Charles Duncan

Elaine S. Kim, on behalf of Charles Duncan, asked about the measures being taken to limit 'professional patients' in trials to maintain effect size and the protocols in place to monitor and prevent suicidality risk.

Answer

Chief Medical Officer Dr. Dan Karlin detailed the robust patient selection process, which includes record reviews and third-party rater interviews. For safety, he explained they use the Columbia Suicide Severity Rating Scale (CSSRS) throughout the trials to monitor risk, noting no suicide signal was observed in the Phase II study.

Charles Duncan from Cantor Fitzgerald & Co. asked about the severity and treatment experience of enrolling patients, whether the sharp dose-response curve was surprising, the role of the 50mcg dose in managing unblinding, and the assumed dropout rate for the adaptive trial design.

Answer

CMO Dr. Dan Karlin stated they expect a patient sample similar to Phase II, with a mean HAM-A score in the severe range. CEO Robert Barrow explained the dose-response was consistent with models and that the 50mcg dose helps sever the link between acute effects and expectancy bias. He confirmed the assumed dropout rate is approximately 15% with a pooled standard deviation of 10 units.

Charles Duncan asked for clarification on the enrollment pacing for the VOYAGE study, the trigger for the interim analysis, and whether phenotypic data like prior therapies would be tracked and if they were drivers of efficacy in Phase IIb.

Answer

Executive Robert Barrow reiterated the guidance for a top-line readout from VOYAGE Part A in the first half of 2026 and explained the interim analysis for sample size reestimation would likely occur around the halfway enrollment point. Chief Medical Officer Dr. Daniel Karlin added that while extensive phenotypic data is tracked, the smaller group sizes in the Phase IIb study did not allow for the detection of any specific predictors of response.

Charles Duncan from Cantor Fitzgerald asked whether concerns about suicidality originated more from the FDA or investors during the study design, and also requested details on the new HealthPort collaboration, particularly its experience with delivering Spravato.

Answer

Dr. Guy Goodwin (CMO) and Kabir Nath (CEO) clarified that the FDA was not the source of suicidality concerns, as it's a known feature of depression; rather, concerns arose from public commentary after the Phase IIb data release. Dr. Steve Levine (CPO) explained that HealthPort serves underserved populations and already delivers Spravato, making them a key partner for ensuring equitable access to new treatments.

Charles Duncan sought more details regarding the recent DSMB review, specifically asking about the expected level of suicidal ideation in the trial's patient population and how the company is informed of any potential safety concerns.

Answer

Chief Medical Officer Dr. Guy Goodwin explained that suicidal ideation is an inherent risk in a treatment-resistant depression population and is being systematically tracked. He stressed that Compass relies on the unblinded DSMB's clinical judgment to assess the data for any safety signals and confirmed that the company would be alerted if the DSMB had any concerns.

Charles Duncan from Cantor Fitzgerald questioned the reasons for the recent timeline changes, asking if the regulatory strategy requiring both trials has shifted. He also inquired about enrollment patterns, specifically antidepressant washout success, and sought clarification on the company's cash runway through the new trial timelines.

Answer

Kabir Nath (Executive) confirmed the regulatory strategy remains unchanged. An unnamed executive (identified as Michael) stated that the antidepressant washout success rate is over 90% and not a logistical obstacle. Regarding the cash runway, Teri Loxam (Executive) reported a cash balance of $207 million, which is expected to fund operations at least into 2026, noting that savings from the announced restructuring are intended to offset the extended trial costs.

Charles Duncan from Cantor Fitzgerald questioned the perceived conservatism of the FIRDAPSE full-year guidance given its strong growth trajectory. He also asked about the potential for FYCOMPA revenue mitigation plans to extend into the next year and if the company has specific goals for completing a business development transaction in 2025.

Answer

CCO Jeffrey Del Carmen defended the FIRDAPSE guidance by citing consistent leading indicators and a stable patient pipeline. Regarding FYCOMPA, he acknowledged the 'stickiness' of anti-seizure medications, but CEO Richard Daly tempered expectations for 2026 due to likely increased generic competition. On business development, Mr. Daly emphasized the goal is to execute the 'right' transaction, not just any transaction, maintaining a discriminating approach.

