Ellie Merle

Ellie Merle inquired about the expected commercial discontinuation rate for Sephience, how long physicians typically wait to assess patient response, and the threshold for what physicians consider a successful response. She also asked about the cadence of new Sephience starts in the U.S., specifically if it's a steady number or if there was an initial bolus, and how this rate is expected to evolve throughout the year.

Answer

Matthew Klein, CEO, and Eric Pauwels, Chief Business Officer, reported very low, single-digit discontinuation rates for Sephience, primarily due to patient decisions rather than clinical reasons, and high refill rates. Pauwels stated they continue to see nice momentum with new patient starts, anticipating this cadence to continue throughout the year, driven by consistent new patient acquisition and maintaining the existing patient base.

Ellie Merle asked about expectations for the commercial discontinuation rate of Sephience, how long physicians typically wait to assess patient response, and the threshold for what physicians consider a successful response. She also inquired about the cadence of new patient starts for Sephience, asking if there was an initial bolus or if a steady number of new start forms are being observed, and how this rate is expected to evolve in the U.S. throughout the year.

Answer

CEO Dr. Matthew Klein and Chief Business Officer Eric Pauwels stated that Sephience is currently seeing very low single-digit discontinuation rates and high prescription renewal rates, which is encouraging for the early launch. Eric Pauwels noted a consistent momentum with new patient starts, not just an initial bolus, and anticipates this cadence to continue, supported by ongoing patient support and medical education.

Tejas Wein, on behalf of Ellie Merle at UBS, inquired if PTC has received any anecdotal coverage approvals for Sefiance yet. He also asked about the distribution of PKU patients in ex-US countries, specifically whether they are concentrated in major centers or more spread out.

Answer

CBO Eric Pauwels explained that it's too early for coverage approvals, as the company is currently in the multi-day process of insurance verification. Regarding patient distribution, he stated that, similar to the U.S., patients in Europe are highly concentrated in centers of excellence in major cities. He used Germany as an example, where their compassionate use program targeted centers overseeing nearly 8,000 patients, indicating a centralized care model.

Ellie Merle asked about the drivers behind the significant growth in diagnosed MASH patients, expectations for category expansion in 2026, and trends in Rezdiffra patient starts and prescriber types amidst the launch of Wegovy.

Answer

CEO Bill Sibold highlighted strong market growth, nearly 50% since late 2023, driven by increased awareness and competitor efforts, projecting double-digit growth. He noted consistent patient profiles (F2/F3 mix) and continued prescription dominance in the hepatology/gastroenterology space, with Rezdiffra establishing itself as the standard of care.

Ellie Merle asked about the drivers behind the significant growth in diagnosed MASH patients, expectations for category growth in 2026, and trends in Rezdiffra patient starts and prescriber types, especially with Wegovy's launch.

Answer

Bill Sibold, Chief Executive Officer, explained that increased awareness and competitor efforts are driving diagnosis growth, leading to a larger addressable market. He noted consistent patient adds, an even mix of F2/F3 patients, and strong prescription growth primarily from hepatology and gastroenterology specialists, with no negative impact from Wegovy.

Ellie Merle of UBS Group AG questioned the outlook for 2026, asking about expectations for sequential quarterly growth once semaglutide is available, how gross-to-net might trend next year, and the potential timing for issuing revenue guidance.

Answer

CFO Mardi Dier responded that the company has no near-term plans to issue revenue guidance. She focused on the remainder of 2025, stating they expect to steadily add patients and that growth will track with other successful specialty launches. Regarding gross-to-net, she confirmed predictability for 2025 and said the company would address 2026 at a later time.

Ellie Merle asked about the evolving mix between retail and hospital settings for JOURNAVX over the year and how this mix might impact gross-to-net revenue and treatment duration.

Answer

Duncan McKechnie, EVP and Chief Commercial Officer, noted that the JOURNAVX mix concluded 2025 at approximately 50/50 between retail and hospital prescriptions, with an anticipated future shift proportionally more towards the retail space. He explained that the impact on gross-to-net depends on several dynamics, including prescription length (typically shorter in hospitals), patient type (commercial, Medicare, Medicaid), and utilization of patient support programs.

Ellie Merle asked about the evolving mix between retail and hospital settings for JOURNAVX prescriptions over the year and how this mix might influence gross-to-net revenue and treatment duration.

