Kv1.1

LONDON--(BUSINESS WIRE)-- EpilepsyGTx, a biotechnology company focused on research and development of cutting-edge gene therapies to treat focal refractory epilepsy, today announced it has raised a total of $10 million in seed funding. The financing was led by the UCL Technology Fund, with participation from Health Technology Holding. The funds raised will be used to complete the preclinical studies for EpilepsyGTx’ lead gene therapy program EPY201, and to prepare a groundbreaking first-in-human, Phase 1/2a clinical study with EPY201 in focal refractory epilepsy. "This funding is a clear vote of confidence from our investors in our vision, the world-class science of the UCL Queen Square Institute of Neurology, and the transformative potential of EPY201 in focal refractory epilepsy. Our mission is to make patients with focal refractory epilepsy seizure-free," said Nicolas Koebel, chief executive officer. Simon Goldman, Partner at AlbionVC, manager of the UCL Technology Fund and EpilepsyGTx Board member, added, “EpilepsyGTx has an objectively world-leading pipeline of genetic therapies for a common and damaging neurological disorder with few treatment options, developed by a globally-renowned clinical, scientific and translational team at the UCL Queen Square Institute of Neurology. We are enormously pleased to have Nicolas Koebel on board as CEO, with a track record of building exceptional global biotech companies from inception to commercial launch. We are excited that this industry-leading team now has the opportunity to translate medicines that have the potential to change the lives of patients with epilepsy and other CNS disorders.” EpilepsyGTx is a spinout company set up with the support of UCL’s commercialisation company UCL Business Ltd (UCLB). Caitriona O’Rourke, UCLB’s Business Manager for EpilepsyGTx commented: “We have been delighted to support Nicolas and his team on their commercialisation journey, and it’s terrific to see them reach this major funding milestone. We are excited by the commercial potential of this technology and its possible contribution to improve the lives of people with focal refractory epilepsy.” Michele Gaiotto, Managing Director at Health Technology Holding, stated, “We were highly impressed by the scientific strategy of the company and the credentials of the leadership team. The targeted, highly localized delivery of gene therapy is the right solution to treat focal refractory epilepsy, and is poised to make an enormous difference in the lives of millions of patients.” About EpilepsyGTx At EpilepsyGTx our mission is to make patients with focal refractory epilepsy seizure-free. We are developing a portfolio of cutting-edge gene therapies which are based on pioneering research from the UCL Queen Square Institute of Neurology. For more information, please visit: About focal refractory epilepsy Focal epilepsy describes a group of disorders in which patients experience seizures that arise from a specific part of the brain. If seizures persist despite trials of at least two tolerated and appropriately chosen antiseizure medicines, epilepsy is deemed refractory. Focal refractory epilepsy (or FRE) affects an estimated 2 million prevalent patients in the United States, the United Kingdom and the European Union, combined. About EPY201 EPY201 is an investigational gene therapy targeting focal refractory epilepsy. EPY201 or AAV9-CAMK2A-EKC uses an AAV9 capsid, an engineered Kv1.1 potassium channel (or “EKC”) and a CAMK2A promoter. EPY201 is delivered directly to the target seizure focus (that is, the part of the brain causing seizures) by intraparenchymal administration. About UCL Technology Fund The UCL Technology Fund exists to help solve the world’s most pressing problems: healthy planet, healthy people and healthy work. It helps UCL innovators across the Physical and Life Sciences scale globally. The Fund supports UCL in achieving the full potential of innovations that have prospects for outstanding societal and market impact, right through the development journey from initial proof of concept to practical commercial application. The Fund is managed by AlbionVC in collaboration with UCL Business. For further information please visit: View source version on businesswire.com: Contacts For enquiries, please contact: communications@epilepsygtx.com Phone: +44 7717 801 246 Source: EpilepsyGTx View this news release online at:

