Sumant Kulkarni

Sumant Kulkarni from Canaccord Genuity asked if Definium agrees that durability of effect, rather than just point separation on scales, should be the higher bar for psychedelic therapeutics compared to standard of care, especially given DT120 ODT's demonstrated durability. He also inquired about Definium's latest thoughts on pricing for MDD and GAD, using SPRAVATO for TRD as a potential benchmark, and how much of the "high-touch, white-glove experience" could be covered by insurers.

Answer

Robert Barrow, CEO, affirmed the importance of durability, noting that demonstrating 12-week durability after a single intervention sets a high standard for DT120 ODT. Regarding pricing, Mr. Barrow stated it's premature but highlighted that disease severity drives burden, and current therapy failures don't define the population. Matt Wiley, CCO, detailed the "high-touch" commercial strategy, including a hub service model, clear reimbursement pathways, and managing patient out-of-pocket costs to ensure seamless patient access.

Sumant Kulkarni asked if investors are unfairly holding psychedelic therapeutics to a higher bar on point separations, suggesting durability of effect should be the key differentiator. He also inquired about Definium's latest thoughts on pricing in MDD and GAD relative to SPRAVATO for TRD, and what fraction of the 'high touch white glove experience' could be covered by insurers.

Answer

Robert Barrow, CEO, agreed on the importance of durability, noting that 12-week durability after a single intervention sets a high bar and is a primary endpoint. Mr. Barrow stated pricing is premature but emphasized that severity drives disease burden. Matt Wiley, Chief Commercial Officer, explained the 'high touch' approach aims to remove patient/provider friction through hub services, clear reimbursement pathways, and managing out-of-pocket costs to ensure a positive patient experience.

Sumant Kulkarni inquired about the implications of the FDA's recent position on needing one robust pivotal trial plus confirmatory evidence for ACP-204 in ADP and Lewy body dementia psychosis, especially if phase II data is strong.

Answer

Elizabeth Thompson, EVP and Head of Research and Development, expressed enthusiasm for regulatory innovation that could accelerate patient access but noted many unknowns regarding the FDA's new position, such as its impact on required safety databases and global acceptability. Catherine Owen Adams, CEO, added that Acadia will inform stakeholders on phase III protocol design based on phase II results and the evolving policy environment.

Sumant Kulkarni asked about the implications of the FDA's recent position on requiring one robust pivotal trial plus confirmatory evidence for ACP-204 in ADP and Lewy body dementia psychosis, especially if Phase 2 data prove to be 'very good.'

Answer

Elizabeth Thompson, EVP and Head of Research and Development, welcomed regulatory innovation that could accelerate patient access to safe and effective products. She noted that while the FDA's new position is promising, questions remain regarding its impact on required safety databases and global development programs. Catherine Owen Adams, CEO, added that ACADIA would inform stakeholders on how Phase 3 trials might be redesigned based on top-line Phase 2 results and evolving policy.

Sumant Kulkarni asked for specifics on how the pipeline asset ACP2591 fits into the company's plans for Rett syndrome relative to the currently marketed Daybue.

Answer

EVP, Head of R&D, Elizabeth Thompson, explained that ACP2591 was attractive due to mechanistic similarities to Daybue, which de-risks it, but with the potential for a differential benefit-risk profile. She stated that the company is currently conducting additional work to verify information needed to advance the program specifically in Rett syndrome and will provide updates at an appropriate time.

Sumant Kulkarni of Canaccord Genuity asked for the latest assumptions on the timing of generic competition for NUPLAZID and whether Acadia expects to recognize revenue from France's paid early access program for trofinetide.

Answer

CFO Mark Schneyer reiterated that the intellectual property for NUPLAZID provides protection within a window of October 2030 to February 2038, and noted an upcoming oral argument for a patent appeal. CEO Catherine Owen Adams confirmed that the company is establishing the mechanism for France's early access program and plans for those patients to transition to commercial product after national reimbursement is secured.

Sumant Kulkarni posed a broader question about potential changes at the FDA and how they might impact future regulatory interactions regarding the Prader-Willi syndrome program.

