Maurice Raycroft

Maurice Raycroft asked about the dose reductions for selinexor and/or ruxolitinib observed in the first 61 patients of SENTRY, and how these compare to phase one or other myelofibrosis phase three studies. He also inquired about the recruitment regions for these initial 61 patients and sought a more specific timing for the SENTRY data readout in March.

Answer

Reshma Rangwala (EVP, Chief Medical Officer and Head of Research) stated that ruxolitinib dose reduction data for the first 61 patients is not yet meaningful due to variable starting doses, but noted that selinexor/placebo dose intensity was good, with a mean relative dose intensity greater than 95%. She confirmed the 61 patients were globally recruited, primarily from North America and the EU. Richard Paulson (President and CEO) reiterated that the data readout is firmly scheduled for March.

Maurice Raycroft from Jefferies asked if the baseline patient profiles in the SENTRY study are tracking as expected. He also inquired about discontinuation rates and dose reductions, and whether the exclusion of fatigue from the absolute TSS endpoint could be a factor in the FDA's approval decision.

Answer

Chief Medical Officer Reshma Rangwala confirmed that baseline patient characteristics in the blinded SENTRY trial are tracking consistently with their Phase I study and other contemporary Phase III trials. While unable to share unblinded data on discontinuations, she stated the rates are within expectations. Dr. Rangwala also clarified that excluding fatigue from the primary TSS analysis is aligned with the FDA and consistent with historical precedent from the COMFORT trials that led to ruxolitinib's approval.

Maurice Raycroft asked for details on the amended Phase III SPd trial in multiple myeloma, including powering assumptions and the regulatory timeline. He also followed up on the myelofibrosis study, asking about patient continuation post-24 weeks and the potential need for longer-term follow-up.

Answer

EVP, Chief Medical Officer Reshma Rangwala explained that positive evolving data allowed for a smaller trial size (120 patients) in the SPd study without compromising statistical power. An amendment is with the FDA, and a timeline update will follow regulatory feedback. For the myelofibrosis study, she confirmed patients continue treatment beyond 24 weeks for long-term endpoints, but the 24-week data on SVR35 and absolute TSS are the key drivers for regulatory decisions.

Maurice Raycroft from Jefferies asked for specifics on the pivotal trial's primary endpoint, including whether it would involve standardized clinical video, and for details on the statistical analysis plan.

Answer

CEO Sean Nolan confirmed the primary endpoint will be objective, clinically meaningful, and easy to measure, consistent with their focus on functional gains. He indicated a single-arm study is likely, which would necessitate bias mitigation measures such as video assessments and blinded raters, on which they have secured FDA alignment.

Maurice Raycroft sought to clarify the timing for finalizing the registrational study design with the FDA and asked if the company had discussed including a younger, 3-to-5-year-old patient cohort in Part B.

Answer

CEO Sean Nolan stated that the company's goal is to align the announcement of the final FDA-agreed trial design with the next data update in the first half of 2025. He also confirmed that the plan for Part B already includes the 3-to-5-year-old cohort, as part of a broader strategy to treat patients of all ages.

Maurice Raycroft asked if the updated data timeline impacts the timing for an end-of-Phase 1 meeting with the FDA and if the H1 2025 data would be sufficient for alignment on a pivotal trial.

Answer

CEO Sean Nolan stated that the company wants to complete Cohort 2 dosing and its natural history analysis before having a comprehensive discussion with the FDA. While the intent is to hold this meeting in the first half of 2025, he noted it's too early to specify the exact amount of follow-up data required. The RMAT process will be leveraged to facilitate ongoing dialogue with the agency and provide more clarity on requirements in the coming quarter.

Maurice Raycroft of Jefferies inquired about the expected timeline between the VIKTORIA-1 data lock in June and the data release in Q3 2025, and asked if an update on overall survival trends would be provided with the top-line results.

Answer

CEO Brian Sullivan confirmed the Q3 2025 timeline for top-line data is certain, following a primary completion in June. He noted the process from database lock to data reporting typically takes less than three months. Sullivan clarified that the initial press release will be limited to median Progression-Free Survival (PFS) and hazard ratios, with full data, including any survival trends, to be presented at a medical conference later in the year.

Maurice Raycroft of Jefferies inquired about the current event rate for the VIKTORIA-1 trial and the company's plans for an NDA filing and potential for priority review following the Q2 data readout.

