Yanan Zhu

Yanan Zhu from Wells Fargo Securities inquired about the cumulative acute pancreatitis (AP) events in the CORE/CORE-2 studies compared to the FCS BALANCE study, the perceived size of the FCS opportunity, and the strategy for managing the pricing transition from the rare FCS indication to the broader SHTG indication.

Answer

CEO Brett Monia confirmed the combined CORE studies have accumulated more total AP events than the FCS study, though the rate is lower. CGO Kyle Jenne stated the FCS market size aligns with their estimate of up to 3,000 patients and noted that the pricing strategy for the SHTG indication is still under review, with the price to be announced upon approval.

Yanan Zhu from Wells Fargo Securities asked for clarification on the drivers of WAINUA's quarterly growth, particularly the role of patient switching, and requested more color on the neurology programs returned by Biogen.

Answer

Chief Global Product Strategy Officer Kyle Jenne attributed WAINUA's growth primarily to new patient starts in an expanding market, though he noted patient switches are occurring, driven by the convenience of self-administration. CEO Brett Monia expressed enthusiasm for regaining full rights to the alpha-synuclein and LRRK2 programs, framing Biogen's decision as one of R&D prioritization and affirming Ionis's commitment to advancing both assets.

Yanan Zhu asked about potential payer pushback on olezarsen's high price for FCS and whether the CARDIO-TTRansform study could be extended. He also requested a comparison of Ionis's Phase III Angelman syndrome trial design against that of its competitor, Ultragenyx.

Answer

Chief Global Product Strategy Officer Kyle Jenne expressed confidence in payer acceptance for olezarsen, citing education on the ultra-rare disease and strong hospitalization data. CEO Brett Monia confirmed commitment to the 140-week CARDIO-TTRansform readout but left the door open for what's best for the drug. He highlighted the strengths of their Angelman trial design, including its placebo-control as the 'gold standard,' without directly comparing it to a competitor's.

Representing Yanan Zhu from Wells Fargo, a speaker asked for the specific number of patients treated with Ocatsol in Q2 and year-to-date. They also inquired about the number of patients expected in the upcoming SLE data readout at ACR and if any were adolescents.

Answer

CEO Christian Itin stated that Autolus has not guided on the specific number of patients treated but noted the figure could be reasonably estimated from the reported revenue. For the SLE data, he confirmed more patients have been enrolled beyond the initial six, but adolescent patients are not expected to be included in the upcoming ACR analysis due to the data cut-off timing.

Yanan Zhu of Wells Fargo sought an estimate of the B-ALL portion of competitor Tecartus's revenue, clarification on the deferred revenue figure, and an overview of Autolus's competitive positioning in lupus nephritis.

Answer

CEO Christian Itin found it difficult to estimate Tecartus's revenue split but suggested B-ALL was historically a minority share. CFO Rob Dolski clarified the $4.7 million in deferred revenue is the sales value, not cost, of delivered but uninfused product. Christian Itin added that infusion timing is variable. He positioned Autolus as being very competitive in lupus nephritis due to a compact, single-arm pivotal trial design, which he contrasted with larger, more complex competitor studies.

Yanan Zhu of Wells Fargo asked if the top 10 B-ALL patient volume centers have been onboarded, requested commentary on the number of apheresis procedures to date, and inquired if and when the company plans to provide sales guidance for AUCATZYL.

Answer

Executive Christian Itin stated that many of the top U.S. institutions are already active, covering a substantial portion of the patient population. He clarified that the company will not guide on apheresis numbers, preferring to report on patients dosed to align with revenue recognition. He also confirmed Autolus will not provide sales guidance for the current year, citing the multiple evolving variables of a new launch, and will instead report on actual patients dosed.

Yanan Zhu from Wells Fargo inquired how to assess treatment effect versus placebo in the open-label CF study, whether FEV1 would be measured post-treatment, and about the expected onset of action for the therapy.

Answer

President and CEO Joseph Payne explained that a formal placebo arm is planned for Phase 3, while the current study uses patients' historical FEV1 data as a self-control. He confirmed an FEV1 measurement will be taken at day 56 (28 days post-treatment) to assess durability. He described the onset of action as biochemically rapid but noted the physiological improvement in lung function could take weeks or months to manifest fully.

