Slide 1: ANX1502 First In Human SAD / MAD Data Overview
ANX1502 First In Human SAD / MAD Data Overview December 2023 Exhibit 99.4
Slide 2: Overview of ANX1502 Program
Overview of ANX1502 Program Potential first oral small molecule inhibitor of the classical pathway in development, targeting the active form of C1s Successfully completed single and multidose Phase I study in healthy volunteers with liquid suspension formulation Observed desired PK (well above minim
Slide 3: ANX1502: First Oral, Small Molecule Inhibitor of Classical Complement Pathway in Development
ANX1502: First Oral, Small Molecule Inhibitor of Classical Complement Pathway in Development Orally administered prodrug ANX1502 which releases the active moiety ANX1502-AM* Targeting active form of C1s responsible for transmitting classical pathway activation from C1q Potent and selective inhibitor
Slide 4: C1q binding to a specific surface substrate activates C1s
C1q binding to a specific surface substrate activates C1s Modified from Sharp et al, PNAS, 2019 C4b C4 C4a C1q C1 complex C1s C1r C4d cleavage fragment released into serum Following C1q Binding to a Specific Target Surface, ANX1502-AM* Observed to Inhibit Activated C1s to Block the Classical Cascade
Slide 5: Minimum Target Drug Level (100 nM) ANX1502-AM for Robust Functional Inhibition of Classical Complement Pathway
Minimum Target Drug Level (100 nM) ANX1502-AM* for Robust Functional Inhibition of Classical Complement Pathway ANX1502-AM* demonstrated robust functional inhibition of classical pathway (IC50 = 5 nM) Comparable to ANX005 and sutimlimab In vitro hemolysis assay w/ high serum (30%) Normal sigmoidal d
Slide 6: Achieved Objectives for ANX1502 Ph1 Program (Healthy Volunteers)
Achieved Objectives for ANX1502 Ph 1 Program (Healthy Volunteers) Demonstrate favorable tolerability of ANX1502 in initial liquid suspension formulation Achieve target levels of active drug consistent with BID dosing Upside: demonstrate initial in vivo pharmacodynamic (PD) signal with biomarkers of
Slide 7: ANX1502 Phase 1 Study Design (Healthy Volunteers)
ANX1502 Phase 1 Study Design (Healthy Volunteers) Single Ascending Dose (SAD): 6 ANX1502 + 2 placebo subjects per dose cohort Doses from 25 mg to 1050 mg evaluated Multiple Ascending Dose (MAD): 9 ANX1502 + 3 placebo subjects per dose cohort Twice daily dosing for 2 weeks (BID) Doses from 200 mg BID
Slide 8: ANX1502 Suspension Formulation Generally Well-Tolerated Across SAD & MAD Cohorts
ANX1502 Suspension Formulation Generally Well-Tolerated Across SAD & MAD Cohorts in Healthy Volunteers Manageable GI tolerability issues ANX1502 generally safe and well tolerated through the highest dose level tested All treatment-emergent adverse events (TEAEs) mild or moderate Most frequent TEAEs
Slide 9: SAD Data: Target Concentration Achieved at Single Doses of 525-1050 mg
SAD Data: Target Concentration Achieved at Single Doses of ANX1502 of 525-1050 mg Dose-proportional PK (AUC) in SAD cohorts across 25 mg – 525 mg cohorts Mean target drug level of 100 nM at 12h observed at single doses > 525 mg Enabled BID dosing regimen in MAD study as planned PK Results from SAD
Slide 10: Serum C4d as a Biomarker of C1s Activation In Vivo
Serum C4d as a Biomarker of C1s Activation In Vivo C1q binding to specific surface substrate activates C1s Activated C1s cleaves C4 to into several fragments Modified from Sharp et al, PNAS, 2019 C4b C4 C4a C1q C1 complex C1s C1r C4d cleavage fragment measurable in serum In vivo activation of C1s le
Slide 11: C4d Previously Validated as a Biomarker of C1 Inhibition with ANX005
C4d Previously Validated as a Biomarker of C1 Inhibition with ANX005 in a Classical Complement Driven Disease Subject A Subject B Subject C Blocked C1q Reduced Disease Biomarker ANX005 blocked C1q, reduced bilirubin (disease-specific biomarker) and decreased serum C4d in Cold Agglutin Patients (CAD)
Slide 12: SAD PK/PD: ANX1502 Suppressed C4d Serum Levels in Healthy Volunteers
SAD PK/PD: ANX1502 (Single Doses of 525–1025 mg) Suppressed C4d Serum Levels in Healthy Volunteers w/ Higher than Median Baseline C4d C4d Levels Did Not Change in Placebo Subjects (n=10) Drop in C4d in Subjects with Higher Baseline C4d Levels is Associated with Drug Exposure (n=6) Drug levels C4d le
Slide 13: MAD Data: ANX1502 Dosing Achieved Target Trough Exposures in 14-Day MAD Cohorts
MAD Data: ANX1502 Dosing at 325 and 525mg BID Achieved Target Trough Exposures in 14-Day MAD Cohorts PK Results from MAD Dose-proportional PK (AUC) was observed in the MAD cohorts At 325 mg BID, and above, steady state drug levels above 100 nM achieved by Day 3 in all subjects At 525 mg BID, steady
Slide 14: ANX1502 Small Molecule Program Summary & Next Steps
ANX1502 Small Molecule Program Summary & Next Steps Observed targeted serum drug levels with suspension formulation of 1502 in healthy volunteers Obtained supportive PD data in subjects with higher C4d baseline measures Data support advancing tablet formulation of 1502 into clinic for assessing effi