Annexon, Inc. (NASDAQ:ANNX) is among the best fast money stocks to buy now. During the first quarter, Nuveen LLC acquired a new position in Annexon, Inc. (NASDAQ:ANNX) through the purchase of 23,491 shares of the company’s stock. According to a recent disclosure with the SEC, the global asset firm now owns 0.14% of the company, translating to an investment of approximately $666,000. What makes Annexon, Inc. (NASDAQ:ANNX) truly exciting is its one-of-a-kind programs. If we consider the Guillain-Barré syndr ...

Company Overview - Annexon Biosciences is focused on classical complement and is pioneering first-in-kind programs targeting immune inflammation across various diseases affecting the body, brain, and eye [3]. Product Development - The company is developing a program for Guillain-Barré syndrome, which is the first and only program in this space in the last 50 years, demonstrating landmark unprecedented data in improving patient outcomes [4].

Core Insights - Annexon is focused on the classical complement pathway, targeting upstream aspects that drive inflammatory diseases across various tissues, including the brain and eye [2][3] - The company has three flagship programs, with Guillain-Barré syndrome being the most advanced, having completed a Phase III program and currently in discussions for global regulatory approval [3] - The second flagship program involves Tanruprubart in geographic atrophy, which is noted as the world's largest Phase III program for this condition, demonstrating significant preservation against disease progression [4]

Summary of Nexon Conference Call Company Overview - **Company**: Nexon - **CEO**: Doug Love - **Focus**: Development of therapies targeting the classical complement pathway, particularly for diseases like Guillain Barre syndrome (GBS) and geographic atrophy (GA) [4][3] Key Programs and Developments - **Flagship Programs**: - **Guillain Barre Syndrome (GBS)**: Most advanced program, completed Phase III trials, in discussions for global approval [4][10] - **Geographic Atrophy (GA)**: Largest Phase III program for GA, showing significant preservation against vision loss [4][87] - **ANX-1502**: First small molecule program targeting the classical complement pathway, currently in early-stage development [5][66] Clinical Outcomes - **GBS Phase III Results**: - 90% of patients improved by week one, compared to a decline in patients receiving standard care [10][11] - Patients treated with Nexon's therapy spent 30 fewer days on ventilation and were discharged from ICU 20 days earlier than those on placebo [11][12] - Demonstrated significant improvements in functional outcomes and disability scales at multiple time points [30][31] Regulatory Strategy - **Real World Evidence Study**: Conducted to demonstrate comparability of Phase III data to U.S. patient populations, showing benefits over IVIG treatment [24][30] - **Regulatory Engagement**: Positive discussions with both FDA and EMA regarding approval pathways, with a focus on substantial evidence from Phase III studies and generalizability of data [36][41] Market Potential - **GBS Market**: Estimated 7,000 to 9,000 patients treated annually, with healthcare costs ranging from $3 billion to $4 billion [61][62] - **Commercial Strategy**: Targeting a concentrated group of hospitals and physicians, with a focus on efficient sales and marketing strategies [62][63] Future Outlook - **Goals**: Aim for approval of GBS therapy and successful commercialization of GA treatment, with a focus on improving patient outcomes and expanding treatment options [89][88] - **ANX-1502 Development**: Exploring oral administration for autoimmune diseases, with ongoing studies to confirm efficacy and safety [66][70] Additional Insights - **Complement Pathway Targeting**: Emphasis on the importance of targeting upstream components of the complement pathway for better clinical outcomes [6][7] - **Ethical Considerations**: Challenges in conducting placebo-controlled studies in the U.S. due to the severe nature of GBS [13][14] This summary encapsulates the critical points discussed during the conference call, highlighting Nexon's strategic focus, clinical advancements, regulatory interactions, and market opportunities.

Financial Data and Key Metrics Changes - The company has demonstrated unprecedented data in treating Guillain Barre syndrome, with 90% of patients showing improvement by week one [5] - The Phase III program for geographic atrophy has enrolled 650 patients ahead of schedule, indicating strong operational execution [6][66] Business Line Data and Key Metrics Changes - The Guillain Barre syndrome program is the first and only one in the last fifty years, showcasing the company's pioneering efforts in this area [5] - The geographic atrophy program is noted as the only vision-sparing program globally, having received PRIME designation [6] Market Data and Key Metrics Changes - In the EU, there are approximately 15,000 patients diagnosed with Guillain Barre syndrome annually, with a significant majority currently treated with IVIG [47] - The U.S. market for Guillain Barre syndrome is highly concentrated, with 175 hospitals controlling 60% of the patient population [41] Company Strategy and Development Direction - The company is focused on not commercializing the ex-U.S. rights for Guillain Barre syndrome, preferring to partner with established hospital-based neuro businesses [39] - The strategy includes a strong emphasis on education and streamlining patient management processes in the U.S. healthcare system [42] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the regulatory engagement with both the FDA and EMA, indicating a strong alignment on approval requirements [15][78] - The company anticipates filing for MAA approval in Europe by 2026, reflecting confidence in the regulatory pathway [14] Other Important Information - The company is actively working on a health economics analysis to demonstrate the value proposition of its treatments, which is expected to be released later this year [48] - The company has a robust safety profile for its drug, comparable to placebo, which supports a favorable benefit-risk analysis [52] Q&A Session Summary Question: How are discussions with regulatory bodies progressing? - The company has had productive meetings with both the FDA and EMA, with significant progress noted in the EU regarding orphan drug designation [11][12] Question: What is the status of the FORWARD study in the U.S.? - The FORWARD study is designed to understand real-world patient management for Guillain Barre syndrome, and it is currently enrolling patients [26][28] Question: What are the expectations for the geographic atrophy program? - The geographic atrophy program is viewed as the flagship initiative, with strong Phase II data supporting its potential [57][58] Question: How does the company plan to approach commercialization in the U.S.? - The company plans to focus on working with commercial payers and ensuring the drug is available in hospitals, rather than traditional hospital-based commercialization [43][45] Question: What is the outlook for the 15O2 program? - The 15O2 program is in early-stage development, with ongoing adjustments to improve drug delivery and tolerability [85][99]

Company Overview - Annexon, Inc. is a biopharmaceutical company focused on developing novel therapies for classical complement-mediated neuroinflammatory diseases affecting the body, brain, and eye [1][2] - The company targets C1q, a key molecule in the classical complement pathway, to prevent tissue damage and inflammation in various diseases [2] Clinical Development - Annexon is advancing a late-stage clinical platform with investigational drug candidates aimed at addressing unmet medical needs for nearly 10 million people globally [2] - The therapeutic pipeline spans three areas: autoimmunity, neurodegeneration, and ophthalmology [2] Investor Engagement - Douglas Love, the president and CEO, will participate in investor conferences in September, including the Wells Fargo Healthcare Conference and the Cantor Global Healthcare Conference [1][3] - Live webcasts of these presentations will be available on the company's website, with replays archived for 30 days [1]

PART I—FINANCIAL INFORMATION [Item 1. Financial Statements (Unaudited)](index=3&type=section&id=Item%201.%20Financial%20Statements%20%28Unaudited%29) Presents Annexon, Inc.'s unaudited condensed consolidated financial statements, covering balance sheets, operations, equity, cash flows, and notes [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) | (in thousands) | June 30, 2025 (Unaudited) | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $132,288 | $49,498 | | Short-term investments | 94,729 | 262,519 | | Total current assets | 230,620 | 316,461 | | Total assets | $264,573 | $350,071 | | **Liabilities and Stockholders' Equity** | | | | Accounts payable | $11,515 | $10,426 | | Accrued and other current liabilities | 26,411 | 17,568 | | Total current liabilities | 40,642 | 30,512 | | Total liabilities | 65,556 | 56,966 | | Total stockholders' equity | 199,017 | 293,105 | | Total liabilities and stockholders' equity | $264,573 | $350,071 | [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) | (in thousands, except share and per share amounts) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $44,160 | $25,026 | $92,339 | $45,989 | | General and administrative | 7,566 | 8,554 | 16,792 | 16,163 | | Total operating expenses | 51,726 | 33,580 | 109,131 | 62,152 | | Loss from operations | (51,726) | (33,580) | (109,131) | (62,152) | | Interest and other income, net | 2,570 | 3,970 | 5,619 | 7,366 | | Net loss | (49,156) | (29,610) | (103,512) | (54,786) | | Net loss attributable to common stockholders | $(51,013) | $(29,610) | $(105,369) | $(54,786) | | Net loss per share, basic and diluted | $(0.34) | $(0.23) | $(0.71) | $(0.43) | | Weighted-average shares used in computing net loss per share, basic and diluted | 148,320,803 | 130,132,960 | 148,215,392 | 126,403,081 | [Condensed Consolidated Statements of Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Comprehensive%20Loss) | (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Net loss | $(49,156) | $(29,610) | $(103,512) | $(54,786) | | Other comprehensive income (loss): | | | | | | Foreign currency translation adjustment | 2 | 1 | 2 | (11) | | Unrealized (loss) income on available-for-sale securities | (4) | 12 | (105) | (26) | | Comprehensive loss | $(49,158) | $(29,597) | $(103,615) | $(54,823) | [Condensed Consolidated Statements of Stockholders' Equity](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) | (in thousands, except share amounts) | Common Stock Shares | Common Stock Cost | Additional Paid-In Capital | Accumulated Other Comprehensive Income (Loss) | Accumulated Deficit | Total Stockholders' Equity | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | Balances as of December 31, 2024 | 109,381,556 | $109 | $1,003,685 | $10 | $(710,699) | $293,105 | | Exercise of stock options | 