PART I—FINANCIAL INFORMATION [Financial Statements (Unaudited)](index=4&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) For the three months ended March 31, 2025, Annexon reported a net loss of $54.4 million, a significant increase from the $25.2 million loss in the same period of 2024, primarily driven by a 130% rise in R&D expenses [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2025, the company's total assets were $303.0 million, a decrease from $350.1 million at the end of 2024, mainly due to a reduction in short-term investments Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 (Unaudited) | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $97,122 | $49,498 | | Short-term investments | $166,574 | $262,519 | | Total current assets | $268,162 | $316,461 | | **Total assets** | **$303,027** | **$350,071** | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $33,547 | $30,512 | | **Total liabilities** | **$59,239** | **$56,966** | | **Total stockholders' equity** | **$243,788** | **$293,105** | [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) For the first quarter of 2025, Annexon reported a net loss of $54.4 million, or $0.37 per share, more than double the net loss of $25.2 million, or $0.21 per share, in the same period of 2024 Statement of Operations Summary (in thousands, except per share data) | Metric | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $48,179 | $20,963 | | General and administrative | $9,226 | $7,609 | | Total operating expenses | $57,405 | $28,572 | | Loss from operations | $(57,405) | $(28,572) | | **Net loss** | **$(54,356)** | **$(25,176)** | | **Net loss per share, basic and diluted** | **$(0.37)** | **$(0.21)** | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) In the first three months of 2025, net cash used in operating activities was $50.1 million, up from $28.3 million in the prior-year period, while investing activities provided $97.6 million in cash Cash Flow Summary (in thousands) | Activity | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(50,055) | $(28,267) | | Net cash provided by (used in) investing activities | $97,620 | $(77,302) | | Net cash provided by financing activities | $59 | $32,412 | | **Increase (decrease) in cash, cash equivalents and restricted cash** | **$47,624** | **$(73,157)** | [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes detail the company's financial position and operations, including an accumulated deficit of $765.1 million and sufficient cash to fund operations for at least the next twelve months - As of March 31, 2025, the company had an accumulated deficit of **$765.1 million** and cash, cash equivalents, and short-term investments of **$263.7 million**[28](index=28&type=chunk) - Management projects that existing cash and investments will fund operating expenses and capital requirements for at least twelve months from the financial statement issuance date[29](index=29&type=chunk) - In March 2024, the company initiated a new At-the-Market (ATM) program for up to **$100.0 million**; as of March 31, 2025, approximately **$95.4 million** remained available under this program[61](index=61&type=chunk) - Total unrecognized stock-based compensation cost related to unvested stock options was **$39.5 million** as of March 31, 2025, expected to be recognized over a weighted-average period of **3.2 years**[71](index=71&type=chunk) - Unrecognized stock-based compensation expense for unvested RSUs was **$4.7 million** as of March 31, 2025, expected to be recognized over a weighted-average period of **2.4 years**[73](index=73&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=24&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the significant increase in operating expenses, particularly a 130% rise in R&D costs to $48.2 million in Q1 2025, driven by manufacturing activities for the tanruprubart BLA submission and the ANX007 program - The company is advancing three priority programs: tanruprubart for Guillain-Barré Syndrome (GBS), ANX007 for Geographic Atrophy (GA), and ANX1502 for autoimmune indications[93](index=93&type=chunk) - Key upcoming milestones include a targeted FDA meeting in Q2 2025 for tanruprubart's BLA, completion of ANX007 Phase 3 enrollment in Q3 2025 (topline data in H2 2026), and ANX1502 proof-of-concept data in mid-2025[93](index=93&type=chunk)[95](index=95&type=chunk) Operating Results Comparison (in thousands) | Expense Category | Q1 2025 | Q1 2024 | Change ($) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Research and development | $48,179 | $20,963 | $27,216 | 130% | | General and administrative | $9,226 | $7,609 | $1,617 | 21% | | **Total operating