Philip Nadeau

Phil Nadeau inquired about Biogen's timeline for returning to top-line growth, the point at which growth products could offset declines in legacy franchises, and the potential role of business development in achieving this.

Answer

Christopher A. Viehbacher, President and CEO of Biogen, acknowledged that while growth products outstripped MS declines last year, 2026 will see full-year Tecfidera generic erosion in Europe and the introduction of a Tysabri biosimilar. He stated that a return to growth hinges on positive Phase 3 results and successful product launches, such as Litifilimab for SLE and Felzartamab for AMR, potentially by 2028. He also confirmed active pursuit of business development opportunities, focusing on acquisitions of companies post-Phase 3 or in early commercialization, typically in the $5-6 billion range, while noting the challenge of finding value-generating targets. He expressed high conviction in the significantly expanded late-stage pipeline.

Philip Nadeau inquired about Biogen's timeline for returning to top-line growth, specifically when growth products are expected to surpass declines in legacy franchises, and the potential role of business development in this trajectory.

Answer

Christopher A. Viehbacher, President and CEO, Biogen, stated that growth products outstripped MS declines in the last year, but 2026 will see full-year Tecfidera generic erosion and biosimilar competition for Tysabri. He emphasized that positive Phase III results and product launches (e.g., litifilimab, felzartamab by 2028) are crucial for growth. He also noted ongoing efforts in business development for post-Phase III or early commercialization assets, but stressed the challenge of finding value-generating acquisitions.

Philip Nadeau of TD Cowen asked about Biogen's AHEAD-three 45 trial for early Alzheimer's, inquiring about the potential for an interim analysis and the key design differences compared to a competitor's trial.

Answer

Priya Singhal, EVP & Head of Development, detailed significant design differences, noting AHEAD-three 45 uses amyloid PET for screening and includes only patients with no cognitive decline (CDR global score of 0). She contrasted this with the competitor's mixed inclusion criteria. Singhal stated the trial readout is planned for 2028 and, while reserving optionality, no interim analysis is currently planned.

Philip Nadeau of TD Cowen asked about Biogen's AHEAD-345 trial for early Alzheimer's, inquiring about the potential for an interim analysis and the key design differences compared to a competitor's trial.

Answer

Priya Singhal, EVP & Head of Development, explained that the AHEAD-345 trial is scientifically distinct, using amyloid PET screening and targeting a truly presymptomatic population with a CDR global score of zero. She contrasted this with a competitor's mixed inclusion criteria. Singhal clarified that the trial has specific biomarker and cognitive endpoints and is planned for a 2028 readout, with no interim analysis currently scheduled.

Philip Nadeau asked about LEQEMBI's short-term trajectory, questioning the dynamics behind its recognized revenue versus in-market sales growth and whether strong ex-U.S. growth is replicable.

Answer

President and CEO Christopher Viehbacher highlighted strong growth in both U.S. and ex-U.S. markets and expects continued steady progress, with future catalysts like subcutaneous formulations and diagnostics taking time to impact the trajectory. CFO Michael McDonnell reiterated the strong sequential growth in global in-market sales (+30%) and U.S. sales (+28%) for the quarter.

Philip Nadeau asked for an update on the filing status for the subcutaneous (subcu) formulation of LEQEMBI, for both maintenance and induction therapy.

Answer

Dr. Priya Singhal, Head of Development, stated that the subcutaneous maintenance filing is expected to be imminent. For the induction indication, she noted that data is being analyzed from the Clarity open-label extension study, with a regulatory outcome anticipated by the first quarter of 2026.

Phil Nadeau asked about CRENESSITY's patient dynamics and new patient starts, specifically inquiring if the lower enrollment forms in Q3 compared to Q2 were due to seasonality or an early launch bonus, seeking insights for future modeling.

Answer

Eric Benevich, Chief Commercial Officer, stated that the 540 new treatment forms in Q3 represented a continuation of strong adoption, characterizing it as a steady launch without clear seasonality yet. Matt Abernethy, Chief Financial Officer, reinforced the positive tone, thanking Phil for asking only one question.

