Annexon, Inc. is a clinical-stage biopharmaceutical company that is pioneering a new class of complement medicines to address the unmet needs of patients suffering from debilitating autoimmune and neurodegenerative diseases. The company's innovative approach targets the classical complement pathway, a core component of the immune system, to suppress excessive or aberrant activity that drives chronic inflammation and tissue damage.
Business Overview and Financials
Annexon was founded in March 2011 by the late Dr. Ben Barres, former member of the National Academy of Sciences and Chair of Neurobiology at Stanford University, and Dr. Arnon Rosenthal, a renowned scientist and industry executive. The company's initial focus was on performing research and development activities, hiring personnel, and raising capital to support these efforts. Since its inception, Annexon has faced the challenge of developing its proprietary platform to identify and characterize the role of the classical complement pathway in autoimmune, neurodegeneration, and ophthalmology diseases.
In its early years, Annexon had to establish its scientific expertise and secure funding through the sale of equity securities to support its research and development efforts. A significant milestone for the company was its initial public offering in July 2020, which provided additional capital to advance its pipeline of product candidates. However, Annexon has continued to face challenges in successfully completing clinical trials and obtaining regulatory approvals for its product candidates.
The company has no products approved for sale and has not generated any revenue from product sales to date. Annexon has incurred net losses each year since its founding, with net losses of $134.2 million and $138.2 million for the years ended December 31, 2023 and 2024, respectively. Despite these challenges, Annexon has made progress in developing its pipeline, demonstrating robust target engagement in the body, brain, and eye, and achieving clinical proof of concept in multiple diseases.
The company's pipeline is led by three flagship programs focused on complement-mediated diseases of the body, brain, and eye. Annexon's lead candidate, ANX005, is being developed as a potential first-in-class treatment for Guillain-Barré Syndrome (GBS), a rare and serious autoimmune disorder. The company's second lead program, ANX007, is advancing as the first potential neuroprotective therapy for geographic atrophy (GA), a leading cause of vision loss in the elderly. Annexon is also developing ANX1502, a novel oral small molecule inhibitor of the classical complement pathway, for autoimmune indications.
Financials
Annexon reported a net loss of $138.2 million for the full year 2024, compared to a net loss of $134.2 million in 2023. The company's research and development expenses increased by 5% year-over-year to $119.5 million in 2024, reflecting the advancement of its late-stage clinical programs. General and administrative expenses rose 16% to $34.6 million, as Annexon continued to bolster its commercial, medical affairs, and health economics capabilities in preparation for potential product launches.
For the most recent quarter (Q3 2024), Annexon reported no revenue and a quarterly net loss of $48.6 million. The company has not provided information on operating cash flow or free cash flow for either the full year or the most recent quarter.
Liquidity
As of December 31, 2024, Annexon had $312 million in cash, cash equivalents, and short-term investments, providing a runway into the second half of 2026 to achieve key milestones across its portfolio. The company's current ratio and quick ratio are both 10.37, indicating a strong short-term liquidity position. During 2024, Annexon raised $116.8 million in net proceeds from the sale of common stock and pre-funded warrants, and an additional $42.8 million through its at-the-market (ATM) offering program.
Guillain-Barré Syndrome (GBS) Advancing ANX005 as a Potential First Targeted Therapy
Annexon's lead candidate, ANX005, is an investigational monoclonal antibody designed to inhibit C1q, the initiating molecule of the classical complement cascade, for the treatment of GBS. GBS is a rare and devastating autoimmune disease that is the leading cause of acute neuromuscular paralysis worldwide, with no approved therapies in the United States.
In 2024, Annexon reported positive topline results from a pivotal Phase 3 trial of ANX005 in 241 GBS patients. The study met its primary endpoint, demonstrating a 2.4-fold improvement in the GBS Disability Scale (GBS-DS) at week 8 compared to placebo (p<0.01). Key secondary endpoints also showed that ANX005 helped patients recover sooner, with rapid increases in muscle strength and more complete functional recovery through 6 months. Importantly, ANX005-treated patients required fewer days on artificial ventilation and achieved independence in walking or being off ventilation faster than those receiving placebo.
