Lisa Walter

Lisa Walter asked for further details on the bivamelagon dose selection for Phase 3 and inquired about the long-term possibility of patients dosing down to a maintenance dose if they achieve a normal BMI in a real-world setting.

Answer

David Meeker, Chairman, CEO, and President, reiterated that 600 mg would be the targeted dose for bivamelagon, with 200 mg likely being subtherapeutic. He clarified that, given the pathophysiology of a hormonal deficiency, patients are not expected to dose down for maintenance after achieving weight loss, and most would likely remain at their target dose, consistent with the experience with setmelanotide.

Lisa Walter asked for further details on bivamelagon dose selection comments and whether, long-term, patients might be able to dose down to a maintenance dose if they achieve a normal BMI in a real-world setting.

Answer

David Meeker, Chairman, CEO, and President, reiterated that 200mg is likely sub-therapeutic, with 400-600mg being the effective range, and 600mg as the target dose for bivamelagon. He explained that due to the hormonal deficiency pathophysiology, patients are expected to remain on their target dose rather than dosing down for maintenance, a trend observed with setmelanotide.

Lisa Walter asked about potential upticks in IPF diagnoses following the TETON 2 results and their positive impact on Tyvaso sales in the coming quarters.

Answer

Martine Rothblatt, Founder, Chairman, and CEO, referred the question to Michael Benkowitz, President and COO. Michael Benkowitz stated that while physicians he spoke with indicated TETON 2 data would prompt more aggressive screening for pulmonary hypertension in IPF patients, it was too early to directly attribute any uptick to the study, but he expects it to logically play out over time.

Lisa Walter asked about the potential for an uptick in IPF diagnoses following the TETON 2 results and its positive impact on Tyvaso sales in upcoming quarters.

Answer

Martine Rothblatt, Founder, Chairman, and CEO, referred the question to Michael Benkowitz, President and COO. Michael Benkowitz confirmed that physicians he spoke with at recent conferences indicated TETON 2 data would prompt more aggressive screening for pulmonary hypertension in IPF patients. He noted it's too early to see a direct uptick but believes it's a logical progression that will play out over time.

Lisa Walter, on for Luca Ici, asked about the regulatory path for Suravec in diabetic retinopathy, sought clarification on the treatment needs of patients who did not achieve a two-step DRSS improvement, and inquired about the enrollment status of the subretinal wet AMD pivotal study.

Answer

President & CEO Curran Simpson stated that enrollment for the subretinal wet AMD studies is "imminent." CMO Dr. Steve Pakola clarified that the regulatory plan for diabetic retinopathy involves two adequate and well-controlled studies, with the new Phase 2b/3 trial intended to be one of them. He also noted that only a minority of patients in the dose level 3 group required any supplemental injections, not the full 50% who didn't meet the primary endpoint without them.

Lisa Walter, representing Luca Issi from RBC Capital Markets, asked if the AFFINITY study for DMD measures cardiac endpoints like LVEF and troponin, and if these could differentiate the program. She also questioned whether REGENXBIO would consider shortening enrollment in the subretinal wet AMD pivotal study to accelerate timelines in a competitive market.

Answer

CEO Curran Simpson noted that preclinical data suggests good cardiac biodistribution but clinical benefits are a longer-term outcome. Chief Medical Officer Dr. Steve Pakola confirmed they measure cardiac endpoints but expect meaningful changes to occur over a longer period in older patients. Regarding the wet AMD trial, Dr. Pakola stated firmly that neither REGENXBIO nor AbbVie would cut enrollment short, emphasizing the importance of fully characterizing safety and efficacy for a global launch and positioning their therapy as a paradigm shift, not an incremental improvement.

Lisa Walter asked if there would be any other pivotal trial updates beyond safety, such as patient retention, and whether the company plans to run an open-label extension study for DuraVu.

Answer

CEO Dr. Jay Duker confirmed that an open-label extension study is currently being planned to provide long-term data on DuraVu's benefits. Regarding interim updates, he reiterated that the company will likely provide basic patient demographics and periodic safety data but will remain cautious to avoid introducing any operational bias into the trials.

Lisa Walter of RBC Capital Markets inquired if any updates beyond safety, such as patient retention, should be expected before the pivotal trial readouts and if the company plans to run an open-label extension study.

Answer

CEO Jay Duker confirmed that the company will conduct an open-label extension study, which is currently in the planning stages. For interim updates, he expects to provide basic demographics of the enrolled population and periodic safety updates, but reiterated the desire to avoid introducing bias by disclosing too much information, a point echoed by CMO Ramiro Ribeiro.

Lisa Walter from RBC Capital Markets sought clarification on the trial protocol, asking whether a rescue due to hemorrhage is considered an on-protocol or off-protocol event.

