Stephen Willey

Stephen Willey asked about the sustained sequential growth of Niktimvo in Q4, anecdotes supporting it, and the outlook for continued double-digit sequential growth. He also inquired about biological similarities and dissimilarities between BOS (chronic GVHD) and IPF, and how AGAVE-201 data translates to IPF.

Answer

Michael Metzger, CEO, and Steve Closter, Chief Commercial Officer, attributed Niktimvo's growth to addressing unmet needs, hitting disease hallmarks, a strong account base, and high persistency, expecting steady or increasing growth. Nick Botwood, Head of R&D and Chief Medical Officer, highlighted biological similarities between BOS and IPF (inflammation, fibrosis, monocytes/macrophages) and expressed confidence in translation due to observed anti-fibrotic activity and cytokine reductions, despite differences in pulmonary manifestation patterns.

Stephen Willey from Stifel asked about Celcuity's launch readiness for Gadafelicitinib, including the required infrastructure build-out and plans for scaling into 2026, given the potential for an accelerated approval pathway.

Answer

CEO Brian Sullivan detailed a proactive, phased approach to commercial readiness that began in early 2024 with the hiring of key commercial leaders. He emphasized that the team is now expanding to build out the salesforce, market access, and commercial operations functions. Sullivan highlighted the strategy of hiring personnel with direct experience in first-time drug launches to ensure all necessary infrastructure is established, stating the company is on track for a successful launch.

Stephen Willey from Stifel asked for Zymeworks' perspective on the clinical data for pasaritamab, a partnered asset with J&J, noting its favorable tolerability but lower PSA50 rates compared to other PSMA-targeting bispecifics, and questioned what drives the molecule's unique profile.

Answer

Chief Scientific Officer Paul Moore attributed the molecule's excellent tolerability to the novel KLK2 target, which provides a superior therapeutic window. He suggested this profile makes the drug a strong candidate for combination therapies to boost efficacy, a strategy J&J is actively exploring. He also noted that CD3 binder affinity is tailored to each specific target.

Stephen Willey from Stifel asked for guidance on the timing of data release for ZW171 and ZW191, questioning if interim updates would be provided. He also inquired whether the company's clinical development capacity could be expanded following potential milestone payments from the zanidatamab program.

Answer

CEO Kenneth Galbraith stated that it is too early to provide specific data timing for ZW171 and ZW191, reiterating that updates will come via abstracts at peer-reviewed conferences. He expressed satisfaction with the current clinical operations infrastructure, which he believes is efficient and sufficient to advance the current pipeline, including the upcoming ZW251 trial, without needing immediate expansion upon receipt of milestone payments.

Stephen Willey inquired about the clinical development strategy for ZW251, specifically the potential for accelerated combination cohorts, and the rationale for prioritizing it over the IND-ready ZW220 (NaPi2b).

Answer

Chair and CEO Kenneth Galbraith confirmed a portfolio-wide strategy to explore combinations early to achieve durable responses, especially for ZW251 in HCC. He stated the prioritization of ZW251 was driven by excitement for the asset and the ability to accelerate its clinical timeline, not by any negative developments for ZW220, which remains a high-interest, differentiated ADC.

Stephen Willey inquired about the dose optimization strategy for the ZW171 and ZW191 Phase I trials and how the preclinical therapeutic index of the company's ADCs informs its combination therapy strategy.

Answer

CEO Kenneth Galbraith explained that they will likely explore multiple doses in expansion cohorts to ensure a clear understanding of tolerability and optimal dosing, avoiding premature acceleration. Chief Scientific Officer Dr. Paul Moore added that combination strategies are being considered for all three ADC programs to move into earlier lines of therapy, with partners chosen based on the specific disease indication.

Stephen Willey asked about the planned registrational development for TPIP in PAH, wondering if it would be a single Phase 3 trial or a broader program similar to sotatercept, targeting different patient subgroups.

