Yaron Werber

Yaron Werber of TD Cowen questioned the expected capacity and growth in Q2, particularly the mix between European and U.S. contributions, and sought confirmation that the new Raritan facility expansion would not require an inspection.

Answer

Alan Bash, President of CARVYKTI, confirmed that the Obelisc facility is now supplying Europe and expects modest growth in Q2 with acceleration in the second half of the year, supported by both European and U.S. capacity. He also affirmed that, as per the CD30 process described by CEO Ying Huang, no inspection is expected for the Raritan physical plant expansion.

Yaron Werber asked for clarification on the fully diluted share count used in the quarter's earnings and inquired about expected data readouts from the early-stage pipeline, including autoimmune programs, within the year.

Answer

Executive Jessie Yeung explained the higher diluted share count was due to reporting a net profit under IFRS, which requires a different calculation, and it would revert if a net loss is reported. Executive Guowei Fang detailed the early pipeline, expecting dose escalation readouts for solid tumor programs (gastric, small cell lung cancer) and multiple readouts from allogeneic programs in China. He also mentioned an autoimmune program targeting CD19/20/22 is expected to have an initial clinical readout.

Speaking on behalf of Yaron Werber, Dana asked about the expected quarter-over-quarter growth cadence for CARVYKTI in Q4 and questioned if the FDA's cap on production is specific to BCMA CAR-Ts, given reports about other CAR-T products.

Answer

CEO Ying Huang reaffirmed expectations for sequential growth in Q4 but did not provide quantitative guidance. He clarified that the FDA regulates capacity for all CAR-T manufacturing facilities, not just for the BCMA class, and highlighted that CARVYKTI has supplied the highest revenue and number of slots in the market 10 quarters post-launch.

Ron Werber asked about the ongoing Moderna litigation, specifically concerning the summary judgment related to U.S. government involvement (1498 question) and its potential impact.

Answer

CEO Matt Gline reiterated the difficulty of commenting on ongoing litigation but clarified the scope of the 1498 question, noting it pertains to a relatively small portion of Moderna's total global COVID vaccine sales. He stated Roivant's position is clearly laid out in their motions and they believe they have a strong case.

Ron Werber asked about the Moderna litigation, specifically the summary judgment concerning the U.S. government's involvement in the EUA and its potential impact on Moderna's arguments.

Answer

CEO Matthew Gline explained the difficulty of commenting on ongoing litigation, clarifying that the 1498 question in summary judgment pertains to a small fraction of total sales. He reiterated Roivant's strong case, while acknowledging the judge's ultimate decision.

Sarah Kai on behalf of Yaron Werber asked how informative prior open-label studies of other JAK1 inhibitors in dermatomyositis are for predicting the success of brepocitinib, given their impressive efficacy.

Answer

CEO Matt Gline responded that while the consistent positive results from prior open-label studies are 'comforting,' they are not a substitute for placebo-controlled data, especially given the known variability of the TIS endpoint. He expressed cautious optimism, noting that he will 'bite my nails and lose sleep' until the Phase 3 data is available. He also added that the dual JAK1/TYK2 inhibition of brepocitinib could provide an additional therapeutic edge.

Yaron Werber of Cowen and Company asked about expectations for the placebo arm's performance in the dermatomyositis (DM) trial, given the limited historical data. He also inquired about the remaining stock buyback authorization and whether a new program is being considered.

Answer

CEO & Director Matt Gline acknowledged the placebo response is a reasonable question, pointing to recently published data from a competitor's myositis study as encouraging, showing a well-behaved placebo arm. Regarding the buyback, Gline and CFO Richard Pulik confirmed they are continuing to execute the existing authorization and will evaluate their capital position before deciding on future programs.

Yaron Werber questioned the statistical powering for the new cutaneous sarcoidosis trial and asked what remission rate would be considered a positive outcome for the Graves' disease study.

