About

Find out more about our team

Background

For several years, we have been modelling and designing synthetic retinoids in order to study their biological effects acting through retinoid signalling pathways and affecting cellular development.

Through BBSRC-funded research we took these studies further to design novel synthetic retinoids as potential neurodegenerative disease drugs. We synthesised a diverse library of new structures and examined their biological activities through screening in a range of bioassays.

This highlighted that some compounds showed both genomic and non-genomic effects which led us to the discovery of novel “dual acting” compounds, i.e. which could be potential drugs for tackling neurodegenerative diseases.

Our lead compounds show particularly good pharmacokinetic properties, high potency and CNS exposure. Indeed, these RARM compounds show a range of key biological characteristics, including increased cell survival, anti-inflammatory and neuroprotective effects, an ability to promote neuroplasticity and neurite outgrowth, support neuromuscular function, control gene regulation, reduce stress granules and potentially senolytic effects.

These are all important for multi-modal drugs that have the potential to treat a range of neurodegenerative diseases. In parallel, we are examining the mechanism of action of this class of compounds and taking our lead through preclinical studies and into more complex, disease-relevant models.

Image Descriptions

  1. Adult mouse lumber spinal cord section immunostained for the retinoic acid synthesizing enzyme RALDH2 showing expression in motorneurons (green).
  2. SH-SY5Y neuroblastoma cell line labelled over 72 hours with DC324 fluorescent RAR ligand.
  3. SH-SY5Y neuroblastoma cell line labelled over 72 hours with DC324 fluorescent RAR ligand.
  4. SH-SY5Y neuroblastoma cell line labelled with LC3B (autophagy marker) together with DC360 fluorescent RAR ligand over 72 hours.
  5. Adult mouse lumber spinal cord section immunostained for the retinoic acid synthesizing enzyme RALDH2 showing expression in motorneurons (green) with bisbenzimide (blue) stained nuclei.
  6. Adult mouse lumber spinal cord section immunostained for the retinoic acid synthesizing enzyme RALDH2 showing expression in a single motorneuron with bisbenzimide stained nuclei.

Core Development Team

The core development team have been working together as part of a close scientific collaboration for a number of years.

The present team started working together more closely and upon a focussed RCUK funded project involving retinoid signalling from 2016 via a BBSRC FoF project which resulted in a number exciting scientific results and importantly, the identification of a lead drug candidate for ALS in 2018.

This compound has continued to show excellent PK/ADME data since then and therefore, we setup a joint Durham and Aberdeen University spin-out company to license the relevant patent into, and to act a commercial development vehicle by which to drive the drug development programme forwards and raise the necessary investment required for the next stages.

Prof Andy Whiting
& Dr Ehmke Pohl
Durham University, Chemistry Department

Combining expertise in molecular modelling, docking and design, synthetic and medicinal chemistry making fluorescent analogues of the lead candidate and photoaffinity-enabled analogues, structural and biomolecular biology, RAR-drug binding.

Prof Peter McCaffery
& Dr Iain Greig
Aberdeen University, Medical Sciences

In vitro cellular biology and cell-based models, examining localisation, mode of action and target identification, PK/ADMET properties and planning toxicity and clinical trials.

Dr Alex Easton
& Dr Paul Chazot
Durham University, Psychology & Biosciences

In vivo animal studies in both wild-type and ALS/FTD animal models (principally mice), uniquely combining biological and behavioural effects, and pathological effects of drug versus disease in a range of tissues, as well as key neural (brain and spinal) tissues.

Executive Leadership Team

James Bromhead

Chairman

 

30+ years of financing SME’s, extensive start up experience in both tech and investment banking, ex-chairman Immersive Labs, Partner at Anticus.

Prof Andy Whiting

Chief Executive Officer

 

Serial organic chemical inventor, with over 35 years experience, Professor of Organic Chemistry at Durham University, experienced university spinout founder and CTO of LightOx Ltd.

Dr Max Noble

NED

 

Founder and CEO of Visformatics, expert in healthcare economics and disease decision algorithms, with over 20 years experience in the pharma industries and entrepreneur.

Dimitri Dimitriou

Strategic Advisor & Board Observer

 

Over 30 years in the pharmaceuticals industry, CEO of ImmuPharma plc, a drug discovery & development company, and founder of DyoDelta Biosciences.

Leadership Team

Prof Andy Whiting

Chief Executive Officer

 

Andy is Professor in Organic Chemistry at Durham University and has published over 200 peer reviewed papers, as well as a number of patents and reviews.