43,113 | — | 62 | — | — | 62 | | Restricted stock vested in the period | 289,735 | — | — | — | — | — | | Stock-based compensation | — | — | 5,078 | — | — | 5,078 | | Other comprehensive loss | — | — | — | (101) | — | (101) | | Net loss | — | — | — | — | (54,356) | (54,356) | | Balances as of March 31, 2025 | 109,714,404 | 109 | 1,008,825 | (91) | (765,055) | 243,788 | | Issuance of common stock per Employee Stock Purchase Plan purchase | 117,743 | 1 | 181 | — | — | 182 | | Stock-based compensation | — | — | 4,205 | — | — | 4,205 | | Other comprehensive loss | — | — | — | (2) | — | (2) | | Net loss | — | — | — | — | (49,156) | (49,156) | | Balances as of June 30, 2025 | 109,832,147 | $110 | $1,013,211 | $(93) | $(814,211) | $199,017 | | (in thousands, except share amounts) | Common Stock Shares | Common Stock Cost | Additional Paid-In Capital | Accumulated Other Comprehensive Loss | Accumulated Deficit | Total Stockholders' Equity | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | Balances as of December 31, 2023 | 78,369,099 | $78 | $823,029 | $(52) | $(572,499) | $250,556 | | Exercise of stock options | 105,526 | — | 217 | — | — | 217 | | Issuance of common stock, net of issuance costs of $933 | 6,639,348 | 7 | 32,191 | — | — | 32,198 | | Exercise of pre-funded warrants | 5,243,400 | 5 | (5) | — | — | — | | Restricted stock vested in the period | 124,695 | — | — | — | — | — | | Stock-based compensation | — | — | 4,660 | — | — | 4,660 | | Other comprehensive loss | — | — | — | (50) | — | (50) | | Net loss | — | — | — | — | (25,176) | (25,176) | | Balances as of March 31, 2024 | 90,482,068 | 90 | 860,092 | (102) | (597,675) | 262,405 | | Exercise of stock options | 35,914 | — | 171 | — | — | 171 | | Issuance of common stock per Employee Stock Purchase Plan purchase | 98,534 | 1 | 214 | — | — | 215 | | Issuance of common stock, net of issuance costs of $480 | 936,719 | 1 | 6,125 | — | — | 6,126 | | Issuance of common stock and pre-funded warrants, net of issuance costs of $8,183 | 13,001,120 | 13 | 116,804 | — | — | 116,817 | | Exercise of pre-funded warrants | 965,427 | 1 | (1) | — | — | — | | Exercise of common warrants | 19,901 | — | — | — | — | — | | Stock-based compensation | — | — | 4,942 | — | — | 4,942 | | Other comprehensive income | — | — | — | 13 | — | 13 | | Net loss | — | — | — | — | (29,610) | (29,610) | | Balances as of June 30, 2024 | 105,539,683 | $106 | $988,347 | $(89) | $(627,285) | $361,079 | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) | (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(88,126) | $(49,976) | | Net cash provided by (used in) investing activities | 170,702 | (173,883) | | Net cash provided by financing activities | 212 | 156,064 | | Increase (decrease) in cash, cash equivalents and restricted cash | 82,788 | (67,795) | | Cash, cash equivalents and restricted cash, Beginning of period | 50,530 | 226,142 | | Cash, cash equivalents and restricted cash, End of period | $133,320 | $158,336 | [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Provides detailed explanations for Annexon, Inc.'s financial statements, covering organization, policies, fair value, and equity [1. Organization](index=10&type=section&id=1.%20Organization) Details Annexon, Inc.'s biopharmaceutical focus, incorporation, and significant accumulated deficit with projected funding - **Annexon, Inc.** is a biopharmaceutical company focused on developing novel therapies for classical complement-mediated neuroinflammatory diseases, incorporated in Delaware in March 2011, with a wholly-owned subsidiary in Australia[28](index=28&type=chunk) - The company has incurred **significant losses and negative cash flows** from operations since inception, with an **accumulated deficit of $814.2 million as of June 30, 2025**. Existing cash and investments are projected to fund operations for **at least twelve months** from the financial statements' issuance date[29](index=29&type=chunk)[30](index=30&type=chunk) [2. Basis of Presentation and Significant Accounting Policies](index=10&type=section&id=2.%20Basis%20of%20Presentation%20and%20Significant%20Accounting%20Policies) Outlines financial statement preparation, management estimates, and recent accounting pronouncement adoptions and evaluations - The unaudited condensed consolidated financial statements are prepared in accordance with **GAAP and SEC rules** for interim reporting, reflecting normal recurring adjustments. Results for interim periods are **not indicative of full-year results**[31](index=31&type=chunk)[32](index=32&type=chunk) - Management makes estimates and assumptions affecting reported amounts, including fair value of investments, borrowing rates, deferred tax assets, clinical trial accruals, and stock-based compensation. **No significant changes to accounting policies** were made from the 2024 Form 10-K[33](index=33&type=chunk)[35](index=35&type=chunk)[37](index=37&type=chunk) - The company adopted **ASU 2023-07 (Segment Reporting)** on January 1, 2024 (annual) and 2025 (interim), which **did not materially impact financial statements**. It is evaluating **ASU 2023-09 (Income Tax Disclosures)** and **ASU 2024-03 (Expense Disaggregation Disclosures)** for future impact[38](index=38&type=chunk)[39](index=39&type=chunk)[40](index=40&type=chunk) [3. Fair Value Measurements](index=12&type=section&id=3.%20Fair%20Value%20Measurements) Describes the fair value hierarchy for financial assets and liabilities, primarily cash equivalents and short-term investments - The company uses a **fair value hierarchy (Level 1, 2, 3)** to categorize inputs for financial asset and liability measurements, prioritizing observable inputs[41](index=41&type=chunk) - **Fair Value Measurements (in thousands)** | (in thousands) | Valuation Hierarchy | Amortized Cost | Gross Unrealized Gains | Gross Unrealized Losses | Aggregate Fair Value | | :--- | :--- | :--- | :--- | :--- | :--- | | **June 30, 2025** | | | | | | | Cash equivalents: | | | | | | | Money market funds | Level 1 | $27,102 | $— | $— | $27,102 | | Government bonds | Level 2 | 96,620 | — | — | 96,620 | | Total cash equivalents | | 123,722 | — | — | 123,722 | | Short-term investments: | | | | | | | Government bonds | Level 2 | 94,738 | 2 | (11) | 94,729 | | Total short-term investments | | 94,738 | 2 | (11) | 94,729 | | **December 31, 2024** | | | | | | | Cash equivalents: | | | | | | | Money market funds | Level 1 | $31,680 | $— | $— | $31,680 | | Government bonds | Level 2 | 15,167 | — | — | 15,167 | | Total cash equivalents | | 46,847 | — | — | 46,847 | | Short-term investments: | | | | | | | Government bonds | Level 2 | 262,424 | 98 | (3) | 262,519 | | Total short-term investments | | 262,424 | 98 | (3) | 262,519 | - All investments as of **June 30, 2025**, had original maturities of **less than two years** and are scheduled to mature within **12 months**. No material realized gains or losses on financial instruments were recognized for the three and six months ended June 30, 2025 and 2024[43](index=43&type=chunk)[44](index=44&type=chunk) [4. Balance Sheet Components](index=14&type=section&id=4.%20Balance%20Sheet%20Components) Details components of cash, prepaid expenses, property and equipment, and accrued liabilities on the balance sheet - Cash equivalents include highly liquid instruments with original maturities of **three months or less**, stated at fair value. Restricted cash relates to letters of credit for office leases[45](index=45&type=chunk)[46](index=46&type=chunk) - **Cash, Cash Equivalents and Restricted Cash (in thousands)** | (in thousands) | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash | $8,566 | $2,651 | | Cash equivalents | 123,722 | 46,847 | | Cash and cash equivalents | 132,288 | 49,498 | | Restricted cash | 1,032 | 1,032 | | Cash, cash equivalents and restricted cash | $133,320 | $50,530 | - **Prepaid Expenses and Other Current Assets (in thousands)** | (in thousands) | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Prepaid research and development costs | $2,233 | $2,640 | | Prepaid insurance | 187 | 700 | | Prepaid and other current assets | 1,183 | 1,104 | | Total prepaid expenses and other current assets | $3,603 | $4,444 | - **Property and Equipment, Net (in thousands)** | (in thousands) | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Leasehold improvements | $17,254 | $17,254 | | Laboratory equipment | 1,871 | 1,838 | | Furniture and fixtures | 730 | 692 | | Computer equipment and software | 39 | 33 | | Construction in progress | 12 | — | | Total property and equipment, gross | 19,906 | 19,817 | | Less: accumulated depreciation | (8,256) | (7,179) | | Total property and equipment, net | $11,650 | $12,638 | - **Accrued and Other Current Liabilities (in thousands)** | (in thousands) | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Accrued research and development expenses | $21,683 | $10,992 | | Accrued compensation | 4,201 | 5,833 | | Accrued professional services | 395 | 602 | | Other accrued and current liabilities | 132 | 141 | | Total accrued and other current liabilities | $26,411 | $17,568 | [5. Commitments and Contingencies](index=16&type=section&id=5.%20Commitments%20and%20Contingencies) Covers operating lease obligations and general indemnification provisions, with no material claims recorded - The company leases its offices and laboratory in Brisbane, California, under a noncancelable lease agreement ending in **October 2031**. As of June 30, 2025, operating lease right-of-use assets were **$16.0 million** and lease liabilities were **$27.6 million**, with a weighted-average remaining lease term of **6.3 years** and an incremental borrowing rate of **8.4%**[53](index=53&type=chunk)[54](index=54&type=chunk) - **Future Minimum Lease Payments (in thousands)** | (in thousands) | Amount | | :--- | :--- | | 2025 (remaining six months) | $2,547 | | 2026 | 5,242 | | 2027 | 5,425 | | 2028 | 5,615 | | 2029 and thereafter | 16,985 | | Total undiscounted lease payments | 35,814 | | Less: Imputed interest | (8,184) | | Total lease liabilities | $27,630 | - The company enters into agreements with general indemnification provisions but has **not recorded related liabilities** as of June 30, 2025, as no material claims were probable or reasonably possible[56](index=56&type=chunk) [6. Stockholders' Equity](index=16&type=section&id=6.