Mohit Bansal

Mohit Bansal asked for an update on the percentage of Repatha prescriptions originating from primary care and how the primary care segment of the market is expected to evolve following the VASALIS data.

Answer

Murdo Gordon, EVP of Global Commercial Operations, stated that approximately 40% of Repatha prescriptions were from primary prevention patients before the VASALIS data, expecting this percentage to increase. He noted strong interest from both cardiologists and primary care physicians in the VASALIS data, particularly for diabetes patients.

Mohit Bansal from Wells Fargo inquired about the current percentage of Repatha prescriptions originating from primary care physicians and the anticipated evolution of this segment following the presentation of the VESALIUS data.

Answer

Murdo Gordon, EVP of Global Commercial Operations, stated that approximately 40% of Repatha prescriptions were from primary prevention patients before the VESALIUS data promotion, a figure he expects to increase. He noted equal interest from cardiologists and primary care physicians, with PCPs showing greater alignment towards adding Repatha to optimized statin therapy. Gordon anticipates continued momentum for Repatha, supported by incremental investments.

Mohit Bansal asked about the expected cadence of biosimilar erosion for the denosumab franchise, which includes Prolia and XGEVA.

Answer

Murdo Gordon, EVP of Global Commercial Operations, confirmed that due to settlement timing, the erosion is expected to be more back-half loaded. He suggested the erosion curves could differ between XGEVA (oncology) and Prolia (osteoporosis) and stated that Amgen's incumbency and market leadership position them well to defend the brands.

Mohit Bansal asked whether the ongoing MariTide Phase II trial, which includes patients with both obesity and diabetes, would be sufficient to provide meaningful data on the drug's A1C profile.

Answer

EVP of R&D James Bradner (misattributed as Murdo Gordon in transcript) responded that while they expect some insights into anti-diabetic activity from the current study, a dedicated Phase II trial in diabetes patients (particularly those without obesity) is necessary for a full characterization, and that study has been initiated.

Mohit Bansal from Wells Fargo & Company sought to understand the target profile for the VESPER Phase 3 trial, specifically whether Pfizer expects higher weight loss than the mid-to-high teens typically seen with optimized GLP-1s while maintaining better tolerability, or if monthly dosing is the primary differentiator.

Answer

Dr. Chris Boshoff, Chief Scientific Officer, Pfizer, stated that the expectation is for both competitive weight loss and competitive tolerability, with monthly dosing being a key differentiator. He noted that predictions for the 9.6 mg dose suggest 16% weight loss at week 28, which is highly competitive. He also mentioned plans for a Phase 3 study evaluating switching patients from weekly to monthly therapy.

Mohit Bansal sought to understand the target profile for Pfizer's VESPER phase III trial, specifically whether the longer-acting GLP-1 is expected to provide higher weight loss with better tolerability, or if monthly dosing is considered the primary differentiator.

Answer

Chief Scientific Officer Chris Boshoff confirmed that Pfizer expects both competitive weight loss and tolerability, with predictions for the 9.6 mg dose showing 16% weight loss at week 28, and monthly dosing as a key differentiator. He also mentioned plans for a phase III study evaluating switching patients from weekly to monthly dosing for maintenance.

Mohit Bansal asked about Pfizer's thought process regarding the pricing of GLP-1 medicines, given potential price declines, and how this context justifies the acquisition price paid for Metsera.

Answer

Albert Bourla, Chairman and CEO, Pfizer, stated that Pfizer's calculations for the Metsera acquisition already took into consideration the expectation that GLP-1 prices would likely decrease due to increasing competition in the market.

Mohit Bansal asked about Pfizer's thought process regarding GLP-1 pricing, especially with news suggesting potential price declines. He questioned how Pfizer justifies the MedSera acquisition price in light of these pricing trends and its long-term view on the obesity landscape.

Answer

Albert Bourla, Chairman and CEO, acknowledged that competition drives prices down and confirmed that Pfizer's calculations for the MedSera acquisition already took into consideration the likelihood of GLP-1 prices starting to decline.

Mohit Bansal from Wells Fargo Securities, LLC asked for the thought process behind maintaining the full-year revenue guidance despite a strong quarter, operational beats, and favorable foreign exchange rates.

Answer

CFO Dave Denton explained that while the underlying business strength is strong, allowing for a 30-cent EPS guidance raise (before the 3S Bio charge), the company believes it is prudent to hold revenue guidance steady. This approach derisks the second half of the year, particularly given the potential volatility in COVID-related revenues.

Mohit Bansal of Wells Fargo Securities, LLC asked for the thought process behind maintaining the full-year revenue guidance despite a strong quarterly performance and other tailwinds like favorable foreign exchange.

Answer

EVP & CFO Dave Denton explained that while the EPS guidance was raised by $0.30 on an operational basis, the company is choosing to de-risk the second half of the year. He cited the potential volatility of COVID-19 revenues, which are concentrated in Q3 and Q4, as the primary reason for prudently holding the revenue guidance at this time.

Mohit Bansal asked whether the administration's focus is on onshoring the entire manufacturing process, including API and drug substance, and how feasible this would be.

Answer

CEO Albert Bourla responded that for products deemed critical to national security, the administration is looking at the entire value chain, including precursors and APIs. He acknowledged that transferring manufacturing is a multi-year process, suggesting the focus would likely be on a manageable number of the most vital products.

