Marc Goodman

Marc Goodman asked for an update on DAYBUE's persistency, patient compliance, and how these metrics have evolved, noting they hadn't been discussed in detail.

Answer

Tom Garner, Chief Commercial Officer, confirmed that DAYBUE discontinuations remain in the low single-digit range and have stabilized, with consumption in the high 60% range. He emphasized that the business is now stabilized and on a growth trajectory, with the STIX formulation expected to unlock the next wave of growth.

Marc Goodman asked for an update on DAYBUE's persistency and patient compliance, and how these metrics have evolved over time.

Answer

Catherine Owen Adams, CEO, and Tom Garner, Chief Commercial Officer, confirmed that DAYBUE's discontinuations remain in the low single-digit range and have stabilized. Consumption rates are consistent with previous quarters, in the high 60% range for the full year, indicating a stable business now poised for growth with the STIX formulation and community expansion.

Marc Goodman asked about Daybue discontinuation rates in the quarter and whether there were any significant inventory changes for either Daybue or NUPLAZID. He also had a follow-up question on the company's tax rate.

Answer

Chief Commercial Officer Thomas Garner stated that Daybue discontinuations remained low, well below 10%. CFO Mark Schneyer reported no significant changes in channel inventory for NUPLAZID and reminded that the concept doesn't apply to Daybue's direct-to-patient model. Mr. Schneyer also explained that the cash tax rate is currently in the mid-teens but will likely go down in the next year or two due to accelerated expensing of capitalized R&D.

An analyst on behalf of Marc Goodman of Leerink Partners requested color on DAYBUE's utilization and compliance rate for the quarter, the average age and weight of patients, and any observed correlation between patient age and discontinuation rates.

Answer

CCO Thomas Garner reported that DAYBUE's compliance rate was in the 'very high 60s,' slightly down from Q4, which may be related to physicians' titration strategies. He noted the patient mix is broad and stable. CEO Catherine Owen Adams added that the company has not observed any correlation between patient age and persistency rates.

An analyst on behalf of Marc Goodman of Leerink Partners asked about Daybue's persistency, questioning if the 60% of patients remaining on therapy at 10 months are all considered responders. He also requested more detail on the primary drivers of discontinuation.

Answer

Executive Brendan Teehan confirmed that the flattening persistency curve suggests patients remaining on therapy are benefiting from the treatment, as confirmed by feedback from family access managers. He reiterated that most discontinuations occur early, within the first one or two fills, and are primarily driven by tolerability issues like diarrhea or vomiting, rather than a lack of efficacy.

Marc Goodman asked about the development plan and excitement for Valiloxybate, inherited in the Avadel acquisition, and whether it's viewed as a replacement for LUMRYZ or an addition, inquiring about the timeline to market and required studies.

Answer

Blair Jackson, COO of Alkermes, described Valiloxybate as an interesting asset for the low-to-no sodium space, with plans to advance it quickly by leveraging PK profile and formulation capabilities. He stated it's too early to determine if it will replace or add to LUMRYZ, and the development path (full plan vs. bridging studies) depends on early data and bioequivalence.

Marc Goodman asked about the development plan for Valiloxybate, inherited from the Avadel acquisition, its potential as a replacement strategy for LUMRYZ, and the timeline to market.

Answer

Blair Jackson, Chief Operating Officer, described Valiloxybate as an interesting asset with potential in the low-to-no sodium space. Alkermes aims to advance the program quickly, leveraging its formulation capabilities to expedite it through the clinic. He noted it's too early to determine if it will replace LUMRYZ or be an addition, depending on early data and bioequivalence.

Marc Goodman of Leerink Partners sought clarification on the 'learnings' for the Phase 3 cataplexy endpoint, asking if they related to statistical methods or different assays. He also asked if insomnia is still considered a transient, early-onset AE.

Answer

Marcus Yountz, VP of Clinical Development, clarified that the learnings relate to the operational implementation of the cataplexy assay, such as standardizing patient recording to reduce variability. Richard Pops, Chairman & CEO, reiterated confidence in the cataplexy signal and deferred questions on the time course of AEs to the World Sleep presentation.

Marc Goodman inquired whether government funding cuts to substance abuse programs were impacting VIVITROL sales and if the competitive launch of Bristol Myers Squibb's Cobenfy had altered prescription patterns for LYBALVI.

