Michael Riad

Michael Riad of Morgan Stanley asked Dr. Darby if a successful outcome in FTD-GRN would increase confidence in using a progranulin-elevating approach for Alzheimer's disease. He also asked how the INFRONT3 analysis normalizes for inter-patient variability in baseline progranulin levels.

Answer

Dr. Ryan Darby stated that success would support the mechanism and open possibilities for other indications. CMO Giacomo Salvadore explained the analysis compares the active arm to placebo and that FTD-GRN mutations consistently cause a ~50% reduction in progranulin. CEO Arnon Rosenthal further clarified the specific genetic nature of FTD-GRN mutations.

Michael Riad, on for Sean Lammond, asked about the growth trajectory for Daybue's new patient additions, questioning whether the current steady rate is expected to accelerate.

Answer

Chief Commercial Officer Thomas Garner expressed satisfaction with the steady growth over the last three quarters, with active patients increasing from 920 in Q4 2024 to 987 in Q2 2025. He stated that the company's plan is for this growth to accelerate as the impact of the new customer model materializes, aiming for more new patient starts quarter-over-quarter.

Michael Riad, on behalf of Sean Lammen at Morgan Stanley, asked for the current INGREZZA volume split by channel (neurology, psychiatry, LTC) and their respective contributions to growth.

Answer

CCO Eric Benevich reported strong growth across all three segments. He stated that psychiatry accounts for approximately 60-65% of the volume, with the remainder split fairly evenly between neurology and long-term care. He confirmed that all three channels are growing at a similar rate.

Michael Riad, on for Sean Laaman at Morgan Stanley, asked for a breakdown of Xywav narcolepsy patient adds (new vs. switches) and for commentary on Xywav's value proposition in IH against potential competition from LUMRYZ.

Answer

Renée Galá, President and COO, stated that recent narcolepsy adds were primarily new-to-oxybate patients. For IH, she highlighted Xywav's status as the only low-sodium option and its flexible dosing. Bruce Cozadd, CEO, added that a recent court ruling upholding their IP makes a near-term competitive launch of LUMRYZ in IH unlikely before their patent expires in 2036.

Michael Riad of Morgan Stanley asked if baseline characteristics for the CardinALS trial would be shared before the topline data and questioned the dynamics of the long-term vatiquinone extension studies.

Answer

CEO Matthew Klein confirmed that key baseline characteristics for CardinALS will be released with the topline results. Regarding vatiquinone, he clarified that the benefit was continuous, not delayed, showing a consistent ~50% slowing in disease progression at both 72 weeks and 3 years, demonstrating sustained preservation of function.

Michael Riad, on for Jeff Hung, asked if the UX111 BLA for Sanfilippo syndrome would include only heparan sulfate data or also downstream markers. He also questioned if the treatment effect seen in the setrusumab Phase 2 study would have been sufficient to trigger an early stop.

Answer

CEO Emil Kakkis confirmed the UX111 BLA will be supported by a chain of evidence, including heparan sulfate, gangliosides, NfL, and brain volume data, all the way to Bayley scores. Regarding setrusumab, he explained that hitting the first interim depends on both a high fracture rate and a large treatment effect, and the combination of these factors gives the analysis a chance to succeed early.

Asked about the influence of background antidepressant therapy on the placebo effect in the MDD trials and whether the studies are balanced in this regard.

Answer

The studies allow various standard background therapies (SSRIs, SNRIs). The company takes measures to mitigate placebo response, such as patient adjudication. While not balanced for specific drugs, the overall approach to background regimens is consistent across the entire MDD program, similar to other approved drugs in the class.