Annexon, Inc.

Previous wording

Guillain-Barré Syndrome, or GBS: We are advancing our lead candidate, tanruprubart (formerly ANX005), an investigational, full-length monoclonal antibody, or mAb, formulated for intravenous administration as the potential first-targeted treatment for patients with GBS. Tanruprubart has consistently demonstrated rapid and sustained functional improvements in multiple placebo-controlled trials. GBS is a rare antibody-mediated autoimmune disease that is the most common cause of acute neuromuscular paralysis, with no therapies in the United States approved by the U.S. Food and Drug Administration, or FDA. The rare and acute nature of GBS has shaped our clinical development program conducted primarily in Southeast Asia to generate a comprehensive data package that includes successful placebo-controlled proof-of-concept and Phase 3 data, Real-World Evidence indirect comparison data of tanruprubart’s treatment effect versus current standard of care, and drug-drug interaction safety data with tanruprubart with current standard of care. We are also preparing to initiate in the second quarter of 2025 the open-label tanruprubart FORWARD study, measuring pharmacokinetics, pharmacodynamics, early efficacy in week 1, and safety in up to 30 subjects in the United States, Canada, and Europe, which is designed to broaden Western patient, physician and healthcare community experience. We anticipate this comprehensive data package to support our Biologics License Application, or BLA, and are targeting a meeting with the Center for Drug Evaluation and Research of the FDA in the second quarter of 2025, ahead of our planned BLA submission. Tanruprubart has been granted Fast Track and orphan drug designation for the treatment of GBS from the FDA. Tanruprubart has also been granted orphan designation from the European Medicines Agency, or EMA.

Current wording

Guillain-Barré Syndrome, or GBS: We are advancing tanruprubart (formerly ANX005), an investigational targeted immunotherapy delivered in a single infusion to rapidly halt aggressive neuroinflammation and damage in GBS, an acute, rare, neuromuscular emergency that affects ~150,000 people worldwide each year. There are currently no therapies approved by the U.S. Food and Drug Administration, or FDA, for GBS and no substantial evidence of effectiveness from the current standard of care. In the placebo-controlled Phase 3 trial, approximately 90% of GBS patients treated with tanruprubart improved by week 1 and more than twice as many treated patients achieved a normal state of health at week 26. Tanruprubart has consistently demonstrated rapid and sustained functional improvements across a comprehensive data package that includes successful placebo-controlled proof-of-concept, or POC, and Phase 3 data, Real-World Evidence, or RWE, indirect comparison data of tanruprubart’s treatment effect versus current standard of care, and drug-drug interaction safety data with tanruprubart with current standard of care. Completed placebo-controlled studies were conducted in Southeast Asia given GBS’ sudden and debilitating disease course and lack of approved comparator in the U.S. The open-label FORWARD study in the U.S. and Europe is ongoing and currently designed to broaden Western experience with tanruprubart by measuring pharmacokinetics, pharmacodynamics, early efficacy in week 1, and safety in up to 30 subjects including pediatric patients. We continue to engage with applicable EU and U.S. regulators to advance tanruprubart towards registration worldwide. Our Marketing Authorization Application, or MAA, submission for registration in Europe is expected in the first quarter of 2026. In parallel, we are in ongoing dialogue with the FDA to gain clarity on the generalizability package to support a BLA submission. Tanruprubart has been granted Fast Track and orphan drug designation for the treatment of GBS from the FDA. Tanruprubart has also been granted orphan designation from the European Medicines Agency, or EMA.