Mohit Bansal inquired about the market share evolution for the Prevnar franchise in pediatric versus adult populations, considering new competition and expanded eligibility.

Answer

Executive Alexandre de Germay noted strong international performance, with Prevnar 20 rapidly recapturing share where approved, such as in Japan. Executive Aamir Malik stated that in the U.S., Pfizer expects to maintain meaningful adult market share despite new competition and sees growth opportunities in the 50-64 age group, while the pediatric market remains stable with high share.

Mohit Bansal asked if there was any channel stocking for ABRYSVO in the quarter and how to think about the product's performance in the coming quarters.

Answer

An executive, likely Chief U.S. Commercial Officer Aamir Malik, confirmed that Pfizer worked with channel partners to ensure appropriate stocking in Q3 to prepare for the vaccination season. He emphasized that performance is also being driven by strong execution and a significant increase in market share, which reached 43% in the retail setting by mid-October.

Mohit Bansal asked about the CD388 (MK-1406) asset, specifically inquiring about the potential for interim data disclosure from the ANCHOR trial, given the strong flu season, and the rationale for running the full trial across two geographies and seasons.

Answer

Dean Li, President of Research Laboratories, Merck & Co. Inc, emphasized the importance of generating robust data across various subpopulations for the MK-1406 ANCHOR trial, especially given the severe flu season. He confirmed that enrollment in the Northern Hemisphere is complete, with parallel recruitment ongoing in the Southern Hemisphere, but did not comment on specific interim disclosure plans.

Mohit Bansal inquired about the CD388 (MK-1406) asset, specifically its potential for interim data given the strong flu season, and whether the trial would run to full completion or if an interim disclosure could be expected.

Answer

Dean Li, President of Research Labs, explained that while the flu season was severe, enrollment for the Northern Hemisphere was complete, and parallel recruitment was ongoing in the Southern Hemisphere. He emphasized the need for robust data across subpopulations and did not commit to specific interim communication plans, highlighting the asset's potential as a first-in-class, once-per-season, strain-agnostic antiviral.

Mohit Bansal of Wells Fargo Securities questioned the updated full-year guidance, noting that the upper end of the ex-FX revenue growth range appeared to be lowered and asked if this reflected any change in the underlying operational business.

Answer

EVP & CFO Caroline Litchfield clarified that the midpoint of the revenue guidance was maintained. She explained that a modest foreign exchange tailwind was offset by headwinds from lower-than-expected COVID cases impacting Lagevrio and an early biosimilar entry for Januvia in Argentina. She reaffirmed confidence in the underlying business growth of 6-8% when excluding the Gardasil China impact.

Mohit Bansal from Wells Fargo Securities asked for clarification on the updated revenue guidance, noting that the upper end of the growth range appeared to be lowered on an FX-neutral basis.

Answer

EVP & CFO Caroline Litchfield clarified that the revenue midpoint was maintained. A modest FX tailwind was offset by headwinds, including lower COVID cases impacting Lagevrio and an early biosimilar entry for pembrolizumab in Argentina. She reiterated confidence in the underlying business growth of 6-8% when excluding Gardasil in China.

Mohit Bansal from Wells Fargo questioned Merck's business development strategy, suggesting recent deals from China appear to be 'chasing frontrunners' rather than pursuing innovation.

Answer

Dr. Dean Li countered by highlighting first-in-class acquisitions like Acceleron and EyeBio, and framed other deals as part of a coordinated strategy combining external assets with Merck's internal pipeline. CEO Robert Davis reinforced this, describing the strategy as balanced between first-in-class and best-in-class opportunities.

Mohit Bansal asked for clarification on the GARDASIL situation in China, specifically questioning the level of inventory held by its partner Zhifei and whether the planned shipment pause would be sufficient to resolve the issue.

Answer

CEO Robert Davis declined to specify inventory levels, citing Zhifei's status as a public company. He explained the intent of the shipment pause is to accelerate the inventory drawdown and improve Zhifei's financial position. He reframed the situation by noting that after this rebasing, GARDASIL in China represents only about 1% of Merck's total revenue, making any future recovery an upside to the company's growth story.

Mohit Bansal of Wells Fargo inquired about the V940 personalized cancer vaccine, asking what earlier-stage data supported the decision to advance into a Phase III trial for lung cancer.

Answer

Dr. Dean Li explained that the strategy leverages KEYTRUDA's proven efficacy in earlier-stage cancers. The V940 lung cancer trial is specifically designed for patients who do not achieve a pathological complete response after perioperative KEYTRUDA-based treatment. This patient population represents a clear unmet need, providing a strong rationale for testing a new combination therapy like V940.

Mohit Bansal asked about the company's confidence in VEGF PD-1 bispecifics, specifically addressing the perception that while VEGF inhibition might be better, the PD-1 component might not be, and the importance of OS benefit in lung cancer given good PFS but potentially borderline OS.

Answer

Uğur Şahin, Chief Executive Officer and Co-founder, stated that confidence in the bispecific class is increasing, based on the overall action of the molecule, which is showing an impact on overall survival. Özlem Türeci, Chief Medical Officer and Co-founder, added that preclinical data demonstrated robust blocking of both PD-1 and VEGF-A pathways, not inferior to individual antibodies. She also highlighted that the PD-1 arm targets the tumor microenvironment, amplifying the effects of both targets, and current clinical data across tumor indications, while not yet Phase III, shows promising PFS effects and duration.

