Samantha Semenkow

Samantha Semenkow asked about the expected mix of treating physicians for the ocular MG patient population (neurologists, ophthalmologists, neuro-ophthalmologists), the education needed to drive utilization, and any changes to the field or targeting strategy for these potential label expansions.

Answer

Sandrine Piret-Gerard, Chief Commercialization Officer, stated that there is a significant overlap between current prescribers (primarily neurologists) and the target group for both seronegative and ocular MG. She noted that argenx doubled its field footprint in early 2024 to target community neurologists, and no further changes to the approach are expected, ensuring they can reach the majority of potential prescribers.

Samantha Semenkow asked about the mix of treating physicians for ocular MG (neurologists, ophthalmologists, neuro-ophthalmologists), the education needed to drive utilization, and any changes to the field or targeting strategy with potential label expansions.

Answer

Karen Massey, COO, and Sandrine Piret-Gérard, CCO, explained there's a significant overlap between current prescribers and the target group for seronegative and ocular MG, primarily neurologists. They do not anticipate changing their field footprint, which was doubled in early 2024 to target both academic medical centers and community neurologists, where the majority of potential prescribers are located.

Samantha Semenkow from Citi asked if the lupus nephritis data could inform future indication selection for ARGX-119 or empasiprubart. She also inquired about plans for additional indication expansion for empasiprubart and the development of a subcutaneous formulation, mirroring the VYVGART playbook.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, confirmed the intention to leverage the subcutaneous platform across all indications. Luc Truyen, Chief Medical Officer, stated that while the lupus nephritis data did not show a clear path to a registration study, argenx is still fully digesting the data, which may inform future decisions on other assets in the portfolio.

Samantha Semenkow asked if any insights from the lupus nephritis data could inform additional indication selection for ARGX-119 or empasiprubart. She also inquired about plans for additional empasiprubart indication expansion and the development of a subcutaneous formulation, similar to VYVGART's playbook.

Answer

Tim Van Hauwermeiren, Chief Executive Officer, confirmed the intention to leverage their subcutaneous platform across all indications. Luc Truyen, Chief Medical Officer, stated that while the lupus nephritis data did not show a path to a registration study, the company is still fully digesting the data, which may inform future decisions for other assets in the portfolio.

Samantha Semenkow from Citigroup asked about the rationale for advancing ARGX-119 into clinical development and whether the early data from the CMS study increases enthusiasm for its potential in larger indications like ALS and SMA, and what the overall market opportunity is.

Answer

CMO Luc Truyen explained that the CMS study was chosen to get the best 'proof of biology' for the agonistic MuSK antibody, which was successfully observed via functional improvements. CEO Tim Van Hauwermeiren added that while there is read-through potential, ALS and SMA are biologically different. He positioned ARGX-119 as a 'pipeline in a product' with exciting potential in nerve regeneration and muscle diseases beyond the current three indications.

Samantha Semenkow asked how the discontinuation rate in CIDP has trended and whether physicians are still commonly giving patients a 12-week trial period.

Answer

Chief Operating Officer Karen Massey confirmed that physicians are still largely using a 12-week trial period. She noted that as the launch has matured, the discontinuation rate has seen a slight uptick, moving closer to what was expected based on the ADHERE trial data. However, she emphasized that the rate remains below that level, indicating that patients are having a positive experience and staying on therapy.

Samantha Semenkow asked about the company's confidence in the FDA granting self-administration for the prefilled syringe (PFS) and how previous FDA concerns about the administration process factored into their strategy.

Answer

CEO Tim Van Hauwermeiren expressed confidence, stating that argenx submitted a 'very strong data set,' including a solid human factor study. He noted that based on the nature of questions from the FDA, the review appears to be on track for the April 10 PDUFA date, and the company is collaborating fully with the agency.

Samantha Semenkow asked if the highlighted growth in VYVGART Hytrulo was a recent acceleration and whether the prefilled syringe (PFS) is expected to have a similar or sharper uptake trajectory.

Answer

COO Karen Massey confirmed that Hytrulo uptake accelerated in Q1, driven by the establishment of payer policies and a J-code. She anticipates the PFS will be another significant growth engine, viewing it as a key advancement that will help move VYVGART into earlier lines of treatment and further expand the prescriber base.

