Annexon, Inc 8-K, filed Jan 11, 2021
Annexon, Inc. (ANNX)
About this 8-K
Annexon, Inc filed this 8-K on January 11, 2021.
Items reported
- Item 7.01: Regulation FD disclosure
- Item 9.01: Financial statements and exhibits
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 11, 2021
ANNEXON, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-39402 | 27-5414423 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification Number) |
180 Kimball Way, Suite 200
South San Francisco, California 94080
(Address of principal executive offices, including Zip Code)
Registrant’s telephone number, including area code: (650) 822-5500
Not Applicable
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class |
Trading Symbol(s) |
Name of each exchange on which registered | ||
| Common Stock, $0.001 par value per share | ANNX | The Nasdaq Stock Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 7.01 | Regulation FD Disclosure. |
Attached hereto as Exhibit 99.1 is an investor presentation that Annexon, Inc. plans to present during the 39th Annual J.P. Morgan Healthcare Conference commencing on January 11, 2021.
| Item 9.01 | Financial Statements and Exhibits. |
| Exhibit No. |
Description | |
| 99.1 | Annexon, Inc. Investor Presentation. | |
The information in this report, including the exhibit hereto, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained herein and in the accompanying exhibit shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission made by Annexon, Inc., whether made before or after the date hereof, regardless of any general incorporation language in such filing.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| ANNEXON, INC. | ||||||
| Date: January 11, 2021 | By: | /s/ Jennifer Lew | ||||
| Jennifer Lew Executive Vice President and Chief Financial Officer | ||||||
Exhibit 99.1 STOPPING CLASSICAL COMPLEMENT AT THE START TREATING DISEASES OF THE BODY, BRAIN AND EYE COMPANY PRESENTATION JANUARY 11, 2021Exhibit 99.1 STOPPING CLASSICAL COMPLEMENT AT THE START TREATING DISEASES OF THE BODY, BRAIN AND EYE COMPANY PRESENTATION JANUARY 11, 2021
Disclaimer This presentation contains “forward‐looking” statements about Annexon, Inc. and our industry that involve substantial risks a nd uncertainties. All statements other than statements of historical facts, including statements regarding our clinical and preclinical programs, timing and commencement of future nonclinical studies and clinical trials and research and development programs, timing of clinical results, strategic plans for our business and product candidates, including additional indications which we may pursue, our financial position and anticipated milestones, are forward‐ looking statements. In some cases, you can identify forward looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. Forward‐ looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: our history of net operating losses; our ability to obtain necessary capital to fund our clinical programs; the early stages of clinical development of our product candidates; the effects of COVID‐ 19 or other public health crises on our clinical programs and business operations; our ability to obtain regulatory approval of and successfully commercialize our product candidates; any undesirable side effects or other properties of our product candidates; our reliance on third‐ party suppliers and manufacturers; the outcomes of any future collaboration agreements; and our ability to adequately maintain intellectual property rights for our product candidates. These and other risks are described in greater detail under the section titled “Risk Factors” contained in our Quarterly Report on Form 10‐ Q for the quarterly period ended September 30, 2020 filed with the Securities and Exchange Commission (SEC) on November 16, 2020 as well as discussions of potential risks, uncertainties and other important factors in our other filings with the SEC. All forward‐ looking statements in this presentation speak only as of the date of this presentation. Except as required by law, we undertake no obligation to publicly update any forward‐ looking statements, whether as a result of new information, future events or otherwise. This presentation concerns drugs that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). These are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. 