Theravance Biopharma, Inc.

Ladies and gentlemen, good afternoon. I'd like to welcome everyone to the Theravance Biopharma fourth quarter 2023 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 the star key followed by the digit 11 on your telephone. Again, that's star 11 to ask a question. If listening via webcast, please mute audio on your webcast device before asking a question over the phone. I'll 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.

Good afternoon, everyone, and thank you for joining the TheraVets Biopharma fourth quarter and full year 2023 earnings results conference call. Turning to slide two, I remind you that this call will contain forward-looking statements that involve risks and uncertainties, including statements about our development pipeline, expected benefits of our product candidates, anticipated timing of clinical trials, regulatory filings, and expected financial results, information-containing factors that can cause results to differ materially from our forward-looking statements as described further in our filings with the SEC. Today, I'm joined by Anya Miller, our Head of Development, Rhonda Farnham, TheraVance's Chief Business Officer, and Aziz Sawaf, our Chief Financial Officer. On slide four, I'll begin by hitting high points for a very productive 2023 for TheraVance. We began the year with the decision to focus on driving upelry growth and maximizing Amplilox Team's value while increasing our capital return program. I'm pleased to report that our team delivered on these objectives. For both the fourth quarter and the full year, we increased upelry's net sales 9% from $61 million and $221 million, respectively, as is recorded by Vietris. We grew hospital volumes at an outstanding 46% for the year and set the business up for continued momentum in 2024. We initiated Amproloxetine Cypress Study and immediately began evaluating and activating sites around the world. In May, we were granted orphan drug status, which confers important financial advantages such as tax credits and user fee exemptions. and Shields Amproloxatine from price negotiation associated with the Inflation Reduction Act. Cypress enrollment remains on track, and we look forward to enrolling the last patient in the open-label portion of the study in the second half of this year. Turning to our corporate progress, I'm proud we delivered on our promise of reaching non-GAAP profitability in the fourth quarter, which involves significant efforts on the part of the entire Theravance team. In addition, we completed our $325 million capital return program within the first few days of January while maintaining a strong financial profile. Now, on slide five, I'll cover plans and anticipated financial performance for the upcoming year, beginning with upelry. We expect to grow upelry net sales in partnership with Vietris and build on profit margin improvements experienced in 2023. We've set ambitious goals for our hospital business in 2024, which we believe will translate into future share gains in the long-acting nebulization market. Finally, we look forward to Vietris submitting a regulatory application for upelry in China by mid-year, which will put us on a path towards achieving meaningful economics in that territory. Turning to ampryloxetine, we're focused on completing the Cypress study. In addition, we expect to initiate regulatory, and early commercialization preparations as we progress through the year. We're very excited to host a virtual investor event during the second quarter where we will bring MSA experts and senior leadership from Theravance together to discuss the unmet need in MSA patients with symptomatic NOH and the expected benefits of ampryloxetine. Turning to our 2024 financial outlook, we expect annual collaboration growth to remain strong and for our quarterly financial results to improve as the year progresses. During the first year, we expect to report losses on a non-GAAP basis. During the second half of the year, subject to timing of upelary growth and Cypress progress, we plan to approach break-even on a non-GAAP basis. We plan to limit cash utilization, and we believe we are in a strong position to achieve the $25 million Trilogy sales milestone in 2024, and possibly the higher $50 million milestone. If you turn to slide six, you'll see an updated summary of our compelling value proposition. In addition to upelry and ampryloxetine, we're in a strong financial position with over $100 million in cash, as well as the potential to accrue significant value through milestones and royalties on upelry and Trilogy over time. Specifically, in addition to the trilogy milestones that I referenced, we stand to receive a one-time sales milestone of $25 million when the US UPelry net sales reach $250 million in any calendar year. Additional information on our milestones and royalties may be found in our SEC filings. Moving to slide 8 to focus on Amproloxatine. We're motivated to make amproloxetine available to patients as expeditiously as possible, should the Cypress results support approval for the tens of thousands of MSA patients around the world who suffer from symptomatic NOH without effective treatment options. Data thus far support amproloxetine's potential to represent a major advance for these patients. The company retains commercial rights to amproloxetine worldwide. On slide nine, I'll start with the considerable unmet need in the United States. MSA is a neurodegenerative disease that shares features with other movement disorders, such as Parkinson's disease. It's often misdiagnosed, with many patients not confirmed to have MSA for months to years after symptoms begin. Unfortunately, most epidemiology research was conducted decades ago On Parkinsonism, more generally using survey techniques with significant limitations. For example, one off-sited study relies on a 25-year-old survey of 15 general practices in London. Using this limited sample, some have suggested that there are approximately 14,000 individuals with MSA in the United States, given the country's current population. In contrast, recent analysis rely on the use of real-world claims databases and capture important geographic variances and demographic trends which affect MSA prevalence estimates. These analyses support a much higher estimate of roughly 50,000 individuals, which is consistent with estimates from both the UCSD Department of Neurosciences and MSA Center of Excellence and the National Institutes of Health. Based on this figure, we believe that the addressable US population for amproloxetine is approximately 40,000 MSA patients suffering from symptomatic NOH. Turning to slide 10, our goal is to make amproloxetine available to MSA patients with symptomatic NOH worldwide. In Europe and Asian countries, including the EU5, Japan, and China, the number of addressable patients is several fold larger than it is in the US. And in some territories, the range of therapeutic options is even more limited than in the U.S. At this point, I'd like to turn the call over to our new head of development, Anya Miller, to characterize the value that we see in Amproloxatine and provide an update on the progress we are making with Cypress. Anya?

