Full Press Release Details
JANUARY 2023 Nasdaq: ANNX 1
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"forward looking" statements about Annexon, Inc. the outcomes of any future collaboration agreements; and our ability to and our industry that involve substantial risks and uncertainties. All adequately maintain intellectual
property rights for our product candidates. statements other than statements of historical facts, including statements These and other risks are described in greater detail under the section titled regarding our clinical and preclinical programs,
timing and commencement of "Risk Factors" contained in our Quarterly Report on Form 10-Q filed with the future nonclinical studies and clinical trials and research and development Securities Exchange Commission (SEC) on November 3, 2022
and our other programs, timing of clinical results, strategic plans for our business and filings with the SEC from time to time. All forward-looking statements in this product candidates, including additional indications which we may pursue, our
presentation speak only as of the date of this presentation. Except as required financial position, runway and anticipated milestones, are forward-looking by law, we undertake no obligation to publicly update any forward-looking statements. In some
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yet been approved for marketing by the U.S. "should," "target," "will," "would" and other similar expressions that are Food and Drug Administration (FDA). These are currently limited by federal
predictions of or indicate future events and future trends, or the negative of law to investigational use, and no representation is made as to their safety or these terms or other comparable terminology. effectiveness for the purposes for which they
are being investigated. Forward-looking statements are not guarantees of future performance and are This presentation also contains estimates and other statistical data made by subject to risks and uncertainties that could cause actual results and
events independent parties and by us relating to market size and growth and other to differ materially from those anticipated, including, but not limited to, risks data about our industry. This data involves a number of assumptions and and
uncertainties related to: our history of net operating losses; our ability to limitations, and you are cautioned not to give undue weight to such estimates obtain necessary capital to fund our clinical programs; the early stages of or statistical
data. Neither we nor any other person makes any representation clinical development of our product candidates; the effects of COVID-19 or as to the accuracy or completeness of such data or undertakes any obligation other public health crises on our
clinical programs and business operations; to update such data after the date of this presentation. 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; 2
A bold mission to free the body, brain and eye from complement- mediated
Annexon Overview: Pursuing Our Mission & Significant Value
Pioneering Classical Complement Platform in Autoimmunity, Neurodegeneration & Ophthalmology Complement clinically / commercially validated with downstream approaches (C1s, C3, C5) ANNX building on prior learnings to block both up
& downstream complement where it starts Pursuing indications where (i) C1q localizes on disease tissue to anchor complement activation & (ii) complement activity drives disease progression Multi-faceted
beach-head' portfolio with informed signal finding' and confirming' trials Clinical POC with lead drug candidate (ANX005) in multiple indications: GBS, HD, CAD, ALS Significant Enterprise
Value' Potential with multiple drivers over the next 3 years Targeting both Orphan and large patient population diseases with 4 Flagship Programs -- ~$10B market opportunity Multiple value driving clinical readouts over 2023
& 2024, including GA & GBS confirming trials Potential 1st-in-class GBS commercialization & initiation of 1st-in-class anti-complement HD pivotal trial Potential 1st-in-class oral compound for Autoimmune diseases
