Stephen Willey

Stephen Willey asked about the anecdotes driving Niktimvo's sustained sequential growth in Q4 and how long double-digit sequential growth might continue. He also inquired about the biological similarities and dissimilarities between BOS (chronic GVHD) and IPF, and how the BOS data translates to IPF.

Answer

Michael Metzger, Chief Executive Officer, and Steve Closter, Chief Commercial Officer, attributed Niktimvo's strong performance to addressing unmet needs, impacting both fibrosis and inflammation, high account penetration, and good persistency, expecting steady or increasing growth. Nick Botwood, Head of R&D and Chief Medical Officer, highlighted underpinning biological similarities between BOS and IPF, including inflammation, fibrotic changes, and increased monocytes/macrophages, despite different patterns. He noted axatilimab's reductions in inflammatory cytokines and cross-references with other IPF drugs showing GVHD activity, giving confidence in translation.

Stephen Willey inquired about the extent of EPO as a second-line competitor, specifically the proportion of patients failing front-line luspatercept and then treated with an ESA, and the crystallized ex-US strategy following European approval, considering MFN pricing.

Answer

Joseph Eid, EVP of Research and Development and Chief Medical Officer, noted that with Reblozyl (luspatercept) moving to first-line, ESAs are less effective post-luspatercept, leading KOLs to prefer imetelstat as a second-line option. Harout Semerjian, President and CEO, added that NCCN guidelines moving HMAs further out also benefit RYTELO's second-line positioning. Regarding Europe, Semerjian confirmed approval but emphasized the need to understand HTA processes and MFN impact to command a premium, with ongoing work to synthesize HTA data and engage potential partners, while remaining opportunistic.

Stephen Willey from Stifel asked about AbCellera's capacity to maintain clinical trial infrastructure for its expanding pipeline, considering multiple IND-enabling programs and a potential pivotal study for ABCL635. He also inquired about the factors influencing the decision for ABCL575's future, weighing internal development against out-licensing opportunities.

Answer

Carl Hansen, President and CEO, stated that AbCellera has completely reshaped the company since late 2023, moving resources into biology, translational medicine, and clinical development to build operational capacity for the expanding pipeline, including a potential Phase 3 study for ABCL635. Sarah Noonberg, Chief Medical Officer, clarified that the decision for ABCL575's future (further development or out-licensing) will largely be based on external factors like the competitive landscape and partnership opportunities, rather than internal Phase 1 data, as the molecule is meeting expectations. She also mentioned considering its use in combination or as a bispecific.

Stephen Willey asked about AbCellera's capacity to maintain clinical trial infrastructure and actively develop multiple programs, especially with two compounds in IND-enabling studies, another expected nomination, and the potential for ABCL635 to move into a pivotal study. He also followed up on ABCL575, asking how the 2027 decision point for further development or out-licensing would be weighed between internal phase I data and external factors like partnership opportunities and strategic appetite.

Answer

Carl Hansen, President and CEO, stated that AbCellera has completely reshaped the company since late 2023 to focus on clinical development, moving resources into biology, translational medicine, and clinical development. He affirmed the company's intent and resources to build operational capacity to meet goals, acknowledging that work is still needed but expressing excitement for the programs. Sarah Noonberg, Chief Medical Officer, indicated that the ABCL575 decision would largely be based on external factors, as internal preclinical data and phase I study results have met expectations without surprises. She emphasized that the bigger decision would hinge on the external landscape, potential partnership opportunities, and considerations for using ABCL575 in combinations or as a bispecific.

Josh, on behalf of Stephen Willie, asked for an update on enrollment progress and dosing for the Phase I ABCL 575 trial, and whether AbCellera remains on track to declare a fourth AbCellera-led development candidate by year-end.

Answer

Carl Hansen, AbCellera's President and CEO, confirmed that the ABCL 575 program is progressing as expected, with enrollment on track, though specific preliminary dosing results are not being disclosed. He also affirmed that the company is on track to bring an additional, fourth development candidate forward before the end of the year.

