Douglas Tsao

Douglas Tsao asked about the broadness of Roivant's thinking regarding the Brepo opportunity, including exploring white space where JAKs haven't been explored, and capital allocation between external and internal R&D investment.

Answer

CEO Matt Gline emphasized creative and thoughtful indication selection, particularly where TYK and JAK mechanisms are both important. CEO Ben Zimmer added that they are evaluating both de-risked indications with existing JAK data and higher-risk, novel opportunities. Matt Gline stated that capital is allocated to the best opportunities, both internal R&D and external business development, as they are funded through profitability.

Douglas Tsao, Managing Director at H.C. Wainwright, asked about the broadness of Roivant's thinking regarding brepocitinib's opportunity, specifically whether it extends beyond indications where JAKs have been explored to entirely new white spaces, and how capital allocation is being considered between external business development and internal R&D investment.

Answer

Matt Gline, CEO of Roivant Sciences, confirmed that Roivant is creatively pursuing indications with high unmet needs, including those where JAKs haven't been explored. Ben Zimmer, CEO of Priovant, emphasized focusing on areas where TYK2 and JAK are both important, leveraging the drug's unique mechanism. Matt Gline added that capital is allocated to the best opportunities, both internal R&D (like brepocitinib's phase 3) and external business development, as Roivant is funded through profitability.

Douglas Tsao asked about the breadth of the brepocitinib opportunity, specifically if Roivant is considering indications where JAKs haven't been explored, and how the company is thinking about capital allocation between external business development and internal R&D investment.

Answer

Matt Gline, CEO of Roivant, stated that the company is creatively pursuing high-unmet-need indications, including those where JAKs have not been extensively explored. Benjamin Zimmer, CEO of Priovant Therapeutics, added that a focus is on areas where both TYK and JAK pathways are important. Gline emphasized that capital is allocated to the best opportunities, whether internal or external, and business development remains a core part of their strategy.

Douglas Tsao inquired about the broadness of the brepocitinib opportunity, considering its success in CS, DM, and NIU, and if there's white space where JAKs haven't been explored. He also asked about capital allocation between external and internal R&D given the expanding horizons for brepocitinib and IMVT-1402.

Answer

Matt Gline, CEO of Roivant, stated they've been creative in targeting high unmet need indications, including where JAKs haven't been explored. Benjamin Zimmer, CEO of Priovant Therapeutics, added that they focus on areas where TYK2 and JAK1 are both important. Matt confirmed capital goes to the best opportunity, internal or external, and BD remains a core part of their strategy.

Douglas Tsao asked about the interrelated Graves' and TED markets, comparing Roivant's strategy with 1402 versus metoclopramide against Argenx's potential dual market approach, and also inquired about exploring Brepocitinib in Sjögren's disease.

Answer

CEO Matt Gline stated that more TED data is needed to inform strategy, emphasizing that the Graves' population is meaningfully larger and upstream of TED, which was 1402's initial focus. For Brepocitinib, he confirmed exhaustive consideration of indications, noting an 'embarrassment of riches' and a focus on market-defining courses.

Douglas Tsao asked about Roivant's strategy for pursuing TED with 1402 versus other molecules, considering Argenx's potential dual market entry, and if BREPO is being considered for Sjogren's disease.

Answer

CEO Matthew Gline stated that upcoming TED data will inform decisions, noting the Graves' population is significantly larger and upstream of TED, which was 1402's initial focus. For BREPO, he confirmed exhaustive consideration of indications, highlighting an 'embarrassment of riches' and a focus on market-defining courses.

Douglas Tsao asked about the steroid taper in the DM study, specifically the timing goal for patients to discontinue steroids. He also questioned the expectations for the 15mg dose of brepocitinib, given that most positive data has come from the 30mg dose.

Answer

CEO Matt Gline explained that the mandatory steroid taper begins at week 12 and concludes at week 36, with the goal of getting patients to the lowest possible dose by the end of that period. He stated that the 15mg dose was included primarily for regulatory purposes and that the company's focus is on the 30mg dose, which is the basis for the primary endpoint.

Douglas Tsao from H.C. Wainwright & Co. asked about Roivant's pricing strategy for its FcRn franchise, considering the increasing competition and the mix of orphan and more prevalent indications like Graves' disease.

Answer

CEO & Director Matt Gline expressed confidence in their pricing flexibility, comparing the current FcRn landscape to the early days of TNF inhibitors. He noted that many FcRn-addressable diseases have high unmet needs and that existing pricing for other therapies in these areas is generally compatible with current FcRn pricing. He stated that final decisions will depend on launch order and data quality, but the overall portfolio fits well into a cohesive promotional model.

Douglas Tsao inquired about the anticipated pace for unveiling new brepocitinib indications and asked if its potential scope could rival Immunovant's target of over ten indications.

Answer

CEO Matthew Gline stated that Roivant is actively evaluating other indications for brepocitinib and will unveil them as they become ready, not at a predetermined pace. While not committing to a specific number, he agreed there is a long list of potential orphan inflammatory indications where brepo could benefit patients. Gline emphasized the focus is on picking the right spots based on competitive dynamics, mechanism fit, and operational capacity to ensure high-quality execution.

Douglas Tsao from H.C. Wainwright & Co. asked for clarification on the uveitis trial protocol regarding patient crossover to brepocitinib upon failure. He also inquired about Roivant's broader business development strategy and whether the move into respiratory signals a new therapeutic focus.

Answer

CEO Matt Gline confirmed that patients who experience treatment failure automatically switch to open-label brepocitinib. On business development, he described the strategy as flexible and opportunistic, stating the company is 'ruthlessly focused' on the best assets regardless of therapeutic area, likening Roivant to the 'excess dough outside of other people's cookie cutters.'

