James Shin

James Shin asked about expectations for the Cadence study's ACC presentation, specifically what information would be revealed, and inquired about potential endpoints for a Phase 3 program in CPCPH due to heart failure with preserved ejection fraction (HFpEF).

Answer

Dean Li, President of Research Labs, stated that the primary and important secondary endpoints from the Phase 2 Cadence study would be provided at ACC. He mentioned ongoing discussions with the FDA regarding Phase 3 endpoints, which would likely include functional activity, clinical events, and biomarkers, emphasizing the need to align on outcomes for this orphan indication.

James Shin asked Dean Li about expectations for the upcoming ACC presentation of the Cadence study data for Winrevair, and sought color on potential endpoints for a Phase III program in Cpc-PH due to HFpEF.

Answer

Dean Li, President of Research Laboratories, Merck & Co. Inc, stated that the ACC presentation will provide data on the primary and important secondary endpoints of the Cadence study. Regarding a future Phase III for Cpc-PH due to HFpEF, he mentioned ongoing discussions with the FDA about endpoints, which would likely include functional activity, clinical events, and biomarkers, emphasizing the need for alignment with the FDA for this orphan indication.

James Shin of Deutsche Bank asked if Merck was notified of Sino Biopharm's interest in its partner Kelun-Biotech (Lenovo) and if this development affects Merck's commitment to their partnered PD-1/VEGF bispecific asset.

Answer

Dr. Dean Li, President of Merck Research Labs, reiterated that Merck's commitment to the program is unchanged and based on its long-standing interest in the scientific space. He confirmed the program is moving forward as planned and declined to comment on business development notifications.

James Shin of Deutsche Bank asked about the PD-1/VEGF bispecific (MK-2010), questioning if Merck was notified of Sino Biopharm's interest in its partner Kelun-Biotech and if this development affects Merck's commitment to the program.

Answer

Dr. Dean Li, President of Merck Research Laboratories, reiterated that Merck's commitment to the space is long-standing, since 2018, and has not changed. He confirmed the program with Kelun-Biotech is moving forward as planned and declined to comment on business development notifications.

James Shin of Deutsche Bank AG questioned the need for more U.S. CapEx and whether recent PD-1/VEGF data would accelerate Merck's own programs.

Answer

CEO Robert Davis confirmed that U.S. investment will likely grow beyond the currently committed figures, independent of tax reform. Dr. Dean Li noted that while the field is watching PD-1/VEGF data, Merck believes it is the 'advantaged owner' for such a combination due to its KEYTRUDA expertise and portfolio, and will move with speed as data evolves.

James Shin asked for Merck's expectations from the upcoming February 2025 ACIP meeting regarding GARDASIL dosing questions, and whether the U.S. market outlook played any role in the decision to withdraw the long-term global guidance for the vaccine.

Answer

CEO Robert Davis confirmed that the U.S. market outlook for GARDASIL is unchanged and did not influence the guidance withdrawal. Dr. Dean Li, President of Merck Research Labs, addressed the ACIP meeting by distinguishing between the CDC's role and the FDA's role in setting the label, noting the FDA has a very high evidentiary bar for changing dosing schedules, which he expects the CDC will consider.

James Shin inquired about any changes to cyclophosphamide dosing in the CARTITUDE-10 study following the removal of fludarabine, whether positive results from CARTITUDE-10 could lead to label inclusion or broad adoption, and any insights from the FDA regarding MRD becoming a formal surrogate endpoint.

Answer

Ying Huang, CEO, confirmed that the first cohort of CARTITUDE-10 is evaluating a fludarabine-free regimen for lymphodepletion, with patient enrollment and dosing underway, but did not specify cyclophosphamide dosing changes. She stated it is premature to discuss label inclusion for CARTITUDE-10 results and that discussions with the FDA regarding MRD as a potential registration endpoint are ongoing.

James Shin asked about changes to cyclophosphamide dosing in the CAR-T2/10 study (where fludarabine is removed), and if successful, whether this regimen could be added to the label or broadly approved by the FDA. He also asked if the primary endpoint of MRD in CAR-T2/10 provides insight into MRD becoming a formal surrogate endpoint.