%20Stockholders'%20Equity) Details equity financing activities, including common stock, pre-funded warrants, and common warrant modifications - In June 2024, the company raised **$116.8 million net proceeds** from selling common stock and pre-funded warrants. In December 2023, it raised **$117.0 million net proceeds** from common stock and pre-funded warrants, with some warrants exercised in early 2024[57](index=57&type=chunk)[58](index=58&type=chunk)[60](index=60&type=chunk) - In July 2022, the company raised **$122.5 million net proceeds** from common stock, pre-funded warrants, and common warrants. In June 2025, common warrants for **6,877,622 shares** were amended to extend their term by **one year** and remove the cashless exercise option, potentially yielding **$39.9 million** if fully exercised for cash. A **deemed dividend of $1.9 million** was recognized due to this modification[61](index=61&type=chunk)[62](index=62&type=chunk)[63](index=63&type=chunk) - **Warrant Activity** | | Number of Common Warrants | Number of Pre-funded Warrants | Weighted-Average Exercise Price | | :--- | :--- | :--- | :--- | | **Balances as of December 31, 2024** | 8,104,615 | 38,543,577 | | | Issued | — | — | $— | | Exercised | — | — | $— | | **Balances as of June 30, 2025** | 8,104,615 | 38,543,577 | | | **Balances as of December 31, 2023** | 8,427,508 | 40,492,923 | | | Issued | — | 7,000,000 | $0.001 | | Exercised | (322,893) | (6,209,871) | $0.307 | | **Balances as of June 30, 2024** | 8,104,615 | 41,283,052 | | [7. Equity Incentive Plans](index=19&type=section&id=7.%20Equity%20Incentive%20Plans) Describes the 2020 Incentive Award Plan, ESPP, and Inducement Plan, along with stock option and RSU activity - The company operates under the **2020 Incentive Award Plan (2020 Plan)** and the **Employee Stock Purchase Plan (ESPP)**, both adopted in July 2020. The 2020 Plan automatically increases reserved shares annually by **4% of outstanding capital stock**, with **656,488 shares available** as of June 30, 2025[69](index=69&type=chunk)[70](index=70&type=chunk)[71](index=71&type=chunk) - The **2022 Employment Inducement Award Plan (Inducement Plan)** was adopted without stockholder approval to grant awards to newly hired employees, with **2,746,483 shares available** as of June 30, 2025[72](index=72&type=chunk)[74](index=74&type=chunk) - **Stock Option Activity** | Stock Option Activity | Number of Shares | Weighted-Average Exercise Price Per Share | Weighted Average Remaining Contractual Term (in years) | Aggregate Intrinsic Value (in thousands) | | :--- | :--- | :--- | :--- | :--- | | Balances as of December 31, 2024 | 14,594,720 | $8.29 | 7.94 | $4 | | Stock options granted | 6,159,513 | $2.55 | | | | Stock options exercised | (43,113) | $1.44 | | | | Stock options forfeited | (690,940) | $6.52 | | | | Balances as of June 30, 2025 | 20,020,180 | $6.60 | 8.08 | $286 | | Vested and Exercisable as of June 30, 2025 | 8,373,556 | $9.99 | 6.50 | $42 | - Total unrecognized stock-based compensation cost for unvested stock options was **$34.6 million as of June 30, 2025**, to be recognized over an estimated weighted-average period of **3.0 years**. The weighted-average grant date fair value of options granted was **$1.97 per share for Q2 2025** and **$4.17 for Q2 2024**[76](index=76&type=chunk) - **RSU Activity** | RSU Activity | Number of Shares | Weighted-Average Grant Date Fair Value Per Share | | :--- | :--- | :--- | | Unvested as of December 31, 2024 | 770,028 | $5.28 | | Granted | 1,072,921 | $2.50 | | Vested | (289,735) | $5.62 | | Cancelled | (100,215) | $3.11 | | Unvested as of June 30, 2025 | 1,452,999 | $3.31 | - Unrecognized stock-based compensation expense for unvested RSUs was **$3.9 million as of June 30, 2025**, to be recognized over a weighted-average period of **2.2 years**[78](index=78&type=chunk) - The ESPP allows eligible employees to purchase common stock at a discount, with **2,959,996 shares available** for future purchase as of June 30, 2025. Stock-based compensation expense related to the ESPP was **$40,000 for Q2 2025** and **$41,000 for Q2 2024**[81](index=81&type=chunk)[82](index=82&type=chunk) - **Stock-Based Compensation Expense (in thousands)** | (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $2,688 | $2,311 | $5,517 | $4,593 | | General and administrative | 1,517 | 2,631 | 3,766 | 5,009 | | Total stock-based compensation expense | $4,205 | $4,942 | $9,283 | $9,602 | - **Black-Scholes Assumptions** | Black-Scholes Assumptions | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Expected term (in years) | 5.50 - 6.08 | 6.08 | 5.50 - 6.08 | 6.02 - 6.08 | | Expected volatility | 93.70% - 93.80% | 96.20% - 97.80% | 92.30% - 93.80% | 95.90% - 97.80% | | Risk-free interest rate | 4.03% - 4.15% | 4.22% - 4.65% | 4.03% - 4.49% | 4.22% - 4.65% | | Dividend yield | — | — | — | — | [8. Net Loss Per Share](index=25&type=section&id=8.%20Net%20Loss%20Per%20Share) Explains basic and diluted net loss per share calculation, noting anti-dilutive securities due to net losses - **Basic net loss per share** is calculated by dividing net loss by the weighted-average common stock outstanding, including pre-funded warrants. **Diluted net loss per share** is the same as basic due to net losses, making potentially dilutive securities anti-dilutive[90](index=90&type=chunk) - **Potentially Dilutive Shares Excluded from Diluted Net Loss Per Share Calculation** | Potentially Dilutive Shares Excluded | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Stock options to purchase common stock | 20,020,180 | 11,937,414 | 20,020,180 | 11,937,414 | | Shares subject to Employee Stock Purchase Plan | 58,184 | 7,850 | 58,184 | 7,850 | | Unvested restricted stock units | 1,452,999 | 867,298 | 1,452,999 | 867,298 | | Common warrants | 8,104,615 | 8,104,615 | 8,104,615 | 8,104,615 | | Total | 29,635,978 | 20,917,177 | 29,635,978 | 20,917,177 | [9. Segment Reporting](index=25&type=section&id=9.%20Segment%20Reporting) Identifies the company's single reportable segment focused on R&D for complement-mediated diseases - The company operates as a **single reportable segment** focused on research and development of product candidates for complement-mediated diseases. The chief operating decision maker (CODM) assesses financial performance and allocates resources based on total operating expenses and consolidated net loss[92](index=92&type=chunk)[93](index=93&type=chunk) - **Consolidated Segment Net Loss (in thousands)** | (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development - external expenses | $31,278 | $15,678 | $65,776 | $27,369 | | Research and development - personnel | 8,376 | 5,479 | 17,422 | 11,103 | | General and administrative - personnel | 2,153 | 1,561 | 4,493 | 3,057 | | Other general and administrative expenses | 5,174 | 5,383 | 11,080 | 9,946 | | Depreciation expense | 540 | 537 | 1,077 | 1,075 | | Stock-based compensation | 4,205 | 4,942 | 9,283 | 9,602 | | Total operating expense | 51,726 | 33,580 | 109,131 | 62,152 | | Loss from operations | (51,726) | (33,580) | (109,131) | (62,152) | | Interest and other income, net | 2,570 | 3,970 | 5,619 | 7,366 | | Consolidated segment net loss | $(49,156) | $(29,610) | $(103,512) | $(54,786) | [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=27&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management's discussion of financial condition, operational results, liquidity, capital resources, and critical accounting policies [Overview](index=27&type=section&id=Overview) Summarizes Annexon's biopharmaceutical focus, pipeline progress, and financial position with accumulated losses - **Annexon** is a biopharmaceutical company developing novel therapies for classical complement-mediated neuroinflammatory diseases by targeting C1q. The company aims to suppress excessive complement activity to halt disease progression while preserving beneficial immune functions[100](index=100&type=chunk)[101](index=101&type=chunk) - Key pipeline programs include **tanruprubart for Guillain-Barré Syndrome (GBS)**, **vonaprument for Geographic Atrophy (GA)**, and **ANX1502 for autoimmune indications**. Tanruprubart has shown rapid functional improvements in Phase 3 GBS trials, with an MAA submission in Europe expected in **Q1 2026**. Vonaprument, a neuroprotective inhibitor for dry AMD with GA, completed enrollment for its global **Phase 3 ARCHER II trial in July 2025**, with topline data expected in **H2 2026**. ANX1502, an oral small molecule for autoimmune indications, is in a POC study for cold agglutinin disease (CAD), with an update planned by **end of 2025**[101](index=101&type=chunk)[106](index=106&type=chunk) - The company has incurred net losses since inception, totaling **$49.2 million for Q2 2025** and **$103.5 million for H1 2025**. As of **June 30, 2025**, the accumulated deficit was **$814.2 million**, with cash and short-term investments of **$227.0 million**[102](index=102&type=chunk) [Components of Operating Results](index=29&type=section&id=Components%20of%20Operating%20Results) Details the components of research and development and general and administrative expenses, and their expected trends [Revenue](index=29&type=section&id=Revenue) States the company has not generated product sales revenue and does not expect to in the foreseeable future - The company has **not generated any revenue from product sales** as its product candidates are not yet approved for commercial sale and does not expect to do so in the foreseeable future[103](index=103&type=chunk) [Operating Expenses](index=29&type=section&id=Operating%20Expenses) Details the components of research and development and general and administrative expenses, and their expected trends [Research and Development](index=29&type=section&id=Research%20and%20Development) Describes R&D expenses, including direct and indirect costs, with expectations for future increases due to pipeline advancement - Research and development (R&D) expenses are a **significant portion of operating expenses**, comprising direct costs (preclinical/clinical services, contract manufacturing, laboratory supplies) and indirect costs (compensation, facilities, other indirect costs)[104](index=104&type=chunk)[105](index=105&type=chunk)[113](index=113&type=chunk) - Future R&D expenses are expected to **increase** due to regulatory pursuits, late-stage clinical trials, commercialization preparations (including manufacturing), and increased personnel[108](index=108&type=chunk) [General and Administrative](index=31&type=section&id=General%20and%20Administrative) Outlines G&A expenses, including compensation and professional fees, with expected increases to support growth - General and administrative (G&A) expenses primarily include compensation, professional fees (accounting, legal, tax), allocated facilities costs, and other administrative expenses[109](index=109&type=chunk) - G&A expenses are expected to **increase** to support R&D, business growth, late-stage clinical trials, regulatory approval, commercialization, and public company operations[110](index=110&type=chunk) [Interest and Other Income, Net](index=31&type=section&id=Interest%20and%20Other%20Income,%20Net) Primarily consists of interest earned on cash equivalents and short-term investments - Interest and other income, net, primarily consists of **interest earned on cash equivalents and short-term investments**[111](index=111&type=chunk) [Results of Operations](index=31&type=section&id=Results%20of%20Operations) Compares financial performance for the three and six months ended June 30, 2025 and 2024, across key operating metrics [Comparison of the Three Months Ended June 30, 2025 and 2024](index=31&type=section&id=Comparison%20of%20the%20Three%20Months%20Ended%20June%2030,%202025%20and%202024) Compares