Yanan Zhu from Wells Fargo asked about the timing and venue for the CF data update, whether there is a minimum response rate required for FEV1 improvement, and about recent FDA interactions concerning the KOSTAIVE BLA filing.

Answer

President and CEO Joseph Payne clarified that the 'mid-year' guidance for the CF data allows time to include results from two cohorts and a venue will be announced soon. He noted there is no specific 'response rate' threshold from the FDA; success will depend on the overall data consistency from the ~12 subjects. He characterized recent FDA interactions as 'normal' and expressed confidence that the strength of the science will drive the regulatory process forward.

Yanan Zhu asked about managing data variability in the upcoming CF readout, the potential for a dose-response, the safety of daily inhaled LNP delivery, and sought details on recent KOSTAIVE sales volumes.

Answer

President and CEO Joseph Payne explained the Phase II CF study's 28-day dosing design should mitigate variability seen in the shorter Phase I study and noted a dose-response is rational but unproven. He expressed confidence in the LNP safety profile based on preclinical data. CFO Andrew Sassine clarified that their partner Meiji revised sales guidance for KOSTAIVE to less than half of the initial 4 million doses.

Yanan Zhu of Wells Fargo inquired about the quarter-over-quarter growth in Amtagvi patient infusions from Q1 to Q2, the impact of the recent price increase on demand, and the outlook for patient numbers relative to full-year guidance.

Answer

Interim CEO Frederick Vogt and CCO Dan Kirby confirmed that patient infusions grew from 85 in Q1 to 102 in Q2 2025. They stated the price increase to $562,000 on April 1st did not negatively impact demand. While declining to provide quarterly patient forecasts, they reiterated confidence in the full-year revenue guidance of $250M to $300M, which implies continued strong demand in the second half of the year.

Yanan Zhu of Wells Fargo pointed out that the math for 500 patient infusions seems to reach the low end of the revenue guidance alone, and asked about the rising Cost of Goods Sold (COGS), specifically the portion related to patient attrition and manufacturing failures.

Answer

Interim CEO Frederick Vogt acknowledged the guidance is conservative and could be exceeded. Chief Financial Officer Jean-Marc Bellemin confirmed the increase in COGS in Q1 was due to a spike in out-of-spec manufacturing relative to lower revenue, but stated this is expected to improve in Q2 and that standard gross margin remained positive.

Yanan Zhu asked for the specific number of infusions performed in Q4, how the quarter-over-quarter growth compared to expectations, and the growth outlook for Q1.

Answer

Interim CEO and President Frederick Vogt reported approximately 95 revenue infusions for Q4. He described the quarter-over-quarter growth as strong and sufficient to meet their targets, noting that growth will fluctuate, similar to early CAR-T launches, but the company is focused on driving continued growth.

Yanan Zhu from Wells Fargo asked about the monthly distribution of the 82 infusions in Q3, the growth trajectory into Q4, and whether growth is driven by demand or improved manufacturing logistics.

Answer

Interim CEO Frederick Vogt stated that there was month-over-month growth in Q3 infusions and this trend is expected to continue. He clarified that growth is primarily driven by manufacturing capacity and slot availability, which accommodates rising demand from both new and existing ATCs, with improving out-of-spec rates also contributing.

Yanan Zhu of Wells Fargo inquired if the statistical planning for MAGNITUDE accounted for differences between first and second-generation stabilizers and asked for updated thoughts on the percentage of patients on silencers in the study.

Answer

CEO John Leonard stated they see no significant clinical difference between stabilizer generations. EVP & CMO David Lebwohl added that the trial design anticipated the availability of silencers and prohibits their use as a first-line agent for trial entry. He noted that potential crossovers from tafamidis to vutrisiran during the trial are factored into the statistical analysis.

Yanan Zhu inquired about the ATTR-CM Phase III study enrollment specifically in the U.S., the potential impact from the recent approval of Amvuttra, and whether the trial protocol allows for patients to switch to that drug.

