Q4 2023 Theravance Biopharma Inc Earnings Call

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Operator: 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.

Speaker Change: Ladies and gentlemen, good afternoon, I'd like to welcome everyone to the thorough Vance 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.

Operator: A question and answer session will follow the company's formal remarks. To ask a question, press the star key followed by the digit 1 1 on your telephone. Again, that's Star 1 1 to ask a question. If listening via webcast, please mute the 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.

Speaker Change: He followed by the digit one one on your telephone again that star one wanted to ask a question.

Speaker Change: If you're listening via webcast. Please mute audio on your webcast device before asking your question over the phone I'll repeat these instructions after management completes their prepared remarks also today's conference call is being recorded.

Speaker Change: Now I'd like to turn the call over to Rick Winningham, Chief Executive Officer. Please go ahead Sir.

Rick E. Winningham: Good afternoon, everyone. And thank you for joining the Theravance 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 and information containing factors that could 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 Suaf, our Chief Financial Officer.

Rick E. Winningham: Good afternoon, everyone and thank you for joining the <unk> Biopharma fourth quarter and full year 2023 earnings results Conference call.

Rick E. Winningham: Turning to slide two I'll 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.

Rick E. Winningham: Anticipated timing of clinical trials regulatory filings and expected financial results.

Rick E. Winningham: Information containing factors that could cause results to differ materially from our forward looking statements is described further in our filings with the SEC.

Rick E. Winningham: Today Im joined by Jim Miller.

Jim Miller: Our head of development Ronda, Farnham thereabouts, as Chief business Officer, and as these swap our chief Financial Officer.

Rick E. Winningham: 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 ambulatory growth and maximizing the 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 the utility's net sales 9% from $61 million and $221 million, respectively, as recorded by Viatris.

Jim Miller: On slide four I'll begin by hitting the high points for a very productive 2023 for thorough events. We began the year with the decision to focus on driving <unk> growth and maximizing <unk> value, while increasing our capital return program.

Jim Miller: I am pleased to report that our team delivered on these objectives for both the fourth quarter and the full year, we increased the power's net net sales nine per sale from.

Jim Miller: From $61 million and $221 million, respectively as as recorded by via trucks, We groove hospital volumes that outstanding 46% for the year and set the business up for continued momentum in 2024.

Rick E. Winningham: We grew hospital volumes by an outstanding 46% for the year and set the business up for continued momentum in 2024. We initiated Amproloxetine's CIPRA 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 Amproloxetine from price negotiations associated with inflation reduction. 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-gap profitability in the fourth quarter, which involved 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.

We initiated the <unk> team Cypress study and began immediately began evaluating and activating sites around the world.

Jim Miller: In May we were granted orphan drug status, which can first important financial advantages such as tax credits and user base.

Jim Miller: Exemptions and shields and philosophy and from price negotiation.

Jim Miller: Associated with the inflation reduction.

Jim Miller: 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.

Jim Miller: Turning to our corporate progress I'm proud we have delivered on our promise of reaching non-GAAP profitability in the fourth quarter, which involve significant efforts on the part of the entire <unk> team. In addition, we completed our $325 million.

Jim Miller: Dollar capital return program within the first few days of January while maintaining a strong financial profile.

Rick E. Winningham: Now, on slide five, I'll cover plans and anticipated financial performance for the upcoming year, beginning with Upelri. We expect to grow Upelri net sales in partnership with Beatrice 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 mark. Finally, we look forward to Vietra submitting a regulatory application for UPAURI in China by mid-year, which will put us on a path toward achieving meaningful economics in that territory.

Jim Miller: Now on slide five I'll cover plans and anticipated financial performance for the upcoming year.

Jim Miller: Beginning with your Perl rate, we expect to grow your powering net sales in partnership with via Trust and build on profit margin improvements experienced in 2023.

Jim Miller: We set ambitious goals for our hospital business in 2024, which we believe will translate into future share gains in the long acting nebulous Asian market.

Jim Miller: Finally, we look forward to vitro submitting our regulatory application for <unk> in China by mid year, which will put us on a path towards achieving meaningful economics in that territory.

Rick E. Winningham: Turning to ampyloxetine, we're focused on completing the CIPR 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 Amprilox. 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 During the second half of the year, subject to the timing of appellary growth and Cypress progress, we plan to approach break-even on a non-GAP basis.

Jim Miller: Turning to <unk>, we're focused on completing the Cypress study. In addition, we expect to initiate.

Jim Miller: Regulatory and early commercialization preparations as we progress through the year.

Jim Miller: We're very excited to host a virtual investor event during the second quarter, where we will bring MSA experts in senior leadership from terror events together to discuss the unmet need in MSA patients with symptomatic NIH and the expected benefits of Ampelopsis team.

Jim Miller: Turning to our 2024 financial outlook, we expect the annual collaboration growth to remain strong for our quarterly financial results to improve as the year progresses during.

Jim Miller: 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 your powering growth in Cyprus progress. We plan to have approached breakeven 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.

Rick E. Winningham: We plan to limit cash utilization, and we believe we're 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 Eupelry and Amproloxetine, 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 the Appellary 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 U.S. upellery net sales reach $250 million in Additional information on our milestones and royalties may be found in our SEC filing.

Jim Miller: Sales milestone in 2024, and possibly the higher 50 million dollar milestone.

Jim Miller: If you turn to slide six you'll see an update and summary of our compelling value proposition. In addition to empowering ample oxitec and 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 <unk> and trilogy over time.

Jim Miller: Specifically in addition to the trilogy milestones that I referenced we stand to receive a one time sales milestone of $25 million when the U S. <unk> net sales reached $250 million in any calendar year.

Jim Miller: Additional information on our milestones and royalties may be found in our SEC filings.

Rick E. Winningham: Moving to slide eight to focus on amyloxetine. 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 Amproloxtene's potential to represent a major advance for these patients. The company retains commercial rights to Amproloxtene 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.

Jim Miller: Moving to slide eight to focus on <unk>.

Jim Miller: We are motivated to make <unk> 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 moh without effective treatment options.

Data, thus far support <unk> potential to represent a major advance for these patients the company retained commercial rights to <unk> worldwide.

Jim Miller: On slide nine I'll start with the considerable unmet need in the United States.

MSA as a neuro degenerative disease.

Jim Miller: Shares features with other movement disorders, such as Parkinsons disease.

Rick E. Winningham: It's often misdiagnosed, with many patients not confirmed to have MSA for months to years after symptoms begin. Unfortunately, most epidemiological research was conducted decades ago on Parkinsonism, more generally using survey techniques with significant limitations. For example, one offline 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 analyses rely on the use of the real world's claims databases and capture important geographic variances and demographic trends which affect MSA prevalence as, 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 the MSA Center of Excellence and the National Institutes of Health.

Jim Miller: It's often misdiagnosed with many patients not confirmed have MSA for months to years after symptoms begin.

Jim Miller: Unfortunately, most epidemiology research was conducted decades ago on parkinsonism more generally using survey techniques with significant limitations.

Jim Miller: For example, one off sided study relies on a 25 year old survey of 15 general practices in London.

Jim Miller: Using this limited sample some have suggested that there.

Approximately 14000 individuals with MSA in the United States, given the country's current population.

Jim Miller: In contrast, recent analysis rely on the use of the real worlds claims databases and capture important geographic variances and demographic trends, which affect MSA prevalence estimates.

These analyses support a much higher estimate of roughly 50000 individuals which is consistent with estimates from both the UCSD Department of neuroscience as an MSA center of excellence and the National Institutes of health.

Rick E. Winningham: Based on this figure, we believe that the addressable U.S. population for amproloxetine is approximately 40,000 MSA patients suffering from symptomatic NOA. 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 U.S. 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 Amproloxetine and provide an update on the Anya?

Jim Miller: Based on this figure we believe that the addressable U S population for <unk> is approximately 40000 MSA patients suffering from symptomatic anyway.

Jim Miller: Turning to slide 10, our goal is to make <unk> available to MSA patients with symptomatic <unk> worldwide and.

Jim Miller: In Europe, and Asian countries, including the EU, five Japan, and China. The number of addressable patients is several fold larger than it is in the U S and in some territories. The range of therapeutic options is even more limited than in the U S.

Speaker Change: At this point I'd like to turn the call over to our new head of development.

Speaker Change: And characterize the value that we see in <unk> and provide an update on the progress we are making with cypress on here.

Speaker Change: Thanks, Rick.

Rick E. Winningham: Again on slide 11.

Speaker Change: <unk> is an incurable neurodegenerative disorder associated with inappropriate deposits of Alpha <unk> in the brain.

Anya Miller: Thanks, Rick. Let's begin with slide 11. MSA is an incurable neurodegenerative disorder associated with inappropriate deposits of alpha-synuclein in the brain.

<unk> patients experience progressive loss of autonomic functions as well as challenges withstanding walking speaking on swallowing money also experienced depression and anxiety.

Anya Miller: 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 hypertension, 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 perfusion in their upper extremities, and face a higher risk of falls.

Speaker Change: Adding to what you guys are amazing 19, UK survey of over 10000 patients with neurological disorders.

Speaker Change: MSA ranks as having the second most of their impact on quality of life of any neurological disorder study ahead of disorders like progressive Supranuclear palsy, Huntington's disease, and Parkinson's disease among others.

Speaker Change: Neurogenic, orthostatic hypotension, which caused a significant and unremitting drop in blood pressure upon standing FX by four and five patients with MSA.

Speaker Change: Patients with symptoms of <unk> Nacional Dizzy sitting or standing.

Speaker Change: Unable to stand or walk or even short periods of time.

Speaker Change: Pain associated with the lack of perfusion and their upper extremities and face a higher risk of hall now.

Speaker Change: <unk>.

Speaker Change: A significant majority of patients with symptomatic NIH report that they have a reduced ability to perform daily activities well money also expressing a loss of independence.

Speaker Change: As I'll discuss on slide 12.

Speaker Change: Patients with symptomatic NIH, not can safe convenient and durable effects of treatment option.

Non pharmacological therapies are available they are often insufficient to control symptoms.

Anya Miller: Not surprisingly, a significant majority of patients with symptomatic NOH report that they have a reduced ability to perform daily activities, while many also express 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.

Speaker Change: About 30 years ago, the FDA approved a product called <unk> on the basis of its ability to increase blood pressure. However, <unk> is not indicated to improve symptoms of NIH must be taken three times daily and carries a black box warning for its potential to lead to a marked elevation of Queensland blood pressure.

Speaker Change: Nearly 20 years later, the FDA approved a second drug contract.

Speaker Change: Two or three different in patients with NIH.

Speaker Change: Just understand a high unmet need for these patients the FDA granted.

A conditional or accelerated approval.

Speaker Change: After initially having rejected the sponsors application and despite trust me know if I haven't sale two of the four phase III studies included in the application.

Anya Miller: 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 droxedopa to treat dizziness in patients with NOH. Based on the still high unmet need for these patients, the FDA granted Droxydopa conditional or accelerated approval, after initially having rejected the sponsor's application, and despite Droxydopa having failed in two of the four Phase III studies included in the application. As with Midodrine, Droxedopa is dosed multiple times a day and carries a black box warning for supine hypertension.

Speaker Change: <unk> is dosed multiple times, a day and carries a black box warning for supine hypertension.

Speaker Change: And I've never demonstrated that durable effect on NOI H symptoms beyond two weeks of treatment in a double blind study and.

Speaker Change: And more recently based on data reported on clinical trials Dot com and failed to demonstrate a benefit in the confirmatory study requested by the FDA known as restore.

Speaker Change: Based on third party analysis of claims in prescription data Trust me, it's still only prescribed to a small percentage of MSA patients, but anyways.

Speaker Change: Let's fast forward to today and it has been more than a decade since MSA patients with symptomatic <unk> have been offered a novel treatment alternatives.

Speaker Change: While we still have important work to do to confirm its clinical profile and the Cypress study, we anticipate that <unk> represents a significant advance for these individuals given the benefit that has demonstrated to date.

Anya Miller: 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, Droxedopa is still only prescribed to a small percentage of MSA patients with NOH. Let's fast forward to today, 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 CIFRS study, we anticipate that amperloxacine will represent a significant advance for these individuals, given the benefits it has demonstrated to date. Ampriloxetine'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.

Speaker Change: <unk> durable impact on a broad range of annual hedge symptoms and MSA patients in study 170, coupled with its safety and Tolerability profile and convenient once daily dosing is expected to drive higher levels of adherence. Moreover, as the first novel therapy in years, we are optimistic we will be able to build.

Speaker Change: Case for a broad access and significant deduction in the population for which it is indicated.

Speaker Change: <unk> be approved.

Speaker Change: Now shifting gears to the Cyprus study on slide 13, I'd like to share our approach and the progress that we're making.

Speaker Change: As many of you know Paramount is directly managing Sony Commvault for cypress, rather than utilizing the traditional payroll model.

Speaker Change: By design, we are deeply involved in identifying sites the highest standard of clinical concept investigators who understand the complexities of managing <unk> MSA and patients the best fits the criteria of the Cypress study.

Speaker Change: We are informed by our experience in study 106, nine and $1 70 and have reinvested money at the same sites and Kols involved in those studies beyond this we have enriched our network to AI effort that leverage claims information and work of data scientists and our own expertise.

Speaker Change: This has allowed us to identify additional product by sites in the United States.

Speaker Change: We are early adopters of telehealth and haven't cooperated option for patients and clinical personnel to participate in Cyprus, even if factors limit patients' ability to undergo evaluations in the clinic.

Anya Miller: Moreover, as the first novel therapy in years, we are optimistic that we will be able to build a case for broad access and significant adoption in the population for which it is indicated, should amperloxidase 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 Cyprus rather than using the traditional CRO model.

Speaker Change: We are pleased with the internal metrics, we're monitoring thus far which are consistent with our expectations and study 170.

Speaker Change: While we don't want to comment specifically on enrollment we continue to make excellent progress activating sites, including money outside of the United States.

Speaker Change: Shifting now to the right hand side of slide 13, we have aligns with the FDA and the design of Cypress, including the use of the origin of a composite score.

Anya Miller: 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 Cyprus 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 across the United States.

Speaker Change: This is an assessment of orange, starting hypotension symptom severity as the primary endpoint.

Speaker Change: When using patient reported outcome measures such as OSA. The FDA recommends anchoring these data in order to determine clinical meaningfulness.

Speaker Change: In November at the Aes annual meeting, we presented data from our anchor based analysis of study 169, and $1 70, which support the use of the origin and composite score for MSI in patients with <unk> as well as the threshold for which is considered a clinically meaningful change.

Speaker Change: Our analysis demonstrated that threshold improvements and worsening of approximately one point on the OSA HSA partners more considered clinically meaningful.

Speaker Change: This is important as it supports our Cypress study design and compares favorably to the one six point benefit we saw on this measure in MSA patients in study 170 <unk>.

Anya Miller: Finally, we are early adopters of telehealth and have incorporated options for patients and clinical personnel to participate in CyPERS even if doctors limit patients' 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 FIBRS, 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 meaningfulness.

Speaker Change: Finally in order to minimize the time from Cypress completion to potential commercial availability, we have already completed much of the work required for NDA submission and are in the progress process of ordering the application at this point I'll turn the call over to Rhonda <unk> Henri.

Rhonda: Thanks Tanya.

Rhonda: Beginning on slide 15, I'm pleased to report that era.

Vance and Beatrice commercial partnership finished the year strong.

Rhonda: Kevin driven repowering net sales growth of 9% for the full year of 2023.

Rhonda: Fourth quarter net sales reached $60 6 million and full year sales reached $221 million with <unk> recording its highest level of profitability since launch.

Rhonda: Although quarter to quarter results can vary depending on the timing of shipments and other seasonal factors.

Rhonda: Main optimistic for <unk> continued growth based on the success, we are delivering in the hospital channel as well as several key performance indicators, we track across the business.

Anya Miller: 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.