Researchers have discovered that extracts from plants used by the Kwakwaka'wakw First Nations peoples in their traditional botanical medicine practices are able to rescue the function of ion channel proteins carrying mutations that cause human Episodic Ataxia. A University of California, Irvine-led team of researchers have discovered that extracts from plants used by the Kwakwaka'wakw First Nations peoples in their traditional botanical medicine practices are able to rescue the function of ion channel proteins carrying mutations that cause human Episodic Ataxia. The study, "Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain" was published in June in Nature Communications. "Episodic Ataxia 1 (EA1) is a movement disorder caused by inherited mutations in the human KCNA1 gene, which encodes Kv1.1, a voltage-gated potassium channel essential for normal function of the human nervous system," said Geoffrey W. Abbott, PhD, vice dean of basic science research and professor in the Department of Physiology & Biophysics at the UCI School of Medicine. "We found that extracts of stinging nettle, bladderwrack kelp and Pacific ninebark can all correct function of the mutation- carrying proteins causing a specific form of ataxia." Abbott's research team also found that two compounds contained in these plants, tannic acid and gallic acid, are each able to rescue activity of the EA1-linked mutation-carrying ion channel proteins. "The plant compounds are the first known compounds to rescue the activity of Kv1.1 carrying EA1-linked loss-of-function sequence variants," said Abbott. "Gallic acid in particular is of therapeutic interest because it is already available over the counter as a nutritional supplement and is very well tolerated in toxicity studies." Individuals with ataxia exhibit abnormal gait, slurring, eye movement abnormalities, difficulties with balance and walking, tremors, and disruption of fine motor skills. "These mutations can cause other disorders, including epilepsy, and so there is therapeutic potential for those conditions as well, " said Abbott. "We have discovered that where modern synthetic drug development techniques have failed to produce a drug that directly rescues EA1-linked mutant channel function, traditional botanical medicine developed by North American First Nation peoples has succeeded." Further research is now needed to explore the efficacy of the plant-derived compounds in preclinical and clinical studies. "We have made a mouse model of a relatively severe form of human EA1 so that we can test the efficacy and safety of gallic acid and also whole plant extracts," said Abbott. "If the preclinical studies go well, our goal is to move to clinical trials. Concurrently, we are synthesizing and testing other plant compounds and derivatives to discover other compounds with potential for treating EA1 and related disorders." There are several forms of ataxia, which is an umbrella term describing loss of coordination or balance. Together with Abbott, the research team comprised Drs. Rian Manville, J. Alfredo Freites, Doug Tobias (UC Irvine) and Richard Sidlow (Valley Children's Hospital). This work was supported by the National Institutes of Health and the National Institute of General Medical Sciences.

A new treatment for neurological and psychiatric diseases, that works by reducing the excitability of overactive brain cells, has been developed. A new treatment for neurological and psychiatric diseases, that works by reducing the excitability of overactive brain cells, has been developed by UCL researchers. Many brain diseases, such as epilepsy, are caused by excessive activity of a small number of brain cells. These conditions often don't respond well to drug treatment, mainly because drugs affect the whole brain. Whilst genetic therapies could be a promising way to treat these conditions, current methods do not distinguish between overactive and normal brain cells. However, the new treatment, outlined in Science and tested in mice, uses a technique that only alters overactive cells and spares those that are acting normally. Corresponding author, Dr Gabriele Lignani (UCL Queen Square Institute of Neurology), said: "We invented a gene therapy that switches on only in overactive cells, and switches itself off if activity returns to normal. "We harnessed the ability of certain DNA sequences to control gene expression in response to metabolic signals. By re-directing this activity-sensing mechanism to drive the production of molecules that stop brain cells from firing, we showed that epileptic seizures can be suppressed." To create the gene therapy, the team screened several genes known to 'switch on' in response to stimulation, and coupled their promoters (DNA sequences that determine whether the DNA is copied to RNA) to potassium channels chosen for their ability to reduce the firing of nerve cells. The promoter-potassium channel combinations were tested both in mice and in miniature brain-like structures grown in dishes -- which were created using skin-derived human stem cells. They found that the immediate early gene cfos promoter, in combination with the KCNA1 potassiumchannel gene, proved to be highly effective in calming neuronal excitability following an induced seizure, and also in suppressing spontaneous seizures -- without having any negative effects on cognition. The new treatment was more effective than previous gene therapies or anti-seizure drugs tested in the same model, with around an 80% reduction in spontaneous seizures in epileptic mice. Researchers say, the gene therapy could eventually -- in theory -- also be used for other disorders where some brain cells are overactive, such as Parkinson's. Co-corresponding author Professor Dimitri Kullmann (UCL Queen Square Institute of Neurology) said: "Our findings indicate that the activity of brain cells can be normalised, and that this approach can be used to treat important neuropsychiatric diseases that do not always respond to medication. "The gene therapy is self-regulated and can therefore be used without deciding a priori which brain cells need to be targeted. "Importantly, it could in principle, be extended to many other disorders such as Parkinson's disease, schizophrenia and pain disorders, where some brain circuits are overactive." The study was funded by Epilepsy Research UK, with contributions from the MRC and Wellcome. UCL academics also received funding from a TAS award (TRO) and from UCL Technology funds.