Yasmeen Rahimi

Yasmeen Rahimi inquired about the initial PALSONIFY script trends in January and February, seeking insights into any evolving patterns from December into the new year.

Answer

CEO Scott Struthers expressed satisfaction with the PALSONIFY launch and real-world experiences but declined to provide quantitative comments on early trends. Chief Commercial Officer Isabel Kalofonos added that the 'efficacy-first' messaging is resonating, and the rapid onset of action (2-4 weeks) is leading to positive experiences for physicians and patients.

Yasmeen Rahimi asked for color on PALSONIFY's starting script trends in January and February, seeking insights into how these trends evolved from December into the new year.

Answer

Dr. Scott Struthers, Founder and CEO, expressed satisfaction with the PALSONIFY launch and accumulating real-world experiences but declined to provide quantitative comments on short-term trends due to the early stage of the launch. Isabel Kalofonos, Chief Commercial Officer, added that the 'efficacy-first' messaging is resonating, with physicians and patients appreciating the rapid action and symptom control.

Yasmeen Rahimi inquired about the statistical powering for the innovative composite primary endpoint in the atumelnant Phase III trial for CAH and asked if any data had been collected from the study's fourth cohort.

Answer

Dr. Alan Krasner, Chief Endocrinologist, explained that the study is very highly powered to detect significant differences. He clarified the endpoint is a composite responder analysis, not a co-primary endpoint. Regarding Cohort 4, he stated that it is currently enrolling and he could not yet comment on the timing of data availability.

An analyst on behalf of Yasmeen Rahimi asked about the expected disclosure cadence with the FDA for paltusotine ahead of its PDUFA date, potential topics for the mid-cycle review, and whether the review had occurred.

Answer

CEO R. Struthers stated that the communication cadence with the FDA is good. Chief Medical and Development Officer Dana Pizzuti confirmed that the mid-cycle review has not yet occurred but is scheduled, and the overall NDA review is proceeding normally with a productive relationship with the agency.

Yasmeen Rahimi asked about the potential clinical development path for the new NDC in neuroendocrine tumors (NETs), given their slow-growing nature, and inquired about the potential market size for this indication.

Answer

Chief Endocrinologist Dr. Alan Krasner outlined an oncology-style Phase I dose-escalation study in patients with progressing SST2-expressing tumors, followed by dose expansion cohorts. CEO R. Struthers added that the market size is significantly larger than the carcinoid syndrome population (which is ~20% of NETs) and could potentially expand to other SST2-expressing cancers.

Yasmeen Rahimi asked about payer and uptake work for non-obstructive HCM, specifically whether a 3-point placebo-adjusted difference in KCCQ would still lead to strong usage, or if statistical separation alone is sufficient for market adoption.

Answer

Robert Blum, President and CEO, Fady Malik, EVP of R&D, and Andrew Callos, EVP and CCO, emphasized that while statistical significance is crucial, the magnitude of change, especially for KCCQ, needs to be meaningful. A positive outcome would create a 'halo effect' on obstructive HCM use and significantly boost non-obstructive HCM demand, as HCPs appreciate a single product for all HCM.

Yasmeen Rahimi asked about ACACIA-HCM, specifically whether a 3-point placebo-adjusted difference in KCCQ would still lead to strong usage, or if statistical separation alone, regardless of magnitude, would be sufficient for physician adoption.

Answer

EVP of R&D Fady Malik explained that while average responses vary, individual patient responses can be larger. EVP and Chief Commercial Officer Andrew Callos noted that statistical significance and approval for non-obstructive HCM would significantly increase demand and create a 'halo effect' for obstructive HCM. President and CEO Robert Blum emphasized that the magnitude of change needs to be meaningful, not just statistically significant.

Yasmeen Rahimi of Piper Sandler asked whether the REMS situation was a simple procedural issue or if there was a deeper meaning behind the FDA's request.

