Gavin Clark-Gartner

Gavin Gartner asked for any commentary on the variability, blinded data, or baseline characteristics observed in the ongoing Aspire Angelman study that provides confidence in the trial.

Answer

Emil Kakkis, CEO and President, stated the study is progressing well but declined to comment on ongoing blinded data. Eric Crombez, Chief Medical Officer, added that the Aspire study utilizes the same entry criteria, endpoints, and patient population as the Phase II study, focusing on patients with full deletion and a consistent, severe phenotype, leading to an anticipation of consistent results with Phase II.

Gavin Gartner asked for any commentary on the variability observed in the blinded data or baseline characteristics of the ongoing ASPIRE Angelman study, seeking insights that provide confidence in the trial's progress.

Answer

Howard Horn, Chief Financial Officer, stated that the study is progressing well, but the company does not typically discuss ongoing trial data. Eric Crombez, Chief Medical Officer, added that the patient population, entry criteria, and endpoints in ASPIRE are very similar to those in the Phase 2 expansion study, focusing on full deletion patients with a consistent and severe phenotype, leading to an anticipation of consistent results.

Gavin Clark-Gartner inquired about the expected control arm TSS reduction from baseline in the BiRCh trial, the baseline TSS score, and the number of patients above or below the 300 eosinophil cutoff.

Answer

Martina Flammer, Chief Medical Officer, referenced other trials (REOPEN, ORION) for placebo assumptions, noting BiRCh patients are on stable steroids with a baseline TSS of 5 or above. She confirmed enrollment includes patients both above and below 300 eosinophils, with the primary endpoint assessment based on the entire population.

Gavin Clark-Gartner asked about the BIRCH trial, specifically the expectation for the control arm's TSS reduction from baseline, the baseline TSS score, and the number of patients above or below the 300 eosinophil cutoff.

Answer

Martina Flammer, Chief Medical Officer, referenced other trials (REOPEN, ORION) for placebo assumptions, noting BIRCH patients are on stable steroid therapy. She stated patients enter with a baseline Total Symptom Score (TSS) of 5 or above (out of 9) and that the study enrolls patients both above and below 300 eosinophils, with the primary endpoint assessed across the entire population.

Gavin Clark-Gartner from Evercore ISI asked about the expected ultimate conversion rate from Yorvipath enrollment to paid therapy and whether the company plans to continue reporting enrollment figures.

Answer

President & CEO Jan Møller Mikkelsen shared a personal success target of a 90% conversion rate at launch maturity, while acknowledging reimbursement challenges will persist for some patients. He confirmed Ascendis will continue to provide necessary KPIs, including enrollment data, until the launch is mature enough for revenue figures to be the primary metric for modeling.

Gavin Clark-Gartner followed up on payer access, asking if negotiations with commercial payers are largely complete and if rebating aligns with expectations. He also asked for the proportion of new YORVIPATH prescriptions from NATPARA-naive versus experienced patients.

Answer

EVP and President, Ascendis U.S. Jay Wu confirmed that payer conversations are progressing well, with favorable policies in place that are consistent with the label, and gross-to-net arrangements reflect the drug's high clinical value. Chief Business Officer Sherrie Glass stated the vast majority of patients come from conventional therapy, with only 10-15% having prior PTH experience, a subset of whom were on NATPARA. CEO Jan Mikkelsen added that remaining NATPARA patients are expected to transition in Q2 and Q3.

Gavin Clark-Gartner questioned payer negotiations, policy similarity, rebating, and the proportion of NATPARA/PTH naive vs. experienced patients.

Answer

CEO Jan Mikkelsen discussed ex-U.S. reimbursement. EVP Jay Wu noted favorable U.S. policies and commensurate gross-to-net arrangements.

Gavin Clark-Gartner asked for details on the 4,000 to 5,000 PTH-experienced patients in the U.S., specifically if they are actively managed and how long it might take to convert them to YORVIPATH.

Answer

Jan Mikkelsen, President and CEO, clarified this group largely consists of former NATPARA patients who could not access the special use program. He expressed confidence that these patients will actively seek treatment and that the company's infrastructure, including the ASAP hub program, is prepared to support a rapid uptake upon launch.