Answer

CEO William Lewis stated that plans would be clearer after their October FDA meeting but noted that enthusiasm for the program has grown significantly. He emphasized TPIP's potential across PAH, PH-ILD, and possibly IPF. CMO Martina Flammer added that the trial design will account for sotatercept's presence on the market, but TPIP's strong Phase 2 data provides high confidence in its competitive profile.

Stephen Willey asked about the percentage of Phase II PAH patients who entered the open-label extension (OLE) for TPIP and whether any OLE data would be shared at the upcoming readout.

Answer

CMO Martina Flammer stated that the 'vast majority' of patients continued into the OLE, with many titrating to higher doses up to 1,280 micrograms. CEO Will Lewis confirmed that OLE data will not be available with the main trial readout. However, he noted that the Phase III study is intended to use the higher 1,280 microgram maximum tolerated dose, suggesting the Phase II results may underrepresent the drug's full potential.

Stephen Willey from Stifel inquired about the nature of the upcoming Phase II PAH data disclosure and the hierarchical importance of the trial's endpoints, such as PVR reduction versus 6-minute walk distance.

Answer

CEO Will Lewis highlighted that a significant reduction in PVR, which is not common in PAH, would be very encouraging, and noted that other markers like NT-proBNP have also shown positive directional trends on a blinded basis. CMO Martina Flammer confirmed that PVR reduction is the primary endpoint for the Phase II study, which is standard for this stage, and that the trial will also assess 6-minute walk, PK, clinical worsening, and quality of life.

Stephen Willey asked about the upcoming Phase II PAH data disclosure and the hierarchical importance of endpoints like PVR reduction and 6-minute walk distance, given the small study size.

Answer

CEO Will Lewis noted that seeing a significant reduction in PVR, which is not common in PAH, would be very encouraging, and that other markers like NT-proBNP have been directionally positive on a blinded basis. CMO Martina Flammer confirmed that PVR reduction is the primary endpoint for the Phase II study, which is standard for assessing hemodynamics at this stage, with other key measures including 6-minute walk and clinical worsening.

Stephen Willey from Stifel Institutional asked about the economic structure of the Janssen trispecific deal, the potential recurring revenue from the Exploration platform, and the proportion of preclinical assets derived from the OmniChicken platform.

Answer

CEO Matthew Foehr clarified the Janssen program is not fully prepaid and includes a $35 million milestone upon first sales. CFO Kurt Gustafson stated that while they have estimates for Exploration's recurring revenue, they are not disclosing them yet. Mr. Foehr added that OmniChicken-derived programs are present in the preclinical pipeline but did not provide a specific breakdown, noting the portfolio's overall average royalty rate has increased.

Speaking on behalf of Stephen Willey, an analyst named Julian asked if there were any observable trends among partners interested in the exploration platform regarding therapeutic targets, indications, or company size. He also asked if the program could be extended to new, future partners.

Answer

Matthew Foehr, President and CEO, confirmed that new partners will have access to purchase the exploration platform as they sign on. Regarding trends, he noted that while specific targets are confidential, the company sees broad interest driven by its technology launches, such as increased activity in CNS, infectious disease, and multi-specifics following the OmniAb launch, in addition to consistent interest in oncology and immunology.

On behalf of Stephen Willey from Stifel, a question was asked about the representation of different platforms within the preclinical discovery programs and the downstream economics for sugemalimab, including its inclusion in the 2025 guidance.

Answer

President and CEO Matthew Foehr stated the preclinical portfolio is diverse, with a mix of programs from OmniRodent, bispecific, and chicken-based technologies. CFO Kurt Gustafson confirmed the royalty rate for sugemalimab is 3% globally and clarified that while the 2025 revenue guidance includes all revenue streams, it does not bake in significant upside from these specific royalties due to limited sales visibility.

Stephen Willey asked for insight into the proportion of new program starts that are multi-specific in nature, the types of targets being pursued, and an update on the blended royalty rate of the portfolio, particularly concerning the Immunovant 1402 asset.