2Disclaimer This presentation contains “forward‐looking” statements about Annexon, Inc. and our industry that involve substantial risks a nd uncertainties. All statements other than statements of historical facts, including statements regarding our clinical and preclinical programs, timing and commencement of future nonclinical studies and clinical trials and research and development programs, timing of clinical results, strategic plans for our business and product candidates, including additional indications which we may pursue, our financial position and anticipated milestones, are forward‐ looking statements. In some cases, you can identify forward looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. Forward‐ looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: our history of net operating losses; our ability to obtain necessary capital to fund our clinical programs; the early stages of clinical development of our product candidates; the effects of COVID‐ 19 or other public health crises on our clinical programs and business operations; our ability to obtain regulatory approval of and successfully commercialize our product candidates; any undesirable side effects or other properties of our product candidates; our reliance on third‐ party suppliers and manufacturers; the outcomes of any future collaboration agreements; and our ability to adequately maintain intellectual property rights for our product candidates. These and other risks are described in greater detail under the section titled “Risk Factors” contained in our Quarterly Report on Form 10‐ Q for the quarterly period ended September 30, 2020 filed with the Securities and Exchange Commission (SEC) on November 16, 2020 as well as discussions of potential risks, uncertainties and other important factors in our other filings with the SEC. All forward‐ looking statements in this presentation speak only as of the date of this presentation. Except as required by law, we undertake no obligation to publicly update any forward‐ looking statements, whether as a result of new information, future events or otherwise. This presentation concerns drugs that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). These are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. 2
Annexon: Pioneering Classical Complement Therapies to Treat Autoimmune, Neurodegenerative and Ophthalmic Diseases • Blocking upstream complement to stop disease processes at the start • Broad platform potential in orphan and large patient populations in autoimmune, neurodegenerative and ophthalmic diseases • Phase 2 pipeline with 3 drug candidates to deliver near‐ and mid‐ term catalysts • Precision medicine approach leveraging complement and disease biomarkers • Well capitalized with worldwide rights to development and commercialization 3Annexon: Pioneering Classical Complement Therapies to Treat Autoimmune, Neurodegenerative and Ophthalmic Diseases • Blocking upstream complement to stop disease processes at the start • Broad platform potential in orphan and large patient populations in autoimmune, neurodegenerative and ophthalmic diseases • Phase 2 pipeline with 3 drug candidates to deliver near‐ and mid‐ term catalysts • Precision medicine approach leveraging complement and disease biomarkers • Well capitalized with worldwide rights to development and commercialization 3
Demonstrated Leadership Advancing Transformative Therapies Doug Love, Esq. Ted Yednock, Ph.D. President & CEO Chief Scientific Officer Genentech, Amgen, Elan Elan, Prothena, Athena Jennifer Lew Sanjay Keswani, M.D. Michael Overdorf Chief Financial Officer Chief Medical Officer Chief Business Officer Aduro, Dynavax, Ernst & Young Roche, Eli Lilly, Amgen, Eli Lilly Bristol‐ Meyers Squibb 4Demonstrated Leadership Advancing Transformative Therapies Doug Love, Esq. Ted Yednock, Ph.D. President & CEO Chief Scientific Officer Genentech, Amgen, Elan Elan, Prothena, Athena Jennifer Lew Sanjay Keswani, M.D. Michael Overdorf Chief Financial Officer Chief Medical Officer Chief Business Officer Aduro, Dynavax, Ernst & Young Roche, Eli Lilly, Amgen, Eli Lilly Bristol‐ Meyers Squibb 4
