BEIJING – Cell therapies specialist Nanjing Iaso Biotherapeutics Co. Ltd. became the latest Chinese biotech to enter the country's fierce CAR T race, after China regulators granted an IND approval to CT-103A, a fully-human BCMA CAR T for treating relapsed or refractory multiple myeloma.

The therapy is co-developed by Nanjing-based Iaso and Innovent Biologics Inc., of Suzhou, China. The two will work together to carry out the clinical trials in China, beginning with a phase Ib/II study to confirm the recommended phase II dose.

"We plan to start clinical trials in the first quarter of 2020," Brian K. Hall, Iaso's vice president of business development, told BioWorld. "The year-long trial will include 60 to 70 patients, with approval of the therapy anticipated in the second half of 2021."

Hall added that Innovent will help his company navigate the path to approval with its team of experts.

CT-103A is designed to effectively treat the disease at lower dosage levels, with an improved safety profile. The dosage level can be as low as 1 x10^6 cells/kg.

According to the company, CT-103A has been developed as a lentiviral vector containing a CAR structure with a fully human scFv, a CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains. Iaso said it has best-in-class potential.

"In our current clinical trial, we have achieved an objective response rate of 100 percent, a stringent complete response and complete response of 70.6 percent and 88.2 percent of all patients experienced a very good partial response [VGPR] or better," Hall said.

"Being a fully human CAR T, CT-103A may also provide patients, having relapsed from a prior CAR T, an option for CAR T retreatment," he explained. "In our current study, we have four patients who have relapsed from a previous CAR T therapy responding very well to CT-103A. All of them have achieved VGPR or better."

As well as achieving a 100% objective response rate with strong persistence and high expansion of the CAR T in vivo, the onset of cytokine release syndrome also occurred within two to five days and resolved within two weeks. Out of the 11 patients being studied, four had previously relapsed from a prior CAR T therapy, a murine anti-BCMA CAR T.

"Many patients who receive CAR T treatments have had their disease recur, and with a nonhuman scFv, re-treatment may not be an option due to immunogenicity," said Chunrui Li, of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology. His institution carried out the investigator-initiated trial program of CT-103A.

"With a fully human BCMA scFv, CT-103A provides an effective option for these patients. These data suggest they should not be excluded from the benefit of future trials," Li added.

Relapsed refractory multiple myeloma is typically associated with a poor prognosis. Most of the patients who have received effective treatment will face the risks of relapse after the first-line treatment stabilizes their condition for three to five years.

CD19 still lead CAR

While CT-103A is Iaso's core asset, the biotech is developing other cures to treat hematological tumors, solid tumors and virus-associated tumors. It has three more CAR T programs, two UCAR T assets and two TCR-like CAR T therapies for tackling gastric cancer, nasopharyngeal carcinoma and viral infection-related solid tumors. They are all in very early stages of development.

Iaso has kept a low profile since its establishment in March 2017. It recently entered the spotlight with the progress of its CT-103A.

Other BCMA-targeting immunotherapies granted trial approvals in China include Carsgen Therapeutics Ltd.'s CT-053, Hrain Biotechnology Co. Ltd.'s unnamed therapy, and Nanjing Legend Biotechnology Co. Ltd.'s LCAR-B38M. Shanghai Unicar-Therapy Biomedicine Technology Co. Ltd. also has a therapy awaiting the nod.

None of the anti-BCMA immunotherapies has been approved for use yet.

A majority of the Chinese biotechs that develop CAR T therapies have their eyes set on CD19. Two CD19-directed CAR T-cell therapies, namely Kymriah (tisagenlecleucel, Novartis AG) and Yescarta (axicabtagene ciloleucel, Kite Pharma Inc./Gilead Sciences Inc.) have been approved for market by the U.S. FDA, which further encouraged China to quickly follow suit.

According to clinical trial data intelligence provider Dingxianyuan, China has 20 anti-CD19 candidates developed by nine companies in the pipeline. Ten are awaiting approvals for their clinical trial applications, nine have been granted the green light and one is undergoing trials.

Shanghai Cell Therapy Group Co. Ltd. is a forerunner in the CD19 race with its BZ-019. Other competitors include JW Therapeutics (Shanghai) Co. Ltd., Fosun Kite Biotechnology Co. Ltd., Beijing-based Juventas Cell Therapy Ltd., Beijing Immunochina Medical Science and Technology, Cellular Biomedicine Group and Guangzhou Bio-gene Technology Co. Ltd.

No Comments