Answer

CEO Matthew Gline clarified that the cutaneous sarcoidosis study is a proof-of-concept trial focused on signal-finding and understanding dose response, rather than being powered for a specific statistical outcome. Regarding Graves' disease, Gline stated that while there's no specific numeric bar, any meaningful amount of remission would be encouraging and would set them up well for the Phase III study, noting even a couple of patients in remission would be a happy outcome.

Yaron Werber asked about the anticipated length of setrusumab treatment for osteogenesis imperfecta, specifically whether patients would be on continuous therapy or if combinations/cycles with bisphosphonates would be explored. He also inquired about concerns regarding bone pain from switching patients off bisphosphonates.

Answer

Howard Horn, Chief Financial Officer, expressed a personal view that bisphosphonates would become obsolete for OI, as anti-sclerostin therapy enables normal bone metabolism. He stated confidence that chronic therapy with setrusumab is necessary to maintain bone gains and health, moving away from the 'build and lock-in' paradigm seen in osteoporosis. He did not address concerns about bone pain from switching.

On behalf of Yaron Werber from TD Cowen, an analyst asked for more detail on the company's plans to control spending and whether contingency plans are being explored in case the resolution of the UX-111 CRL takes longer than anticipated.

Answer

Emil Kakkis, CEO, expressed confidence that the CRL issues are 'very doable' and not expected to be delayed. Howard Horn, CFO, reiterated the 2027 GAAP profitability goal and explained that spending associated with delayed programs is being prudently deferred. This includes pausing hiring for commercial launches and managing overall headcount.

Yaron Werber inquired about the upcoming second interim analysis for setrusumab, asking for clarification on management's comments about 'dispersion' in the study and for details on the fracture reduction rate observed at the 14-month mark in the Phase II study.

Answer

CEO and President Emil Kakkis clarified that he referred to 'variation' in baseline fracture rates, not 'dispersion,' which is managed by stratification and statistical methods. He explained that while the 67% fracture reduction rate was consistent between the 6-month and 14-month Phase II data cuts, the p-value improved dramatically to 0.0014 at 14 months because the longer duration allowed the treatment and placebo groups' cumulative fracture counts to separate further, increasing statistical power.

Yaron Werber asked if the Orbit study for OI stratifies patients by disease type (I, III, and IV) and if there is a secondary endpoint analyzing fracture rates by type.

Answer

CMO Eric Crombez and CEO Emil Kakkis clarified that the study stratifies patients by baseline fracture rate and age, not directly by OI type. While they will conduct sensitivity analyses on fracture rates by subtype, it is not a formal secondary endpoint.

Yaron Werber asked if Ultragenyx would disclose the hazard ratio and p-value if the setrusumab study is stopped early at an interim analysis. He also inquired about the status of the tech transfer for DTX401 and the expected impact on margins and COGS.

Answer

CEO Emil Kakkis stated that if an interim analysis is successful, the company will only announce that the threshold was met, without releasing specific data like the hazard ratio until the full database is locked. On DTX401, he confirmed the tech transfer to their own plant is complete, with PPQ lots running, and expects this to reduce costs by around 40% compared to a contract manufacturer, which will improve margins.

Yaron Werber from TD Cowen asked for clarification on the design and expected insights from the second year of the MariTide phase 2 chronic weight management study, particularly regarding maintenance strategies, dosing, and potential presentation at a medical meeting.

Answer

James Bradner, EVP of Research and Development, explained that part two is primarily a maintenance study testing low-dose monthly and full-dose quarterly against placebo and continued treatment. He noted it's designed to inform phase 3 strategy and maintenance, with less power for significant weight loss insights between arms, but will follow patients who did not plateau in part one.

Yaron Werber sought clarification on the expected MariTide phase 2 part 2 data readout by year-end, specifically regarding two-year weight loss data, the washout period post-week 52, anticipated weight loss in year two versus year one, and the disclosure approach.

