About TB006

Introduction to Drugs and Mechanisms

TB006 is an investigational drug for the treatment of Alzheimer’s disease/dementia, which has shown promising safety and preliminary efficacy in a Phase IIa clinical trial. Based on these positive results, the drug has been approved for inclusion in the Expanded Access Program (EAP) to provide early access to patients with unmet needs.

In 2023, TB006, developed by TrueBinding, received FDA approval to initiate an expanded access program for a moderate number of patients—the only such program approved that year. This program has been extended in 2024 and 2025, aiming to provide this promising investigational therapy to eligible demented patients (including Alzheimer’s Disease, Parkinson’s Disease, Frontal Temporal Dementia, and Lewy Body Dementia) who lack other effective treatment options.

TB006 offers a potentially novel anti-inflammatory therapeutic approach by targeting the galactolectin-3 (Gal3) protein.

TB006 has potential to reverse AD progress by blocking Gal-3

TB006 has potential to reverse AD progress by blocking Gal-3, which could promote Abeta oligomerization, plaque formation and tau pathology. Alzheimer’s Disease is a brain disorder that starts slowly, then gradually worsens and robs people of their memory as well as other cognitive abilities that are required for daily living. It leads to the most common form of dementia and is characterized by abnormal clumping of amyloid beta (Abeta) proteins into toxic plaques, as well as the aggregation of hyperphosphorylated tau into neurofibrillary tangles. These pathological deposits disrupt neuronal communication, ultimately leading to cognitive decline.

In addition to amyloid plaques, another key protein, Galectin-3 (Gal3), has been implicated in the pathogenesis of Alzheimer’s disease (AD). Gal3 is found at abnormally high levels in the brains of AD patients, where it binds to amyloid-beta (Aβ) and facilitates its aggregation. Acting as a molecular scaffold, Gal3 promotes the self-assembly of Aβ into toxic oligomers and plaques. These Aβ deposits accumulate on neuronal surfaces, disrupting synaptic signaling and contributing to cognitive decline in AD.

TB006 is an investigational monoclonal antibody designed to target Gal3. By selectively binding to Gal3, TB006 inhibits its adhesive function, thereby preventing the aggregation of Aβ, facilitating the dissolution of existing plaques and reducing tau pathology. This mechanism restores synaptic integrity, potentially mitigating neurotoxicity and improving cognitive function in AD patients.

TB006 has potential to reverse AD progress by blocking Gal-3

TB006 has the potential to reverse the progression of Alzheimer’s Disease (AD) by blocking Gal-3, which may otherwise promote amyloid-beta (Aβ) oligomerization, plaque formation, and tau pathology. Alzheimer’s Disease is a neurodegenerative disorder that begins gradually, progressively impairing memory and other cognitive
functions essential for daily living. It is the most common cause of dementia and is characterized by the abnormal accumulation of Aβ proteins into toxic plaques, as well as the aggregation of hyperphosphorylated tau into neurofibrillary tangles. These pathological deposits disrupt neuronal communication, ultimately leading to cognitive decline.

This dual effect on Aβ and tau helps restore synaptic integrity, potentially mitigating neurotoxicity and improving cognitive function in patients with Alzheimer’s Disease.

Targeting Galectin-3

In Alzheimer’s Disease, overactivated microglia contribute to chronic neuroinflammation, which exacerbates neuronal damage and accelerates cognitive decline. TB006 targets Gal-3, a key regulator of microglial activation, and by blocking Gal-3, it helps normalize microglial activity. This reduces the release of pro-inflammatory cytokines, prevents further neuronal injury, and may create a more favorable environment for the clearance of amyloid-beta plaques and tau aggregates. This multifaceted mechanism helps restore synaptic integrity, potentially mitigating neurotoxicity and improving cognitive function in patients with Alzheimer’s Disease.

Low-complexity domains (LCDs) — flexible, disordered protein regions that drive neurodegeneration through pathological protein aggregation. A key focus is the LCD of Galectin-3, a protein increasingly implicated in diseases like Alzheimer’s and Parkinson’s.Galectin-3’s N-terminal LCD acts as a molecular “sticky switch” that promotes aggregation in two main ways:

Self-association and scaffolding, forming oligomers that capture misfolded proteins like amyloid-beta or alpha-synuclein.
Liquid-liquid phase separation (LLPS), creating dense droplets that concentrate amyloidogenic proteins and accelerate toxic aggregate formation.