Gavin Clark-Gartner asked about the timing of new SKYTROFA access policies and their expected impact on prescriptions, and also inquired about trends in IQVIA data capture rates.

Answer

President and CEO Jan Mikkelsen stated the new access policies were implemented gradually through the first half of 2024, with the full effect on volume growth expected in the second half. Regarding IQVIA data, Mikkelsen expressed skepticism, noting that its sampling methodology can be unreliable during shifts in market access and PBM coverage, making it not 'useful' for tracking real-time performance.

Gavin Clark-Gartner of Evercore ISI asked about LIVMARLI's therapy persistence rates and whether they have changed, and also inquired about any blinded data from the VISTA PSC trial that could increase confidence.

Answer

COO & President Peter Radovich reported that for Alagille syndrome, LIVMARLI persistence is approximately 70-75% after one year, with lower attrition thereafter, noting it was too early for PFIC data. Chief Medical Officer Joanne Quan added that the VISTA study's conservative powering and consistent baseline characteristics provide confidence in the trial's progression.

Gavin Clark-Gartner asked about the updated volixibat data in PBC from the EASL abstract, specifically the deepening pruritus benefit and discontinuation rates. He also inquired about the intellectual property and commercial adoption outlook for the new LIVMARLI tablet formulation.

Answer

CEO Christopher Peetz confirmed the pruritus response deepened over time and highlighted the low discontinuation rate as a testament to the drug's benefit. He also noted a newly allowed patent for the tablet formulation extending to 2043. President and Chief Operating Officer Peter Radovich added that the tablet is expected to be an attractive option for patients over 25 kilos.

Gavin Clark-Gartner inquired about Mirum's broader strategy regarding business development and capital allocation, especially given the company's strong stock performance relative to its convertible notes.

Answer

CEO Chris Peetz emphasized Mirum's unique position to acquire rare disease assets, leveraging its financial strength. CFO Eric Bjerkholt added that the convertible notes mature in four years and do not meaningfully impact current plans, affirming the company has significant flexibility for attractive business development opportunities.

Gavin Clark-Gartner asked about the newly acquired Fragile X syndrome program, MRM-3379, inquiring about the current registrational endpoints, the potential for an accelerated approval pathway, and whether Mirum plans to engage with regulators before initiating the Phase II study.

Answer

Chief Medical Officer Joanne M. Quan explained that Mirum believes the NIH toolbox can serve as a registrational endpoint and plans to engage with the FDA early next year. She highlighted the molecule's selectivity and high brain penetration as key differentiators. CEO Christopher Peetz added that the reliance on patient-conducted tests aligns with Mirum's expertise in patient-reported outcomes.

Gavin Clark-Gartner from Evercore ISI requested more quantitative commentary on the expected Q3 revenue slowdown and inquired about the current mix of RDEB versus DDEB patients.

Answer

Chairman & CEO Krish Krishnan declined to quantify the Q3 slowdown but noted summer pauses are typical. VP of Corporate Development Stéphane Paquette stated the RDEB/DDEB mix was stable at roughly 64/36, similar to the previous quarter.

Gavin Clark-Gartner asked how VYJUVEK compliance is tracking on a quarterly basis, as opposed to the 'since launch' metric, and sought clarification on whether patients who pause therapy are excluded from the compliance calculation.

Answer

Krish Krishnan, Chairman and CEO, acknowledged a quarterly metric would differ but expressed caution in providing one due to the unpredictable nature of patient pausing. Jennifer McDonough, SVP of Patient Access, clarified the calculation methodology, stating that patients are not removed from the denominator; if they pause and restart, their compliance rate is adjusted downward to reflect missed doses over their entire therapy period.

Gavin Clark-Gartner questioned the mix of new patients, noting a potential Q4 increase in dominant DEB patients and its impact on compliance assumptions. He also asked about capital allocation strategy, specifically regarding share buybacks given the strong cash position.

