Maury Raycroft

Maury Raycroft of Jefferies inquired about the timing of data disclosure for MDX-2001, the proportion of evaluable patients for efficacy, and whether OPKO Health plans to advance to a sixth dose level or backfill existing cohorts. He also asked about the key drivers behind the increase in NGENLA profit shares and the assumptions for the 2026 guidance.

Answer

Dr. Elias Zerhouni, Vice Chairman and President, stated that for MDX-2001, the company is refining the dose regimen and expects to announce Phase 1A results at an upcoming conference, with Phase 1B results by the end of 2026. Adam Logal, SVP and CFO, explained that NGENLA's Q4 profit share increase was driven by global growth, regions moving up in tiering structure, and Pfizer gaining market share, affirming the 2026 guidance is achievable.

Maury Raycroft asked about the timing of MDX-2001 data disclosure, the proportion of evaluable patients from the 25 dosed, and whether OPKO plans to advance to a 6th dose level or backfill existing cohorts. Additionally, he inquired about the key drivers behind the increase in NGENLA profit shares to $12.5 million and the assumptions underpinning the 2026 guidance of $34 million-$37 million.

Answer

Elias Zerhouni, Vice Chairman and President, OPKO Health, stated that the company is refining the MDX-2001 regimen at the current dose level, not planning a much higher dose. He confirmed 25 patients have been dosed with signs of efficacy, and formal Phase 1a results will be announced at an upcoming conference, with Phase 1b entry and results shared by the end of 2026. Adam Logal, SVP and CFO, OPKO Health, attributed the NGENLA profit share increase to global growth, certain regions moving up in tiering structure, and Pfizer gaining market share, noting the 2026 guidance is achievable at current growth rates.

Maury Raycroft asked about potential differences in baseline patient characteristics, such as BMI or background prophylaxis use, between the primarily ex-U.S. Phase 1/2 HAE data and the global Phase 3 HAELO trial, and how these might impact the reproducibility of results, particularly in the control arm.

Answer

President and CEO John Leonard, with an initial comment from EVP and CFO Edward Dulac, explained that the Phase 3 patient population largely overlaps with the Phase 2 group, designed to represent a standard HAE patient demographic. He noted that U.S. patients in the trial underwent a washout period and baseline attack rate assessment before the placebo double-blind phase, suggesting the Phase 2 data is largely representative of what's expected demographically for the U.S. Phase 3 trial.

Maury Raycroft asked about potential differences in baseline patient characteristics, such as BMI or background prophylaxis use, between the ex-U.S. Phase 1/2 and global Phase 3 HAELO trials for lonvo-z, and how this might impact the reproducibility of results, particularly in the control arm.

Answer

EVP and CFO Edward Dulac confirmed the Phase 1/2 was ex-U.S. and Phase 3 is global. President and CEO John Leonard clarified that Phase 3 patient populations are largely overlapping with Phase 2, not skewed, and represent a standard HAE patient population. He noted U.S. patients in the trial were willing to wash out from existing drugs, indicating high interest, and demographics are expected to be comparable.

Maury Raycroft asked about the extent of in vitro data available for different PKU variants, the practicalities of adding new variants to the Phase I/II study, how dosing for new variants would work, and if the AATD study informs initial PKU dosing.

Answer

CEO John Evans, CMO Amy Simon, and CSO Gopi Shanker responded. John Evans stated that preclinical preparations are far along, with FDA support for appending additional mutations to the same IND. Amy Simon and Gopi Shanker explained that initial dose selection and escalation for PKU would be based on non-clinical data and PKPD modeling, similar to past programs, with modest LNP doses showing effective Phe reduction in preclinical work.

Maury Raycroft inquired about the specifics of in vitro data for different PKU variants, the practicalities of adding new variants to the Phase I/II study, and how dosing would work. He also asked if the AATD study (BEAM-302) would inform initial PKU dosing.

Answer

CEO John Evans, Chief Medical Officer Amy Simon, and Chief Scientific Officer Gopi Shanker stated that preclinical preparations are far along, with supportive FDA interactions for the adaptive approach. They confirmed that additional mutations can be appended to the same IND over time as the research team brings them forward. Initial dose selection and escalation for BEAM-304 will be standard, based on non-clinical data and PKPD modeling, with preclinical data showing efficacy at relatively low LNP doses.