Answer

James Bradner, EVP of Research and Development, explained that part two is primarily a maintenance study designed to inform Amgen's maintenance strategy and future phase 3 designs, testing quarterly full-dose and monthly low-dose regimens against placebo and continued treatment. He noted that the study is not strongly powered for significant insights into weight loss differences between arms, but will follow patients who did not achieve a weight loss plateau in part one for the second year. The disclosure approach will be communicated in due course.

Yaron Werber asked about the level of detail expected in Q4 for the second-year data of the obesity drug Meritide, specifically concerning maintenance dosing schedules.

Answer

James Bradner, EVP of R&D, responded that data from the Phase 2 study's second part is expected in 2025 and that more details about the data readout would be shared in due course, without confirming the specific granularity requested.

Yaron Werber of TD Cowen posed two questions on MariTide: first, whether 76-week data from the Phase II obesity study would be presented at ADA, and second, if Amgen would consider conducting a 'switch study' for patients transitioning from other GLP-1 therapies.

Answer

James Bradner, EVP of R&D, clarified that the ADA presentation will focus on the first 52 weeks of data and mechanistic studies, with the 76-week data expected at year-end. Regarding a switch study, he confirmed that management agrees it is an important clinical question and intends to generate that data in the future.

Yaron Werber inquired about the mechanism of action for the obesity drug AMG 513, which is on clinical hold, and asked about the sustainability of strong sales for the biosimilar AMGEVITA.

Answer

James Bradner, EVP of R&D, stated that the mechanism for the investigational obesity medicine AMG 513 remains undisclosed due to competitive reasons. Murdo Gordon, EVP of Global Commercial Operations, expressed confidence in the continued growth of the biosimilar portfolio, including AMGEVITA, which grew 16% in the previous year.

Yaron Werber asked about Enbrel's performance, noting the lack of a typical Q3 rebound, and questioned if mentioning the large number of Prolia provider accounts was a deliberate signal regarding upcoming biosimilar competition.

Answer

EVP of Global Commercial Operations Murdo Gordon confirmed Enbrel's quarter was soft due to net price declines and an unfavorable sales deduction adjustment, though volume grew 4%. For Prolia, he acknowledged the broad provider base demonstrates its utility and that this market presence could be an advantage against future biosimilar competition.

Yaron Werber followed up on BNT323 (TPEM), asking for more explicit details on the need to generate additional data for filing. He inquired if the plan is to file for breast cancer next year and sought clarity on the feedback received for endometrial cancer, and if filing for that indication is still planned.

Answer

Özlem Türeci, Chief Medical Officer and Co-founder, clarified that the BNT323 BLA submission delay to 2026 is for endometrial cancer, stemming from ongoing discussions with the FDA requiring follow-up data and further analysis, not new data generation. She reiterated that the breast cancer study is ongoing and its data will read out later in 2026.

Yaron Werber followed up on the BNT323 BLA filing delay, asking for more explicit details on whether additional data is needed for a breast cancer filing next year and seeking clarity on the plans for endometrial cancer filing.

Answer

Özlem Türeci, Chief Medical Officer and Co-founder, clarified that the endometrial cancer discussions with the FDA are about follow-up data and further analysis, which pushed the timeline to 2026 but does not change the submission strategy. She reiterated that endometrial cancer is the first submission, and the breast cancer Phase III study is ongoing with data expected later in 2026.

Yaron Werber asked about the competitive differentiation of BNT327, specifically whether it exhibits a cooperative binding effect similar to a competitor's asset and what other differentiating features exist.

Answer

CEO Ugur Sahin responded that the mechanism of BNT327 is more complex than simple cooperative binding and that more detailed data will be presented mid-next year. He described the mechanism as binding to PD-L1 within the tumor microenvironment, which in turn creates an opportunity to bind to VEGF-A, resulting in synergistic activity.

Yaron Werber asked about development plans for BNT327 in second-line EGFR mutant NSCLC and requested details on the upcoming data for BNT323 in second-line endometrial cancer, including endpoints and the basis for a potential filing.