Answer

CEO Brian Sullivan stated that Celcuity is not commenting on specifics regarding event rates but reiterated the guidance for a Q2 2025 top-line data release. He explained the company hopes to request a Real-Time Oncology Review (RTOR) or priority review, leveraging its breakthrough status, to shorten the review time and would begin submitting the package within months of approval.

Maurice Raycroft of Jefferies asked for clarification on the updated VIKTORIA-1 trial timelines, questioning if the change was driven by the event rate or slower enrollment. He also inquired about Celcuity's view on the evolving treatment landscape following Roche's inavolisib approval and its potential impact on gedatolisib.

Answer

Executive Brian Sullivan clarified that the timeline adjustment is solely due to the rate of progression events, not enrollment, which is actually ahead of schedule. Regarding competition, Sullivan stated that the inavolisib approval supports Celcuity's hypothesis that inhibiting all three key pathways is beneficial. He asserted that it does not reduce the addressable second-line market for gedatolisib, as the VIKTORIA-2 trial is designed to more comprehensively address the first-line, endocrine-resistant population.

Maurice Raycroft of Jefferies inquired about the specifics of the upcoming top-line data for the Fabry disease program (ST-920), asking what endpoints like eGFR slope and quality of life would be included, and if a natural history analysis would be provided. He also asked about the status of discussions with potential commercialization partners for the program.

Answer

Chief Development Officer Nathalie Dubois-Stringfellow confirmed the top-line data will feature the mean eGFR slope and that the statistical plan has been agreed upon with the FDA. CEO Alexander Macrae added that the dataset is robust, with 19 patients reaching two years of follow-up. Regarding partnerships, Macrae stated that Sangamo is in discussions with multiple potential partners, noting that the recent positive FDA Type B meeting on CMC has been beneficial for these negotiations.

Maurice Raycroft sought confirmation on the timing for the third STAC-BBB license agreement, the potential upfront payment size, and the outlook for operating expenses (OpEx).

Answer

CEO Sandy Macrae confirmed the company aims to finalize the third STAC-BBB deal by the end of the quarter, suggesting the upfront payment would be comparable to previous agreements. CFO Prathyusha Duraibabu stated that operating expenses have been significantly reduced and are expected to remain at current levels in 2025 to support the neurology pipeline.

Maurice Raycroft asked whether the FDA would place more weight on comparing eGFR slope versus baseline or versus propensity-matched control data in the Fabry filing. He also inquired about the status of obtaining this control data and clarified the receipt of the $50 million milestone payment from Genentech.

Answer

CEO Sandy Macrae stated the FDA will consider the 'totality of the data,' which includes the eGFR slope, sustained alpha-Gal levels, lyso-Gb3 control, and patient-reported outcomes, noting all 18 patients on ERT have successfully withdrawn. Chief Financial Officer Prathyusha Duraibabu confirmed that the full $50 million from Genentech has been received, although only $40 million was reflected in the quarter-end cash balance.

Maurice Raycroft inquired about Arrowhead's expectations for initial data from its obesity programs, ARO-INHBE and ARO-ALK7, both as monotherapy and in combination, focusing on desired outcomes for weight loss, body composition, and key biomarkers.

Answer

Chief Medical Officer and Head of R&D, Dr. James Hamilton, stated that while the company is not providing specific guidance on first-in-human data, the key potential benefits being evaluated are the quality of weight loss, including visceral fat reduction and lean muscle mass preservation. He noted that initial data for ARO-INHBE is expected around the end of 2025, with ARO-ALK7 data to follow.

Maurice Raycroft asked for details on the SHASTA-5 study, including the timeline to data and the strategic purpose, and questioned if positive pancreatitis data could potentially replace the need for a cardiovascular outcomes trial (CVOT).

Answer

An executive, likely Dr. Bruce Given, explained that the SHASTA-5 timeline is uncertain as it's an event-driven outcomes study focused on pancreatitis, primarily for payers and ex-U.S. health authorities. He clarified that it would not replace a CVOT, as atherosclerotic risk from triglycerides is a separate clinical question from pancreatitis risk.

Maurice Raycroft inquired about the additional details expected for plozasiran in FCS at the upcoming ESC meeting, the potential label differentiation versus competitors like Ionis' olezarsen, and the number of patients in the expanded access program.

Answer

Dr. Bruce Given, Interim Chief Medical Scientist, stated that the ESC presentation will offer more detail on primary and secondary endpoints. He highlighted the statistical significance on pancreatitis as an exciting and important part of their FDA filing. Dr. Christopher Anzalone, President and CEO, clarified that the company has not disclosed the number of patients in the expanded access program.