Maury Raycroft asked for expectations regarding Q1 new patient starts and how insurance resets or other variables might influence sales relative to Q4 2025. He also inquired about any discussions with the FDA on the FSGS label and the latest expectations for its appearance.

Answer

Peter Heerma, Chief Commercial Officer, noted strong demand continued into Q1 but cautioned about quarter-over-quarter variability and higher gross-to-net discounts in Q1. Bill Rote, Chief Research Officer, stated that label negotiations are expected closer to the action date, and they anticipate a broad label for FILSPARI in FSGS, applicable across all forms. Chris Cline, Chief Financial Officer, reiterated the expectation for a higher Q1 gross-to-net discount.

Maury Raycroft asked for expectations regarding Q1 new patient starts and how insurance resets or other variables could influence sales relative to Q4 2025. He also asked about discussions with the FDA on the FSGS label and current expectations for its appearance.

Answer

Peter Heerma (Chief Commercial Officer) stated that while Q4 demand was strong, it's too early to call it a new baseline, and variability is expected, but he is confident in sustainable growth. Bill Rote (Chief Research Officer) noted that it's too early for label negotiations but expects broad applicability across all FSGS forms. Chris Cline (Chief Financial Officer) added that Q1 will see the biggest effect of higher gross-to-net discounts compared to Q4.

An analyst on behalf of Maury Raycroft asked about the company's business development strategy for the year, specifically whether the focus would be on in-licensing assets in the rare renal space or prioritizing the FSGS launch.

Answer

CEO Eric Dube confirmed that Travere is actively exploring in-licensing opportunities to diversify its pipeline, leveraging its existing capabilities in the rare renal space. However, he stressed that the number one priority remains the preparation and execution of a successful launch for FILSPARI in FSGS.

Maury Raycroft asked for more details on the Angelman study's patient baseline profile compared to Phase I/II enrolled patients, specific parameters expected to influence control arm cognition performance, and the latest expectations for cognition in both treatment and control arms.

Answer

Emil Kakkis, Chief Executive Officer and President, stated that the baseline data from the Phase II expansion trial (cohorts A and B, ex-U.S.) is reflective of what is being seen in the Phase III program. He expects minimal cognitive change (1 point or less) in the control arm, noting Bayley is a rigorous measure not prone to placebo effect. He also highlighted the use of a central firm for Bayley testing to ensure quality and consistency.

Maury Raycroft inquired about the baseline patient profile in the fully enrolled Angelman study compared to Phase 1/2 patients, and which specific parameters are expected to influence control arm performance on cognition. He also asked for the latest expectations for cognition in both treatment and control arms.

Answer

CEO Emil Kakkis stated that the baseline data from the Phase 2 expansion trial (cohorts A and B, ex-U.S.) is reflective of what is being seen in the Phase 3 program, providing comfort regarding the broader population. He expects minimal cognitive change (1 point or less) in the control arm, citing Bayley as a rigorous measure not prone to placebo effect. Kakkis also mentioned the use of a central firm for testers to ensure quality and consistency of assessments, and highlighted the Multidomain Responder Index for a broader view with more power.

Maury Raycroft inquired about quantitative data from the open-label extension of the Phase II osteogenesis imperfecta study and the range of fracture reduction effect sizes considered successful for the Phase III analysis.

Answer

Emil Kakkis, CEO and President, stated that no new quantitative Phase II data was available, but observations remained consistent with prior reports. He indicated that a 40%-70% fracture reduction in Phase III would be clinically meaningful, emphasizing patient function as a key driver for adoption, similar to Crysvita's experience in XLH. Joshua Higa, VP of Investor Relations, reiterated the drug's transformative potential.

Maury Raycroft followed up on osteogenesis imperfecta, seeking a more quantitative perspective on observations from the Phase 2 open-label extension and asking about the anticipated range of effect sizes for fracture reduction needed for success in the Phase 3 final analysis.

Answer

Emil Kakkis, CEO and President, stated that no new quantitative Phase 2 data had been released, but observations remained consistent with prior reports. He reiterated that a 40% to 70% reduction in fractures would be clinically meaningful, stressing that functional improvements for patients would be equally, if not more, important for product adoption.