Answer

Robert I. Blum, President and CEO, firmly rejected the term "mishap," characterizing the events as a normal part of the iterative FDA review process. He stressed that the FDA's request does not reflect any new safety concerns but rather a shift in how the risk will be managed—formally through a REMS rather than just labeling, without changing the underlying differentiated profile of aficamten.

Yasmeen Rahimi of Piper Sandler asked for commentary on the recently published baseline demographics of the competitor's ODYSSEY study in nHCM and how they compare to expectations for Cytokinetics' ACACIA trial.

Answer

EVP of R&D Fady Malik commented that the ODYSSEY baseline characteristics were not surprising, showing patients with significant symptoms, elevated biomarkers, and reduced exercise capacity. He noted the striking similarity to oHCM patients, which he believes bodes well for the potential effectiveness of CMIs in this population. He also highlighted that the rapid enrollment in both trials indicates nHCM is a significant unmet need.

Yasmeen Rahimi of Piper Sandler asked about the market size of oHCM patients who fail beta-blockers and the potential cost-effectiveness arguments for aficamten as a first-line therapy.

Answer

Andrew Callos, EVP and CCO, cited market research indicating ~25% of patients have contraindications and 80-90% experience side effects with beta-blockers. He explained the value argument for aficamten would be elevated beyond cost to focus on superior outcomes (e.g., KCCQ, NYHA class, avoiding surgery), with the MAPLE trial serving to expand the prescriber market.

Yasmeen Rahimi (via Emma) asked about the tracking of blinded event rates for the MAESTRO-NASH outcomes trial in F4C, potential guidance tightening for data timing, and whether additional open-label NAFLD data follow-up would be provided to reinforce conviction in success.

Answer

David Soergel, Chief Medical Officer, confirmed that event rates for MAESTRO outcomes are tracking as expected for 2027 data delivery, but more time is needed to refine timing guidance. He noted that sufficient information has already been gathered from the 122-patient open-label NAFLD-1 study, showing positive effects of Rezdiffra in F4C patients, including those with clinically significant portal hypertension.

Yasmeen Rahimi inquired about how the upcoming AASLD data, particularly non-invasive test (NIT)-driven responses, could further de-risk the Maestro NASH outcomes trial, which is expected to read out in 2028, and sought visibility on the trial's timeline.

Answer

Bill Sibold, Chief Executive Officer, expressed excitement for AASLD, noting significant progress with gastroenterologists. David Soergel, Chief Medical Officer, explained that the new data from the F4C open-label cohort, showing sustained efficacy in severe patients, provides strong confidence in the Maestro NASH outcomes trial due to similar patient populations and baseline characteristics.

Yasmeen Rahimi asked about how the upcoming AASLD data, particularly NIT-driven responses, could further de-risk the Maestro NASH outcomes trial (reading out in 2028), and what visibility Madrigal has on the trial's progress.

Answer

CEO Bill Sibold highlighted positive feedback from the recent ACG meeting and expressed excitement for AASLD. CMO David Soergel explained that new AASLD data from the two-year open-label F4C cohort, showing promising efficacy in severe patients, is very similar to the Maestro outcomes trial population, thus increasing confidence in the 2028 readout.

Yasmeen Rahimi of Piper Sandler Companies asked how Madrigal plans to maintain its strong growth trajectory with the anticipated market entry of semaglutide, particularly concerning pricing, rebates, and the potential for payers to require step-edits.

Answer

CEO Bill Sibold stated that Madrigal expects its growth trend to continue, having planned for all scenarios, including the semaglutide launch. He noted that step-edits are complex for patients with comorbidities and it's too early to know specifics. CFO Mardi Dier added that combination use is already common, with about 50% of ResDiffera patients having current or prior exposure to GLP-1s, a dynamic that is already factored into their performance.

Yasmeen Rahimi inquired about the patient compliance and adherence rates observed after more than a year of Rezdiffra being on the market.

Answer

CEO William Sibold noted that while it is still early for definitive data, all early signs point to promising adherence rates consistent with other well-tolerated oral therapies. He attributed this to the drug's favorable profile and the positive biomarker feedback physicians are sharing with patients, which encourages continued use.

