François Brisebois

Francois Brisebois asked about the clinically meaningful delta for MDD, comparing it to the 6.4-point MADRS change seen in the prior GAD trial and noting any caveats. He also inquired why delta often shrinks from Phase 2 to Phase 3 and if this is a concern for Definium.

Answer

Robert Barrow, CEO, stated that for MDD, Definium aims for a placebo-adjusted effect greater than 4 points and a double-digit absolute magnitude of change, noting the 6.4-point MADRS difference in the GAD study was from a milder population. Regarding delta compression, Mr. Barrow acknowledged it can happen but highlighted that Definium's Phase 2 was designed like Phase 3 with minimal operational changes, and improved patient retention (10% non-evaluable rate in Voyage vs. >25% in Phase 2) due to Part B access gives confidence.

Francois Brisebois from LifeSci Capital asked for Definium's expectations for a clinically meaningful delta in the upcoming MDD readouts, comparing it to existing MDD treatments and reminding of the previously observed MADRS results from the GAD Phase II trial. He also questioned the common perception that placebo-adjusted deltas typically shrink from Phase II to Phase III.

Answer

Robert Barrow, CEO, stated that for MDD, Definium aims for a placebo-adjusted effect greater than four points and a double-digit absolute magnitude of change, noting the 6.4-point MADRS difference in the GAD Phase II was from a lower baseline. Regarding delta compression, Mr. Barrow acknowledged historical trends but highlighted that Definium's Phase II was designed similarly to Phase III with minimal operational changes, and the Part B open-label access has improved patient retention, leading to confidence in maintaining strong results.

Francois Brisebois asked for expectations regarding upcoming elsunersen EMBRAVE data, the significance of the EMBRAVE3 single-arm design, and Praxis Precision Medicines' ex-US efforts and launch trajectory for ulixacaltamide.

Answer

President and CEO Marcio Souza noted that EMBRAVE Part A (9 patients) will provide safety, efficacy, and PK data, with the FDA's support for a single-arm, baseline-controlled EMBRAVE3 accelerating development. He confirmed a U.S.-centric focus for ulixacaltamide's launch due to its magnitude, with strong patient demand and a clear understanding of the prescriber base indicating a successful launch trajectory.

Francois Brisebois asked for an update on elsunersen, setting expectations for the upcoming EMBRAVE data, and clarifying the significance of the single-arm, baseline-controlled design for EMBRAVE3. He also inquired about ex-US efforts for ulixacaltamide and the launch trajectory, specifically regarding patient identification.

Answer

CEO Marcio Souza explained that the upcoming EMBRAVE Part A data (9 patients, 3:1 randomized to sham/drug) will provide further insights into safety, efficacy, and PK, with the FDA leaving the door open for its overall program value. He noted the agency's push for the single-arm EMBRAVE3 design reflects confidence in accelerating development for drugs with high translatability. For ulixacaltamide, he stated the company's laser focus is on the U.S. launch due to the significant unmet need and well-understood patient population, with daily patient inquiries and mapped prescribers indicating strong demand and a positive launch trajectory.

François Brisebois questioned the potential disclosure scenarios for the ulixacaltamide interim analysis, including whether data would be shared, and asked about the commercial potential for the DEE franchise in the U.S. versus ex-U.S. markets.

Answer

CEO Marcio Souza outlined that if the study is stopped for overwhelming efficacy, results for both Study 1 and Study 2 would be released simultaneously. He also noted the most probable scenario is an increase in Study 1's size. Regarding the DEE market, he described it as a multibillion-dollar opportunity, with modeling showing approximately 70% of the value in the U.S. from a patient population just under 200,000.

François Brisebois questioned whether to expect a p-value with the relutrigine data readout and asked for clarification on the design differences between the parallel and randomized withdrawal studies for essential tremor.

Answer

CEO Marcio Souza explained that for the relutrigine readout, the focus would be on the distribution of patient responses and the drug's very good tolerability, with a full discussion to follow. Regarding the Essential3 design, he detailed that the randomized withdrawal portion mimics real-world use, while the parallel group study leverages learnings from Essential1 to manage a heterogeneous population, creating a robust registrational package for a planned NDA filing.