Maury Raycroft asked for perspective on the range of effect sizes for Annualized Fracture Rate (AFR) reduction that would be needed for the setrusumab trial to succeed at its second interim analysis.

Answer

CEO Emil Kakkis noted that a 30-40% reduction is generally considered clinically meaningful. However, he explained that trial success is less about a specific effect size at one point in time and more about the statistical power gained as the cumulative fracture curves for the treatment and placebo groups separate over time. A consistent reduction percentage leads to greater statistical significance the longer the trial runs.

Farzin Haque, on behalf of Maury Raycroft, sought clarification on whether the 18-month data would be required for the filing package if the second interim analysis is successful.

Answer

CEO Emil Kakkis clarified that if the second interim analysis is positive, the filing package would include all available data, with patients having at least 12 months of exposure. He confirmed they would not delay the filing to wait for 18-month data and that this approach has been discussed with the FDA.

Maury Raycroft asked for more details on the 'select external innovation' component of the five-year strategy, which is part of the approximate 30% revenue R&D spend, inquiring if additional partnerships or licensing deals are anticipated, and about their potential timing, size, and scope.

Answer

Yvonne Greenstreet, CEO, emphasized the company's focus on its rich internal pipeline but noted that a strengthening financial position allows for openness to select external innovation. She stated that any external opportunities would need to complement the existing portfolio and R&D pipeline, meeting a very high scientific and financial bar.

Maury Raycroft at Jefferies asked for clarification on AMVUTTRA's inventory demand for Q3 2025 and projections for Q4, details on gross-to-net deductions, and expectations for Q4 revenues in Europe, including the anticipated ramp-up trajectory.

Answer

Jeff Poulton, CFO, explained that Q3 inventory dynamics were similar to Q2, with days on hand constant but channel inventory growing due to ramping demand, which was offset by increased gross-to-net deductions, primarily from ONPATTRO. He noted the TTR franchise's gross-to-net for the year reflects a mid-single-digit net price decline. Tolga Tanguler, Chief Commercial Officer, stated that ex-U.S. market contribution would remain modest in Q4, primarily from Germany (early stages of pricing discussions) and Japan (pleasing momentum). He emphasized that ex-U.S. markets would be a mid-to-late 2026 story, highlighting strong year-over-year growth in the ex-U.S. PN business despite new competition.

Maury Raycroft asked for commentary on inventory demand for Q3 and expectations for Q4, along with gross-to-net trends. He also sought insights into Q4 revenues in the EU and the anticipated ramp-up in that region.

Answer

Jeff Poulton, Chief Financial Officer, explained that Q3 saw inventory growth in the channel due to ramping demand, which was offset by an increase in gross-to-nets, primarily from ONPATTRO®. Tolga Tanguler, Chief Commercial Officer, stated that ex-U.S. contribution would remain modest in Q4 (Germany and Japan), with the main ramp-up expected in mid-to-late 2026, while highlighting the robust performance of the hereditary ATTR polyneuropathy business in Europe.

Maury Raycroft from Jefferies asked whether there was a one-time bolus effect in the Q2 cardiomyopathy scripts and questioned the extent of channel stocking's contribution to revenue growth.

Answer

CEO Yvonne Greenstreet asserted that the results are not a 'flash in the pan' and reflect sustainable growth from strong execution. CFO Jeff Poulton clarified that demand was the primary driver, with an estimated $150 million from cardiomyopathy patients. He noted a $25 million inventory benefit was driven by higher demand calculations, not increased days on hand, and was largely offset by a gross-to-net headwind.

Maury Raycroft asked about the dose reductions for selinexor and/or ruxolitinib observed in the first 61 patients of the CENTURY futility analysis group, how these compare to Phase 1 data, and to other myelofibrosis Phase 3 studies. He also asked about the recruitment regions for these first 61 patients and if the March data readout would be earlier or later in the month.

Answer

Reshma Rangwala (CMO) stated that specific ruxolitinib dose reductions for the first 61 patients are not meaningful to comment on due to variable starting doses and blinded data, but noted that selinexor dose intensity was greater than 95%. She confirmed that the first 61 patients were globally recruited, primarily from North America and the EU. Richard Paulson (CEO) reiterated that the data readout would be in March, without specifying earlier or later.