Douglas Tsao asked about the thyroid eye disease (TED) study, specifically if argenx is targeting a particular time point in disease progression and if it's realistic or possible to demonstrate disease modification, such as preventing progression to CIDP.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, stated that the company would not comment on specific trial design details at this time, promising to present them at appropriate conferences. He noted that the hypothesis of disease modification is interesting but requires more data for a firm conclusion.

Douglas Tsao from H.C. Wainwright asked about argenx's strategy for targeting a specific time point in the progression of thyroid eye disease (TED) and Graves' disease, and if it's realistic to demonstrate disease modification in terms of progression to CIDP.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, stated that argenx would not comment on specific trial design details for Graves' disease at this time, noting that such information would be presented at appropriate conferences soon. He added that while disease modification is an interesting hypothesis, more data is needed for a firm conclusion.

Douglas Tsao from H.C. Wainwright & Co. relayed physician feedback about challenges in securing patient access to the prefilled syringe (PFS) and asked if this was due to isolated issues or if demand was outstripping supply.

Answer

COO Karen Massey acknowledged that some access hurdles are normal in the first quarter of any launch while payer policies are established, but noted the team is ahead of schedule, having already secured coverage for 70% of commercial lives. She stated that general feedback is very positive regarding the speed of access. CFO Karl Gubitz added definitively that the issue is not related to inventory, as supply is sufficient.

Douglas Tsao asked how a potential approval in ocular MG might affect the overall MG treatment paradigm and whether it could be viewed as a disease-modifying therapy by encouraging earlier treatment.

Answer

Chief Operating Officer Karen Massey embraced the 'disease-modifying' framing, stating the company's strategy is that earlier treatment leads to better outcomes. She noted that with 80% of ocular MG patients generalizing, there is potential to show a delay in generalization with real-world data over time, which would be transformative.

Douglas Tsao asked where the prefilled syringe (PFS) is expected to ultimately fit within the VYVGART portfolio and if it has the potential to become the dominant formulation.

Answer

CEO Tim Van Hauwermeiren positioned the PFS as the 'closing piece' in a complete product offering. He explained that the IV formulation (Medicare Part B) will remain important for some, while the PFS with self-administration will primarily target the Medicare Part D channel, allowing Argenx to serve the preferences of different patient and physician segments comprehensively.

Douglas Tsao inquired about the potential impact of a lapse in ACA subsidies on Alkermes' commercial business and the drivers behind Lybalvi's recent success, specifically regarding physician familiarity and awareness.

Answer

Richard Pops, CEO, noted the political virtue of continuing ACA subsidies and Alkermes' advocacy for carve-outs for serious mental illness and addiction patients. Todd Nichols, Chief Commercial Officer, attributed Lybalvi's success to its strong efficacy profile, broad label (schizophrenia and bipolar), commercial execution, increased share of voice, and positive physician experience leading to expanded prescribing breadth and depth.

Douglas Tsao asked about the decision-making process for advancing Project Saturn molecules into new indications and whether the selection of an indication is dependent on the pharmacokinetic profiles observed in early human studies.

Answer

CEO Richard Pops and COO Blair Jackson confirmed that they expect to advance multiple drugs into different therapeutic areas under Project Saturn. They explained that the molecules have distinct properties, and the data from initial SAD/MAD studies, combined with preclinical work, will be crucial for matching the best agent to the most appropriate indication.

Douglas Tsao asked for perspective on Alkermes's competitive advantages in the orexin space, focusing on chemistry challenges and the durability of its first-mover advantage, and whether to be cautious of competitors' preclinical potency data.

Answer

CEO Richard Pops detailed the high difficulty of developing an effective oral orexin agonist. He argued Alkermes's advantage lies in having positive data across NT1, NT2, and IH with a flexible, adjacent dosing range. He agreed that preclinical data is insufficient, stating that potency is table stakes and that tolerability and efficacy can only be truly assessed in patients.

Douglas Tsao asked what indications would be pursued for the second-generation orexin molecules based on Phase 1 data, and sought more detail on why a potential olanzapine long-acting injectable would not impact LYBALVI.

Answer

CEO Richard Pops indicated that the company has a good sense of where to take the next-gen orexin agents but will formally commit after completing initial human studies. CCO Todd Nichols explained that LYBALVI is insulated from a potential olanzapine LAI because the rate-limiting factor for any olanzapine therapy is weight gain. Since LYBALVI solves this issue, it has become the standard of care for olanzapine-based therapy, a position an LAI is unlikely to disrupt without also addressing weight mitigation.

Douglas Tsao from H.C. Wainwright & Co. requested more color on the recent increase in change orders, asking if there was a thematic reason behind them.

Answer

CEO Christian Wojczewski clarified that the increase was not a systematic trend and was primarily driven by scientific reasons or specific customers reallocating funds to later-stage projects. He emphasized there was no discernible pattern and that the trend had already reversed at the beginning of the third quarter.

Douglas Tsao from H.C. Wainwright & Co. asked if potential cuts to U.S. NIH funding could create new opportunities for Evotec in early-stage research. He also followed up by asking if discussions around potential U.S.-China tariffs were making Evotec's U.S.-based Just Biologics manufacturing site more attractive to clients.

Answer

CEO Christian Wojczewski responded that Evotec's direct exposure to NIH funding is limited, so no direct impact is expected, though the company is prepared for market shifts. On the topic of tariffs, he noted that the Just Biologics business is experiencing strong inbound demand regardless of the specific trigger, be it technology or geopolitics. He stated that while clients are cautious amid the dynamic environment, there is sufficient activity to be confident in the business's continued growth.

