Full Press Release Details
Vigil Neuroscience, Inc. ALSP KOL Event
FORWARD-LOOKING STATEMENTS 2
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 VGL101 and small molecules active against TREM2, and to enable success in ALSP in clinical development; beliefs about TREM2 agonism's importance in 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 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 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; the effect of the COVID-19 pandemic, including mitigation efforts and economic
impacts, on any of the foregoing or other aspects of our business operations, including our preclinical studies and clinical trials; 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 revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Certain information contained in this presentation relates to or is
based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have
not independently verified, and we make no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources
Introduction & Corporate Overview
Vigil 2022 ALSP Key Opinion Leader
Event - Agenda 8:30 - 10:00 AM Opening Remarks & Corporate Overview Ivana Magov evi -Liebisch, PhD, JD Chief Executive Officer Vigil Neuroscience, Inc. What is ALSP? David S. Lynch, MD, PhD Consultant Neurologist National
Hospital for Neurology & Neurosurgery, Queen Square & UCL Institute of Neurology, London, U.K. Clinical Lead, Adult Inherited White Matter Disorders Highly Specialist Service, NHS England ALSP History & Diagnosis Christina Sundal, MD,
PhD Chief Executive Officer NeuroClinic Norway Senior Consultant University Hospital, Oslo, Norway 8:30 - 10:00 AM (continued) ALSP Treatment & Unmet Medical Need Troy Lund, MSMS, PhD, MD, FAAP Associate Professor Associate Director
Metabolic Program Leukodystrophy Center of Excellence, Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy University of Minnesota, A NORD Rare Disease Center of Excellence 10:00 - 10:15 AM Break 10:15 - 10:45
AM ILLUMINATE Natural History Study: Interim Findings VGL101 Phase 2 IGNITE Trial Design & Objectives Spyros Papapetropoulos, MD, PhD Chief Medical Officer Vigil Neuroscience, Inc. 10:45 - 11:30 AM Closing and Q&A Vigil
Vigil Neuroscience Vigil Neuroscience
is a clinical-stage microglia-focused therapeutics company Our purpose: to treat rare and common neurodegenerative diseases by restoring the vigilance of microglia, the brain's sentinel immune cells We are utilizing the tools of modern
Vigil's Mission: Restoring
Microglial Vigilance to Create Disease-Modifying Treatments for Neurodegenerative Diseases Discovering and developing novel therapeutics designed to leverage microglial biology breakthroughs that activate and restore microglial function
Precision-based development strategy first in rare microgliopathies with plans to advance into larger patient populations First product candidates target microglial receptor protein TREM2 Evaluating new microglial targets and indications IPO in
Vigil's Precision Medicine
Strategy to Target Broad Range of Neurodegenerative Diseases First Indication Rare Microgliopathy Data Driven Expansion in Other Rare Microgliopathies Pipeline Candidates for Genetically Defined Subpopulations in Common Indications Further Expansion
Vigil TREM2 Agonists: Differentiated
Strategy & Multiple Modalities ALSP: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia TREM2 mAb in Development for ALSP: VGL101 Small Molecule TREM2 Agonist in Development for Larger Indications The ONLY targeted drug
Our Pipeline Vigil Has Exclusive Rights
to All Programs Discovery Preclinical Phase 1 Alzheimer's Disease VGL101 Healthy Volunteer SAD & MAD Phase 1 Trial (interim data announced)* Healthy Volunteer IND-Enabling Studies Small Molecule TREM2 Agonist Program Phase 2 Preclinical
PoC Evaluation Other Leukodystrophies SAD: single ascending dose; MAD: multiple ascending dose; Phase 1 completed dosing and interim analysis for certain cohorts ** Additional observational Natural History Study in ALSP is ongoing ALSP* Phase 2
VGL101 - Human mAb Agonist of
TREM2 with a Compelling Profile High TREM2 selectivity; induces microglial genes with sub-nanomolar potency Preclinical proof of concept in human iPSC derived microglia Favorable safety & tolerability profile with linear, dose proportional PK in
HVs Dose dependent, robust & durable CNS target engagement in HVs Established manufacturing competency, strong IP position, and obtained ODD & FTD mAb: monoclonal antibody; HVs: healthy volunteers; ODD: Orphan Drug Designation; FTD: Fast
Summary of Interim Topline VGL101
showed linear, predictable characteristics across doses Half-life supports monthly dosing Demonstrated proof of target engagement and pharmacological activity Dose-dependent, robust and durable reductions in sTREM2, and durable increases in sCSF1R
with repeat dosing 1st antibody to report durability of TREM2 engagement in a clinical setting Phase 1 data support VGL101 20 mg/kg as a pharmacologically active dose for Phase 2 proof-of-concept trial in ALSP patients Phase 2 IGNITE trial in ALSP
initiated VGL101 is an investigational therapy and has not been reviewed or approved by any regulatory authority
Driving ALSP Awareness via
Comprehensive Stakeholder Engagement Focused on increasing accurate & timely diagnosis Building Strong Foundation with Patient Advocacy Groups (PAGs) Established relationships with regional & global PAGs across relevant neurodegenerative
diseases (including ALSP, leukodystrophies, MS, FTD) Incorporating Patient & Caregiver Insight/Perspectives Established Patient & Caregiver Advisory Council Executing Natural History Study in ALSP Enhancing resources on patient journey,
& genetic testing & counseling Promoting Disease Awareness on Multiple Fronts Launched patient-facing ALSPinfo.com & social media accounts Developed disease education materials Engaging KOLs in diseases ALSP is frequently misdiagnosed
(e.g. MS, FTD) Increasing Clinical Trial Awareness Cross-Functionally Launched clinical trial websites Provided PAGS with trial awareness materials Collaborating with ALSP KOLs Engaging MS and FTD specialists Vigil Neuroscience, Inc. 2022.