Answer

Chairman and CEO Krish Krishnan confirmed the Q4 increase in dominant patients but stated the mix varies quarterly and is not expected to materially alter compliance. Regarding capital allocation, he acknowledged the company's financial flexibility and confirmed that a share buyback program is a valid point of discussion that management is seriously considering.

Gavin Clark-Gartner requested details on the upcoming AATD data, including the number of patients, cohort details, use of augmentation therapy, and timing of lavages. He also asked whether lavages or bronchoscopies would be more informative and what constitutes a successful outcome.

Answer

President of R&D Suma Krishnan explained that the year-end update will focus on Cohort 2, with data from a couple of ZZ phenotype patients (some on augmentation therapy). The goal is to see good expression levels of at least one micromolar of A1AT in the ELF and confirm its functionality. Chairman and CEO Krish Krishnan added that as a redosable therapy, even getting close to the target could be sufficient to advance the program into a redosing study.

Gavin Clark-Gartner from Evercore ISI asked if AstraZeneca's recent forecast that 40% of MG patients will be on self-administered therapies by 2030 aligns with argenx's own market research and early experience with the prefilled syringe (PFS).

Answer

CEO Tim Van Hauwermeiren declined to comment on a competitor's specific forecast but agreed that self-administration is a critical factor for patients. He referenced argenx's own increased total addressable market expectations for MG, which were driven by the potential of self-administration to unlock a significant number of new patients, validating the importance of this trend.

Gavin Clark-Gartner asked about the company's assumptions for the number of payer contracts for the pre-filled syringe that will include value-based agreements (VBAs), particularly for CIDP, and if this could offset gross-to-net pressure.

Answer

Chief Operating Officer Karen Massey emphasized that the core strategy is to provide broad access and allow patient choice based on lifestyle fit, not price. She expressed confidence in the market access team's ability to secure agreements quickly. Chief Financial Officer Karl Gubitz added that, generally, VBAs are less important in the pharmacy channel compared to the medical channel.

Gavin Clark-Gartner sought to clarify that with value-based agreements (VBAs) phasing out for the prefilled syringe, if the associated cap on use in CIDP contracts would also be removed.

Answer

Chief Financial Officer Karl Gubitz confirmed this understanding. He explained that for a pharmacy benefit product, they expect to provide incremental rebates instead of VBAs, and therefore, the caps associated with the VBAs would not be part of the new payer contracts.

Gavin Clark-Gartner asked about the rates of ANA or dsDNA titer elevations in the empasiprubart MMN study, following up on comments about the absence of drug-induced lupus cases.

Answer

CEO Tim Van Hauwermeiren stated that no increase in such titers has been observed in the empasiprubart studies. He noted this aligns with the theoretical safety advantages of an anti-C2 antibody and reiterated the clean safety and tolerability profile seen in Phase I data.

Gavin Clark-Gartner of Evercore ISI questioned if there was an increase in COMP006 trial enrollment following the positive COMP005 data and asked for an estimate of SPRAVATO use in single versus group room settings.

Answer

CEO Kabir Nath confirmed the positive COMP005 data was well-received by investigators, leading to strong recruitment for the COMP006 trial. Chief Patient Officer Steve Levine added that SPRAVATO is delivered primarily in individual rooms, which aligns well with the existing infrastructure needed for COMP360.

Gavin Clark-Gartner asked if the Phase IIb MADRS delta of approximately 5 points is a reasonable expectation for the COMP005 top-line results and what the company aims to learn from an upcoming advisory committee meeting regarding its PTSD program.

Answer

CEO Kabir Nath confirmed that the Phase IIb data serves as the benchmark for powering the Phase III studies, making the 5-point delta a reasonable guide. Regarding the advisory committee meeting, he stated Compass will focus on how the committee views the PTSD patient population and interprets changes in the CAPS-5 score, which will inform their own study design.

An analyst from Evercore ISI, on behalf of Gavin Clark-Gartner, asked for details on the safety reporting for the COMP 005 trial, specifically how the independent Data Safety Monitoring Board (DSMB) defines a suicidal ideation 'imbalance' and what the update will entail.