Answer

EVP of R&D Elizabeth Thompson acknowledged the evolving regulatory environment but stated that Acadia has not yet seen any impact on its interactions with the FDA. She confirmed that the timing and tenor of discussions have remained consistent, and the company will continue to monitor the situation closely.

Sumant Kulkarni of Canaccord Genuity asked to identify the key bottleneck preventing new Daybue patient starts, beyond the COE vs. non-COE dynamic, and what main variable needs to be addressed to see a sales inflection.

Answer

Executive Brendan Teehan identified the primary focus as education on real-world efficacy, especially outside of academic centers. The key variable to drive inflection is effectively translating clinical trial endpoints (CGII, RSBQ) into tangible daily improvements for families and physicians. This is being done through peer-to-peer programming and sharing caregiver testimonials about long-term benefits, tailored to different patient age groups.

Sumant Kulkarni asked about the recent sale of Neurocrine's U.K. and European rare commercial business, its implications for crinecerfont development in Europe, whether Neurocrine will remain U.S.-focused, and the role of potential Most Favored Nations pricing in this decision.

Answer

Kyle Gano, Chief Executive Officer, explained that the EU programs were not aligned with Neurocrine's current portfolio, leading to their sale. He stated that the company is currently focused on the U.S. market for CRENESSITY's launch and will explore ways to bring CRENESSITY and other future medicines to Europe. He added that Neurocrine is not primarily considering Most Favored Nations pricing as much as focusing on the U.S. market, but will seek clarity on evolving policy before making definitive decisions outside the U.S.

Sumant Kulkarni inquired about the recent sale of Neurocrine's UK and European rare commercial business, its implications for crinecerfont development in Europe, whether Neurocrine will remain U.S.-focused, and the role of potential Most Favored Nations pricing enforcement in this decision.

Answer

CEO Kyle Gano explained that the EU business programs were not well-aligned with Neurocrine's current portfolio, leading to their sale. He stated the company is currently focused on the U.S. market for CRENESSITY and other future medicines, and will seek clarity on evolving policies like Most Favored Nations pricing before making definitive decisions outside the U.S.

Sumant Kulkarni asked about the potential impact of the Inflation Reduction Act (IRA) on INGREZZA, specifically concerning patient profiles or prescriber types, and the maximum number of products the expanded neuropsych sales team could leverage.

Answer

Eric Benevich, Chief Commercial Officer, stated that the sales team expansion sets up well for launching Directlidine and osavampator later in the decade, potentially reducing future changes needed, though it wouldn't fully cover primary care prescribers for a broader launch. Matt Abernethy, Chief Financial Officer, added that existing INGREZZA patients are expected to stay on therapy, and the current focus is maximizing new patients before 2027, while learning from IRA negotiations.

Sumant Kulkarni asked about the potential impact of the Inflation Reduction Act (IRA) on INGREZZA once it kicks in for competitors, specifically regarding patient or prescriber profiles, and the maximum number of products the expanded neuropsych sales team could leverage.

Answer

Eric Benevich, Chief Commercial Officer, stated that the expanded neuropsych sales team is designed to set up for potential launches of Directlidine and osavampator later in the decade, potentially handling both, though it wouldn't fully cover primary care prescribers needed for osavampator. Matt Abernethy, Chief Financial Officer, noted that existing INGREZZA patients are expected to stay on therapy during the IRA window, and the company is maximizing patient numbers before 2027, controlling what they can.

Sumant Kulkarni from Canaccord Genuity Group Inc. asked about the potential of using Neurocrine's CRF1 receptor antagonist approach for weight loss, given the one-year data from Crinesity and the development of a long-acting version.

Answer

Strategic Advisor Eiry Roberts acknowledged the encouraging data and the company's deep expertise in CRF biology. She stated that Neurocrine is considering a broad range of potential indications for the mechanism and has other research programs that could also address challenging diseases like obesity.

Sumant Kulkarni noted the recurring debate on INGREZZA's growth trajectory and asked for the company's latest philosophy on providing guidance for eventual peak sales potential to help settle the uncertainty.

