Mani Foroohar

Mani Foroohar asked for a detailed breakdown of REDEMPLO prescriptions between Expanded Access Program (EAP) and non-EAP patients, and the expected transition of the remaining EAP pool to commercial drug. He also inquired about expectations for new datasets, novel tissue types, and further platform expansion over the next 12-18 months.

Answer

Andy Davis, SVP and Head of Global Cardiometabolic Franchise, reiterated that the majority of REDEMPLO prescriptions are APOC3 naive, with EAP and switch patients evenly split, but declined further specifics. James Hamilton, Chief Medical Officer and Head of R&D, stated that no guidance on new datasets or platform expansion for the next 12-18 months could be provided, emphasizing focus on existing pipeline readouts while confirming ongoing platform development.

Mani Foroohar asked for a breakdown of Redemplo prescriptions between expanded access program (EAP) and non-EAP patients, and the expected total pool of EAP patients transitioning to commercial drug. He also inquired about expectations for future datasets, novel tissue types, and platform expansion over the next 12-18 months.

Answer

Andy Davis, SVP and Head of Global Cardiometabolic Franchise, stated that the vast majority of patients were APOC3 naive, with the remainder split evenly between EAP transitions and switch patients. James Hamilton, Chief Medical Officer and Head of R&D, added that no specific guidance on novel tissue types or platform expansion has been given, but the company is continuously developing its platform and insights.

Mani Foroohar asked for clarification on whether the pro forma cash balance guidance included debt principal repayment or just interest service. He also questioned the gating factors and capital requirements for initiating a plozasiran cardiovascular outcomes trial (CVOT).

Answer

CFO Ken Myszkowski clarified that the cash forecast includes contractually required debt payments tied to milestones, not voluntary principal paydown. CEO Dr. Christopher Anzalone stated that despite the current cash position, a substantial additional influx of capital from new partnerships would be required before the company would feel comfortable starting the expensive CVOT, given other value-driving investments in obesity and CNS.

An analyst on behalf of Mani Foroohar requested details on the Sixth Street credit facility, specifically asking what proportion of future partnership proceeds must be used to repay the loan and whether the repayment structure is front- or back-loaded.

Answer

Executive Vincent Anzalone explained that the repayment structure is highly customized, with different payback economics for different 'buckets' of assets, and some transactions require zero repayment. He stated that the company is not providing more specific guidance on the structure at this time but that a redacted version of the contract will be filed.

Mani Foroohar inquired about Scholar Rock's financing strategy, specifically the prioritization of debt, royalty, or equity, and the relative cost of capital. He also asked about the operational risks associated with transitioning between fill-finish facilities during the early launch phase and how these risks are being mitigated.

Answer

Vikas Sinha, Chief Financial Officer, outlined the financing hierarchy, prioritizing loan facility expansion, followed by royalty financing, and then equity as a last resort to minimize dilution. David Hallal, Chairman and Chief Executive Officer, addressed the second fill-finish facility, emphasizing the seamless operational transition expected in the marketplace and the rapid progress in securing commercial capacity and initiating tech transfer.

Mani Foroohar inquired about Scholar Rock's financing strategy, specifically the prioritization of debt, royalty, or equity for future capital needs, considering relative cost of capital. He also asked about potential operational risks during the transition between fill-finish facilities in the early launch phase and how these risks are being addressed.

Answer

Chief Financial Officer Vikas Sinha stated that the primary objective is to bridge financing until approval, prioritizing expanding the existing loan facility, followed by royalty financing, and using equity as a last resort to minimize dilution. CEO David Hallal explained that the company aims for a seamless operational transition between the Bloomington facility and the new second vialer by maintaining consistent vial configuration and analytical testing, with tech transfer already underway.

Mani Foroohar of Leerink Partners asked about the biomarker and functional thresholds for a potential accelerated approval of BBP-418 in LGMD2I, and also inquired about the competitive dynamics with Alnylam and Pfizer regarding pricing, contracting, and patient acquisition.

Answer

Christine Siu, CEO of ML Bio Solutions, outlined the criteria for LGMD2I success: a robust effect on biomarkers, a significant reduction in CK, and a positive trend on functional outcomes. CEO Neil Kumar addressed the competitive landscape, stating that pressure from Alnylam is more pronounced in patient switches, while Pfizer is a more direct competitor for naive patients. He affirmed that BridgeBio is not engaging in aggressive price-based contracting.

