Joseph Schwartz

Joseph Schwartz asked about Wave Life Sciences' AATD regulatory strategy, specifically how it aligns with or differs from competitors' recently established biomarker-based accelerated approval frameworks with the FDA.

Answer

President and CEO Paul B. Bolno explained that Wave's strategy is well-aligned with the biomarker approach seen in existing AATD therapies and recent peer company feedback. He highlighted that WVE-006's ability to produce only M-AAT protein, without bystander edits, positions it favorably for discussions on active protein requirements. Wave anticipates receiving regulatory feedback on a potential accelerated approval pathway by mid-2026, noting encouraging comments from the FDA on using the Plausible Mechanism Framework for AATD.

Joseph Schwartz of Leerink Partners asked about the potential M-protein levels achievable with WVE-006 based on enzyme kinetics and the dose regimens. He also asked how Wave has optimized WVE-006 to be competitive and 'best-in-class' compared to other RNA editing therapies in development.

Answer

President & CEO Paul Bolno stated that preclinical models indicate they have not yet hit peak saturation of the ADAR enzyme, suggesting ample room for increased protein production with multi-dosing and higher doses. He defined 'best-in-class' for WVE-006 by its use of GalNAc for efficient, subcutaneous delivery without LMPs, combined with proprietary chemistry like PN and N3-uridine modifications that optimize the AIMER editing platform for high hepatocyte uptake and intracellular stability.

Joseph Schwartz from Leerink Partners sought insights into the anticipated effects of WVE-006 after multiple doses, based on existing data, and asked about the WVE-007 obesity trial, specifically regarding treatment duration before the data readout and whether the key comparison metric should be total weight loss or body composition changes.

Answer

President and CEO Paul Bolno explained that based on platform chemistry, multiple doses of WVE-006 are expected to increase protein production and durability compared to a single dose. For WVE-007, he emphasized that while weight loss will be tracked, the key differentiator from GLP-1s will be demonstrating healthy weight loss through body composition changes, specifically fat loss without muscle reduction, which the initial data will aim to establish.

Joseph Schwartz asked how clinicians currently risk stratify patients for ELEVIDYS, considering factors like liver enzymes, age, weight, steroid exposure, and concomitant medications, and if Sarepta's view of ideal candidates has evolved.

Answer

President and Chief Executive Officer Doug Ingram and Executive VP and Chief Commercial Officer Patrick Moss stated their view of ideal candidates hasn't changed, emphasizing the broad ambulatory population. They noted some physicians lean younger without full information and that about 25% of sites are proactively using sirolimus, which may impact patient amenability.

Joseph Schwartz asked how clinicians are currently risk stratifying patients for ELEVIDYS, considering factors like liver enzymes, age, weight, steroid exposure, and concomitant medications, and whether Sarepta's view of ideal candidates has evolved based on accumulating experience.

Answer

Doug Ingram, President and Chief Executive Officer, clarified that Sarepta's view of ideal candidates has not changed, emphasizing the vast addressable ambulatory population and the compelling need to dose as early as possible based on muscle MRI data. Patrick Moss, Executive VP and Chief Commercial Officer, noted that each patient's situation is unique, influencing physician and family decisions. Doug also highlighted that approximately 25% of sites are proactively using sirolimus, either prophylactically or reactively, which may influence physician perceptions of patient amenability.

Joseph Schwartz asked about the impact of recent meetings with patient advocacy groups like PPMD and the company's plans to emphasize the positive risk-benefit of ELEVIDYS at upcoming conferences.

Answer

President and CEO Douglas Ingram (speaking in place of Dallan Murray) described the patient webinar as very meaningful but just one part of a broader educational effort. He stressed the need to communicate the complete evidence package—both the safety profile and the impressive efficacy data, like the muscle MRI results—to the entire patient and physician community to underscore the therapy's value and the urgency of treatment.

Joseph Schwartz of Leerink Partners asked for perspective on the current stage of the ELEVIDYS launch and any potential constraints to growth in 2025, noting that guidance implies more moderate growth.

Answer

CEO Douglas Ingram disagreed with the characterization of modest growth, highlighting the projected 160% year-over-year growth for ELEVIDYS in 2025. He described the launch as being in a robust growth phase, explaining that the quarterly cadence is dictated by a predictable, roughly four-month process for each patient from start form to infusion, which the company had anticipated and is managing effectively.

Joseph Schwartz of Leerink Partners asked for details on the next planned MRI study for ELEVIDYS, including how it will differ from data presented at the World Muscle Society, whether it will use gadolinium, and if it will evaluate global longitudinal strain.

