Matthew Guggenbiller

Matthew Guggenbiller asked about the registrational potential of the INT Phase II RCC study, what hazard ratio would be compelling, and if a Phase III is needed, whether Keytruda or a Keytruda-belzutifan combo would be the preferred comparator arm.

Answer

Stephen Hoge, President, explained that while the Phase II RCC study is blinded and powered, it could be registrational if a significant benefit is observed, though it wasn't initially designed as a Phase III. The primary goal was to confirm INT's efficacy across various tumors, particularly where it could improve upon pembrolizumab. He acknowledged the evolving standard of care, including belzutifan, and stated that any future decisions on INT's path, including potential combinations, would depend on the data and discussions with Merck.

Matthew Guggenbiller asked about the RCC program, specifically what makes Moderna confident that Phase II could be registrational, what hazard ratio or benefit would be compelling, and if a Phase III is needed, whether Keytruda or the Keytruda-belzutifan combo would be the appropriate comparator arm.

Answer

Stephen Hoge, President, stated that the blinded Phase II RCC study could be registrational if it shows a dramatic and highly statistically significant benefit, though it wasn't initially powered as such. Its primary goal was to confirm INT's hypothesis across tumors. He acknowledged the evolving standard of care and said future decisions would depend on the data.

Representing Alex Stranahan of Bank of America, Matthew Guggenbiller asked if the changes to enrollment targets and stabilizer percentage in the MAGNITUDE study have altered the company's thinking on the likelihood or timing of a potential interim readout.

Answer

President and CEO John Leonard confirmed that the adjustments increase the overall statistical power of the study for both the primary outcome and the stabilizer subgroup. He stated an expectation that these changes would "favorably affect the ability to find an effect" at the point of a future interim analysis.

Matthew Guggenbiller of Bank of America inquired about the educational strategy to drive Pyrokine uptake beyond the initial target patients in thalassemia and asked if development plans for the PKU asset, AG-181, have changed following a competitor's recent approval.

Answer

CCO Tsveta Milanova detailed plans to expand to less acute non-transfusion-dependent patients by educating on long-term complications. CMO Dr. Sarah Gheuens stated there are no changes to the PKU program, emphasizing AG-181's novel mechanism and the remaining unmet need in the patient population.