Maze Therapeutics, Inc. · NASDAQ:MAZE
Maze Therapeutics — Investor Presentation (March 2022)
37 slides from Maze Therapeutics's investor presentation, March 2022
Slide 1: Maze Therapeutics
Maze Therapeutics March 2022 | 1
Slide 2: Harnessing the power of human genetics to transform the lives of patients
harnessing the power of human genetics to transform the lives of patients March 2022 | 2
Slide 3: Our Rapid Progress
Pipeline programs established 9 6 wholly-owned, 3 partnered First program entered clinic 2022, target to clinic in 3 years Additional identified targets, genetic insights 10+ in research validation Key therapeutic areas of focus in renal, cardiology, neurology, metabolic diseases Scientists and top
Slide 4: A Broad Spectrum of Indications and Modalities
A Diverse Pipeline A Broad Spectrum of Indications and Modalities Therapeutic Area Indication Modality Target Preclinical Phase I Ownership Rare Metabolic Pompe Disease Small molecule GYS1 Phase 1 Clinical Proof of Mechanism Expected YE 2022 Maze Diseases Phenylketonuria Small molecule Confidential
Slide 5: The scientific community is discovering disease-gene associations at a remarkable pace
Common 1994 Rare 1995 Complex Disease Monogenetic Disease Genome-wide significant association 1996 Genes harboring variants causal for signals monogenetic disease 1997 1998 1999 A critical time for genetics 2000 The scientific community is 2001 2002 2003 discovering disease-gene 2004 2005 associatio
Slide 6: Connecting a gene to a disease is just the beginning
Why is variant functionalization so important? VARIANT DRUG THERAPY SELECTION RESEARCH DEVELOPMENT Evaluating which of the Discerning the variant Mimicking the genetic 100’s to 1,000’s of function with protein association and drugging the gene variants are driving structure / binding pocket target V
Slide 7: Translating genetic insights into therapies
Our key strength leverages proprietary technology and traditional discovery tools for Translating genetic insights into therapies M A Z E C O R E D I F F E R E N T I AT O R VARIANT DISCOVERY VARIANT TO FUNCTION FUNCTION TO THERAPY Identifying meaningful GWAS hits Empowering, Accelerating Genetic Tra
Slide 8: Translating genetic insights into therapies
Our key strength leverages proprietary technology and traditional discovery tools for Translating genetic insights into therapies MAZE CORE DIFFERENTIATOR VARIANT DISCOVERY VARIANT TO FUNCTION FUNCTION TO THERAPY Protein structure / variant function relationship Variant Structure based Drug function
Slide 9: Rapidly advance from genetic signal to drug program
Our Compass Platform can Rapidly advance from genetic signal to drug program VARIANT DISCOVERY VARIANT TO FUNCTION FUNCTION TO THERAPY Clinical GWAS Mapping to Genes Single Cell Functionalization Translation Data Analysis Analysis Variant Location Clinical Phenotype Genetic Variants Cell Type Multim
Slide 10: Case study: Undisclosed Target in CKD
Case study: UNDISCLOSED TARGET IN CKD 250X potency increase with 10% of the compounds in ½ the time of a traditional lead optimization Computational predictions of protein structure combined with CryoEM can lead to rapid development of potent molecules March 2022 | 10
Slide 11: Leveraging genetics to improve clinical development precision and efficiency
Genetics influence on clinical trials Leveraging genetics to improve clinical development precision and efficiency Understanding Predicting Informing the the patient population treatment effect therapeutic window • utilizing polygenic risk scores or biomarkers to • better prediction of clinical tria
Slide 12: Launch programs at any phase of development
Our end-to-end platform allows us to Launch programs at any phase of development VARIANT DISCOVERY VARIANT TO FUNCTION FUNCTION TO THERAPY OUR CURRENT PIPELINE WAVE I Focused on known targets that were previously unable to translate to drugs THE “NEXT” PCSK9 WAVE II Identifying and developing transf
Slide 13: Wave 2 Targets: Discovering The Next PCSK9
PCSK9’s bidirectionality connects the cause of disease with its solution and will serve as a Wave 2 Targets: Discovering “The Next PCSK9” model for Maze’s strategy for its next We are building an generation pipeline engine for Specific PCSK9 mutation discovering the genetic “levers” of disease Propr
