David Hoang

David Hoang inquired about the commercial opportunity for remlifanserin, specifically the $4 billion peak sales potential (split between ADP/LBDP, U.S. market scope, KarXT competition, and ramp to peak sales), and sought clarification on the cash versus non-cash components of the NUPLAZID IRA rebate for the quarter and full year, and the likelihood of future reconciliations.

Answer

Catherine Owen Adams, CEO, stated that the $4 billion peak sales potential for remlifanserin is roughly equally weighted between ADP and LBDP, primarily U.S.-focused, and represents a strong opportunity in larger markets. Mark Schneyer, CFO, clarified that the $108 million IRA payment was cash, while the $20 million net sales reduction was a non-cash adjustment reflecting operational performance, and future reconciliations are not expected to be of the same magnitude as this initial adjustment.

David Hoang asked for clarification on the $4 billion peak sales potential for remlifanserin in ADP and LBDP, including the split between indications, market scope, competition, and ramp to peak sales. He also sought reconciliation of cash versus non-cash components of the IRA rebate approval for NUPLAZID.

Answer

Catherine Owen Adams, CEO, stated the $4 billion peak sales for remlifanserin is roughly equally weighted between ADP and LBDP, primarily U.S. market, representing a strong opportunity. Mark Schneyer, CFO, clarified that the IRA rebate payment of $108 million was cash, resulting in a net cash flow of $30 million over the year, and that adjustments to net sales were non-cash, reflecting operational performance.

David Hoang asked about the open-label extension for the ACP101 Phase 3 study, specifically regarding the rollover rate, and whether the company would consider adding a randomized withdrawal design.

Answer

EVP, Head of R&D, Elizabeth Thompson, noted that there has been good interest in the open-label extension. She explained that the company is currently focused on the parallel-arm study because a positive result would clearly demonstrate what to expect upon therapy initiation. While a randomized withdrawal study could be considered in the future, the current parallel-group design is the immediate priority.

David Hoang of Deutsche Bank asked whether the 12-month persistency rate for DAYBUE could be improved or if the focus should be on adding new patients. He also inquired about the commercial positioning of Acadia's Prader-Willi asset against a competitor's recently launched product.

Answer

CCO Thomas Garner stated that the 12-month persistency rate of over 50% is expected to remain stable, and the primary commercial focus is now on driving new patient starts. Regarding Prader-Willi syndrome, executives noted the market has significant unmet need with room for multiple therapies with different mechanisms, and they see potential for combination therapy in the future.

David Hoang asked about the distribution of the ulixacaltamide prescriber base in essential tremor, specifically whether it would be prescribed by general neurologists or academic centers. He also inquired how vormatrigine fits into the evolving focal epilepsy landscape, particularly against other potassium channel-focused therapies, and what factors physicians would consider when selecting a therapy.

Answer

CEO Marcio Souza stated that the distribution of patients, drug, and prescribing patterns for ulixacaltamide are very well understood, with the vast majority of prescribers being general neurologists who are eager to engage. For vormatrigine, he welcomed competition, stating it's not a zero-sum game and that multiple positive readouts benefit patients. He emphasized that vormatrigine's unique path to first-line treatment differentiates it, while competition might exist in refractory patients, there's none in earlier lines.

David Hoang inquired about the distribution of the ulixacaltamide prescriber base, specifically whether it would be prescribed by general neurologists. He also asked how vormatrigine fits into the evolving focal epilepsy landscape with other potassium channel-focused therapies.

Answer

President and CEO Marcio Souza stated that the prescriber base for ulixacaltamide is very well understood, with the vast majority being general neurologists eager to engage. For vormatrigine, he welcomed competition, emphasizing that it's not a 'zero-sum game,' and believes vormatrigine's path to first-line treatment differentiates it from competitors, which primarily target refractory patients.

David Hoang from Deutsche Bank asked about the company's strategy for using the new mood endpoint and the POWER-3 monotherapy study to enhance the drug's label and achieve market differentiation.