Rhonda: While realized sales this quarter closely track with demand generation, we have traditionally experienced seasonal dips and reported net sales as we transition from the fourth quarter to the first quarter of the following year.

Rhonda: Moving to slide 16.

Speaker Change: I'm also very pleased to share with you the exceptional finish to the year our hospital team was able to deliver.

Rhonda Farnham: 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 altering the application. At this point, I'll turn the call over to Rhonda to discuss. Thanks, Anya.

Speaker Change: Hospital doses shipped in the fourth quarter increased 37% year over year with full growth reaching 46%.

Speaker Change: It was easily the highest volume quarter for the hospital channel delivered since launch.

Speaker Change: As you know our goal continues to be to increase the number of patients.

Speaker Change: Those did you pillory during hospitalization.

Speaker Change: Then discharged on mute Hillary as maintenance patients.

Speaker Change: This is achieved by gaining farming.

Rhonda Farnham: Beginning on slide 15, I'm pleased to report that the Theravance and Beatrice commercial partnership finished the year strong, having driven annual net sales growth of 9% for the full year of 2023. Fourth quarter net sales reached $60.6 million, and full year sales reached $221 million, with Upelri recording its highest level of profitability since long. Although quarter-to-quarter results can vary depending on the timing of shipments and other seasonal factors, we remain optimistic about Upelri's continued growth based on the success we are delivering in the hospital channel, as well as several key performance indicators we track across the business. While Real Eye sales this quarter closely track demand generation, we have traditionally experienced seasonal dips in reported net sales as we transition from the fourth quarter to the first quarter of the following year.

Speaker Change: Gaining support for formulary inclusion implementation of hospital protocols involving all nebulous Asian strategy and therapeutic interchanges and.

Speaker Change: And equally important high touch transition of care program.

Speaker Change: Our market research continues to demonstrate that the vast majority of patients to initiate your <unk> in the hospital setting receive a prescription of <unk> maintenance care at discharge.

Speaker Change: It is with the execution of this winning strategy that are small, but focused commercial organization is able to make a considerable contribution to the overall <unk> business.

Speaker Change: With directly and indirectly.

Speaker Change: Turning to slide 17 on the left side you can see the impact our efforts have had on our hospital market share.

Speaker Change: During the quarter, our share of the long acting <unk> market in the hospital segment increased to 16, 6% while on the right side of the slide <unk> achieved a 31% share in the community.

Rhonda Farnham: Moving to slide 16, I'm also very pleased to share with you the exceptional finish to the year our hospital team was able to deliver. Hospital doses shipped in the fourth quarter increased 37% year over year, with full growth reaching 46%. This was easily the highest volume quarter for the hospital channel delivered since launch. As you know, our goal continues to be to increase the number of patients exposed to upillary during hospitalization who are then discharged on upillary as maintenance patients. This is achieved by gaining support for formulary inclusion, implementation of hospital protocols involving all nebulization strategies, and therapeutic interchanges, an equally important high-touch transition of care program. Our market research continues to demonstrate that the vast majority of patients who initiate upelry in the hospital setting receive a prescription for upelry maintenance care at discharge. It is with the execution of this winning strategy that our small but focused commercial organization is able to make a considerable contribution to the overall retail business, both directly and indirectly.

Speaker Change: Up nearly four percentage points year over year.

Speaker Change: We attribute both segments share growth to the increasing traction of our concomitant therapy messaging.

Speaker Change: This taps into the significant number of COPD patients, who remain symptomatic on LABA therapy and could benefit from the addition of a llama, which is foundational in the treatment of COPD and references to 2022 changes to the gold report guidelines, which recommend duo LABA.

Speaker Change: <unk> therapy or category, B and <unk> patients.

Speaker Change: As a basis for speaking to the trends we have achieved in the retail setting where we have our most real time and current demand do you outside of the hospital channel.

Speaker Change: We felt it might be helpful to share another visual.

Speaker Change: If you turn to slide 18, we provide data on the fulfillment growth trends in both the total community and retail segment settings through the third quarter of the year.

Speaker Change: At the time that we share our quarterly results, we do not have a completed data capture of fulfillment in the <unk> channel.

Speaker Change: Which accounts for approximately 60% of our total community business.

Speaker Change: Because retail which accounts for the other 40% generally correlates with total community fulfillment overtime.

Speaker Change: We have historically offered this view.

Rhonda Farnham: Turning to slide 17, on the left side, you can see the impact our efforts have had on our hospital market share. During the quarter, our share of the long-acting NEM market in the hospital segment increased to 16.6%, while on the right side of the slide, Upelri achieved a 31% share in the community, up nearly 4 percentage points year-over-year. We attribute both segments share growth to the increasing traction of our concomitant therapy messaging. This taps into the significant number of COPD patients who remain symptomatic on LABA therapy and could benefit from the addition of a LAMA, which is foundational in the treatment of COPD and references the 2022 changes to the Gold Report guidelines, which recommend dual LABA and LAMA therapy for Category B and E patients.

Speaker Change: You will find our most up to date performance in the retail channel on slide 19.

Speaker Change: Looking at the left side of slide 19, retail prescriptions grew a robust 7% sequentially during the quarter.

Speaker Change: Which is consistent with recent brand performance trends looking to the right side of this slide we also grow new product starts a sequential 7% in Q4.

Speaker Change: You may remember from our last update that we had experienced some quarter to quarter seasonality and new starts which is not atypical for this metric in Q3.

Speaker Change: As anticipated however, we were able to drive a sequential returned to growth in Q4.

Speaker Change: Finishing on slide 20, we think it is important to highlight the unique and compelling value proposition, we offer patients and caregivers as the only once daily <unk> Lama for maintenance treatment of COPD.

<unk> has demonstrated consistently meaningful lung function benefits is typically available at low out of pocket costs and requires only a few minutes to administer once per day.

Speaker Change: As such we believe <unk> plays a key role in the COPD market, where there remains a substantial opportunity to reach patients who could benefit from <unk>.

Rhonda Farnham: As a basis for speaking to the trends we have achieved in the retail setting, where we have our most real-time and current demand view outside of the hospital channel, we felt it might be helpful to share another visual. If you turn to slide 18, we provide data on the fulfillment growth trends in both the total community and retail segment settings through the third quarter of the year. At the time that we share our quarterly results, we do not have a completed data capture of fulfillment in the DME channel, which accounts for approximately 60% of our total community business. Because retail, which accounts for the other 40%, generally correlates with total community fulfillment over time, we have historically offered this view.

Speaker Change: Our go to market strategy aligns with this profile, which we believe is why <unk> is only one of three branded COPD maintenance therapies in the U S that is delivering consistent growth.

Speaker Change: Looking ahead, we expect to achieve continued growth and value creation for your power driven both by continued penetration of the U S maintenance COPD market.

Speaker Change: And the potential launch of <unk> in China.

Speaker Change: Lastly in the U S. We are eligible to receive a one time sales milestone of $25 million from Beatrice when <unk> net sales reached $250 million in any calendar year.

Speaker Change: In China, where <unk> is planning to file for regulatory approval by the middle of this year, we are eligible to receive a $7 $5 million milestone upon approval as.

Rhonda Farnham: You will find our most up-to-date performance in the retail channel on Slide Night. Looking at the left side of slide 19, retail prescriptions grew a robust 7% sequentially during the quarter, which is consistent with recent brand performance trends. Looking to the right side of the slide, we also grew new product starts by sequential 7% in Q4. You may remember from our last update that we had experienced some quarter-to-quarter seasonality in new starts, which is not atypical for this metric in Q3.

Speaker Change: As well as additional sales milestones and I'll quickly tiered royalties of between 14 and 20%.

Speaker Change: That brings us to the end of the salary update so I will turn things over to <unk> to cover our financials.

Thanks, Rhonda starting off with the results for the quarter Slide 22, and 'twenty three cover the detailed financials.

Rhonda Farnham: As anticipated, however, we were able to drive a sequential return to growth in Q4. Finishing on slide 20, we think it is important to highlight the unique and compelling value proposition we offer patients and caregivers as the only once daily nebulized llama for maintenance treatment of COPD. Upalry has demonstrated consistently meaningful lung function benefits, is typically available at low out-of-pocket costs and requires only a few minutes to administer once per day

Speaker Change: I'll cover the highlights on slide 24, starting with collaboration revenue reported an all time high of $17 4 million representing year over year growth of 19% on.

Speaker Change: Operating expenses were in line with expectations for the quarter, resulting in full year operating expenses, excluding share based comp to be under the low end of R&D guidance and within the range for SG&A in total opex.

Speaker Change: Combination of judicious expense management and increased salary net sales led to a non-GAAP profit of $1 $4 million in the quarter. Please.

Speaker Change: Please note that our GAAP loss of $8 $5 million was affected by a larger than expected income tax expense in the quarter, primarily due to better than expected results and other noncash charges from one of our operating entities.

Aziz Suaf: As such, we believe upellery plays a key role in the COPD market, where there remains a substantial opportunity to reach patients who could benefit from upellery. Our go-to-market strategy aligns with this profile, which we believe is why Upelri is only one of three branded COPD maintenance therapies in the U.S. that is delivering consistent growth. Looking ahead, we expect to achieve continued growth and value creation for Upellry, driven both by continued penetration of the US maintenance COPD market and a potential launch of Upellry in China. Lastly, in the U.S., we are eligible to receive a one-time sales milestone of $25 million from Beatrice when Upelri net sales reach $250 million in any calendar year. In China, where Viatris is planning to file for regulatory approval by the middle of this year, we are eligible to receive a $7.5 million milestone upon approval, as well as additional sales milestones and upwardly tiered royalties of between 14 and 20%. That brings us to the end of the Pellery update. So I will turn things over to Aziz to cover our financials. Aziz.

Speaker Change: However, this is a noncash item and we expect to have immaterial, if any cash taxes payable for 2023.

Speaker Change: In Q4, we repurchased approximately $30 million worth of shares leaving 400000 on the return of capital program at quarter end.

Speaker Change: Which was completed in early January.

Speaker Change: This reduced our share count by 3 million shares in the quarter by 31 million shares from the program's inception.

Speaker Change: 37% reduction in share count.

Speaker Change: We closed the period with $102 million in cash and approximately 48 million shares outstanding.

Speaker Change: On slide 25, I'll provide an update on our potential to earn milestones from trilogy, noting that GSK delivered another excellent quarter of growth quarterly.

Speaker Change: Quarterly and year to date sales reached $737 million and $2 7 billion, respectively up 35% and 28% year over year.

Speaker Change: As a result, we are well positioned to achieve milestones in 2024 and beyond compared with 2023 actuals, we need only 5% growth in annual net sales to achieve the first $25 million milestone and 17% to achieve the second $50 million milestone.

Aziz Suaf: Thanks, Rhonda. Starting off with the results for the quarter, slides 22 and 23 cover the detailed financials; I'll cover the highlights on slide 24. Starting with collaboration revenue, we reported an all-time high of $17.4 million, representing year-over-year growth of 19%. Operating expenses were in line with expectations for the quarter, resulting in full-year operating expenses, excluding share-based comp, to be under the low end of R&D guidance and within the range for SG&A and total operating expenses.

Speaker Change: As a reminder, these milestones are not cumulative.

Speaker Change: Both milestones were to be achieved we would receive a total of $50 million not $75 million.

Speaker Change: Lastly, turning to financial guidance on Slide 26, we will continue to provide R&D and SG&A operating expense guidance, excluding share based comp in 2024. In addition to enhance our financial disclosure, we will be adding noncash share based compensation to our guidance metrics.

Speaker Change: For R&D Opex, excluding share based comp, we are expecting between 30% and $36 million, which will be exclusively allocated to <unk> and <unk>.

Speaker Change: The majority of this will be for the Cypress study execution.

Speaker Change: In addition guidance includes gated spend towards NDA preparation, primarily during the second half of the year.

Aziz Suaf: The combination of judicious expense management and increased superior net sales led to a non-gap profit of $1.4 million in the quarter. Please note that our gap loss of $8.5 million was affected by a larger-than-expected income tax expense in the quarter, primarily due to better-than-expected results and other non-cash charges from one of our operating entities. However, this is a non-cash item, and we expect to have immaterial if any cash tax is payable for 2023. In Q4, we repurchased approximately $30 million worth of shares, leaving $400,000 on the return of capital program at quarter end, which was completed in early January. This reduced our share count by 3 million shares in the quarter and by 31 million shares from the program's inception, a 37% reduction in the share count. We close the period with 102 million in cash and approximately 48 million shares outstanding.

Speaker Change: The gating of the spend will depend on being on track with Cypress enrollment in line with industry best practices.

Speaker Change: For SG&A Opex, excluding share based comp, we're expecting between 45 and $55 million.

Our <unk> related spend will be largely flat year over year guidance includes incremental spend for ample oxiclean prelaunch commercial activities.

Speaker Change: Marilee in market research Medical affairs, and market access, which will occur mostly in the second half of the year.

Speaker Change: Given our focus on expected given our focus on expected return on invested capital any incremental spending for prelaunch activities will be gated based on Cyprus enrollment and will be subject to board approval.

Speaker Change: Partially offsetting these increases is a reduction of G&A spend by approximately 20% driven by ongoing cost cutting initiatives.

Speaker Change: Starting in Q1, we will breakout G&A separately from SG&A within our MD&A commentary in our 10-Qs and 10-K.

Speaker Change: For share based comp, we are expecting between 18 and $22 million the midpoint, reflecting a year over year reduction of approximately 20%.

Aziz Suaf: On slide 25, I'll provide an update on our potential to earn milestones from Trellogy, noting that GSK delivered another excellent quarter of growth. Quarterly and year-to-date sales reached $737 million and $2.7 billion, respectively, up 35% and 28% year-over-year. As a result, we are well positioned to achieve milestones in 2024 and beyond. Compared with 2023 actuals, we need only 5% growth in annual net sales to achieve the first $25 million milestone and 17% to achieve the second $50 million milestone. As a reminder, these milestones are not cumulative. If both milestones were to be achieved, we would receive a total of $50 million, not $75 million.

Speaker Change: In terms of our non-GAAP metric, we expect we will turn from our non-GAAP profit in Q4 2023 to a non-GAAP loss in early 2020 for.

This is due to an expected decrease in collaboration revenue in Q1 from Q4 of 2023, driven by typical seasonality for <unk> net sales as mentioned by Rhonda combined with a temporary increase in R&D spend due to the expected ramp in patient enrollment and site initiation for the Cypress study.

Speaker Change: Turning to the second half of 2024, we expect our non-GAAP metric to approach breakeven, which will be dependent on continued net sales growth for <unk> as well as the amount of spend on <unk> team prelaunch commercialization.

Speaker Change: As discussed on prior earnings calls this non-GAAP metric as a proxy for cash flow and we therefore expect limited cash burn in 2024, most of which will be incurred earlier in the year.

Speaker Change: Given multiple potential milestones in 2024 and beyond such as 25 or $50 million milestone for trilogy, we.

Speaker Change: We expect to generate net cash prior to the Cypress topline data readout in 2025.

Speaker Change: Lastly, we may continue to incur non cash income tax expense of several million each quarter.

Speaker Change: However, we continue to expect that immaterial, if any cash taxes in 2024 from ongoing operations.

Aziz Suaf: Lastly, turning to financial guidance on slide 26, we will continue to provide R&D and SG&A operating expense guidance excluding share-based comp in 2024. In addition, to enhance our financial disclosure, we will be adding non-cash share-based compensation to our guidance metric. For R&D OPEX excluding share-based comp, we are expecting between $30 and $36 million, which will be exclusively allocated to EPRLOC.

Speaker Change: With that I'll pass it back to Rick to conclude Rick.

Rick E. Winningham: Thanks, Chris These on slide 27, we summarize their advances compelling vision and value we offer shareholders.

