Jason Zemansky

Jason Zemansky asked if the growth in NPM1 patients represents a bolus of patients prior to approval and for qualitative comments on any impact from competitors on Revuforj prescribing.

Answer

Michael Metzger, CEO, and Steve Closter, Chief Commercial Officer, explained that NPM1 growth is more of an 'on-ramp' acceleration rather than a sharp bolus, with a steady ramp from 10% to 20% to 30% of new starts. Michael Metzger stated they haven't felt much impact from competitors, expect to dominate due to a superior product profile and execution, and have strong enthusiasm for the year.

Jason Zemansky asked how much of the growth in NPM1 patients represents a bolus prior to approval and qualitatively commented on whether competitor entry has impacted Revuforj prescribing.

Answer

Steve Closter, Chief Commercial Officer, explained that NPM1 growth is more like an 'on-ramp' acceleration rather than a sudden bolus, with a steady ramp from 10% to 20% to at least 30% of new starts. Michael Metzger, Chief Executive Officer, stated that they haven't felt much impact from competitors, had a great Q4, and expect to dominate the space due to a superior product profile and execution.

Jason Zemansky inquired about the company's assumptions for peak market penetration in the KMT-2A population and the expected competitive market split once Revuforge is approved for NPM1 AML.

Answer

CCO Steve Closter stated that they expect to reach 50% of the KMT-2A market this year with further upside, as Revuforge is the standard of care with no near-term competitors. CEO Michael Metzger added that for NPM1, they expect to 'dominate' and capture a 'significant percentage' of the market by leveraging their first-to-market advantage and best-in-class profile. He also stressed that duration of therapy is a key growth driver beyond new patient starts.

Jason Zemansky from Bank of America asked about the timing for getting Revuforj's NPM1 data included in NCCN Guidelines, specifically if it could happen by the May 19 meeting or if an ad hoc meeting was possible.

Answer

CEO Michael Metzger expressed optimism about making the May 19 NCCN meeting, following the recent acceptance of their manuscript for publication. He noted that if they miss the date, an ad hoc committee meeting is also a possibility, as has happened for other practice-changing medicines. He reiterated the expectation for inclusion in the near term, consistent with prior guidance for Q2.

Jason Zemansky of Bank of America inquired if the HOVON-led trial in unfit AML patients has a protocol design that could support an accelerated approval path and asked how Syndax is strategically prioritizing between the first-line fit versus unfit patient populations.

Answer

President and Head of R&D Dr. Neil Gallagher confirmed the company is positioned to utilize any opportunity for accelerated approval but would not discuss specifics of regulatory interactions. CEO Michael Metzger explained that the unfit population represents the highest unmet need, making the HOVON trial a top priority, but stressed that trials in the fit population will also be initiated in 2025.

Jason Zemansky of BofA Securities inquired about the potential for Breakthrough Therapy Designation for Revumenib in NPM1 and whether the 20% CR/CRh efficacy floor for approval still applies.

Answer

CEO Michael Metzger explained that Syndax did not apply for Breakthrough Therapy Designation because the Phase 1 dataset at the recommended dose had too few patients to meet the requirement. He reiterated that a CR/CRh rate of 20% or higher is the historical precedent for AML approvals and expressed confidence in the upcoming data.

Jason Zemansky asked Peter Heerma about the potential 'halo effect' of an FSGS approval on IgAN, specifically regarding increased awareness or reduced friction points for IgAN prescribers, given the 80% prescriber base overlap.

Answer

Peter Heerma (Chief Commercial Officer) confirmed that there will absolutely be a halo effect and crosstalk between the two indications due to the largely same prescriber base. Eric Dube (President and CEO) added that they expect synergistic effects, particularly in simplifying processes for busy offices, but it's too early to quantify the magnitude.

Jason Zemansky asked about the potential for a 'halo effect' if FILSPARI receives approval in FSGS, specifically how it might increase awareness or lower friction points for IgA nephropathy prescribers.

Answer

Peter Heerma, Chief Commercial Officer, and Eric Dube, President and CEO, confirmed an expected synergistic 'halo effect' due to the largely overlapping prescriber base, leading to increased confidence and simplified processes for offices, though quantification is difficult at this stage.

Jason Zemansky from Bank of America inquired about the current headwinds or bottlenecks in Filspari's uptake and whether there is a measurable difference in drug use between newer, healthier patient segments versus more advanced ones.

Answer

CCO Peter Heerma identified the main challenge as overcoming the historical inertia and creating an urgency to treat, which new market entrants and guidelines should help. He noted the upcoming REMS modification to quarterly monitoring is well-aligned with clinical practice for lower-proteinuria patients, representing a key opportunity as these patients are typically seen every three months.