expenses** | **$57,405** | **$28,572** | **$28,833** | **101%** | - The **130% increase** in R&D expenses was primarily due to a **$14.1 million** increase in contract manufacturing for tanruprubart BLA preparation and ANX007 technology transfer, plus higher personnel and clinical trial costs[107](index=107&type=chunk) - As of March 31, 2025, the company had **$263.7 million** in cash, cash equivalents, and short-term investments, which is expected to fund operations into the second half of 2026[111](index=111&type=chunk)[119](index=119&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=34&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This section is not applicable for the reporting period - The company has indicated that quantitative and qualitative disclosures about market risk are not applicable[130](index=130&type=chunk) [Controls and Procedures](index=34&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, including the CEO and CFO, evaluated the company's disclosure controls and procedures and concluded they were effective as of March 31, 2025 - The CEO and CFO concluded that as of the end of the quarter, the company's disclosure controls and procedures are effective[131](index=131&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that materially affected, or are reasonably likely to materially affect, these controls[132](index=132&type=chunk) PART II—OTHER INFORMATION [Legal Proceedings](index=35&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings but may become involved in various legal matters that arise in the ordinary course of business - As of the report date, the company is not involved in any material legal proceedings[134](index=134&type=chunk) [Risk Factors](index=35&type=section&id=Item%201A.%20Risk%20Factors) The company outlines significant risks to its business, primarily related to its clinical-stage status, financial condition, and dependence on the success of its product candidates - The company is a clinical-stage biopharmaceutical firm with a history of significant losses (**$765.1 million** accumulated deficit as of March 31, 2025) and expects to incur losses for the foreseeable future[138](index=138&type=chunk)[139](index=139&type=chunk) - Substantial additional financing is required to achieve goals, and failure to obtain capital could force delays, reductions, or termination of development programs[140](index=140&type=chunk) - The business is heavily dependent on the successful development, regulatory approval, and commercialization of its product candidates, particularly tanruprubart, ANX007, and ANX1502[153](index=153&type=chunk) - The company relies on third-party suppliers for manufacturing and does not have its own manufacturing capabilities, creating dependence and risk related to cGMP compliance, supply chain disruptions, and quality control[217](index=217&type=chunk) - The company conducts clinical trials outside the United States, and there is a risk that the FDA and other regulators may not accept data from these trials, which could require additional, costly studies[206](index=206&type=chunk)[209](index=209&type=chunk) - Cybersecurity threats, including ransomware and phishing attacks, pose a significant risk to the company's IT systems and sensitive data, which could lead to operational disruptions, regulatory actions, and financial loss[361](index=361&type=chunk)[363](index=363&type=chunk)[364](index=364&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=116&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) There were no unregistered sales of equity securities during the reporting period - No unregistered sales of equity securities occurred during the quarter[381](index=381&type=chunk) [Other Information](index=116&type=section&id=Item%205.%20Other%20Information) This section discloses the adoption of a Rule 10b5-1 trading plan by a company director, Dr. William H. Carson, on March 17, 2025 - On March 17, 2025, Director William H. Carson, M.D., adopted a Rule 10b5-1 trading plan for the purchase of **28,805 shares** of common stock, with an expiration date of January 30, 2026[385](index=385&type=chunk) [Exhibits](index=117&type=section&id=Item%206.%20Exhibits) This section provides an index of the exhibits filed with the Form 10-Q, including CEO and CFO certifications and Inline XBRL documents - The report includes required certifications from the Principal Executive Officer and Principal Financial Officer, as well as XBRL data files[388](index=388&type=chunk)

