Mike DiFiore

Mike DiFiore asked for color on the range of scenarios considered for significant competition from Nucresiran impacting AMVUTTRA, specifically how quickly AMVUTTRA sales might erode if Nucresiran is approved and launched in 2030. He also requested updates on the market for synthetic royalties in the obesity space.

Answer

Marshall Urist, EVP Head of Research and Investments, explained that for AMVUTTRA, they considered a broad range of scenarios for Nucresiran's timing and market entry, using the Onpattro to AMVUTTRA transition as a case study, and remains confident in a low double-digit IRR or better. On the obesity market, he reiterated that it's on their radar, but they are disciplined in waiting for important, differentiated products that create shareholder value. Pablo Legorreta, CEO and Chairman, directed the question to Marshall Urist.

Mike DiFiore asked for color on the range of scenarios factoring in significant competition from Nucresiran for Amvuttra, specifically how quickly Amvuttra sales might erode if Nucresiran launches in 2030. He also requested an update on the market for synthetic royalties in the obesity space.

Answer

Marshall Urist, EVP and Head of Research and Investments, explained that for Amvuttra, they considered a broad range of scenarios for Nucresiran's market entry, using the Onpattro to Amvuttra transition as a case study, and remains confident in a low double-digit IRR or better. For the obesity market, he stated it remains on their radar, but they are disciplined in waiting for important, differentiated products that create shareholder value.

Mike DiFiore sought clarification on the MariTide phase 2 part 2 trial design, specifically regarding the availability of two-year weight loss data, the washout period post-week 52, and the expectation for weight loss in year two compared to year one, given that most patients would have lost weight in year one.

Answer

James Bradner, EVP of Research and Development, reiterated that part two is primarily a maintenance study designed to inform Amgen's strategy for MariTide maintenance and further phase 3 programming. He clarified that while patients needed to achieve over 15% weight loss in part one to participate in part two, the study is not strongly powered for significant insights into weight loss differences between arms, but will track patients who did not reach a weight loss plateau in the first year.