Answer

Kabir Nath (Executive) and an unnamed executive (Michael) explained that the DSMB is independent and has significant latitude in its assessment. They clarified that an 'imbalance' is not based on a rigid quantitative threshold but is a clinical interpretation considering the severity and nature of the cases. Therefore, they could not provide a specific number that would trigger such a finding.

Gavin Clark-Gartner from Evercore ISI asked a direct question about whether to expect updated data for the 989 program in essential thrombocythemia (ET) alongside the myelofibrosis (MF) data later in the year.

Answer

President and Head of R&D Pablo Cagnoni provided a clear confirmation, stating 'Yes, Gavin. There will be an update on ET data as well later this year.' He added that the company is moving quickly in ET with the goal of starting pivotal trials in early 2026.

Gavin Clark-Gartner sought to confirm the data timeline for the Tafasitamab first-line DLBCL trial and asked if the 0.73 hazard ratio from Polivy's trial is a reasonable efficacy benchmark.

Answer

Executive Steven Stein clarified that the event-driven trial is nearing its required events, so the data readout could occur soon but may track into the second half of the year. He agreed that the Polivy result is 'in the ballpark of a reasonable benchmark' given the similar high-risk patient population.

Gavin Clark-Gartner of Evercore ISI asked about the INCB00262 study in chronic spontaneous urticaria (CSU), inquiring about the number of omalizumab-naive versus experienced patients and if there could be subgroups with greater efficacy, like IgE-low patients.

Answer

An unnamed executive declined to provide details on prior therapy beyond confirming all patients were refractory to antihistamines. He also stated he would not speculate on potential efficacy differences in patient subsets at this time, noting that the drug's mechanism is different from an anti-IgE antibody like omalizumab.

Gavin Clark-Gartner questioned the rationale for using a single time point at 32 weeks for the Phase III primary endpoint, rather than an average, and asked about the potential risk of A4 variability leading to incorrect non-responder classifications.

Answer

Dr. R. Struthers, CEO, responded that responder analyses are typically conducted at single time points. He expressed high confidence in the endpoint, noting that A4 is one of the least variable biomarkers in CAH and that requiring both components of the composite endpoint to be met makes the result highly specific and less susceptible to random variability.

Gavin Clark-Gartner requested additional details on Cohort 4 of the TouCAHn study for atumelnant and asked when data from this cohort might be released.

Answer

CEO R. Struthers stated that the company is not yet discussing Cohort 4 details. He indicated that more information on the overall Phase III program design will be shared in the near future, at which point it may be relevant to discuss Cohort 4. He anticipated providing more clarity by the next earnings call.

Yesha, on behalf of Gavin Clark-Gartner, asked about the company's engagement with the FDA, particularly in light of recent leadership changes at the agency.

Answer

CEO Robert Barrow affirmed that engagement with the FDA has remained strong and that the agency continues to be an 'incredible partner.' He stated that the company is not seeing any direct impact from leadership changes and continues to receive timely responses.

Gavin Clark-Gartner from Evercore ISI asked if MindMed plans to provide more granular enrollment updates for its GAD trials and sought confirmation on the design of the sample size re-estimation, including whether it involves alpha spend or futility criteria.

Answer

CEO Robert Barrow stated that enrollment updates will follow industry standards, with a formal announcement likely near completion. He confirmed the sample size re-estimation is a 'no alpha spend blinded re-estimation' with no futility analysis, designed as a protective measure based on nuisance parameters like dropout rate and variance. The analysis is anticipated after about half the patients complete the 12-week mark.

Gavin Clark-Gartner of Evercore ISI inquired about the potential scenarios for the tebipenem HBr Phase III trial's interim analysis, asking about the rationale for continuing the trial if it shows early success, the statistical alpha spend, and the overall criteria for success.

Answer

Esther Rajavelu, an executive at Spero, explained that the company cannot speculate on continuing the trial post-interim analysis until receiving a recommendation from the Independent Data Monitoring Committee (IDMC). She confirmed a small amount of alpha is being spent, which was accounted for in the study's design. Rajavelu outlined three likely outcomes: the trial stops for success based on the 10% non-inferiority margin, it stops for futility, or enrollment continues.