Charles Duncan inquired about the drivers behind the precise 2025 guidance for FIRDAPSE, including new patient additions and discontinuation rates, and questioned the company's strategy for deploying cash to replace potential lost revenue from FYCOMPA after its patent expiry.

Answer

CEO Richard Daly and CCO Jeffrey Del Carmen explained that FIRDAPSE guidance is precise due to extensive experience with the product and a well-understood patient pipeline of over 500 diagnosed individuals. Del Carmen noted a steady, low annual discontinuation rate of 15% provides further confidence. Regarding capital deployment, Daly stated that while the FYCOMPA acquisition helped build cash reserves, the company's M&A focus remains on orphan and differentiated products, not necessarily in the retail epilepsy space unless the opportunity is also for a rare disease.

Charles Duncan questioned the commercial synergies between FIRDAPSE and AGAMREE given their different sales models, and requested more details on the AGAMREE SUMMIT study, including its near-term expectations and the target product profile for an enhanced label.

Answer

CCO Jeffrey Del Carmen explained the strategies are distinct: FIRDAPSE requires a broad educational reach for a dispersed prescriber base, while AGAMREE is a highly targeted, competitive sale to about 100 centers of excellence. Executive Gary Ingenito detailed that the 5-year SUMMIT study is in site activation and aims to collect high-quality, long-term data on bone health, growth, and mobility to strengthen AGAMREE's label.

Elaine Kim, on behalf of Charles Duncan from Cantor Fitzgerald, asked if specific patient subsets in the Phase III COMPASS trial are more likely to respond to treatment and requested additional details about the upcoming R&D Day.

Answer

An executive, likely Head of R&D Elizabeth Thompson, responded that based on existing data, no specific patient subsets have been identified as more or less likely to respond. CEO Catherine Owen Adams added that the R&D Day will provide a deep dive into all clinical-stage programs, including new data on their essential tremor program.

Charles Duncan asked about the ACP-101 trial in Prader-Willi syndrome, specifically about the potential for an age-related effect given the wide age range, and inquired about the open-label extension study.

Answer

EVP of R&D Elizabeth Thompson confirmed the existence of an open-label extension study with good patient rollover. She explained that while data is limited, studying the wide age range is important because Prader-Willi is a lifelong disease, and the trial is designed to understand the drug's impact across the full patient population.

Charles Duncan of Cantor Fitzgerald asked for clarification on the data release protocol for the ACP-204 program, specifically whether Phase II efficacy data would be released while the Phase III studies are enrolling.

Answer

Executive Elizabeth Thompson confirmed that the current expectation is to release some data from the Phase II portion at an appropriate time. She added that the original plan always allowed for using Phase II data to make modifications to the Phase III studies as needed.

Charles Duncan of Cantor Fitzgerald inquired about the strategy and return on investment for the Fanapt direct-to-consumer (DTC) campaign, key data points to expect from the upcoming Bysanti bioequivalence presentation, and Vanda's European commercialization strategy for Fanapt and HETLIOZ.

Answer

President and CEO Dr. Mihael Polymeropoulos confirmed the DTC campaign for bipolar disorder is active and has received positive feedback, validating the promotional sensitivity of the market. He stated the upcoming Bysanti presentation will detail two pivotal bioequivalence studies. For Europe, he acknowledged a tough pricing environment but noted an appetite for long-acting injectables, confirming that Day 120 questions from the EMA have been received and are being addressed, leveraging Vanda's existing German presence.

Charles Duncan of Cantor Fitzgerald inquired about the source of Fanapt's commercial traction, the sufficiency of the expanded sales force, the strategy behind the direct-to-consumer (DTC) campaign, the clinical rationale for studying Bysanti in Major Depressive Disorder (MDD), and the reason for the imsidolimab BLA filing timeline.

Answer

CEO Mihael Polymeropoulos explained that Fanapt's growth stems from prescribers treating bipolar disorder, a new segment for the drug. He described the sales force expansion to 300 representatives as a measured approach to ensure quality, while acknowledging potential competition. Dr. Polymeropoulos confirmed the DTC campaign targets bipolar I patients to raise awareness and noted that Bysanti's potential in MDD is supported by extensive data on its parent compound, iloperidone. Regarding imsidolimab, he stated that a pre-BLA meeting with the FDA provided confidence for a filing this year.

