Biomedical Catalyst – Drug product production, clinical support studies, and phase 1 trial of a new MS drug

Lead Research Organisation: University College London

Abstract

We have invented a new, first in class, drug for the treatment of multiple sclerosis (MS). This drug has the potential to become the standard of care for the treatment of muscle spasticity in MS with fewer and less severe side effects for patients than current drugs. In particular earlier treatment should be achievable, countering the onset of disability and allowing a normal life to be sustained for longer. This drug has now passed pre-clinical safety studies including two species 28 day toxicology.
We are now actively seeking additional funds to enable the clinical support studies, GMP manufacture, formulation, encapsulation, and phase 1 studies on this drug. The first phase 1 study will be a SAD/MAD safety study in volunteers. Part funding has already been secured from the Wellcome Trust, and UCL business. The first volunteer is expected to be dosed in Q3 2013.

Technical Summary

We have invented a new, first in class, drug for the treatment of multiple sclerosis (MS). This drug has the potential to become the standard of care for the treatment of muscle spasticity in MS with fewer and less severe side effects for patients than current drugs. In particular earlier treatment should be achievable, countering the onset of disability and allowing a normal life to be sustained for longer. This drug has now passed pre-clinical safety studies including two species 28 day toxicology.
We are now actively seeking additional funds to enable the clinical support studies, GMP manufacture, formulation, encapsulation, and phase 1 studies on this drug. The first phase 1 study will be a SAD/MAD safety study in volunteers. Part funding has already been secured from the Wellcome Trust, and UCL business. The first volunteer is expected to be dosed in Q3 2013.
 
Description CHARACTERISATION OF THE MECHANISM OF A POTENTIAL NEW GLAUCOMA DRUG
Amount £168,765 (GBP)
Funding ID 1858/1859 
Organisation Fight for Sight 
Sector Charity/Non Profit
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 09/2016 
End 09/2019
 
Description Detect and treat hearing loss and tinnitus
Amount £96,096 (GBP)
Funding ID CDE100571 
Organisation Defence Science & Technology Laboratory (DSTL) 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 07/2016 
End 12/2017
 
Description Industry CASE studentship competition
Amount £120,165 (GBP)
Organisation MRC-UK 
Sector Public
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2016 
End 09/2020
 
Description The Development Of Selective Ion Channel Activators For Neuroprotection
Amount $551,726 (USD)
Funding ID FF-1602-07939 
Organisation National Multiple Sclerosis Society 
Sector Charity/Non Profit
Country United States of America
Start 09/2016 
End 10/2018
 
Title Candidate drug for spasticity in Multiple Sclerosis 
Description We have identified novel and extremely potent activators of a specific potassium channel that could prove useful as pharmacological tools and possibly as drugs. These agents have been protected by a new patent application (see IP section). 
Type Of Material Technology assay or reagent 
Provided To Others? Yes  
Impact This funding has enabled a Phase I trial in healthy volunteers to be completed successfully. A phase II trial in people with MS is now underway. 
URL http://www.canbex.co.uk/
 
Title RNAseq data for mouse model of multiple sclerosis 
Description We have generated a new dataset of RNAseq data for the mouse model of spasticity (EAE) in multiple sclerosis. This dataset shows the changes in gene expression in going from normal to EAE mice and provides insight into the changes that can also go on in the human disease. This raw sequencing data was uploaded to the Gene Expression Omnibus (GEO) with accession number GSE78996. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact The RNAseq data is rationalised and discussed in the publication. 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE78996
 
Description Assays of test materials in sympathetic neurotransmission models. 
Organisation University of Aberdeen
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Supply of test materials and expertise.
Collaborator Contribution Assays of test materials in sympathetic neurotransmission models.
Impact Identification of small molecules with potent activity in this assay.
Start Year 2014
 
Description Effects of test drugs on TASK currents from transiently expressed channels. 
Organisation University of Kent
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Supply of research materials and expertise.
Collaborator Contribution Study of the effects of drugs on TASK currents from transiently expressed channels.
Impact Too early.
Start Year 2014
 
Description Excitatory or inhibitory transmission at single synapses 
Organisation University of Reading
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Supply of research materials and expertise.
Collaborator Contribution Expert electrophysiology studies on excitatory and inhibitory transmission at single synapses.
Impact Too early.
Start Year 2014
 
Description Investigation of T-type calcium channel bioactivity. 
Organisation National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS)
Country France, French Republic 
Sector Public 
PI Contribution Supply of research materials and expertise.
Collaborator Contribution Investigation of T-type calcium channel bioactivity of test compounds.
Impact Too early.
Start Year 2014
 
