Paul Choi

Paul Choi inquired about the range of PSA responses, specifically PSA50s and PSA90s, observed across different prior lines of therapy, with a particular focus on patients who received prior radiotherapy. He also asked how the current VIR-5500 data reflects on the probability of success for Vir Biotechnology's other T-cell engager programs.

Answer

Marianne De Backer, CEO and Director, highlighted that the data validates the PRO-XTEN dual-masking platform, showing lower systemic immune activation, a wider therapeutic window, and strong concordance between PSA, RECIST, and PSMA PET responses, which bodes well for other programs. Mark Eisner, EVP and Chief Medical Officer, noted the heavily pretreated patient population and pointed to a specific case of a post-radiotherapy patient achieving a PSA99 response. He added that disambiguating specific effects of prior treatments is challenging due to the overall heavy pretreatment.

Paul Choi inquired about the range of PSA responses observed across different prior lines of therapies, specifically asking for details on PSA50s and PSA90s in patients with prior radiotherapy. He also asked how the presented data reflects on the probability of success for Vir Biotechnology's other T-cell engager programs.

Answer

Marianne De Backer, CEO and Director, highlighted that the data validates their dual masking PRO-XTEN platform, showing limited CRS toxicity, a wider therapeutic window, and strong concordance across PSA, RECIST, and PSMA PET responses, which bodes well for other programs. Mark Eisner, EVP and Chief Medical Officer, noted the heavily pretreated patient population and strong PSA responses at higher doses, citing a specific case with prior radioligand treatment showing a PSA99 response. He mentioned difficulty in disambiguating specific effects of prior lines due to heavy pretreatment.

Daniel, on behalf of Paul Choi from Goldman Sachs, asked if there would be additional data cuts from the Phase 2 SOLSTICE study for HDV and whether the next VIR-5500 (PSMA) update would include PFS data or radiology-based measurements.

Answer

EVP & Chief Medical Officer Dr. Mark Eisner confirmed that Vir plans to provide a complete 48-week data update from the SOLSTICE study by the end of the year. For the next VIR-5500 data cut, he stated that while guidance on timing is not yet available, the company aims for a meaningful update that will provide clear evidence of dose response, depth, and durability of PSA responses and other measures.

Paul Choi asked about the Nrf2 program, specifically which area of fibrosis might allow for the shortest clinical development time and time to market. He also inquired about the latest thoughts on indication selection for the NLRP3 program and where the target focus might be.

Answer

Matthew Klein, CEO, explained that for the Nrf2 program, they are still conducting indication selection, focusing on areas where the target pathway and drug mechanism align with disease states, aiming for rare diseases with objective biomarkers to facilitate accelerated development. For the NLRP3 program, he stated that initial targets would be lung inflammation and fibrosis, given the overlap between NLRP3 pathways and lung fibrosis, with the first focus on pulmonary fibrotic conditions.

Paul Choi asked about PTC Therapeutics' Nrf2 program, specifically which area of fibrosis or fibrotic disease offers the shortest clinical development time and path to market. He also requested an update on the NLRP3 program's indication selection, including the latest thoughts and target focus.

Answer

CEO Dr. Matthew Klein explained that for the Nrf2 program, PTC is still doing indication selection but aims for rare diseases with clear evidence that targeting Nrf2 can deliver clinical effect, looking for objective biomarkers to facilitate development and potential accelerated approval. For the NLRP3 program, initial targets will be lung inflammation and fibrosis, given the overlap between NLRP3 pathways and lung fibrosis, with final indications still being honed.

Daniel Ni, on behalf of Paul Choi at Goldman Sachs, asked about the pricing assumption for Sefiance in Germany after the initial six-month free-pricing period concludes.

Answer

CBO Eric Pauwels explained that PTC's global strategy is to maintain a very narrow pricing corridor, with U.S. and German launch prices already set closely. In Germany, after the six-month free-pricing period, the company will enter negotiations following a medical benefit assessment. He expressed optimism that the clinical data, real-world evidence gathered in the interim, and KOL support will help maintain a price within that narrow corridor through the 12-month AMNOG process.

An analyst on behalf of Paul Choi asked for any feedback from the FDA regarding the use of natural history data from the FACOMS registry for the vatiquinone approval submission.