Jason Zemansky of Bank of America inquired about the extent to which the nephrology community has adopted more aggressive treatment approaches based on draft KDIGO guidelines and the expected impact of their finalization.

Answer

CCO Peter Heerma and CMO Dr. Jula Inrig confirmed a significant impact is already occurring, with physicians conducting earlier biopsies and adopting more aggressive treatment targets. Heerma cited market research showing 75% of nephrologists now target lower proteinuria levels. They expect a continued 'trickling down' effect and cementing of this practice change upon final publication of the guidelines.

Jason Zemansky requested more detail on pre-launch activities for FSGS, particularly regarding the education on proteinuria as a key biomarker and whether awareness is a potential bottleneck in the broader community.

Answer

CMO Dr. Jula Inrig confirmed the educational focus on reinforcing proteinuria's role in kidney failure progression for all practitioners. CCO Peter Heerma added that with an over 80% prescriber overlap with IgAN, brand familiarity is already high. Pre-launch efforts are focused on mapping the FSGS patient journey, identifying intervention points, and building the specific health economic value story for payers.

Jason Zemansky requested additional color on the softer dynamics of BRINSUPRI's patient journey, including the impact of DTC efforts on awareness and whether interest is more patient-driven or prescriber-driven.

Answer

Will Lewis, Chairman and CEO of Insmed, highlighted clear enthusiasm from patients, evidenced by social media posts, and strong physician awareness due to commercial efforts. He noted it's too early to discern broader adoption patterns, which will become clearer in Q4 and 2026.

Jason Zemansky requested additional color on the softer dynamics of Brensupri's patient journey, including the impact of DTC efforts on awareness and whether interest is driven more by patients or prescribers.

Answer

Will Lewis, Chairman and CEO, highlighted clear enthusiasm from patients, evidenced by social media posts of them holding the product. He also noted that physicians are well aware of the medicine due to commercial team efforts. However, he cautioned that it's too early to discern specific patterns of behavior regarding patient awareness translating into broader adoption, which will be clearer in Q4 and 2026.

Jason Zemansky asked about the practical mechanics Insmed is using to capture patients for the brensocatib launch in non-cystic fibrosis bronchiectasis (NCFB), given it is a new indication without an established treatment market.

Answer

CEO William Lewis detailed a multi-pronged strategy, referencing the successful playbook from the ARIKAYCE launch. He highlighted the early deployment of the sales force for disease state awareness, detailed physician profiling to identify high-potential prescribers, and the 'Enlighten' patient support program designed to create a 'frictionless' experience. CFO Sara Bonstein added that the creation of the COPD Foundation's care center network is another tangible element to aid the patient journey.

Jason Zemansky inquired about the key levers and potential headwinds for achieving a 'frictionless launch' for Brensocatib, seeking to understand how patient interest will be converted into prescriptions.

Answer

CEO William Lewis stated the initial focus is on diagnosed patients with two or more exacerbations, with a parallel effort to encourage diagnosis in other symptomatic patients. He highlighted Insmed's strong reputation and commercial team. CFO Sara Bonstein added that the COPD Foundation's creation of specialized treatment sites is an encouraging factor for patient access.

Jason Zemansky inquired about the key levers for converting interested patients to therapy to achieve a 'frictionless launch' for Brensocatib and any potential headwinds.

Answer

CEO William Lewis explained the initial focus is on diagnosed bronchiectasis patients with two or more exacerbations, a group for which physicians are already prepared. He mentioned a secondary effort to encourage diagnosis in symptomatic patients who lack a CT scan. CFO Sara Bonstein added that the COPD Foundation's initiative to create specialized NTM and bronchiectasis treatment sites is an encouraging development for patient access.

Jason Zemansky asked about expectations for brensocatib's potential label, specifically regarding restrictions like exacerbation counts, and the potential for payer pushback.

Answer

CEO Will Lewis stated that while the company has an ambition for a broad label, their commercial forecast assumes payers will restrict access to patients with two or more exacerbations per year, consistent with the trial's entry criteria. The strategy to manage this is to use modest contracting to secure a frictionless process based on verbal physician attestation for both initial prescriptions and reauthorizations.

Jason Zemansky of Bank of America questioned the efficacy expectations for the BiRCh study in CRS, the potential translatability of results to other indications, and what criteria define an ideal future I&I condition for brensocatib.