financial results for Q2 2025 and Q2 2024, highlighting changes in operating expenses and net loss - **Operating Results (in thousands)** | (in thousands) | June 30, 2025 | June 30, 2024 | Dollar Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development | $44,160 | $25,026 | $19,134 | 76% | | General and administrative | 7,566 | 8,554 | (988) | (12%) | | Total operating expenses | 51,726 | 33,580 | 18,146 | 54% | | Loss from operations | (51,726) | (33,580) | (18,146) | 54% | | Interest and other income, net | 2,570 | 3,970 | (1,400) | (35%) | | Net loss | $(49,156) | $(29,610) | $(19,546) | 66% | - **Research and Development Expenses (in thousands)** | (in thousands) | June 30, 2025 | June 30, 2024 | Dollar Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Clinical and nonclinical outside services | $16,519 | $7,905 | $8,614 | 109% | | Contract manufacturing | 6,896 | 2,970 | 3,926 | 132% | | Consulting and professional services | 6,925 | 3,835 | 3,090 | 81% | | Compensation and personnel-related | 11,669 | 8,158 | 3,511 | 43% | | Total research and development expenses | $44,160 | $25,026 | $19,134 | 76% | - **General and Administrative Expenses (in thousands)** | (in thousands) | June 30, 2025 | June 30, 2024 | Dollar Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Compensation and personnel-related | $3,791 | $4,324 | $(533) | (12%) | | Consulting and professional services | 2,382 | 3,089 | (707) | (23%) | | Other | 778 | 504 | 274 | 54% | | Total general and administrative expenses | $7,566 | $8,554 | $(988) | (12%) | - Interest and other income, net, **decreased by $1.4 million (35%)** due to lower average cash and investment balances[116](index=116&type=chunk) [Comparison of the Six Months Ended June 30, 2025 and 2024](index=34&type=section&id=Comparison%20of%20the%20Six%20Months%20Ended%20June%2030,%202025%20and%202024) Compares financial results for H1 2025 and H1 2024, detailing changes in operating expenses and net loss - **Operating Results (in thousands)** | (in thousands) | June 30, 2025 | June 30, 2024 | Dollar Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Research and development | $92,339 | $45,989 | $46,350 | 101% | | General and administrative | 16,792 | 16,163 | 629 | 4% | | Total operating expenses | 109,131 | 62,152 | 46,979 | 76% | | Loss from operations | (109,131) | (62,152) | (46,979) | 76% | | Interest and other income, net | 5,619 | 7,366 | (1,747) | (24%) | | Net loss | $(103,512) | $(54,786) | $(48,726) | 89% | - **Research and Development Expenses (in thousands)** | (in thousands) | June 30, 2025 | June 30, 2024 | Dollar Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Clinical and nonclinical outside services | $27,081 | $14,611 | $12,470 | 85% | | Contract manufacturing | 22,761 | 4,728 | 18,033 | >200% | | Consulting and professional services | 13,389 | 6,061 | 7,328 | 121% | | Compensation and personnel-related | 24,416 | 16,331 | 8,085 | 50% | | Total research and development expenses | $92,339 | $45,989 | $46,350 | 101% | - **General and Administrative Expenses (in thousands)** | (in thousands) | June 30, 2025 | June 30, 2024 | Dollar Change | % Change | | :--- | :--- | :--- | :--- | :--- | | Compensation and personnel-related | $8,536 | $8,285 | $251 | 3% | | Other | 1,347 | 924 | 423 | 46% | | Total general and administrative expenses | $16,792 | $16,163 | $629 | 4% | - Interest and other income, net, **decreased by $1.7 million (24%)** for the six months ended June 30, 2025, compared to the same period in 2024, primarily due to lower average cash and investment balances[122](index=122&type=chunk) [Liquidity and Capital Resources](index=35&type=section&id=Liquidity%20and%20Capital%20Resources) Discusses historical funding, cash flows, future funding requirements, and various financing activities [Sources of Liquidity](index=35&type=section&id=Sources%20of%20Liquidity) Details historical funding through equity sales and current cash/investment balances against accumulated deficit - The company has historically funded operations through **equity security sales**, with **$227.0 million** in cash, cash equivalents, and short-term investments as of **June 30, 2025**, and an accumulated deficit of **$814.2 million**[123](index=123&type=chunk) [Historical Cash Flows](index=35&type=section&id=Historical%20Cash%20Flows) Analyzes cash flows from operating, investing, and financing activities for the six months ended June 30, 2025 and 2024 - **Cash Flow Summary (in thousands)** | (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(88,126) | $(49,976) | | Net cash provided by (used in) investing activities | 170,702 | (173,883) | | Net cash provided by financing activities | 212 | 156,064 | | Increase (decrease) in cash, cash equivalents and restricted cash | $82,788 | $(67,795) | - Cash used in operating activities **increased to $88.1 million in H1 2025** from **$50.0 million in H1 2024**, driven by higher net loss partially offset by non-cash charges and changes in operating assets/liabilities[125](index=125&type=chunk)[126](index=126&type=chunk) - Cash provided by investing activities was **$170.7 million in H1 2025**, a significant shift from **$173.9 million used in H1 2024**, primarily due to proceeds from maturities of available-for-sale securities[127](index=127&type=chunk)[128](index=128&type=chunk) - Cash provided by financing activities **decreased substantially to $0.2 million in H1 2025** from **$156.1 million in H1 2024**, as 2024 included significant proceeds from common stock and warrant issuances[129](index=129&type=chunk)[130](index=130&type=chunk) [Funding Requirements](index=36&type=section&id=Funding%20Requirements) Outlines the need for substantial additional financing to fund operations beyond Q4 2026 and potential risks of failure - The company expects existing cash and investments to fund operations into **Q4 2026** but will require **substantial additional financing** for regulatory approval, late-stage clinical trials, commercialization, and increased personnel[131](index=131&type=chunk)[132](index=132&type=chunk)[134](index=134&type=chunk) - Future funding needs are dependent on factors such as the scope and cost of R&D, clinical trials, regulatory approvals, manufacturing, commercialization, and intellectual property costs. Failure to obtain funding could lead to **delays or termination of programs**[132](index=132&type=chunk)[134](index=134&type=chunk)[161](index=161&type=chunk)[163](index=163&type=chunk) [2024 Financing](index=38&type=section&id=2024%20Financing) Details the June 2024 financing, raising $116.8 million net proceeds from common stock and pre-funded warrants - In June 2024, the company raised approximately **$116.8 million in net proceeds** from the sale of **13,001,120 shares of common stock** and pre-funded warrants for **7,000,000 shares**[135](index=135&type=chunk) [2023 Financing](index=38&type=section&id=2023%20Financing) Describes the December 2023 financing, raising $117.0 million net proceeds from common stock and pre-funded warrants - In December 2023, the company raised approximately **$117.0 million in net proceeds** from the sale of **25,035,000 shares of common stock** and pre-funded warrants for **18,379,861 shares**. Some pre-funded warrants were exercised in February and April 2024[136](index=136&type=chunk) [2022 Financing](index=38&type=section&id=2022%20Financing) Details the July 2022 financing, raising $122.5 million net proceeds, and the June 2025 common warrant amendment - In July 2022, the company raised approximately **$122.5 million in net proceeds** from the sale of common stock, pre-funded warrants, and common warrants. Common warrants to purchase **6,877,622 shares** were amended in June 2025 to extend their term and remove cashless exercise, potentially generating **$39.9 million** upon cash exercise[137](index=137&type=chunk)[138](index=138&type=chunk) - A **deemed dividend of $1.9 million** was recognized in additional paid-in capital due to the modification of common warrants, with **no net impact on stockholders' equity**[139](index=139&type=chunk) [Pre-Funded and Common Warrants](index=38&type=section&id=Pre-Funded%20and%20Common%20Warrants) Summarizes the activity and balances of common and pre-funded warrants as of June 30, 2025, and December 31, 2024 - **Warrant Activity** | | Number of Common Warrants | Number of Pre-funded Warrants | Weighted-Average Exercise Price | | :--- | :--- | :--- | :--- | | **Balances as of December 31, 2024** | 8,104,615 | 38,543,577 | | | Issued | — | — | $— | | Exercised | — | — | $— | | **Balances as of June 30, 2025** | 8,104,615 | 38,543,577 | | | **Balances as of December 31, 2023** | 8,427,508 | 40,492,923 | | | Issued | — | 7,000,000 | $0.001 | | Exercised | (322,893) | (6,209,871) | $0.307 | | **Balances as of June 30, 2024** | 8,104,615 | 41,283,052 | | [2024 At-the-Market (ATM) Program](index=40&type=section&id=2024%20At-the-Market%20%28ATM%29%20Program) Describes the $100.0 million ATM program established in March 2024, with no sales made to date - In March 2024, the company established a **$100.0 million ATM program** with TD Cowen. **No sales** were made under this program during the six months ended June 30, 2024 and 2025, with approximately **$95.4 million remaining available**[142](index=142&type=chunk) [2021 At-the-Market (ATM) Program](index=40&type=section&id=2021%20ATM%20Program) Details the expired 2021 ATM program, which generated $38.4 million in net proceeds during H1 2024 - The **2021 ATM program**, which allowed for up to **$100.0 million** in common stock sales, **expired on August 15, 2024**. During the six months ended June 30, 2024, the company sold **7,576,067 shares** for net proceeds of approximately **$38.4 million**[143](index=143&type=chunk) [Critical Accounting Policies and Estimates](index=40&type=section&id=Critical%20Accounting%20Policies%20and%20Estimates) Confirms reliance on U.S. GAAP, management estimates, and no material changes to policies in Q2 2025 - Management's discussion relies on condensed consolidated financial statements prepared in accordance with **U.S. GAAP**, requiring estimates and assumptions. **No material changes** to critical accounting policies or estimation methodologies occurred during Q2 2025[144](index=144&type=chunk)[145](index=145&type=chunk) [Recent Accounting Pronouncements Not Yet Adopted](index=40&type=section&id=Recent%20Accounting%20Pronouncements%20Not%20Yet%20Adopted) Refers to Note 2 for information on recent accounting pronouncements and their potential impact - Information on recent accounting pronouncements and their potential impact is detailed in **Note 2** to the unaudited condensed consolidated financial statements[146](index=146&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=41&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) States that there are no quantitative and qualitative disclosures about market risk applicable to the company - The company has **no applicable quantitative and qualitative disclosures** about market risk[147](index=147&type=chunk) [Item 4. Controls and Procedures](index=41&type=section&id=Item%204.