Answer

Dr. Louise Rodino-Klapac, Head of R&D, explained that the long-term follow-up from the EMBARK study will track patients over time and compare them to natural history. The study will continue to use MRI/MRS and T2 imaging to assess inflammation and edema, and she confirmed that strain analysis is a component of the MRI results.

Representing Joseph Schwartz, Will asked about the perceived disconnect with some in the Duchenne community regarding the company's mission and what Sarepta is doing to address it, especially with potential competition emerging.

Answer

CEO Douglas Ingram asserted that the company has been wholly committed to the Duchenne community for over seven years, successfully launching four transformative therapies. He believes the vast majority of the informed patient and physician communities understand and support Sarepta's efforts, citing the high demand for ELEVIDYS as evidence. He emphasized that the team's track record in serving the community is second to none.

Joseph Schwartz inquired about the encouraging VOC data, asking for additional insight into which patients experienced VOCs and when they occurred. He also asked how well the 20-mg cohort represents the broader sickle cell patient population for a Phase III trial and in major markets, considering haplotype dependency.

Answer

Iain Fraser, SVP of Early Development, explained that VOCs were spread throughout the treatment period, noting that patients had not reached steady state HbF levels and those with lower HbF increases tended to have more VOCs. Regarding population representation, Mr. Fraser clarified that the 20-mg cohort, with more patients from Nigeria, likely represents a middle slice of heterogeneity, more akin to the U.S. population, without overrepresentation of low or high responders.

Joseph Schwartz from Leerink Partners inquired about the specifics of vaso-occlusive crises (VOCs) observed, including their timing and patient distribution, and how well the 20-milligram cohort's haplotype representation aligns with the broader sickle cell disease patient population for future trials in the U.S. and major markets.

Answer

Alex C. Sapir (President and CEO) and Iain Fraser (SVP of Early Development) explained that VOCs were spread throughout the short 12-week treatment period, with more occurring in patients with lower HbF increases. Fraser also detailed the cohort's epidemiological representation, noting the 20-milligram cohort's heterogeneity is more representative of the U.S. population compared to the 12-milligram cohort, which had a higher prevalence of the CAR haplotype.

Joseph Schwartz of Stifel asked for details on the upcoming data from the 12-milligram PIONEER cohort, including the follow-up duration for the 16 patients and whether data on hemolysis markers would be shared. He also inquired about the specifics of the >90% patient adherence rate and how it is tracked.

Answer

Iain Fraser, Head of Development, confirmed that hematological parameters indicating hemolysis, like bilirubin, will be reported. He stated that full 3-month treatment data for all 16 patients will be available, with follow-up data for a subset. Executive Alexander Sapir explained that the high adherence rate is captured using an AI tool called AiCure, which provides more timely and accurate data than traditional pill counts by having patients record themselves taking the medication.

Joseph Schwartz from Leerink Partners asked for insights into the types of patients enrolling in the PIONEER trial, particularly after Oxbryta's withdrawal, and questioned the specific hurdles the DSMB requires pociredir to clear before advancing to the 20mg cohort.

Answer

CEO Alexander Sapir stated that the 10 enrolled patients are from the U.S. and South Africa and tend to be on the more severe side, with high adherence rates above 90%. Executive Iain Fraser added that the withdrawal of Oxbryta has created a new pool of eligible patients. Regarding the DSMB, Fraser clarified its primary focus is on reviewing safety and tolerability data from the 12mg cohort to approve advancement to the 20mg dose.

Joseph Schwartz asked for details on the extended timeline for pociredir's Cohort 3 enrollment and what is being done to accelerate it. He also asked about the expected output from the work defining the minimally clinically relevant difference for the RSA endpoint.

Answer

CEO Alexander Sapir explained the pociredir delay is due to the long lead times required to activate new academic sites, as previous sites did not have patients matching the new, stricter inclusion criteria. For losmapimod, executive Iain Fraser clarified the goal is to define a 'meaningful score difference' (MSD) for individual patients, and the trial results will likely be analyzed based on the proportion of patients who exceed that MSD.

Joseph Schwartz asked about BioMarin's initiatives to identify undiagnosed Fabry and Pompe patients, specifically if they had seen results from Amicus's pilot programs and if they aligned with BioMarin's rollout expectations.

Answer

Cristin Hubbard, Chief Commercial Officer, confirmed Amicus has been running pilot programs with different models. BioMarin is currently diving into these programs to understand them, while operating as two independent businesses pre-close. She highlighted that the real opportunities for Galafold and Pompe are increasing diagnosis rates and, for Pompe, driving switches, fitting well within BioMarin's enzyme therapy business unit model.

Joseph Schwartz asked about BioMarin's initiatives to identify undiagnosed Fabry and Pompe patients, specifically if BioMarin had reviewed results from Amicus's pilot programs and if they align with BioMarin's rollout expectations.

