Our Science

What is Blood-Brain Barrier (BBB)?

The Blood brain barrier (BBB) is composed of tight junctions formed around the blood vessels in the brain with endothelial cells, pericytes and astrocytes. The BBB possesses highly selective permeability, only allowing the necessary molecules  (water, carbon dioxide, and oxygen), fat-soluble substances (anesthetics and alcohols), and very small molecules with molecular weight less than 500Da to penetrate through from the blood vessel to the brain’s extracellular space.

How can you deliver therapeutics into the brain?

Generally, therapeutic antibodies, which have molecular weight of 150kDa, have  negligible BBB penetration rates below 0.1%. Large molecules like antibodies require a pathway called the receptor-mediated transcytosis (RMT) to pass through the BBB. A BBB-crossing platform would work like a ‘Trojan horse’, binding to one of the receptors expressed on brain endothelial cells, and carrying therapeutics across the BBB, into the brain.

What is special about AIMEDBIO’s BBB crossing platform?

Why do you need brain immune modulation?

Brain immune system plays crucial roles in the pathogenesis of neurodegenerative diseases and brain tumors. However, our understanding of the brain and its mechanism of immune homeostasis has been relatively poor compared with other organs. This has been a major hurdle for development of treatments for neurological diseases.

Recent advances in neuroimmunology research has shed light on how imbalances of brain immune homeostasis can lead to neurodegenerative diseases and brain tumors. By targeting key factors causing these imbalance, we aim to restore brain immune homeostasis, thereby reversing from disease state to healthy state.

How can you deliver therapeutics into the brain?

Brain Immune Homeostasis Possible cause of neurodegenerative disease and brain tumors when imbalanced

What is special about AIMEDBIO’s immune modulator development?

What are Antibody-Drug Conjugates (ADCs)?

Conventional chemotherapy for cancer is a powerful treatment but there are many unwanted adverse effects as chemotherapy agents cannot differentiate cancer cells from healthy cells. Antibody, on the other hand, can be delivered specifically to its target, but have limited potency. Combining only the advantages of these two therapeutics, ADCs are designed to specifically bind to their target cells and deliver toxin payload directly into these cells, minimizing off-target killing of healthy cells and unwanted side-effects.

ADCs are composed of 1) monoclonal antibody (mAb) that binds a specific antigen on the surface of target cells, 2) linker molecule which functions as a stable bridge between the mAb and the payload, and 3) a potent toxin payload which induces cell killing.

What is special about AIMEDBIO’s ADC?

Optimal balance between
target indication, anibody, payload

Strategic Development for brain tumor-specific targets:

Targets are selected based on big data analysis and validation through patient-derived cell and xenograft (PDC/PDX) system.

Superior linker-payload against brain tumors:

AIMEDBIO’s proprietary linker-payloads, AIMEDuoca™ and AIMEDecan™, confirmed to have higher sensitivity to brain tumors and brain metastasis tumors compared with other commonly used payloads.

Verification of ADC efficacy with patient-derived in vitro/in vivo models:

valuation of the best combination of antibody-linker-payload through:
1) in vitro high-throughput screening system using 3D-organoid
2) in vivo orthotopic PDX models which represent the genomics of tumor models

What is Multi-Omics?

Multi-omics platform helps us gain insights required for neuro-oncology and neurodegenerative disease treatment and enables us to select most relevant indications to our targets with higher speed and accuracy.

How does AIMEDBIO use Multi-Omics data?

Why is patient derived models (PDC/PDX) important?

For development of tumor-targeting drugs, immortalized tumor cell lines, are widely used. However, cell lines lack the genetic complexity found in patients, and thus may not adequately recapitulate patient tumor biology, causing difficulties in prediction of clinical outcome. 
 
Patient-derived cells (PDCs) are cells directly generated from patients’ tumor specimens, and patient-derived xenografts (PDXs) are cancer models which are made by implanting patients' tumor tissue or cells into mice. PDCs/PDXs allow for a more relevant drug efficacy assessment by representing each patient’s heterogeneous characteristics compared with cell lines. The reason cell lines are mostly used is because PDCs can be challenging to obtain and culture.