Answer

Duncan McKechnie (Chief Commercial Officer, Vertex Pharmaceuticals) reported that JOURNAVX ended 2025 with a 50/50 split between retail and hospital prescriptions, anticipating a future shift proportionally towards the retail space. He explained that the impact on gross-to-net and treatment duration depends on various factors, including prescription length (shorter in hospitals), patient type (commercial, Medicare, Medicaid), and participation in patient support programs.

Ellie Merle from UBS Group AG asked about the progress of real-world evidence generation for Gernavix and its expected impact on formulary placement, as well as the future of patient support programs and their effect on gross-to-net.

Answer

President and CEO Dr. Reshma Kewalramani highlighted ongoing Phase 4 studies showing positive data on pain control and opioid reduction. EVP and CCO Duncan McKechnie added that the patient support program is a temporary bridge that will be retired as national payer coverage is achieved, which is expected by year-end.

Ellie Merle asked for insights into the most exciting or de-risked programs within Alnylam's emerging early-stage pipeline, and also inquired about the expected net price decrease for 2027, following the mid-single-digit decrease projected for 2026, especially considering potential new competitors.

Answer

Chief Research and Development Officer Pushkal Garg highlighted nucresiran and zilebesiran as highly de-risked programs, citing TTR silencing efficacy and compelling blood pressure lowering, respectively. He also pointed to upcoming de-risking data in 2026-2027 for Huntington's, CAA, obesity/diabetes, and plasminogen programs. Chief Financial Officer Jeff Poulton stated that a gradual mid-single-digit net price decrease is expected for 2026 and across the longer-term 25% CAGR guidance. Chief Commercial Officer Tolga Tanguler added that Alnylam is well-positioned for access and durability, with 2030 goals incorporating competitive dynamics.

Ellie Merle asked for insights into which emerging early-stage pipeline programs Alnylam is most excited about or considers most de-risked. She also inquired about expectations for U.S. net price decreases in 2027, specifically if they would be similar to 2026 or potentially more or less with a new competitor.

Answer

Pushkal Garg, Chief Research and Development Officer, highlighted nucresiran and zilebesiran as highly de-risked programs, citing proven TTR silencing and compelling blood pressure lowering, respectively. He also pointed to upcoming de-risking data in 2026-2027 for programs like Huntington's, CAA, obesity/diabetes, and plasminogen. Jeff Poulton, CFO, stated that gradual net price reductions are expected over time, with a mid-single-digit decrease in 2025 and 2026, and the longer-term 25% CAGR guidance incorporates this expectation. Tolga Tanguler, Chief Commercial Officer, added that Alnylam is well-positioned for potential new competition.

Ellie Merle from UBS Group AG asked about the expected quarterly rate of new patient starts for Amvuttra going forward and how the mix between newly diagnosed and progressor patients is anticipated to evolve.

Answer

CCO Tolga Tanguler stated that while they expect both patient segments to continue growing from the strong 1,400-patient start in Q2, the company will not report specific patient numbers quarterly. He cited the difficulty of precisely tracking the cardiomyopathy indication with Amvuttra's single SKU.

Ellie Merle asked about Ascendis Pharma's strategy for commercializing TransCon CNP ex-U.S., considering that the majority of VOXZOGO sales are ex-U.S., and the degree of investment required for global launches. She also inquired about the cadence of uptake for TransCon CNP in the U.S. and which segments (treatment-naive vs. switches) are expected to drive the most uptake.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, explained that the global commercial infrastructure established for Europats, which covers over 30 countries and aims for 60-70 in 2-3 years, will be leveraged for TransCon CNP. He noted that partnerships in Japan (Teijin) and China cover all three products, eliminating the need for new infrastructure. He did not provide specific details on U.S. segment uptake but reiterated the product's strong benefits.

Ellie Merle inquired about Ascendis Pharma's strategy for commercializing TransCon CNP ex-U.S., considering that the majority of VOXZOGO sales are ex-U.S., and the anticipated investment required. She also asked about the expected cadence of uptake for TransCon CNP in the U.S., differentiating between treatment-naive patients and switches.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, explained that Ascendis Pharma's global commercial infrastructure was established through the YORVIPATH launch, enabling them to leverage this existing setup for TransCon CNP. He expects to reach 60-70 countries within 2-3 years, noting that existing collaborations (e.g., Teijin in Japan, VISEN in China) cover all three products, streamlining the process without needing new agreements. The question regarding treatment-naive vs. switches was not explicitly addressed.

Ellie Merle of UBS Group AG inquired about the expected indication statement for TransCon CNP (e.g., treatment of achondroplasia vs. increasing growth) and the company's view on the intellectual property landscape for weekly CNP therapies.

