Therini Bio, Inc., a clinical-stage biotech company, has announced positive results from a Phase 1a trial of its lead candidate THN391 in healthy volunteers. The novel monoclonal antibody, designed to treat neurodegenerative diseases by targeting fibrin-driven neuroinflammation, demonstrated favorable safety and pharmacokinetic profiles that support further clinical development.
The randomized, double-blind, placebo-controlled trial evaluated single and multiple ascending doses of THN391, with results showing the drug was well-tolerated with no Serious Adverse Events reported. Importantly, the antibody maintained a clean hematological profile without interfering with coagulation and fibrinolysis pathways, a critical safety consideration for this mechanism of action.
"The results of this trial mark an important milestone for a new class of drugs for the treatment of neurodegenerative diseases," said Tara Nickerson, Ph.D., Chief Executive Officer of Therini Bio. "By targeting vascular dysfunction and chronic neuroinflammation, we aim to address fundamental root causes of neurodegeneration."
Novel Mechanism Targeting Vascular Dysfunction
THN391 represents a potential first-in-class therapy with a unique approach to treating neurodegenerative conditions. The high-affinity, humanized monoclonal antibody selectively blocks fibrin-mediated neuroinflammation without disrupting normal coagulation processes.
The scientific rationale stems from the understanding that at sites of vascular dysfunction, deposited fibrin binds to complement receptors on innate immune cells, triggering inflammation and subsequent neuronal damage in both the brain and retina. Preclinical studies in Alzheimer's disease and retinal disease models showed that antibodies blocking fibrin inflammation effectively protected against vascular and neuronal degeneration.
This approach differs from many current neurodegenerative disease treatments that target downstream effects rather than underlying causes of neuronal damage.
Pharmacokinetic Profile Supports Monthly Dosing
A key finding from the Phase 1a trial was THN391's pharmacokinetic profile, which demonstrated dose-proportional exposure and a half-life that supports once-monthly dosing. This dosing schedule could offer significant advantages for patient compliance and quality of life compared to more frequent administration regimens.
Additionally, the drug did not induce an anti-drug antibody response in trial participants, suggesting a reduced risk of treatment-limiting immunogenicity with repeated dosing.
Upcoming Clinical Development
The company plans to present detailed data from this trial at the Alzheimer's Association International Conference 2025 (AAIC 25) in Toronto, Canada, on July 30, 2025.
Building on these positive Phase 1a results, Therini Bio intends to immediately advance THN391 into two Phase 1b trials. These studies will evaluate the drug in patients with Alzheimer's Disease and Diabetic Macular Edema, two conditions where destructive neuroinflammation plays a central role in disease progression.
"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," Dr. Nickerson added.
Market Context and Unmet Needs
Neurodegenerative diseases represent a significant global health burden with limited effective treatment options. Alzheimer's disease alone affects approximately 6.7 million Americans, with numbers expected to rise dramatically as the population ages. Current therapies primarily focus on symptom management or target specific pathological features like amyloid plaques, but have shown limited success in modifying disease progression.
Diabetic Macular Edema, a leading cause of vision loss in working-age adults with diabetes, similarly lacks treatments that address underlying vascular and inflammatory mechanisms.
THN391's novel approach targeting fibrin-driven neuroinflammation could potentially address fundamental disease mechanisms common to multiple neurodegenerative conditions, offering hope for more effective treatment options.
About Therini Bio
Therini Bio specializes in developing immunotherapies for neuroinflammation in diseases driven by vascular dysfunction. The company's pipeline focuses on potential first-in-class therapies that selectively target toxic fibrin accumulation in conditions where neuroinflammation plays a central role.
The company is backed by an impressive syndicate of life sciences investors, including the Alzheimer's Drug Discovery Foundation, SV Health Investors' Biotech Fund and Dementia Discovery Fund, Angelini Ventures, Apollo Health Ventures, Dolby Family Ventures, Dreavent Biotech Investments, Eli Lilly and Company, Foundation for a Better World, MRL Ventures Fund (Merck & Co., Inc.), and Sanofi Ventures.