[Q1 2025 Overview and Corporate Update](index=1&type=section&id=Annexon%20Reports%20First%20Quarter%202025%20Financial%20Results%2C%20Portfolio%20Progress%20and%20Key%20Anticipated%20Milestones) Annexon reported significant progress across its late-stage clinical portfolio in Q1 2025, ending the quarter with **$263.7 million** in cash and investments, providing an operational runway into the second half of 2026 - Annexon is advancing a late-stage clinical platform of novel therapies targeting classical complement-mediated neuroinflammatory diseases of the body, brain, and eye[1](index=1&type=chunk) - The company's CEO, Douglas Love, highlighted that the C1 platform has produced multiple late-stage programs showing positive patient outcomes by stopping harmful neuroinflammation[2](index=2&type=chunk) Key Anticipated Milestones | Program | Milestone | Anticipated Timing | | :--- | :--- | :--- | | **Tanruprubart (GBS)** | FDA Meeting for BLA Submission | Q2 2025 | | **Tanruprubart (GBS)** | Initiation of Open-Label FORWARD Study | Q2 2025 | | **ANX007 (GA)** | Completion of Phase 3 ARCHER II Enrollment | Q3 2025 | | **ANX007 (GA)** | Pivotal Topline Data | H2 2026 | | **ANX1502 (CAD)** | Completion of Proof-of-Concept Trial | Mid-2025 | - As of March 31, 2025, the company has **$263.7 million** in cash, cash equivalents, and short-term investments, which is expected to fund operations into the second half of 2026[1](index=1&type=chunk)[2](index=2&type=chunk) [Clinical Program Updates](index=1&type=section&id=Recent%20Corporate%20and%20Clinical%20Program%20Updates) Annexon is advancing its three flagship programs: Tanruprubart for Guillain-Barré Syndrome (GBS), ANX007 for Geographic Atrophy (GA), and the oral inhibitor ANX1502 for autoimmune diseases [Tanruprubart (ANX005) in Guillain-Barré Syndrome (GBS)](index=1&type=section&id=Tanruprubart%20(ANX005)%20in%20Guillain-Barr%C3%A9%20Syndrome%20(GBS)) Tanruprubart, a first-in-kind monoclonal antibody for GBS, is advancing towards a Biologics License Application (BLA) submission, with a key FDA meeting scheduled for Q2 2025 - Tanruprubart is a first-in-kind monoclonal antibody designed to block C1q with a single infusion to halt neuroinflammation in GBS, a condition affecting approximately **150,000 people worldwide annually**[3](index=3&type=chunk) - A meeting with the FDA's Center for Drug Evaluation and Research (CDER) is scheduled for **Q2 2025**, preceding the planned BLA submission[1](index=1&type=chunk)[9](index=9&type=chunk) - The open-label FORWARD study will initiate in **Q2 2025** to provide experience with tanruprubart to patients and physicians in the United States, Canada, and Europe[1](index=1&type=chunk)[9](index=9&type=chunk) [ANX007 in Geographic Atrophy (GA)](index=3&type=section&id=ANX007%20in%20Dry%20Age-Related%20Macular%20Degeneration%20(AMD)%20Patients%20with%20Geographic%20Atrophy%20(GA)) ANX007 is being developed as a potential first-in-kind, vision-preserving treatment for dry AMD with Geographic Atrophy (GA), with enrollment in the pivotal Phase 3 ARCHER II trial expected to complete in Q3 2025 - ANX007 is a non-pegylated antigen-binding fragment (Fab) designed to block C1q locally in the eye, targeting a leading cause of blindness affecting over **eight million people globally**[5](index=5&type=chunk) - Enrollment in the global, pivotal Phase 3 ARCHER II trial is expected to complete in **Q3 2025**[1](index=1&type=chunk)[9](index=9&type=chunk) - Pivotal topline data from the ARCHER II trial is expected in the **second half of 2026**[1](index=1&type=chunk)[9](index=9&type=chunk) [ANX1502 for Autoimmune Conditions](index=3&type=section&id=ANX1502%20for%20Autoimmune%20Conditions) ANX1502 is a first-in-kind oral small molecule C1s inhibitor being developed for autoimmune conditions, with its proof-of-concept study in cold agglutinin disease (CAD) expected to complete in mid-2025 - ANX1502 is an oral small molecule designed to inhibit C1s, a key enzyme in the classical complement cascade, offering a potential convenient treatment for antibody-mediated autoimmune diseases[6](index=6&type=chunk) - Completion of the proof-of-concept (POC) trial in up to seven patients with cold agglutinin disease (CAD) is anticipated in **mid-2025**[1](index=1&type=chunk)[9](index=9&type=chunk) [First Quarter 2025 Financial Results](index=3&type=section&id=First%20Quarter%202025%20Financial%20Results) For the first quarter of 2025, Annexon reported a net loss of **$54.4 million**, an increase from the **$25.2 million** loss in Q1 2024, primarily due to a significant rise in R&D expenses to **$48.2 million** [Financial Summary](index=3&type=section&id=Financial%20Summary) In Q1 2025, Annexon's R&D expenses more than doubled to **$48.2 million** from **$21.0 million** in Q1 2024, resulting in a net loss of **$54.4 million**, or **$0.37** per share - Cash, cash