Samantha Semenkow sought clarification on the bivamelagon Phase 3 enrollment strategy, specifically how primarily enrolling outside the U.S. (in countries where setmelanotide is unavailable) impacts U.S. enrollment. She also asked about the latest thinking on a Prader-Willi Syndrome (PWS) Phase 3 trial, inquiring whether both setmelanotide and RM-718 would be advanced or if one would be chosen.

Answer

David Meeker, Chairman, CEO, and President, confirmed that the bivamelagon Phase 3 would predominantly enroll ex-U.S. due to setmelanotide's impending approval in the U.S., making U.S. enrollment more complex, though a U.S. site isn't entirely ruled out. For PWS, he explained the trade-offs between advancing setmelanotide (quicker sNDA) and RM-718 (next-generation, long-term goal), indicating a decision would be made based on the RM-718 program's readiness to potentially avoid running two separate studies.

Samantha Semenkow sought clarification on the enrollment strategy for the Acquired Hypothalamic Obesity (HO) Phase 3 trial, specifically how primarily enrolling outside the U.S. would impact U.S. enrollment. She also asked about Rhythm Pharmaceuticals' latest thinking on a potential Prader-Willi Syndrome (PWS) Phase 3 trial, inquiring if both setmelanotide and RM-718 would be advanced or if one would be chosen.

Answer

David Meeker, Chairman, CEO, and President, explained that the HO Phase 3 trial would predominantly enroll ex-U.S. due to setmelanotide's anticipated approval in the U.S., providing patients with an option. For PWS, he noted that setmelanotide offers a supplemental NDA path, while RM-718 is the long-term goal. The decision to advance one or both depends on the timing gap between starting their respective Phase 3 trials, with a preference to potentially wait for RM-718 to avoid running two separate studies.

Samantha Semenkow asked about Beam's regulatory path for addressing multiple PKU mutations, the timeline for moving beyond the R408W mutation, and how the risto-cel financing might reallocate capital to additional liver-targeted indications.

Answer

CEO John Evans, Chief Scientific Officer Gopi Shanker, Chief Medical Officer Amy Simon, and CFO Sravan Emany explained that research for additional mutations is underway with expected fast timelines due to the platform approach. They anticipate bringing multiple mutations under one program, with initial proof of concept for R408W. The financing provides flexibility to redirect capital to pipeline growth, leveraging fixed investments for subsequent programs.

Samantha Semenkow asked about Beam Therapeutics' regulatory path for addressing multiple PKU mutations, the timeline for moving beyond R408W, and how the risto-cel strategic financing might reallocate capital to additional liver-targeted indications.

Answer

CEO John Evans, CSO Gopi Shanker, CMO Amy Simon, and CFO Sravan Emany responded. Gopi Shanker explained that research for additional mutations is underway, with rapid timelines expected due to the platform approach and unique guide RNAs. Amy Simon highlighted FDA collaboration on adaptive trial designs to accelerate development. Sravan Emany noted the financing provides flexibility to redirect capital to pipeline growth, leveraging fixed investments in the platform.

Samantha Semenkow from Citigroup inquired about the potential efficacy trade-off for the ESCAPE program if it proves safer but less effective than chemotherapy, and asked about safety concerns for the BEAM-103 (CD117 antibody) ahead of its healthy volunteer study.

Answer

CEO John Evans stated that based on current non-human primate data, they are achieving 'fairly full efficacy' with ESCAPE, mitigating concerns about a trade-off. President Dr. Giuseppe Ciaramella added that other anti-CD117 antibodies have shown a favorable safety profile with only mild, transient neutropenia, supporting the potential for an outpatient regimen and making a healthy volunteer study an efficient path to gather PK/PD data.

Samantha Semenkow of Citigroup Inc. asked about the potential efficacy versus safety trade-off for the ESCAPE platform and inquired about any known safety concerns related to targeting CD117 with the BEAM-103 antibody.

Answer

CEO John Evans stated that based on current data, they expect to achieve full efficacy with ESCAPE, avoiding a trade-off. President Dr. Giuseppe Ciaramella added that other studies with anti-CD117 antibodies have shown only transient, mild neutropenia, not myeloablation, suggesting a favorable safety profile that could even enable outpatient treatment.