Answer

Todd Nichols, CCO, stated that VIVITROL is not seeing an impact from federal funding changes, as the business has been re-engineered to focus on the alcohol dependence indication. He also confirmed LYBALVI continues to see healthy growth with no impact from competitors, noting that market data shows Cobenfy is used primarily as an adjunctive therapy and does not directly compete.

Marc Goodman asked for more details on Alkermes's next-generation orexin candidates and for an update on the company's business development activities and the likelihood of a deal in 2025.

Answer

CEO Richard Pops stated that specifics on the next-gen orexin indications will be shared after initial clinical studies are complete. On business development, he said the company is always looking for clinical-stage neuroscience assets and ways to leverage its commercial infrastructure but feels no urgency and has a high bar for potential deals.

Marc Goodman asked how to model VIVITROL after its loss of exclusivity (LOE) with a single generic entrant, questioned the EBITDA growth trajectory beyond the 2025 reset, and asked if the share buyback implies a lack of viable business development opportunities.

Answer

CEO Richard Pops described the base case for VIVITROL post-2027 as maintaining promotional support against a single entrant, not a typical generic erosion, given the market's growth dynamics. He stated that while the company will manage for profitability, future EBITDA growth depends on annual assessments of pipeline and market needs. He refuted the idea that buybacks signal a lack of BD options, stating the company has ample firepower but maintains a high bar for diligence.

Marc Goodman sought information on JZP047, asking about its background, whether it's a cannabidiol from the GW deal, available preclinical data, proof of concept, mechanism of action, and the rationale for targeting absence seizures.

Answer

Rob Iannone, EVP of Research and Development, clarified that JZP047 is a novel chemical entity discovered and developed in-house by Jazz, not a cannabinoid. He confirmed strong preclinical data supporting its development for absence epilepsy, with initial Phase 1 studies focusing on healthy volunteers to assess safety and efficacious exposures.

Marc Goodman sought further information on JZP047, including its background, whether it is a cannabidiol, available preclinical data, proof of concept, mechanism of action, and the rationale for targeting absence seizures.

Answer

Rob Iannone, EVP of Research and Development, clarified that JZP047 is a novel chemical entity developed in-house, not a cannabinoid, with strong preclinical data in absence epilepsy. He noted that the initial Phase I healthy volunteer trial aims to de-risk the asset by evaluating safety and exposures before patient studies.

Marc Goodman of Leerink Partners asked for a quantification of the potential full-year financial impact of tariffs on an annualized basis, assuming the company did not have its current inventory buffer.

Answer

Bruce Cozadd, Chairman and CEO, declined to speculate on hypothetical scenarios, stating the impact would depend on specific tariff rates and affected geographies. He reiterated that the company is well-positioned for 2025 due to its inventory strategy and has effective mitigation options for its oxybate products through its U.S. supplier.

Marc Goodman of Leerink Partners inquired about the JZP-441 (orexin) program's safety margin and dosing progress, and also requested the specific date for the recently announced Epidiolex patent settlement.

Answer

Bruce Cozadd, Chairman and CEO, addressed the Epidiolex settlement, stating that while confidentiality prevents disclosing the exact date, the agreements with all 10 ANDA filers extend to the "very late 2030s." Robert Iannone, EVP and Global Head of R&D, noted there were no new updates on the JZP-441 trial but confirmed it is designed to help define a better therapeutic index.

Marc Goodman inquired about the JZP-441 (orexin) program's safety margin progress and requested the specific settlement date for the Epidiolex patents.

Answer

CEO Bruce Cozadd stated the Epidiolex settlements with all 10 ANDA filers extend to the "very late 2030s" but could not be more specific due to confidentiality. EVP, Global Head of R&D Rob Iannone provided no new updates on the JZP-441 trial but noted it will help define a better therapeutic index.

Marc Goodman requested Jazz's latest perspective on the orexin drug class in light of recent competitor data, and asked for more details on their own asset, JZP441, including any available data and commentary on its adverse event profile.

Answer

EVP, Global Head of R&D Robert Iannone commented that the orexin field is still early and the ideal best-in-class profile is not yet defined, highlighting potential differentiators like hepatic safety and half-life. For JZP441, he confirmed a Phase Ib study is planned for the first half of 2025 in NT1 patients to evaluate its therapeutic index and inform future development.

