Jonathan Miller

Jonathan Miller asked for an update on Legend Biotech's progress within the Virginia Oncology Associates (VOA) network, including patient treatment status and plans for expansion beyond Virginia, as well as adoption expectations in community-specific practices for 2026.

Answer

Alan Bash, President of CARVYKTI, confirmed that patient treatment has begun at VOA with positive feedback, and Legend Biotech plans to engage with VOA and other practices. He highlighted that 50% of current patients are treated in an outpatient setting, and the removal of REMS restrictions is a tailwind for patients to be monitored closer to home, supporting community adoption.

Jonathan Miller asked for an update on Legend Biotech's community progress, specifically regarding patient treatment and uptake in the VOA network, plans for expansion beyond Virginia, and adoption expectations in community-specific practices for 2026.

Answer

Alan Bash, President of CARVYKTI, explained the community strategy involves leveraging existing community/regional hospitals, engaging referring community physicians, and expanding community networks like VOA, where patient treatment has begun with positive feedback. He highlighted that 50% of patients are treated outpatient, and REMS removal further supports community access.

Jonathan Miller requested a breakdown of CARVYKTI patients in second and third-line settings specifically and asked how J&J's bispecific T-cell engagers will be positioned relative to CARVYKTI.

Answer

Alan Bash, President of CARVYKTI, noted that while a specific line-by-line breakdown would not be provided, nearly 60% of orders come from the second-to-fourth line population, which CARVYKTI 'owns' within the J&J portfolio. CEO Ying Huang added that second and third-line patients are the fastest-growing revenue contributors and that J&J is exploring combination and sequencing strategies.

Jonathan Miller of Evercore ISI requested clarification on the price difference between the U.S. and the lowest-cost global market, asked for an update on administering CAR-T in community centers, and questioned the differentiation of their in vivo CAR-T approach versus competitors.

Answer

Alan Bash, President of CARVYKTI, declined to specify the lowest price but noted a pricing band is maintained. He stated that plans are in the works to have large community networks administering CARVYKTI this year. Guowei Fang, President of R&D, outlined five key differentiators for their in vivo platform: T-cell recognition mechanisms, proprietary lentivirus engineering to reduce nonspecific transduction, CAR design expertise, robust CMC process, and rapid clinical execution.

Jonathan Miller inquired about the company's plans for a clinical trial to more aggressively manage neurotoxicity for CARVYKTI, similar to an Arcellx-like management system, and asked about potential data presentations at the upcoming ASCO meeting.

Answer

Jessie Yeung, an executive, explained that investigator-initiated trials are planned to explore risk mitigation strategies using absolute lymphocyte count (ALC) as a predictive biomarker, with a harmonized cutoff of 3,000. An Unknown Executive added that internal CARTITUDE studies have already been amended to incorporate ALC monitoring and a specific dexamethasone dosing regimen. Regarding ASCO, the executive stated they could not comment on specifics until abstracts are accepted but noted that both Legend and J&J are excited about potential presentations.

Jonathan Miller of Evercore ISI questioned the drivers of the Hepatitis B vaccine market's shift to retail, its impact on long-term guidance, and the company's capital allocation strategy following the completion of its share repurchase program.

Answer

Chief Commercial Officer Donn Casale explained the shift to retail mirrors trends in other adult vaccines, driven by pharmacy outreach and patient convenience, which supports Dynavax's long-term guidance. CFO Kelly MacDonald described the $200 million share buyback as a discrete and efficiently executed program to return excess capital, affirming the company's ongoing commitment to prudent capital allocation to drive shareholder value.

Jonathan Miller followed up on the FDA topic, asking if the agency's potential new requirement for placebo-controlled trials would affect Dynavax's programs. He also questioned the commercial strategy for the new Lyme disease vaccine, given that competitors are significantly ahead in development, and asked if Dynavax expects competitors to establish a reliable correlate of protection.

Answer

CEO Ryan Spencer stated that a potential placebo-controlled trial requirement would not negatively impact their shingles program, as a placebo-controlled efficacy study was already planned. For the Lyme vaccine, Spencer argued that a differentiated product profile featuring fewer doses or boosters, enabled by the CpG 1018 adjuvant, could not only capture market share but also expand the overall market by improving patient uptake. He added that while he doesn't expect a formal correlate of protection to be established, competitor data will provide a useful antibody threshold for measuring the success of their own early-stage studies.

