Exegenesis Bio and Modalis Therapeutics Corporation are joining forces to accelerate the development of a potentially transformative treatment for Duchenne muscular dystrophy (DMD).

 

This by combining Exegenesis Bio's next-generation muscle-targeting delivery technology with Modalis' proprietary CRISPR-GNDM epigenome-editing platform.

 

The companies have signed a research collaboration and license agreement to advance MDL-201, an innovative therapeutic candidate for DMD.

 

Under the collaboration, Modalis will receive rights to use EMC181, an engineered muscle-tropic AAV capsid developed by Exegenesis Bio, for MDL-201. By bringing together EMC181's muscle-targeted delivery capabilities with Modalis' CRISPR-GNDM payload and development expertise, the companies aim to accelerate MDL-201's path from research toward potential clinical application.

 

DMD is a rare and devastating genetic disease caused by a deficiency of dystrophin, a protein essential for maintaining muscle-cell integrity. The disease progressively impairs skeletal, cardiac, and respiratory muscles, ultimately leading to severe functional decline.

 

Although advances in nucleic acid medicines and other therapeutic modalities have expanded treatment options, significant challenges remain. In particular, achieving durable control of disease progression across the broad DMD patient population remains difficult, underscoring the need for new approaches that can complement existing therapies or address the disease through distinct mechanisms.

 

MDL-201 is designed to pursue such an approach.

 

The therapy is being developed to sustainably and selectively activate utrophin in muscle tissue using Modalis' proprietary CRISPR-GNDM technology. Rather than cutting double-stranded DNA, the epigenome-editing approach is designed to regulate gene expression and increase utrophin production. Because utrophin may complement some of the functions normally performed by dystrophin, this strategy could offer a mutation-agnostic therapeutic approach with the potential to address a broad range of DMD patients.

 

A central element of the collaboration is EMC181, Exegenesis Bio's engineered AAV capsid designed for preferential delivery to muscle tissue.

 

EMC181 combines high muscle tropism with liver-detargeting properties, characteristics that may help increase delivery to the intended target tissues while reducing exposure to the liver and other non-target organs. The companies believe this combination could potentially improve the therapeutic profile of MDL-201 as development progresses.

 

By pairing EMC181 with Modalis' CRISPR-GNDM payload, the companies aim to achieve more efficient delivery to muscle tissue while pursuing a durable therapeutic effect that does not depend on a patient's specific DMD mutation.

 

The collaboration brings together two complementary technology platforms.

 

Exegenesis Bio contributes its gene therapy research and development platform and its muscle-tropic, liver-detargeting AAV capsid technology, including EMC181. Modalis contributes its proprietary CRISPR-GNDM epigenome-editing technology, payload capabilities, and development experience from programs including MDL-101.

 

Together, the companies aim to integrate targeted delivery with precise and durable gene regulation, potentially overcoming important challenges associated with systemic gene therapy while advancing MDL-201 toward nonclinical and clinical development.

 

Zhenhua Wu, CEO of Exegenesis Bio, stated: "We are pleased to collaborate with Modalis to advance MDL-201. EMC181 was developed to enable efficient muscle targeting while reducing liver exposure, and we believe its combination with Modalis' innovative CRISPR-GNDM® payload represents a compelling approach for DMD. 

 

"This collaboration reflects our strategy of applying our next-generation AAV capsid platform to differentiated gene therapies with the potential to address significant unmet medical needs."

 

Haruhiko Morita, CEO of Modalis Therapeutics, commented: "We are excited to partner with Exegenesis Bio to advance MDL-201. Combining our CRISPR-GNDM payload with EMC181 brings together two highly complementary technologies - precise, durable activation of utrophin and efficient muscle-targeted delivery. 

 

"We believe this collaboration has the potential to accelerate MDL-201 toward the clinic and to establish a differentiated, mutation-agnostic treatment approach for DMD. We remain committed to bringing this potential new treatment to patients as quickly as possible."