Marc Goodman of Leerink Partners LLC requested an update on the company's perspective on the competitive orexin class and sought more details on their own candidate, JZP441.

Answer

EVP, Global Head of R&D, Rob Iannone, stated that the orexin field is still evolving and a best-in-class profile remains undefined, citing potential safety issues like hepatic toxicity and visual disturbances as key differentiators. He confirmed that Jazz plans to initiate a Phase Ib trial for JZP441 in narcolepsy type 1 patients in the first half of 2025 to assess its therapeutic window and inform future development.

Marc Goodman asked for details on AXS-17's development plan for epilepsy, including the specific types of epilepsy being considered and the existing patient data from its prior development.

Answer

Herriot Tabuteau, CEO, explained that AXS-17 was previously studied for generalized anxiety disorder, providing extensive safety data from chronic dosing. The current focus on epilepsy is based on broad preclinical studies, and the company is assessing specific epilepsy indications, with more details to be provided later in the year.

Marc Goodman asked for details on AXS-17, specifically the types of epilepsy being considered for development, the development plan, and the existing patient data history for the product.

Answer

Herriot Tabuteau (CEO, Axsome Therapeutics) explained that AXS-17 has been studied in generalized anxiety disorder, providing safety data from chronic dosing across a range of doses. He noted that the epilepsy direction is based on preclinical studies predictive of clinical success, and the team is assessing specific epilepsies to target first, with updates expected later in the year.

Marc Goodman asked for details on the company's 'precision medicine approach' to ADHD and whether this strategy extends to the adolescent population.

Answer

Chief Executive Officer Dr. Herriot Tabuteau clarified that the 'precision medicine approach' mentioned in prepared remarks referred to solriamfetol for major depressive disorder (MDD), not ADHD. For ADHD, he noted the disease continuum from childhood to adulthood implies that efficacy in adults bodes well for pediatrics.

Marc Goodman of Leerink Partners asked for the timing of the direct-to-consumer (DTC) advertising campaign for Auvelity and inquired about how Axsome's narcolepsy drug, AXS-12, is positioned to compete with the anticipated arrival of orexin agents in the market.

Answer

Ari Maizel, Chief Commercial Officer, confirmed that a national DTC campaign for Auvelity is planned for later in the year. Regarding AXS-12, he expressed optimism, citing positive feedback on its compelling profile, including daytime dosing and strong efficacy on cataplexy. He acknowledged the enthusiasm for orexins but noted that questions about their safety and tolerability remain.

Marc Goodman requested guidance on how to model expenses for the upcoming year and asked about the specific gating factors for the AXS-12 narcolepsy filing scheduled for the second half of the year.

Answer

Chief Financial Officer Nick Pizzie indicated that R&D spend likely peaked in Q4 2024 and will moderate in 2025, while overall OpEx will increase but at a slower rate than sales. Chief Operating Officer Mark Jacobson explained the AXS-12 filing is gated by the pre-NDA meeting and the work of building the submission, noting it involves the same FDA division as the AD agitation filing.

Marc Goodman of Leerink Partners asked about the evolving real-world use of Auvelity, the sales force strategy for the upcoming migraine launch, and the filing requirements for reboxetine (AXS-12), specifically if the ENCORE study needs to be positive.

Answer

CCO Ari Maizel noted Auvelity use remains around 50% first/second-line and 50% monotherapy/adjunct, with improving trends, and confirmed the migraine launch will involve a separate, targeted sales force. CEO Herriot Tabuteau clarified the AXS-12 ENCORE study is not required to be positive for an NDA filing, as its primary purpose is long-term safety data.

Marc Goodman sought clarification on the -4% INGREZZA price decline for 2026 relative to 2025, and asked how Neurocrine views the potential future use of ACTH antagonists, specifically if they would be an add-on or competitive product.

Answer

Matt Abernethy, Chief Financial Officer, clarified that the -4% price impact for INGREZZA is year-on-year, concentrated in the first half of 2026, but net revenue per script is expected to be stable throughout 2026. Kyle Gano, Chief Executive Officer, stated that CRENESSITY and ACTH antagonists are different programs at different stages, emphasizing CRENESSITY's approved status, successful launch, multi-year head start, and its profile in changing the standard of care, expressing confidence that it will not be displaced by future medicines.