Representing Maury Raycroft of Jefferies, Amy asked about the enrollment progress for the Phase III endometrial cancer trial and sought clarification on how the protocol amendment for the SENTRI-2 study would boost enrollment and what the new bar for success would be.

Answer

Chief Medical Officer Reshma Rangwala stated that enrollment for the endometrial cancer trial is steady, with a good flow of patient samples for biomarker screening, and the company remains on track for a 2026 data readout. For SENTRI-2, she explained the amendment will expand eligibility to all JAK-naive patients with platelet counts above 50,000 (removing the upper cap), which should accelerate enrollment now that the main SENTRY trial is full. The bar for success remains unchanged, targeting a response rate above 25-30% in this high-unmet-need population.

Maury Raycroft inquired about Arrowhead's discussions with the FDA regarding the development path for their obesity programs, ARO-INHBE and ARO-ALK7. He asked about potential timelines for Phase II starts and whether all existing data, including combination data, is required before determining the next steps.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, stated that FDA discussions for the obesity programs are anticipated around mid-year, with an IND filing shortly thereafter. He clarified that not all data from all cohorts would be necessary before determining the next development steps.

Maury Raycroft inquired about discussions with the FDA regarding the development path for the obesity programs (ARO-INHBE and ARO-ALK7), timelines for Phase 2 initiation, and whether all current data is required before determining next development steps.

Answer

James Hamilton, Chief Medical Officer and Head of R&D, indicated that FDA discussions would likely occur around mid-year, with an IND filing shortly thereafter. He clarified that not all data from all cohorts would be necessary to determine the next steps for the development path.

Maury Raycroft asked for estimates on acute pancreatitis (AP) event accrual based on the SHTG pivotal studies' patient baseline characteristics and the impact of broadening the AP adjudication criteria.

Answer

Bruce Given, Chief Medical Officer, explained that estimating AP events is challenging due to the recent adoption of the modified Atlanta criteria, which is a new scale for them. He indicated that the upcoming patient baseline profile will show the percentage of patients with a history of pancreatitis, suggesting a good chance of accruing the necessary number of events.

Maury Raycroft with Jefferies followed up on the SHTG pivotal studies, seeking estimates for acute pancreatitis (AP) event accrual based on patient baseline characteristics and inquiring about the impact of broadening AP adjudication criteria.

Answer

Bruce Given, Chief Medical Officer for Arrowhead Pharmaceuticals, explained that it's difficult to estimate exact AP event numbers due to the recent adoption of modified Atlanta criteria, which is a new scale for them. He indicated that the percentage of patients with a history of pancreatitis enrolled in the study, to be disclosed next week, would suggest a good chance of necessary events.

Maury Raycroft inquired about the potential timing of the Lyme phase III readout, specifically if a later Q2 2026 announcement would imply analysis delays, and asked for details on Valneva's proposed remedy to the FDA regarding the IXCHIQ BLA suspension and any contingency options.

Answer

CEO Thomas Lingelbach stated that Pfizer controls the Lyme readout process, acting professionally and expeditiously, and does not foresee major delays from the early 2026 timeline. Regarding IXCHIQ, he explained that Valneva's response to the FDA focused on medical evidence, individual case analysis, and the positive risk-benefit ratio, noting an ongoing phase IIII program and stringent pharmacovigilance review.

Maury Raycroft inquired about the potential timing of the Lyme phase 3 readout, specifically if a later Q2 2026 announcement would indicate delays beyond the expected mid-1Q 2026, and also asked about Valneva's proposed remedy to the FDA for the IxchIQ BLA suspension and any contingency options.

Answer

CEO Thomas Lingelbach stated that Pfizer controls the Lyme readout process, but he doesn't foresee major delays from the expected timelines. Regarding IxchIQ, he explained Valneva's response focused on medical evidence, individual case analysis, positive risk-benefit ratio, an ongoing Phase 4 program, and stringent pharmacovigilance.

On behalf of Maury Raycroft, an analyst from Jefferies asked about the revenue recognition timing for the 40,000 IXCHIQ doses sold to the French government and the potential demand scenarios for the vaccine through year-end given recent outbreaks.

