Tyler Van Buren

Tyler Van Buren inquired about Regeneron's broader R&D strategy, asking if immunology & inflammation, ophthalmology, and oncology will remain a bigger focus than other therapeutic areas, or if the company is committed to a balanced approach.

Answer

Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Regeneron Pharmaceuticals, stated that Regeneron takes an agnostic approach guided by genetics, which has historically proven successful. He emphasized using large-scale human genetics and AI to identify targets, leading to new drugs for new indications across all therapeutic areas, not just protecting existing franchises.

Tyler Van Buren questioned Regeneron's broader R&D strategy, asking if immunology & inflammation, ophthalmology, and oncology would remain primary focus areas or if the company aims for a balanced approach across all six therapeutic areas.

Answer

Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Regeneron Pharmaceuticals, emphasized an agnostic R&D approach guided by genetics, aiming to discover new drugs for new indications rather than 'me-too' products. He highlighted the power of human genetics and AI in target selection across all therapeutic areas, ensuring innovation.

Tyler Van Buren with TD Cowen asked about the probability of approval for EYLEA HD's RVO and every four-week dosing filing with a new filler by late December, and whether this is the same alternate filler used for the recent Libtayo adjuvant cutaneous squamous cell carcinoma approval.

Answer

Regeneron President and CEO, Leonard Schleifer, clarified that it is a different filler. He explained the complicated timeline, noting that the new filler requires FDA review and inspection. Ideally, approval before the late November PDUFA date for RVO Q4 would wrap everything up. If not, they hope for December approval of the filler, followed by rapid resubmission and FDA action, as they believe no other issues remain for the application.

Tyler Van Buren asked about the probability of a late December decision for EYLEA HD's RVO and every four-week dosing filing with a new filler, and whether this is the same alternate filler used for the recent LIBTAYO adjuvant cSCC approval.

Answer

President and CEO Leonard Schleifer clarified that it's a different filler. He explained that the new filler needs FDA review and inspection, and if approved before the late November PDUFA date for RVO Q4, the approval could be wrapped up then. Otherwise, they hope for December approval of the filler, followed by rapid resubmission and FDA action, as they believe no other issues remain for the application.

Tyler Van Buren from TD Cowen asked about the drivers behind the strong quarterly rebound in EYLEA HD sales and requested more details on the Catalent manufacturing site inspection issue, including potential resolution timelines.

Answer

President & CEO Dr. Leonard Schleifer explained the Catalent FDA observations were procedural, not structural, and expressed confidence in an expeditious resolution. EVP of Commercial Marion McCourt attributed the 16% sequential growth in EYLEA HD demand to strong physician appreciation for its clinical profile, safety, and durability.

Tyler Van Buren from TD Cowen asked for the reasons behind the strong quarter-over-quarter rebound in EYLEA HD sales and sought more details on the Catalent site inspection issue, including the potential resolution timeline.

Answer

President & CEO Dr. Leonard Schleifer explained the Catalent inspection issues were procedural, not structural, and expects an expeditious resolution. EVP of Commercial Marion McCourt attributed the 16% sequential demand growth for EYLEA HD to physicians' appreciation for its clinical efficacy, safety, and durability.

Tyler Van Buren of Leerink Partners inquired about the Complete Response Letter (CRL) for the EYLEA HD prefilled syringe, asking for details on the FDA's questions and a comparison to the resolution timeline of the previous EYLEA HD CRL.

Answer

President and CEO Dr. Leonard Schleifer explained the CRL pertains to an FDA question for a third-party component supplier, a process Regeneron is not directly party to. He conveyed that the supplier has responded expeditiously and that the issue does not involve safety, efficacy, or require a reinspection. While the timeline is uncertain, he expressed hope for a swift resolution, noting the previous CRL took a few months to resolve.

Tyler Van Buren from TD Cowen inquired about the timing of the new dividend, asking why the company initiated it now rather than after the Sanofi development balance is fully paid off.

Answer

EVP and CFO, Chris Fenimore, explained the decision reflects strong confidence in future cash flows and the eventual paydown of the Sanofi balance. He noted it diversifies their capital return strategy and expands the potential shareholder base to include dividend-mandated funds, though share repurchases will remain the primary method of capital return.