equivalents, and short-term investments totaled **$263.7 million** as of March 31, 2025, which is expected to fund planned operating expenses into the second half of 2026[1](index=1&type=chunk)[9](index=9&type=chunk) Q1 2025 vs. Q1 2024 Financial Highlights | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | **R&D Expenses** | $48.2 million | $21.0 million | | **G&A Expenses** | $9.2 million | $7.6 million | | **Net Loss** | $54.4 million | $25.2 million | | **Net Loss Per Share** | $0.37 | $0.21 | [Condensed Consolidated Statements of Operations](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20(Unaudited)) The unaudited statement of operations for the three months ended March 31, 2025, details a total operating expense of **$57.4 million**, leading to a net loss of **$54.4 million**, or **$0.37** per share Statement of Operations (in thousands, except per share data) | | Three Months Ended March 31, | | :--- | :--- | :--- | | | **2025** | **2024** | | **Operating expenses:** | | | | Research and development | $48,179 | $20,963 | | General and administrative | $9,226 | $7,609 | | **Total operating expenses** | **$57,405** | **$28,572** | | **Loss from operations** | **($57,405)** | **($28,572)** | | Interest and other income, net | $3,049 | $3,396 | | **Net loss** | **($54,356)** | **($25,176)** | | **Net loss per share, basic and diluted** | **($0.37)** | **($0.21)** | [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets%20(Unaudited)) As of March 31, 2025, Annexon's balance sheet showed total assets of **$303.0 million**, a decrease from **$350.1 million** at year-end 2024, with total stockholders' equity at **$243.8 million** Balance Sheet Highlights (in thousands) | | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $97,122 | $49,498 | | Short-term investments | $166,574 | $262,519 | | **Total current assets** | **$268,162** | **$316,461** | | **Total assets** | **$303,027** | **$350,071** | | **Liabilities and Equity** | | | | Total current liabilities | $33,547 | $30,512 | | **Total liabilities** | **$59,239** | **$56,966** | | **Total stockholders' equity** | **$243,788** | **$293,105** | [About Annexon and Forward Looking Statements](index=3&type=section&id=About%20Annexon%20and%20Forward%20Looking%20Statements) Annexon is a biopharmaceutical company focused on developing first-in-kind treatments for serious neuroinflammatory diseases by targeting C1q, with its pipeline addressing unmet needs in autoimmunity, neurodegeneration, and ophthalmology - Annexon's therapeutic approach is centered on targeting C1q, the initiating molecule of the classical complement pathway, to stop neuroinflammation before it causes tissue damage[8](index=8&type=chunk)[10](index=10&type=chunk) - The company's pipeline addresses unmet needs in autoimmunity, neurodegeneration, and ophthalmology, aiming to help nearly **10 million people worldwide**[10](index=10&type=chunk) - This press release contains forward-looking statements regarding trial timelines, regulatory submissions, potential therapeutic benefits, and financial runway. These statements are not guarantees of future performance and are subject to risks described in the company's SEC filings[11](index=11&type=chunk)

Core Insights - Annexon, Inc. is advancing a late-stage clinical platform of novel therapies targeting classical complement-mediated neuroinflammatory diseases, with significant progress in its portfolio and financial results for Q1 2025 [1][2][9] Group 1: Clinical Development Updates - The FDA meeting for Tanruprubart (formerly ANX005), a potential treatment for Guillain-Barré Syndrome (GBS), is scheduled for Q2 2025 ahead of a planned Biologics License Application (BLA) submission [1][2] - The open-label Tanruprubart FORWARD study is set to initiate in Q2 2025, aimed at broadening patient and healthcare community experience in North America and Europe [1][8] - The Phase 3 ARCHER II trial for ANX007, targeting dry age-related macular degeneration (AMD) with geographic atrophy (GA), is on track for completion in Q3 2025, with pivotal topline data expected in the second half of 2026 [1][2][8] - Completion of the proof-of-concept trial for ANX1502, an oral C1s inhibitor for cold agglutinin disease, is anticipated by mid-2025 [1][2][8] Group 2: Financial Performance - As of March 31, 2025, the company reported $263.7 million in cash, cash equivalents, and short-term investments, providing a runway into the second half of 2026 [1][7] - Research and development expenses for Q1 2025 were $48.2 million, significantly higher than $21.0 million in Q1 2024, reflecting the advancement of priority programs [7][13] - General and administrative