Metagenomi Therapeutics (MGX) Jefferies 2024 Global Healthcare Conference summary

Platform and technology overview

• Leveraging metagenomics to discover thousands of novel gene editing systems and enzymes, enabling both small edits and large integrations.

• Proprietary CRISPR nucleases are small, efficient, and show minimal off-target activity, broadening targetability across the genome.

• Developed base and prime editing systems with high efficiency and multiplexing capabilities, targeting up to 95% of adenines in the genome.

• Built high-throughput automation and mRNA/guide RNA optimization to accelerate discovery and translation to clinic.

• Flexible delivery approaches include LNP, viral vectors, and in-house GMP manufacturing for clinical-grade materials.

Pipeline and clinical progress

• Lead program targets hemophilia A, using a two-step delivery system to insert Factor VIII gene into the albumin locus in the liver.

• Non-human primate studies show 1–3% integration levels, achieving clinically relevant Factor VIII expression (10–150% of normal).

• Ongoing 12-month durability study with data expected in the second half of the year; platform could be extended to other secreted liver diseases.

• Partnership with Ionis supports multi-target programs and expansion beyond liver to neuromuscular and other organs.

• IND filing for hemophilia A program targeted for 2026, with regulatory feedback aligning expectations and de-risking development.

Innovation and AI integration

• AI and ancestral sequence reconstruction used to engineer rare programmable enzymes, boosting activity from <10% to nearly 100%.

• Proprietary database of over 7 billion proteins from ongoing environmental sampling fuels generative AI for novel enzyme discovery.

• AI-driven approaches accelerate protein engineering and expand the gene editing toolbox.