Marc Goodman sought clarification on the -4% price impact for INGREZZA in 2026, specifically if it's relative to the full-year 2025 net price, and asked for Neurocrine's perspective on how a future ACTH antagonist drug might be used in relation to CRENESSITY.

Answer

CFO Matt Abernethy clarified that the -4% price impact for INGREZZA is year-on-year, concentrated in the first half of 2026, but net revenue per script is expected to be stable throughout 2026. CEO Kyle Gano emphasized CRENESSITY's approved status, multi-year head start, and strong profile across efficacy, safety, and formulations, expressing confidence that it will not be displaced by future medicines.

Marc Goodman asked about CRENESSITY's gross-to-net, noting its better-than-expected adoption and inquiring if gross-to-net discounts are expected to continue decreasing to more normalized levels for an orphan product.

Answer

Matt Abernethy, Chief Financial Officer, guided that CRENESSITY's gross-to-net discount is anticipated to be less than 20% in the foreseeable future. He explained that dynamics include a base of Medicaid patients requiring statutory rebates, but emphasized strong reimbursement rates (above 80%) and high adjudication success (9 out of 10 patients).

Marc Goodman asked about CRENESSITY's gross-to-net dynamics, specifically if they would continue to decrease to more normalized levels for an orphan product over the next three to four quarters, given the better-than-expected reimbursement.

Answer

Matt Abernethy, Chief Financial Officer, guided that the gross-to-net discount for CRENESSITY is anticipated to be less than 20% in the foreseeable future. He explained that dynamics include a base of Medicaid patients requiring statutory rebates, but overall reimbursement is strong, with over 80% of patients receiving approval.

Marc Goodman of Leerink Partners sought clarification on the negative 5% INGREZZA average selling price (ASP) decline for 2025, asking if the stable 2026 pricing outlook is based on the full-year 2025 average or the lower exit rate.

Answer

CFO Matt Abernethy confirmed that the outlook for similar pricing in 2026 is based on the trajectory at which Neurocrine exits 2025. He also clarified that the negative 5% price impact is a full-year 2025 figure, meaning the price headwind is more concentrated in the second half of the year due to the timing of new contracts.

Marc Goodman requested an updated net revenue per script figure for INGREZZA and an update on the progress of the broader muscarinic portfolio beyond the lead asset, NBI-'568.

Answer

Chief Financial Officer Matthew Abernethy declined to provide a specific net revenue per script number but guided that gross-to-net would be 'sequentially down just slightly' in Q2 versus Q1. Chief Medical Officer Dr. Eiry Roberts detailed the rest of the muscarinic pipeline, noting that the dual M1/M4 agonist NBI-'570 is on track to begin a Phase II study in acute psychosis by the end of the year.

Marc Goodman asked if Q4 INGREZZA sales were helped by inventory changes and inquired about the characteristics and differentiation of the NBI-570 (M1/M4) molecule compared to Karuna's drug.

Answer

Chief Financial Officer Matthew Abernethy clarified his earlier comment was about a potential Q1 2025 ordering pattern phenomenon due to the calendar, not a Q4 inventory build. Chief Medical Officer Eiry Roberts explained that NBI-570 is a selective dual M1/M4 agonist, unlike Karuna's pan-muscarinic drug. This selectivity avoids M2, M3, and M5 receptors, which she anticipates will result in a different side effect profile without requiring a co-formulated peripheral agent.

Marc Goodman of Leerink Partners asked for clarification on the INGREZZA competitive environment, referencing investor concerns that Teva was growing faster and had a greater share of voice.

Answer

CCO Eric Benevich acknowledged that both brands are growing in an expanding market and that the competitor's growth was expected with its new formulation. However, he reinforced that INGREZZA remains the most prescribed VMAT2 inhibitor. He cited the recent sales force expansion in psychiatry and long-term care as a testament to Neurocrine's conviction in INGREZZA's long-term growth opportunity.

Marc Goodman of Leerink Partners asked for clarification on the magnitude and real-world clinical meaningfulness of the cognitive and behavioral improvements observed in the Vineland-3 OLE data, and whether the continued improvement from 24 to 36 months was surprising.