Well-Capitalized with Additional Opportunities Runway into 2025 Robust IP estate Wholly-owned with specific therapeutic-area partnering opportunities 4
Meaningful Progress Across Our Portfolio of Complement- targeted
Therapies in 2022 Positive clinical outcomes with ANX005 in patients with HD, CAD & ALS Favorable safety profile with ANX005 across >200 people treated Enrollment completed early for Phase 2 trial of ANX007 for GA First-in-kind oral small
molecule shows target drug levels achieved $130M capital raise to expand and extend runway into 2025 5
Revolutionizing Complement Biology in Pursuit of Our Mission Targeting
C1q & classical complement cascade to treat autoimmune and neurodegenerative disease 2007 2014 - 2022 1960-70s Understanding C1q's role in Discovery of C1q's role in Annexon launched & advanced into autoimmune disease brain &
eye neurodegeneration mid- and late-stage trials by ANNX founder, Dr. Ben Barres targeting C1q-mediated diseases of the body, brain & eye C1q initiates a powerful inflammatory C1q C1q anchors damaging cascade that can lead to r/s complement
activation 1 tissue damage Validated role of C1q in autoimmune & on photoreceptor 2 neurodegenerative disease synapses in GA Full target engagement with multiple drug Immune cell Immune cell recruitment candidates attack
Clinical POC in multiple diseases Well-capitalized with runway into 2025 Talented Warrior Spirit' team Membrane damage 3 C1q Drives Removal of Functioning Synapses 1 2 3 McGonigal et al. Acta Neuropathologica
Communications (2016) 4:23 ; C1q bound to photoreceptor synapses in aged mice: Annexon data on file; Stevens, et al., 2007, Cell 6
CSF C1q ( g/mL) Mean SD Robust Clinical Target Engagement of
C1q Demonstrated in the Body, Brain & Eye Full C1q Inhibition in Full C1q Inhibition in Full C1q Inhibition in Serum with ANX005 CSF with ANX005 Aqueous Humor with ANX007 10 CSF Levels ANX005 0.03 1 0.1 0.1 0.002 CSF C1q 0.01 0 6 12 18 24 30 36
Week 7 CSF ANX005 ( g/mL) Mean SD
Clinical Proof-of-Concept Demonstrated in Both Autoimmune and
Neurodegenerative Indications Guillain-Barr Syndrome (GBS) Huntington's Disease (HD) ANX005 ANX005 28% patients 75% patients 3 pt improvement improved Composite Unified Huntington's Disease Rating Scale Amyotrophic Lateral
Sclerosis (ALS) Cold Agglutinin Disease (CAD) ANX005 All patients improved or maintained Hemoglobin Levels ANX005 progression rate during treatment Patients showed Both patients that stayed on drug > 2-point improvement continued to improve All
patients who went off treatment declined 8
Achieving Our Mission With FOUR FLAGSHIP PROGRAMS Stopping Harmful
Inflammation and Tissue Damage in the Body, Brain & Eye Guillain-Barr Huntington's Geographic Orally Administered Syndrome (GBS) Disease (HD) Atrophy (GA) Small Molecule AUTOIMMUNE NEURODEGENERATION OPHTHALMOLOGY AUTOIMMUNE
Well-validated MOA Pioneering MOA Well-validated MOA Well-validated MOA Fast path to market in No disease-modifying Localized inhibition in eye Ease and convenience of rare disease treatments available oral dosing st st st st 1 complement inhibition
1 up & downstream 1 oral compound targeting 1 placebo-controlled trial in a brain disorder complement approach classical complement in ~40 years 9
Flagship Programs Advancing in Mid-stage and Pivotal Trials 2023
ANTICIPATED INDICATION CANDIDATE PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONE Complete Phase 3 Guillain-Barr Syndrome ANX005 enrollment in 2H 2023 Initiate Phase 2/3 trial Huntington's Disease ANX005 2023 Report Phase 2 data Geographic
Atrophy ANX007 mid-2023 Complete MAD trial Autoimmune Indications ANX1502 and initiate POC trial in patients 10
ANX005 Powerfully Inhibits C1q and Entire Classical Complement Pathway
in the Body and Brain Key Attributes Diverse: Utilized in autoimmune & neurodegenerative trials Potency: High binding affinity to C1q (<10 pM) Target Engagement: Full C1q inhibition in blood and CSF ANX005
Safety: Generally well-tolerated in acute and chronic trials No drug-related deaths & no serious infections observed IV administered monoclonal antibody No autoimmune events observed post enhanced ANA screening / monitoring
Clinical: Rapid clinical benefit demonstrated in GBS, HD, CAD & ALS Administered to >200 patients to date 12