Answer

CMO Martina Flammer stated the BiRCh study is powered to detect a clinically meaningful difference on the sinus symptom score, comparable to existing therapies. She noted both CRS and HS are driven by neutrophil inflammation. CEO Will Lewis expanded on this, explaining that success with brensocatib validates the broader DPP1 inhibition mechanism, for which Insmed is developing a library of second-generation candidates targeting diseases like rheumatoid arthritis and COPD.

Jason Zemansky questioned the efficacy expectations for the BiRCh study in CRS, its translatability to other indications, and what criteria define an ideal future indication for brensocatib.

Answer

CMO Martina Flammer stated the study is powered to detect a 1.34 to 1.55 point difference on the symptom score, which is in line with an approved therapy. CEO Will Lewis added that positive results in CRS and HS would further validate the DPP1 inhibition mechanism, supporting the development of a library of second-generation DPP1s for new indications like rheumatoid arthritis and COPD.

Jason Zemanski asked about the key assumptions behind Infigratinib's projected $2 billion opportunities in achondroplasia and hypochondroplasia, specifically whether these numbers reflect capturing share from competitors or growing the overall market, and the confidence in these figures.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, explained that their estimates begin with the treatable patient population, aiming to both capture market share and expand the market. He emphasized that current suboptimal therapies do not fully address the substantial unmet needs, particularly those not met by once-daily injectables. Kumar noted that the unmet need is well-described, and patient identification is not a challenge, giving confidence in the market potential.

Jason Zemanski asked about the key assumptions behind Infogratinib's projected $2 billion opportunities in achondroplasia and hypochondroplasia, considering the competitive landscape, and whether this growth is driven by capturing market share or expanding the overall market.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, explained that estimates begin with the treatable patient population. For an already launched product, the goal is both to capture share and grow the market. He highlighted that substantial unmet needs are not addressed by once-daily injectables, citing patient and physician feedback. He believes it's inaccurate to define the market size based on suboptimal therapies and that the unmet need is well-described with identifiable patients, requiring an appealing therapeutic offering.

Jason Zemansky from Bank of America asked for more detail on the contribution from switch patients to Attruby's growth, inquiring about the near-term dynamics and whether the company is working through a bolus of refractory patients.

Answer

VP of Strategic Finance Chinmay Shukla and CCO Matt Outten both confirmed that they did not see a patient bolus at launch. They reiterated that the primary focus is on the treatment-naive market, where they are seeing consistent monthly growth. While they initially captured 100% of the switch market, they expect that share to evolve with new competition, and they find it difficult to predict the long-term trend for switches.

Jason Zemansky asked for a comparison of Acumen's brain shuttling technology with Roche's trontinemab, questioning how to benchmark it and what Roche's observed plaque reduction implies for Acumen's oligomer-focused epitope.

Answer

President & Chief Development Officer Jim Doherty explained that while both technologies aim to enhance brain delivery, Acumen's key differentiator is its target: toxic synaptotoxic oligomers, which they believe is a more direct mechanism for patient benefit. He noted the complex biology linking oligomers and plaques. Chief Medical Officer Dr. Eric Siemers added that Roche's program is in Phase 1, whereas Acumen's Phase 2 ALPITUDE AD study is set for a topline readout in late 2026.

Jason Zemansky asked about Acumen's interest in pursuing preclinical Alzheimer's trials, especially given the positive subcutaneous formulation data, and inquired about the possibility of integrating the subcutaneous formulation into the ongoing ALTITUDE-AD study.

Answer

CEO Daniel O'Connell stated that while the company is aware of the potential for preclinical studies, the immediate focus is on executing the ALTITUDE-AD trial. Dr. James Doherty, President and Chief Development Officer, added that the team is currently evaluating the most efficient way to incorporate the subcutaneous formulation into the broader sabirnetug program and will provide updates later.

Jason Zemansky asked about the commercial dynamics in relapsed/refractory NPM1-mutant AML, specifically how Kura will address a competitor's first-to-market advantage, and what the company expects regarding the evolution of NCCN guidelines for the Menin inhibitor class.

Answer

CEO Dr. Troy Wilson and CCO Brian Powl emphasized Kura's two-year preparation and confidence in Zifdomenib's profile to compete effectively upon launch. Regarding guidelines, Mr. Powl and CMO Dr. Mollie Leoni stated they will submit for inclusion promptly after approval and expect specific drugs to be named, rather than just the class, due to distinct data packages.

Cameron Bozdog, on behalf of Jason Zemansky at Bank of America, asked what would be considered a successful outcome for the ziftomenib plus 7+3 chemotherapy combination data at EHA, particularly regarding response rates and MRD negativity, and what would build confidence for an accelerated approval pathway.