To further support the potential efficacy of ANX005 in a Western patient population, Annexon completed a real-world evidence (RWE) study that matched 79 patients from the Phase 3 trial to a cohort from the International GBS Outcomes Study (IGOS). This RWE analysis found that ANX005 provided rapid and greater improvements in muscle strength and disability scores compared to standard of care treatments like intravenous immunoglobulin (IVIg) or plasma exchange (PE).
Annexon plans to meet with the FDA in the first half of 2025 for a pre-BLA meeting and is targeting submission of a Biologics License Application (BLA) for ANX005 in GBS soon thereafter. The company's GBS program has received Fast Track and Orphan Drug designations from the FDA, as well as Orphan designation from the European Medicines Agency (EMA).
Geographic Atrophy (GA) Establishing a Global Registration Path for ANX007
Annexon's second lead program, ANX007, is a novel antigen-binding fragment (Fab) formulated for intravitreal administration, designed to block C1q and protect against complement-mediated damage in the eye. ANX007 is being developed as the first potential neuroprotective therapy for GA, a leading cause of vision loss in the elderly that affects over 8 million people globally and currently has no approved treatments.
In a completed Phase 2 ARCHER trial, ANX007 demonstrated significant protection against vision loss in GA patients, as measured by best-corrected visual acuity (BCVA). Importantly, ANX007 also showed substantial preservation of central retinal photoreceptors, which are critical for visual acuity. These results positioned ANX007 as the only investigational therapy in GA to date that has shown significant vision protection in both standard and low light conditions.
Building on these promising Phase 2 data, Annexon initiated the pivotal Phase 3 ARCHER II trial in 2024. The global, sham-controlled, double-masked study is expected to enroll approximately 630 GA patients, with the primary endpoint focused on prevention of 15-letter BCVA loss. Topline results from ARCHER II are anticipated in the second half of 2026.
Notably, ANX007 has received Priority Medicines (PRIME) designation from the EMA, providing early and proactive support for the program's development as a potentially major therapeutic advance in GA. Annexon is no longer planning a second injection-controlled Phase 3 trial, as the company believes the single ARCHER II study can support global registration in both the U.S. and Europe.
Autoimmune Indications Advancing ANX1502, a First-in-Kind Oral C1s Inhibitor
Annexon's third flagship program is ANX1502, a novel oral small molecule inhibitor of the classical complement pathway that the company believes is first-in-kind. The company is initially evaluating ANX1502 in a proof-of-concept study in patients with cold agglutinin disease (CAD), an autoimmune hemolytic anemia driven by excessive classical complement activation.
In a completed Phase 1 trial, ANX1502 was generally well-tolerated and demonstrated target engagement, supporting its advancement into the ongoing CAD study. Annexon expects to report proof-of-concept data for ANX1502 in CAD in the first quarter of 2025. If successful, the company plans to further evaluate the oral C1s inhibitor in a range of serious complement-mediated autoimmune diseases.
Risks and Potential Catalysts
As a clinical-stage biopharmaceutical company, Annexon faces the inherent risks associated with drug development, including the potential for delays or failures in its clinical trials, regulatory approvals, and commercialization efforts. The company's reliance on third-party manufacturers and contract research organizations also exposes it to supply chain and operational challenges.
However, Annexon has demonstrated robust target engagement and proof-of-concept data across its portfolio, positioning the company for several potential catalysts in the near-to-medium term. Key upcoming milestones include:
- ANX005 in GBS: Pre-BLA meeting with the FDA in 1H 2025, followed by BLA submission - ANX007 in GA: Completion of enrollment for the Phase 3 ARCHER II trial in 2H 2025, with topline data expected in 2H 2026 - ANX1502 in autoimmune diseases: Proof-of-concept data in cold agglutinin disease expected in 1Q 2025
Annexon's strong financial position, with approximately $312 million in cash and investments as of the end of 2024, provides the runway to advance these late-stage programs and continue building its pipeline of novel complement therapeutics.
Conclusion
Annexon is at the forefront of developing a new class of complement medicines to address the devastating effects of aberrant immune system activation in a range of autoimmune and neurodegenerative diseases. The company's lead programs in GBS, GA, and autoimmune indications have demonstrated promising results, positioning Annexon for potential near-term regulatory filings and approvals that could transform the treatment landscape for these debilitating conditions. With a robust clinical pipeline, a strong financial foundation, and an experienced management team, Annexon appears well-positioned to continue pioneering innovative solutions for patients in need.