Answer

Cristin Hubbard, Chief Commercial Officer, confirmed that Amicus has been running pilot programs for patient identification using different models. She stated that BioMarin is currently diving into these programs to understand what makes sense for integration, emphasizing the significant opportunity to increase diagnosis rates for both Galafold and Pompe.

An analyst on behalf of Joseph Schwartz of Leerink Partners asked about the specific strategies being implemented to drive further patient adoption of VOXZOGO, particularly in the U.S. market.

Answer

Cristin Hubbard, Executive Vice President and Chief Commercial Officer, detailed a strategy focused on driving adoption across all age groups, especially the newly-labeled 0-4 population. Key initiatives include increasing awareness to expand the prescriber base, particularly among pediatric endocrinologists, and investing in additional field personnel. She noted the new business unit structure enhances focused execution on these strategies.

Joseph Schwartz questioned the practical business benefit of BMN 333, given its projected 2030 launch seems close to the base CNP patent expiry. He also asked why the next-generation Palynziq, BMN 390, would have a similarly long development timeline as its predecessor.

Answer

President and CEO Alexander Hardy clarified that the company's IP for Voxzogo extends to the mid-2030s, providing ample time to convert the market to a more efficacious BMN 333. EVP, Worldwide R&D Greg Freiberg added that the development timeline for BMN 390 represents an 'upper error bar' and the company will actively look for opportunities to accelerate it.

Heidi Jacobson, on behalf of Joseph Schwartz, asked how the TransCon CNP launch, including launch investment and early revenue contribution, factors into Ascendis Pharma's EUR 500 million operating cash flow target for 2026.

Answer

Jan Møller Mikkelsen, President and Chief Executive Officer, clarified that the TransCon CNP launch is not incorporated into the current EUR 500 million operating cash flow target. He stated that Ascendis Pharma will provide updated guidance once initial uptake is observed, particularly with the utilization of U.S. approval for international markets.

Joseph Schwartz asked whether the administrative capacity of physician offices to handle payer negotiations could become a bottleneck for YORVIPATH growth. He also inquired about the clinical benefit Ascendis hopes to demonstrate in the COACH combination trial.

Answer

EVP and President, Ascendis U.S. Jay Wu asserted that their patient support hub is a 'well-oiled machine' with extensive experience from the SKYTROFA launch, supported by a strong field reimbursement team, ensuring office burden will not be a bottleneck. On the COACH trial, CEO Jan Mikkelsen expressed high confidence that the combination of TransCon CNP and growth hormone could set a new standard for treatment, improving not only height but also other medical complications of achondroplasia.

Joseph Schwartz asked about endocrinologist resources for payer interactions and the clinical benefit of TransCon CNP/hGH combination.

Answer

CEO Jan Mikkelsen and EVP Jay Wu discussed hub experience and field reimbursement support. Jan Mikkelsen shared insights on achondroplasia research.

Joseph Schwartz inquired how the YORVIPATH U.S. launch might compare to Europe and if the calcium monitoring requirement could be a deterrent. He also asked for the reason behind the adjustment to SKYTROFA's 2024 revenue guidance.

Answer

Jan Mikkelsen, President and CEO, stated he expects a much faster and larger uptake for YORVIPATH in the U.S. compared to Europe and does not see the monitoring as a deterrent. Scott Smith, EVP and CFO, explained the SKYTROFA guidance adjustment was due to slightly lower-than-expected Q3 volume and a cautious outlook for Q4.

Joseph Schwartz asked about the competitive landscape for the Angelman program (GTX-102), specifically how patients, parents, and caregivers might make treatment decisions given multiple ASOs in development, and whether decisions would be purely data-driven or influenced by factors like dosing schedules, specific endpoints, or safety profiles.

Answer

Erik Harris, Chief Commercial Officer, emphasized that Ultragenyx's ASO is considered the most potent with the best long-term data. He stated that parents primarily focus on their children's overall well-being rather than specific primary or secondary endpoints. He noted that dosing schedules for leading programs are converging to Q3, and ultimately, potency and safety will be the most critical factors. He also highlighted the importance of Ultragenyx's patient support programs.

An analyst on behalf of Joseph Schwartz asked about the evolving competitive landscape for Angelman syndrome, given multiple ASOs in development, and how Ultragenyx plans to differentiate its treatment.

Answer

CEO Emil Kakkis acknowledged the competitive environment, stating that the most potent and effective drug will likely lead the market. He positioned GTX-102 as the most potent ASO based on existing data and highlighted the company's extensive long-term data from nearly 70 patients in the expanded Phase II study as a key differentiator. He affirmed Ultragenyx's goal to be the long-term leader in Angelman syndrome treatment.