expenses increased to $9.2 million in Q1 2025 from $7.6 million in Q1 2024 [7][13] - The net loss for Q1 2025 was $54.4 million, or $0.37 per share, compared to a net loss of $25.2 million, or $0.21 per share, in Q1 2024 [7][13] Group 3: Market Potential and Strategic Positioning - Tanruprubart is positioned as the first potential therapy for GBS, addressing a significant unmet need with no FDA-approved treatments currently available [2][3] - ANX007 aims to be the first vision-preserving treatment for dry AMD with GA, potentially benefiting over eight million patients globally [2][5] - The company's innovative C1 platform is designed to halt harmful neuroinflammation, with a focus on addressing the unmet needs of nearly 10 million people worldwide [2][9]

Core Insights - The International Guillain-Barré Syndrome Outcomes Study (IGOS) presented real-world evidence showing improved outcomes with tanruprubart compared to current standards of care in matched patient populations [1][2] - Tanruprubart, a first-in-kind monoclonal antibody, is designed to block C1q to halt neuroinflammation and nerve damage in Guillain-Barré Syndrome (GBS) [2][3] - The drug has received Fast Track and Orphan Drug designations from the U.S. FDA and the European Medicines Agency for GBS treatment [5] Company Overview - Annexon, Inc. is focused on developing novel therapies for classical complement-mediated neuroinflammatory diseases affecting the body, brain, and eye [1][7] - The company aims to deliver innovative treatments targeting C1q to prevent tissue damage and loss in various neuroinflammatory conditions [7] - Annexon's pipeline includes investigational drug candidates addressing unmet needs in autoimmune, neurodegenerative, and ophthalmic diseases, potentially benefiting over 8 million people globally [7] Industry Context - GBS is a rare autoimmune disease with no FDA-approved therapies, characterized by rapid progression and severe weakness, often leading to paralysis [2][6] - The disease results in over 22,000 hospitalizations annually in the U.S. and Europe, contributing to significant morbidity and economic costs to the healthcare system [6] - The long-term burden of GBS has led to a multi-billion-dollar annual economic impact on the U.S. healthcare system [6]

Core Insights - Annexon, Inc. announced positive Phase 2 ARCHER trial results for ANX007, a novel therapy aimed at preserving vision in patients with dry age-related macular degeneration (AMD) and geographic atrophy (GA) [1][2][3] - The company is preparing for a Phase 3 trial, ARCHER II, which will enroll approximately 630 patients globally [1][10] Group 1: ANX007 and Its Mechanism - ANX007 is a first-in-kind, non-pegylated antigen-binding fragment designed to inhibit C1q locally in the eye, addressing neurodegeneration caused by classical complement pathway activation [3][4] - The therapy has shown significant vision preservation in clinical endpoints such as best corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) [3][6] - ANX007 has received Fast Track designation from the FDA and Priority Medicine (PRIME) designation in the EU, indicating its potential therapeutic advantage [5] Group 2: Clinical Trial Results - In the Phase 2 ARCHER trial, ANX007 demonstrated statistically significant protection against vision loss, with a time and dose-dependent effect observed [6][8] - The treatment effect was maintained during a six-month off-treatment period, suggesting a durable benefit [8] - ANX007 was well-tolerated, with no increase in choroidal neovascularization rates or retinal vasculitis events reported [8] Group 3: Future Developments - The Phase 3 ARCHER II trial aims to prevent ≥15-letter loss of BCVA, a well-established functional endpoint for ophthalmology drug approvals [10] - Topline data from the ARCHER II trial is expected in the second half of 2026 [10] - The trial will further assess safety and visual function outcomes, including low-luminance visual acuity and photoreceptor integrity [10]

Core Insights - The article discusses the investment analysis service provided by Biotech Analysis Central, focusing on pharmaceutical companies and offering a subscription model for in-depth research [1][2]. Company Overview - Annexon (NASDAQ: ANNX) is highlighted as a company of interest, particularly in relation to its technology for complement inhibition in Guillain-Barré syndrome (GBS) [2]. Service Features - The Biotech Analysis Central service includes a library of over 600 biotech investing articles, a model portfolio of more than 10 small and mid-cap stocks, live chat, and various analysis and news reports aimed at assisting healthcare investors [2].