Answer

SVP & Head of Neurology Kimberly Parkerson described the 8-10 point changes as 'profound,' noting that caregivers had previously identified 1-3 point changes as clinically meaningful. She conveyed the internal excitement and emotion at seeing the durable improvements. CMO Barry Ticho added that the concurrent trend toward greater seizure reduction on the maintenance dose further validates the drug's mechanism of action.

Marc Goodman from Leerink Partners asked about the key gating issues between the final data release and the NDA filing, focusing specifically on CMC (Chemistry, Manufacturing, and Controls) and long-term safety data requirements.

Answer

Chief Medical Officer Hendrik Scholl confirmed they will meet the long-term safety requirement of 300 subjects on drug for 12 months by Q1 of next year by pooling data from the PHOENIX trial. Chairman & CEO Tom Lin added that they are on track with the registration batches and have ongoing CMC discussions with the FDA.

Marc Goodman of Leerink Partners asked for Avadel's perspective on the overall oxybate market's size and growth rate. He sought to understand if LUMRYZ is expanding the market or primarily taking share, referencing competitor reports.

Answer

CEO Gregory Divis explained that while they lack full visibility into competitor data, Avadel sees clear signs of market expansion. He cited adding new prescribers who had never written for oxybates before and bringing back patients who had discontinued prior therapies as evidence. COO Susan Rodriguez added that they are persistently drawing from discontinued and switch patients, driving momentum.

Marc Goodman of Leerink Partners asked for the average selling price or net revenue per patient in Q1 and how that metric is expected to trend for the remainder of the year.

Answer

CFO Thomas McHugh explained that Q1 is always heavily impacted by gross-to-net deductions, resulting in an annualized average net revenue per patient of just under $80,000. He expects a similar percentage improvement from Q1 to Q2 as seen in the prior year and anticipates overall improvement for the full year. CEO Gregory Divis added that the metric will improve as more patients remain on therapy longer at steady doses.

Madhu, on behalf of Marc Goodman from Leerink Partners, asked if there are geographic regions with lower cardiovascular comorbidity rates where LUMRYZ might have a competitive advantage, and inquired about specific initiatives to improve persistency for new-to-oxybate patients.

Answer

Executive Gregory Divis responded that the company has not observed a specific geographic pattern for cardiovascular risk and noted that research shows it is not a top-20 comorbidity in narcolepsy. To improve persistency, he outlined a three-part strategy: direct patient engagement via nurses, communication with physician office staff, and collaboration with pharmacy partners. Executive Thomas McHugh added that improving persistency is a key lever for driving revenue growth.

Marc Goodman asked about the clinical infrastructure for treating PBH patients, such as the existence of centers of excellence, and requested details on the statistical powering assumptions for the Phase III LUCIDITY trial.

Answer

Co-CEO & Co-Founder Josh Cohen described the call point as adult endocrinologists, with some managing hundreds of PBH patients at academic centers. Chief Medical Officer Dr. Camille Bedrosian detailed the trial's powering, stating it has over 90% power to detect an effect even if it's a conservative 35% reduction versus placebo.

Madhu Yennawar, on behalf of Marc Goodman from Leerink Partners, asked if Amylyx is screening for postprandial hyperinsulinism in its PBH trial, given some patients may not exhibit it. She also requested guidance on how to think about the potential pricing for avexitide.

Answer

Co-CEO Joshua Cohen explained that their trial's inclusion criteria are nearly identical to prior successful studies and that hyperinsulinism is a common feature. Co-CEO Justin Klee added that the drug's mechanism directly targets the excessive GLP-1 response that causes severe insulin secretion in PBH. Regarding pricing, Joshua Cohen noted it is too early for specifics but suggested looking at other orphan drug analogs and emphasized the significant quality-of-life impact the drug could have for patients.

Marc Goodman of Leerink Partners sought to reconcile the sudden drop in orders in late June with the reported recovery in July, asking how customer purchasing patterns could shift so quickly. He also inquired about the competitive impact from Hugel's recent market entry.

Answer

President & CEO David Moatazedi clarified that the late-quarter drop was tied to Evolus's quarterly pricing tier program, where customers deferred large volume purchases. He described the July improvement as "incremental" and not a full market rebound, cautioning that macro headwinds remain. He stated that Hugel's impact was not a key driver of Q2 market dynamics.

