Will Soghikian

Will Soghikian asked about the basis for the claim that GTX-102 (Angelman) is the most potent ASO in development, specifically whether it's based on UBE3A knockdown, mRNA/protein increases preclinically, and the relationship between knockdown and protein expression. He also requested an update on the DTX-301 program.

Answer

CEO Emil Kakkis explained that potency estimates come from non-human primate studies, where GTX-102, being identical to the non-human primate sequence, showed substantial knockdown of the antisense transcript and induction of UBE3A expression across the brain at low doses (1-2 mg). He noted that comparable Bayley cognition effects are being achieved in human studies at 5-14 mg, while competitors use higher doses (40-80 mg), substantiating the preclinical findings. Regarding DTX-301 (OTC), Kakkis confirmed the Phase 3 is continuing, with data on the ammonia endpoint expected later this year.

Will Soghikian asked about the basis for the claim that GTX-102 is the most potent ASO for Angelman syndrome, specifically whether it's based on UBE3A knockdown, mRNA, or protein increases preclinically, and the relationship observed between knockdown and protein expression. He also requested an update on the DTX-301 program for OTC.

Answer

Emil Kakkis, Chief Executive Officer and President, explained that potency estimates come from non-human primate studies, where GTX-102 (identical to non-human primate sequence) showed substantial antisense transcript knockdown and UBE3A expression induction at low doses (1-2 mg over a few doses). He noted that comparable Bayley cognition improvements are seen in their study at 5-14 mg doses, versus 40-80 mg for competitors, substantiating preclinical findings. For DTX-301, he stated the Phase III trial is continuing, with ammonia endpoint data expected later this year.

Will Devroe Soghikian asked how Angelman syndrome patients, parents, and caregivers might make treatment decisions given multiple ASOs in development, considering factors like data, dosing schedules, specific endpoints, and safety.

Answer

Erik Harris, Chief Commercial Officer, emphasized that parents prioritize overall patient well-being over specific endpoints, looking at the 'whole story' across various domains. He noted that dosing schedules for competing ASOs are converging, making potency and safety the most critical factors. He also highlighted Ultragenyx's patient support programs as a key differentiator and expressed confidence in their ASO's potential to be a leading option.

Will Soghikian of Leerink Partners inquired about the nature of recent FDA interactions, particularly with CBER, and whether any meaningful changes in messaging or personnel have been observed amid leadership transitions at the agency.

Answer

Emil Kakkis, Founder, President & CEO, stated that recent interactions with the FDA following the Complete Response Letter (CRL) have been productive. He expressed satisfaction with the progress toward submitting the Type A meeting package, noting that despite agency turmoil, things have been proceeding well.

Will Soghikian sought more details on the patient profile beyond prior therapy, specifically asking about meaningful patterns in attack rate severity, frequency, and typical attack rates before initiating ECTERLEET treatment.

Answer

Nicole Sweeny, Chief Commercial Officer, stated that while market research indicated high-burden patients would be early adopters, adoption was observed across a wide array of patient types, including those on various prophylactic therapies, aligning with overall market share.

Will Soghikian of Leerink Partners inquired about the potential major topics for the upcoming Filspari advisory committee (AdCom) for FSGS and the company's strategy for messaging to a panel that may include both nephrologists and cardiologists.

Answer

Dr. Jula Inrig, Chief Medical Officer, stated that Travere is prepared to educate the mixed panel on the pathophysiology of FSGS, the harm of proteinuria, and the importance of blocking both the RAS system and endothelin-1. She emphasized their readiness to present the biologic plausibility of proteinuria as a validated endpoint and the strong clinical data for sparsentan.

Will Soghikian of Leerink Partners asked for color on field dynamics following the approval of a competitor therapy in IgAN and whether FILSPARI's data and longer experience position it as a preferred choice.

Answer

Chief Commercial Officer Peter Heerma noted that while it's early, increased competition helps raise market awareness about the need to treat IgAN. He reported that FILSPARI's demand continued to grow in April, the first month of competition, attributing this to physician confidence in its strong data profile, including long-term kidney preservation and convenience.

Will Soghikian of Leerink Partners inquired about the dynamics behind the Q3 dip in new patient start forms (PSFs) for FILSPARI, asking if factors beyond seasonality and sales force training were at play, and about trends early in Q4.

Answer

President and CEO Dr. Eric Dube expressed satisfaction with the results, after which Chief Commercial Officer Peter Heerma attributed the Q3 numbers to typical summer seasonality and a week of sales team training. Heerma highlighted that despite this, over 500 new patient start forms were added and noted an encouraging upward inflection in demand in the weeks following full approval, indicating a strong end to the year.

Will Soghikian of Leerink Partners inquired about the status of formulation work for AUR-200 (Aratinircept), specifically regarding an auto-injector, and its timeline relative to upcoming studies. He also asked for guidance on future R&D spending as development ramps up and whether Aurinia expects to remain cash flow positive.

Answer

President and CEO Peter Greenleaf confirmed the goal is a patient-friendly formulation like an auto-injector, which seems attainable and is being developed on a parallel path. CFO Joe Miller stated that while R&D costs will increase, the company is not providing specific long-term guidance on expenses or cash flow. Mr. Greenleaf added that operational efficiency remains a key priority.

Will Soghikian questioned the status of formulation work for AUR-200 (Aratinacept), particularly regarding an auto-injector, and sought clarity on future R&D spending and the company's ability to remain cash flow positive.

Answer

President and CEO Peter Greenleaf confirmed that work on a patient-friendly formulation like an auto-injector is proceeding in parallel with clinical development and appears attainable. CFO Joe Miller stated that while R&D costs will increase, no specific long-term guidance on OpEx or cash flows is being provided. Peter Greenleaf added that operational efficiency and positive cash flow remain key priorities.

Will Soghikian questioned the progress of formulation work for AUR-200 (Aratinacept), particularly the potential for an auto-injector, and its completion timeline relative to upcoming studies. He also asked about the expected trajectory of R&D spending and whether the company anticipates remaining cash flow positive during the asset's development.

Answer

CEO Peter Greenleaf confirmed the goal is a patient-friendly formulation like an auto-injector, stating that early data suggests this is attainable and work is proceeding in parallel with clinical development. CFO Joe Miller stated that while R&D costs will increase with trial progression, the company is not providing specific long-term guidance on OpEx or cash flows. Greenleaf added that operational efficiency and cash flow remain a key priority.

Will Soghikian questioned the status of formulation work for AUR-200 (Aratinacept), asking if an auto-injector is the goal. He also asked how R&D spending will trend with AUR-200's advancement and whether the company expects to maintain positive cash flow.

Answer

President and CEO Peter Greenleaf confirmed the goal is a patient-friendly formulation like an auto-injector, which they believe is attainable and is being developed in parallel. CFO Joe Miller stated that while R&D costs will increase, the company is not providing specific forward-looking guidance on OpEx or cash flows. Greenleaf added that operational efficiency remains a key priority.

Will Soghikian requested more color on the Q3 commercial environment, noting the regression in Patient Start Forms (PSFs) compared to the prior year. He also asked how Aurinia plans to differentiate AUR200 in the increasingly crowded anti-APRIL space and what indications are being considered.

Answer

President and CEO Peter Greenleaf addressed the PSF question by reiterating that the most accurate view of new patient growth comes from the combination of PSFs, patient restarts, and the hospital business, which showed robust combined growth. He noted that like-for-like comparisons for all three metrics will be available starting with Q4 results. Regarding AUR200, he deferred commenting on competitive differentiation or target indications until human clinical data from the SAD/MAD studies is available to inform the strategy.