Yasmeen Rahimi of Piper Sandler questioned when Madrigal might feel comfortable providing formal financial guidance for 2025 or 2026, following up on the CFO's commentary about market consensus.

Answer

CFO Mardi Dier reiterated that the company is not providing formal guidance at this time as it is too early in the launch. However, she extended her positive commentary to the full year, stating that based on current momentum, they expect the full-year 2025 consensus to also narrow and increase slightly.

Yasmeen Rahimi inquired about Madrigal's forecast for the fourth quarter and its growth trajectory into 2025, following the strong Q3 performance of Rezdiffra.

Answer

CEO William Sibold stated the launch is tracking well against top-tier specialty medicine benchmarks, which typically see around 50% growth in the third quarter of a launch. CFO Mardi Dier added that while specific 2025 guidance is not yet available, they anticipate that expectations for 2025 will increase to reflect the current robust growth.

Yasmeen Rahimi inquired about the current pre-commercial activities for Praxis's pipeline and the expected cadence throughout 2026, as well as details on new data presentations anticipated at the upcoming American Academy of Neurology (AAN) meeting.

Answer

CFO Tim Kelly outlined key pre-commercial activities including talent acquisition for the commercial organization, ensuring sufficient inventory for launches, and disease awareness campaigns. CEO Marcio Souza elaborated on the 15 different presentations at AAN, focusing on oral presentations of clinical data for the Essential3 program, expanding understanding of the mADL11 primary measure, and other robust new data points geared towards future prescribers.

Yasmeen Rahimi of Piper Sandler Companies inquired about the response rates of vormatrogene based on different background therapies, the key factors behind the company's strong clinical trial execution, and requested confirmation on the timeline for the POWER-1 study.

Answer

President & CEO Marcio Souza confirmed that vormatrogene showed robust efficacy across various background anti-seizure medications (ASMs), including in patients on cenobamate. He attributed strong trial recruitment to their effective operational engine, which is now being applied to POWER-1. Souza also reaffirmed previous guidance that the POWER-1 study is expected to be completed by the end of the year.

Yasmeen Rahimi asked for the rationale behind moving the ulixacaltamide interim analysis to Q1 2025, clarification on the disclosure sequence for Study 1 and Study 2, and details on the potential re-initiation of the Parkinson's disease program.

Answer

CEO Marcio Souza stated the interim analysis for ulixacaltamide was moved to Q1 2025 to safeguard the overall program and prevent any potential negative influence on the Study 2 readout. Regarding the Parkinson's program, he explained that growing confidence in the essential tremor outcome prompted planning for a Phase II/III study, leveraging prior FDA feedback, to be ready for initiation post-ET results.

Yasmeen Rahimi inquired about the enrollment progress for the Essential3 trial, the nature of the newly mentioned interim analysis, and the predictive value of the RADIANT study for the subsequent POWER studies.

Answer

CEO Marcio Souza confirmed that Essential3 enrollment remains on track and the interim analysis was planned from the outset as an 'insurance policy' to potentially increase sample size if needed, thereby maximizing the probability of success. He explained that the RADIANT study for PRAX-628 will provide crucial intermediate safety, PK, and efficacy data, helping to characterize the drug in an epilepsy population and serving as a first step into generalized epilepsy, all of which will support the overall registration package.

Yasmeen Rahimi inquired about the enrollment progress for the Essential3 trial, the details of the newly mentioned interim analysis, and the predictive value of the RADIANT study for the subsequent POWER studies.

Answer

Executive Marcio Souza explained that the interim analysis for Essential3 is a pre-planned 'insurance policy' to potentially increase sample size if needed, influenced by external factors rather than internal trial issues. He clarified this does not represent a delay. Souza also stated that the RADIANT study will provide crucial safety, PK, and efficacy data for PRAX-628, helping to characterize the molecule and offering an early look at its potential in generalized epilepsy, which will support the overall registration package.