Thanks, Rick. Let's begin on slide 11. MSA is an incurable neurodegenerative disorder associated with inappropriate deposits of alpha-synuclein in the brain. MSA patients experience a progressive loss of autonomic function, as well as challenges with standing, walking, speaking, and swallowing. Many also experience depression and anxiety. According to a 2018-19 UK survey of over 10,000 patients with neurological disorders, MSA ranks as having the second most severe impact on quality of life of any neurological disorder studied, ahead of disorders like progressive supranuclear palsy, Huntington's disease, and Parkinson's disease, among others. Neurogenic or dystatic hypotension, which causes significant and unremitting drops in blood pressure upon standing, affects about four in five patients with MSA. Patients with symptoms of NOH may feel dizzy upon sitting or standing, can become unable to stand or walk for even short periods of time, feel pain associated with a lack of profusion in their upper extremities, and face a higher risk of falls. Not surprisingly, a significant majority of patients with symptomatic NOH report that they have a reduced ability to perform daily activities, while many also expressing a loss of independence. As I'll discuss on slide 12, MSA patients with symptomatic NOH lack a safe, convenient, and durable effective treatment option. While non-pharmacological therapies are available, they are often insufficient to control symptoms. About 30 years ago, the FDA approved a product called Midodrine on the basis of its ability to increase blood pressure. However, Midodrine is not indicated to improve symptoms of NOH, must be taken three times daily and carries a black box warning for its potential to lead to a marked elevation of supine blood pressure. Nearly 20 years later, the FDA approved a second drug called Droxidopa to treat dizziness in patients with NOH. Based on the still high unmet need for these patients, the FDA granted Droxidopa a conditional or accelerated approval. after initially having rejected the sponsor's application and despite Droxidopa having failed two of the four phase three studies included in the application. As with Midodrine, Droxidopa is dosed multiple times a day and carries a black box warning for supine hypertension. It has never demonstrated a durable effect on NOH symptoms beyond two weeks of treatment in a double-blind study. And more recently, based on data reported on clinicaltrials.gov, it failed to demonstrate a benefit in the confirmatory study requested by the FDA known as Restore. Based on third-party analysis of claims and prescription data, Droxidopa is still only prescribed to a small percentage of MSA patients with NOH. Let's fast forward to the day, and it has been more than a decade since MSA patients with symptomatic NOH have been offered a novel treatment alternative. While we still have important work to do to confirm its clinical profile in the CYPR study, we anticipate that amperloxacin will represent a significant advance for these individuals, given the benefits it has demonstrated to date. Amproloxetine's durable impact on a broad range of NOH symptoms in MSA patients in study 170, coupled with its safety and tolerability profile, and convenient once daily dosing, is expected to drive high levels of adherence. Moreover, as the first novel therapy in years, we are optimistic we will be able to build a case for a broad access and significant adoption in the population for which it is indicated, should Amproloxetine be approved. Now shifting gears to the Cypress study on slide 13, I'd like to share our approach and the progress that we are making. As many of you know, Theravance is directly managing study conduct for Cypress rather than utilizing the traditional CRO models. By design, we are deeply involved in identifying sites with high standards for clinical conduct, investigators who understand the complexities of managing NOH and MSA, and patients who best fit the criteria of the Cypress study. We are informed by our experience in studies 169 and 170 and have re-enlisted many of the same sites and KOLs involved in those studies. Beyond this, we have enriched our network through AI efforts that leverage claims information, the work of data scientists, and our own expertise. This has allowed us to identify additional qualified sites in the United States. Finally, we are early adopters of telehealth and have incorporated options for patients and clinical personnel to participate in Cypress, even if factors limit patient's ability to undergo evaluations in the clinic. We are pleased with the internal metrics we are monitoring thus far, which are consistent with our expectations and Study 170. While we don't comment specifically on enrollment, we continue to make excellent progress activating sites, including many outside of the United States. Shifting now to the right-hand side of slide 13, we have aligned with the FDA and the design of Cypress, including the use of the OHSA composite score, a six-item assessment of orthostatic hypertension symptom severity as the primary endpoint. When using patient-reported outcome measures such as OHSA, the FDA recommends anchoring these data in order to determine clinical meaningful consequences. In November, at the AAS annual meeting, we presented data from our anchor-based analysis of studies 169 and 170, which support the use of the OHSA composite score for MSA patients with NOH, as well as the threshold for which is considered a clinically meaningful change. Our analysis demonstrated that threshold improvements and worsening of approximately one point on the OHSA composite were considered clinically meaningful. This is important as it supports our Cypress study design and compares favorably to the 1.6-point benefit we saw on this measure in MSA patients in Study 170. Finally, in order to minimize the time from Cypress completion to potential commercial availability, we have already completed much of the work required for our NDA submission and are in the process of ordering the application. At this point, I'll turn the call over to Rhonda to discuss Tupelary.