Samantha Semenkow from Citigroup asked about the potential efficacy trade-off for ESCAPE's improved safety profile and inquired about any safety concerns with the BEAM-103 (anti-CD117) antibody.

Answer

CEO John Evans stated that initial NHP data for ESCAPE shows 'fairly full efficacy,' suggesting a compelling profile without a trade-off. President Dr. Giuseppe Ciaramella added that other anti-CD117 antibodies have shown only mild, transient neutropenia, supporting a favorable safety profile and the potential for an outpatient procedure. A healthy volunteer study will further define the PK/PD profile.

Samantha Semenkow asked about the cadence of ACTIVASE scripts since approval, specifically if they increased after the REMS became fully operational, and inquired about the potential outcomes from the planned sNDA meeting with the FDA on sickle cell disease.

Answer

Brian Goff, CEO, stated they would stick to the reported 44 scripts. Tsveta Milanova, Chief Commercial Officer, expressed encouragement for early demand, noting prescriptions from both transfusion-dependent and engaged non-transfusion-dependent patients, with a healthy breadth of community prescribers. Sarah Gheuens, Chief Medical Officer and Head of R&D, indicated the pre-sNDA meeting in Q1 aims to gain insights on regulatory pathways for mitapivat, presenting data for full approval based on RISE UP's anti-hemolytic profile and clinical benefits, noting FDA's view of hemoglobin as a surrogate endpoint.

Samantha Semenkow inquired about the cadence of ACTIVASE scripts since approval, specifically if there was an increase after January 30th when REMS became fully operational, and asked about the potential outcomes from the planned pre-sNDA meeting with the FDA for sickle cell disease.

Answer

CEO Brian Goff stated they would stick with the 44 reported scripts. Chief Commercial Officer Tsveta Milanova reiterated satisfaction with early demand and execution, noting prescriptions from anticipated patient profiles and broad geographic distribution. Chief Medical Officer and Head of Research and Development Dr. Sarah Gheuens explained the pre-sNDA meeting's goal is to gain insights into regulatory pathways for mitapivat, aiming for full approval based on RISE UP data, and mentioned planning to update after meeting minutes.

Samantha Semenkow asked about the percentage of Brepo study patients with organ involvement, any data collected on brepocitinib's impact on organ-specific manifestations, and the path to expand into other forms of sarcoidosis.

Answer

CEO Matt Gline confirmed that Roivant would evaluate further places to study Brepo, both within and outside sarcoidosis. CEO Ben Zimmer noted that around 60% of patients had pulmonary involvement and 30% had other organ involvement (mostly ocular), but the study was not designed to evaluate benefit in those systems, so meaningful data is not expected.

Samantha Semenkow, VP and SMid Biotech Equity Research Analyst at Citi, asked about the percentage of patients with organ involvement in the Beacon study, whether brepocitinib's impact on organ-specific manifestations was assessed, and the potential path to expand into other forms of sarcoidosis.

Answer

Matt Gline, CEO of Roivant Sciences, confirmed that Roivant would evaluate further expansion for brepocitinib, including other sarcoidosis forms. Ben Zimmer, CEO of Priovant, specified that around 60% of patients had pulmonary involvement and 30% had other organ involvement (mostly ocular). He noted that while exploratory endpoints were collected, the study wasn't designed to evaluate benefit in those systems, and meaningful insights are not expected.

Samantha Semenkow inquired about the percentage of patients with organ involvement in the Beacon study, whether data was collected on organ-specific manifestations, and the potential path to expand brepocitinib into other forms of sarcoidosis.

Answer

Matt Gline, CEO of Roivant, confirmed they would evaluate further places to study brepocitinib, both inside and outside sarcoidosis. Benjamin Zimmer, CEO of Priovant Therapeutics, noted that around 60% of patients had pulmonary involvement and 30% had other organ involvement, but the study was not designed to evaluate benefit in those systems, so meaningful learning isn't expected.

Samantha Semenkow asked about the percentage of patients with organ involvement in the brepocitinib cutaneous sarcoidosis study, whether data was collected on organ-specific manifestations, and if there's a path to expand into other forms of sarcoidosis.