Steven Willey asked if the majority of BRINSUPRI patient reauthorizations are expected to occur six months after starting therapy, and inquired about the seamlessness of the reauthorization experience observed thus far, particularly with early payers.

Answer

Will Lewis, Chair and CEO, stated that refills for BRINSUPRI are 'going very well' in the first quarter, which is a positive sign. He noted that the greatest point of friction typically occurs when patients change medical plans in Q1, but expressed confidence in how things have progressed, indicating no significant difficulties or breaks in the reauthorization process.

Stephen Willey asked if the single Phase III PAH trial for TPIP would target a patient population similar to Phase II, and about feedback on potential label claims and additional studies for broader functional class patients.

Answer

Will Lewis, Chairman and CEO of Insmed, highlighted TPIP's 35.5% PVR reduction as potentially best-in-class. Martina Flammer, Chief Medical Officer, confirmed that the Phase III study design would be consistent with Phase II, but would allow for titration up to 1280 micrograms (maximum tolerated dose) based on open-label extension experience.

Stephen Willey asked if the single Phase 3 PAH trial for TPIP, aligned with the FDA, would target a patient population similar to Phase 2, and inquired about potential label claims and additional studies for broader functional class patients.

Answer

Will Lewis, Chairman and CEO, highlighted TPIP's potential for patient impact and convenience due to its titratability and once-daily dry powder formulation, noting its 35.5% PVR reduction in Phase 2. Martina Flammer, Chief Medical Officer, confirmed that Phase 3 will aim for consistency with Phase 2, but will allow titration up to 1280 micrograms, the maximum tolerated dose, based on OLE safety experience.

Stephen Willey asked if zanzalintinib dose optimization data would inform the starting dose for STELLAR-316 and if any additional dose optimization data would be submitted as part of the ongoing NDA review.

Answer

Dana Aftab (EVP of Research and Development) confirmed that the company's approach is always to use the optimal dose appropriate for each individual setting, considering factors like disease stage, combination partner, and expected treatment duration, which will apply to STELLAR-316. She also mentioned that strong data supporting contribution of components for STELLAR-303 were shared with the agency as part of the review.

Stephen Willey asked if ongoing zanzalintinib dose optimization data would inform the starting dose for STELLAR-316 and if this data would be submitted as part of the ongoing NDA review.

Answer

Dana Aftab (EVP of Research and Development, Exelixis) confirmed that Exelixis always uses the optimal dose appropriate for each pivotal study setting, which can be influenced by factors like disease stage and combination partners, and this approach will continue for STELLAR-316. She also mentioned that strong data supporting contribution of components for STELLAR-303 were shared with the agency.

Stephen Willey inquired about the planned phase III trial in post-chemo adjuvant colorectal cancer, specifically asking if additional dose exploration for Zanzalintinib is intended, given the relatively low dose intensity observed in STELLAR-303, to ensure tolerability in a setting where it is highly prioritized.

Answer

Dana Aftab, Executive Vice President of Research and Development, confirmed that the company plans to explore earlier lines of therapy for Zanza in colorectal cancer, including the adjuvant setting, due to the positive STELLAR-303 results. She indicated that, similar to other agents, exploring different doses as Zanza moves into earlier lines of therapy is a natural consideration, advising to 'stay tuned' for more details upon trial launch.

Stephen Willey asked about the planned Phase 3 trial in post-chemo adjuvant colorectal cancer (CRC) and whether Exelixis intends to conduct additional dose exploration work for Zanzalintinib to ensure tolerability, given its low dose intensity in Stellar-303.

Answer

Dana Aftab, EVP of Research and Development, confirmed that the adjuvant CRC trial is a natural progression from Stellar-303's positive results in non-MSI-H patients, targeting a high unmet need population with high recurrence risk. She indicated that Exelixis intends to look at other doses for Zanzalintinib, as is common when moving to earlier lines of therapy, with more details to follow upon trial launch.

Stephen Willey asked about the rationale behind targeting an IC35 exposure for the mutant selective JAK inhibitor (058), whether this target is limited by cross-reactivity on wild type, and if the new formulation is expected to achieve significantly higher than IC35.

