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Maze's Compass Platform - A data fabric for drug discovery and development

Maze Therapeutics has developed the Compass Platform, an informatics framework for drug discovery. The platform integrates multiple data sources to translate genetic insights into potential drug targets. It uses a data lake architecture to store over 50 billion records from public and experimental sources. Maze's new Sightline portal provides an overview of the company's research and development portfolio based on this integrated data. The initial focus is on analyzing allelic series to increase confidence in target concepts.

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Drug Discovery Insights• Semantic Web•
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CONFIDENTIAL Maze’s Compass Platform A data fabric for drug discovery and development October 26, 2022
Overview • Maze Therapeutics and the Compass Platform • Informatics framework for target discovery and validation • Sightline Data architecture Confidential © 2022 Maze Therapeutics 2
Mazehasbuiltapowerfulenginefordrugdiscovery SinceitsfoundinginOctober2018 Pipeline programs established 7 wholly-owned, 2partnered First program completing phase I: target to clinic in 3 years Second program expected to enter clinic in 2H2023 9 2018 2019 2020 2021 2022 MZE-001 IND 171 Oyster Point MZE-001 Phase 1 10+ Additional identified targets, genetic insights in research validation Key therapeutic areas of focus in renal, cardiology, neurology, metabolic diseases Scientists and top talent brought into Maze Housed in state of the art 65,000+ sq ft lab & office HQ in South San Francisco 120+
May 2022 | 4
Translate genetic insights into medicines MAZE COMPASSTM PLATFORM V A R I A N T T O F U N C T I O N F U N C T I O N T O T H E R A P Y V A R I A N T D I S C O V E R Y Mazeappliesaunifiedapproachto May 2022 | 5
V A R I A N T D I S C O V E R Y V A R I A N T T O F U N C T I O N F U N C T I O N T O T H E R A P Y Clinical Data Clinical Phenotype Proteinuria Hypertension eGFR Potassium Level Serum Creatine Level (sCR) Fluid Overload Rapidly advance from genetic signal to drug program Our Compass Platform is designed to GWAS Analysis Genetic Variants CATGACTG CATGCCTG …hundreds more …differentiated, interesting GWAS Hits Mapping to Genes Variant Location Exon Intron Enhancer Promoter Single Cell Analysis Cell Type Endothelium Proximal Tubule Podocyte Loop of Henle Distal Convoluted Tubule Lymphocyte Macrophage Functionalization Multimodal Profiling Functional Assays Localization RNAseq Proteomics Protein Levels In Silico Modeling Translation Drug Discovery to Mimic Variant Function CryoEM Screen 15 Billion Compound DEL Traditional HTS in parallel Novel Assays EX. CKD 4+ Y E A R S F O R P C S K 9 T O E N T E R D R U G D I S C O V E R Y 1.5M+ Individuals 200+ Loci Thousands of variants Millions of data points and petabytes (1015) of data 1 Prioritized Drug Project Confidential © 2022 Maze Therapeutics May 2022 | 6
The Compass Data Map supports evolving knowledge Confidential © 2022 Maze Therapeutics 7 V A R I A N T T O F U N C T I O N F U N C T I O N T O T H E R A P Y V A R I A N T D I S C O V E R Y External Data (Pay-to-Play and Open Access) Experiment Data Drug Discovery Data ELN Data Lake: Summary Stats (50+ billion records) Analyses (100+ results) Analysis Results Project Compounds (16k+ w/data) pheno variant disease gwas target concept allelic series joint analysis qpcr screen crispr analysis md analysis weekly assay business intel exper. design program results protein struct compound clinic Assay Data
SIGHTLINE is Maze’s new portal into our Data Map Confidential © 2022 Maze Therapeutics 8 V A R I A N T T O F U N C T I O N F U N C T I O N T O T H E R A P Y V A R I A N T D I S C O V E R Y Data Lake: Summary Stats (50+ billion records) Analyses (100+ results) Project Compounds (16k+ w/data) pheno variant disease gwas target concept allelic series joint analysis qpcr screen crispr analysis md analysis weekly assay business intel exper. design program results protein struct compound clinic SIGHTLINE
Sightline Data Architecture • What is a data lake, lake house, warehouse? ‒ Structured, Semi-structured, and unstructured data in object storage • Leveraging cloud-native data formats formats (e.g., parquet) ‒ Breaks up data into smaller chunks with compression ‒ A variety of compute engines enable parallel processing ‒ Storage is cheap, compute can be serverless (e.g., Athena) • Lifting data out of the lake ‒ Open graph data formats enable linking data lake tables ‒ Statistical relationships within/between tables are modeled using a graph ‒ Provides a conceptual model for understanding how questions are answered • Data-centric appli Confidential © 2022 Maze Therapeutics 9
Sightline presents a global overview of Maze’s R&D portfolio Confidential © 2022 Maze Therapeutics 10
Insights from multiple sources increase confidence in a target concept Confidential © 2022 Maze Therapeutics 11 Effect Size CommoneQTLvariant Rareprotein- altering variants Wildtype / referenceprotein Protein function <redacted> in CKD Population and disease datasets
Sightline’s MVP release focuses on allelic series Confidential © 2022 Maze Therapeutics 12
Sightline’s MVP release focuses on allelic series Confidential © 2022 Maze Therapeutics 13
More modules are in progress Confidential © 2022 Maze Therapeutics 14
The Maze Data Architecture and Sightline Teams Data Science: ‒ Nolan Nichols (Lead Platform Architect) ‒ Juan Arrivillaga ‒ Matt Brauer ‒ Michel Dumontier, Maastricht University, advisor ‒ Developers • Datavisyn: Dominic Girardi, Vanessa Stoiber, Daniela Moitzi, Zach Cutler • Keitaro: Blagoja Stojkosk Human Genetics: ‒ Sahar Mozaffari (genetics project lead) ‒ Robert Graham (project visionary) ‒ Karol Estrada Confidential © 2022 Maze Therapeutics 15