Previous wording

Geographic Atrophy, or GA: We are advancing ANX007, an antigen-binding fragment, or Fab, formulated for intravitreal administration, as the first potential program with a global registration path to approval in Europe and the United States for the treatment of dry AMD with GA. Dry AMD with GA is a leading cause of vision loss in the elderly, that affects more than an estimated eight million people globally, and there are no approved therapies targeting the preservation of vision in this disease. ANX007 is designed to block C1q locally in the eye, to provide more complete protection against excess classical complement activity and the loss of photoreceptor neurons. It is the only investigational therapy in GA to show significant vision preservation on assessments of best corrected visual acuity, or BCVA, and low luminance visual acuity, or LLVA, demonstrating significant protection from vision loss in both normal and low light conditions, as well as significant preservation of central retinal photoreceptors necessary for visual acuity as demonstrated in the Phase 2 ARCHER trial. In 2024, we initiated our Phase 3 ARCHER II trial, a global, sham-controlled, double-masked trial expected to enroll ~630 patients who have dry AMD with GA. The primary endpoint of ARCHER II is prevention of ≥15-letter loss of BCVA, and a secondary objective structural measure is prevention of ellipsoid zone (EZ) loss. The single-study program will be analyzed as two sub-studies for the U.S. in accordance with the FDA’s two-trial recommendation. Accordingly, we no longer plan to conduct a second injection-controlled head-to-head Phase 3 trial. We expect to complete enrollment of ARCHER II in the third quarter of 2025 and report topline data in the second half of 2026. ANX007 is the first and only therapeutic candidate for the treatment of GA to receive Priority Medicine, or PRIME, designation by the EMA, which provides early and proactive support to developers of promising medicines that may offer a major therapeutic advantage over existing treatments or benefit to patients without treatment options.

Current wording

Geographic Atrophy, or GA: We are advancing vonaprument (formerly ANX007), an investigational neuroprotective inhibitor of C1q and the classical complement cascade delivered intravitreally for dry AMD with GA, a leading cause of blindness affecting more than eight million people worldwide. There are no approved therapies for GA targeting the preservation of vision. Vonaprument is the only investigational therapy in GA to show significant vision preservation on assessments of best corrected visual acuity, or BCVA, and low luminance visual acuity, or LLVA, demonstrating significant protection from vision loss in both normal and low light conditions, as well as significant preservation of central retinal photoreceptors necessary for visual acuity as demonstrated in the Phase 2 ARCHER trial. In July 2025, we completed enrollment of 659 patients in ARCHER II, a global, sham-controlled, double-masked Phase 3 trial. The primary endpoint of ARCHER II is prevention of ≥15-letter loss of BCVA, and a secondary objective structural measure is prevention of ellipsoid zone, or EZ, loss. We have established a global registration path with the FDA and EMA which supports the potential of vonaprument to be the first treatment approved in both Europe and the U.S. for the protection of vision in patients who have dry AMD with GA, assuming positive Phase 3 results. We plan to report topline data in the second half of 2026. Vonaprument is the first and only therapeutic candidate for the treatment of GA to receive Priority Medicine, or PRIME, designation by the EMA, which provides early and proactive support to developers of promising medicines that may offer a major therapeutic advantage over existing treatments or benefit to patients without treatment options. Vonaprument was also selected by EMA for Product Development Coordinator (PDC) Pilot launched in July 2025 to help PRIME designation holders efficiently navigate regulatory interactions including expedited scientific advice, MAA submission readiness activities, and ad-hoc queries throughout the development program.

Previous wording

ANX1502 for Autoimmune Indications: We are advancing ANX1502, a novel oral small molecule inhibitor of classical complement which we believe is first-in-kind. In a Phase 1 single-ascending dose, or SAD, and multiple-ascending dose, or MAD, clinical trial in healthy volunteers designed to evaluate the safety, tolerability, pharmacokinetics, or PK, and pharmacodynamics, or PD, ANX1502 was generally well tolerated across cohorts with no serious adverse events, achieved target levels of active drug and showed supportive impact on a PD biomarker of complement activity. We are evaluating a tablet formulation of ANX1502 in an ongoing proof-of-concept study in patients with cold agglutinin disease, or CAD, to assess PK, PD and clinical efficacy endpoints (e.g., hemolysis as measured by reduction of elevated bilirubin) and data are expected in mid-2025. Following the successful completion of the proof-of-concept study, we intend to evaluate ANX1502 in a host of diseases, including serious complement-mediated autoimmune diseases, with the aim of providing enhanced efficacy and offering convenient dosing administration for long-term treatment of chronic conditions.