Yasmeen Rahimi asked about expectations for the 1402 D2T-RA readout, preparations for filing, and readiness for the first Phase 3 registrational study.

Answer

CEO Matt Gline explained that while the bar for efficacy in these high unmet need RA patients is relatively low, there's little precedent data for late-stage RA with this level of pretreatment, making it hard to predict. He indicated that Roivant would share guidance on criteria for a second study before data release and that a base case expectation is multiple studies due to the smaller randomized withdrawal trial.

Yasmeen Rahimi, Senior Research Analyst at Piper Sandler, asked about expectations for the upcoming 1402 RA readout, Roivant's preparation for potential filing, and the timeline for initiating a phase 3 registrational study.

Answer

Matt Gline, CEO of Roivant Sciences, explained that while the bar for efficacy in these high unmet need RA patients is relatively low, there's limited precedent data for such pretreated patients. He indicated that Roivant would share guidance on criteria for a second study before data release and that a phase 3 plan would be developed after agency engagement, likely involving multiple studies given the current trial's size.

Yasmeen Rahimi inquired whether Immunovant would provide an update from the open-label portion of the RA trial before the second part begins and asked what magnitude of clinical change the study is powered to detect in this difficult-to-treat population.

Answer

Executive Peter Salzmann confirmed that a key benefit of the trial design is the ability to disclose data from the open-label period, creating a catalyst. He stated the trial is fully powered for its primary endpoint. Dr. Peter Taylor added that achieving DAS28 remission is 'enormously meaningful' for these patients and that other metrics could be even more impressive.

Yasmeen Rahimi of Piper Sandler & Co. inquired about the RA trial's open-label portion, asking if updates would be provided before Part 2 begins. She also asked about the statistical powering of the study and what magnitude of change would be considered clinically meaningful in this difficult-to-treat population.

Answer

Executive Peter Salzmann confirmed that a key benefit of the trial design is the ability to disclose data from the open-label period, creating a catalyst before the final readout. He affirmed the trial is fully powered as a pivotal study. Dr. Peter Taylor added that DAS28 remission is an enormously meaningful outcome, and metrics that don't include CRP, like the CDAI, could show even more impressive results.

Yasmeen Rahimi sought color on expectations for the 1402 D2T-RA readout, Roivant's preparation for filing, and how soon the company could be ready for the first phase 3 registrational study.

Answer

Matt Gline, CEO of Roivant, explained that while the efficacy bar for these burned-out RA patients is relatively low, precedent data is scarce. He indicated that guidance on running a second study would be shared before data release and that this trial is likely one of a couple needed for registration due to its smaller, randomized withdrawal design.

Yasmeen Rahimi asked about expectations for the upcoming 1402 D2T-RA readout, how Roivant is preparing for a potential filing, and the readiness for a first Phase III registrational study.

Answer

Matt Gline, CEO of Roivant, noted the high unmet need in RA and the relatively low bar for efficacy, but also the lack of precedent data for late-stage RA with this level of pretreatment. He indicated that guidance on criteria for running a second study would be shared before the data release, and a second study is likely given the smaller randomized withdrawal trial.

Dominic on behalf of Yasmeen Rahimi asked about the upcoming six-month remission data for batoclimab in Graves' disease, inquiring what Roivant hopes to report at the ATA conference and the overall importance of this data.

Answer

CEO Matt Gline expressed hope that the data will highlight a 'paradigm-shifting opportunity' for Graves' patients by demonstrating that remission is achievable for severe, refractory cases. He outlined the data's threefold importance: defining the commercial opportunity, boosting patient and physician enthusiasm for trial enrollment, and strengthening the drug's overall clinical profile.

Dominic, on behalf of Yasmeen Rahimi from Piper Sandler, asked what the IMVT-1402 CIDP study is powered for regarding its endpoints and questioned the rationale for selecting the 600mg dose for the trial.