Building a Leading Multi-Faceted Complement Company 2020: A Foundational Year ü $100M Series D in June and $263M Nasdaq IPO in July ü Robust ANX005 and ANX007 patient data demonstrating tolerability, full target engagement, biomarker/clinical data 0 ü Rapidly advancing into multiple Ph2 autoimmune, neurodegenerative and ophthalmic trials ü Developing innovative next generation drug candidates • ANX009 subcutaneous Firstin ‐ H ‐ uman trial ongoing • Followo ‐ n small molecule and monoclonal antibody candidates advancing to IND 5Building a Leading Multi-Faceted Complement Company 2020: A Foundational Year ü $100M Series D in June and $263M Nasdaq IPO in July ü Robust ANX005 and ANX007 patient data demonstrating tolerability, full target engagement, biomarker/clinical data 0 ü Rapidly advancing into multiple Ph2 autoimmune, neurodegenerative and ophthalmic trials ü Developing innovative next generation drug candidates • ANX009 subcutaneous Firstin ‐ H ‐ uman trial ongoing • Followo ‐ n small molecule and monoclonal antibody candidates advancing to IND 5
Robust Clinical Pipeline of C1q Inhibitors for Body, Brain & Eye Multiple clinical stage drug candidates with diverse routes of administration INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 2/3 CURRENT STATUS ANX005 (IV) Guillain-Barré Syndrome (GBS) Ph 2/3 Ongoing Warm Autoimmune Hemolytic Ph 2 Initiating Anemia (wAIHA) Huntington’s Disease (HD) Ph 2 Ongoing Amyotrophic Lateral Sclerosis (ALS) Ph 2 Initiating ANX007 (IVT) Geographic Atrophy (GA) Ph 2 Initiating ANX009 (SubQ) Autoimmune Ph 1 Ongoing 6Robust Clinical Pipeline of C1q Inhibitors for Body, Brain & Eye Multiple clinical stage drug candidates with diverse routes of administration INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 2/3 CURRENT STATUS ANX005 (IV) Guillain-Barré Syndrome (GBS) Ph 2/3 Ongoing Warm Autoimmune Hemolytic Ph 2 Initiating Anemia (wAIHA) Huntington’s Disease (HD) Ph 2 Ongoing Amyotrophic Lateral Sclerosis (ALS) Ph 2 Initiating ANX007 (IVT) Geographic Atrophy (GA) Ph 2 Initiating ANX009 (SubQ) Autoimmune Ph 1 Ongoing 6
Significant Catalysts in 2021 and Beyond Sufficient cash-runway to achieve these milestones INDICATION 1H 2021 2H 2021 2022 2023 ANX005 (IV) Guillain-Barré Syndrome (GBS) DDI data Ph2/3 data Warm Autoimmune Hemolytic Ph2 data Anemia (wAIHA) Ph2 initial data Huntington’s Disease (HD) Amyotrophic Lateral Sclerosis (ALS) Ph2 initial data ANX007 (IVT) Geographic Atrophy (GA) Ph2 data ANX009 (SubQ) Autoimmune Ph1 data Ph2 data 7Significant Catalysts in 2021 and Beyond Sufficient cash-runway to achieve these milestones INDICATION 1H 2021 2H 2021 2022 2023 ANX005 (IV) Guillain-Barré Syndrome (GBS) DDI data Ph2/3 data Warm Autoimmune Hemolytic Ph2 data Anemia (wAIHA) Ph2 initial data Huntington’s Disease (HD) Amyotrophic Lateral Sclerosis (ALS) Ph2 initial data ANX007 (IVT) Geographic Atrophy (GA) Ph2 data ANX009 (SubQ) Autoimmune Ph1 data Ph2 data 7
Why C1q and the Classical Complement Pathway? C1q is key driver of disease processes for indications Annexon has targeted C1q directly binds to tissue, initiating and anchoring complement in diseases of the body, brain and eye GBS HEMOLYTIC ANEMIA HUNTINGTON’S GEOGRAPHIC ATROPHY C1q C1q C1q C1q C1q Targeting the C1q Targeting C1q Targeting Striatal C1q Targeting Neuromuscular Junction Red Blood Cells Synapses Photoreceptor Synapses Halstead, et al. 2004 Brain 127: 2109–2123 C1q bound to antibody coated RBC Jiao, et al., 2018 Mol Neurodegen 14:45 C1q bound to photoreceptor cells synapses in Annexon data on file aged mice: Annexon data on file 8Why C1q and the Classical Complement Pathway? C1q is key driver of disease processes for indications Annexon has targeted C1q directly binds to tissue, initiating and anchoring complement in diseases of the body, brain and eye GBS HEMOLYTIC ANEMIA HUNTINGTON’S GEOGRAPHIC ATROPHY C1q C1q C1q C1q C1q Targeting the C1q Targeting C1q Targeting Striatal C1q Targeting Neuromuscular Junction Red Blood Cells Synapses Photoreceptor Synapses Halstead, et al. 2004 Brain 127: 2109–2123 C1q bound to antibody coated RBC Jiao, et al., 2018 Mol Neurodegen 14:45 C1q bound to photoreceptor cells synapses in Annexon data on file aged mice: Annexon data on file 8
