Incident: Keji Pharmaceutical announced that two case reports of CT041, a CAR-T cell targeting Claudin18.2 to treat metastatic pancreatic cancer were published in the “Journal of Hematology & Oncology” (IF 23.186).
Keji Pharmaceutical announced that it has initiated a cooperation agreement with Medena (Nasdaq: MRNA) to study the combined effects of Keji Pharmaceutical's Claudin18.2 CAR-T candidate product (CT041) and Medena's experimental Claudin18.2 mRNA cancer vaccine.
Case 1 is a 58-year-old female pancreatic cancer patient with lung and lymph node metastases. After successive treatments with first-line albumin paclitaxel plus gemcitabine and second-line irinotecan combined with 5-fluorouracil, failed. After pre-treatment with fludarabine, cyclophosphamide, and paclitaxel regimen, patients received CT041 cell infusion (250 x 106 cells) in September 2021. Patients developed grade 2 cytokine release syndrome (CRS) after infusion and recovered after receiving tocilizumab. According to the RECIST v1.1 standard, the patient's tumor assessment achieved partial remission (PR), and pulmonary metastases were significantly reduced.
Case 2 is a 75-year-old female pancreatic cancer patient who underwent surgical resection in May 2019. The diagnosis was stage pT2n0 pancreatic cancer. Lung metastasis was discovered during 5 months of post-operative follow-up. First-line S-1 monotherapy began in December 2019, and lung metastasis occurred during palliative radiotherapy in the surgical field. After pre-treatment with fludarabine, cyclophosphamide, and paclitaxel regimen, patients were transfused with CT041 cells (250 x 106 cells) in July 2021. The patient developed grade 2 CRS after infusion and recovered after treatment with tocilizumab. The patient achieved PR when the initial tumor assessment was performed 4 weeks after CT041 infusion, and the target lesion in the posterior lung disappeared further and achieved complete remission.
The patient was in continuous remission as of the last follow-up in July 2023.
The number of CAR copies in peripheral blood of both patients increased rapidly after infusion and peaked within 2 weeks; at the same time, flow cytometry results showed an increase in the proportion of CD8+ T cells and Treg cells in peripheral blood, and a decrease in the proportion of CD4+ T cells to B cells. These immune cell phenotypic changes were more long-lasting than changes in cytokine levels.
CT041, the potential first CAR-T therapy for solid tumors, has entered confirmatory clinical trials, collaborating with Moderna to expand application boundaries. CAR-T therapy CT041, which targets CLDN18.2, is the world's first candidate for solid tumor treatment with CAR-T cells to enter confirmed clinical trials. The first confirmed phase 2 clinical GC/GEJ patient enrollment in China was completed in March 2022, approved by the CDE in April 2023 to conduct post-operative adjuvant treatment clinical trials for pancreatic cancer expressing positive Claudin18.2 expression, and initiated treatment in May 2023 for GC/GEJ expressing positive GC/GEJ with at least second-line treatment Phase 2 clinical trial in the US. This time, a cooperation was reached with Moderna. CT041 combined with the CLDN18.2 mRNA cancer vaccine was used to carry out preclinical research and phase I clinical trials. The company's R&D capabilities were recognized by overseas pharmaceutical companies.
An emerging racetrack specializing in cell therapy, the product echelon has been formed, and the technology platform layout is forward-looking. The company focuses on research and development of cell therapy for solid tumors and hematoma, forming an innovative pipeline that includes various CAR-T products. Currently, 1 product has submitted a marketing application, 8 products are in the clinical development stage, and 3 are in the pre-clinical stage. CT041 for CLDN18.2 positive gastrointestinal tumors and CT011 for liver cancer lead the world, with differentiated product design and global layout. At the same time, in order to meet the development trend of the cell therapy industry, Forward-looking has established an integrated cell therapy platform, laid out next-generation solid tumor CAR-T and general CAR-T technology, and maintained the competitive advantage of the industry.
Profit forecasts and investment recommendations. Based on the current state of the company's operations, we lowered our profit forecast. The company's revenue for 2023-2025 is estimated to be 200 million yuan, 150 million yuan, and 490 million yuan respectively; net profit to the mother is 790 million yuan, -83 million yuan, and 650 million yuan respectively. We have been optimistic about the company's development for a long time and maintained a “buy” rating.
Risk warning: risk of R&D failure; risk of product price reduction; risk of product sales falling short of expectations.