The need for RNA therapy
- As a next-generation genetic drug, sufficient potential has been verified through the COVID-19 vaccine.
- Normalizes intracellular pathological mechanisms that are difficult to target with existing drugs.
- With the development of RNA stability and delivery technology, many obstacles for the development of RNA therapeutics are being resolved.
Advantages of RNA Therapeutics
- It fundamentally cures diseases by blocking disease-expressing genes.
- As a substance originally present in the body, it is not toxic by itself, and unlike DNA therapy, it does not affect the host genome, so there is little concern about safety.
- The production process is relatively simple and inexpensive.
Rapid growth of the RNA therapeutics market
- The global market is showing high growth every year as siRNA treatment was approved by the FDA in 2018.
- As a first-in-class new drug, active technology export is possible even in the early stages of development.
Pipeline status in NEORNAT
|Code name||Target validation||Proof of concept||In vivo efficacy||Non Clinical||IND Approval||Phase 1||Indication||Target|
|NRT-YHD_001||2024' 4Q||HCC||Macrophage immune-check point inhibitor|
|Macrophage immune-check point inhibitor|
|NRT-YHD_003||Pancreatic cancer||Macrophage immune-check point inhibitor|
|NRT-KSY_001||HCC||Competing endogenous RNA inhibitor|
|NRT-NMJ_001||HCC||DNA replication enzyme inhibitor|
|DNA replication enzyme inhibitor|
|NRT-RD_MCMD||L/O to KPS CORP||Early diagnosis of HCC||Hepatocellular carcinoma|
Macrophage immune-check point inhibitor
RNA immunotherapy that activates macrophages by blocking the macrophage immune-check point In NEORNAT Inc., macrophage activity is inhibited by TSP1, and it was confirmed that TSP1 expression was reduced by miRNA (Let-7i-5p) in cancer cells. Due to the decreased TSP1, CD47 of cancer cells binds to SIRPα of macrophages, and the activity of macrophages is inhibited, and phagocytosis does not occur (Don't eat me). Based on this, we are developing a first-in class RNA immunotherapy that activates macrophages by increasing TSP1 by blocking miRNAs associated with cancer cells. This activation of macrophages is expected to become an anticancer drug that can fundamentally remove cancer cells by activating the adaptive immune response including T-cells.
1. NRT-YHD-001 : RNA agent for Liver cancer with treatment RNA preparation with anticancer action of NRT-YHD mechanism
NRT-YHD-001 is an RNA liver cancer treatment pipeline with the mechanism of NRT-YHD. It restores the production of TSP1 in liver cancer tissue, binds TSP1 to CD47 of cancer cells, and activates macrophages to treat liver cancer. NRT-YHD-001 is an RNA liver cancer treatment pipeline with the mechanism of NRT-YHD. It restores the production of TSP1 in liver cancer tissue, binds TSP1 to CD47 of cancer cells, and activates macrophages to treat liver cancer. It is a drug that solves the problems of stability and tissue selectivity, which are problems with antisense RNA therapeutics, and has a high anticancer effect on liver cancer.
2. NRT-YHD-002 : RNA agent for Lung cancer with RNA preparation with anticancer activity of NRT-YHD
NRT-YHD_002 is an RNA lung cancer treatment pipeline with the mechanism of NRT-YHD, confirmed to be useful in lung cancer by big data analysis. NRT-YHD_002 confirmed in a human lung cancer cell line for increased TSP1 and activates macrophages and growth inhibition. in vivo validation, we plan to develop the first macrophage immune checkpoint inhibitor an anticancer drug for lung cancer.
3. NRT-YHD-003 : RNA agent for Pancreatic cancer with RNA preparation with anticancer activity of NRT-YHD
NRT-YHD_003 is an RNA pancreatic cancer treatment pipeline with the mechanism of NRT-YHD, confirmed to be useful in pancreatic cancer by big data analysis. NRT-YHD_003 confirmed in a human pancreatic cancer cell line for increased TSP1 and activates macrophages and growth inhibition. in vivo validation, we plan to develop the first macrophage immune checkpoint inhibitor an anticancer drug for intractable pancreatic cancer.
Competing endogenous RNA inhibitor
In liver cancer, SMARCA4 binds to the enhancer region of the oncogene IRAK1 and promotes the transcription of IRAK1, thereby promoting malignant liver cancer. In a normal hepatocyte, the expression of genes is regulated by various mechanism, a commonly known mechanism is regulation by miRNA. The miRNA that regulates oncogene expression is sponging by long non-coding RNA (lncRNA) and does not regulate suppression of oncogene expression, thus it is reported to be involved in the development of liver cancer.
NRT-KSY is a pipeline with a mechanism to simultaneously block the expression of SMARCA4, which plays a major role in hepatocarcinogenesis, and lncRNA, sponging SMARCA4 binding miRNA, with two siRNA. Therefore, complete suppression of the oncogenic SMARCA4 expression by NRT-KSY-001, in liver cancer cells effectively inhibits the formation and growth of liver cancer.
DNA replication enzyme inhibitor
The DNA replication enzyme, the target of NRT-NMJ, is very well known as an enzyme that corrects errors in the DNA replication process. However, it was confirmed that the expression of DNA replication enzymes was increased in most solid tumors by analysis of large cohort genomic datasets. NEORNAT has verified that this DNA replication enzyme can act as an oncogene in tumorigenesis. DNA replication enzyme affects the expression of DNA methyltransferases that methylate DNA, creating a favorable environment for tumors to develop by transcription of several genes, including tumor suppressor gene. Therefore, blocking the DNA replication enzyme in tumorigenesis regulates the expression of DNA methyltransferases, resulting in the expression of tumor suppressor gene and tumor suppression.
NRT-NMJ is a pipeline that increases the transcription of tumor suppressor genes by inhibiting the expression of this DNA methyltransferases with siRNAs that target DNA replication enzyme, high anticancer effect was confirmed in liver cancer cells.
Liver Cancer Early Diagnosis Kit
Early diagnosis of liver cancer is a very important factor in the patient's prognosis. Therefore, if diagnosed at an early stage, most liver cancer is curable. Early diagnosis of liver cancer is very important. Currently, most in vitro diagnostic devices related to cancer diagnosis use a method of confirming the presence or absence of a specific cancer by identifying specific biomarkers in the patient's blood. However, most of the developed cancer diagnostic kits are diagnostics for the purpose of detecting one specific marker and have low accuracy and sensitivity. In order to diagnose early liver cancer, we have developed an in vitro diagnostic device in the form of a panel kit that simultaneously measures and diagnoses multiple liver cancer markers with high specificity, and this technology is transferred to KPS Inc. in 2021 and is under development for commercialization.
Multiple HCC markers developed by NEORNAT Inc. have higher sensitivity and specificity than the existing single marker for liver cancer diagnosis. It can accurately diagnose early liver cancer.