Answer

Steven Stein, CMO, clarified that the IC35 focus for 058 is specific to the molecule's selectivity, with animal model data suggesting an ideal window between mutant and wild-type effects around IC35. He stated that preclinical data indicates the current formulation should achieve this exposure, with clinical data expected in the second half of 2026 to confirm, and reiterated full commitment to the target with backup programs.

Stephen Willey asked about the rationale for the IC35 exposure target for the mutant selective JAK inhibitor (058), whether it's limited by cross-reactivity on wild type, and if the new formulation can achieve meaningfully higher than IC35.

Answer

Steven Stein, CMO, Incyte, explained that the IC35 focus is specific to 058's selectivity, representing the ideal window between mutant and wild-type effects based on animal model data. He believes the current formulation should achieve this exposure, with clinical data expected in H2 2026, and reiterated commitment to the target with backup programs if needed.

Stephen Willey asked what to expect from the 989 abstract publication relative to the full presentation, and about the read-through of Sanofi's failed frontline trial with Resurrect steroids to Naktinvo's ongoing Phase 3 trial, including potential biological differences in newly diagnosed patients.

Answer

President Pablo Cagnoni advised focusing on the later 989 presentation before year-end, as it will include a later data cut, more patients, and longer follow-up than the abstract. Chief Medical Officer Steven Stein explained that the controversy around primary endpoint measurement (event-free survival) and event definitions is key in first-line GVHD trials, expressing confidence in Naktinvo's robust endpoint definition and its potential for steroid withdrawal. CEO Bill Meury highlighted Naktinvo's two combination studies (with steroids and Jakafi) as significant opportunities to expand its addressable population and potentially offer a non-steroid regimen.

Stephen Willey inquired about the reasons behind the extension of the Maya ovarian trial's interim analysis timeline from Q4 2026 to Q1 2027, specifically asking if it was due to enrollment timelines, accrual rates, or the accumulation of PFS events.

Answer

President and CEO Eran Ophir and CMO Michelle Mahle explained that the revised timeline reflects updated estimates based on factors like site activation, particularly for academic centers and the French Arcadia Gyneco group, which took longer to open. They emphasized that the company has sufficient cash runway into Q3 2027 to support the trial's progression.

Stephen Willey asked about the extension of the Maya ovarian trial's interim analysis timeline from Q4 2026 to Q1 2027, inquiring if it's due to enrollment timelines, accrual, or the accumulation of PFS events.

Answer

Eran Ophir, President and CEO of Compugen, and Michelle Mahle, CMO, explained that the revised timeline reflects optimized predictions based on the kinetics of trial development, including site opening (especially academic and French centers) and anticipated enrollment ramp-up. They confirmed that the company's cash runway extends into Q3 2027, supporting the trial's progression.

Tully on for Steven Wiley of Stifel questioned if the initial QTCs are a good proxy for future patient numbers, whether the two active centers are sufficient to meet 2025 guidance, and if the Q2 SG&A spend is a reliable run-rate.

Answer

CEO Vishwas Seshadri and CCO Madhav Vasanthavada confirmed the two active QTCs have identified enough patients (~50) to support the 2025 guidance of 10-14 patients and build a strong funnel for 2026. CFO Joseph Vazzano clarified that while the overall operating burn trend is indicative, the Q2 SG&A figure itself will fluctuate quarterly due to the accounting mix of production and engineering costs between R&D, COGS, and SG&A.

Stephen Willey from Stifel questioned the expected patient throughput at qualified treatment centers (QTCs), both at launch and at steady-state, and asked how the PRV sale impacts the prioritization of the company's early-stage pipeline.

Answer

Chief Commercial Officer Dr. Madhav Vasanthavada stated that physicians at potential QTCs are comfortable with a throughput of two patients per month per site, with some institutions indicating capacity for up to four. CEO Dr. Vish Seshadri addressed the pipeline, confirming that the RS1 ophthalmology program remains on track for in-human studies in the second half of 2026, a cadence that fits well with the ZEVASKYN commercial ramp. He noted the PRV proceeds support this without accelerating timelines that are dictated by scientific processes.