Answer

CEO Dr. Matthew Klein explained that the comparison to the FACOMS natural history database is a key piece of confirmatory evidence. He noted the FDA is highly familiar with this robust registry, as it was used to support the SKYCLARYS approval, and it is considered a model for how such data can support regulatory decision-making.

Paul Choi of Goldman Sachs inquired about payer feedback on vatiquinone, its potential pricing relative to Skyclarys, and the company's appetite for business development given its strong cash position.

Answer

CEO Matthew Klein stated it's early for specific payer discussions on vatiquinone but emphasized its differentiated profile and the clear unmet need in pediatric patients. Regarding business development, he said the company's strong cash balance supports its planned launches while allowing it to remain opportunistic for strategic assets that could fill out its ex-U.S. portfolio or fit its existing infrastructure.

Paul Choi inquired about the timeline for filing an SNDA for the newborn infant population following the phase 2 reach-in study's primary completion next month. He also asked if the phase 3 combination study design for achondroplasia allows for the inclusion of newborn patients or if a separate study would be required.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, explained that regulatory approaches differ, with the U.S. being more stringent for infant label expansion without data, while Europe is more flexible with rolling data submissions, and Japan potentially the easiest. He confirmed that data is being generated in a placebo-controlled trial, and Aimee Shu, Chief Medical Officer, added that 'Sentinel kids' (non-randomized) are showing positive progress in tolerability, growth, and early signals of other benefits, particularly in radiology.

Paul Choi asked if Ascendis Pharma plans to file an SNDA for the newborn infant population for TransCon CNP this year, given the phase II run-in study's primary completion next month. He also inquired if the phase II combination study design allows for newborn patients or if a separate study would be required, based on discussions with the FDA and EMA.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, explained that regulatory approaches differ: the U.S. is more stringent, likely requiring data in hand for infant label expansion, while Europe is more flexible with rolling data additions. Japan might be the easiest for immediate infant approval. He confirmed they are generating the necessary data in a placebo-controlled trial. Aimee Shu, Chief Medical Officer, added that the 'Sentinel kids' (non-randomized patients) are tolerating the medicine well, growing, and showing early signals of benefits, particularly in radiology.

Paul Choi of Goldman Sachs inquired about the timeline for submitting data to the FDA for the 60mcg dose of Yorvipath and asked what portion of the patient population this higher dose would potentially address.

Answer

President & CEO Jan Møller Mikkelsen confirmed a clear need for a higher dose. He described the newly initiated trial as small and short (26 weeks) and stated the company will file for approval as quickly as possible. He indicated an unmet need exists, as some patients currently require supplementation or may be receiving higher doses through off-label means.

Paul Choi asked for color on the etiology of patients receiving YORVIPATH, specifically the mix of post-surgical versus genetic causes. He also inquired about development plans for TransCon CNP in the youngest patient population (birth to three years old).

Answer

CEO Jan Mikkelsen and Chief Medical Officer Aimee Shu clarified that the commercial patient mix mirrors the general hypoparathyroidism population and their clinical trial demographics, with approximately 80% being post-surgical and 20% from genetic or other causes. They noted that clinicians are prescribing YORVIPATH to all types of hypopara patients, as the label is not restrictive based on etiology.

Paul Choi inquired about Yorvipath patient types and TransCon CNP development plans for the youngest patient population.

Answer

CEO Jan Mikkelsen and CMO Aimee Hsu discussed patient demographics and genetic variants seen in clinical trials.

Paul Choi (on behalf of Kyuwon Choi) asked about the scope of the SKYTROFA payer contract true-up and whether the new Royalty Pharma deal represents the final capital needed before reaching breakeven.

Answer

President and CEO Jan Mikkelsen addressed the first question, explaining that the new payer contracts were implemented during Q1 and Q2, and the U.S. coverage is now 'reset.' He expects the resulting gross-to-net percentage to remain stable for the second half of 2024 and for the next five years, suggesting the issue is resolved. The second question regarding the financing was not directly answered before the call moved to the next questioner.

Paul Choi asked about recent 340B purchasing behavior, expectations for its increase, and the potential impact of Part D redesign on zanzalintinib's commercialization in 2027.