Beyond aggregation, Galectin-3’s LCD also fuels neuroinflammation by:

Activating microglia (the brain’s immune cells),
Creating a vicious feedback loop between aggregation and inflammation,
Directly amplifying inflammatory signaling via receptor clustering.

In essence, Galectin-3’s LCD is a critical driver of both protein aggregation and chronic inflammation—two central, self-reinforcing mechanisms in neurodegenerative disease progression. To learn more about TB006, you can also visit the site https://www.truebinding.com/ourscience

Promising Preclinical Results

The potential therapeutical efficacy of TB006 was supported by strong pre-clinical AD animal model studies. Significant reduction in total Abeta plaques and other neurodegeneration biomarkers were achieved after just two -week treatment with mTB001, a surrogate of TB006, in two transgenic (APPSwe, 5xFAD) and Abeta injection induced AD mouse models

Galectin-3’s N-terminal LCD acts as a molecular “sticky switch” that promotes aggregation in two main ways:

Self-association and scaffolding, forming oligomers that capture misfolded proteins like amyloid-beta or alpha-synuclein.
Liquid-liquid phase separation (LLPS), creating dense droplets that concentrate amyloidogenic proteins and accelerate toxic aggregate formation.

Beyond aggregation, Galectin-3’s LCD also fuels neuroinflammation by:

Activating microglia (the brain’s immune cells),
Creating a vicious feedback loop between aggregation and inflammation,
Directly amplifying inflammatory signaling via receptor clustering.

In essence, Galectin-3’s LCD is a critical driver of both protein aggregation and chronic inflammation—two central, self-reinforcing mechanisms in neurodegenerative disease progression.

To learn more about TB006, you can also visit the site https://www.truebinding.com/ourscience

Treatment Plan and Safety Monitoring

Dosage regimen

Patients receive an intravenous infusion of TB006 every 28 days (±5 days) at a dose of 4000 mg, with the infusion time being approximately 1 hour.

Treatment duration

Treatment will continue while benefits outweigh risks and the study or TB006 development has not been terminated or approved locally.

Safety Monitoring

Patient safety will be monitored through clinical and laboratory assessments, imaging and cognitive testing, with only adverse events and serious adverse events collected by the sponsor.

Eligibility and Project Scale

Key qualification criteria:

Patients diagnosed with mild, moderate, and moderate-to-severe Alzheimer’s disease, and whose other health conditions are well-controlled and stable.
Unable to receive other Alzheimer’s disease drug treatments due to intolerance, contraindications, or poor efficacy;
Unable to or ineligible to participate in any Alzheimer’s disease clinical trials.
LGAL3 SNP gene testing, complete blood count, blood biochemistry, liver and kidney function tests, and electrocardiogram all meet the requirements.

Number of participants:

This project is an open program with no upper limit on the number of participants.

Statistics and Supervision

Statistical considerations:

Safety analysis will be performed on all patients who received at least one dose of TB006. Adverse events will be coded using the latest version of the Medical Dictionary of Regulatory Activities (MedDRA) and their incidence will be statistically analyzed by system organ classification and preferred terminology, while also being categorized and summarized according to severity, relevance to treatment, and circumstances leading to discontinuation of treatment. No pre-defined statistical analysis plan exists.

Data monitoring:

No dedicated data monitoring committee has been established.

Frequently Asked Questions

Are there any ongoing clinical trials for TB006?

TrueBinding has completed patient recruitment for its Phase Ib/II clinical trial and open-label extension (OLE) trial of TB006 for the treatment of Alzheimer’s disease.

What is the Expanded Early Access Program?

Expanded Access Program (also known as compassionate use) is a program that allows patients with serious or life-threatening illnesses to access investigational drugs outside of clinical trials.

Is there a fee to participate in this project?

Currently, participation in the TB006 Extended Early Access Program incurs associated costs.