ALEC

• Arnon Rosenthal highlighted the upcoming INFRONT-3 trial data readout mid-Q4 2025 for latozinemab in FTD-GRN, noting collaboration with GSK on launch readiness. - Dr. Sara Kenkare-Mitra spoke about the ABC platform for efficient brain delivery of therapeutic modalities. - Giacomo Salvadore detailed the INFRONT-3 trial, including the addition of plasma progranulin as a co-primary endpoint per FDA request, and the well-tolerated nature of latozinemab. - Neil Berkley provided financial guidance, stating collaboration revenue expected between $13M and $18M, R&D between $130M and $140M, G&A between $55M and $65M, with $307.3M cash on hand.

• Collaboration revenue is anticipated to be between $13 million and $18 million. - Research and development guidance is between $130 million and $140 million. - General and administrative guidance is between $55 million and $65 million. - $307.3 million in cash provides runway into the second half of 2027.

No specific product segment financial performance discussed in detail; focus is on clinical programs and pipeline.

• Diagnostic complexity in frontotemporal dementia (FTD), including frequent misdiagnosis or late diagnosis. - Trial design challenges due to variable symptoms in FTD, making it hard to track disease progression. - Urgent need for disease-modifying therapies, especially in genetic subtypes like FTD-GRN.

Q: Clarify on the statistical analysis plan change and ABC platform.

A: Giacomo Salvadore said the change to include progranulin as a co-primary endpoint was in response to FDA request; Sara Kenkare-Mitra noted ABC platform lead programs depend on transferrin-mediated process.

Q: Why did FDA reviewer request plasma progranulin and clinical benefit in Alzheimer's?

A: FDA requested progranulin inclusion as it's mechanistically meaningful; Arnon Rosenthal said restoring progranulin levels could support Alzheimer's potential.

Q: Impact of SAP change on INFRONT-3 power and progranulin in labeling?

A: Arnon Rosenthal said power for CDR sum of boxes unchanged, and no discussion on progranulin in labeling yet.

Q: FDA's progranulin threshold and study power?

A: Arnon Rosenthal said FDA didn't specify threshold, study is 90% powered for 40% disease progression slowdown.

Q: Thoughts on progranulin restoration in FTD and ARIA risk?

A: Arnon Rosenthal said restoring to normal levels shows intervention can impact, Giacomo Salvadore said ARIA not observed in INFRONT-3.

Q: Approval chances if progranulin hits but clinical data equivocal?

A: Arnon Rosenthal said would pursue full approval if data supports, citing regulatory precedents in CNS diseases.

Q: Presymptomatic patients and OLE progression?

A: Arnon Rosenthal said primary analysis on symptomatic patients, OLE progression details not disclosed but shows persistence of benefit potential.