Answer

Chris Senner (CFO, Exelixis) noted variability in 340B purchasing throughout 2025 and expected variability in 2026, which could impact gross-to-net due to heavy discounting. P.J. Haley (EVP of Commercial, Exelixis) added that zanzalintinib's channel design would be optimized based on experience from cabozantinib and current market conditions.

Paul Choi inquired about recent 340B purchasing behavior, expectations for its increase, and how the Part D redesign might impact zanzalintinib's commercialization in 2027.

Answer

Chris Senner (CFO) noted variability in 340B purchasing behavior throughout 2025 and expected it to continue in 2026, potentially impacting gross-to-net due to heavy discounts. P.J. Haley (EVP of Commercial) stated that zanzalintinib's channel would be designed to optimize results, leveraging CABO's market experience and customizing for current market conditions.

Paul Choi asked about factors that could expand the US market for Infigratinib in achondroplasia, given the current approved product's sales split (three-quarters ex-US, one-quarter US), and the incremental opportunity from hypochondroplasia sales.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, refrained from commenting on competitor tactics but noted no fundamental differences in unmet need between Europe and the US. He suggested that the competitor's slower US ramp might be due to needle phobia in the US and the easier identification of patient populations in European centers of excellence. Kumar reiterated the large unmet need for both achondroplasia and hypochondroplasia, which translates into a substantial total addressable market.

Paul Choi asked about market expansion factors for the US market in achondroplasia, given that the current approved product's sales are predominantly ex-US, and the incremental opportunity of hypochondroplasia for Infogratinib sales.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, declined to comment on competitors' commercial tactics but stated that a solid therapy should perform well in both markets, expecting normal drug product sales ratios. He attributed the competitor's slower US ramp to needle phobia in the US market and differences in European centers of excellence. He reaffirmed the large unmet need and total addressable market for both achondroplasia and hypochondroplasia, even under conservative assumptions.

Paul Choi from Goldman Sachs inquired about the potential for clinical success with incaleret in ADH1 to translate to the broader hypoparathyroidism indication, particularly regarding how responder rates might compare to other therapies.

Answer

COO Ananth Sridhar stated that a positive ADH1 study would significantly de-risk the hypoparathyroidism program, with key read-throughs on safety and the ability to rapidly normalize calcium levels. He highlighted upcoming data showing 80% of hypoparathyroidism patients achieved normalization and noted key differentiators for incaleret: its oral formulation, potential to normalize urine calcium, and avoidance of long-term bone resorptive effects.

Paul Choi of Goldman Sachs asked a policy question regarding the potential impact of tariffs on BridgeBio's business as sales scale and how ex-U.S. royalty streams would affect the company's margin and profitability profile.

Answer

CFO Tom Trimarchi stated that the impact from tariffs is expected to be 'very, very minor.' He explained this is because Attruby is manufactured in the U.S., the company is American, and its intellectual property is domiciled in the U.S. He clarified that ex-U.S. royalties are based on top-line revenue, so any tariff implications would be handled by their partners.

Paul Choi asked about the reasons why 55% of ARCALYST patients do not restart therapy after an initial treatment period and Kiniksa's commercial efforts for these patients. He also inquired about the higher-than-modeled collaboration expense and tax rate, asking if there were one-offs or if this is a new run rate. Finally, he sought Kiniksa's perspective on an upcoming competitor's phase 2 inflammasome inhibitor data in recurrent pericarditis, comparing it to ARCALYST's Rhapsody data.

Answer

Ross Moat (Chief Corporate and Commercial Officer, Kiniksa Pharmaceuticals) explained that the average initial treatment duration is 17.5 months, with 45% of patients restarting, usually within eight weeks. He noted that Kiniksa doesn't collect precise data on why others don't restart but assumes some may be through the disease. Mark Ragosa (CFO, Kiniksa Pharmaceuticals) stated that collaboration expenses increased due to strong ARCALYST sales growth, and tax drivers remain consistent (U.K., Switzerland, U.S. income, net of R&D and stock-based comp credits), without specifying one-offs but implying sales growth as the primary driver. John Paolini (CMO, Kiniksa Pharmaceuticals) discussed that the competitor's inflammasome inhibitor phase 2 data would likely be short-term and single-arm, similar to Kiniksa's early REG data, and while it might reduce C-reactive protein, it targets a downstream pathway. He emphasized ARCALYST's focus on blocking both IL-1α and IL-1β, as demonstrated in the long-term Rhapsody program with a 99.5% event reduction, setting a high bar for effective therapy.

