Operator?

Thank you. Once again, if you would like to ask a question, you may do so by pressing the star key followed by the digit one on your touchtone phone. If listening via the webcast, please mute audio on your webcast device before asking a question over the phone. If you're using a speakerphone 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 the roster. We'll have our first question from Mark Fram from TD Cowan. The line's open.

Hey, thanks for taking my questions. Maybe

I'll

have one kind of on Ampriloxetine and then I'll have a follow-up on the commercial performance around it. To start on the Ampriloxetine side, I appreciate your comments that you have some time before NDA has even filed, let alone launching the product in the US. So you have some time to maybe adjust to whatever policies may come out. Can you just kind of give a status update of where the current plan for manufacturing is in terms of locations and where that IP resides? Is that in Ireland or has that already been placed in the United States?

Yeah, thanks Mark for the question. Yeah, the IP for Ampriloxetine currently is in Ireland. Manufacturing of the API is outside the United States in Taiwan. So we will, obviously we've got a lot of time to adjust what, where supplies are, et cetera, but we feel pretty good about where we are right now and the flexibility that we've got.

Okay, that's helpful. And then Rhonda, from the slides you presented, I mean the performance of your team, the hospital team is, it seems tremendous in terms of the growth that we're seeing there over the past year. What efforts are you kind of tweaking over time to maybe try to increase the rate at which those hospital prescriptions turn into filled chronic prescriptions once the patient leaves?

Thanks Mark, and I'm glad you appreciate the work and results the team's delivering. The importance and the critical nature of that transition of care patient, given the increasing volume of hospital patients is obviously the whole purpose of why we are focused in that side of care. And in partnership with Beatrice at the local geographies, the teams are working very closely, not only in recognizing where patients are leaving the hospital with a script in hand to ensuring that they're getting the support through patient fulfillment programs, getting that patient to the right fulfillment site, and then ensuring the follow-up with the maintenance care. So it is a handoff and very, very close partnership

that's occurring at the local level.

But I guess any kind of,

as you're doing that handoff, any refinements that are happening here, because it does seem that's been a few quarters of the real strength in the hospital, and I appreciate it takes time to translate into the broader franchise, but it does seem to be maybe not completely translated.

Well, definitely where we're seeing it translates, you see and have very clear understanding of the best practices that's occurring in those local geographies. And as you can imagine with sales team members, when there's a known entity of what's working in award-winning territories, there's others that want to employ those strategies. So I would say our hospital transition of care voucher program really plays a critical role in ensuring that not only the healthcare provider has high confidence of making the right decision for ensuring that patient leaves with a script in hand, but that they will move very quickly and easily through their fulfillment and onto maintenance care. So it's a matter of ensuring that where those territories are having great success, that the teams are very clear on what works in those individual situations.

Okay, thank you. Thank you. Our next question comes

from the line, Julian Harrison from BTIG. The line's open.

Hi, this is Riyan for Julian. Thank you for taking our question. Just a couple for us. First on Amperloxetine, have you received any feedback yet from payers on Amperloxetine and NOH, or is that something that likely occurs after top line data is released? We have data from Cyprus. And if like on that point, what end points do you expect payers to be most receptive to?

Rhonda, you wanna take a quick shot at that and then I'll follow up.

Yes, thanks Riyan for the question. As you would likely anticipate, we have started engagement with payers to ensure not only they have an appreciation of the significant need and the burden this disease has on patients so that they fully appreciate what role a therapy like Amperloxetine can serve in this patient population. And we're working very closely to ensure that education on the end point and likely scenarios of data input from the study readout itself. The messaging and their reaction and questioning and additional educational support that they may need in a post-approval situation that they are armed with the right details and support. So we're definitely very active in that space now, but obviously we've got a bit of time to ensure that we have that segment and critical element

in

access set up.

Got it, thank you. Yeah, I think clearly,

you know,

just to

compliment what Rhonda's saying is that, you know, for Amperloxetine, the breadth of the composite score in terms of the overall wellbeing of the patient and their ability to function, et cetera. I mean, this is very meaningful and this, you know, the broad composite score, as well as the elements in the composite, this has not been demonstrated before. So it can be a significant advantage really for us. And obviously a significant benefit for patients as well as caregivers, given the nature of the components of the composite score.

Got it, thank you. And if I could ask one on you, Palri, could you provide us with an update on the paragraph for filers? Have settlements been reached for all parties?

Yeah, sure, we've settled with

five of the eight filers. We have three outstanding litigants. Really no other update other than outside of that.

Got it, thank you. Thank you, it appears we

have no further questions on the phone. I would now like to turn the conference back to Mr. William. Please, go ahead, sir.

Yeah, thank you very much, operator, and thank you for joining us today and the questions that you've asked. We look forward to keeping you updated through the course of the year as we approach a very exciting period

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