ANX005 Generally Well-Tolerated in Several Patient Populations KEY
TAKEAWAYS Leveraged learnings to No drug related 6 completed and optimize safety profile deaths & no serious 2 ongoing acute and infections observed chronic autoimmune Low grade, transient IRRs throughout all studies &
neurodegenerative during first infusion: trials managed by infusion rate and pre-medication >100 patients from completed trials Single serious event of autoimmunity (SLE/ lupus- >110 patients in like syndrome): no
further ongoing trials events of autoimmunity Exposure up to 1 year observed post enhanced ANA screening / safety monitoring to date 13
ANX005 Generally Well-Tolerated Across Clinical Trials Safety
Population Study Deaths and Serious Adverse Events (N=116*) Treatment Emergent Adverse All CTCAE CTCAE No deaths and no serious infections observed Events (TEAE) Grade 3 Grades 3 observed serious adverse events related to
ANX005 N (%) N (%) 1 IRR in NHV prior to dosing optimization Any reported TEAEs, N (%) 116 (100.0) 38 (32.8) Most Common TEAE, N (%) 2 in HD P2a trial (lupus like syndrome and idiopathic pneumonitis) prior to implementation of ANA
screening and safety monitoring Infusion Related Reaction (IRR) 38 (32.8) 3 (2.6) plan Most Common TEAEs (non-IRR), N (%) Headache 37 (31.9) 0 (0) Adverse Events of Note Pain in extremity 24 (20.7) 0 (0) Infusion Related Reactions (IRR)
primarily first dose effect Rash** 26 (22.4) 7 (6.0) across indications (~95%) and almost always associated with Pyrexia 18 (15.6) 0 (0) transient rash Lab abnormality - CPK 15 (12.9) 7 (6.0) Adverse events coded as rash were primarily IRR
Constipation 13 (11.2) 0 (0) No IRR observed after 2nd dose of ANX005 Pruritus 13 (11.2) 0 (0) Elevated creatine phosphokinase (CPK) seen in placebo and Serious TEAEs, N (%) 14 (12.1) 14 (12.1) ANX005 treated GBS patients -
consistent with GBS Related to ANX005 3 (2.6) 3 (2.6) Infections 0 (0) 0 (0) * All completed and open label studies with ANX005 as per 01/05/2023; Includes: FIH, GBS P1b, GBS DDI, HD P2a, ALS P2a, CAD P2, wAIHA P2 trials ** Primarily initial dose
IRRs, but coded as rash 14
Flagship Programs Guillain-Barr Syndrome (GBS)
Huntington's Disease (HD) Geographic Atrophy (GA) Oral small molecule 15 15
First-In-Class Treatment for GBS Acute, antibody-mediated autoimmune
disease driven by aberrant C1q activation GBS Overview Role of C1q ANX005 Rapid onset of Fast Track & Orphan Drug C1q binds autoantibodies on nerve neuromuscular weakness Designations components, anchoring complement and paralysis
activation, inflammation & tissue damage Pursuing monotherapy label 12,000 patients ANX005 blocks all inflammatory / diagnosed/year in North damaging components of classical pathway Phase 3 pivotal trial ongoing America &
Europe for rapid recovery Productive engagement with FDA No FDA-approved therapies C1q targeting the on the statistical analysis plan for neuromuscular the ongoing pivotal trial junction C1q 16 16
ANX005 Demonstrated Clinical POC in GBS Placebo-Controlled Trial Early
improvement in muscle strength and reduction in neuronal damage preceding gain of function Impact on Muscle Strength Impact on Key Neuronal Biomarker Impact on Clinical Function Statistically significant early NfL Patients achieving 3 point
Rapid increase in muscle strength within first week of treatment reduction (weeks 2-4) improvement in 8 weeks 90 Change in MRC ANX005 30 30 28% patients with 25 ANX005 3 point gain 20 0 20 15 Placebo -30 10 10 Placebo 0% -60 5 P<0.05 0 0
-90 ANX005 Placebo 0 2 4 6 8 ANX005 Placebo Weeks (18-75 mg/kg) Guillain-Barr Mean Change in MRC Score from Baseline 6-Point Disability Scale All graphs: ANX005 n=18, Placebo, n=8 17 MRC (Change from Baseline) % Change in NfL % Patients
ANX005 GBS Phase 3 Pivotal Trial Underway On track to complete expanded
enrollment in 2H23 with Phase 3 data in 1H24 Trial Design Specifications Randomized, double-blind trial (N~220) Recently diagnosed severe patients (3 or higher on GBS-DS) Placebo (n=~75) Primary endpoint: GBS Disability Scale
at week 8 ANX005 30 mg/kg (n=~75) Patients stratified for baseline muscle strength and time from symptom onset ANX005 75 mg/kg (n=~75) Productive engagement with FDA on the statistical analysis plan for the ongoing pivotal trial Day
