Zaki Molvi

Zaki Molvi questioned the timing of revising 2027 estimates before BridgeBio's phase three data readout, asking if the lower end assumes superior efficacy for BridgeBio and if the most bullish scenario is capped at $4 billion or lower.

Answer

Brian Mueller, Chief Financial Officer, explained that the update was driven by significant investor interest and the need to reflect a full range of outcomes given various key assumptions across the portfolio. He clarified that the lower-end estimate, which includes two competitors launching successfully, still aligns with current consensus for 2027. Mueller stated he was not characterizing the lower end as a 'worst-case' or the $4 billion (excluding Roctavian) as a 'best-case,' but rather illustrating a range of lower and higher case estimates, with the upside potentially including intellectual property defense success or broader portfolio success.

Zaki Molvi from Jefferies, on for Akash Tewari, asked about the potential for event variability to be a swing factor in the CORE studies' acute pancreatitis (AP) analysis, referencing a late-occurring AP event in the BALANCE study's treatment arm.

Answer

CEO Brett Monia and Chief Clinical Development Officer Eugene Schneider responded that they are taking steps to maximize statistical power for the AP analysis. This includes combining the CORE and CORE-2 studies and assessing the AP endpoint at the 12-month mark, which maximizes both patient numbers and observation time to account for such variability.

Zaki Molvi, on for Akash Tewari at Jefferies, asked about dosing in the ACACIA trial for nonobstructive HCM, questioning the ability to maintain patients on the higher 20mg dose without ejection fraction issues and whether slower titration might be better.

Answer

EVP of R&D Fady Malik responded that the dosing strategy in ACACIA is based directly on the Phase 2 REDWOOD data, where 85% of patients reached 15mg within six weeks, with many eligible for 20mg. He noted that NT-proBNP decreased in a dose-dependent manner in REDWOOD and expects a similar or higher dose distribution in ACACIA. He expressed confidence in the current dosing and titration speed, seeing no fundamental difference in cardiac function between nHCM and oHCM patients.