Answer

Chief Financial Officer Matthew Abernethy and CEO Kyle Gano both declined to provide a peak sales forecast. Abernethy pointed out that original models were for $500 million, a figure the drug nearly achieved in year-over-year growth alone in 2024. Gano added that the underlying prevalence of tardive dyskinesia is growing, making the market size dynamic and suggesting significant growth potential remains as 9 out of 10 patients are still untreated with a VMAT2 inhibitor.

Sumant Kulkarni of Canaccord Genuity Inc. questioned the outlook for growth in Myclifa patient enrollment forms, the impact of competition, and the current pace of enrollment in the DISCOVER trial for ciliprolol.

Answer

CEO Neil McFarlane and CCO Joshua Schafer detailed their strategy to grow enrollments by targeting diagnosed-but-untreated and undiagnosed patients, citing Europe's mature market as a model and Myclifa's 5-year durability data as a key differentiator. For the DISCOVER trial, Chief Medical Officer Adrian Quartel highlighted a new genetic testing initiative and strong physician interest, expressing optimism for improved enrollment outcomes in the coming quarter.

Sumant Kulkarni of Canaccord Genuity inquired about the number of patients actively on MIPLYFFA from the 122 enrollment forms, the split of reimbursed patients, and the primary reasons for initial reimbursement denials. He later asked for an update on the enrollment timeline for the celiprolol Phase III trial.

Answer

Chief Commercial Officer Joshua Schafer stated that while the exact number isn't disclosed, the majority of the 122 enrollments are on active drug, with others in the benefits investigation process. He explained that initial denials are typical for rare disease drugs and are usually overcome through medical exception processes, leveraging MIPLYFFA's strong clinical data. President and CEO Neil McFarlane added that the product's differentiated clinical profile is key to overcoming access challenges. Regarding celiprolol, Mr. McFarlane confirmed the trial size and detailed new strategies to accelerate enrollment, such as focusing on genetically confirmed patient centers, expressing confidence that these efforts will increase the enrollment rate.

Sumant Kulkarni inquired about the key variables that will influence the trajectory of MIPLYFFA patient enrollment forms going forward. He also asked for a breakdown of diagnosed NPC patients treated at Centers of Excellence versus other settings and the timeline for seeing an inflection from the new OLPRUVA strategy.

Answer

CCO Joshua Schafer explained the initial enrollment surge was driven by ready-to-go EAP patients and future growth depends on expanding to new sites. CEO Neil McFarlane added that the rapid EAP conversion far exceeded typical timelines. Regarding OLPRUVA, Schafer stated no specific timeframe for an inflection has been set, but emphasized the strategic synergies the product creates for the commercial team.

Sumant Kulkarni asked for a breakdown of EAP versus new patients among the approved MIPLYFFA prescriptions, commentary on competition from IntraBio's product, the company's preferred strategic alternatives for KP1077, and the level of patient demand for the celiprolol trial.

Answer

President and CEO Neil McFarlane stated they are not parsing approved prescriptions by EAP status and declined to comment on competitors, instead emphasizing MIPLYFFA's differentiated data showing it halts disease progression. Chief Commercial Officer Joshua Schafer explained the search for a partner for KP1077 is driven by the need for a larger commercial footprint than Zevra's rare disease focus. Neil McFarlane described patient demand for the celiprolol trial as a 'big surprise' with very strong interest since restarting enrollment.

Sumant Kulkarni from Canaccord Genuity Group questioned the new CFO on the adequacy of financial resources for the ongoing pivotal trials and asked for management's perspective on the industry notion that shorter in-clinic time is superior for psychedelic therapies.

Answer

CFO Brandi Roberts affirmed confidence in the company's cash position, guiding for a runway into 2027 and at least 12 months beyond the first Phase 3 GAD readout, citing operational efficiencies and a recent debt agreement amendment for flexibility. CEO Robert Barrow added that while shorter clinic time is an easy assumption, the significant magnitude and durability of MM120's effect could create a different value proposition for patients and providers.