Jonathan Miller questioned the company's confidence in executing on business development versus returning capital, what level of safety differentiation for the shingles vaccine would be commercially meaningful, and the long-term durability of HEPLISAV-B's market share against larger competitors.

Answer

CEO Ryan Spencer expressed high confidence in finding suitable business development targets that fit Dynavax's high bar and strategic goals. He also suggested the safety differentiation seen in the Phase I shingles data is significant and commercially relevant. Chief Commercial Officer Donn Casale and Mr. Spencer affirmed the durability of HEPLISAV-B's market share, citing strong partnerships and retail channel strategy, but emphasized it will require a sustained commercial effort.

Jonathan Miller of Evercore ISI asked for more detail on HEPLISAV-B's gross margin evolution, given the strong Q3 performance against the full-year guidance. He also questioned whether the new $200 million share repurchase plan signals a lower priority for external business development (BD) and asked about the expected cadence for executing the buyback.

Answer

CFO Kelly MacDonald explained that while full-year gross margin is progressing well, quarterly fluctuations are normal due to accounting and the timing of cost recognition, particularly from their Germany facility. CEO Ryan Spencer clarified that the share repurchase is part of a balanced capital allocation strategy and does not diminish the company's focus on growth through external BD. MacDonald added that the company intends to execute the repurchase program within the next 12 months, subject to market conditions.

Jonathan Miller from Evercore ISI asked for updated feedback from Intellia's commercial team on anticipated payer reactions to gene editing therapies, particularly in HAE, and whether there is a specific efficacy bar for pricing.

Answer

President and CEO John Leonard emphasized a thoughtful pharmacoeconomic approach, aiming for a "win-win" scenario rather than setting unprecedented prices. He reported that early interactions with payers have corroborated their strategy, which hinges on demonstrating clear clinical benefit. He believes the combination of excellent outcomes and the ease of a one-time outpatient therapy will present a positive value proposition for payers.

Jonathan Miller asked about the success criteria for the full ARV-102 patient dataset that would provide confidence for later-stage trials. He also inquired about which combination therapies Arvinas might prioritize for its BCL6 degrader, ARV-393, in clinical studies.

Answer

CMO Noah Berkowitz explained that for ARV-102, the goal is to confirm in older Parkinson's patients the same positive results seen in young healthy volunteers, particularly regarding bioavailability, brain penetration, and biomarker movement. CEO John Houston stated that for ARV-393, the primary interest is in combination therapies, particularly with bispecific antibodies like glofitamab in DLBCL, citing strong preclinical rationale and the potential to enhance bispecific activity by increasing CD20 expression.

Jonathan Miller asked for the rationale behind not proceeding with the first-line vepdegestrant and atirmociclib trial, and questioned what level of data can be expected from the BCL6 program, ARV-393.

Answer

CEO John Houston explained that the first-line trial decision was made with Pfizer, which prefers to see more mature internal and external data before committing to a large trial, despite Arvinas's belief in vepdegestrant's potential. For the BCL6 program, CMO Noah Berkowitz stated that initial safety and efficacy data from several dose-escalation cohorts are expected by the end of the year.

Jonathan Miller asked about the key gating factors for initiating the first-line Phase III trial of vepdegestrant with atirmociclib and the amount of data required from the TACTIVE-K study. He also inquired about the progress of commercial preparations for a potential vepdegestrant launch.

Answer

Chief Medical Officer Noah Berkowitz identified health authority discussions as the primary gating factor for the first-line trial, noting that extensive (e.g., six months) data is not considered a prerequisite. CEO John Houston confirmed that the company is well-prepared for a commercial launch, with the initial organizational structure in place for its U.S. lead role in partnership with Pfizer.

Jonathan Miller from Evercore ISI asked about the strategy for the vepdegestrant combination Phase 3 trials, why certain partners like ribociclib or abemaciclib were not prioritized for first-line, and when to expect data from the TACTIVE-K trial with atirmociclib.

Answer

CMO Noah Berkowitz explained the first-line focus is on palbociclib or atirmociclib, with the atirmociclib combination being particularly exciting as a potentially differentiating, best-in-class regimen. He noted that other CDK4/6 inhibitors don't offer the same strategic advantage. For second-line, a partner like abemaciclib is still a possibility. He confirmed that data on vepdegestrant's broad combinability will be presented, starting at the San Antonio Breast Cancer Symposium.