Answer

CEO Ugur Sahin noted encouraging data for BNT327 in the EGFR mutant population and that they are considering ADC combinations. For BNT323, CMO Özlem Türeci explained the potential BLA submission would be based on a single-arm trial in a broad HER2-positive population, with objective response rate (ORR) as the primary endpoint. She confirmed they are in ongoing discussions with regulators.

Yaron Werber from Cowen inquired about the process for COVID-19 vaccine strain selection for the upcoming season, particularly in light of recent changes to the ACIP meeting schedule.

Answer

CSO Ryan Richardson stated that BioNTech is closely monitoring the U.S. policy environment. He expressed the company's expectation that a strain selection will be made and affirmed that BioNTech is prepared to respond rapidly, consistent with its performance in previous years.

Yaron Werber followed up on BNT327, asking if the Phase III trial in TNBC will target patients with CPS less than 10 or all CPS levels, and whether the small cell lung cancer trial's comparator will be chemotherapy alone or chemo plus Tecentriq.

Answer

CEO Dr. Ugur Sahin clarified the initial TNBC trial is intended for the patient population with CPS below 10, with the comparator being chemotherapy alone, but they are evaluating additional trials for the above 10% population. Chief Strategy Officer Ryan Richardson confirmed the comparator for the small cell lung cancer trial will be chemo plus Tecentriq.

Yaron Werber from TD Cowen requested an update on pipeline assets ARGX-121 (IgA sweeping platform) and ARGX-213 (long-acting VHHs of efgartigimod). He also asked for a breakdown of VYVGART's sales growth, specifically how much was driven by CIDP versus gMG, given the doubling of quarterly sales year-over-year and the launch of CIDP and PFS.

Answer

Karen Massey, Chief Operating Officer, confirmed strong growth contributions from both MG and CIDP, noting that MG is the number one biologic brand and growing faster than the market, while CIDP is expanding market share a year post-launch. Tim Van Hauwermeiren, Chief Executive Officer, stated that ARGX-119, ARGX-121, and ARGX-213 are progressing swiftly through Phase I studies, with safety and tolerability as primary interests, and that initial data disclosures are expected soon.

Yaron Werber requested an update on the progress of ARGX-121, the IgA sweeping platform, and ARGX-213, the long-acting VHHs of efgartigimod. He also asked for a breakdown of how much of the recent sales growth was driven by CIDP versus gMG.

Answer

Karen Massey, Chief Operating Officer, confirmed strong growth across both gMG and CIDP, with gMG being the number one biologic and expanding its market, and CIDP showing increased market share. Tim Van Hauwermeiren, Chief Executive Officer, reported that ARGX-119, ARGX-121, and ARGX-213 are swiftly progressing through Phase 1 studies, with a focus on safety, tolerability, and PD effect, and anticipated data disclosure soon.

Yaron Werber from TD Cowen requested an update on the IV-to-subcutaneous switch dynamics for Vyvgart and asked about the trial design and strategy for the new ENERGIZE Phase 3 study of empasiprubart (EMPA) in CIDP, which is a placebo-controlled trial.

Answer

COO Karen Massey reiterated that the subcutaneous strategy is for market expansion, not a forced switch, noting that the IV business continues to grow. CMO Luc Truyen explained the ENERGIZE trial is designed to broaden EMPA's potential by studying it in IVIG-refractory or naive patients, complementing the head-to-head IVIG study and addressing the one-third of CIDP patients who may not be IgG-dependent.

Yaron Werber asked for the number of CIDP patients on therapy at the end of Q1 and sought to triangulate this with the real-world patient data of 1,316 presented at AAN.

Answer

Chief Operating Officer Karen Massey stated that the company is not updating the specific patient number at this time but will do so at future milestones, consistent with past launch practices. She reiterated that the launch shows consistent patient and prescriber growth, with 85-90% of patients switching from IVIG or SCIG, which is in line with expectations and signals a long growth trajectory ahead, to be further driven by the PFS launch.

