Cunde Therapeutics Files IPO Prospectus: Pioneering Neoantigen-Based Personalized Immunotherapy to Combat Tumor Recurrence and Metastasis

In May 2014, Science reported a case in which a patient with advanced malignant cholangiocarcinoma was successfully treated using tumor neoantigens. In the patient’s metastatic tumor tissue, researchers identified 26 clinically significant gene mutations and the corresponding abnormal proteins synthesized by these mutations, which were absent in normal tissues. One of these abnormal proteins, ERBB2IP (a 185-kDa cell membrane receptor encoded by the erbB-2 proto-oncogene), was recognized by a subset of T cells (CD4-positive T cells) isolated from the patient. Subsequently, researchers expanded and activated these T cells and infused them back into the patient, resulting in complete remission that persisted for several years. Personalized cancer therapies based on tumor neoantigens, as well as research into cancer vaccines, have also garnered widespread attention.

CUNDE is a biotechnology company focused on personalized tumor immunotherapy. It was incubated through Chongqing Lummy Pharmaceutical’s internal entrepreneurship program and is currently a subsidiary in which Lummy holds an equity stake. Cornerstone investors include professional institutions such as BGI Miracle Light and Beijing Enterprises Healthcare. In April 2015, Lummy Pharmaceutical and Argos reached an agreement for the transfer of Chinese rights to AGS-003. Lummy obtained the rights to manufacture, develop, and commercialize AGS-003 in China. AGS-003 is a therapeutic agent developed by Argos based on its Arcelis platform for personalized immunotherapy targeting tumor neoantigens, intended for the treatment of metastatic renal cell carcinoma (mRCC) and other cancers, and has entered Phase III clinical trials. In November 2016, CUNDE was formally established to carry out technology transfer, secondary development, application, and promotion of innovative technologies in China, with a particular focus on developing personalized tumor immunotherapy platforms. By the end of 2017, CUNDE completed the construction of its pilot production base located in the Tianfu Life Science Park within the Chengdu High-Tech Zone, with the entire workshop fully compliant with GMP standards.

The development of novel oncology drugs is rarely a smooth journey. In early 2017, the Independent Data Monitoring Committee (IDMC) recommended that Argos Therapeutics discontinue the Phase III clinical trial of its product AGS-003. Although the development of AGS-003 faced setbacks, it created new opportunities for CUNDE’s drug R&D. “Building on our original platform, we pursued secondary innovation by screening immunological indicators and identifying new biomarkers. We eliminated ineffective information related to tumor mRNA from the original treatment regimen and independently developed three neoantigen-based oncology drug pipelines with independent intellectual property rights, as well as an innovative pipeline targeting liver cirrhosis,” stated Dr. Ding Ping, CEO of CUNDE.

Prior to the establishment of CUNDE, Mr. Ding Ping earned his master’s degree from the College of Life Sciences at Sichuan University. In 2006, he went to Germany to pursue his doctoral degree. After graduation, he worked in Germany for several years. Upon returning to China, he joined Lai Mei Pharmaceutical as the Director of the Major Projects Department, where he was responsible for the introduction of overseas products and technologies, as well as outbound investments.CUNDE’s team covers all stages of drug development, from research and development (R&D) to market launch and production, including R&D, manufacturing, quality control, and drug registration. The heads of each business unit possess more than ten years of relevant industry experience. This comprehensive team structure enables CUNDE to navigate the new drug development process with greater ease and proficiency. To date, CUNDE has three investigational pipelines based on tumor neoantigens, targeting advanced metastatic ovarian cancer, acute myeloid leukemia, and advanced metastatic liver cancer, respectively. Additionally, the company is developing a therapeutic pipeline for mid-to-late stage liver cirrhosis and is advancing preclinical studies for all its pipelines.

Dr. Ding Ping, CEO of CUNDE

Ovarian cancer ranks as the third most common malignant tumor of the female reproductive system. Due to the difficulty in early diagnosis and its high degree of malignancy, data show that two-thirds of patients are already at an advanced stage at their initial consultation. Furthermore, current first-line treatment regimens are relatively outdated, consisting primarily of platinum-based chemotherapy combined with paclitaxel, with no effective targeted therapies or immunotherapies available. Given the extremely poor prognosis, many patients experience recurrence within a short period after initial chemoradiotherapy, or develop metastases to the abdomen, uterus, intestines, and other sites. The five-year survival rate for ovarian cancer patients is less than 30%. According to the latest research forecast by the renowned market research firm GlobalData, the global ovarian cancer market was valued at $1.8 billion in 2018 and is projected to grow at a compound annual growth rate (CAGR) of 14.4%, reaching a market size of $6.7 billion by 2028.

“Immunotherapy for tumors should consist of two components: first, enabling the body to recognize the tumor, and second, stimulating the body’s immune response. The advantage of our ovarian cancer pipeline based on tumor neoantigens lies in its combination with first-line drugs, targeting multiple sites to act jointly on tumor tissue, thereby inhibiting tumor recurrence and metastasis,” introduced Dr. Ding Ping. CUNDE’s technology platform first isolates monocytes from the patient’s blood cells and induces them to generate dendritic cells (DCs). Subsequently, genetic testing is performed on the patient’s tumor tissue to analyze and screen for neoantigens. The mRNA encoding specific neoantigens is then electroporated into the DCs. Finally, the mature DCs present antigen information to cytotoxic T cells, stimulating T-cell proliferation to target the tumor and its metastatic tissues.

“Dendritic cells (DCs) are the primary antigen-presenting cells (APCs). They possess considerable potential for genetic modification and exert relatively direct effects; however, their modification and production are technically challenging, presenting an exceptionally high barrier to entry. Immunotherapeutic regimens targeting tumor neoantigens via mRNA-based pathways demonstrate more stable efficacy compared to those utilizing peptide-based approaches. After careful consideration and comparative experiments, we ultimately decided to enter the field of tumor neoantigen immunotherapy through the mRNA avenue,” stated Dr. Ding Ping.

“The clinical value of this combination therapy is not limited to the initial killing of tumor cells; rather, it works by periodically stimulating the immune system to elicit a host response against tumor tissue,” continued Dr. Ding Ping. The treatment course for this combination therapy is relatively long, encompassing a comprehensive five-year postoperative and health management plan. The initial treatment phase lasts approximately two years. After two years, patients undergo follow-up evaluations. If tumor metastasis or new tumors are detected, circulating tumor DNA (ctDNA) analysis or biopsy will be performed to identify newly generated tumor neoantigens. Patients will then receive immunotherapy tailored to these secondary tumor neoantigens, ultimately suppressing tumor recurrence and metastasis.

Zhao Weiwen, Partner at Miracle Light Venture Capital Fund—a cornerstone investor in CUNDE—believes that tumor vaccines represent an important branch of immunotherapy, with neoantigens poised to become a breakthrough for such vaccines. CUNDE boasts an internationally leading dendritic cell (DC)-based tumor vaccine technology platform. By integrating this platform with the most advanced neoantigen prediction technologies currently available, it can more effectively activate the immune system to target and destroy tumors. The management team at CUNDE possesses a global perspective and comprehensive professional expertise spanning the entire process from drug R&D to production and market launch. We look forward with great anticipation to CUNDE’s future performance.

Currently, CUNDE’s innovative pipeline for ovarian cancer has received support from the National 13th Five-Year Major Special Project, and it is collaborating with West China Second University Hospital to establish a joint laboratory for research and development in cell therapy.