Will Soghikian, on behalf of Joseph Schwartz, asked about the characteristics of patients who experienced fractures during the Phase II OI study and about the company's launch strategy for the UX111 gene therapy.

Answer

CEO Emil Kakkis noted that fractures in the Phase II study were not limited to severe OI types, as some Type I patients also fractured. Regarding UX111, CEO Emil Kakkis and CCO Erik Harris stated they will leverage learnings from other gene therapy launches like Zolgensma, focusing on payer engagement and the disease's urgency. The existing commercial team for Dojolvi is already engaged with the target treatment centers.

Joseph Schwartz asked for details on the setrusumab program, including how the effect size is calculated in the Orbit study, the separation needed for statistical significance at interims, and the powering assumptions for the head-to-head Cosmic study against bisphosphonates.

Answer

CEO Emil Kakkis stated the Orbit study was powered assuming a 50% fracture rate reduction, but noted the Phase 2 data showed a 67% reduction on top of prior bisphosphonate use. He explained this gives them confidence in the design. For the Cosmic study, a similar 50% reduction assumption was used, noting that the higher fracture rate in younger children allows for a smaller study size.

Joseph Schwartz asked about the perceived 'frictionless' nature of the Brensupri launch to date, based on the amount of documentation physicians have had to provide to payers, and any early insights into this dynamic.

Answer

Will Lewis, Chairman and CEO, indicated that the launch has been 'so far so good,' with a mix of documentation requirements. He noted that even when extensive documentation (CT scans, exacerbation records) was required, physicians found it manageable. He reiterated the company's efforts to simplify the process through modest discounting and emphasized Brensupri's strong efficacy and safety profile as factors aiding market access.

Joseph Schwartz asked about the 'frictionless' nature of BRINSUPRI's launch to date, specifically concerning the amount of documentation physicians have had to provide to payers.

Answer

Will Lewis, Chairman and CEO of Insmed, described the situation as 'so far so good,' noting a mix of requirements, with some cases needing CT scans and exacerbation documentation. He emphasized that physicians found these requirements manageable and that BRINSUPRI's strong efficacy and safety profile should aid market access.

Joseph Schwartz requested more detail on the 'positive signs' observed in the blinded data from the Birch trial in CRS and asked about potential factors that could delay the data readout.

Answer

CEO William Lewis clarified that while they do not anticipate any specific delays, the timing of the readout depends on ensuring the data is cleaned to submission-level quality. Regarding the blinded data, he stressed that it does not confirm efficacy but that the overall pattern of results is consistent with what one would expect to see if the drug were working. He cautioned against over-interpreting this observation.

Joseph Schwartz asked for context on the New England Journal of Medicine editorial that questioned Brensocatib's benefit magnitude and also inquired why exacerbation severity isn't a more common discussion point.

Answer

CEO William Lewis positioned the dual Phase II and Phase III publications in the NEJM as an extremely rare and positive event. He contextualized the editorial's mention of macrolides as a perspective from rationed healthcare systems, a view not encountered in Insmed's target markets and one that carries significant clinical risks like antibiotic resistance.

Joseph Schwartz asked for clarification on whether a CT scan is required for a Brensocatib prescription and questioned how the company addresses the NEJM editorial's points on the magnitude of benefit and macrolide use.

Answer

CEO William Lewis confirmed a high-resolution CT scan is required for a definitive bronchiectasis diagnosis. Regarding the editorial, he contextualized it as a perspective from rationed healthcare systems, stating macrolide monotherapy is not a standard of care in target markets and is not encountered in payer discussions. CMO Martina Flammer highlighted that over 60% of views on the NEJM article came from the public, indicating strong patient interest.

Joseph Schwartz asked about the key controllable factors for a strong brensocatib launch beyond clinical data and sales force, and inquired about the risk of FDA staffing shortages.

Answer

CEO Will Lewis identified market access as the most critical controllable element, emphasizing a strategy for a 'frictionless launch' through verbal physician attestation and minor contracting. CFO Sara Bonstein added that the field access team has been augmented. Regarding the FDA, Lewis expressed confidence, noting that review staff are funded by PDUFA fees and should be insulated from general government staffing issues.

Joseph Schwartz of Guggenheim Securities inquired about the effectiveness of the expanded sales force for the brensocatib launch, the impact of disease state awareness activities, and the company's perspective on analyst sales estimates and pricing strategies for the 10mg versus 25mg doses.

Answer

CEO Will Lewis expressed high confidence in the newly expanded sales force, highlighting their experience and ability to call on every U.S. pulmonologist, comparing the pre-launch strategy to the successful ARIKAYCE launch. CFO Sara Bonstein pointed to successful respiratory launches like DUPIXENT as analogs for the potential revenue ramp, while reiterating the $5 billion-plus peak sales opportunity for brensocatib in bronchiectasis. Will Lewis noted that no final decisions on pricing have been made.