Inhibiting C1q Shuts Down Entire Classical Complement Pathway Blocks C1q binding to tissues and downstream activation of C4, C3, C5 and C9 Lectin pathway C6-C8 C2 FD,FB Classical C1r C1s C1q C4 C3 C5 C9 Pathway Alternative pathway Potential Efficacy Advantages Potential Safety Advantages 1 ü Anti-C1q stops the cascade before it starts Inhibiting C1q upstream ü Selectively targets C1q in indications where the classical cascade is a key driver ü Shuts down all tissue-damaging components of 1 classical pathway (C1q, C4, C3, C5, C9) ü Allows normal immune functions of lectin and 1 2 alternative complement pathways ü C1q levels similar to C5, and 10-fold lower than C3 1 2 Data on file; Glovsky, Ann Allery Asthma Immunol 2004, 93:513 9Inhibiting C1q Shuts Down Entire Classical Complement Pathway Blocks C1q binding to tissues and downstream activation of C4, C3, C5 and C9 Lectin pathway C6-C8 C2 FD,FB Classical C1r C1s C1q C4 C3 C5 C9 Pathway Alternative pathway Potential Efficacy Advantages Potential Safety Advantages 1 ü Anti-C1q stops the cascade before it starts Inhibiting C1q upstream ü Selectively targets C1q in indications where the classical cascade is a key driver ü Shuts down all tissue-damaging components of 1 classical pathway (C1q, C4, C3, C5, C9) ü Allows normal immune functions of lectin and 1 2 alternative complement pathways ü C1q levels similar to C5, and 10-fold lower than C3 1 2 Data on file; Glovsky, Ann Allery Asthma Immunol 2004, 93:513 9
Leveraging Biomarkers to Increase Probability of Clinical Success Measuring objective classical complement and disease markers in patients Right Indication and Optimal Dose and Objective Measures Patient Selection Dosing Regimen of Treatment Effect Target population for initial study – 25% of lupus nephritis patients – 55% of lupus nephritis patients in flare Higher Classical Complement Activation Inhibition of C1q observed in CSF High Dose ANX005 (18-75 mg/kg) in Patients with Lupus Nephritis, at 18-75 mg/kg Led to Significant Early NfL Reduction Particularly Those in Flare (Weeks 2 – 4) * Annexon data on file 10Leveraging Biomarkers to Increase Probability of Clinical Success Measuring objective classical complement and disease markers in patients Right Indication and Optimal Dose and Objective Measures Patient Selection Dosing Regimen of Treatment Effect Target population for initial study – 25% of lupus nephritis patients – 55% of lupus nephritis patients in flare Higher Classical Complement Activation Inhibition of C1q observed in CSF High Dose ANX005 (18-75 mg/kg) in Patients with Lupus Nephritis, at 18-75 mg/kg Led to Significant Early NfL Reduction Particularly Those in Flare (Weeks 2 – 4) * Annexon data on file 10
IMPROVING PATIENT OUTCOMES IN AUTOIMMUNE DISEASES • G u i l l a i n-Barré Syndrome • Warm Autoimmune Hemolytic Anemia 11IMPROVING PATIENT OUTCOMES IN AUTOIMMUNE DISEASES • G u i l l a i n-Barré Syndrome • Warm Autoimmune Hemolytic Anemia 11
GBS, a Destructive Neuromuscular Autoimmune Disease Severe disease that causes acute paralysis GUILLAIN-BARRÉ SYNDROME (GBS) Rare orphan disease: • 12K patients diagnosed annually in North America/Europe • No approved therapy in the U.S. Autoantibody attack on peripheral nerves, triggering complement (C1q) and neurodegeneration Anti-C1q blocks autoantibody activation of complement and potentially prevents disability 12 0 0GBS, a Destructive Neuromuscular Autoimmune Disease Severe disease that causes acute paralysis GUILLAIN-BARRÉ SYNDROME (GBS) Rare orphan disease: • 12K patients diagnosed annually in North America/Europe • No approved therapy in the U.S. Autoantibody attack on peripheral nerves, triggering complement (C1q) and neurodegeneration Anti-C1q blocks autoantibody activation of complement and potentially prevents disability 12 0 0
