Multiple Partnerships Help Drive Precision Medicine Trial For Parkinson's

A conversation with Neuron23 Chief Medical Officer Sam Jackson, MD

Neuron23 is moving beyond the “one-size-fits-all” approach. That’s true for both its clinical research partnerships and its outlook for the treatment of neurological diseases, namely Parkinson’s disease. The Company intends to pioneer precision medicine in neurology, starting with its NEULARK trial evaluating the safety and efficacy of NEU-411 for patients with Parkinson's disease driven by genetic signatures related to increased activity in leucine-rich repeat kinase 2 (LRRK2).

In this Q&A, CMO Sam Jackson, MD, explains the company’s desire to set a new standard in precision medicine for neurology, backed by well-aligned partnerships and fit-for-purpose digital biomarker solutions.

What inspired the decision to bring a patient stratification approach to Parkinson’s disease, and how does it set your trial apart?

Parkinson’s disease has long been treated as a single disease, despite growing evidence that it consists of multiple subtypes with distinct underlying biological drivers. Unlike oncology, where precision medicine has revolutionized treatment by, in many cases, using underlying biology to link the right therapy to the right patient, neurology has lagged behind in applying these principles. We saw an opportunity to pursue a more refined patient selection approach in Parkinson’s disease.

Our approach is built on the idea that we can improve clinical trial success rates and, ultimately, treatment outcomes, by ensuring that only patients who are more likely to respond to a therapy are included in a trial. LRRK2 has been a target of interest in Parkinson’s disease for around 20 years. A question that has vexed the field, however, is whether inhibiting LRRK2 could impact all people with Parkinson’s, only individuals with a rare set of inherited genetic mutations, or a much larger group of patients who carry a genetic signature, which we call “LRRK2 driven.”

We developed a companion diagnostic (CDx) that has identified approximately 30% of people with Parkinson’s have LRRK2-driven disease and are incorporating this CDx into the NEULARK trial, a clinical trial evaluating the safety and efficacy of an investigational drug, NEU-411, compared to a placebo. Through this approach, we believe we are not only increasing our chances of demonstrating efficacy for NEU-411 but setting a precedent for how to study and treat neurodegenerative diseases in the future.

What role does the identification of single-nucleotide polymorphisms (SNPs) play in stratifying patients for the NEULARK trial? How does this approach improve the likelihood of trial success?

There is a wealth of evidence leading us to believe that LRRK2 is driving Parkinson’s disease in a group of people with Parkinson’s beyond just those with inherited LRRK2 mutations. Our team developed a robust panel of single-nucleotide polymorphisms (SNPs) and an algorithmic predictive model, which together help us identify individuals more likely to have elevated LRRK2 pathway activity. This work allows us to go beyond inherited genetic mutations alone and pinpoint a broader group of patients who may respond to LRRK2 inhibition.

By selecting individuals who are more likely to benefit from NEU-411, we are reducing the heterogeneity of our study population. This reduces the likelihood of enrolling patients who may not respond to treatment, making it easier to detect a true treatment effect and increasing the likelihood of a successful trial outcome. It’s a targeted approach designed to maximize both trial efficiency and impact.

You’ve selected a few key partners for this trial.  How does each of them — Qiagen, Quest Diagnostics, and Sano Genetics — contribute to the trial’s success?

Qiagen is a leader in developing, validating, and commercializing diagnostic assays for applications in oncology and has a strong interest in expanding into additional therapeutic areas such as neurology, making them an ideal partner in this effort. CDx development requires technical rigor, regulatory expertise, and validation to ensure accuracy and reliability. Qiagen has helped us design a robust, validated assay to accurately identify individuals with LRRK2-driven Parkinson’s disease. By leveraging Qiagen’s expertise and experience working with regulatory agencies on companion diagnostics, we ensure our patient selection process is robust, scalable, and aligned with global regulatory expectations.

The ability to deploy our CDx assay at scale and in a regulatory-compliant manner is crucial. Our collaboration with Quest Diagnostics enables high-throughput execution of the CDx with a rapid turnaround and high level of consistency and efficiency. This reduces time to enrollment, helping us confirm patient eligibility quickly while maintaining the integrity of our precision medicine approach.

One of the biggest challenges in Parkinson’s disease trials is finding the right patients — especially when genetic biomarkers are involved. Our collaboration with Sano Genetics is designed to remove barriers to participation and directly empower patients to understand their potential eligibility. This partnership provides:

• saliva-based testing to provide a non-invasive alternative to traditional genetic testing, eliminating the need for blood draws or in-clinic visits during the prescreening phase
• genetic counseling to ensure that participants clearly understand what their test results mean and how they relate to their potential eligibility for the NEULARK trial
• referral tools to help seamlessly connect eligible individuals with the nearest NEULARK trial site, reducing the logistical burden of participation and improving access to the study.

