Angela

Angela, on behalf of Whitney Ijem, asked if Arcturus is still assessing efficacy in the 15mg CF cohort, what endpoints are being used, and if that data will be shared. She also inquired if another 12-week study using 15mg would be run, or if the optionality to dose up is part of the current 10mg study.

Answer

Joseph Payne, President and CEO, stated that the focus is on the 12-week, N of 20 study (fourth cohort), and it's unlikely more data from the first three cohorts will be shared. He clarified that the 12-week study will initiate at 10mg, and they have the flexibility to increase the dose to 15mg within this open-label study if needed, based on ongoing data collection.

Angela asked for expectations regarding WVE-007's body composition and fat reduction from the 240mg (six-month) and 400mg (three-month) cohorts, and for WVE-006's AAT levels from the 400mg multi-dose (MAD) cohort.

Answer

Paul Bolno, President and CEO, stated that for WVE-007, they expect continued fat loss, lean mass stabilization, and a reduction in total body mass, building on the profile seen at three months (fat loss similar to GLP-1s, higher visceral fat reduction, lean mass preservation). For WVE-006, the goal is to confirm the therapeutic threshold to an MZ phenotype, ensuring patients can respond to acute exacerbations (20 micromolar AAT seen at lowest dose). They anticipate observing durability, potential for increased M protein over time as the liver health improves, and sustained editing efficiency at the 400mg MAD cohort.

Angela asked about expectations for the upcoming BEAM-302 (AATD) readout, specifically what constitutes good AAT levels from the 75mg and 60mg double dose, and the company's confidence in selecting a pivotal dose from the next data update.

Answer

CEO John Evans explained that the update will include comprehensive data, with additional 60mg patients and exploration of 75mg and 2x60mg doses. The company will assess A1AT increases versus saturation, efficacy and safety in Part B (sicker livers), and durability (12+ months follow-up). He expressed confidence in having sufficient insight this year to finalize the dose and schedule for the pivotal study.

Angela asked about expectations for the upcoming BEAM-302 (AATD) readout, what constitutes 'good' AAT levels for the 75mg and 60mg double dose, and the company's confidence in selecting a pivotal dose from the next data update.

Answer

CEO John Evans stated that the update will include comprehensive data on additional 60mg patients, 75mg dose, and 2x60mg schedule, looking for increases in alpha-1 levels and proximity to liver editing saturation. He also mentioned data from patients with sicker livers (Part B) and durability data extending beyond 12 months. He expressed confidence in having sufficient insight early this year to finalize the dose and schedule for pivotal development.