François Brisebois sought clarification on whether to expect a p-value for the relutrigine data readout and asked about the design differences in the Essential3 program (parallel vs. randomized withdrawal) that provide Praxis with confidence.

Answer

Executive Marcio Souza did not directly confirm if a p-value would be shared for the relutrigine readout, instead emphasizing the importance of the distribution of patient responses and the drug's very good tolerability. Regarding the Essential3 design, he explained that the randomized withdrawal study mimics real-world use, while the parallel group study leverages learnings from Essential1 to manage a heterogeneous population, with the overall goal of maximizing the probability of success for a future NDA filing.

François Brisebois of Oppenheimer & Co. Inc. inquired about the estimated cost and timeline for the Phase III trial of larsucosterol and asked for elaboration on the time-to-dose variations observed between U.S. and ex-U.S. patients in the Phase IIb study.

Answer

An executive, James Brown, estimated the Phase III trial would cost approximately $20 million and take about two years to reach top-line data. Brown, along with executives Norman Sussman and Weiqi Lin, explained that the time-to-dose variation is critical in an acute disease like alcohol-associated hepatitis. They noted that U.S. patients were treated much faster (around 4 days) than in some ex-U.S. regions (up to 2 weeks), which significantly impacted outcomes. The upcoming Phase III trial will control for this by ensuring all patients are dosed within approximately 9 days.

Asked about the timeline for receiving FDA meeting minutes and the next corporate update, differences between U.S. and EU sites in the AHFIRM trial, the impact of liver transplants on the endpoint, the location of the upcoming AASLD meeting, and the terms of the company's outstanding loan.

Answer

The company expects FDA minutes in about 4+ weeks and will provide an update then. They acknowledged significant regional differences in patient management that explain the data variance between the U.S. and EU. Liver transplant is not a major factor due to scarcity, so the focus remains on mortality. The AASLD meeting is in San Diego. The Oxford loan terms were detailed, including monthly payments, interest rate, and final payment date.

François Brisebois asked for more details on the positive impact of the recent Medicare LCD update for MediWound and requested a reminder of the timing and potential outcomes for the EscharEx Phase III trial's interim analysis.

Answer

Executive Barry Wolfenson clarified that the new Medicare LCD, effective April 2025, heightens the requirement for complete debridement and granulation tissue before CTP use, which strongly positions EscharEx as an optimal choice. CEO Ofer Gonen explained the trial's interim assessment is expected by mid-2026. The outcomes could be stopping enrollment early due to a high probability of success or adding a few dozen patients to maintain the study's 90% statistical power.

An associate for François Brisebois asked if the recent protocol amendment to include TPA nonresponders has improved ReMEDy2 enrollment rates. He also requested more color on KOL feedback regarding DM199 following the recent IST conference.

Answer

Dietrich Pauls, an executive, confirmed a 'very encouraging' increase in enrollment since the start of the year, partly due to the protocol amendment. He added that the failure of three competing mechanical thrombectomy studies at the IST conference was viewed positively by KOLs, as it reduces competition for patients and may increase site capacity for the ReMEDy2 trial.

A representative for Francois Brisebois asked for updated guidance on the timeline for completing enrollment for the new 200-patient interim analysis cohort.

Answer

CEO Dietrich Pauls stated that with the interim analysis results now expected in Q4 2025, the company anticipates completing the enrollment of the 200-patient cohort sometime in the summer of 2025.

François Brisebois asked for details on the expected sales ramp following the planned Q3 2026 launch, including more color on the physician and patient segmentation strategy. He also sought clarity on the likelihood of securing a partner versus launching independently and requested a breakdown of the fully diluted share count, including warrants.

Answer

Chief Commercial Officer Jaime Xinos projected a slow initial sales ramp, with a focused strategy targeting the top 10% of varenicline prescribers and highly motivated patients. CEO Richard A. Stewart reiterated that while the company is planning for a self-launch, it remains open to a strategic partner to optimize U.S. revenue and global expansion. Chief Financial Officer Mark Oki clarified the fully diluted share count, estimating it would add approximately 20 million shares from options and warrants.

Dan, on behalf of Francois Brisebois from Oppenheimer, asked about any additional steps required before the NDA submission after the ORCA-OL data analysis is complete, and whether the positive DSMC feedback provides sufficient confidence to proceed.