Mani Foroohar of Leerink Partners asked about the current velocity of new patient scripts for Attruby and questioned the regulatory viability of the biomarker-based endpoint for the upcoming Limb-Girdle Muscular Dystrophy (LGMD2I) data.

Answer

CCO Matt Outten noted that new patient growth for Attruby is strong and consistent across all segments, with a primary focus on the treatment-naive population. On the LGMD2I program, CEO Neil Kumar expressed confidence in the biomarker strategy, citing positive recent interactions with the FDA on other programs and the supportive clinical trends seen in Phase II. He believes the agency's guidance on the filability of the biomarker endpoint will hold.

Mani Foroohar of Leerink Partners inquired about the specific timing for the FDA's acceptance of the RGX-121 BLA for Hunter syndrome and the potential for an approvability bar shift for RGX-202 in DMD, given competitor issues and changes at CBER.

Answer

President and CEO Curran Simpson stated that the RGX-121 BLA acceptance is "imminent" and FDA interactions have been "business normal." For RGX-202, he expressed increased conviction in their accelerated approval strategy, emphasizing their plan to provide strong functional data and a superior benefit-risk profile, which he believes aligns with the FDA's supportive stance on rare disease development.

Mani Foroohar of Leerink Partners asked if data from the initial RGX-202 patients will be included in the pivotal data set and requested clarification on the financial recognition of the upcoming RGX-314 milestone payment from AbbVie.

Answer

CEO Curran Simpson confirmed that data from Phase I/II patients at dose level 2 will be used in the pivotal submission, highlighting the advantage of a consistent manufacturing process. Dr. Steve Pakola, CMO, added this is logical since the primary endpoint for accelerated approval is microdystrophin. Regarding the milestone, CFO Mitchell Chan stated it would be recognized as a one-time, non-recurring payment upon receipt and would be reflected on the balance sheet and P&L in the same quarter.

Mani Foroohar asked about customer dynamics, contrasting Schrödinger's strong results with competitors' reports of delays from large pharma and budget constraints at smaller biotechs. He also asked about the threat from other native AI companies and the metrics used to defend against them.

Answer

CFO Geoffrey Porges stated that growth is driven by large accounts while the emerging biotech segment is holding steady, with no pushback on renewals. CEO Ramy Farid addressed the AI threat, emphasizing that their deep domain expertise, physics-based methods, and the fundamental importance of high-quality training data provide a strong competitive moat.

Mani Foroohar of Leerink Partners inquired if the reduced drug discovery guidance was a timing issue benefiting 2025 and asked about trends in new, smaller customer additions.

Answer

CFO Geoff Porges confirmed the guidance reduction was due to timing uncertainty for milestones expected near year-end, expressing confidence for 2025, which will be bolstered by the Novartis deal. He noted positive inquiry from smaller, private companies but stated they are not yet a significant contributor to growth, as the company's focus remains on scaling up large and mid-sized customers.

Ryan, on behalf of Mani Foroohar, asked for details on the regulatory pathway for the CVGBM glioblastoma asset, including whether CureVac has had discussions with regulators and if recent changes at the FDA have impacted their programs.

Answer

CEO Alexander Zehnder stated that they have not observed any negative impact from FDA changes, noting the IND for their squamous lung cancer program cleared on time. CSO Myriam Mendila added that for the CVGBM program, they plan to await more data from the Phase I expansion cohort before engaging with regulatory authorities. If the data is positive, the next step would likely be a randomized Phase II study.

Ryan, on behalf of Mani Foroohar, asked for details on the regulatory pathway for the CVGBM glioblastoma asset and whether recent changes at the FDA have impacted any of CureVac's programs or discussions.

Answer

CEO Alexander Zehnder stated that they have not seen any negative impact from FDA changes, noting the squamous NSCLC IND cleared on time. CSO Myriam Mendila added that the next step for CVGBM would be a randomized Phase II trial, but discussions with regulators are pending further data from the ongoing Phase I study.

Asked about the regulatory pathway for the CVGBM glioblastoma asset and the potential impact of recent changes at the FDA on their programs.