Douglas Tsao asked if potential cuts to U.S. NIH funding could create new opportunities for Evotec. He also inquired if the Just Biologics business is seeing increased interest from clients looking to shift manufacturing to the U.S. due to potential tariffs.

Answer

CEO Christian Wojczewski stated that Evotec's direct exposure to NIH funding is limited, but the company is prepared with its U.S. footprint. Regarding Just Biologics, he confirmed strong inbound activity but noted the market is too dynamic for clients to make definitive decisions based on tariffs alone, though the business continues to grow rapidly.

Asked if potential cuts to U.S. NIH funding could create new opportunities for Evotec and whether the prospect of tariffs is driving clients to consider shifting manufacturing to the company's U.S.-based Just Biologics facility.

Answer

The company stated its direct exposure to NIH funding is limited, but it is prepared for any opportunities that arise from shifts in early-stage research. For Just Biologics, there is strong inbound interest driven by multiple factors, including technology and potential supply chain shifts, and the business is expected to continue growing regardless of the specific trigger.

Douglas Tsao of H.C. Wainwright & Co. inquired about the drivers for YUPELRI's improved sales pull-through and the company's progress toward an optimal channel mix.

Answer

Chief Business Officer Rhonda Farnum attributed the improved pull-through to increased volume in the specialty pharmacy channel, which enhances pricing, patient persistency, and fulfillment. CEO Rick Winningham added that improved hospital-to-home care transitions, facilitated by specialty pharmacy, also contribute to this trend.

Douglas Tsao of H.C. Wainwright & Co. inquired about the key drivers behind the strong Q4 performance of YUPELRI in the hospital channel, the timing of therapeutic interchange wins, and the expected trajectory for gross-to-net improvements in 2025.

Answer

Chief Business Officer Rhonda Farnum attributed the hospital success to strong execution of their strategy, particularly in securing formulary wins with therapeutic interchange protocols, which can double market share in those accounts. She noted that improvements in gross-to-net, driven by pricing discipline and a better channel mix, occurred faster than initially anticipated.

Douglas Tsao of H.C. Wainwright & Co. asked about the progress in improving YUPELRI's Average Selling Price (ASP) and whether the initiatives to achieve this faced any customer resistance or volume disruption.

Answer

Chief Business Officer Rhonda Farnum clarified that ASP improvements have a two-quarter lag, so the Q3 sales strength was driven by channel mix and execution rather than price. She expects ASP improvements to materialize in early 2025 and confirmed the initiatives were implemented smoothly without 'ruffling feathers.' CEO Rick Winningham added praise for the strong collaboration with partner Viatris. Ms. Farnum also elaborated on YUPELRI's value proposition across key patient segments.

Douglas Tsao of H.C. Wainwright & Co. asked for clarification on the impact of NCCN guidelines in the community setting, questioning whether adoption is simply slower or if community oncologists are not adhering to them as closely as academic centers.

Answer

EVP of Commercial Sameer Goregaoker explained that the guidelines prompted rapid adoption in high-volume academic centers. He clarified that in the community setting, the issue is not a lack of adherence but rather that physicians see very few NPC patients, making the new guidelines less top-of-mind. He described an ongoing, focused educational effort to establish Loktorzi as the standard of care in this segment.

Douglas Tsao of H.C. Wainwright & Co. asked if physician education focuses on the general value of a PD-1 in NPC or on LOQTORZI's specific differentiation, and requested more detail on the positive early experiences physicians are reporting.

Answer

Chief Medical Officer Dr. Rosh Dias stated that LOQTORZI's data is compelling as it's the first to show a profound survival benefit in this unmet need, which, along with the premier NCCN listing, faces no real objections. He added that physicians report their real-world patient experiences are consistent with the impressive clinical trial data. Executive Vice President, Commercial, Sameer Goregaoker, noted that the unequivocal NCCN recommendation is only three months old, and educational efforts are now fully underway.

Probed the extent of off-label I-O use in NPC post-NCCN guideline update, the timeline and strategy to capture this market share for LOQTORZI, and the dynamics between academic and community settings.

Answer

The company stated it's an ongoing process to build awareness of the NCCN guidelines (currently ~40%) and convert off-label users. The strategy involves targeted education at the time of diagnosis. They emphasized the need to succeed in both academic and community settings, as a significant amount of treatment occurs in the community.

Asked about the UDENYCA resupply, including the timeline to meet full market demand, the expected recovery trajectory in Q1 2025, and whether any customers plan to reduce future orders due to the disruption.

Answer

The company expects to produce 120,000 units within five weeks, allowing them to meet demand quickly by the end of the year. The Q1 recovery pace depends on how quickly accounts switch patients back, but they are bullish due to the product's strong competitive position. No customers have indicated they will reduce future purchase volumes.

Douglas Tsao inquired about the impact of the Medicare Part D redesign, asking to what extent it has become a tailwind and how much of the recent growth was driven by new prescriptions versus improved fill rates.

Answer

CEO John Tucker confirmed that the Medicare Part D redesign shifted from a headwind in Q1 to a tailwind in Q2, a trend he expects to continue. He emphasized that the 45% quarter-over-quarter increase in units shipped was driven more by new prescriptions being written than by an increase in the fill rate alone. Tucker added that the company hopes higher fill rates will create a positive feedback loop, boosting physician confidence and future prescriptions.

Douglas Tsao questioned if scPharmaceuticals has visibility into when patients hit their out-of-pocket maximum under the Part D redesign to prompt script fills. He also asked whether the CKD launch is primarily attracting patients with comorbidities or if they are seeing CKD-only patients.

Answer

Executive John Tucker explained that while real-time visibility is limited, their hub identifies patient copays and actively promotes the smoothing program to doctors and patients. SVP of Commercial, Steve Parsons, confirmed they are seeing prescriptions for CKD-only patients, but also noted a 'double bonus' of gaining heart failure patients with CKD from nephrologists they previously did not call on.