Core Insights - Annexon, Inc. presented Phase 3 data for tanruprubart, a novel therapy for Guillain-Barré Syndrome (GBS), demonstrating rapid recovery and durable benefits for patients [1][5][6] - GBS affects over 150,000 people globally each year, with no FDA-approved treatments currently available [2][10] - Tanruprubart is a first-in-class monoclonal antibody that targets C1q to halt neuroinflammation and nerve damage in GBS patients [3][4] Clinical Trial Results - The Phase 3 trial involved 241 patients and showed that tanruprubart met its primary endpoint, with a 2.4-fold higher likelihood of better health status at Week 8 compared to placebo (p=0.0058) [5][6] - At Week 1, treated patients were 14-fold more likely to perform the Timed Up and Go (TUG) test and showed over a 2-point improvement on the Overall Neuropathy Limitation Scale (ONLS) [6][7] - By Week 26, twice the number of patients treated with tanruprubart fully recovered to normal compared to placebo [7] Real World Evidence - A Real World Evidence (RWE) study matched tanruprubart-treated patients with those receiving standard care (IVIg or PE), showing faster muscle strength recovery and more complete recovery with tanruprubart [7] Disease Education Campaign - Annexon launched the "Move GBS Forward™" campaign to raise awareness about GBS among healthcare providers, emphasizing the urgent need for prompt diagnosis and treatment [8][9] - The campaign aims to address the misunderstanding and misdiagnosis of GBS, which can lead to severe patient trauma [9] Company Overview - Annexon is focused on developing therapies that target classical complement-driven neurodegeneration, with a pipeline addressing autoimmune, neurodegenerative, and ophthalmic diseases [11] - The company aims to deliver innovative treatments to improve the lives of millions affected by serious neuroinflammatory diseases [11]

Oral Plenary Presentation on Tuesday, April 8 Features Phase 3 Data for ANX005, the First Potential Targeted Therapy for GBS, Showing Rapid and Durable Benefit Across Clinical Measures and Time Points Educational Symposium Focuses on Advancing GBS Care and Role of Classical Complement Pathway New Disease Education Campaign “Move GBS Forward” Draws Attention to Life-altering Physical and Mental Impact of GBS BRISBANE, Calif., April 03, 2025 (GLOBE NEWSWIRE) -- Annexon, Inc. (Nasdaq: ANNX), a biopharmaceutic ...

Product Development and Trials - Annexon is advancing ANX005 for Guillain-Barré Syndrome (GBS), with a Phase 3 trial showing improvement in muscle strength and functional recovery in 241 patients, targeting a Biologics License Application (BLA) submission in the first half of 2025[22]. - ANX007 is being developed for Geographic Atrophy (GA) associated with dry AMD, with a Phase 3 trial (ARCHER II) expected to enroll ~630 patients, aiming to prevent ≥15-letter loss of best corrected visual acuity (BCVA) and report topline data in the second half of 2026[23]. - ANX1502, a novel oral small molecule inhibitor, is in a proof-of-concept study for cold agglutinin disease (CAD), with data expected in mid-2025, aiming to provide a first-in-kind treatment for chronic autoimmune conditions[22]. - The company is evaluating ANX009 for lupus nephritis, demonstrating target engagement and complement inhibition in a completed Phase 1b trial[29]. - The clinical-stage pipeline includes multiple "next wave" programs, providing potential for portfolio growth and diversification beyond flagship programs[26]. - The company aims to leverage learnings from flagship programs to inform the development of additional therapies targeting classical complement-mediated diseases[31]. - ANX005 is being developed as a first-line monotherapy for GBS, with a Phase 1b trial showing it was well-tolerated and resulted in faster recovery compared to placebo[48][50]. - The Phase 1b trial included a follow-up of eight weeks, with dosing levels ranging from 3 mg/kg to 75 mg/kg[50]. - The Phase 3 trial enrolled 241 patients diagnosed with GBS, stratified by muscle strength and time from symptom onset[58]. - A Phase 2 trial of ANX005 for Huntington's Disease enrolled 28 patients, showing stabilization of disease progression over 9 months, with significant benefits observed in patients with higher baseline complement activity[89]. - In a Phase 2a trial for ALS, 13 patients were treated with ANX005, showing rapid target engagement and better outcomes in patients with elevated baseline