Rick E. Winningham: Having focused our organization's efforts behind <unk> team. The <unk> team is now unified in pursuit of three objectives first we will work to drive U S. Repowering net sales growth in the hospital, while collaborating closely with our partners at Beatrice to maximize the brand's overall potential of the hospital and community settings.

Aziz Suaf: A significant majority of this will be for the Cypress study execution. In addition, guidance includes gated spend towards NDA preparation, primarily during the second half of the year. The ungating of this spend will depend on being on track with Cypress enrollment in line with industry best practices. For SG&A OPEX, excluding share-based comp, we are expecting between $45 and $55 million.

Rick E. Winningham: Second we will continue to work diligently in pursuit of the Cypress studies successful completion, while making appropriate regulatory preparations and laying the ground work for its broad access if approved.

Rick E. Winningham: Third we will maintain a strong capital structure as we work to deliver value for shareholders.

Rick E. Winningham: Based on the choices, we made regarding <unk> and trilogy believe we are at the crossroads with their advances evolution, where we stand poised to deliver significant incremental value through our operational assets as well as near term milestones royalties, while making limited incremental investments and managing risk.

Aziz Suaf: While our euphoria-related spend will be largely flat year over year, guidance includes incremental spend for Amperloch's team for pre-launch commercial activities, primarily in market research, medical affairs, and market access, which will occur mostly in the second half of the year. Given our focus on expected return on invested capital, any incremental spending for prelaunch activities will be gated based on Cypress enrollment and will be subject to board approval. Partially offsetting these increases is a reduction in GNA spend by approximately 20% driven by ongoing cost-cutting initiatives.

Speaker Change: We thank you for your time and attention this afternoon, and we're ready to take your questions.

Speaker Change: Operator.

Speaker Change: Thank you Sir once again, if you'd like to ask a question you may do so by pressing the star key followed by the digits. One one on your telephone if listening via webcast. Please mute audio on your webcast device before asking your question over the phone if youre using a speakerphone for todays call. Please make sure your mute function.

Rick E. Winningham: Starting in Q1, we will break out GNA separately from sGNA within our mDNA commentary in our 10 Qs and 10 Ks. For share-based comp, we are expecting between $18 and $22 million, the midpoint reflecting a year-over-year reduction of approximately 20%. In terms of our non-gap metric, we expect we will turn from a non-gap profit in Q4 2023 to a non-gap loss in early 2024. This is due to an expected decrease in collaboration revenue in Q1 from Q4 2023 driven by typical seasonality for upellery net sales, as mentioned by Rhonda, combined with a temporary increase in R&D spend due to the expected ramp in patient enrollment Turning to the second half of 2024, we expect our non-gap metric to approach break-even, which will be dependent on continued net sales growth for Upellery, as well as the amount of spend on Amperloch's team for pre-launch commercialization.

Speaker Change: Just turned off to allow your signal to reach our equipment again Thats star one if you'd like to ask a question and we'll pause for a moment to assemble our roster.

Speaker Change: And our first question comes from the line of Douglas Tsao from H C. Wainwright Your question. Please.

Speaker Change: Okay.

Douglas Tsao: Hi can you hear me.

Douglas Tsao: Yes, we can hear you okay.

Douglas Tsao: Good afternoon, and congrats on the progress.

Douglas Tsao: Just a couple of questions.

Douglas Tsao: First maybe starting with <unk>.

Douglas Tsao: I'm just curious when we think about the share gains that youre seeing especially those in the hospital to what extent are those coming from.

Douglas Tsao: Adding new accounts versus.

Douglas Tsao: Gaining share within the existing account base.

Speaker Change: And then I've got a follow up.

Speaker Change: Thanks, Doug Great question.

Speaker Change: <unk> thinking about that share gain up to 16, 6% for the quarter that is drawn both from the new accounts, but I would say that predominantly.

Doug: There is from those accounts that continue to build upon their base business, where we are converting them to therapeutic interchange and for those accounts, where we do have that all night strategy implementation as well as therapeutic interchanged, we see that the market share is even higher in those accounts.

Rick E. Winningham: As discussed on prior earnings calls, this non-gap metric is a proxy for cash flow, and we therefore expect limited cash burn in 2024, most of which will be incurred early in the year. Given multiple potential milestones in 2024 and beyond, such as the $25 or $50 million milestone for Trilogy, we expect to generate net cash prior to the Cyprus top-line data readout in 2025. Lastly, we may continue to incur non-cash income tax expense of several million each quarter. However, we continue to expect to have immaterial, if any, cash taxes in 2024 from ongoing operations. With that, I'll pass it back to Rick to conclude. Rick.

Doug: Okay.

Doug: Okay.

Speaker Change: Typically maybe just as a follow up to that.

Speaker Change: Rhonda whats the process or how long does it take to get the hospitals to sort of move to that therapeutic interchange and all nap approach.

Rhonda: If we are moving from their initial formulary to therapeutic interchange that can range anywhere from six months to a year, if we're converting prior existing formulary.

Rhonda: Review approvals.

Rhonda: Usually six to nine months.

Rhonda: Okay on average.

Rhonda: And within your account base I mean, what percent would you say are.

Rhonda: You guys sort of doing that has achieved therapeutic interchange and then all of that approach.

Rhonda:

Rhonda: That varies based on the growing base, but roughly.

Rhonda: Two thirds of our volume already have a therapeutic interchange or I should say two thirds of our volume is driven from those therapeutic interchange accounts if that makes sense.

Rick E. Winningham: Thanks, Aziz. On slide 27, we summarize Theravance's compelling vision and value we offer shareholders. Having focused our organization's efforts behind Eupelry and Amproloxetine, the Theravance team is now unified in pursuit of three objectives. First, we'll work to drive U.S. CalReNet sales growth in hospitals while collaborating closely with our partners at Beatrice to maximize the brand's overall potential in the hospital and community setting. Second, we'll continue to work diligently in pursuit of the CIPHR study's successful completion while making appropriate regulatory preparations and laying the groundwork for its broad access, if approved. Third, we'll maintain a strong capital structure as we work to deliver value for shareholders.

Rhonda: And then as a follow up to that though that what percentage of your accounts are therapeutic interchange because obviously you have given that two thirds. It would seem that there is significant growth by getting accounts to that to that.

Speaker Change: Yes, yes, you've got it Doug if we move them to therapeutic interchange that automatic substitution is what converts every existing llama.

Speaker Change: Other handheld.

Speaker Change: From the past experience over so that is the ultimate of what we are trying to achieve here with these new games.

No I get it but what percentage of your overall accounts are there.

Speaker Change: Have you achieved that.

Speaker Change: At 10%, 20%, 30%.

Speaker Change: Sort of help understand the magnitude of the opportunity still in front of you.

Speaker Change: Roughly 35% of our COPD focus accounts have a therapeutic interchanges.

Operator: Based on the choices we've made regarding upellery, anaphyloxy, and trellogy, I believe we're at the crossroads of Theravance's evolution, where we stand poised to deliver significant incremental value through operational assets, as well as near-term milestones and royalties, while making limited incremental investments and managing risk. We thank you for your time and attention this afternoon, and we're ready to take your questions. Operator

Speaker Change: Okay. That's helpful. Thank you. So yes, that's really helpful. And then just as a follow up.

Speaker Change: Obviously.

Speaker Change: You have now problem yourself and the company to expense management.

And some difficult choices to a point, where your cash burn is pretty minimal.

Speaker Change: You are also.

Speaker Change: Costello seemingly restarting to bring into milestone via for challenges as well as it seems like the payout rate, which could begin to enhance your cash balance.

Operator: Thank you, sir. Once again, if you'd like to ask a question, you may do so by pressing the star key followed by the digits 1 1 on your telephone. If listening via webcast, please mute the audio on your webcast device before asking a question over the phone.

Speaker Change: When you think about your calorie and the success you are achieving in the hospital.

Speaker Change: It ever.

How closer to the point, where it would make sense strategically to gain.

Speaker Change: Leverage with that sales organization and bring in another product and not <unk>.

Operator: 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 1 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 Tsao from HC Wainwright. Your question, please. Hi, can you hear me? Yeah, hello?

Speaker Change: Is there really one.

Speaker Change: Even if the same.

Speaker Change: The magnitude of opportunities you calorie, but just something that could give you some efficiency or some additional leverage because in theory, even a small product could drive some pretty nice incremental margins on that sales force. Thank you.

Speaker Change: Yes, Doug that's a good question a couple a couple of points one.

Speaker Change: We see such a significant opportunity.

Operator: We can hear you. Okay. Good afternoon and congratulations on the progress. A couple of questions. First, maybe starting with you, Pelri.

Speaker Change: Ample occitane and the execution of the Cypress study.

Speaker Change: The preparatory work over the next over the next year, both on the regulatory side as well as some very early commercial.

Rhonda Farnham: Rhonda, I'm just curious, when we think about the share gains that you're seeing, especially those in the hospital, to what extent are those coming from adding new accounts versus gaining share within the existing account base? Thank you, and then I've got a follow-up. Thanks, Doug.

Speaker Change: Preparation work that any distraction from anything else I think would be harmful.

From from where we are right now I'd say the second point is as Rhonda mentioned.

Rhonda Farnham: Actually, thinking about that share gain of up to 16.6% for the quarter, that is drawn both from new accounts, but I would say the predominant growth there is from those accounts that continue to build upon their base business where we are converting them to therapeutic interchange. And for those accounts where we do have that all-med strategy implementation, as well as therapeutic interchange, we see that the market share is even higher in those accounts, typically maybe just as a follow-up to that. Rhonda, what's the process or how long does it take to get a hospital to sort of move to that therapeutic interchange and all MEV approach? If we are moving from their initial formulary to therapeutic interchange, that can range anywhere from six months to a year. If we're converting prior existing formulary review approvals, it's usually six to nine months.

Speaker Change: We have a we have a small sales force they are doing an outstanding job executing a particular strategy and we are early we are in the early days.

Speaker Change: The execution of the strategy, both the <unk>, let's say in particular in combination with <unk>.

Speaker Change: The efforts of via trusts so.

Speaker Change: We've got a significant amount of opportunity I think within the hospital with your Perl rate and we would pay some opportunity cost by by shifting.

Speaker Change: Our focus to anything else, given sort of where we set with.

Speaker Change: Those accounts, where we've where we're on formulary and we need to move and take the next step towards third therapeutic interchange and those steps those institutions, largely which are multi hospital sort of groups of going from.

Speaker Change: Not being.

Speaker Change: Not being on formulary to being on formulary with therapeutic interchanges so.

Rhonda Farnham: Okay, and within your account base, I mean, what percent would you say are at, you know, sort of doing, or have achieved therapeutic interchange in an all-in-one approach? That varies just based on the growing base, but roughly, two-thirds of our volume already has a therapeutic interchange, or I should say two-thirds of our volume is driven from those therapeutic interchange accounts, if that makes sense. Well, but I guess, and then as a follow-up to that, though, what percentage of your accounts are therapeutic interchange? Because obviously, you know, given that two-thirds, it would seem that there's significant growth by getting accounts to that, to that, you know, to that. Yes, yes. You've got it, Doug.

Speaker Change: We really view is there just such significant opportunity behind both <unk> and the <unk> team that we need to keep our focus on those two assets.

Speaker Change: Okay, great. Thank you so much.

Speaker Change: Thank you one moment for our next question.

Speaker Change: And our next question comes from the line of David Risinger from Leerink Partners. Your question. Please.

David Risinger: Yes, thanks very much.

David Risinger: Thank you for the update so.

David Risinger: My first question is can you talk a little bit about.

David Risinger: How youre thinking about the introduction of <unk>.

David Risinger: <unk> from Verona.

David Risinger: And what implications that might have for you Pal re and then second if you could just provide.

Rhonda Farnham: If we move them to therapeutic interchange, that automatic substitution is what converts every existing LLAMA, whether handheld, from the past experience over. So that is the ultimate goal of what we are trying to achieve here with these new games. No, no, no, I get it, but what percentage of your overall accounts are there? How have you achieved that?

David Risinger: A little bit more detail on the execution of the <unk> trial from here.

David Risinger: <unk> pass and then the likely timing of the press release with the results. Thank you.

Speaker Change: Okay, Rod do you want to take <unk>.

David Risinger: Absolutely.

Rod: Thanks, David for the question.

Rod: We're very excited about the opportunity for incident trend, having additional share of voice focused on an annualized asset.

Rhonda Farnham: Is it 10%, 20%, 30%? Just to sort of help understand the magnitude of the opportunity still in front of you. Roughly 35% of our COPD focus accounts have a therapeutic interchange. Okay, great.

<unk> maintenance space would be tremendous.

Rod: And.

Rod: Thinking about as well.

Rod: That particular product would enter the market and.

Rod: Most likely still meeting the backbone or the foundation of therapy thinking about that as an add on therapy.

Rod: A great opportunity for us to both.

Rick E. Winningham: Thank you. Yes, that's really helpful. And then just, Rick, as a follow-up, obviously... You have now brought yourself and the company to expense management and some, you know, difficult choices to a point where your cash burn is pretty minimal. You are also, you know, on the cusp of, seemingly, seemingly, we're starting to bring in some milestones via Petrology, as well as, it seems like, DuPalry, which could begin to enhance your cash balance. When you think about DuPalry and the success you're achieving in a hospital, does it ever, you know, how close are you to the point where it would make sense strategically to gain some leverage with that sales organization and bring in another product? And not necessarily one of the same, you know, magnitude of opportunities as DuPalry but just something that, you know, could give you some efficiency or sort of some additional leverage, because, in theory, even Thank you. Yeah, Doug, that's a good question.

Rod: Ensure that the patients that.

Rod: The benefit from both products have that chance.

Rod: So on the <unk> obviously.

Rod: Sure.

Rod: We've initiated a lot of sites.

Rod: On your hip on her.

Rod: It's high quality.

Rod: High quality sites with physicians, who understand the MSA patients understand the care of OSA patients.

Rod: To understand the execution of the clinical trial will continue to activate.

Rod: Continue to activate sites and there is some some work that's done.

Rod: <unk>, there, but the more and more work obviously is focused on just getting patients into and through through the sites for <unk>.

For the study were making making very good progress making.

Rod: Making very good progress there and I think if you split that we've got.

Rod: This year is really about.

Rod: There's a little bit tilted towards patients as opposed to sites.

Rod: And Thats, where our focus will be.

Rick E. Winningham: A couple of points. One, we see such a significant opportunity for amproloxetine and the execution of the Cypress study and the preparatory work over the next year, both on the regulatory side as well as some very early commercial preparation work that, you know, any distraction from anything else would be harmful from where we are right now. I'd say the second point is, as Rhonda mentioned, we have a small sales force and they're doing an outstanding job executing a particular strategy. And we are early; we are in the early days of the execution of the strategy, both at Theravance and, I would say, in particular, in combination with the efforts of Vietra.

Rod: In terms of the.

Rod: The where the study is I think.

Rod: <unk>.

Rod: Enroll or target.

Right now that's what we believe we can do is enroll the last patient into the open label portion in the second half of the year.

Rod: This would sort of lead data probably some time in the in the first half of next year span.

Rod: That's what that's what we'd be looking looking forward to but stay tuned as we as we progress throughout the year.

Rod: I think the.

Rod: From at least from the science and the medicine part of <unk> team and the value that it can provide.

Rod: Four.

Rod: Patients with MSA and NIH I think hopefully our investor event that we have in the second quarter, we will be able to provide.

Rick E. Winningham: So, you know, we've got a significant amount of opportunity, I think, within the hospital with you, Pelri, and we would pay some opportunity costs by shifting our focus to anything else, given the sort of where we are with those accounts where we're on formulary, and we need to move and take the next step toward therapeutic interchange. And those steps, those institutions, largely multi-hospital sort of groups, going from not being on formulary to being on formulary with therapeutic interchange. So, you know, we really view there's just such a significant opportunity behind both you, Pelri, and amproloxetine that we need to keep our focus, you know, on those two assets. Okay, great. Thank you so much.

Rod: Good information to investors about the about the opportunity that we see there.