Douglas Tsao asked how the promotional frequency for the CKD launch will compare to the heart failure launch, whether it might reduce focus on cardiologists, and if there's a risk of duplicative effort by promoting to both specialists for overlapping patient populations.

Answer

Executive John Tucker asserted that the sales team can maintain its call frequency in heart failure while launching in CKD, which improves rep efficiency. He also noted the company could expand the sales force or create a dedicated nephrology team if needed. SVP of Commercial Steve Parsons added that targeting both specialists is not duplicative but rather an additive strategy that reinforces the product's value and increases reach to the shared cardiorenal patient population.

Douglas Tsao of H.C. Wainwright & Co. asked for clarification on the dynamics that led to a slower end to the third quarter than the company had anticipated.

Answer

CEO John Tucker attributed the Q3 slowdown to the impact of Medicare coverage gap rebates, which were larger than anticipated. This negatively affected the Gross-to-Net (GTN) discount, pushing it to 15.7%, and increased patient co-pays, leading to higher script abandonment rates in the second half of the quarter. He emphasized that underlying script demand continued to grow.

Douglas Tsao of H.C. Wainwright & Co. asked if the glucocorticoid (GC) tapering protocol in Part B of the pediatric BALANCE CAH study will replicate the protocol used in the adult COMCAH study.

Answer

Chief Medical & Development Officer Dana Pizzuti clarified that while the goal is the same—to demonstrate A4 reduction and GC tapering—the pediatric protocol is not exactly the same. She explained that there is more caution and flexibility in the pediatric setting for how investigators carefully titrate GC doses down. The objective is to get patients to normal A4 and then reduce GCs, with a requirement for a stable GC dose for the final four weeks of the 28-week trial.

Douglas Tsao followed up on the CAH pediatric program, asking if it would be an adaptive design to avoid multiple studies and whether the primary endpoint would be the same as in the adult trial.

Answer

Dr. R. Struthers, CEO, and Dr. Alan Krasner, Chief Endocrinologist, responded. Struthers confirmed the study is a seamless Phase II/III design, not two separate trials. Krasner added that the ultimate treatment goal—normalizing both GCs and A4 levels—is the same for pediatric and adult patients, so he anticipates a very similar endpoint.

Douglas Tsao asked if the TSH antagonist program could provide compelling proof-of-mechanism data in a Phase I study, similar to past Crinetics programs, and how that might inform the initial development strategy between Graves' disease and Thyroid Eye Disease (TED).

Answer

Chief Endocrinologist Dr. Alan Krasner confirmed that the TSH antagonist is well-suited for a Phase I proof-of-concept study. He explained that biomarkers like thyroid hormone levels (T4) could provide rapid evidence of hitting the pharmacologic target, although measuring efficacy in TED would require a longer timeframe.

Douglas Tsao from H.C. Wainwright & Co. inquired about the adoption dynamics among physicians, specifically how long it takes for them to begin prescribing Zareve for multiple indications and what factors drive this behavior. He also asked why some prescribers might still be using it for only a single indication.

Answer

Chief Commercial Officer Todd Edwards explained that physicians who have prior experience with Zareve tend to adopt new indications and formulations rapidly, as it creates prescribing efficiencies. He stated that prescribers who use Zareve for only one indication are the exception, and this is typically due to practice-specific patient populations. The commercial team continues to educate all prescribers on the full portfolio.

Douglas Tsao from H.C. Wainwright & Co. asked about the expected adoption trajectory for ZORYVE foam's upcoming scalp and body psoriasis indication, comparing it to the rapid uptake seen with the seborrheic dermatitis launch, and inquired about its promotional sensitivity.

Answer

CEO Frank Watanabe cautioned against expecting a repeat of the 'vertiginous' uptake seen with the seborrheic dermatitis launch, which he described as a unique situation with huge unmet need. For scalp psoriasis, while ZORYVE is a very competitive option, other treatments exist. He expects the new indication will contribute to a continued, steady growth trajectory rather than a sudden spike. He also noted that the indication is highly promotionally sensitive and that educating clinicians on the compelling efficacy and safety data will be important for driving incremental upside and streamlining reimbursement.

Douglas Tsao of H.C. Wainwright & Co. asked about the reimbursement dynamic, questioning how the clinical desire to move away from topical steroids reconciles with payers who may still require them as a first-line therapy, and whether ZORYVE could become a first-line treatment.

Answer

President and CEO Frank Watanabe explained that the steroid step-edit is largely irrelevant for their target market of 16 million patients who are already on steroids and have thus met the requirement. Chief Medical Officer Patrick Burnett added that clinical practice is evolving to use steroids for acute flares and non-steroidals like ZORYVE for chronic management, a paradigm that aligns well with current payer utilization criteria.

Douglas Tsao of H.C. Wainwright & Co. inquired about the development strategy for NMRA-215 in the competitive obesity space, asking if the company, as a CNS-focused entity, would seek a partnership after reaching a certain stage of clinical development.

Answer

Joshua Pinto, President, explained that Neumora is committed to following the science, and the growing evidence for centrally acting drugs in obesity makes it a strong fit for the company's expertise in brain-penetrant chemistry. He positioned NMRA-215 as a potential best-in-class NLRP3 inhibitor. While not commenting on future partnership plans, Pinto confirmed that progressing NMRA-215 through the DIO model and into Phase 1 is fully funded and included in the current operating plan, which is supported by a cash runway into 2027.

Douglas Tsao of H.C. Wainwright & Co. inquired about the impact of new operational changes on enrollment pace for the navacaprant KOASTAL studies and asked for details on the K2 Health Ventures debt facility, including prepayment terms.