Tyler Van Buren of TD Cowen asked for an outlook on EYLEA HD's Q4 growth considering a disclosed wholesaler inventory headwind and inquired about any sales tailwind from a competitor's Avastin supply disruption.

Answer

EVP of Commercial Marion McCourt expressed strong confidence in EYLEA HD's product profile but confirmed a $40 million favorable inventory impact in Q3 would negatively affect Q4 sales, without providing specific guidance. She noted that while monitoring the Avastin situation, no material sales impact had been seen yet. CEO Dr. Leonard Schleifer added the mid-2025 prefilled syringe launch will be a key catalyst for acceleration.

Tyler Van Buren (represented by Greg On) asked about the expected evolution of the split between mNEXSPIKE and Spikevax in COVID vaccinations, given mNEXSPIKE's current majority, and the feedback received from pharmacists and clinicians about mNEXSPIKE so far.

Answer

Stephen Hoge, President, expressed satisfaction with mNEXSPIKE's launch, noting it exceeded expectations and became the leading product, particularly for higher-risk populations. He anticipates older adults and higher-risk individuals will migrate to mNEXSPIKE, while Spikevax will retain its role for pediatric populations. He mentioned that feedback from large customers aligns with this product differentiation, but no specific guidance on the future split was provided.

Tyler Van Buren (Cowen Inc.) asked about the expected evolution of the split between mNEXSPIKE and Spikevax in Moderna's COVID vaccinations, given mNEXSPIKE's current majority share, and sought feedback from pharmacists and clinicians on mNEXSPIKE.

Answer

President Stephen Hoge expressed satisfaction with mNEXSPIKE's launch, noting it exceeded expectations and became the leading product due to its clinical profile and market momentum towards higher-risk populations. He anticipates mNEXSPIKE will continue to grow, while Spikevax will retain its role in pediatrics. Feedback from large customers indicates they are already differentiating product use based on patient risk profiles.

Tyler Van Buren asked for specifics on regulatory interactions for the mRNA-1283 (next-gen COVID) review and expressed concern about approval confidence given the upcoming PDUFA date and a recent competitor denial.

Answer

President Stephen Hoge stated that interactions with the FDA have been "business as usual," characterized by constructive and positive scientific exchanges. He affirmed that, to date, there has been no indication of any issue that would jeopardize their ability to meet the scheduled PDUFA date, though the review remains ongoing.

Tyler Van Buren questioned whether the CMV vaccine could still achieve a high efficacy threshold at its final analysis, even though the criteria for early efficacy were not met at the interim review, possibly due to a wide confidence interval.

Answer

President Stephen Hoge confirmed it is 'very much possible' for the CMV vaccine to show favorable efficacy at the final, fully powered analysis. He explained that the interim look was not sufficiently powered for high confidence, and the company remains blinded to the data while more cases accrue for the final readout.

Tyler Van Buren asked for clarification on the significant expected decline in U.S. COVID vaccine sales from Q3 to Q4 2024, questioning if it reflects a new seasonal dynamic or potentially conservative guidance.

Answer

CEO Stéphane Bancel explained that the sales cadence is different this year due to an earlier season start in the retail channel and limited visibility into the IDN and government channels. CFO Jamey Mock added that the Q3 sales were higher because earlier FDA approval allowed the company to ship more product within the third quarter compared to the prior year.

Tyler Van Buren inquired about the momentum in ATTR-CM diagnosis rates since Attruby's launch and the market dynamic of some centers preferring Amvuttra due to its higher ASP (buy and bill), asking if this impacts BridgeBio's strategy.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, confirmed robust and continued growth in ATTR-CM diagnosis rates, driven by new practices and physicians. He stated that PYP reimbursement concerns were overstated and that the buy-and-bill dynamic is not a significant profit driver for high-volume heart failure practices. Kumar believes good data, efficacy, safety, cost, and eventual payer control will favor small molecule stabilizers over high-cost knockdowns.

Tyler Van Buren inquired about ATTR-CM diagnosis rates and the continued momentum since Atrobi's launch, as well as the impact of the 'buy and bill' dynamic (referencing Amvuttra's higher ASP) on BridgeBio's strategy and specific treatment centers.