Sumant Kulkarni of Canaccord Genuity Group posed a question to the new CFO about the adequacy of financial resources for the ongoing trials and asked about the company's view on the investor perception that less time in the clinic is always better for psychedelics.

Answer

CFO Brandi Roberts affirmed her confidence in the company's financial position, citing trial efficiencies and prudent spending, and reiterated the cash runway guidance into 2027. CEO Robert Barrow addressed the commercial model, stating that while a shorter duration is an easy assumption, MM120's profound and durable effect, combined with favorable practice economics, makes its single-visit model highly compelling.

Sumant Kulkarni asked new CCO Matt Wiley how his prior experience with scheduled products would aid in commercializing MM-120 and what unique challenges are associated with LSD.

Answer

CCO Matthew Wiley highlighted his experience with REMS programs, particularly with sodium oxybate at Jazz, as highly relevant. He identified the primary challenge for LSD as market education, specifically reframing the scientific understanding of the underlying disease states and how MM-120 fits into the treatment paradigm.

Sumant Kulkarni of Canaccord Genuity asked for details on recent FDA interactions under the Breakthrough Therapy Designation and questioned what MM120's key selling point would be against potential shorter-acting competitors.

Answer

CEO Robert Barrow described frequent, constructive, and highly aligned interactions with the FDA, which have not been impacted by external factors. Against competitors, he highlighted MM120's potential for superior magnitude and durability of effect, as shown in large, well-controlled studies. He also noted the favorable site economics of a single-dose treatment compared to therapies requiring high patient throughput.

Sumant Kulkarni asked how the integrity of the treatment's durability effect would be maintained in the 40-week open-label extension and what level of non-MM-120 rescue therapy might be considered optimal in a clinical trial setting.

Answer

Chief Medical Officer Dr. Daniel Karlin explained that the same restrictions on concomitant medications from the double-blind period will apply during the extension phase. He clarified that the primary 'rescue' is redosing with MM-120, with up to four treatments available. If a participant still requires other therapies, they would be withdrawn from the study, and the missing data would be handled with statistical methods.

Sumant Kulkarni of Canaccord Genuity Inc. asked about the earliest possible NDA filing date for COMP360, the timeline for reporting Part B data from the COMP005 trial, and if any new data was included in the priority review application.

Answer

CEO Kabir Nath stated it is premature to speculate on a filing date before meeting with the FDA. He clarified that the Part B data from COMP005 will be released only after COMP006 Part A is complete to avoid data confounding. He also confirmed the priority review application was a 350-word abstract and contained no new, non-public Phase III data.

Sumant Kulkarni of Canaccord Genuity asked about the optimal time frame before suicidality is no longer attributable to a single COMP360 dose and whether the company has observed any changes within the FDA regarding support for psychedelic therapies.

Answer

Dr. Guy Goodwin, Chief Medical Officer, stated that determining the time frame for suicidality attribution is complex and that they will need to analyze the data before making any predictions. CEO Kabir Nath reported no changes in their routine day-to-day interactions with the FDA, although they are monitoring higher-level shifts that could create favorable tailwinds for the field.

Sumant Kulkarni questioned if COMP360 needs to achieve a higher-than-typical MADRS improvement for real-world success, how it will compete with shorter-acting psychedelics, and how the current political and FDA environment might impact the regulatory process.

Answer

CEO Kabir Nath and CMO Dr. Guy Goodwin argued that the efficacy bar for TRD is likely lower than for MDD due to the lack of approved treatments. Chief Patient Officer Dr. Steve Levin addressed competition by highlighting new CPT codes that reimburse on an hourly basis, supporting the economic model. CEO Kabir Nath described the political environment as neutral to potentially positive, particularly for PTSD, but noted no change in FDA interactions yet.

Sumant Kulkarni of Canaccord Genuity asked why Compass is releasing 6-week data for COMP 005 instead of waiting for the 26-week results. He also questioned if the current Phase III program will provide sufficient data on treatment schedules to inform commercial pricing.

