Raju Prasad

Raju Prasad asked about the clinical progression plan for the Danon program now that the high dose is discontinued, specifically regarding adult versus pediatric populations, and requested clarification on changes to the immunosuppression regimen.

Answer

CEO Gaurav Shah stated the company intends to move forward immediately with the pediatric population at the low dose. Regarding the immunosuppression regimen, he described the changes as refinements and tightening of the protocol but declined to provide specifics during an active dialogue with the FDA.

Rajiv Prasad of William Blair asked for a comparison of the current Pompe construct versus the previous one, particularly regarding potency and biodistribution, and questioned if the muscle-directed approach was also being applied to the DMD program.

Answer

CEO Matt Patterson explained that the only change to the Pompe product was the promoter, which was fine-tuned to optimize expression levels, and that the preclinical data is very strong. He emphasized the approach is focused on muscle expression. He clarified that the DMD program utilizes a different scientific approach, vectorized exon skipping, which involves a different promoter situation than the direct protein expression used in Pompe.

Raju Prasad of William Blair asked about the doses used in the AT845 non-GLP study, the strategic decision on the CASQ2-CPVT program, and the potential cost savings from in-house plasmid manufacturing.

Answer

Matt Patterson, Chairman and CEO, confirmed that multiple relevant doses were used in the AT845 non-GLP study, boosting confidence for future studies. He explained that the CPVT program is being out-licensed due to a smaller-than-expected patient population and a strategic shift to focus on neuromuscular diseases. Regarding plasmid manufacturing, he did not provide specific numbers but stated it is a powerful investment that significantly reduces costs, timelines, and supply chain risk, and will 'pay for itself very rapidly,' confirming plasmid is the most expensive raw material.

Raju Prasad from William Blair & Co. asked about regulatory opinions on patient numbers per jurisdiction, the patient capacity of the 1000L manufacturing scale, and whether the Pompe IND would include non-human primate study data.

Answer

President and CEO Matthew Patterson stated that patient numbers per jurisdiction has not been a topic with regulators. He declined to specify patient capacity but reiterated confidence in meeting global demand. He confirmed the Q3 Pompe IND filing will be supported by a completed 12-week non-human primate toxicology study.