Derek Archila

Derek Archila asked if ocular MG approval would increase utilization in less advanced MG patients and if future data could demonstrate prevention of progression to generalized disease.

Answer

Karen Massey, COO, stated that ocular MG data supports the strategy of expanding biologic use to earlier lines in MG, reinforcing VYVGART's leadership. Luc Truyen, CMO, added that long-term data collection will allow for future statements on delaying progression to generalized MG, comparing to natural progression rates.

Derek Archila asked if approval in ocular MG would increase utilization in less advanced MG patients and if future data could demonstrate prevention of progression to more generalized disease.

Answer

Karen Massey, Chief Operating Officer, confirmed the hypothesis that ocular MG data will support earlier biologic use, noting that most MG patients initially present with ocular symptoms and many progress to generalized MG. Luc Truyen, Chief Medical Officer, added that long-term data collection from the open-label extension will allow for statements on delaying progression, comparing to natural progression rates.

Derek Archila inquired about the revenue potential of the five pivotal readouts expected in 2026, asking how they might compare to the opportunities in gMG and CIDP. He also sought clarification on the diligence that led to pursuing thyroid eye disease (TED) with VYVGART, given previous debates about unmet need.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, stated that each of the Phase 3 indications roughly represents an 'MG-like opportunity' in terms of revenue potential. He explained that Graves disease (part of the thyroid space) has always been on their list due to a clear biological rationale, established clinical trial methods, and a substantial subset of patients with high unmet needs despite available medications.

Derek Archila from Wells Fargo asked about the revenue potential of VYVGART's upcoming pivotal readouts in 2026, seeking a comparison to the current MG and CIDP opportunities. He also inquired about the specific diligence that led argenx to pursue thyroid eye disease (TED) with VYVGART, given perceived debates about unmet need.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, stated that each of the Phase III indications roughly represents an MG-like revenue opportunity, with more detailed information to be provided closer to market. He explained that argenx's decision to pursue TED was based on a clear biological rationale, established clinical trial methods, and a deep understanding of the substantial unmet need in a subset of patients not responding to existing treatments.

Derek Archila from Wells Fargo asked for a breakdown of the 40% of prefilled syringe (PFS) users who switched from existing Vyvgart formulations, specifically between the Hytrulo vial and the IV version.

Answer

COO Karen Massey, with an introduction from CEO Tim Van Hauwermeiren, explained that the company does not provide a specific split by product presentation. She reiterated that Hytrulo drives the majority of growth and that the PFS strategy is focused on market expansion, not cannibalization, as evidenced by 50% of PFS patients being new to Vyvgart.

Derek Archila asked if the company is assuming an increasing number of treatment cycles in gMG patients, based on the ADAPT-NXT data, as part of its growth calculation to offset Part D exposure.

Answer

Chief Executive Officer Tim Van Hauwermeiren clarified that the material consumption between cyclical and continuous dosing is net-net the same, so it is not expected to materially impact VYVGART dosing or offset Part D exposure. He emphasized that the significance of the ADAPT-NXT data is the ability to offer a full spectrum of individualized dosing, from cyclical to continuous, to best suit each patient's needs.

Derek Archila questioned the expected quarter-over-quarter growth cadence for myasthenia gravis (MG) in 2025 and whether to anticipate seasonal impacts in the first quarter.

Answer

Chief Operating Officer Karen Massey stated she expects continued momentum in MG by moving into earlier treatment lines and broadening the prescriber base. She confirmed that Q1 seasonality, driven by insurance benefit re-verification, is an industry-wide phenomenon to consider, referencing the company's 6% growth in the prior year's Q1 as an example.

Derek Archila asked for details from Argenx's market research on the percentage of CIDP patients who have indicated they would switch to VYVGART and the primary reasons driving that decision.

Answer

COO Karen Massey explained that while market research shows 88% of CIDP patients experience residual symptoms, switching is a significant decision. She highlighted that the most compelling factors for patients and physicians are VYVGART's novelty as the first innovation in decades, the large trial data, the high response rate, functional improvements, and the favorable safety and low treatment burden profile.

