Annexon, Inc. reported progress across its broad portfolio of complement therapies and outlined its focus on four programs to support its advancement to a late-stage biopharmaceutical company developing first-in-class treatments for complement-mediated diseases of the body, brain and eye. Annexon has prioritized resources and execution of late-stage development of its four programs: Guillain-Barré syndrome, Huntington's disease, geographic atrophy and its first-in-kind oral small molecule, ANX1502. In so doing, Annexon's goal is to create near-term value for patients, physicians and stakeholders with the achievement of the following objectives by the end of 2023: Complete expanded enrollment in its ongoing pivotal Phase 3 trial for ANX005 in patients with GBS – the first placebo-controlled trial in this indication in nearly 40 years; Initiate a pivotal Phase 2/3 trial for ANX005 in patients with HD – the first complement inhibitor in development to treat a brain disorder; Demonstrate clinical efficacy in an ongoing Phase 2 trial for ANX007 in patients with GA – the first up- and downstream complement approach for this indication; Initiate a clinical proof-of-concept trial with ANX1502 and expand into additional autoimmune indications – the first oral small molecule therapy targeting classical complement.

Program Progress: ANX005 Pivotal Phase 3 Trial for GBS Underway: Annexon is evaluating ANX005, a monoclonal antibody (mAb) designed to fully inhibit C1q and the entire classical complement pathway, in a randomized, double-blind, placebo-controlled Phase 3 trial in patients with GBS. GBS is an autoimmune condition with no FDA-approved therapies, and where maximum suppression of C1q and the classical cascade early in the disease process may act to rapidly prevent nerve damage and irreversible neurological disability. Following a productive engagement with the FDA regarding the statistical analysis plan for the ongoing pivotal trial, the company increased the study population by approximately 40 patients for a total of 220 patients.

Expanded enrollment is expected to be completed in the second half of 2023 with pivotal data anticipated in the first half of 2024. Initiation of a Pivotal Trial for ANX005 for HD Planned in 2023:Annexon successfully completed a Phase 2 clinical trial in 2022 in patients with HD, a slowly progressing, inherited and fatal neurodegenerative disease that leads to excessive synapse loss and neuronal damage. Following Phase 2 trial results demonstrating benefit in clinical outcomes in HD patients and a productive engagement with the FDA, the company plans to advance ANX005 into a randomized, double-blind, placebo-controlled Phase 2/3 pivotal trial for patients with HD in 2023.

ANX007 Phase 2 Trial in GA On-track for Initial Data in Mid-2023: ANX007 is being evaluated in a global Phase 2 clinical trial in patients with GA, the leading cause of blindness resulting from damaged and dying retinal cells. ANX007 is designed to block C1q locally in the eye, to provide more complete protection against excess classical complement activity, a key driver of disease. Enrollment in the trial is complete and the company anticipates reporting initial data in mid-2023, with additional data to be presented after the conclusion of the six-month off-treatment period by the end of 2023.

Additionally, Annexon is continuing to collaborate with DelSiTech to further optimize ANX007 for an extended-release formulation designed to enable less frequent administration. ANX1502 Achieved Target Drug Levels and was Well-Tolerated in Phase 1 Single-Ascending Dose (SAD) Trial Preliminary Data; Advancing into Multiple Clinical Trials in 2023:Annexon is evaluating ANX1502 in an ongoing Phase 1 SAD trial in healthy volunteers. In the SAD trial, a single dose of ANX1502 has achieved target drug levels in plasma in patients dosed at 450 mg, consistent with twice daily dosing.

Additionally, ANX1502 has been generally well-tolerated with no safety signals observed. The SAD trial is ongoing to identify the maximum tolerated dose, and Annexon is preparing to initiate a multiple-ascending dose (MAD) study of ANX1502 in the first half of 2023, as well as a proof of concept study in 2023 in patients with cold agglutinin disease (CAD), which is supported by positive data generated by ANX005 in CAD patients. Preliminary Phase 2a Data with ANX005 in Amyotrophic Lateral Sclerosis (ALS) Show Slowing of Disease Progression During Treatment; Full Data Expected in 2023: ANX005 is being evaluated in a Phase 2a signal-finding trial in patients with ALS, a fatal neurodegenerative disorder characterized by loss of central and peripheral motor neurons.

Preliminary data (n=8) showed that treatment with ANX005 has resulted in a reduction in neurofilament light and slowing of disease progression, as measured by reductions in revised ALS functional rating scores, during the initial 12-week on-treatment period, followed by an increase in disease progression while off treatment. Deprioritizing wAIHA to Focus on Diseases with a Clearly Defined Role for C1q Inhibition: Annexon completed its Phase 2 signal-finding trials in two types of autoimmune hemolytic anemia, CAD and warm autoimmune hemolytic anemia (wAIHA). ANX005 achieved full target engagement and blocked complement deposition on red blood cells in both CAD and wAIHA.

ANX005 improved clinical outcomes for the CAD patients (n=3) but demonstrated a mixed effect on hemolysis and anemia in wAIHA patients (n=5). The company's enrichment strategy selected patients with signs of excess complement activation; however, patients enrolled exhibited heterogeneity in other factors contributing to disease. Following an assessment of the market opportunity in wAIHA and a range of additional autoimmune indications, Annexon has determined not to advance development in wAIHA.

The company intends to evaluate its anti-C1q drug candidates, including ANX1502, in indications where classical complement is an understood driver of disease, such as CAD and MMN. Data from Signal-finding Trial of ANX009 for Lupus Nephritis (LN) Expected in the First Half of 2023: The company's Phase 1b signal-finding trial of ANX009 using a precision medicine approach for patients with LN who have high baseline complement activity is underway. LN is an autoimmune disease for which pathogenic autoantibodies against C1q enhance activity and uniquely amplify kidney inflammation and damage.

ANX009 is a subcutaneously administered agent designed to selectively inhibit C1q in the vascular space for use as a chronic treatment. Enrollment in the trial is ongoing with multiple patients dosed and data are expected in the first half of 2023. Continued Progress with ANX105 in Phase 1 SAD Study: Annexon is evaluating ANX105, its next-generation full-length mAb, in a Phase 1 SAD study in healthy volunteers.

Enrollment is ongoing and initial data are expected in 2023.