Answer

CEO Thomas Lingelbach stated that Valneva is actively monitoring chikungunya outbreaks and is prepared to respond, though he did not commit to specific actions. CFO Peter Bühler clarified that the revenue for the 40,000 doses was fully recognized in the first half of 2025, with no impact expected in Q3.

Maury Raycroft asked about the patient trends for early EKTERLY adopters, specifically high-burden patients, the breakdown of the 937 start forms, and how these trends might evolve. He also inquired about the conversion rate to paid drug versus free drug for new starts.

Answer

Ben Palleiko, Chief Executive Officer, and Nicole Sweeney, Chief Commercial Officer, explained that roughly half of early EKTERLY patients are high-burden, self-reporting two or more attacks per month, leading to higher refill rates and larger quantities. They anticipate these trends will normalize as adoption expands. Ms. Sweeney noted broad switching from all on-demand therapies, predominantly Firazyr and icatibant. She also highlighted increasing paid rates week-to-week, successful medical exception utilization, and clarity from new EKTERLY policies, with Mr. Palleiko confirming all start forms represent actual prescriptions.

Maury Raycroft asked about the trends for types of patients switching to EKTERLY early on, specifically high-burden patients, inquiring about the breakdown of the 937 start forms and how these trends might evolve. He also followed up on the proportion of start forms converting to paid versus free drug.

Answer

Ben Palleiko (CEO) explained that roughly half of early EKTERLY switchers are high-burden patients with two or more attacks per month, who refill at higher rates and in larger quantities. Nicole Sweeny (Chief Commercial Officer) added that patients are switching from all on-demand therapies, primarily Firazyr and icatibant, and noted a consistent increase in paid rates for prescriptions. Ben Palleiko clarified that all start forms reflect actual prescriptions.

Maury Raycroft requested a July versus August breakdown of the 460 start forms to understand if demand was influenced by clinical study rollovers or a bolus effect, and whether this early demand suggests a linear trajectory. He also asked about stockpiling dynamics and their impact on future revenue numbers.

Answer

Ben Palleiko, CEO, clarified that the 460 start forms do not represent a one-time bolus or significant rollover from the open-label extension, but rather a sustained and continually growing level of broad patient interest. Brian Piekos, CFO, explained that specialty pharmacies are expected to hold 2-4 weeks of inventory, consistent with other rare disease launches, and that this dynamic is not expected to be different for EKTERLY.

Maury Raycroft asked for a July versus August breakdown of the 460 start forms to understand if demand was from clinical study rollovers or a launch bolus, and whether a linear trajectory is expected. He also questioned the dynamics of stockpiling for future revenue recognition.

Answer

Benjamin Palleiko, CEO, clarified that demand was not a one-time bolus from OLE rollover (dozens, not hundreds) but represented sustained, continually growing interest with a fairly linear growth curve. Brian Piekos, CFO, stated that inventory at specialty pharmacies is expected to be two to four weeks, consistent with other rare disease launches.

Maury Raycroft asked for a breakdown of the 460 start forms between July and August to understand if early demand was driven by clinical study rollovers or a bolus effect, and if a linear trajectory is expected. He also inquired about the dynamics of specialty pharmacy stockpiling and its impact on future revenue numbers.

Answer

Ben Palleiko, CEO, clarified that the 460 start forms did not represent a one-time bolus or significant rollover from the open-label extension (which involved dozens, not hundreds, of U.S. patients). He stated that demand has been sustained, continually growing, and broader than anticipated, showing a fairly linear growth curve. Brian Piekos, CFO, added that specialty pharmacies are expected to hold 2-4 weeks of inventory long-term, consistent with other rare disease launches, with some variability in the early launch phase.

Amin on for Maury Raycroft of Jefferies asked about the number of procedures a center needs to perform to become proficient with ZevaSkin, the maximum surgical capacity of these centers, and the potential patient volume at the next wave of QTCs.

Answer

CEO Vishwas Seshadri and CCO Madhav Vasanthavada stated that proficiency is expected quickly, after just one or two treatments, due to the centers' existing expertise in treating RDEB. They noted that physician conviction is already high, with more patients being identified even before the first commercial treatment. The next QTCs are expected to add a couple of dozen patients each to the funnel, creating a compounding effect on demand.

