[Edaily Reporter Kim Jinsoo ] Genome&Company(314130)is aiming for its third technology export deal, led by its next-generation antibody-drug conjugate (ADC) candidate, “GENA-120.” Although GENA-120 is still in the early clinical stages, it targets “integrin beta-4 (ITGB4),” a new target where global competition is just beginning. Given that it has secured a higher drug-to-antibody ratio (DAR) and selective activity against cancer cells compared to competitors’ candidates, the prospects for a technology export are considered favorable.

According to Genome&Company on the 1st, discussions regarding the technology export of “GENA-120,” currently under development as an ADC, are progressing smoothly. Consequently, Hong Yu-seok, CEO of Genome&Company, is expected to fulfill his promise of “one technology export per year.”

GENA-120 is an ADC in the topoisomerase 1 (TOP1) inhibitor class, and its most distinctive feature is that it targets ITGB4. ITGB4 is an integrin protein found on the cell membrane and is known to be involved in cancer growth and metastasis. It is attracting attention as an ADC target because it is highly expressed in solid tumors—including head and neck cancer, cervical cancer, colorectal cancer, and esophageal cancer—compared to normal tissues.

The key to an ADC lies in its ability to distinguish between cancer cells and normal cells. Identifying targets that are highly expressed in tumors but only minimally expressed in normal tissues is advantageous for enhancing therapeutic efficacy and safety. Since ITGB4 is highly expressed in various solid tumors, it is gaining attention as a new target in the already highly competitive ADC market.

This is particularly advantageous for securing a competitive edge, especially given that ADCs targeting HER2 and TROP2 are being developed at a rapid pace. Furthermore, if Genome&Company accelerates its drug development, it has the potential to become the first-in-class candidate in this class.

The high unmet medical need is another competitive advantage. In head and neck cancer, treatment options are limited after failure of PD-1-class immune checkpoint inhibitors. In particular, ITGB4 is known to be highly expressed even in HPV-negative head and neck cancer, which has a relatively poor prognosis. In colorectal cancer as well, demand for therapies targeting new mechanisms is high, as some patients with metastatic disease show limited response to immunotherapy. Accordingly, Genome&Company has identified colorectal cancer and head and neck cancer as the priority indications for GENA-120.

The weapon to surpass competitor Cistone

The development of ADCs targeting ITGB4 is still in its early stages globally. Currently, on the global stage, Genome&Company’s GENA-120 and China’s Cistone’s CS5006 are being developed to target ITGB4. Both compounds are similar in that they consist of an ITGB4 antibody conjugated to an exatecan-class TOP1 inhibitor payload, and both are in the preclinical stage.

However, they differ in terms of linkers and drug-to-antibody ratio (DAR), with GENA-120 showing slightly superior performance. According to data released by CS CORPORATION, CS5006 has an average DAR of 4, using its proprietary hydrophilic linker and exatecan. In contrast, GENA-120 uses its proprietary hydrophilic “Linker E” to achieve a DAR of 8, with eight payloads attached to each antibody.

DAR refers to the number of drug payloads bound to a single antibody. All other conditions being equal, a higher DAR allows for a greater amount of drug to be delivered to a single cancer cell, thereby enhancing therapeutic efficacy. However, since an increased number of payloads raises the risk of toxicity, safety concerns must be addressed first.

Based on research findings to date, GENA-120 is expected to pass safety assessments without issue. According to Genome&Company, GENA-120 demonstrated high stability in mouse, monkey, and human serum; after binding to ITGB4-positive cancer cells, it was taken up into the cells and transported to the lysosomes. It also demonstrated strong tumor growth inhibition in xenograft models using colorectal and head and neck cancer cell lines. In a single-dose study in mice, the maximum tolerated dose of 140 mg per kg was not reached, and no dose-limiting toxicity was observed.

Genome&Company explained, “We developed our own linking technology to design the compound so that it can deliver more anticancer agents to cancer cells while maintaining stability even when eight payloads are attached. We believe this leads to the difference in efficacy.”

Furthermore, a comparison of select data on head and neck cancer and colorectal cancer—published separately by Genome&Company and C-Stone—confirmed that, at the same drug concentration, GENA-120 exhibited anticancer activity approximately 8 to 10 times stronger than CS5006. Furthermore, according to Genome&Company, GENA-120 did not bind to control targets lacking ITGB4, and its cytotoxicity was ITGB4-dependent.

A representative from Genome&Company stated, “Since these figures are not based on a direct comparison but rather on a comparison of experiments conducted separately by each company, there may be some variation in actual comparisons,” adding, “The significance of this comparison lies in the fact that it confirms the potential of GENA-120.”