Derek Archila inquired about the design of the bivamelagon Phase 3 trial, specifically if enrollment criteria or other features would differ from the setmelanotide Phase 3 study. He also asked about the potential evolution of Acquired Hypothalamic Obesity (HO) treatment guidelines, particularly for early intervention in post-surgical patients.

Answer

David Meeker, Chairman, CEO, and President, confirmed the bivamelagon Phase 3 trial would largely mimic the setmelanotide Phase 3 in sample size and duration, with ongoing evaluation of patient-reported outcome measures. Regarding HO guidelines, Dr. Meeker noted that while the trial had a six-month post-surgery entry, the clinical consensus is for earlier intervention in the real world, similar to other hormonal deficiencies, and that guidelines would evolve over time.

Derek Archila inquired about the design of the bivamelagon Phase 3 trial, specifically if enrollment criteria or other features would differ from the setmelanotide Phase 3, and also asked about the potential evolution of Acquired Hypothalamic Obesity (HO) treatment guidelines for post-surgical patients.

Answer

David Meeker, Chairman, CEO, and President, stated that the bivamelagon Phase 3 trial would largely mimic the setmelanotide Phase 3 in terms of sample size and duration, with potential modifications to patient-reported outcome measures. He also noted that while current trial entry criteria for HO require 6 months post-surgery, real-world consensus suggests earlier intervention is preferable once the treating physician is comfortable.

Derek Archila asked about the drivers behind the changes to the ongoing Prader-Willi trial (extension to 52 weeks, potential for adding sites) and any FDA discussions regarding the HO indication statement, specifically if it could include hyperphagia.

Answer

David Meeker, Chairman, CEO and President, clarified that the PWS trial updates were housekeeping, allowing patients to continue beyond six months and adding sites as a contingency. He noted that regulatory interactions for HO have been routine, but specific labeling discussions, including the indication statement and hyperphagia, had not yet commenced.

Derek Archila inquired about the reasons behind the changes to the ongoing Prader-Willi trial for Imcivree, specifically the extension to 52 weeks and the potential addition of sites, and also asked about any FDA discussions regarding the indication statement for HO, including hyperphagia.

Answer

David Meeker, Chairman, CEO and President, Rhythm Pharmaceuticals, clarified that the Prader-Willi trial updates were for housekeeping: allowing patients to continue treatment beyond six months if desired and adding flexibility for additional sites if needed, though only one site is currently active. Regarding HO, he noted that regulatory interactions have been routine, and specific labeling discussions, including the hyperphagia indication, typically occur later in the approval process.

Derek Archila of Wells Fargo asked if Rhythm would provide updated prevalence estimates for hypothalamic obesity (HO) at its September commercial day and what drives the confidence in the higher end of the current range. He also inquired about the outlook for ex-US revenue growth.

Answer

David Meeker, Chairman, President & CEO, explained that confidence in the 5,000-10,000 patient estimate for HO comes from literature, claims data from multiple countries, and field team validation, but was non-committal on providing a new formal estimate in September. CFO Hunter Smith noted that while ex-US growth is strong, Q3 can be seasonally slower in Europe and named patient sales are variable, though overall growth is expected to continue.

Derek Archila from Wells Fargo sought confirmation on whether Rhythm plans to share efficacy data from the RM-718 Part C study by year-end and asked for elaboration on the changes in patient compliance noted during the quarter.

Answer

David Meeker, Chairman, CEO, and President, stated that for the open-label RM-718 study, the company hopes to have enough patients treated for a sufficient duration to share data by year-end. Hunter Smith, CFO, clarified that patient compliance, typically in the low 80% range, was strong in Q4 2024 but returned to a more normalized level in Q1 2025.

Derek Archila inquired about the data release timing for the RM-718 SAD/MAD study and the anticipated mix of adult versus pediatric patients in the Phase III hypothalamic obesity (HO) trial.