Jonathan Miller from Evercore ISI questioned the discrepancy between Apellis's reported Cyfovri growth and market share figures versus a competitor's claims of majority market share and higher growth, asking for clarification on how both could be true.

Answer

Co-Founder and CEO Cedric Francois asserted Apellis's clear leadership across all key metrics, including revenue, market share, and scientific presence. He attributed this to the quality of Cyfovri's four-year data and noted that Apellis uses a much larger database (representing 50% of injections) for tracking market dynamics compared to their competitor's smaller dataset (approx. 10%).

Jonathan Miller of Evercore ISI asked for clarification on the geographic atrophy (GA) market, questioning how to reconcile Apellis's reported mid-single-digit growth for Cyfovri with a competitor's claims of over 20% growth and majority market share.

Answer

Co-Founder and CEO Dr. Cedric Francois stated that Apellis holds clear leadership across every metric, including revenue, new patient share, and overall market share. He attributed this to Cyfovri's superior long-term data, with four years of follow-up showing increasing effects, and a more comprehensive market tracking database that represents approximately 50% of office injections, compared to the competitor's 10%.

Jonathan Miller of Evercore ISI asked for clarification on the geographic atrophy (GA) market dynamics, questioning how Apellis reports mid-single-digit growth and over 60% market share for Cyfovri while a competitor claims over 20% growth and majority share.

Answer

Co-Founder and CEO Dr. Cedric Francois stated that Apellis holds clear leadership across every metric, including revenue, new patient share, and total market share. He emphasized that Apellis tracks the market using a much larger dataset (~50% of injections) than its competitor (~10%) and attributed Cyfovri's success to its differentiated efficacy profile supported by four years of data.

Jonathan Miller of Evercore ISI asked for clarification on the geographic atrophy (GA) market dynamics, questioning how to reconcile Apellis's reported mid-single-digit growth and market leadership for Cyfovri with a competitor's claims of over 20% growth and majority market share.

Answer

Co-Founder and CEO Dr. Cedric Francois asserted Apellis's clear leadership across every metric, including revenue, new patient share, and overall market share. He emphasized the strength of Cyfovri's four-year data and noted that Apellis tracks the market using a significantly larger database (representing ~50% of injections) compared to its competitor (~10%), providing a more accurate view.

Jonathan Miller asked for clarification on SYFOVRE's Q1 2025 volume dynamics, seeking to reconcile disclosures about inventory, demand growth, and the impact from co-pay assistance funding shortages between Q4 2024 and Q1 2025.

Answer

Executive Cedric Francois highlighted that total injection demand grew quarter-over-quarter, representing the true measure of demand. Executive Timothy Sullivan explained that a Q4 inventory build at both distributor and physician levels was drawn down in Q1, which accounted for most of the revenue decline. He added that the co-pay assistance shortage increased sample usage, a trend expected to continue. Executive David Acheson noted that Apellis is educating practices to help transition patients from samples to commercial doses over time.

Jonathan Miller of Evercore ISI inquired about the EMPAVELI kidney indication, asking if Apellis plans to publicly present 24-hour endpoint data and about the company's confidence in a H2 2025 launch.

Answer

CEO Dr. Cedric Francois confirmed the 24-hour data was consistent with the spot test endpoint and was included in the FDA submission. He emphasized the strength of the data across proteinuria, C3 deposit clearance, and eGFR stabilization. Dr. Francois also stated that while they don't control macro factors, there is currently no indication of a delay to the H2 2025 launch timeline.

Jonathan Miller of Evercore ISI inquired about the evolution of SYFOVRE's market share against its competitor and the effectiveness of initiatives to drive new patients to specialists. He later asked about the potential label for the kidney indications (C3G/IC-MPGN) compared to Novartis, considering the trial design differences.

Answer

CEO Dr. Cedric Francois emphasized SYFOVRE's differentiated efficacy profile as its core strength. COO Adam Townsend stated SYFOVRE's market share is 65% by injection and that new patient starts rebounded to nearly 50%. Regarding the kidney indications, Dr. Francois highlighted that Apellis's VALIANT study was broader than the competitor's, including diverse patient groups, and that the FDA accepted their filing based on robust 6-month data.

Jonathan Miller of Evercore ISI asked about the internal capacity for early-stage development, seeking to understand how many programs Zymeworks can support internally and what factors drive decisions on external collaborations for its preclinical assets.

