Brian Abrahams

Brian Abrahams of RBC Capital Markets asked about the strategy behind contracting for INGREZZA mid-year, the duration of these contracts, and whether more contracting should be expected after the competitor's IRA price is established.

Answer

CEO Kyle Gano explained the decision was driven by a strategy to maximize patient access and gain flexibility ahead of the IRA implementation. These contracts were initially targeted for 2026 but were accelerated into 2025. CFO Matt Abernethy added that this sets them up well for 2026, and he does not anticipate further major contracts that would significantly alter the pricing trajectory from the 2025 exit rate.

Brian Abrahams asked for specifics on CRENESSITY's use in centers of excellence versus community settings and how physicians manage glucocorticoid titration. He also inquired about INGREZZA's future contracting cadence and pricing trends.

Answer

Chief Commercial Officer Eric Benevich explained CRENESSITY adoption is broad across all endocrinologist segments, not just centers of excellence. Chief Medical Officer Dr. Eiry Roberts added that the drug's label allows for individualized steroid reduction. On INGREZZA, Benevich noted recent contracts expanded Medicare access and no further immediate agreements are anticipated, providing stability into 2026.

An analyst on behalf of Brian Abrahams from RBC Capital Markets asked for elaboration on INGREZZA's growth drivers, the contribution from demand versus gross-to-net, and the on-the-ground competitive landscape.

Answer

CCO Eric Benevich stated that Q3 growth was primarily driven by new patient demand and strong compliance. He acknowledged the market is growing and that while competitors are also growing, INGREZZA remains the most prescribed VMAT2 inhibitor. He emphasized that with less than 20% of the market treated, there is a long opportunity ahead, supported by the recent sales force expansion.

Brian Abrahams of RBC Capital Markets inquired about Regeneron's Factor XI antibody program, specifically what the company is looking for from the ongoing Phase II study in AFib to advance into registrational studies for AFib and other large indications.

Answer

Regeneron President and CSO, George Yancopoulos, explained that the Phase II AFib study is a run-in for anticipated Phase III pivotal programs. He emphasized that the program's success hinges on the benefit-risk ratio of their two distinct antibodies, with decreases in bleeding risk potentially being more crucial than anticoagulation effect in many settings. He believes their dual-antibody approach allows for customized patient treatment, optimizing for either minimal bleeding risk or higher anticoagulation, opening opportunities beyond SPAF where current anticoagulant use is limited by bleeding concerns.

Brian Abrahams inquired about the Factor XI antibody program, specifically expectations from the large Phase II AFib study and the criteria for moving into registrational studies for AFib and other large indications.

Answer

President and CSO George Yancopoulos explained that the Phase II AFib study is a run-in for anticipated Phase III pivotal programs. He stated that the focus is on understanding the benefit-risk ratio for their two distinct antibodies, emphasizing that decreases in bleeding risk are often more important than anticoagulation effect alone. He believes their two-antibody approach allows for customized treatment, optimizing for bleeding risk or higher anticoagulation capability, opening opportunities beyond SPAF where anticoagulant use is currently limited by bleeding concerns.

Brian Abrahams from RBC Capital Markets asked for insights into why one of the two itepekimab studies in COPD failed to meet its primary endpoint and if this would lead to adjustments in other ongoing studies.

Answer

President & CSO Dr. George Yancopoulos noted that one of the two studies 'turned south' after six months. He speculated that the COVID-19 pandemic created unusual trial conditions, such as lower exacerbation rates, which may have been a factor. He confirmed they are discussing next steps, including a potential additional Phase 3 study.

Brian Abrahams from RBC Capital Markets asked for insights into why one of the two itepekimab studies in COPD failed its primary endpoint and about the feasibility of mitigating this in future studies.

Answer

President & CSO Dr. George Yancopoulos noted that one of the two replicate studies 'turned south' after six months. He speculated that a major factor was the trial's execution during the COVID-19 pandemic, when exacerbation rates dropped precipitously worldwide. He confirmed they are analyzing the data and discussing a potential additional Phase 3 trial with Sanofi.

Brian Abrahams of RBC Capital Markets asked about itepekimab, seeking updates on the scientific understanding of IL-33 as a target, the rationale for its benefit in former smokers with COPD, and how results will guide future development.