Answer

Executives stated they have not seen any negative impact from FDA changes on their programs. For the CVGBM asset, they will await more data from the Phase I expansion cohort before engaging with regulators, but a potential next step would be a randomized Phase II trial if the data shows meaningful clinical activity.

Mani Foroohar from Leerink Partners requested more detail on the financial impact of the voluntary leaver program on the cash runway. He also asked about the company's strategy for selecting indications for its oncology programs, particularly in light of competitor data, and when a comparable dataset might be available.

Answer

CFO Pierre Kemula explained the cash runway extension is a net effect of lower raw material costs, reduced PPA revenue, and savings in SG&A and CapEx, without detailing the leaver program's specific impact. CDO Myriam Mendila described a strategic process for indication selection based on medical need and commercial opportunity, cautioning that the current glioblastoma trial is for platform validation and not directly comparable to competitor trials in other indications.

Mani Foroohar of Leerink Partners requested details on the financial assumptions behind the cash runway extension, particularly the voluntary leaver program. He also asked about the strategic approach to oncology indication selection in light of competitor data and when a comparable dataset might be available.

Answer

CFO Pierre Kemula attributed the runway extension to savings from the PPA wind-down, reduced raw material commitments, lower OpEx, and decreased CapEx, without detailing the leaver program's specific impact. CDO Myriam Mendila described a strategic evaluation process for oncology indications based on medical need and commercial opportunity. She and CEO Alexander Zehnder cautioned against direct cross-trial comparisons, noting their current GBM trial has no direct mRNA competitor and highlighting the MD Anderson collaboration as key for future differentiation.

Asked about the company's view on the declining COVID vaccine market and for details on their strategy and timeline for a combined COVID/flu vaccine.

Answer

The company acknowledged the changing COVID market but sees an opportunity for a competitive product, especially as a springboard to a combination vaccine. They believe a combo vaccine is valuable for at-risk populations to improve adherence and ease healthcare system burdens. Data from ongoing Phase II trials in 2024 will inform the development of the combination product.

Mani Foroohar asked for an update on the expected pace of operating expense decline in 2025 following the restructuring and the OpEx trajectory over the next several years, given the costs of large, ongoing pivotal studies.

Answer

CFO Edward Dulac, prompted by CEO John Leonard, explained that while Q1 2025 will have some wind-down costs, the benefits of the restructuring will accrue throughout the year. He noted that ongoing costs for three Phase III studies will be offset by these savings. Dulac stated that he believes peak operating expenses are behind the company and that OpEx through early 2027 is unlikely to reach the levels seen in 2024.

A representative for Mani Foroohar asked about the rationale for the 2:1 randomization in the Phase III HAELO study compared to the 1:1 randomization in the MAGNITUDE study, and if it was intended to speed up enrollment.

Answer

CMO David Lebwohl explained that the 2:1 randomization is attractive to patients, as it gives them a higher chance of receiving the active drug, and all patients can cross over later. This design is expected to drive rapid enrollment and provide more data on the active arm for the BLA submission.

Mani Foroohar asked for clarification on the driver of the noted tax benefit and whether this benefit is expected to be a recurring event.

Answer

Chief Financial Officer Jeff Poulton explained the benefit was due to a release of a valuation allowance for deferred tax assets in their Swiss entity, which has demonstrated sustained profitability. He stated it is difficult to predict further releases and noted that valuation allowances in the U.S. have not yet been released.

Mani Foroohar asked about the source of WAINUA's growth in TTR polyneuropathy, specifically the split between new patients and those switching from other therapies. He also questioned if Ionis was facing any reimbursement headwinds for WAINUA as a Part D drug compared to in-office Part B competitors.

Answer

CEO Brett Monia emphasized that growth is primarily driven by identifying new, previously untreated patients, though he acknowledged switching occurs due to the convenience of self-administration. He stated there are no significant reimbursement headwinds, citing the benefits of the Inflation Reduction Act and robust patient support programs that result in very good access and low out-of-pocket costs for most patients.

Mani Foroohar of Leerink Partners asked about the clinical and regulatory strategy for the BEAM-302 AATD program, given the heterogeneous patient population with both lung and liver phenotypes and the differing regulatory endpoints for each.