Answer

President & CEO Marcio Souza explained that the mood endpoint is intended to secure a potential label claim, leveraging a known class effect to improve patient well-being. He positioned the POWER-3 switch-to-monotherapy study as a "game changer" aimed at moving vormatrogene into first- and second-line treatment, dramatically expanding the market opportunity from the refractory setting. He noted vormatrogene's profile makes it the only drug suitable for this strategy, aiming to replace less effective and well-tolerated standards of care.

David Hoang from Deutsche Bank asked for the current patient mix between switch and naive users and the desired future trend. He also sought details on what the increased commercial investment aims to achieve with prescribers, specifically regarding depth versus breadth of prescribing.

Answer

COO Susan Rodriguez stated that over half of current patients are switch patients. She described a consistent adoption cycle where new prescribers start with switch patients and then rapidly expand to new and discontinued patients. She noted growth comes evenly from both increasing depth with existing prescribers and expanding the breadth of the prescriber base. CEO Gregory Divis added that investments also target patient activation.

David Hoang of Deutsche Bank inquired about the patient mix in Q1, specifically if there was a better mix of switch versus new-to-oxybate patients. He also asked about the tactics used to improve persistency and if there was room for further improvement.

Answer

CEO Gregory Divis confirmed that all patient segments improved, with an acceleration in switch patients, driven by expanded commercial reach. On persistency, he credited the expansion of the nursing support team, which allowed for more in-depth patient engagement, particularly in the first 90 days of treatment. He affirmed that there is still room to improve this metric further. CFO Thomas McHugh added that the company has reached a critical mass where every new patient contributes to profitability.

David Hoang from Deutsche Bank requested specifics on the initiatives aimed at improving persistency for naive or new-to-brand patients and asked about the expected long-term persistency rates for LUMRYZ compared to twice-nightly oxybates.

Answer

Executive Gregory Divis reiterated the company's three-pronged persistency strategy involving direct engagement with patients via nurses, communication with physician office staff, and support from pharmacy partners. He stated that while LUMRYZ persistency rates are already superior to legacy twice-nightly products, the company is actively working to improve them further. Positive early results from these initiatives are expected to increase net patients on therapy and drive revenue.

Asked about the confidence in Epidiolex reaching blockbuster status this year and for an update on the potential impact of multi-source oxybate generic entry.

Answer

The company is highly confident Epidiolex will reach blockbuster status, noting it requires less than 3% growth from 2024 and that underlying demand remains strong despite Q2 inventory dynamics. Regarding generics, multi-source entry is possible at year-end, but entrants would need their own REMS program. Jazz continues to focus on differentiating Xywav as the only low-sodium oxybate and the only approved therapy for IH.

David Hoang from Deutsche Bank asked for details on the data expected in the Fragile X top-line release, including visibility on patient methylation status and the subsequent filing strategy. He also inquired about the factors influencing the upper versus lower end of the full-year Wakix revenue guidance.

Answer

Chief Medical & Scientific Officer Dr. Kumar Budur stated the top-line release will include standard demographic, safety, and efficacy data, and a positive result would prompt a rapid pre-NDA meeting and submission. For Wakix, EVP & CCO Adam Zaeske highlighted strong patient adds and broad payer coverage as key drivers. CFO & CAO Sandip Kapadia added that underlying demand is the primary driver, with typical factors like patient adds, gross-to-net, and trade inventory influencing the final position within the guidance range.

David Hoang asked about the potential timeline for an NDA filing for ZYN002 in Fragile X if data is positive, and what the commercialization strategy and value proposition for the product might look like.

Answer

Dr. Kumar Budur, CMSO, stated that with positive data, they would file the NDA 'as soon as possible' and expect a priority review. CEO Dr. Jeffrey Dayno added they would move 'swiftly' and outlined a 'centers of excellence' commercial model to target the ~80,000 U.S. patients, leveraging deep engagement with the patient community.