Speaker Change: Great. Thank you very much.

Speaker Change: Thanks, David.

Speaker Change: Thank you one moment for our next question.

Speaker Change: And our next question comes from the line of EBIT for T. Rowe from Cowen Your question. Please.

Speaker Change: Yes.

EBIT: Hi, guys congrats on the great quarter, and thanks for taking our questions.

EBIT: I have a question about the Q2 investor events for <unk>.

It would be any additional analyses that we haven't seen before.

EBIT: Yeah. Thanks, Steve I think relative to <unk> I think the additional analysis will be relatively limited I think.

EBIT: As we mentioned we will have opinion opinion leaders there that that percent present other analyses, obviously in both <unk> and MSA patients.

Operator: Thank you. One moment for our next question. And our next question comes from the line of David Reisinger from Lee Ring Partners. Your question, please. Yes, thanks very much.

Operator: And thank you for the update. So my first question is, can you talk a little bit about how you're thinking about the introduction of encephentrine from Verona and what implications that might have for upelry? And then second, if you could just provide a little bit more detail on the execution of the ampyloxetine trial from here, the event path, and then the likely timing of the purse release with the results. Thank you. Okay, Ron, do you want to take encephalopentrin? Absolutely.

EBIT: Part of their part of their presentations that outline the.

EBIT: The medical need and the.

EBIT: Opportunity that <unk> has to meet that medical need through.

EBIT: Through the data that they that they have in that.

EBIT: That is currently published but certainly consolidating it.

EBIT: Into one particular event.

Speaker Change: Got it that's helpful and another one from me.

How should we think about <unk> market opportunity relative to north ore, which I believe achieved $400 million in peak sales given all smart there its shortcomings and <unk> differentiation, how much bigger Gregg <unk>.

Gregg: Well I think we're very we're optimistic on all of the ample occitane and Thats one of the reasons why we.

Rhonda Farnham: Thanks, David, for the question. We're very excited about the opportunity for INSEP and TRIN. Having additional share of voice focused on a nebulized asset in the COPD maintenance space would be tremendous. And thinking about as well how that particular product would enter the market, and most likely still meeting the backbone or the foundation of therapy, thinking about that as an add-on therapy. It's a great opportunity for us to both ensure that the patients that could benefit from both products have that chance. So, you know, on amproloxetine, obviously, you know, we've initiated a lot of sites, as Anya pointed out in her comments, high-quality sites with physicians who understand MSA patients, understand the care of MSA patients, and understand the execution of the clinical trial.

Gregg: Focused on both.

Gregg: My comments as well as obvious comments on.

Gregg: Patient populations the.

Gregg: The fact that there really is no.

Gregg: No solution.

Gregg: <unk>.

Gregg: Thats adequate out there for patients that have MSA.

Gregg: Okay.

Gregg: But in a population of 40000 patients with MSA and NIH and given that you presented.

Gregg: This is in fact, a debilitating condition that keeps many of them.

Gregg: Really unable to interact with.

Gregg: Their environment I think that.

Gregg: Being able to show among multiple different.

Parameters as measured by the <unk> HSA composite score.

Gregg: That we improve the well being of these patients I should I think should open up <unk>.

Rhonda Farnham: We'll continue to activate sites, and there is some work that's necessary there, but more and more work, obviously, is focused on just getting patients into and through the sites for the study. We're making very good progress there, and I think if you split that, this year is a little bit tilted towards patients as opposed to sites, and that's where our focus will be. In terms of where the study is, I think we'll enroll our target, and right now, that's what we believe we can do, is enroll the last patient into the open-label portion in the second half of the year. This would mean data probably sometime in the first half of next year, and that's what we'd be looking forward to, but stay tuned as we progress throughout the year. I think, at least from the science and medicine part of Amproloxetine and the value that it can provide for patients with MSA and NOH, I think, hopefully, our investor event that we have in the second quarter will be able to provide good information to investors about the opportunity that we see there. Great, thank you very much. Yeah,

Gregg: <unk> opportunity.

Gregg: The opportunity for us.

Gregg: And as a reminder, we did we were granted orphan drug designation. This is an orphan drug for a.

Gregg: For a rare disease. So we're.

Gregg: Excited about obviously continuing to progress with the study.

Gregg: The investor event that we have in the in quarter, two which I think they will fill in some more information.

Gregg: And then continue to provide additional information as we work towards closing the study.

Gregg: And and data so.

Speaker Change: Perfect. Thank you and congrats again.

Yes.

Thank you one moment for our next question.

Speaker Change: Yeah.

Speaker Change: And our next question comes from the line of Julian Harrison from <unk>. Your question. Please.

Julian Harrison: Hi, congrats on the quarter and thank you for taking my questions. It was great to see a positive outcome from your phase III trial of <unk> in China back in November.

Julian Harrison: Wondering if you could remind us about how you're thinking about the China market opportunity there and what are the gating steps to filing later this year.

Julian Harrison: And then on Cyprus do you have a good sense now for what the U S. Ex U S enrollment split will likely look like.

Rick E. Winningham: Thanks, David. Thank you. One moment for our next question, and our next question comes from the line of Eva Prevatira from Cowan. Your question, please. Hi, guys.

Julian Harrison: Any big differences there relative to the 107 zero study. Thank you.

Julian Harrison: Ron do you want to comment on China.

Ron: Maybe you can give just a high level comment on U S. Non U S on Cyprus.

Operator: Congratulations on a great quarter, and thanks for taking our questions. I have a question about the Q2 investor events for Amproloxetine. Will there be any additional analyses that we haven't seen before? Yeah, thanks, Eva.

Speaker Change: Rhonda <unk>.

Rhonda: Yes, Thanks, Julien for the question and recognizing in a positive outcome.

Rhonda: That phase III that the interest completed so they will be continuing to prepare and as they've indicated.

Rick E. Winningham: I think, relative to amfraloxetine, additional analysis will be relatively limited. I think, as we mentioned, we will have opinion leaders there that present other analyses, obviously, in both NOH and MSA patients as part of their presentation that outline the medical need and the opportunity that amfraloxetine has to meet that medical need through the data that they have and that is currently published, but certainly consolidating it into one particular event. I got it.

Rhonda: We will be striving to make that filing for the application by the midpoint of this year.

Rhonda: And thinking about.

Rhonda: The the market.

Rhonda: Hi.

Rhonda: For poor you tolerate.

Rhonda: We havent made.

Rhonda: Our.

Rhonda: Communication around an absolute.

Rhonda: Absolute market projection and just thinking about certainly.

Rhonda: Very significant financial burden on that healthcare system, not too dissimilar from the U S.

Rick E. Winningham: That's helpful. And another one from me: how should we think about Amproloxetine's market opportunity relative to Northera, which I believe achieved $400 million in peak sales, given all of Northera's shortcomings? And with Ampulloxidine differentiation, how much bigger could Ampulloxidine be?

Speaker Change: We can ensure that we continue to evaluate what that opportunity can be for you Corey.

And I think just to add to that Julian.

Speaker Change: Beatrice will be will be commercializing the medicine in China, they have a substantial or.

Rick E. Winningham: Well, I think we're very, you know, we're optimistic on, on amproloxetine. That's one of the reasons why we focused on both in, in my comments, as well as Anya's comments on, you know, patient populations, and the fact that there really is no, no solution that's adequate out there for patients that have MSA and NOH. But in a population of 40,000 patients with MSA and NOH, and given that, as Anya presented, this is in fact a debilitating condition that keeps many of them really unable to interact with their environment.

Speaker Change: Organization in China, which is one of the reasons that.

Speaker Change: We licensed <unk>.

Speaker Change: In China.

Speaker Change: I think that.

Speaker Change: <unk>.

Speaker Change: Since it is sort of their their commercial responsibility.

They have.

Speaker Change: I think Theyre calls coming up and then you may you may get some.

Speaker Change: Ask the question of them on an opportunity, but obviously the China market and COPD is is very very large and it's about capturing as much of that opportunity is.

Rick E. Winningham: I think that being able to show among multiple different parameters as measured by the OHSA composite score that we improve the well-being of these patients should open up a significant opportunity for us. And as a reminder, we were granted orphan drug designation. This is an orphan drug for a rare disease, so we're quite excited about obviously continuing to progress with the study, and the investor event that we have in quarter two, which I think will fill in some more information and then continue to provide additional information as we work towards closing the study and data. Perfect. Thank you. Congratulations again.

Speaker Change: It really makes economic sense.

Speaker Change: Julian just to give you some fact bases for the China market itself.

Speaker Change: PD effects of about 100 million patients in that marketplace.

Speaker Change: And a significant roughly 40% of those patients are moderate to very severe patients suffering with COPD. So as you can think about that relative to that being a focus for us here in the U S that can give you some estimates.

Speaker Change: Julian Hey, it's disease. Thanks for the question one additional point to in our 10-K, which we'll file in a couple of days now we're going to be actually disclosing the <unk> economics for both the U S sales.

Julian Harrison: Sales milestones and the China milestones and royalty rates in more detail.

Operator: Thank you. Please take a moment for our next question. And our next question comes from the line of Julian Harrison from BTIG. Your question, please. Hi, congratulations on the quarter, and thank you for taking my questions. It was great to see a positive outcome from your Phase 3 trial of upellery in China back in November. I'm wondering if you could remind us about the China market opportunity there, and what are the gating steps to filing later this year? And then on Cyprus, do you have a good sense now for what the U.S.-ex-U.S. enrollment split will likely look like, any big differences there relative to the 1-7-0 study? Thank you. Ron, do you want to comment on China and then Anya maybe give just a high-level comment on the U.S. non-U.S. position on Cyprus? Rhonda first.

Julian Harrison: Actually break out the sales.

Sales milestone and you can see for the first time, we broke out the actual percentage of the royalties, 14% to 20% so a pretty significant royalty.

Julian Harrison: Each market, obviously, so we're really excited about the opportunity in the economics there.

Speaker Change: Do you want to talk about.

Speaker Change: Epsilon <unk> Julian Thanks for the question on the Cypress study as I alluded to earlier, we've already made a lot of great progress activating sites in Europe and the U S.

Julian Harrison: And we have re engaged in a lot of the sites in the U S and Europe that we had previously engaged and deploy our studies.

Julian Harrison: Would expect that the majority of patients will still come from Europe as it did in the previous program. Although we are making efforts to expand our footprint in the U S and identify additional qualified sites and I spoke about.

Rhonda Farnham: Yes, thanks Julian for the question and recognizing the positive outcome of that phase three that Vietra has completed. So they will be continuing to prepare and, as they've indicated, will be striving to make that filing for the application by the midpoint of this year, and thinking about, you know, the market, you know, for you power users. We haven't made, you know, an outward communication around an absolute, absolute market projection. And just thinking about it, certainly, it's a very significant financial burden on that healthcare system, not too dissimilar from the US.

Julian Harrison: We're going about that in terms of using an AI tool.

Julian Harrison: So overall.

Julian Harrison: I think the more patients will come from Europe, but the actual percentage uplift may differ for Cypress study.

Speaker Change: Hopefully that's helpful very helpful. Thank you again.

Speaker Change: Thank you. This does conclude the question and answer session of today's program I'd like to hand, the program back to Mr. Winningham for any further remarks.

Yes, I'd like to thank you I'd like to just thank everyone for joining us today.

Winningham: Pleased with the accomplishments of 2023 and look forward to.

Winningham: What we can accomplish in 2024, both through effective financial management of the business as well as the growth of <unk> and the execution on the Cypress study in order to bring what we believe will be an important medicine to patients with MSA and an NIH. Thank you very much.

Rick E. Winningham: We can ensure that we continue to evaluate what that opportunity can be for you, Corey. Yeah, and I think, yeah, just to add to that, Julian, you know, Beatrice will be commercializing the medicine in China. They have a substantial organization in China, which is one of the reasons that, you know, we licensed Upelrig to them in China. I think that, you know, they've since it is sort of their, you know, commercial responsibility.

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

Rick E. Winningham: They have a I think their call is coming up, and you may you may get some ask a question of them on that opportunity. But obviously, the Chinese market and COPD are very, very large. And it's about capturing, you know, as much of that opportunity as it really makes economic sense.

Winningham: Okay.

Winningham: Okay.

Winningham: [music].

Winningham: Okay.

Winningham: Okay.

Winningham: [music].

Aziz Suaf: Julian, just to give you some facts about the Chinese market itself, COPD affects about 100 million patients in that marketplace. And a significant, roughly 40 percent of those patients are moderate to very severe patients suffering with COPD. So as you can think about that relative to that being the focus for us here in the U.S., I think that can give you some estimates. Hey, Julian.

Winningham: Okay.

Winningham: Okay.

Winningham: Okay.

Winningham: [music].

Winningham: Yes.

Winningham: [music].

Anya Miller: Thanks for the question. One additional point, in our 10k, which we'll file in a couple days now, we're going to be disclosing the upholstery economics for both the US and China, Sales Milestones and the China Milestones and Royalty Rates in More Detail, so we'll actually break out the sales milestones, and you can see for the first time we broke out the actual percentage of the royalties, 14 to 20%, so a pretty Anya, do you want to talk about AmpliOxyzine? Julian, thanks for the question on the Pfeiffer study.

Winningham: Okay.

Winningham: [music].

Winningham: Okay.

Winningham: Yes.

Winningham: Yes.

Winningham: [music].

Operator: As I alluded to earlier, we've already made a lot of great progress with activating Pfeiffer in Europe and the U.S., and we have re-engaged a lot of the sites in the U.S. and Europe that we had previously engaged in prior studies. I would expect that the majority of patients will still come from Europe, as it did in the previous program, although we are making efforts to expand our footprint in the U.S. and identify additional qualified sites, and I spoke about how we're going about that in terms of using an AI tool. So overall, I think more patients will come from Europe, but the actual percentage of the split may differ for a cypress study. Hopefully, that's helpful. Very helpful. Thank you again.

Winningham: Okay.

Winningham: [music].

Winningham: Okay.

Winningham: [music].

Winningham: Yes.

Winningham: [music].

Winningham: Yes.

Winningham: [music].

Rick E. Winningham: Thank you. This does conclude the question and answer session of today's program. I'd like to hand the program back to Mr. Winningham for any further remarks. Yeah. Thank you.

Winningham: Okay.

[music].

Operator: I'd like to just thank everyone for joining us today. We're pleased with the accomplishments of 2023 and look forward to what we can accomplish in 2024, both through effective financial management of the business, as well as the growth of Upellery and the execution of the CIPHR study in order to bring what we believe will be an important medicine to patients with MSA and NOH. Thank you very much.

Winningham: Yes.

Winningham: [music].

Winningham: Okay.

Winningham: Thanks.

Winningham: Yes.

Winningham: [music].

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

Operator: Good day. Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Tyler Buren, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc, ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Tyler Buren, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc, © The Bulletproof Executive 2013 ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Tyler Buren, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, Theravance Biopharma Inc Tazeen Ahmad, Umer Raffat, Douglas Tsao, Josh Schimmer, Brett Haumann, Frank Pasqualone, Andrew Hindman, 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.

Winningham: Okay.

Winningham: [music].

Winningham: Okay.

Winningham: [music].

Winningham: Okay.

Winningham: Yes.

Winningham: Yes.

Winningham: Okay.

Winningham: [music].

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Winningham: Okay.

Winningham: [music].

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[music].

Winningham: Okay.

Winningham: Yes.

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Winningham: [music].

Winningham: Okay.

Winningham: Okay.

Winningham: Okay.

Winningham: Great.

Winningham: Sure.

Winningham: Yes.

Winningham: [music].

Rick E. Winningham: A question and answer session will follow the company's formal remarks. To ask a question, press the star key followed by the digit 1 1 on your telephone. Again, that's Star 1 1 to ask a question. If listening via webcast, please mute the 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.

Winningham: Sure.

Winningham: Yes.

Winningham: [music].

Winningham: Sure.