Paul Choi from Goldman Sachs questioned the company's plans for expanding the sales force or using direct-to-consumer (DTC) marketing to drive Arcalis growth, and also asked about the anticipated administration setting for KPL-387 (in-office vs. self-administered).

Answer

CEO Sanj Patel noted that the company continuously analyzes sales force size and is heavily focused on leveraging digital marketing and new technologies like AI for patient identification. EVP & CCO Ross Moat added that KPL-387's target monthly profile aligns well with at-home, outpatient administration, similar to Arcalis, and they do not foresee a substantial need for in-hospital use.

Paul Choi inquired about physician awareness of ARCALYST for first-recurrence patients in the context of treatment guidelines and asked for an update on the enrollment timeline for the abiprubart Phase IIb study.

Answer

Chief Medical Officer John Paolini explained that while formal guidelines predate ARCALYST, an evidence-based approach is driving its use as a second-line therapy after NSAIDs and colchicine fail, which often occurs at the first recurrence. Regarding the abiprubart study in Sjögren’s Disease, he confirmed it is actively enrolling and dosing patients but did not provide specific guidance on enrollment timelines.

Paul Choi from Goldman Sachs inquired about the expected dose-response for the 15mg and 25mg doses in the Phase III epilepsy trial and the filing strategy for these doses. He also asked if Xenon would explore combining its Nav1.7 inhibitor with a Nav1.8 inhibitor post-proof of concept.

Answer

President and CEO Ian Mortimer stated that while long-term combinations in pain are interesting, the immediate focus is on single-agent proof of concept. Regarding dosing, both Mortimer and Chief Medical Officer Christopher Kenney confirmed they expect a dose-response and plan to file with multiple doses to provide flexibility for physicians, a strategy consistent with FDA discussions. Kenney added that the study is well-powered for both dose levels.

An analyst on for Paul Choi asked about the trial design for bipolar depression (BPD), specifically whether the company plans to stratify patients by BPD Type 1 and Type 2 to enhance the signal-to-noise ratio.

Answer

Chief Medical Officer Dr. Chris Kenney confirmed the studies will enroll a mix of Bipolar I and II patients. He acknowledged the validity of the question, stating that stratification is something the company is 'definitely seriously considering' given the potential for different responses and an uneven mix of patient types. More details on the trial design will be shared when the first study initiates mid-year.

Paul Choi of Goldman Sachs asked about the plague vaccine program's reliance on government funding and the potential impact of seasonality on patient enrollment for the future Lyme disease clinical trials.

Answer

CEO Ryan Spencer confirmed the plague program is fully aligned with and dependent on the U.S. Department of Defense, noting that funding is already secured through the first half of 2027. Regarding the Lyme disease program, he acknowledged that seasonality will be a critical factor in designing the future efficacy trial to demonstrate durability, although near-term studies will focus on safety and immunogenicity.

An analyst on behalf of Paul Choi asked about the drivers behind the strong Q1 start for HEPLISAV-B, how that strength is reflected in the full-year guidance, and the expected timing and cadence of the guided increase in 2025 operating expenses.

Answer

CEO Ryan Spencer attributed the strong Q1 start to retail pharmacies pivoting to non-respiratory vaccine initiatives earlier than in the previous year, which supports the company's annual guidance. CFO Kelly MacDonald explained the high-teens percentage increase in R&D expenses is activity-based and will be driven by a full year of costs for the DoD plague program and ongoing expenses for the Phase I/II shingles study through the first three quarters.

Paul Choi of Goldman Sachs inquired if UGN-103 could address different patient segments than ZYSTIRI and asked about the role of non-physicians, like nurse practitioners, in administering the product.

Answer

CMO Mark Schoenberg and CEO Liz Barrett confirmed UGN-103 is being evaluated in the same population as ZYSTIRI to replicate the ENVISION trial, though future life cycle studies will explore other populations. CCO David Lin added that while physicians will oversee the process initially, they expect administration to eventually be handled by nurses specializing in intravesical therapies, and UroGen's sales approach targets the entire office staff.