An analyst on behalf of Steven Willey at Stifel asked about the patient demographics in the Tivesimig trial and the confidence that they reflect historical trial populations, given the lower-than-expected death rate. He also inquired about the preclinical safety data for CTX-10726.

Answer

CEO Thomas Schuetz responded that while it's hard to make cross-trial comparisons without the final data, the randomization was stratified by key prognostic variables (performance status, metastatic disease location, anatomic subtype), ensuring the treatment arms should be well-balanced. He confirmed that preclinical data for CTX-10726 will be presented at a scientific conference later in the year.

An analyst on behalf of Steven Willey at Stifel asked about confidence in the Tivesimig patient population being reflective of historical trials, given the lower-than-expected death rate, and inquired about preclinical safety data for CTX-10726.

Answer

CEO Thomas Schuetz addressed the Tivesimig question by highlighting that the study's randomization was stratified by three key prognostic variables, ensuring the treatment arms should be well-balanced. For CTX-10726, he confirmed that preclinical data, including safety, will be presented at a scientific conference later in the year.

Asked about screening protocols for pneumonitis and whether dyspnea could be miscategorized. Also requested the median duration of follow-up for the study arms and the distribution of patients based on prior ARPI stability.

Answer

The executive confirmed there is no routine pneumonitis screening protocol as it wasn't a prior signal, and the recent cases are under investigation. He did not provide the median follow-up but noted the mean number of doses is now five. The split of patients by prior ARAT exposure duration was approximately 40% to 60%.

Asked about the enrollment kinetics (new vs. experienced sites), whether a go-forward dose has been selected between the 2.7 and 2.0 mg regimens, and if rPFS data maturity would delay the initiation of new expansion cohorts.

Answer

Scott Koenig clarified that the rapid enrollment surge in late 2023 was primarily from newly opened sites in Europe. He stated it's too early to decide on a final go-forward dose, as they are waiting for more complete data, and the data safety monitoring committee recommended continuing both doses. The rPFS data maturity will not slow down the initiation of the new expansion cohorts.

Inquired about the specifics of the planned CUE-101 Phase II trial, including the second dose being considered, the trigger for the interim analysis, the rationale for a standalone Phase II versus a seamless Phase II/III design, and how recent competitor data influences expectations.

Answer

The company is considering 4 mg/kg and likely 2 mg/kg as the two doses for the Phase II trial. The interim analysis will be triggered when 70-80% of patients have completed their cycle 5 scan. A standalone Phase II was chosen as a more cost-effective and confidence-building step before a larger Phase III investment, a decision reinforced by unexpected results in other recent trials. The final analysis of the Phase II, not the interim, would support moving to Phase III.

Stephen Willey of Stifel inquired about the expected response rates for venetoclax retreatment in the voruciclib AML trial and whether patients in the ME-344 study would be naive to salvage therapies like LONSURF. He also asked for context on the 20% 4-month PFS threshold for ME-344 and questioned the significant sequential drop in Q4 R&D spending.

Answer

President and CEO David Urso indicated that a 20-30% response rate for the voruciclib combination in relapsed/refractory AML would be considered exciting. Chief Medical Officer Dr. Richard Ghalie clarified that ME-344 patients are not required to be naive to LONSURF or regorafenib and that the 20% PFS is a 'floor,' with the data's significance depending on the enrolled patients' prior treatments. CFO Jay File explained the R&D decline was due to the wind-down of the zandelisib trials, which accounted for approximately $26 million of the annual R&D spend.

Stephen Willey from Stifel asked for guidance on the continued paydown of the 9% notes, commentary on a citizen petition regarding the closed triple, insights into BREO scripts written with LAMA, and the reason for the timing of the new ANORO DTC campaign.

Answer

CFO Eric d'Esparbes confirmed the plan to continue paying down the 2029 notes remains active. CEO Michael Aguiar addressed the closed triple, acknowledging the logic of a competitor's petition but expressing confidence in their filing with the FDA. He estimated that about 40% of the COPD LABA/ICS market involves an 'open triple' combination. Regarding the ANORO DTC campaign, he declined to comment on specific timing decisions but noted its positive launch and expected contribution to growth.