Oncology Antibody Candidates

Trellis’ cancer monoclonal antibodies follow in the footsteps of recent scientific advances made towards targeted approaches against tumors, via antibodies targeting well-characterized tumor-associated antigens and immune checkpoint modulators. Trellis is the first company to characterize anti-ICM antibodies naturally present in healthy immune systems.


Immune Checkpoint Modulators (ICMs) and Tumor-Associated Antigens (TAAs)

Cancer is the second most common cause of death in the United States, accounting for nearly 1 in 4 deaths, 595,000 deaths estimated in 2016 (American Cancer Society).

Most Lethal Types:
- Lung and bronchial
- Colorectal
- Pancreatic
- Breast
- Liver and intrahepatic bile duct
- Prostate

Cancer Incidence Rates by State, 2008-2012 (all cancer types, per 100,000)

Sources: American Cancer Society.; North American Association of Central Cancer Registries (NAACCR), 2015.

Trellis antibodies fight cancer through two methods:

Immune Checkpoint Modulators (ICMs)

The immune surveillance concept asserts that a healthy individual’s immune system not only neutralizes foreign agents but also eliminates emerging tumor cells before they cause overt disease.

One of the methods in which cancer proliferates is through the supression of the patient’s immune system via immune checkpoint modulators (ICMs).

Anti-ICM antibodies blocking the PD-1/PD-L1 interaction between T Cells and cancer cells have demonstrated great success against multiple types of cancer in clinical trials.

However, anti-PD-1/anti-PD-L1 antibodies do not cover the entire breadth of cancer types. Fully successful treatment will likely require multiple anti-ICM antibodies which offer a robust immune checkpoint blockade, in combination with other methods.

Trellis antibodies, Anti-KIR and Anti-TIM3 mAbs target novel receptors implicated in the immune checkpoint interaction and aid stimulation of the natural immune system, thereby improving the body’s natural ability to fight cancer.

CellSpot identified optimal mAb, TRL8605 (green curve),
with greatest binding affinity to KIR2DL3 extracellular domain.

Tumor-Associated Antigens (TAAs)

Other Trellis antibodies target TAAs, like TRL10001 that recognizes the extracellular domain of Anaplastic Lymphoma Kinase (ALK).

ALK plays a role during the development of the nervous system and is associated to many cancers including lung, thyroid and many brain tumors, while is not present in normal tissues.

TRL10001 is high affinity (100pM) human antibody that rapidly internalizes in neuroblastoma cells, which makes it an ideal candidate for an Antibody Drug Conjugate.

Antibodies, including our Anti-ALK candidate, which target tumor-associated antigens, may function as antibody conjugates and therefore be coupled with small molecule drug treatments. Due to the antibody specificity, the coupled conjugates can deliver concentrated doses of the drug directly to the tumor cell, minimizing side effects by sparing healthy tissue.

In vitro pulse-chase experiment:
Trellis anti-ALK mAb, TRL10001, bound to ALK-expressing cells and was internalized within 30 minutes.

Frequencies of memory B-cells specific for ICMs are very low (single digits per 105 B-cells) but Trellis has found and cloned high affinity antibodies to several ICMs: KIR, TIM-3 B7-H3, LAG-3 and CEACAM1:

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