ANX005 Well-Tolerated, Achieved Full Target Engagement, Reduced NfL and Prevented Disability in GBS Phase 1b Dose-Ranging Trial Full Target Engagement in CSF Significant Early NfL Reduction 28% of High Dose Patients Improved by ≥ 3 pts on at Higher Doses (18-75 mg/kg) (Weeks 2 – 4) GBS-Disability Scale by Wk 8 ANX005 Placebo n=18 n=8 Dose Dependent Decrease High Dose ANX005 (18-75 mg/kg) vs Placebo High Dose ANX005 (18-75 mg/kg) vs Placebo of CSF Free C1q Annexon data on file 13 Free C1q (ng/ml)ANX005 Well-Tolerated, Achieved Full Target Engagement, Reduced NfL and Prevented Disability in GBS Phase 1b Dose-Ranging Trial Full Target Engagement in CSF Significant Early NfL Reduction 28% of High Dose Patients Improved by ≥ 3 pts on at Higher Doses (18-75 mg/kg) (Weeks 2 – 4) GBS-Disability Scale by Wk 8 ANX005 Placebo n=18 n=8 Dose Dependent Decrease High Dose ANX005 (18-75 mg/kg) vs Placebo High Dose ANX005 (18-75 mg/kg) vs Placebo of CSF Free C1q Annexon data on file 13 Free C1q (ng/ml)
Ongoing GBS Phase 2/3 Trial with ANX005 Fast Track and Orphan Drug designations granted Placebo (n=~60) • Randomized, double-blind trial (N=~180) • Primary endpoint: GBS Disability Scale ANX005 30 mg/kg (n =~60) • Patients stratified for baseline muscle strength and time from symptom onset ANX005 75 mg/kg (n =~60) • Data expected 2023 Single Dose Treatment 14Ongoing GBS Phase 2/3 Trial with ANX005 Fast Track and Orphan Drug designations granted Placebo (n=~60) • Randomized, double-blind trial (N=~180) • Primary endpoint: GBS Disability Scale ANX005 30 mg/kg (n =~60) • Patients stratified for baseline muscle strength and time from symptom onset ANX005 75 mg/kg (n =~60) • Data expected 2023 Single Dose Treatment 14
Targeting Life Threatening RBC Autoantibody Attack in wAIHA WARM AUTOIMMUNE HEMOLYTIC ANEMIA (wAIHA) Autoantibodies attack and destroy RBCs, resulting in anemia, can develop rapidly or gradually • ~30,000 patients globally • No approved therapy in U.S. Complement activation amplifies RBC destruction in certain patients Targeted strategy to select patients who meet specific biomarker criteria of complement activation 15 0Targeting Life Threatening RBC Autoantibody Attack in wAIHA WARM AUTOIMMUNE HEMOLYTIC ANEMIA (wAIHA) Autoantibodies attack and destroy RBCs, resulting in anemia, can develop rapidly or gradually • ~30,000 patients globally • No approved therapy in U.S. Complement activation amplifies RBC destruction in certain patients Targeted strategy to select patients who meet specific biomarker criteria of complement activation 15 0
Antibody-Mediated Complement Activation in wAIHA Patient Sera – Identifying an Enriched Patient Population ANX005 inhibits complement activation ACTIVITY FULLY INHIBITED BY ANX005 in wAIHA in vitro (n=1) • Detected complementa ‐ ctivating antibodies in 4 of 12 wAIHA patients (literature suggests 20 – 30 %) ANX005 • Activity fully inhibited by ANX005 in vitro • Precision medicine approach will enable appropriate patient selection for Phase 2 study 16Antibody-Mediated Complement Activation in wAIHA Patient Sera – Identifying an Enriched Patient Population ANX005 inhibits complement activation ACTIVITY FULLY INHIBITED BY ANX005 in wAIHA in vitro (n=1) • Detected complementa ‐ ctivating antibodies in 4 of 12 wAIHA patients (literature suggests 20 – 30 %) ANX005 • Activity fully inhibited by ANX005 in vitro • Precision medicine approach will enable appropriate patient selection for Phase 2 study 16
Planned Phase 2 wAIHA Trial with ANX005 • Open label trial (n= up to 12) • Using Phase 0 ‘feeder’ study to identify/ select patients for Phase 2 ANX005 100 mg/kg 8 weeks Phase 0 at weeks 0 and 1 follow up • Objective endpoints: safety, PK/PD, (n= up to 12) hemolysis markers, improvement in hemoglobin • Plan to initiate 1H 2021 17Planned Phase 2 wAIHA Trial with ANX005 • Open label trial (n= up to 12) • Using Phase 0 ‘feeder’ study to identify/ select patients for Phase 2 ANX005 100 mg/kg 8 weeks Phase 0 at weeks 0 and 1 follow up • Objective endpoints: safety, PK/PD, (n= up to 12) hemolysis markers, improvement in hemoglobin • Plan to initiate 1H 2021 17
TACKLING BLINDNESS IN RETINAL DISEASES • Geographic Atrophy 18TACKLING BLINDNESS IN RETINAL DISEASES • Geographic Atrophy 18
