Technology

Patients with Herceptin-resistant or recurrent breast cancer.

AP402, developed by AP Biosciences and integrated with T-cube Bispecific Antibody Platform, specifically targets the p95HER2 variant, a common HER2 variant that lacks the extracellular domain, making it untargetable by conventional HER2 therapies. This variant is expressed in 30-40% of HER2+ breast cancer cases and is associated with poorer outcomes. AP402 addresses this challenge by activating CD137 to induce multiple anti-tumor responses, including antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). By targeting HER2 variants and activating T cells, AP402 enhances T cell activity within the tumor microenvironment, offering a potentially effective and durable treatment for patients with resistant forms of HER2-positive breast cancer.

1. Completion of functionality validation by cell-based assay and animal model.
2. Ongoing CMC manufacturing, pharmacokinetics studies, and toxicology research for AP402.
3. Undergoing patent reviews in multiple countries.

1. 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 HER2v on cancer cells. This design minimizes the risk of cytokine release syndrome typically associated with CD3-based bispecific antibodies, ensuring higher safety levels.
2. The bivalent binding activity of AP402 to both HER2v and CD137 is superior to monovalent binding of other bispecific antibodies. AP402 can efficiently trigger CD137 activation in T cells through HER2v clustering.
3. The oppositely binding regions of HER2v and CD137 facilitate the bridging between HER2v-expressing cancer cells and CD137-expressing T cells without spatial hindrance.
4. Simultaneously harnessing the anti-tumor mechanisms of ADCC, CDC, and ADCP similar to monoclonal antibody, to enhance the tumor-suppressive effects through multiple mechanisms.
5. 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.

Heterogeneity is the one of the main challenges in breast cancer treatment. Gene expression analysis reveals at least five distinct biological subtypes of breast cancer. Advances in molecular biology have led to a trend in breast cancer treatment to find specific factors within a patient's cancer cells and target the individual processes related to cancer cell growth, differentiation, life cycle, or vascular nourishment, known as "personalized therapy" or "targeted therapy." Approximately 25-30% of breast cancer patients have HER2 overexpression in their tumors, and research has shown that the prognosis for these patients is worse than those without HER2 overexpression. Targeted therapy for HER2, most notably the humanized monoclonal antibody "Herceptin," activates the host immune response by binding to the HER2 receptor on the surface of breast cancer cells. This, in turn, leads to the clearance of breast cancer cells by macrophages and effector cells, contributing significantly to the improved survival rates for breast cancer patients over the past few decades.

However, for other patients who are not eligible for or who develop resistance to Herceptin, it has been discovered that this may be due to the presence of different-sized HER2 variants (HER2v). APBio has pioneered the development of AP402, a fully human bispecific antibody created using the T-cube platform. This innovative antibody can simultaneously target both HER2v and CD137 and achieved anti-tumor activity through multiple mechanisms in the TME. It offers treatment options for breast cancer patients with Herceptin resistance or relapse.