Answer

Chief Medical Officer David Lebwohl confirmed that enrollment remains brisk globally, including in the U.S., and has even accelerated recently despite Amvuttra's approval. He noted that physicians intending to use Amvuttra are advised not to enroll patients in the study, and the company does not expect significant crossover, as the trial offers a chance to add a potentially superior therapy on top of tafamidis.

Yanan Zhu asked about the potential incremental learnings from the long-term ATTR data readout expected later in the year and how it might further inform the product's profile.

Answer

CEO John Leonard explained that the update would extend the follow-up on previously reported measures. Key learnings would be to confirm a continued low rate of disease progression, observe if more patients show improvement from baseline, and validate the low clinical event rate, which provides further confidence for the ongoing Phase III trial.

Yanan Zhu asked about the MAGNITUDE-2 trial design for ATTR polyneuropathy, questioning why it is a small, 50-patient, placebo-controlled study and whether patients could receive other treatments like TTR silencers.

Answer

CEO John Leonard explained the small size is possible due to the large expected effect size of TTR reduction. He and CMO David Lebwohl clarified that the placebo-controlled design was agreed upon with the FDA and is feasible because the trial is conducted ex-U.S. where silencers are not available, meaning patients will not receive them.

Yanan Zhu from Wells Fargo Securities asked for clarification on the pivotal trial's patient population for the B-ALL program, the potential trial size relative to autologous CAR-T programs, and the potential size of milestone payments from the Servier arbitration.

Answer

Chief Medical Officer Dr. Adrian Kilcoyne explained that the trial will target a broad, late-stage patient population with multiple prior therapies. He suggested the trial size would be in the 'ballpark' of other autologous CD19 CAR-T programs, as it's driven by the safety database requirement. CFO & Chief Business Officer Arthur Stril declined to comment on the potential Servier milestone size, citing the ongoing legal nature of the matter.

Asked for more details about the Grade 5 adverse event reported in the UCART22 abstract, its potential impact on the study, and whether its cause could be attributed to the therapy or lymphodepletion.

Answer

The Grade 5 event was a bacterial infection in a patient who was in a leukemia-free state, occurring weeks after the Day 28 assessment. It is not expected to affect the study's conduct. The event is considered less likely related to UCART22, as no cells were believed to be remaining, and more likely due to the patient being extremely heavily pretreated with multiple prior therapies.

Yanan Zhu from Wells Fargo Securities asked for clarification on whether propensity-matched and propensity-weighted analysis methodologies produced similar results in the company's evaluations and how the choice of method impacts the sample size of the external control arm.

Answer

Chief Medical Officer Walid Abi-Saab explained that while the SAP submission to the FDA contains methodologies and not results, their internal evaluations showed that both methods produced 'very similar' estimates of three-year disease decline. He noted that weighting uses a larger dataset (~3,000) while matching uses a smaller subset (200-600), but the final estimate of decline is robust and not materially different, giving them confidence in the approach.

Yanan Zhu sought confirmation on the follow-up duration for the BLA filing data (not longer than 3 years) and the specific natural history study to be used as a control. He also asked for uniQure's view on PTC Therapeutics' recent data.

Answer

CMO Dr. Walid Abi-Saab confirmed the primary analysis will be on 3-year data from a pre-agreed data cutoff. He noted that while they evaluated multiple natural history studies like TRACK-HD and Enroll-HD, the choice doesn't significantly alter outcomes, pointing to similar results seen in PTC's data. CEO Matthew Kapusta declined to comment on competitor data directly but highlighted uniQure's 80% slowing of disease progression and differentiated target.

Yanan Zhu of Wells Fargo asked how the FDA-aligned trial design compared to Taysha's original proposal and whether the lack of a formal end-of-phase meeting was related to FDA resource constraints.

Answer

CEO Sean Nolan clarified that the FDA endorsed the design Taysha proposed. He attributed the streamlined process not to FDA resource issues but to the productive, data-driven discussions enabled by the RMAT designation, which allowed them to achieve alignment on key trial elements without needing a formal meeting to resolve disagreements.

Representing Yanan Zhu, an analyst asked for Taysha's perspective on competitor data from Neurogene and inquired whether dosing TSHA-102 above the current high dose of 1x10^15 vg is a possibility.