Pioneering Treatment of Complement-Mediated Neurodegeneration Well-researched role of C1q inhibition to protect against synapse loss and neurodegeneration Ben Barres, M.D., Ph.D. Discoverer of C1q Technology Scientific Co‐ Founder, Annexon • Synapse loss is a major driver of neurological disability and blindness • Precedes loss of neurons • Correlates with functional loss / cognitive decline 19Pioneering Treatment of Complement-Mediated Neurodegeneration Well-researched role of C1q inhibition to protect against synapse loss and neurodegeneration Ben Barres, M.D., Ph.D. Discoverer of C1q Technology Scientific Co‐ Founder, Annexon • Synapse loss is a major driver of neurological disability and blindness • Precedes loss of neurons • Correlates with functional loss / cognitive decline 19
Differentiated Neuroprotective Approach for Geographic Atrophy Targeting up and downstream complement activity associated with retinal nerve loss GEOGRAPHIC ATROPHY (GA) Loss of vision due to loss of neurons (photoreceptors) • ~1 million U.S. patients; ~5 million worldwide • No approved therapies to prevent onset or progression Aberrant C1q activity results in neuronal loss Anti‐ C1q is neuroprotective in GA models 20 0Differentiated Neuroprotective Approach for Geographic Atrophy Targeting up and downstream complement activity associated with retinal nerve loss GEOGRAPHIC ATROPHY (GA) Loss of vision due to loss of neurons (photoreceptors) • ~1 million U.S. patients; ~5 million worldwide • No approved therapies to prevent onset or progression Aberrant C1q activity results in neuronal loss Anti‐ C1q is neuroprotective in GA models 20 0
Intravitreal Administration of Anti-C1q Provides Neuroprotection in a Mouse Model of Photoreceptor Cell Loss / Geographic Atrophy Intravitreal Administration of ANX007 Protects Photoreceptor Cells and Retinal Function Anti-C1q Protects Photoreceptor Protects Retinal Cells / Retinal Thickness Function • C1q is locally produced in the retina and a key driver of cell loss • Upstream activator of C3 • Selective C1q inhibition allows normal function of lectin and alternative pathway Jiao,, et al., 2018 Mol Neurodegener 13(1):45 * p < 0.05; **<0.001 21Intravitreal Administration of Anti-C1q Provides Neuroprotection in a Mouse Model of Photoreceptor Cell Loss / Geographic Atrophy Intravitreal Administration of ANX007 Protects Photoreceptor Cells and Retinal Function Anti-C1q Protects Photoreceptor Protects Retinal Cells / Retinal Thickness Function • C1q is locally produced in the retina and a key driver of cell loss • Upstream activator of C3 • Selective C1q inhibition allows normal function of lectin and alternative pathway Jiao,, et al., 2018 Mol Neurodegener 13(1):45 * p < 0.05; **<0.001 21
Intravitreal ANX007 Effectively Inhibits C1q in Phase 1b Patients Full inhibition at low and high doses support monthly or less frequent dosing Free C1q Levels in Aqueous Humor ANX007 DATA SUMMARY • ANX007 well-tolerated at all dose levels • Single intravitreal injection inhibited C1q in aqueous humor for at least 29 days at both low and high doses • Repeat doses, N = 17 D1 = Day 1 (before ANX007 dosing) st D29 = Day 29 (post‐ 1 dose) Annexon data on file 22Intravitreal ANX007 Effectively Inhibits C1q in Phase 1b Patients Full inhibition at low and high doses support monthly or less frequent dosing Free C1q Levels in Aqueous Humor ANX007 DATA SUMMARY • ANX007 well-tolerated at all dose levels • Single intravitreal injection inhibited C1q in aqueous humor for at least 29 days at both low and high doses • Repeat doses, N = 17 D1 = Day 1 (before ANX007 dosing) st D29 = Day 29 (post‐ 1 dose) Annexon data on file 22
Initiating GA Phase 2 Trial with ANX007 in Q1 2021 • Randomized, double-masked trial ANX007 5.0 mg/eye 1x monthly (n=~80) (N= ~240) Sham once monthly (n=~40) • Primary endpoint: change in area of 6 month geographic atrophy on FAF Off-treatment follow up • Leveraging experience from related ANX007 5.0 mg/eye every 2mo (n=~80) complement trials Sham every 2 months (n=~40) • Data expected 2023 12mo Treatment Period 23Initiating GA Phase 2 Trial with ANX007 in Q1 2021 • Randomized, double-masked trial ANX007 5.0 mg/eye 1x monthly (n=~80) (N= ~240) Sham once monthly (n=~40) • Primary endpoint: change in area of 6 month geographic atrophy on FAF Off-treatment follow up • Leveraging experience from related ANX007 5.0 mg/eye every 2mo (n=~80) complement trials Sham every 2 months (n=~40) • Data expected 2023 12mo Treatment Period 23