classical complement activation[90]. - The ongoing open-label study of ANX1502 in patients with CAD has enrolled 3 patients, showing reductions in key clinical and biomarker outcomes, with data from up to 7 patients expected by mid-2025[87]. Regulatory Designations and Approvals - ANX005 has received Fast Track and orphan drug designations from the FDA, addressing an unmet need for the estimated 150,000 patients diagnosed with GBS annually[31]. - ANX007 is the first therapeutic candidate for GA to receive Priority Medicine (PRIME) designation by the EMA, indicating its potential for significant therapeutic advantage[31]. - A product candidate may receive Fast Track designation if it addresses unmet medical needs for serious conditions, allowing for rolling review of the application[137]. - Orphan Drug designation is granted for products intended to treat rare diseases affecting fewer than 200,000 individuals in the U.S.[141]. - A product with Orphan Drug designation can receive exclusivity for seven years if it is the first to be approved for the designated condition[142]. - The FDA requires a series of preclinical and clinical trials before a drug can be marketed, including the submission of an Investigational New Drug application (IND)[125]. - The FDA aims to review standard applications within ten months and priority applications within six months after acceptance for filing[133]. Financial Performance and Funding - The company reported a net loss of approximately $138.2 million for the year ended December 31, 2024, compared to a net loss of $134.2 million for 2023, resulting in an accumulated deficit of $710.7 million as of December 31, 2024[170]. - The company has incurred significant operating losses since its inception in March 2011, with losses primarily attributed to research and development expenses and general administrative costs[170]. - As of December 31, 2024, the company had capital resources of approximately $312.0 million, expected to fund operations into the second half of 2026[172]. - The company anticipates requiring substantial additional financing to support ongoing product development and clinical trials, with potential delays or limitations if funding is not secured[171]. - The company has not generated any revenue from product sales and does not expect to do so in the foreseeable future until product candidates are approved for commercialization[175]. Market Competition and Challenges - The pharmaceutical industry is characterized by intense competition, with competitors potentially having greater financial resources and established market presence[115]. - There are currently no approved therapies for Guillain-Barré Syndrome (GBS) in the U.S., with investigational products in development by other companies[117]. - Two treatments for Geographic Atrophy (GA) received FDA approval in 2023, indicating a competitive landscape for the company[118]. - The company faces challenges in recruiting patients for clinical trials due to the presence of two FDA-approved therapies for geographic atrophy (GA) in the United States[180]. Regulatory Compliance and Risks - The company is aware of the regulatory complexities involved in drug approval processes, which require substantial time and financial resources[124]. - The company is navigating the regulatory landscape to ensure compliance with various requirements for its product candidates[124]. - The company must comply with varying regulatory requirements across jurisdictions, which could increase costs and complicate the approval process for product candidates[199]. - Regulatory authorities may require additional clinical trials or impose restrictions on product distribution, impacting the company's ability to market its products effectively[201]. - The company faces risks associated with third-party contractors, including potential non-compliance with regulatory requirements and inadequate quality controls[204]. Clinical Trial Outcomes and Efficacy - ANX005 demonstrated a 2.4-fold improvement on the GBS-disability scale at week 8 compared to placebo (p = 0.0058) in the Phase 3 trial[60]. - Patients treated with ANX005 showed early gains in muscle strength with a p-value of <0.0001 at day 8 and p = 0.0351 at week 8[60]. - ANX005-treated patients had a median of 28 fewer days on artificial ventilation through week 26 (p = 0.0356) and a 31-day reduction in median time to walk independently (p = 0.0211) compared to placebo[60]. - A