Answer

CEO Sean Nolan positioned the competitor's data as a positive for the Rett community, validating MECP2 as a therapeutic target, but refrained from direct comparisons. He confirmed that Taysha could dose higher, noting their non-human primate toxicology studies were clean at 2x10^15 vg, but stated that the current high dose is considered optimal based on preclinical evidence.

Yanan Zhu asked for clarification on the H1 2025 data release timeline, enrollment progress, and whether the 42-day safety stagger between patients is fixed.

Answer

CEO Sean Nolan confirmed the first-half guidance provides flexibility and expressed confidence in meeting it. He acknowledged the current protocol specifies a 42-day stagger but hinted that this is a topic under consideration and could potentially change in the future, contingent on continued positive safety data. He affirmed the company is comfortable with its current guidance.

Yanan Zhu from Wells Fargo Securities asked how Cost of Goods Sold (COGS) is tracking, whether the view on the annual patient incidence rate has changed, and if the current patient flow is from a 'warehoused' population or reflects the true incidence rate.

Answer

Gavin Wood stated that the Q1 gross margin was high at 78% but is expected to normalize to around 70% long-term. Cintia Piccina confirmed the patient onboarding pace aligns with their forecast of ~1,000 new synovial sarcoma diagnoses annually. She added that while they are currently treating the prevalent patient pool, they did not see a large 'bolus' of warehoused patients and expect to transition to the incident population by next year.

Kwan, on behalf of Yanan Zhu, asked about the remaining steps needed to start the rolling BLA for lete-cel and how a patient eligible for both lete-cel and Tecelra might choose between the two therapies.

Answer

CEO Adrian Rawcliffe outlined the three key components for the BLA: the positive pivotal clinical data, the CMC module for manufacturing, and the parallel filing for the NY-ESO companion diagnostic. For patient choice, he noted that while target expression and physician familiarity will play a role, the current sales projections conservatively assume only NY-ESO positive, MAGE-A4 negative patients receive lete-cel, representing an incremental opportunity.

Yanan Zhu from Wells Fargo & Company sought clarification on the regulatory pathway for the Fabry program, specifically asking if the BLA filing will be based on 52-week eGFR data and whether a 'static versus baseline' result is the required benchmark for eGFR.

Answer

Chief Development Officer Nathalie Dubois-Stringfellow affirmed that Sangamo is pursuing the agreed-upon pathway with the FDA to use 52-week eGFR data from all 32 patients for the BLA submission. CEO Alexander Macrae emphasized the strength of the data, noting the eGFR slope remains positive, a significant outcome compared to the natural decline in Fabry patients, and is supported by positive trends in all other secondary endpoints.

Yanan Zhu's representative, Kwan, questioned whether potential Fabry program partners have been shown updated efficacy data beyond the WORLDSymposium presentation and asked for confirmation on the consistency of recent internal eGFR data.

Answer

CEO Sandy Macrae, confirmed by Chief Development Officer Nathalie Dubois-Stringfellow, clarified that potential partners have not seen new efficacy data, though they have reviewed manufacturing and other supporting information. Macrae expressed that the company remains "very encouraged" by the latest internal data for 30 patients but did not comment on specific metrics.

An associate on for Yanan Zhu asked for the timing of the next data update from the Fabry program. They also asked if the positive eGFR slope changes as patient follow-up gets longer and if the slope is affected when patients withdraw from ERT.

Answer

Chief Development Officer Nathalie Dubois-Stringfellow explained that since the study is now registrational, they will share top-line data in Q2 2025 after the final data is available and cleaned. CEO Sandy Macrae added that the longest-treated patient is over four years out with stable alpha-Gal levels, but it's too early to calculate a meaningful long-term eGFR slope on the small number of patients with such follow-up. Dubois-Stringfellow confirmed the positive eGFR slope is observed across all patient subgroups, including those who were on ERT.

Yanan Zhu asked for a reconciliation of the lowered guidance with the commentary about an anticipated uptick in demand, and whether the company's peak sales estimate for ELEVIDYS has changed.

