Maxwell Skor

Maxwell Skor inquired about key learnings from recent clinical data, specifically the Lancet GRACE data and the FDA's relacorilant CRL, that informed the clinically meaningful endpoints and overall study structure for the EQUILIBRIUM ADCS phase II/III design.

Answer

Dr. Alan Krasner, Chief Endocrinologist, explained that the basic structure for Cushing's disease studies is well-precedented, with normalization of urine-free cortisol as the primary endpoint. He differentiated Atumelnant's mechanism from glucocorticoid receptor antagonists like relacorilant, which complicate cortisol measurement, noting Crinetics can measure both cortisol and clinical outcome benefits.

Maxwell Skor asked about key learnings from recent clinical data (Lancet, GRACE, relacorilant CRL) that informed the Phase 2/3 study design for ADCS, specifically regarding clinically meaningful endpoints and overall study structure.

Answer

Chief Endocrinologist Alan Krasner explained that the basic structure of Cushing's disease studies is well-precedented, with normalization of urine-free cortisol as the primary endpoint. He differentiated atumelnant's mechanism, which allows direct cortisol measurement, from glucocorticoid receptor antagonists that require downstream surrogates. CEO Scott Struthers deferred the question to Dr. Krasner.

An analyst on behalf of Maxwell Skor from Morgan Stanley asked about expectations for placebo response in the global Phase III study for CAH and any potential impacts from different geographies.

Answer

Chief Medical & Development Officer Dana Pizzuti explained that due to the ambitious endpoint, which requires addressing both A4 levels and reducing glucocorticoids to physiologic levels, the company does not expect a high placebo response rate. She stated it would be very difficult for a placebo patient to achieve this endpoint, regardless of their position on the CAH spectrum.

Maxwell Skor asked for commentary on the evolving regulatory environment and any potential implications for the rare disease space, acknowledging Crinetics' interactions are not with CDER for paltusotine.

Answer

Dr. R. Struthers, CEO, stated that their interactions with the FDA (CDER) have not shown any significant changes and that business is proceeding as normal across all their programs, most of which are for rare diseases. He sees no differences at this point.

Maxwell Skor asked about the potential incremental uplift to the obstructive HCM launch trajectory in 2026, assuming a positive ACACIA readout, and inquired about the expected timing of the ACACIA readout within Q2.

Answer

Robert Blum, President and CEO, declined to specify the timing within Q2 for the ACACIA readout. Andrew Callos, EVP and CCO, indicated that market research suggests a 15-20% 'halo effect' uplift on obstructive HCM use if non-obstructive HCM is approved, though this depends on the data and compliant promotional activities.

Maxwell Skor asked about any incremental uplift to the obstructive HCM launch trajectory in 2026 that could result from a positive ACACIA readout, and inquired about the expected timing of the ACACIA readout within the second quarter.

Answer

President and CEO Robert Blum declined to specify the exact timing within Q2 for the ACACIA readout. EVP and Chief Commercial Officer Andrew Callos estimated a potential 'halo effect' of 15%-20% uplift on obstructive HCM sales from a positive ACACIA readout and subsequent approval, while emphasizing compliance with promotional guidelines.

Maxwell Skor of Morgan Stanley asked if the recently submitted REMS for aficamten differs from what might have been submitted initially, considering the recent Camzyos REMS update.

Answer

Robert I. Blum, President and CEO, described the situation as fluid and avoided speculating on a hypothetical earlier submission. He confirmed that Cytokinetics has been closely monitoring all developments, including the Camzyos REMS modification, and has submitted a REMS they believe will secure a distinct and differentiated profile for aficamten.

Maxwell Skor asked how pulmonologists are expected to navigate payer requirements for ruling out COPD or asthma as the primary driver of symptoms, and what changes are needed in clinical practices to recognize bronchiectasis as the main driver in comorbid patients.

Answer

Will Lewis, Chair and CEO, explained that 15-20% of BRINSUPRI trial patients had comorbid conditions. He noted that a definitive bronchiectasis diagnosis requires a CT scan and pulmonologist evaluation. With BRINSUPRI now available, physicians are encouraged to consider CT scans for exacerbating COPD/asthma patients, review existing scans for evidence of bronchiectasis, or order new ones, as this would make them 'on label' for the drug.

Maxwell Skor asked for a characterization of Brensupri's performance to date relative to the provided launch analogs and expectations for the next two and four quarters.

Answer

Will Lewis, Chairman and CEO, clarified that the company has not provided formal guidance but has used benchmarks of strong respiratory launches (high double-digit millions in first two full quarters combined) as ambitions. He cautioned against over-interpreting the first six weeks of data due to inventory build, initial trials, and early adopter effects, stating that Q4 data will provide clearer insights into the launch trajectory.