His area of expertise is organic synthesis, synthetic methodology and molecular design, as well as working on asymmetric synthesis, catalysis and natural product synthesis. He has collaborated widely with biologists, especially working on the control of cellular development, which led to the design and use of synthetic retinoids to examine retinoic acid signalling pathways. These compounds are being developed for applications as potential neurodegenerative disease treatments, with particular emphasis upon ALS through Nevrargenics.

He has also developed fluorescent imaging analogues of the synthetic retinoids being applied for cellular imaging and phototherapeutic applications through LightOx Ltd, for whom he is  CTO.

Prof Ehmke Pohl

Chief Scientific Officer

 

Ehmke is a Reader in Structural Biology in a joint appointment between the Chemistry Department and the Department for Biosciences.

In addition, he is Co-Director of the Biophysical Sciences Institute (BSI) at Durham University. He is an expert in computational, biophysical and structural methods to investigate protein-ligand interactions.

His group has developed high-throughput methods for drug discovery that have been commercialised and determined crystal structures of a large range of protein and protein-ligand complexes as part of structure-based drug design projects.

He has published over 125 papers in chemistry, biosciences and on the interface between physical and medical  sciences.

Dr Iain Greig

Chief Technology Officer

 

Iain is a Reader in Medicinal Chemistry at the University of Aberdeen and Visiting Professor at the University of Toronto. He has a broad scientific background, including a PhD in physical organic chemistry from the University of St Andrews, postdoctoral experience in biophysics at Cornell University and an MSc in clinical pharmacology. He has worked as a medicinal chemist in biomedical research institutions for over 25 years and is an expert in early-stage drug discovery, project management and commercialization in an academic setting.

He invented, developed and licensed (to J&J) a first-in-class drug for the treatment of rheumatoid arthritis. At >$350 million this was the largest licensing deal signed in Europe in 2014, and the drug has now successfully met its Phase IIa primary objectives. His current preclinical drug discovery programmes include first-in-class treatments for multiple sclerosis and schizophrenia. He has authored more than 20 patent applications, of which 9 have now been granted in all major markets, and has previously spun out two companies (OsteoRx Ltd – rheumatoid arthritis, currently subject to an option with JNJ following successful Phase IIa studies) and Signal Pharma Ltd (programmes for diastolic heart failure and for neuropathic pain).

He has also licensed drugs for the treatment of multiple sclerosis – details currently subject to confidentiality – and is currently developing a funding package to commercialise drugs for the treatment of schizophrenia and bipolar disorder.

Prof Peter McCaffery

Non Executive Director

 

Peter is Professor of Translational Neuroscience at the University of Aberdeen, Scotland. He has published over 100 articles on the function of retinoic acid in the developing, and adult nervous system, and has extensive expertise in methods to study retinoic acid; how it is controlled in the brain; and how it controls the brain.

His work when in the Department of Psychiatry at Harvard Medical School, showed the importance of the enzymes regulating retinoic acid concentrations in nervous tissue.  His later work demonstrated the importance of retinoic acid in the hypothalamus, moderating body homeostasis, and hippocampus, mediating learning and memory.

His work over the last several years has focused on the retinoic acid receptors (RARs) acting via genomic/non-genomic mechanisms to protect against neurodegenerative disease, with a particular emphasis through Nevrargenics, on ALS.

Key Partners
Nevrargenics uses Definition IP (UK) as IP advisors and has worldwide, exclusive licenses to the previous research in this field, and has patents to cover all existing species and applications.
Further to this Nevrargenics has taken a strategic approach to further extend its IP portfolio to cover new compounds, applications and therapeutic targets.

Key Papers

A Bioluminescence Reporter Assay for Retinoic Acid Controlof Translation of the GluR1 Subunit of the AMPA Glutamate Receptor

T. Khatib, B. Müller, A. Whiting, D. Chisholm, C. Redfern and P. McCaffery, Mol. Neurobiol., 2019,

DOI: 10.1007/s12035-019-1571-9

Genomic and non-genomic pathways areboth crucial for peak induction of neuriteoutgrowth by retinoids

T. Khatib, P. Marini, S. Nunna, D. R. Chisholm, A. Whiting, C. Redfern, I. Greig and P. McCaffery, Cell Commun. Signal., 2019,

DOI: 10.1186/s12964-019-0352-4

Novel Fluorescence Competition Assay for Retinoic Acid BindingProteins

C. Tomlinson, D. R. Chisholm, R. Valentine, A. Whiting and E. Pohl, ACS Med. Chem. Lett., 2018, 9, 1297-1300

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