Phil Nadeau asked about CRENESSITY's patient dynamics and new patient starts in Q3 compared to Q2, inquiring if observed trends were due to seasonality or an early launch bonus, seeking insights for future modeling.

Answer

Eric Benevich, Chief Commercial Officer, stated that 540 new treatment forms in Q3 continued strong adoption, consistent with expectations for a steady launch. He noted weekly adoption was consistent over the summer and did not attribute trends to seasonality. Matt Abernethy, Chief Financial Officer, reinforced the focus on answering the first question asked.

Philip Nadeau of TD Cowen inquired about the strong launch of Crinesity, asking if the impressive Q2 sales number was influenced by a bolus of warehoused patients and whether the growth is sustainable.

Answer

CCO Eric Benevich stated that the strong adoption was not due to a patient bolus but rather steady and consistent uptake as patients flow through endocrinology practices. He noted that the ENDO conference helped accelerate awareness. Strategic Advisor Eiry Roberts added that patients from the clinical trial program are also transitioning steadily to commercial product, not in a single bolus.

Philip Nadeau asked about the expected magnitude of INGREZZA's sequential sales growth from Q1 to Q2 2025 and requested details on the time it takes from a CRENESSITY prescription to the patient receiving the drug.

Answer

Chief Financial Officer Matthew Abernethy projected a 'nice step up' for INGREZZA sales in Q2, driven by an additional order week and new patient momentum, though this will be partially offset by a slight sequential increase in gross-to-net deductions from new contracts. He noted it was too early to provide a specific time-to-fill metric for CRENESSITY but described the typical process as taking 5-7 days.

Philip Nadeau inquired about Neurocrine's expectations for the trajectory of new patient start forms for CRENESSITY and what the company would consider a successful ramp.

Answer

Chief Commercial Officer Eric Benevich and Chief Financial Officer Matthew Abernethy responded that while they would not provide specific guidance on the pace of new start forms, they were very pleased with the early launch dynamics, including 11 forms received in just a few working days at the end of 2024. They emphasized that as the first new medicine for CAH in over 70 years, the adoption curve will be measured, but they are confident in its long-term potential, citing strong initial receptivity.

An analyst on behalf of Phil Nadeau from TD Cowen asked if upcoming data from emracladine would influence the pivotal trial plans for NBI-568 and requested details on the broader pivotal strategy.

Answer

CMO Eiry Roberts stated that while the team is encouraged by data suggesting M4 agonism is sufficient for efficacy, their focus is primarily on their own emerging Phase II data to design the Phase III program for NBI-568. CEO Kyle Gano added that their selective, direct activation approach offers a key differentiation. Specific trial design details will be shared after the end-of-Phase II FDA meeting.

Phil Nadeau asked about BioMarin's updated 2027 revenue guidance, seeking clarification on the scenarios considered and the rationale for rescinding the previous guidance. He also inquired about the company's revised appreciation of competitive impact on VOXZOGO.

Answer

Brian Mueller (CFO, BioMarin Pharmaceutical) explained that the original 2027 outlook was reassessed due to factors like potential VOXZOGO competition, the Enzyme acquisition, BMN-401 launch, and ROCTAVIAN divestment. He outlined a range of outcomes, with the lower end aligning with current FactSet consensus (excluding ROCTAVIAN) and assuming two successful competitors, while the higher end reflects delayed competition or successful intellectual property events. Mueller noted a different view on competitive impact based on observed market trends.

Phil Nadeau inquired about BioMarin's decision to rescind its 2027 revenue guidance, seeking clarification on the underlying scenarios and how the company's assessment of competitive impact, particularly for Voxzogo, has evolved since the initial guidance was issued.

