Following positive Phase 1 trial results, fibrin-targeting drug shifts into evaluations for treatment of Alzheimer’s and DME.
Neurodegeneration-focused biotech Therini Bio has announced encouraging results from a Phase 1a clinical trial evaluating its lead drug candidate, THN391, in healthy volunteers. The therapy is being investigated for its potential as a treatment for neurodegenerative diseases by addressing fibrin-driven neuroinflammation, a key pathological process linked to vascular dysfunction.
THN391 is a high-affinity, humanized monoclonal antibody designed to selectively block the inflammatory effects of fibrin without interfering with its role in coagulation. Fibrin deposits, which accumulate at sites of vascular injury, are known to bind complement receptors on innate immune cells, triggering chronic inflammation and subsequent neuronal damage in the brain and retina. This mechanism is believed to play a central role in the development and progression of age-related diseases such as Alzheimer’s disease and diabetic macular edema (DME).
Building on the scientific foundation established by its co-founder Dr Katerina Akassoglou, a leading researcher in neurovascular brain immunology, Therini’s preclinical studies demonstrated that targeting the inflammatory epitope on fibrin deposits with antibodies like THN391 can protect against vascular and neuronal degeneration. By intervening at this upstream point in the inflammatory cascade, the company aims to alter the course of neurodegenerative and retinal diseases rather than merely alleviating symptoms.
In its first-in-human trial, THN391 was administered in single and multiple ascending doses in a randomized, double-blind, placebo-controlled study. The treatment was well-tolerated with no serious adverse events, demonstrated no impact on coagulation or fibrinolysis, and did not provoke an anti-drug antibody response. Pharmacokinetic analysis revealed dose-proportional exposure and a half-life supportive of once-monthly dosing.
Following the positive Phase 1a results, Therini Bio plans to initiate two Phase 1b trials – one to evaluate the potential of THN391 patients with Alzheimer’s and another looking at DME.
“By targeting vascular dysfunction and chronic neuroinflammation, we aim to address fundamental root causes of neurodegeneration,” said Therini Bio CEO Dr Tara Nickerson. “Galvanized by the encouraging data and compelling preclinical evidence, we are eager to accelerate the development of THN391 to potentially ameliorate the lives of patients devastated by debilitating diseases, including Alzheimer’s and Diabetic Macular Edema.”
Data from the completed Phase 1a study will be presented at the Alzheimer’s Association International Conference 2025 in Toronto.
