LC-002 Migraine Treatment

Overview

A novel calcitonin gene-related peptide antagonist targeting migraine

LC-002 is a receptor blocker targeting calcitonin gene-related peptide (CGRP), a neuropeptide hormone found in the nervous system.  Research shows a link between heightened levels of CGRP and migraine. Activation of the CGRP receptors causes migraine. LC-002 is one of an emerging class of compounds that block the actions of CGRP, either antibodies or potentially longer-acting compounds that block CGRP receptors. It is currently in pre-clinical trials underway at the University of Auckland.

Migraine is a significant disabling condition with an unmet need for effective medicines. The World Health Organisation compares severe migraine to dementia, quadriplegia and psychosis in terms of debilitation. There are safety and tolerability issues with current treatments as they are only partially effective and require frequent administration. Patients with other conditions such as depression and hypertension have their treatment options further restricted.

Scientific Advisory Board Members

Professor Debbie Hay

Professor Debbie Hay

Professor of Biochemistry and Pharmacology at the University of Auckland and the Acting Head of the School of Biological Sciences.
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Distinguished Prof. Dame Margaret Brimble

Distinguished Prof. Dame Margaret Brimble

Director of Medicinal Chemistry at the University of Auckland, and Chair and Director of Medicinal Chemistry.
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Dr John Villiger

Dr John Villiger

Dr John Villiger is an Honorary Academic at the University of Auckland and an experienced pharmaceutical product development executive and co-founded The Medicines Company.
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Dr Barry Snow

Dr Barry Snow

Dr Barry Snow is a senior neurologist at Auckland City Hospital and Director of Adult Medical Services at the ADHB. He is Chair of the Neurological Foundation Council and sits on the board of Mercy Hospice.
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Professor Debbie Hay

Professor Debbie Hay

Professor of Biochemistry and Pharmacology at the University of Auckland and the Acting Head of the School of Biological Sciences.
Read Bio +
Distinguished Prof. Dame Margaret Brimble

Distinguished Prof. Dame Margaret Brimble

Director of Medicinal Chemistry at the University of Auckland, and Chair and Director of Medicinal Chemistry.
Read Bio +
Dr John Villiger

Dr John Villiger

Dr John Villiger is an Honorary Academic at the University of Auckland and an experienced pharmaceutical product development executive and co-founded The Medicines Company.
Read Bio +
Dr Barry Snow

Dr Barry Snow

Dr Barry Snow is a senior neurologist at Auckland City Hospital and Director of Adult Medical Services at the ADHB. He is Chair of the Neurological Foundation Council and sits on the board of Mercy Hospice.
Read Bio +
Professor Debbie Hay

Professor Debbie Hay

Professor of Biochemistry and Pharmacology at the University of Auckland and the Acting Head of the School of Biological Sciences.

Professor of Biochemistry and Pharmacology at the University of Auckland and the Acting Head of the School of Biological Sciences.

Her research focuses on G protein-coupled receptors (GPCRs) and aims to contribute to the development of medicines to treat migraine, cancer, lymphatic insufficiency, cardiovascular disease, obesity and diabetes. Dr Hay is also interested in receptor nomenclature in association with the International Union of Pharmacology.

Distinguished Prof. Dame Margaret Brimble

Distinguished Prof. Dame Margaret Brimble

Director of Medicinal Chemistry at the University of Auckland, and Chair and Director of Medicinal Chemistry.

Director of Medicinal Chemistry at the University of Auckland, and Chair and Director of Medicinal Chemistry.

Distinguished Professor Dame Margaret Brimble has become the first New Zealand woman to be inducted into the American Chemical Society Division of Medicinal Chemistry Hall of Fame.

Professor Brimble’s research sits at the interface of chemistry and medicine, recognition for her achievements include being named Dame Companion in New Zealand’s 2019 New Year’s Honours list, her election as a Fellow of the Royal Society of London and winning the 2019 KiwiNet Supreme Award for commercialisation.

Dr John Villiger

Dr John Villiger

Dr John Villiger is an Honorary Academic at the University of Auckland and an experienced pharmaceutical product development executive and co-founded The Medicines Company.

Dr John Villiger is an Honorary Academic at the University of Auckland and an experienced pharmaceutical product development executive and co-founded The Medicines Company.

Dr Villiger is an experienced pharmaceutical product development executive, who currently consults to various organisations. Notably, Dr Villiger is on the University of Auckland Centre for Brain Research Advisory Board and consults to the University in drug development.

Dr Barry Snow

Dr Barry Snow

Dr Barry Snow is a senior neurologist at Auckland City Hospital and Director of Adult Medical Services at the ADHB. He is Chair of the Neurological Foundation Council and sits on the board of Mercy Hospice.

Dr Barry Snow is a senior neurologist at Auckland City Hospital and Director of Adult Medical Services at the ADHB. He is Chair of the Neurological Foundation Council and sits on the board of Mercy Hospice. 

Dr Snow has extensive experience in general neurology and specific expertise in Parkinson’s disease and movement disorders. He has expertise in botulinum toxin injections for movement disorders and for chronic migraine.

After completing his general neurology training in Auckland, Dr Snow was awarded the Neurological Foundation Chapman Fellowship which allowed him to take up a research fellowship at the University of British Colombia, Vancouver.

Development to Date

Calcitonin gene-related peptide (CGRP) is a neuropeptide hormone found throughout the central and peripheral nervous system. Research has identified a link between higher levels of CGRP and migraine. CGRP receptors are located within pain signalling pathways, intracranial arteries and mast cells. Activation of these receptors causes migraine. 

There is an emerging class of compounds that block the actions of CGRP, either antibodies or potentially longer-acting compounds that block CGRP receptors. Current receptor blockers in development with global pharmaceutical companies may have issues of side effects or toxicity.  It may be possible to avoid such issues by using novel peptide analogues of the CGRP structure that have been modified with a fatty acid group in order to increase half life in vivo. These CGRP analogues present a range of new opportunities in migraine treatment.

Pre clinical studies of one such innovative compound, LC-002, are under way at the at the University of Auckland under lead investigators, Professor Debbie Hay and Associate Professor Kerry Loomes. The University has global patent protection for LC-002 which has been synthesised by Distinguished Professor Margaret Brimble. LC-002 has been shown to inhibit capsaicin-induced vasodilation.

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Future Development

Professor Debbie Hay and her team are completing pre-clinical characterisation of LC-002. In vivo activity is currently in progress. Once these studies are complete a Phase I clinical trial is the next step. The trial would aim to establish safety and efficacy using a single ascending dose of LC-002 and would likely be conducted in Auckland by the Auckland Clinical Studies Trust.  The study would involve three groups of eight participants each (six active and two placebo).  We now anticipate initiating the Phase I study in 2021. In this study we will be able to measure blood levels to support once daily dosing, giving an almost instant measure of success.

Positive clinical efficacy data would be used to out license LC-002 to a global pharmaceutical company to fully commercialise it. We have already engaged with interested global parties and have discussed potential deal structures.

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