FORWARD-LOOKING STATEMENTS This presentation contains "forward-looking statements," which are made pursuant to the safe harbor provisions of the federal securities laws, including the Private Securities Litigation Reform

JP Morgan Healthcare Conference

FORWARD-LOOKING STATEMENTS This

presentation contains "forward-looking statements," which are made pursuant to the safe harbor provisions of the federal securities laws, including the Private Securities Litigation Reform Act of 1995. Any statements that are not

statements of historical fact may be deemed to be forward-looking statements. Such statements may contain words such as "may," "might," "will," "could," "should," "would,"

"expect," "intend," "plan," "prepare," "look," "seek," "anticipate," "believe," "estimate," "predict," "potential,"

"possible," "continue," "ongoing" or the negative of these terms, or other comparable words. These forward-looking statements include, among others, statements relating to: our plans to deliver precision-based

therapies to improve the lives of patients and their families and to target a broad range of neurodegenerative diseases; plans to discover and develop novel therapeutics to leverage microglial biology, such as iluzanebart (VGL101), VG-3927 and

current or future product candidates, identify additional indications for our current product candidates, and to enable success in clinical development; beliefs about TREM2 agonism's importance in ALSP & Alzheimer's disease; beliefs

about the profiles and potential, including the commercial potential, of our pipeline and the strength of our intellectual property position; our analyses and beliefs about data, including pathology and disease biomarkers and the signaling,

engagement and potency as an agonism of TREM2 in microglia; plans and upcoming milestones, including estimated timelines, for our pipeline program development activities and pipeline expansion opportunities; expected timing and next steps regarding

data announcement, clinical trial activities and regulatory filings and potential approvals; expectations regarding our ability to develop and advance our current and future product candidates and discovery programs; and the belief that we are

well-positioned to execute on our mission. These forward looking statements, which are only predictions, involve risks and uncertainties, many of which are beyond our control and are based on our current beliefs, expectations and assumptions

regarding our business. As such, you should not place undue reliance on any forward-looking statements because such risks and uncertainties could cause actual results, performance or achievement to differ materially and adversely from those

anticipated or implied in the forward-looking statements. Factors that could cause actual results to differ from those predicted in our forward-looking statements include, among others, risks and uncertainties related to product development,

including delays or challenges that may arise in the development and regulatory approval of our current and future product candidates or programs; uncertainties as to the availability and timing of results and data from preclinical and clinical

studies; the timing of our ability to submit and obtain regulatory clearance for investigational new drug applications and initiate additional clinical trials; our ability to initiate and complete our current and expected clinical trials; our

ability to establish and maintain collaborations, strategic relationships and supply arrangements, or that we will not realize the intended benefits from such relationships or arrangements; whether our cash resources will be sufficient to fund our

foreseeable and unforeseeable operating expenses and capital expenditure requirements; our ability to raise additional funding on favorable terms, or at all; the rate and degree of market acceptance and clinical utility of our product candidates;

the ability and willingness of our third-party collaborators to continue research and, development and manufacturing activities relating to our product candidates; the accuracy of our data analyses or estimates for the potential and market for our

products; our ability, and the ability of our collaborators, to protect our intellectual property and to conduct activities for the development and commercialization of our candidates in view of third party intellectual property positions; our

financial performance; our ability to retain and recruit key personnel, as well as the potential contribution of our employees and board to our growth and success as a Company; developments and projections relating to our competitors or our

industry; our ability to work with the FDA to successfully remove the partial clinical hold on VG-3927; changes in general economic conditions and global instability, in particular economic conditions in the markets on which we or our suppliers

operate; changes in laws and regulations; and those risks and uncertainties identified in our filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our most-recently filed Annual Report

on Form 10-K or Quarterly Report on Form 10-Q, and such other risks and uncertainties that may be described in subsequent filings we may make with the SEC. You should not rely upon forward-looking statements as predictions of future events or

performance, or as a representation or warranty (express or implied) by us or any other person that we will achieve our objectives and plans in any specified time frame, on such specified terms, or at all. Although our management believes that the

expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. These forward-looking statements

speak only as of the date such statements are made. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or