Answer

Daljit Aurora, Chief Operating and Development Officer, confirmed that new screening measures are working as expected to enroll appropriate patients without negatively impacting timelines. President Joshua Pinto added that the K2 debt facility's initial $20 million draw extends the company's cash runway into 2027, with further details available in the 10-Q. He also noted that another $20 million is available at the company's discretion in 2025.

Douglas Tsao asked for an update on the enrollment progress for the KOASTAL-2 and 3 studies, the potential impact of the new trial modifications, and if any factors were identified that could explain the gender-based efficacy differences seen in KOASTAL-1.

Answer

President Joshua Pinto explained that site experience in other recent positive MDD Phase III studies was a key factor in performance for both male and female subjects in KOASTAL-1. Chief Operating and Development Officer Daljit Aurora added that while specific enrollment numbers would not be provided, the studies have a substantial number of patients yet to be enrolled, giving management confidence that the implemented changes can be meaningful.

Douglas Tsao of H.C. Wainwright asked about the potential catalyst for resizing the KOASTAL studies and sought commentary on how a competitor's negative M4 program readout might influence Neumora's own M4 franchise.

Answer

Robert Lenz, Head of R&D, clarified that the ability to increase sample size was part of the original FDA-submitted design. While declining to comment on competitor data, he reiterated confidence in Neumora's M4 franchise, citing its multiple programs with unique chemistry from Vanderbilt and the plan to advance the next M4 PAM to the clinic in H1 2025.

Douglas Tsao from H.C. Wainwright & Co. asked if the increasing efficacy over time is a unique function of the drug's sodium channel interaction, about differentiating side effects from the drug versus background therapies, and if the mood benefits were anecdotal.

Answer

CSO Steven Petrou linked the effect to the molecule's unique biophysical profile. President & CEO Marcio Souza noted AEs were reduced when background drugs were tapered and confirmed mood benefits were initially anecdotal, prompting the addition of a formal mood endpoint in the POWER-two study.

Douglas Tsao sought confirmation on the weekly patient randomization pace, asked about the preparatory work needed for Vormatrigine's move into pain indications, and requested clarification on the elsunersen development plan and any changes to its global registration strategy.

Answer

CEO Marcio Souza confirmed the 20-30 patient per week figure refers to randomized patients. For Vormatrigine, he said work is underway to assess pharmacology and ideal pain targets. For elsunersen, he clarified the Brazil study is exploring different doses, separate from the planned global study. A pending FDA meeting has slightly delayed the final global protocol, but they remain open to adjusting the dose based on emerging data.

Douglas Tsao questioned why the RADIANT study wasn't designed exclusively for generalized epilepsy patients given the high interest, and asked about the rationale for the different dosing strategies between the RADIANT and POWER studies.

Answer

CEO Marcio Souza responded that RADIANT's design provides flexibility to first understand the drug's impact in both focal and generalized epilepsy, which could inform a future dedicated study. He explained the dosing difference is strategic: RADIANT's higher starting dose aims to maximize efficacy quickly, while the POWER studies' titration schedule is designed to gather data at different concentrations to inform regulatory discussions and labeling.

Douglas Tsao questioned why the RADIANT study for PRAX-628 wasn't focused solely on generalized epilepsy patients, given the interest. He also asked about the different dosing strategies between RADIANT (straight to 30mg) and the POWER studies (titration from 20mg).

Answer

Executive Marcio Souza explained that RADIANT's broader design allows Praxis to understand the drug's impact across both focal and generalized epilepsy before launching a dedicated controlled study in generalized epilepsy. He stated the direct 30mg dose in RADIANT aims to drive maximum efficacy and offers flexibility, while the 20mg starting dose in the POWER studies is to establish efficacy at a lower concentration, which is important for future regulatory discussions and potential labeling.

Douglas Tsao of H.C. Wainwright & Co. asked if the utilization of free goods is consistent across all retina specialists or concentrated in certain practices. He also inquired if patient flow is shifting more towards new referrals versus coming from existing practice populations.

Answer

EVP David Acheson emphasized that true demand is growing and that the company's reimbursement teams are actively educating offices on benefit design to manage access. He noted that while referral programs are working, a significant opportunity remains within the existing patient populations of treating retina specialists, as about 50% of the total market already sits in those offices.

Douglas Tsao of H.C. Wainwright & Co. asked about the consistency of free goods utilization across practices and whether patient referrals are increasing relative to treatments from existing patient populations.

Answer

EVP David Acheson noted that while referral programs are working, a significant opportunity remains within existing retina specialist practices, where about 50% of the market already resides. He also highlighted the role of reimbursement teams in educating offices on benefit design to manage patient costs.

Douglas Tsao of H.C. Wainwright & Co. asked if free goods utilization is consistent across all retina specialists and if the company is seeing more patients from direct referrals versus existing practice populations.

Answer

EVP David Acheson explained that the reimbursement team is actively educating offices on benefit design to manage patient access. He also confirmed that while referral programs are working, a significant opportunity remains within the existing patient populations of treating retina specialists, as about 50% of the total market already sits in those offices.

Douglas Tsao of H.C. Wainwright asked about the consistency of free goods utilization across practices and whether Apellis is seeing more patient referrals from outside the existing specialist base.

Answer

EVP David Acheson highlighted strong underlying demand and the work of reimbursement teams to educate offices on benefit design. He confirmed that referral programs are working but also noted that a significant opportunity (~50% of the market) still resides within the existing patient populations of treating retina specialists.

Douglas Tsao asked for more detail on the specific steps Apellis is taking to mitigate the co-pay impact and whether SYFOVRE's every-other-month dosing provides a greater advantage in the current environment.