Answer

President and CEO Douglas Ingram (speaking in place of Dallan Murray) explained the guidance was lowered due to a multifactorial drop-off, including the safety event's impact, but the company is now seeing an uptick in start forms that supports a projected summer recovery. Regarding peak sales, he stated the ultimate opportunity (area under the curve) remains unchanged, but the timing to reach peak sales may be delayed, and the company will update its view later.

Yanan Zhu asked if the initiation of the VY-7523 MAD study was ahead of schedule and questioned whether the tau knockdown program could ultimately become a more promising approach than the antibody therapy.

Answer

CMO Dr. Toby Ferguson confirmed the study started slightly ahead of guidance due to strong execution. He and CEO Dr. Al Sandrock explained that both tau programs are being advanced because they may be appropriate for different patient populations or disease stages. They emphasized that the field is in its early days and decisions will be driven by emerging internal and external data.

Yanan Zhu from Wells Fargo Securities inquired about the expression of the ALPL receptor in other tissues and its potential impact on drug delivery, and also asked for Voyager's perspective on its competitive standing in BBB-penetrating capsids following the ASGCT meeting.

Answer

Executive Todd Carter explained that while ALPL is expressed broadly, it is particularly crucial for crossing the blood-brain barrier, which conventional capsids cannot do. He also highlighted that their capsids show significant de-targeting from the liver. Executive Alfred Sandrock commented that while competition is increasing, Voyager is proud of its capsids' ability to achieve high transduction rates (80-90%+) at low doses, with proven cross-species translatability and three development candidates already selected.

Asked about the submission status for the H1 2025 AFM24 presentation, the required PFS improvement over standard of care to be considered strong, and data expectations for the Hodgkin lymphoma update at ASH, particularly regarding cohorts with more NK cells.

Answer

The company responded that it's too early for abstract submissions for H1 2025 conferences. They consider the current PFS of 5.9 months a meaningful improvement and noted the shape of the survival curve is also important. The ASH update for Hodgkin lymphoma will be an early look at response rates from fully recruited cohorts, and while the current 87% ORR is already paradigm-changing, it's too soon to speculate on further improvements.

Asked about a potential dose-response on the CR rate for acimtamig between cohorts 1 and 2, and requested an update on progression-free survival (PFS) data and benchmarks for the AFM24 program.

Answer

The company confirmed no difference in response rates, including CR rate, has been seen between the 200mg and 300mg acimtamig doses. For AFM24, the previously reported PFS for the wild-type cohort was 5.9 months. Mature PFS for the mutant cohort is not yet available, but current data is encouraging compared to the standard-of-care benchmark of around 4-4.5 months.

Yanan Zhu from Wells Fargo Securities inquired how the higher fetal hemoglobin (HbF) induction seen with BEAM-101 could translate to superior clinical benefits compared to existing therapies, where vaso-occlusive crisis (VOC) resolution is already high.

Answer

President Dr. Giuseppe Ciaramella explained that the high HbF induction is coupled with a reduction of sickle hemoglobin (HbS) to below 40%, a ratio similar to asymptomatic sickle cell trait individuals. He highlighted that HbF is also anti-sickling, which could lead to a deeper resolution of disease manifestations. Dr. Ciaramella pointed to biomarker data showing a near-complete elimination of HbS-only cells, suggesting a potential for improvement even beyond the strong VOC resolution seen with approved products.

Yanan Zhu asked how the higher fetal hemoglobin (HbF) induction observed with BEAM-101 could translate into additional clinical benefits compared to already approved products, given their strong performance on vaso-occlusive crises (VOCs).

Answer

President Dr. Giuseppe Ciaramella explained that achieving an HbF to HbS ratio of over 60/40, similar to sickle cell trait, is a key differentiator. He noted this deeper correction, combined with the near-complete elimination of HbS-only cells, could lead to a more profound resolution of disease markers and potentially improve upon the VOC reduction seen with other therapies.

Yanan Zhu from Wells Fargo asked how the higher fetal hemoglobin (HbF) induction seen with BEAM-101 could translate into additional clinical benefits over currently approved products, which already show strong VOC reduction.

Answer

President Dr. Giuseppe Ciaramella explained that achieving an HbF/HbS ratio of over 60/40 mimics the profile of asymptomatic sickle cell trait individuals. He added that HbF is inherently anti-sickling and that biomarker data shows a near-complete elimination of the HbS-only cells most likely to cause sickling, suggesting the potential for a deeper and more durable clinical resolution beyond just VOCs.