Winningham: Thanks.

Winningham: Yes.

Winningham: Okay.

Winningham: [music].

Okay.

Winningham: [music].

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Winningham: Okay.

Winningham: Okay.

Winningham: Okay.

Winningham: Yes.

Winningham: Yes.

Winningham: Okay.

Winningham: [music].

Rick E. Winningham: Good afternoon, everyone, and thank you for joining the Theravance 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 and 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.

Winningham: Okay.

Winningham: Okay.

Okay.

Winningham: Okay.

Winningham: [music].

Winningham: Yes.

Winningham: Okay.

Winningham: [music].

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Winningham: [music].

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Winningham: Yes.

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Winningham: Sure.

Winningham: Okay.

Winningham: Sure.

Winningham: <unk>.

Winningham: Yes.

Winningham: Okay.

Winningham: Yes.

Winningham: [music].

Rick E. Winningham: Our Head of Development, Rhonda Farnham, Theravance's Chief Business Officer, and Aziz Suaf, 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 ancillary growth and maximizing AmpliLox'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 the power net sales by nine percent from sixty one million and two hundred and twenty one million, respectively, as recorded by Vietras.

Winningham: Yes.

Winningham: Okay.

Winningham: Okay.

Winningham: Thanks.

Winningham: Okay.

Winningham: Okay.

Winningham: Okay.

Winningham: Okay.

Winningham: Yes.

Winningham: Yes.

Winningham: Yes.

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Winningham: Okay.

Winningham: Yes.

Winningham: Yes.

Winningham: Sure.

Winningham: Yes.

Winningham: Okay.

Winningham: Okay.

Rick E. Winningham: We grew hospital volumes and an outstanding 46 percent for the year and set the business up for continued momentum in twenty twenty four. We initiated Amproloxetine's CIPRA study and began, 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 Amproloxetine from price negotiations associated with inflation reduction. 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-gap profitability in the fourth quarter, which involved significant efforts on the part of the entire Theravance team. In addition, we completed our $325 million, $1,000,000 Capital Return Program within the first few days of January while maintaining a strong financial profile.

Winningham: Thanks.

Winningham: Yes.

Winningham: Okay.

Winningham: Thank you.

Winningham: Yes.

Winningham: Okay.

Winningham: Thank you.

Winningham: Okay.

Winningham: Okay.

Winningham: Yes.

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Winningham: Yes.

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Winningham: Okay.

Winningham: [music].

Winningham: Thank you.

Winningham: Thanks.

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Winningham: Okay.

Winningham: Yes.

Winningham: Thanks.

Winningham: Yes.

Winningham: Okay.

Winningham: Okay.

Winningham: [music].

Speaker Change: Ladies and gentlemen, good afternoon, I would like to welcome everyone to the thorough Vance 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.

Rick E. Winningham: Now, on slide five, I'll cover plans and anticipated financial performance for the upcoming year, beginning with Upelri. We expect to grow Upelri net sales in partnership with Beatrice 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 Viatris submitting a regulatory application for UPAURI in China by mid-year, which will put us on a path toward achieving meaningful economics in that territory.

Speaker Change: One one on your telephone again Thats star one to ask a question.

Speaker Change: If listening via webcast. Please mute audio on your webcast device before asking your 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.

Rick E. Winningham: Turning to ampyloxetine, we're focused on completing the CYPR 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 Ampriloxy. 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-GAP. During the second half of the year, subject to the timing of upellery growth and Cypress progress, we plan to approach break-even on a non-GAP.

Rick E. Winningham: Good afternoon.

Rick E. Winningham: New to everyone and thank you for joining the <unk> Biopharma fourth quarter and full year 2023 earnings results Conference call.

Rick E. Winningham: Turning to slide two I'll 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.

Rick E. Winningham: Anticipated timing of clinical trials regulatory filings and expected financial results and information containing factors that could cause results to differ materially from our forward. Looking statements is described further in our filings with the SEC.

Rick E. Winningham: I'm joined by Anya Miller.

Rick E. Winningham: Our head of development, Ronda, Florida, Thereabouts, as Chief business Officer, and as these swap our Chief Financial Officer.

Rick E. Winningham: We plan to limit cash utilization, and we believe we're 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 Upelri and Amproloxetine, 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 the Appellary 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 U.S. upellery net sales reach $250 million Additional information on our milestones and royalties may be found in our SEC filings.

Rick E. Winningham: On slide four I'll begin by hitting the high points for a very productive 2023 for thorough events. We began the year with the decision to focus on driving <unk> growth and maximizing <unk> value, while increasing our capital return program.

Rick E. Winningham: I am pleased to report that our team delivered on these objectives for both the fourth quarter and the full year, we increased the power or is that net sales nine per sale from.

Rick E. Winningham: From $61 million and $221 million, respectively as as recorded by via trips, we groove hospital volumes that outstanding 46% for the year and set the business up for continued momentum in 2024.

Rick E. Winningham: We initiated <unk> Cypress study and began immediately began evaluating and activating sites around the world.

Rick E. Winningham: In May we were granted orphan drug status, which confers important financial advantages such as tax credits and user fee Act exemption.

Rick E. Winningham: Exemptions and shields and philosophy and from price negotiations.

Rick E. Winningham: Moving to slide eight to focus on amyloxetine. 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 Amproloxtene's potential to represent a major advance for these patients. The company retains commercial rights to Amproloxtene 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.

Rick E. Winningham: Associated with the inflation reduction there.

Rick E. Winningham: 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.

Rick E. Winningham: Turning to our corporate progress I'm proud to have delivered on our promise of reaching non-GAAP profitability in the fourth quarter, which involve significant efforts on the part of the entire <unk> team.

Rick E. Winningham: In addition, we completed our 325 million.

Rick E. Winningham: Dollar capital return program within the first few days of January while maintaining a strong financial profile.

Rick E. Winningham: Now on slide five I'll cover plans and anticipated financial performance for the upcoming year, beginning with your Perl rate, we expect to grow your powering net sales in partnership with via Trust and build on profit margin improvements experienced in 2023.

Rick E. Winningham: It's often misdiagnosed, with many patients not confirmed to have MSA for months to years after symptoms begin. Unfortunately, most epidemiological research was conducted decades ago on Parkinsonism, more generally using survey techniques with significant limitations. For example, one offline 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 analyses rely on the use of the real world's claims databases and capture important geographic variances and demographic trends which affect MSA prevalence as, 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 the MSA Center of Excellence and the National Institutes of Health.

Rick E. Winningham: We set ambitious goals for our hospital business in 2024, which we believe will translate into future share gains in the long acting nebulous Asian market.

Rick E. Winningham: Finally, we look forward to vitro submitting our regulatory application for <unk> in China by mid year, which will put us on a path towards achieving meaningful economics in that territory.

Rick E. Winningham: Turning to <unk>, we are focused on completing the Cypress study. In addition, we expect to initiate.

Rick E. Winningham: Regulatory and early commercialization preparations as we progress through the year.

Rick E. Winningham: We're very excited to host a virtual investor event during the second quarter, where we will bring MSA experts in senior leadership from Terra events together to discuss the unmet need in MSA patients with symptomatic NIH and the expected benefits of <unk>.

Rick E. Winningham: Turning to our 2024 financial outlook, we expect the annual collaboration growth to remain strong 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 your <unk> growth in Cyprus progress we.

Rick E. Winningham: Based on this figure, we believe that the addressable U.S. population for ampyloxacine is approximately 40,000 MSA patients suffering from symptomatic NOA. 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 U.S. 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 Amproloxetine and provide an update on the progress Anya?

Rick E. Winningham: Turning to approach breakeven 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 hire of $50 million.

Rick E. Winningham: Nope.

Rick E. Winningham: If you turn to slide six Youll see an updated summary of our compelling value proposition in.

Rick E. Winningham: In addition to empowering ample oxitec and 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 the palmary enterology over time.

Rick E. Winningham: Specifically in addition to the trilogy milestones that I referenced we stand to receive a onetime sales milestone of $25 million when the U S. <unk> net sales reached $250 million in any calendar year.

Anya Miller: Thanks, Rick. Let's begin with slide 11. MSA is an incurable neurodegenerative disorder associated with inappropriate deposits of alpha-synuclein in the brain.

Anya Miller: 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 perfusion in their upper extremities, and face a higher risk of falls.

Rick E. Winningham: Additional information on our milestones and royalties may be found in our SEC filings.

Rick E. Winningham: Moving to slide eight to focus on <unk>.

Rick E. Winningham: We're motivated to make <unk> available to patients as expeditiously as possible.

Rick E. Winningham: The Cypress results support approval for the tens of thousands of MSA patients around the world, who suffer from symptomatic moh without effective treatment options.

Rick E. Winningham: Data, thus far support <unk> potential to represent a major advance for these patients the company retained commercial rights to <unk> worldwide.

Rick E. Winningham: On slide nine I'll start with the considerable unmet need in the United States.

Rick E. Winningham: MSA as a neuro degenerative disease that shares features with other movement disorders, such as Parkinsons disease.

Rick E. Winningham: It's often misdiagnosed with many patients not confirmed have MSA for months to years after symptoms begin.

Rick E. Winningham: Unfortunately, most epidemiology research was conducted decades ago on parkinsonism more generally using survey techniques with significant limitations.

Anya Miller: Not surprisingly, a significant majority of patients with symptomatic NOH report that they have a reduced ability to perform daily activities, while many also express 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.

Rick E. Winningham: For example, one off sided study relies on a 25 year old survey of 15 general practices in London.

Rick E. Winningham: Using this limited sample some have suggested that there are.

Rick E. Winningham: Approximately 14000.

Rick E. Winningham: Digital's with MSA in the United States, given the country's current population.

Rick E. Winningham: 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.

Anya Miller: 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 Droxedopa to treat dizziness in patients with NOH. Based on the still high unmet need for these patients, the FDA granted Droxydopa conditional or accelerated approval, after initially having rejected the sponsor's application, and despite Droxydopa having failed in two of the four Phase III studies included in the application. As with Midodrine, Droxedopa is dosed multiple times a day and carries a black box warning for supine hypertension. However, it has never demonstrated a durable effect on NOH symptoms beyond two weeks of treatment in a double blind study.

Rick E. Winningham: These analyses support a much higher estimate of roughly 50000 individuals which is consistent with estimates for both the UCSD Department of Neurosciences and MSA Center of excellence and the National Institutes of health.

Rick E. Winningham: Based on this figure we believe that the addressable U S population for <unk> is approximately 40000 MSA patients suffering from symptomatic anyway.

Rick E. Winningham: Turning to slide 10, our goal is to make <unk> available to MSA patients with symptomatic <unk> worldwide and.

In Europe, and Asian countries, including the EU, five Japan, and China. The number of addressable patients is several fold larger than it is in the U S 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.

Speaker Change: To characterize the value that we see in <unk> and provide an update on the progress, we're making with Cypress Anya.

Speaker Change: Thanks, Rick.

Anya Miller: 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, droxedopa is still only prescribed to a small percentage of MSA patients with NOH. Let's fast forward to today, 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 CIFRS study, we anticipate that amperloxacine will represent a significant advance for these individuals, given the benefits it has demonstrated to date, and praloxetine'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.

Rick E. Winningham: Again on slide 11.

Speaker Change: <unk> is an incurable neurodegenerative disorder associations with inappropriate deposits of Alpha <unk> in the brain.

Rick E. Winningham: MSA patients experience, a progressive loss of autonomic function as well as challenges withstanding walking speaking on swallowing money also experienced depression and anxiety.

Rick E. Winningham: Adding to what you guys are amazing 19, UK survey of over 10000 patients, but neurological disorders.

Rick E. Winningham: MSA ranks as having the second most of their impact on quality of life of any neurological disorder study ahead of disorders like progressive Supranuclear palsy, Huntington's disease, and Parkinson's disease among others.

Rick E. Winningham: Neurogenic, orthostatic hypotension, which caused a significant and unremitting drop in blood pressure upon standing FX by four and five patients with MSA.

Rick E. Winningham: Patients with symptoms of Noaa's may feel dizzy sitting or standing.

Rick E. Winningham: Unable to stand or walk or even short periods of time feel pain associated with the lack of perfusion and their upper extremities and face a higher risk of hall.

Rick E. Winningham: Not surprisingly a significant majority of patients with symptomatic <unk> report that they have a reduced ability to perform daily activities. While money also expressing a loss of independence.

Anya Miller: Moreover, as the first novel therapy in years, we are optimistic that we will be able to build a case for broad access and significant adoption in the population for which it is indicated, should amperloxidase 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 Cyprus rather than using the traditional CRO model.

Rick E. Winningham: As I'll discuss on slide 12, MSA patients with symptomatic NIH lack of safe convenient and durable effects of treatment option.

Rick E. Winningham: While non pharmacological therapies are available they are often insufficient to control symptoms.

Rick E. Winningham: 30 years ago, the FDA approved a product called <unk> on the basis of its ability to increase blood pressure. However, <unk> is not indicated to improve symptoms of <unk> must be taken three times daily and carries a black box warning for its potential to lead to a marked elevation of <unk> blood pressure.

Anya Miller: 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 Cyprus 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 across the United States.

Rick E. Winningham: Nearly 20 years later, the FDA approved a second drove call. It roughly two to three business in patients with NIH based understand a high unmet need for these patients the FDA granted roughly to open a conditional or accelerated approval.

After initially having rejected the sponsors application and despite trustee to Elfa sale two of the four phase III studies included in the application.

Rick E. Winningham: <unk> is dosed multiple times, a day and carries a black box warning specified hypertension.

Rick E. Winningham: And have never demonstrated a durable effect on NOI H symptoms beyond two weeks of treatment in a double blind study and.

Rick E. Winningham: And more recently based on data reported on clinical trials Dot Gov and failed to demonstrate a benefit in the convert Mitre study requested by the FDA known as restore.

Anya Miller: Finally, we are early adopters of telehealth and have incorporated options for patients and clinical personnel to participate in CyPERS even if factors limit patients' 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 PFIPRS, 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 meaning.

Rick E. Winningham: Based on third party analysis of claims on prescription data dressy dopa is still only prescribed to a small percentage of MSA patients, but anyways.

Rick E. Winningham: Let's fast forward to today and it has been more than a decade since MFA patients with symptomatic <unk> have been offered a novel treatment alternatives.

Rick E. Winningham: While we still have important work to do to confirm its clinical profile and the Cypress study, we anticipate that philosophy and when represents a significant advance for these individuals given the benefit that has demonstrated to date.

Rick E. Winningham: <unk> durable impact on a broad range of annual hedge symptoms and 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.

Rick E. Winningham: Hey for a broad access and significant reduction in the population for which it is indicated.

Rick E. Winningham: <unk> be approved.

Rick E. Winningham: Now shifting gears to the Cyprus study on slide 13, I'd like to share our approach and the progress that we're making.

Anya Miller: 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.

Rick E. Winningham: As many of you know Paragon is directly managing study commvault for cypress, rather the unutilized in the traditional payroll model.

Rick E. Winningham: By design, we are deeply involved in identifying sites the highest standard for clinical conduct investigators who understand the complexities of managing <unk> MSA and patients the best credits that criteria of the Cypress study.

Rick E. Winningham: We are informed by our experience in study 106, 9% and 170 and have reinvested money at the same sites and Kols involved in those studies beyond this we have enriched our network to AI efforts, but leverage claims information and work of data scientists and our own expertise.

Anya Miller: 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 17. 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 altering the application. At this point, I'll turn the call over to Rhonda to discuss two powers.

Rick E. Winningham: This has allowed us to identify additional product by sites in the United States.

Rick E. Winningham: Finally, we are early adopters of telehealth and haven't cooperated option for patients and clinical personnel to participate in Cyprus, even if factors limit patients' ability to undergo evaluations and mechanic.

Rick E. Winningham: We are pleased with the internal metrics, we're monitoring thus far which are consistent with our expectations and study 170.