Description Investigation of VSN16R in Fragile X syndrome models, collaboration with FRAXA 
Organisation FRAXA Research Foundation
Country United States of America 
Sector Charity/Non Profit 
PI Contribution We initiated a collaboration with FRAXA (https://www.fraxa.org/ ) a foundation committed to finding treatments for Fragile X syndrome. Fragile X is the major genetic condition leading to profound learning disabilities in adults. It affects approximately 1 in 4000 males and 1 in 6000 females. We arranged testing of our candidate MS drug VSN16R in genetic models of the disease in their contracting laboratory in Santiago, Chile. The molecule showed highly promising activity giving responses in 4/5 behavioral readouts.
Collaborator Contribution FRAXA is a foundation and is solely committed to finding a cure for fragile X. FRAXA organise resources and funding including testing of candidate drugs in experimental (genetic) models of disease.
Impact 1 Testing of one molecule in the genetic (FMRP knockout) model of fragile X.
Start Year 2015
 
Description Investigation of test drugs in glaucoma. 
Organisation Imperial College London (ICL)
Department Imperial College Trust
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Charity/Non Profit 
PI Contribution Supply of test materials and expertise.
Collaborator Contribution Investigation of test drugs in models of glaucoma.
Impact Multi-disciplinary. Chemistry. Opthalmology in vivo glaucoma models. Pharmacology ex-vivo outflow models. Immunology, in vivo optic neuritis models.
Start Year 2014
 
Description Investigation of test drugs in glaucoma. 
Organisation University College London (UCL)
Department Institute of Ophthalmology UCL
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Supply of test materials and expertise.
Collaborator Contribution Investigation of test drugs in models of glaucoma.
Impact Multi-disciplinary. Chemistry. Opthalmology in vivo glaucoma models. Pharmacology ex-vivo outflow models. Immunology, in vivo optic neuritis models.
Start Year 2014
 
Description Investigation of test materials on functional signalling in mesenteric arteries. 
Organisation St George's University of London
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution Supply of research materials and expertise.
Collaborator Contribution Functional studies on potassium channel signalling in mesenteric arteries.
Impact Too early.
Start Year 2014
 
Description Patch clamp studies on endothelial cell ion channel signalling. 
Organisation Medical University of Graz
Country Austria, Republic of 
Sector Academic/University 
PI Contribution Supplied research tools and expertise.
Collaborator Contribution Provided expertise in patch clamp electrophysiology on endothelial cell systems.
Impact Provided pivotal data in the identification of the mode of action of our new Multiple sclerosis drug. This outcome later confirmed by many additional studies. The mode of action identification was key in enabling the licensing of this drug to the Ipsen Pharmaceutical company.
Start Year 2014
 
Title BENZAMIDE DERIVATIVES USEFUL IN THE TREATMENT OF MUSCULAR DISORDERSAND PAIN AND FOR CONTROLLING SPASTICITY AND TREMORS 
Description A composition of matter patent on new analogues with activity against spasticity. These molecules may be useful new drugs for the treatment of a wide range of conditions such as MS related spasticity, fragile X and epilepsy. 
IP Reference WO2015082938(A1) 
Protection Patent application published
Year Protection Granted 2015
Licensed No
Impact Too early.
 
Title BKCa Channel activator for treating muscular disorder 
Description The present invention relates to BKCa activators for use in the treatment of a muscular disorder, or for controlling spasticity or tremors, for example, spasticity in MS. 
IP Reference WO2016128772 (A1) 
Protection Patent application published
Year Protection Granted
Licensed Yes
Impact None so far.
 
Title CRYSTALLINE FORM OF VSN16 
Description The present invention relates to a compound of formula (I) in crystalline form, wherein said compound is in the form of the free base or a pharmaceutically acceptable salt thereof, or a solvate of the free base or salt form thereof.The invention also relates to a pharmaceutical composition containing said crystalline form as an active ingredient, and use thereof in the prevention or treatment of disease. The invention further relates to a process for preparing the crystalline form. 
IP Reference WO2014111720 
Protection Patent application published
Year Protection Granted 2014
Licensed Commercial In Confidence
Impact Enabled phase I study conducted in the UK.
 
Title Compounds for treating disorders associated with BK channel modulation 
Description Compounds of a specified general formula for the treatment of disorders associated with BK channel modulation. 
IP Reference WO2016128771 (A1) 
Protection Patent application published
Year Protection Granted
Licensed Yes
Impact None yet.
 
Title MODULATORS OF CANNABINOID RECEPTORS 
Description Composition of matter patent for our MS drug. 
IP Reference WO05080316 
Protection Patent granted
Year Protection Granted
Licensed Commercial In Confidence
Impact Phase I clinical study in the UK completed. phase II clinical study in the UK ongoing, expected to complete Q4 2016.
 