Answer

CEO David Meeker stated that the RM-718 SAD/MAD data will likely be released with the Part C update in the second half of 2025, noting that progress implies positive results. He also confirmed the Phase III HO trial has a roughly 50/50 split between adult and pediatric patients.

An analyst on behalf of Derek Archila asked if the real-world data from French hypothalamic obesity (HO) patients is predictive for the Phase III trial, inquired about prior GLP-1 use in those patients, and questioned if the HO population might be larger than estimated due to radiation-induced cases.

Answer

Chairman, CEO and President David Meeker stated that the consistency of response in the French real-world data is reassuring and predicts well for a positive Phase III outcome. He could not specify which of the 5 patients were on GLP-1s but noted only 3 of the 8 total patients were on them, primarily for diabetes. He also acknowledged hearing anecdotal evidence of radiation-induced HO but confirmed the company has no firm estimates on that population's size.

Derek Archila sought clarification on the expected impact of seasonality on patient visits and scripts in Q1, beyond the previously discussed effects on pricing and free drug rates, and also asked for comments on inventory and stocking forecasts.

Answer

Anish Bhatnagar, Chairman and CEO, stated that as the first hyperphagia drug, they are learning about visit cadences, noting that younger PWS patients typically have 4-6 healthcare provider touch points annually. Jim Mackaness, CFO, mentioned working with PANTHERx Rare, their specialty pharmacy, and reported nothing untoward regarding inventory.

Derek Archila sought clarification on the expected impact of Q1 seasonality on patient visits and scripts, beyond the gross-to-net revenue effect, and asked for comments on inventory and stocking forecasts.

Answer

Meredith Manning, Chief Commercial Officer, reiterated that the company is not commenting on Q1 numbers directly but noted the impact of copay resets on gross-to-net. Anish Bhatnagar, Chairman and CEO, explained that PWS patients, especially younger ones, have regular touch points with healthcare providers, but the specific Q1 cadence is still being observed. He added that nothing untoward was observed regarding inventory with their specialty pharmacy, PANTHERx Rare.

Derek Archila inquired about the level of visibility the company has into the Empaveli patient pipeline for C3G and IC-MPGN, including granularity at specific sites and outreach efforts. He also asked whether Syfovre's prefilled syringe (PFS) is expected to primarily expand the market or drive share gains against competitors.

Answer

Co-Founder, CEO, and President Cedric Francois described the Empaveli patient pipeline as gratifying, noting that the upstream pipeline is now larger than before launch, indicating continued patient identification and expected steady growth. He stated that the PFS for Syfovre will be a very important driver of market share, citing examples from the anti-VEGF space where PFS offers a significant competitive advantage. Chief Medical Officer Dr. Caroline Baumal added that the PFS is a real innovation that will be highly meaningful for physicians, supporting efficient treatment and helping to expand the geographic atrophy market.

Derek Archila inquired about the visibility into Empaveli's patient pipeline for C3G and IC-MPGN, including granularity and outreach efforts. He also asked whether the Syfovre prefilled syringe (PFS) is expected to primarily expand the market or drive share gains against competitors.

Answer

Co-founder, CEO, and President Dr. Cedric Francois highlighted the gratifying aspect of Empaveli's pipeline, noting that the upstream pipeline is now larger than before launch, supporting expectations for steady growth. He stated that the PFS for Syfovre will be a very important driver of market share, citing examples from the wet AMD space where PFS provides a significant competitive advantage. Chief Medical Officer Dr. Caroline Baumal added that the PFS is a real innovation that will be highly meaningful for physicians, helping to expand the geographic atrophy market and support Syfovre adoption.

An analyst on for Derek Archila asked for an update on the company's cash runway and path to profitability, given that Q1 sales were lower than expected.

Answer

Executive Timothy Sullivan stated that Apellis is not changing its guidance on cash runway or profitability. He characterized the Q1 revenue impact as transient, related to inventory and a shift to samples. He reiterated that the company expects 2025 operating expenses to remain in line with 2024 and anticipates the upcoming launch of EMPAVELI in C3G will meaningfully contribute to the top line, maintaining the path to profitability.