Rick E. Winningham: While we don't want to comment specifically on enrollment we continue to make excellent progress activating sites, including money outside of the United States.

Rhonda Farnham: Thanks, Anya. Beginning on slide 15, I'm pleased to report that the Theravance and Beatrice Commercial Partnership finished the year strong, having driven annual net sales growth of 9% for the full year of 2023. Fourth quarter net sales reached $60.6 million, and full-year sales reached $221 million, with Upelri recording its highest level of profitability since long. Although quarter to quarter results can vary depending on the timing of shipments and other seasonal factors, we remain optimistic about Upelry's continued growth based on the success we are delivering in the hospital channel as well as several key performance indicators we track across the business. While Real Eye sales this quarter closely tracked demand generation, we have traditionally experienced seasonal dips in reported net sales as we transition from the fourth quarter to the first quarter of the following year.

Rick E. Winningham: Shifting now to the right hand side of slide 13, we have aligned with the FDA on the design of Cypress, including the use of the Orange Bank composite score.

Rick E. Winningham: <unk> is an assessment of orthostatic hypotension symptom severity as the primary endpoint.

Rick E. Winningham: When using patient reported outcome measures such as OSA. The FDA recommends anchoring these data in order to determine clinical meaningfulness.

Rick E. Winningham: In November at the AAN annual meeting, we presented data from our anchor based analysis of study 106, nine and $1 70, which support the use of the Orange is a composite score for MSA patients that NIH as well as the threshold for which is considered a clinically meaningful change.

Rick E. Winningham: Our analysis demonstrated that threshold improvements and worsening of approximately one point on the OSA alright, Thank and partners more considered clinically meaningful.

Rick E. Winningham: This is important as it supports our Cypress study design and compares favorably to the one six point benefit we saw on this measure in MSA patients in study 170 <unk>.

Rick E. Winningham: Finally in order to minimize the time from Cypress completion to potential commercial availability, we have already completed much of the work required for NDA submission and are in the progress process of ordering the application at this point I will turn the call over to Rhonda <unk> Henri.

Rhonda Farnham: Moving to slide 16, I'm also very pleased to share with you the exceptional finish to the year our hospital team was able to deliver. Hospital doses shipped in the fourth quarter increased 37% year over year, with full growth reaching 46%. This was easily the highest volume quarter for the hospital channel delivered since launch. As you know, our goal continues to be to increase the number of patients exposed to upillary during hospitalization who are then discharged on upillary as maintenance patients. This is achieved by gaining support for formulary inclusion, implementation of hospital protocols involving all nebulization strategies and therapeutic interchanges, and equally important, high-touch transition of care program. Our market research continues to demonstrate that the vast majority of patients who initiate upelry in the hospital setting receive a prescription for upelry maintenance care at discharge.

Rhonda: Thanks Tanya.

Rhonda: Beginning on slide 15, I'm pleased to report that the theater events and Beatrice commercial partnership finished the year strong.

Rhonda: Having driven repowering net sales growth of 9% for the full year of 2023.

Rhonda: Fourth quarter net sales reached $60 6 million and full year sales reached $221 million with <unk> recording its highest level of profitability since launch.

Rhonda: Although quarter to quarter results can vary depending on the timing of shipments and other seasonal factors.

Rhonda: Remain optimistic for <unk> continued growth based on the success, we are delivering in the hospital channel as well as several key performance indicators, we track across the business.

Rhonda: While realized sale this quarter closely track with demand generation.

Rhonda: Have traditionally experienced seasonal dips and reported net sales as we transition from the fourth quarter to the first quarter of the following year.

Rhonda: Moving to slide 16.

Rhonda Farnham: It is with the execution of this winning strategy that our small but focused commercial organization is able to make a considerable contribution to the overall retail business, both directly and indirectly. Turning to slide 17, on the left side, you can see the impact our efforts have had on our hospital market share. During the quarter, our share of the long-acting MIM market in the hospital segment increased to 16.6%, while on the right side of the slide, Upelry achieved a 31% share in the community, up nearly four percentage points year over year. We attribute both segments' share growth to the increasing traction of our concomitant therapy messaging. This taps into the significant number of COPD patients who remain symptomatic on LABA therapy and could benefit from the addition of a LAMA, which is foundational in the treatment of COPD and references the 2022 changes to the Gold Report guidelines, which recommend dual LABA and LAMA therapy for Category B and E patients.

Speaker Change: I'm also very pleased to share with you the exceptional finish to the year our hospital team was able to deliver.

Speaker Change: Hospital doses shipped in the fourth quarter increased 37% year over year with full growth reaching 46%.

Speaker Change: This was easily the highest volume quarter for the hospital channel delivered since launch.

Speaker Change: As you know our goal continues to be to increase the number of patients.

Speaker Change: Suppose to Du pillory during hospitalization, who are then discharged on mute Hillary as maintenance patients.

Speaker Change: This is achieved by gaining forming.

Speaker Change: Gaining support for formulary inclusion implementation of hospital protocols involving all <unk> strategies, and therapeutic interchanges and equally important high touch transition of care programs.

Speaker Change: Our market research continues to demonstrate that the vast majority of patients to initiate <unk> in the hospital setting.

Speaker Change: If a prescription of <unk> maintenance care at discharge.

Speaker Change: It is with the execution of this winning strategy that are small, but focused commercial organization is able to make a considerable contribution to the overall <unk> business, both directly and indirectly.

Rhonda Farnham: As a basis for speaking to the trends we have achieved in the retail setting, where we have our most real-time and current demand view outside of the hospital channel, we felt it might be helpful to share another visual. If you turn to slide 18, we provide data on the fulfillment growth trends in both the total community and retail segment settings through the third quarter of the year. At the time that we share our quarterly results, we do not have a completed data capture of fulfillment in the DME channel, which accounts for approximately 60% of our total community business. Because retail, which accounts for the other 40%, generally correlates with total community fulfillment over time, we have historically offered this view.

Speaker Change: Turning to slide 17 on the left side you can see the impact of our efforts have had on our hospital market share.

Speaker Change: During the quarter, our share of the long acting <unk> market in the hospital segment increased to 16, 6% while on the right side of the slide <unk> achieved a 31% share in the community.

Speaker Change: Up nearly four percentage points year over year.

Speaker Change: We attribute both segments share growth to the increasing traction of our concomitant therapy messaging.

Speaker Change: This taps into the significant number of COPD patients, who remain symptomatic on LABA therapy and could benefit from the addition of a llama, which is foundational in the treatment of COPD and references to 2022 changes to the gold report guidelines, which recommend duo LABA.

Rhonda Farnham: You will find our most up-to-date performance in the retail channel on Slide Night. Looking at the left side of slide 19, retail prescriptions grew a robust 7% sequentially during the quarter, which is consistent with recent brand performance trends. Looking to the right side of the slide, we also grew new product starts by sequential 7% in Q4. You may remember from our last update that we had experienced some quarter-to-quarter seasonality in new starts, which is not atypical for this metric in Q3.

Speaker Change: Llama therapy or category, B and <unk> patients.

Speaker Change: As a basis for speaking to the trends we have achieved in the retail setting where we have our most real time and current demand do you outside of the hospital channel we felt it might be helpful to share another visual.

Speaker Change: If you turn to slide 18, we provide data on the fulfillment growth trends in both the total community and retail segment settings through the third quarter of the year.

Speaker Change: At the time that we share our quarterly results, we do not have a completed data capture of fulfillment in the <unk> channel.

Speaker Change: Which accounts for approximately 60% of our total community business.

Rhonda Farnham: As anticipated, however, we were able to drive a sequential return to growth in Q4. Finishing on slide 20, we think it is important to highlight the unique and compelling value proposition we offer patients and caregivers as the only once daily nebulized llama for maintenance treatment of COPD. Upelry has demonstrated consistently meaningful lung function benefits, is typically available at low out-of-pocket costs and requires only a few minutes to administer once per day

Speaker Change: Because retail which accounts for the other 40% generally correlate with total community fulfillment overtime.

Speaker Change: We have historically offered this SKU.

Speaker Change: You will find our most up to date performance in the retail channel on slide 19.

Speaker Change: Looking at the left side of slide 19, retail prescriptions grew a robust 7% sequentially during the quarter, which is consistent with recent brand performance trends looking to the right side of the slide we also grow new product starts a sequential 7% in Q4.

Rhonda Farnham: As such, we believe upelry plays a key role in the COPD market, where there remains a substantial opportunity to reach patients who could benefit from upelry. Our go-to-market strategy aligns with this profile, which we believe is why Upelri is only one of three branded COPD maintenance therapies in the U.S. that is delivering consistent growth. Looking ahead, we expect to achieve continued growth and value creation for upell driven both by continued penetration of the US maintenance COPD market and a potential launch of Upellry in China. Lastly, in the U.S., we are eligible to receive a one-time sales milestone of $25 million from Beatrice when Upelri net sales reach $250 million in any calendar year. In China, where Viatris is planning to file for regulatory approval by the middle of this year, we are eligible to receive a $7.5 million milestone upon approval, as well as additional sales milestones and upwardly tiered royalties of between 14 and 20%. That brings us to the end of the Pellery update. So I will turn things over to Aziz to cover our financials. Aziz.

Speaker Change: May remember from our last update that we had experienced some quarter to quarter seasonality and new starts which is not atypical for this metric in Q3.

Speaker Change: As anticipated however, we were able to drive a sequential returned to growth in Q4.

Speaker Change: Finishing on slide 20, we think it is important to highlight the unique and compelling value proposition, we offer patients and caregivers as the only once daily Nebulizer Lama for maintenance treatment of COPD.

Speaker Change: <unk> has demonstrated consistently meaningful lung function benefits is typically available at low out of pocket cost and requires only a few minutes to administer once per day.

Speaker Change: As such we believe <unk> plays a key role in the COPD market, where there remains a substantial opportunity to reach patients who could benefit from <unk>.

Speaker Change: Our go to market strategy aligns with this profile, which we believe is why <unk> is only one of three branded COPD maintenance therapies in the U S that is delivering consistent growth.

Speaker Change: Looking ahead, we expect to achieve continued growth and value creation for your power driven both by continued penetration of the U S maintenance COPD market.

Aziz Suaf: Thanks, Rhonda. Starting off with the results for the quarter, 522 and 23 cover the detailed financials; I'll cover the highlights on slide 24. Starting with collaboration revenue, we reported an all-time high of $17.4 million, representing year-over-year growth of 19%. Operating expenses were in line with expectations for the quarter, resulting in full-year operating expenses, excluding share-based comp, to be under the low end of R&D guidance and within the range for ST&A and total operating expenses.

And the potential launch of <unk> in China.

Speaker Change: Lastly in the U S. We are eligible to receive a one time sales milestone of $25 million from Beatrice when you're powering net sales reached $250 million in any calendar year.

Speaker Change: In China, where <unk> is planning to file for regulatory approval by the middle of this year, we are eligible to receive a $7 $5 million milestone upon approval as.

Speaker Change: As well as additional sales milestones and I'll quickly tiered royalties of between 14 and 20%.

Aziz Suaf: The combination of judicious expense management and increased capillary net sales led to a non-gap profit of $1.4 million in the quarter. Please note that our gap loss of $8.5 million was affected by a larger-than-expected income tax expense in the quarter, primarily due to better-than-expected results and other non-cash charges from one of our operating expenses. However, this is a non-cash item, and we expect to have immaterial if any cash tax is payable for 2023. In Q4, we repurchased approximately $30 million worth of shares, leaving $400,000 on the return of capital program at quarter end, which was completed in early January. This reduced our share count by 3 million shares in the quarter and by 31 million shares from the program's inception, a 37% reduction in the share count. We closed the period with 102 million in cash and approximately 48 million shares outstanding.

Speaker Change: That brings us to the end of the salary update so I will turn things over to <unk> to cover our financials.

Thanks, Rhonda starting off with the results for the quarter Slide 22, and 'twenty three cover the detailed financials I'll cover the highlights on slide 24, starting with collaboration revenue reported an all time high of $17 4 million representing year over year growth of 19% on operating expenses.

Speaker Change: We're in line with expectations for the quarter, resulting in full year operating expenses, excluding share based comp to be under the low end of R&D guidance and within the range for SG&A in total Opex. The combination of judicious expense management and increased salary net sales led to a non-GAAP profit of $1 $4 million in the.

Speaker Change: Sure.

Speaker Change: Please note that our GAAP loss of $8 $5 million was affected by a larger than expected income tax expense in the quarter.

Speaker Change: <unk> due to better than expected results and other noncash charges from one of our operating entities. However.

Speaker Change: However, this is a noncash item and we expect to have immaterial, if any cash taxes payable for 2023.

Speaker Change: In Q4, we repurchased approximately $30 million worth of shares leaving 400000 on the return of capital program at quarter end.

Speaker Change: Which was completed in early January.

Speaker Change: This reduced our share count by 3 million shares in the quarter by 31 million shares from the program's inception.

Aziz Suaf: On slide 25, I'll provide an update on our potential to earn milestones from Trilogy, noting that GSK delivered another excellent quarter of growth. Quarterly and year-to-date sales reached $737 million and $2.7 billion, respectively, up 35% and 28% year-over-year. As a result, we are well-positioned to achieve milestones in 2024 and beyond. Compared with 2023 actuals, we need only 5% growth in annual net sales to achieve the first $25 million milestone and 17% to achieve the second $50 million milestone. As a reminder, these milestones are not cumulative. If both milestones were to be achieved, we would receive a total of $50 million, not $75 million. Lastly, turning to financial guidance on slide 26, we will continue to provide R&D and SG&A operating expense guidance excluding share-based comp in 2024. In addition, to enhance our financial disclosure, we will be adding non-cash share-based compensation to our guidance metric. For R&D OPEX, excluding share-based comp, we are expecting between $30 and $36 million, which will be exclusively allocated to EPRLOC.

Speaker Change: 37% reduction in share count.

We closed the period with $102 million in cash and approximately 48 million shares outstanding.

Speaker Change: On slide 25, I'll provide an update on our potential to earn milestones from trilogy.

Speaker Change: The GSK delivered another excellent quarter of growth quarter.

Speaker Change: Quarterly and year to date sales reached $737 million and $2 7 billion, respectively up 35% and 28% year over year.

Speaker Change: As a result, we are well positioned to achieve milestones in 2024 and beyond compared with 2023 actuals, we need only 5% growth in annual net sales to achieve the first $25 million milestone and 17% to achieve the second $50 million milestone.

Speaker Change: As a reminder, these milestones are not cumulative.

Speaker Change: Both milestones were to be achieved we would receive a total of $50 million not $75 million.

Lastly, turning to financial guidance on Slide 26, we will continue to provide R&D and SG&A operating expense guidance, excluding share based comp in 2024. In addition to enhance our financial disclosure, we will be adding noncash share based compensation to our guidance metrics.

Speaker Change: For R&D Opex, excluding share based comp we are expecting between 30 and $36 million, which will be exclusively allocated to <unk> team.

Aziz Suaf: A significant majority of this will be for the Cypress study execution. In addition, guidance includes gated spend towards NDA preparation, primarily during the second half of the year. The ungating of this spend will depend on being on track with Cypress enrollment in line with industry best practices. For SG&A OPEX, excluding share-based comp, we are expecting between $45 and $55 million.

Speaker Change: I forget the majority of this will be for the Cypress study execution.

Speaker Change: In addition guidance includes gated spend towards NDA preparation, primarily during the second half of the year.

Speaker Change: The gating of the spend will depend on being on track with Cypress enrollment in line with industry best practices.

For SG&A Opex, excluding share based comp, we're expecting between 45 and $55 million.

Aziz Suaf: While our UPALRI-related spend will be largely flat year over year, guidance includes incremental spend for AMPRLOC's team pre-launch commercial activities, primarily in market research, medical affairs, and market access, which will occur mostly in the second half of the year. Given our focus on expected return on invested capital, any incremental spending for pre-launch activities will be gated based on Cypress enrollment and will be subject to board approval. Partially offsetting these increases is a reduction in G&A spend by approximately 20% driven by ongoing cost-cutting initiatives.

