Emma

Emma asked for more detail on why the FDA was comfortable lifting the clinical hold for the PN study but not the CM study, given they use the same product, and what specific factors differentiate the FDA's view across the two indications.

Answer

President and CEO John Leonard explained that the FDA views the patient populations as distinct. PN patients are typically younger (sometimes decades younger) than CM patients, who are often in their seventies or older, frequently have wild-type genes, polypharmacy, and other medical problems. This demographic difference, combined with a good safety profile in the PN study, likely drives the FDA's differentiated view. He reiterated significant progress with the CM hold.

Emma asked for elaboration on why the FDA was comfortable lifting the clinical hold for the PN study but not the CM study, given they involve the same product, and if specific factors differentiate the FDA's view across the two indications.

Answer

President and CEO John Leonard explained that the FDA views the patient populations as somewhat distinct. He highlighted that PN patients tend to be younger, sometimes decades younger than CM patients, who are typically in their seventies or beyond, often have wild-type genes, polypharmacy, and other medical problems. He noted that these demographic differences, coupled with a good safety profile in the PN study thus far, likely drive the FDA's differentiated approach, while substantial progress is being made with the FDA on the CM study.

Emma asked for an update on tracking blinded event rates for the MAESTRO-NASH outcomes trial in F4C, the likelihood of on-time data delivery, and any potential for additional open-label NAFLD data to reinforce conviction.

Answer

Chief Medical Officer David Soergel confirmed that MAESTRO outcomes events are tracking as expected, with data anticipated in 2027, though more time is needed to tighten guidance. He stated no additional open-label data is planned, as sufficient insights have been gained from the NAFLD-1 study, demonstrating positive effects in patients with clinically significant portal hypertension.