Answer

Neil Kumar, CEO and Founder, BridgeBio Pharma, reported robust and continued growth in ATTR-CM diagnoses, with new practices and doctors identifying more patients. He dismissed concerns about PYP reimbursement being a drag. Regarding the 'buy and bill' dynamic, he stated it's not a significant profit center for high-volume heart failure practices and that cardiologists prioritize data, efficacy, safety, and cost. He believes good data and eventual payer control will drive market share towards small molecule stabilizers.

Tyler Van Buren from TD Cowen asked about the trends in utilization of the 28-day free trial, patient assistance programs, and the gross-to-net percentage during Q2 compared to Q1, and the outlook for these metrics.

Answer

CEO Neil Kumar and VP of Strategic Finance Chinmay Shukla confirmed that these metrics normalized in Q2. Kumar elaborated that the company's generous access programs are a crucial long-term strategy to serve underpenetrated populations and build market share, and that the gross-to-net percentage is expected to remain at these normalized levels going forward.

Tyler Van Buren from TD Cowen inquired about quantifying Attruby's paid conversion rate and channel inventory levels, and also asked about the potential market opportunity for the upcoming ADH1 and LGMD2I readouts.

Answer

CCO Matt Outten stated that conversion rates are at or above benchmarks and channel inventory is low, at about 1-2 weeks. CFO Tom Trimarchi confirmed sales were demand-driven with minimal inventory impact. Regarding the pipeline, CEO Neil Kumar highlighted the significant market sizes for LGMD2I (7,000-8,000 patients US/EU) and ADH1 (10,000-12,000 patients US), emphasizing their potential as major commercial opportunities.

Tyler Van Buren asked for an update on Summit Therapeutics' interactions with the FDA regarding the Biologics License Application (BLA) submission for ivonescimab based on HARMONi data. He also asked how recent approvals for amivantamab or Dato-DXd might support ivonescimab's approval, and if the latest overall survival data from World Lung was discussed with the FDA.

Answer

Urte Gayko, Chief Regulatory Quality and Safety Officer, confirmed the BLA filing in Q4 2025, noting continuous FDA interaction and the relevance of recent approvals for amivantamab and Dato-DXd, despite the FDA's expectation for an OS benefit in their setting. She confirmed close contact with the FDA and sharing information but declined to detail specific discussions.

Tyler Van Buren of TD Cowen asked about the benchmark for success regarding the Minimal Residual Disease (MRD) conversion rates in the ALPHA-three trial's upcoming futility analysis.

Answer

President and CEO Dr. David Chang explained that a delta of approximately 30% in MRD conversion rates between the active and control arms would be considered meaningful. He referenced the pivotal trials for Yescarta and Breyanzi in second-line lymphoma, which showed complete remission rate deltas of 33% and 27% respectively, and subsequently demonstrated significant event-free survival benefits.

Tyler Van Buren asked if ALPHA3 site issues varied between community and academic centers, the likelihood of an EFS readout by late 2026, and why the new CBER director's critical view on MRD as an endpoint may not apply to the trial.

Answer

CEO David Chang clarified that ALPHA3 uses MRD for high-risk patient identification, not as a surrogate endpoint, and the trial's randomized design with an EFS endpoint aligns with the FDA's evidence-based standards. EVP of R&D and CMO Dr. Zachary Roberts noted no significant difference in delays between site types. Management deferred providing a specific timeline for the EFS readout, promising more clarity in H1 2026.

Tyler Van Buren of TD Cowen asked for a comparison between the low disease burden patients in the recent JCO publication and those being enrolled in the ALPHA3 trial, and the potential read-through for complete response rates.

Answer

Dr. David Chang, President and CEO, explained that the strong inverse correlation between disease volume and response likelihood seen in CAR T therapies bodes well for ALPHA3. He noted that MRD-positive patients in ALPHA3 have approximately 200-fold less disease volume than second-line patients, a reduction comparable to the low-volume cohorts in the JCO paper, supporting expectations for high efficacy.

Tyler Van Buren inquired about the timeline for completing the ALLO-316 expansion cohort for RCC and starting a pivotal trial, and also asked about the data read-throughs for the ALLO-329 autoimmune program, particularly regarding safety and reducing lymphodepletion.

Answer

Dr. Zachary Roberts, EVP of R&D and CMO, stated the ALLO-316 expansion cohort aims to enroll approximately 20 patients with a program update expected next year. He expressed high confidence that the Dagger technology's success in reducing lymphodepletion in the ALLO-316 program will translate to the ALLO-329 program. Dr. David Chang, President and CEO, added that while they have learned much about managing safety, the read-through to autoimmune disease must be clinically tested due to different patient populations and target burdens.