Answer

President and CEO Dr. Leonard Schleifer highlighted that the rationale stems from the Regeneron Genetics Center, which links the IL-33 pathway to COPD risk. He noted the Phase III studies passed an interim analysis, boosting confidence. CSO Dr. George Yancopoulos added that strong genetic links support expansion into other areas, such as ASCO, pending the COPD results.

Brian Abrahams of RBC Capital Markets asked if consensus expectations for a ~7% annual sales decline for the EYLEA franchise are reasonable, considering competitive pressures against the potential for an EYLEA HD acceleration.

Answer

EVP of Commercial, Marion McCourt, reiterated that Regeneron does not provide guidance but expressed confidence in EYLEA HD's strengthening profile due to an upcoming prefilled syringe, a potential RVO indication, and enhanced dosing flexibility. She acknowledged expected competitive pressure on standard EYLEA but highlighted the franchise's strong 46% market share in Q4.

Brian Abrahams of RBC Capital Markets asked about the potential for the EYLEA HD prefilled syringe to create a sales inflection point and inquired about the gating factors affecting its development timeline.

Answer

President and CEO Dr. Leonard Schleifer confirmed the company anticipates launching the prefilled syringe by mid-2025. He acknowledged a market preference for this format and agreed it could create an inflection point in adoption. He noted that there are additional U.S.-specific requirements the company is working through to ensure the product is highly reliable and avoids issues like inflammation.

Brian Abrahams of RBC Capital Markets questioned if the final size of the EXTOL-two study might exceed the planned 360 subjects and asked about the company's latest assumptions for seizure reduction delta and dropout rates, given the historically high translatability between Phase II and Phase III epilepsy trials.

Answer

President and CEO Ian Mortimer clarified that the target remains approximately 360 subjects and the study is highly powered, making over-enrollment unnecessary. He emphasized that the primary goal for EXTOL-two is achieving statistical significance to support the NDA filing. Chief Medical Officer Christopher Kenney added that blinded metrics on patient characteristics and rollover rates appear consistent with the successful Phase IIb EXTOL study.

Brian Abrahams asked about the reasons for the slight timeline delay for X-TOLE2 and its potential competitive or commercial implications. He also questioned if the robust results from the Mount Sinai MDD study in a milder population would impact the Phase III MDD trial design.

Answer

President and CEO Ian Mortimer characterized the delay as minor, resulting from normal trial variability with no change in competitive dynamics. Chief Medical Officer Dr. Chris Kenney stated that while the investigator-sponsored trial (IST) results are reassuring, they will not alter the existing Phase III MDD program, attributing the strong IST data to the controlled nature of a two-site study.

Brian Abrahams inquired about the key focus areas of the upcoming 36-month X-TOLE open-label extension (OLE) data, confidence in the long-term safety profile, and the main objectives for engagement at the upcoming AES meeting.

Answer

CEO Ian Mortimer highlighted that the 36-month data will show continued seizure reduction and an increasing 12-month seizure freedom rate with a consistent safety profile. CMO Dr. Christopher Kenney noted updated retention rates will also be presented. CCO Christopher Von Seggern emphasized AES as a key opportunity to engage with future prescribers and gather feedback on azetukalner's market potential.

Brian Abrahams from RBC Capital Markets questioned the reasons for the improved tolerability profile in the Phase III myelofibrosis study compared to Phase I, particularly regarding antiemetic use. He also asked about the company's confidence in its alignment with the FDA on trial endpoints, given recent leadership changes at the agency.

Answer

Chief Medical Officer Reshma Rangwala attributed the improved tolerability, especially the significant reduction in nausea and vomiting, directly to the mandatory use of dual antiemetics for the first two cycles in the Phase III trial, a requirement not consistently enforced in Phase I. Regarding the FDA, she confirmed there has been no new feedback since the alignment on co-primary endpoints in 2024 and expressed confidence in the agency's position, as it is well-documented. CEO Richard Paulson added positive remarks about the FDA's focus on accelerating innovation.

Kevin, on behalf of Brian Abrahams from RBC Capital Markets, asked for more detail on the characteristics of dMMR endometrial cancer patients who are ineligible for checkpoint inhibitors. He also questioned if such patients were present in the original SIENDO study and how they performed.