TACKLING PATIENT DISABILITY IN DEVASTATING NEURODEGENERATIVE DISEASES • Huntington’s Disease • ALS 24TACKLING PATIENT DISABILITY IN DEVASTATING NEURODEGENERATIVE DISEASES • Huntington’s Disease • ALS 24
Pioneering Classical Complement Approach in Huntington’s Disease Targeting synaptic loss and neuronal death to tackle neurodegeneration HUNTINGTON’S DISEASE (HD) Progressive movement disorder, dementia, psychosis • ~35,000 U.S. patients (Orphan) • Subjects have high and sustained NfL levels Aberrant C1q activity drives synaptic loss and disability C1q inhibition protects against synapse loss and neurodegeneration in HD models 25 0Pioneering Classical Complement Approach in Huntington’s Disease Targeting synaptic loss and neuronal death to tackle neurodegeneration HUNTINGTON’S DISEASE (HD) Progressive movement disorder, dementia, psychosis • ~35,000 U.S. patients (Orphan) • Subjects have high and sustained NfL levels Aberrant C1q activity drives synaptic loss and disability C1q inhibition protects against synapse loss and neurodegeneration in HD models 25 0
ANX005 Reduced Key Markers of Disease Activity in HD Mice Decreased Complement Activation on Synapses, CSF NfL and Synapse Loss Decreased Complement Decreased Levels of CSF NfL Protection Against Synapse Loss Activation on Synapses Fold-Change in Complement CSF NfL (pg/mL) Fold Change Synapse Number Deposition on Synapses Annexon data on file; Collaboration w/ Dan Wilton and Annexon data on file. Study run in R6/2 model Annexon data on file; Collaboration w/ Dan Wilton and Beth Stevens, Harvard Beth Stevens, Harvard * p < 0.05; ** p < 0.01; **** p < 0.0001 26ANX005 Reduced Key Markers of Disease Activity in HD Mice Decreased Complement Activation on Synapses, CSF NfL and Synapse Loss Decreased Complement Decreased Levels of CSF NfL Protection Against Synapse Loss Activation on Synapses Fold-Change in Complement CSF NfL (pg/mL) Fold Change Synapse Number Deposition on Synapses Annexon data on file; Collaboration w/ Dan Wilton and Annexon data on file. Study run in R6/2 model Annexon data on file; Collaboration w/ Dan Wilton and Beth Stevens, Harvard Beth Stevens, Harvard * p < 0.05; ** p < 0.01; **** p < 0.0001 26
Ongoing HD Phase 2 Trial with ANX005 Leveraging biomarkers to inform next stage of development and future neuro indications • Open label trial (N= ~24) • Objective endpoints: Safety, C1q target 3 month engagement, and NfL reduction from 6mo Treatment Off-treatment baseline (n=~24) follow up • Development informed by large natural history cohorts • Initial data expected 2H 2021 27Ongoing HD Phase 2 Trial with ANX005 Leveraging biomarkers to inform next stage of development and future neuro indications • Open label trial (N= ~24) • Objective endpoints: Safety, C1q target 3 month engagement, and NfL reduction from 6mo Treatment Off-treatment baseline (n=~24) follow up • Development informed by large natural history cohorts • Initial data expected 2H 2021 27
Targeting Downstream Neuronal Loss in ALS Only upstream approach targeting both CNS and PNS aspects of the disease AMYTROPHIC LATERAL SCLEROSIS (ALS) Progressive weakness of limb and respiratory muscles • ~30,000 patients globally (Orphan) • Subjects have high baseline NfL levels Aberrant C1q activity potentially drives synaptic/ NMJ loss and disability Strong preclinical data supporting anti‐ C1q approach 28 0Targeting Downstream Neuronal Loss in ALS Only upstream approach targeting both CNS and PNS aspects of the disease AMYTROPHIC LATERAL SCLEROSIS (ALS) Progressive weakness of limb and respiratory muscles • ~30,000 patients globally (Orphan) • Subjects have high baseline NfL levels Aberrant C1q activity potentially drives synaptic/ NMJ loss and disability Strong preclinical data supporting anti‐ C1q approach 28 0