Paul Choi asked if the 340B utilization trend seen with JELMYTO is expected for UGN-102 and inquired about the internal bar for the go/no-go decision on advancing the UGN-301 program.

Answer

CEO Liz Barrett stated they expect 340B discounts to be less significant for UGN-102 over time due to a larger community-based business mix. For UGN-301, Chief Medical Officer Dr. Mark Schoenberg explained that as a Phase I trial, the focus is on safety, but they are encouraged by early responses and will assess durability before making a decision later in the year. Liz Barrett added that the efficacy bar is now higher and they will be critical before proceeding, also considering their UGN-501 asset.

On behalf of Paul Choi, an analyst asked for an overview of how the commercial launch process for UGN-102 will be improved based on learnings from challenges with JELMYTO's administration, reimbursement, and access.

Answer

CCO David Lin explained that they will apply learnings by immediately pairing clinical conviction with operational and financial support. President and CEO Liz Barrett added that UGN-102's launch will be fundamentally different and easier, as it treats a more common disease and its administration is simpler, avoiding the 'heavy lift' associated with JELMYTO.

Paul Choi from Goldman Sachs inquired about the potential impact of economic sensitivity on end-user demand for HUTCHMED's oncology products in China. He also asked for the expected timeline for clinical entry of the next-generation SYK inhibitor and its partnering strategy.

Answer

CEO Weiguo Su acknowledged the commercial turbulence in China but expressed confidence in a second-half recovery, citing strong performance momentum in the past three months and stable underlying patient demand. For the next-generation SYK inhibitor, Dr. Su projected an IND submission around Q2 of the following year, highlighting a potentially rapid clinical development path and the intent to secure a partner for co-development or licensing by the time it enters the clinic.

Paul Choi of Goldman Sachs asked for physician feedback on venoprazan's potential role in eosinophilic esophagitis (EoE) and inquired about the timing for a pediatric study to secure additional market exclusivity.

Answer

Steven Basta, President, CEO & Director, explained that venoprazan has the potential to become a first-line EoE treatment, disrupting the current use of PPIs. He stated the upcoming Phase 2 trial is in adults and is a prerequisite for future discussions with the FDA about a Phase 3 program and a potential pediatric study that could lead to a six-month exclusivity extension.

Paul Choi inquired about the IP strategy for the ODT formulation, specifically the sequencing of a pediatric extension versus a formulation patent, and asked for clarification on the components of the 57% gross-to-net calculation.

Answer

COO Azmi Nabulsi explained the ODT patent and pediatric exclusivity are independent and will be pursued in parallel, with the formulation patent expected to provide full 20-year protection. CFO Molly Henderson clarified the GTN calculation is based on the different WAC prices for the retail ($680) and BlinkRx ($50) channels, with the lion's share being rebates and wholesaler discounts.

Paul Choi asked about the company's confidence in the DMD program's regulatory path in the absence of a permanent CBER head and how it is thinking about long-term pricing for its retinal products given downward pressure on VEGF reimbursement.

Answer

President & CEO Curran Simpson stated it is too early to comment on retinal pricing strategy, as those discussions with AbbVie will occur closer to data readouts. On the FDA, he expressed confidence, noting the pivotal protocol was reviewed by a team that remains largely intact. He added that continued enrollment into the confirmatory study provides flexibility to adjust to any new regulatory feedback.

Paul Choi of Goldman Sachs inquired about Amarin's U.S. formulary negotiation outlook for 2026, the strategic role of a potential authorized generic, and what metrics investors should use to track the progress of the new Recordati partnership in Europe.

Answer

CEO Aaron Berg stated that Amarin expects to maintain its exclusive formulary positions in the U.S. through 2025, with more clarity on 2026 coming by year-end. He explained that launching an authorized generic is not yet optimal as the branded product continues to compete effectively. Regarding the Recordati partnership, Berg noted that the transition is underway and full commercial control will be handed over by the end of 2025. The company will report on European end-market demand as it develops and will continue to provide quarterly financial results.

On behalf of Paul Choi, an associate asked for more detail on the drivers of revenue growth in the 'rest of the world' segment and requested a more specific geographical breakdown of the contributions.