Maxwell Skor asked how BRINSUPRI's performance to date compares to launch analogs and about expectations for the next two full quarters and the following four quarters.

Answer

Will Lewis, Chairman and CEO of Insmed, clarified that no formal guidance has been provided, only benchmarks from strong respiratory launches (high double-digit millions in the first two full quarters combined). He reiterated caution due to the very early data (six weeks), inventory build, and initial trials, emphasizing that Q4 will provide clearer insights into the launch trajectory.

Maxwell Skor asked for early insights from the first DMD patient dosed in the ASCEND trial and how Insmed's intrathecal delivery approach is differentiated from other gene therapies.

Answer

CEO William Lewis reported 'so far so good' but emphasized a highly cautious 'belt and suspenders' approach. He explained the key differentiation is that intrathecal delivery avoids the first-pass liver effect, allowing for a lower viral dose while achieving remarkable tissue transduction, which could improve safety and efficacy. CMO Martina Flammer added that another important distinction is that the study does not use weight-based dosing.

Maxwell Skor asked about the TPIP readout in PAH, questioning the rationale for measuring PVR versus baseline and what the primary endpoint would be for a potential Phase III trial.

Answer

CMO Martina Flammer explained that PVR is measured at baseline and end-of-study to assess the reduction over the treatment period. She stated that the recognized registrational endpoint for a Phase III trial in PAH is the 6-minute walk distance, which they anticipate using as the primary endpoint.

Maxwell Skor asked for the rationale for measuring PVR versus baseline in the TPIP trial, expectations for placebo rates, and what the primary endpoint for a potential Phase III trial might be.

Answer

CMO Martina Flammer explained that PVR is measured at baseline and end-of-study to assess reduction over the treatment period. She stated that the recognized registrational endpoint for Phase III is 6-minute walk distance, which is what they anticipate using as the primary endpoint, though clinical worsening would also be considered.

Maxwell Skor asked for a description of the site training for uniform conduct of Bayley-IV in the ASPIRE study for Angelman syndrome, and any practical considerations or added complexity when administering the assessment to older versus younger pediatric patients.

Answer

Emil Kakkis, Chief Executive Officer and President, detailed that Ultragenyx has a dedicated Endpoint Development Strategy group that developed comprehensive training for all sites. Additionally, for Bayley cognition, a centralized company provides expert testers knowledgeable about Angelman to ensure quality and consistency across as many sites as possible. He emphasized the importance of this area and the extensive work done by Dr. Schreiner and her team.

Maxwell Skor asked for a description of the site training for uniform conduct of Bayley-IV in the ASPIRE study and any practical considerations or added complexity when administering the assessment in older pediatric patients versus younger ones.

Answer

CEO Emil Kakkis emphasized Ultragenyx's extensive efforts in endpoint design, evaluation, and training, led by their dedicated Endpoint Development Strategy (EDS) group. He detailed that a comprehensive training program was developed for all sites. Additionally, for Bayley cognition, a centralized company with experts knowledgeable about Angelman and Bayley administration is providing testers at as many sites as possible to ensure quality and consistency, especially given the complexities of assessing older versus younger pediatric patients.

Maxwell Skor asked about physician perspectives on initiating Setrusumab for osteogenesis imperfecta, specifically whether they would prioritize younger patients or those with more advanced disease, based on KOL interactions.

Answer

Howard Horn, Chief Financial Officer, indicated that initial adoption would likely prioritize patients with the most severe disease (Type IIIs and IVs), often younger, but noted that adult patients with Type I OI also experience significant bone dysfunction. He anticipated use across the spectrum, with younger, more severe patients gaining immediate access, drawing parallels to Crysvita's growing adult use.

Maxwell Skor asked about physician perspectives on initiating setrusumab for osteogenesis imperfecta, specifically whether they would prioritize younger patients or those with more advanced disease, and sought feedback from the KOL community.

Answer

Howard Horn, Chief Financial Officer, indicated that initial adoption would likely be highest among patients with the most severe disease (Type 3s and 4s), often affecting younger individuals. He also noted that a significant fraction of Type 1 patients with substantial fractures or activity limitations would seek treatment, drawing a parallel to the growing adult use of Crysvita in XLH.

Maxwell Skor of Morgan Stanley inquired about how proceeds from Priority Review Vouchers (PRVs) are being factored into the company's path to GAAP profitability by 2027 and the level of confidence in receiving all three anticipated PRVs.

Answer

Howard Horn, CFO, confirmed that PRVs from three programs are factored into their financial planning. Emil Kakkis, CEO, added that even if the PRV program is not reauthorized (affecting the OI voucher), the other two would proceed, and their likely higher value would result in a similar overall cash impact, maintaining their financial trajectory.