Answer

Chief Medical Officer Reshma Rangwala explained that medical ineligibility for checkpoint inhibitors is typically due to pre-existing comorbidities, like autoimmune conditions, rather than any specific tumor characteristics. She noted that while they have not specifically analyzed the SIENDO data for this sub-population, the primary driver of selinexor's efficacy appears to be the p53 wild-type status, which showed robust benefit regardless of MMR status in the original exploratory analysis.

Brian Abrahams inquired about the SENTRY trial's powering assumptions, given the observed magnitude of change in average total symptom score (TSS), and asked whether the TSS50 endpoint would still be evaluated as a secondary measure.

Answer

EVP, Chief Medical Officer Reshma Rangwala explained that the powering assumptions are based on the delta between the study arms, and Karyopharm's data suggests a potential delta significantly higher than that seen in competitor trials. She confirmed that TSS50 has been completely replaced by absolute TSS as a co-primary endpoint, reflecting an evolution in regulatory and clinical consensus on the most sensitive way to measure symptom improvement in myelofibrosis.

Kevin Meli, on behalf of Brian Abrahams at RBC Capital Markets, asked about the expected uptake of Sefiance in EU countries with early access programs beyond Germany and the general outlook for the EU opportunity. He also sought to confirm if there would be no SG&A impact from the EU launch.

Answer

CEO Dr. Matthew Klein confirmed no OpEx changes are expected for the Sefiance launch, as it leverages existing infrastructure. CBO Eric Pauwels added that the European opportunity is significant, with Germany being the second-largest market. He anticipates leveraging early access programs in 5 to 10 other key European markets this year and into next, in addition to upcoming launches in Japan and Brazil, to build global momentum.

An analyst on behalf of Brian Abrahams asked for updated thoughts on the PTC518 Huntington's disease program, specifically on balancing an accelerated approval timeline with demonstrating clear drug benefits.

Answer

CEO Dr. Matthew Klein expressed satisfaction with the Phase II data, noting it confirmed target engagement, safety, and positive biomarker signals. He stated the results support the hypothesis that Stage 2 patients are the optimal trial population and that the data on HTT and NFL lowering provides a strong basis for discussions with regulators about an accelerated path.

Joe, on behalf of Brian Abrahams, asked about the anticipated payer perspective on utilization management for sepiapterin, for both patients switching from existing treatments and those who are treatment-naive.

Answer

CBO Eric Pauwels stated that extensive payer research indicates a clear understanding of sepiapterin's value proposition, including diet liberalization and improved Phe control. He noted that payers see no issue with first-line use in poorly controlled or therapy-failed patients and have indicated a willingness to pay a premium price.

Brian Abrahams of RBC Capital Markets asked about market reaction to the sepiapterin Lancet data, payer confidence in premium pricing, and review timelines for Translarna in the U.S. and Europe.

Answer

CEO Matthew Klein addressed Translarna, stating the European Commission has approximately 67 days for its review, while the U.S. FDA has no set PDUFA date for the resubmission but a review is expected in the coming months. CBO Eric Pauwels added that for sepiapterin, payers recognize the drug's differentiated efficacy and the high unmet need in PKU, which supports a premium pricing strategy.

An analyst on behalf of Brian Abrahams asked about the preclinical study design for the NMRA-215 obesity program, inquiring about the diet model, potential combinations with GLP-1s, comparator arms, and specific endpoints like weight loss quality or maintenance.

Answer

Joshua Pinto, President, detailed the three key goals for the diet-induced obesity (DIO) mouse model study for NMRA-215. He explained the study will assess NMRA-215 as a monotherapy, as an add-on in combination with semaglutide (a GLP-1), and as a maintenance therapy after initial combination treatment to see if it can prevent weight regain after GLP-1 withdrawal. Pinto highlighted the potential for incretin-like weight loss with better tolerability and the goal of providing a long-term, cost-effective option.

Brian Abrahams inquired about the specific differences between the previous vendor and the newly implemented SAFER approach for the KOASTAL studies, and asked about any changes to site auditing or patient caps for KOASTAL-2 and 3.

Answer

Chief Operating and Development Officer Daljit Aurora explained that the SAFER approach, from Mass General Hospital, involves an independent review by clinical psychiatrists to verify MDD diagnosis and patient appropriateness. President Joshua Pinto emphasized that SAFER is an additive measure on top of existing protocols, not a replacement, to further enhance the quality of patient enrollment.

Brian Abrahams from RBC Capital Markets asked about Neumora's confidence in the conduct of the KOASTAL studies and the specific quality control measures being used to mitigate high placebo rates.