Joseph Schwartz inquired about the effectiveness of the expanded sales force for the brensocatib launch, the impact of disease state awareness activities, and the potential pricing strategy for brensocatib's different doses.

Answer

CEO Will Lewis highlighted the high quality and experience of the 184-rep sales force, noting they can call on every U.S. pulmonologist and are replicating the successful ARIKAYCE launch model. CFO Sara Bonstein pointed to respiratory launch analogs like DUPIXENT, which achieved high double-digit millions in revenue in their first two quarters, underscoring brensocatib's $5 billion-plus peak sales potential. Lewis stated that no final decisions on pricing have been made.

Joseph Schwartz of Leerink Partners inquired about the potential impact of Neurocrine's Crinesity launch on the enrollment pace for Crinetics' Phase III studies in congenital adrenal hyperplasia (CAH) and whether it selects for specific patient types.

Answer

Founder and CEO R. Scott Struthers responded that he views the Crinesity launch as a positive development that raises disease awareness and should actually benefit enrollment, noting that the bulk of Crinetics' trial enrollment is outside the U.S. Chief Medical & Development Officer Dana Pizzuti added that Crinetics is targeting a broader CAH patient population, aiming to address the full spectrum of the disease, which is a key distinction.

Joseph Schwartz asked about strategies to motivate acromegaly patients in community settings and about the expected timeline for Phase III enrollment for atumelnant in CAH, given the competitive landscape.

Answer

CEO R. Struthers addressed the CAH trial, stating he does not expect the newly approved competitor drug to significantly impact global enrollment, anticipating better recruitment than prior trials. CCO Isabel Kalofonos explained the patient activation strategy involves disease awareness campaigns highlighting unmet needs, educational events, media outreach, and a comprehensive patient support hub.

Joseph Schwartz inquired about the selection criteria for the TSH antagonist development candidate, how the development hurdle compares to other programs, and the biological rationale for its potential efficacy relative to IGF-1 antagonists.

Answer

CEO R. Struthers explained that for large indications like Graves' disease, the company applies extra scrutiny regarding scalability and physicochemical properties. Biologically, he noted that since TSH receptor activation is the root cause of Graves' and also cross-activates the IGF-1 receptor, blocking the TSH receptor directly should be at least as efficacious as targeting the downstream IGF pathway.

Jenny Gonzalez-Armenta, on for Joseph Schwartz at Leerink Partners, asked if the FDA indicated any potential delays for the vutiquinone review due to staffing issues. She also inquired if the Skyclaris launch is a good template for a potential vutiquinone launch and if there's potential for combination use with Skyclaris.

Answer

CEO Dr. Matthew Klein stated there was no discussion of delays in the vutiquinone review. He and CBO Eric Pauwels differentiated the potential launch from Skyclaris, highlighting PTC's experienced pediatric neurology team, the different patient dynamics (especially for pediatrics), and the lack of a monitoring requirement for vutiquinone. Dr. Klein added that the FA community generally believes a cocktail of therapies will be optimal, so combination use with Skyclaris is certainly something that could be explored by physicians.

An analyst on behalf of Joseph Schwartz asked about PTC's early-stage pipeline beyond PTC518 and whether the company was actively pursuing business development opportunities.

Answer

CEO Dr. Matthew Klein confirmed PTC has earlier-stage programs leveraging its splicing and ferroptosis platforms, including a DHODH inhibitor and an NLRP3 inhibitor. He also affirmed that the company is actively evaluating various business development opportunities, from early-stage assets to commercial licenses, to complement its portfolio.

Joseph Schwartz noted that the placebo arm in the initial PIVOT-HD data appeared to decline faster than natural history and asked if this affects the strategy for showing clinical associations, and if the company would switch to natural history controls after one year.

Answer

CEO Dr. Matthew Klein defended the placebo group as the most appropriate 'gold standard' benchmark for the trial, highlighting the heterogeneity of Huntington's disease. He emphasized that having 12 months of placebo-controlled data is a significant strength and that while they could use natural history to augment longer-term data, the concurrent placebo control is crucial.

Joseph Schwartz of Leerink Partners asked how patient perceptions of SKYCLARYS might affect the market reception for vatiquinone and about the mechanistic goals of targeting ferroptosis in ALS with utreloxastat.

Answer

CEO Matthew Klein positioned vatiquinone as acting upstream of SKYCLARYS and stressed the significant unmet need for a therapy in pediatric and adolescent FA patients, also noting potential for combination use. For utreloxastat, he highlighted the strong preclinical data supporting the rationale of targeting ferroptosis, a key pathological element in the complex and aggressive nature of ALS.

