Next-generation modality designed to overcome tumor penetration limitations of ADCs
Hanmi Pharmaceutical has unveiled a next-generation anticancer modality designed to target not only cancer cells but also the tumor microenvironment, expanding its drug discovery efforts into a new area of oncology.
The Korean pharmaceutical company said on Oct. 6 that it presented preclinical research on a small-molecule drug conjugate, or SMDC, targeting fibroblast activation protein (FAP) at Discovery on Target 2026, held in Boston from Sept. 28 to Oct. 1.
The approach is designed to address some of the limitations associated with antibody-drug conjugates, or ADCs, by using smaller molecules that can more effectively penetrate tumor tissue and reach targets within the tumor microenvironment.
Targeting FAP to Complement ADC Approaches
ADCs have emerged as a major class of anticancer therapeutics by delivering cytotoxic drugs to tumor-associated antigens expressed on the surface of cancer cells.
Their relatively large molecular size, typically around 150 kDa or more, however, can limit penetration and drug distribution within solid tumors. Access to cancer cells can be particularly challenging in tumor microenvironments densely populated with cancer-associated fibroblasts, or CAFs, and extracellular matrix components.
Hanmi Pharmaceutical has focused on SMDCs as a potential approach to complement these limitations. Because SMDCs are considerably smaller than antibody-based conjugates, the company is exploring their ability to penetrate tumor tissue and the surrounding microenvironment.
For its new modality, Hanmi selected FAP as the target.
FAP is highly expressed in CAFs within the tumor microenvironment but has limited expression in most normal adult tissues. High levels of FAP have also been observed across multiple solid tumors, including lung cancer, soft tissue sarcoma and gastrointestinal cancers such as pancreatic and colorectal cancer.
New Compound Identified Through DEL Screening
Hanmi Pharmaceutical used its DNA-Encoded Library, or DEL, screening technology to identify a novel class of small molecules that selectively bind to FAP.
The company then developed an SMDC by conjugating a cytotoxic payload to the FAP-targeting molecule.
The modality incorporates a linker designed to remain stable in the bloodstream and become selectively activated within the tumor microenvironment, allowing the drug payload to act at the tumor site.
In preclinical studies presented at the conference, the SMDC demonstrated antitumor activity in mouse models implanted with FAP-expressing cells.
Hanmi also reported strong tumor growth inhibition and prolonged survival in an orthotopic pancreatic cancer mouse model.
The company said the approach differs from conventional ADC strategies that rely on the expression of specific antigens on individual cancer cells. Instead, the SMDC targets FAP expressed by CAFs, a common component of the tumor microenvironment across a range of cancer types.
This could potentially broaden the therapeutic approach from directly targeting cancer cells to addressing the surrounding environment that supports tumor growth.
Research to Be Presented at MD Anderson Cancer Center
Hanmi Pharmaceutical is also presenting the findings at another international scientific meeting.
The research is scheduled for an oral presentation at the “Nature Conference – Next Generation Cancer Therapeutics,” being held from Oct. 6 to 8 at the MD Anderson Cancer Center in Texas.
The program reflects Hanmi Pharmaceutical’s broader effort to expand its research portfolio beyond metabolic diseases, including obesity, into next-generation oncology modalities.
“The SMDC modality is differentiated from conventional ADCs in that it can deliver drugs by targeting FAP expressed in cancer-associated fibroblasts within the tumor microenvironment, rather than depending on the expression of a specific antigen on individual cancer cells,” a Hanmi Pharmaceutical official said.
“The findings demonstrate the potential of this approach to expand the therapeutic target from cancer cells themselves to the surrounding tumor microenvironment,” the official added.
