Circular mRNA-based oncotherapy: CureMed is expected to obtain the first domestic IND for treatment of tumor.

On July 2, 2022, CureMed submitted its application of treating tumors with circular mRNA, cmRNA1210, to the CDE for Class III meeting. At present, the application is currently in the "processing" status. And it will be the first communication and exchange meeting on circular mRNA in China.

This product, circular mRNA encoding IL-12, is based on the circular mRNA platform independently developed by CureMed and is a class Ⅰ biological agent for the treatment of unresectable and advanced solid tumors. After finishing the work about the preliminary proof of concept, pilot production process development, analytical method development, etc, CureMed further developed proposals for the evaluation of toxicology and efficacy on GLP animals and clinical development. The aim of the application for CDE Class III meeting is to actively communicate with CDE on a series of core issues, and thus ascertain the standard of circular mRNA and lay the groundwork for declaring IND.

About cmRNA1210

This product is an injection agent of circular mRNA encoding single-chain human interleukin 12. After intratumoral injection, the mRNA is taken up, expressed and secreted by cells. The resulting interleukin 12 with high concentration promotes the killing efficiency of CD8 T cells and NK cells in the tumor microenvironment and boosts the body’s anti-tumor immunity . Combined with the immune checkpoint inhibitor, anti-PD-1 antibody, the product can better inhibit the growth of tumor and generate a systemic anti-tumor response.

IL-12, composed of two subunits, p35 and p40, is an anti-inflammatory cytokine mainly secreted by antigen-presenting cells. It has a powerful anti-tumor effect owing to its multiple functions. (1) Promoting Th1 transformation (2) Enhancing the killing effect of NK cells and T cells (3) Impairing immunosuppressive cells such as tumor-associated macrophages and MDSCs (4) Inhibiting angiogenesis (5) Upregulating MHCⅠ in tumor cells.. Although IL-12 has demonstrated its strong anti-tumor effect in preclinical phases, its clinical application has been greatly limited mainly due to the toxic side effects related to systemic administration.. Therefore, it is necessary to seek other ways for the application of IL-12. At present, more clinical trials choose to inject IL-12 directly into the tumor to activate NK cells and CD8T cells inside it, so as to maximize the function of IL-12 and avoid the toxic effects from its systemic distribution.

The different natures of different drug affect its pharmacokinetic characteristics, thereby affecting the pharmacodynamics. Compared with DNA plasmids, mRNA expresses proteins directly in the cytoplasm with no need to enter the nucleus for transcription. Moreover, mRNA is safer because there is no risk of genomic integration. Compared with traditional linear mRNA, circular mRNA is simpler to manufacture for no requirement of capping and tailing, expresses proteins for a longer time, and is less immunogenic for no nucleotide modifications. cmRNA, a new type of circular mRNA fully-owned by CureMed, has been verified its advantages of higher expression for a longer time and lower immunogenicity in multiple animal models. By using its circular mRNA platform technology, CureMed has perfectly solved the problem of high expression of IL-12 mRNA for a long time in tumors. It generates excellent anti-tumor immune responses not only locally but also in other remote parts in mouse models.

As reported, the Project MEDI1191 of Moderna, which adopts modified linear mRNA to treat solid tumors, acquired good therapeutic effects in animal models and has entered phase I clinical trials. Immorna’s JCXH-211, an IL-12 mRNA drug based on self-replicating mRNA, has obtained the IND clearance from the US FDA.

At present, the main technical directions in the field of mRNA, linear modified mRNA, self-replicating mRNA and circular mRNA have all of them been deployed in the intratumoral injection of IL-12. The use of mRNA technology platform may revive the formerly promoted IL-12 medicine.

About Us

Located on the 1st and 2nd floor of Building C, Tengfei Science and Technology Park, Suzhou Industrial Park, SuZhou CureMed Biomedical Technology Co., Ltd.has a 4,000㎡ laboratory that meets GMP standards, and a 10,000㎡ GMP-compliant production plant and R&D platform under construction.

Focusing on the research and development of a new generation of circular mRNA drugs, CureMed has applied for more than 30 invention patents for core platform technology in the field of circular mRNA, a number of PCT international patents, and 2 software copyrights. A novel circularization frame, Clean-PIE system, independently developed by CureMed does not require the addition of exogenous sequences, and has accurate and efficient circularization, lower in immunogenicity, higher expression efficiency and longer expression time.  The company also developed an LNP system for nucleic acid delivery with independent intellectual property rights, of which the core patent has been authorized, realized the mass production of LNP nucleic acid drugs. The circular mRNA technology with independent intellectual property rights is leading at home and comparable to the greatest technologies abroad.

CureMed, committed to building a comprehensive circular mRNA pharmaceutical platform, actively deploys product pipelines in infectious diseases, tumor immunity, protein replacement, gene therapy, cell therapy, etc. to meet the huge clinical demands. At present, the IND application of circular mRNA drugs is being actively promoted.