1: 6-month Off-treatment Follow-up Increased study population by ~40 patients Single Dose 18
First-In-Class Treatment for HD Progressive neurodegenerative disease
involving excessive synapse loss and neuronal damage HD Overview Role of C1q ANX005 Progressive, inherited C1q triggers synapse damage, synapse Phase 2 results demonstrated 2,3 neurodegenerative removal and neuroinflammation benefit in
clinical outcomes disorder ANX005 blocks classical complement Orphan Drug Designation 80K people affected activation to protect synapses, reduce 1 globally; ~300K at-risk neuroinflammation and improve clinical Productive engagement
with FDA outcomes No approved treatments that reverse or slow Pivotal trial design aimed at C1q Targeting the C1q targeting disease progression slowing rate of disease Neuromuscular synapses on Junction progression striatal neurons of 3 HD
patient Phase 2/3 trial expected to initiate in 2023 1 2 3 1GlobalData and market research reports, Wilton 2021 doi.org/10.1101/2021.12.03.471180; Hong 2016 Science doi 10.1126/science.aad8373; Stevens 2007 Cell doi
10.1016/j.cell.2007.10.036; Fonseca, 2004, J Neurosci; Dejanovic, 2018, Neuron; Vukojicic, 2019, Cell Reports; Howell, 2011, J Clin Inves; Williams, 2016, Mol Neurodegen; Jiao, 2018, Mol Neurodeg; Lui, 2016, Cell 165:921; Krukowski, 19 19 2018,
Int.JMol Sci; Holden, 2021, Science; Annexon NfL reduction in SOD1 model, unpublished; Absinta, Nature, 2021
ANX005 Improved Clinical Outcomes in HD Phase 2 Trial Reduced
Downstream Complement Reduced Neuroinflammation Improved Clinical Function HD inflammation marker (YKL-40*) CSF C3 levels decreased in all patients Benefit at all time points in high reduced in patients with high baseline during on and off treatment
period complement group (cUHDRS) complement activity (C4a/C4) CSF YKL-40 c cUHDRS UHDRS CSF C3 CSF YKL-40 C4aH.L AM 01.03.23 CSF YKL-40 Impvr.NonImpvr AM 01.03.23 10 10 2 C4a/C4 Low (n=11) Non-improver (n=10) Off Off Off 1.00 treatment treatment
treatment C4a/C4 High (n=12) Improver (n=13) 5 5 1 0.75 0 0 0 0.50 -5 -5 -1 0.25 0.00 -10 -2 -10 0 6 12 18 24 30 36 0 6 12 18 24 30 36 0 6 12 18 24 30 36 0 6 12 18 24 30 36 CSF YKL-40 Impvr.NonImpvr AM 01.03.23 Weeks CSF YKL-40 C4aH.L AM 01.03.23
CSF YKL-40 C4aH.L AM 01.03.23 CSF YKL-40 Impvr.NonImpvr AM 01.03.23 Weeks Time (weeks) Time (weeks) 10 10 10 10 C4a/C4 Low (n=11) Non-improver (n=10) C4a/C4 Low (n=11) Non-improver (n=10) C4a/C4 High (n=12) Improver (n=13) C4a/C4 High (n=12)
Improver (n=13) 5 5 5 5 0 0 0 0 *Produced by activated glia - Elevated in HD and other neurological diseases -5 -5 -5 -5 20 -10 -10 -10 -10 0 6 12 18 24 30 36 0 6 12 18 24 30 36 0 6 12 18 24 30 36 0 6 12 18 24 30 36 Time (weeks) Time (weeks) Time
(weeks) Time (weeks) CSF C3 levels (Fold change from baselin % Change (Median +/- QR) % Change (Median +/- QR) % Change (Median +/- QR) % Change (Median +/- QR) cUHDRS Change from Baseline % Change (Median +/- QR) % Change (Median +/- QR)
Initiating Pivotal Phase 2/3 Trial of ANX005 in HD Trial Design Key
Objectives Randomized, double-blind, placebo-controlled Disease progression measured by cUHDRS and TFC Leveraging precision medicine approach for patients with elevated baseline complement levels Confirm observations
with rapid drug impact on high complement baseline patients Patient motor, cognition, behavior, functional capacity and quality of life assessments Patient Population Safety and tolerability of ANX005 Patients with manifest
and pre-manifest HD CAP score > 400 UHDRS independence score 80 EXPECT TO INITIATE IN 2023 21
First-In-Class for Early Complement Inhibition in GA Progressive
neurodegenerative retinal disease involving C1q-driven synapse and photoreceptor loss GA Overview Role of C1q ANX007 Leading cause of C1q drives tissue damage in the retina by Targeting up and blindness in the elderly anchoring complement
activation on drusen, downstream complement photoreceptor cells and synapses activation 1M people diagnosed in US; 5M people globally ANX007 has potential to provide more Aim to slow rate of lesion complete protection by shutting down all