Answer

Ying Huang, CEO, confirmed the CAR-T2/10 study's first cohort evaluates a fludarabine-free regimen for lymphodepletion. He stated it's premature to discuss label inclusion but if data is positive, they would approach the FDA. Regarding MRD as a registration endpoint, discussions with the FDA are ongoing to determine suitable settings.

James Shin asked what the Virginia Oncology Associates (VOA) partnership specifically provides for Legend, what portion of community practices are awaiting CARVYKTI slots, and if a 'lighter' FACT accreditation is the main driver for community adoption.

Answer

Alan Bash, President of CARVYKTI, described the VOA partnership as a key first milestone in penetrating community network practices. He confirmed that efforts are underway to create a 'FACT light' or 'FACT umbrella' system to ease adoption. CEO Ying Huang added that Texas has already passed legislation removing the FACT accreditation requirement for reimbursement, a trend they expect to continue.

James Shin from Deutsche Bank inquired about the endpoint strategy for the CARTITUDE-6 trial, particularly the potential use of MRD, and asked about the status of an industry coalition aimed at lowering accreditation requirements for community-based CAR-T administration.

Answer

Chief Medical Officer Mythili Koneru stated they are confident in their approach for CARTITUDE-6 and plan to meet with the FDA in the next two months. Alan Bash, President of CARVYKTI, confirmed that industry discussions for a 'fact-light' accreditation are ongoing and could help unlock community opportunity.

James Shin asked for updates on removing FACT accreditation requirements to broaden outpatient use and whether data from CARTITUDE-5 and -6 will be broken out for patients who did or did not require intervention based on ALC levels.

Answer

Executive Alan Bash explained that the strategy is more about leveraging affiliations, where smaller centers can operate under the FACT accreditation umbrella of a larger institution, rather than removing the requirement wholesale. Executive Jessie Yeung clarified that the ALC mitigation strategy was not incorporated into CARTITUDE-5 as it had already completed enrollment. An Unknown Executive added that based on their database, about 20% of patients could potentially reach the ALC threshold and benefit from the intervention.

James Shin questioned how a competitor with a short CRS onset could succeed in the outpatient setting, given the challenges seen with similar products like Abecma.

Answer

CMO Mythili Koneru and SVP Steven Gavel both emphasized that CARVYKTI's unique, delayed CRS onset is what makes robust outpatient administration possible. Gavel pointed to Abecma's acute CRS as the reason it has not seen significant outpatient adoption, reinforcing that this profile is a distinct clinical and commercial advantage for CARVYKTI.

James Shin asked if the SVR, TSS, and anemia burden kinetics for 989 should be expected to look similar to Ruxolitinib. He also sought insights into the timing, financial, and regulatory aspects of 989's frontline MF development path and its alignment with Jakafi's loss of exclusivity (LOE).

Answer

President Pablo Cagnoni confirmed the importance of demonstrating 989's effect on clinical endpoints (SVR25, SVR35, TSS50, anemia) in myelofibrosis, as these are critical for approval and will be part of the upcoming update. CEO Bill Meury explained that 989 aims to build a long-duration revenue stream beyond 2029, not just fill a gap. He highlighted the intrinsic appeal of the first targeted therapy in MPNs, addressing residual symptoms, thrombotic risk, and transformational risk in ET. For MF, he noted that all patients on Jakafi progress, creating an opportunity for 989 either as an add-on or sequential therapy, with pivotal studies starting mid-2026 potentially leading to approvals around 2029-2030.

James Shin asked about the week 18 povorcitinib data, specifically if placebo crossover patients experienced rapid pain reduction and if a pre- and post-biologic exposure breakout could be provided for this group.

Answer

Executive Steven Stein highlighted the rapid drug effect, noting a 20-30% absolute improvement in HiSCR rates within six weeks for the crossover group. While confirming that about one-third of the total study population was biologic-exposed and that activity was seen across all groups, he did not provide a specific breakout for the crossover patients.

James Shin from Deutsche Bank asked about the disclosure plan for the povorcitinib STOP-HS1 and 2 Phase III trial data. He also requested an update on the axatilimab (262) program for chronic spontaneous urticaria (CSU).

Answer

Pablo Cagnoni, President, Head of R&D, stated that the povorcitinib HS data will be disclosed via a press release, likely accompanied by a conference call. Regarding axatilimab, he noted that the company is still completing its evaluation of the preclinical toxicology findings and will provide an update later in the year.