Answer

CEO Kenneth Galbraith quantified the company's capacity, stating the current clinical team can handle approximately five internal programs through Phase I, with the preclinical organization supporting about ten programs total. He explained that decisions to partner assets are evaluated regularly, weighing factors like acceleration of development, non-dilutive funding, and conservation of internal resources against the value of retaining unencumbered assets.

Jonathan Miller asked about the current ranking of ZW220 (NaPi2b) within the pipeline, the nature of the remaining regulatory milestones for zanidatamab, and the expected timing for initial data disclosure from the ZW171 and ZW191 trials.

Answer

Chair and CEO Kenneth Galbraith confirmed ZW220 remains a high-interest, IND-ready asset but the focus is on accelerating ZW251. He declined to provide specifics on future zanidatamab milestones, noting they will be reported as they occur. Regarding data disclosure, he stated the company will wait for a meaningful data package to present at a peer-reviewed medical meeting before providing guidance on timing.

Jonathan Miller asked what efficacy signals in the Phase I metastatic NSCLC trial would be sufficient to advance to an early-stage setting, if more preclinical data on novel antigens would be shared, and about the differences between the upheld EPO patent and the one previously struck down in the U.K.

Answer

CSO Myriam Mendila stated that demonstrating strong immune responses would be the primary goal and sufficient to justify moving the NSCLC program to earlier-stage trials. CEO Alexander Zehnder addressed the IP question by noting the U.K. and EPO assessments are different and offered a more detailed follow-up call with the IP team.

Asked about the data needed from the Phase I lung cancer trial to advance to earlier-stage studies, plans for disclosing more about novel antigen selection, and the differences between the EPO and U.K. patent case outcomes.

Answer

The primary goal for the Phase I lung cancer trial is demonstrating strong immune responses, which would be sufficient to justify moving to earlier-stage settings where clinical activity is more expected. The company is considering when to disclose more details about its novel antigen selection process. Regarding the IP case, the executive noted the complexity and differences between the U.K. and German court systems and offered a follow-up call for more detail.

Jonathan Miller asked what efficacy signals from the Phase I trial in late-stage lung cancer patients would justify moving to an early-stage setting. He also inquired about plans to share more data on the novel non-exome antigens and asked about the difference between the EPO patent ruling and the prior U.K. court decision.

Answer

CSO Myriam Mendila stated that the primary hurdle for advancing the lung cancer program to earlier stages is demonstrating strong immune responses against the encoded antigens, with clinical activity being a secondary, albeit encouraging, signal. She confirmed they are discussing when to disclose more preclinical data. CEO Alexander Zehnder noted the U.K. and EPO patent assessments are different and offered a follow-up call with the IP team for a more detailed explanation.

Jonathan Miller questioned why MacroGenics is not pursuing lorigerlimab in more traditionally 'hot' tumors where competitors are active and asked about plans for proactive combinations with non-IO agents, given the drug's potentially superior toxicity profile.

Answer

Dr. Scott Koenig, President and CEO, responded that the company must prioritize its studies and chose ovarian cancer as an initial focus due to the significant unmet need, but has not excluded pursuing other tumor types in the future. He confirmed that exploring combinations is a key part of the strategy, stating that if the LORIKEET study successfully demonstrates the ability to combine with a toxic agent like docetaxel, they will look to combine lorigerlimab with other agents like ADCs and TKIs in the future.

Jonathan Miller of Evercore ISI asked about the paused vobra duo and lorigerlimab combination study, specifically how many patients were dosed, if that data might be released, and the future landscape for lorigerlimab combinations.

Answer

Dr. Scott Koenig, President and CEO, stated that a double-digit number of patients were dosed across various tumor types in the 3+3 dose escalation, but no single cohort was large enough for a formal data presentation. James Karrels, an executive, clarified that the study never proceeded to dose expansion. Dr. Koenig added that future lorigerlimab combinations will be assessed after data from the LORIKEET study becomes available in 2025.

Challenged the claim of improved safety versus Phase I by citing similar discontinuation and interruption rates, asking for a specific data point to prove the improvement. Also asked about prior lines of therapy, efficacy comps, and the potential for vobra duo in combination therapy in earlier lines.