Charles Duncan asked for details on the Fanapt relaunch for bipolar I disorder, including feedback from sales reps, sales force optimization, and prescription trends (TRx vs. NRx). He also inquired about the potential competitive impact from Bristol's Cobenfy and the relative importance and development timelines for the Fanapt LAI versus milsaperidone.

Answer

CEO Mihael Polymeropoulos confirmed that the 90% increase in new-to-brand prescriptions (NBRx) is leading to growth in new (NRx) and total (TRx) prescriptions. He stated the sales force is not yet optimized as expansion continues to drive growth. He does not foresee a direct negative impact from Cobenfy, which is approved for schizophrenia, and believes it will renew interest in the therapeutic class. Dr. Polymeropoulos noted the milsaperidone NDA filing is gated by stability data expected in Q1 2025 and highlighted the significant opportunity in expanding to major depression. Executive Kevin Moran added that sales force interactions with prescribers increased three- to fourfold from Q1 to Q3.

An analyst on for Charles Duncan of Cantor Fitzgerald asked about the catalysts and market dynamics supporting the company's confidence in Epidiolex achieving blockbuster status in 2025.

Answer

Bruce Cozadd, CEO, noted the product is already at a blockbuster run rate. Renée Galá, President and COO, detailed the growth drivers, including its differentiated profile, data on non-seizure benefits, strong momentum in the adult and long-term care settings, high-quality access, and a Nurse Navigator program that improves patient persistency.

Charles Duncan of Cantor asked if the strategy for submitting MAPLE-HCM data post-approval would also apply to regulatory bodies in the EMEA and China.

Answer

Fady Malik, EVP of R&D, confirmed the strategy is consistent across all jurisdictions. He explained that adding the MAPLE-HCM data to applications already deep into their review cycles would be disruptive, so the plan is to submit it as a supplementary filing after initial approvals are secured.

Charles Duncan of Cantor Fitzgerald asked about the Sanofi deal for aficamten in China, inquiring about the unmet need, the potential pace of development, and the likelihood of receiving milestone payments this year or early next.

Answer

EVP & CBO Isaac Ciechanover noted Sanofi's strong engagement and the clear unmet need in China, where there are no REMS programs. He confirmed milestones are tied to a potential approval this year. EVP & CCO Andrew Callos added that China is a concentrated market with about 400,000 diagnosed patients, primarily treated in just over 1,000 hospitals. President & CEO Robert I. Blum stated they could be eligible for up to $35 million in total milestones this year across all partners, tied to clinical and regulatory events.

Charles Duncan inquired about WAKIX demand trends early in Q2 and whether guidance relies more on demand or marketing efforts. He also asked about the rate-limiting step for initiating the pitolisant HD Phase III trials.

Answer

CCO Adam Zaeske and CEO Dr. Jeffrey Dayno confirmed strong momentum exiting Q1 underpins the full-year guidance, which is primarily demand-driven. Dr. Kumar Budur, CMSO, explained that initiating the large, global Phase III trials for pitolisant HD requires completing multiple steps, including final formulation work, protocol finalization, and regulatory submissions, all of which are on track for a Q4 start.

Charles Duncan inquired about the ZYN002 Phase III RECONNECT trial, seeking details on patient enrollment characteristics like methylation rates, weight, and age, as well as the rollover rate into the open-label extension.

Answer

Dr. Kumar Budur, Chief Medical and Scientific Officer, stated the trial is on track for Q3 2025 data. He confirmed enrollment includes patients with both complete and partial methylation, ages 3-30, with higher doses for patients over 50kg. Dr. Budur highlighted the "unprecedented" persistency in the long-term extension, with some patients on ZYN002 for over 8 years, suggesting durable effectiveness.

Charles Duncan asked for the breakdown of new WAKIX patients from oxybate versus non-oxybate prescribers and questioned why the full-year 2024 revenue guidance was not narrowed despite strong performance.