%20Controls%20and%20Procedures) Details the evaluation of disclosure controls and procedures and confirms no material changes in internal control [Evaluation of Disclosure Controls and Procedures](index=41&type=section&id=Evaluation%20of%20Disclosure%20Controls%20and%20Procedures) Concludes that disclosure controls and procedures were effective as of June 30, 2025, ensuring timely reporting - Management, with CEO and CFO participation, concluded that **disclosure controls and procedures were effective as of June 30, 2025**, providing reasonable assurance that required information is recorded, processed, summarized, and reported timely[148](index=148&type=chunk) [Changes in Internal Control over Financial Reporting](index=41&type=section&id=Changes%20in%20Internal%20Control%20over%20Financial%20Reporting) Confirms no material changes in internal control over financial reporting during the quarter ended June 30, 2025 - **No changes in internal control over financial reporting** occurred during the quarter ended June 30, 2025, that materially affected, or are reasonably likely to materially affect, the company's internal control over financial reporting[149](index=149&type=chunk) PART II—OTHER INFORMATION [Item 1. Legal Proceedings](index=42&type=section&id=Item%201.%20Legal%20Proceedings) States the company is not currently involved in any material legal proceedings, but may encounter them ordinarily - The company is **not currently party to any material legal proceedings** but may become involved in various legal proceedings in the ordinary course of business[151](index=151&type=chunk) [Item 1A. Risk Factors](index=42&type=section&id=Item%201A.%20Risk%20Factors) Outlines significant risks affecting the company's business, financial condition, and results of operations [Risk Factor Summary](index=42&type=section&id=Risk%20Factor%20Summary) Summarizes key risks related to limited operating history, financial needs, product development, and intellectual property - The company is a **clinical-stage biopharmaceutical company** with a **limited operating history** and **no approved products**, incurring significant losses and facing difficulty in assessing future viability - **Substantial additional financing is required** to achieve goals; failure to obtain it could delay, limit, reduce, or terminate product development and commercialization efforts - Business heavily depends on **successful development, regulatory approval, and commercialization of product candidates**, some in early clinical stages - Research and development of biopharmaceutical products is **inherently risky**; no assurance of regulatory approval for any product candidates - Potential for **substantial delays in clinical trials** or inability to complete them on expected timelines - Clinical trials for product candidates are conducted outside the U.S., and foreign regulatory data may not be accepted by the FDA or comparable authorities - **Adverse events or undesirable side effects** from product candidates could halt development, delay/prevent approval, limit commercial potential, or result in negative consequences - Reliance on **third-party suppliers for manufacturing** product candidates; loss or non-compliance of these suppliers would materially and adversely affect the business - Commercialization depends on **adequate coverage, reimbursement, and pricing policies** from governmental authorities and health insurers; failure to obtain these could limit marketability and revenue - Future collaboration arrangements may not be successful, impacting ability to develop and commercialize product candidates - Inability to obtain, maintain, and enforce **intellectual property protection** could allow competitors to make, use, or sell similar products - Stock price has been and could remain **volatile**, risking inability to resell shares at or above purchase price - Failure to comply with **data protection laws** could lead to enforcement actions, penalties, litigation, or adverse publicity - Actual or perceived failure to comply with applicable data protection laws, regulations, standards, contractual obligations and other requirements related to data privacy and security could lead to government enforcement actions and civil or criminal penalties, private litigation (including class actions) or adverse publicity and otherwise could negatively affect our results of operations and business[154](index=154&type=chunk)[159](index=159&type=chunk) [Risks Related to Our Limited Operating History, Financial Condition and Capital Requirements](index=43&type=section&id=Risks%20Related%20to%20Our%20Limited%20Operating%20History,%20Financial%20Condition%20and%20Capital%20Requirements) Details risks from limited operating history, significant losses, substantial financing needs, and resource prioritization - As a clinical-stage biopharmaceutical company with **no approved products**, Annexon has a **limited operating history** and has incurred **significant net losses** since inception (**$49.2 million for Q2 2025**, **$103.5 million for H1 2025**, and an **accumulated deficit of $814.2 million as of June 30, 2025**). The company expects to continue incurring losses, making future viability assessment difficult[155](index=155&type=chunk)[156](index=156&type=chunk) - The company requires **substantial additional financing** beyond its **$227.0 million in capital resources** (as of June 30, 2025, expected to fund operations into **Q4 2026**) to complete product development and commercialization. Failure to secure funding on acceptable terms could force delays, reductions, or termination of programs, leading to dilution for stockholders or restrictive debt covenants[157](index=157&type=chunk)[158](index=158&type=chunk)[161](index=161&type=chunk)[162](index=162&type=chunk)[163](index=163&type=chunk) - Due to limited resources, the company must **prioritize development of certain product candidates** (e.g., **tanruprubart in GBS**, **vonaprument in GA**). Incorrect prioritization or inability to secure sufficient funding could lead to missed opportunities or program termination[165](index=165&type=chunk)[166](index=166&type=chunk) - Conducting the global **Phase 3 ARCHER II trial for vonaprument in dry AMD with GA** is expensive and time-consuming. There is **no assurance** that the FDA and foreign regulatory authorities will accept the data as sufficient for approval, potentially requiring additional capital or delaying commercialization[167](index=167&type=chunk)[168](index=168&type=chunk) - Quarterly and annual results of operations may **fluctuate significantly** due to factors like R&D costs, clinical trial timing, manufacturing costs, and competitive landscape, making future results difficult to predict and potentially causing stock price declines[169](index=169&type=chunk)[170](index=170&type=chunk)[171](index=171&type=chunk)[174](index=174&type=chunk) [Risks Related to Our Business](index=49&type=section&id=Risks%20Related%20to%20Our%20Business) Covers risks associated with product development, clinical trials, regulatory approvals, manufacturing, and competition - The company's success hinges on the **successful development, regulatory approval, and commercialization of its product candidates**, which is a highly uncertain and lengthy process. **C1q inhibition is a novel therapeutic approach**, carrying risks that product candidates may not be effective or that biomarker-driven approaches may not translate to therapeutic effectiveness[172](index=172&type=chunk)[173](index=173&type=chunk)[176](index=176&type=chunk) - **Public health crises**, like pandemics, can materially disrupt clinical trials, business, and financial results through delays in patient enrollment, site initiation, supply chains, and regulatory interactions[177](index=177&type=chunk)[179](index=179&type=chunk)[180](index=180&type=chunk)[183](index=183&type=chunk) - Biopharmaceutical R&D is **inherently risky**; product candidates may fail preclinical/clinical trials, show harmful side effects, become obsolete due to competitors, or be unproducible at acceptable costs. Regulatory agencies may require additional trials or impose restrictions, delaying or preventing approval[181](index=181&type=chunk)[182](index=182&type=chunk)[186](index=186&type=chunk)[187](index=187&type=chunk)[190](index=190&type=chunk) - **Delays in clinical trials** can occur due to issues like patient enrollment, regulatory disagreements, investigator recruitment, IRB approvals, safety concerns, or product supply. For **tanruprubart in GBS**, ongoing dialogue with the FDA for a generalizability package may lead to delays or additional data requirements, impacting U.S. approval[191](index=191&type=chunk)[192](index=192&type=chunk)[195](index=195&type=chunk)[199](index=199&type=chunk) - **Difficulties in patient enrollment**, driven by disease severity, eligibility criteria, competition from other trials, or availability of approved therapies, could delay clinical development and adversely affect the company's ability to advance product candidates[202](index=202&type=chunk)[203](index=203&type=chunk) - **Adverse events or unforeseen side effects** from product candidates could halt clinical development, delay regulatory approval, limit commercial potential, or lead to significant negative consequences, including regulatory actions, product recalls, or liability claims[204](index=204&type=chunk)[206](index=206&type=chunk)[207](index=207&type=chunk)[208](index=208&type=chunk) - Interim, 'top-line,' and preliminary data from studies are **subject to change** as more data become available and undergo audit, potentially differing materially from final results. Regulatory agencies or others may also interpret data differently, impacting program value or approvability[209](index=209&type=chunk)[210](index=210&type=chunk)[212](index=212&type=chunk) - Even with regulatory approval, product candidates may **fail to achieve broad physician and patient adoption** due to competitive factors, pricing, reimbursement issues, or physician/patient preferences, adversely affecting commercial success[213](index=213&type=chunk)[214](index=214&type=chunk)[216](index=216&type=chunk) - **Orphan Drug designation** for **tanruprubart (GBS, HD)** and **vonaprument (GBS)** provides financial incentives and market exclusivity, but does not guarantee faster development or approval, nor does it prevent competition from different drugs for the same condition or from clinically superior products[215](index=215&type=chunk)[217](index=217&type=chunk)[218](index=218&type=chunk)[219](index=219&type=chunk)[220](index=220&type=chunk) - **Breakthrough Therapy, Fast Track, and PRIME designations**, while offering enhanced regulatory interaction, do not guarantee faster development, review, or approval, nor do they increase the likelihood of marketing