Pipeline is scalable to broad indications

As of Feburary 2025

Discovery / Preclinical
Clinical

Code
Indication
Ownership
Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

Muscle disorder(disease)
MDL-101
LAMA2-CMD(*1)

In-house

【Disease information】

A type of muscular dystrophy caused by mutations in the LAMA2 gene, affecting 8.3 in every million people. The condition tends to develop at birth or shortly after birth. Children with LAMA2-CMD show severe muscle weakness and face serious problems such as difficulty walking, speaking, and breathing, heart failure, joint deformation, and scoliosis (a disease in which the spine bends). Many patients do not live past adolescence.

【Our approach】
　
MDL-101 is a gene therapy product designed to reach muscle cells with a single dose and increase the expression of LAMA1, a protein that is functionally complementary to LAMA2, using CRISPR-GNDM® technology. Given the similarities between LAMA1 and LAMA2, expression of LAMA1 has been shown to alleviate disease symptoms in mouse models of LAMA2-CMD.

MDL-202
DM1(*2)

In-house

【Disease information】

The age of onset varies from 20 to 70 years old, and it is the most common hereditary progressive muscle disease, with a frequency of 1 in 2300 people. It causes muscle weakness in voluntary muscles, and symptoms such as muscle stiffness, muscle atrophy, decreased heart function, and dyspnea.

【Our approach】
　
Since DM1 is a disease caused by abnormal splicing of the DMPK (DM protein kinase) gene, MDL-202 is expected to inhibit the transcription of DMPK mRNA and allow the MBNL protein to perform its original function.

MDL-201
DMD(*3)

In-house

【Disease information】

This is a progressive type of muscular dystrophy caused by mutations in the dystrophin gene, and affects approximately 1 in 5,000 boys born during childhood (between the ages of 3 and 6). In early childhood, motor development begins to slow down, and by the age of 12, the child is confined to a wheelchair due to progressive muscle weakness. Later, the child develops cardiomyopathy and scoliosis, and respiratory complications and other serious clinical symptoms occur.

【Our approach】
　
MDL-201 (GNDM-UTRN) is expected to reboot expression of utrophin, a fetal form of dystrophin, and compensate for the abnormal function of dystrophin.

MDL-103
FSHD(*4)

In-house

【Disease information】

FSHD is a progressive muscle disease that affects 1 in 15,000 people and is caused by the over-expression of the DUX4 gene. It causes muscle weakness and destruction in the face, shoulder blades and upper arms.

【Our approach】
　
MDL-103 is expected to suppress the expression of the Dux4 gene product, which is injurious.

Cardiomyopathy
MDL-105
DCM(*5)

In-house

【Disease information】

This is a cardiomyopathy caused by truncated mutations in the Titin(TTN) gene, the largest gene in human, and affects 1 in 2,000 people. Due to a decrease in the contractile force and pumping function of the myocardium, congestive heart failure, arrhythmia, and thromboembolism can occur, and about 50% of cases result in sudden death.

【Our approach】
　
MDL-105 targets a gene called Titin, and by increasing its expression, it is expected to activate the transcription of TTN and restore the amount of TTN protein to normal levels.

CNS disorder
MDL-104
Tauopathy

In-house

【Disease information】

A neurodegenerative disease in which tau protein accumulates abnormally in the brain, causing damage to nerve cells. One in nine people over the age of 65 (55 million people worldwide) are affected. After onset, the disease progresses slowly and chronically, causing memory loss, language impairment and a decline in motivation.

【Our approach】
　
MDL-104 is expected to suppress the progression of the pathological condition and symptoms of tauopathy by suppressing the production of tau protein by inhibiting Tau at the transcription level.

MDL-206
Angelman Syndrome

In-house

【Disease information】

A neurological genetic disorder that occurs in 1 in 15,000 newborns (500,000 cases worldwide) and is caused by a loss of function in the UBE3A gene. It is accompanied by severe mental developmental delay, epileptic seizures, and ataxic movement disorders.

【Our approach】
　
MDL-206 is expected to restore UBE3A expression by restoring expression from the paternal UBE3A gene, which is normally suppressed by a silencing mechanism, in cases where a mutated gene in the maternal UBE3A gene causes a loss of function.