Speaker Change: Our <unk> related spend will be largely flat year over year guidance includes incremental spend for <unk> prelaunch commercial activities.

Speaker Change: Marilee in market research Medical affairs, and market access, which will occur mostly in the second half of the year.

Speaker Change: Given our focus on expected given our focus on expected return on invested capital any incremental spending for prelaunch activities will be gated based on Cyprus enrollment and will be subject to board approval.

Partially offsetting these increases is a reduction of G&A spend by approximately 20% driven by ongoing cost cutting initiatives.

Aziz Suaf: Starting in Q1, we will break out GNA separately from sGNA within our mDNA commentary in our 10 Qs and 10 Ks. For share-based comp, we are expecting between $18 and $22 million, the midpoint reflecting a year-over-year reduction of approximately 20 percent. In terms of our non-gap metric, we expect we will turn from a non-gap profit in Q4 2023 to a non-gap loss in early 2024. This is due to an expected decrease in collaboration revenue in Q1 from Q4 2023 driven by typical seasonality for upellery net sales, as mentioned by Rhonda, combined with a temporary increase in R&D spend due to the expected rapid patient enrollment and Turning to the second half of 2024, we expect our non-gap metric to approach breakeven, which will be dependent on continued net sales growth for Upellery, as well as the amount of spend on Amperloch's team for pre-launch commercialization.

Speaker Change: Starting in Q1, we will breakout G&A separately from SG&A within our MD&A commentary in our 10-Qs and 10-K.

Speaker Change: For share based comp, we are expecting between 18 and $22 million the midpoint, reflecting a year over year reduction of approximately 20%.

Speaker Change: In terms of our non-GAAP metric, we expect we will turn from our non-GAAP profit in Q4 2023 to a non-GAAP loss in early 2020 for.

Speaker Change: This is due to an expected decrease in collaboration revenue in Q1 from Q4 of 2023, driven by typical seasonality for <unk> net sales as mentioned by Rhonda combined with a temporary increase in R&D spend due to the expected ramp in patient enrollment and site initiation for the Cypress study.

Speaker Change: Turning to the second half of 2024, we expect our non-GAAP metric to approach breakeven, which will be dependent on continued net sales growth for <unk> as well as the amount of spend on <unk> team prelaunch commercialization.

Aziz Suaf: As discussed on prior earnings calls, this non-GAAP metric is a proxy for cash flow, and we therefore expect limited cash burn in 2024, most of which will be incurred early in the year. Given multiple potential milestones in 2024 and beyond, such as the $25 or $50 million milestone for Trilogy, we expect to generate net cash prior to the Cyprus top-line data readout in 2025. Lastly, we may continue to incur non-cash income tax expense of several million each quarter. However, we continue to expect to have immaterial, if any, cash taxes in 2024 from ongoing operations. With that, I'll pass it back to Rick to conclude. Rick.

Speaker Change: As discussed on prior earnings calls this non-GAAP metric as a proxy for cash flow and we therefore expect limited cash burn in 2024, most of which will be incurred early in the year.

Speaker Change: Given multiple potential milestones in 2024 and beyond such as 25 or $50 million milestone for trilogy, we.

Speaker Change: We expect to generate net cash prior to the Cypress topline data readout in 2025.

Speaker Change: Lastly, we may continue to incur non cash income tax expense of several million each quarter.

Speaker Change: However, we continue to expect that immaterial, if any cash taxes in 2024 from ongoing operations.

Speaker Change: With that I'll pass it back direct to conclude Rick.

Rick E. Winningham: Thanks, Aziz. On slide 27, we summarize Theravance's compelling vision and value we offer shareholders. Having focused our organization's efforts behind you, Powerian Amphyloxaceteam, the Theravance team is now unified in pursuit of three objectives. First, we'll work to drive U.S. capillary net sales growth in the hospital while collaborating closely with our partners at Viatris to maximize the brand's overall potential in the hospital and community setting. Second, we'll continue to work diligently in pursuit of the CIPHR study's successful completion while making appropriate regulatory preparations and laying the groundwork for its broad access, if approved. Third, we'll maintain a strong capital structure as we work to deliver value for shareholders.

Rick E. Winningham: Thanks, Chris These on slide 27, we summarize <unk> compelling vision and value we offer shareholders.

Rick E. Winningham: Having focused our organization's efforts behind <unk> team. The <unk> team is now unified in pursuit of three objectives first we will work to drive U S. Repowering net sales growth in the hospital, while collaborating closely with our partners at Beatrice to maximize the brand's overall potential in the hospital and community settings.

Rick E. Winningham: Second we will continue to work diligently in pursuit of the Cypress studies successful completion, while making appropriate regulatory preparations and laying the ground work for its broad access if approved.

Rick E. Winningham: Third we will maintain a strong capital structure as we work to deliver value for shareholders.

Rick E. Winningham: Based on the choices we made regarding upellery, anaphyloxy, and trellogy, we believe we're at the crossroads of Theravance's evolution where we stand poised to deliver significant incremental value through operational assets as well as near-term milestones and royalties while making limited incremental investments and managing risk. We thank you for your time and attention this afternoon, and we're ready to take your questions. Operator.

Rick E. Winningham: Based on the choices, we made regarding your powering <unk> and trilogy believe we are at the crossroads is their advances evolution, where we stand poised to deliver significant incremental value through our operational assets as well as near term milestones and royalties, while making limited incremental investments and managing risk.

Speaker Change: We thank you for your time and attention this afternoon, and we're ready to take your questions.

Operator: Thank you, sir. Once again, if you'd like to ask a question, you may do so by pressing the star key followed by the digits 11 on your telephone. If listening via webcast, please mute the audio on your webcast device before asking a question over the phone.

Speaker Change: Operator.

Speaker Change: Thank you Sir once again, if you'd like to ask a question you may do so by pressing the star key followed by the digits. One one on your telephone if listening via webcast. Please mute audio on your webcast device before asking a question over the phone if youre using a speakerphone for todays call. Please make sure your mute function.

Operator: 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 11 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 Tsao from HC Wainwright. Your question, please. Hi, can you hear me? Yes, hello. We can hear you.

Speaker Change: Just turned off to allow your signal to reach our equipment again Thats star one if you'd like to ask a question and we'll pause for a moment to assemble our roster.

Speaker Change: And our first question comes from the line of Douglas Tsao from H C. Wainwright Your question. Please.

Speaker Change: Okay.

Douglas Tsao: Hi can you hear me.

Douglas Tsao: Yes, we can hear you okay.

Rhonda Farnham: Okay, good afternoon, and congrats on the progress. A couple of questions. First, maybe starting with you, Pelri.

Douglas Tsao: Good afternoon, and congrats on the progress.

Douglas Tsao: Just a couple of questions.

Douglas Tsao: First maybe starting with <unk>.

Rhonda Farnham: Rhonda, I'm just curious, when we think about the share gains that you're seeing, especially those in the hospital, to what extent are those coming from adding new accounts versus gaining share within the existing account base? Thank you, and then I've got a follow-up. Thanks, Doug.

Douglas Tsao: I'm just curious when we think about the share gains that youre seeing especially those in the hospital to what extent are those coming from.

Douglas Tsao: Adding new accounts versus.

Douglas Tsao: Gaining share within the existing account base.

Speaker Change: And then I've got a follow up.

Speaker Change: Thanks, Doug Great question.

Rhonda Farnham: Actually, thinking about that share gain of up to 16.6% for the quarter, that is drawn both from new accounts, but I would say the predominant growth there is from those accounts that continue to build upon their base business where we are converting them to therapeutic interchange. And for those accounts where we do have that all-med strategy implementation, as well as therapeutic interchange, we see that the market share is even higher in those accounts. Thank you, typically, maybe just as a follow-up to that. Rhonda, what's the process or how long does it take to get a hospital to sort of move to that therapeutic interchange and all NEB approach? If we are moving from their initial formulary to therapeutic interchange, that can range anywhere from six months to a year. If we're converting prior existing formulary review approvals, it's usually six to nine months.

Speaker Change: <unk> thinking about that share gain up to 16, 6% for the quarter that is drawn both from the new accounts, but I would say that predominantly.

Doug: There is from those accounts that continue to build upon their base business, where we are converting them to therapeutic interchange and for those accounts, where we do have that all nab strategy implementation as well as therapeutic interchanged, we see that the market share is even higher in those accounts.

Doug: Okay.

Doug: And.

Doug: Typically maybe just as a follow up to that.

Doug: Rhonda whats the process or how long does it take to get the hospitals to sort of move to that therapeutic interchange and all nap approach.

Rhonda: If we are moving from their initial formulary to therapeutic interchange that can range anywhere from six months to a year, if we're converting prior existing formulary.

Review approvals.

Rhonda: Usually six to nine months.

Rhonda Farnham: Okay, and within your account base, I mean, what percent would you say are at, you know, sort of doing this, have achieved therapeutic interchange in an all-in-one approach? That varies just based on the growing base, but roughly, two-thirds of our volume already has a therapeutic interchange, or I should say two-thirds of our volume is driven from those therapeutic interchange accounts, if that makes sense. Well, but I guess, and then as a follow-up to that, though, what percentage of your accounts are therapeutic interchange? Because obviously, you know, given that two-thirds, it would seem that there's significant growth by getting accounts to that, to that, you know, to that. Yes, yes. You've got it, Doug.

Rhonda: Okay on average.

Rhonda: And within your account base I mean, what percent would you say are you guys sort of doing that has achieved therapeutic interchange and then all of that approach.

That varies based on the growing base, but roughly.

Rhonda: Two thirds of our volume already have a therapeutic interchange or I should say two thirds of our volume is driven from those therapeutic interchange accounts if that makes sense.

Rhonda: But I guess and then as a follow up to that though that what percentage of your accounts are therapeutic interchange because obviously.

Rhonda: Given that two thirds it would seem that there is significant growth by getting accounts to that to that.

Rhonda: Yes, yes, you've got it Doug if we move them to therapeutic interchange that automatic substitution is what converts every existing llama.

Rick E. Winningham: If we move them to therapeutic interchange, that automatic substitution is what converts every existing LLAMA, whether handheld, from the past experience over. So that is the ultimate goal of what we are trying to achieve here with these new games. Well, no, no, I get it, but what percentage of your overall accounts are there? How do you achieve that?

Rhonda: Other handheld.

Rhonda: From the past experience over so that is the ultimate of what we are trying to achieve here with these new games.

No I get it but what percentage of your overall accounts are there.

Speaker Change: Have you achieved that is it.

Rick E. Winningham: Is it 10%, 20%, 30%? Just to sort of help understand the magnitude of the opportunity still in front of you. Roughly 35% of our COPD focus accounts have a therapeutic interchange. Okay, great. Thank you. Yes, that's really helpful. And then just, Rick, as a follow-up, you know, obviously... You have now brought yourself and the company to expense management and some difficult choices to a point where your cash burn is pretty minimal. You are also on the cusp of seemingly restarting to bring in some milestones, via Petrology as well as, it seems like, Upelry, which could begin to enhance your cash balance. When you think about Upelry and the success you are achieving in the hospital, does it ever – how close are you to the point where it would make sense strategically to gain some leverage with that sales organization and bring in another product, and not necessarily one even of the same magnitude of opportunity as Upelry, but just something that could give you some efficiency or sort of some additional leverage, because, in theory, even a small product could drive some pretty nice incremental margins Yeah, Doug, that's a good question.

Speaker Change: 10%, 20%, 30%.

Speaker Change: Sort of help understand the magnitude of the opportunity still in front of you.

Speaker Change: Roughly 35% of our COPD focus accounts have a therapeutic interchanges.

Speaker Change: Okay. That's helpful. Thank you. So yes, that's really helpful. And then just as a follow up.

Speaker Change: Obviously.

Speaker Change: You have now problem yourself and the company to expense management.

Some difficult choices.

Speaker Change: What are your cash burn is pretty minimal.

You are also.

Speaker Change: Costello seemingly restarting to bring into milestone for <unk> as well as it seems like the payout rate, which could begin to enhance your cash balance.

Speaker Change: When you think about your calorie and the success you are achieving in the hospital.

Speaker Change: It ever how closer to the point, where it would make sense strategically to gain leverage with that sales organization and bring in another product.

Speaker Change: Necessarily one.

Speaker Change: Even at the same.

Speaker Change: Magnitude of opportunity as you tell rebid, just something that could give you some efficiency or some additional leverage because in theory, even a small product could drive some pretty nice incremental margins on that sales force. Thank you.

Speaker Change: Yes, Doug that's a good question a couple a couple of points one.

Operator: A couple of points. One, we see such a significant opportunity for Amproloxetine and the execution of the Cypress study and the preparatory work over the next year, both on the regulatory side, as well as some very early commercial preparation work that, you know, any distraction from anything else, I think, would be net harmful from where we are right now. I'd say the second point is, as Rhonda mentioned, we have a small sales force and they're doing an outstanding job executing a particular strategy, and we are early, we are in the early days of the execution of the strategy, both at Theravance and, I would say, in particular, in combination with the efforts of Vietra.

Speaker Change: We see such a significant opportunity.

Speaker Change: Ample occitane and the execution of the Cypress study.

Speaker Change: The preparatory work over the next over the next year, both on the regulatory side as well as some very early commercial.

Speaker Change: Preparation work that any distraction from anything else I think would be harmful.

Speaker Change: From from where we are right now I'd say the second point is as Rhonda mentioned.

Speaker Change: We have a we have a small sales force they are doing an outstanding job executing.

Speaker Change: Particular strategy and we are early we are in the early days of the execution of the strategy. Both the <unk>, let's say in particular in combination with <unk>.

Operator: So, you know, we've got a significant amount of opportunity, I think, within the hospital with Upelri, and we would pay some opportunity costs by shifting our focus to anything else, given sort of where we sit with those accounts where we're on formulary and we need to move and take the next step towards therapeutic interchange and those steps that those institutions, largely, which are multi-hospital sort of groups, have taken from not being on formulary to So, you know, we really view there's just such a significant opportunity behind both Upelri and Amproloxa as a team that we need to keep our focus, you know, on those two assets. Okay, great.

Speaker Change: The efforts of via trusts so.

Speaker Change: We've got a significant amount of opportunity I think within the hospital with your Perl rate and we would pay some opportunity cost by by shifting.

Speaker Change: Our focus to anything else, given sort of where we set with.

Speaker Change: Those accounts, where we've where we're on formulary and we need to move and take the next step towards third therapeutic interchange and those steps.

Speaker Change: Institutions Lara.

Speaker Change: Largely which are multi hospital sort of groups of going from.

Speaker Change: Not being not.

Speaker Change: Not being on formulary to being on formulary with therapeutic area. So.

Speaker Change: We really view is there just such significant opportunity behind both <unk> and the <unk> team that we need to keep our focus on those two assets.

Operator: Thank you so much. Thank you. One moment for our next question. And our next question comes from the line of David Reisinger from Lee Ring Partners. Your question, please. Yes, thanks very much. And thank you for the update. So my first question is, can you talk a little bit about how you're thinking about the introduction of encephentrine from Verona and what implications that might have for upelry?

Speaker Change: Okay, great. Thank you so much.

Speaker Change: Thank you one moment for our next question.

Speaker Change: And our next question comes from the line of David Risinger from Leerink Partners. Your question. Please.

David Risinger: Yes, thanks, very much and thank you for the update so.

David Risinger: My first question is can you talk a little bit about.

David Risinger: How youre thinking about the introduction of.

David Risinger: And so <unk> from Verona, and what implications that might have for you Pal re and then second if you could just provide.

Rhonda Farnham: And then second, if you could just provide a little bit more detail on the execution of the amperloxetine trial from here, the event path, and then the likely timing of the first release of the results. Thank you. Okay, Rhonda, do you want to take encephalopentrin? Absolutely.