James Shin of Deutsche Bank AG asked about the ruxolitinib cream Phase III trial in hidradenitis suppurativa (HS), specifically the time point for the HiSCR 75 assessment and whether the mid-2027 approval timeline implies data would be expected in 2026.

Answer

Steven Stein, an executive, stated it was too early to provide precise timelines beyond what was presented. He confirmed the endpoint is HiSCR 75 as agreed with regulators and noted that while they expect the trial to enroll well due to the high unmet need, a more precise update on the endpoint timing will be provided later.

James Shin from Deutsche Bank inquired about the decision to delay the Ocatsol launch in Germany, asking if it was a change from a previously positive outlook. He also asked about the future sales cadence once hospitals adapt to the new split reimbursement model in the U.S.

Answer

CEO Christian Itin explained that the European market access process, designed for randomized controlled trials, poses a methodological challenge for single-arm cell therapies, necessitating a disciplined, country-by-country approach to ensure economic viability. CFO Rob Dolski clarified that while the revenue recognition change itself has little impact, the administrative adjustments at centers slowed enrollment in Q2, an effect expected to resolve by Q4.

James Shin asked about the revenue recognition policy for AUCATZYL following a CMS coding update, the potential impact of U.S. tariffs on products manufactured in the U.K., and whether a potential leadership change at the FDA's CBER could affect agreed-upon clinical trial designs for lupus.

Answer

CEO Christian Itin and CFO Rob Dolski clarified that Q1 revenue was recognized on the first dose, but all patients received both doses. They are evaluating the new CMS split-coding but don't expect a material full-year impact. On tariffs, Itin noted they are based on lower manufacturing costs, not list price, and blood products are often exempt. Regarding the FDA, Itin expressed confidence in their agreed-upon trial design for lupus nephritis, citing the high unmet medical need of the patient population.

James Shin of Citigroup Inc. inquired about the initial demand and order book for the AUCATZYL launch and asked whether outpatient administration is currently happening or planned, given the drug's favorable safety profile.

Answer

Christian Itin, an executive, responded that while it's too early for specifics, the company sees a 'very good dynamic' and significant interest, driven by the enthusiasm of activated centers. Regarding outpatient use, Itin acknowledged that physicians are interested in exploring it for patients with low tumor burden due to the attractive safety profile, but stated it's too early in the launch to guide on its current use, noting it will evolve as physicians gain more experience.

James Shin asked if the European Union approval for obe-cel is still on track for mid-2025 and whether the product's safety profile, with a later onset of CRS, would be more favorable for outpatient administration compared to competitors.

Answer

CEO Christian Itin confirmed that the EU and UK approval timelines remain on track for mid-2025. He added that obe-cel's safety profile, particularly for patients with low disease burden, creates a significant opportunity for administration in a hospital outpatient setting as physicians gain more experience with the therapy.

James Shin of Deutsche Bank asked for confirmation that ImmunoCor has recently checked in with the FDA regarding the TEBI-AM trial design and inquired how the duration of therapy for Chemtrac in Europe is trending relative to the U.S.

Answer

David Berman, EVP of R&D, noted the last interaction was last year but emphasized the trial is a randomized Phase III with an OS endpoint, unlike the single-arm trial that faced recent issues. He believes the control arm design will be sufficient. Ralph Torbay, EVP of Commercial, explained that European duration is excellent and similar to the U.S. in mature markets like Germany and France, while still maturing in newer launch countries.

James Shin of Deutsche Bank asked what changes investors should expect in the early-stage pipeline and BD strategy under the incoming Chief Medical Officer, and if this could shift the company's projected earnings trough.

Answer

CEO Chris Boerner responded that the entire management team is already focused on shortening the earnings trough. He expects the new CMO, Christian Masacezi, to bring a sharp focus on execution, talent development, and accelerating the use of new technologies, while building on the strong foundation already in place.

James Shin asked what specific macro policy decision, such as tax reform or tariff rates, would be a key data point for the company's planning. He also inquired about the competitiveness of recent PD-1/VEGF combination data sets.

Answer

CEO Christopher Boerner emphasized that while multiple policy areas are important, competitive tax policy is critically important for encouraging U.S. R&D investment. CMO Samit Hirawat commented that the PD-1/VEGF data is evolving and will be monitored, but noted that BMS has a large, precision-driven portfolio in lung cancer and is focused on its own IO franchise.