approval[221](index=221&type=chunk)[222](index=222&type=chunk)[223](index=223&type=chunk)[224](index=224&type=chunk)[225](index=225&type=chunk) - Disruptions at the FDA and other government agencies (e.g., funding shortages, global health concerns) could **hinder their ability to review, approve, or commercialize products** in a timely manner, negatively impacting the business[226](index=226&type=chunk)[227](index=227&type=chunk) - Clinical trials conducted outside the U.S. may **not have their data accepted by the FDA** or comparable foreign regulatory authorities if conditions (e.g., applicability to U.S. population, GCP compliance, on-site inspection validation) are not met, potentially requiring additional costly and time-consuming trials[228](index=228&type=chunk)[229](index=229&type=chunk)[231](index=231&type=chunk)[232](index=232&type=chunk)[233](index=233&type=chunk) - Regulatory approval in one jurisdiction **does not guarantee approval in others**, limiting market opportunities and adversely affecting the business if international approvals are not obtained[234](index=234&type=chunk) - Product candidates approved as biologics may face **competition sooner than anticipated** due to abbreviated approval pathways for biosimilar products, potentially shortening exclusivity periods[235](index=235&type=chunk)[236](index=236&type=chunk) - The company relies entirely on **third-party suppliers for manufacturing product candidates** and lacks internal manufacturing capabilities. Loss of these suppliers or their failure to comply with cGMPs, quality standards, or provide sufficient quantities could **materially and adversely affect the business**, requiring costly and time-consuming alternative arrangements[237](index=237&type=chunk)[238](index=238&type=chunk)[239](index=239&type=chunk)[240](index=240&type=chunk)[242](index=242&type=chunk)[243](index=243&type=chunk) - Reliance on third parties (CROs, investigators) for preclinical and clinical trials carries risks of **non-compliance, missed deadlines, or compromised data quality**, which could delay or prevent regulatory approval and harm business prospects[244](index=244&type=chunk)[245](index=245&type=chunk) - Failure to identify, develop, and commercialize additional product candidates would **impair business expansion and strategic objectives**, as development efforts may not yield viable commercial products or may divert resources from better opportunities[246](index=246&type=chunk)[247](index=247&type=chunk) - The pharmaceutical industry is **highly competitive**, with many competitors having greater resources, marketing capabilities, and R&D expertise. This intense competition may prevent the company from achieving significant market penetration, especially if competitors develop superior or cheaper alternatives, or gain regulatory approval faster[248](index=248&type=chunk)[249](index=249&type=chunk) - Commercial success depends on **adequate coverage, reimbursement, and pricing policies** from governmental and private payors. Failure to obtain these, or if reimbursement levels are inadequate, could limit marketability and revenue, especially for high-priced, physician-administered drugs[250](index=250&type=chunk)[252](index=252&type=chunk)[253](index=253&type=chunk)[254](index=254&type=chunk)[255](index=255&type=chunk)[256](index=256&type=chunk)[257](index=257&type=chunk) - The company currently lacks a sales organization and must build or partner for marketing, sales, and distribution capabilities. Failure to establish these effectively could **prevent commercialization and lead to significant losses**[258](index=258&type=chunk)[259](index=259&type=chunk) - The company needs to expand its organization and may face **difficulties managing growth**, requiring effective management of clinical trials, commercialization, employee recruitment, and operational controls[260](index=260&type=chunk)[261](index=261&type=chunk) - Failure to attract and retain senior management and key scientific personnel could **materially and adversely affect the business**, delaying product development and commercialization[262](index=262&type=chunk)[263](index=263&type=chunk)[264](index=264&type=chunk) - **Product liability lawsuits**, arising from clinical testing or commercialization, pose an inherent risk. Unsuccessful defense could lead to **substantial liabilities**, limit commercialization, and incur significant financial and management resources, even if successfully defended[265](index=265&type=chunk)[267](index=267&type=chunk)[268](index=268&type=chunk) - Future collaboration arrangements may **not be successful**, potentially delaying or terminating product development, diverting resources, or leading to disputes over intellectual property, adversely affecting the ability to develop and commercialize product candidates[269](index=269&type=chunk)[270](index=270&type=chunk)[271](index=271&type=chunk) - Unfavorable global and macroeconomic or political conditions (e.g., financial crises, inflation, geopolitical conflicts) could **adversely affect business, financial condition, and results of operations** by weakening demand, impacting capital raising, or disrupting supply chains[272](index=272&type=chunk) - International trade policies, including tariffs and trade barriers, could **increase R&D expenses**, disrupt supply chains (especially with foreign suppliers), and delay development timelines, materially affecting business and growth prospects[273](index=273&type=chunk)[274](index=274&type=chunk)[275](index=275&type=chunk)[276](index=276&type=chunk) - The company's operations are **vulnerable to natural disasters** (e.g., earthquakes, wildfires) or other unforeseen events, particularly in the San Francisco Bay Area. Limited business continuity and disaster recovery plans, coupled with lack of specific insurance, could **severely disrupt operations** and incur substantial expenses[278](index=278&type=chunk)[279](index=279&type=chunk)[280](index=280&type=chunk) - Misconduct by employees or third-party contractors, including noncompliance with regulatory standards or fraud, could lead to **significant penalties, governmental investigations, reputational harm, and adverse financial impacts**[281](index=281&type=chunk) - Business operations involve **hazardous materials**, requiring compliance with environmental laws and regulations. Risks of contamination, accidental injury, and non-compliance could lead to **costly clean-up, liabilities, fines, and operational restrictions**[282](index=282&type=chunk)[283](index=283&type=chunk)[285](index=285&type=chunk)[286](index=286&type=chunk) [Risks Related to Intellectual Property](index=86&type=section&id=Risks%20Related%20to%20Intellectual%20Property) Addresses risks concerning patent protection, infringement, trade secrets, licensing, and global IP enforcement - The company's commercial success depends on its ability to develop and market products **without infringing third-party patents**. It faces risks of **costly litigation, substantial damages, and limitations on commercialization** if found to infringe, or if its own patents are challenged or invalidated[287](index=287&type=chunk)[288](index=288&type=chunk)[289](index=289&type=chunk) - The company has **not conducted a comprehensive freedom-to-operate search**, and may be unaware of patents that could block commercialization. Patent law is uncertain, and changes in interpretation or legislation could affect patent protection[290](index=290&type=chunk)[291](index=291&type=chunk)[292](index=292&type=chunk)[293](index=293&type=chunk)[302](index=302&type=chunk)[303](index=303&type=chunk) - Failure to obtain, maintain, and enforce **intellectual property (IP) protection** (patents, trademarks, trade secrets) could allow competitors to use similar technologies, harming competitive position and business. Patent applications may not issue, or issued patents may be challenged, narrowed, or circumvented[294](index=294&type=chunk)[295](index=295&type=chunk)[296](index=296&type=chunk)[297](index=297&type=chunk)[300](index=300&type=chunk)[301](index=301&type=chunk) - Maintaining patent applications and issued patents requires compliance with procedural and payment provisions; **noncompliance can lead to loss of patent rights**. International IP protection is expensive and laws vary, making enforcement difficult in some countries[304](index=304&type=chunk)[305](index=305&type=chunk)[306](index=306&type=chunk)[307](index=307&type=chunk)[308](index=308&type=chunk)[309](index=309&type=chunk) - Inability to prevent disclosure of **trade secrets or confidential information** to third parties could impair competitive position. Confidentiality agreements or security measures may be breached, and enforcement is difficult and costly[310](index=310&type=chunk) - Licenses for third-party intellectual property are subject to **early termination** if the company fails to comply with obligations, potentially leading to loss of material rights or technology. Licensing is competitive, and larger companies may have an advantage[311](index=311&type=chunk)[313](index=313&type=chunk)[314](index=314&type=chunk)[315](index=315&type=chunk) - Disagreements over contract interpretation in IP agreements could **narrow rights or increase financial obligations**. Jointly owned patent rights may limit out-licensing ability or allow co-owners to license without consent[316](index=316&type=chunk)[317](index=317&type=chunk)[318](index=318&type=chunk)[319](index=319&type=chunk) - Claims challenging inventorship or ownership of patents could lead to **litigation, loss of IP rights, or infringement liability**. Reliance on third-party consultants or collaborators could result in shared ownership or rights to patents[320](index=320&type=chunk)[321](index=321&type=chunk)[322](index=322&type=chunk) - Inadequate protection of **trademarks and trade names** could hinder brand recognition. Trademark applications may be rejected or challenged, and foreign registrations may be difficult to obtain or enforce. Regulatory authorities may also object to proposed product names[323](index=323&type=chunk)[324](index=324&type=chunk) - Protecting IP rights globally is expensive, and foreign laws may not offer the same extent of protection as in the U.S. This could allow competitors to use technologies in unprotected jurisdictions or export infringing products, diminishing the commercial advantage of the company's IP[325](index=325&type=chunk)[326](index=326&type=chunk) [Risks Related to Government Regulation](index=96&type=section&id=Risks%20Related%20to%20Government%20Regulation) Highlights risks from ongoing regulatory requirements, healthcare legislation, generic competition, and compliance laws - Approved products remain subject to **extensive ongoing regulatory requirements** for manufacturing, labeling, promotion, and post-marketing studies. Non-compliance with cGMPs or other regulations can lead to restrictions, withdrawal of approval, or enforcement actions, adversely affecting commercialization and