By combining precision medicine with a patient-friendly approach, we aim to improve recruitment and retention, which are critical to the success of any clinical trial.

What was compelling about Roche’s offering with navify, a digital biomarker solution, and how did this collaboration come to fruition?

When evaluating digital biomarkers for the NEULARK trial, we sought a solution that was both clinically validated and capable of capturing Parkinson’s disease progression with greater precision. Roche develops digital health solutions for movement disorders, and this particular solution aligns with our goal of advancing clinical trial design by incorporating more objective and continuous measurement tools. Participants will use a smartphone equipped with proprietary software that frequently measures relevant symptoms such as slowed movement and tremor, as well as non-motor symptoms such as cognition. By leveraging real-world high-frequency data collection, it has the potential to provide a more comprehensive assessment of NEU-411’s impact while reducing reliance on traditional episodic clinical evaluations.

We evaluated many potential partners and selected Roche due to the robustness of their data package, their experience engaging with regulators on novel endpoints, and their collaborative approach.

In what ways might using navify result in better data collection and more precise insights into Parkinson’s disease progression?

Traditional clinical rating scales have long played a critical role in Parkinson’s disease research, providing structured and validated measures of disease progression. However, because these assessments are typically conducted at eight- to 12-week intervals in clinical trials, they will not capture the full spectrum of daily symptom fluctuations. Integrating digital biomarkers into a clinical trial testing regimen offers a different approach, enabling more frequent objective measurements that can provide additional insights into disease progression.

With a smartphone-based digital biomarker solution such as navify, we can:

• capture near-continuous data on motor and non-motor symptoms, providing a higher-resolution picture of disease progression
• reduce variability by using an objective sensor-based system
• enhance endpoint sensitivity, allowing us to detect treatment effects that might not be apparent using traditional methods.

By integrating digital biomarkers into the trial, we hope to set a new standard for how to measure Parkinson’s disease, ultimately leading to more reliable and meaningful clinical insights.

How will the navify solution reduce the burden on patients and improve their trial experience compared to traditional clinical outcome assessments?

Participating in a clinical trial can be demanding — especially for people with Parkinson’s disease, who may have mobility challenges. Using a digital biomarker solution helps ease this burden in several ways:

• More frequent real-world monitoring: Traditional clinical assessments provide valuable insights but are limited to scheduled visits. Digital biomarkers enable continuous symptom tracking in a patient’s natural environment, capturing changes that might otherwise go undetected.
• Seamless smartphone integration: Since navify runs on a standard smartphone, it’s easy for participants to incorporate into their daily routine.
• Higher compliance and retention: Making data collection less intrusive and more convenient helps ensure that participants remain engaged throughout the study.
• Reducing barriers to participation in research: The use of at-home monitoring reduces the frequency and duration of study visits, thereby reducing the burden on patients and sites.

Ultimately, by enabling real-world high-frequency symptom monitoring, digital biomarker tools like navify have the potential to provide a more comprehensive view of disease progression while complementing standard clinical assessments.

By incorporating precision medicine and digital health technologies into the NEULARK trial, how do you hope to influence the broader landscape of Parkinson’s disease treatment and neurology research?

Precision medicine is the future of neurology. For too long, neurodegenerative diseases have been treated with a one-size-fits-all approach, despite clear evidence that different patient populations may respond very differently to treatment.

With the NEULARK trial, we are demonstrating that it’s possible to stratify patients based on their underlying biology, just as oncology has done for decades. If successful, this approach could potentially:

• pave the way for broader industry adoption of precision medicine in neurology
• set a new standard for integrating companion diagnostics and genetic stratification into clinical trials
• expand the impact of digital endpoints, making clinical research more efficient, patient-friendly, and scientifically rigorous.

We’re committed to leading this transition to a precision-medicine approach — not just in Parkinson’s disease but across neurodegenerative and immunological diseases where precision medicine can make a real difference.

About The Expert:

Sam Jackson, MD, joined Neuron23 as chief medical officer in 2022 and is a board-certified emergency physician with fellowship training in medical toxicology. Before joining Neuron23, Dr. Jackson was the interim chief medical officer and senior vice president of clinical development at Alector, where he led programs in Alzheimer’s disease and frontotemporal dementia, as well as clinical due diligence discussions that resulted in an alliance with GlaxoSmithKline. Prior to Alector, Dr. Jackson held roles of increasing responsibility at Amgen, Genentech, Dynavax, and Alkahest. At Dynavax, he ran a pivotal Phase 3 trial and was part of the small team that filed the BLA resulting in approval of a novel vaccine for hepatitis B. At Alkahest, he served as chief medical officer, where he helped build the clinical organization and designed and initiated four Phase 2 trials in neurologic and ophthalmologic diseases. Dr. Jackson graduated from Stanford University and received his MD and MBA from the University of Pennsylvania.