Eddie

Eddie asked for clarification on the regulatory filing strategy for the EMANATE sub-studies, specifically whether they would be submitted as a combined sNDA or mutation-specific approvals, and how this might evolve for next-generation therapies. He also inquired about observations of better results in bivamelagon HO patients not on GLP-1s and the biological rationale.

Answer

David Meeker, Chairman, CEO, and President, clarified that EMANATE sub-studies would be filed as individual sNDAs, with no current path for a broader mechanistic approval, though it might be possible in the future. Regarding GLP-1s, he explained that in the setmelanotide Phase 3 trial, patients on GLP-1s who had not responded initially showed a better response with setmelanotide, suggesting that correcting the underlying hormonal deficiency can restore the ability to respond to other anti-obesity medications.

Eddie, on behalf of Joseph Stringer, asked about the regulatory filing strategy for the EMANATE sub-studies, specifically whether they would be submitted as a combined sNDA or require mutation-specific approvals, and how this might evolve for next-generation therapies. He also sought clarification on whether bivamelagon HO OLE showed better results in patients not on GLP-1, and the biological rationale.

Answer

David Meeker, Chairman, CEO, and President, clarified that EMANATE sub-studies would be filed individually as separate sNDAs, and while a future mechanistic approval for broader MC4R pathways is possible, regulators are not currently there. He corrected the understanding regarding GLP-1 patients, explaining that in the setmelanotide Phase 3 trial, patients who received setmelanotide after being on a GLP-1 had a better response, suggesting that correcting the underlying MC4R defect can restore responsiveness to other anti-obesity medications.