Yaron Werber asked how value-based agreements (VBAs) expire with the shift to Medicare Part D and whether physicians are formally using scales like INCAT to assess CIDP patient response in the initial 12 weeks.

Answer

Chief Financial Officer Karl Gubitz explained that payer agreements will be re-established for the PFS, and they expect VBAs will not be part of the new pharmacy benefit contracts. Chief Operating Officer Karen Massey added that physicians are generally not using formal scales like INCAT in clinical practice, instead relying on simpler assessments and patient conversations to determine response.

Yaron Werber asked about the potential topics for a future R&D Day and the scientific rationale for prioritizing systemic scleroderma after discontinuing the ANCA-associated vasculitis (AAV) program.

Answer

CEO Tim Van Hauwermeiren said an R&D Day would feature full data for empasiprubart in MMN. He explained that systemic scleroderma was prioritized due to its strong IgG-driven biology, validation from passive transfer models, and a clearer clinical path. This contrasts with AAV, where the confounding effects of background medications posed an unmanageable risk.

Yaron Werber questioned whether the reduction in acute pancreatitis (AP) events for olzarsen would primarily be in patients with a history of AP or if it would show prevention of new events in AP-naive patients. He also asked for clarification on the estimated U.S. HAE patient population, noting discrepancies with other companies' estimates.

Answer

Brett Monia, CEO, Ionis, stated that the AP data would show more events in the high-risk patient population, consistent with expectations that higher triglycerides and prior AP events increase risk. Kyle Jenne, Chief Global Product Strategy Officer, Ionis, confirmed the company is still working with an estimate of 7,000 HAE patients in the U.S., focusing on the 75% on prophylactic therapy as a switch market, and was not aware of an 11,000 patient estimate.

Yaron Werber asked about the potential impact of the Medicare Part D redesign on WAINUA uptake and whether the $6 million Q1 TRYNGOLZA sales figure represents a solid baseline for future growth, given the need for patient identification.

Answer

Chief Global Product Strategy Officer Kyle Jenne stated that partner AstraZeneca believes the Part D redesign will be a net positive for WAINUA, potentially increasing patient starts and compliance due to lower out-of-pocket costs. Regarding TRYNGOLZA, he noted that while new patients are being identified, growth will take time and effort. CEO Brett Monia added that WAINUA's ex-U.S. launches will also contribute to revenue growth.

Yaron Werber from TD Cowen asked how the Angelman Phase III study was powered and questioned which specific milestones were driving the second-half weighted revenue guidance for the year.

Answer

Chief Clinical Development Officer Eugene Schneider explained the Angelman study's powering was based on natural history data and the very encouraging Phase II results for the expressive communication endpoint. CFO Beth Hougen clarified the R&D revenue guidance is not dependent on any single large milestone but rather on continued funding from AstraZeneca for a large study and a host of smaller, back-end loaded milestones from various partnerships.

Yaron Werber from TD Cowen asked about the European cohort in the EMPORER trial, specifically if the 20 patients would be analyzed with the main group and if 1:1 randomization would be used. He also inquired about the expected duration of effect for STK-002 in the ADOA trial.

Answer

Interim CEO Ian Smith clarified that the 20-patient European cohort was added to satisfy specific regulatory requirements for a needle-prick sham and to maintain the integrity of the main 150-patient study. CMO Barry Ticho confirmed 1:1 randomization applies to this cohort. For ADOA, he noted that based on long oligonucleotide half-lives in animal models (9+ months), a single injection is expected to have an effect for the full 12-month trial.

Yaron Werber of TD Cowen inquired about the clinical timeline for ZW191, asking when initial Phase 1 data might be released and seeking more information on the folate receptor alpha expression in non-small cell lung cancer (NSCLC) to characterize the market opportunity.

