Rallybio (RLYB) Status Update summary

Program and Manufacturing Updates

• Manufacturing process enhancements for RLYB116 completed in 3Q 2024 are expected to improve tolerability, with host cell protein impurities effectively eliminated using a new purification process and supported by analytical data.

• The new process allows for higher dosing, with confidence in tolerability at doses above 100 mg.

• Residual host cell protein is now at very low levels, and similar proteins have been well tolerated in other biologics.

Clinical and Biomarker Data

• Phase 1 MAD study showed >99% reduction in free C5 at 24 hours and sustained reductions of 93% at Day 29, with no severe adverse events observed.

• Biomarker analyses indicate RLYB116 achieved greater complement inhibition than initially reported due to assay overestimation of free C5.

• Discrepancy in free C5 assay results was traced to assay limitations, leading to underestimation of complement inhibition.

• Hemolysis assays confirm RLYB116's potency is comparable or superior to approved C5 inhibitors like zilucoplan and ravulizumab.

• The threshold for complete complement inhibition is ~0.5 μg/mL free C5, but the clinical assay overestimated this by ~10-fold.

Next Steps and Clinical Plans

• A confirmatory PK/PD study in healthy volunteers is planned for Q2 2025 to demonstrate improved tolerability and confirm complete, sustained C5 inhibition.

• Doses of 150 mg and 225 mg once weekly will be assessed, with both hemolysis and free C5 assays used for pharmacodynamic evaluation.

• Initial data from the confirmatory study is expected by year-end 2025.

• Manufacturing improvements are expected to further enhance safety and patient experience.