Derek Archila of Wells Fargo asked about 2025 OpEx growth expectations and how Q1 seasonal factors and sampling would impact gross margin trends.

Answer

CFO Tim Sullivan stated that 2025 operating expenses are expected to be 'more or less the same' as 2024, with increased R&D spending offset by other cost savings. He did not guide on gross margin but noted the estimated Q1 sample increase is approximately 5,000 vials, which analysts can use to model the revenue impact.

Derek Archila from Wells Fargo asked for help reconciling the company's path to profitability with modest near-term sales growth, questioning the implied 2025 growth and OpEx levels, and the role of selling receivables in their funding strategy.

Answer

CFO Timothy Sullivan explained that the company is already near breakeven on a cash operating expense basis. He clarified that monetizing receivables is a working capital tool to bring in their own cash sooner, not a primary funding strategy. He stated that with their current expense structure and the upcoming C3G launch, it does not take significant growth for the company to become cash flow positive.

Derek Archila questioned Ascendis Pharma's confidence in YORVIPATH's ex-U.S. growth, asking if Germany and Austria serve as good proxies for uptake, or if growth will primarily come from increased depth in existing markets versus expansion into 10 additional countries, and the sequencing of this growth.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, explained the high heterogeneity of ex-U.S. markets, making direct comparisons difficult due to varying penetration speeds (e.g., Germany's fewer endocrinologists leading to slower uptake vs. faster uptake in Spain and France). He anticipates an acceleration in patient uptake as 10 more countries transition to full commercial reimbursement from named patient programs in 2026, with continued growth into 2027 and 2028.

Derek Archila questioned Ascendis Pharma's confidence in Europat's ex-U.S. growth, asking if Germany and Austria serve as good proxies for other markets or if growth will come more from depth in existing countries versus expansion into 10 additional countries, and how this sequencing will occur.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, explained the heterogeneity of ex-U.S. markets, noting different speeds of penetration (e.g., Germany with fewer endocrinologists vs. Spain/France with more). He emphasized that named patient programs in 30-35 countries will see accelerated patient uptake upon full commercialization, with 10 additional countries expected to achieve full reimbursement in 2026. He also mentioned recent approval in Canada.

Derek Archila of Wells Fargo & Company inquired about the three-month timeframe from patient enrollment to treatment conversion for Yorvipath and asked what steps are being taken to shorten this period.

Answer

President & CEO Jan Møller Mikkelsen stated that the situation is consistent with Q1 commentary and that improvements are expected in the latter half of the year as new initiatives are implemented. Jay Donovan Wu, EVP & President - US Market, detailed a multi-pronged approach, including payer education, optimizing hub processes to reduce paperwork cycles, and streamlining workflows with specialty pharmacies.

Derek Archila inquired about the depth of YORVIPATH prescribing, such as the number of physicians prescribing to multiple patients, and whether patients who are newly diagnosed or well-controlled on conventional therapies are switching to the drug.

Answer

President and CEO Jan Mikkelsen explained that they cannot precisely track patient control status as it is not part of the reimbursement process. However, he believes they are reaching a high percentage of uncontrolled and partly controlled patients due to a commercial strategy focused on endocrinologists with high patient visit frequencies. Chief Business Officer Sherrie Glass supported this, noting the large populations of uncontrolled (10k-15k) and partly controlled (30k-35k) patients ensure a steady flow of potential candidates.

Derek Archila inquired about the depth of prescribing for Yorvipath and whether newly diagnosed or well-controlled patients are switching.

Answer

CEO Jan Mikkelsen and CBO Sherrie Glass discussed the patient mix and the focus on uncontrolled patients seeing endocrinologists frequently.

Derek Archila questioned the payer feedback on YORVIPATH's U.S. pricing and asked for context on the patient penetration and launch trajectory in Germany and Austria.

