BEIJING – CAR T specialist Wuhan Bio-Raid Biotechnology Co. Ltd. said its BRD-01, an anti-CD30 CAR T therapy candidate, has been granted IND approval by China’s NMPA. It is the first CD30 candidate to enter the clinic stage amid an increasingly heated CAR T race dominated by candidates targeting CD19 and BMCA.
The trial green light came slightly earlier than expected, as Bio-Raid had expected to receive it in the third quarter of this year. BRD-01 will enter phase I trials for CD30-positive relapsed/refractory hematological tumors, including Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma (ALCL), in patients ages 18 to 70.
“We plan to initiate the clinical trial in September 2020,” Shangkun Zhang, vice general manager at Bio-Raid, told BioWorld. “The initial plan is to conduct the trial at Wuhan Tongji Hospital.”
“This CAR T cell is genetically modified by transduction of the lentiviral vector packaged using the third-generation four-plasmid lentiviral packaging system,” he explained. “After optimization, BRD-01 shows a very high CAR-positive expression rate ranging from 50% to 90%, hence shortening the culture time of CAR T cells in vitro and increasing CAR T-cell activity.”
BRD-01 showed promising preclinical results. In an open-label, single-center and single-arm pilot study in patients with relapsed, refractory and high-risk CD30-positive lymphoproliferative diseases, 11 out of 13 subjects achieved complete response, one achieved partial response and another one showed stable disease. The objective response rate was 92.3% and the complete response rate was 84.6%. Among the follow-up subjects, the longest remission time was 38 months.
“In conclusion, our work demonstrated that CD30 CAR T-cell therapy is efficient and safe for HL and ALCL patients, providing a new option in treating CD30-positive relapsed/refractory lymphomas, while a larger study scale was further demanded in our trial to obtain more robust support,” researchers noted in an article submitted to The American Society of Hematology in November 2018.
BRD-01 is Bio-Raid’s most advanced program for now. It also has another candidate targeting CD19/CD22 for leukemia and lymphoma and plans to complete pilot studies. “We’re developing a dual-target CAR T-cell product and we plan to file for an IND by the end of this year,” Zhang told BioWorld.
Bio-Raid was founded in 2014 to specialize in CAR T therapies. Over six years, it has established a pipeline of CAR T product candidates covering blood and solid tumors and infectious diseases such as HIV. It plans to have submitted five IND applications to Chinese drug regulators by 2021.
Several Chinese biotech players are pushing forward their CAR T programs. As of February 2020, there were 15 cellular immunotherapy products in clinical trials in China, all of which target either CD19 or BCMA. Adding Bio-Raid’s CD30-targeting BRD-01 to the clinical pipeline could diversify China’s CAR T competitive landscape.
Another Asian player, Singapore-based Tessa Therapeutics Pte Ltd., said its CD30 CAR T-cell therapy was granted a regenerative medicine advanced therapy designation by the U.S. FDA in February.
Ivan Horak, president of R&D at Tessa, told BioWorld in a previous interview that the therapy could target number of other non-Hodgkin lymphomas where CD30 is also expressed, including “a variety of nasal natural killer (NK)/T-cell lymphomas and B-cell lymphomas.”
CD30 is originally described as a marker of Hodgkin's and R-S cells in Hodgkin lymphoma. The promising target has been a popular research subject, with 75 ongoing clinical trials related to CD30, according to data on ClinicalTrials.gov.
While Bio-Raid certainly stands out in the race at home with the first anti-CD30 CAR T therapy to enter trials, the biotech said it also looking at many more targets, including CD30, CD19, CD22, CD99, CD20, MMSA-1, BCMA, GP120, EGFR/EGFRVIII and mesothelin.
Bio-Raid, led by Zhang Tong Cun, the dean of College of Life Science and Health at Wuhan University of Science and Technology, is among the most active CAR T therapy developers in China, which also include Fosun Kite Biotechnology Co. Ltd., Legend Biotech Corp., Carsgen Therapeutics Ltd., JW Therapeutics (Shanghai) Co. Ltd. and Hrain Biotechnology Co. Ltd.
While China has not approved any CAR T therapies to date, the candidate that will most likely score the first approval is Legend Biotech’s LCAR-B38M for relapsed/refractory multiple myeloma, which is being co-developed with Janssen Biotech under a 2017 deal. Legend is said to be planning for a U.S. IPO.
According to market intelligence firm Frost & Sullivan, China’s cancer immunotherapy market is estimated to have reached ¥1.9 billion (US$268 million) in 2018, and is expected to grow to ¥82.4 billion in 2023 and ¥229.1 billion in 2030. Cancer immunotherapy is expected to become one of the major cancer therapies in the Chinese market.