Answer

CEO John Evans explained that BEAM-302 is designed to address both phenotypes by correcting the underlying genetic cause, with the goal of developing a single dose for the entire population. From a regulatory perspective, he stated the first step is generating a compelling Phase 1 dataset. This data will then inform discussions with regulators about the path forward, which could involve pursuing separate endpoints for liver and lung or potentially using universal biomarkers of protein correction as a primary endpoint.

Mani Foroohar of Leerink Partners asked about the market opportunity and clinical path for BEAM-302 in AATD, questioning the enrollment strategy for patients with lung versus liver phenotypes and the potential regulatory pathway for a therapy addressing both.

Answer

CEO John Evans explained that BEAM-302 is designed to benefit both lung and liver manifestations by correcting the underlying genetic defect. He noted that while the initial trial focuses on a clean patient profile, the ultimate goal is to develop a single dose for the entire ZZ phenotype population. He acknowledged the regulatory path requires further discussion with agencies post-Phase 1 data, but endpoints based on protein correction could be universal.

Mani Foroohar of Leerink Partners asked about the clinical, commercial, and regulatory path for BEAM-302 in AATD, given the heterogeneous patient population with differing lung and liver phenotypes.

Answer

CEO John Evans explained that BEAM-302's mechanism addresses both disease manifestations, allowing for a unified approach. He stated the initial regulatory step is to generate a compelling Phase 1 data set. This data will then inform discussions with regulators about the path forward, which could involve distinct endpoints for liver or lung, or potentially a universal biomarker-based endpoint reflecting the correction of the underlying protein deficiency.

Asked for color on the depth of the patient backlog for LYFGENIA and inquired about the specific demand metrics and data that were provided to Hercules Capital during their due diligence for the recent term loan.

Answer

The company cited strong patient demand with multiple enrollments across various treatment centers and anecdotal reports of long waitlists. Regarding the Hercules loan, they confirmed that customary information, including multi-year financial projections, was shared. They clarified that the patient start milestones in the loan agreement are progress markers, not official company guidance.

Mani Foroohar asked if protocol changes for Danon disease would alter the proportion of eligible patients and inquired whether Rocket would be participating in the upcoming FDA Advisory Committee meeting.

Answer

CEO Gaurav Shah responded that refining eligibility criteria to exclude end-stage fibrotic patients does not change the overall addressable market. He also confirmed that Rocket has not been invited to participate in the ADCOM but will be listening to the proceedings.

Mani Foroohar from SVB Leerink questioned how patient behavior and trial enrollment were influenced by the COVID-19 pandemic and how the easing of the pandemic might affect the patient population enrolling in the upcoming Phase 3 trials.

Answer

CEO Laurent Fischer highlighted the successful enrollment of the INFINITY study during the pandemic. Dr. Arshad Khanani (Managing Director, Sierra Eye Associates) elaborated that since wet AMD can lead to irreversible blindness, patient care and trial participation continued with enhanced safety protocols. He noted the pandemic underscored the need for durable therapies like ADVM-022 to reduce clinic visits for high-risk patients and did not foresee issues enrolling the pivotal trials.

Mani Foroohar of SVB Leerink asked for clarification on two points: the timing of regulatory discussions for the pivotal trial, and whether the 'recurrent uveitis' event in one patient was a recurrence of a pre-existing condition or an event within the trial.

Answer

Chief Medical Officer Aaron Osborne clarified that the uveitis was recurrent within the trial for patient #2 in Cohort 1, who had a prior inflammation event at week 16. Regarding the regulatory path, he stated that while ongoing discussions with the FDA exist for trials like INFINITY, formal end-of-phase discussions for the wet AMD pivotal program have not yet occurred but are planned ahead of a mid-2021 trial start.

Mani Foroohar asked about the washout period for prior anti-VEGF treatments in the INFINITY trial and whether the single-injection comparator arm could be used in a Phase III study. He also sought to clarify if patients in the trial were all known anti-VEGF responders or if some were treatment-naive.

Answer

Chief Medical Officer Aaron Osborne explained that the INFINITY trial includes recently-diagnosed DME patients, some of whom are treatment-naive, which differs from the heavily pre-treated OPTIC population. He clarified that a Phase III trial would likely require a comparator arm using the approved standard-of-care regimen, not the single-injection design of the current Phase 2 study.