Answer

President and CEO Jan Mikkelsen characterized the U.S. pricing as 'responsible' and stated they have not received negative feedback. Regarding the European launch, he and an executive (likely CCO Camilla Harder Hartvig) noted they are pleased with the uptake, with ~250 patients and ~125 prescribers. They highlighted an 'extremely strong' 98% patient retention rate and stated the launch is benchmarking well against other rare disease launches, with switches from Natpar accelerating.

Derek Archila asked about the revenue contribution from Jakafi XR included in the 2026 Jakafi guidance and sought clarification on the target penetration level for Jakafi in PV before its loss of exclusivity (LOE), given the current 30% penetration.

Answer

Bill Meury, President and CEO, stated that no incremental revenue from Jakafi XR is factored into the 2026 guidance. He projected Jakafi to grow in the mid-to-high single digits until the end of 2028, driven by PV and GVHD. He estimated that a 20% conversion rate for XR could result in nearly $250 million in XR sales by 2029.

Derek Archila asked about the revenue contribution from Jakafi XR baked into the 2026 Jakafi guidance and the target penetration level for Jakafi in polycythemia vera (PV) before its loss of exclusivity (LOE).

Answer

Bill Meury, President and CEO, Incyte, clarified that no incremental revenue from Jakafi XR is included in the 2026 guidance. He stated that Jakafi's PV and GVHD indications are growing double-digits, projecting mid-to-high single-digit growth for Jakafi overall until the 2028 LOE. He estimated a 20% conversion rate for XR could lead to almost $250 million in XR sales by 2029.

Derek Archila asked whether 989's pivotal trials in MF and ET next year would use IV or the on-body pump from Enfuse. He also inquired about the Ruxolitinib XR launch strategy, including positioning with payers and the base case for share conversion from Jakafi pre-generics.

Answer

CEO Bill Meury praised the ENABLE partnership for high-volume subcutaneous administration. President Pablo Cagnoni stated that ET trials are too far along for Enfuse initially, but the goal is to deploy Enfuse for MF studies as quickly as possible for subcutaneous administration, though timing needs more clarity. EVP and General Manager, North America, Mohamed Issa stated XR is a great addition, offering convenient once-daily dosing, expecting 15-30% conversion from IR by 2028, contributing incrementally through 2030+. The launch strategy focuses on quick formulary access, HCP adoption, and patient preference.

Derek Archila of Wells Fargo & Company asked if Incyte has characterized the tryptase reduction seen with INCB00262 in earlier trials. He also inquired whether the recent growth in Jakafi's myelofibrosis (MF) market is from share gains or overall market expansion.

Answer

An unnamed executive explained that while tryptase is being measured for INCB00262, the reduction is not expected to be as dramatic as with mast cell-depleting antibodies due to its targeted action on mast cells in the skin. Another executive confirmed that Jakafi's MF market is growing overall, with a 4% increase in total patients, as patients are being started on therapy earlier and treated in later lines of therapy more frequently.

Derek Archila inquired about the read-through from nipocalimab's systemic lupus erythematosus (SLE) data to IMVT-1402 in cutaneous lupus erythematosus (CLE), and the commercial synergy between brepocitinib and IMVT-1402, particularly regarding sales force deployment.

Answer

Matt Gline, CEO of Roivant, congratulated J&J on their positive SLE data, which supports FcRns, but noted that every lupus study is unique, and IMVT-1402 will need to succeed in CLE on its own. For commercial synergy, he emphasized that while field forces are typically program-specific, Roivant is focused on expansive contracting to maximize commercial scale benefits across the portfolio.

Derek Archila asked about the read-through from positive nipocalimab data in systemic lupus to cutaneous lupus for Immunovant's IMVT-1402, and the commercial synergy between brepocitinib and IMVT-1402, specifically regarding cost-effective sales force deployment.

Answer

Matt Gline, CEO of Roivant, congratulated J&J on SLE data, noting it supports FcRns in complex immune diseases, but emphasized that every lupus study is unique. For commercial synergy, he stated that de novo launches typically use specific field forces but they are considering expansive contracting for maximal portfolio benefit.

