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Our drugs – selectivity and neuroprotection

Our small molecule drugs are unique – dual-acting, sub-nanomolar active with highly selective modulation capabilities – termed retinoic acid receptor modulators. Evidence from patients and disease models support the concept that small molecule drugs that mimic retinoic acids have potential for treatment of neurodegenerative and other diseases– i.e. there is a strong rationale for clinical trials using small molecules that selectively bind retinoic acid receptors.

Mechanism of Action

Our priorities

ALS & FTD

RAR modulators could contribute to protein metabolism and also modulate autophagic response. RAR-modulation correlates with axon outgrowth and nerve regeneration and maintenance.

Parkinson's

RAR-modulators are likely to be important for midbrain dopaminergic neurons since RARs and retinoic acid metabolising enzymes are highly expressed in these neurons and their target regions.

Alzheimer's

RAR deficiency is causative of Alzheimer’s - vitamin A deficiency results in amyloid-beta deposition in cerebral blood vessels. We have shown many neuroprotective genes to be induced by RARs.

Our capabilities are

State-of-the-art

  • Small molecule drug-receptor structural studies (crystallography)
  • Small molecule drug-receptor binding studies
  • Modelling small molecule drug-receptor interaction in silico
  • In silico design of new potential small molecule drugs
  • Small molecule drug synthesis and supply for range of assays
  • Build up structure-activity relationships
  • Optimise physical and chemical properties
  • Identify lead small molecule drug for further development
  • Platform-based drug development programme to develop unique drugs for each neurodegenerative disease

Therapeutic areas

Our small molecule drugs are unique – dual-acting, sub-nanomolar active with highly selective modulation capabilities – termed retinoic acid receptor modulators. Evidence from patients and disease models support the concept that small molecule drugs that mimic retinoic acids have potential for treatment of neurodegenerative and other diseases– i.e. there is a strong rationale for clinical trials using small molecules that selectively bind retinoic acid receptors. The area of primary focus of Nevrargenics is CNS diseases, but Retinoid Acid Receptors play a key role in some liver diseases and also diseases of the eye, areas that we can expand into with other pharma companies in these areas.

Alzheimer’s, Parkinson’s, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Frontotemporal Dementia, Eye Diseases, Ophthalmology, AMD, Age-related Macular Degeneration, Retina Degeneration, Live Diseases, NASH, NAFLD, Fatty Liver, treatments, therapeutics, drugs

What makes our drugs

Unique

One of our key discoveries after years of research was that for RAR modulation to exhibit strong neurite outgrowth, a drug needs to have both strong genomic AND non-genomic inducing activity, i.e. unique dual-mode action.

Our dual-acting RAR- modulating drugs have major impact upon cell survival and gene regulation, have anti-inflammatory effects, are neuroprotective, promote neuroplasticity and neurite outgrowth, support neuromuscular function, reduce excitotoxicity and stress granules and have senolytic effects.

Novel therapeutic for Alzheimer’s, Parkinson’s, Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Frontotemporal Dementia, new drugs

Our lead drug – NVG0645

  • NVG0645 protects neurons against excitotoxic damage, while increasing the formation of synapses.
  • NVG0645 reduces stress granules and reduces oxidative stress which otherwise results neuronal cell death.
  • NVG0645 has also been recently shown to improve behaviour and neuronal survival in a Parkinson’s disease model.
  • Current efficacy studies underway in ALS and MS models, and longer term Parkinson’s disease models.
  • NVG0645 has exceptional drug-like properties, good bioavailability, selectivity and safety profile.
  • NVG0645 has good solubility while retaining amphiphilic properties which results in exceptional blood-brain barrier penetration and CNS exposure.

Our technology