Therini Bio has announced the dosing of the first patient in a Phase 1b clinical trial evaluating THN391, a potential first-in-class humanized monoclonal antibody designed to target chronic neuroinflammation in Alzheimer's disease. The Sacramento-based clinical-stage biotech company is pioneering an approach that addresses vascular dysfunction-driven neurodegeneration through selective targeting of toxic fibrin deposits.
Novel Mechanism Targets Neuroinflammation
THN391 represents a departure from traditional Alzheimer's therapeutic approaches by selectively targeting the inflammatory epitope on fibrin, a protein involved in blood clotting that can accumulate in brain tissue and trigger destructive inflammatory cascades. In preclinical studies using Alzheimer's disease models, THN391 demonstrated protective activity against neuronal degeneration by blocking the activation of inflammatory pathways caused by toxic fibrin deposits.
The drug's mechanism addresses what researchers increasingly recognize as a key driver of neurodegeneration: chronic neuroinflammation resulting from vascular dysfunction. This approach comes as mounting evidence points to the critical role of vascular pathology in Alzheimer's disease progression.
Phase 1a Safety Profile Supports Advancement
Prior to the current Phase 1b trial, THN391 underwent evaluation in a randomized, double-blind, placebo-controlled Phase 1a study in healthy volunteers. The trial demonstrated that THN391 was well-tolerated, with no serious or drug-related adverse events reported. Importantly, the antibody showed no adverse effects on coagulation parameters, addressing a key safety concern given fibrin's role in blood clotting.
The Phase 1a study also revealed favorable pharmacokinetic properties, with THN391 exhibiting dose-proportional pharmacokinetics and a 40-day half-life that supports monthly dosing regimens. This extended half-life could provide significant advantages for patient compliance and treatment convenience.
Phase 1b Trial Design and Endpoints
The ongoing Phase 1b trial employs a randomized, double-blind, placebo-controlled design to assess the safety, tolerability, and pharmacokinetics of multiple ascending doses of THN391. The study targets patients aged 65-85 years with early Alzheimer's disease and documented vascular risk factors, reflecting the drug's mechanism of action.
The trial structure includes at least three dose cohorts, with patients in each cohort receiving three monthly doses of THN391 or placebo, followed by evaluation extending to five months. Beyond standard safety and pharmacokinetic assessments, the study incorporates comprehensive biological and clinical endpoints designed to detect early signs of efficacy.
These assessments include pharmacodynamic disease biomarkers measured in both plasma and cerebrospinal fluid, MRI imaging studies, and cognitive evaluations. The multi-modal approach aims to capture potential therapeutic effects across different aspects of Alzheimer's pathology and clinical presentation.
Expert Perspective on Therapeutic Potential
Brad Navia, M.D., Ph.D., Chief Medical Officer – Neurology of Therini Bio, emphasized the significance of the therapeutic approach. "THN391 represents a promising new approach to treating Alzheimer's disease by directly addressing one of its primary causes, neuroinflammation," said Navia, whose experience includes leadership roles at Johnson & Johnson, Eisai Pharmaceuticals, and Sunovion Pharmaceuticals.
Navia highlighted the timing of the development, noting that "its development also comes at an exciting time in the field as more research emerges on the important role of vascular dysfunction in AD." He emphasized that the flexible trial design enables engagement with an early Alzheimer's population known to have vascular risk factors while employing innovative biomarkers aimed at detecting early signs of efficacy.
Company Pipeline and Investment Support
Therini Bio is developing a pipeline of potential first-in-class therapies that selectively target toxic fibrin accumulation across multiple diseases where destructive neuroinflammation plays a central role. Beyond Alzheimer's disease, the company's pipeline includes treatments for Diabetic Macular Edema, expanding the potential applications of their fibrin-targeting platform.
The company has assembled a notable syndicate of life sciences investors, including the Alzheimer's Drug Discovery Foundation, Angelini Ventures, Apollo Health Ventures, SV Health Investors' Biotech Fund and Dementia Discovery Fund, Dolby Family Ventures, Dreavent Biotech Investments, Eli Lilly and Company, Foundation for a Better World, MRL Ventures Fund (the therapeutics-focused corporate venture fund of Merck & Co., Inc.), and Sanofi Ventures.
Timeline and Next Steps
Initial data from the Phase 1b trial is expected to be available in mid-2026. The comprehensive endpoint assessment strategy, including biomarker analysis and cognitive evaluations, is designed to provide insights into both safety and potential efficacy signals that could inform future development decisions.
The trial's focus on patients with early Alzheimer's disease and vascular risk factors aligns with growing recognition of the heterogeneous nature of Alzheimer's pathology and the potential for targeted therapeutic approaches based on underlying disease mechanisms.
