Transforming Focal Epilepsy Treatment: Our Investment in EpilepsyGTx
Simon Goldman, Partner
Posted
1% of the world’s population suffer from epilepsy – that’s tens of millions of people who can’t drive, have difficulties in daily work and life and have a significantly increased mortality rate. 70% of those have what’s called ‘focal’ epilepsy – one part of the brain has uncontrolled excitation which spreads and causes a spectrum of seizure disorders. For many decades, anti-epileptic drugs (AEDs) have provided the mainstay of therapy for this condition, but 20-30% of patients become refractory to these drugs and have uncontrolled seizures with very few therapeutic options – only an extremely small number of the most severe patients go on to have resective surgery to remove the epileptic focus.
Our conviction in the stellar EpilepsyGTx team is based on the potential to provide a safe, curative therapeutic option for so many people with so few options. EPY-201 is a gene therapy, using an AAV9 viral vector, delivered directly into the epileptic focus through a small hole in the skull, carrying the instructions for the neurons transduced by the virus to produce a potassium channel (Kv1.1) on their cell surface. This has the effect of increasing the threshold for activation only within the epileptic focus – thereby dialling down activity in the part of the brain responsible for seizures and preventing their occurrence.
Here are just a few of the other, many many reasons I’m just so incredibly excited about this company:
Drug-refractory patients desperately want a solution, but of course they want it to be as minimally invasive as possible. Part of the reason so few patients do get surgically resected for FRE is that nobody wants (and neurologists don’t recommend) damage to brain tissue, let alone have a big chunk taken out. So, the market opportunity for a potentially long-term curative gene therapy which dials down overactivity just in excitatory neurons in the epileptic focus – and which preserves brain tissue – is not just the surgical population but the much, much larger group of patients for whom existing standard of care is not advised.
The first cohort of patients to be offered the therapy will be those already cleared for resection, providing not only a significantly de-risked trial structure from a safety perspective, but it would be fascinating indeed if any of the dosed patients then withdrew their consent for surgery (because the therapy abrogates their seizures).
The preclinical models in which outstanding efficacy has already been demonstrated have a 50-year history of successful translation into human outcomes in clinic. I can’t think of many indications with this level of translatability.
The biodistribution of AAV9 from the infusion site is the same volume as the average human seizure focus(!). Even then, as the UCL team have shown in preclinical models, only a small proportion of the seizure focus needs to be transduced to show efficacy. Moreover, there is negligible (if that) leakage to adjacent brain regions, let alone systemically – and it’s the systemic side effects which have been such a problem for many gene therapy programs. This avoids that risk entirely.
This is not like any other gene therapy you’ve seen before. It doesn’t require any sophisticated (or expensive) new delivery process and instead piggybacks on existing, minimally invasive neurosurgical techniques used worldwide. Hardly any vector is required and – if demonstrated to be safe and efficacious – has the potential to provide long-term curative therapy for so, so many patients.
It has been, and continues to be, an entirely humbling experience to work with Profs Stephanie Schorge, Matthew Walker, Gabriele Lignani and Dimitri Kullmann; and CEO Nicolas Koebel. What an incredible team, with endless expertise spanning novel modalities, the most-incredible preclinical factory at the wonderful UCL Queen Square Institute of Neurology, direct patient and surgical experience, gene therapy commercialisation…the list goes on. I look forward to bringing a hugely impactful drug to patients worldwide together.
Simon Goldman, Partner, AlbionVC
View the press release here.
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