Maxwell Skor requested additional information on the once-monthly TransCon Semaglutide program, including any gating factors and expectations for future updates.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, explained the design of 'packed-in semaglutide,' which aims for slow liberation and a long Tmax, resulting in a less steep concentration curve compared to 'naked' GLP-1 molecules. This design is intended to achieve maximal weight loss as quickly as possible with an optimized tolerability profile.

Maxwell Skor requested an update on the once-monthly TransCon semaglutide program, including any gating factors and expected timelines for further updates.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, described the program's design philosophy: to achieve fast weight loss with high tolerability by using 'packed-in semaglutide.' This approach ensures slow liberation, a very long Tmax, and a less steep concentration slope, thereby mitigating tolerability issues often seen with 'naked' GLP-1 molecules, while still providing a large AUC over the month.

Maxwell Skor of Morgan Stanley asked if a single pivotal trial for the TransCon CNP and growth hormone combination could be sufficient for approval, given the impressive growth velocity seen in the COACH trial.

Answer

President & CEO Jan Møller Mikkelsen did not directly confirm if one trial would suffice but highlighted the unprecedented growth velocity observed. He discussed a potential treatment paradigm where patients could receive the combination therapy for 1-2 year 'boosts' and then maintain on CNP monotherapy, suggesting a focus on defining the optimal clinical use rather than just the regulatory path.

Maxwell Skor of Morgan Stanley asked for an update on Amicus's confidence in its Galafold intellectual property position and the potential for a settlement with Aurobindo, particularly after reviewing Aurobindo's brief for summary judgment.

Answer

President and CEO Bradley Campbell reiterated the company's high confidence in the strength and longevity of its Galafold IP. He stated that the recent settlement with Teva reinforces their case against remaining litigants and noted that statistically, such cases often lead to settlement, especially after one party has already settled. He refrained from commenting on specific litigation details.

Maxwell Skor of Morgan Stanley inquired about other potential indications for DMX-200's mechanism and asked for insights on potential FDA changes to improve rare disease drug development.

Answer

President and CEO Bradley Campbell expressed hope for regulatory modernization, including greater use of real-world evidence and more flexibility on placebo controls in rare diseases. Chief Development Officer Dr. Jeff Castelli identified other rare kidney diseases with unaddressed inflammatory components, like proliferative lupus nephritis, as potential future indications for DMX-200. Campbell concluded that achieving profitability will provide the resources to pursue such portfolio expansions.

Maxwell Skor of Morgan Stanley inquired about the status of the treatment Emergency Use Authorization (EUA) for PEMGARDA, including any feedback from the FDA, and asked what factors would restore the company's confidence in providing revenue guidance.

Answer

Marc Elia, Chairman of the Board, stated that the treatment EUA application is being updated and they are awaiting feedback from the FDA. Regarding guidance, he explained that confidence is tied to recent performance trends and that the company feels it has moved past the recent period of market confusion. Chief Commercial Officer Timothy Lee added that he is pleased with current growth trends and ongoing commercial initiatives, which support a positive outlook.

Inquired about the timeline and potential market size for a second Emergency Use Authorization (EUA) for treatment, and asked about the accuracy and expansion of the PEMGARDA infusion site locator, particularly regarding large academic centers.

Answer

The company stated that while a year-end timeline for the treatment EUA seems reasonable, the decision is ultimately up to the FDA. The opportunity is seen as potentially large and additive to the prevention rollout. The infusion site locator is being updated in real-time and does not yet fully reflect all available sites. A dedicated team is actively working to onboard major academic centers and private infusion sites to improve access.

Maxwell Skor of H.C. Wainwright & Co. asked for details on Invivyd's marketing strategy for PEMGARDA, including direct-to-consumer plans and target physicians, and inquired about the planned compact clinical trial for the treatment indication.

Answer

Marc Elia, Chairman, explained the compact trial is a confirmatory study for the treatment EUA, focusing on safety, pharmacokinetics, and virology based on existing data. Jeremy Gowler, Interim CEO, stated the initial marketing focus is on healthcare provider (HCP) awareness, with direct-to-consumer (DTC) campaigns being explored for the future, noting strong organic interest from the highly-engaged patient community.

Maxwell Skor inquired about the payer dynamics for Hepatitis C, specifically asking what percentage of chronic HCV patients are on Medicaid and if they are typically prescribed generic Epclusa.

Answer

Chief Commercial Officer John Vavricka explained that government-supported programs like Medicaid and Medicare represent the majority of the payer mix for HCV. He clarified that both branded Epclusa and its authorized copy are utilized, with the choice dictated by individual payer financial models. CEO and Founder Dr. Jean-Pierre Sommadossi added that true generics for current treatments are not anticipated until at least 2036 due to existing intellectual property.