Exegenesis Bio and Modalis Partner to Advance MDL-201 Gene Therapy for Duchenne Muscular Dystrophy
Exegenesis Bio and Modalis Therapeutics Corporation (TOKYO: 4883) have entered into a research collaboration and license agreement aimed at advancing MDL-201, an investigational therapeutic candidate being developed for Duchenne muscular dystrophy (DMD). The collaboration combines Exegenesis Bio’s engineered muscle-targeting AAV capsid technology with Modalis’ proprietary CRISPR-GNDM® (Guide Nucleotide-Directed Modulation) epigenome editing platform, with the goal of accelerating the development of a potentially differentiated treatment approach for patients living with DMD.
The agreement is scheduled to become effective on September 14, 2026. Under the terms of the collaboration, Modalis will receive rights to use EMC181, an engineered AAV capsid developed by Exegenesis Bio and designed to demonstrate high tropism for muscle tissue, in connection with the development of MDL-201.
By bringing together the two companies’ technologies, Exegenesis Bio and Modalis aim to address two important challenges associated with genetic medicines for muscular disorders: delivering therapeutic payloads efficiently to skeletal and other relevant muscle tissues while limiting exposure to non-target organs, particularly the liver. The companies believe that combining EMC181 with Modalis’ CRISPR-GNDM® payload could help support the advancement of MDL-201 through research and development and toward potential clinical evaluation.
Targeting a Major Unmet Need in Duchenne Muscular Dystrophy
Duchenne muscular dystrophy is a rare and progressive genetic disorder associated with a deficiency of dystrophin, a protein that plays a critical structural role in maintaining the integrity of muscle cells. The disease can lead to progressive deterioration of skeletal muscle function and can also affect cardiac and respiratory muscles.
The progressive nature of DMD can significantly affect mobility and physical function, while involvement of cardiac and respiratory muscles can contribute to serious complications as the disease advances. Although therapeutic development in DMD has progressed considerably, researchers continue to seek approaches capable of providing sustained benefits across a broad population of patients.
The emergence of nucleic acid-based medicines and other genetic technologies has expanded the range of treatment strategies being investigated for DMD. However, the companies noted that maintaining long-term suppression of disease progression across patients remains a substantial challenge.
This continuing unmet need has encouraged researchers to investigate approaches that operate through mechanisms distinct from existing therapies. Modalis and Exegenesis Bio believe MDL-201 could represent one such approach by targeting utrophin, a protein that may complement dystrophin function in muscle.
MDL-201 Uses CRISPR-GNDM® to Activate Utrophin
MDL-201 is designed to use Modalis’ proprietary CRISPR-GNDM® epigenome editing technology to selectively and sustainably increase expression of utrophin in muscle tissue.
Unlike conventional gene-editing approaches that are designed to cut DNA, CRISPR-GNDM® is intended to regulate gene expression without creating double-stranded DNA breaks. This approach is designed to modify the activity of targeted genes at the epigenetic level rather than permanently cutting the underlying DNA sequence.
For MDL-201, the objective is to activate the expression of utrophin in muscle cells. Utrophin is a naturally occurring protein that has structural and functional similarities to dystrophin and has been investigated as a potential therapeutic target for DMD.
By increasing utrophin expression, MDL-201 is intended to potentially compensate for some of the functional consequences associated with dystrophin deficiency. The companies believe that this mechanism could provide a treatment strategy that is not dependent on correcting individual dystrophin mutations.
That characteristic could be particularly important in DMD, which can be caused by a range of different genetic mutations. A therapeutic strategy capable of addressing the disease independently of a patient’s specific mutation could potentially have broader applicability than mutation-specific approaches.
Exegenesis Bio Contributes Muscle-Tropic EMC181 Capsid
A central component of the collaboration is EMC181, an engineered AAV capsid developed by Exegenesis Bio. The capsid has been developed with the goal of achieving enhanced delivery to muscle tissues.
Adeno-associated virus, or AAV, vectors are widely investigated as delivery vehicles for genetic medicines because they can transport therapeutic genetic material into target cells. However, achieving efficient delivery to the desired tissue while limiting exposure to other organs remains an important consideration in the development of AAV-based therapies.
Exegenesis Bio describes EMC181 as having high tropism for muscle tissue along with liver-detargeting properties. According to the companies, these characteristics may help increase exposure to muscle while reducing exposure to the liver and other non-target tissues.
The companies plan to combine EMC181 with Modalis’ CRISPR-GNDM® payload for MDL-201. The resulting therapeutic strategy is intended to bring together targeted delivery and precise gene regulation within a single development program.
The collaboration therefore represents a combination of complementary technologies rather than simply the licensing of a delivery vehicle. Exegenesis Bio brings its AAV capsid engineering capabilities, while Modalis contributes its epigenome editing technology and experience in developing CRISPR-GNDM®-based therapeutic programs.
Potential Mutation-Agnostic Treatment Strategy
One of the potential advantages of MDL-201 is its intended mutation-agnostic mechanism.
DMD is associated with numerous genetic mutations affecting the dystrophin gene. Approaches that directly address particular mutations may therefore have a limited patient population depending on the specific molecular defect being targeted. By contrast, a therapy designed to increase utrophin expression could potentially operate independently of the underlying dystrophin mutation.
Modalis and Exegenesis Bio are pursuing MDL-201 with the objective of developing an approach that could potentially be applicable to a broad range of DMD patients.
However, the program remains in the research and development stage, and additional nonclinical and clinical studies will be necessary to determine whether the proposed mechanism can translate into meaningful therapeutic benefits in patients. The collaboration announcement does not establish clinical efficacy or safety for MDL-201.