Answer

Matt Gline, CEO of Roivant, confirmed that the company will evaluate further study places for brepocitinib, both within and outside sarcoidosis. Benjamin Zimmer, CEO of Priovant Therapeutics, noted that around 60% of patients had pulmonary involvement and 30% had other organ involvement (mostly ocular), but the study was not designed to evaluate benefit in those systems, so meaningful learning is not expected.

Samantha Semenkow asked about the Graves' disease remission data, specifically how much the high-dose batoclimab contributed to the observed remission rates, given the competitive landscape.

Answer

CEO Matthew Gline indicated that deeper IgG reductions are expected to drive remission, and while being cautious due to competition, he expressed confidence in Roivant's level of IgG suppression at high dose in the BATO trial.

Samantha Semenkow asked about the Graves' remission data, specifically how the high-dose Batoclimab contributed to the observed remission rates, especially in the context of the competitive landscape.

Answer

CEO Matt Gline explained that deeper IgG reductions are expected to drive longer remission, and the high-dose Batoclimab in the study showed significant TRAb lowering and speed of response. He expressed confidence in their level of IgG suppression in the program.

Samantha Semenkow of Citi asked about the status of the protocol amendment to close the FCA arm, whether enrollment could continue, and if patients screened during the process would remain eligible.

Answer

CMO Dr. Zachary Roberts confirmed the protocol amendment is with IRBs and expected to be approved within days, causing minimal to no disruption. He assured that patients screened during this period will remain eligible for enrollment into the standard FC arm once the amendment is approved.

Samantha Semenkow asked about the expected size of the initial ALLO-329 data set needed for a lymphodepletion decision and whether similar site staffing challenges from ALPHA3 are anticipated for the RESOLUTION study.

Answer

CEO David Chang acknowledged that based on the ALPHA3 experience, they are proactively addressing potential site staffing issues for the autoimmune trial, which has added logistical complexity. He indicated the initial data would come from a 'handful of patients' and that the study is designed to evaluate both lymphodepletion regimens (with and without) before making a selection.

Samantha Semenkow from Citigroup asked how Allogene views the infrastructure build-out by autologous CAR-T competitors in community centers and how it could be leveraged for a potential cema-cel launch.

Answer

Dr. David Chang, President and CEO, characterized the expansion of CAR-T infrastructure into community centers as a positive development for the entire field. He asserted that allogeneic CAR-T is particularly well-positioned to benefit from this due to its logistical simplicity and scalability, which are significant advantages in the community setting.

Samantha Semenkow asked if targeting CD70 via the Dagger technology could be a contributing factor to the Grade 5 events seen with ALLO-316 and how this safety profile might translate to the autoimmune program and influence dose selection.

Answer

Dr. David Chang, President and CEO, responded that while the Dagger technology enhances the CAR-T's pharmacodynamic effect, the safety events are highly confounded by the patients' advanced disease state. He stated there is not a direct read-through to the autoimmune population. The key to development, as with any active drug, is finding the right dose and lymphodepletion regimen to balance safety and efficacy, which will be a primary goal of the ALLO-329 Phase I study.

Samantha Semenkow asked about Catalyst's strategy for educating oncologists on the LEMS opportunity for Firdapse, the metrics used to track the campaign's success, the expected timeline for oncology to become a larger revenue segment, and plans to leverage data from the Phase 1 DMD switching study for Agamry.

Answer

EVP & Chief Commercial Officer Jeff Del Carmen detailed a three-step oncology strategy involving frictionless VGCC antibody testing, leveraging new NCCN guidelines, and establishing care pathways in oncology practices. He noted success will be tracked by increased testing from oncologists, with a meaningful revenue impact expected in 2026 and beyond. Chief Medical Officer Dr. Will Andrews added that the Agamry switching study is exploratory, with data expected in late 2025 to early 2026 to inform potential future studies.

Samantha Semenkow asked about early trends in AGAMREE's patient durability, the stability of the patient switch mix from EMFLAZA and prednisone, and the specific drivers behind the observed 15% discontinuation rate.

