Neuron23 Unveils Groundbreaking Phase 2 Trial in Early Parkinson’s Disease

South San Francisco, California – November 19, 2024: Neuron23® Inc., a clinical-stage biotechnology company focused on developing­­ precision medicines for genetically defined neurological and immunological diseases, today unveiled details around its global ­­Phase 2 NEULARK clinical trial of NEU-411, a brain-penetrant, potent and selective inhibitor of LRRK2, in people with early Parkinson’s disease (PD). The NEULARK trial represents a significant advancement in precision medicine, utilizing a state-of-the-art digital biomarker and patient stratification approach to identify individuals with LRRK2-driven PD who may be most likely to respond to treatment with NEU-411. While LRRK2 mutations are the most common cause of familial PD, representing 2% of the patient population, it is estimated that up to 30% of people with PD have LRRK2-driven disease.

“The NEULARK trial represents a new dawn in the evolution of Parkinson’s disease research and treatment. With no therapies currently available that impact the underlying disease progression of Parkinson’s, existing options are limited to alleviating symptoms,” said Nancy Stagliano, Ph.D., Chief Executive Officer of Neuron23. “By utilizing a digital biomarker as the primary endpoint and the first precision medicine patient stratification approach in Parkinson’s clinical development, we are shedding new light on how we can effectively identify and measure therapeutic impact in people with LRRK2-driven Parkinson’s disease. Our LRRK2 program is a key driver of innovation within our neuroimmunology pipeline, and we are on track to initiate this trial early in 2025.”

NEU-411: A Potent and Selective LRRK2 Inhibitor

NEU-411, Neuron23’s most advanced clinical program, is designed to inhibit LRRK2 in people with PD. In a Phase 1 clinical trial, NEU-411 was safe and well tolerated in over 100 healthy volunteers for up to 28 days. NEU-411 also demonstrated robust target engagement of the LRRK2 pathway using fluid-based biomarkers that can be detected in healthy individuals, demonstrating NEU-411’s ability to inhibit LRRK2. Extensive pharmacodynamic, pharmacokinetic and chronic safety studies in animals have provided a strong foundation for NEU-411’s clinical development.

LRRK2’s Role in Parkinson’s Disease and the Potential of LRRK2 Inhibition

Mutations in the LRRK2 gene are among the most common genetic causes of PD, affecting approximately 2% of people with the disease. Individuals who inherit gain-of-function mutations in LRRK2 are at higher risk of developing PD later in life. Additionally, there is emerging evidence that LRRK2 activity may play a role in a subset of the larger population of people with non-familial PD, known as idiopathic PD, suggesting that therapies targeting LRRK2 could be beneficial to a broader patient population than just individuals with rare, familial LRRK2 mutations.

Neuron23 has identified single-nucleotide polymorphisms (SNPs) – variations in an individual’s DNA sequence – that are predicted to drive LRRK2 overactivity in up to 30% of people with idiopathic PD. People with PD who have these SNPs, together with those who have LRRK2 gene mutations, make up the population collectively referred to as LRRK2-driven PD and represent who Neuron23 believes is most likely to benefit from LRRK2 inhibition.

By specifically inhibiting the overactive LRRK2 kinase pathway, NEU-411 aims to address an underlying cause of disease progression in people with LRRK2-driven PD, offering a more precise and potentially more effective approach compared to existing treatment options that only address some symptoms of PD.

Precision Medicine Approach to Parkinson’s Disease

The Phase 2 NEULARK clinical trial of NEU-411 (NCT06680830) is a global, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of this potent and selective LRRK2 inhibitor, as compared to placebo in people with early-stage PD. The trial will utilize an investigational clinical trial assay developed in collaboration with QIAGEN to select people with LRRK2-driven PD for the trial. This assay leverages whole exome next-generation sequencing (NGS) to detect Neuron23’s selected panel of SNPs and an algorithmic predictive model to define people who are likely to have elevated LRRK2 pathway activity.

Under an exclusive agreement, Quest Diagnostics, a leader in diagnostic information services, will deploy the assay at its advanced diagnostics laboratory in San Juan Capistrano, Calif., to identify trial candidates. This rigorous screening process is designed to maximize the likelihood of enrolling people who have the highest potential for benefit from treatment with NEU-411 – those with LRRK2-driven PD – significantly enhancing the trial's potential impact and likelihood of success.

Neuron23 has also partnered with Sano Genetics to streamline patient referrals and assist in identification of people with PD who may be eligible to participate in the NEULARK clinical trial. Under a separate protocol, Sano will offer saliva test kits that can identify people with LRRK2-driven PD and will provide genetic counseling and engagement tools, including tailored educational content. Individuals identified by Sano Genetics will be referred to the nearest NEULARK clinical trial site for a complete eligibility evaluation and potential enrollment.

Once enrolled in the trial, disease progression will be measured utilizing an innovative digital biomarker developed by Roche Information Solutions (RIS), the Roche group focused on digital health solutions. Participants will use a smartphone equipped with proprietary software that frequently measures PD symptoms such as slowed movement and tremor, as well as non-motor symptoms such as cognition.

“By integrating an advanced digital biomarker developed by Roche Diagnostics, the NEULARK trial has the potential to set a new benchmark for monitoring Parkinson’s disease progression with unprecedented resolution and precision,” said Sam Jackson, M.D., Chief Medical Officer of Neuron23. “This cutting-edge technology allows patients to seamlessly incorporate monitoring into their daily lives, yielding additional valuable insights that traditional in-clinic assessments cannot provide. Combined with our enhanced understanding of disease architecture – including biological drivers linked to LRRK2 dysfunction – this approach uniquely positions us to identify people with PD whom we believe are more likely to respond to our potentially best-in-class LRRK2 inhibitor, NEU-411. This trial has the potential to redefine how we conduct trials in Parkinson’s disease.”

About Parkinson’s Disease

Parkinson’s disease (PD) is a brain disorder that causes unintended or uncontrollable movements, such as shaking, stiffness and difficulty with balance and coordination. Symptoms usually begin gradually and worsen over time. As the disease progresses, people may have difficulty walking and talking. Additional symptoms can include mental and behavioral changes, such as sleep problems, depression, memory difficulties and fatigue.

Some cases of PD appear to be hereditary, and a few cases can be traced to specific genetic mutations. Currently, there is no cure or therapy that impacts underlying disease progression available for PD, and treatment options are only used to alleviate some symptoms.

About Neuron23®

Neuron23® Inc. is a clinical-stage biotechnology company focused on developing precision medicines for genetically defined neurological and immunological diseases. Neuron23 combines recent advances in human genetics with a state-of-the-art drug discovery and biomarker platform using advanced techniques in machine learning and artificial intelligence to advance therapeutics for devastating diseases. The Company’s focus areas are neurodegenerative diseases, neuroinflammatory diseases, and systemic autoimmune and inflammatory diseases. Founded in 2018, Neuron23 has assembled a world-class team of experts and entrepreneurs located in South San Francisco, CA. For more information, please visit www.neuron23.com.