Answer

CEO Kenneth Galbraith indicated that initial ZW191 data could be presented at a peer-reviewed medical conference in 2025 or 2026, contingent on abstract acceptance. Chief Scientific Officer Paul Moore confirmed folate receptor alpha expression in a subset of NSCLC patients and noted ZW191's design, including its bystander effect, is well-suited for this indication.

Yaron Werber of Cowen and Company asked for an approximate breakdown of Q2 Yorvipath revenue between the U.S. and ex-U.S. markets and sought guidance on a normalized sequential patient growth rate in the U.S.

Answer

President & CEO Jan Møller Mikkelsen confirmed the analyst's assumption of €4-5 million in sequential ex-U.S. revenue growth was accurate, implying the remainder of the growth was from the U.S. He stated it was too early in the launch to provide a normalized growth forecast but noted that new patient enrollment numbers were similar in Q2 compared to Q1.

Yaron Werber inquired about the timing of Takeda's NATPARA withdrawal from the market in both the U.S. and Europe, and how its inventory depletion would impact the YORVIPATH launch.

Answer

Jan Mikkelsen, President and CEO, explained that the timing is controlled by Takeda but expects the major transition to occur in the next year. He noted different uptake patterns in Germany versus Austria, with some physicians switching existing NATPARA patients and others prioritizing new patients, suggesting a dynamic situation for the U.S. launch.

Yaron Werber asked for clarification on the SKYTROFA revenue figures, questioning if the new guidance includes the reported or adjusted first-half revenue and if the adjusted Q2 revenue is a good run rate.

Answer

President and CEO Jan Mikkelsen and CFO Scott Smith clarified the numbers. Mikkelsen confirmed that the 'real' Q2 net sales were approximately €53.4 million after adding back the true-ups, representing a strong sequential increase. He noted the full-year guidance was conservative and did not include potential seasonal upside. Smith added that the reported H1 revenue of €91.2 million was already net of a €7.6 million true-up, meaning the underlying H1 performance was closer to €100 million.

An analyst on behalf of Yaron Werber from TD Securities asked how Genmab views Epkinley's differentiation and opportunity versus Roche's Lunsumio, particularly in follicular lymphoma.

Answer

Chief Medical Officer Tahamtan Ahmadi detailed several differentiators: having a positive Phase III result in second-line follicular lymphoma where the competitor does not, consistently better efficacy signals, the advantage of subcutaneous administration, and a comparable safety profile.

Jaina, on behalf of Yaron Werber from TD Cowen, asked how Genmab views Epkinley's opportunity and differentiation specifically against Roche's Lunsumio, as follicular lymphoma becomes a more significant part of the discussion.

Answer

Tahamtan Ahmadi, EVP & Chief Medical Officer, detailed several differentiators: Genmab has positive Phase III data in second-line FL where the competitor does not; Epkinley has shown superior efficacy signals (ORR/CR rates); its subcutaneous administration is an advantage; and its CRS safety profile is now comparable. He concluded that Genmab feels very positive about its competitive position.

Dinah on for Yaron Werber of TD Securities inquired about the efficacy bar for Rina-S in endometrial cancer and asked for details on the timing and success criteria for the acasunlimab data update.

Answer

CMO Tahamtan Ahmadi noted that while historical second-line endometrial cancer therapies have response rates of 10-15%, he is confident Rina-S data will show a best-in-class profile. CDO Judith Klimovsky stated the acasunlimab update is planned for H2 2025 to allow for meaningful follow-up on the overall survival endpoint, which must beat the comparator's 11-month median.

An associate on behalf of Yaron Werber at TD Cowen asked for a breakdown of DARZALEX market share across different lines of therapy. They also questioned the competitive advantages of EPKINLY's subcutaneous administration versus fixed-duration dosing and asked if EPKINLY would also adopt a fixed-duration regimen.

