Abpro’s Holdings’ bispecific T-cell engager could become a leader in the HER2-targeting race according to preclinical data presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 yesterday. The data suggest potential for superior tumor selectivity, potent efficacy, and an improved safety profile.
“These compelling preclinical data position ABP-102/CT-P72 as a potential best-in-class HER2-targeting bispecific T-cell engager,” said Robert J. Markelewicz, Jr., MD, MMSc, Chief Medical Officer of Abpro. “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.
HER2-positive tumors represent up to 30 percent of all cases of breast, gastric, pancreatic, colorectal and other forms of cancer. The world market for HER-2 drugs for breast cancer alone is more than $3B.
ABP-102/CT-P72 is a tetravalent bispecific HER2 x CD3 T-cell engager co-developed with Celltrion. The drug is engineered to selectively target HER2-overexpressing tumors while reducing the risk of on-target, off-tumor toxicity in normal tissues.
T-cell engagers are antibodies engineered to redirect the immune system’s T cells to recognize and kill cancer cells. They are designed to work against specific target antigens expressed on a cancer cell.
Key findings presented were:
- Highly Selective Tumor Killing: ABP-102/CT-P72 achieved potent cytotoxicity in HER2-overexpressing breast and gastric cancer models while significantly reducing activity against HER2-low cells, addressing a key limitation of prior HER2-targeted T-cell engagers.
- Enhanced Tumor Growth Inhibition: In vivo studies showed ABP-102/CT-P72 had up to a two-fold increase in tumor suppression compared to a biosimilar of runimotamab, a benchmark HER2 x CD3 bispecific antibody.
- Reduced Cytokine Release: Engineered for functionally monovalent CD3-binding, ABP-102/CT-P72 minimizes cytokine-related toxicities, as demonstrated by reduced cytokine release in HER2-low cell models while maintaining potent cytotoxicity in HER2-high models.
- Improved Tolerability: Dose escalation studies in cynomolgus monkeys confirmed that ABP-102/CT-P72 was well tolerated, even at doses exceeding 180 times the maximum tolerated dose observed with the parental antibody, suggesting a broader therapeutic window.
Soo Young Lee, Senior Vice President and Head of the New Drug Division at Celltrion Inc., added, “ABP-102/CT-P72 represents a breakthrough in the bispecific antibody space, addressing the long-standing toxicity barriers that have hindered the development of HER2-targeted T-cell engagers. The strong preclinical efficacy and safety data support its potential to redefine treatment options for patients with HER2-positive cancers.”
The companies said the combination of HER2-selective T-cell activation, reduced cytokine release in HER2-low environments, and high tolerability in non-human primates underscores how ABP-102/CT-P72’s functionally monovalent CD3 binding strategy successfully mitigates on-target off-tumor toxicity.
“These attributes position ABP-102/CT-P72 as a potentially safer alternative to previous HER2-targeting T-cell engagers, paving the way for a broader therapeutic window in clinical trials, which are planned to start in the first half of 2026,” they said in their press release.
