Experimental drug BT-267 shows promise in Parkinson’s study
LRRK inhibitor reaches clinically meaningful levels in the brain
Written by |
- BT-267, an LRRK2 inhibitor for Parkinson's, has shown promise by reaching meaningful levels in the brain in early trials.
- Phase 1b and Phase 2 studies are planned for Parkinson's patients.
- BT-409, an NLRP3 inhibitor targeting neuroinflammation in Parkinson's, began Phase 1 trials.
BT-267, an LRRK2 inhibitor being developed by Brenig Therapeutics as a treatment for Parkinson’s disease, has reached sustained, clinically meaningful levels in the brain, according to early results from a study in healthy volunteers.
The therapy is being developed for both idiopathic Parkinson’s, where the cause is unknown, and cases linked to mutations in the LRRK2 gene. To date, BT-267 has shown a favorable safety and tolerability profile. Brenig plans to launch a Phase 1b study later this year and is preparing for a Phase 2 proof-of-concept trial in Parkinson’s patients.
Brenig also announced the start of a first-in-human Phase 1 trial of BT-409, a small-molecule inhibitor of NLRP3, an inflammatory protein believed to drive chronic neuroinflammation in Parkinson’s disease. Participant dosing is expected to begin soon.
“The emerging clinical profile of BT-267 supports its potential as a best-in-class LRRK2 inhibitor,” Tien Dam, MD, chief medical officer of Brenig, said in a company press release. “We believe [central nervous system]-optimized LRRK2 inhibition remains one of the most compelling therapeutic strategies in Parkinson’s disease, and we are focused on advancing BT-267 efficiently into patient studies.”
BT-267 designed to selectively inhibit LRRK2 in the brain
Parkinson’s disease is caused by the loss of dopaminergic neurons, nerve cells that produce a brain chemical messenger called dopamine. This leads to motor symptoms, including tremors, muscle stiffness, and slow movement, and nonmotor symptoms, such as cognitive impairment, depression, and sleeping issues.
Although the cause of the disease is unknown in most cases, about 5% to 10% of Parkinson’s cases are caused by genetic mutations, including mutations in the LRRK2 gene that encodes the leucine-rich repeat kinase 2 (LRRK2) enzyme. Dysregulation of LRRK2 activity is associated with dysfunction of lysosomes, the cells’ recycling and waste disposal system, and mitochondria, cellular structures that provide energy to cells.
BT-267 is a small molecule designed to selectively inhibit LRRK2 in the brain. Its profile allows sustained, high exposure in the brain while limiting exposure elsewhere, reducing the risk of side effects.
Early data from the first-in-human clinical trial in healthy volunteers, which has started dosing participants, support its sustained exposure in the central nervous system, made up of the brain and spinal cord, at levels predicted to be above those required for BT-267 to exert its effect.
We are focused on translating this program efficiently into the clinic with the goal of delivering meaningful new treatment options for patients affected by neuroinflammatory and neurodegenerative diseases.
The company is also developing BT-409, a brain-selective small-molecule NLRP3 inhibitor, licensed from Mwyngil Therapeutics and designed using Mwyngil’s drug accelerator platform, which leverages artificial intelligence and machine learning.
NLRP3 is a component of the inflammasome, a protein complex that, when activated, triggers a strong inflammatory response. In Parkinson’s disease, the excessive activation of the NLRP3 inflammasome is thought to contribute to chronic neuroinflammation.
Brenig has recently initiated a Phase 1 trial to assess the safety, tolerability, and pharmacological properties of BT-409 at single and multiple ascending doses in healthy volunteers.
Pending the successful completion of this study, the company plans to advance studies in people with Parkinson’s and multiple sclerosis, another neurological condition marked by increased neuroinflammation. These studies will assess the therapeutic potential of BT-409 across several neurological diseases.
“We are focused on translating this program efficiently into the clinic, with the goal of delivering meaningful new treatment options for patients affected by neuroinflammatory and neurodegenerative diseases,” said Megan McGill, MD, PhD, Brenig’s CEO.