Building Toward Success in ALSP
Clinical Development Retrospective Biomarker & Chart and Systematic Literature Reviews Phase 1* SAD/MAD Trial Patient & KOL Engagement Natural History Study Phase 2** Proof-of-Concept Trial Phase 3** Trial Vigil Neuroscience, Inc.
Featured Key Opinion Leaders David
S. Lynch, MD, PhD Consultant Neurologist, National Hospital for Neurology & Neurosurgery, Queen Square & UCL Institute of Neurology, London, U.K. Clinical Lead, Adult Inherited White Matter Disorders Highly Specialist Service, NHS England
Troy Lund, MSMS, PhD, MD, FAAP Associate Professor, Associate Director Metabolic Program, Pediatric Blood and Marrow Transplant Fellowship Director, Leukodystrophy Center of Excellence, Division of Pediatric Blood and Marrow Transplantation
& Cellular Therapy, University of Minnesota, A NORD Rare Disease Center of Excellence, Stem Cell Institute, Global Pediatrics Christina Sundal, MD, PhD CEO, NeuroClinic Norway Senior Consultant, University Hospital of Oslo, Norway
What is ALSP? David S. Lynch, MD,
PhD Consultant Neurologist National Hospital for Neurology & Neurosurgery, Queen Square & UCL Institute of Neurology, London Clinical Lead Inherited White Matter Disorders Highly Specialist Service, NHS England
Adult-onset Leukoencephalopathy with
Axonal Spheroids and Pigmented Glia (ALSP) An inherited neurodegenerative disorder Rare and under-recognized Primarily causing degeneration of brain white matter (i.e., an Inherited White Matter Disorder' or
leukoencephalopathy/leukodystrophy') The hallmark axonal spheroids' (swellings) and pigmented glia give the disorder its name
ALSP Has been known by a number of
alternative names, largely hangovers from the era before MRI and genetics were widely available First described as pigmentary orthochromatic leukodystrophy (POLD) in 1936 Later, the name hereditary diffuse leukoencephalopathy with spheroids (HDLS)
became more widely used because of an influential and important report on the disease in 1984 In recent years, ALSP has become the preferred term as it recognizes the importance of both the axonal spheroids and abnormal microglia Wider et al. Neurol
ALSP Symptoms A progressive,
neurodegenerative disorder Demyelination (destruction) of white matter in the brain has widespread and devastating effects Symptoms can be similar to more widely recognized diseases Cognitive symptoms: similar to Frontotemporal Dementia (FTD) Motor
symptoms: similar to Progressive MS, Parkinson Disease
ALSP Symptoms Symptoms most often
develop in the 40s but the range is wide (18-86 years) Cognitive and neuropsychiatric' symptoms are often first to emerge Word Finding Difficulty Executive Dysfunction Insomnia Agitation Depression Confusion Memory Loss
ALSP Symptoms Personality change New
anxiety, depression Difficulty in work, decision making Inappropriate behavior Memory problems Word finding and speech problems Cognitive As the Disease Progresses, Symptoms Multiply
ALSP Symptoms Gait and balance
problems Stiffness, slowness of movement Incoordination, tremor Swallowing and speech difficulty Motor As Symptoms Progress, Patients Become More Immobile to the Point of Being Bedbound and Totally Dependent for Care
Relentlessly Progressive ALSP
Progression 75% survival for approximately 3 years, 50% for 5 years, 25% for 10 years and < 5% for 30 years Papapetropoulos et al. American Academy of Neurology Conference 2022
Symptom Overlap with Other Diseases
(Misdiagnosis) Frontotemporal Dementia (FTD) Alzheimer Disease (AD) Primary Progressive Multiple Sclerosis (PPMS) Parkinson Disease (PD) Other inherited white matter disorders Mostly Cerebral Autosomal Dominant Arteriopathy with Sub-cortical
Infarcts and Leukoencephalopathy (CADASIL) Corticobasal Syndrome
ALSP Magnetic Resonance Imaging
Normal MRI ALSP D. Lynch unpublished data
ALSP Typical Imaging A B C D E F G F
Wade & Lynch: Handbook of Clinical Neurology, Inherited White Matter Disorders
Misdiagnosis D. Lynch unpublished
data ALSP Progressive MS The Direction of Misdiagnosis is the Failure to Recognize ALSP
Neuropathology - Axonal
Swellings (Spheroids) and Pigmented Glia Lynch DS et al, Journal of Neurology, Neurosurgery & Psychiatry 2016.
Epidemiology Inherited white matter
disorders (IWMD) are rare but recognition is growing due to: Better access to genetics Widespread availability of imaging Increased understanding of phenotypes, particularly in adults UK has just established first national specialist service for
IWMD >300 Reported Cases globally; Significant Underestimate Papapetropoulos et al. Front Neurol 2022
Epidemiology - at Least