Joseph Schwartz of Leerink Partners inquired about the status of the Pombility/OpFolda manufacturing facility in Ireland, including its operational timeline, production capacity, and the amount of drug stockpiled in the U.S. to mitigate potential tariff impacts.

Answer

President and CEO Bradley Campbell confirmed that all necessary Pombility/OpFolda material for 2025 U.S. commercial and clinical use has already been imported, negating any material P&L impact from tariffs this year. He stated the Ireland facility will supply Europe in late 2025 and the U.S. in 2026, with sufficient capacity for forecasted global demand. He also highlighted a diverse supply strategy, including a new U.S. drug product partnership with Sharp.

Joseph Schwartz of Leerink Partners requested details on the diligence process for the DMX-200 licensing deal, the strategic rationale for entering rare renal disease, and the asset's differentiation from competitors.

Answer

President and CEO Bradley Campbell stated the deal aligns with their strategy for late-stage, de-risked assets with synergies to their rare disease capabilities. Confidence was built on strong Phase II data, high unmet need, and recent FDA alignment on proteinuria as a primary endpoint. Chief Development Officer Dr. Jeff Castelli added that DMX-200 is differentiated by its unique mechanism targeting monocyte-driven inflammation, unlike competitors focused on hemodynamics.

Joseph Schwartz inquired about the cadence of new patient additions for Pombiliti, noting a recent slowdown, and asked about the outlook for Q4 and 2025 given current trends and street expectations.

Answer

President and CEO Bradley Campbell explained that Q2 had benefited from a new country launch and clinical trial conversions, making Q3 a more normalized quarter. He noted that the gap between prescriptions and treated patients is closing as insurance processes improve. He stated that the 2025 outlook depends on the year-end patient count and the timing of new country launches, which are contingent on reimbursement outcomes.

An analyst on behalf of Joseph Schwartz asked if the number of new Pombiliti and Opfolda patients added in Q2 was in line with expectations and about the expected inflection point in the second half of the year.

Answer

President and CEO Bradley Campbell confirmed that the rate of new patient additions is progressing as expected and is higher than last year. He anticipates momentum will build through the second half as new countries launch, but noted the revenue impact will be more significant in 2025. The current focus is maximizing the total number of patients on therapy by year-end to establish a strong revenue run-rate for next year.

Joseph Schwartz asked about the rationale for extending the PROSERA study enrollment and pushing the data readout to February 2026, and how the more global patient population in PROSERA might influence results compared to the TORREY trial.

Answer

CEO Faheem Hasnain explained the extension was to honor commitments to patients and physicians amid high demand, ensuring goodwill for future studies like PH-ILD. He, along with CMO Dr. Richard Aranda, noted that the global patient base includes 'purer' PAH patients with fewer comorbidities, who have historically shown a larger treatment effect. CFO & COO Bryan Giraudo added that the previous TORREY study was more US-focused due to the COVID-19 pandemic.

Joseph Schwartz questioned Aurinia's potential exposure to new U.S. federal policies, including tariffs on its Swiss-made API, transfer pricing for a Canadian company, and Most Favored Nation (MSN) drug pricing legislation. He also asked for details on IP domicile, product stockpiling in the U.S., and the government payor mix for LUPKYNIS.

Answer

President and CEO Peter Greenleaf stated that any tariff impact would be minimal for several years, as the company has multiple years of API stockpiled on U.S. soil and the API represents a small portion of COGS. He noted that changing transfer pricing rules would likely require an act of Congress, not just an executive order. Greenleaf confirmed the company is watching all policy developments closely, noting that Aurinia's payer mix is split evenly between private and government payers.

A representative for Joseph Schwartz questioned the decision to stop reporting patient-level metrics (PSF) and asked how to assess the launch trajectory without them. He also asked if AUR200's higher potency could lead to a more favorable dosing schedule.

Answer

President and CEO Peter Greenleaf explained that after five years on the market, the company believes its historical financial results provide sufficient insight, making patient-level metrics unnecessary. Chief Medical Officer Dr. Greg Keenan confirmed that preclinical data for AUR200 suggests high potency, which could potentially allow for lower or less frequent dosing, but that this will be confirmed in human studies.

Jenny Leigh Gonzalez-Armenta, on behalf of Joseph Schwartz, asked about uniQure's relationship with Huntington's disease patient advocacy groups, their interactions with the FDA, and the general sentiment of the HD community towards expedited development.