Asked for clarification on the in vivo upregulation strategy (targeting the mutated gene vs. a compensatory gene) and for an update on the CAFC patent dispute timeline.

Answer

The in vivo strategy can accommodate both scenarios: upregulating a compensatory gene for a recessive defect (like reni-cel and gamma-globin) or upregulating the functional wild-type allele in a haploinsufficiency case. Regarding the patent dispute, a decision from the CAFC is anticipated before the end of the year following oral arguments in May.

Yanan Zhu asked if the in vivo program upregulates the disease-causing gene itself or a different compensating gene, and requested an update on the timing of the CAFC patent dispute.

Answer

Chief Scientific Officer Linda Burkly confirmed that both approaches are possible: upregulating a compensating gene (like in reni-cel) or upregulating a wild-type allele in cases of haploinsufficiency. CEO Gilmore O'Neill added that a decision in the CAFC patent dispute is anticipated before the end of the year.

Asked about the number of patient samples used for off-target analysis, the potential for high fetal hemoglobin levels to be a key differentiator, and the correlation between total hemoglobin and hemolysis markers.

Answer

The company is using a larger number of patient samples and more advanced methods for off-target analysis than discussed at the AdCom. They are pleased with early high fetal hemoglobin levels but need more data to confirm it as a differentiator. They believe their approach enhances red blood cell production, contributing to higher total hemoglobin, and are pleased with the hemolytic marker results.

Asked about the competitive potential of bispecific antibodies versus cell therapy, including depth of B-cell depletion and repeat dosing, and also inquired about the potential for multi-dosing FT819.

Answer

The company acknowledged T-cell engagers as a competitive modality. They highlighted that a key advantage of their off-the-shelf cell therapies is the potential for multi-dosing without harsh conditioning, positioning them to be delivered as add-on strategies in community settings, similar to a monoclonal antibody.

Yanan Zhu of Wells Fargo Securities asked about the comparative depth of B-cell depletion between bispecific antibodies and cell therapy, the competitive potential of repeat-dosed bispecifics, and whether multi-dosing is a possibility for FT819.

Answer

CEO Scott Wolchko acknowledged the potential of bispecifics to drive deep responses and stated Fate is developing its products to compete directly. He noted that while multi-dosing is a strength of engagers, off-the-shelf cell therapy also has this potential, particularly if it can move away from harsh conditioning. The ultimate goal is to develop therapies that can be dosed as add-ons to standard regimens, similar to monoclonal antibodies.

Asked about tissue trafficking requirements for treating SLE, the specific patient population being enrolled, and the competitive landscape for patient enrollment in SLE trials.

Answer

The company believes their cells can traffic to necessary tissues based on clinical data from their oncology trials. The SLE study will enroll patients with moderate-to-severe disease who are refractory to multiple prior therapies. While the landscape is competitive, they believe the off-the-shelf nature of their product offers distinct advantages in convenience and accessibility, which will be a key differentiator.

Asked how the FT819 lymphodepletion regimen compares to the one used by the German Group, about the expected T-cell removal at the starting dose of the FT522 no-lymphodepletion arm, and what the catalyst would be for advancing FT522 into autoimmune disorders.

Answer

The company confirmed the lymphodepletion regimen is 'exactly the same' as the German Group's. For FT522, they clarified the ADR technology is not for broad lymphodepletion but for defending against and potentiating the NK cell by targeting alloreactive T-cells. The decision to move FT522 into autoimmunity could be informed by the oncology study, and they could imagine a similar trial design testing with and without conditioning.

Asked for clarification on the term 'enrollment' for LYFGENIA patients, the key gating factors for treatment, and the differences in gross-to-net discounts between the products and future expectations.

Answer

The company explained that 'enrollment' is a multi-step process including insurance approval and medical readiness, with the latter being a key variable gating factor. They clarified that the current 19% gross-to-net differs between products partly due to outcomes-based agreements. With LYFGENIA's higher Medicaid mix, they expect the overall gross-to-net discount to increase to a 20% to 25% range.