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Exegenesis and Modalis combine muscle-targeting AAV with epigenome editing for preclinical DMD candidate

Edited by Robert McTiernan··2 min read
Exegenesis and Modalis combine muscle-targeting AAV with epigenome editing for preclinical DMD candidate

Exegenesis Bio and Japan-based Modalis Therapeutics Corporation (Tokyo: 4883) signed a research collaboration and license agreement to advance MDL-201, a preclinical epigenome editing candidate for Duchenne muscular dystrophy (DMD), combining Modalis' CRISPR-GNDM (Guide Nucleotide-Directed Modulation) payload with Exegenesis Bio's EMC181 engineered muscle-tropic AAV capsid. The agreement becomes effective September 14, 2026, with Modalis retaining lead development responsibility.

MDL-201 uses Modalis' CRISPR-GNDM platform to transcriptionally activate endogenous utrophin expression in muscle tissue without cutting double-stranded DNA, offering a mutation-agnostic approach applicable across DMD patients regardless of their specific dystrophin gene mutation. Under the license terms, Modalis receives rights to use EMC181 — an AAV capsid engineered by Horsham, Pennsylvania-based Exegenesis Bio for high muscle tropism and active liver-detargeting properties — to deliver the CRISPR-GNDM payload. The companies said the combination is intended to enhance muscle delivery while reducing off-target hepatic exposure. MDL-201 remains at the preclinical stage, with the parties targeting nonclinical and subsequent clinical development.

Financial terms were not disclosed. Modalis said the financial impact on its current fiscal year results is expected to be immaterial, with no revision to its earnings forecast.

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Modalis has applied the CRISPR-GNDM platform across multiple neuromuscular programs. Its lead asset, MDL-101, a CRISPR-GNDM-based epigenome editing therapy for LAMA2-related congenital muscular dystrophy (LAMA2-CMD), received both Orphan Drug Designation and Rare Pediatric Disease Designation from the US FDA, with preclinical data published in Human Gene Therapy demonstrating robust LAMA1 activation and favorable safety in non-human primates. Exegenesis Bio has separately disclosed EMC023, an earlier muscle-specific capsid, and has three clinical-stage programs in wet age-related macular degeneration, spinal muscular atrophy, and Fabry disease. In DMD, the epigenome editing approach competes conceptually with gene replacement strategies such as Sarepta Therapeutics' delandistrogene moxeparvovec (Elevidys) and exon-skipping programs from Entrada Therapeutics, though MDL-201's mutation-agnostic utrophin activation mechanism is mechanistically distinct from dystrophin replacement or exon skipping.

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