Answer

CEO Rick Stewart outlined the sequential process following the completion of 6-month data collection for 300 patients. He stated the company must monitor the data, incorporate it into the Integrated Safety Summary (ISS), insert the ISS into the NDA, and then conduct a full quality control check on the entire NDA package before submission.

François Brisebois inquired about the importance of Anaphylm's launch timing relative to market seasonality and sought reassurance on the product's safety profile, particularly concerning Cmax, repeat dosing, and physiological epinephrine levels.

Answer

Executive Sherry Korczynski described the planned Q1 2026 launch as 'perfect timing' ahead of the peak allergy season. CEO Daniel Barber defended the product's safety, highlighting a robust data package and arguing a strong second dose is critical for severe reactions. Executive Carl Kraus added that the epinephrine levels are within the body's capacity to handle stress and do not pose a concern.

François Brisebois of Oppenheimer & Co. Inc. asked about the importance of the efficacy data from the Anaphylm OASIS study for driving real-world physician adoption and whether treating at the site of symptoms could be a key market differentiator. He also sought clarification on the percentage of oral allergy syndrome (OAS) cases that progress to anaphylaxis.

Answer

CEO Daniel Barber emphasized that the OASIS study data is a key differentiator that physicians are paying attention to. Chief Medical Officer Carl Kraus added that KOLs widely support the idea that localized delivery holds promise and that the study provides a potentially predictive model for evaluating anaphylaxis. Barber clarified that literature shows about 10% of OAS reactions progress to more severe reactions, with 2% of total OAS cases resulting in anaphylaxis.

François Brisebois of Oppenheimer inquired about the evolution of Avadel's sales representative count, the company's strategy for direct-to-consumer (DTC) marketing, the distinct roles of the field support and nurse teams, and which commercial effort is most critical for securing switch patients.

Answer

Executive Gregory Divis detailed a 15% increase in the sales team to 53 reps and a doubling of both the field support and nurse teams to 28 each, effective January 2025. He confirmed increased investment in patient education media channels. Divis clarified that field support teams assist physician offices with post-prescription logistics, while nurse teams engage directly with patients. He emphasized that a cumulative, multi-faceted approach is necessary to drive patient switches. Executive Thomas McHugh added that these investments are already showing positive early trends in Q1 2025.

François Brisebois inquired about insurance dynamics for new-to-oxybate patients, specifically regarding step-through requirements for authorized generics (AGs). He also asked about the planned sales force expansion, revenue expectations versus consensus, and the latest updates on the company's ongoing litigation.

Answer

Executive Richard Kim explained that step-throughs are rare due to strong payer access, with 85% commercial coverage secured. He noted the sales force is expanding by just over 10% to increase reach with moderate and low-volume prescribers. CFO Thomas McHugh commented on Q4 expectations, highlighting the need to assess new patient persistency and seasonality. CEO Gregory Divis provided a detailed legal update on the Delaware patent trial, the IH injunction appeal, and the antitrust action against Jazz.

François Brisebois asked about the rationale for the new Chief Patient Officer role, the timing of the 26-week COMP005 data, the recency of the last DSMB review, and if more reviews are expected before the readout.

Answer

Chief Patient Officer Dr. Steve Levin and CEO Kabir Nath explained the CPO role is to integrate patient and provider perspectives into all strategic planning. Nath reiterated that the COMP005 26-week data readout is gated by the completion of Part A of the COMP006 trial. He also confirmed the last DSMB review occurred in February 2025 and that future reviews would follow a quarterly cadence, depending on the final data release timing.

François Brisebois of Oppenheimer asked for more detail on the differences between the clinical and commercial settings and inquired about the key activities required between the final data readouts and a potential product launch.

Answer

Lori Englebert (Executive) highlighted the company's current pre-commercial activities. These include increasing awareness of TRD, educating KOLs on Phase II data, preparing for state-level DEA rescheduling, optimizing patient flow models through collaborations, and building a robust health economics dataset for future payer discussions. She reiterated confidence by citing Spravato as a successful market analog.

François Brisebois asked for details on the strategy to motivate physicians to increase XDEMVY prescribing frequency and inquired about the market's evolution from new prescriptions (NRx) to total prescriptions (TRx). He also asked about key medical conferences and the Q1 impact from weather events.