Maurice Raycroft asked for clarification on the 2025 guidance, questioning if Q1 is typically the lowest quarter and what early Q2 trends suggest for the rest of the year. He also inquired about the strategy and risks associated with the numerous ANDA filers challenging the LUPKYNIS 2037 dosing patent.

Answer

President and CEO Peter Greenleaf corrected that historically, the second or third quarter has been softer due to summer effects, and suggested using past performance as the best predictor for the year's cadence. On the ANDA filings, Greenleaf confirmed that patent infringement lawsuits have been filed against all challengers, triggering a 30-month stay. He emphasized that the company will vigorously defend its patents and is focused on ensuring the long-term value of LUPKYNIS.

Maurice Raycroft asked about the fourth-quarter sales outlook, questioning if the high end of the reiterated guidance might be conservative given historical Q4 strength. He also sought details on insights from the ENLIGHT-LN registry regarding real-world LUPKYNIS use and the growing trend of patient restarts.

Answer

President and CEO Peter Greenleaf explained that maintaining the guidance range is a conservative approach that accounts for potential Q4 variables like holidays and year-end insurance changes. On the ENLIGHT-LN study, Dr. Greg Keenan, Chief Medical Officer, noted it reveals high LUPKYNIS use in African-American populations and emerging use in combination with other therapies. Peter Greenleaf added that the 'restart' phenomenon reflects current physician practice, but he sees a significant growth opportunity as treatment guidelines evolve toward longer, continuous therapy.

Maurice Raycroft asked about the rationale for lowering the minimum age in the HAELO Phase III trial to 16 and requested more specific guidance on where ATTR cardiomyopathy enrollment might land by year-end, given it's tracking ahead of expectations.

Answer

CEO John Leonard explained the age change for HAELO reflects the goal of achieving the broadest possible label. Regarding ATTR-CM enrollment, he confirmed it is well ahead of schedule and that the company's guidance to exceed 550 patients by year-end is a conservative estimate they may over-deliver on, guaranteeing it will be more than 100.

Maurice Raycroft inquired about the latest assumptions for the Phase 3 event accrual rate for nex-Z (NTLA-2001) and whether there were more details on what could enable an interim analysis for the MAGNITUDE study.

Answer

CMO David Lebwohl responded that event rates are expected to be similar to other recent TTR trials. He highlighted that the favorable Phase 1 data, showing a low event rate and disease stabilization, suggests a good possibility of positive findings at an interim analysis that could potentially stop the study early, with more details to be provided in the future.

Maurice Raycroft asked for expectations regarding the upcoming AHA data update for nex-z, specifically about biomarkers, functional capacity, and whether individual patient or cardiac imaging data would be presented.

Answer

CEO John Leonard and CMO David Lebwohl expressed enthusiasm for the AHA presentation. They confirmed it will include biomarker, functional, and clinical data for all 36 patients at the 12-month mark, linking deep TTR reduction to clinical outcomes. Lebwohl noted their study includes a sicker patient population than competitor trials, providing a robust test of the therapy.

Maurice Raycroft from Jefferies inquired about the next steps for the IXCHIQ label, specifically the status of the adolescent label extension with the FDA and any potential new safety language. He also asked about the p-value threshold for the primary endpoint in the Phase III Lyme study and the antibody titer expectations for protection.

Answer

CEO Thomas Lingelbach stated that the FDA review for the adolescent label extension is ongoing. Regarding safety, he confirmed investigations are active, particularly concerning frail older individuals, and the company is supporting regulators to determine if additional precautions are warranted. For the Lyme study, Lingelbach declined to disclose the specific p-value but noted the study is sufficiently powered. He mentioned that while there is no established immunological correlate for Lyme, a joint publication with Pfizer hypothesizes a potential protective threshold.

Maurice Raycroft of Jefferies asked about the status of the IXCHIQ adolescent label extension with the FDA, the next steps regarding potential label language updates due to safety events, and the p-value threshold for the Phase III Lyme disease study.

Answer

CEO Thomas Lingelbach confirmed the FDA review for the adolescent label extension is ongoing. Regarding safety, he stated that investigations into adverse events in frail older individuals are continuing and Valneva is supporting regulators to determine if additional precautions are warranted. For the Lyme study, he declined to disclose the specific p-value but affirmed the study is sufficiently powered, noting the historical difficulty in establishing an immunological correlate for Lyme disease.

Maurice Raycroft asked for details on the specific actions that led to the unexpectedly rapid improvement in converting patients to paid ORLADEYO therapy and whether this rate is sustainable. He also requested more specifics on what drove the improvement in gross-to-net during the first quarter.