Derek Archila asked about Brepocitinib in DM, the competitive landscape including Viscot and CAR-T, the evolution of the treatment paradigm, and plans to explore other myositis subtypes.

Answer

CEO Matt Gline highlighted Brepocitinib's oral advantage, multi-year head start in DM, and broad patient access, positioning it to define the market. He differentiated CAR-T as a distinct intervention. He also mentioned an 'embarrassment of riches' for other indications, with many exciting places to take the molecule.

Derek Archila asked about the competitive landscape for BREPO in DM, including VISCOT and CAR-T, and if Roivant plans to explore BREPO in other myositis subtypes.

Answer

CEO Matthew Gline emphasized BREPO's multi-year head start and oral formulation as key differentiators in DM, viewing CAR-T as a different intervention for different patients. He believes Roivant will define the DM market. For other myositis subtypes, he reiterated having many exciting places to take the molecule.

Derek Archila asked about the read-through of nipocalimab's positive SLE data to cutaneous lupus for Immunovant's 1402, and the commercial synergy between Brepo and 1402, specifically regarding sales force and cost-effectiveness.

Answer

CEO Matt Gline congratulated J&J on SLE data, noting it supports FcRn use in complex immune diseases and has some pathophysiological overlap with CLE, but each lupus study is unique. For commercial synergy, he stated that while field forces are typically program-specific, Roivant is actively thinking about expansive contracting to maximize benefit from commercial scale across the portfolio.

Derek Archila, Managing Director at Wells Fargo, inquired about the read-through from positive nipocalimab data in systemic lupus erythematosus (SLE) to cutaneous lupus for Immunovant's IMVT-1402, and the strategy for achieving commercial synergy between brepocitinib and IMVT-1402, particularly regarding sales force deployment and cost-effectiveness.

Answer

Matt Gline, CEO of Roivant Sciences, congratulated J&J on the SLE data, noting it supports FcRn use in complex immune diseases and suggests some pathophysiological overlap with CLE, but emphasized that each lupus study is unique. For commercial synergy, he stated that while de novo launches typically use product-specific field forces, Roivant is focused on expansive contracting and leveraging commercial scale across the portfolio for maximal benefit.

Derek Archila from Wells Fargo asked how the different doses in the KT-621 Phase 2b study are expected to differentiate and what strategic optionality the follow-on STAT6 degrader provides.

Answer

CEO Nello Mainolfi stated the Phase 2b study aims to identify the optimal risk-reward profile by exploring both maximal and lower levels of degradation to inform the Phase 3 dose. Regarding the follow-on molecule, he explained it is an IND-ready asset that supports the franchise, provides strategic options for the future, and reinforces their competitive position, though there are no immediate plans to file an IND.

On behalf of Derek Archila from Wells Fargo, Simone Nasroodin asked about the development pace for ZW1528 and the company's business development strategy, specifically which in-house program is the top priority for partnering.

Answer

CEO Kenneth Galbraith stated that ZW1528 is expected to advance rapidly, consistent with other pipeline assets. Regarding partnering, he explained that the company is not prioritizing any single asset, but rather has open discussions across its entire portfolio of six nominated candidates and is also exploring earlier-stage, broader collaborations.

A representative for Derek Archila at Wells Fargo asked if learnings from the development of ZW171 and ZW191 could be applied to optimize or expedite the development of other candidates in the ADC and T-cell engager pipeline.

Answer

Chief Scientific Officer Dr. Paul Moore confirmed that learnings are definitely applied across the portfolio. He noted that the designs of ZW171 and ZW191 incorporated learnings from the broader field, and in turn, insights from these ongoing trials will inform the development of future programs. He indicated more details on trial design would be shared in upcoming 'trial in progress' posters.

Derek Archila inquired about the scope of the upcoming R&D Day, specifically regarding the expansion into autoimmune diseases and the target selection process for the new trispecific T-cell engager.