Answer

Robert Lenz, Head of Research and Development, detailed a multi-faceted approach to increase the probability of success. This includes conducting three replicate trials, using the MADRS scale to better capture anhedonia, implementing equal placebo allocation to reduce bias, and utilizing central raters, video compliance checks, and a placebo script to manage study execution.

Brian Abrahams asked for qualitative learnings from Daybue's expansion outside Centers of Excellence, focusing on physician receptivity and education. He also inquired about any recent changes in overall Daybue persistence trends.

Answer

Chief Commercial Officer Thomas Garner noted clear receptivity outside COEs but acknowledged that these physicians require more ongoing education due to seeing Rett patients less frequently. Regarding persistence, he reported that the 12-month rate remains above 50% and the 18-month rate is now above 45%, indicating a stable, long-term patient base.

Brian Abrahams from RBC Capital Markets inquired about the potential impact of 'most favored nation' policy, the company's Medicaid exposure, and its capital deployment strategy, particularly regarding M&A.

Answer

President & CCO Charlie Gayer noted that while they monitor policy, they see no immediate impact from MFN and that Medicaid represents a small patient segment (10-15%). CFO Babar Ghias outlined a strategy to become a 'consolidator of rare disease assets,' leveraging the company's strong cash flow to acquire late-stage or commercial products. CEO Jon Stonehouse added that the current capital-constrained environment for many biotechs creates significant opportunities for BioCryst.

Speaking on behalf of Brian Abrahams, Nevin asked if the significant improvement in paid drug percentage and gross-to-net implied a potential dip in the total number of patients on ORLADEYO. He also inquired about the underlying drivers for the growing patient preference for oral prophylaxis therapy.

Answer

Chief Commercial Officer Charlie Gayer firmly denied any dip in patient numbers, citing extremely consistent demand and patient retention. CEO Jon Stonehouse clarified that the quarterly revenue pattern has shifted due to the rapid conversion to paid drug, but underlying growth remains strong. Regarding patient preference, Gayer explained that after four years on the market, patients and physicians are now confident that ORLADEYO delivers both high efficacy and the convenience of an oral therapy, which is driving the preference shift.

Brian Abrahams asked about the tolerability of the pediatric ORLADEYO formulation compared to the adult version, the regulatory requirements for approval, international filing plans, and the drivers behind the Q4 increase in ex-U.S. ORLADEYO revenue.

Answer

Chief R&D Officer Dr. Helen Thackray confirmed the pediatric oral granules were well-tolerated, with a profile similar to adults, and that the regulatory path is a straightforward pediatric extrapolation. CEO Jon Stonehouse added that filings are also planned in Japan. CFO Anthony Doyle explained the Q4 ex-U.S. uptick was driven by distributor shipment timing and a revised agreement in Japan, but noted strong U.S. growth may temper the ex-U.S. percentage of total revenue in 2025.

Brian Abrahams asked for clarification on the implied slight slowdown in ORLADEYO's Q4 sales growth based on guidance, and whether 2025 consensus expectations for slower growth are supported by any internal observations.

Answer

Chief Commercial Officer Charlie Gayer attributed the Q4 guidance to typical seasonality, including a slowdown in achieving paid drug status for new patients late in the year. For 2025, he confirmed no slowdown in demand is being observed and expressed confidence in continued strong performance, while CEO Jon Stonehouse reiterated the company's target of a 20% compound annual growth rate through 2029.

Brian Abrahams of RBC Capital Markets inquired about the enrollment progress of the VOYAGE study, whether it had reached the point for an interim analysis, and the company's current commercial preparation activities, particularly regarding site education.

Answer

CEO Robert Barrow confirmed strong enrollment trends but did not provide specific numbers or confirm if the interim analysis milestone had been reached. Chief Commercial Officer Matt Wiley detailed commercial readiness efforts, including focusing on market access, reimbursement pathways, practice economics, and developing a targeting methodology for high-volume GAD facilities.

Brian Abrahams of RBC Capital Markets asked about the enrollment status of the VOYAGE study relative to the 50% mark for interim analysis and inquired about the company's current commercial preparatory activities, particularly regarding site education.