Answer

CEO Matt Foehr confirmed a growing interest and increase in multi-specific programs, driven by technologies like OmniAb, but did not provide a specific percentage. CFO Kurt Gustafson stated he had no update to the previously disclosed blended royalty rate but noted it was unlikely to have changed significantly. He clarified the Immunovant deal structure is via a third party (Henal) but confirmed the effective royalty rate to OmniAb is consistent with their standard low-to-mid-single-digit range.

Stephen Willey requested qualitative commentary on early Q3 demand trends for Rytello and asked if there were any rate-limiting factors, such as screen failures, affecting enrollment in the IMPACT MF trial.

Answer

Jim Ziegler, EVP & CCO, expressed 'conscious optimism' for continued demand in Q3 but emphasized focusing on longer-term trends. Dr. Joseph Eid, EVP of R&D, stated that IMPACT MF trial enrollment is strong, with screen failures decreasing as sites gain experience, and confirmed they are on track to complete enrollment by year-end.

Stephen Willey from Stifel requested a breakdown of the 900 ordering accounts by prescriber decile and academic versus community setting. He also asked about utilization trends for luspatercept in the frontline setting.

Answer

Dr. Joseph Eid, EVP of R&D, stated that the majority of the 900 ordering accounts are on Geron's target list and reflect the broader market, with a split of approximately one-third academic and two-thirds community. Regarding luspatercept, he confirmed that claims data shows growth in its frontline use. He reiterated that RYTELO's label is for ESA relapsed/refractory or ineligible patients, though NCCN guidelines are broader.

Stephen Willey of Stifel inquired about the patient mix in the second-line setting, specifically regarding RS status and prior therapies. He also asked about plans for generating new data to support Rytelo's value proposition and whether the U.S. launch performance would alter the timeline for European commercialization.

Answer

Jim Ziegler, CCO, noted that while Rytelo is used across all lines, there's an opportunity to sharpen messaging for the large RS-negative population. An executive added that data generation efforts include analyzing Phase III data and exploring new combinations and sequencing. CEO John Scarlett emphasized that the U.S. launch is the overwhelming priority, with over 90% of the company's focus dedicated to getting the U.S. trajectory on track before committing heavily to European expansion.

Stephen Willey from Stifel asked about the utilization split between academic and community prescribers, how dose management for cytopenias is performing in the real world, the gross-to-net figure for the quarter, and a steady-state cost of goods assumption.

Answer

EVP & CCO Jim Ziegler reported a utilization split of approximately 65% community and 35% academic, adding that physicians are managing cytopenias well. EVP & CFO Michelle Robertson confirmed the quarterly gross-to-net was in the mid-double digits and projected that fully loaded cost of goods sold will be in the mid-single digits going forward, excluding the royalty.

Stephen Willey of Stifel asked about the baseline characteristics of the myelofibrosis (MF) patients enrolled in the Phase 1 study of 989 and the expected duration of follow-up for the upcoming data release.

Answer

President and Head of R&D Pablo Cagnoni described the patient population as 'typical' for those who have been exposed to Jakafi (intolerant or progressed), with no overly restrictive enrollment criteria. He noted that follow-up will be variable, but some patients from early dose cohorts will have been followed for more than a year.

Stephen Willey of Stifel requested clarification on the decision-making process for halting the STELLAR-305 trial, asking about the timing of the competitive assessment relative to the unblinding of the data.

Answer

EVP & CMO Amy Peterson confirmed the trial had a pre-planned gate for review and that the company reviewed the unblinded data. The decision to halt was made to prioritize other indications and reallocate resources, though she noted a future path in head and neck is not entirely ruled out.

Stephen Willey asked for details on the STELLAR-303 trial design, specifically the expected distribution of RAS wild-type versus mutant patients and whether the primary endpoint had changed.