MDL-207
Dravet Syndrome

In-house

【Disease information】

Dravet syndrome, also known as infantile severe myoclonic conversion, is a severe form of childhood epilepsy that occurs in infants under the age of one, with a frequency of one in 40,000 cases. Due to a genetic mutation (mutation in the SCN1a gene), the condition is triggered by fever or bathing, and manifests as generalized or unilateral convulsive seizures. The condition often progresses to status epilepticus, in which seizures continue and do not stop, and there is often a delay in intellectual development, and the patient may also experience unsteadiness when walking. It is said that approximately 10-20% of patients die before adulthood.

【Our approach】
　
MDL-207 is expected to increase the expression of the SCN1a protein.

muscle disoder(disease)

Code MDL-101
IndicationLAMA2-CMD(*1)
OwnershipIn-house

【Disease information】

A type of muscular dystrophy caused by mutations in the LAMA2 gene, affecting 8.3 in every million people. The condition tends to develop at birth or shortly after birth. Children with LAMA2-CMD show severe muscle weakness and face serious problems such as difficulty walking, speaking, and breathing, heart failure, joint deformation, and scoliosis (a disease in which the spine bends), and it is said that many of them do not live past adolescence.

【Our approach】

MDL-101 is a gene therapy product designed to reach muscle cells with a single dose and increase the activity of the LAMA1 gene using CRISPR-GNDM® technology. It is expected to alleviate the symptoms of LAMA 2-CMD by supplementing the deficiency of the LAMA2 protein to produce a protein similar to LAMA2 and restore muscle function.

Discovery
Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

CodeMDL-202
IndicationDM1(*2)
OwnershipIn-house

【Disease information】

The age of onset varies from 20 to 70 years old, and it is the most common hereditary progressive muscle disease, with a frequency of 1 in 2300 people. It causes muscle weakness in voluntary muscles, and symptoms such as muscle stiffness, muscle atrophy, decreased heart function, and dyspnea.

【Our approach】

Since DM1 is a disease caused by abnormal splicing of the DMPK (DM protein kinase) gene, MDL-202 is expected to inhibit the transcription of DMPK mRNA and allow the MBNL protein to perform its original function.

Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

CodeMDL-201
IndicationDMD(*3)
OwnershipIn-house

【Disease information】

This is a progressive type of muscular dystrophy caused by mutations in the dystrophin gene, and affects approximately 1 in 5,000 boys born during childhood (between the ages of 3 and 6). In early childhood, motor development begins to slow down, and by the age of 12, the child is confined to a wheelchair due to progressive muscle weakness. Later, the child develops cardiomyopathy and scoliosis, and respiratory complications and other serious clinical symptoms occur.

【Our approach】

MDL-201 (GNDM-UTRN) is expected to reboot expression of utrophin, a fetal form of dystrophin, and compensate for the abnormal function of dystrophin.

Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

CodeMDL-103
IndicationFSHD(*4)
OwnershipIn-house

【Disease information】

FSHD is a progressive muscle disease that affects 1 in 15,000 people and is caused by the over-expression of the DUX4 gene. It causes muscle weakness and destruction in the face, shoulder blades and upper arms.

【Our approach】

MDL-103 is expected to suppress the expression of the Dux4 gene product, which is injurious.

Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

Cardiomyopathy

CodeMDL-105
IndicationDCM(*5)
OwnershipIn-house

【Disease information】

This is a cardiomyopathy caused by truncated mutations in the Titin(TTN) gene, the largest gene in human, and affects 1 in 2,000 people. Due to a decrease in the contractile force and pumping function of the myocardium, congestive heart failure, arrhythmia, and thromboembolism can occur, and about 50% of cases result in sudden death.

【Our approach】

MDL-105 targets a gene called Titin, and by increasing its expression, it is expected to activate the transcription of TTN and restore the amount of TTN protein to normal levels.

Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

CNS disorder

CodeMDL-104
IndicationTauopathy
OwnershipIn-house

【Disease information】

A neurodegenerative disease in which tau protein accumulates abnormally in the brain, causing damage to nerve cells. One in nine people over the age of 65 (55 million people worldwide) are affected. After onset, the disease progresses slowly and chronically, causing memory loss, language impairment and a decline in motivation.