real-world evidence study showed ANX005-treated patients had more than a 10-point improvement in muscle strength over those treated with IVIg or PE (p < 0.0001)[66]. - Approximately half as many ANX005-treated patients required mechanical ventilation compared to those treated with IVIg or PE (15 of 79 vs. 32 of 79, p = 0.022)[70]. - ANX007 demonstrated a 72% reduction in the hazard of ≥15-letter loss in BCVA in the monthly treatment arm compared to sham (p = 0.006)[77]. Employee and Organizational Structure - As of December 31, 2024, the company had 100 full-time employees, with 80 engaged in research and development, including 38 with advanced degrees[163]. - The company emphasizes the importance of attracting and retaining qualified personnel, offering competitive compensation and benefits[164]. Future Outlook and Strategic Plans - The company is currently focused on developing product candidates for classical complement-mediated autoimmune and neurodegenerative diseases, including ANX005, ANX007, and ANX1502[177]. - The company plans to seek FDA approval for ANX005 for the treatment of GBS, with a pre-BLA meeting targeted for the first half of 2025[205]. - The data package for ANX005 includes a successful Phase 3 trial showing faster and more complete functional recovery compared to placebo, but the FDA may require two adequate Phase 3 trials for approval[205].

Drug Development Progress - ANX005 for Guillain-Barré Syndrome (GBS) has shown early and durable functional improvements, with a pre-BLA meeting targeted for the first half of 2025 ahead of the planned BLA submission[1]. - ANX007 has established a groundbreaking global registration path to potentially become the first approved treatment for dry age-related macular degeneration (AMD) with geographic atrophy (GA) in Europe and the U.S., with Phase 3 data expected in the second half of 2026[1]. - ANX1502 is currently in a proof-of-concept trial for cold agglutinin disease (CAD), with data from up to seven patients expected by mid-2025[8]. - The Phase 3 ARCHER II trial for ANX007 is enrolling approximately 630 patients, with completion expected in the second half of 2025[8]. Financial Performance - Cash, cash equivalents, and short-term investments were approximately $312 million as of December 31, 2024, providing a runway into the second half of 2026[9]. - Research and development (R&D) expenses for Q4 2024 were $43.4 million, up from $23.3 million in Q4 2023, reflecting advancements in priority programs[9]. - General and administrative (G&A) expenses for Q4 2024 were $9.1 million, compared to $6.7 million in Q4 2023[12]. - The net loss for Q4 2024 was $48.6 million, compared to a net loss of $27.9 million in Q4 2023[12]. - The company reported a total operating expense of $52.5 million for Q4 2024, compared to $30.0 million in Q4 2023[14]. - The weighted-average shares used in computing net loss per share for the year ended December 31, 2024, were 137,404,145, resulting in a net loss per share of $1.01[14]. Asset and Liability Changes - Total assets increased to $350.071 million in 2024, up from $297.674 million in 2023, representing a growth of approximately 17.6%[16]. - Current assets rose to $316.461 million in 2024, compared to $263.860 million in 2023, reflecting an increase of about 19.9%[16]. - Total liabilities increased to $56.966 million in 2024, up from $47.118 million in 2023, marking a rise of approximately 20.2%[16]. - Stockholders' equity grew to $293.105 million in 2024, compared to $250.556 million in 2023, indicating an increase of around 17.0%[16]. - The accumulated deficit widened to $(710.699) million in 2024 from $(572.499) million in 2023, representing an increase of approximately 24.2%[16]. - Accounts payable increased significantly to $10.426 million in 2024, up from $5.487 million in 2023, which is an increase of about 90.5%[16]. - Accrued and other current liabilities rose to $17.568 million in 2024, compared to $10.276 million in 2023, reflecting an increase of approximately 71.1%[16]. - Operating lease liabilities, non-current, decreased to $26.454 million in 2024 from $29.190 million in 2023, a decline of about 9.4%[16]. - Cash and cash equivalents decreased to $49.498 million in 2024 from $225.110 million in 2023, a significant drop of approximately 78.0%[16]. - Short-term investments surged to $262.519 million in 2024, compared to $34.606 million in 2023, representing an increase of approximately 658.5%[16].