Slide 14: Aggregating paired data sets to lay the foundation for drug discovery
Our Starting Point Aggregating paired data sets to lay the VARIANT DISCOVERY foundation for drug discovery Standalone genetic databases Deep phenotypic and clinical data on Expertise provide only partial insight more than 1.5M+ diverse individuals in genetic data interrogation for lack of paired cli
Slide 15: An engine for discovering genetic levers of disease
Maze’s 2nd Wave An engine for discovering genetic “levers” of disease Genetic insights alone are not enough Bidirectionality provides critical efficacy and safety information The nature of these insights is critical Understanding the gene’s causal role in the disease Improvement in Likelihood of PCS
Slide 16: Maze's 2nd Wave Examples
Maze’s 2nd Wave Examples Broadly integrating large scale human genetics, variant functionalization, structural biology and drug discovery Undisclosed target UNC13A ANGPTL7 Bidirectional allelic series analyses leading Bidirectional allelic series analyses and Allelic series analyses and variant to d
Slide 17: Focusing on genetically validated targets in indications with high unmet need
Focusing on genetically validated COMPASS targets in indications with high unmet medical need COMMON DISEASE RARE DISEASES Renal Cardio Neuro Metabolic genetic subsets and genetic genetically defined subsets rare genetic diseases focused on rare monogenic diseases amenable to drivers of renal diseas
Slide 18: What we look for in an indication
Genetic and Paired Clinical Data that allows us to leverage the Maze Compass Platform for genetic insights and drug discovery Our Strategy Available Cellular Models What we look either previously discovered in the literature or via for in an indication Maze’s proprietary Compass platform Disease Are
Slide 19: Maze ecosystem to develop genetic medicines at scale
Maze ecosystem to develop genetic medicines at scale Variant functionalization tools Built upon strategic academic relationships Wholly owned pipeline & partnerships Internalized paired clinical data Rare diseases, genetic subsets of common diseases Licenses to databases pairing genetic and clinical
Slide 20: Pompe Disease & Glycogen Storage Disorders
Pompe Disease & Glycogen Storage Disorders A rare, multisystemic, hereditary disease caused by a deficiency of acid alpha-glucosidase (GAA) leading to glycogen GYS1 accumulation and progressive weakness and respiratory failure A rare genetic disease that is understood, Estimated Pompe Disease Patien
Slide 21: What we knew, what we didn't know: GYS1
T H E C U R R E N T S TAT E O F T H E S C I E N C E What we knew What we didn’t know Inhibiting GYS1 can theoretically reduce the The structure of muscle buildup of muscle lysosomal glycogen caused by glycogen synthase a deficiency in GAA HEALTHY STATE POMPE DISEASE POMPE DISEASE + INHIBITOR The imp
Slide 22: The power of the Maze platform
T H E P O W E R O F T H E M A Z E P L AT F O R M Genetic Analysis Drug Discovery Drug Development to demonstrate safety of to solve the CryoEM to potentially create the first oral substrate glycogen depletion structure of GYS1 reduction therapy for Pompe Disease Exercise test max work (W) Utilizing
Slide 23: Human genetics suggests ~65% reduction in muscle glycogen is safe
HUMAN GENETICS SUGGESTS ~65% REDUCTION IN M U S C L E G LY C O G E N I S S A F E & W E L L T O L E R AT E D * Healthy Cell PPP1R3A No Significant Associations Loss of function variant across hundreds of phenotypes for humans with 65% less muscle glycogen No difference in exercise capacity Muscle Gly
Slide 24: MZE001 is a potent and selective GYS1 inhibitor
MZE001 IS A POTENT AND SELECTIVE GYS1 INHIBITOR IN VITRO AND IN VIVO D O S E D E P E N D E N T I N H I B I T I O N O F D E N O V O G LY C O G E N S Y N T H E S I S I N P O M P E P AT I E N T F I B R O B L A S T S POMPE MICE WITH MZE001 100 Gastrocnemius [GYS1] Heart [GYS1] Diaphragm [GYS1] Liver [GY
Slide 25: GYS1 SRT and ERT combination therapy normalizes tissue glycogen