Answer

Brian Mueller, Chief Financial Officer, explained that the updated outlook incorporates a year of assessing various factors, including potential Voxzogo competition, the Enzyme Pharma acquisition, BMN-401 launch potential, and the decision to divest Roctavian. He outlined scenarios ranging from two competitors taking significant share by 2027 (lower end, aligning with current consensus) to significant delays in competition due to successful intellectual property events (higher end, reaching $4 billion). Mueller noted a different, more conservative view on competitive impact compared to the initial forecast.

Philip Nadeau of TD Cowen inquired about the revenue trajectory for VOXZOGO, specifically whether a flat Q1 to Q2 trend implies a quarterly decline, and asked for quantification of the potential financial impact from hypothetical U.S. and E.U. pharmaceutical tariffs.

Answer

Brian Mueller, Executive Vice President and Chief Financial Officer, clarified that VOXZOGO's revenue may appear flat in the first half of 2025 due to global order timing dynamics, not a decline in patient growth, with more substantial growth expected in the second half. Regarding tariffs, he stated that while the company is modeling scenarios, it will not speculate on the financial impact of potential future tariffs until policies are clearer, noting that BioMarin's global business model provides some insulation.

Philip Nadeau questioned the deceleration in VOXZOGO's growth guidance for 2025, asking for details on the expected sources of growth by territory and the key factors that could lead to outperformance or underperformance.

Answer

Chief Financial Officer Brian Mueller explained that while the growth rate is decelerating from 56% in 2024, the nearly $200 million in absolute dollar growth is strong and keeps the company on track for its long-term CAGR target of over 25%. Chief Commercial Officer Cristin Hubbard added that growth will come from the U.S. (especially the 0-5 age cohort), highly penetrated markets like Germany, and expanding international markets like Brazil, supported by increased commercial investment.

Philip Nadeau inquired about the maturity of the Voxzogo launch in the U.S., asking if new patient starts are nearing the incident population, and questioned the ideal development phase for BioMarin's business development targets under $1.5 billion.

Answer

EVP, Chief Commercial Officer Cristin Hubbard explained that the majority of new U.S. Voxzogo starts are in the 0-5 age group due to the recent label expansion, and in markets with higher penetration, new starts are shifting to the 0-2 incident population. President and CEO Alexander Hardy added that business development will focus on leveraging BioMarin's global footprint for later-stage assets and bolstering the early-stage pipeline.

Phil Nadeau from TD Cowen asked about HEPLISAV-B's strong quarterly performance, questioning if any one-time factors like inventory builds contributed, and requested more detail on the 'Other' market segment where market share is lowest.

Answer

Chief Commercial Officer Donn Casale stated that the record quarter was driven by widespread adoption, particularly in retail, with no significant one-time stocking issues. He clarified that the 'Other' segment comprises a long tail of smaller customers (military, corrections, small clinics) and that the company's strategy is to capture these patients as they increasingly utilize the retail pharmacy channel, where Dynavax is strongest.

Philip Nadeau asked about the drivers behind the lower-than-usual seasonality for HEPLISAV-B in Q1 and whether this represents a new trend. He also sought clarity on the upcoming shingles vaccine data, questioning if the Q3 readout would be sufficient for a go/no-go decision. Lastly, he inquired about the company's interactions with the FDA amidst leadership changes in Washington.

Answer

CCO Donn Casale attributed the strong Q1 performance and flattened seasonality to a purposeful focus by major retailers on non-flu vaccines, including Hepatitis B. CEO Ryan Spencer clarified that the Q3 shingles data is an important stage-gate for advancing the program and unlocking further investment, but the ultimate decision to proceed to a pivotal trial will require a more comprehensive data package in 2026, including long-term durability and data from the older patient cohort. Spencer also noted that Dynavax is somewhat insulated from immediate FDA changes, as its next major interaction for the shingles program is not until late 2026.

Philip Nadeau asked about HEPLISAV-B's commercial performance, including Q1 2025 seasonality, the specific impact of the new Medicare reimbursement policy, and for more clarity on the hierarchy of immunological endpoints for the shingles program's go/no-go decision.