Current wording

ANX1502 for Autoimmune Indications: We are advancing ANX1502, a novel oral small molecule inhibiting the activated form of C1s, an enzyme carried by C1q to initiate the classical cascade, which we believe is first-in-kind and has the potential to offer the advantages of selective upstream classical complement inhibition with the convenience and flexibility of oral administration. In a Phase 1 single-ascending dose, or SAD, and multiple-ascending dose, or MAD, clinical trial in healthy volunteers designed to evaluate the safety, tolerability, pharmacokinetics, or PK, and pharmacodynamics, or PD, ANX1502 was generally well tolerated across cohorts with no serious adverse events, achieved target levels of active drug and showed supportive impact on a PD biomarker of complement activity. We are evaluating a tablet formulation of ANX1502 in an ongoing POC study in patients with cold agglutinin disease, or CAD. Exposure exceeded target concentrations in fasted patients treated to date in the POC study, and evaluation of PK/PD in relation to food intake, and reduction in complement and bilirubin markers as a measure of hemolysis, are ongoing. We anticipate that PK/PD learnings from CAD patients will inform application of ANX1502 in a broad array of other autoimmune indications, and we plan to provide an update by the end of 2025.

Previous wording

We were incorporated in March 2011 and commenced operations later that year. To date, we have focused primarily on performing research and development activities, hiring personnel and raising capital to support and expand these activities. We do not have any products approved for sale, and we have not generated any revenue from product sales. We have incurred net losses each year since our inception. Our net losses were $54.4 million and $25.2 million for the three months ended March 31, 2025 and 2024, respectively. As of March 31, 2025, we had an accumulated deficit of $765.1 million and cash and cash equivalents and short-term investments of $263.7 million.

Current wording

We were incorporated in March 2011 and commenced operations later that year. To date, we have focused primarily on performing research and development activities, hiring personnel and raising capital to support and expand these activities. We do not have any products approved for sale, and we have not generated any revenue from product sales. We have incurred net losses each year since our inception. Our net losses were $49.2 million and $29.6 million for the three months ended June 30, 2025 and 2024, respectively, and $103.5 million and $54.8 million for the six months ended June 30, 2025 and 2024, respectively. As of June 30, 2025, we had an accumulated deficit of $814.2 million and cash and cash equivalents and short-term investments of $227.0 million.

Previous wording

Research and development expenses increased by $27.2 million, or 130%, for the three months ended March 31, 2025 compared to the same period in 2024. The change was primarily attributable to a $14.1 million increase in contract manufacturing expenses related to the timing of activities for tanruprubart (ANX005) supporting the preparation of the BLA submission, as well as the initiation of the manufacturing technology transfer of ANX007 to a commercial-ready facility. In addition, compensation and personnel-related expenses increased by $4.6 million, driven by higher headcount. Consulting and professional services expenses increased by $4.2 million, primarily to support the preparation of our BLA submission for tanruprubart in GBS and to provide ongoing support for the ARCHER II clinical trial. We also incurred $3.9 million in additional direct clinical and nonclinical outside services costs associated with continued advancement of the ARCHER II clinical trial.

Current wording

Research and development expenses increased by $19.1 million, or 76%, for the three months ended June 30, 2025 compared to the same period in 2024. The change was attributable to $8.6 million in additional direct clinical and nonclinical outside services costs associated with the Phase 3 ARCHER II clinical trial and the initiation of the tanruprubart FORWARD study in GBS. Contract manufacturing expenses increased $3.9 million due to activities for tanruprubart (ANX005) supporting the preparation of the BLA submission, as well as the manufacturing technology transfer of vonaprument (ANX007) to a commercial-ready facility. In addition, compensation and personnel-related expenses increased by $3.5 million, driven by higher headcount. Consulting and professional services expenses increased by $3.1 million, primarily to support the preparation of our BLA submission for tanruprubart in GBS and to provide ongoing support for the ARCHER II clinical trial.