C1q Deposition Correlated w/ Muscle Weakness in Mouse Model and Preceded Denervation in ALS Patients; NfL Elevated w/ Disease C1q Levels in NMJ of ALS Mouse C1q Deposition in NMJ of ALS Serum NfL Elevated in ALS Patients a Year Prior to Symptom Onset Model Correlate with Weakness Patients Prior to Denervation ALS Control *** P=0.0003 r=‐ 0.6624 NMJ Muscle Strength (N) Reference ALS animal model: Lee et al., Bahia El Idrissi et al. Journal of Reference ALS patient data: Benatar, et al., (2018) J Neuroinflam 15:171 Neuroinflammation (2016) 13:72 2018, Ann Neurol 84:130 29 C1q LevelsC1q Deposition Correlated w/ Muscle Weakness in Mouse Model and Preceded Denervation in ALS Patients; NfL Elevated w/ Disease C1q Levels in NMJ of ALS Mouse C1q Deposition in NMJ of ALS Serum NfL Elevated in ALS Patients a Year Prior to Symptom Onset Model Correlate with Weakness Patients Prior to Denervation ALS Control *** P=0.0003 r=‐ 0.6624 NMJ Muscle Strength (N) Reference ALS animal model: Lee et al., Bahia El Idrissi et al. Journal of Reference ALS patient data: Benatar, et al., (2018) J Neuroinflam 15:171 Neuroinflammation (2016) 13:72 2018, Ann Neurol 84:130 29 C1q Levels
Planned ALS Phase 2 Trial with ANX005 Leveraging biomarkers to inform next stage of development and future neuro indications • Open label trial (N= ~24) • Objective endpoints: Safety, PK/PD, C1q target engagement, and NfL reduction 3 month 3mo Treatment from baseline Off-treatment (n=~24) follow up • Targeting all forms of ALS • Plan to initiate early 2021 • Initial data expected 2H 2021 30Planned ALS Phase 2 Trial with ANX005 Leveraging biomarkers to inform next stage of development and future neuro indications • Open label trial (N= ~24) • Objective endpoints: Safety, PK/PD, C1q target engagement, and NfL reduction 3 month 3mo Treatment from baseline Off-treatment (n=~24) follow up • Targeting all forms of ALS • Plan to initiate early 2021 • Initial data expected 2H 2021 30
Potential to Expand Platform Across A Breadth of Diseases Current indications and future opportunities in both orphan and large patient populations AUTOIMMUNE NEURODEGENERATION (warm Autoimmune wAIHA Hemolytic Anemia) HD (Huntington’s Disease) GBS (Guillain-Barré Syndrome) ALS (Amyotrophic Lateral Sclerosis) CAD (Cold Agglutin Disease) Lupus Nephritis CIDP FTD (Frontal Temporal Dementia) (Chronic Idiopathic Demyelinating Polyneuropathy) Bullous Skin Diseases SMA (Spinal Muscular Atrophy) MMN (Multifocal Motor Neuropathy) HIT (Heparin Induced Thrombocytopenia) AD (Alzheimer’s Disease) PMS (Progressive Multiple Sclerosis) Rheumatoid Arthritis TBI (Traumatic Brain injury) ON (Optic Neuritis) Crohn’s Disease OPHTHALMOLOGY GA (Geographic Atrophy) GLA (Glaucoma) Current Indications 31Potential to Expand Platform Across A Breadth of Diseases Current indications and future opportunities in both orphan and large patient populations AUTOIMMUNE NEURODEGENERATION (warm Autoimmune wAIHA Hemolytic Anemia) HD (Huntington’s Disease) GBS (Guillain-Barré Syndrome) ALS (Amyotrophic Lateral Sclerosis) CAD (Cold Agglutin Disease) Lupus Nephritis CIDP FTD (Frontal Temporal Dementia) (Chronic Idiopathic Demyelinating Polyneuropathy) Bullous Skin Diseases SMA (Spinal Muscular Atrophy) MMN (Multifocal Motor Neuropathy) HIT (Heparin Induced Thrombocytopenia) AD (Alzheimer’s Disease) PMS (Progressive Multiple Sclerosis) Rheumatoid Arthritis TBI (Traumatic Brain injury) ON (Optic Neuritis) Crohn’s Disease OPHTHALMOLOGY GA (Geographic Atrophy) GLA (Glaucoma) Current Indications 31
Poised to Drive Value in 2021 and Beyond • Targeting aberrant C1q / classical pathway activation to treat devastating tissue damage in the diseases we’re pursuing • Broad platform potential in orphan and large patient populations in autoimmune, neurodegenerative and ophthalmic diseases • Great momentum and well-resourced to deliver on 2021 priorities § Execute 5 clinical trials § Report initial clinical data from 4 diverse trials § Advance to IND next generation small molecule and mAB drug candidates 32Poised to Drive Value in 2021 and Beyond • Targeting aberrant C1q / classical pathway activation to treat devastating tissue damage in the diseases we’re pursuing • Broad platform potential in orphan and large patient populations in autoimmune, neurodegenerative and ophthalmic diseases • Great momentum and well-resourced to deliver on 2021 priorities § Execute 5 clinical trials § Report initial clinical data from 4 diverse trials § Advance to IND next generation small molecule and mAB drug candidates 32
THANK YOU 33THANK YOU 33