revenue[327](index=327&type=chunk)[328](index=328&type=chunk)[329](index=329&type=chunk)[330](index=330&type=chunk)[331](index=331&type=chunk)[332](index=332&type=chunk) - Healthcare legislation, such as the **ACA and IRA**, has increased costs and scrutiny on drug pricing, potentially limiting reimbursement and affecting profitability. Future legislative or administrative actions could further impact drug approval, pricing, and market access[333](index=333&type=chunk)[335](index=335&type=chunk)[336](index=336&type=chunk)[337](index=337&type=chunk)[338](index=338&type=chunk)[339](index=339&type=chunk)[341](index=341&type=chunk)[342](index=342&type=chunk)[343](index=343&type=chunk) - If the company develops a small molecule product, it could face **generic competition via ANDAs or 505(b)(2) NDAs**, potentially leading to rapid sales decline if patents are challenged or exclusivity periods expire[344](index=344&type=chunk)[345](index=345&type=chunk)[346](index=346&type=chunk) - Business operations are subject to various **healthcare regulatory laws** (e.g., Anti-Kickback Statute, False Claims Act, HIPAA, Sunshine Act, FCPA). Non-compliance could result in **significant civil/criminal penalties, exclusion from healthcare programs, reputational harm, and costly defense**[347](index=347&type=chunk)[348](index=348&type=chunk)[350](index=350&type=chunk) [Risks Related to Our Common Stock](index=104&type=section&id=Risks%20Related%20to%20Our%20Common%20Stock) Discusses stock price volatility, public company costs, internal control weaknesses, dilution, and anti-takeover provisions - The company's stock price has been and could remain **highly volatile** due to factors like clinical trial results, regulatory approvals, financing announcements, competition, and general economic conditions. This volatility makes future stock performance unpredictable[351](index=351&type=chunk)[352](index=352&type=chunk) - As a **'smaller reporting company,'** the company benefits from reduced disclosure and governance requirements, which may make its common stock less attractive to some investors due to less available information[353](index=353&type=chunk) - Operating as a public company incurs **significant legal, accounting, and compliance costs**, requiring substantial management time. Failure to comply with public company rules could result in sanctions or penalties[354](index=354&type=chunk) - The company is subject to **Section 404 of the Sarbanes-Oxley Act**. Future material weaknesses in internal controls could lead to inaccurate financial reporting, adversely affecting investor confidence and stock value. Establishing and maintaining effective controls is resource-intensive and subject to human error or fraud[355](index=355&type=chunk)[356](index=356&type=chunk)[357](index=357&type=chunk)[358](index=358&type=chunk) - Principal stockholders and management own a **significant percentage of stock**, allowing them to exert substantial control over matters requiring stockholder approval, potentially discouraging acquisition proposals[359](index=359&type=chunk) - Future issuance of common stock or convertible securities, including through ATM programs or warrant exercises, will cause **immediate dilution for existing stockholders**, and the dilutive impact of future financings may be difficult to compute[360](index=360&type=chunk) - Sales of a **substantial number of shares** by existing stockholders in the public market could cause the stock price to fall[361](index=361&type=chunk) - The company's ability to use **net operating loss (NOL) carryforwards** and other tax attributes may be limited due to past and potential future **'ownership changes' under Sections 382 and 383 of the Internal Revenue Code**, potentially reducing future tax benefits[362](index=362&type=chunk)[363](index=363&type=chunk)[364](index=364&type=chunk)[365](index=365&type=chunk) - Provisions in charter documents and Delaware law (e.g., classified board, no cumulative voting, board's right to fill vacancies) could **discourage takeovers and entrench management**[366](index=366&type=chunk)[368](index=368&type=chunk) - Claims for indemnification by directors and officers may **reduce available funds** to satisfy third-party claims and impact cash position, as insurance may not cover all liabilities[367](index=367&type=chunk)[369](index=369&type=chunk)[372](index=372&type=chunk) - **Exclusive forum provisions** in charter documents designate Delaware courts for certain disputes and federal courts for Securities Act claims, potentially limiting stockholders' ability to choose a favorable judicial forum and discouraging lawsuits[370](

[Executive Summary & Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Highlights) This section provides an overview of Annexon's Q2 2025 financial results, clinical portfolio progress, and CEO commentary [Second Quarter 2025 Financial Results, Portfolio Progress and Key Anticipated Milestones](index=1&type=section&id=Second%20Quarter%202025%20Financial%20Results%2C%20Portfolio%20Progress%20and%20Key%20Anticipated%20Milestones) Annexon reported its second quarter 2025 financial results, highlighting significant progress across its clinical portfolio, including Tanruprubart for GBS, Vonaprument for Dry AMD with GA, and ANX1502 for autoimmune conditions. The company's cash position is projected to support operations into the fourth quarter of 2026 - Annexon reported Q2 2025 financial results and highlighted portfolio progress for Tanruprubart (GBS), Vonaprument (Dry AMD with GA), and ANX1502 (oral C1s inhibitor), with cash supporting operations into **Q4 2026**[1](index=1&type=chunk) - Tanruprubart for GBS is advancing through regulatory interactions, with MAA submission in Europe anticipated in **Q1 2026** and ongoing discussions with FDA for BLA support[1](index=1&type=chunk) - Enrollment for the global Phase 3 ARCHER II trial of Vonaprument for Dry AMD with GA was accelerated, with topline data expected in **H2 2026**[1](index=1&type=chunk) - ANX1502, a first-in-kind oral C1s inhibitor, exceeded target concentration in fasted patients, with an update on the proof-of-concept CAD study expected by **year-end 2025**[1](index=1&type=chunk) [CEO Commentary](index=1&type=section&id=CEO%20Commentary) CEO Douglas Love emphasized the consistent validation of Annexon's C1 platform across its therapeutic candidates, highlighting strong Phase 3 results for Tanruprubart, accelerated enrollment for Vonaprument, and promising initial exposure data for ANX1502 - CEO Douglas Love emphasized the consistent validation of Annexon's C1 platform across multiple potential best-in-class therapeutics for complement-mediated diseases[2](index=2&type=chunk) - In GBS, approximately **90% of tanruprubart-treated patients improved by week 1**, and more than twice as many achieved normal health at week 26 vs. placebo in Phase 3[2](index=2&type=chunk) - Accelerated enrollment in the Phase 3 ARCHER II trial for vonaprument in dry AMD with GA, with topline data on pace for **H2 2026**, aims to provide a new vision-preserving treatment[2](index=2&type=chunk) - Annexon is capitalized into **Q4 2026**, through pivotal Phase 3 data in GA[2](index=2&type=chunk) [Recent Corporate and Clinical Program Updates](index=1&type=section&id=Recent%20Corporate%20and%20Clinical%20Program%20Updates) This section details recent advancements in Annexon's clinical programs, including regulatory progress, trial enrollment, and initial data [Tanruprubart (ANX005) in GBS](index=1&type=section&id=Tanruprubart%20(ANX005)%20in%20GBS) Tanruprubart, an immunotherapy for Guillain-Barré Syndrome (GBS), is progressing towards global registration, with MAA submission in Europe anticipated in Q1 2026 and ongoing discussions with the FDA regarding a BLA submission - Tanruprubart is a targeted immunotherapy for GBS, a rare neuromuscular emergency affecting **~150,000 people worldwide annually**, with no FDA-approved therapies[3](index=3&type=chunk) - MAA submission for European registration is expected in **Q1 2026**[3](index=3&type=chunk)[7](index=7&type=chunk) - Ongoing discussions with the FDA regarding the generalizability package to support a BLA submission, with an update expected upon further regulatory clarity[3](index=3&type=chunk)[7](index=7&type=chunk) - Completed a generalizability package including a Real-World Evidence study showing favorable outcomes versus SOC, and a drug-drug interaction safety study with IVIg[7](index=7&type=chunk) [Vonaprument (ANX007) in Dry AMD with GA](index=3&type=section&id=Vonaprument%20(ANX007)%20in%20Dry%20AMD%20with%20GA) Vonaprument, a neuroprotective inhibitor for dry Age-related Macular Degeneration (AMD) with Geographic Atrophy (GA), has completed accelerated enrollment for its global Phase 3 ARCHER II trial, with topline data anticipated in H2 2026 - Vonaprument is a neuroprotective inhibitor for dry AMD with GA, a leading cause of blindness affecting over **eight million worldwide**, with no approved vision-preserving therapies[4](index=4&type=chunk) - Accelerated enrollment of **659 patients** completed for the global, pivotal, sham-controlled, double-masked Phase 3 ARCHER II trial[7](index=7&type=chunk) - Global registration path established with U.S. and European regulators, supporting potential for first approval in both regions for vision protection in GA[7](index=7&type=chunk) - Topline Phase 3 ARCHER II trial data is expected in the **second half of 2026**[7](index=7&type=chunk) [ANX1502 for Autoimmune Conditions](index=3&type=section&id=ANX1502%20for%20Autoimmune%20Conditions) ANX1502, a first-in-kind oral C1s inhibitor for autoimmune conditions, has demonstrated exposure exceeding target concentrations in fasted patients during its ongoing proof-of-concept (POC) study for cold agglutinin disease (CAD), with an update expected by year-end 2025 - ANX1502 is a first-in-kind oral small molecule inhibiting activated C1s, offering potential for selective upstream classical complement inhibition with oral administration convenience[5](index=5&type=chunk) - Exposure exceeded target concentrations in fasted patients in the ongoing open-label POC study for cold agglutinin disease (CAD)[7](index=7&type=chunk) - Evaluation of PK/PD in relation to food intake, and reduction in complement and bilirubin markers as a measure of hemolysis, are ongoing[7](index=7&type=chunk) - An update on the POC trial in CAD is anticipated by **year-end 2025**[7](index=7&type=chunk) [Second Quarter 2025 Financial Results](index=3&type=section&id=Second%20Quarter%202025%20Financial%20Results) This section presents Annexon's Q2 2025 financial performance, covering cash position, operating runway, operating expenses, and net loss [Cash and Operating Runway](index=3&type=section&id=Cash%20and%20Operating%20Runway) As of June 30, 2025, Annexon reported $227.0 million in cash, cash equivalents, and short-term investments, which is expected to fund operations and late-stage milestones into the fourth quarter of 2026 | Metric | June 30, 2025 | | :----- | :------------ | | Cash and cash equivalents and short-term