【Our approach】

MDL-104 is expected to suppress the progression of the pathological condition and symptoms of tauopathy by suppressing the production of tau protein by inhibiting Tau at the transcription level.

Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

CodeMDL-206
IndicationAngelman Syndrome
OwnershipIn-house

【Disease information】

A neurological genetic disorder that occurs in 1 in 15,000 newborns (500,000 cases worldwide) and is caused by a loss of function in the UBE3A gene. It is accompanied by severe mental developmental delay, epileptic seizures, and ataxic movement disorders.

【Our approach】

MDL-206 is expected to restore UBE3A expression by restoring expression from the paternal UBE3A gene, which is normally suppressed by a silencing mechanism, in cases where a mutated gene in the maternal UBE3A gene causes a loss of function.

Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

CodeMDL-207
IndicationDravet Syndrome
OwnershipIn-house

【Disease information】

Dravet syndrome, also known as infantile severe myoclonic conversion, is a severe form of childhood epilepsy that occurs in infants under the age of one, with a frequency of one in 40,000 cases. Due to a genetic mutation (mutation in the SCN1a gene), the condition is triggered by fever or bathing, and manifests as generalized or unilateral convulsive seizures. The condition often progresses to status epilepticus, in which seizures continue and do not stop, and there is often a delay in intellectual development, and the patient may also experience unsteadiness when walking. It is said that approximately 10-20% of patients die before adulthood.

【Our approach】

MDL-207 is expected to increase the expression of the SCN1a protein.

Discovery Research
Lead
Optimization
IND
Enabling
Phase I/Ⅱ
Pivotal

*1:LAMA2-related congenital muscular dystrophy
*2:Myotonic Dystrophy Type1
*3:Duchenne Muscular Dystrophy
*4:Facioscapulohumeral muscular dystrophy
*5:Dilated Cardiomyopathy

Technical Terms

Lead optimization

This is the process of further improving new drug candidates in the early stages of pharmaceutical development to obtain more effective and safer candidates.

Preclinical

This refers to in vitro tests using cells and other materials, and in vivo tests using animals such as mice, with the aim of verifying the effectiveness, safety and toxicity of new drug candidates and therapeutic drugs.

IND filing

IND is an abbreviation for Investigational New Drug, and is a clinical trial notification form used to begin clinical trials in the United States. Under the clinical trial notification system in the United States, in principle, an IND application is required before the start of clinical trials using unapproved drugs, or clinical trials that expand the approved indications or change the dosage and administration, even after approval. Each country has its own counterpart.

IND enabling study

The main part of preclinical studies is the safety evaluation and biodistribution/pharmacokinetic evaluation studies (and some efficacy evaluation studies) that are conducted to meet the requirements set by the regulatory authorities for IND applications.

GMP manufacturing

GMP is an abbreviation for Good Manufacturing Practice, and refers to the practice of manufacturing in accordance with manufacturing and quality control standards. In order to manufacture investigational drugs, it is necessary to follow these standards, and this is an important element, along with IND enabling studies, for IND applications.

Clinical trial

Based on the results of preclinical trials, this is a scientific test conducted on humans to evaluate the safety and efficacy of new drug candidates and treatments. Clinical trials are conducted in accordance with strict ethical standards and regulations.

Pivotal study

This is the most important and largest clinical trial in which the efficacy and safety of a treatment are finally confirmed during clinical trials, and an application for manufacturing and marketing approval is submitted to the regulatory authorities of each country (e.g. the FDA in the US, the PMDA in Japan).

Muscle disorder(disease)

This is a general term for diseases and disorders related to muscles. These are diseases that affect the function and structure of muscles, causing symptoms such as muscle weakness, loss of motor function, pain, and muscle atrophy.

Cardiomyopathy

Although the heart is anatomically a cardiovascular organ, from a physiological perspective, its characteristics as muscle tissue are important, and many heart diseases are caused by a decline in the function of the heart muscle. Cardiomyopathy is a general term for diseases in which there are abnormalities in the heart muscle (myocardium) among muscle diseases, and as a result, the heart is unable to maintain its function.

CNS(central nervous system) disorder

This is a general term for diseases and disorders that affect the central nervous system (brain and spinal cord). The central nervous system plays an important role in regulating various functions of the body, and problems in this area can affect functions such as physical movement, sensation, thought, cognition, and emotion.