Gavin Clark-Gartner from Evercore ISI asked about the long-term terminal value of ELEVIDYS, questioning the plausibility of consensus estimates which imply 850-900 treated patients annually and seeking clarity on U.S. incidence.

Answer

CEO Douglas Ingram clarified that the annual U.S. incident population is in the low 400s. He noted that the company's terminal value will be driven by more than just incident ELEVIDYS patients, pointing to the enduring PMO franchise, the potential for redosing by the 2030s, and multiple upcoming blockbuster launches from the LGMD and Arrowhead (FSHD, DM1) pipelines.

Gavin Clark-Gartner from Evercore ISI asked for an update on the ESSENCE confirmatory trial for golodirsen and casimersen, questioning if the 2026 data readout timeline is still accurate and what the regulatory standard would be to remove the drugs from the market.

Answer

President and CEO Doug Ingram confirmed the data readout for the ESSENCE trial is expected in 2026. He clarified that any regulatory decision on the drugs' status would be based on the 'totality of evidence,' which includes study results, data trends, and real-world evidence, not on a single trial outcome.

Gavin Clark-Gartner questioned why peak sales for ELEVIDYS would not occur sooner, such as in 2026, given that most rare disease launches, including Sarepta's own PMOs, see their steepest ramp in the first one to two years.

Answer

CEO Douglas Ingram responded that based on their detailed modeling of capacity and process, peak sales will not be in 2026. He stressed the importance of a responsible, thoughtful rollout for a one-time therapy to ensure patient safety. CCO Dallan Murray added that their high confidence in the forecast comes from granular, patient-level visibility at each site, which allows them to map out the launch trajectory in great detail.

Asked about the status of discussions with global regulators for Bexicaserin's broad DEE path and inquired about LP659's half-life and its cardiac impact (heart rate, QTC) at the most effective dose.

Answer

Discussions with global regulators for Bexicaserin are underway and are expected to be positive, influenced by the FDA's Breakthrough Therapy designation. For LP659, no clinically significant cardiac effects, including QTC prolongation, were observed. The half-life will be properly assessed after the multiple ascending dose (MAD) study.

Gavin Clark-Gartner of Evercore ISI questioned whether the FDA would require dose-ranging work in TED patients for the VRDN-003 pivotal program. He also asked if the company could share details on how the baseline characteristics of the THRIVE trial compare to those of TEPEZZA's Phase III studies.

Answer

President and CEO Stephen Mahoney stated that while he could not provide specific details on the VRDN-003 trial design pending FDA minutes, the company feels positive about the meeting and is confident in its plan to start a pivotal program mid-year. Regarding THRIVE's baseline characteristics, he explained it was too early to comment as enrollment had just recently completed.

Gavin Clark-Gartner inquired about how Aclaris expects physicians to perceive the safety profile of ATI-2138 relative to other JAK inhibitors, citing potential learnings from the alopecia and rheumatoid arthritis markets.

Answer

Interim CEO Neal Walker stated that based on his experience and market data, black box warnings have not been a significant hindrance to the adoption of effective JAK inhibitors like baricitinib and RINVOQ. He argued that physicians and patients prioritize rapid and substantial disease relief, and the superior efficacy of JAK inhibitors over biologics is a compelling factor that often outweighs the safety discussions.

Gavin Clark-Gartner inquired about how Aclaris expects healthcare providers to view the safety profile of ATI-2138 relative to other JAK inhibitors, and if there are any learnings from the alopecia or rheumatoid arthritis markets.

Answer

Interim CEO Neal Walker acknowledged that while a black box warning can seem like a hurdle, real-world evidence from drugs like baricitinib and upadacitinib shows it has not been a major hindrance to adoption. He argued that patients and physicians prioritize the rapid and significant efficacy that JAK inhibitors offer over biologics. Walker believes the desire for quick and substantial disease relief is a powerful driver that often outweighs the concerns associated with the safety warning.