Vigil Neuroscience: A Clinical-Stage

Microglia-Focused Therapeutics Company Focused on treating rare and common neurodegenerative diseases by restoring vigilance of microglia, the brain's sentinel immune cells Precision-based strategy for developing microglia therapeutics Only

company known to have 2 modalities for TREM2 agonism - monoclonal antibody and oral small molecule Multiple value-driving clinical milestones for lead development programs in 2024 Vigil Neuroscience, Inc. 2024. All rights

Restoring Microglia with TREM2 as a

neurodegenerative diseases TREM2 is Essential for Microglial Function

Vigil's Precision Medicine

Strategy to Target Broad Range of Neurodegenerative Diseases First Indication Rare Microgliopathy (ALSP) Data Driven Expansion in Other Rare Microgliopathies Pipeline Candidates for Genetically Defined Subpopulations in Common Indications (AD)

Further Expansion into Broader Populations in Common Indications Apply learnings from genetically defined subpopulations to larger indications ALSP: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; AD: Alzheimer's

Vigil TREM2 Agonists: Differentiated

Strategy & Multiple Modalities Iluzanebart (VGL101): TREM2 mAb in development for ALSP VG-3927: Small Molecule TREM2 Agonist in development for AD ONLY targeted drug candidate in clinical development for ALSP 1st & ONLY TREM2 small molecule

Building a Robust Pipeline in Rare

& Common Neurodegenerative Diseases Vigil has exclusive rights to all programs Alzheimer's Disease Iluzanebart (VGL101): Fully Human Monoclonal Antibody Healthy Volunteer Phase 1 Trial1 (Completed) Healthy Volunteer VG-3927: Oral Small

Molecule TREM2 Agonist Discovery Preclinical Phase 1 Phase 2 Preclinical PoC Evaluation Other Leukodystrophies Complete Phase 1 data presented at ANA 2023 (please see Meier et al. ANA 2023 Poster M151 on Vigil's Publications webpage

(https://www.vigilneuro.com/press-releases-publications) IND for VG-3927 open; Phase 1 clinical trial in healthy volunteers allowed to proceed with partial clinical hold related to maximum exposure limit ALSP Phase 2 Proof-of-Concept

Iluzanebart (VGL101) Antibody TREM2

Epidemiology 10% adult-onset

leukodystrophies: Including ~10K patients in U.S. & ~15K patients in EU27+UK Monogenic Disease Autosomal dominant CSF1R gene mutations Clinical Phenotype Average age of onset in mid-40s Cognitive, neuropsychiatric and motor

symptoms Commonly misdiagnosed Rapid Progression Incapacitated in 3-4 years; average time to death: 6-7 years No Treatment No approved therapies or experimental treatments ALSP: A Genetically-linked Microgliopathy with Significant Unmet Need

Lakshmanan et al, Neurol Genet 2017; Hayer et al, Neurology 2018; Lynch et al. J Neurol Neurosurg Psychiatry 2016; Konno et al. Neurol 2018; Ahmed et al. J Neurol Neurosurg Psych 2014; Papapetropoulos et al. Front. Neurol. 2022 Vigil

Validation: Iluzanebart

TREM2 Agonism via Iluzanebart Pharmacological Rescue of ALSP-associated CSF1R Signaling & Human Microglia Dysfunction In Vitro ALSP Disease Hallmark: Microglial Loss in CNS Control Gray Matter ALSP Gray Matter Survival Phagocytosis Proliferation

Motility Hypothesis: TREM2 Activation Compensates for CSF1R LoF in ALSP * p < 0.05; ** p < 0.01

Proof of target engagement and

pharmacological activity in healthy volunteers 1st antibody to report durable effect on microglial activity biomarkers in clinical setting Summary of Iluzanebart Phase 1 Data in Healthy Volunteers SAD: single ascending dose; MAD: multiple ascending

dose; PK: pharmacokinetics; PD pharmacodynamics Favorable safety & tolerability profile demonstrated Human PK linearity/predictability & long half-life supports monthly dosing Phase 1 data support

ILLUMINATE: First Natural History

characterize MRI & CSF biomarkers, and clinical measures of disease progression in ALSP Potential to serve as synthetic control for interventional trial(s) & support disease modeling Setting up for clinical success in ALSP

Baseline Fluid Biomarker Levels

Altered in ALSP NfL levels highly elevated in symptomatic sTREM2 levels similar across all populations sCSF1R levels significantly reduced in prodromal and symptomatic sTREM2 concentration (pg/ml) 0 1000 2000 3000 4000 51 4 7 Healthy Prodromal