Answer

CEO & Director Matt Gline stated that the company has not yet disclosed the study's statistical powering but may share more in the coming months. He justified the 600mg dose by referencing data from the batoclimab study showing deeper IgG suppression leads to better outcomes. He argued that in a severe disease like CIDP and a competitive market, maximizing efficacy with the highest dose is paramount for success and will also aid in trial enrollment.

Yasmeen Rahimi from Piper Sandler Companies asked for insights into the blinded safety and efficacy data for the cystic fibrosis program and questioned the progress made with regulatory agencies on using biomarkers like glutamine as a registrational endpoint for the OTC deficiency program.

Answer

President and CEO Joseph Payne addressed safety by highlighting Arcturus's proprietary LUNAR delivery technology and mRNA purification processes, which are designed to mitigate toxicology and tolerability issues seen in prior inhaled RNA therapies. For the OTC program, he confirmed the FDA is aware of their biomarker strategy, including the N15 Ureagenesis Assay, and that achieving regulatory alignment on a pivotal trial design is a key upcoming objective.

Yasmeen Rahimi from Piper Sandler requested details on the upcoming interim data readout for the cystic fibrosis program (ARCT-032), asking about the potential cohort size, the company's definition of success, and the characteristics of the patient population.

Answer

President and CEO Joseph Payne stated that the mid-2025 interim data will draw from two cohorts and include approximately 6 to 9 subjects. He defined the bar for success as achieving reasonable safety and tolerability over the 28-day treatment period and demonstrating a lung function (FEV) improvement of at least 3%. Payne also noted the patient population consists of individuals who do not respond to CFTR modulators, with about half being Class I subjects.

Yasmeen Rahimi asked for details on the upcoming interim data for the cystic fibrosis (CF) program, including the expected cohort size, the number of doses to be reported, and the bar for establishing a strong proof-of-concept.

Answer

President and CEO Joseph Payne stated that the interim update, expected by the end of Q2 2025, will include data from multiple patients at multiple dose levels. He reiterated that a 3% absolute improvement in FEV1 lung function would be a key benchmark for advancing the program, based on historical precedents in the CFTR modulator space. He did not provide guidance on the specific method of data disclosure.

Jim, on behalf of Yasmeen Rahimi, asked for details on the Phase II cystic fibrosis study, including its size, cohorts, and planned doses. He also inquired about what the company believes is needed to demonstrate proof of concept in this study.

Answer

CSO Padmanabh Chivukula stated that while the specific study design is not disclosed, they will be evaluating various biomarkers similar to competitors. CEO Joseph Payne added that the study is open-label, will evaluate multiple doses, does not include bronchoscopy, and will measure FEV throughout. He indicated more details would be shared at a later time.

Yasmeen Rahimi of Piper Sandler asked for insights into the competitive product profile Nektar is targeting for Respag in alopecia areata (AA) to justify late-stage development, and whether data from the longer extension arm would be available at the time of the top-line readout.

Answer

Chief Research & Development Officer Jonathan Zalevsky explained that with no approved biologics for AA, Respag has an opportunity to be a first-in-class therapy with a sustained effect, a key differentiator from JAK inhibitors. He provided benchmarks for the primary endpoint (percent change in SALT score), aiming for a 30-40% reduction to be competitive with JAKs, and highlighted the importance of registrational endpoints like SALT20 and SALT10. He emphasized the potential for Respag to become the first biologic approved in this indication.

Yasmeen Rahimi of Oppenheimer inquired about Nektar's expectations for dose response in the REZOLVE-AD trial and the specific criteria for patients to advance from the induction to the maintenance phase.

Answer

Chief Research and Development Officer Dr. Jonathan Zalevsky explained the rationale for the three dose cohorts (24mcg/kg twice-monthly, 24mcg/kg once-monthly, and 18mcg/kg twice-monthly), which were designed to model Treg pharmacodynamics and build upon Phase Ib data. He clarified that patients must achieve an EASI-50 or better response at the end of the 16-week induction period to be eligible for re-randomization into the maintenance phase.