investments | $227.0 million | - Cash, cash equivalents, and short-term investments are expected to fund planned operating expenses and late-stage milestones into **Q4 2026**[6](index=6&type=chunk) [Operating Expenses and Net Loss](index=4&type=section&id=Operating%20Expenses%20and%20Net%20Loss) Annexon's R&D expenses significantly increased in Q2 2025 to $44.2 million, reflecting accelerated program advancement, while G&A expenses slightly decreased, resulting in a net loss of $49.2 million, or $0.34 per share | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | Change (YoY) | | :-------------------------------- | :--------------------- | :--------------------- | :----------- | | Research and development (R&D) expenses | $44,160 | $25,026 | +76.4% | | General and administrative (G&A) expenses | $7,566 | $8,554 | -11.6% | | Net loss | $(49,156) | $(29,610) | +66.0% | | Net loss per share, basic and diluted | $(0.34) | $(0.23) | +47.8% | - R&D expenses increased significantly due to the advancement of priority programs (GBS, GA, ANX1502)[10](index=10&type=chunk) [Financial Statements (Unaudited)](index=7&type=section&id=Financial%20Statements%20(Unaudited)) This section provides unaudited condensed consolidated financial statements, including statements of operations and balance sheets [Condensed Consolidated Statements of Operations (Unaudited)](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20(Unaudited)) The condensed consolidated statements of operations show a net loss of $49.2 million for the three months ended June 30, 2025, an increase from $29.6 million in the prior year, primarily driven by higher research and development expenses | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $44,160 | $25,026 | $92,339 | $45,989 | | General and administrative | $7,566 | $8,554 | $16,792 | $16,163 | | Total operating expenses | $51,726 | $33,580 | $109,131 | $62,152 | | Loss from operations | $(51,726) | $(33,580) | $(109,131) | $(62,152) | | Interest and other income, net | $2,570 | $3,970 | $5,619 | $7,366 | | Net loss | $(49,156) | $(29,610) | $(103,512) | $(54,786) | | Net loss attributable to common stockholders | $(51,013) | $(29,610) | $(105,369) | $(54,786) | | Net loss per share, basic and diluted | $(0.34) | $(0.23) | $(0.71) | $(0.43) | | Weighted-average shares used in computing net loss per share, basic and diluted | 148,320,803 | 130,132,960 | 148,215,392 | 126,403,081 | | Stock-based compensation expense (R&D) | $2,688 | $2,311 | $5,517 | $4,593 | | Stock-based compensation expense (G&A) | $1,517 | $2,631 | $3,766 | $5,009 | [Condensed Consolidated Balance Sheets (Unaudited)](index=8&type=section&id=Condensed%20Consolidated%20Balance%20Sheets%20(Unaudited)) The condensed consolidated balance sheets show a decrease in total assets from $350.1 million at December 31, 2024, to $264.6 million at June 30, 2025, primarily due to a reduction in short-term investments, with total stockholders' equity also decreasing over the same period | Metric (in thousands) | June 30, 2025 | December 31, 2024 | | :------------------------------------ | :-------------- | :---------------- | | **Assets** | | | | Cash and cash equivalents | $132,288 | $49,498 | | Short-term investments | $94,729 | $262,519 | | Total current assets | $230,620 | $316,461 | | Total assets | $264,573 | $350,071 | | **Liabilities and Stockholders' Equity** | | | | Total current liabilities | $40,642 | $30,512 | | Total liabilities | $65,556 | $56,966 | | Total stockholders' equity | $199,017 | $293,105 | | Total liabilities and stockholders' equity | $264,573 | $350,071 | [About Annexon](index=4&type=section&id=About%20Annexon) Annexon Biosciences is a biopharmaceutical company focused on developing first-in-kind therapeutics to halt classical complement-driven neuroinflammation by targeting C1q, the initiating molecule of the classical complement pathway - Annexon is a biopharmaceutical company developing first-in-kind therapeutics targeting classical complement-driven neuroinflammation for serious neuroinflammatory diseases[8](index=8&type=chunk) - Their scientific approach focuses on C1q, the initiating molecule of the classical complement pathway, to stop neuroinflammatory cascades[8](index=8&type=chunk) - The pipeline spans autoimmunity, neurodegeneration, and ophthalmology, aiming to address unmet needs for nearly **10 million people worldwide**[8](index=8&type=chunk) [Forward-Looking Statements](index=4&type=section&id=Forward%20Looking%20Statements) This section contains forward-looking statements regarding Annexon's future performance, therapeutic benefits, regulatory timelines, clinical trial outcomes, commercialization efforts, and financial outlook, which are subject to various risks and uncertainties - The press release contains forward-looking statements regarding potential therapeutic benefits, regulatory timings, clinical trial results, commercialization efforts, financial runway, and other future events[9](index=9&type=chunk) - These statements are subject to risks and uncertainties that could cause actual results to differ materially, as detailed in SEC filings[9](index=9&type=chunk) - Annexon undertakes no obligation to publicly update any forward-looking statements, except as required by law[9](index=9&type=chunk) [Contacts](index=4&type=section&id=Contacts) This section provides contact information for investor relations and media inquiries [Investor Contact](index=4&type=section&id=Investor%20Contact) For investor inquiries, please contact Joyce Allaire at LifeSci Advisors via email - Investor inquiries can be directed to Joyce Allaire at LifeSci Advisors via jallaire@lifesciadvisors.com[10](index=10&type=chunk) [Media Contact](index=6&type=section&id=Media%20Contact) For media inquiries, please contact Beth Keshishian via phone or email - Media inquiries can be directed to Beth Keshishian at **917-912-7195** or beth@bethkeshishian.com[11](index=11&type=chunk)

Core Insights - Annexon, Inc. is advancing its late-stage clinical platform for novel therapies targeting complement-mediated neuroinflammatory diseases, with significant progress in its product pipeline and regulatory interactions [1][2][8] Product Development Updates - **Tanruprubart (ANX005)**: Aimed at treating Guillain-Barré Syndrome (GBS), with approximately 90% of treated patients showing improvement by week 1 and more than double achieving normal health by week 26 compared to placebo. The company plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in Q1 2026 and is in discussions with the FDA regarding a Biologics License Application (BLA) [2][3][6] - **Vonaprument (ANX007)**: Targeting dry age-related macular degeneration (AMD) with geographic atrophy (GA), with accelerated enrollment in the Phase 3 ARCHER II trial. Topline data is expected in the second half of 2026, and the product has been selected for the EMA's PRIME program to facilitate regulatory interactions [1][4][6] - **ANX1502**: A first-in-kind oral C1s inhibitor showing promising exposure levels in fasted patients. Ongoing evaluations are expected to provide updates by the end of 2025 [1][5][6] Financial Overview - As of June 30, 2025, the company reported cash and cash equivalents of $227 million, sufficient to support operations through Q4 2026 [10] - Research and development expenses for Q2 2025 were $44.2 million, up from $25 million in Q2 2024, reflecting the advancement of key programs [10][14] - The net loss for Q2 2025 was $49.2 million, or $0.34 per share, compared to a net loss of $29.6 million, or $0.23 per share, in Q2 2024 [10][14] Strategic Initiatives - The company is actively engaging in global regulatory discussions to facilitate the commercialization of tanruprubart for GBS and is exploring collaborations with pharmaceutical companies for its commercialization [3][6] - The appointment of Lloyd Clark, M.D., as senior vice president for ophthalmology strategy and innovation aims to enhance the company's expertise in bringing novel therapies to market [6] Market Context - The company targets a significant unmet need in treating complement-mediated diseases, with a focus on neuroinflammatory conditions affecting millions globally [8] - The potential approval of vonaprument could position it as the first treatment for GA in both Europe and the U.S., addressing a critical gap in the market [4][6]

Summary of Annexon (ANNX) FY Conference - August 13, 2025 Company Overview - **Company**: Annexon Biosciences - **Industry**: Ophthalmology and Neuroinflammatory Diseases - **Key Focus**: Development of therapies targeting complement-mediated diseases, particularly in ophthalmology Core Points and Arguments 1. **Leadership and Experience**: Lloyd Clark, a retina specialist with 25 years of experience, has joined Annexon to advance their lead candidate for dry Age-related Macular Degeneration (AMD) through Phase 3 trials, aiming for a potential blockbuster treatment option [5][6][34] 2. **Product Pipeline**: - **Lead Candidate**: Vonapruvment (formerly known as ANX007) for geographic atrophy associated with dry AMD, which has shown vision preservation in clinical trials [12][13][29] - **Other Candidates**: - Tanrupebar, a systemic C1Q inhibitor for Guillain-Barré syndrome, has completed Phase 3 trials with positive results [7][11] - An oral complement inhibitor in earlier phases targeting multiple indications [8] 3. **Scientific Approach**: The company utilizes a pioneering scientific approach to inhibit the classical complement pathway, specifically targeting C1Q to mitigate neuroinflammation across various diseases [9][10][30] 4. **Clinical Data**: - Positive Phase 2 results for vonapruvment indicate significant visual acuity preservation and anatomical benefits, with a 73% risk reduction in 15-letter loss compared to sham treatment [23][31] - The ARCHER II Phase 3 trial has completed enrollment with over 630 patients, focusing on those with potential for vision preservation [26][33] 5. **Regulatory Progress**: - Vonapruvment has received PRIME designation in the EU, marking it as the first dry AMD drug to achieve this status [16][28] - The company is in discussions with global regulators to bring therapies to market [8][11] Important but Overlooked Content 1. **Market Need**: There are currently no approved therapies for geographic atrophy outside the US, highlighting a significant unmet medical need for patients suffering from severe blinding eye diseases [14][16] 2. **Safety Profile**: The ARCHER study indicated a favorable safety profile for vonapruvment, with minimal adverse events reported, including only one case of endophthalmitis [25][32] 3. **Future Outlook**: The company anticipates reporting top-line data from the ARCHER II trial in 2026, with a strong cash runway to support ongoing development [34] This summary encapsulates the key insights from the conference, focusing on Annexon's strategic direction, product pipeline, and the significant clinical advancements in treating neuroinflammatory diseases and ophthalmological conditions.