Previous wording

Interest and other income, net, decreased by $0.3 million, or 10%, for the three months ended March 31, 2025 compared to the same period in 2024. The decrease was primarily due to lower average cash and investment balances.

Current wording

Interest and other income, net, decreased by $1.4 million, or 35%, for the three months ended June 30, 2025 compared to the same period in 2024. The decrease was primarily due to lower average cash and investment balances.

Previous wording

We have funded our operations primarily through the sale of equity securities. As of March 31, 2025, we had available cash and cash equivalents and short-term investments of $263.7 million and an accumulated deficit of $765.1 million.

Current wording

We have funded our operations primarily through the sale of equity securities. As of June 30, 2025, we had available cash and cash equivalents and short-term investments of $227.0 million and an accumulated deficit of $814.2 million.

Previous wording

Cash used in operating activities for the three months ended March 31, 2024 was $28.3 million, which consisted of a net loss of $25.2 million and a net change of $7.5 million in our operating assets and liabilities, partially offset by $4.4 million in non-cash charges. The non-cash charges consisted of stock-based compensation of $4.7 million, depreciation and amortization of $0.5 million and a reduction in the carrying amount of right-of-use assets of $0.3 million, partially offset by accretion of discount on available-for-sale securities of $1.1 million.

Current wording

Cash used in operating activities for the six months ended June 30, 2025 was $88.1 million, which consisted of a net loss of $103.5 million, partially offset by $8.0 million in non-cash charges and a net change of $7.4 million in our operating assets and liabilities. The non-cash charges consisted of stock-based compensation of $9.3 million, depreciation and amortization of $1.1 million and a reduction in the carrying amount of right-of-use assets of $0.7 million, partially offset by accretion of discount on available-for-sale securities of $3.1 million.

Previous wording

Cash used in operating activities for the three months ended March 31 , 2025 was $50.1 million, which consisted of a net loss of $54.4 million, partially offset by $4.1 million in non-cash charges and a net change of $0.2 million in our operating assets and liabilities. The non-cash charges consisted of stock-based compensation of $5.1 million, depreciation and amortization of $0.5 million and a reduction in the carrying amount of right-of-use assets of $0.4 million, partially offset by accretion of discount on available-for-sale securities of $1.9 million.

Current wording

Cash used in operating activities for the six months ended June 30, 2024 was $50.0 million, which consisted of a net loss of $54.8 million and a net change of $3.6 million in our operating assets and liabilities, partially offset by $8.4 million in non-cash charges. The non-cash charges consisted of stock-based compensation of $9.6 million, depreciation and amortization of $1.1 million and a reduction in the carrying amount of right-of-use assets of $0.6 million, partially offset by accretion of discount on available-for-sale securities of $2.9 million.

Previous wording

Cash provided by investing activities for the three months ended March 31, 2025 was $97.6 million, which consisted of $159.5 million of proceeds from maturities of available-for-sale securities, partially offset by $61.8 million of purchases of available-for-sale securities and $0.1 million of purchases of property and equipment.

Current wording

Cash provided by investing activities for the six months ended June 30, 2025 was $170.7 million, which consisted of $291.3 million of proceeds from maturities of available-for-sale securities, partially offset by $120.5 million of purchases of available-for-sale securities and $0.1 million of purchases of property and equipment.

Previous wording

Cash used in investing activities for the three months ended March 31, 2024 was $77.3 million, which consisted of $100.3 million of purchases of available-for-sale securities, partially offset by $23.0 million of proceeds from maturities of available-for-sale securities.

Current wording

Cash used in investing activities for the six months ended June 30, 2024 was $173.9 million, which consisted of $266.2 million of purchases of available-for-sale securities, partially offset by $92.3 million of proceeds from maturities of available-for-sale securities.

Previous wording

Cash provided by financing activities for the three months ended March 31, 2025 was $0.1 million, which consisted of $0.1 million of proceeds from the exercise of common stock options.