Yasmeen Rahimi of Piper Sandler & Co. inquired about the enrollment progress for the REZPEG studies in atopic dermatitis and alopecia areata, asking for more quantification, and questioned the ability to extrapolate efficacy data to biologically experienced patients.

Answer

Chief Medical Officer Dr. Mary Tagliaferri responded that while enrollment is on track for a first-half 2025 data readout in atopic dermatitis, the company will not provide further quantification but will update clinicaltrials.gov upon completion. She added that the current Phase IIb study is in biologic-naive patients, and it is too early to extrapolate efficacy to experienced patients without more data from other drugs in that specific population.

Yasmeen Rahimi of Piper Sandler Companies inquired about the monthly prescription trends for VICAT XR in July and the remainder of the quarter, as well as the current time-to-fill for new prescriptions.

Answer

CEO Anish Bhatnagar declined to provide post-quarter data but affirmed confidence in VICAT XR becoming the standard of care. CCO Meredith Manning explained that the time-to-fill is variable as more payer policies are established. While encouraged by the 33% of lives covered, she noted that as more policies are added, turnaround times could fluctuate before settling toward a target of approximately 30 days.

Yasmeen Rahimi of Piper Sandler Companies inquired about the monthly prescription trends for VICAT XR in July and the outlook for the rest of Q3. She also asked about the current time-to-fill for prescriptions and how that metric is expected to evolve.

Answer

CEO Anish Bhatnagar declined to provide post-quarter data but expressed confidence that VICAT XR is on track to become the standard of care. Chief Commercial Officer Meredith Manning addressed the time-to-fill, noting that as more payer policies are established, the turnaround time could initially slow before stabilizing. She stated that a 30-day turnaround is a standard target in the rare disease space.

Yasmeen Rahimi inquired about the expected timeline for converting patient start forms into recognized revenue and the projected prescription fill times for the remainder of 2025.

Answer

CFO James MacKaness stated that due to the multi-step process and anticipated caution from specialty pharmacies in building inventory, Q2 revenues are expected to be modest. CCO Meredith Manning added that while it's too early for specific metrics, the conversion speed is consistent with typical rare disease launches.

Yasmeen Rahimi inquired about the timeline for converting patient start forms into recognized revenue and the projected 'time to fill' for prescriptions during 2025.

Answer

Executive James MacKaness advised that Q2 revenues are expected to be modest due to the multi-step conversion process and cautious inventory building by specialty pharmacies. CCO Meredith Manning added that while it is too early to provide specific metrics, the current turnaround time is consistent with other rare disease launches.

Yasmeen Rahimi asked if baseline PVR is an endpoint in PROSERA, whether another baseline data cut would be provided, and if there is a potential read-through from the PROSERA results to the PH-ILD study, given the shared 6-minute walk test endpoint.

Answer

CEO Faheem Hasnain stated that the current baseline data is not expected to materially change and confirmed enrollment completion by mid-June, with no further updates planned before top-line results. CMO Dr. Richard Aranda clarified that while PVR was an entry criterion, it is not an endpoint. He noted a positive PROSERA result would be a positive signal for the PH-ILD study, as those patients are generally sicker, fitting the thesis that the drug is effective in more severe populations. Mr. Hasnain also highlighted seralutinib's potential antifibrotic properties as an added benefit for PH-ILD.

Yasmeen Rahimi of Piper Sandler questioned if FDA feedback on the pilavapadin Phase III design is a gating factor for partnership discussions. She also asked for details on the additional PROGRESS study data to be presented and how the SONATA trial was designed to ensure a homogeneous nonobstructive HCM population.

Answer

CEO Michael Exton clarified that the end-of-Phase II meeting with the FDA is not considered a gating factor for ongoing strategic partnership discussions for pilavapadin. Dr. Craig Granowitz added that future data presentations will detail secondary endpoints like pain quality and functionality, plus pharmacokinetic data. For the SONATA trial, he explained that the key inclusion criterion is symptomatic disease, reflecting diastolic dysfunction, and that they have high confidence in the nonobstructive cohort based on prior HFpEF and LVH data.