Answer

CEO Robert Barrow declined to provide specific enrollment numbers but confirmed the interim analysis is planned. CCO Matt Wiley detailed commercial preparations, including focusing on market access, reimbursement, practice economics, and building a targeting methodology for high-volume GAD facilities. He noted they are also developing product positioning and messaging platforms.

Brian Abrahams inquired about initial learnings from the GAD trial enrollment regarding epidemiology and provider engagement, and how that informs the commercial strategy. He also asked about the role of the 50-microgram dose and evolving regulatory perspectives.

Answer

CEO Robert Barrow stated the 50mcg dose is a methodological control to aid blinding and is irrelevant to the primary efficacy analysis. Chief Medical Officer Dr. Dan Karlin added that learnings from the Phase IIb trial and growing societal awareness of anxiety are benefiting enrollment and the commercial outlook.

Brian Abrahams of RBC Capital Markets asked about the expanding use of blood-based biomarkers for Alzheimer's, how Biogen is educating physicians, and what is needed for these tests to replace PET or CSF scans.

Answer

Alisha Alaimo, President & Head of North America, noted that adoption is evolving at an "incredible pace," with testing nearly tripling in the past year. She explained that physicians currently use them for triage but still confirm with PET or CSF. The key to broader adoption is establishing them as the standard for confirmation, which requires education on new guidelines, real-world evidence, and clarity on reimbursement.

Brian Abrahams of RBC Capital Markets asked about the expanding use of blood-based biomarkers for Alzheimer's, including how Biogen is educating physicians and what is needed for these tests to replace PET or CSF scans.

Answer

Alisha Alaimo, President & Head of North America, reported that adoption is evolving at an "incredible pace," with testing nearly tripling in the past year. She noted that while awareness is high, the tests are currently used mainly for triage, with physicians often still confirming positive results with PET or CSF. She stated the key to broader adoption is education on new guidelines, real-world evidence, and clarity on reimbursement.

Brian Abrahams inquired about Biogen's rollout strategy for LEQEMBI in Europe, including the anticipated reimbursement process and market amenability.

Answer

CEO Christopher Viehbacher explained that the European rollout will be a gradual, market-by-market process. He noted that as a first-in-class therapy, LEQEMBI is an incremental addition to healthcare budgets, which requires time for adoption. However, he believes the rigorous EMA approval process, which assessed efficacy, safety, and economic impact, will aid in reimbursement discussions across the continent.

Brian Abrahams asked for more detail on SKYCLARYS launch dynamics, including methods to accelerate U.S. patient identification and the nature of ex-U.S. reimbursement hurdles.

Answer

President and CEO Christopher Viehbacher described the strategy as 'looking for needles in haystacks,' utilizing AI, increased genetic testing, and omnichannel marketing to find patients. He noted that U.S. reimbursement is manageable with patient support, while ex-U.S. reimbursement is a country-by-country process where strong initial uptake is encouraging for negotiations.

Brian Abrahams inquired about the expected timing for LEQEMBI's expanded commercial efforts to show results and asked for details on other potential commercial acceleration strategies.

Answer

CFO Michael McDonnell noted the launch is complex and the collaboration is reviewing strategies, highlighting the future subcutaneous version as a key catalyst. Alisha Alaimo, President of North America, added that new prescribers grew 40% in Q3 and the expanded sales force, in the field since September, is already showing accelerated growth in specific territories due to established physician relationships.

Brian Abrahams of RBC Capital Markets asked about the dynamics underlying Opzelura's performance, including the impact of the pending pediatric indication, ex-U.S. growth cadence, and the long-term opportunity from moderate AD data.

Answer

CEO Bill Meury characterized the pediatric indication as an 'incremental growth driver,' with the core AD and vitiligo businesses being the primary engine. He noted strong ex-U.S. growth in key European markets and Canada. EVP & GM of U.S. Dermatology Matteo Trotta added that the pediatric approval would be a 'great tailwind' for the brand's already strong value proposition.

Brian Abrahams of RBC Capital Markets asked about the clinical development of the BET inhibitor, questioning its foreseen role as a monotherapy in the post-Jakafi setting and the latest thinking on its frontline development path, including what data is needed to advance the combination therapy.

Answer

Pablo Cagnoni, President, Head of R&D, positioned the BET inhibitor as a very good near-term option for patients who progress after Jakafi, which is why the second-line program is being accelerated. For frontline use, he stated that more data is needed on the combination's safety and efficacy, noting that while ASH data was encouraging, more evidence is required before deciding on a first-line study.