Symptomatic sCSF1R concentration (pg/ml) 0 40000 80000 120000 160000 51 4 7 Healthy Prodromal Symptomatic 0 2000 4000 6000 8000 10000 7 Healthy Prodromal Symptomatic 10000 NfL in CSF concentration (pg/ml) 0 30 60 90 120 150 67 17 14 Healthy

Healthy: healthy volunteers from Vigil's VGL101 Phase 1 trial; Prodromal: participants with confirmed CSF1R mutation and MRI findings with <3 ALSP-related clinical signs or symptoms in Vigil's Natural History Study ILLUMINATE

(NCT05020743); Symptomatic: subjects with CSF1R mutations and >3 ALSP-related clinical signs or symptoms in ILLUMINATE; CSF1R: Colony Stimulating Factor 1 Receptor; CSF: cerebrospinal fluid; NfL: neurofilament light chain

Gray Matter Volume Change from

Baseline at Month 12 Montreal Cognitive Assessment (MoCA)* MoCA Change from Baseline Prodromal (11) Symptomatic (6) Cognitive Worsening 2 1 0 1 -2 -3 -4 MRI Biomarkers of Disease Progression Precede Cognitive Decline Plots are Mean SE *

Montreal Cognitive Assessment: 30-point assessment on multiple cognitive domains including executive function, memory, visuospatial ability, language, and attention Volume Change from Baseline (%) Prodromal (13) Symptomatic (9) Volume Change from

Baseline (%) Prodromal (13) Symptomatic (9) Disease Progression Disease Progression 8 7 6 5 4 3 2 1 0 10 0 -10 -20 -30 Greater ventricular expansion, gray matter atrophy & cognitive impairment (MoCA) in symptomatic vs. prodromal patients

MRI Biomarkers of Disease

Ventricular Volume Changes (mL) MoCA Changes Gray Matter Volume Changes (mL) MoCA Changes R = -0.65 p = 0.00053 R = 0.58 p = 0.0027

Evaluating Iluzanebart for ALSP in

patients Treatment Duration 12 months (with opportunity for further extension), monthly IV administration of iluzanebart Outcome Assessments Safety and tolerability of Iluzanebart in ALSP patients MRI-based assessment of brain and ventricular

volume, and white matter lesions CSF biomarkers for neurodegeneration and PD (NfL, sCSF1R, sTREM2, osteopontin) Clinical outcome measures (MoCA, CBFS, CDR+NACC+FTD) and PK Clinicaltrials.gov identifier: NCT05677659 Screening Iluzanebart (20mg/kg IV;

12 months) Iluzanebart (40mg/kg IV; 12 months) Interim Analysis 6 months (n=6: 20 mg/kg); Completed Primary Analysis 6 months (all subjects: 20 mg/kg + 40 mg/kg) Final Analysis 12 months (all subjects: 20 mg/kg + 40 mg/kg)

IGNITE Phase 2 Interim

Readout: Favorable Safety & Tolerability Profile Safety data summary Summary of Safety Outcomes (N=6)a Patients with TEAEs Any AE, n (%) 4 (66.7) Treatment-related AEs, n (%)b 2 (33.3) Mildc

2 (33.3) Moderatec 1 (16.7) Severe 0 Treatment-related AEs occurring in 2 participants, n (%) 0 SAEs, n (%) 1 (16.7) Treatment-related serious AEs, n (%) 0 Discontinuation of study drug due to

AEs, n (%) 0 a IGNITE Ph2 interim data cut as of 22 September 2023 bEvents determined by investigator to be "related" to study drug. cMild to moderate AEs include 1 patient with mild hepatic enzyme increase and;

1 patient with both mild irritability, tremor and lethargy, and moderate pruritus, lethargy and amnestic disorder (memory loss) AE: adverse event; SAE: serious adverse event; TEAE: treatment emergent adverse event Overview of Safety &

Tolerability: Iluzanebart was generally well tolerated Majority of patients did not report treatment-related AEs No treatment-related severe AE or SAE No discontinuations due to AE One patient was briefly hospitalized for non-treatment related

Emerging Patient Segments in IGNITE

Phase 2 Interim Readout NfL significantly higher than age-normal range MoCA <26 Significant neurodegeneration with cognitive impairment as one of ALSP symptoms NfL higher than age-normal range MoCA >26 Evidence of neurodegeneration Have other

ALSP symptoms except cognitive Progressive Disease at baseline NfL within age-normal range MoCA >26 Have other ALSP symptoms except cognitive Cognitively Normal at baseline Potentially Converting at baseline Vigil Neuroscience, Inc. 2024.