Mohit Bansal asked about the VEGF PD-1 bispecific class, noting that experts often perceive them as better VEGF inhibitors but not necessarily better PD-1 inhibitors. He sought BioNTech's perspective on this and the importance of a superior PD-1 component, given observed PFS benefits and borderline OS benefits in lung cancer trials.

Answer

Uğur Şahin, Chief Executive Officer and Co-founder, stated that confidence in the class is increasing, driven by the bispecific molecule's overall impact, including on overall survival. Özlem Türeci, Chief Medical Officer and Co-founder, added that preclinical data showed robust blocking of both PD-1 and VEGF-A pathways, not inferior to individual antibodies. She also highlighted the PD-1 arm's role in targeting the tumor microenvironment to amplify the effects of both targets.

Mohit Bansal inquired about the timeline for completing the Phase II portion of the Rosetta Lung-02 study and sought commentary on the importance of BNT327's molecular differences, such as using a PD-L1 binder and its specific format.

Answer

CMO Özlem Türeci stated the Phase II portion will conclude later this year, providing the dose for the Phase III portion, which will also begin this year. She explained the PD-L1 component was deliberately chosen for its potential for superior anchoring in the tumor microenvironment, and the molecular format was selected for optimal cross-ligation.

Fadi Arman, on behalf of Mohit Bansal from Wells Fargo, asked about the potential read-through from competitor data to BNT327 in lung cancer and how BioNTech's NSCLC development strategy differs.

Answer

CEO Ugur Sahin detailed their distinct approach for the BNT327 non-small cell lung cancer trial. He described it as a comprehensive study covering the full spectrum of first-line patients, including PD-L1 high, low, and negative populations across both squamous and non-squamous histologies. The trial uses pembrolizumab plus chemotherapy as the comparator arm.

Mohit Bansal asked about the competitive outlook for oral IL-23s versus SKYRIZI or RINVOQ and the importance of a portfolio of assets (like amylin with Gubra) to compete in the obesity segment.

Answer

Roopal Thakkar, Executive Vice President, Research and Development, Chief Scientific Officer, emphasized SKYRIZI's strong psoriasis efficacy, quarterly dosing, head-to-toe benefits, and long-term X-ray progression data in psoriatic arthritis, positioning it strongly against oral competitors. Jeff Stewart, Executive Vice President, Chief Commercial Officer, reiterated confidence in SKYRIZI's competitive position. On obesity, Roopal Thakkar stated that AbbVie's amylin focus is on tolerability and durability, exploring combinations with GLPs and other orthogonal approaches to maintain bone/muscle, given low long-term adherence to incretins.

Mohit Bansal asked about AbbVie's competitive strategy against oral IL-23s compared to SKYRIZI and RINVOQ, and the importance of having a portfolio of obesity assets, including Amlin, to compete effectively.

Answer

EVP, Research and Development, and CSO Roopal Thakkar and EVP and CCO Jeff Stewart emphasized SKYRIZI's strong psoriasis efficacy (PASI 90/100 rates), quarterly dosing, head-to-toe benefits, and long-term maintenance, positioning it strongly against oral and injectable competitors. Roopal Thakkar also discussed the Amlin asset's focus on tolerability and durability, and the ongoing exploration of combination agents and orthogonal approaches in obesity.

Mohit Bansal of Wells Fargo Securities questioned the potential impact of STELARA biosimilars on AbbVie's SKYRIZI and RINVOQ sales momentum, asking if it could mirror the dynamic seen with HUMIRA biosimilars.

Answer

EVP & Chief Commercial Officer Jeffrey Stewart explained that while some patient movement occurs, the primary driver for SKYRIZI and RINVOQ growth is their strong clinical data, making the biosimilar impact minor. CEO Robert Michael reinforced this, noting SKYRIZI's share gains against STELARA pre-dated the biosimilar launch due to superior head-to-head trial results.

Mohit Bansal of Wells Fargo & Company asked for AbbVie's strategic thinking on its Amylin obesity program, specifically whether it's viewed primarily as a stand-alone agent for patients who can't tolerate other therapies or as part of a combination strategy.

Answer

CSO Roopal Thakkar explained that AbbVie is thinking broadly about the Amylin program's potential. As a monotherapy, its tolerability could be key to addressing high discontinuation rates seen with current assets. It could also serve as a follow-on therapy. For combinations, the asset's neutral pH formulation is an advantage, and AbbVie remains interested in adding other mechanisms to drive further weight loss while prioritizing tolerability and durability.

Mohit Bansal asked about the underlying market dynamics driving rapid volume growth in the immunology space, beyond the benefit from Humira biosimilar disruption, and the long-term outlook for overall market growth.

Answer

EVP & CCO Jeffrey Stewart explained that while some volume comes from Humira switches, the primary driver is buoyant market growth fueled by the expansion of second and third lines of therapy, especially in atopic dermatitis and IBD. CEO Robert Michael provided specific market growth projections: high single-digits for psoriasis and IBD, mid-teens for atopic dermatitis, and low-to-mid single digits for rheumatoid arthritis.