Answer

Chief Commercial Officer Jeffrey Dierks stated that approximately 60% of new patients come from oxybate REMS-enrolled prescribers and 40% from non-oxybate prescribers. Chief Financial Officer Sandip Kapadia explained that the guidance range was already narrow and the company remains comfortable with it, expecting continued quarter-over-quarter growth.

Charles Duncan of Cantor Fitzgerald asked for details on the SYMBRAVO sales force expansion, including its size and focus, and inquired about the potential timing for presenting recent clinical data, such as for patients with inadequate response to CGRPs, possibly at the upcoming American Headache Society (AHS) meeting.

Answer

Ari Maizel, Chief Commercial Officer, reported that the SYMBRAVO sales team build-out of approximately 100 representatives is nearly complete, with a focus on high-volume migraine prescribers. Herriot Tabuteau, CEO, confirmed that the AHS meeting will be an important scientific venue for the company and that they expect to have a presence there.

Charles Duncan asked for details on the recent Auvelity sales force expansion, its potential synergies with the Symbravo launch, and sought more specific timing for the AXS-05 NDA submission in H2 2025.

Answer

Chief Financial Officer Nick Pizzie stated the Auvelity sales team was expanded by approximately 40 representatives, a 10-15% increase, and confirmed expected synergies with Symbravo prescribers in primary care. Chief Operating Officer Mark Jacobson clarified the AXS-05 submission is gated by building the submission, not a stability time point, and is a top priority to be filed as early as possible in the second half.

Charles Duncan of Cantor Fitzgerald inquired about Auvelity's traction with psychiatrists versus primary care physicians (PCPs), the role of its rapid response profile, and its potential differentiation for ADA. He also asked about the ADVANCE-2 sample size and open-label extension study enrollment for AXS-05.

Answer

CCO Ari Maizel confirmed strong performance in both psychiatry and primary care, noting PCPs were the fastest-growing segment in Q3, and that rapidity of response is a key driver. CEO Herriot Tabuteau added that the high rollover rate into the AXS-05 open-label extension is a positive sign that helps meet safety exposure requirements for a potential NDA filing.

Charles Duncan asked for a breakdown of LYBALVI's prescription sources between schizophrenia and bipolar disorder, and questioned what attributes of ALKS 2680, beyond its high potency, support the company's investment.

Answer

Todd Nichols, Chief Commercial Officer, stated that LYBALVI's total prescriptions are split roughly 50/50 between schizophrenia and bipolar, with new patient starts trending higher for bipolar at 55%. CEO Richard Pops added that ALKS 2680 is also a true once-daily agent with dose flexibility and a wide therapeutic index, which contributed to positive data across all three patient populations in Phase 1b.

Charles Duncan asked about competitive dynamics for LYBALVI and ARISTADA, the magnitude of the sales force expansion, and the relative enrollment progress and potential readout timing for the VIBRANT 1 and 2 orexin studies.

Answer

CCO C. Nichols addressed the commercial questions, stating the sales force is expanding by approximately 80 representatives to maintain a competitive share of voice. CEO Richard Pops handled the pipeline question, explaining that both the NT1 and NT2 studies are enrolling well and that the company hopes they will finish around the same time in the second half of 2025.

Charles Duncan asked about LYBALVI's market dynamics, specifically where new scripts are coming from and the potential impact of new muscarinic competitors, and also inquired about the types of indications being considered for next-generation orexin compounds.

Answer

CCO Todd Nichols explained that LYBALVI's growth is strong in both bipolar I and schizophrenia, with new patient starts increasingly coming from bipolar I. He expressed confidence that LYBALVI's established profile and real-world evidence will be key differentiators against new entrants. CEO Richard Pops noted that potential indications for the orexin pipeline could span psychiatry, neurology, and even rare diseases, with specific development paths to be determined after early clinical characterization.

Charles Duncan from Cantor Fitzgerald asked about the distinction between statistical significance and clinical meaningfulness for birtamimab, and whether KOL feedback suggests demand would vary based on the magnitude of the survival benefit.

Answer

President and CEO Gene G. Kinney asserted that given the complete lack of therapies addressing early mortality, any result meeting the SPA's statistical threshold (p<=0.10) would be highly meaningful. COO Brandon Smith supported this, stating that market research with physicians and payers confirms that any demonstrated early survival benefit would be met with strong interest due to the well-understood unmet need.