Combining Delivery and Epigenome Editing Technologies
The partnership reflects a growing focus within genetic medicine on the importance of both therapeutic payload design and delivery technology.
A highly specific genetic payload may have limited therapeutic potential if it cannot reach the appropriate tissues at sufficient levels. Similarly, an efficient delivery system must be paired with a therapeutic payload capable of producing the desired biological effect.
The companies believe that EMC181 and CRISPR-GNDM® address these complementary aspects of therapeutic development. EMC181 is intended to improve targeting of muscle tissue and reduce liver exposure, while CRISPR-GNDM® is designed to provide targeted and durable activation of utrophin without cutting double-stranded DNA.
By integrating these technologies, the companies hope to improve the overall development profile of MDL-201 and accelerate its progression toward nonclinical and, potentially, clinical development.
The collaboration also builds on Modalis’ previous experience with its CRISPR-GNDM® platform, including programs such as MDL-101. That experience is expected to contribute to the development of MDL-201 as the companies evaluate the therapeutic candidate in additional research.
Leadership Perspectives
Zhenhua Wu, CEO of Exegenesis Bio, said the company is pleased to collaborate with Modalis to advance MDL-201. He highlighted EMC181’s development for muscle targeting and reduced liver exposure and said the company believes combining its capsid technology with Modalis’ CRISPR-GNDM® payload creates a potentially compelling approach for DMD.
Wu added that the collaboration is consistent with Exegenesis Bio’s strategy of applying its next-generation AAV capsid platform to differentiated gene therapies addressing significant unmet medical needs.
Haruhiko Morita, CEO of Modalis Therapeutics, also expressed enthusiasm about the partnership. He emphasized the complementary nature of the two technologies, describing the combination as bringing together durable and precise activation of utrophin with muscle-targeted delivery.
Morita said the collaboration could potentially accelerate MDL-201 toward clinical development and support the establishment of a differentiated, mutation-agnostic treatment strategy for DMD. He also reiterated Modalis’ commitment to advancing the program toward patients.
Financial Impact Expected to Be Limited
From a financial perspective, Modalis expects the research collaboration to have an immaterial impact on its results for the current fiscal year. The company stated that there is no revision to its current earnings forecast as a result of the agreement.
The financial disclosure indicates that the immediate economic impact of the collaboration is not expected to materially alter Modalis’ near-term financial outlook. The principal focus of the agreement is therefore on research and development and the potential advancement of MDL-201 rather than near-term financial contribution.
Advancing Toward Future Development
The collaboration between Exegenesis Bio and Modalis represents an effort to combine advanced AAV delivery technology with epigenome editing to address the complex biology of DMD.
MDL-201 is designed to increase utrophin expression in muscle through Modalis’ CRISPR-GNDM® platform while using Exegenesis Bio’s EMC181 capsid to support muscle-targeted delivery and potentially reduce liver exposure. If the approach demonstrates favorable results in future studies, it could provide a new avenue for developing a broadly applicable treatment that does not depend on a patient having a specific dystrophin mutation.
For now, MDL-201 remains an investigational program, and its potential safety, efficacy and durability will need to be established through appropriate preclinical and clinical development. The companies’ immediate objective is to leverage their combined technologies to advance the program through research and toward future clinical evaluation.
With the agreement becoming effective on September 14, 2026, Exegenesis Bio and Modalis are beginning a collaboration centered on one of the key challenges in DMD treatment: developing therapies capable of reaching muscle tissue efficiently while producing sustained biological effects. Their combined approach could help expand the range of therapeutic strategies being explored for Duchenne muscular dystrophy and potentially support the development of a mutation-agnostic treatment option for a broad patient population.
About Utrophin and Its Therapeutic Rationale in DMD
Utrophin is a naturally occurring protein that is structurally and functionally related to dystrophin, the protein that is deficient in patients with Duchenne muscular dystrophy (DMD). During early muscle development, utrophin is expressed broadly in muscle fibers and performs functions similar to those of dystrophin. As muscle matures, dystrophin becomes the predominant protein, while utrophin expression becomes more restricted.
Importantly, experimental studies have shown that increasing utrophin expression can compensate, at least in part, for the loss of dystrophin and improve muscle function in models of DMD. Because utrophin is encoded by a gene distinct from the dystrophin gene, therapeutic activation of endogenous utrophin has the potential to benefit patients regardless of the specific mutation in the dystrophin gene.
Modalis is developing MDL-201 to selectively and sustainably activate endogenous utrophin expression in muscle using its CRISPR-GNDM® epigenome editing technology. This mutation-agnostic approach is designed to harness a naturally occurring compensatory mechanism and has the potential to provide a differentiated therapeutic strategy for a broad range of patients with DMD.
About Exegenesis Bio
Exegenesis Bio is a biopharmaceutical company focused on gene therapies and oligonucleotide-based drugs. The company advances research and development and business development with globally leading delivery technologies, with the goal of creating new treatment options for serious diseases. For more information, please visit https://exegenesisbio.com
About Modalis Therapeutics Corporation
Modalis Therapeutics Corporation (TOKYO: 4883), founded in 2016 with R&D facilities in Massachusetts, USA, is a leading company in the development of therapeutics using CRISPR-based epigenome editing technology. Based on our highly scalable platform technology, we are developing treatments for patients suffering from serious genetic diseases such as muscular diseases, CNS diseases, and cardiomyopathy. For more information, please visit https://www.modalistx.com/en