Answer

Chief Medical Officer Amy Peterson clarified that the primary endpoint was modified to focus on patients without liver metastases, a stronger prognostic factor than RAS status. President and CEO Michael Morrissey added that data from Merck's LEAP-17 trial, which showed a better hazard ratio in RAS mutants, supported this strategic shift away from a RAS-focused endpoint.

Stephen Willey asked for clarification on the STELLAR-305 study, questioning if the Phase 2 portion has formally transitioned to Phase 3 and if the metrics for that decision would be disclosed.

Answer

Chief Medical Officer Amy Peterson confirmed that STELLAR-305 is a Phase 2/3 study that is still enrolling. She stated that data from the trial will be disclosed once it is mature.

Stephen Willey of Stifel inquired about commercial performance, specifically patient persistency and compliance for XOLREMDI in WHIM syndrome, the typical prescription supply duration, and the assumed patient dropout rate for the 4WARD trial.

Answer

Executive Mark Baldry stated that patient compliance and adherence rates are higher than typical for a daily oral medication and that patients currently receive a one-month supply. CEO Paula Ragan added that the 4WARD trial's target of 150 enrolled patients already accounts for potential dropouts and that based on current data, the trial remains on track for full enrollment in Q3 or Q4 2025.

Stephen Willey from Stifel asked for details on the regulatory discussions that led to tightening the 4WARD trial's ANC threshold, whether this change could slow enrollment, and for an update on distributor inventory levels and early gross-to-net discounting for XOLREMDI.

Answer

Paula Ragan (Executive) and Christophe Arbet-Engels (Executive) explained the trial protocol change was aligned with the FDA and EMA to focus on moderate-to-severe patients, maximizing the chance of success without impacting enrollment timelines. Adam Mostafa (Executive) noted that inventory levels reflect Q4 stocking and will likely be lumpy. Mark Baldry (Executive) confirmed the company is not currently engaging in product discounting.

Stephen Willey from Stifel questioned if the Phase II data showed any correlation between CN subtype or baseline G-CSF dose and the magnitude of G-CSF reduction. He also asked for a more precise metric on how many targeted HCPs are actively screening for WHIM.

Answer

CEO Paula Ragan and Chief Medical Officer Christophe Arbet-Engels responded that mavorixafor's effect was robustly consistent and the Phase II sample size was too small to draw definitive correlations, which will be analyzed in the larger Phase III trial. Chief Commercial Officer Mark Baldry added that the commercial team is focused on making physicians aware of WHIM through claims analysis and conference presence to encourage screening, rather than tracking a specific number of active screeners at this stage.

Stephen Willey asked about the kinetics of the reimbursement process for XOLREMDI, how the company plans to communicate enrollment progress for the Phase III 4WARD trial, and for an explanation of the sequential decrease in SG&A expenses.

Answer

Chief Commercial Officer Mark Baldry reported that the reimbursement process is working smoothly through prior authorizations and medical exceptions, supported by the X4Connect patient hub. President and CEO Dr. Paula Ragan noted that meaningful updates on 4WARD trial enrollment are expected in 2025. CFO Adam Mostafa clarified that Q2 SG&A represents a more typical run-rate, as Q1 was inflated by one-time launch preparation costs.

Stephen Willey asked for commentary on the event accrual rate for the LORIKEET study, whether disclosable data like ORR could be released in the second half of the year absent an rPFS trigger, and for the highest non-toxic dose of MGC026 and MGC028 in preclinical primate trials.

Answer

Dr. Stephen Eck, SVP, Clinical Development and Chief Medical Officer, stated it was too early to comment on the LORIKEET event rate but confirmed that ORR data could be disclosed and show differentiation. Dr. Scott Koenig, President and CEO, added that an rPFS event in the second half of the year is possible. Regarding the ADCs, Dr. Koenig disclosed that for both MGC026 and MGC028, they achieved doses of 50 mg/kg in primate studies without reaching a toxic dose.