David Hoang asked about the rationale for studying fatigue and sleep inertia with Pitolisant HD and if these would be pursued for labeled indications. He also inquired about the planned design for the first-in-human study of their orexin 2 receptor agonist.

Answer

CEO Dr. Jeffrey Dayno explained that sleep inertia is a key symptom in IH, making it a focus for a differentiated label. Dr. Kumar Budur, Chief Medical and Scientific Officer, added that the goal is to get these symptoms into the label. Regarding the orexin agonist, Dr. Budur confirmed an IMPD submission is planned for mid-2025, with first-in-human studies in H2 2025, but did not detail the specific study design.

David Hoang from Deutsche Bank inquired about the rationale for selecting an 18mg upper dose in the NT2 and IH studies, given a 25mg dose was used in Phase 1b, and asked about the ideal dose to advance into Phase 3.

Answer

Craig Hopkinson, EVP, R&D and Chief Medical Officer, explained that the Phase 2 doses were determined using sophisticated modeling that incorporated all available data from the healthy volunteer and Phase 1b studies.

David Hoang inquired about the planned timing for regulatory interactions, such as end-of-Phase II meetings with the FDA, and asked how many doses of ALKS 2680 the company might advance into Phase III studies.

Answer

CEO Richard Pops stated that the plan is to bring data from both the NT1 and NT2 studies to a combined end-of-Phase II meeting with the FDA. He also confirmed the intention is to take multiple doses into the Phase III program to leverage the drug's wide therapeutic index, with the final decision being informed by the Phase II results and regulatory feedback.

David Hoang asked if anecdotal experience from commercial ELEVIDYS use matches the EMBARK trial data and how to think about PMO franchise cannibalization given the changing ELEVIDYS uptake curve.

Answer

President and CEO Douglas Ingram shared that while anecdotal, the stories from families of commercially treated patients are extraordinary and align with the trial evidence. He did not directly address PMO cannibalization in his response, focusing on the positive real-world feedback for ELEVIDYS.

David Hoang of Deutsche Bank asked for Sarepta's thoughts on a competitor's recent DMD gene therapy data and how families might weigh receiving commercial ELEVIDYS versus enrolling in a clinical trial for an experimental product.

Answer

CEO Douglas Ingram stated that while they are thrilled to see more research in Duchenne, ELEVIDYS is the only approved, transformative, disease-modifying gene therapy available. Dr. Louise Rodino-Klapac emphasized the importance of the quality and functionality of the dystrophin construct, noting ELEVIDYS's design has been validated in hundreds of patients across multiple studies, which is a critical factor for families and physicians to consider.

David Hoang inquired about feedback from treatment centers regarding post-administration patient monitoring and whether this logistical consideration impacts the speed of the launch.

Answer

CEO Douglas Ingram confirmed that thoughtful follow-up monitoring is a crucial part of the process and does factor into the number of infusions a center can perform. He emphasized that this is essential for responsible dosing and patient safety. He also noted that based on this monitoring, the company is seeing a very stable safety profile for ELEVIDYS.

David Hoang of Deutsche Bank requested more color on the expected evolution of payer coverage for Auvelity throughout the year. He also asked for insights into the growth drivers for Sunosi, specifically comparing the narcolepsy and obstructive sleep apnea (OSA) indications.

Answer

Ari Maizel, Chief Commercial Officer, stated that the commercial team is focused on increasing covered lives and reducing utilization management for Auvelity, with expectations for access to expand this year. For Sunosi, he noted that while both indications are growing, the larger OSA patient population is experiencing faster growth due to significant unmet need.

David Hoang inquired about expectations for the seasonal cadence of Auvelity prescriptions in 2025, the potential impact of the sales force expansion, and whether the company would consider providing forward-looking product guidance.