Answer

Pravin Dugel, Executive Chairman, President & CEO, explained that while physicians always retain discretion to rescue a patient for safety, the SOUL-one protocol explicitly defines on-protocol rescue as either a 15-letter loss of vision or a hemorrhage that threatens the macula. He emphasized that the vast majority of rescues have been based on the 15-letter loss criterion, indicating strong protocol adherence.

Lisa Walter from RBC Capital Markets asked for details on the path for Empaveli to achieve blockbuster status and whether it would require further label expansions beyond the current indications.

Answer

CEO Dr. Cedric Francois outlined the path based on the current approval, estimating a 5,000-patient market for C3G and ICMPGN. He noted that with limited competition in most sub-segments and potential revenue of approximately $500 million per 1,000 patients, blockbuster status is achievable with the current label. Future approvals in FSGS and DGF would be additive to this potential.

Lisa Walter from RBC Capital Markets asked for a walkthrough of the path for Empaveli to achieve blockbuster status and whether it would require further label expansions beyond the current indications.

Answer

Co-Founder and CEO Cedric Francois outlined the path based on the current approval, estimating 5,000 patients in the U.S. for C3G and IC-MPGN. He noted that every 1,000 patients could represent approximately $500 million in revenue, indicating blockbuster potential from this indication alone. He added that potential future approvals in FSGS and DGF would be additive to this opportunity.

Lisa Walter of RBC Capital Markets asked for details on the path for Empaveli to achieve blockbuster status and whether it would require further label expansions beyond the recent C3G and ICMPGN approval.

Answer

CEO Dr. Cedric Francois outlined the path, stating that with an estimated 5,000 patients in the C3G/ICMPGN market, every 1,000 patients treated could represent approximately $500 million in revenue. This suggests the current approval alone provides a clear route to blockbuster potential, with future indications like FSGS and DGF being additive.

Lisa Walter from RBC Capital Markets asked for details on the path for Empaveli to achieve blockbuster status and whether that potential relies on further label expansions beyond the current indications.

Answer

CEO Dr. Cedric Francois outlined the path, noting the ~5,000 patients in the newly approved C3G/IC-MPGN indications. He stated that every 1,000 patients treated could represent about $500 million in revenue, suggesting blockbuster potential is achievable with the current label alone. Future indications like FSGS and DGF would be additive to this.

Lisa Walter asked if Apellis would consider exploring EMPAVELI in other kidney indications like IgAN, given recent data from a competitor, and requested an update on ex-U.S. launch plans for SYFOVRE.

Answer

Executive Cedric Francois stated that after a thorough analysis, Apellis has prioritized initiating two new Phase III trials for EMPAVELI in delayed graft function and focal segmental glomerulosclerosis, and that IgAN is not one of its next target indications. Regarding SYFOVRE ex-U.S., he noted it is early in the Australian launch but enthusiasm is high. He affirmed the company continues to work with regulators in other regions, leveraging growing long-term data to secure the best possible global access.

Lisa Walter of RBC Capital Markets asked about the outlook for SYFOVRE approval in other ex-U.S. geographies like the UK, Australia, and Canada following the negative CHMP opinion, and if other large foreign markets were being targeted.

Answer

COO Adam Townsend confirmed that Apellis is continuing to pursue regulatory approval in the UK, Switzerland, Canada, and Australia, as these processes are independent of the EMA. He also mentioned they are moving forward in markets that accept the U.S. file, such as Brazil, and are using distributors to access other smaller markets, underscoring the large unmet need for GA treatment outside the U.S.

Lisa Walter from RBC Capital Markets inquired about the requirements to initiate a Phase II study for the A1AT program, including the target serum level, and questioned the potential regulatory path, including whether a head-to-head trial might be necessary.

Answer

President and CEO Dr. Paul Bolno responded that the current study will inform the Phase II design by defining the achievable dynamic range of M protein levels and establishing durability to set a dosing frequency. Regarding the regulatory path, he believes an accelerated pathway based on restoring healthy protein levels is a distinct and viable approach compared to IV protein replacement. He also highlighted the long-term strategy of pursuing both liver and lung endpoints to treat the complete AATD disease profile, a plan being developed with their partner.

Lisa Walter from RBC Capital Markets questioned the dosing strategy for Wave's RNA editing platform, asking for context on its higher doses (e.g., 400mg for WVE-006) compared to lower doses used in DNA editing and siRNA therapies, and inquired about potential safety risks.

Answer

President and CEO Paul Bolno explained that direct dose comparisons are complex and that Wave's absolute dosing is within the range of other approved drugs like Inclisiran. He emphasized that as a leader in ADAR editing, exploring a wide dose range is crucial to understand the kinetics and optimize both efficacy and durability. He reassured that extensive safety data from healthy volunteer studies support the exploration of these higher doses.