Hanmi Pharm unveils FAP-targeting SMDC to overcome ADC limitations at US conference

Hanmi Pharm has made its global debut with a next-generation anticancer technology designed to overcome the penetration limitations of conventional antibody-drug conjugates and directly target the tumor microenvironment.

Hanmi Pharm, the core operating company of Hanmi Science, announced Tuesday that it presented research findings on a small-molecule drug conjugate targeting fibroblast activation protein in the tumor microenvironment at Discovery on Target 2026, a global academic conference held in Boston from Sept. 28 through Oct. 1.

Antibody-drug conjugates, which have drawn significant attention in the oncology market, carry a structural drawback: their molecular weight of roughly 150 kilodaltons or more limits their ability to penetrate the tumor microenvironment, which is densely packed with cancer-associated fibroblasts and extracellular matrix.

To address this, Hanmi Pharm turned to small-molecule drug conjugates — which use far smaller compounds in place of antibodies — and selected fibroblast activation protein as the target to maximize tumor tissue penetration. FAP is rarely expressed in normal adult tissue but is highly expressed in cancer-associated fibroblasts of hard-to-treat solid gastrointestinal tumors such as pancreatic and colorectal cancers, which show low sensitivity to ADCs.

Using its proprietary drug discovery platform, DEL screening technology, the company identified novel small-molecule compounds that selectively bind to FAP and paired them with a linker that remains stable in the bloodstream but activates specifically within the tumor microenvironment to deliver a cytotoxic payload, completing the SMDC modality.

Preclinical studies showed strong anticancer efficacy in FAP-expressing cell line transplant models, with particularly potent tumor suppression and extended survival demonstrated in an orthotopic pancreatic cancer mouse model.

"Unlike conventional ADCs, which depend on the expression of specific antigens on individual cancer cells, the SMDC modality targets FAP in the tumor microenvironment — a feature common across a wide range of cancer types — to deliver the drug," a Hanmi Pharm official said. "We have confirmed the potential of an innovative modality that extends the therapeutic scope beyond cancer cells themselves to the surrounding microenvironment."

The research represents an effort to secure proprietary small-molecule technology that goes beyond the limitations of conventional antibody-based anticancer drugs and establish a distinct competitive edge in the global oncology market. Hanmi Pharm is also scheduled to present the findings orally at the Nature Conference, being held at MD Anderson Cancer Center in Texas from Tuesday through Thursday.