Answer

Chief Commercial Officer Donn Casale noted that Q1 2025 is off to a stronger start than the prior year, with a less profound sequential decline expected, driven by an earlier retail focus on non-respiratory vaccines. He explained the Medicare change allows for Part B roster billing in pharmacies, creating equal access for HEPLISAV-B. CEO Ryan Spencer and Chief Medical Officer Rob Janssen reiterated that while CD4 T-cells are critically important for the shingles program, the decision will be based on a 'constellation' of all immune response data.

Phil Nadeau of TD Cowen inquired about the process for identifying and recruiting patients for the ECLIPSE-2 trial who have not responded to Hepcludex. He also asked if Vir would release the VIR-5818 monotherapy dose-escalation data separately from the combination data.

Answer

EVP & Chief Medical Officer Dr. Mark Eisner explained that identifying patients for ECLIPSE-2 is straightforward, as investigators know which of their patients are on bulevirtide and can test them for viremia to determine eligibility. He noted the trial is appealing for these patients. Regarding VIR-5818 data, Dr. Eisner stated that the company has not yet decided whether to release the monotherapy data alone or wait to present it with the combination data, as they are currently analyzing the totality of the data.

Philip Nadeau asked two questions: first, whether the multiple new dose levels tested for VIR-5500 since January have continued to show a dose response. Second, he asked for clarification on whether the new HDV prevalence figures represent overall or diagnosed patients and what the diagnosis rate is.

Answer

Mika Derynck (Executive) declined to comment on the ongoing VIR-5500 dose escalation but noted encouragement from the dose response observed in the VIR-5818 program. Marianne De Backer (Executive) clarified that the HDV figures are for RNA-positive, actively viremic patients eligible for treatment, not just diagnosed patients, and detailed the methodology used to arrive at the 61,000 U.S. patient estimate.

Philip Nadeau of TD Cowen asked for the basis of management's confidence that higher doses of VIR-5500 will lead to better PSA responses, given the lack of a clear dose response in initial data. He also asked about the expected quality and quantity of data for the next updates on VIR-5500 and VIR-5818.

Answer

CEO Dr. Marianne De Backer stated the company will share meaningful updates as data on safety, efficacy, and durability develops from ongoing dose escalations. Dr. Mark Eisner, CMO, emphasized that the PSMA program is still very early in dose escalation with significant room to increase the dose. He cited a colorectal cancer patient in the HER2 program who saw deepening responses with dose escalation as an example of the platform's potential, expressing anticipation for similar results in the PSMA program.

Philip Nadeau asked if Vir will disclose the final HDV trial design and timelines at the upcoming analyst meeting. He also questioned whether the T-cell engagers need to demonstrate clear differentiation in Phase I or if being safe and effective is sufficient to advance them.

Answer

Dr. Mark Eisner, Chief Medical Officer, responded that more information on the final HDV trial design will be shared at the investor event, but timelines may not be fully clarified at that point. Regarding the T-cell engagers, he explained that advancement will be a data-driven decision focused on proof of concept from the initial monotherapy data expected in Q1.

Philip Nadeau of TD Cowen sought more detail on what constitutes 'good data' for the Prader-Willi trial, specifically regarding BMI decrease, hunger reduction, and consistency. He also asked a housekeeping question about the trajectory of stock-based compensation.

Answer

David Meeker, Chairman, President & CEO, identified weight loss as the primary endpoint, targeting a BMI decrease of at least 5% at one year, as any weight loss is significant in this population. He noted hyperphagia data will be collected but is harder to interpret in an open-label study. CFO Hunter Smith addressed the second question, stating that the Q2 stock compensation level is a fair baseline moving forward, driven by the stock price increase.

Philip Nadeau from TD Cowen asked about the purpose of the upcoming FDA meeting for the HO filing, requested quantification of the Q1 revenue impact from insurance reauthorizations, and inquired about the payer mix for BBS and expectations for HO.

