The C1q inhibitor ANX009 was found to be safe, tolerable, and have favorable pharmacology in a phase 1 clinical trial with healthy individuals, supporting its advancement into testing its efficacy in patients with complement-mediated autoimmune disorders such as cold agglutinin disease (CAD).

These trial results were presented as a poster at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition on December 13, 2021.

“We are pleased to present these data at ASH, which further support our approach of targeting C1q in order to fully block the downstream components of the complement pathway,” Sanjay Keswani, MBBS, FRCP, executive vice president and chief medical officer of Annexon said.

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All doses tested in the study were well-tolerated with no serious adverse events, adverse events leading to discontinuation, dose-limiting toxicities, or drug-related safety signals being observed. However, mild and transient local injection site reactions were observed.

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In the single ascending dose (SAD) portion of the clinical trial, a dose-response relationship was observed. The 2 lowest dose levels resulted in a negligible reduction in C1q levels, while the third dose led to a maximum 80% reduction in C1q, and the fourth and highest dose led to a full reduction in C1q.

The maximum reduction was observed at 48 hours after the third dose level and through 72 hours for the highest dose. In the multiple ascending dose (MAD) portion of the trial, a full reduction of C1q was also observed and was maintained for 4 days after the final dose was administered. The reduction was observed in both a daily-dosing cohort and a twice-weekly-dose cohort.

“ANX009 was shown to be well-tolerated with complete and sustained C1q inhibition, supporting its continued clinical advancement,” Keswani said.

During the phase 1 clinical trial (NCT04535752), 48 healthy volunteers were recruited to participate in 1 of 4 SAD cohorts or 1 of 2 MAD cohorts. Volunteers were randomized (6:2) to receive subcutaneous ANX009 or a placebo.

One MAD cohort received daily doses of ANX009 for 7 days while the other received twice-weekly doses for a total of 4 doses. In addition to safety and tolerability assessments, serum pharmacokinetics, pharmacodynamics, and an ex vivo of C1q activity were also measured.


Grover A, Teigler J, Radomile E, et al. Safety, tolerability, and clinical pharmacology of ANX009, an inhibitory antibody Fab fragment against C1q, administered subcutaneously to healthy volunteers. Poster presented at: American Society of Hematology (ASH) Annual Meeting & Exposition 2021: December 13, 2021; Atlanta, Georgia.

Annexon Biosciences announces clinical and preclinical data highlighting potential of complement-targeting programs at the 63rd ASH Annual Meeting & Exposition. News Release. Annexon Biosciences; December 13, 2021.