Answer

Chief Operating Officer Anthony Mancini reported that DARZALEX's growth is driven by frontline use, where new patient share reached 53%. He noted that growth in frontline and second-line settings came at the expense of later lines. Chief Medical Officer Tahamtan Ahmadi described the fixed-duration debate as 'academic,' confirming that EPKINLY will be given for a fixed duration in combination studies due to higher efficacy. He emphasized that subcutaneous delivery is a more fundamental advantage, enabling treatment in more diverse healthcare settings.

Yaron Werber asked what percentage of the 70 new Iptrozy patients were conversions from clinical studies and how many US patients were in the nTrust program. He also questioned if clinical study patients would convert to commercial drug and how the $25 million milestone from their Japanese partner would be recorded.

Answer

CEO Dr. David Hung stated that zero of the 70 new patients were from clinical trials and that patients in the nTrust program will remain on trial to collect long-term durability data. CFO Philippe Sauvage explained that the $25 million milestone payment from their Japanese partner is expected to be recognized at once as revenue later in the year.

Yaron Werber asked what percentage of the 70 new patients were conversions from clinical studies and how many U.S. patients were in the nTrust program. He also questioned whether clinical trial patients would convert to commercial product and how the $25 million milestone payment from their Japanese partner would be recorded.

Answer

David Hung, Founder, President & CEO, stated that zero of the 70 patients were from clinical trials and that 50 U.S. patients were in the nTrust program. He noted that trial patients would remain in the study to track long-term durability. CFO Philippe Sauvage added that the $25 million milestone is expected to be recognized at once as revenue in the latter part of the year.

Yaron Werber from Cowen and Company asked for clarification on the STELLAR-304 trial's dual primary endpoints (PFS and ORR) and about performance expectations for the control arm in the STELLAR-303 trial.

Answer

EVP & CMO Amy Peterson clarified that for STELLAR-304, hitting either of the dual primary endpoints of PFS or ORR would constitute a positive study. She declined to comment on the control arm performance in STELLAR-303, stating the data would be shared at a future medical conference.

Yaron Werber asked about the financial impact of the Medicare Part D redesign in Q1, the company's payer mix, and the breakdown of the $1 billion NET market opportunity between different lines of therapy.

Answer

CFO Christopher Senner noted no significant quarter-over-quarter impact from the Part D redesign and stated the payer mix is roughly equal between commercial and Medicare Part D. EVP of Commercial P.J. Haley clarified the $1 billion NET market is across all lines, but oral small molecules, like CABOMETYX, represent the majority of use in the second and third-line settings, which is a substantial opportunity.

Yaron Werber asked if a zanzalintinib-belzutifan triplet combination should be considered the future first-line RCC therapy and what the go/no-go criteria are for advancing the STELLAR-305 trial to Phase III.

Answer

President and CEO Michael Morrissey addressed the RCC question by stating that the company's overarching goal is to improve the standard of care for patients, which is the strategic driver for its work with zanzalintinib. He deferred specific comments on the trial designs with Merck until an appropriate future time.

Yaron Werber noted the increased emphasis on late-stage deals and asked if this was a new focus and whether the company was open to acquisitions in addition to in-licensing.

Answer

President and CEO Michael Morrissey clarified that the focus on late-stage opportunities is not new, as the company's early-stage pipeline is already full. He confirmed that Exelixis is open to virtually any type of transaction, including acquisitions, provided it is the right asset at the right valuation that can deliver clinically differentiated data.

Yaron Werber asked about the Q1 performance of BRUKINSA, specifically questioning the extent to which the Medicare Part D redesign impacted the BTK inhibitor class. He also requested a sales breakdown for TEVIMBRA by region and an update on API manufacturing capacity for BRUKINSA from the Swiss facility.

Answer

CFO Aaron Rosenberg detailed the Q1 impact of the Part D redesign, noting a net favorability due to the elimination of the coverage gap liability, balanced by their new liability under the small manufacturer designation. Matt Shaulis, GM of North America, added that typical Q1 seasonality, including inventory drawdown and fewer shipping days, also affected revenue. He stated that TEVIMBRA sales are not broken out by region but noted U.S. patient starts are in line with expectations. Rosenberg confirmed the Swiss API supplier approval and mentioned work to secure another supplier in Spain to enhance supply chain resiliency.

