Potential neuroprotective effect in neurodegenerative diseases

and a favorable safety profile

Pridopidine is an orally bioavailable small molecule investigational drug exhibiting potential neuroprotective effect in multiple neurodegenerative diseases with a favorable safety profile.

Pridopidine is the most selective high affinity Sigma-1-receptor (S1R) agonist. The S1R regulates key cellular processes relevant to neurodegenerative diseases, such as calcium homeostasis, cytoskeleton dynamics, restoring mitochondrial health and neurotrophic factor release. S1R is implicated in cellular differentiation, neuroplasticity, neuroprotection, and cognitive functioning of the brain.

Pridopidine positively influences S1R regulated pathways across neurodegenerative and neurodevelopmental indications, including protection against axonal and neuronal injury, restoring spine impairments, enhancing BDNF secretion and restoring mitochondrial function. These mechanisms have been validated in multiple disease models including Huntington Disease (HD), ALS, Neurodegenerative eye disease, Parkinson’s Diseases (PD), Rett Syndrome (RTT), Fragile X and Alzheimer Disease (AD).  Pridopidine’s occupancy of the S1R (full occupancy at low doses) has been validated using PET imaging in humans.

Pridopidine is the first drug to show statistically significant effect on maintenance of functional capacity in HD, as measured by Total Functional Capacity (TFC). This effect was most prominent in early HD patients. This clinical validation further supports the potential effect of Pridopidine on maintenance of functional capacity in HD and other neurodegenerative diseases.


While at low doses, Pridopidine affects S1R, at higher doses it interacts with other targets including dopamine D3, adrenergic α2C and serotoninergic 5-HT1A, which are established therapeutic targets for Parkinson’s Disease Levodopa Induced Dyskinesia (PD-LID). This is the likely mechanism for the clear effect seen in the “gold standard” non-human primate model for PD-LID – the MPTP-Lesioned Macaques. This model is considered highly translatable to success in phase 2 clinical trials.

Pridopidine’s favorable safety profile has been established in clinical trials in 1260 people, exposed to various doses for a total of ~1000 patient years. This extensive safety evaluation supports a favorable safety and tolerability profile which has been well defined.

Pridopidine is currently in Phase 2 clinical development for the treatment of patients suffering from PD-LID, and we are planning to initiate a phase 3 trial in Huntington Disease in the near future. Additional clinical studies in other indications are also under consideration.



The first drug to ever show effect on maintenance of functional capacity in HD; phase 3 planned in the near future

HD is a fatal, inherited, neurodegenerative disorder where every child of an HD patient has a 50% chance of inheriting the gene. Usually starting at around 40 years of age, HD patients suffer from progressive functional and cognitive decline, psychiatric disturbances, behavioral symptoms and movement disorder. Following diagnosis, functional, motor and cognitive functions decline steadily, ultimately leading to immobility, dementia and premature death.

The prevalence of HD in North America, North-Western Europe and Australia ranges from 5.96-13.7 cases per 100,000 people. In the US alone, approximately 40,000 are believed to have HD, and at least 75,000 are gene carriers in whom the disease will appear if they live long enough. Similar numbers are estimated for Europe.

Currently there is no approved treatment for functional decline in HD. Only two drugs are approved for relieving certain motor symptoms.

Pridopidine is the first drug to show statistically significant effect on maintenance of functional capacity in HD, as measured by Total Functional Capacity (TFC), in a clinical trial. This effect was most prominent in early HD patients (HD1 and HD2), for which pridopidine 45 mg bid showed significant functional benefit. Prilenia plans to initiate a phase 3 study to further assess pridopidine’s effect on function and other aspects of HD in the near future.

There is extensive preclinical evidence that further supports pridopidine’s potential neuroprotective effect in HD. This effect is mediated by the S1R, as shown in multiple models where S1R is deleted or antagonized.Prilenia has an orphan drug designation for pridopidine for the treatment of HD in both the US and Europe.


Promising results in the “gold standard” non-human primate model; in active clinical trial in the US

PD-LID is a highly debilitating disease associated with chronic use of Levodopa treatment. It causes involuntary movements (dyskinesia) that result in frustration, isolation and depression. Patients and caregivers suffer from poor quality of life as well as an increased burden of care and costs. Treatments for PD-LID have been ranked #3 at the top 10 research priorities in PD. Dyskinesia can be disabling and render a patient housebound and unsafe to go outdoors without a caregiver. Once established, PD-LID is difficult to treat. There is currently one approved drug for PD-LID but it has had limited uptake, and therefore patients, caregivers and treating physicians continue to look for new treatments.

Pridopidine was tested in the “gold standard” non-human primate model for PD-LID – the MPTP-Lesioned Macaques. This model is considered highly translatable to success in phase 2 clinical trials. Pridopidine demonstrated clear effect on reducing dyskinesia without causing increase in parkinsonian disability. This effect suggests a strong potential for success in the clinic. Pridopidine’s effect on PD-LID is likely mediated by dopamine D3, adrenergic α2C and serotoninergic 5-HT1A mechanisms, which are established therapeutic targets for PD-LID.

Pridopidine is currently in phase 2 trial for PD-LID. Our target is to bring Pridopidine to PD-LID patients by 2023.



Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 500,000 people worldwide. ALS causes the progressive degeneration of motor neurons, resulting in progressive muscle weakness and atrophy.

Pridopidine’s compelling preclinical data and mechanism on action as a selective S1R agonist further supports the therapeutic potential of pridopidine in ALS. In SOD1G93A motor neurons (MNs), pridopidine exerts neuroprotective effects via activation of the S1R. Specifically, pridopidine increases MN survival, improves BDNF and GDNF axonal transport, and restores the neuro-muscular junction (NMJ) synaptic activity. In-vivo, pridopidine treatment of SOD1G93A mice reduces toxic protein aggregates and ameliorates muscle fiber wasting.

Clinical support for the validity of the S1R as a potential target for ALS can be derived from a prior trial using a non-selective S1R agonist, showing S1R activation may enhance bulbar and speech function in ALS patients. Pridopidine in-vivo target engagement in humans is validated by PET imaging, providing support of the optimal clinical dose.

Pridopidine has recently been selected by the Sean M. Healey & AMG Center for ALS at Mass General Hospital, as the first of three potential new treatments to be included in the launch of the first ever Platform Trial in ALS

Pridopidine was chosen by an independent review committee out of 30 competing investigational treatments based on human genetic data, efficacy in preclinical models, favorable safety profile, readiness of drug supply, as well as pridopidine’s mechanism of action as a highly selective S1R agonist.

The Trial design aims to accelerate the development of effective treatments for people living with ALS, by testing and evaluating multiple treatments simultaneously.

More information about the trial will be shared in the near future.


preclinical evidence shows promise

Prilenia is continuing the clinical and preclinical evaluation of Pridopidine in various neurodegenerative and neurodevelopmental indications and plans to initiate additional clinical studies in the near future.



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