Answer

David Meeker, CEO, described the FDA meeting as a standard pre-filing interaction to align on the data presentation. CFO Hunter Smith quantified the insurance reauthorization impact at approximately $700,000. Jennifer Chien, Head of North America, stated the BBS payer mix is roughly an equal split between commercial and Medicaid, totaling about 80%, and that the HO mix is still under evaluation.

Philip Nadeau asked for clarification on what management considers 'doing well' for the HO pivotal trial's primary endpoint and questioned if a Q4 inventory build would lead to a destock in Q1.

Answer

CEO David Meeker stated that while the regulatory hurdle is 5% weight loss, they would be disappointed with less than 10%, emphasizing the drug's proven efficacy. CFO Hunter Smith confirmed they anticipate a destocking of inventory in Q1 2025, noting the first quarter can often be 'lumpy'.

Philip Nadeau inquired about the financial impact of the Q3 revenue pull-forward from Q4 and asked about the criteria and timeline for advancing a gene population from the DAYBREAK trial into a pivotal study.

Answer

Chief Financial Officer Hunter Smith estimated the revenue pull-forward from Q4 into Q3 was approximately $0.5 million. Chairman, CEO and President David Meeker explained that advancing a DAYBREAK gene requires a better understanding of which genetic variants are true loss-of-function. He noted that a gene like PHIP could be advanced with a next-generation program, positioning it as a potential 2026 activity.

Phil Nadeau questioned the market penetration of Revuforge in the incident KMT-2A population, asking how much growth remains before the NPM1 label expansion. He also requested an update on the inclusion of NPM1 in NCCN guidelines.

Answer

CCO Steve Closter clarified that having treated over 500 patients represents about 25% of the annual 2,000-patient KMT-2A market, with a target to reach 50% by year-end, indicating further growth potential. CEO Michael Metzger added that the company has submitted data for NCCN guideline inclusion for NPM1 and expects an update before the sNDA approval, which would aid the launch.

Philip Nadeau from TD Cowen asked if the updated KMT2A data is what the FDA is currently reviewing and whether the Revumenib dose for the frontline combination trial has been finalized with the FDA.

Answer

CEO Michael Metzger declined to confirm specifics of the FDA review but noted the new data is highly supportive of approval. Dr. Neil Gallagher, President and Head of R&D, confirmed that the frontline pivotal study is initiating with a Revumenib dose of 160 milligrams.

Alex, on for Phil Nadeau, asked about Apellis's potential tariff exposure for SYFOVRE and EMPAVELI, the location of its ex-U.S. manufacturing, and where its key intellectual property is domiciled.

Answer

Executive Timothy Sullivan stated that the company is analyzing potential tariff exposure and mitigation tactics but could not provide details. He reiterated public disclosures that drug substance for SYFOVRE is manufactured in Switzerland and Japan but did not disclose the location for drug product manufacturing or where the company's IP is domiciled.

Philip Nadeau from TD Cowen asked for more detail on the co-pay assistance funding shortage causing increased sampling and about the marketing focus for EMPAVELI in C3G/IC-MPGN.

Answer

CEO Dr. Cedric Francois explained the funding gap is with independent, third-party organizations and that physicians use samples to bridge this temporary gap for patients. For EMPAVELI, he highlighted the broad efficacy across all patient subgroups (C3G/ICGN, pre/post-transplant) and noted the drug is building a strong reputation among transplant nephrologists.

Philip Nadeau of TD Cowen asked for the specific gross-to-net percentage in Q3 and inquired whether adverse event reports concerning a competitor's drug have had any noticeable impact on SYFOVRE prescribing.

Answer

CFO Timothy Sullivan clarified that the Q3 gross-to-net was at the high end of the previously guided 10% to 20% range. CEO Dr. Cedric Francois declined to comment on competitor safety issues but reiterated that Apellis believes the primary differentiator between the products is SYFOVRE's superior and durable efficacy profile.

Philip Nadeau inquired about the manufacturing requirements for filing GLPG5101 in the U.S. and Europe, how well-defined these are with regulators, and the estimated number of Decentralized Manufacturing Units (DMUs) needed to serve the market.