Asked for updates on three programs: enrollment progress and timeline for the SONATA (sotagliflozin in HCM) study, the timing for the FDA end-of-Phase II meeting for pilavapadin, and the rate-limiting steps for the LX9851 IND filing.

Answer

For the SONATA (HCM) study, enrollment is progressing well with sites open in the U.S. and internationally, targeting final results by late 2026 and an FDA filing in Q1 2027. For pilavapadin, they plan for an end-of-Phase II meeting with the FDA in the second half of the year, with a potential Phase III start before the end of 2025. For LX9851, they are on track to complete IND-enabling studies and file the IND in 2025.

An analyst on behalf of Yasmeen Rahimi inquired about the specifics of the blinded efficacy and safety data Lexicon is reviewing for its LX9211 pain program. She also asked if it is reasonable to expect a dose-response in the study.

Answer

Dr. Craig Granowitz, SVP & Chief Medical Officer, explained that the blinded data they receive is extremely limited and primarily focused on safety monitoring. He reiterated that the tolerability profile in the current study appears different from the pilot trial but could not comment further on the overall drug profile or potential for a dose response.

Yasmeen Rahimi of Piper Sandler & Co. inquired about the baseline characteristics of the IMPACT MASH trial, the ideal patient population for pemvidutide, and the company's strategy for potential partnerships.

Answer

An executive, likely CSO Dr. Scot Roberts, confirmed that the IMPACT trial's baseline demographics are very similar to other MASH studies. CBO Ray Jordt explained the target population is MASH with obesity, leveraging the drug's dual action on the liver and weight loss. Jordt also stated that while Altimmune is open to compelling partnerships, moving to Phase 3 is not contingent on securing one.

Yasmeen Rahimi of Piper Sandler & Co. asked about the potential design of the Phase III NASH trial, specifically regarding the incorporation of non-invasive tests (NITs) and whether a study in cirrhosis patients would be initiated concurrently.

Answer

CMO Dr. Scott Harris explained that while Altimmune is at the forefront of using NITs like MRI-PDFF, the FDA's future acceptance of them as endpoints is uncertain. He noted strong internal interest in a cirrhosis study but stated that any disclosure would likely occur around the end-of-Phase II meeting, expressing high confidence in pemvidutide's potential success in the F4 population.

Yasmeen Rahimi of Piper Sandler inquired about the significance of the FDA alignment on the VELOCITY Phase III program for strategic partnership discussions, the potential sequencing of the four trials, and details on the new indications being pursued for pemvidutide.

Answer

CEO Dr. Vipin Garg described the FDA alignment as a "very important milestone" that provides clarity for potential partners. He explained the new indications leverage glucagon's benefits and will be detailed after regulatory clearance. CMO Dr. Scott Harris added that while the VELOCITY trials would ideally run in parallel, the exact sequencing is still under review.

Yasmeen Rahimi asked why Ohtuvayre's rapid sales growth couldn't continue, given the strong Q1 performance. She sought clarity on the potential full-year run rate and inquired about the current gross-to-net percentage and its expected trend.

Answer

CFO Mark Hahn stated that the gross-to-net discount was 'well below 20%' in Q1 and is beginning to stabilize with little room for further dramatic improvement. CEO David Zaccardelli added that while Q1 growth was blunted by industry-wide seasonality, the company expects substantial continued growth driven by an expanding prescriber base and a 'stacking phenomenon' of new and refilling patients. He emphasized that the launch is still in its early stages with plenty of room to grow.

Yasmeen Rahimi from Piper Sandler asked about the potential for Ohtuvayre's sales to continue growing as rapidly as the Q4 to Q1 doubling, how the strong Q1 results might affect the full-year run rate, and the current gross-to-net (GTN) percentage.