Answer

The executive clarified the safety improvement claim is based on a direct comparison to the Phase I *prostate cohort* at a similar time point (~16 weeks), which shows a 2-3x better profile. He stated efficacy is tracking well against a ~25% ORR benchmark. The company is actively pursuing combinations, particularly with lorigerlimab, and expects to start expansion studies soon.

Jonathan Miller of Evercore ISI challenged the characterization of improved safety for vobra duo versus Phase I, asked for details on prior lines of therapy and efficacy comps, and inquired about the drug's potential in combination therapies.

Answer

Dr. Scott Koenig, President and CEO, reiterated that the safety comparison was specific to the Phase I prostate cohort at a similar time point, where side effects were 2-3x more frequent. He noted ORR expectations are being met or exceeded. For combinations, he highlighted the ongoing study with lorigerlimab, citing orthogonal mechanisms and plans to define go-forward doses for expansion cohorts soon.

Jonathan Miller of Evercore ISI requested details on the unconfirmed partial responses for casdatifan in the ARC-20 study and asked how the drug's differentiation in primary progression rate versus belzutifan might translate to a combination setting with TKIs.

Answer

COO Jennifer Jarrett clarified that one patient in the 100mg cohort and one in the 50mg cohort were awaiting confirmatory scans, noting the maximum potential confirmed ORR for the 100mg cohort is 31%. CEO Terry Rosen and CMO Dimitry Nuyten explained that in a combo setting, casdatifan could still reduce the primary progression rate on top of a TKI, potentially improving all subsequent efficacy measures.

Jonathan Miller of Evercore ISI sought confirmation on the objective response rates (ORR) for the 50mg and 100mg casdatifan cohorts relative to Merck's benchmark, asked about evidence of a dose-response, and inquired about the future breadth of the casdatifan late-stage development program.

Answer

COO Jennifer Jarrett confirmed that both the 50mg and 100mg casdatifan cohorts are showing ORRs higher than the 21.9% reported for LITESPARK-005. CEO Terry Rosen added that a clear dose-response on ORR is not yet apparent, and differences may emerge in durability. Jarrett outlined that the near-term focus is on the two planned Phase III studies in RCC, with further exploration to follow.

Jonathan Miller of Evercore ISI asked several questions about the HIF-2 alpha program. He questioned why the 50mg dose cohort data for casdatifan would not be released with the 100mg data, whether the ORR had increased in the past three months, and what criteria would be used to select a TKI partner between cabozantinib and zanzalintinib.

Answer

CEO Terry Rosen clarified that the 50mg cohort was enrolled after the 100mg cohort and is not yet mature enough for the upcoming medical conference presentation. He reiterated that the data continues to look good but declined to provide an interim update on the ORR. Regarding TKI partners, Rosen described the choice as strategic and timing-dependent, with plans for different settings and lines of therapy to be revealed later in the year for competitive reasons. COO Jennifer Jarrett added that HIF-2 alpha has slow response kinetics, with an average time to response of about four months.

Jonathan Miller asked about the competitive landscape for COVID-19 treatments, noting Pfizer's development of a next-generation Paxlovid, and questioned Atea's expected competitive edge and commercialization strategy.

Answer

Chief Development Officer Dr. Janet Hammond stated that having multiple mechanisms of action available for COVID-19 is beneficial and highlighted that bemnifosbuvir, as a nucleoside analog, has a lower potential for resistance than protease inhibitors. Chief Commercial Officer John Vavricka outlined the commercial plan, stating Atea intends to co-promote its COVID-19 therapy in the U.S. with a pharmaceutical partner possessing strong primary care and managed care infrastructure.

Asked for the number of enrolled patients who don't meet the new trial criteria and requested a deeper justification for the claim that stage 4 patients receive the most benefit, given the data presented.

Answer

Of the 80+ patients enrolled in proact 1, about 50 meet the new criteria. The focus on stage 4 patients is a strategic decision based not only on the internal data analysis but also on feedback from clinicians about unmet needs, patient perspective, and the high cost and risk associated with this group from a payer perspective.

Sought clarification on which anticipated payments are included in the cash runway guidance to Q3 2025 and how much of the CAR-T program development is covered by this runway.

Answer

The cash runway guidance includes the potential $100 million in regulatory milestone payments, which are tied to various steps leading up to and including BLA approval. The runway is expected to fund the initiation of the ATA3219 study in lymphoma and autoimmune disease, IND-enabling studies for ATA3431, and the continuation of the EMBOLD study.