Proprietary Technology Platform
BsAbs (bispecific antibodies) can recognize two epitopes on the same target or two different targets concurrently to provide improved efficacy via multiple molecular mechanisms or synergistic effects. However, the design principles require a high level of immunological understanding to modulating affinity ratio between targets/epitopes, and the challenges in CMC, including mis-pairing in dimerization of light and heavy chain, low yield and lack of stability, as well as narrow therapeutic index have resulted in fewer bsAbs than mAbs in the market.
YiChenBio has developed four innovative (and proprietary) technology platforms of bsAbs: Monovalent Bi-Targeting Antibody (MoBiT), Immune Checkpoint Inhibitor-Antibody Fusion (ICiAF), Tumor-relevant Immune Effector cell Modulator (TrIEM) and Directed Immune Modulatory Antibody (DIMA), which solve the key issues of current bsAbs in manufacturability and therapeutic profiles. Based on MoBiT, YiChenBio has developed a novel bsAb-drug conjugation construct (MoBi-DC) with high stability and highly homogeneous drug-to-antibody ratio (DAR).
In addition, the epitope-directed mAb screening platform enables eliciting antibody responses to the specific target epitope in vivo, and thus feasible to screen epitope-directed mAbs. The long-acting therapeutic protein platform aims to develop recombinant proteins which have pharmacological properties and CMC process similar to mAbs.
Bispecific antibody platform
MoBiT is a proprietary TAA-directed CD3 T cell engager, which overcomes the key issues of current BiTEs including difficulties in CMC and narrow therapeutic window. The advantages of MoBiT include:
- No heavy/light chain mis-pairing issues, but not using scFv, VHH
- Similar manufacturability and pharmacological properties to mAb
- Easily adapt to various therapeutic target/epitope pairs
- Capable of engaging two target cells in close proximity to enhance efficacy
- Flexible to modulate target affinities to balance potency and safety
- Smaller molecular size than mAb, improving tissue penetration
ICiAF is next generation tumor-target immune checkpoint blocker of anti-tumor mAb armed with tumor-specific immune checkpoint (IC) blocker with the following distinguished advantages:
- Highly selective immune checkpoint blockade on tumor, reducing system IC blockade
- Enhanced efficacy of anti-tumor mAb
- Easily adapt to varieties of TAA&IC pairs
- No heavy/light chain mis-pairing issues
- Similar manufacturability and pharmacological properties to mAb
- Enhanced therapeutic index in drug combination strategies
TrIEM is an innovative cytokine-antibody fusion platform applicable to various pairs of cytokine and TAA. TrIEM is expected to overcome the current barrier of immuno-cytokine in balancing long half-life and toxicity. TrIEM could significantly improve the therapeutic window while obtaining a prolonged PK profile. The advantages of TrIEM are as follows:
- Innovative cytokine-antibody fusion platform; Applicable to various pairs of cytokine and tumor antigens
- No heavy/light chain mis-pairing issues; Similar manufacturability and properties to mAb
- Enhanced therapeutic index by balanced tumor targeting and immune-cytokine activities
- Prolonged half-life
- Improved therapeutic index in combination therapy with immune checkpoint inhibitors
DIMA is a first-in-class cell-directed immunosuppressant bivalent bispecific antibody blocking IL-1 signaling.with the following distinguished advantages
- First-in-class immunosuppressant bispecific antibody blocking IL-1 signaling on inflammation relevant cells
- Similar manufacturability and pharmacological properties to mAb
- Enhanced efficacy and reducing sides effects of systemic IL-1 signaling blockade
- Optimized half-lives of the two binding motifs
Bs-ADC platform
Bispecific antibody-drug conjugates represent a fast-growing class of next generation ADCs due to their potential in enhancing specificity and internalization, improving efficacy, and overcoming drug resistance. However, compared to mAbs, the current bsAb formats are not optimal as a carrier to develop bispecific antibody conjugates for challenges such as the complicated CMC process, low stability for conjugation and difficulties in controlling DAR.
Bs-ADC, a proprietary platform based on MoBiT, is a novel bispecific antibody-drug conjugation platform to overcome the current challenges of bispecific antibody conjugates in manufacture and efficacy. Advantages of YiChen’s Bs-ADC platform includes:
- Based on innovative monovalent bispecific antibody platform (MoBiT)
- Compatible to clinically validated conjugation methods and linker/payload moieties
- High stability of the drug conjugated product
- Highly homogeneous DAR of the conjugated products
- Combination of high specificity and high internalization enables selective and high activities
Long-acting protein
Peptides and proteins account for a significant type of therapeutic modality due to their important roles in many different disease pathologies. However, the clinical potential of these biomolecules is often hampered by their inherent short serum half-life. A number of long-acting technologies can extend the half-life of protein and peptide therapeutics and significantly improve patient compliance, while also optimizing the physicochemical properties and enhancing their safety and efficacy.
- Innovative design of therapeutic protein with prolonged half-lives
- Similar manufacturability and pharmacological properties to mAb
- Low immunogenicity
Epitope directed mAb screening platform
Therapeutic antibodies often require binding to a specific epitope in an antigen to exert their functions, such as blocking ligand-receptor interactions, stimulating agonistic activities on receptors, or recruiting two proteins to form complexes. This epitope-dependence exerts a great challenge to current selection methods facing epitope bias issue: antibodies produced from hybridoma or phage screening are usually enriched to immune-dominant B cell epitopes, thus diminishing the probability of identifying antibodies binding to the desired epitopes.
Our proprietary epitope-directed mAb screening platform enables eliciting antibody responses to the specific target epitope in vivo, and coupled with a unique epitope-directed antibody selection technology make it possible to generate epitope-directed mAbs with high efficiency and rate of success.