David Risinger: A little bit more detail on the execution of the <unk> trial from here.

David Risinger: Advent path and then the other.

David Risinger: Likely timing of the press release with the results. Thank you.

David Risinger: Okay, Ron do you want to take <unk>.

Rick E. Winningham: Thanks, David, for the question. We're very excited about the opportunity for INSEP and TRIN. Having additional share of voice focused on a nebulized asset in the COPD maintenance space would be tremendous, and thinking about as well how that particular product would enter the market, and most likely still needing the backbone or the foundation of therapy.

David Risinger: Absolutely.

Ron: Thanks, David for the question.

Ron: We're very excited about the opportunity for incident trend, having additional share of voice focused on an annualized asset in the COPD maintenance space would be tremendous.

Ron: And.

Speaker Change: Thinking about as well.

Speaker Change: Particular product would enter the market and.

Speaker Change: Most likely still meeting the backbone or the foundation of therapy thinking about that as an add on therapy.

Rick E. Winningham: Thinking about that as an add-on therapy, it's a great opportunity for us to ensure that the patients that could benefit from both products have that chance. So, you know, on amproloxetine, obviously, you know, we're, You know, we've initiated a lot of sites, as Anya pointed out in her comments, high-quality, you know, high-quality sites with physicians who understand MSA patients, understand the care of MSA patients, and understand the execution of the clinical trial. We'll continue to activate sites, and there is some work that's necessary there. But more and more work, obviously, is focused on just getting patients into and through the sites for the study.

Speaker Change: Have a great opportunity for us to both.

Ensure that the patients that could.

<unk> benefits from both products have that chance.

Speaker Change: So on the <unk> obviously.

Speaker Change: Sure.

Speaker Change: We've initiated a lot of sites.

Speaker Change: On you hit on her comments high quality high quality sites with physicians, who understand the MSA patients understand the care of MSA patients.

Speaker Change: I understand the execution of the clinical trial will continue to activate.

Speaker Change: Continue to activate sites and there is some some work that's necessary there, but the more and more work. Obviously is focused on just getting patients into and through through the sites for for the study were making making very good.

Rick E. Winningham: We're making, you know, making very good progress, making very good progress there, and I think, you know, if you split that, we've got, this year is really about, is a little bit tilted towards patients as opposed to sites, and that's where our focus will be. In terms of where the study is, I think we'll enroll our target, and right now, that's what we believe we can do, is enroll the last patient into the open-label portion in the second half of the year. This would mean data probably sometime in the first half of next year, and that's what we'd be looking forward to, but stay tuned as we progress throughout the year.

Speaker Change: Progress.

Speaker Change: Making very good progress there and I think if you <unk>.

Speaker Change: Flip that we've got.

Speaker Change: This year is really.

Speaker Change: There's a little bit tilted towards patients as opposed to sites.

Speaker Change: And Thats, where our focus will be.

Speaker Change: In terms of the where.

Speaker Change: Where the where the study is I think we will.

Speaker Change: Enrol or target.

Speaker Change: Right now that's what we believe we can do is enroll the last patient into the open label portion in the second half of the year.

Speaker Change: This would sort of lead data probably some time in.

Speaker Change: In the first half of next year span.

Speaker Change: That's what that's what we'd be looking looking forward to but stay tuned as we as we progress throughout the year.

Rick E. Winningham: I think, at least from the science and medicine part of Amproloxetine and the value that it can provide for patients with MSA and NOH, I think, hopefully, our investor event that we have in the second quarter will be able to provide good information to investors about the opportunity that we see there. Great, thank you very much. Yeah.

Speaker Change: I think the.

Speaker Change: From at least from the science and the medicine part of <unk> team and the value that it can provide.

Speaker Change: Four.

Speaker Change: Patients with MSA.

Speaker Change: I think hopefully our investor event that we have in the second quarter, we will be able to provide.

Speaker Change: Good information to investors about the about the opportunity that we see there.

Speaker Change: Great. Thank you very much.

Operator: Thanks, David. Thank you. One moment for our next question, and our next question comes from the line of Eva Prevatira from Cowan. Your question, please. Hi, you guys.

Speaker Change: Thanks, David.

Thank you one moment for our next question.

Speaker Change: And our next question comes from the line of EBIT for T. Rowe from Cowen Your question. Please.

Rick E. Winningham: Congratulations on a great quarter, and thanks for taking our questions. I have a question about the Q2 investor events for Amproloxetine. Will there be any additional analyses that we haven't seen before? Yeah, thanks, Eva. I think relative to amfraloxetine, I think the additional analysis will be relatively limited. I think, as we mentioned, we will have opinion leaders there that present other analyses, obviously, in both NOH and MSA patients, as part of their part of their presentations that outline the medical need and the opportunity that amfraloxetine has to meet that medical need, you know, through the data that they have and that that is currently published, but certainly Got it. That's helpful. And another one from me. How should we think about Amproloxetine's market opportunity relative to Northera, which I believe achieved 400 million in peak sales, given all of Northera's shortcoming? Ampulloxidine differentiation; how much bigger could Ampulloxidine be?

EBIT: Hi, guys congrats on the great quarter, and thanks for taking our questions.

EBIT: I have a question about the Q2 investor events for <unk>.

EBIT: It would be any additional analyses that we haven't seen before.

EBIT: Yeah. Thanks, Steve I think relative to <unk> I think the additional analysis will be relatively limited I think.

EBIT: As we mentioned we will have opinion opinion leaders there that that percent present other analyses, obviously in both <unk> and MSA patients.

EBIT: Part of their part of their presentations that outline the.

EBIT: The medical need and the.

EBIT: Opportunity that <unk> has to meet that medical need through.

EBIT: Through the data that they that they have in that.

EBIT: That is currently published but certainly consolidated yet.

EBIT: Into one particular event.

Speaker Change: Got it that's helpful and another one from me.

Speaker Change: How should we think about <unk> market opportunity relative to north ore, which I believe achieved $400 million in peak sales given all of north <unk> shortcomings, and <unk> differentiation, how much bigger Gregg <unk>.

Rick E. Winningham: Well, I think we're very, you know, we're optimistic on on amproloxetine. That's one of the reasons why we focused on both in in my comments, as well as Anya's comments on, you know, patient populations and the fact that there really is no, no solution that's adequate out there for patients that have MSA and NOH. But in a population of 40,000 patients with MSA and NOH, and given that, as Anya presented, you know, this is, in fact, a debilitating condition that keeps many of them really unable to interact with their environment.

Gregg: Well I think we're very we're optimistic on all of the ample occitane and Thats one of the reasons why we.

Gregg: Focused on both.

Gregg: My comments as well as obvious comments on.

Gregg: Patient populations the.

Gregg: The fact that there really is no.

Gregg: No solution.

Gregg: That's that's adequate out there for patients that have MSA.

Gregg: <unk>.

Gregg: But in a population of 40000 patients with MSA and NIH and given that is all.

You presented.

Gregg: This is in fact, a debilitating condition that keeps them many of them.

Gregg: Really unable to interact with.

Rick E. Winningham: I think that, you know, being able to show among multiple different parameters as measured by the OHSA composite score that we improve the well-being of these patients should open up a significant opportunity for us. And, you know, as a reminder, we did receive orphan drug designation. This is an orphan drug for a rare disease. So we're, you know, quite excited about, you know, obviously continuing to progress with the study, the investor event that we have in quarter two, which I think will fill in some more information and then and then continue to provide additional information as we work towards closing the study and data. So thank you very much. Thank you. Perfect. Thank you. Congratulations again.

Gregg: Their environment I think that.

Gregg: Being able to show among multiple different.

Gregg: Parameters as measured by the <unk> HSA composite score.

Gregg: We improved.

Gregg: The well being of these patients I should I think should open up a significant.

Gregg: Opportunity for us.

Gregg: And as a reminder, we did we were granted orphan drug designation. This is an orphan drug.

Gregg: For a rare disease. So we're.

Gregg: Quite excited about obviously continuing to progress with the study.

Gregg: The investor event that we have in the in quarter, two which I think they will fill in some more information and then and then continue to provide additional information as we work towards closing the study.

Gregg: And and data so.

Speaker Change: Perfect. Thank you and congrats again.

Operator: Thank you. One moment for our next question. And our next question comes from the line of Julian Harrison from BTIG. Your question, please. Hi, congrats on the quarter.

Speaker Change: Yes.

Speaker Change: Thank you one moment for our next question.

Speaker Change: Yeah.

Speaker Change: And our next question comes from the line of Julian Harrison from <unk>. Your question. Please.

Julian Harrison: Hi, congrats on the quarter and thank you for taking my questions. It was great to see a positive outcome from your phase III trial of <unk> in China back in November.

Rhonda Farnham: And thank you for taking my questions. It was great to see a positive outcome from your phase three trial of upellery in China back in November. I'm wondering if you could remind us about the China market opportunity there and what the gating steps to filing later this year. And then on Cyprus, do you have a good sense now for what the U.S.-ex-U.S. enrollment split will likely look like, any big differences there relative to the 1-7-0 study? Thank you. Ron, do you want to comment on China, and then Anya, maybe give just a high-level comment on the U.S. and non-U.S. positions on Cyprus? Rhonda first.

Wondering if you could remind us about how youre thinking about the China market opportunity there and what are the gating steps to filing later this year.

Julian Harrison: And then on Cyprus do you have a good sense now for what the U S. Ex U S enrollment split will likely look like.

Julian Harrison: Any big differences there relative to the 107 zero study. Thank you.

Julian Harrison: Ron do you want to comment on China.

Ron: Maybe you can give just a high level comment on U S. Non U S on Cyprus.

Rhonda Farnham: Yes, thanks Julian for the question and recognizing the positive outcome of that phase three that Vietra has completed. So they will be continuing to prepare and, as they've indicated, will be striving to make that filing for the application by the midpoint of this year, and in thinking about, you know, the market, you know, for you power users. We haven't made, you know, an outward communication around an absolute, absolute market projection. And just thinking about it, certainly, it's a very significant financial burden on that health care system, not too dissimilar from the US.

Ron: Rhonda.

Rhonda: Yes, Thanks, Julien for the question and recognizing in a positive outcome.

Rhonda: That phase III that VHS completed so they will be continuing to prepare and as they've indicated.

Rhonda: We will be striving to make that filing for the application by the midpoint of this year.

Speaker Change: And thinking about.

Speaker Change: The the market.

Speaker Change: Right.

Speaker Change: For poor you tolerate.

Speaker Change: We havent made.

Speaker Change: Our.

Speaker Change: Communication around an absolute.

Speaker Change: Absolute market projection and just thinking about certainly.

Speaker Change: Very significant financial burden on that healthcare system, not too dissimilar from the U S.

Rick E. Winningham: We can ensure that we continue to evaluate what that opportunity can be for you, Corey. Yeah, and I think, yeah, just to add to that, Julian, you know, Viatris will be commercializing the medicine in China. They have a substantial organization in China, which is one of the reasons that, you know, we licensed Upelrig to them in China. I think that, you know, they've since it is sort of their, you know, commercial responsibility.

Speaker Change: We can ensure that we continue to evaluate what that opportunity can be for you Corey.

Speaker Change: And I think just to add to that Julian.

Speaker Change: Beatrice will be will be commercializing the medicine in China, they have a substantial.

Speaker Change: Organization in China, which is one of the reasons that.

Speaker Change: We licensed <unk>.

Speaker Change: In China.

Speaker Change: I think that they've seen.

Since it is sort of their their commercial responsibility.

Rick E. Winningham: They have a I think their calls coming up, and you may you may get some ask a question of them on the opportunity. But obviously, the Chinese market and COPD are very, very large. And it's about capturing, you know, as much of that opportunity as it really makes economic sense. Julian, just to give you some facts about the Chinese market itself, COPD affects about 100 million patients in that marketplace. And a significant, roughly 40 percent of those patients are moderate to very severe patients suffering with COPD. So as you can think about that relative to that being the focus for us here in the U.S., I think that can give you some estimates. Julian, hey, it's Aziz.

Speaker Change: <unk>.

Speaker Change: I think Theyre calls coming up and then you may you may get some.

Speaker Change: Ask the question of them on an opportunity, but obviously the China market in COPD.

Speaker Change: It is very very large and it's about capturing as much of that opportunity is really makes economic sense.

Speaker Change: Julian just to give you some fact bases for the China market itself.

Speaker Change: PD effects of about 100 million patients in that marketplace.

Speaker Change: And a significant roughly 40% of those patients are moderate to very severe patients suffering with COPD. So is you can think about that relative to that being the focus for us here in the U S that can give you some estimates.

Speaker Change: Hey, Julien.

Aziz Suaf: Thanks for the question. One additional point, in our 10k, which we'll file in a couple days now, we're going to be disclosing the upholery economics for both the U.S. Sales Milestones and the China Milestones and Royalty Rates in more detail, so we'll actually break out the sales milestones, and you can see for the first time we broke out the actual percentage of the royalties, 14 to 20%, so a pretty significant royalty in a huge market, obviously, so we're really excited about the opportunity and the economics there.

Speaker Change: At disease. Thanks for the question one additional point to in our 10-K, which we'll file in a couple of days now we're going to be actually disclosing the calorie economics for both the U S sales.

Julien: Sales milestones and the China milestones and royalty rates in more detail.

Julien: Actually break out the sales.

Julien: Sales milestone and you can see for the first time, we broke out the actual percentage of the royalties, 14% to 20% so a pretty significant royalty.

Julien: Each market, obviously, so we're really excited about the opportunity in the economics there.

Anya Miller: Anya, do you want to talk about Amprolon-15? Julian, thanks for the question about the Pfeiffer study. As I alluded to earlier, we've already made a lot of great progress activating Pfeiffer in Europe and the U.S., and we have re-engaged a lot of the sites in the U.S. and Europe that we had previously engaged in the prior studies. I would expect that the majority of patients will still come from Europe, as it did in the previous program, although we are making efforts to expand our footprint in the So overall, I think more patients will come from Europe, but the actual percentage of the split may differ for a Pfizer study.

Speaker Change: Do you want to talk about.

Speaker Change: Epsilon theme Julian Thanks for the question on the Cypress study as I alluded to earlier, we've already made a lot of great progress activating sites in Europe and the U S.

Julian Harrison: And we have re engaged in a lot of the sites in the U S and Europe that we had previously engaged and deploy our studies.

Julian Harrison: Would expect that the majority of patients will still come from Europe as it did in the previous program. Although we are making efforts to expand our footprint in the U S and identify additional qualified sites and I spoke about.

Julian Harrison: We're going about that in terms of using an AI tool.

Julian Harrison: So overall.

Julian Harrison: I think the more patients will come from Europe, but the actual percentage uplift may differ for cypress.

Operator: Hopefully, that's helpful. Very helpful indeed. Thank you again. Thank you. This does conclude the question and answer session for today's program. I'd like to hand the program back to Mr. Winningham for any further remarks. Yeah, thank you. I'd like to just thank everyone for joining us today. We're pleased with the accomplishments of 2023 and look forward to what we can accomplish in 2024, both through effective financial management of the business, as well as the growth of Upellery and the execution of the CIFRA study in order to bring what we believe will be an important medicine to patients with MSA and NOH. Thank you very much. Thank you, ladies and gentlemen, for your participation in today's conference. This does conclude the program. You may now disconnect. Good day.

Speaker Change: Hopefully that's helpful very helpful. Thank you again.

Speaker Change: Thank you. This does conclude the question and answer session of today's program I'd like to hand, the program back to Mr. Winningham for any further remarks.

Rick E. Winningham: Yes. Thank you I'd like to just thank everyone for joining us today.

Winningham: Pleased with the accomplishments of 2023 and look forward to what we can accomplish in 2024, both through effective financial management of the business as well as the growth of <unk> and the execution on the Cypress study in order to bring what we believe will be.

Winningham: <unk> medicine to patients with MSA and NIH. Thank you very much.

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