Tyler Van Buren from TD Cowen inquired about the early uptake of Yes2Go, asking for details on the initial launch trajectory and whether prescription growth is expected to be linear or exponential.

Answer

Chief Commercial Officer Johanna Mercier described the Yes2Go launch as very strong, citing high pre-launch awareness (72% unaided), over 25,000 customer calls, and rapid first injections. She highlighted key access wins, including an October 1 J-code and formulary inclusion in major states like California and Florida, keeping them on track for 75% access in six months. CEO Daniel O’day added that he was impressed with the team's execution.

Tyler Van Buren of TD Cowen inquired about the early uptake of Yes2Go, asking for details on the launch trajectory and whether it is expected to be linear or exponential.

Answer

Chief Commercial Officer Johanna Mercier described the Yes2Go launch as very strong, attributing success to the readiness of cross-functional teams, high pre-launch awareness (72% unaided), and rapid first prescriptions. Mercier highlighted early access wins, including a J-code effective October 1st and formulary inclusion in key states like California and Florida. She confirmed Gilead is on track to meet its access goals of 75% coverage in six months and 90% in twelve months, primarily through medical exceptions while formal formulary decisions are made.

Tyler Van Buren asked for clarification on the drivers behind the quarter-over-quarter decline in Trodelvy sales, specifically whether it was due to competitive pressure or other factors.

Answer

Chief Commercial Officer Johanna Mercier clarified that the sequential decline was primarily due to inventory dynamics and lower demand following a particularly strong Q4. She noted the year-over-year performance was also impacted by inventory and channel mix, but underlying demand increased. She expressed confidence in Trodelvy's stable market share in its key indications.

Tyler Van Buren asked about the specific factors driving the 16% year-over-year growth in the PrEP market and whether these factors would serve as lasting tailwinds for the upcoming lenacapavir launch.

Answer

CCO Johanna Mercier attributed the growth to two key factors: heightened awareness around prevention driven by positive data from the PURPOSE trials, and Gilead's own doubled-down market development efforts. She confirmed that the company believes this momentum will carry through and potentially accelerate the lenacapavir launch.

Tyler Van Buren of TD Cowen questioned Gilead's ability to scale manufacturing for anito-cel upon its expected 2026 launch, asking if the process is similar enough to Yescarta and Tecartus to allow for a faster ramp-up.

Answer

An executive, likely EVP of Kite Cindy Perettie, confirmed that all learnings from Yescarta and Tecartus have been applied to anito-cel production. The technology transfer to the Maryland facility is complete, and the IMAGINE-3 study is being supplied with similar turnaround times to commercial products. The company has no concerns about its ability to scale and has not received FDA feedback suggesting a slower ramp-up would be required.

Tyler Van Buren from TD Cowen inquired about the expected long-term average duration of therapy for Chemtrac and whether a recent CRL for another company's drug signals a change in the FDA's stance that could affect ImmunoCor's programs.

Answer

Ralph Torbay, EVP of Commercial, noted the current duration is 13 months and expects it to moderate as the launch matures. David Berman, EVP of R&D, stated they have not seen any changes in FDA stance, emphasizing their Phase III trials are well-designed, randomized, use a survival endpoint, and were developed with FDA input.

Tyler Van Buren of TD Cowen sought further clarity on the HIV program, questioning if the 12-week post-interruption time point is sufficient to build confidence in long-term viral control and what profile potential strategic partners would want to see.

Answer

David Berman, Head of R&D, explained that the 12-week interruption period is standard for initial Phase I trials to detect any signal of activity, given that the historical rate of viral control at this point is extremely low (around 1%). He emphasized that no therapy has yet demonstrated reliable viral control, and referred to a published white paper for details on a commercially acceptable target product profile.

Tyler Van Buren from TD Cowen questioned if the benchmark for the brenetafusp chemo combo in ovarian cancer should be ELAHERE (mirvetuximab) and asked if successful combination with non-platinum chemo implies a high likelihood of success with platinum chemo.

Answer

David Berman, Head of R&D, clarified their strategy is to add-on to chemotherapy, not replace it like mirvetuximab. Mohammed Dar, an executive, stated that while it's early, they expect to be able to combine with platinum-based chemotherapies and plan to move into those combinations in the coming months.

