Metagenomi Therapeutics, Inc. · NASDAQ:MGX
Metagenomi Therapeutics — Corporate Update (March 2025)
31 slides from Metagenomi Therapeutics's corporate update, Mar 17, 2025
Slide 1: Unlocking 4 Billion Years of Microbial Evolution to Create Curative Genetic Medicines
Nasdaq: MGX March 2025 Unlocking 4 Billion Years of Microbial Evolution to Create Curative Genetic Medicines
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation includes forward-looking statements, including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of historical facts contained in this presentation are forward looki
Slide 3: Our Vision: Harness the power of our metagenomics platform
Our Vision: Harness the power of our metagenomics platform to create curative genetic medicines for patients Programmable Genome Editing Tools Precise Human Gene Modification Curative Genetic Medicines AI-Driven Metagenomics Platform
Slide 4: Programmable Genome Editing Tools and Our Strategy
Programmable Genome Editing Tools AI-Driven Metagenomics Platform Precise Human Gene Modification Curative Genetic Medicines Our diverse and modular genome editing toolbox is designed to precisely target any site in the human genome, yielding the potential to address the full spectrum of genetic dis
Slide 5: Hundreds of millions of people have diseases potentially treatable with gene editing
Hemophilia A More than 500,000 patients globally 5 Refractory Hypertension 900,000 patients in the US 7 Transthyretin Amyloidosis (TTR) 300,000–500,000 patients globally with wild-type ATTR 6 Hundreds of millions of people worldwide have diseases that are potentially treatable with gene editing Over
Slide 6: The metagenomics platform is the foundation of our gene editing toolbox
Proprietary Sampling Exploring diverse microbe- rich ecosystems to extract DNA from environmental samples AI-powered Screening Leveraging AI, ancestral reconstruction, proprietary algorithms, robotics, and automation to reveal novel cellular machinery Complete Genome Editing Capabilities Building a
Slide 7: Our proprietary toolbox enables precise edits of the human genome
Our proprietary toolbox enables precise edits of the human genome Programmable chassis with additional effector enzymes to cause single nucleotide changes Knockdown, knock-in, exon skipping Single nucleotide changes Proprietary library of highly precise and efficient nucleases, including ultra-small
Slide 8: Pipeline disease target selection criteria
Pipeline comprised of disease targets with: Metagenomi Translation Engine Disease Target Selection Criteria: FOCUS Liver targeting for hematologic, cardiometabolic and hepatic diseases Various LNP & AAV delivery options ADDITIONAL FOCUS Extrahepatic Disease Various AAV and novel non-viral delivery o
Slide 9: Development and GMP manufacturing capabilities
Measured, phase-appropriate investments in development and GMP manufacturing designed to rapidly and reliably progress development and manufacturing for Metagenomi’s development and clinical pipeline Product Characterization State-of-the-art screening, optimization, and characterization, streamlinin
Slide 10: Strategic collaborations complement our development capabilities
Strategic collaborations compliment our development capabilities Next-generation cell therapies enhanced by multiplex genome editing targeting TCR ex vivo immuno-oncology cell therapies Co-founded by world- renowned experts in cancer immunotherapy Metagenomi to receive options, milestones and royalt
Slide 11: Pipeline by program, editing platform and stage
Editing Platform Delivery Indication / Editing Target Discovery Lead Optimization IND-Enabling Clinical LIVER LNP + AAV Hemophilia A / ALB Knock-in Undisclosed secreted protein diseases Knockdown LNP Transthyretin Amyloidosis / TTR Refractory Hypertension / AGT Undisclosed cardiovascular disease Und
Slide 12: 2024 milestones and key publications
Hemophilia A Program Cardiometabolic Programs Other Therapeutic Programs / Technology Development Declared MGX-001, wholly-owned Development Candidate (DC) Factor VIII activity sustained in NHP study for more than 16 months presented at ASH 1 Initial regulatory engagement with FDA GxP Manufacturing
Slide 13: Anticipated milestones allow advancement towards the clinic
2025 2026 Hemophilia A Program Complete ongoing NHP durability study Conduct Pre-IND and ex-US regulatory meetings IND / CTA filings Cardiometabolic Programs Other Therapeutic Programs / Technology Development Continue to advance early-stage pipeline for multiple future IND filings Nominate 1-2 DCs
Slide 14: Pipeline Overview
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Slide 15: Hemophilia A disease background and prevalence
Disease Background Most common X-linked inherited bleeding disorder; vast majority of patients are male Caused by large variety of mutations in the Factor VIII (FVIII) gene leading to loss of functional FVIII protein Intracranial bleeding is of greatest concern as this can lead to major morbidity an