Yaron Werber inquired about the Q1 performance of BRUKINSA, asking how much of the market weakness was attributable to the Medicare Part D redesign. He also requested a geographic sales breakdown for TEVIMBRA and asked for an update on BRUKINSA's API supply chain, particularly regarding the Swiss supplier's capacity for the U.S. market.

Answer

CFO Aaron Rosenberg noted that while the Part D redesign has an impact, BeiGene benefits from a small manufacturer designation, resulting in some Q1 favorability. Matt Shaulis, GM of North America, added that Q1 seasonality and inventory changes were also factors and that the company does not break out TEVIMBRA sales by region. Rosenberg confirmed they are diversifying their API supply chain with suppliers in Switzerland and Spain and have significant stockpiles.

Yaron Werber asked about the Q1 performance of BRUKINSA, specifically the impact of the Medicare Part D redesign on the BTK class. He also requested a geographic sales breakdown for TEVIMBRA and inquired about the U.S. supply capacity of their new Swiss API source for BRUKINSA.

Answer

CFO Aaron Rosenberg detailed the Part D redesign's impact, noting some Q1 favorability offset by new manufacturer liabilities phased in over five years. Matt Shaulis, GM of North America, attributed Q1 seasonality to inventory shifts and insurance resets, and stated TEVIMBRA sales are not broken out by region. Rosenberg confirmed the Swiss API approval and mentioned an additional supplier in Spain to enhance supply chain resiliency.

Asked for details on the INFRONT-3 trial, including the statistical power for the primary endpoint, whether the upcoming data readout will be the final dataset, and if it will include key biomarker data.

Answer

The trial is well-powered, with ~90% power to detect a 40% slowing of disease progression. The year-end data will be the complete 96-week dataset for all participants, plus long-term extension data. The FDA has agreed to review the totality of the evidence, including progranulin levels as confirmatory and other biomarkers as supportive, which could provide a path to approval even if the primary clinical endpoint is not met.

Brendan Smith, on behalf of Yaron Werber from TD Cowen, asked about the potential timing of the AbbVie opt-in payment for AL002 and which of Alector's earlier pipeline programs might be the next to enter clinical trials.

Answer

Management, likely CFO Dr. Marc Grasso, clarified that the AL002 data package will be sent to AbbVie in Q4 2024, and AbbVie's 90-day decision window places a potential opt-in payment in late Q1 or early Q2 2025. Regarding the pipeline, the company has several programs and will provide updates on advancement in the coming year without specifying which is next.

An analyst on behalf of Yaron Werber from Cowen inquired about the development plan for IMM-6-415, including ongoing preclinical data collection, potential Phase 1 trial design, and the approach to selecting tumor indications.

Answer

President and CEO Benjamin Zeskind confirmed the IND filing for IMM-6-415 is planned for the end of 2023. He described it as a "universal MAPK" program with a shorter half-life than IMM-1-104, likely for twice-daily dosing. Zeskind emphasized the initial clinical focus would be on monotherapy, citing promising preclinical data. Chief Medical Officer Scott Barrett added that the program's design is evolving to address multiple aspects of the MAP kinase pathway.

Yaron Werber questioned if there were left ventricular ejection fraction or stroke volume benefits in the Danon trial, requested an update on six-minute walk test data, and asked about the potential primary endpoint for a pivotal study.

Answer

CEO Gaurav Shah explained that most patients have preserved ejection fraction until late-stage disease but noted improvements in cardiac output. He added that all three low-dose patients showed stabilization or improvement in the six-minute walk test. For a pivotal trial, endpoints could include biomarkers like BNP, functional measures like the six-minute walk test, or quality of life metrics like NYHA class, pending FDA discussions.