Answer

Kabir Nath (Executive) reiterated that the company has consistently guided to a 6-week data release for COMP 005, highlighting that its design is different from COMP 006, where blinding is a higher priority. Lori Englebert (Executive) affirmed her belief that the Phase III program will provide important and relevant information on treatment schedules that will be valuable for discussions with payers regarding pricing.

Sumant Kulkarni of Canaccord Genuity asked what is needed for a significant sales inflection for ZURZUVAE to surpass SG&A costs, in the context of the company's cash runway and pipeline timelines.

Answer

CEO Barry Greene pointed to the greater than 20% quarter-over-quarter growth and the fully deployed sales force as key drivers for future growth. He reiterated the company's goal for the ZURZUVAE brand to become cash flow positive by the end of 2026. He also confirmed that Sage's current cash runway is expected to last into mid-2027, with future spending decisions dependent on clinical data.

Sumant Kulkarni questioned whether the collaboration with Biogen is necessary for successful commercialization and asked about the sales force's level of focus given the background noise of the company's strategic review.

Answer

CEO Barry Greene affirmed that the collaboration with Biogen is the existing operational structure. He stated unequivocally that the joint commercialization teams are 'laser-focused' on executing the ZURZUVAE launch and helping patients, and that there are 'no distractions' from the strategic review process.

Sumant Kulkarni asked if Sage would consider using its cash position to acquire external assets to bolster its pipeline, especially after the SAGE-324 setback.

Answer

CEO Barry Greene acknowledged that the company is 'intellectually curious' and actively scans for external opportunities. He stated that while they would act on a compelling strategic fit, there was 'nothing active to report' at the present time.

Sumant Kulkarni asked what specific results from external programs would be necessary for Voyager to make a firm go/no-go decision on its own anti-tau antibody program, or if the decision would depend solely on internal data.

Answer

CEO Dr. Al Sandrock stated he is looking for external data to establish a clear quantitative link between the degree of tau PET reduction and a clinically meaningful benefit, which he defined as roughly a 30% effect on the CDR sum of boxes. He explained that once this relationship is understood from the broader field, it will provide a clear efficacy bar that Voyager's internal antibody data can be measured against to make a go/no-go decision.

Sumant Kulkarni from Canaccord Genuity asked about the pros and cons of targeting extracellular versus intracellular tau and the potential risks of a permanent tau-silencing gene therapy, given tau's biological functions.

Answer

CEO Dr. Al Sandrock noted that targeting extracellular tau is likely safer but has efficacy questions, while a knockdown approach has theoretical risks but is supported by viable tau knockout animal models. He emphasized that long-term human safety data from Biogen's BIIB080 program will significantly de-risk Voyager's approach. CSO Dr. Todd Carter added that preclinical data in rodents and NHPs have shown tau reduction to be 'remarkably benign'.

Sumant Kulkarni of Canaccord Genuity asked about the SOD1 ALS program, including potential preclinical work involving tofersen, trial recruitment strategies in light of tofersen's approval, and what level of neurofilament (NFL) reduction is considered clinically relevant.

Answer

CMO Dr. Toby Ferguson highlighted Voyager's strong preclinical data showing high transduction in motor neurons and significant mRNA reduction. He noted that lessons from tofersen, particularly around biomarkers like NFL, will be applied. Executive Alfred Sandrock drew a parallel to SMA, suggesting a gene therapy could be used alongside existing treatments like tofersen. Regarding NFL, Ferguson stated that while a specific number isn't defined, any reduction must be substantial and the tofersen data informs the required magnitude.

Sumant Kulkarni of Canaccord Genuity inquired about the status of negotiations with large investors regarding financial covenants and the strategic importance of the SERENITY At-Home trial for securing future partnerships.

Answer

Executive Vimal Mehta responded that discussions with all stakeholders, including strategic partners, are ongoing and collaborative. The primary focus is on strengthening the balance sheet to reach the data readout. Regarding partnerships, Mehta highlighted that the company is in an advanced position with the SERENITY trial enrolling and the TRANQUILITY In-Care trial ready to start, and it is pursuing all paths to maximize shareholder value.