Current wording

Cash provided by financing activities for the six months ended June 30, 2025 was $0.2 million, which consisted of proceeds from the exercise of common stock options and employee stock purchase plans.

Previous wording

Cash provided by financing activities for the three months ended March 31, 2024 was $32.4 million, which consisted of $32.2 million of net proceeds from the issuance of common stock under our 2021 ATM program and $0.2 million of proceeds from the exercise of common stock options.

Current wording

Cash provided by financing activities for the six months ended June 30, 2024 was $156.1 million, which consisted of $116.8 million of net proceeds from the issuance of common stock and pre-funded warrants under our 2024 financing, $38.4 million of net proceeds from the issuance of common stock under our 2021 ATM program and $0.6 million of proceeds from the exercise of common stock options and employee stock purchase plans.

Previous wording

Based upon our current operating plan, we believe that our existing cash and cash equivalents and short-term investments will enable us to fund our operating expenses and capital expenditure requirements into the second half of 2026. We will require substantial additional financing to achieve our goals, and a failure to obtain this necessary capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development programs, commercialization efforts or other operations. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect. Until such time, if ever, as we can generate substantial product revenue, we will be required to seek additional funding in the future and currently intend to do so through public or private equity offerings or debt financings, credit or loan facilities, collaborations or a combination of one or more of these funding sources. Additional funds may not be available to us on acceptable terms or at all. If we fail to obtain necessary capital when needed on acceptable terms, or at all, we could be forced to delay, limit, reduce or terminate our product development programs, commercialization efforts or other operations. If we raise additional funds by issuing equity securities, our stockholders will suffer dilution and the terms of any financing may adversely affect the rights of our stockholders. In addition, as a condition to providing additional funds to us, future investors may demand, and may be granted, rights superior to those of existing stockholders. Debt financing, if available, is likely to involve restrictive covenants limiting our flexibility in conducting future business activities, and, in the event of insolvency, debt holders would be repaid before holders of our equity securities received any distribution of our corporate assets.

Current wording

Based upon our current operating plan, we believe that our existing cash and cash equivalents and short-term investments will enable us to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2026. We will require substantial additional financing to achieve our goals, and a failure to obtain this necessary capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development programs, commercialization efforts or other operations. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect. We will be required to seek additional funding in the future until such time, if ever, as we can generate substantial product revenue, and currently intend to do so through public or private equity offerings or debt financings, credit or loan facilities, collaborations or a combination of one or more of these funding sources. We may also need to seek additional funds sooner than planned as result of changes in our development plans and regulatory requirements to support registration of our product candidates. Additional funds may not be available to us on acceptable terms or at all. If we fail to obtain necessary capital when needed on acceptable terms, or at all, we could be forced to delay, limit, reduce or terminate our product development programs, commercialization efforts or other operations. If we raise additional funds by issuing equity securities, our stockholders will suffer dilution and the terms of any financing may adversely affect the rights of our stockholders. In addition, as a condition to providing additional funds to us, future investors may demand, and may be granted, rights superior to those of existing stockholders. Debt financing, if available, is likely to involve restrictive covenants limiting our flexibility in conducting future business activities, and, in the event of insolvency, debt holders would be repaid before holders of our equity securities received any distribution of our corporate assets.

Previous wording

In July 2022, we raised net proceeds of approximately $122.5 million after deducting fees and expenses through the sale of an aggregate of 9,013,834 shares of common stock, pre-funded warrants to purchase up to 24,696,206 shares of our common stock and accompanying common warrants to purchase up to 8,427,508 shares of our common stock. The offering price per share and accompanying common warrant was $3.87125 per share and the offering price per pre-funded warrant and accompanying common warrant was $3.87025 per share, which equals the per share offering price for the shares of common stock less the $0.001 exercise price for each such pre-funded warrant. The pre-funded warrants remain exercisable until exercised in full. The common warrants have an exercise price of $5.806875 per share and expire on June 30, 2025. Both the pre-funded and common warrants are immediately exercisable, subject to beneficial ownership limitations. We issued an aggregate of 2,582,557 shares of common stock upon the cashless exercise of the pre-funded warrants in March 2023. We issued an aggregate of 19,901 and 2,739,096 shares of common stock upon the cashless exercise of the common warrants and pre-funded warrants in June 2024 and November 2024, respectively.

