Antibody discovery platform

The bispecific/trispecific TCE platform

Antibody–cytokine fusion proteins

The PROTiNb (proteolysis targeting intra-nanobody) platform

Antibody discovery platform

Mammalian cell display platform

Mouse hybridoma

Phage display

NGS

AI-powered drug design

Rabbit single B cell

Mammalian cell display platform

Benefits

Single copy—connection between genotype and phenotype

Display of VHH, IgG and bsAb antibody structures

Identical post-translational modifications for better druggability

Cell surface display; high expression levels

Capacity up to 10E7

Applications

Significantly reduced time to lead compounds

Activity analysis during the high-throughput screening phase

Display and screening for multi-functional antibodies

Directed evolution—affinity maturation, druggability optimization, targeted mutagenesis

Discovery of antibodies with complex structures

NGS/AI-enabled drug development

The bispecific/trispecific TCE platform

The low infiltration of T cells and the suppressive tumor microenvironment significantly inhibit T cell engager's (TCE) therapeutic efficacy in solid tumors. Our trispecific T-cell engager (TCE) platform, utilizing proprietary nanobodies, incorporates second signals to mimic dual-signal T-cell activation. This approach effectively activates T cell proliferation within the tumor microenvironment, addressing T-cell dysfunction or apoptosis that arises from insufficient second signals. The next-generation nanobody-based trispecific TCE can preferentially target CD8+ T cells, inducing stronger cytotoxic activity and lower cytokine toxicity. Our Fibody platform replaces CH1/CL of the antibody moiety with a receptor/ligand to avoid light chain mispairing and enhance the activation mechanism of the T cell's third signals (cytokines). The platform can be used to construct TCEs from IgGs.

We have developed the TCE platform with anti-TCR/CD3 nanobodies, instead of traditional anti-CD3 FAB/scFv, thereby avoiding complex protein engineering.

The next-generation trispecific TCEs, incorporating co-stimulatory signals or exhibiting CD8+ T-cell bias, demonstrate greater efficacy compared to traditional bispecific TCEs.

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●Compared to traditional anti-CD3 FAB/scFv, anti-TCR/CD3 nanobodies are smaller and can avoid light chain mispairing, laying a solid foundation for constructing trispecific TCEs.

●Human/cynomolgus monkey cross-reactivity makes it easier to assess toxicities.

●The second signals of the next-generation trispecific TCEs help better activate T cells, solving the problem of T cell exhaustion when only first signals are present.

●The next-generation trispecific TCEs with CD8+ T cell-bias demonstrate stronger cytotoxicity and lower cytokine risk.

We develop a TCE platform with anti-TCR/CD3 nanobodies, instead of traditional anti-CD3 Fab/scFv, and avoid complex protein engineering.

Next-generation T-cell-engaging (TCE) trispecific antibodies with second signals/CD8 bias modifications demonstrate greater efficacy compared to traditional TCE bispecific antibodies.

Existing bispecific antibody technologies are facing challenges of druggability due to complex structures, or lack of general application due to reliance on VHH, scFv, etc.

Fibody is designed based on our early experience of fusion protein development. A receptor/ligand replaces CH1/CL of the antibody moiety to avoid light chain mispairing and retain the antibody conformation for greater druggability.

Antibody–cytokine fusion proteins

Currently, about 70% of cancer patients do not respond to immune checkpoint inhibitor (ICI)-based therapies with CD8+ T cell exhaustion being the main contributing factor. IL-10 has been found to exhibit greater cytotoxicity by directly activating terminally exhausted tumor-infiltrating CD8+ T cells. IL-10 has proven to be relatively safe in Phase I/Phase Ib clinical trials. However, IL-10 can cause severe side effects, such as grade 3-4 hematological toxicity, limiting its development and clinical applications.

Given that, we have developed the IL-10M platform. The activity of IL-10M is reduced through engineering, after which the IL-10M/antibody fusion protein is formulated. The fusion protein is enriched in the tumor microenvironment via the antibody moiety, which reduces toxicity and enhances efficacy. We have developed several fusion proteins with promising pre-clinical anti-tumor efficacy. These engieered molecules include FP008 (IL-10M/anti-PD-1), FPE017 (IL-10M/anti-EGFR), and FPR016 (IL-10M/anti-VEGFR2).

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The PROTiNb (proteolysis targeting intra-nanobody) platform

While similar technologies are at their nascence, ours is at the global forefront, demonstrating substantial potential.

Degrading undruggable targets (higher specificity than PROTACs)

Demonstrating superior safety profile thanks to the specific binding property of antibodies

Selecting E3 ligase from a wide range (wider than PROTACs), irrespective of the E3 expression levels at different sites; broad application enhanced by the ability to engineer the effector molecule