Mohit Bansal from Wells Fargo asked about the head-to-head trial of SKYRIZI against ENTYVIO, seeking insight into the company's confidence and whether the trial aims for superiority or non-inferiority.

Answer

CSO Roopal Thakkar explained that confidence stems from SKYRIZI's very high endoscopic improvement rates in naive ulcerative colitis patients. He stated the trial will aim for superiority on the objective endpoint of endoscopic improvement, which is highly predictive of long-term outcomes.

Mohit Bansal asked for Lilly's thoughts on the EVOKE trial and GLP/GIPs in Alzheimer's disease, how the space is evolving, and if brunepatide, a new GLP/GIP with neural properties, could be a drug for Alzheimer's.

Answer

Dan Skovronsky, CSO and President of Lilly Immunology, stated that Lilly closely follows the space as leaders in both Alzheimer's and incretin therapy. He acknowledged retatrutide's attributes for CNS indications, including potential for Alzheimer's, but noted no specific plans are laid out yet. He anticipates informative EVOKE data and believes Lilly has opportunities to build in the space regardless of the outcome.

Mohit Bansal sought insights on the EVOKE trial and the broader role of GLP/GIPs in Alzheimer's disease, specifically asking if brunepatide, with its neural properties, could be a potential treatment for Alzheimer's.

Answer

Dan Skovronsky, Chief Scientific Officer and President of Lilly Immunology, confirmed close monitoring of the space and excitement for retatrutide's CNS attributes. He mentioned awaiting EVOKE data and seeing opportunities to build on Lilly's strong portfolio regardless of that outcome.

Mohit Bansal from Wells Fargo Securities, LLC asked about the gender split in the orforglipron ATTAIN-1 study and whether there were any notable differences compared to prior GLP-1 trials.

Answer

Kenneth Custer, President of Lilly Cardiometabolic Health, stated that the gender split was approximately 64% female, which was well-balanced across all study arms. He concluded that there was 'nothing really to remark on' regarding the demographic.

Mohit Bansal revisited the CVS announcement, asking for Lilly's view on whether it signals a price war or is a strategic move by CVS to provide more affordable access to a smaller employer base, and how the GLP-1 versus access dynamic will evolve.

Answer

CEO David Ricks suggested the questions were better directed to competitors and CVS but noted the formulary change applies to a smaller book of business with low employer opt-in rates. He acknowledged the possibility that a lower net price from a competitor could increase employer opt-ins, which would be a net positive for the category. However, he reiterated Lilly's focus on innovation and differentiation, stating that reducing patient choice seems like the wrong approach for this market.

Mohit Bansal from Wells Fargo & Company asked about prescriber and payer discussions for Zepbound's sleep apnea indication, particularly regarding the potential bottleneck from a shortage of sleep specialists.

Answer

Executive Patrik Jonsson acknowledged the need for significant medical education. He said efforts are starting with the receptive sleep specialist community but that the strategy requires moving into primary care to reach the large, undiagnosed patient population.

Mohit Bansal of Wells Fargo asked about the market access outlook for 2025, considering the ramp-up in demand generation and reports of some payers tightening restrictions.

Answer

Patrik Jonsson, President of Lilly Cardiometabolic Health and Lilly USA, reported strong access for Mounjaro (93%) and Zepbound (nearly 90% commercial), with a positive trend in employer opt-ins and growing Medicaid coverage. Ilya Yuffa, President of Lilly International, added that OUS access is also progressing well in key markets for both reimbursed and self-pay channels.

Mohit Bansal asked for Bristol Myers Squibb's impression of the overall survival (OS) data from Summit's VEGF PD-1 program and inquired about the strategic approach for their own VEGF PD-1 program, specifically whether it targets indications where PD-1s or VEGFs work well, or if it aims to improve VEGF efficacy.

Answer

Adam Lenkowsky, Chief Commercialization Officer, expressed encouragement by the magnitude and consistency of the PFS data, anticipating it will translate into survival benefit, and affirmed conviction in their broad development plan for pomitomig. He outlined a twofold strategy: becoming a new standard of care in indications like NSCLC and SCLC, and expanding beyond traditional PD-1/PD-L1 areas into MSS CRC. He also highlighted the potential for combining pomitomig with novel combinations.

Mohit Bansal asked for Bristol Myers Squibb's impression of Summit's VEGF PD-1 data, particularly regarding overall survival (OS). He also inquired about the strategic approach for VEGF PD-1 bispecifics, whether it involves targeting indications where PD-1s or VEGFs work well, or if it aims to improve VEGF efficacy.

Answer

Chief Commercialization Officer Adam Lenkowsky stated that the magnitude and consistency of the PFS data seen, including competitor data, adds to the conviction in Pumitomig's broad development plan, expecting it to translate into survival benefit. He outlined a twofold strategy: establishing Pumitomig as a new standard of care in indications like first-line non-small cell lung cancer and small cell lung cancer, and expanding into areas where PD-1/PD-L1s have shown limited activity, such as MSS CRC. He also highlighted the potential for novel combinations.

Mohit Bansal asked a high-level question about the company's R&D strategy and risk tolerance for its future pipeline, particularly in light of recent clinical setbacks and ongoing cost rationalization efforts.