Answer

Chief Scientific Officer Dr. Paul Moore confirmed the R&D Day will cover specific autoimmune programs, not just platform potential. For the trispecific T-cell engager, he explained the design requires targets with tumor-biased expression and that its conditional CD28 engagement enhances safety, with encouraging preclinical tolerability for targets like DLL3 and Claudin 18.2.

Derek Archila from Wells Fargo asked about the expected revenue trajectory for the NET indication in the coming quarters and the breadth of prescribing physicians observed so far.

Answer

CEO Michael Morrissey declined to give forward-looking quarterly guidance. EVP of Commercial P.J. Haley confirmed they are seeing broad prescription uptake from both academic and community settings, as well as from both new and existing cabozantinib prescribers, indicating widespread market activation.

An analyst on behalf of Derek Archila asked for expectations for the STELLAR-304 study in non-clear cell RCC and what has been seen from competitor therapies in this population.

Answer

Chief Medical Officer Amy Peterson expressed high confidence in the study, noting it's the first Phase III trial in this specific patient population. She stated the comparator is sunitinib, which has a reported PFS of about 5-6 months. She highlighted that since cabo/nivo has beaten sunitinib and zanzalitinib is believed to be superior to cabozantinib, the trial has a high probability of success.

On behalf of Derek Archila, an analyst asked how de-risked the LRRK2 target is and what results can be expected from the upcoming single ascending dose (SAD) cohort data in Parkinson's disease patients.

Answer

CMO Noah Berkowitz addressed known class-related safety concerns for LRRK2 inhibitors, stating that Arvinas's degrader has shown a differentiated and more favorable preclinical safety profile. He expects the upcoming patient data to show a greater than 50% LRRK2 reduction, similar to what was seen in healthy volunteers, but from the higher baseline levels characteristic of PD patients.

Derek Archila inquired about the data release schedule for the TACTIVE-U trial cohorts and whether this data would influence the choice of a CDK4/6 inhibitor for the second-line combination therapy. He also asked about the preclinical basis for the therapeutic level of LRRK2 degradation and how that translates to human trials.

Answer

Chief Medical Officer Noah Berkowitz stated that while data from TACTIVE-U is maturing, no specific guidance on timing is available. The choice of a second-line CDK4/6 partner is not solely dependent on this data, as vepdegestrant has shown good combinability with multiple agents. Chief Scientific Officer Angela Cacace explained that preclinical and genetic data suggest a 50% reduction in LRRK2 protein is the therapeutic target, which the company aims to demonstrate in the central nervous system.

Asked for a comparison of net patient adds between Q2 and Q3, the potential impact of seasonality on Q4, and expectations for BLU-808's profile (tryptase reduction and safety) relative to antibodies.

Answer

The company reiterated its focus on the long-term growth trajectory of patients on therapy rather than quarter-to-quarter numbers. For BLU-808, they believe the small molecule approach offers a differentiated profile by allowing fine-tuning of the dose to optimize the therapeutic index, potentially improving on the safety/efficacy balance seen with antibodies.

Derek Archila of Wells Fargo asked if competitor data from Natera de-risks the path to a Phase IIb trial for VTX3232 in Parkinson's disease and how Ventyx's compound is expected to differentiate itself.

Answer

CEO Raju Mohan responded that while positive data from any drug in the class is encouraging, Ventyx is focused on its own data. He emphasized that VTX3232 is an "extremely well-behaved compound" suitable for once-daily dosing at low doses, expecting to hit the target hard and establish its own robust biomarker profile in the upcoming 28-day study.

Adam, on behalf of Derek Archila from Wells Fargo, asked about the factors driving the BLA submission timeline for VRDN-001 to the second half of 2025, whether the STRIVE safety study needed to be fully completed for submission, and if its safety data could be leveraged for VRDN-003.

Answer

President and CEO Stephen Mahoney clarified that the BLA timeline is primarily driven by the follow-up period required for the THRIVE 2 trial after its top-line data readout at year-end 2024. He noted that STRIVE is not the rate-limiting factor and can be submitted with a data cut. He also confirmed that VRDN-003, as a different molecule, will require its own separate safety database.