M102

M102 is a proprietary disease-modifying drug therapeutic based on recently understood disease pathways in neurodegenerative diseases, particularly in ALS. M102 was identified as a lead therapeutic candidate by the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield, UK, in an effort to identify central nervous system (CNS) penetrant activators of the NRF2-ARE pathway. M102 is an orally administered, once daily, small molecule drug and a new chemical entity (NCE). 

Pathomechanisms

Biology

Impact

Therapeutic
Biomakers

Development

Growth
Opportunities

Pathomechanisms

Biology

Impact

Therapeutic Biomakers

Development

Growth Opportunities

Pathomechanisms

M102, a potential best-in-class drug, takes a much broader mechanistic approach to treat ALS, in that M102 has effects on nine of the eleven ALS disease pathomechanisms.

Biology

M102 is a dual activator of the NRF2 and HSF1 pathways, and an inhibitor of NFkB pathway, which are newly understood disease-modifying pathways that are downregulated in ALS and affect these nine ALS pathomechanisms.

By NRF2 and HSF1 activation, M102 reduces oxidative stress and inflammation, enhances mitochondrial biogenesis and initiates autophagy. In addition, M102 refolds misfolded proteins, disaggregates aggregated proteins, and clears misfolded and aggregated proteins.

Impact

M102 has four sets of translational data from three in vivo pharmacology studies in ALS models and one in vitro study in the ALS patient cellular model. All datasets indicate strong efficacy in both familial and sporadic ALS. Particularly in the TDP-43 mouse model, M102 has stopped disease progression and reverted disease animals back towards the healthy state. TDP-43 proteins exist in 97% of all ALS patients.

Therapeutic Biomakers

To further reduce the clinical risk, Aclipse has developed a comprehensive set of therapeutic biomarkers to confirm target and pathway engagement, optimize clinical dose regimen, and enable a precision medicine approach for the M102 treatment. More specifically, our technology allows the identification of M102 drug responders, which constitute 60% of all ALS patients. Meanwhile, industry data show that the application of a targeted therapy (i.e., a precision medicine approach) increases the probability of clinical success by 3.1-fold.

Development

M102 is protected by pending patent families protecting composition-of-matter, use and biology, pharmacokinetics, and formulation with patent life extended to 2040. M102 has received the FDA orphan drug designation and the European Medicines Agency (EMA) orphan designation, which add meaningful protections for our product. M102 is also eligible for additional FDA regulatory exclusivities and/or programs, including Fast Track, Breakthrough Therapy, Priority Review and NCE exclusivities at the appropriate times of drug development.
M102 represents a therapeutic development program with a strong intellectual property package.
  • Established four patent families protecting composition-of-matter, use and biology, pharmacokinetics, and formulation
  • Current patent families extend patent life to 2040
  • Granted the US FDA orphan drug designation and the European Medicines Agency (EMA) orphan designation
  • Eligible for Fast Track, Breakthrough Therapy, Priority Review programs and NCE exclusivities

Growth Opportunities

M102 also has significant upside uses in other neurodegenerative diseases. Neurodegenerative diseases represent a range of medical conditions which primarily affect the neurons in the human brain. Neurons are the building blocks of the nervous system which includes the brain and spinal cord. Normally, neurons do not reproduce or replace themselves, so when they become damaged or dead, they cannot be replaced by the body. Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neuron cells. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. There are many parallels between different neurodegenerative disorders, including atypical protein assemblies and induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry, ranging from molecular to systemic. Potential additional applications of M102 includes Parkinson’s Disease, Huntington’s Disease, and Friedreich’s Ataxia.

Indications for M102

ALS

Amyotrophic lateral sclerosis is a specific disease which causes the death of neurons controlling voluntary muscles. This disease is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size. This results in difficulty speaking, swallowing, and eventually breathing. Amyotrophic lateral sclerosis afflicts about 25,000 patients in America.

Friedreich's Ataxia​

Friedreich's ataxia is an autosomal recessive inherited disease that causes progressive damage to the nervous system. It manifests in initial symptoms of poor coordination such as gait disturbance; it can also lead to scoliosis, heart disease and diabetes, but does not affect cognitive function. Friedreich's ataxia affects around 1 in 50000 people in the United States.

Parkinson's Disease

Parkinson's disease is a neurodegenerative disorder that affects predominately dopaminergic neurons in a specific area of the brain called substantia nigra. People with this disease may experience tremor, slowness of movements, limb rigidity, as well as gait and balance problems. Symptoms generally develop slowly over years. Every year, about 60,000 Americans are diagnosed with Parkinson's disease.

Huntington's Disease​

Huntington’s disease is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. It deteriorates a person’s physical and mental abilities during their prime working years and has no cure. Today, there are approximately 30,000 symptomatic Americans and more than 200,000 at-risk of inheriting the disease.
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