Answer

President & CEO Jan Møller Mikkelsen responded that it was too early to discuss specific label language but highlighted that their placebo-controlled data demonstrates benefits beyond linear growth, such as improved leg bowing and muscle function, which he sees as a key differentiator. Regarding IP, he expressed strong confidence in their position, noting extensive filings on optimal and sustained-release profiles dating back to 2015.

Ellie Merle asked about feedback on the YorbaPaF titration process and early refill rates.

Answer

CEO Jan Mikkelsen highlighted adherence rates and low dropout rates, mirroring clinical trial results.

Ellie Merle of UBS Group asked for details on clinical findings with the first-gen IRAK4, confidence in the target for AD/HS, and learnings from using molecular glues (for CDK2) versus heterobifunctional degraders.

Answer

CEO Nello Mainolfi stated he could not comment on IRAK4 clinical data per Sanofi's guidance but noted asthma and COPD are high-priority indications. He explained that molecular glues and heterobifunctional degraders are complementary technologies. For CDK2, a molecular glue was used to achieve high selectivity against CDK1, which is a challenge for traditional binders.

Ellie Merle inquired about Regenxbio's potential strategy for non-ambulatory DMD patients and what would constitute a clinically meaningful profile for the subretinal wet AMD Phase 3 data, especially regarding secondary endpoints.

Answer

President & CEO Curran Simpson stated that the company is taking a cautious approach to non-ambulatory DMD and will first establish a robust safety database in the ambulatory population before engaging in detailed FDA discussions. CMO Dr. Steve Pakola explained that for wet AMD, a key secondary endpoint is reducing injection burden, with at least a 50% reduction being a clinically meaningful target that would create a compelling value proposition.

Ellie Merle asked about expectations for U.S. COVID vaccine pricing for the upcoming season, how net price might compare to last year, and any key takeaways from contracting discussions.

Answer

CFO Jamey Mock stated that the U.S. product sales guidance of $1 to $1.5 billion already incorporates variability from competitive pressures, including pricing and contracting. He confirmed that contracting is now 'basically complete' but declined to provide specific pricing details, expressing confidence in the current financial framework.

Ellie Merle from UBS inquired about Revolution Medicines' perspective on RAF upregulation as a resistance mechanism to RAS inhibitors and the company's thoughts on RAF degradation versus inhibition, particularly in the G12D cancer space.

Answer

President of R&D Steve Kelsey acknowledged that amplification of the mutant RAS allele is a major escape mechanism, particularly for multi-selective inhibitors, but noted it can be overcome therapeutically, for instance with a RAS-ON doublet. He stated there is currently no evidence that a degrader is superior to an inhibitor for any oncology target, pending clinical data from degrader companies. CEO Mark Goldsmith added that this resistance mechanism validates the effectiveness of diraxonrasib.

Sam, on behalf of Ellie Merle, asked about the potential strategies and timing for a Phase III study in first-line pancreatic cancer, and whether the company would wait for second-line data before proceeding.

Answer

Dr. Mark Goldsmith, Chairman and CEO, stated they will not wait for second-line Phase III results to initiate a first-line study. Dr. Wei Lin, CMO, added that the current second-line data provides sufficient proof-of-concept. The plan for the first-line Phase III trial includes a monotherapy arm and potentially arms combining RMC-6236 with standard-of-care chemotherapy. He expressed confidence that efficacy will translate to the first-line setting as RAS is a fundamental driver across lines of therapy.

An analyst on behalf of Ellie Merle from UBS inquired about the development timeline for VOXZOGO in other growth disorders like ISS and SHOX, and whether the company would wait for success in those indications before studying BMN 333 for the same uses.

Answer

Greg Friberg, Chief R&D Officer, stated that current studies for other short stature indications are on track to enable the start of pivotal trials in 2027. He explained that the development timeline for BMN 333 in achondroplasia will provide the necessary data to make informed decisions about its potential use in other indications later, suggesting the timelines align well for strategic planning.

Ellie Merle of UBS asked about the changes in expectations for the ex-U.S. launch cadence of Pombiliti/Opfolda and how much this, along with the situation in the Netherlands, contributed to the revised guidance.

Answer

President and CEO Bradley Campbell attributed the guidance change to two main factors: a timing delay in patient starts in newly reimbursed countries shifting from Q1 to later in the year, and the unexpected impact of the U.K.'s VPAG rebate. He noted the Netherlands is a significant opportunity with over 150 patients, but uptake is slowed by a single-center treatment bottleneck, with growth expected in the second half of the year.