Answer

Executive David Acheson confirmed the dosing flexibility is a key advantage, as fewer annual co-pays are easier for patients. He elaborated on mitigation tactics, explaining that the reimbursement team is educating offices on patient benefit designs to avoid unnecessary use of foundation support. Additionally, the Apellis Assist program helps offices identify when a patient's out-of-pocket maximum is met, enabling a switch to commercial treatment.

Douglas Tsao of H.C. Wainwright asked about the biological rationale for the next-generation SYFOVRE combination therapy and the potential impact of the Medicare redesign.

Answer

CEO Dr. Cedric Francois confirmed the rationale for the combo therapy is to better protect RPE cells by lowering systemic C3 from the choroidal side, complementing SYFOVRE's strong effect on photoreceptors. EVP of Commercial David Acheson stated that quantifying the impact of the Medicare redesign is challenging at this time.

Douglas Tsao of H.C. Wainwright & Co. asked for more detail on the specific messaging that resonated with physicians to drive the rebound in market share and which points might have been previously misunderstood.

Answer

COO Adam Townsend explained that they simplified their efficacy messages to focus on key differentiators like up to 42% lesion growth reduction, flexible dosing, and a well-documented safety profile. He stressed that efficacy is the primary driver. CMO Dr. Caroline Baumal added that the company's alignment with the ASRS and the growing body of real-world data have also significantly increased physician confidence.

Douglas Tsao inquired about Daré's partnership strategy for its compounded products, manufacturing capacity for Sildenafil cream, and the pharmaceutical industry's reaction to the company's 503B compounding approach.

Answer

CEO Sabrina Johnson explained that Daré plans to secure multiple partnerships for each individual product to ensure broad access across various channels, including telehealth and online retailers. She stated that the Q4 launch timeline for Sildenafil cream provides adequate time to scale up GMP manufacturing with their 503B partner and conduct provider education. Johnson also noted that feedback from traditional pharmaceutical peers on the 503B strategy has been 'fantastic and complementary,' recognizing it as a creative way to accelerate market access.

Asked about the Ovaprene study's new clinical sites, specifically how quickly they can begin enrolling, their potential contribution to total enrollment, and if they will add different patient demographics. Also inquired about the upfront funding required to begin the Sildenafil program.

Answer

The new Ovaprene sites are ones the company has worked with before, allowing for an efficient and quick start-up process in the new year; they are expected to make a meaningful contribution and enhance patient diversity. For the Sildenafil program, each of the two Phase III trials costs about $15 million. The full amount for a trial is not needed upfront to start, but they would need confidence in their ability to fund the trial to completion.

Douglas Tsao of H.C. Wainwright & Co. asked about the Sildenafil Cream program, questioning whether another meeting with the FDA would be necessary to finalize the Phase III trial design. He also inquired about the company's strategy for prioritizing its pipeline programs given its current balance sheet.

Answer

CEO Sabrina Johnson responded that while the company is open to further meetings with the FDA for Sildenafil Cream, it is not yet clear if one will be required as the current interactions are focused on providing detailed psychometric analysis data. Regarding pipeline prioritization, Johnson affirmed that Ovaprene and Sildenafil Cream remain the top financial and operational priorities, but the company is also advancing its menopause programs in a capital-responsible manner due to significant recent interest.

Douglas Tsao asked for details on the broader market softness, questioning which segments are most affected and how the weakness is manifesting—whether it's fewer new patient starts or existing patients extending the time between treatments.

Answer

CEO David Moatazedi responded that the slowdown is consistently heard as a slight slowing in clinic schedules, primarily driven by fewer new patients entering the category. He noted some early signs of patients extending treatment intervals, but this is a smaller factor. CFO Sandra Beaver added that the continued strong adoption of the loyalty program is a positive indicator of underlying patient demand, suggesting that while wallet-conscious, consumers remain engaged.

Douglas Tsao asked about the process for accounts to begin using the new Evolysse fillers, specifically regarding account prioritization, and whether the launch would prompt changes to customer loyalty programs.

Answer

CEO David Moatazedi explained that the company will leverage its extensive training platform to go broad and fast with the launch, rather than prioritizing only top-tier accounts. He confirmed that Evolysse will be integrated into existing loyalty programs immediately in Q2 for co-branded media benefits, with consumer rewards for combined treatments to be introduced shortly thereafter, ahead of Q3.

Douglas Tsao of H.C. Wainwright & Co. asked for the reason behind narrowing the revenue guidance by lowering the upper end, and also inquired about the competitive environment, including any proactive steps being taken in anticipation of a new market entrant.

Answer

CFO Sandra Beaver explained that narrowing guidance is a standard Q4 practice for providing clarity and not a sign of concern. President and CEO David Moatazedi added that the competitive landscape has been consistent and that Evolus is well-prepared for new entrants, expressing confidence in their own differentiated strategy and sustained growth.

Douglas Tsao of H.C. Wainwright & Co. sought clarification on prescribing behavior after an HCP's first ZURZUVAE script and asked about any potential seasonal impacts on Q1 results.

Answer

CEO Barry Greene clarified that when a healthcare provider prescribes ZURZUVAE, their practice subsequently treats a significantly higher number of PPD patients overall. He reiterated that with over 70% of ZURZUVAE scripts being for first-line new treatment, there are no major obstacles to adoption. Regarding seasonality, he stated it is too early to identify any trends but noted that ZURZUVAE is not subject to the typical Q1 Medicare issues seen with other drugs.

Douglas Tsao asked if Sage had consulted with the FDA on the dalzanemdor endpoint change, its implications for a potential filing, and whether the original HD-CAB composite is still a secondary endpoint.