Answer

CEO Christopher Boerner asserted that his confidence in the internal R&D pipeline remains unchanged, noting the recent setbacks have minimal financial impact and do not alter the company's long-term growth prospects. Chief Medical Officer Samit Hirawat highlighted the R&D organization's high productivity, citing 43 major approvals in five years and a plan for over 10 new molecular entities by the end of the decade.

Mohit Bansal of Wells Fargo inquired about the growth outlook for Eliquis in 2025, noting previous expectations that it could see a tailwind from the Medicare Part D redesign.

Answer

CFO David Elkins confirmed that Eliquis will see favorability in the U.S. from the Part D redesign, which will invert its historical sales pattern, making Q1 the lowest quarter and the second half of the year stronger than the first. Despite this quarterly shift, he affirmed that the company expects strong double-digit growth for Eliquis for the full year, driven by its growing market share.

An analyst on for Mohit Bansal asked about the KarXT (Cobenfi) development plan, specifically regarding the dosing regimen in the Alzheimer's disease psychosis trial and the design of the upcoming cognition trial.

Answer

Head of Global Drug Development Samit Hirawat explained that while the current AD psychosis program uses three-times-daily dosing, the company is actively developing a twice-daily (BID) formulation for new studies and is planning a bridging program to incorporate it into the ongoing AD psychosis study. He cited the drug's dual M1/M4 mechanism as the basis for its potential in cognition.

Mohit Bansal asked for more information and timelines regarding the Department of Justice investigation mentioned in the 10-Q filing.

Answer

Kyle Gano, Chief Executive Officer, confirmed receipt of a Civil Investigative Demand (CID) from the DOJ in August, requesting documents related to INGREZZA's sales, marketing, and promotion. He stated the company is fully cooperating, has a robust compliance program, and will continue business as usual, updating the community on material information.

Mohit Bansal asked for more information regarding the Department of Justice investigation mentioned in the 10-Q filing and its potential timelines.

Answer

Kyle Gano, Chief Executive Officer, confirmed receipt of a Civil Investigative Demand (CID) from the DOJ in August, requesting documents related to INGREZZA's sales, marketing, and promotion. He stated the company is fully cooperating, has a robust compliance program, and will continue business as usual, providing updates when material information is available.

A representative for Mohit Bansal asked for clarification on INGREZZA's gross-to-net dynamics, including any tailwind from Part D redesign, and inquired about the design of the NBI-'568 Phase III program.

Answer

CFO Matthew Abernethy confirmed the Medicare Part D redesign provided a slight tailwind of about 1%, but this was more than absorbed by new contracting. CMO Dr. Eiry Roberts detailed that the first NBI-'568 Phase III study is U.S.-only, uses a simple 1:1 randomization against placebo with the 20mg dose, and leverages learnings from Phase II to maintain efficiency.

Mohit Bansal pointed out that the low end of INGREZZA's guidance implies flat sales from Q4 and asked if this reflects a major change in contracting or pricing, and if the sales force expansion benefit is included in the guidance.

Answer

Chief Financial Officer Matthew Abernethy clarified that new contracts with incremental rebates largely offset the annual price increase, resulting in a 'flattish' year-over-year price. He confirmed the guidance range does include the expected benefit from the sales force expansion, which is anticipated to build momentum in the second half of the year, with the high end of the range reflecting a quicker contribution.

Mohit Bansal of Wells Fargo asked for Neurocrine's perspective on upcoming competition in the congenital adrenal hyperplasia (CAH) space, particularly from an ACTH antagonist.

Answer

CEO Kyle Gano explained that Crinecerfont works upstream to regulate the HPA axis by controlling ACTH, which in turn reduces androgens and allows for lower glucocorticoid use. He positioned the competitor's ACTH antagonist as working downstream, focusing only on androgens. He expressed confidence in Crinecerfont's position due to its strong efficacy and safety data in both adults and children.

Mohit Bansal noted that experts believe ivonescimab's VEGF component is superior to previous VEGFs, but its PD-1 component's superiority is less clear. He asked if this distinction poses an issue for achieving an OS benefit, given that PD-1s are often associated with long-term survival tails, and sought clarification on Summit Therapeutics' confidence in OS.

Answer

Jack West, VP of Clinical Development, stated that it's difficult to over-impute the value of one side of a molecule and that the focus should be on the totality of the data (efficacy and tolerability). Allen Yang, Head of R&D Strategy, added that the two components are hypothesized to cooperate, with data showing they are better than the sum of their parts, and that VEGF may play a role in immunotherapy. He also highlighted the safety profile as a differentiator.

Mohit Bansal asked if it's fair to assume that most Overall Survival (OS) events in the HARMONi-2 trial occurred in the low PD-L1 patient subgroup. He also inquired about the company's strategy for pursuing indications outside of lung cancer where a VEGF/PD-1 combination could offer a more pronounced benefit.

Answer

Executive Dave Gancarz deferred comment on the HARMONi-2 OS subgroup analysis to their partner Akeso. For indications beyond lung cancer, Gancarz pointed to promising Phase II data in microsatellite stable colorectal cancer and triple-negative breast cancer. Chief Medical Officer Dr. Allen Yang added that the company has a clear plan based on scientific rationale and Akeso's data. Dr. Jack West noted that ivonescimab's cooperative binding mechanism, not just its VEGF component, may be key to its efficacy in tumors where PD-1 inhibitors have previously failed.