Brian Abrahams from RBC Capital Markets asked for updates on the pivotal plans for the CDK2 inhibitor, including the balance between late-line versus maintenance settings, and for more color on the companion diagnostic.

Answer

Steven Stein, an executive, detailed the strategy for the CDK2 inhibitor in ovarian cancer. For the platinum-refractory setting, a single-arm study could support a U.S. approval, while a randomized study would be needed for ex-U.S. markets. He also expressed significant interest in the platinum-sensitive maintenance setting in combination with bevacizumab. For the companion diagnostic, he noted they are focused on Cyclin E1 protein expression via IHC, which represents a larger patient population, and are in discussions with regulators.

Brian Abrahams asked if Sarepta has had additional meetings with new FDA leadership regarding its limb-girdle muscular dystrophy (LGMD) programs and if the data for the 2E program (EMERGENE) is still expected by mid-2025.

Answer

President and CEO Douglas Ingram confirmed positive and consistent interactions with the FDA's OTP, with no change in approach. Head of R&D Dr. Louise Rodino-Klapac added that OTP confirmed the accelerated approval pathway for SRP-9003 (LGMD 2E) and accepted a rolling review, keeping the program on track. She did not comment on the specific timing of the public data disclosure.

Brian Abrahams asked about treatment center capacity being a potential gating factor, inquiring about limitations, necessary infrastructure, and how capacity expansion is factored into guidance.

Answer

CEO Douglas Ingram and CCO Dallan Murray clarified there is no fundamental capacity issue, with over 75 sites available, which is sufficient even for peak years. Murray explained that centers are currently in an adjustment period, managing the unprecedented overnight demand from the entire Duchenne population. He expressed confidence in the centers' ability to ramp up, as they have successfully managed previous complex launches like Zolgensma.

Brian Abrahams from RBC Capital Markets inquired about the level of ZURZUVAE awareness among OB/GYNs and patients, and what metrics Sage uses to track awareness and PPD screening rates.

Answer

COO Chris Benecchi stated that based on tracking studies, ZURZUVAE has approximately 90% aided awareness among physicians, which he described as remarkably high for this stage of the launch. He also noted a key trend: once a physician prescribes ZURZUVAE, they tend to increase their overall screening and diagnosis of PPD, effectively growing the addressable patient population within their practice.

An analyst on behalf of Brian Abrahams asked about the characteristics of OB/GYNs who are not yet prescribing ZURZUVAE and whether the barrier is primarily awareness or another factor.

Answer

COO Chris Benecchi explained that the issue is primarily one of reach and frequency, not a lack of interest. He noted that when an OB/GYN is engaged, the response is highly positive, with over 60% becoming repeat prescribers. CEO Barry Greene added that once an office adopts ZURZUVAE, they see a significant increase in the number of PPD patients treated in that practice, suggesting the key is education and initial trial.

Brian Abrahams questioned what specific outcomes on the primary (SDMT) and secondary endpoints in the DIMENSION study would be required for Sage to advance dalzanemdor, and how the bar for success has evolved post-restructuring.

Answer

Chief Medical Officer Laura Gault explained that the company is looking for a clinically meaningful change on the SDMT primary endpoint. This result would need to be supported by meaningful changes on key secondary endpoints, including a functional scale specific to Huntington's disease.

Brian Abrahams asked about what constitutes a clinically meaningful change on the new SDMT endpoint for dalzanemdor and the mechanistic rationale for its sensitivity in this population.

Answer

CMO Laura Gault noted that literature suggests a 4-point change on the SDMT is clinically meaningful. CSO Mike Quirk explained the mechanistic rationale, stating that the SDMT assesses executive functions tied to brain circuits damaged in Huntington's disease. He also connected it to the company's original thesis involving the endogenous ligand 24S-hydroxycholesterol, which has shown correlation with SDMT performance.

Brian Abrahams asked about the on-the-ground dynamics for the lenacapavir PrEP launch, including physician awareness, site readiness for administration, and provider capacity.

Answer

Chief Commercial Officer Johanna Mercier detailed a highly targeted launch plan, noting that awareness is already high. The initial focus is on the core group of HIV prescribers who also handle PrEP. She confirmed readiness to support both 'buy and bill' and 'white bagging' through specialty pharmacies. A full field team, including nurse educators and reimbursement managers, is mobilized to ensure a smooth customer experience and assist with medical exceptions during the access build-out phase.

