2022 ASCO ANNUAL MEETING Shanghai Cell Therapy Group Announces Phase I Clinical Safety and Preliminary Efficacy of Alpaca Nanobody-Based CAR-T Cell Therapy for Solid Tumors

2022 ASCO ANNUAL MEETING

The 2022 American Society of Clinical Oncology (ASCO) Annual Meeting will be held June 3-7, 2022 in Chicago, USA. At the meeting, Shanghai Cell Therapy Group (hereinafter referred to as the "Group") demonstrated the Phase I clinical safety and preliminary efficacy of aPD1-mesCAR-T cells in the treatment of malignant mesothelioma, demonstrating the breakthrough progress of CAR-T cell therapy in overcoming solid tumors.

CAR-T cell therapy has achieved very good results in the treatment of hematological tumors. Recently, Shanghai Cell Therapy Group's CAR-T therapy has also achieved encouraging clinical data in solid tumors. Most CAR-T cell therapies need to target cancer cell-associated membrane proteins, but Shanghai Cell Therapy Group uses a new method to not only target cancer cell-associated membrane proteins, but also secrete antibodies to change the microenvironment around the tumor. This method Derived from "nanobodies" naturally produced by alpacas and camels, the "nanobodies" in alpacas help CAR-T cells treat solid tumors. Shanghai Cell Therapy Group established a large-scale alpaca breeding base in Shengzhou, Zhejiang (covering an area of ​​1,300 mu). In 2018, it introduced alpaca (Alpaca) from Australia. llama), and set up a research and development center in San Francisco to promote nanobody research. On April 4, 2022, the Shengzhou Alpaca Base of Zhejiang Nanobody Technology Research Center welcomed the birth of the second little alpaca, marking the group's preliminary mastery of alpaca breeding technology. On June 1, 2022, the Shengzhou Alpaca Breeding Base imported 8 Bactrian camels from Alxa, known as the "Hometown of Camels". So far, the base has three kinds of nanobody-producing animals, llama, alpaca and bactrian camel. The nanobody obtained by the group through AI technology has better affinity, lower immunogenicity and stability than traditional antibody drugs. stronger.

Under the guidance of the innovation-driven development strategy, from July 20, 2020 to April 30, 2022, Shanghai Cell Therapy Group conducted autocrine PD1 nanobodies at the Tenth People's Hospital affiliated to Tongji University in Shanghai and Mengchao Cancer Hospital affiliated to Shanghai University. Mesothelin CAR-T cell IIT clinical trial. The patients with advanced epithelial tumors enrolled in the study had high tumor malignancy and short survival time. The survival time of relapsed and refractory patients was less than 8 months, and the patients who failed standard treatment had no cure.

This study has included 10 patients with advanced relapsed/refractory mesothelioma, all of whom have failed at least 2 lines of chemotherapy. 7 patients received 1 or 2 aPD1-mesCAR-T cell reinfusions respectively, and the reinfusion dose ranged from 1×106-1.5×107CAR-T/kg, and 6 patients completed the post-infusion safety and preliminary efficacy evaluation. No product-related dose toxicity and neurotoxicity (ICNS) occurred in all patients after reinfusion, including 1 patient with grade 3 CRS and 3 patients with grade 3 to 4 hematological adverse events. It returned to normal within a week, and there were no other obvious side effects. Twenty-eight days after the reinfusion, patients underwent enhanced CT or PET-CT to evaluate the preliminary efficacy of the product. Of the 6 evaluable mesothelioma patients, 1 achieved complete remission (CR), 2 achieved partial remission (PR), and the ORR was 50%; in PDL1+≥5% mesothelioma patients, 3 achieved objective Remission, ORR reached 100%; as of press time, all mesothelioma patients in the group have continued to survive after reinfusion, and the longest survival time has reached 22 months. CAR-T autocrine PD-1 nanobodies were continuously detected in the peripheral blood of CR patients for 9 months. Clinical studies have shown that autocrine PD1 nanobody mesothelin CAR-T cells can bring clinical benefits to patients with relapsed/refractory mesothelioma, especially those with PDL1+ tumors, by reducing tumor burden and prolonging survival. Tumor clearance and long-term tumor-free survival. The study confirmed the scientific design of nanobody-based aPD1-mesCAR-T cell drug and the biological mechanism of tumor treatment.

aPD1-mesCAR-T uses a non-viral vector system instead of traditional viral vectors. The breakthrough of curative effect is inseparable from the progress of the underlying technology. The Group is accelerating the research and development of a new generation of non-viral vectors, cooperating with many top laboratories at home and abroad to obtain new high-efficiency transposases and a new generation of plasmids that significantly exceed the functions of existing products in the world, and at the same time realize non-viral vector systems. It has achieved key technological breakthroughs, making Shanghai Cell Therapy Group's CAR-T more effective, safer and lower-cost, allowing more cancer patients to enjoy cell therapy technology with good efficacy and low price.