LP-003 Anti-Obesity

Overview

Long-acting Pramlintide, a peptide drug that reduces caloric intake targeting obesity

“Pramlintide is currently marketed for the treatment of diabetes. In patients with diabetes, pramlintide is known to cause weight loss. By structural modification, we are developing a drug to treat morbid obesity. The development of therapies for the treatment of obesity has been historically controversial. Nevertheless, there is a huge need for treatment options. We are excited by the preclinical activity to date of our lead compound that has been generated using a novel chemistry platform.”  - Professor Debbie Hay and Distinguished Professor Margaret Brimble.

Obesity is a risk factor for many health conditions such as diabetes, cardiovascular disease, osteoarthritis and cancer. Two million New Zealanders will be obese in 20 years’ time according to a report from the University of Otago published in the Australian and New Zealand Journal of Public Health in 2018. In 2014 more than 600 million adults worldwide were obese. In 2016 FDA-approved obesity medication sales were US$455 million, predicted to reach US$2.9 billion in 2021.

Scientific Advisory Board Members

Professor Debbie Hay

Professor Debbie Hay

Professor of Biochemistry and Pharmacology at the University of Auckland
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Distinguished Prof. Dame Margaret Brimble

Distinguished Prof. Dame Margaret Brimble

Director of Medicinal Chemistry at the University of Auckland
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Dr Rinki Murphy

Dr Rinki Murphy

Associate Professor in Medicine at the University of Auckland
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Dr John Villiger

Dr John Villiger

Experienced pharmaceutical product development executive
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Dr Christian Schwabe

Dr Christian Schwabe

Managing Director of Auckland Clinical Studies
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Associate Professor Alex Tups

Associate Professor Alex Tups

Associate Professor at Centre for Neuroendocrinology, University of Otago
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Professor Debbie Hay

Professor Debbie Hay

Professor of Biochemistry and Pharmacology at the University of Auckland
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Distinguished Prof. Dame Margaret Brimble

Distinguished Prof. Dame Margaret Brimble

Director of Medicinal Chemistry at the University of Auckland
Read Bio +
Dr Rinki Murphy

Dr Rinki Murphy

Associate Professor in Medicine at the University of Auckland
Read Bio +
Dr John Villiger

Dr John Villiger

Experienced pharmaceutical product development executive
Read Bio +
Dr Christian Schwabe

Dr Christian Schwabe

Managing Director of Auckland Clinical Studies
Read Bio +
Associate Professor Alex Tups

Associate Professor Alex Tups

Associate Professor at Centre for Neuroendocrinology, University of Otago
Read Bio +
Professor Debbie Hay

Professor Debbie Hay

Professor of Biochemistry and Pharmacology at the University of Auckland

Professor of Biochemistry and Pharmacology at the University of Auckland
Head (Acting) – 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

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 Rinki Murphy

Dr Rinki Murphy

Associate Professor in Medicine at the University of Auckland

Dr Murphy is Associate Professor in Medicine at the University of Auckland and Principal investigator at the Maurice Wilkins Centre for Biodiscovery. Diabetologist at Auckland and Counties Manukau DHBs.

Dr Murphy is an endocrinologist with special interest in monogenic causes of diabetes and severe insulin resistance.  She researches genetics and physiology of diabetes and obesity.

Dr John Villiger

Dr John Villiger

Experienced pharmaceutical product development executive

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 Christian Schwabe

Dr Christian Schwabe

Managing Director of Auckland Clinical Studies

Dr Christian Schwabe, MD, MPharmMed, trained in General Surgery at the University Hospital of Hamburg-Eppendorf and is the Managing Director of Auckland Clinical Studies.

Dr Schwabe is responsible for ACS clinical operations and has been Principal Investigator and co-investigator on ACS studies.

Associate Professor Alex Tups

Associate Professor Alex Tups

Associate Professor at Centre for Neuroendocrinology, University of Otago

Professor Alex Tups is an Associate Professor at the Centre for Neuroendocrinology at the University of Otago.

The focus of Professor Tups’ research is the neuroendocrine regulation of metabolism, and the mechanisms that link obesity, diabetes and Alzheimer’s disease.  Alex has published 31 research papers and received awards in neuroendocrine research in the UK (Michael Harbuz Price 2009) and in Germany (Ernst and Berta Sharrer Award 2014).

Development to Date

Pramlintide is an amylin receptor stimulant. Amylin is the natural hormone satiation signal that is a physiological regulator of meal size. Pramlintide is an FDA-approved peptide drug that mimics the actions of amylin to control blood glucose. It is approved for type 1 and type 2 diabetes in conjunction with insulin.

Pramlintide also reduces caloric intake, resulting in weight loss. This means it could be a valuable tool for mitigating one of the biggest risk factors for prediabetes/diabetes – obesity. Pramlintide in its current format has limitations chiefly it is short-acting, with a half-life of 48 minutes in healthy subjects so needs to be administered (by injection) several times a day.

LP-003 is a long acting pramlintide analogue which was synthesised by Distinguished Professor Margaret Brimble at the University of Auckland. The project is targeting a once daily injection which can be validated in a clinical study where blood level and food intake can be measured after a single injection of LP-003.  LP-003 is protected by a global patent.

Under lead investigator, Professor Debbie Hay at the University of Auckland, the project has completed pre-clinical characterisation of LP-003. This encompasses in vitro profiling, biomarker bioassay, pharmacokinetics and toxicology. In vivo activity is in progress under Associate Professor Alex Tups at the University of Otago. This activity is examining food intake, body weight changes, and energy expenditure.

chemist

Future Development

We are prioritising the LC-002 migraine treatment project and will resume development of LP-003 for obesity as funds allow.

Once the in vivo studies at Otago are completed, the next step is a Phase I clinical trial using a single ascending dose and measuring safety as well as blood glucose levels and food intake. 

With encouraging pharmacokinetic, safety and efficacy data from the Phase I study we intend to seek partners to collaborate on the expansion of the clinical development program towards commercialisation.

LP-003 is an attractive out licence candidate to treat morbid obesity. We have already engaged with interested global parties and have discussed potential deal structures, formulation and delivery technology.

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