Slide 16: MGX-001 genome editing approach
Genome Editing Approach MG nuclease creates efficient and specific cut at safe harbor locus in albumin gene Factor VIII donor DNA is inserted at cut site Strength of albumin promoter provides high level of FVIII expression even at low integration rates Mechanistically different from AAV gene therapy
Slide 17: Robust in vivo data supports advancing to the clinic
Robust in vivo data supports advancing to the clinic Durable FVIII activity achieved in non-human primates (NHP) Wild-type FVIII activity levels sustained for 16.5 months (Data cutoff: 11-13-24) Days post LNP dosing cFVIII Activity (IU/mL) Factor VIII activity values are the mean and standard deviat
Slide 18: Summary of safety findings
SUMMARY OF SAFETY FINDINGS Data cutoff at 16.5 months, 11-13-24 Transient elevation of liver function tests after the infusion of AAV and LNP No significant change in total bilirubin post AAV and LNP Integration of the FVIII gene at the albumin locus had no impact on circulating albumin levels Anima
Slide 19: Bioengineered FVIII yields higher plasma FVIII activity in NHPs
Bioengineered FVIII yields significantly higher plasma FVIII activity despite similar integration frequency in NHPs Significantly higher plasma FVIII activity from the bioengineered FVIII despite similar integration frequency is expected to enable therapeutic FVIII activity at lower AAV doses with a
Slide 20: Addressing secreted protein diseases with large gene insertion
Addressing secreted protein diseases with large gene insertion Secreted Protein Deficiencies mRNA splicing Tx Gene Tx Gene A Tx Gene B Tx Gene C Tx Gene A Tx Cargo Gene Leveraging the MGX-001 approach from the Hemophilia A program to accelerate timelines and reduce costs to IND AAV delivers Transgen
Slide 21: Refractory Hypertension rodent proof-of-concept
Prevalence: 900,000 adults with refractory hypertension in the US2 95% protein knockdown in spontaneous hypertensive rats Dose dependent editing, mRNA and protein knockdown in primary human hepatocytes >85% editing, 90% mRNA and protein knockdown Refractory Hypertension Rodent proof-of-concept achie
Slide 22: Technology Platform
ofl" Metagenomi Technology Platform
Slide 23: Highly efficient nucleases designed for any target in the human genome
Pipeline comprised of disease targets with: Metagenomi Translation Engine Highly efficient nucleases designed for any target in the human genome 23 Editing efficiency in mammalian cells determined based on the frequency of InDels detected by next generation sequencing (“NGS”) at genomic sites target
Slide 24: Generative AI informs optimization of efficient SMART nucleases
Pipeline comprised of disease targets with: Metagenomi Translation Engine Generative AI trained on proteins from nature informs optimization of efficient SMART nucleases 24 SpCas9 1376 amino acids Characterize small CRISPR-associated nucleases (SMall ARginine-rich sysTems: “SMART”) Search our metage
Slide 25: Base editing platform with broad targetability
Pipeline comprised of disease targets with: Metagenomi Translation Engine Base editing platform with broad targetability achieves efficient multiplex editing for cell engineering 25 ABE, CBE and nuclease are efficient for multiplexed knockout in primary T cells Reprogrammed chassis increases genome
Slide 26: Programmable large genome integration with CAST and RIGS
Pipeline comprised of disease targets with: Metagenomi Translation Engine Next generation technology for programmable large genome integration to address complex genetic diseases 26 CAST (DNA-Mediated Integration Systems) DNA Template Transposase CAST (DNA-Mediated Integration Systems) DNA Template
Slide 27: Technology innovations continue
27 2021-2022 Discovered large gene integration systems (CAST and RIGS) Discovered compact systems (SMART) Developed base editing platform Proof-of-concept (PoC) for in vivo liver editing with nuclease 2023 2024 2025 and beyond Compact systems: in vitro PoC for neuromuscular target RIGS: in vitro PoC
Slide 28: Corporate Highlights
28 Corporate Highlights
Slide 29: Recent milestones achieved and anticipated milestones
Recent milestones achieved 2025 2026 Hemophilia A Program Complete ongoing NHP durability study Conduct Pre-IND and ex-US regulatory meetings IND / CTA filings Cardiometabolic Programs Other Therapeutic Programs / Technology Development MGX-001 Development Candidate (DC) Factor VIII activity sustain
Slide 30: Metagenomi: Pipeline advancing, positioned for success
Metagenomi: Pipeline advancing, positioned for success Well capitalized with cash runway into 2027 Harnessing the power of our metagenomics platform to create curative genetic medicines for patients Advancing cardiometabolic programs with Ionis Progressing additional wholly-owned therapeutic candida
Slide 31: Thank you
Thank you 31 Investor Contact: IR@metagenomi.co