Draig Therapeutics, a start-up based in Cardiff, Wales, has emerged from stealth to develop new drugs for major depressive disorder. Deriving its name from the Welsh word for “dragon, the serpentine start-up is launching with $140 million in funding, which the company says provides a 3-year runway.
The firm has already completed safety trials for its main drug candidate, and it plans to begin Phase 2 trials later this year. That lead candidate, DT-101, is a positive allosteric modulator targeting the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in the brain and was developed by Cardiff University professors John Atack and Simon Ward.
Depression is thought to be partially caused by imbalances in the glutamate and γ-aminobutyric acid (GABA) pathways in the brain, which are the main excitatory and inhibitory pathways, respectively. But these pathways must be adjusted subtly; going overboard can result in either too much glutamate or GABA, which can overexcite or over inhibit neurons.
DT-101 strikes this balance activating AMPA only when glutamate is already present, says Ruth McKernan, operating partner at venture capital firm SV Health Investors and cofounder and executive chair of Draig. It selectively activates AMPA receptors, making them more receptive to the neurotransmitter glutamate.
Atack and Ward used magnetoencephalography, an imaging method that detects tiny electrical changes in neurons, to verify that DT-101 works where it should. McKernan says this method is very new to neuropsychiatric drug development.
The business has two other molecules in development, both of which target GABA for depression.
“People say, ‘Well, you’ve got two molecules. What if they both work?’ And I say, ‘Happy days,’” McKernan says. “New mechanisms in depression are far and few between, and there’s quite a range of different types of depression, different depressive symptoms. So if doctors have more choices, that can only be good for patients.”
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