Brian Abrahams requested more detail on the early launch of Livdelzi, asking about observed usage patterns, the prescriber base, patient types, and the expected trajectory for the year given the strong initial uptake.

Answer

CCO Johanna Mercier reported that the Livdelzi launch is exceeding expectations with strong week-over-week growth and positive feedback on its differentiated profile. She noted that use is primarily in second-line naive patients, per the label, with good payer access. She anticipates the strong momentum will continue through 2025.

Brian Abrahams of RBC Capital Markets asked about the HIV franchise's exposure to Medicaid and how potential cutbacks under a new administration could impact access, reimbursement, and the company's outlook.

Answer

Johanna Mercier, Chief Commercial Officer, estimated that Medicaid represents the mid-to-high 20% range of the total HIV business. She explained that patients have fallback options like the ADAP program, so access is generally not an issue due to various 'parachutes.' Mercier noted that the company is more closely tracking the growth of the 340B channel and will monitor any potential Medicaid changes, though none have been announced.

Brian Abrahams asked for details on the registrational requirements for GLPG5101 in Mantle Cell Lymphoma (MCL), the potential design of a pivotal trial, and the expected time cushion between the pivotal data readout and the company's cash runway.

Answer

CEO Paulus Stoffels cited the high unmet medical need in MCL as the rationale for its selection. Omotayo Fasan, Clinical Program Head, Oncology, explained that a single-arm trial is a viable pathway for an initial indication, to be followed by a confirmatory randomized controlled study. CFO Thad Huston confirmed that the company's capital allocation ensures the cash runway extends into 2028, aligning with the anticipated timing of the pivotal data.

Asked about the timeline for building the commercial infrastructure for birtamimab and the company's strategy and expectations for regulatory approval in Europe.

Answer

The company expects productive dialogue with global regulators, including in Europe, because the high unmet need for a therapy addressing early mortality is universal. Post-data and pre-launch, the focus will be on market education. After approval, the goal is to ensure seamless access for patients, physicians, and payers. The build-out will be gradual, aiming for a positive first launch experience.

Brian Abrahams of RBC Capital Markets asked about the expected cadence of the commercial infrastructure build-out for birtamimab, both before and after the AFFIRM-AL data, and about the company's regulatory strategy for Europe.

Answer

President and CEO Gene G. Kinney expressed confidence in a productive dialogue with global regulators, including in Europe, due to the universal unmet medical need. COO Brandon Smith outlined a phased approach to the commercial build, focusing first on market education about the mechanism of action, followed by building the brand identity post-approval, without providing specific hiring or spending timelines.

Brian Abrahams of RBC Capital Markets asked about the expected cadence of the commercial infrastructure build-out both before and after the AFFIRM-AL data readout, as well as the company's regulatory strategy and plans for Europe.

Answer

President and CEO Gene G. Kinney expressed confidence in productive dialogues with global regulators, including in Europe, due to the universal unmet medical need. COO Brandon Smith outlined a two-phase commercial build-out: first, market education on the mechanism of action leading up to the launch, and second, building the brand identity and ensuring seamless patient access post-approval.

Brian Abrahams asked about the expected cadence of the commercial infrastructure build-out for birtamimab, both before and after the AFFIRM-AL data readout, and inquired about the company's regulatory path and plan for Europe.

Answer

CEO Gene G. Kinney stated that the unmet medical need is global, so they expect productive dialogues with regulatory authorities worldwide, including in Europe. Chief Operating Officer Brandon Smith explained the commercial build-out will focus on ensuring a seamless experience for patients and physicians. The plan involves market education pre-launch, followed by brand identity development post-approval to get patients access.

Inquired about the Phase II TSC study data that builds confidence for the Phase III trial, specifically regarding subgroup analyses, seizure reduction consistency, and the number of patients who have entered the Phase III open-label extension.

Answer

Over 90% of patients completing the Phase III study are rolling into the open-label extension, with over 100 patients already transitioned. This high rollover and a low discontinuation rate (<7%) provide confidence. Phase II subgroup data showed stronger responses in patients with focal seizures and those on everolimus, which are well-represented populations in the Phase III trial.

Brian Abrahams from RBC Capital Markets asked about generalizable learnings from the COMP360 data, the level of confidence in the GRX-917 program, and the types of assets being targeted for business development.