Answer

Mark Hahn, Chief Financial Officer, stated that the gross-to-net discount was 'well below 20%' in Q1 and is beginning to stabilize. CEO David Zaccardelli added that while Q1 growth was blunted by industry-wide seasonality, he expects substantial continued growth driven by a 'stacking phenomenon' of new patient starts and strong refills, noting the launch is still in its early stages with significant room to grow.

Yasmeen Rahimi asked about potential headwinds or risks to Ohtuvayre's strong launch trajectory and sought details on the company's European strategy, including market opportunity, pricing, and potential commercialization costs.

Answer

Executive David Zaccardelli responded that the company does not foresee specific market or competitive headwinds due to the significant unmet need in COPD, identifying standard operational execution (manufacturing, regulatory) as the primary risk-management focus. Regarding Europe, he clarified that the current strategy is to advance the regulatory process in the EU and UK to strengthen their position for partnering discussions, not to establish their own commercial operations.

Yasmeen Rahimi inquired about the potential for 2025 revenue guidance early next year, the types of patients being prescribed Ohtuvayre, and the company's physician outreach goals for year-end and mid-2025.

Answer

Executive David Zaccardelli called it premature to give 2025 guidance but expects an 'enormous year of growth.' He confirmed that nearly 50% of prescriptions are for patients already on triple therapy, but use is broad across all patient types. Chief Commercial Officer Chris Martin added that the commercial focus remains on increasing the frequency of interactions with their 14,500 Tier 1 and Tier 2 physicians to accelerate adoption.

Emma, on behalf of Yasmeen Rahimi, asked for color on the initial patient starting forms to understand uptake and what specific launch metrics the company plans to share in future earnings calls to track progress.

Answer

CEO David Zaccardelli stated that while the company aims for transparency, the specific metrics shared will evolve as the launch matures. He highlighted the strong early momentum, with over 100 healthcare providers (HCPs) prescribing Ohtuvayre within the first few days of launch, indicating significant initial uptake.

Yasmeen Rahimi asked for evidence to build investor confidence in the upcoming Huntington's disease data for dalzanemdor, following recent pipeline setbacks.

Answer

CEO Barry Greene pointed to the strong Zurzuvae launch momentum. Chief Medical Officer Laura Gault highlighted the strong scientific rationale for dalzanemdor in Huntington's, noting the role of the NMDA receptor and that the genetically defined, younger, and more homogeneous patient population makes it easier to detect a clinical signal.

Yasmeen Rahimi questioned whether the PPD market needs to be unlocked primarily through OB/GYNs and asked for details on the reach to this group and the strategy for expansion.

Answer

CEO Barry Greene affirmed that OB/GYNs are the critical audience to unlock the PPD market. He noted that due to early success, Sage plans to expand its sales force in Q4 to deepen its reach. CBO Chris Benecchi added that early data shows physicians who prescribe ZURZUVAE begin to diagnose and treat more PPD patients overall, signaling a significant paradigm shift in their practices.

Asked for an update on lonigutamab Cohort 3, timing for Cohort 4 data, the ideal patient profile for the Phase III TED trial, and how the company will manage potentially competitive trial enrollment.

Answer

The company plans to present data from the entire Phase II program after its FDA meeting to provide a complete picture. They are targeting the chronic TED population due to high unmet need and are confident in their ability to enroll the Phase III trials based on their current Phase II experience.

Asked about the design of the Phase III ENSURE studies, specifically the built-in futility analysis and the potential for sample size adjustments. Also inquired about expectations for the primary and key secondary endpoints of the Phase II CALLIPER trial, including what would be considered clinically meaningful.

Answer

The futility analysis in the ENSURE trials was planned from the start for the event-driven study to ensure its success and proper investment. For the CALLIPER trial, the primary endpoint is brain volume change, with key secondary endpoints like disability worsening (EDSS) also being crucial. While specific thresholds weren't given, any improvement in non-relapsing secondary progressive MS would be considered a success due to the high unmet need.