Mohit Bansal asked if it's fair to assume most OS events in HARMONi-2 occurred in low PD-L1 patients and inquired about other indications outside lung cancer where a VEGF/PD-1 combo could show a more pronounced benefit.

Answer

Executive Dave Gancarz deferred the HARMONi-2 subgroup question to partner Akeso. For other indications, he pointed to Akeso's Phase II data in areas like microsatellite stable colorectal cancer. Chief Medical Officer Dr. Allen Yang added that their expansion plan is driven by Akeso's Phase II data and where VEGF/PD-1 activity overlaps. Dr. H. Jack West, VP, noted ivonescimab's cooperative binding mechanism may also be key to its broad potential.

An analyst on behalf of Mohit Bansal from Wells Fargo asked about managing potential overlapping toxicities with Pfizer's vedotin-based ADCs, patient characteristics in the HARMONi study regarding prior TKI usage, and how the PFS curve might differ in the global study versus the China-only HARMONi-2 trial.

Answer

An executive explained that safety run-ins are standard for any new combination. Dr. Allen Yang, Chief Medical Officer, added that emerging data with similar combinations suggest feasibility and they don't expect surprises. Dr. Yang also clarified that HARMONi study patients were eligible regardless of prior TKI sequencing and they expect no efficacy differences. An executive pointed to the Phase II AK112-201 data as the best early indicator for the ivonescimab plus chemotherapy combination.

Mohit Bansal from Wells Fargo Securities inquired about the logistical dynamics of the Yes2Go launch, specifically how Gilead is managing the transition for prescribers from oral medications to an in-office injectable.

Answer

Chief Commercial Officer Johanna Mercier detailed a flexible, multi-channel approach prepared for the launch. This includes options for clinics to use buy-and-bill, send prescriptions to a specialty pharmacy for fulfillment, or refer patients to an alternate site of care. She highlighted the success of their 'pod' model, where cross-functional teams (including nurse educators and reimbursement specialists) meet with clinics together to streamline the process and answer all logistical questions at once, which has been highly effective and appreciated by customers.

Mohit Bansal from Wells Fargo Securities asked about the launch logistics for Yes2Go, specifically how Gilead is managing the shift from orals to an injectable and navigating the buy-and-bill versus specialty pharmacy models.

Answer

Chief Commercial Officer Johanna Mercier explained that Gilead offers flexibility: physicians can use buy-and-bill, prescribe via specialty pharmacy, or refer to an alternate care site. She noted a key success factor is the use of cross-functional 'pods' (sales, medical, reimbursement) that meet with clinics together to simplify the process and answer all logistical questions at once, which has been received very positively by customers.

Mohit Bansal asked for commentary on two macro themes: the potential impact of NIH funding cuts on HIV awareness, and the potential impact of Medicaid cuts on Gilead's business.

Answer

CEO Daniel O'Day stated that it is too early to speculate on Medicaid and that no impact has been seen from funding discussions that would alter their HIV launch plans. CCO Johanna Mercier added that Gilead is prepared to accelerate its own community and education programs to fill any potential gaps. Regarding Medicaid, she expressed confidence that HIV patients would find other coverage channels if needed, supported by state and Gilead programs, due to the critical nature of the therapy.

Mohit Bansal sought clarification on the drivers of HIV sales growth, asking if the mention of 'favorable inventory dynamics' year-over-year implied a larger-than-normal inventory build in the fourth quarter.

Answer

Chief Commercial Officer Johanna Mercier explained that while strong demand was the primary driver, the inventory build in 2024 was more concentrated in Q4 compared to 2023, when it was spread across Q3 and Q4. This timing difference accounted for the year-over-year dynamic.

Mohit Bansal from Wells Fargo asked about the conversion rate of patient start forms to patients on drug, the current market penetration, and how the market might evolve with more competition. He also followed up on the expected cadence of patient start forms going forward.

Answer

CCO Peter Heerma stated the conversion rate is at the top end of rare disease benchmarks and that the key opportunity is in the 70% of patients with proteinuria below 1.5 g/g. CEO Dr. Eric Dube noted that penetration is still below 10% of the addressable market, leaving significant room for growth. Regarding competition, Heerma expressed confidence that Filspari will remain the market leader due to its strong, recognized profile.

An analyst on behalf of Mohit Bansal asked for details on the expanding prescriber base post-full approval, specifically the average number of IgAN patients treated by new prescribers, to gauge the depth of the market.

Answer

CCO Peter Heerma explained that their strategy involves targeting approximately 6,000 of the 10,000 U.S. nephrologists, who collectively treat about 85% of IgAN patients. He noted that many of these physicians have 5-10 IgAN patients. CEO Eric Dube added that unlike other rare diseases, IgAN is not highly concentrated in a few centers, which requires a broad commercial reach but also signals a substantial, untapped opportunity for growth.

Mohit Bansal of Wells Fargo Securities, LLC inquired about the potential risk to Vertex from the government's 'most favored nation' letters, particularly concerning the company's Medicaid exposure.

Answer

President and CEO Dr. Reshma Kewalramani confirmed that Vertex has not received a letter regarding this matter. She added that the company maintains open lines of communication with Washington D.C. and is closely monitoring the situation.