Stephen Willey from Stifel asked about the MGC028 Phase I study, inquiring if it will pre-specify enrollment by tumor type and which tumors are of interest, especially given the change in payload from the previous ImmunoGen collaboration.

Answer

Dr. Scott Koenig, President and CEO, confirmed that the MGC028 study will limit enrollment to specific tumor types based on preclinical and IHC data showing ADAM9 overexpression. He mentioned lung cancer and pancreatic cancer as examples of tumors that would be included, aiming to see activity signals and assess the safety profile more effectively.

Stephen Willey from Stifel Financial Corp. asked about pneumonitis screening protocols, median follow-up duration in the TAMARACK study, and the patient distribution based on prior ARPI therapy duration.

Answer

Dr. Scott Koenig, President and CEO, explained there was no routine pneumonitis screening as it was not an anticipated event. He did not have the median follow-up duration readily available but noted the mean number of doses administered is now five. He recalled a roughly 40/60 split for patients with less than versus more than 12 months of prior ARAT exposure.

Stephen Willey sought specifics on the COM701 study's interim analysis trigger, whether a futility threshold exists, and details on the GS-0321 dose escalation study, including biopsy requirements and pharmacodynamic data collection.

Answer

Chief Medical Officer Dr. Michelle Mahler stated the interim analysis is triggered by a combination of follow-up time and PFS events, with a predefined futility boundary. Regarding GS-0321, she confirmed that on-treatment biopsies are mandatory in certain cohorts to collect pharmacodynamic data, but did not elaborate on further details.

Stephen Willey of Stifel inquired about the patient criteria for the upcoming Phase 2 trial of COM701, specifically the required prior lines of platinum therapy, and the rationale for pursuing a single-agent development path initially.

Answer

Chief Medical Officer Dr. Michelle Mahler clarified that the trial will target patients with at least two prior lines of platinum-based chemotherapy who are not candidates for further maintenance with bevacizumab or a PARP inhibitor. Guest investigator Dr. Oladapo Yeku added that the vast majority of patients pass through a platinum-sensitive stage and would have been exposed to these agents. President and CEO Dr. Anat Cohen-Dayag explained that the single-agent approach is designed to establish a clear baseline of COM701's contribution, which then provides a strong foundation for evaluating future combination therapies.

Stephen Willey of Stifel inquired about AbCellera's strategy of being 'indication agnostic' and the competencies required for clinical trials across diverse areas. He also asked about the specifics of the AbbVie T-cell engager (TCE) collaboration and whether competitive headwinds from China are impacting business development.

Answer

CEO Carl L. Hansen explained that being indication agnostic allows them to pursue the best opportunities broadly. He stated that clinical development teams are being built 'on time' to support the initial programs, with future hiring focused on development roles. Regarding the AbbVie deal, he described it as a significant first collaboration on a small number of targets. Hansen also noted that while they see competitive dynamics from China, AbCellera's focus on highly differentiated, first-in-class assets provides a robust defense.

Stephen Willey of Stifel asked about the number of T cell engager programs AbCellera could advance independently, the timeline for its ongoing portfolio review, and whether Canadian government funding mandates that clinical development occurs in Canada.

Answer

President and CEO Dr. Carl Hansen addressed the pipeline, stating the company has nearly $900 million in liquidity to fund an anticipated 2-3 new development candidates per year and that the portfolio review will conclude by December. CFO Andrew Booth confirmed that the government funding requires Phase I trials to be conducted in Canada, which they plan to do for ABCL575 and ABCL635 without anticipating any issues.

Stephen Willey of Stifel inquired about the trafficking capacity of CUE-501, the prevalence of CMV positivity in the population, and whether more mature CUE-101 survival data could enhance strategic partnership interest.

