Korsana Biosciences (KRSA) investor relations material

Alzheimer’s treatment landscape

• Two disease-modifying therapies are marketed; both slow cognitive decline but leave room for improvement, while trontinemab has shown faster plaque clearance and lower ARIA rates, alongside infusion reactions and anemia concerns.

• Pyroglutamate-targeting antibodies donanemab and remternetug provide the rationale for KRSA-028’s target, with reported evidence of fast, deep plaque reduction.

• Transferrin-receptor shuttling may raise brain exposure at lower doses and peripheral concentrations, potentially reducing ARIA versus unshuttled antibodies.

KRSA-028 design and differentiation

• Designed to target pyroglutamate-modified amyloid; preclinical work preserved phagocytosis while reducing CDC and ADCC, with the aim of clearing plaques while sparing reticulocytes.

• The shuttle uses the same target, epitope and affinity as trontinemab; head-to-head mouse and non-human-primate studies informed development, with a novel sequence elsewhere in the molecule.

• Modeling suggests ~150 mg subQ once monthly could achieve brain concentrations comparable to trontinemab’s phase III dose; at 150 mg/mL, the target injection volume is ~1 mL.

• Development aims include lower-volume subQ dosing, improved local tolerability, reduced anemia and potentially very low ARIA rates; these remain goals pending clinical data.

Clinical development plan

• The phase I/II study is designed to enable phase III: healthy-volunteer single ascending dose, early Alzheimer’s patient multiple ascending dose, then expansion cohorts to characterize safety and select dose(s).

• Healthy-volunteer data are targeted for mid-2027, including subQ absorption, half-life, CSF levels as an indicator of shuttle activity, and initial safety and tolerability.

• Interim patient proof-of-concept data are targeted for late 2027 or Q1 2028; PET plaque clearance in the first one or two cohorts is the main readout, with 5–10 patients expected to provide a precise read on clearance speed and depth.

• Early cohorts will provide an initial ARIA read; expansion cohorts are intended to characterize the safety profile over time.

• Initial development will focus on early Alzheimer’s disease; preclinical disease is a longer-term opportunity, with safety, tolerability and convenience especially important for potentially asymptomatic patients.