Current wording

In July 2022, we raised net proceeds of approximately $122.5 million after deducting fees and expenses through the sale of an aggregate of 9,013,834 shares of common stock, pre-funded warrants to purchase up to 24,696,206 shares of our common stock and accompanying common warrants to purchase up to 8,427,508 shares of our common stock. The offering price per share and accompanying common warrant was $3.87125 per share and the offering price per pre-funded warrant and accompanying common warrant was $3.87025 per share, which equals the per share offering price for the shares of common stock less the $0.001 exercise price for each such pre-funded warrant. The pre-funded warrants remain exercisable until exercised in full. The common warrants had an exercise price of $5.806875 per share and expired on June 30, 2025. Both the pre-funded and common warrants were immediately exercisable, subject to beneficial ownership limitations. We issued an aggregate of 2,582,557 shares of common stock upon the cashless exercise of the pre-funded warrants in March 2023. We issued an aggregate of 19,901 shares of common stock upon the cashless exercise of the 322,893 common warrants in June 2024.

Previous wording

The following summarizes warrant activity during the three months ended March 31, 2025 and 2024:

Current wording

The following summarizes warrant activity during the six months ended June 30, 2025 and 2024:

Previous wording

In March 2024, we entered into a sales agreement with Cowen and Company LLC, or TD Cowen, as sales agent, or 2024 ATM program, pursuant to which we may issue and sell shares of our common stock for an aggregate maximum offering of $100.0 million. TD Cowen is entitled to compensation up to 3% of the aggregate gross proceeds for the common stock sold through the 2024 ATM program. As of March 31, 2025, approximately $95.4 million remained available for the offer and sale of shares of common stock under the 2024 ATM program.

Current wording

In March 2024, we entered into a sales agreement with Cowen and Company LLC, or TD Cowen, as sales agent, or 2024 ATM program, pursuant to which we may issue and sell shares of our common stock for an aggregate maximum offering of $100.0 million. TD Cowen is entitled to compensation up to 3% of the aggregate gross proceeds for the common stock sold through the 2024 ATM program. No sales were made under the 2024 ATM program during the six months ended June 30, 2024 and 2025. As of June 30, 2025, approximately $95.4 million remained available for the offer and sale of shares of common stock under the 2024 ATM program.

Previous wording

In August 2021, we entered into a sales agreement with TD Cowen, as sales agent, pursuant to which we may issue and sell shares of our common stock for an aggregate maximum offering of $100.0 million under an at-the-market offering program, or 2021 ATM program. TD Cowen is entitled to compensation up to 3% of the aggregate gross proceeds for the common stock sold through the 2021 ATM program. During the three months ended March 31, 2024, we sold 6,639,348 shares of common stock under the 2021 ATM program for net proceeds of approximately $32.2 million, after deducting commissions paid to TD Cowen and other financing costs. The Form S-3 registration statement, which registered the 2021 ATM Program, expired on August 15, 2024. As a result, no shares of common stock may be sold under the 2021 ATM Program.

Current wording

In August 2021, we entered into a sales agreement with TD Cowen, as sales agent, pursuant to which we may issue and sell shares of our common stock for an aggregate maximum offering of $100.0 million under an at-the-market offering program, or 2021 ATM program. TD Cowen is entitled to compensation up to 3% of the aggregate gross proceeds for the common stock sold through the 2021 ATM program. During the six months ended June 30, 2024, we sold 7,576,067 shares of common stock under the 2021 ATM program for net proceeds of approximately $38.4 million, after deducting commissions paid to TD Cowen and other financing costs. The Form S-3 registration statement, which registered the 2021 ATM Program, expired on August 15, 2024. As a result, no shares of common stock may be sold under the 2021 ATM Program.