Answer

Executive Darren Opland expects Q1 to be a growth quarter for Auvelity, albeit slower than the back half of 2024, with the sales force expansion impact likely visible by late Q1. Chief Financial Officer Nick Pizzie added that the company does not plan to provide sales guidance currently due to market unpredictability but reiterated peak sales estimates of $1B-$3B for Auvelity in MDD.

David Hoang inquired about Biogen's level of commitment to the ZURZUVAE launch, whether they would also expand their sales force, and the expected impact of the expansion on key metrics.

Answer

CEO Barry Greene stated the expansion is expected to cause a 'profound uptick' in metrics. CBO Chris Benecchi clarified that Sage is funding its own Q4 sales force expansion, while Biogen is currently piloting approaches with existing resources to inform their future investment decisions. He underscored the strong collaboration and shared mission between the partners.

David Hoang from Citigroup inquired about how the anti-tau antibody fits into the Alzheimer's treatment landscape compared to the tau-silencing gene therapy, and to what extent Voyager has investigated other transporters besides ALPL for blood-brain barrier crossing.

Answer

Executive Alfred Sandrock and CMO Dr. Toby Ferguson contrasted the two approaches: the antibody targets extracellular tau spread with regular infusions, while the gene therapy is a 'once and done' approach to silence all tau forms. Regarding other transporters, Executive Todd Carter confirmed Voyager has identified multiple capsid families targeting different receptors and is evaluating all of them for non-viral delivery, noting any chosen target would need to perform at least as well as existing transporters.

David Hoang from SMBC asked about the translation of Talicia's prescription growth to revenue, potential changes in gross-to-net, the expected growth cadence for 2022, and whether the RHB-204 NTM study's endpoint could support a full or accelerated approval.

Answer

CFO Micha Ben Chorin confirmed Talicia's growth pace is increasing and later clarified that Talicia revenues grew 17% from Q3 to Q4. CEO Dror Ben-Asher and executive Rick Scruggs expect growth to accelerate due to the waning pandemic, improved clinic access, and a new customer engagement team. Regarding the NTM study, COO Gilead Raday explained that the six-month co-primary endpoint is expected to potentially support an accelerated approval, with longer-term data intended to support a full approval.

David Hoang of SMBC asked about the certainty of conducting a confirmatory trial for opaganib and whether it was definite or subject to regulatory feedback. He also sought to understand the gross-to-net dynamics for Talicia and inquired about the expected development timelines for RHB-104 in Crohn's disease.

Answer

COO Gilead Raday stated that plans for a confirmatory opaganib trial are subject to regulatory feedback. SVP Bob Gilkin explained that Talicia's gross-to-net is well within industry standards due to a conservative approach to discounting. CEO Dror Ben-Asher expressed high commitment to RHB-104, noting that recent progress in MAP diagnostic technology could accelerate the program, with validation of a new test expected within weeks.

David Hoang questioned the primary growth drivers for Talicia in the second half of the year and asked about the strategic rationale for developing opaganib for inpatients and RHB-107 for outpatients with COVID-19.

Answer

Chief Commercial Officer Rick Scruggs explained that Talicia's growth depends heavily on the pandemic's impact on physician access, despite strong sales force capacity and payor coverage. CEO Dror Ben-Asher detailed that opaganib targeted hospitalized patients due to the urgent need and clearer regulatory path, while the once-daily RHB-107 was aimed at the larger outpatient market, allowing RedHill to cover the full disease spectrum.

David Hoang asked if discontinuing the high dose for Danon disease, which was intended to provide extra-cardiac benefits, impacts the therapy's overall value proposition and whether a potential approval would be accelerated or full.

Answer

CEO Gaurav Shah asserted that addressing the fatal cardiac aspect of the disease is the ultimate value proposition. CMO Jonathan Schwartz added that the low dose may still provide non-cardiac benefits over time. Regarding approval, Shah noted it was too early to speculate, but biomarkers could support an accelerated path while a mortality benefit remains the ultimate goal.