Ben Burnett

Ben Burnett asked for color on the protocol for the alixorexton split dosing program, including when the second dose would be taken and if it could potentially eliminate food restrictions.

Answer

Richard Pops, CEO, stated that the objective of the split dose strategy is to extend wakefulness into the later hours for patients desiring it. He noted that Alkermes has a good understanding from Phase 2 modeling on how to administer two doses to maximize extended wakefulness while minimizing side effects. He indicated that specific details on the split dose strategy are proprietary but will differentiate the product commercially.

Ben Burnett asked for details on the alixorexton split dosing program protocol, specifically when the second dose is taken and if food restrictions could be avoided.

Answer

Richard Pops, CEO of Alkermes, stated the objective of split dosing is to extend wakefulness into later hours. He noted that phase II modeling provides a good sense of how to administer two doses to maximize wakefulness and minimize side effects, but specific protocol details are proprietary. He believes a once-daily anchor dose with a split-dose option will significantly differentiate the product commercially.

Ben Burnett asked about the phase three scenarios for Elixerextant, specifically if two phase three studies are needed and if an NT2 study combined with an NT1 phase three would suffice for approval in both indications.

Answer

Richard Pops, CEO, confirmed that the current assumption is two phase three studies (standalone for NT1 and a similar study for NT2) to seek labeling for narcolepsy, pending confirmation from the FDA.

Ben Burnett asked about the expected Q1 dynamics for Sephience, including any typical Q1 patterns or discounting. He also inquired about where the majority of future demand for Sephience is expected to come from, specifically whether switches from existing therapies or 'lost to follow-up' patients will be the more important group.

Answer

Matthew Klein, CEO, addressed the demand sources, stating that early in the launch, Sephience has seen broad uptake across age, severity, and patient segments, with the majority coming from therapy-naive patients or those who have tried and failed previous therapies. He expects this breadth to continue, with switches from existing therapies likely increasing over time as centers prioritize patients without current effective treatment. Klein also noted that over 80% of PKU Centers of Excellence in the U.S. have already prescribed Sephience.

Ben Burnett asked about the expected Q1 dynamics for Sephience, including any typical Q1 discounting or other trends that should be considered for modeling. He also inquired about the anticipated source of the majority of future demand for Sephience, specifically whether it will primarily come from patients switching from other therapies or from the 'lost to follow-up' and therapy-naïve patient groups.

Answer

CEO Dr. Matthew Klein explained that the launch has shown broad uptake across all patient segments, including therapy-naïve and those who tried and failed previous therapies, which have constituted the majority of demand thus far. He expects continued broad penetration, with switches from current therapies likely increasing over time as centers prioritize getting therapy to those without current options. Dr. Klein also highlighted that over 80% of U.S. centers of excellence have already prescribed Sephience.

Ben Burnett asked about physician feedback and appetite for using BRINSUPRI in more moderate patients or those with only one recent exacerbation, beyond the initial focus on severe patients.

Answer

Will Lewis, Chairman and CEO of Insmed, stated that it's still early, but physicians' initial focus aligns with the ASPEN study criteria (two or more exacerbations, moderate-to-severe profile). He noted the broad label and potential for comorbid COPD/asthma patients, emphasizing that physician experience will shape broader use over time.

Ben Burnett asked about physician feedback and appetite for using Brensupri in more moderate patients or those with only one recent exacerbation, beyond the initial focus on severe patients.

Answer

Will Lewis, Chairman and CEO, noted that it's still early, but physicians are currently focused on patients matching the ASPEN study criteria (two or more exacerbations), which represents a moderate to severe profile. He acknowledged the broader opportunity in other populations, including COPD and asthma comorbid patients, but emphasized a 'one step at a time' approach as physicians gain experience.

Carolina Ibanez-Ventoso on for Ben Burnett asked for the specific timing of the MRD conversion measurement for the mid-2025 interim analysis of the cema-cel ALPHA3 trial.

Answer

EVP of R&D and CMO Dr. Zachary Roberts responded that the company has not disclosed the exact timing of the MRD sample draw. He also noted that the lymphodepletion decision will be based on an assessment of multiple elements, not just the MRD conversion data.

On behalf of Ben Burnett from Stifel, an analyst asked what the ex-vivo data from the SLE patient sample implies about the necessary FT819 dose and expansion required to achieve deep B-cell depletion in vivo.

Answer

Dr. Bob Valamehr, Chief Research and Development Officer, explained that the data showed effective B-cell elimination at a 2:1 effector-to-target ratio. Given an estimated disease burden of 100-300 million B-cells in an SLE patient, the current dose of 360 million cells is well-positioned to match the effective dose seen in vitro, providing confidence in its potential for in-vivo efficacy.

Ben Burnett inquired about the expected duration of SDMA and SAM level reduction required to observe a clinical response and asked if the company plans to continue dose escalation until an MTD is reached.

Answer

Chief Scientific Officer Michael White explained that the time to response could vary by indication but requires continuous, strong target suppression. CEO & President Yujiro Hata added that they believe they are in the efficacious range at Cohort 6 and could start expansion there while continuing to escalate in parallel to formally define the MTD.