Answer

President and CEO Aaron Berg explained that growth in the rest of the world is still in its early stages and is driven by the efforts of regional partners. He highlighted recent progress, including launches in China (EddingPharm) and Australia (CSL Seqirus), and expanded public access in Canada (HLS). Berg noted that it takes time to establish medical advocacy and secure reimbursement in each market and did not provide a specific numerical breakdown, emphasizing the foundational work being done.

Daniel, on behalf of Paul Choi, asked about the likelihood of PYLARIFY revenue transitioning to ASP-based pricing and inquired about the current growth trends in the PET scan market for Alzheimer's disease.

Answer

CEO Brian Markison and CCO Amanda Morgan described the potential shift to ASP as 'murky' but noted conversations with CMS are ongoing. President Paul Blanchfield highlighted the long-term PSMA PET market potential of $3.5B by 2030 and noted 'very robust growth' in claims data for Alzheimer's PET scans, expressing optimism for the company's combined portfolio in that space.

Paul Choi asked about any remaining gating items before the pre-NDA meeting for vepdegestrant and the expected timing for the next data update from the LRRK2 program.

Answer

CMO Noah Berkowitz confirmed that the pre-NDA meeting with the FDA has already taken place, and the company has a clear path to move forward with its submission. For the LRRK2 program, he guided that the next data update will be later in the year, likely from the single ascending dose (SAD) patient cohort, as multiple ascending dose (MAD) data may not be ready in time.

Paul Choi asked what initial clinical data from ARV-393 would be needed to support expansion into more challenging populations, such as post-stem cell transplant or elderly patients. He also sought confirmation on the venue for the initial Phase I data presentation (EHA or ASH).

Answer

Chief Medical Officer Noah Berkowitz noted it was premature to comment on specific expansion populations, though combination therapies are a likely path forward. Chief Scientific Officer Angela Cacace added that they are preclinically evaluating ARV-393 in post-CAR-T refractory models. Dr. Berkowitz declined to provide guidance on the specific conference for the data release.

Asked if the triple combination development is a joint effort with their European partner and requested clarification on the annualized net interest expense following recent financing activities.

Answer

The triple combination is being developed concurrently and in collaboration with their European partner, Daiichi Sankyo. The net interest expense is expected to remain consistent with Q4 levels, with a large portion being non-cash related to deal accounting.

Paul Choi from Goldman Sachs inquired about Biohaven's 2022 commercial strategy, specifically asking if the company plans to pivot from virtual selling to more 'feet on the street'. He also asked for details on the clinical strategy for the new SMA asset, including whether there would be a focus on a specific patient subpopulation.

Answer

CEO Vlad Coric and CCO BJ Jones responded that the company will maintain its successful 'digital-first' approach with only modest, targeted increases to its sales force, aiming to increase impact rather than size. Chief Medical Officer Elyse Stock explained that for the SMA trial, they are collaborating with experts and patient advocacy groups to determine the optimal design, as the field is evolving beyond traditional classifications due to the effectiveness of current therapies.

Paul Choi from Goldman Sachs asked about the strategic synergies considered in the Pfizer deal, particularly regarding portfolio overlap in migraine. He also requested guidance on the expected data cadence for the BHV-1100 antibody recruiting molecule (ARM) program in multiple myeloma.

Answer

CEO Dr. Vlad Coric explained that Pfizer's extensive ex-U.S. primary care and pain footprint presented clear synergies, making them the ideal partner to globalize NURTEC. Regarding BHV-1100, Dr. Coric and CMO Dr. Elyse Stock expressed excitement about enrolling the first patient and anticipate initial data in the next year, which would serve as the first human validation of the platform's technology in immuno-oncology.

Paul Choi from Goldman Sachs inquired about Biohaven's positioning and messaging for NURTEC ODT's prevention launch, especially with potential competition, and asked about the relative brand awareness in the market.

Answer

CEO Vlad Coric clarified that Q2 results primarily reflect the acute indication's growth, with the prevention launch impact expected in future quarters. CCO BJ Jones emphasized the clear messaging of NURTEC ODT as the "first and only" dual-acting therapy to both treat and prevent migraines, leveraging the brand's existing high awareness. Dr. Coric added that the ability for patients to customize their therapy represents a significant paradigm shift.