Answer

Executive Mollie Leoni responded that a 'win' would involve maintaining the backbone's high efficacy while augmenting it with improved durability and MRD negativity, rather than just a higher ORR. She suggested a 40% MRD negativity rate in bone marrow would be a good benchmark for the data.

Jason Zemansky from Bank of America asked what would constitute encouraging data from the KOMET-007 study's 7+3 combination, particularly regarding MRD negativity. He also inquired about the strategy to address the 'other mutations' AML patient segment.

Answer

CMO Dr. Mollie Leoni stated that achieving an MRD negativity rate in the 50-60% range, an increase from the 40-45% standard, would be very encouraging. CEO Troy Wilson addressed the 'other mutations' by highlighting potential expansion into FLT3-mutant AML, possibly through a frontline combination study with quizartinib, funded by the Kyowa Kirin collaboration.

Jason Zemansky of Bank of America asked about the benchmarks for a successful data update at ASH for ziftomenib combinations and inquired about the acceptable rate for differentiation syndrome (DS).

Answer

EVP of Clinical Development, Dr. Mollie Leoni, outlined that for relapsed/refractory patients, any improvement over the poor prognosis is significant, while for frontline adverse risk, the benchmark is a ~60% composite response rate. Regarding DS, she stated a manageable rate of 20% or less is tolerable. CEO Dr. Troy Wilson added that the full data set will show the DS rate dropping to single-digit percentages.

Jason Zemansky from Bank of America Merrill Lynch asked about the path for bempedoic acid to reach blockbuster status, the timing of a major growth inflection, and how the company plans to navigate potential competition from new oral agents and pricing pressures.

Answer

President & CEO Sheldon Koenig asserted that a growth inflection is already underway, as shown in the presentation, and that growth in a large primary care market is steady rather than a sharp 'hockey stick.' He expressed confidence in reaching their goals through sustained double-digit growth across all metrics. He reiterated that future competitors are years away and lack the crucial outcomes data that Esperion already possesses, giving them a significant long-term advantage.

Asked about prescriber awareness levels for bempedoic acid and whether the sales force size is optimal or could be increased.

Answer

Aided awareness is very high (95%), and the focus is on communicating efficacy and expanded insurance coverage. The company believes the sales force is currently sized appropriately for its goal of achieving profitability, but they continue to evaluate it. Consumer-directed marketing is also a key lever.

Jason Zemansky of Bank of America asked why Cytokinetics didn't submit a REMS initially to avoid the risk of a delay, given its importance for the drug class.

Answer

Robert I. Blum, President and CEO, explained that it was a calculated risk based on a consensus view from internal and external regulatory experts. The team concluded that submitting without a REMS was a reasonable strategy to best position aficamten, while also having a contingency plan in place should the FDA request one, which ultimately occurred.

Jason Zemansky from BofA Securities asked about the strategy to expand aficamten into the first-line setting, the challenges of engaging community prescribers, and the dependency of this strategy on the final REMS program.

Answer

EVP & CCO Andrew Callos clarified that first-line use is not a near-term concern, as it would typically follow guideline updates. He noted that positive data from studies like MAPLE-HCM could motivate community physicians who are currently less engaged with CMIs. He described a typical linear launch curve for cardiovascular drugs, with high growth occurring after 2-4 years as prescribing expands beyond the initial ~500 specialists to thousands of cardiologists, a process that MAPLE could help accelerate.

Jason Zemansky of Bank of America questioned the decision to use only progression-free survival (PFS) as the primary endpoint for the PEAK-1 study and asked how Arcus intends to differentiate its combination from Merck's, considering a potential first-mover advantage.

Answer

CMO Dimitry Nuyten stated that PFS is the established registrational endpoint and outlined several differentiators for PEAK-1: using the physician-preferred TKI cabozantinib, the ability to enroll post-adjuvant patients for a broader label, and the emerging efficacy differentiation of casdatifan itself. He expressed confidence in achieving both a tolerability and efficacy edge.

Jason Zemansky of Bank of America inquired about the adenosine pathway program. He asked if Arcus has "cracked the code" on which tumors are most likely to respond, given varied results, and what signals provide confidence in the mechanism for potential future indications.

Answer

CEO Terry Rosen explained that the "sweet spot" for the adenosine pathway appears to be less about the specific organ and more about the treatment biology, particularly when combined with immunogenic chemotherapy. He noted that in settings where chemo causes cell death and ATP release, adenosine is produced, suppressing T-cells. Mitigating this effect is the core hypothesis, which is being validated in pancreatic and colorectal cancer studies. President Juan Jaen added that tumors with high CD73 expression, common in the GI tract, are also a key factor.