Answer

CMO Dr. Walid Abi-Saab emphasized the long and critical history of working with patient advocacy groups like CHDI, calling them balanced, scientifically driven, and essential for developing the natural history data used in trials. He affirmed that uniQure's progress would not have been possible without their collaboration, which is well-respected by the FDA.

Joseph Schwartz noted the gap between the 3,600+ patient start forms (PSFs) since launch and the estimated 2,000 patients on therapy, asking for context on the PSF-to-therapy conversion rate and discontinuation rates.

Answer

CCO Peter Heerma explained that while the fulfillment rate has improved significantly since the early launch, a 100% conversion is never expected, citing an 85-90% pickup rate even for retail nephrology products. CEO Eric Dube added that patient compliance and persistence rates are very high once on therapy, indicating the main focus is on improving the initial conversion from a PSF to a paid prescription.

Joseph Schwartz inquired about Selecta's strategy to prioritize liver diseases for its IL-2 program, asking about the role of known antigens in diseases like PBC and the identification of other potential targets. He also asked a follow-up question regarding the resources Sobi is allocating for the commercial launch of SEL-212 and what new data from the Phase III trials should be anticipated.

Answer

CEO Carsten Brunn and CMO Peter Traber explained that liver diseases are a prime target due to their T-cell-mediated nature, the presence of known autoantigens, and preclinical data showing ImmTOR's accumulation in the liver. They view this as a strategic entry point to broader autoimmune applications. Regarding Sobi, Carsten Brunn stated that while he cannot comment on Sobi's specific resource allocation, Sobi is highly committed to the program and is targeting a BLA filing in the first half of 2024, with full data to be presented at a future scientific conference.

Joseph Schwartz asked about the strategic rationale for prioritizing liver diseases for the ImmTOR IL program, specifically questioning the role of antigen awareness in PBC. He also inquired about the resources Sobi will deploy for the SEL-212 launch and what new data from the DISSOLVE trials can be expected.

Answer

CEO Carsten Brunn and CMO Peter Traber explained that the focus on liver diseases is driven by their T-cell mediated nature and promising preclinical data. Traber noted that success in liver diseases could pave the way for broader autoimmune applications. Regarding Sobi, Brunn confirmed their strong commitment and a planned BLA filing in H1 2024, with full data from the DISSOLVE trials to be presented at a future scientific conference.

Joseph Schwartz asked about the strategy to develop the ImmTOR IL-2 candidate in liver diseases, the role of antigen awareness in PBC, and whether other antigens have been identified. He also inquired about the resources Sobi will commit to the SEL-212 launch and what new data to expect from the Phase III DISSOLVE studies.

Answer

CEO Carsten Brunn and CMO Peter Traber explained that liver diseases are a primary target due to being T-cell mediated and the presence of known autoantigens in conditions like PBC. Dr. Traber noted the approach could extend to other autoimmune diseases. Regarding Sobi, Mr. Brunn stated that while he couldn't comment on specific resources, Sobi is highly committed, with a BLA filing planned for H1 2024 and more data to be presented at a future scientific conference.

Joseph Schwartz of SVB Securities inquired about Selecta's strategy to develop its ImmTOR IL-2 candidate in liver diseases, the role of specific antigens in this approach, and the resources Sobi is committing to the SEL-212 launch.

Answer

CEO Carsten Brunn and CMO Peter Traber explained that liver diseases are a prime target due to their T-cell-mediated nature and the fact that ImmTOR accumulates in the liver. Traber noted that preclinical data shows additive effects and that findings could extend to other autoimmune diseases. Regarding SEL-212, Brunn confirmed Sobi is highly committed, with a BLA filing planned for H1 2024 and full data to be presented at a future scientific conference.

Joseph Schwartz of SVB Securities inquired about the expected timing and content of the initial data from the SEL-302 trial for MMA, and asked for the company's perspective on a recent IL-2 trial failure by another company, questioning why Selecta's ImmTOR-IL program is better positioned for success.

Answer

President and CEO Carsten Brunn confirmed that interim data for SEL-302, including safety, biomarkers, and Nab response from the first patient with ImmTOR, is expected toward the end of the year. He differentiated the ImmTOR-IL program by highlighting its first-in-class approach of inducing and expanding Treg-selective cells, and noted the strategic focus on liver diseases where ImmTOR accumulates and has shown hepatoprotective effects in models.

Joseph Schwartz of SVB Securities inquired about the expected timing and content of the initial data readout for the SEL-302 trial in MMA, and also asked for the company's perspective on a recent IL-2 trial failure by a competitor and the rationale for pursuing liver diseases with the ImmTOR-IL program.