Answer

CEO Paulus Stoffels stated that Galapagos is in continuous discussion with the FDA and EMA and has a well-defined development path for manufacturing to meet the 2028 commercial launch target. CFO Thad Huston added that the strategy is evolving towards a regional hub model, which would require fewer DMUs than a point-of-care approach to cover large territories.

Philip Nadeau of TD Cowen asked for an update on the timing of the next data presentations for the CAR-T programs GLPG5101 (NHL), GLPG5201 (CLL), and GLPG5301 (multiple myeloma).

Answer

Jeevan Shetty, Head of Development Oncology, stated that new and updated durability data for the 5101 and 5201 programs will be presented at upcoming hematology conferences in 2024. He noted that it is too early for data from the 5301 multiple myeloma study, as it has just recently begun recruitment.

Philip Nadeau inquired about the remaining steps required to file the IND for the tau gene silencing program in 2026 and asked about the potential applications and development timeline for the ALPL non-viral shuttle.

Answer

CEO Dr. Al Sandrock stated that the primary remaining task for the tau gene therapy IND is the completion of the GLP toxicology study. Regarding the ALPL shuttle, he explained it is being assessed for delivering proteins and oligonucleotides across the blood-brain barrier for various CNS diseases, which could significantly improve drug delivery. CSO Dr. Todd Carter added that early data on the shuttle may be shared later in the year.

Philip Nadeau asked about translating tau PET imaging results into cognitive benefits following the recent CTAD data, the potential timing for proof-of-concept data from the SOD1 ALS gene therapy trial, and the accounting treatment for recent milestone payments from partners.

Answer

Dr. Toby Ferguson, Chief Medical Officer, and Dr. Alfred Sandrock, CEO, explained that patient selection, particularly by tau burden, will be critical for translating tau PET imaging to clinical outcomes. They noted that the relationship will become clearer as more tau-targeting drugs generate data. For the SOD1 program, they pointed to the tofersen trials as a precedent, where biomarker effects were seen in as little as 12 weeks, with surrogate outcomes like NfL showing changes within six months. Chief Financial Officer Nathan Jorgensen confirmed the $15 million from Novartis and $3 million from Neurocrine would be booked in the fourth quarter.

Philip Nadeau from TD Cowen inquired about the planned doses for the VY-TAU01 single ascending dose trial, how PK data will inform the multiple ascending dose trial, and for any new details on the frataxin candidate selected with Neurocrine.

Answer

Chief Medical Officer Dr. Toby Ferguson and Executive Alfred Sandrock explained that while specific doses for VY-TAU01 are undisclosed, preclinical data in primates and mouse models inform the starting range. They expect the SAD study to provide safety and PK data to guide dosing for the MAD trial. Regarding the frataxin candidate, Sandrock deferred to their partner Neurocrine for disclosures, but confirmed the selection was based on mechanistic effects and manufacturability criteria.

Philip Nadeau asked whether third-party prescription data for JOURNAVX would be accurate and what the expected duration of therapy would be. He also inquired about the status and resolution timeline for the royalty dispute with Royalty Pharma concerning ALYFTREK.

Answer

CEO Reshma Kewalramani asserted that the ALYFTREK royalty obligation is clearly defined by their contract with the CF Foundation and is not a matter of opinion. COO Stuart Arbuckle projected an average JOURNAVX script duration of around 14 days and noted that while third-party data varies, Vertex will provide its own metrics on prescriptions and covered lives.

Philip Nadeau from TD Cowen requested more detail on the commercialization of suzetrigine, asking for an update on contracting discussions with payers and inquiring about other strategic launch initiatives beyond co-pay assistance programs.

Answer

COO Stuart Arbuckle reported that payer discussions are progressing well, with a high appreciation for the unmet need. In addition to patient financial assistance, he highlighted a second key strategic initiative: investing to secure broad national retail distribution to ensure suzetrigine is on pharmacy shelves at launch.