Speaking on behalf of Ellie Merle, an analyst asked about the estimated market size for vepdegestrant monotherapy, the expected cadence of cost reductions from the restructuring, and potential milestone payments from Pfizer.

Answer

CEO John Houston outlined a significant market opportunity, estimating a pool of up to 25,000 new patients annually in the second-line plus ESR1 mutant setting. CFO Andrew Saik explained that the financial impact of the restructuring would begin to be seen prior to Q4, with the full run-rate savings realized in Q4 2025, and a related charge would be recorded in Q2.

Jasmine, on behalf of Ellie Merle, inquired about CureVac's latest collaboration strategy for its oncology and non-respiratory infectious disease programs, specifically what it intends to partner versus develop independently.

Answer

CEO Alexander Zehnder responded that CureVac is focusing on its core competencies of technology innovation, research, and early-stage clinical development (Phase I and potentially Phase II). He clarified that the strategic goal, particularly for broad indications like oncology, is to partner its programs for late-stage development and commercialization with companies that have the necessary scale and expertise.

Jasmine, on behalf of Ellie Merle, asked about CureVac's latest strategy on collaborations and partnerships for its oncology and non-respiratory infectious disease programs.

Answer

CEO Alexander Zehnder explained that CureVac's strategy is to focus on its core strengths of innovation and early-stage development. While capable of running Phase I and some Phase II trials internally, the ultimate goal for large indications like oncology is to partner with a larger company for late-stage development and commercialization.

Speaking on behalf of Ellie Merle from UBS, an analyst asked about CureVac's and GSK's prioritization of a combined COVID/flu vaccine versus monovalent shots and inquired about the specific proof-of-concept metrics for the upcoming oncology data readout.

Answer

CEO Alexander Zehnder highlighted that a combination vaccine holds significant value and is a focus for GSK, with more guidance to come after Phase II data is analyzed. CDO Myriam Mendila explained the oncology proof-of-concept will be based on safety and immunogenicity, including T-cell activation, to validate the platform's effectiveness in an oncology setting.

Speaking on behalf of Ellie Merle from UBS, an analyst asked about CureVac and GSK's prioritization of a COVID/flu combination vaccine versus monovalent shots and inquired about the specific proof-of-concept metrics CureVac is looking for in its upcoming oncology data readout.

Answer

CEO Alexander Zehnder emphasized that a combination vaccine holds significant value and is a focus for GSK, with more guidance to come after Phase II data is finalized. CDO Myriam Mendila explained that the glioblastoma trial's proof-of-concept will be assessed via immunogenicity endpoints, including T-cell activation, and that the company has defined internal success hurdles but will not disclose them publicly.

Jasmine, on behalf of Ellie Merle, asked if the Phase I/IIa trial for the obesity candidate ARO-INHBE will provide weight loss or body composition data, and what PK/PD results would instill confidence for further development.

Answer

Dr. James Hamilton, Chief of Discovery and Translational Medicine, confirmed that Part 1 of the study will assess body composition using full-body MRI and weight loss. He added that they will also evaluate standard Phase I metrics like safety, pharmacokinetics, and the direct biomarker for gene target knockdown.

Jasmine, on behalf of Ellie Merle from UBS, asked how the recent top-line data from the competitor's ESSENCE trial in MASH affects Altimmune's perspective on what constitutes a competitive profile for incretins in the MASH space.

Answer

CMO Dr. Scott Harris stated the ESSENCE results were modest and expected, requiring a longer 72-week duration. He expressed high confidence that pemvidutide's superior liver fat reduction will enable it to show statistically significant MASH resolution and fibrosis improvement at a much earlier 24-week time point, combined with meaningful weight loss, setting a new standard of care. CEO Dr. Vipin Garg added that this offers a "complete solution" for MASH patients.

Jasmine, on behalf of Ellie Merle at UBS, asked for more color on the STAT3 opportunity in Hodgkin's lymphoma and inquired about the MDM2 strategy for solid tumors, including when an update on patient selection would be provided.

Answer

CMO Jared Golub highlighted the encouraging complete responses for STAT3 in heavily pretreated Hodgkin's lymphoma, consistent with the disease's genetics. For MDM2, he confirmed a biomarker-based patient selection strategy for solid tumors will be presented at a medical meeting later this year, which will detail the preclinical work guiding the approach.