Charles Duncan from Cantor Fitzgerald questioned the relationship between statistical significance and clinical meaningfulness for birtamimab, asking if market research indicates physician demand would vary based on the magnitude of the survival benefit.

Answer

President and CEO Gene G. Kinney asserted that given the lack of treatments for early mortality, any benefit meeting the SPA's p-value of ≤ 0.10 would be highly meaningful. COO Brandon Smith supported this, stating that market research confirms the unmet need is so profound that any statistically significant early survival benefit would drive strong interest from physicians and payers.

Charles Duncan inquired about the distinction between statistical significance and clinical meaningfulness for birtamimab's survival benefit, and how different effect sizes might impact physician demand.

Answer

CEO Gene G. Kinney emphasized that given the lack of treatments addressing early mortality, any benefit meeting the SPA's statistical threshold (p-value < 0.10) would be highly meaningful. Chief Operating Officer Brandon Smith added that market research confirms KOLs and payers recognize this unmet need, and any early survival separation would drive strong interest, as the all-cause mortality endpoint is considered the gold standard.

Asked about the specific regulatory indication being sought for adjunctive MDD, the rationale for using ITI-1284 instead of lumateperone for generalized anxiety disorder (GAD), and the timeline for potential pediatric data.

Answer

The company is seeking an indication for the adjunctive treatment of MDD, consistent with the Phase 3 program design. For GAD, they are exploring ITI-1284 due to its profile and will reevaluate other indications over time. Pediatric study results for lumateperone are not expected in 2025 as these trials take longer than adult studies.

Asked about the potential impact of new muscarinic agonists for schizophrenia and for clarification on Bristol-Myers' role with CAPLYTA.

Answer

The company does not expect a significant impact from new schizophrenia drugs, as CAPLYTA's growth is increasingly driven by bipolar depression and future MDD potential. They confirmed Bristol-Myers has no marketing role and only receives a royalty.

Asked about the possibility of an interim analysis, the specific steps leading to the Q2 2025 trial start, the status of FDA protocol finalization, and the budget for the Phase III trial.

Answer

The company will not conduct an interim analysis. The timeline to Q2 2025 involves finalizing the protocol, placebo manufacturing, site selection, and extensive regulatory and contractual work. Finalizing the protocol with the FDA involves points of clarification. The estimated budget remains $85-$100 million to support operations through 2026.

Inquired about the Phase III trial design, specifically regarding enrollment criteria, the nature of the co-primary endpoints, and whether bone health monitoring is required. Also asked for perspective on what drove the FDA's shift in viewing LUM-201 as a stimulator rather than a mimetic.

Answer

The Phase III enrollment criteria will be very similar to Phase II with minor adjustments to the age limit and bone age delay. The trial has two true co-primary endpoints (12-month growth and 6-month placebo comparison), and it will be powered for both. The FDA does not require bone density imaging. The key driver for the FDA's perspective shift was the extensive data showing LUM-201's ability to restore the natural pulsatile rhythm of growth hormone, demonstrating a more efficient and distinct mechanism of action.

Charles Duncan of Cantor Fitzgerald inquired about atai's strategy for navigating turbulent biotech markets, including potential acquisitions and cash management. He also asked for key takeaways from COMPASS Pathways' COMP360 Phase 2b data, the scientific rationale for RL-007 in schizophrenia-associated cognitive impairment, and the company's strategic thinking on short versus long-acting psychedelics like DMT.

Answer

CEO Florian Brand described the market downturn as a significant investment opportunity, particularly in neuropsychiatry, and confirmed atai's strong cash position of $335 million allows for disciplined execution and continued screening for new assets. CSO Srini Rao highlighted the rapid onset and durable efficacy from the COMP360 data as key learnings. Regarding RL-007, Rao explained its unique mechanism modulates multiple neurotransmitter systems, offering a broad effect for a heterogeneous condition. Brand and Rao concluded by explaining their DMT program targets a moderate duration of effect (45-60 minutes) to fit within existing clinical paradigms, viewing it as an optimal balance of therapeutic potential and commercial viability.