Amin Makarem, on behalf of Maury Raycroft at Jefferies, asked for clarification on the timing of the Tivesimig PFS/OS analysis, questioning if events could accrue in Q4 2025 for an early Q1 2026 readout, and inquired about the scope of the initial data release.

Answer

CEO Thomas Schuetz explained that projecting the exact timing is difficult as the event rate has slowed, but the current projection is for a Q1 2026 readout. He stated the company plans to release a priority dataset including PFS, OS, demographic data, and top-line safety, with the full dataset reserved for a subsequent medical meeting.

An analyst from Jefferies inquired about the company's latest thinking on the pivotal trial design for its Netherton syndrome program and what outcomes from the current DME study would inform the design of future trials.

Answer

Chief R&D Officer Dr. Helen Thackray explained the Netherton pivotal trial will likely focus on patient-centric endpoints like skin healing and itching, potentially allowing for a streamlined path to registration. For DME, CEO Jon Stonehouse stated the current goal is to confirm activity and dose. Chief Medical Officer Dr. Donald Fong added that the Phase 2 study will assess retinal thickness, a key indicator of efficacy, which would inform a pivotal trial designed around the registrational endpoint of best corrected visual acuity.

Maury Raycroft asked for specifics on the GSK data package, including whether it's contingent on reaching MTD and if Cohort 6 data will be included. He also questioned the impact on bilirubin and any differences observed versus AG-270.

Answer

CEO & President Yujiro Hata clarified that the data package contents depend on cohort progression, with the working assumption being the potential to expand at Cohort 6. Matt Maurer, Head of Clinical Oncology, added that IDE397 has not shown significant liver toxicity or the enzyme liabilities associated with other drugs in the class.

Maury Raycroft sought clarification on the new manufacturing process for SGT-001, asking if there were any fundamental changes beyond scaling and transient transfection. He also asked about the meaning of a 'new outsource process' and the contribution of Forge Biologics to this new strategy.

Answer

Chief Operating Officer Dr. Joel Schneider explained that the new process is already at a commercial scale, provides broader access to supply chain networks, and improves overall manufacturability. He clarified that while Forge Biologics is a partner for SGT-003, the company is establishing a relationship with a new, different vendor for SGT-001 to leverage external expertise in transient production and diversify its manufacturing base.

Maury Raycroft from Jefferies Financial Group Inc. requested an example of the tumor heterogeneity observed with ORIC-101 and asked about potential pharma partnerships and the combination strategy for the ORIC-533 program.

Answer

CEO Jacob Chacko provided an example of tumor heterogeneity from the prostate study, where patients in the target population acquired new resistance mechanisms like AR-V7 or loss of P10/TP53 while on treatment. Regarding ORIC-533, he declined to comment on specific partnership discussions but affirmed the strategy is to move quickly into multiple combination studies in parallel with the single-agent trial if even modest activity is observed, referencing advice from Dr. Ken Anderson.

Maury Raycroft of Jefferies inquired about the timing of the DUBLIN-3 data readout relative to ASCO, the specific additional analyses from the PROTECTIVE-2 trial to be presented, and the latest feedback from payers regarding launch pricing for plinabulin, considering both its CIN and potential anticancer benefits.

Answer

Dr. Lan Huang, Co-Founder, Chairwoman and CEO, confirmed that DUBLIN-3 data would not be ready for ASCO and is expected mid-year. She and Dr. Ramon Mohanlal, EVP of R&D and CMO, detailed that upcoming ASCO presentations will show additional data on febrile neutropenia, hospitalization, quality of life, and bone pain. Richard Daly, COO, explained that payers view the CIN benefit favorably on its own and that positive DUBLIN-3 data would provide additional pricing power, creating greater value.

Maury Raycroft from Jefferies & Co. asked about FDA guidance on FVC (forced vital capacity) as an endpoint, potential combination strategies in a commercial setting for patients with worsening FVC, and the degree of site and investigator overlap between the SSc and dermatomyositis studies.

Answer

CMO Dr. Barbara White stated the SSc study is not powered for statistical significance on FVC but expects to show a positive trend. CCO Craig Millian added that lenabasum would be viewed as a complementary therapy for patients on immunosuppression for lung disease. Dr. White confirmed significant site overlap between the SSc and DM studies, attributing the strong DM enrollment to high unmet need and positive investigator experience with the drug.