Answer

CEO Barry Greene stated that if the data are robust, they will have a package to move forward with regulators, but he declined to comment on specific FDA interactions. CMO Laura Gault clarified that the full HD-CAB composite is no longer a secondary endpoint, though some of its individual components are being evaluated as secondary measures.

Douglas Tsao from H.C. Wainwright asked for details on the endpoints used to measure mood benefits in the focal onset seizure (FOS) study and whether they could appear on the label. He also inquired about the outlook for R&D spending.

Answer

CEO Ian Mortimer stated it was premature to comment on the label, emphasizing that mood endpoints are exploratory and not powered for statistical significance. CMO Dr. Chris Kenney specified that the GAD-7 and Beck Depression Inventory scales are being used to assess anxiety and depression. CFO Sherry Aulin confirmed the cash runway into 2027 accounts for a 'meaningful increase' in R&D spending in 2025-2026, driven by multiple Phase III trials and advancing preclinical assets.

Douglas Tsao questioned the reason for the BLA filing delay to Q1 2025, asking if enrollment was behind schedule. He also asked about the inventory investment for the European launch and its potential use for the U.S. market.

Answer

Executive C. Trenary explained the delay was due to an aggressive internal goal to finish enrollment by July-end, which was missed, pushing the BLA submission into early 2025. He noted enrollment is still twice the industry average. Regarding inventory, he stated that product prepared for the original U.S. launch is available for Europe and/or the U.S., and they are extending its shelf life to an expected 30-36 months.

Asked for the specific reason for the BLA filing delay from Q4 to Q1, and inquired about inventory investments for the European launch and whether that supply could also be used for the U.S.

Answer

The executive explained the filing delay was due to a very aggressive internal goal for enrollment completion that was narrowly missed, pushing the submission into early next year. Regarding inventory, he stated that they have existing inventory prepared for the original U.S. launch which is available for both the EU and U.S. markets, and they are currently working on extending its shelf life to 30-36 months.

Asked for clarification on the timing of the 30% enrollment milestone for NORSE EIGHT, the progression of site activation, the company's plans for DME and BRVO indications, and the commercialization strategy in Europe (direct vs. partnership).

Answer

The 30% enrollment was as of the previous day, with site activation reaching full strength in April. The company plans to pursue DME and BRVO indications and will align with the FDA on study requirements. For Europe, the current focus is on a direct launch leveraging Cencora's infrastructure, but the company remains open to partnership discussions that could offer better value.

Douglas Tsao sought clarification on the timing of the 30% enrollment figure for NORSE EIGHT, the progression of site activation, the company's plans for DME and BRVO indications, and whether the European commercialization strategy was fixed or if partnerships were still being considered.

Answer

Executive C. Trenary clarified that 30% enrollment was as of the previous day and that sites reached full strength in April. He confirmed that DME and BRVO indication studies are planned to broaden the product's label and that the company will engage with the FDA to define study requirements. Regarding European commercialization, he stated that while the current focus is a self-launch supported by Cencora, the company remains open to partnership discussions that could maximize shareholder value.

Asked for an analysis of the IV ganaxolone trial results by site to understand physician behavior, and also inquired about the discontinuation and continuation rates in the long-term extension of the TSC trial.

Answer

Analysis showed a stronger drug signal at larger sites, but the company believes the primary endpoint (advancement to IV anesthesia) was fundamentally too subjective and would not be used again. The focus with the FDA will be on agreeing to a more objective durability endpoint. Long-term extension data for TSC is encouraging, showing robust durability, and will be presented at upcoming events.

The analyst asked two main questions: first, about the evolution of the prescriber base for ZTALMY and where new patients are coming from; second, about the plan for super-refractory status epilepticus (SRSE), specifically whether the goal is to get a higher dose regimen on the label or just to get higher dosing limits approved.

Answer

For ZTALMY, new patients come from a mix of Centers of Excellence and community physicians, with no major shifts in the prescriber base; targeting has been broadened for 2024. For SRSE, the initial label will reflect the RAISE trial regimen. The company plans a proof-of-concept study with a higher dose after aligning with the FDA on its safety. The long-term goal would be to get safety data for the higher dose into the label, but it's a step-by-step process starting with the PoC trial.

Asked for Dr. Clauw's view on prioritizing TRV045 indications, whether upcoming NIH data is a gating factor for partnerships, and the possibility of having separate partners for pain and epilepsy.

Answer

Dr. Clauw sees broad potential in CNS-driven chronic pain conditions like osteoarthritis and fibromyalgia. The company stated the upcoming NIH data is not a gating factor for partnerships but will enhance the asset's story. They would likely choose a single partner for the asset, though different potential partners have interest in either pain, epilepsy, or both.

Douglas Tsao of H.C. Wainwright & Co. asked for a reminder of other issues the FDA had previously identified and whether they were resolved, and also inquired about the remaining economics Minerva is entitled to for seltorexant.

Answer

Executive Chairman and CEO Dr. Remy Luthringer confirmed that all previously raised FDA issues were addressed in their recent meeting, leading to the NDA filing, and he anticipates further dialogue during the in-depth review. President Geoff Race detailed the seltorexant economics, stating approximately $95 million in potential milestones remain, including $10 million for a Phase 3 study and about $60 million for regulatory approvals.

Douglas Tsao of H.C. Wainwright inquired about other potential review issues previously identified by the FDA beyond study conduct and asked for a reminder of the remaining economics Minerva is eligible to receive for seltorexant.

Answer

Executive Chairman and CEO Dr. Remy Luthringer confirmed that all previously raised FDA issues were addressed in their presentation, leading to the NDA filing, though he expects more in-depth questions during the review. President Geoff Race detailed the seltorexant economics, stating approximately $95 million in milestones remain, including $10 million for a Phase 3 study and $60 million for regulatory approvals.