Answer

Chief Commercial Officer Charlie Gayer attributed the paid-rate success to team expertise, the positive impact of the Inflation Reduction Act on Medicare affordability, and improved execution in the commercial segment. He stated the current rate should be a sustainable 'floor' for the future. For gross-to-net, Gayer explained that the improvement was driven by a favorable mix change from more paid Medicare patients and more disciplined management of co-payment assistance for commercial patients.

Maurice Raycroft inquired about BioCryst's strategy to identify underdiagnosed Netherton syndrome patients for its clinical program and future commercialization. He also asked about pricing plans for the ORLADEYO pediatric formulation.

Answer

Chief Commercial Officer Charlie Gayer detailed a strategy that includes using claims data for a key feature ('bamboo hair'), expanding clinical trial sites, and educating dermatologists. CEO Jon Stonehouse added they will follow established rare disease playbooks, leveraging genetic testing and patient advocacy groups. Regarding pricing, he stated that while no final decision has been made, the pediatric formulation would likely be priced comparably to the adult version.

Maurice Raycroft inquired about the 67 new U.S. prescribers added in the quarter, asking if this was better than expected and for the Tier 1 vs. Tier 2 split. He also asked about expectations for the Phase IV ORLADEYO switching study.

Answer

Chief Commercial Officer Charlie Gayer noted that the 67 new prescribers represented one of the best quarters in two years but was consistent with the strong average of 62, with an even split between Tier 1 and Tier 2 physicians. Chief R&D Officer Dr. Helen Thackray explained the Phase IV study is observational, designed to capture how physicians manage the transition and to describe the patient experience post-switch to inform other prescribers.

Maurice Raycroft of Jefferies asked for the split between new and repeat prescribers for FILSPARI and for more detail on compliance and persistence rates, such as average time on treatment.

Answer

Chief Commercial Officer Peter Heerma indicated the prescriber mix is 'slightly more skewing to experienced prescribers' but with a healthy rate of new prescribers. On compliance, he did not provide a specific duration but stated that rates are at the 'very high end' of benchmarks for chronic, non-symptomatic diseases, reflecting high patient satisfaction.

Maurice Raycroft of Jefferies inquired about the timeline for BioReference to achieve profitability, the strategy for balancing spending with the expansion of its oncology testing menu, and the potential size of the Phase 2 milestone payment from Merck for the EBV vaccine program.

Answer

Adam Logal, an executive, projected that BioReference is on a path to reach breakeven in Q1 2025 and achieve profitability thereafter, noting that significant new investment in the test menu is not required. Regarding the EBV vaccine, executive Phillip Frost indicated a decision from Merck on advancing to Phase 2 could come in Q3 2025, but Adam Logal clarified that the specific milestone value is confidential until it is earned.

Maurice Raycroft inquired about the development strategy for the oxyntomodulin analog, asking about the next steps for both the subcutaneous and oral forms, the timeline for a potential Phase I study, and the rationale for pursuing both versions in parallel. He also asked for the expected timing and nature of the initial data release for the MDX2001 study.

Answer

Elias Zerhouni, an executive at OPKO, explained that the oral form, developed with Entera Bio, shows competitive potential and that preclinical work on the once-weekly injectable is advancing. He noted the company is actively pursuing partnerships for this differentiated GLP-1/glucagon co-agonist. For MDX2001, Zerhouni projected that initial safety and tolerability data would be available towards the end of the first half of 2025, with efficacy data from larger cohorts expected around mid-2026.

Maurice Raycroft inquired about the progress of FDA label discussions for vutrisiran and whether Alnylam is advocating for unique language related to quality of life and functional capacity.

Answer

Chief Medical Officer Pushkal Garg expressed enthusiasm for the ongoing FDA review, stating it remains on track. He expects the label to reflect the study's demonstrated benefits on mortality and hospitalizations, as well as ancillary benefits like preservation of functional ability and quality of life, which were statistically significant, predefined endpoints.

Maurice Raycroft of Jefferies asked how the favorable Medicare reimbursement designation impacts commercial payer discussions, sought details on the pricing strategy for initial and subsequent treatments, and requested a forecast for the number of patients treatable by year-end 2025 and an operational timeline for the new manufacturing facility.

Answer

CCO Madhav Vasanthavada clarified that while the MS-DRG 018 designation is for Medicare, it positively signals the technology's value to commercial payers, and the new ICD-10-PCS code will streamline billing for all. He stated pricing will be a flat rate per treatment kit, with subsequent treatments billed as new, separate events. CEO Vishwas Seshadri added that demand will likely exceed initial supply, which can ramp to ~10 patient runs per month by the end of 2025, while the new facility's timeline is still in the design phase.

