Abpro and Celltrion's ABP-102/CT-P72 Shows Promise as Best-in-Class HER2 T-Cell Engager
核心洞察
Preclinical data presented at AACR 2025 demonstrates ABP-102/CT-P72 (搜索)'s superior tumor selectivity and reduced toxicity compared to existing HER2 (搜索)-targeted T-cell engagers.
The novel bispecific antibody showed up to two-fold greater tumor suppression versus runimotamab biosimilar while maintaining safety at doses 180 times higher than the parental antibody's maximum tolerated dose.
Developed through Abpro (搜索) and Celltrion's strategic partnership, ABP-102/CT-P72 (搜索) targets HER2 (搜索)-positive cancers that represent up to 30% of breast, gastric, pancreatic, and colorectal malignancies.
Abpro (搜索) Holdings and Celltrion unveiled promising preclinical data for their jointly developed HER2 (搜索) x CD3 (搜索) T-cell engager, ABP-102/CT-P72 (搜索), at the American Association for Cancer Research (AACR) Annual Meeting 2025. The data suggests the bispecific antibody could potentially overcome key limitations of existing HER2-targeted therapies by offering enhanced tumor selectivity, potent efficacy, and an improved safety profile.
The tetravalent bispecific antibody is engineered to selectively target HER2 (搜索)-overexpressing tumors while minimizing activity against normal tissues with low HER2 expression, addressing a significant challenge in current HER2-targeted therapies.
"These compelling preclinical data position ABP-102/CT-P72 (搜索) as a potential best-in-class HER2 (搜索)-targeting bispecific T-cell engager," said Robert J. Markelewicz, Jr., MD, MMSc, Chief Medical Officer of Abpro (搜索). "The demonstrated ability to drive tumor-selective cytotoxicity while mitigating toxicity challenges seen with prior HER2 T-cell engagers marks a significant advancement in the field."
Key Preclinical Findings
The data presented at AACR highlighted several advantages of ABP-102/CT-P72 (搜索) over existing therapies:
-
Selective Tumor Targeting: The antibody demonstrated potent cytotoxicity against HER2 (搜索)-overexpressing breast and gastric cancer (搜索) models while significantly reducing activity against HER2-low cells.
-
Superior Tumor Suppression: In vivo studies showed up to two-fold greater tumor inhibition compared to a biosimilar of runimotamab, a benchmark HER2 (搜索) x CD3 (搜索) bispecific antibody.
-
Minimized Cytokine Release: The functionally monovalent CD3 (搜索) binding design reduced cytokine-related toxicities in HER2 (搜索)-low cell models while maintaining strong cytotoxic effects in HER2-high models.
-
Exceptional Tolerability: Dose escalation studies in cynomolgus monkeys showed ABP-102/CT-P72 (搜索) was well-tolerated even at doses exceeding 180 times the maximum tolerated dose of the parental antibody.
Soo Young Lee, Senior Vice President and Head of the New Drug Division at Celltrion Inc., emphasized the significance of these findings: "ABP-102/CT-P72 (搜索) represents a breakthrough in the bispecific antibody space, addressing the long-standing toxicity barriers that have hindered the development of HER2 (搜索)-targeted T-cell engagers. The strong preclinical efficacy and safety data support its potential to redefine treatment options for patients with HER2-positive cancers."
Addressing a Significant Unmet Need
HER2 (搜索)-positive cancers represent up to 30 percent of all cases of breast, gastric, pancreatic, colorectal, and other forms of cancer. While HER2-targeted therapies have revolutionized treatment for these malignancies, existing approaches often face challenges with on-target, off-tumor toxicity due to HER2 expression in normal tissues.
ABP-102/CT-P72 (搜索)'s unique design features a tetravalent IgG1-[L]-scFv format that enables bivalent HER2 (搜索) binding with functionally monovalent CD3 (搜索) engagement. This architecture is specifically designed to optimize tumor selectivity and reduce cytokine-related toxicity, potentially offering a safer alternative to previous HER2-targeting T-cell engagers.
Strategic Partnership
The development of ABP-102/CT-P72 (搜索) stems from an exclusive collaboration between Abpro (搜索), a Massachusetts-based biotechnology company focused on next-generation antibody therapies, and Celltrion, a leading South Korean biotechnology company ranked among the world's top 25 by market capitalization.
The partnership leverages Abpro (搜索)'s proprietary DiversImmune® platform and Celltrion's extensive experience in biopharmaceutical development and commercialization. Together, they aim to advance ABP-102/CT-P72 (搜索) for the treatment of HER2 (搜索)-positive breast, gastric, pancreatic, colorectal, and other cancers.
Path Forward
Based on the encouraging preclinical results, Abpro (搜索) and Celltrion plan to initiate clinical trials for ABP-102/CT-P72 (搜索) in the first half of 2026. The companies believe the antibody's broader therapeutic window could allow for more effective dosing strategies in patients with HER2 (搜索)-positive cancers.
"The combination of HER2 (搜索)-selective T-cell activation, reduced cytokine release in HER2-low environments, and high tolerability in non-human primates underscores how ABP-102/CT-P72 (搜索)'s functionally monovalent CD3 (搜索) binding strategy successfully mitigates on-target off-tumor toxicity," explained Dr. Markelewicz. "These attributes position ABP-102/CT-P72 as a potentially safer alternative to previous HER2-targeting T-cell engagers."
As the development of ABP-102/CT-P72 (搜索) progresses, oncologists and patients alike will be watching closely to see if these promising preclinical results translate into clinical benefits for those battling HER2 (搜索)-positive cancers.