Mohit Bansal of Wells Fargo asked for a comparison between the mechanisms of action for Lyrica and suzetrigine (VX-548), and questioned whether Lyrica has shown efficacy in neuropathic pain related to lumbosacral radiculopathy (LSR).

Answer

CEO Dr. Reshma Kewalramani clarified that the mechanisms are entirely different: gabapentinoids like Lyrica are CNS depressants, whereas suzetrigine specifically targets NaV1.8 pain channels in the peripheral nervous system. She noted that while Lyrica is approved for DPN, it is not approved for LSR in the U.S.

Mohit Bansal from Wells Fargo questioned the potential for zanidatamab to become a first-line agent in HER2-positive breast cancer, noting physician comfort with the existing Cleopatra regimen, and asked about the necessary clinical trials.

Answer

Bruce Cozadd, Chairman and CEO, clarified that the primary strategy is not to replace the frontline standard but to position zanidatamab *after* ENHERTU, which is moving into the frontline setting. He emphasized that the ongoing EmpowHER BC 303 trial is designed to show activity in this post-ENHERTU setting, a space where no other HER2 therapies are being evaluated, representing a very meaningful opportunity.

Mohit Bansal of Wells Fargo requested a deeper understanding of the HERIZON-GEA trial design, particularly the role of the triplet arm (Arm C), and asked how investors should interpret the data given it is not powered to show superiority over the doublet arm (Arm B).

Answer

Robert Iannone, EVP and Global Head of R&D, clarified that Ziihera aims to be the HER2 agent of choice regardless of PD-L1 status. He explained that for the triplet regimen to be approved, it must demonstrate superiority over the control arm (Arm A) and a favorable benefit/risk profile compared to the doublet arm (Arm B), but a direct statistical win of Arm C over Arm B is not a required component of the trial design.

Mohit Bansal of Wells Fargo asked for more detail on the triplet arm (Arm C) of the HERIZON-GEA trial, its market importance, and how investors should interpret the results given its statistical design.

Answer

EVP, Global Head of R&D Rob Iannone argued that the standard of care remains Herceptin-chemo for a high proportion of patients. He stated that Ziihera aims to be the HER2 agent of choice regardless of PD-L1 status. For the triplet arm to be approved, it must be superior to the control arm (Arm A) and offer a better benefit/risk profile than the doublet arm (Arm B).

An analyst on behalf of Mohit Bansal at Wells Fargo asked if the lowered oncology guidance was solely due to the Rylaze protocol change or if slower uptake in the AYA market was also a contributing factor.

Answer

CEO Bruce Cozadd provided a direct response, confirming that the revision to the oncology guidance was entirely attributable to the temporary revenue impact on Rylaze resulting from the updated treatment protocols.

An analyst on behalf of Mohit Bansal asked if the lowered oncology guidance was entirely due to the Rylaze pediatric protocol change or if slower-than-expected uptake in the adolescent and young adult (AYA) market was also a factor.

Answer

CEO Bruce Cozadd gave a direct response, stating, 'It's entirely due to that temporary impact we're seeing on Rylaze. That's what drove the change.'

An analyst on behalf of Mohit Bansal from Wells Fargo asked about the upcoming BMN 351 data, specifically whether the 10% dystrophin level is the sole determinant for the program's future or if other parameters will be considered.

Answer

Greg Friberg, Chief R&D Officer, clarified that while the 10% dystrophin level at steady state is a key goal, the decision will be informed by the totality of data, including safety and PK. He noted that a model predicts the initial 25-week data will provide a line of sight to achieving that goal, and that functional outcomes, while being measured, will be more informative later in the study.

Mohit Bansal asked about the assumed length of the BMN 333 pivotal trial and if there was room to accelerate its timeline before 2030. He also inquired about the strategy driving Naglazyme's strong performance and its future outlook.

Answer

EVP, Worldwide R&D Greg Freiberg noted that while there are too many variables to define the Phase III design for BMN 333 now, there are scenarios where the timeline could be accelerated if the product profile is strong. EVP, Chief Financial Officer Brian Mueller explained that Naglazyme's performance, which benefited from some order timing, exemplifies the durability of the ERT portfolio, with future growth expected from new initiatives not yet implemented.

Mohit Bansal asked for clarification on the guided 10% sequential royalty decline for Q1 2025 and how the uptake of the VYVGART prefilled syringe is factored into the company's financial guidance.

Answer

CFO Nicole LaBrosse attributed the sequential royalty decline to annual contractual rate resets, primarily for DARZALEX, which temporarily lowers the rate at the start of the year. President and CEO Dr. Helen Torley added that the company's guidance already incorporates the potential upside from the VYVGART prefilled syringe, as it is based on projections provided by their partner, Argenx.

Mohit Bansal from Wells Fargo & Company asked about Halozyme's guidance philosophy for future years and how differentiated the MDASE platform is from ENHANZE, particularly concerning potential conflicts with existing exclusive partner licenses.

Answer

CFO Nicole LaBrosse stated that the focus is on the current year's guidance, with 2025 details to come in the new year. President and CEO Dr. Helen Torley clarified that MDASE covers different molecular structures and a distinct patent portfolio from ENHANZE. Therefore, licensing MDASE does not conflict with or infringe upon exclusive ENHANZE partner agreements.