Answer

CCO Jeffrey Del Carmen reported a strong and stable discontinuation rate for AGAMREE of around 15%, which aligns with forecasts. He noted the patient switch mix (45% from EMFLAZA, 43% from prednisone) is also stable and expected to continue. Del Carmen clarified that discontinuations are often temporary pauses as patients evaluate new treatments like gene therapy, rather than being driven by efficacy or side effect concerns, and that patients are expected to return to AGAMREE.

Samantha Semenkow from Citi inquired about the WVE-007 program, asking how the Activin E reduction in cohort one compared to preclinical models and about the expected correlation between knockdown and weight loss. For the AATD program, she asked about the target Z-to-M protein conversion rate.

Answer

President & CEO Paul Bolno explained that WVE-007 showed a dose response in preclinical models and that cohort one data demonstrated good consistency with their PK/PD modeling, which is why they expanded cohort two. For the AATD program (WVE-006), he stated the goal has always been to convert ZZ patients to an MZ phenotype, which they surpassed in the single-dose data. He noted that while they expect more protein with multi-dosing, achieving a 50% correction to the MZ level is the key therapeutic goal.

Samantha Semenkow asked about the 'plug-and-play' potential of the ALPL non-viral shuttle for different molecules and what to expect from the preclinical data set anticipated later in the year.

Answer

CEO Dr. Al Sandrock explained that while some shuttles are 'plug-and-play,' different receptors like ALPL have unique properties that may be tailored to specific diseases, suggesting a future of more selective shuttles. He indicated the upcoming data would likely feature in vivo animal results, comparing ALPL to TFR-based shuttles and potentially demonstrating its utility with multiple payloads.

Asked if the success bar for uveitis is 'better than Humira' and how the inclusion of biologic-experienced patients might impact study results.

Answer

Yes, the company is generally looking for a profile superior to adalimumab (Humira). The study includes biologic-experienced patients and stratifies for them at randomization to analyze their outcomes, acknowledging this is a difference from the original Humira trials which enrolled naive patients.

Asked for an explanation of why the observed cases of tinnitus in the lonigutamab study were confined to Cohort 1 and whether there was a common factor among the affected patients.

Answer

The company has not identified a specific reason for the transient tinnitus cases in Cohort 1 and does not believe it is related to dose exposure, especially since it was not seen in Cohort 2. The cases were transient and resolved, and no patients experienced hearing impairment or audiogram changes.

Samantha Semenkow inquired about apheresis rates in Q4 compared to Q3 and the expected trajectory into 2025, acknowledging the impact of seasonality mentioned in the guidance.

Answer

William Baird confirmed that while Q4 is impacted by holiday seasonality, the underlying demand since the third-line approval remains strong. He expressed encouragement with the growth seen in Q3 and stated they are working to support it commercially, with more details on 2025 to come later.

Asked for insights on Abecma's utilization trends, the types of patients receiving it, and how physicians decide to use it versus other therapies.

Answer

The executive explained that utilization is highly site-specific and depends on what other therapies (other CAR-Ts, T-cell engagers) are available at a given center. They do not see Abecma being niched for a particular patient subset but rather used broadly.

Samantha Semenkow asked if the lipid nanoparticle (LNP) delivery system for the in vivo program's target tissue will be fully optimized by the POC readout, or if it will require further work afterward.

Answer

Chief Scientific Officer Linda Burkly explained that Editas is evaluating LNPs with multiple partners to target different tissues. She did not disclose the specific tissue for the upcoming POC but stated that information on the targeting aspect of the LNP would be shared when the data is released.

Samantha Semenkow of Citi asked for updated thoughts on the variability of buccal cells versus skin, whether baseline frataxin levels were similar to Phase I, what level of frataxin increase would be considered clinically meaningful, and for more detail on the pharmacokinetic data regarding drug accumulation.

Answer

Dr. Carole Ben-Maimon, President and CEO, reiterated that skin is a less variable tissue than buccal cells but emphasized the importance of evaluating both. She confirmed baseline frataxin levels were similar to Phase I. Dr. Ben-Maimon explained that while a specific target for frataxin increase has not been set, it is not necessarily 50% of normal, as any increase could be beneficial. On pharmacokinetics, she clarified that the drug reached steady state by day 14 with no further accumulation, and exposure decreased proportionally with every-other-day dosing.