Answer

Chief Commercial Officer Aziz Mottiwala detailed a four-part strategy to deepen prescribing habits, citing near-term drivers like the expanded sales force and 90% insurance coverage, and mid-to-long-term drivers like the DTC campaign and compelling MGD data. An executive added that the retreatment rate is currently in the mid-single digits but is expected to reach a steady state of 20%. Chief Financial Officer Jeff Farrow confirmed that impacts from LA fires and winter storms were factored into Q1 guidance.

François Brisebois of Oppenheimer & Co. Inc. asked newly appointed Chief Medical Officer Dr. Elizabeth Yeu about the timing of her joining the company and her perspective on XDEMVY. He also inquired about the company's strategy regarding mergers and acquisitions.

Answer

Chief Medical Officer Dr. Elizabeth Yeu stated she joined to amplify her ability to care for patients on a larger scale, citing Tarsus's excellence in execution and its inspirational leadership team. CEO Bobak Azamian added that her leadership in evidence and education is timely. Regarding M&A, Azamian said the focus remains on XDEMVY, but the company is preparing to leverage its platform to add both development-stage and commercial assets over time to become a broader eye care leader.

François Brisebois inquired about the large pharma commitment to PK Analytics, asking if this was an expected development. He also sought clarity on the temporary service project postponements, questioning if they would impact the rest of the year or be resolved in the second quarter.

Answer

Executive Shawn O'Connor explained that the large pharma commitment was not a surprise but the result of a sustained, long-term business development effort. Regarding the Services segment, he stated that while client budget constraints at the end of the calendar year caused some project ramp-up delays, robust bookings and a strong backlog provide confidence in the full-year outlook, and the company's guidance already factors in this dynamic.

François Brisebois requested an explanation for how the Pro-ficiency acquisition doubles the company's Total Addressable Market (TAM). He also asked about the company's future M&A strategy, questioning if they would pause to integrate the large Pro-ficiency acquisition.

Answer

Executive Shawn O'Connor clarified that the incremental $4 billion TAM from Pro-ficiency is split between the market for clinical trial training services and the medical communications market, which includes pre-approval regulatory support and post-approval commercialization work. Regarding M&A, he stated that while resources are devoted to the current integration, the company's strategy to supplement organic growth with acquisitions is unchanged and remains active, though there is no specific guidance for a deal in 2025.

François Brisebois questioned if MindMed would wait for Part B data before announcing Part A results, whether the interim analysis could trigger an early stoppage for efficacy or futility, and asked for thoughts on the recent U.S. elections' impact on the space.

Answer

Executive Robert Barrow confirmed that the company intends to lock the database and announce top-line results for Part A upon its completion after 12 weeks. He clarified the interim analysis is a blinded sample size reestimation with no inferential testing for early efficacy or futility. Regarding the election, he noted broad, bipartisan awareness and enthusiasm for addressing the mental health crisis.

François Brisebois asked about the rate of concomitant use of WAKIX and oxybate, related reimbursement trends, and the potential impact of future orexin therapies on the market.

Answer

Chief Commercial Officer Jeffrey Dierks reported that concomitant use with oxybate has remained consistent in the low double-digits (teens) with stable reimbursement. He noted that rare disease categories are typically less managed by payers and suggested that future enhanced-efficacy products like pitolisant HD could potentially reduce the need for controlled substances, a positive for both patients and payers.

Francois Brisebois of Oppenheimer inquired about the optimal duration for DPD inhibition for Next Generation Capecitabine (NGC), the potential need for multiple Phase 2 trials under the FDA's Project Optimus, the magnitude of efficacy for PCS12852 in gastroparesis, and an update on patient recruitment for the PCS499 trial. He also asked about the safety profile and potential for higher dosing of PCS12852.

Answer

President & CEO Dr. David Young explained that a longer DPD inhibition, closer to 72 hours, would be ideal for NGC. He clarified that under Project Optimus, the company plans for a single Phase 2B trial before a pivotal trial, similar to other indications. For gastroparesis, he highlighted the significant unmet need in moderate to severe patients and noted that PCS12852's safety profile could allow for doses higher than 0.5mg. Dr. Young also acknowledged recruitment difficulties for PCS499 due to a small patient population and frequent misdiagnosis prior to screening.