Mohit Bansal of Wells Fargo asked about the expected differences between ambulatory (ABPM) and in-office (AOBP) blood pressure results, the read-through from Advance-HTN to Launch-HTN, and how lorundrostat's half-life affects nighttime blood pressure coverage.

Answer

Executive Jon Congleton highlighted the tight concordance between measurement methods in the Target-HTN trial but was hesitant to project a direct read-through from Advance to Launch due to differing study designs. He reiterated strong confidence in 24-hour coverage, noting that morning trough measurements in Target-HTN showed a significant effect. Chief Medical Officer Dr. David Rodman added that the 10-12 hour half-life is considered ideal for balancing efficacy with a restoration of normal circadian rhythm.

Sadia, on behalf of Mohit Bansal from Wells Fargo, asked if the Launch-HTN trial is targeting similar patient demographics as Advance-HTN, particularly regarding obese and Black/African American patients. She also inquired about the potential for a higher placebo response in the global Launch-HTN trial and if this was factored into its powering.

Answer

Executive Jon Congleton stated that while Launch-HTN demographics haven't been released, he doesn't expect the global nature to dilute the BMI effect, as the obesity-hypertension link is strong worldwide. CMO Dr. David Rodman added that they will distinguish between African-American and European Black populations due to genetic differences. He also confirmed that Launch-HTN is 'super powered,' making any potential increase in placebo variability a non-significant issue.

Mohit Bansal of Wells Fargo requested more color on the expected cadence of EYLEA HD uptake during the year, asking if the prefilled syringe and label expansion could create an inflection point.

Answer

EVP of Commercial, Marion McCourt, did not provide a specific cadence but highlighted the growth opportunity from both naive and switch patients. CEO Dr. Leonard Schleifer pivoted the conversation to the broader pipeline, emphasizing upcoming data in COPD, melanoma, and myasthenia gravis to underscore the company's diversified growth strategy.

Mohit Bansal of Wells Fargo asked how EYLEA HD uptake is tracking against internal expectations and what levers Regeneron can pull to accelerate its adoption.

Answer

President and CEO Dr. Leonard Schleifer stated that while the company doesn't give specific guidance on conversion rates, he feels the progress is solid and expects it to continue. He reiterated that key catalysts for acceleration next year include potential approval in RVO and, more importantly, the launch of the prefilled syringe by mid-year. He noted that original EYLEA remains a sticky product due to physician familiarity and trust.

Mohit Bansal asked for clarification on the dynamics of a prior-quarter charge reversal and why it wasn't impacting guidance, and also questioned the reason for the expected increase in Ironwood's share of LINZESS profit in Q4.

Answer

Sravan Emany, COO and CFO, explained that the expected Q4 profit increase is due to the brand's historical cyclicality, with Q4 typically being the strongest quarter. He attributed the charge reversal to timing differences in recording gross-to-net adjustments with partner AbbVie, which are expected to balance out by year-end.

Mohit Bansal asked for clarification on why LINZESS pricing pressure is worse than anticipated in Q1, how to view the revenue trajectory, and about the T cell response data from previous CNP-104 studies.

Answer

COO & CFO Sravan Emany explained that since Q1, Medicaid utilization has been even higher than anticipated due to lower-than-expected impact from redeterminations, the AMCAP repeal, and state-level eligibility changes, necessitating the revised guidance. Chief Medical Officer Michael Shetzline clarified that the current CNP-104 study is the first-in-human for PBC, distinguishing it from a past study on the COUR platform for celiac disease.

Mohit Bansal questioned if the updated payer mix that led to the LINZESS gross-to-net adjustment is expected to persist through 2024. He also asked about the CNP-104 trial, specifically whether the 120-day timeframe is sufficient to observe a benefit on endpoints like ALP, given the mechanism of action.

Answer

CFO Sravan Emany responded that the 2024 guidance accounts for the anticipated channel mix for the full year and reiterated that the expected net sales decline is predominantly driven by the one-time adjustment. CMO Michael Shetzline explained that CNP-104's mechanism is distinct from precedents, as it targets the root cause of PBC. He stated that while they believe there is an opportunity to see an early clinical signal at 120 days, they will learn from the data.

Mohit Bansal of Citigroup inquired about the rationale for using the EASI-50 endpoint in the Phase 2 trial versus the IGA endpoint, and asked for clarification on which FDA division is overseeing the review of FB-401.

Answer

CMO Dan Birch explained that IGA is a standard Phase 3 endpoint, but smaller Phase 2 trials are typically not powered for it, making EASI-50 a common alternative. CEO Paul Wagner added that IGA is included as a secondary endpoint. Regarding the FDA, Paul Wagner clarified that the therapy is overseen by the division of vaccines and related products, which has historical oversight of live bacteria therapies, but it works in close collaboration with the dermatology division. He noted this division was very responsive, granting Fast Track designation during the COVID-19 pandemic.

Mohit Bansal from Citigroup asked about the role of Medicaid in the XLMTM market and the company's perspective on innovative, installment-based pricing models for gene therapies.

Answer

President and CEO Matthew Patterson confirmed that Medicaid is an important payer for the XLMTM patient population and a key focus of commercial planning. He expressed strong support for creative payment-over-time options to improve market access for one-time therapies and noted the company is closely monitoring developments in this area.