Tyler Van Buren from TD Cowen questioned if the true benchmark for the brenetafusp chemo combo in platinum-resistant ovarian cancer is ELAHERE (mirvetuximab), and whether a successful combo with non-platinum chemo implies a high likelihood of success with platinum chemo.

Answer

David Berman, Head of R&D, clarified that Immunocore's strategy is to add on to chemotherapy, not replace it like mirvetuximab, and that brenetafusp could eventually be an add-on to mirvetuximab. Mohammed Dar, an executive, noted it's early for chemo combinations but the expectation is they can combine, with plans to move from non-platinum to platinum-based chemotherapies.

Tyler Van Buren from TD Cowen asked to what extent the Q2 revenue was influenced by an initial patient bolus or channel stocking, and whether the older average patient age implies a higher average patient weight and price.

Answer

CFO Jim Mackaness clarified that there was no unusual channel stocking, noting their distributor holds only 7-10 days of inventory. He did acknowledge a strong initial bolus of patient start forms that may moderate. CEO Anish Bhatnagar agreed it is a 'reasonable assumption' that the older commercial patients are heavier than the trial average.

Tyler Van Buren from TD Cowen questioned the extent to which the Q2 revenue figure included an initial patient bolus or channel stocking. He also asked if the older average age of commercial patients implies a higher average weight and thus a higher average price.

Answer

CFO Jim Mackaness stated there was no anomalous channel stocking, as their single distributor orders weekly. He acknowledged a strong initial bolus of start forms that may moderate. CEO Anish Bhatnagar confirmed it is a reasonable assumption that the commercial patient population is, on average, heavier than the clinical trial population.

Tyler Van Buren requested elaboration on the rescue criteria for the LUGANO and LUCIA trials and how these criteria align with real-world clinical practice.

Answer

CEO Dr. Jay Duker detailed the strict rescue criteria, which require both a vision loss of more than five letters and at least 75 microns of new fluid, or a new sight-threatening hemorrhage. He explained this was based on Phase 2 data showing that rescuing for fluid or vision loss alone was ineffective. He noted that physician discretion for rescues was removed in Phase 3 to maintain trial integrity.

Tyler Van Buren of TD Cowen requested elaboration on the rescue criteria for the pivotal trials and how they align with real-world clinical practice, especially in light of recent competitive updates.

Answer

CEO Jay Duker detailed the strict rescue criteria, which require both a vision loss of over five letters and 75 microns of new fluid, or a new sight-threatening hemorrhage. He explained this was based on learnings from the Phase 2 trial, where rescues for fluid or vision loss alone were not effective. He emphasized that physician discretion for rescues has been removed in Phase 3 to ensure consistency and data integrity, acknowledging that trial criteria are necessarily stricter than individualized real-world treatment decisions.

Tyler Van Buren asked if the accelerated enrollment timeline for the wet AMD trials would make it sensible to initiate a cost-efficient Phase II study in Retinal Vein Occlusion (RVO).

Answer

President and CEO Dr. Jay Duker acknowledged RVO as a potential long-term indication for DURAVYU but stated that the company's immediate focus is on executing the wet AMD program and preserving its cash runway. He indicated that an RVO trial is not a short-term priority at this time.

Tyler Van Buren of TD Cowen asked if the accelerated trial timelines would allow for a cost-efficient Phase II study in Retinal Vein Occlusion (RVO) to explore an additional market opportunity while awaiting Phase III data.

Answer

President and CEO Dr. Jay Duker responded that while RVO is a potential long-term indication, the company is currently focused on the wet AMD program and preserving its cash runway. He stated that initiating an RVO trial now is not a path they would take, but it could be considered as part of a longer-term program after successful Phase III data.

Ikenna C. O, on for Tyler Van Guren, asked if Pfizer has indicated a willingness to revise the Vepdeq collaboration or return the rights, why they would return it after significant investment, and if a return would require a cash outlay from Arvinas.

Answer

CEO John Houston reiterated that the current 50/50 deal is less attractive for Pfizer now that development is focused only on second-line monotherapy. He confirmed Pfizer has shown no interest in funding further development. He stated clearly that if the asset is returned to Arvinas, the company will not spend its own money on further development but will instead run a process to find a new partner, thus avoiding a significant cash outlay.