Progressive Disease Cognitively

Normal Potentially Converting IGNITE Phase 2: Summary of Biomarker Changes 6-month interim analysis1 Patient1 Baseline NfL (pg/mL) Baseline MoCA MRI Venticular2 MRI Gray Matter2 sCSF1R CSF3 NfL Serum4 VGL101 Impact Based on

Biomarker Changes A 80 17 Slowing progression B 159 21 Slowing progression F 54 25 Slowing progression D 10 28 Stabilization E 12 28 Stabilization C 42 30 Variable impact 1. Please refer to presentation of interim Phase 2 IGNITE data (including

individual patient data) on our corporate website (www.vigilneuro.com); 2. MRI trajectories for 0 to 6 mos in IGNITE vs pre-IGNITE run-in data (from ILLUMINATE) for each patient - MRI Ventricular: change to ventricular MRI trajectory,

MRI Gray Matter: change to gray matter MRI trajectory; 3. sCSF1R levels in cerebrospinal fluid (CSF) at 6 mos vs 0 mos (IGNITE baseline); 4. NfL trajectories for 0 to 6 mos vs pre-IGNITE run-in data (from ILLUMINATE; for Patients B, D, E &

F) or for 6 to 9 mos vs 0 to 6 mos in IGNITE (Patients A & C) Meaningful changes in a direction consistent with treatment benefit Limited changes in a direction consistent with treatment benefit Limited changes in a direction not consistent with

Positioning Iluzanebart for

Potential Accelerated Development Pathway Iluzanebart (VGL101) Target engagement with mechanistic link - iluzanebart increased sCSF1R levels (very low in untreated patients) Directionally supportive changes on MRI & NfL for iluzanebart in Ph2

MRI biomarkers correlating with cognitive changes NfL levels indicative of disease severity Fatal, rare, rapidly progressing neurodegenerative disorder No approved therapy Several regulatory engagements planned for 2024 Discuss NHS

& interim Ph2 data for potential accelerated development Addressing Serious Unmet Medical Need Demonstrated Pharmacological Activity Planned Regulatory Meetings Establishing Surrogates of Disease Activity Vigil Neuroscience, Inc. 2024.

VG-3927 Small Molecule TREM2

Human Microglia Play a Central Role

in Alzheimer's Disease (AD) Loss of TREM2 Function Worsens Neurodegeneration in AD Models TREM2 Small Molecule Agonist: Broad Potential to Reduce AD Pathology via Oral Dosing AD risk variants impair microglia clustering around A plaques

TREM2 deficiency is associated with both A and tau pathology in in vivo models Importance of TREM2 Agonism in Alzheimer's Disease TREM2-WT TREM2-R47H IBA1/A Parhizkar et al. Nat Neurosci. 2019; Yuan et al Neuron 2016 Microglia

(IBA-1 staining) Amyloid plaques Microglia (IBA-1 staining) Amyloid plaques (A staining) Vehicle VG-3927 vs Preclinical evidence suggests TREM2 agonism has potential to reduce A pathology Microglia (IBA-1 staining) Amyloid plaques

Increased Versatility Improved

Safety VG-3927: First & Only Clinical-stage Small Molecule TREM2 Agonist VG-3927 Potential Differentiation Small molecule optimal for future combination therapy & preventive paradigms Wider therapeutic window: synergy with natural

microglial repair functions Impact broader disease pathophysiology

VG-3927 Potentiates Signaling of

Damage-associated Ligands Focusing Efficacy in Pathological Microenvironments Plaque-burdened AD State Potentiation of TREM2 Activation VG-3927 Sulfatide Alone VG-3927 Alone VG-3927 + Sulfatide TREM2 Activation Vigil Neuroscience, Inc. 2024.

VG-3927 Protects Against Biomarkers

of Inflammation-induced Neurodegeneration ANOVATreatment, p<0.05 VG-3927 Suppresses Extracellular NfL & Tau Accumulation in LPS Model TREM2 Agonism Activates Anti-inflammatory Benefit VG-3927 Neuro- inflammation Neurodeg Stimulus LPS/IFNy