James Shin of Deutsche Bank asked about the company's expectations for the PANSS score benefit in the RISE trial and how the data from the ADAPT 2 trial for Cobenfy will be disclosed.

Answer

CMO Samit Hirawat stated that for the RISE trial, the focus is on the difference between arms, where even small changes are clinically meaningful. For the ADAPT trial, he explained that per standard practice, a positive result would be announced via a top-line press release, with the full data set reserved for presentation at a future medical conference.

James Shin returned to the milvexian trial, asking if there was any observable separation between the treatment arms or any color on bleed rates from the blinded data.

Answer

Head of Global Drug Development Samit Hirawat explained that because the trial is blinded, the company does not have access to data separated by arm. Therefore, he could not comment on specifics like treatment separation or bleed rates, reiterating that their update was based on the overall blended event rate.

James Shin asked if the company's guidance for a mid- to high-single-digit price headwind for the year remains intact following the CVS formulary decision on Zepbound and recent movements in foreign exchange rates.

Answer

An executive, likely CFO Lucas Montarce, reaffirmed the full-year guidance and confirmed that the expectation for mid- to high-single-digit price erosion remains unchanged. He noted that the Q1 price decline of 6% was consistent with this forecast and that dynamic market events like the CVS decision are factored into their ongoing forecasting process.

James Shin of Deutsche Bank asked how the slower titration schedule in Orforglipron's Phase III trials might impact results compared to the faster titration in Phase II.

Answer

Executive Daniel Skovronsky explained the strategy is similar to what was successfully used for tirzepatide. The goal is to mitigate GI side effects and improve tolerability while still achieving the expected plateau efficacy in longer-term studies.

James Shin from Deutsche Bank AG asked about the current price versus volume dynamics in the immunology franchise, specifically if the previously guided low single-digit price headwind is being realized and how it is blended across Humira, Skyrizi, and Rinvoq.

Answer

CFO Scott Reents explained that for Skyrizi and Rinvoq, Q1 performance was driven by strong demand, with a slight favorable price impact due to effective co-pay management and earlier-than-expected channel mix changes. However, he reiterated the expectation for negative pricing headwinds on a full-year basis. For Humira, he confirmed the negative impact from both volume erosion and price compression from rebating dynamics in the new contract year.

James Shin from Deutsche Bank asked about managing the placebo effect in the upcoming emraclidine readout, given the potential for efficacy erosion seen in other schizophrenia trials.

Answer

CSO Roopal Thakkar detailed the strategic measures Cerevel took to control for placebo response, including limiting sites, central review, and rigorous rater training. He emphasized that with a strong effect size in Phase Ib, emraclidine's highly competitive safety and tolerability profile would be a key differentiator.

James Shin asked about the strong performance of Descovy in the quarter and whether this has positive read-throughs for the upcoming lenacapavir for PrEP launch.

Answer

Chief Commercial Officer Johanna Mercier confirmed there is a positive implication. She attributed Descovy's 38% year-over-year growth to higher demand and realized price, which were driven by 16% PrEP market growth, focused commercial execution that grew Descovy's share, and improved unrestricted access. She stated these factors create a favorable environment for the lenacapavir launch.

James Shin requested details on the indications for the MARITIME Phase III program, set to begin in the first half of 2025, and whether it would include head-to-head trials against competitors.

Answer

James Bradner, EVP of R&D, listed the broad focus areas for the MARITIME program, including chronic weight management, cardiovascular and kidney disease, and sleep apnea. However, he stated that it was premature to disclose specific trial designs, such as head-to-head comparisons, as discussions with regulators are ongoing.

James Shin inquired about whether the company was investigating T-cell exhaustion signals as a potential reason for progression in patient one and asked about any changes to the cell product resulting from the new cryopreservation process.

Answer

VP of Research and Development, Drew Deniger, confirmed they are looking at exhaustion markers in patient one, noting they were encouraged that T-cells were infiltrating the tumor. VP of Technical Operations, Abhi Srivastava, explained that the cryopreservation process does not significantly alter the product, with qualification runs showing similar high purity, viability, and TCR positivity compared to the fresh product.