Philip Nadeau from TD Cowen asked for the mechanistic rationale behind ziftomenib's improved safety at higher doses and inquired about efforts to develop next-generation menin inhibitors for hematologic malignancies.

Answer

EVP of Clinical Development, Dr. Mollie Leoni, explained that higher doses lead to faster blood count recoveries, reducing patient susceptibility to infections and improving the safety profile. CEO Dr. Troy Wilson added that while they have next-gen molecules for heme malignancies, the focus is on ziftomenib in combinations, with next-gen efforts currently aimed at diabetes and other solid tumors.

Philip Nadeau inquired about the specific details to be disclosed in the upcoming mid-November data release, including CR rate, safety, and durability, and asked about the necessary steps for an FDA filing post-data.

Answer

Dr. David Roth, Chief Medical Officer, confirmed the data release will include the primary endpoint (CR rate), safety data, duration of response, and time to response for the initial 190 patients, but not overall survival data. He stated that following the data release, the company will proceed with routine regulatory interactions to submit the filing as quickly as possible.

Philip Nadeau of TD Cowen inquired about the timeline and data requirements for a go/no-go decision on a pivotal study for tamibarotene in AML. He also asked about the European commercialization strategy and sought clarification on the recent decline in operating expenses.

Answer

Chief Medical Officer Dr. David Roth stated that the company needs to see the upcoming SOHO data for over 40 patients in the SELECT-AML-1 trial before deciding on next steps, emphasizing the importance of the delta between the arms and response quality. CEO Conley Chee explained that Syros plans to find a partner to commercialize in the fragmented European market while handling the U.S. launch internally. CFO Jason Haas confirmed that the lower expenses represent a new run rate due to a strategic reprioritization to focus resources on the lead programs.

Asked for clarification on the expected efficacy delta in the SELECT-AML trial, the expected control arm performance, and the reason for the updated enrollment timeline for the SELECT-MDS trial.

Answer

Executives clarified that the SELECT-AML trial will provide the first data on the ven/aza control arm in the RARA-positive population, and they are hopeful for a triplet response rate similar to the 83% seen in the safety lead-in. The minor delay in the SELECT-MDS trial enrollment is due to more precise forecasting as the trial nears completion.

Asked about the timeline for seeing clinical differentiation for reni-cel (e.g., on end-organ damage) and the target market size for their initial orphan in vivo indications.

Answer

For reni-cel differentiation, improvements in end-organ function could potentially be seen around the 1-year mark, based on data from allogeneic transplants. For the in vivo program, the company is targeting orphan indications with a market size of approximately $400-500 million, which they consider meaningful to drive growth while establishing the technology's safety profile.

Philip Nadeau asked about the timeline to see clinical differentiation for reni-cel on measures like end-organ damage, and what patient population size is considered a good return for an orphan in vivo indication.

Answer

Chief Medical Officer Baisong Mei noted that data from allogeneic transplants suggest end-organ improvement can be seen at one year. CEO Gilmore O'Neill stated that for in vivo programs, a market size of $400-500 million is considered meaningful for an initial orphan indication, allowing the company to drive growth while building a safety profile for the technology.

Asked about the progress of the commercial manufacturing scale-up process, whether a CMC package has been agreed upon with the FDA, and if there's a requirement for pivotal trial patients to be dosed with commercial-grade material.

Answer

The company is in a 'very good place' with its CMC package and is progressing well. They are building commercial capacity to be ready for launch and are making excellent progress on processes to be BLA- and inspection-ready.

Asked for more detail on the magnitude of the royalty from Pierre Fabre and for the company's go/no-go decision criteria for advancing ATA188 into Phase III trials based on the upcoming EMBOLD data.

Answer

The company cannot disclose more than "significant double-digit tiered royalties" due to the partnership agreement. The go/no-go decision for ATA188 depends on the data; a "go" for Phase III would be based on a statistically significant result or a very strong trend supported by biomarkers. If there is evidence of effect that requires more study, the program would continue with additional work rather than immediately advancing to Phase III.

