Indication
CD73 highly expressed cancers, such as lung cancer, pancreatic cancer, bladder cancer and ovarian cancer.
Mechanism of Action
AP601 is engineered to bind both CD73 and CD137 with high affinity, ensuring precise and efficient T cell activation only in the presence of cancer cells. Its symmetrical structure and true target-dependent T cell activation minimize the risk of cytokine release syndrome typically seen with CD3-based bispecifics. Moreover, by inhibiting CD73 activity, AP601 prevents the generation of adenosine, reducing the immunosuppressive environment and allowing for a more potent immune response. This design not only enhances the therapeutic efficacy against tumors but also maintains a favorable safety profile, making it a promising candidate for combination with other cancer therapies.
Status
- Completion of functionality validation by cell-based assay and animal model.
- Ongoing CMC manufacturing, pharmacokinetics studies, and toxicology research for AP601.
- Undergoing patent reviews in multiple countries.
Strength
- A true target-dependent T cell activation of the bispecific antibody, it activates cytotoxic T cells expressing CD137 only upon binding with both CD137 and CD73 on cancer cells. This design minimizes the risk of cytokine release syndrome typically associated with CD3-based bispecific antibodies, ensuring higher safety levels.
- The bivalent binding activity of AP601 to both CD73 and CD137 is superior to monovalent binding of other bispecific antibodies. AP601 can efficiently trigger CD137 activation in T cells through CD73 clustering.
- The oppositely binding regions of CD73 and CD137 facilitate the bridging between CD73-expressing cancer cells and CD137-expressing T cells without spatial hindrance.
- There is no hook effect for CD73 binding domain in AP601, providing a better dose-response relationship.
- The symmetrical structure expressing only heavy and light chains is advantageous for antibody expression and formation. It can be adapted the downstream purification processes established for monoclonal antibodies, eliminating the need to develop new processes for asymmetric bispecific antibodies.
Market
In the tumor microenvironment, the high expression of CD73 leads to the abundant production of adenosine, which in turn suppresses the activation of immune cells. Therefore, the strategy of inhibiting CD73 activity through CD73 antibodies is a major focus of current drug development. In clinical practice, it can be used in combination with existing cancer therapies to enhance the effectiveness of current treatments. APBio independently developed AP601 is an emerging bispecific antibody based on the T-cube bispecific antibody platform. It can simultaneously recognize CD73, inhibit CD73 activity, and activate the CD137 pathway through a triple mechanism. This enhances the killing effect of T cells or NK cells in the tumor microenvironment, ultimately leading to the elimination of tumor cells. In the future, AP601 is expected to compete in the multi-billion-dollar drug markets for various solid tumors, including lung cancer ($23.14 billion in 2022), pancreatic cancer ($2.01 billion in 2017), bladder cancer ($2 billion in 2021), ovarian cancer ($1.68 billion in 2021), and others.
Development Progress
The product is currently in the pre-clinical research phase.
- Candidate
- Target/Mechanism
- Indication
- Partner