Marc Goodman asked for clarification on the recent market dynamics, questioning how much of the Q4 and Q1 disruption was caused by a competitor's loyalty program issues versus a general market slowdown. He also directly asked if Evolus had announced the pricing for its new Evolysse filler.

Answer

CEO David Moatazedi acknowledged the competitor's loyalty program changes but stated that Evolus's share gain assumptions for Q1 already factor in that impact, and the company still believes it outperformed the market. He confirmed that Evolus does not publicly disclose Evolysse's list price but stated it is priced in line with market-leading products. He added that the Evolux loyalty program offers pricing benefits on Evolysse and increased co-branded media spend for accounts purchasing both Jeuveau and Evolysse.

Marc Goodman of Leerink Partners inquired about MindMed's perspective on recent clinical data released by other psychedelic companies and its implications for MindMed's own programs.

Answer

CEO & Board Director Robert Barrow highlighted the unique magnitude and durability of MM120's effect seen in Phase 2 data, which he noted has not yet been demonstrated by other programs in the class. He expressed excitement for the field and confidence in MindMed's pivotal readouts expected in 2026.

Marc Goodman of Leerink Partners asked for MindMed's perspective on recent clinical data released by other psychedelic companies and how it compares to MindMed's own programs.

Answer

CEO Robert Barrow responded that while it's an exciting time for the field, MindMed's Phase 2 data for MM120 showed a magnitude and durability of effect that has not yet been seen from other programs in the class. He emphasized the company's excitement for its three pivotal trial readouts in 2026, which they hope will replicate these strong, durable results.

Marc Goodman asked for clarification on the MM-120 trial design for Major Depressive Disorder (MDD), questioning if a low-dose arm would be included and if the 100-microgram dose found effective in Generalized Anxiety Disorder (GAD) is expected to work for MDD.

Answer

Chief Medical Officer Dr. Dan Karlin explained that the initial MDD trial, Emerge, is a two-arm study (100mcg vs. placebo) but noted a low-dose control might be used in future MDD studies. He affirmed that the 100-microgram dose is being used for MDD based on its demonstrated efficacy against depressive symptoms in the GAD Phase IIb trial.

Marc Goodman requested more color on the U.S. dynamics for SPINRAZA, including competition, inventory, and pricing.

Answer

President and CEO Christopher Viehbacher emphasized that SPINRAZA competes on efficacy in a crowded market. He highlighted the upcoming high-dose formulation and a novel port device (expected ~2026) as key future drivers to enhance patient experience. CFO Michael McDonnell added that there were no material inventory or channel dynamics to report for the quarter.

Marc Goodman requested more clarification on the 'pricing and reimbursement dynamics' that impacted SKYCLARYS revenue during the quarter.

Answer

CEO Christopher Viehbacher explained that in Europe, patient demand is generated through early access programs while country-by-country reimbursement is negotiated. This leads to lumpy revenue recognition. The dynamic mentioned refers to revenue adjustments for early access programs where the final negotiated price may be lower than the initial price charged.

An analyst on behalf of Marc Goodman asked for color on the gross-to-net percentage in the fourth quarter and inquired whether any patients have required retreatment with a second course of ZURZUVAE.

Answer

CEO Barry Greene clarified that the flat revenue despite demand growth was a function of channel inventory management, not a change in gross-to-net. Regarding retreatment, he stated that real-world performance is mirroring the rapid and durable response seen in clinical trials, and the company is not observing significant, if any, need for retreatment with a second 14-day course.

Marc Goodman asked about Sage's business development strategy, questioning if they are looking at external assets, and also requested details on the channel inventory change for Zurzuvae during the quarter.

Answer

CEO Barry Greene stated that Sage remains open to external business development but has found target assets to be expensive. On inventory, Chief Business Officer Chris Benecchi said levels have normalized after the initial launch build and that the strong Q3 revenue growth was primarily driven by a ~40% increase in demand (shipped units).

Marc Goodman requested an update on the overall strategy for the MDD program, specifically regarding the timing and staggering of the second and third Phase III trials.

