The Science Behind Supports Synendos Therapeutics' Successful Phase I Clinical Trial at Richmond Pharmacology

Project Overview

The Science Behind (TSB) is proud to have supported Synendos Therapeutics’ first-in-human Phase I clinical trial of SYT-510, a novel Selective Endocannabinoid Reuptake Inhibitor (SERI), conducted at Richmond Pharmacology.

SYT-510 is a SERI developed by Synendos Therapeutics AG for central nervous system (CNS) disorders such as anxiety, PTSD, and other neuropsychiatric conditions. As the first SERI to enter clinical development, SYT-510 represents a new class of drugs that modulate the endocannabinoid system by gently increasing the brain’s natural cannabinoids, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), to help restore normal brain communication and plasticity. It does this by reversibly blocking a newly identified transport mechanism, which controls how these endogenous cannabinoids are transported and broken down.

The Phase I clinical program, of which part was conducted at Richmond Pharmacology, included single ascending dose (SAD) and multiple ascending dose (MAD) studies to evaluate the safety, tolerability, pharmacokinetics (PK), and explorative pharmacodynamic markers (PD) of SYT-510. EEG was included as a key pharmacodynamic measure to characterise central effects of this first-in-class mechanism, complementing traditional PK and safety endpoints.

The study marked a significant milestone in the development of this first-in-class therapy targeting neuropsychiatric disorders. Synendos announced highly promising topline results, demonstrating that SYT-510 was well tolerated across all doses, with a favourable safety profile, CNS penetration, and pharmacodynamic EEG effects consistent with known anxiolytic treatments.

Our Role

TSB’s role focused on the design, execution, and data management of EEG assessments, which were a critical component in characterising the neurophysiological effects of SYT-510.

Working closely with both Richmond Pharmacology’s clinical operations team and Synendos’ scientific and data teams, TSB ensured that all EEG data were collected under stringent, standardised conditions, compliant with Good Clinical Practice (GCP) and aligned with study timelines.

Our team produced and implemented a comprehensive an operational EEG manual detailing the procedures for equipment setup, participant preparation, data acquisition, quality control, and data transfer. This manual served as the reference point for all EEG-related activities across the study and ensured reproducibility and consistency throughout the trial.

EEG Methodology and Implementation

EEG recordings were performed using a 32-channel system with electrode caps configured to the international 10-20 system (Fp1-O2), with mastoid references and embedded ground/forehead electrodes. Data were collected at a sampling rate of 3000 Hz with no applied filters, to maintain high-fidelity raw data.

Each recording session included:

• Resting-state eyes open (RS_EO) and eyes closed (RS_EC) conditions (5 minutes each)
• Standardised timepoints according to the study schedule of assessments (SoA)
• Continuous impedance monitoring, maintaining all electrodes below 5 kΩ
•  Real-time quality checks and artefact annotation by TSB technicians

Our team also conducted pilot testing prior to participant dosing to ensure minimal electrical noise in the ward and verify setup reliability.

On-Site Operations and Collaboration

Throughout the study, two experienced TSB EEG technicians were present on site during each dosing day, arriving 50 minutes before assessments for equipment setup, COVID testing, and co-ordination with Richmond’s study team.

We worked seamlessly alongside clinic staff and nurses to ensure that EEG assessments were perfectly aligned with pharmacokinetic sampling and other scheduled procedures (e.g., blood draws). This required continuous communication and coordination between TSB and Richmond’s clinical operations to avoid delays or data conflicts.

Each day involved:

• EEG preparation, recording, and cleaning cycles for up to three participants per day
• Meticulous participant preparation protocols to optimise signal quality (e.g., hair preparation, impedance checks, comfort adjustments)
• Immediate post-session data review and documentation in the participant source workbook
• Signed verification of session details by both EEG technicians and Richmond clinical staff

Data Management and Blinding Procedures

Following each recording, EEG data were exported in EDF+ format and stored using a predefined file-naming convention that captured key metadata (Subject ID, Study Day, Timepoint, and Condition).

TSB collaborated directly with the Richmond Pharmacology data management team and Synendos’ statistical group to implement a robust data blinding and transfer workflow.

• Raw (blinded) EEG files were securely uploaded to Richmond’s BOX environment within one working day.
• Richmond’s unblinded data management staff masked subject identifiers before transferring the alias datasets to Synendos.
• TSB technicians ensured data integrity and traceability at every stage, documenting any technical events, artifacts, or interruptions with precise timestamps for inclusion in the electronic Case Report Forms (eCRFs).

This controlled data handling process was instrumental in ensuring the accuracy, reliability, and regulatory compliance of the EEG dataset for subsequent pharmacodynamic and statistical analyses.

Results and Impact

EEG served as a direct, non-invasive biomarker to monitor SYT-510’s effects on brain activity. The analyses revealed EEG patterns consistent with anxiolytic drug profiles, supporting the hypothesised mechanism of action of SYT-510 and providing early translational evidence of its impact on central nervous system function.

The success of this program underscores the growing importance of neurophysiological biomarkers in CNS drug discovery and development. By combining technical precision, operational reliability, and scientific interpretation, The Science Behind enables sponsors like Synendos to gain early translational insights - bridging the gap between preclinical neuroscience and clinical pharmacology.

As Synendos prepares to advance SYT-510 into Phase II trials in patients with anxiety-related disorders, TSB remains committed to supporting innovative CNS research through state-of-the-art EEG acquisition, analysis, and integration into the broader drug development process.