On behalf of Tyler Van Buren, an analyst questioned Pfizer's commitment to the vepdegestrant partnership and asked about the potential role of the KAT6 inhibitor combination in the treatment paradigm.

Answer

CEO John Houston affirmed that Pfizer's commitment remains strong, with joint teams working "full blast" on regulatory and launch plans for the second-line ESR1 mutant indication. CMO Noah Berkowitz clarified that the KAT6 combination is an exploratory Phase 1 study to identify value-adding combinations, and it is too early to project its future role in treatment.

Tyler Van Buren of TD Cowen followed up on the VERITAC-2 trial, asking how the median PFS is expected to improve specifically for the ESR1 mutant population, given the company's guidance of a 'few months better' than control in the overall ITT population.

Answer

CMO Noah Berkowitz reiterated the expectation of a 3-4 month PFS for the fulvestrant arm and 'a few months better' for the vepdegestrant arm. While not providing specific numbers, he stated that they expect the ESR1 mutant population to perform 'a little better' than the overall ITT population due to the underlying tumor biology.

Tyler Van Buren of TD Cowen inquired about the characteristics of the top-performing Authorized Treatment Centers (ATCs), asking if they were prior clinical trial sites and what barriers are preventing other centers from increasing their utilization of Amtagvi.

Answer

Interim CEO Frederick Vogt clarified that only a few top ATCs were clinical trial sites, noting it's not a direct correlation. Chief Commercial Officer Daniel Kirby added that top-performing centers had pre-existing cell therapy infrastructure, and newer centers are ramping up as they build out capabilities like billing and lab processes.

An analyst on behalf of Tyler Van Buren asked if the 2025 revenue guidance includes a potential price increase and what impact ex-U.S. expansion might have on the guidance.

Answer

Interim CEO and President Frederick Vogt confirmed that the anticipated April price increase for both Amtagvi and Proleukin is already factored into the 2025 guidance. He also clarified that the current guidance does not include any potential revenue contribution from ex-U.S. markets.

Tyler Van Buren of TD Cowen asked about the potential impact of upcoming holidays on Q4 Amtagvi infusions and whether the company could still meet annual guidance given the strong start to the quarter.

Answer

Interim CEO Frederick Vogt confirmed that while there might be a holiday-related lull, it has been factored into their projections. He affirmed that the company is on track to perform well in Q4 and meet its annual guidance, as the team can see infusion schedules far in advance.

Tyler Van Buren from TD Cowen asked for the current split of ZORYVE patients between dermatology and primary care settings and inquired about the specific barriers to PCP prescribing and the tactics being employed by partner Kowa to overcome them.

Answer

CEO Frank Watanabe stated that while the addressable market is split 50/50, Arcutis's business is currently 'overwhelmingly dermatology' as the primary care effort is still nascent. Todd Edwards, Chief Commercial Officer, elaborated that the PCP selling cycle requires more frequent engagement to build familiarity, as Kowa is the first to promote modern non-steroidals in this segment. He said Kowa is focused on educating providers and staff on ZORYVE's profile and the prescription fulfillment process, with positive early signals emerging.

Tyler Van Buren from TD Cowen asked for more detail on the drivers behind the significant quarter-over-quarter prescription growth in Q4, particularly the impact of the recent sales force expansion, and whether further expansion is planned.

Answer

Chief Commercial Officer Todd Edwards attributed the strong performance to a 'versatility effect,' where positive clinical experience across ZORYVE's multiple indications amplifies overall use. He confirmed the June sales force expansion was a key driver of increased prescription growth in Q4 and stated that the commercial team is currently considered 'right sized' for the dermatology market.

Tyler Van Buren of TD Cowen inquired about Travere's interactions with the FDA regarding the FILSPARI sNDA for FSGS and whether feedback publicized by competitor Dimerix aligns with their experience.

Answer

Chief Research Officer Dr. William Rote confirmed that interactions with the FDA are progressing as expected and are consistent with the prior IgAN review process. Dr. Rote noted that it was positive to see the FDA provide consistent feedback to a competitor, supporting the use of proteinuria as an approval endpoint for FSGS.

An analyst on behalf of Tyler Van Buren asked about the pathway to full removal of the FILSPARI REMS, assuming the modification to quarterly monitoring is approved, and whether a precedent exists for such a removal.

