Metagenomi Therapeutics (MGX) Chardan's 10th Annual Healthcare Conference summary

Genome editing approaches

• Epicrispr’s approach disables the Cas nuclease and uses proprietary modulators to regulate gene expression up or down without cutting DNA; modulation includes methylation and histone acetylation.

• Metagenomi uses a proprietary nuclease library for targeted editing and gene insertion; MGX-001 integrates factor VIII into the albumin gene rather than relying on episomal delivery.

EPI-321 in FSHD

• EPI-321 targets abnormal DUX4 expression in FSHD, affecting 40,000–50,000 people in the U.S.; its compact Cas construct, modulator and guide fit within an AAV payload.

• At six months, all first six patients gained lean muscle volume versus projected losses; strength gains aligned with the muscle areas showing volume gains.

• DUCZ, a cell-free DNA biomarker reflecting the DUX4 target ZBTB17, declined; patient levels shifted from the severe range at baseline to between no symptoms and very mild symptoms at six months.

• 12-patient, 12-month data are expected in 2027.

MGX-001 in hemophilia A

• In juvenile NHPs, factor VIII activity peaked within two weeks and remained stable through ~19 months; activity correlated with measured gene integration.

• In target-dose NHP cohorts, most animals reached the normal 50%–150% factor VIII range, none exceeded 150%, and both AAV and LNP components showed dose-dependent responses.

• Normal factor VIII activity was achieved at 5e12 vg/kg, more than 10x below Roctavian’s dose level; the endogenous albumin promoter avoids added promoter elements in the AAV cassette.

• MG29-1’s shorter guide RNA supports improved yield and purity; clinical-supply batches have been manufactured and released.