G Y S 1 S R T A N D E R T C O M B I N AT I O N T H E R A P Y N O R M A L I Z E S T I S S U E G LY C O G E N I N P O M P E M O U S E M O D E L E R T + S R T ( G Y S 1 I N H I B I T O R ) C O M B I N A T I O N D ATA I N P O M P E M O U S E M O D E L – 1 2 W E E K S uGlc4 PBMC Glycogen • GYS1 inhibitio
Slide 26: Efficient clinical development will cover entire disease spectrum
EFFICIENT CLINICAL DEVELOPMENT WILL COVER E N T I R E D I S E A S E S P E C T R U M O F L AT E O N S E T POMPE DISEASE (LOPD) PROPOSED PHASE 2 & PHASE 3 PHASE 1 CLINICAL DESIGN CLINICAL DESIGN In combo with ERT Objectives: Assess safety, tolerability, PK/PD and food effect of MZE001 in healthy volun
Slide 27: Current status: MZE001
C U R R E N T S TAT U S Early KOL Engagement Plans for Expansion Oral Therapy Phase 1 Clinical Trial first substrate reduction therapy to other glycogen avoids prolonged intravenous Ongoing approach displays consistent, storage diseases with potential to be infusions with biomarkers for potential po
Slide 28: Chronic Kidney Disease: APOL1
Chronic Kidney Disease A gradual loss of kidney function over time that can APOL1 ultimately lead to end-stage renal failure A common disease Patients in the United States 1 with a ~37M ~1M PEOPLE WITH CKD AND THAT CARRY TWO RISK VARIANTS disproportionate $13B+ Estimated APOL1-linked Drug Market 13%
Slide 29: What we knew, what we didn't know: APOL1
T H E C U R R E N T S TAT E O F T H E S C I E N C E What we knew What we didn’t know Patients with two copies of The mechanism by which APOL1 variants have Inhibition Increased APOL1 variants translate to increased risk of CKD of APOL3 APOL1 expression nephrotoxicity Reduced APOL1 degradation The ap
Slide 30: Insights from Compass platform support a pore-blocking strategy for APOL1
Maze Insight I N S I G H T S F R O M C O M PA S S P L AT F O R M S U P P O R T S A P O R E - B L O C K I N G S T R AT E G Y F O R APOL1 Human Genetics Functional Genomics Therapeutic Approach APOL1 variant (N264K) associated generate APOL1 N264K in vitro and small molecule inhibition of APOL1 with r
Slide 31: Powerful proof of concept data enabled by Compass
Maze data P O W E R F U L P R O O F O F C O N C E P T D ATA E N A B L E D BY C O M PA S S D I R E C T I M P A C T O N A P O L 1 C O N D U C TA N C E S T R O N G C O R R E L AT I O N & C YTOTOX I C I TY R ESC U E A C R O S S P O T E N C Y A S S AY S March 2022 | 31
Slide 32: Current status: APOL1 candidate
C U R R E N T S TAT U S Maze Designed Candidate Expected Efficient Clinical Compass Insights oral therapy APOL1 inhibitor Early 2022 Strategy helped solve decade-long designed to correct the effects with diagnostic partner for across the range of APOL1- debate and likely uncovered the of toxic gain-
Slide 33: Our vision is to build the next generation precision medicines company
Long term strategy Our vision is to build the next generation precision medicines company 2019–2021 Today 2023–2026 established Maze infrastructure and • first program entered clinic 1Q • 6+ clinical programs talent, Compass platform and first- 2022 generation pipeline • 10-15 programs between Maze
Slide 34: A multidisciplinary team purpose-built for the Maze platform
A MULTIDISCIPLINARY TEAM PURPOSE-BUILT FOR THE MAZE PLATFORM Jason Coloma, PhD Sarah Noonberg, MD, PhD president & chief medical officer ceo Eric Green, MD, PhD David Morgans, head of research PhD drug discovery Tara Nickerson, PhD chief business officer Matt Krause human resources Atul Dandekar chi
Slide 35: Progress and upcoming milestones
Progress and U P C O M I N G A N T I C I PAT E D M I L E S T O N E S upcoming YE 2022 MZE001 entered clinic Q1 2022 milestones MZE001 for Pompe disease expected Phase 1 Proof of Mechanism via biomarkers in healthy volunteers • Entered the clinic for first program, MZE001 – concept On track to enter
Slide 36: Executive Summary
Executive Summary A World Class End-to-End Clinical Stage Platform Company A Flexible Business Genetics Discovery Engine nine pipeline programs in development with Model with Upside that embeds genetics into every stage of novel genetic insights across four therapeutic allows for development of whol
Slide 37: Thank You
Thank You March 2022 | 37
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