Charles Duncan of Cantor Fitzgerald inquired about the definition of 'good versus great' results for PCN-101 and its potential to surpass S-ketamine. He also asked about the planned dosing for the RL-007 Phase IIa trial and whether future earnings calls would focus more on pharmacology or digital therapeutics.

Answer

CEO Florian Brand defined a 'win' for PCN-101 as hitting the primary MADRS endpoint with a strong therapeutic index, noting preclinical data suggests potential for superior efficacy and duration over S-ketamine. CSO Dr. Srini Rao confirmed RL-007 dosing will be in the 20-40mg range. Florian Brand concluded that future calls will cover both pharmacological agents and their integration with digital therapeutics.

Charles Duncan from Cantor Fitzgerald requested more detail on the earlier-than-expected return to prescription growth in Q1 and asked what key message Biohaven wants prescribers to hear to accelerate the adoption of oral CGRPs, particularly NURTEC ODT.

Answer

Chief Commercial Officer BJ Jones explained that the return to growth, which began in February, is a positive trend across the entire oral CGRP class, fueled by increased promotion. He stated the key message for prescribers is that NURTEC ODT offers a low-risk, high-upside, convenient single-product solution to both treat and prevent migraines, a message that is resonating and driving market growth.

Charles Duncan from Cantor Fitzgerald asked about the pharmacoeconomic considerations for pricing in European and Asian markets compared to the U.S. He also inquired if Pfizer had expressed interest in the U.S. market during negotiations.

Answer

CEO Dr. Vlad Coric explained that the core value proposition of reducing disability, a leading issue for people under 50, will be a key argument for payers globally, similar to the U.S. strategy. He reiterated that Biohaven's priority was securing an ex-U.S. partner and that the company successfully maintained full flexibility and optionality for the U.S. market.

Charles Duncan from Cantor Fitzgerald sought more detail on new prescription sources, asking if they came from new prescribers or deeper prescribing. He also asked about Zavegepant's positioning relative to Rimegepant and other drugs.

Answer

CCO BJ Jones confirmed that prescription growth is driven by both an increase in new prescribers and deeper prescribing from existing users. CMO Dr. Elyse Stock positioned intranasal Zavegepant for rapid onset and the oral version for daily prevention. CEO Vlad Coric highlighted that Zavegepant's favorable CGRP tolerability profile will be a key differentiator against older mechanisms with known side effects.

Charles Duncan from Cantor Fitzgerald asked how vazegepant will fit within the CGRP franchise and what risk-reduction strategies were implemented for the Troriluzole and verdiperstat trials in difficult-to-treat indications.

Answer

CEO Vladimir Coric positioned intranasal vazegepant as a complementary, ultra-rapid option and the oral version for daily prevention and non-migraine indications. He explained that the Troriluzole and verdiperstat trials were de-risked by designing them based on positive Phase 2 data, which allowed for optimized dosing, sample sizes, and endpoints.

Charles Duncan from Cantor Fitzgerald & Co. asked for the timing of clinical updates for the CYB003 trial in MDD. He also inquired about the trial's design, specifically patient follow-up beyond six weeks and the biological rationale for a shorter psychedelic experience driving efficacy. Finally, he asked about the key differentiators of the newly patented CYB004.

Answer

CEO Douglas Drysdale stated that the CYB003 trial is on track for a mid-year start, with initial PK and safety data expected by year-end. He explained that the shorter duration of CYB003 (around 2 hours) combined with a second dose is a favorable trade-off for achieving long-term durability. Regarding CYB004, he highlighted that the patent covers composition of matter and that deuteration slows its breakdown, creating a smoother, longer therapeutic window and reducing the anxiety often associated with classical DMT.

Charles Duncan from Cantor Fitzgerald inquired about the confidence in CYB003's best-in-class potential following recent data from Compass Pathways, the capital efficiency of its development path, and its new chemical entity (NCE) intellectual property status.

Answer

CEO Doug Drysdale explained that the Compass data confirmed psilocybin's efficacy but also its known limitations, such as side effects and durability concerns, which CYB003 is designed to overcome with a lower dose, reduced variability, and shorter duration. He affirmed the development path is capital-efficient and that CYB003 is considered an NCE with a strong patent portfolio based on its deuteration, which enhances bioavailability and brain penetration.