Syndeio Launches with $90M for Synapse Repair, Backed by AbbVie and Lilly

Syndeio Biosciences has garnered attention for its novel approach to treating psychiatric and neurodegenerative disorders by directly addressing synaptic structure and function. The company, co-founded by Derek Small, aims to tackle the root causes of circuit dysfunction, which sets it apart from existing treatments. This biotechnology startup recently unveiled its operations, backed by a substantial $90 million investment, and currently has two assets undergoing Phase II clinical trials. The investor group includes Catalio Capital Management, Innoviva, Tenmile, Luson Bioventures, and Palo Santo, with pharmaceutical giants AbbVie and Eli Lilly as strategic shareholders.

Syndeio's focus is on central nervous system disorders characterized by synaptic dysfunction, such as major depressive disorder (MDD), Alzheimer’s disease, and schizophrenia. Traditional treatments for MDD typically involve neurotransmitter blockade using dopamine or serotonin antagonists. While these may alleviate symptoms, they do not address the underlying issue of circuit dysfunction, according to Small. He further pointed out that targeting amyloid or tau proteins in Alzheimer’s treatment has limited effectiveness unless synaptic integrity is restored.

The company is particularly optimistic about its lead drug candidate, zelquistinel, an N-methyl-D-aspartate receptor (NMDAR) positive allosteric modulator (PAM). This compound is designed to enhance signaling and plasticity associated with neuronal activity. Currently in Phase II trials for MDD, zelquistinel is also set to begin a groundbreaking trial focusing on synaptic function biomarkers for Alzheimer’s disease. This trial will be the first of its kind, aiming not just to manage symptoms but to repair cognitive and emotional mechanisms, as Small stated.

In addition to zelquistinel, Syndeio is developing another NMDAR PAM called apimostinel, intended for acute treatment of MDD. This candidate is being assessed in an investigator-led Phase IIa study in collaboration with the University of Pittsburgh.

Central to Syndeio’s innovative methodology is its Boost Synapse Pharmacology Platform. While NMDAR has been a known target for years, Small asserts that their approach to modulating this receptor is distinctive. This platform not only employs scientifically validated mechanisms but also integrates the translational discipline necessary to transform biological potential into therapeutic outcomes. Significant investments have been made to rigorously mitigate risks in both clinical and non-clinical programs, with the aim of developing a strong translational platform rather than merely advancing individual compounds.

The Boost platform incorporates various technological and scientific elements such as electrophysiology, behavioral assays, and biomarker analyses like EEG and polysomnography. Furthermore, it includes retrospective validation from previous CNS programs to help predict treatment outcomes and inform dosing strategies for synaptogenic agents. Small emphasized that this platform aids in asset selection, pipeline prioritization, clinical trial design, patient selection, and dose optimization.

Beyond NMDAR, Syndeio is investigating other synaptic targets, such as AMPAR, mGluR, and 5HT2A, to assess their potential in restoring synaptic plasticity. While these targets are not new to the field, historical pharmacological approaches have, according to Small, relied on outdated models focused on receptor occupancy and chronic exposure. This has often ignored the dynamic processes of synaptic potentiation and depotentiation, which have been understood since the 1970s. Sustained stimulation of these receptors can sometimes paradoxically inhibit synaptic function, counteracting therapeutic effects. Syndeio’s innovative approach aims to overcome these challenges by revitalizing synaptic responses to achieve better therapeutic outcomes.