Answer

President and CSO Dr. Anish Suri explained that the CUE-500 platform can use various viral epitopes, like SARS-CoV-2, which has near-universal seropositivity, and that past imaging studies support good tissue penetration. Executive Daniel Passeri added that maturing survival data is crucial for differentiating CUE-101 and attracting partners, emphasizing that the emerging data appears very impressive and will strengthen their competitive position.

Stephen Willey of Stifel asked about the expected response rates for voruciclib plus venetoclax in AML, the trial design for ME-344 regarding prior patient therapies like LONSURF, the context for the 20% PFS threshold given recent data from other studies, and the reasons for the sequential decline in R&D spending.

Answer

President and CEO David Urso stated that a 20-30% response rate for voruciclib in venetoclax-relapsed AML patients would be considered exciting. Chief Medical Officer Dr. Richard Ghalie clarified that while not required, some patients in the ME-344 trial are expected to have received prior LONSURF or regorafenib, and the 20% PFS threshold is a floor, with the data's significance depending on the patient's treatment history. Chief Financial Officer Jay File explained the R&D decline is due to the wind-down of the zandelisib trials (COASTAL and TIDAL).

Stephen Willey of Stifel inquired about the approval pathway for zandelisib in light of the FDA's Project FrontRunner and Project Optimus, specifically asking if a final COASTAL endpoint read is now required and about plans for additional dose exploration.

Answer

President and CEO Dan Gold explained that MEI is still in discussions with the FDA about using randomized data from the COASTAL study for a potential accelerated filing. Regarding dosing, Gold detailed the extensive dose exploration already conducted and stated the company is analyzing its robust dataset to further justify the 60mg intermittent dose, which the FDA has deemed 'reasonable'.

Stephen Willey of Stifel Financial Corp. inquired about the rationale for adding a 10 mg/kg dose of IGM-8444 to the randomized Phase 2 trial, its impact on study powering, and the company's interest in exploring IGM-2644 for autoimmune diseases.

Answer

Chief Medical Officer Dr. Chris Takimoto explained that the decision to add the 10 mg/kg dose was driven by biomarker data showing increased caspase-3 levels and supportive FDA feedback. He and CEO Fred Schwarzer noted the trial's flexible design could support accelerated approval. President of Autoimmunity and Inflammation Dr. Mary Beth Harler added that while IGM-2644 is of interest for autoimmune diseases, they will first await safety data from its multiple myeloma trial.

Stephen Willey inquired about the severity of the Grade 3 Cytokine Release Syndrome (CRS) event in a patient on the 50mg dose of IGM-2323, the kinetics of responses including a patient's progression from partial to complete response post-ASH, the potential for a mid-year data update, and the enrollment mix of lymphoma histologies.

Answer

Chief Medical Officer Daniel Chen explained that the Grade 3 CRS event was an isolated case in a patient with prior CAR-T treatment and circulating B-cells, a very small subset for whom dosing will be adjusted. He noted that other patients at that dose had no CRS. Dr. Chen confirmed seeing deepening and rapid responses, attributing the varied kinetics to IGM-2323's multiple mechanisms of action. He stated a data update is on the table for mid-year, triggered by determining the recommended Phase II dose, and confirmed the trial continues to enroll a broad range of NHL histologies.

Stephen Willey of Stifel Nicolaus inquired about IGM's commitment to presenting IGM-2323 dose escalation data by year-end, the B cell depletion efficacy of the 30 mg dose based on nonhuman primate studies, and the development timeline for next-generation bispecific antibody programs like CD123 and CD38.

Answer

CEO Fred Schwarzer affirmed the company's intention to provide a clinical trial update by the end of the year. Chief Scientific Officer Bruce Keyt explained that the 30 mg equivalent dose in monkeys resulted in over 50% depletion of peripheral B cells. Both Schwarzer and Keyt confirmed that the CD123 and CD38 programs are advancing rapidly, with preclinical data showing potent tumor cell killing without the significant cytokine release seen in comparable IgG antibodies, reinforcing the platform's safety profile.