James Condulis

James Condulis asked about the commercial opportunity and pricing strategy for volixibat, particularly in the context of the PSC opportunity and how it compares to PPARs in the PBC market.

Answer

CEO Chris Peetz explained that while PPARs in PBC serve as a planning benchmark, the final pricing decision for volixibat will be made closer to launch, emphasizing its unique positioning in PSC with no other approved therapies.

James Condulis asked about Mirum Pharmaceuticals' commercial strategy and pricing considerations for volixibat, particularly in the context of the PBC opportunity and its potential pricing relative to PPARs, as well as the unique pricing considerations for the PSC opportunity given the lack of approved therapies.

Answer

CEO Chris Peetz explained that while PPARs in PBC serve as a planning benchmark, volixibat's unique positioning in PSC, where no approved therapies exist, will influence the final pricing decision closer to launch.

James Condulis inquired about the importance of a positive ACACIA-HCM outcome in de-risking the broader HFpEF opportunity, given the overlapping pathology, and asked for an update on the timing and win criteria for AMBER-HFpEF data.

Answer

Robert Blum, President and CEO, and Stuart Kupfer, SVP and CMO, confirmed that ACACIA-HCM could inform the potential benefit of a CMI in HFpEF, particularly for patients with hypercontractility, due to clinical and structural similarities to nHCM. They stated it is too early to provide specific timing for AMBER-HFpEF results.

James Condulis inquired about the importance of a positive ACACIA-HCM outcome in de-risking the broader HFpEF opportunity, given overlapping pathology, and asked for an estimated timeline and win criteria for initial data from the AMBER-HFpEF trial.

Answer

President and CEO Robert Blum and SVP and Chief Medical Officer Stuart Kupfer highlighted that ACACIA-HCM could further inform the potential benefit of a cardiac myosin inhibitor in HFpEF patients with hypercontractility, given clinical and structural similarities. Stuart Kupfer stated it is too soon to provide specific timelines for AMBER-HFpEF results.

James Condulis from Stifel Nicolaus asked about the upcoming HFpEF data for ulicamten, what constitutes a successful outcome, and the importance of the nHCM trial results for confirming its mechanism.

Answer

Stuart Kupfer, SVP & Chief Medical Officer, outlined that a 'win' for the Phase 2 AMBER HFpEF trial would include symptomatic improvement (KCCQ, NYHA), better biomarkers, and improved diastolic function. He and Fady Malik, EVP of R&D, confirmed that positive data from nHCM studies inform the potential benefit in HFpEF due to the shared pathophysiology.

James Condulis of Stifel asked if the FDA's request for a REMS came after the mid-cycle review and requested more color on that meeting.

Answer

Robert I. Blum, President and CEO, confirmed the timing was around the mid-cycle review, as indicated in a prior 8-K filing. He stated that the company has provided all the detail it can on the matter and will maintain consistency with its previous disclosures.

James Condulis of Stifel asked about the potential for the REMS program for mavacamten (Camzyos) to be eased and how that might impact the competitive differentiation for aficamten's own potential REMS.

Answer

President & CEO Robert I. Blum acknowledged BMS's application to ease the Camzyos REMS and stated that market research indicates several meaningful points of differentiation for aficamten beyond echo frequency. EVP & CCO Andrew Callos added that if the entire CMI category sees relaxed monitoring, it would be a positive for market growth, as it could encourage more physicians to treat patients. Blum reiterated the goal is to expand CMI use and expressed confidence in aficamten's differentiated profile.

James Condulis asked for any additional safety follow-up beyond the December data cutoff and expressed curiosity about Fulcrum's comfort level with the current data set for the FDA to approve expanding the study population.

Answer

Iain Fraser, SVP of Early Development, stated that no untoward safety events have been reported since the December 23rd data cutoff, reinforcing the generally well-tolerated profile of pociredir at 20mg. He emphasized the significant unmet need in sickle cell disease, especially with recent therapeutic setbacks, which supports proposing a registration-enabling study to the agency. Dr. Martin Steinberg, Professor of Medicine, Pediatrics, Pathology, and Laboratory Medicine, further underscored the 'huge' unmet need, highlighting hydroxyurea's limitations and the unimpressive effects of other downstream agents, stressing the importance of better HbF-inducing oral agents.

James Condulis from Stifel asked for any additional safety follow-up beyond the late December data cutoff and about Fulcrum's comfort level with the current data set for FDA approval to expand the study population over time.

Answer

Iain Fraser (SVP of Early Development) confirmed no new untoward safety events since the December 23rd cutoff, reiterating the generally well-tolerated profile of pociredir. He emphasized the significant unmet medical need in sickle cell disease, especially with recent therapeutic setbacks, which supports proposing a registration-enabling study. Dr. Martin Steinberg (Professor of Medicine, Boston University) underscored the 'huge' unmet need, highlighting hydroxyurea's limitations and the unimpressive effects of other downstream agents, stressing the importance of better HbF-inducing oral agents like pociredir.

James Condulis of Stifel Nicolaus asked whether the initial patient start forms were driven by routine physician visits or by proactive patients seeking treatment off-cycle. He also inquired about the primary rate-limiting factor for the launch going forward.

Answer

Chief Commercial Officer Meredith Manning explained that they are seeing both proactive patients and those coming in during normal cycles. She noted a positive trend of clinics establishing dedicated PWS clinic days, which should help create a steadier patient flow. She did not identify a specific rate-limiter, stating there is significant opportunity ahead.

James Condulis of Stifel Nicolaus asked if the initial patient starts were driven by normal physician visit cadences or by proactive, off-cycle patient requests, and also inquired about the primary rate-limiting factor for uptake going forward.

Answer

CCO Meredith Manning responded that they are seeing both proactive patients scheduling early and patients coming in during normal cycles. She noted that many clinics are now establishing dedicated PWS clinic days, which should help create a steadier patient flow and manage the high demand, which appears to be the main logistical factor.

James Condulis asked about the typical conversion rate from patient start forms to paid prescriptions in rare disease launches and whether the pace of new start forms is expected to accelerate.

Answer

CCO Meredith Manning responded that it is too early to provide a specific conversion percentage but that the company expects results comparable to other strong rare disease launches. Executive James MacKaness added that the significant unmet need in PWS should support a conversion rate that is at least comparable to peers.

James Condulis asked about the typical conversion rate from patient start forms to paid prescriptions in rare disease launches and whether the pace of new start forms is expected to accelerate.

Answer

CCO Meredith Manning responded that while it is too early to provide a specific percentage, they expect the conversion rate to be comparable to other strong rare disease launches. CFO James MacKaness added that the significant unmet need for a PWS treatment should support a conversion rate that is at least on par with industry benchmarks.