Answer

CSO Dr. Srini Rao noted that a key learning from COMP360 is the importance of redosing for long-term remission and expressed high confidence in GRX-917 due to etifoxine's extensive safety history. CEO Florian Brand stated that business development is modality-agnostic and focused on the company's three strategic pillars: rapid-acting interventions, digital support, and precision health. CFO Greg Weaver confirmed there is budget for such activities.

Brian Abrahams asked about the company's confidence in IGM-2323 achieving competitive response rates, rapidity, and durability within the planned dosing range. He also questioned if the low CRS rate is attributed more to complement-driven killing or patient characteristics like prior CAR-T, and inquired about the scope of the IGM-8444 data expected in the second half of the year.

Answer

Chief Medical Officer Daniel Chen expressed high confidence in IGM-2323's potential best-in-class safety profile, citing a very low CRS rate compared to competitors, which should appeal to community oncologists. He noted that while rapid responses are being seen, durability is the primary goal. Dr. Chen stated that both the hypothesis of a shift to complement-dependent killing and the identification of a sensitive patient subset are in play. For IGM-8444, he anticipates presenting data from the single-agent dose escalation in the second half of 2021 at a scientific meeting.

Brian Abrahams inquired about the rationale for shortening the Phase 3 dermatomyositis study, asking about the potential impact on study power, the safety database, and any required regulatory approvals. He also asked for more details on the limitations observed with the CRB-4001 compound and the characteristics and timeline for its next-generation replacements.

Answer

Chief Medical Officer and Head of Research, Barbara White, explained that the dermatomyositis study duration was shortened from 52 to 28 weeks to align with competitor trial timelines, which range from 16 to 24 weeks. She noted that blinded data indicates approximately 85% of patient improvement occurs by week 28, suggesting a minimal loss of efficacy signal. Regarding CRB-4001, Dr. White stated the compound was difficult to formulate and, more critically, expanded toxicology studies revealed accumulation in primate brains, leading to its discontinuation. The next-generation compounds reportedly have more favorable properties and do not show these early safety concerns.

Brian Abrahams of RBC Capital Markets inquired about the rationale for shortening the dermatomyositis study to 28 weeks, asking about its impact on study power, expected efficacy timeline, and any required regulatory amendments. He also asked for details on the limitations observed with the CRB-4001 compound and the characteristics of the next-generation CB1 inverse agonists.

Answer

Barbara White, Chief Medical Officer and Head of Research, explained that the dermatomyositis study duration was shortened to align with competitor trials, which range from 16 to 24 weeks. She noted that blinded data suggests approximately 85% of patient improvement occurs by week 28, minimizing the loss of signal. Regarding CRB-4001, Dr. White confirmed issues with both insolubility and concerning levels found in primate brains, which prompted its discontinuation. She stated the new compounds have more favorable physical-chemical properties and do not show the same early signals of brain accumulation.

Brian Abrahams of RBC Capital Markets inquired about the regulatory view on the ACR CRISS score, particularly its patient-reported outcome components, the anticipated timeline between top-line data and NDA filing for systemic sclerosis, and the impact of COVID-19 on data collection and statistical analysis.

Answer

Chief Medical Officer Dr. Barbara White explained that Key Opinion Leaders (KOLs) increasingly favor the holistic ACR CRISS score over mRSS alone and that the FDA will review the totality of the data. She noted that supportive Phase 1 studies are underway and a pre-NDA meeting is anticipated by year-end. Dr. White also confirmed that despite some missed assessments due to COVID-19, the RESOLVE-1 study remains over 90% powered, and the statistical plan aligns with FDA guidance.

Brian Abrahams from RBC Capital Markets requested an update on the initial HB-201 cohorts, details on dosing schedules for the planned backfill cohorts, and any contingency plans for the HB-101 trial enrollment amid potential COVID-19 disruptions.

Answer

CMO Igor Matushansky reported that the HB-201 trial escalated smoothly from dose level one to two with no safety concerns. He explained that backfill cohorts will test more aggressive dosing schedules, such as weekly or bi-weekly, to potentially accelerate immunogenicity. Regarding HB-101, Igor Matushansky noted that samples for 2020 milestones are largely collected, and for future enrollment, protocols allow for local blood draws and drug shelf-life has been extended to manage delays.