Answer

President and CEO Carsten Brunn confirmed that interim data for SEL-302, focusing on safety, biomarkers, and neutralizing antibody (Nab) response, is expected toward the end of the year, likely after the first ImmTOR-dosed patient. Regarding ImmTOR-IL, Brunn stated that Selecta's combination approach is a first-in-class Treg-selective therapy. He highlighted that the liver is a strategic focus because ImmTOR accumulates there and has shown hepatoprotective properties in models, with more preclinical data to be shared after the DISSOLVE readout.

Joseph Schwartz asked for a summary of the key risk mitigation protocols for SGT-001 and inquired about the next steps for the program, including the timeline for returning to the clinic, the target patient population for the next study, and the status of an end-of-Phase II meeting with the FDA.

Answer

SVP and Head of Clinical Development Roxana Donisa Dreghici stated that the company is confident in SGT-001's risk-benefit profile, highlighting an optimized eculizumab regimen and close patient monitoring as key parts of the mitigation strategy, which will be reassessed for the new manufacturing material. CEO Ilan Ganot added that engagement with regulators has begun, with the goal of having new material ready to dose patients in early 2023, while the final clinical trial design is still being determined.

Joseph Schwartz of SVB Leerink asked about the encouraging long-term SGT-001 expression data, its potential correlation with specific clinical endpoints like the six-minute walk test, and how this could support regulatory approval. He also asked for details on the path forward for dosing more patients and the nature of the serious adverse event (SAE) in Patient 8.

Answer

Chief Scientific Officer Carl Morris acknowledged an apparent correlation in the data but cautioned it was from a small sample size (n=3). Acting Chief Medical Officer Dr. Cathryn Clary added that while the results are encouraging for designing a future registration trial, more data is needed. Regarding the SAE, Dr. Clary described it as an expected inflammatory response whose complexity requires thorough analysis before dosing Patient 9, a process being conducted with the DSMB and FDA.

Joseph Schwartz from SVB Leerink asked for more detail on the methods used to quantify microdystrophin expression, such as mass spectrometry or western blot. He also inquired about the company's strategic thinking on exploring other AAV vectors for SGT-001, either through in-house development or via additional partnerships similar to the Ultragenyx deal.

Answer

CTO Joel Schneider confirmed that the company uses multiple orthogonal methods to quantify microdystrophin, including immunofluorescence, western blot, and mass spectrometry. He highlighted the development of a quantitative in vitro expression assay that was instrumental in getting the FDA clinical hold lifted. CEO Ilan Ganot elaborated on strategy, stating that the company is constantly exploring next-generation vectors through both in-house research and collaborations to create more options for patients, viewing the Ultragenyx partnership as a key example of this approach.

Joseph Schwartz from SVB Leerink asked for details on the methods used to quantify microdystrophin expression, such as mass spectrometry or western blot. He also inquired about the company's strategy for exploring other vectors beyond the Ultragenyx collaboration, either through in-house development or additional partnerships.

Answer

Chief Technology Officer Joel Solomon Schneider confirmed that the company uses multiple orthogonal methods to quantify microdystrophin, including immunofluorescence, western blot, and mass spectrometry. He also highlighted a new quantitative in vitro expression assay that was key in getting the FDA clinical hold lifted. CEO Ilan Ganot elaborated on vector strategy, stating that Solid is continuously exploring next-generation vectors through in-house research and remains open to further collaborations to ensure more therapeutic options for patients.

Representing Joseph Schwartz of SVB Leerink, an associate asked about the key drivers for adoption in the under-penetrated PKU market and the commercial strategies to compete. A second question concerned the Ginkgo collaboration, asking about the expected number of future programs and how SYNB1353 differs from other candidates.

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President and CEO Aoife Brennan deferred to Chief Business Officer Molly Harper, who explained that low PKU treatment rates are due to the limited efficacy of current therapies for the majority of patients, not a lack of awareness. She stated the community needs a safe, convenient, and broadly effective oral option. David Hava then addressed the Ginkgo collaboration, noting that while SYNB1353 uses the same core platform as other programs, Ginkgo's expertise is in identifying novel molecular components like transporters and enzymes, which accelerates development and improves potency.

Joseph Schwartz from SVB Leerink inquired about the impact of PTG-300 on other blood components like leukocytes and reticulocytes and its connection to the drug's mechanism. He also asked for an update on the trial's next steps, the timeline for initiating a pivotal study, and the potential design and endpoints for such a trial.

Answer

Dr. Ronald Hoffman of Mount Sinai Hospital responded that platelet and leukocyte counts have remained steady during treatment, with no thrombotic events or disease evolution observed. Samuel Saks, Chief Medical Officer, added that the company is currently designing the pivotal study with thought leaders and plans to discuss it with the FDA, with further data updates expected in the second half of the year. President and CEO Dinesh Patel noted that enrollment is strong and the company will share more data as it becomes available.