François Brisebois of Oppenheimer & Co. Inc. inquired about the PCS499 trial, asking whether the enrollment challenge was due to a high screening failure rate or difficulty attracting patients for screening. He also asked about the impact of the new patient-facing website and requested an updated timeline for preliminary results from the PCS6422 trial.

Answer

President and CEO Dr. David Young clarified that for PCS499, the issue is not a high screening failure rate but a low volume of patients presenting for screening, which he attributed to COVID-19 concerns. He noted that supplemental recruitment programs and the new website are beginning to increase patient interest. For PCS6422, Dr. Young projected interim results for the new cohorts in late summer (August/early September), with the overall study timeline remaining on track to complete enrollment by the end of 2022.

Francois Brisebois inquired about the rationale behind CVS Caremark's decision to first add restrictions and then grant formulary coverage for EYSUVIS. He also asked for clarity on the timing of gross-to-net improvements, the current ratio of written versus filled prescriptions, and the competitive landscape for KPI-012 in the PCED market.

Answer

President and COO Todd Bazemore explained the initial restrictions were a standard payer tactic for a non-contracted drug gaining momentum, which was resolved by negotiating a formulary contract. He anticipates significant gross-to-net improvements in the second half of 2022. While granular filled vs. written data has a lag, he noted that a drop in copay assistance use from 70% to 54% alongside accelerating script growth are positive indicators. Head of R&D and CMO Kim Brazzell described the PCED landscape, identifying Dompe's OXERVATE as the only approved competitor but with a narrower indication (neurotrophic keratitis) and a more complex administration process compared to KPI-012's broader, more convenient approach.

Franc Brisebois from Oppenheimer followed up on the gross-to-net pressure, asking for the specific reason it worsened in Q4. He also questioned the relative importance of Medicare versus commercial wins for improving gross-to-net and asked for a reminder on how long a single EYSUVIS prescription typically lasts for a patient.

Answer

Todd Bazemore, President and COO, explained that a larger percentage of filled prescriptions in Q4 had no insurance benefit, requiring a full buy-down from the WAC, which pressured gross-to-nets. He clarified that commercial wins improve gross-to-net, while Medicare wins primarily open up demand fulfillment. He also estimated that one prescription covers at least a couple of flares. Mary Reumuth, CFO, confirmed that the increase in units going through the co-pay card was the primary driver of the gross-to-net issue.

François Brisebois from Oppenheimer sought clarification on EYSUVIS net revenue trends, asking why patient assistance program usage increased despite growing coverage. He also inquired about the potential pricing strategy for PCED relative to the competitor OXERVATE and asked about the underlying causes and diagnosis of PCED.

Answer

COO Todd Bazemore clarified that EYSUVIS revenue increased 10% quarter-over-quarter, while volume grew 19%, with the difference due to higher utilization of the co-pay assistance program to capture more rejected scripts. He positioned OXERVATE's ~$100,000 price as a good analog for rare disease pricing. Chief Medical Officer Kim Brazzell explained that PCED results from various underlying conditions, such as neurotrophic keratitis, viral infections, or surgical issues, that impair the cornea's ability to heal.

François Brisebois of Oppenheimer sought clarification on the repeat-dosing protocol for the CYB003 trial. He asked about the timing of the two doses and whether this design would limit the duration of follow-up data for patients receiving both doses to only three weeks.

Answer

CEO Douglas Drysdale detailed the dosing schedule: patients receive the first dose at time zero, with an initial assessment at week 3. At that point, the active group receives a second dose, and the placebo group receives its first dose. A final assessment occurs at week 6, allowing for a comparison between one and two doses. While he confirmed the 3-week interval between doses, he also suggested that longer-term follow-up is being considered but could not share specifics at this time.

Francois Brisebois of Oppenheimer questioned the strategic choice of MDD over TRD, the approach to managing the placebo effect, and whether scalability advantages for CYB003 stem from administration time or the EMBARK program.

Answer

CEO Doug Drysdale explained that MDD represents a larger population and a less risky initial path to proof-of-concept than TRD. He noted they use a secondary screening tool to mitigate placebo effects. He clarified that scalability is a multi-pronged strategy, combining the shorter clinic time of CYB003 for better adoption with the open-source EMBARK program to ensure a supply of trained therapists.