xB3 platform to enhance blood brain barrier crossing

xB3 platform: Enabling Targeted CNS Delivery

The xB3 platform is a proprietary technology designed to overcome one of the most significant barriers in neurology: the blood-brain barrier (BBB).

How xB3 Works

Derived from melanotransferrin, xB3 utilizes the low-density lipoprotein-related protein 1 (LRP1) as a receptor for its action. The LRP1 receptor is specifically expressed on the endothelium of cerebral vessels (Strickland & Muratoglu, Arteriosl Thromb Vasc Biol 2016). xB3 carries payloads across the BBB via a process of endocytosis and transcytosis.

Payload Flexibility

This transport is applicable to a variety of active molecules including antibodies, enzymes and oligonucleotides, with a potential for repurposing them in a tailored manner for CNS delivery drugs with proven pharmacological efficacy.

The xB3 technology is exclusively licensed from Bioasis Technology Inc, Canada/US, for use in neuroinflammatory conditions.

xB3 Platform Illustration

Superior Performance Over Other BBB Technologies

The xB3 technology demonstrated successful delivery of siRNA, IL-1 receptor antagonists, and monoclonal antibodies, such as trastuzumab into the brain. For example, when coupled to trastuzumab, xB3 allowed its delivery and clinical efficacy against brain metastatic HER2 positive cancer cells. Trastuzumab alone failed to pass the blood brain barrier.

In the figures, trastuzumab conjugated to xB3 (here labelled as BT2111) penetrates into the brain and is significantly more efficacious than trastuzumab alone (here BTA) for cancer cell destruction (Nounou et al 2016)

Moreover, xB3 increases penetration and increase CNS exposure to large biological molecules by selective expression of receptors on brain vessels.

xB3 Performance Comparison

Applications in Autoimmune Neuroinflammatory Disorders

Across Pharmaceuticals Inc is advancing xB3-conjugated therapies to enhance CNS penetration of biologics, to optimize their specific anti-neuroinflammatory effects in the brain and to reduce exposure in the general circulation.

The aimed initial target indications are:

  • Auto-immune central neuroinflammatory disorders, including multiple sclerosis, Alzheimer’s disease and Huntington’s disease.

The toxicology and GMP manufacturing have been optimized with xB3. Hence, by combining with approved compounds, preclinical experiments can rapidly progress from preclinical to clinical development.

Across Pharmaceutical’s lead program, xB3 + EGF, is poised to transform treatment paradigms in multiple sclerosis by combining targeted delivery with powerful regenerative action.

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