Naivek Develops 'Cell-Permeable Bio-PROTAC' Inhibiting Cancer-Inducing KRAS Mutation... "Applicable to mRNA and Other Gene Therapies"

[Asia Economy Reporter Hyunseok Yoo] Nivec announced on the 23rd that it has succeeded in developing a 'cellular delivery functional bio-PROTAC' protein by combining its drug delivery material platform 'NIPEP-TPP' with 'PROTAC' technology that forcibly degrades disease-causing proteins, and has also completed related patent applications.

PROTAC is a technology that induces the degradation of specific proteins and has recently become a new drug development platform among global pharmaceutical companies. U.S. companies such as Arvinas and Kymera are currently conducting Phase 1 clinical trials, and even global pharmaceutical companies are still in the early stages of development in this field.

Nivec applied 'bio-PROTAC' to the tumor oncogene 'KRAS G12C', which exhibits mutations in various cancer types, and confirmed that not only the expression of KRAS G12C but also the expression of downstream signaling proteins and proteins causing resistant cancer were dramatically reduced. Nivec’s bio-PROTAC technology can also be applied to gene therapies such as mRNA and siRNA, and the company is promoting the application of this technology in the gene therapy field.

PROTAC is an abbreviation for 'Proteolysis-targeting chimera,' discovered during the process of identifying chimera molecules composed of two small molecules. One of the small molecules is designed to bind to the target protein, while the other is designed as a small molecule compound that can recruit the 'proteasome' to degrade the target protein, resulting in a dual molecular structure.

PROTAC utilizes the 'ubiquitin-proteasome system,' a protein degradation pathway present in the human body. Here, 'ubiquitin' binds to the target protein to promote protein degradation, and the 'proteasome' degrades the protein bound to ubiquitin. Drugs applying PROTAC technology are based on a mechanism that induces the forced degradation of disease-causing 'proteins.'

A Nivec official stated, “Despite its excellent target protein removal function, the reason PROTAC technology is difficult to commercialize is due to poor water solubility and difficulty in intracellular delivery,” adding, “Nivec succeeded in deriving a 'peptide sequence' that directly binds to KRAS mutant proteins and a 'protein sequence' that recruits KRAS degradation enzymes instead of small molecules using its proprietary 'TOPSCOVERY technology,' and combined these with its own drug delivery platform NIPEP-TPP to successfully deliver the dual molecule inside cells.”

He continued, “This means that the issues that were obstacles to the commercialization of PROTAC technology have been resolved, and the related patent technology has also been completed.”

Nivec confirmed through preliminary tests applying the bio-PROTAC substance that tumor size was reduced by 90%, and it showed excellent anticancer effects even on resistant cancers. Since Nivec was conducting joint research with global pharmaceutical companies to develop treatments for existing KRAS mutant tumors, the development of anticancer new drugs based on bio-PROTAC will also be promoted through joint research. Bio-PROTAC is effective against resistant cancers, and research has already begun to apply it as a platform for treating various tumors with resistance.

A Nivec official said, “Since PROTAC technology has not yet been commercialized and entered the market, if applied to anticancer new drugs, it can establish itself as a unique therapeutic agent,” adding, “Because all tumor treatments cause resistant cancer and metastasis after administration, there is a need for second-line anticancer drugs, and the related market growth rate is evaluated to exceed 40% annually.”

With global pharmaceutical companies with whom Nivec has been continuously collaborating, safety and efficacy tests on 'KRAS antibody delivery transport' are progressing steadily. With the addition of bio-PROTAC technology, the 'packaging of tumor treatment' has been perfected, and the company explained that it is receiving collaboration requests from various global pharmaceutical companies.