Neurona Therapeutics NRTX-1001 Has Shown Promising Early Signs of Safety and Efficacy in Drug-Resistant Epilepsy

Cory R. Nicholas, PhD

This is the second part of an interview with Cory R. Nicholas, PhD. For the first part, click here.

Neurona Therapeutics is currently evaluating its allogeneic regenerative neural cell therapy for the drug-resistant mesial temporal lobe epilepsy, dubbed NRTX-1001, in a phase 1/2 clinical trial (NCT05135091). Late last year, at the Annual Meeting of the American Epilepsy Society (AES), held December 1-5, 2023, in Orlando, Florida, results from the first 5 patients treated in the study were announced.

Shortly after the close of the conference, CGTLive™ spoke with Cory R. Nicholas, PhD, the cofounder and CEO of Neurona Therapeutics, about the trial design and the key findings. He noted that the first-in-human study is focused primarily on establishing safety, but promising signs of efficacy have also been observed.

CGTLive: Can you give an overview of the design of the phase 1/2 clinical trial for NRTX-1001?

Cory R. Nicholas, PhD: So the trial is a first-in-human phase 1/2 in people who have drug-resistant epilepsy coming from 1 temporal lobe in the brain. The phase 1, which we call the stage 1, is in 10 patients as in open-label single-arm fashion, and it comprises a 2 dose escalation. The first 5 patients get a starting dose of the NRTX-1001 inhibitory neurons, and then the second 5 patients get a 2-fold higher dose of the inhibitory neurons.

Once we complete the open-label phase, we will move on to the stage 2 (phase 2) of the trial, which is a randomized controlled trial evaluating the cell therapy in 20 additional people compared to a control arm, which is going to be a sham cohort in 10 people. So it’s 40 patients total, with an open-label followed by a randomized controlled trial. We've just completed dosing the first 5 patients in the open-label phase and we're now moving into the second cohort of that open-label phase at the higher dose level.

What progress has been made so far in the trial and what are the key results that have been reported?

We've successfully dosed the first 5 subjects, as I mentioned, and the therapy has been well tolerated. There haven't been any serious or severe adverse events related to the cells or the procedure to date. There was a data safety monitoring board meeting that was recently conducted after we enrolled the first 5 subjects, and the safety board agreed that things are going well and that we can continue enrolling. So we're now cleared to enroll the next 5 subjects at the higher dose level, which we're starting to enroll now [in December 2023] into early 2024.

Safety wise, obviously it's an ongoing trial, but it is going well. Safety is the primary endpoint in the study; efficacy is a secondary endpoint in this first-in-human study. It's also early, but preliminary data looks very positive. The first 2 subjects have both passed the 1-year mark in the study (1 year after the single dose of NRTX1001). This is a one and done procedure and now we're looking at seizure counts in the 12 months after the single dose administration of the cell therapy. What we've seen in the first 2 subjects is very encouraging signs of seizure control and seizure elimination, with over 96% of their seizures from their baseline counts being eliminated now. They're seeing overall 96% reduction of their seizure frequency. They're both reporting out that they're doing well, which is very encouraging. As I mentioned, we've dosed an additional 3 subjects to make up the 5 in the first cohort. The most recent 3 patients' data were announced at the AES Meeting this past week in Orlando. It's still early—just about 3months postadministration on these 3 subjects—but they're also doing very well overall and largely tracking what we've seen in the first 2.

Then finally, we're looking at neurocognitive measures as part of the trial as well. One of the main adverse effects of a lobectomy where the hippocampus is removed is that up to half of people can get worse on their neurocognitive performance. So we are, of course, looking very closely at this to evaluate whether the cell therapy has that same negative adverse reaction. So far in the first 2 patients, where we've looked at cognition (which we start doing at the 6 month mark posttransplant and beyond) we've not seen any additional deficits on cognition. In fact, on some of the cognitive scores, their performance has improved, which points to the potential for this type of regenerative cell therapy modality to possibly be restorative to brain function, rather than destructive as the standard of care lobectomy surgeries [can be.]

This transcript has been edited for clarity.

REFERENCES
1. Neurona Therapeutics presents new clinical data from first cohort in ongoing phase I/II open-label trial of NRTX-1001 cell therapy for drug-resistant mesial temporal lobe epilepsy (MTLE). News release. Neurona Therapeutics. December 1, 2023. Accessed January 28, 2024. https://www.neuronatherapeutics.com/news/press-releases/120123/