Phil Nadeau from Cowen & Co asked for clarification on the cellular inflammation data for the 2E11 dose, how aflibercept would be dosed in the comparator arm, the company's confidence in matching its efficacy, and how physicians would monitor patients post-treatment in a real-world setting.

Answer

CMO Aaron Osborne confirmed that at the most recent time point, no patients on the 2E11 dose had cellular inflammation. He stated the aflibercept comparator arm will be dosed per its label (every eight weeks after three initial injections). Confidence in matching efficacy stems from the stable anatomy and continuous VEGF suppression observed in OPTIC. Dr. Arshad Khanani (Managing Director, Sierra Eye Associates) added that in practice, after an initial six-month monitoring period, stable patients could likely be seen every six months.

Phil Nadeau from Cowen and Co. addressed the key debate around ADVM-022, asking for the physician's perspective on how much anterior inflammation and steroid use would be considered excessive or concerning for the broader clinical community, given the therapy's benefits.

Answer

Dr. Arshad Khanani responded that as long as inflammation is anterior, reversible, responsive to treatment, and does not cause long-term vision loss, it is considered manageable and acceptable by clinicians. He stressed that the benefit of a potential one-time treatment that preserves vision far outweighs the risk of low-grade, manageable inflammation, noting the low incidence of IOP issues and the high value this therapy provides to patients.

Phil Nadeau inquired about the rescue criteria in the INFINITY trial, asking how they compare to other DME trials and standard clinical practice. He also asked for an update on enrollment for Cohort 4 of the OPTIC study and the potential risk of delays due to COVID-19.

Answer

Chief Medical Officer Aaron Osborne explained that the rescue criteria are at the most stringent end used in DME trials to support the study's hypothesis. President & CEO Leone Patterson addressed the second question, stating that while the long-term impact of COVID-19 is still unfolding, the company remains on track to present data from all four OPTIC cohorts by the end of the year.

Phil Nadeau of Cowen and Company questioned if the steroid regimen for the diabetic retinopathy trial is finalized or awaiting more data. He also asked for details on what has been observed in the open-label Cohort 3, specifically how many patients are past the six-week steroid regimen, and about the flexibility of the topical steroid dosage.

Answer

President and CEO Leone Patterson indicated that based on positive observations from Cohort 3, the company is proceeding with the same six-week topical steroid eyedrop regimen for Cohort 4, suggesting high confidence. While the final DR protocol is pending the IND submission, a topical steroid approach is likely. She confirmed several Cohort 3 patients are past the six-week mark. Chief Medical Officer Aaron Osborne detailed the current steroid tapering schedule and confirmed that the dosage frequency could be increased if needed, though the current regimen has been sufficient.

Phil Nadeau from Cowen and Company inquired about XOMA's forward-looking operating expenses, the timeline for the go/no-go decision on the pyoderma gangrenosum (PG) trial, and the data disclosure strategy for the ongoing XOMA 358 study.

Answer

SVP Paul Rubin and CFO Tom Burns confirmed that OpEx estimates were in the right ballpark, with a pro forma cash balance of $69 million funding operations through Q1 2017. CEO John Varian and SVP Paul Rubin added that the PG trial's first decision point is expected around the end of Q1. For the open-label XOMA 358 study, data will be disclosed after at least one cohort is complete to ensure meaningful results.

Phil Nadeau of Cowen and Company inquired about the future development milestones for XOMA 358 and asked for a comparison between its mechanism of action and a competing compound from Zealand Pharma.

Answer

CEO John Varian initiated the response, which was detailed by Paul Rubin, SVP of R&D and CMO. Rubin explained that two proof-of-concept, single-dose trials for XOMA 358 are designed and ready to launch in the near future for congenital hyperinsulinism and post-bariatric surgery hypoglycemia. He highlighted that XOMA 358 works at the insulin receptor level, making it effective regardless of the underlying genetic defect, and offers a more convenient dosing schedule (monthly vs. continuous infusion) compared to the competitor's compound.