Title PROCESS FOR PREPARING CARBOXYLIC ACID AMIDES USEFUL IN THE TREATMENT OF MUSCULAR DISORDERS 
Description A process patent on the manufacture of our new MS drug, this patent protects the main process route and variations thereof, it is granted in Europe 
IP Reference WO2010116116 
Protection Patent granted
Year Protection Granted 2010
Licensed Commercial In Confidence
Impact Phase I trial conducted in the UK.
 
Title VSN16R 
Description New investigational drug for MS related spasticity. Phase II study. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2017
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Trial still ongoing. Readout expected in 2017. 
URL https://clinicaltrials.gov/ct2/show/NCT02542787?term=VSN16R&rank=1
 
Title VSN16R 
Description We have invented a new treatment for spasticity in multiple sclerosis and have recently (June 2014) completed the phase I studies and reproductive toxicology for this drug. This drug has the potential to become the standard of care for the treatment of muscle spasticity in MS with fewer and less severe side effects for patients than current drugs. In particular earlier treatment should be achievable, countering the onset of disability and allowing a normal life to be sustained for longer. We are now actively seeking additional funds to enable the clinical proof of concept phase IIa study in MS patients. This study will be conducted in the University College Hospital (UCH), London, with first recruitment expected in 2015. This drug is now ready for a phase II clinical study. The most recent principle source of funding for this development was the TSB grant (this project submission). 
Type Therapeutic Intervention - Drug
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2014
Development Status Under active development/distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier QLON-2013-VSN16R-001
Impact Wide use of mostly UK based clinical and pre-clinical contract research organisations, direct spend of the grant money in these organisations stimulating economic activity. Building research expertise in UK universities. Building clinical expertise in the treatment of MS. 
URL http://www.canbex.co.uk/
 
Company Name Canbex Therapeutics Ltd 
Description Canbex Therapeutics is a spin-out company from University College London. Canbex is a capital-efficient, single-asset, low-burn vehicle that was established expressly to develop the VSN compound series. In addition to its pioneering scientific founders, Canbex has assembled a highly skilled and experienced team of managers and advisors. Development activities are carried out through professionally managed outsourcing to well-established CROs and CMOs. 
Year Established 2004 
Impact Canbex is building on years of work by pioneering scientists and leading clinicians, who set out to address a medical need in multiple sclerosis that is poorly served by existing therapies. Spasticity is among the most painful, damaging and debilitating symptoms of MS. Spasticity is characterized by sudden and uncontrollable movements of limb and torso musculature. Current drug treatments have a high level of undesirable side effects, and many patients are treated with palliative measures alone, such as pads or slings, or confined to a wheelchair. The company's lead compound VSN16R, discovered in the labs of its scientific founders, is a novel orally active small molecule compound that was designed to be substantially more tolerable than existing anti-spastic agents. In tests to date, VSN16R does not cause the flaccidity, sedation or other side-effects that are major disadvantages of other agents. A phase II study in patients is ongoing.
Website http://www.canbex.co.uk/index.html
 
Description BLOG 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact There are up to 250,000 visits to the site each month and about 7,000-9,000 a day.
The audience is clinicians , basic scientists, pharmaceutical industry, charities, people with disease, regulators

We got first line drug approval for an MS drug. Did our campaign on the blog contribute, who knows?
We got clinical trials funded for a number of MS drugs. Did our campaign and post influence this, who knows?
We champion elimination of bad laboratory practice in relation to animal experimentation in MS. Does this influence practice who knows?

Hard to tell
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
URL http://multiple-sclerosis-research.blogspot.co.uk/
 
Description Cafe Scientific Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Gave a lecture in a Cafe Scientific format for the Fight for Sight charity detailing some of our work on glaucoma. This was held in the Silver Cup pub in Harpenden.
Year(s) Of Engagement Activity 2016
URL https://www.eventbrite.co.uk/e/new-drugs-for-glaucoma-its-all-about-the-electricity-tickets-28833426...
 
Description Research Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact Full day of interaction with people with MS and their families.

The talk has been uploaded to Youtube ejs6r95NZhA linked from our Research Website.. (http://multiple-sclerosis-research.blogspot.com/2014/09/ms-day-whats-new-in-lab.html). http://www.MS-res.org. This site for people with MS attracts 1 60,000 visits a month.
Year(s) Of Engagement Activity 2013,2014
URL http://multiple-sclerosis-research.blogspot.com/2014/09/ms-day-whats-new-in-lab.html
 
Description School visit by year 12 pupils 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact This was an event for y12 science students at a local school in Hertfordshire (Stanborough Academy). The objective was to give the students exposure to practical methods in chemistry, biology and physics. The students crystallised a protein in the lab and then conducted an X-ray experiment to show how protein structures are determined. Feedback from this day was very positive. This event was repeated in 2017.
Year(s) Of Engagement Activity 2016,2017
URL http://www.stanborough.herts.sch.uk/news_and_events_post16_chemistry_day_at_ucl_jan2016_.html