Douglas Tsao of H.C. Wainwright questioned the path forward for roluperidone, asking if an additional clinical study might be the most efficient path to approval and whether current FDA discussions include plans for such a study.

Answer

CEO Remy Luthringer responded that the FDA has not asked for an additional study and that Minerva's current focus is on securing a full review of the existing NDA data package. He defended the monotherapy development strategy and stated that any new trials would be considered post-approval. Luthringer clarified that current discussions with the agency are aimed at getting the existing data set reviewed based on its merits, not on planning a new study, emphasizing the need for complete clarity from the FDA before committing to further clinical work.

Douglas Tsao of H.C. Wainwright & Co., LLC asked if the FDA's Refusal to File (RTF) letter for roluperidone cited specific reasons for the decision and whether those reasons were largely the same issues that the agency had raised in previous interactions.

Answer

CEO Remy Luthringer confirmed that the FDA's letter did provide specific reasons for the RTF, and those topics will be the focus of the upcoming Type A meeting. However, he declined to elaborate on the details of those reasons or compare them to past feedback, emphasizing the company's ongoing dialogue with the agency and the goal of clarifying open items in the meeting.

Douglas Tsao from H.C. Wainwright asked about the strategic importance of the monotherapy versus adjunct therapy discussion with the FDA, the strongest supporting evidence for monotherapy, and whether Minerva would seek a specific monotherapy label.

Answer

CEO Remy Luthringer emphasized the strong rationale for monotherapy, citing poor adherence to existing antipsychotics and evidence that they can worsen negative symptoms. He pointed to Minerva's data, where patients switched to roluperidone monotherapy showed stable positive symptoms and a very low relapse rate over one year, as key evidence. While acknowledging roluperidone could be used as an adjunct, Luthringer believes the best patient outcomes are achieved with monotherapy and hopes the FDA will recognize the strength of the data supporting this specific use.

Douglas Tsao of H.C. Wainwright inquired about sales force retention amid recent corporate uncertainty, the drivers behind ANNOVERA's strong revenue growth, the status of previously high rejection rates for ANNOVERA, and the long-term vision of key shareholders.

Answer

CEO Hugh O'Dowd and Chief Commercial Officer Mark Glickman addressed employee retention, stating turnover is at a reasonable rate and the team remains committed. Glickman confirmed ANNOVERA's revenue surge was primarily driven by end-user demand and volume, despite some necessary channel restocking. He also explained that the root cause of historical ANNOVERA rejection rates, related to its unique annual dosage form, has been identified and addressed with payers. O'Dowd noted that recent financing provides runway while the board evaluates all strategic options, directing investors to SEC filings for more detail.

Douglas Tsao of H.C. Wainwright & Co. asked for an update on the ANNOVERA manufacturing issues, including confidence in resolution and the ability to meet future demand, and questioned if the commitment to EBITDA profitability was limiting a full reset of the commercial organization.

Answer

CEO Hugh O’Dowd detailed five specific actions being taken to resolve ANNOVERA supply issues, expressing confidence in meeting demand from Q2 even without FDA approval of a manufacturing supplement. Chief Business Officer Mark Glickman confirmed a full commercial reset is underway with a new HCP-focused strategy. O'Dowd affirmed the company remains on a path to EBITDA breakeven through expense reduction and strong demand.

Douglas Tsao of HC Wainwright questioned the specifics of the ANNOVERA manufacturing disruption and supply outlook, sought clarification on the meaning of 'accountability' in the commercial strategy, and asked for the percentage of sales calls that are currently in-person.

Answer

President Hugh O'Dowd explained the ANNOVERA manufacturing issue stems from a narrow FDA release specification and that an NDA supplement with a December 12 PDUFA date is expected to resolve it, ensuring supply for Q4. Chief Commercial Officer Mark Glickman defined accountability as executing a clear plan with measurable activity and performance metrics. He also confirmed that the reported increase in sales calls reflects entirely in-person visits, as virtual calls are not currently counted in that metric.

Douglas Tsao of H.C. Wainwright & Co. commented on the new-to-brand (NBRx) script data, noting it has become more competitive, and asked for insights into the near-term dynamics of the acute migraine treatment market.

Answer

CEO Vladimir Coric advised against over-interpreting weekly script data, attributing some shifts to changes in their affordability programs that optimize the payer mix. CCO BJ Jones added that NBRx share has been competitive for months and expressed confidence that NURTEC ODT will become the market leader over time, supported by positive market research and the upcoming prevention launch.

Douglas Tsao of H.C. Wainwright inquired about the potential indications beyond IBD for the new IL-23 antagonists nominated by Janssen and asked if Phase 1 data would help determine the development path for these candidates.

Answer

CEO Dinesh Patel clarified that the collaboration with Janssen is focused on the IL-23 receptor antagonist pathway broadly, not limited to IBD, which provides multiple strategic options. He confirmed that as data from ongoing Phase 1 and Phase 2 studies become available, the clinical options will become clearer. Patel agreed that Phase 1 data, including bioavailability and PK profiles, will be crucial in determining which indications each candidate is best suited for.

Douglas Tsao of H.C. Wainwright & Co. asked if the PN-943 Phase II study is designed to answer new questions beyond the proof-of-concept established by PTG-100, and whether the dosing strategy aims for strong efficacy at a low dose or maximal efficacy at a higher dose.

Answer

President and CEO Dinesh Patel confirmed the PN-943 Phase II study is designed to be highly informative, with the goal of preparing for a potential pivotal study. He stated that the trial will explore both a low and a high dose, aiming to demonstrate good efficacy at the low dose and potentially superior efficacy at the higher dose. More details on the trial design are expected in the second quarter.