Ellen Horste

Ellen Horste of TD Cowen asked about the expected pace of SG&A expense increases associated with the Ampreloxetine commercial build-out, both before and after data.

Answer

CFO Aziz Sawaf stated that SG&A spending will remain stable until the CYPRESS data readout. If the data is positive, SG&A will increase for launch preparations, but he emphasized it would be a targeted and focused launch, not requiring 'huge levels' of incremental spend. CEO Rick Winningham reinforced this, noting the rare disease population of ~40,000 patients allows for an efficient commercial strategy.

Ellen Horste asked about the biggest potential risks to the pivotal program timelines that could delay data past 2028 and whether there is any risk associated with running combined studies for both KMT2A and NPM1 populations.

Answer

Chief Medical Officer Dr. Mollie Leoni responded that the 2028 timeline was set conservatively and they remain confident in meeting it. She added that based on robust data from the COMET-seven trial, the company has extensively modeled the combined populations and does not see it as a risk, viewing it as a strength of the trial design.

Ellen Horste from TD Cowen asked about the definition of success for the BMN 401 ENERGY-3 trial, including functional endpoints for ex-U.S. approval, and inquired about the number of identified patients for ENPP1 deficiency.

Answer

Gregory Friberg, EVP and Chief R&D Officer, explained that success in Europe is defined by co-primary endpoints: normalization of pyrophosphate levels and a functional measure of bone quality via a radiologic index. Cristin Hubbard, EVP and CCO, added that while the total addressable population is estimated at 2,000-2,500, over 600 patients have already been identified, and BioMarin will leverage its diagnostic expertise to find more.

Ellen Horste from TD Cowen asked what would constitute success for the BMN-401 (formerly INZ-701) ENERGY-3 trial, including functional endpoints, and inquired about the number of identified patients and the strategy for finding the estimated 2,000-2,500 total patients.

Answer

EVP & Chief R&D Officer Gregory Friberg explained that success involves co-primary endpoints of normalizing pyrophosphate levels and improving a radiologic index of bone quality. EVP & CCO Cristin Hubbard added that while Inozyme had identified over 600 patients, BioMarin will leverage its established infrastructure and diagnostic expertise within its enzyme therapy unit to find the remaining patient population, as the treating specialists overlap significantly.

Ellen Horste from TD Cowen asked for color on the month-over-month trends for new Revuforj patient starts in Q1 and details on the free drug rate and its expected trajectory.

Answer

Chief Commercial Officer Steven Closter stated that while specific monthly numbers would not be provided, there was a strong ramp from Q4 2024 into Q1 2025. He mentioned it would take at least two full quarters to see a stable run rate. Regarding patient assistance, he reported that the free drug rate is very low, in the single digits, due to efficient execution, strong formulary coverage, and a well-defined patient assistance program.