[Edaily Reporter Hong Ju-yeon] #Genome & Company is transforming from a microbiome company into a firm specializing in antibody-drug conjugates (ADCs). As recently as two years ago, the company was strongly associated with the development of immunotherapy and microbiome-based new drugs. However, building on the success of consecutive technology transfers, Genom & Company is now positioning ADCs targeting new targets as its next-generation core business.

First Step into the ADC Market with a 2024 Technology Transfer to a Swiss Company

The turning point dates back to 2024. Genom & Company took its first step into the ADC market by licensing the antibody GENA-111, designed for a new-target ADC, to the Swiss company DiBioPharm in a deal valued at 5860억원. GENA-111 is an antibody that targets CD239, which is primarily overexpressed in ovarian cancer. Combined with DebioPharm’s proprietary linker-payload platform, Multilink™, it is currently preparing for Phase 1 clinical trials under the code name Debio 0633. Building on this technology export, Genom & Company is now moving into the stage of developing ADCs in-house.

Genome & Company has identified three ADCs as its future growth engines. These consist of: △ GENA-104 ADC, which targets CNTN4; △ GENA-120, which targets ITGB4; and △ GENB-120, a bispecific antibody ADC that simultaneously targets ITGB4 and TROP2. All three candidate compounds are based on novel targets identified through the company’s proprietary genomic analysis platform, GNOCLE. The portfolio is structured to differentiate itself through an immunomodulatory ADC, a traditional solid tumor ADC, and a next-generation bispecific antibody ADC, respectively.

The GENA-104 ADC targets the novel immune checkpoint molecule CNTN4. CNTN4 is a molecule that binds to the amyloid precursor protein (APP) on the surface of T cells to inhibit T-cell activity; it has been confirmed to be highly expressed in various solid tumors, including melanoma, liver cancer, and endometrial cancer. However, its low expression in normal tissues makes it an ideal target for an ADC.

Its expression is particularly prominent in sarcomas, where treatment options are limited; analysis of patient-derived xenograft (PDX) models confirmed high CNTN4 expression in four out of five sarcoma models. Its dual mechanism of action is cited as a key differentiator. Conventional ADCs focus on a mechanism where the drug is released after antibody internalization to directly kill cancer cells.

However, the GENA-104 ADC simultaneously activates T-cell-mediated antitumor immune responses by blocking the CNTN4 immune checkpoint. It utilizes an exatecan payload and a proprietary linker (Linker E), and has demonstrated potent antitumor efficacy in animal models of fibrosarcoma and hepatocellular carcinoma. High CNTN4 expression (H-score ≥ 250) was observed in 11 (47%) of 23 PDX tissues. Genom & Company plans to complete PDX model evaluations and non-GLP toxicity studies by the end of the year to compile a data package.

GENA-120 targets ITGB4. GENA-120 has demonstrated high expression levels and excellent antitumor activity in specific solid tumors, including △head and neck cancer, △cervical cancer, △colorectal cancer, and △esophageal cancer. ITGB4 is a protein that promotes cancer cell migration and invasion and is associated with resistance to chemotherapy and targeted therapy; it is highly expressed in head and neck cancer and esophageal cancer.

Conversely, its expression is low in normal tissues, giving it a profile suitable for use as a therapeutic target. The drug, which consists of a humanized anti-ITGB4 antibody linked to an exatecan payload via the company’s proprietary linker (Linker E), demonstrated potent antitumor activity in animal models of ITGB4-positive colorectal cancer (COLO205, LS174T) and head and neck cancer (FaDu).

Its efficacy was confirmed regardless of KRAS mutation status. In some models, a tumor growth inhibition (TGI) rate of over 100% and cases of complete remission (CR) were observed. The safety profile is also favorable, as the maximum tolerated dose (MTD) was not reached even at doses up to 140 mg/kg following a single administration in mice. GENA-120 is currently undergoing research and development in the preclinical stage.

Although GENB-120 is in the earliest stage among the three candidates, it incorporates a next-generation bispecific antibody ADC strategy. Currently, concerns have consistently been raised regarding TROP2-targeted ADCs, as TROP2 is also expressed in normal epithelial tissue, leading to off-target (non-targeted cleavage) toxicity that limits the therapeutic index. Based on analysis using the Genocl platform, Genom & Company noted that ITGB4 and TROP2 are highly co-expressed in pancreatic, lung, and bladder cancers, as well as in HER2-negative breast cancer, but show low co-expression in normal tissues. Drawing on this insight, the company designed GENB-120 to selectively deliver the cytotoxic payload only to cancer cells that express both targets.

In preclinical studies, GENB-120 demonstrated superior cytotoxicity and antitumor efficacy in TROP2/ITGB4 double-positive cancer cells compared to existing TROP2-monotargeted ADCs. It also maintained a safe profile in normal cells. GENB-120 is currently in the early preclinical stage, with optimization underway to compare various valency structures.

Meanwhile, the parent antibody of the GENA-104 ADC—the CNTN4 antibody GENA-104—was licensed to UK-based Ellipsis Pharma last February as an immuno-oncology drug (EP0089). Ellipsis Pharma is currently preparing to administer the drug in a Phase 1/2a clinical trial for solid tumor patients in South Korea and Australia. The company plans to expand the trial to the U.S. and Europe in the future, recruiting approximately 190 patients. Genom & Company retains separate rights to ADC development, so the immunotherapy and the ADC are being developed independently based on the same antibody.

The company aims to secure early-stage technology transfers for all three candidates (GENA-104 ADC, GENA-120, and GENB-120) while they are still in the preclinical phase. A representative from Genom & Company stated, “We are continuing to engage with companies showing interest in our various new drug pipelines,” adding, “Discussions regarding global partnerships are currently underway.”

Hong Yu-seok, CEO of Genom & Company, said, “We will establish a foundation for sustainable growth by developing differentiated ADCs targeting novel targets and aiming to achieve at least one technology transfer deal per year.”