Sumant Kulkarni inquired about the data availability timeline and potential cost changes for the TRANQUILITY In-Care trial. He also asked about the company's alignment with the FDA on the SERENITY At-Home trial, the role of childproof packaging, and potential FDA discussion points for the TRANQUILITY protocol.

Answer

Vincent O'Neill, an executive at BioXcel, responded that the company is not providing specific timing for TRANQUILITY In-Care data and sees no change in cost estimates. He affirmed they are 'very aligned' with the FDA on the SERENITY At-Home trial, with CMC work complete. For TRANQUILITY, he noted that repeat dose efficacy is a key point of interest for the FDA.

Sumant Kulkarni asked about the capital required for the TRANQUILITY and SERENITY trials relative to cash on hand, the expected enrollment of patients on Rexulti, and whether the current operating expense base is optimized.

Answer

Executive Vimal Mehta explained that the TRANQUILITY trial cost is expected to be similar to TRANQUILITY II, while the smaller SERENITY trial would be about 50% less. Executive Robert Risinger noted that patients on Rexulti are not excluded, citing that about 50% of patients in TRANQUILITY II were on concomitant antipsychotics. CFO Richard Steinhart added that the company continuously evaluates its operating overhead for optimization.

Asked about the risk of agitation not being episodic during longer-term studies, compliance with financing covenants, and potential future pricing for BXCL501 in Alzheimer's agitation.

Answer

The company believes agitation is episodic and acute treatment is needed. They are working collaboratively with financing partners on covenants. They see pricing flexibility in the Alzheimer's market, citing the price of Rexulti, and are evaluating options.

Asked about the commercial potential and internal prioritization of oral difelikefalin for non-dialysis CKD, and what specific data and outcomes to expect from the KIND 1 Part A readout.

Answer

The company is very bullish on the advanced CKD market due to a different reimbursement system and significant unmet need, and it considers all three pipeline programs (CKD, AD, NP) as equally valuable. For the KIND 1 Part A readout, it is not powered for statistical significance but is designed to select a dose and determine the sample size for the pivotal program.

Sumant Kulkarni from Canaccord Genuity questioned the revised timeline for DMX-1002 safety data, the gating factors for a full acquisition of Compass Pathways, and atai's plans for investing in clinical infrastructure to support its therapies.

Answer

CSO Dr. Srini Rao explained the DMX-1002 trial is focused on assessing the risk-benefit profile, particularly cardiovascular effects, to inform Phase II dose selection. CEO Florian Brand stated that atai's core focus is CNS drug development, and while it will partner with infrastructure providers, it does not plan to invest in brick-and-mortar clinics. He also highlighted atai's first-mover advantage in building its broad pipeline.

Sumant Kulkarni of Canaccord Genuity inquired about Cybin's regulatory interactions, specifically with the FDA versus the U.K.'s MHRA, and the potential for future FDA guidance on psychedelics. He also asked about the pipeline, including how CYB003 might interact with alcohol and details on the CYB004 inhalation dosing platform and its patentability.

Answer

CEO Douglas Drysdale confirmed a productive meeting with the MHRA and stated that an IND for CYB003 will be filed in Q2 2022 without a prior FDA meeting. He noted that FDA guidance is not expected soon but may come as more Phase II data becomes available. For the pipeline, he explained that CYB004 is being developed for a nebulizer to avoid regulatory hurdles and is protected by a patent family covering delivery methods. He also clarified that for CYB003, Major Depressive Disorder (MDD) is being prioritized over Alcohol Use Disorder (AUD).

Sumant Kulkarni of Canaccord sought confirmation that CYB003 was definitively advancing to clinical trials, asked for preclinical data comparing its psychedelic intensity to psilocybin, and inquired about the spending outlook for its development.

Answer

CEO Doug Drysdale confirmed CYB003 is the lead candidate moving forward. Chief R&D Officer Mike Palfreyman added that animal models, which correlate with human response, show CYB003 has similar peak efficacy but a more favorable dose-response. Mr. Drysdale noted that combining MDD and AUD indications and pursuing accelerated regulatory pathways would create development and cost efficiencies.