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From research funding to pharma company – with a brand-new concept for anti-depressant therapy

A new anti-depressant inspired by psychedelics is the backbone of the small Danish pharmaceutical company Lophora. The Lundbeck Foundation provided funding for the research, which is now about to be commercialised.

A team of researchers from the Department of Drug Design and Pharmacology at the University of Copenhagen is preparing to test an unprecedented type of anti-depressant on humans. The candidate in question is LPH-5, and the team, headed by Professor Jesper Langgaard Kristensen, based the design of the drug on their knowledge of the mechanisms of action of psychedelics.

If everything goes according to plan, the researchers will begin testing the drug on humans in late 2021. The team has applied for a patent in the drug class to which LPH-5 belongs and has founded a company, Lophora, to handle commercialisation of the discovery.

LPH-5 is a prime example of global interest in developing new drug therapies for depression with an eye to psychedelics such as LSD, mescaline and psilocybin. In Denmark, the latter is found in the wild in the relatively common liberty cap mushroom (Psilocybe semilanceata).

When it comes to treatment of depression, psychedelics, and not least psilocybin, are interesting for several reasons:

Firstly, psilocybin – also used by many non-depressed mushroom gatherers for recreational purposes – has shown beneficial effects in medical trials with depressed individuals.

Secondly, researchers in both the EU countries and the USA regard psychedelics – and solutions based on the mechanisms of action of these non-addictive drugs – as an opportunity to develop alternatives to conventional anti-depressants in the long term.

Professor Jesper Langgaard Kristensen explains that although the anti-depressants already on the market help many patients, there are also plenty who do not experience any significant benefit from the drugs:

‘Furthermore, anti-depressant drugs can have a range of side effects such as sexual dysfunction, obesity and a feeling of emotional flatness. So, all in all, we hope to bypass these side effects by allowing the biochemical mechanisms that cause psychedelics to work to take centre stage in novel anti-depressants. And that’s what we’re working towards.’

‘The psychedelic receptor’
The story of LPH-5 is also a narrative about the need to operate within the scope of the lengthy time scale for developing novel drug therapies. It includes both the researchers in the laboratories and the foundations that are devoted to funding the research and, therefore, help finance the studies.

Jesper Langgaard Kristensen, who has a background as a pharmacist, began working with psilocybin back in 2005. At that time, the task was to develop tracers for use in connection with the PET scans carried out at CIMBI (Centre for Integrated Molecular Brain Imaging).

The University of Copenhagen, the Technical University of Denmark and prominent universities in the UK, USA and Germany were involved in the research partnership, and the Lundbeck Foundation was one of the principal sponsors.

‘Professor Gitte Moos Knudsen, who’s currently head of the Neurobiology Research Unit (NRU) at Rigshospitalet, University of Copenhagen, was also one of the key CIMBI researchers. Among other things, she needed tracers that would cause the brain receptor affected by psilocybin – in reality, the ‘button’ that triggers a psychedelic effect when people take the drug – to show up on a PET scan. This is the same ‘button’ that comes into play in LSD use, and I was part of the team that developed this tracer,’ says Professor Kristensen.

And the more time he spent studying this button – the psychedelic receptor found in all mammals – the more he realised that it could be key to treating depression: We could develop a drug that heads straight for this receptor and triggers a feeling and an experience that neutralise depressive emotions.

‘This was how our work with LPH-5 began,’ says Professor Kristensen. ‘And we succeeded in developing a drug that primarily affects the button we want to hit. By contrast, psilocybin – in addition to hitting this button – is also biochemically programmed to seek out a range of other receptors to about the same degree, for instance in the heart muscle. So, in this context, psilocybin is more difficult to control, nor can it be patented because, chemically, it is well known and well described.’

In the course of his development activities, Jesper Langgaard Kristensen had the help of two other researchers at the Department of Drug Design and Pharmacology: Emil Marcher-Rørsted, a Lundbeck Foundation PhD fellow, and Associate Professor Anders A. Jensen. Today, together with Bo Tandrup, who specialises in developing biotech businesses, these three own Lophora and, thus, the rights to LPH-5.

The drug has been tested in cell trials and animal models with mice and rats. The aim of the animal trials was to prove that the drug has a positive effect on depression. Professor Kristensen explains that depression is induced in the animals when they move through mazes that stress them:

‘Both the cell trials and the animal trials were so successful that we expect to launch the first clinical trials – in humans – in late 2021. Before we begin, we need to perform a range of new toxicity trials in animals – to double check that LPH-5 has no undesired side effects. And once that’s done, we can start applying for permission for the first clinical trials.’

LPH-5 has generated a great deal of interest in biotech circles, and Lophora has recently received a grant of DKK 10 million from the BioInnovation Institute.

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