Answer

SVP of R&D, Dr. Bill Rote, outlined a two-step process. The first step is the pending modification to change liver monitoring from monthly to quarterly. The second step, full removal, would be considered by the FDA after the company accumulates sufficient post-marketing safety data, specified as approximately 3,000 patients with two years of exposure. Dr. Rote noted they are making good progress toward this goal.

Tyler Van Buren inquired about the launch preparations for paltusotine in acromegaly, potential surprises for investors with conservative expectations, and the company's global strategy.

Answer

CEO R. Struthers highlighted the strong clinical data and the EMA's orphan drug designation, which recognizes a clinically relevant advantage. CCO Isabel Kalofonos detailed the launch readiness, including building a talented sales and field reimbursement team, positive payer engagement due to the drug's value proposition (fast onset, sustained effect, favorable profile), and ongoing educational activities. She also outlined the European strategy, starting with a hub in Switzerland and expanding into Germany.

Tyler Van Buren of Piper Sandler asked for specifics on the Phase 3 trial design, including confirmation of the non-inferiority margin, the expected standard deviation for vision in the newly diagnosed patient population, and details on the supplemental injection criteria compared to the OPTIC study.

Answer

CMO Aaron Osborne confirmed the non-inferiority margin will be four letters. He explained that the trial design includes an initial injection before baseline to reduce visual acuity variability, which lowers the standard deviation and allows for a smaller trial size. He also stated that the supplemental injection criteria will remain very similar to those used in the OPTIC study, with final details to be confirmed closer to initiation.

Tyler Van Buren from Piper Sandler inquired about the efficacy and safety of ADVM-022, specifically asking if Cohort 4's results align more with Cohort 1 or Cohorts 2/3, questioning the reasons for anatomical improvements, and seeking confidence that the observed inflammation is not posterior inflammation similar to that seen with abicipar or Beovu.

Answer

Chief Medical Officer Aaron Osborne explained that anatomical improvements in some cohorts were due to the continuous delivery of ADVM-022 effectively reducing baseline fluid in difficult-to-treat patients. He affirmed that inflammation was manageable with topical steroids. Dr. Arshad Khanani, a key investigator, added that the inflammation is anterior, unlike the posterior inflammation seen in abicipar trials, and that ADVM-022 uses aflibercept, a well-established molecule, providing confidence in its safety profile.

Tyler Van Buren asked about the novel trial design for the INFINITY study in DME, seeking clarification on whether 'time to worsening' equates to a rescue injection. He also inquired about the FDA interactions that informed this design and its potential implications for a future registrational trial.

Answer

Chief Medical Officer Aaron Osborne confirmed that the rescue criteria define disease worsening and projected that over half of aflibercept patients would need rescue by week 16, highlighting the trial's high probability of success. He and CEO Leone Patterson noted that the robust, double-masked design resulted from close collaboration with the FDA and scientific advisors and could support the future data package, though a pivotal trial would likely require traditional vision endpoints.

Tyler Van Buren of Cowen and Company asked for clarification on the respiratory market's macro environment, the Q3 rebate adjustment for BREO, the potential impact of TRELEGY on BREO sales, and the strategy behind the $80 million share buyback versus debt repayment.

Answer

CEO Michael Aguiar confirmed that the respiratory pricing environment was in line with expectations and that quarter-over-quarter revenue volatility, like the Q3 rebate true-up, is common and not reflective of underlying demand. He noted that TRELEGY's launch is expected to be slow and target a specific patient subset, mitigating cannibalization of BREO. CFO Eric d'Esparbes explained the $80 million buyback is a firm commitment under an ASR program, with future capital allocation decisions to be reviewed by the board.

Tyler Van Buren of Cowen and Company requested color on the ongoing cost structure review, future expectations for litigation costs, clarity on the generic Advair situation, and any strategic shifts at GSK following recent leadership changes.

Answer

CEO Michael Aguiar stated that the Board-led cost structure review is comprehensive and results will be shared by the end of Q3, but he could not provide specifics. He noted litigation costs are outside of the company's control. On generic Advair, he reiterated guidance for a potential market entry around mid-2018. Lastly, he expressed strong confidence in the new leadership at GSK, including CEO Emma Walmsley, highlighting positive interactions and a strong ongoing partnership.