Answer

CEO Ian Mortimer explained that the Phase III MDD studies (X-NOVA2, X-NOVA3, X-NOVA4) will run in parallel, similar to the epilepsy program, but with a natural stagger between their initiations. He confirmed that the start of subsequent trials is not gated by the outcomes of the earlier ones. The immediate focus is on initiating the X-NOVA2 study.

Asked about the expected growth trajectory for CAPLYTA in Q1 2024, considering seasonality, and requested details on the planned DTC campaign.

Answer

The company has strong momentum from Q4's 10% prescription growth but expects typical Q1 seasonal headwinds from insurance changes and deductible resets. Growth is expected to reaccelerate in Q2. The response did not provide details on the new DTC campaign.

Asked about ZTALMY's gross-to-net percentage, the total addressable patient population for CDD, and whether there is any off-label use.

Answer

The gross-to-net deduction for ZTALMY is consistently just under 20%. The company believes the addressable pediatric patient population of 2,000 is achievable, with ICD-10 codes suggesting over 800 patients and growing. They are also seeing an upside from adult patients being treated. The response did not directly address off-label use but focused on the on-label population.

Marc Goodman of SVB Securities inquired about the side effect profile of Aldeyra's oral RASP modulator, ADX-629, and its potential positioning against currently marketed treatments.

Answer

President and CEO Dr. Todd Brady explained that the RASP modulation platform targets a family of inflammatory mediators rather than a single protein, which contributes to a favorable safety and tolerability profile. He stated that in trials to date involving approximately 110 patients, ADX-629 has demonstrated very few side effects and no serious adverse events deemed related to the drug.

Marc Goodman asked about Aldeyra's commercialization strategy for reproxalap, the evolution of the dry eye market, and the drug's differentiation against new and existing products.

Answer

President and CEO Dr. Todd Brady explained that while the dry eye market has new entrants, it remains a significant unmet medical need. He emphasized that reproxalap is uniquely positioned as the only novel drug with a new chemical entity and target. Dr. Brady highlighted its key differentiator: a rapid onset of action, providing symptomatic improvement within minutes, which will be the central focus of their commercial positioning.

Marc Goodman of SVB Leerink inquired about the current dynamics of the dry eye market, particularly the impact of RESTASIS going generic, and asked who would lead potential partnering discussions for reproxalap following the CFO transition.

Answer

CEO Dr. Todd Brady explained that while a generic RESTASIS means payers will likely require a step-through, many patients have already failed the drug. Aldeyra aims to position reproxalap as the branded drug of choice, citing head-to-head trial data showing superiority over Xiidra in tolerability and symptom protection. He clarified that the commercial lead, Kelly Mizer, is leading business development and partnering discussions, which are focused on label positioning and branding.

An analyst on behalf of Marc Goodman at SVB Leerink asked for data on patient durability and adherence for NURTEC ODT. They also requested commentary on the scientific rationale and opportunity for Verdiperstat in ALS following the negative results in the MSA study.

Answer

CEO Dr. Vlad Coric reported that patient durability on NURTEC ODT is strong, with refill rates reflecting monthly migraine frequency. Regarding Verdiperstat, Dr. Coric and CMO Dr. Elyse Stock clarified that the negative MSA trial does not have a direct read-through to the ALS study due to different underlying disease pathologies. They remain optimistic about the ALS trial, which targets neuro-inflammation and is nearing enrollment completion.

Marc Goodman from SVB Leerink asked about the patient affordability program, its impact on the quarter's results, and how these programs are expected to evolve through the rest of the year and into 2022 payer negotiations.

Answer

CEO Vlad Coric stated that building the market is the top priority and that affordability programs are continuously tweaked based on incoming data. He acknowledged that favorable pricing improvements occurred sooner than expected but warned of potential volatility as the dual indication is still in its launch phase. He suggested a more stable view would emerge by year-end.

Marc Goodman of SVB Leerink LLC asked for an explanation of the lower-than-expected gross-to-net (GTN) in Q1 and the outlook for the year. He also questioned the significant increase in spending and whether it included one-time items.

Answer

CEO Vladimir Coric explained that the improved GTN resulted from successfully modifying affordability programs to convert more non-paying to paying customers, but he cautioned about future volatility. CFO Jim Engelhart attributed higher spending to factors like stock-based compensation and the timing of brand investments, suggesting the non-GAAP view offers better clarity.