Maurice Raycroft asked about key learnings from the setrusumab Phase 2 14-month data that inform expectations for the interim analyses and sought clarification on whether new patient data would be included in the upcoming Angelman update.

Answer

CEO Emil Kakkis explained that the 14-month setrusumab data showed a profound and rapid separation between treatment groups, giving them confidence to implement the interim analyses. For Angelman, he clarified the upcoming update will focus on existing patients through day 338 to demonstrate the potential outcome at the end of the Phase 3 trial, rather than introducing new patient data.

Maurice Raycroft of Jefferies Financial Group inquired about the next steps to position the CUE-500 series for partnering and whether there was potential to accelerate milestones from the ONO Pharmaceuticals collaboration.

Answer

Executive Daniel Passeri stated that the company is in late-stage discussions with several potential pharma partners for CUE-501, which is viewed as a highly differentiated and attractive asset. Regarding the ONO deal, he explained that it would not make sense to renegotiate at this time, as the partnership is highly productive and both parties are aligned on the current path forward.

Asked about the projected timeline for completing the run-in phase and starting the randomization phase of the LuminICE study, whether FDA feedback is needed to proceed, and for clarification on the data mix and comparison between the two dose cohorts presented.

Answer

The company does not need to go back to the FDA to start the randomized phase. A full data update on the first two cohorts is expected in Q3, after which they can provide better guidance on timelines for cohorts 3 and 4. The data presented was a mix from both cohorts, and so far, no differences in efficacy or safety have been observed between the two dosing strategies.

Maurice Raycroft of Jefferies inquired about the status of Plinabulin for chemotherapy-induced neutropenia (CIN) in both China and the U.S., asking for feedback from China's NMPA and details on the required additional U.S. study. He also questioned the potential regulatory path forward for non-small cell lung cancer (NSCLC) in the United States.

Answer

Executive Lan Huang stated that discussions with China's NMPA for CIN are positive and ongoing. Chief Medical Officer Dr. Ramon Mohanlal confirmed that an additional Phase III study for CIN will be required in the U.S. and design discussions are active with the FDA. For NSCLC in the U.S., Dr. Mohanlal noted that while the data is positive, its applicability is under discussion with the FDA due to the high percentage of Chinese patients in the DUBLIN-3 study.

Maurice Raycroft from Jefferies asked if PK bridging data between Western and Chinese patients would be disclosed at ESMO or before the NDA filing. He also inquired about the status of regulatory interactions for the CIN NDA, specifically asking about mid-cycle review communications and any label discussions with the FDA.

Answer

CEO Lan Huang confirmed that extensive population PK data shows comparability between Asian and Western patients and has been submitted to regulators, though it is not typically presented at medical conferences like ESMO. Regarding the CIN NDA, she reported frequent and supportive communication with the FDA, a completed mid-cycle review, and noted that label discussions typically begin one to two months prior to the PDUFA date and had not yet started.

Maurice Raycroft of Jefferies asked for an update on the Phase 3 DUBLIN study, specifically if the required 439 events for final analysis had been reached and the expected timing for top-line data. He also inquired about patient baseline characteristics, including the proportion of PD-1 failure patients.

Answer

Dr. Lan Huang, Co-Founder, Chairwoman and CEO, confirmed that the 439 death events for the DUBLIN-3 final analysis have been reached and data cleaning is in process, maintaining the mid-year guidance for top-line data release. She stated that baseline characteristics are balanced, the study focuses on EGFR wild-type patients, and more detailed information on the study design would be provided at the upcoming R&D Day.

Maurice Raycroft from Jefferies asked for specifics on the dermatomyositis study, including the number of patients in the open-label extension and the discontinuation rate. He also sought more detail on the potential regulatory path for lenabasum in systemic sclerosis (SSC) following Roche's Actemra approval, questioning if it's contingent on the dermatomyositis study results.

Answer

Barbara White, Chief Medical Officer and Head of Research, reported a low discontinuation rate of around 8% for the dermatomyositis study, with 166 patients completing the week 28 visit and 90% of eligible subjects enrolling in the open-label extension. Regarding SSC, she noted the Actemra approval was of great interest and that Corbus is re-examining its own forced vital capacity data. She confirmed that supportive data from the dermatomyositis study will be crucial, and any decision to approach the FDA would follow the analysis of that data, likely in the second half of the year.