Affinity (Shanghai) Biopharmaceutical Co., Ltd. announced a groundbreaking achievement at the 2026 American Association for Cancer Research (AACR) Annual Meeting: the world’s first dualpayload ADC technology incorporating a panRAS inhibitor. Leveraging its tumor microenvironmentactivated TMEA linker platform, the company’s drug candidates IMD2146 and an undisclosed TAA candidate enable simultaneous and rapid release of panRAS inhibitor and Topo1 inhibitor (Topo1i) specifically in the tumor microenvironment.

Using its proprietary Legumainactivatable linker, Affinity has achieved synchronized, rapid release of dual payloads upon Legumain activation, generating high local concentrations of active molecules within the tumor microenvironment. The tumorspecific linker avoids damage to normal tissues by panRASi, while potent antitumor activity has been validated in drugresistant models. This breakthrough overcomes two major industry bottlenecks: offtarget toxicity of panRASi and Topo1ibased ADC resistance. It eliminates toxicities of conventional panRASi in normal tissues (e.g., skin) and delivers synergistic antitumor activity via corelease of dual payloads, even in resistant tumors. It demonstrates promising clinical translation potential as highly effective, welltolerated, and broadspectrum therapy for both KRASmutant and wildtype solid tumors.

Bispecific Antibody-Based Dual-Load ADC with Synchronous Release Design

IMD2146 showed robust antitumor activity, whereas singlepayload ADC (EGFRTROP2TMEAlinkerDXd) did not achieve tumor shrinkage greater than 60%

IMD2146 Plasma Stability and Safety Study Data

· A. At 37°C, less than 1% of free panRASi (QHLP1711) was released from IMD2146 in human plasma from day 7 to day 21, confirming excellent stability.

· B.Cynomolgus monkey PK: High plasma levels of intact IMD2146 with minimal free panRASi and free DXd further validated stability in circulation.

By addressing core pain points in targeted therapy development, Affinity’s data provides a breakthrough solution for RASmutant tumors and ADC resistance. The technology validates that the TMEA linker platform can be extended to additional target combinations and is poised to become a universal platform for nextgeneration ADCs.

About IMD2146

Using the dualpayload TMEA linker, Affinity conjugated panRASi (QHLP1711) and DXd to an EGFRTROP2 bispecific antibody to create IMD2146, the world’s first bispecific dualpayload ADC incorporating a panRAS inhibitor. The highly hydrophilic linker resolves longstanding CMC challenges of conventional dualpayload ADCs and enables homogeneous manufacturing with a drugtoantibody ratio (DAR) of 8+8.

Affinity’s TMEA linker is a clinically validated, tumor microenvironment (TME)specific activation technology. It is only activated by Legumain, which is highly expressed in the tumor microenvironment but nearly absent in dermal endothelial cells, thereby eliminating skin toxicity at the source.

About the American Association for Cancer Research (AACR)

The AACR Annual Meeting is a premier global platform for advancing cancer research. Scientists, clinicians, healthcare providers, cancer survivors, patients, and advocates convene annually to share cuttingedge breakthroughs. The congress spans population science, prevention, cancer biology, translational and clinical research, survivor care, and patient advocacy, showcasing the full spectrum of innovative cancer science and medicine.

About Affinity (Shanghai) Biopharmaceutical Co., Ltd. ("Affinity")

Leveraging its globally first-in-class and proprietary Tumor Microenvironment-Activated (TMEA) technology platform, Affinity develops and advances highly selective, low-toxicity innovative anti-cancer drugs. The company is dedicated to solving the toxicity challenges of traditional chemotherapy and targeted therapies, focusing on unmet medical needs in oncology, with the potential to transform traditional treatment approaches and reshape the cancer care paradigm.

Looking ahead, Affinity aims to become a fully integrated biopharmaceutical company with robust manufacturing and commercialization capabilities.

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