HONG KONG - China and U.S.-based I-Mab Biopharma Co Ltd. has won two IND clearances for TJ-202/MOR-202 from China's National Medical Products Administration (NMPA).

The candidate is a human monoclonal antibody (MAb) derived from Martinsried, Germany-based Morphosys AG's HuCAL antibody technology.

Through an agreement in November 2017, I-Mab had licensed the exclusive rights for the development and commercialization of TJ-202/MOR-202 in mainland China, Taiwan, Hong Kong and Macau.

According to I-Mab, TJ-202/MOR-202 is an antibody directed against CD38 on the surface of multiple myeloma cells, which has been characterized as one of the most strongly and uniformly expressed antigens on the surface of malignant plasma cells.

With the NMPA's green light, I-Mab will now expand two ongoing clinical trials with TJ-202/MOR-202 in Taiwan.

A phase II study initiated in March is designed to evaluate the efficacy and safety of TJ-202/MOR-202 as a third-line treatment in patients with relapsed or refractory multiple myeloma (MM).

Additionally, a phase III study, commenced in April, assesses the efficacy and safety of the combination of TJ-202/MOR-202 plus lenalidomide (LEN) and dexamethasone (DEX) vs. the combination of LEN and DEX in patients with relapsed or refractory MM who received at least one prior line of treatment.

"Obtaining the clearance from the NMPA enables us to advance with the two planned registrational trials in China rapidly in our effort to bring the drug to the market as efficiently as possible. We have identified the appropriate clinical trial sites in China, which should allow us to initiate the studies quickly," Joan Shen, the head of R&D at I-Mab, told BioWorld.

I-Mab has a strategy for making sure the study cycle has been seamless.

"One of the major advantages of conducting trials in Taiwan is that the approval of [a] clinical trial application by the Taiwan FDA can be rapid, often taking only 30 days, when there is an approval of IND/first-in-human study by [the] U.S. FDA, which there was for our product," said Shen.

That enabled I-Mab to initiate clinical studies in Taiwan without delay, while it continued to discuss and work with China's NMPA on initiating trials in mainland China.

"We presented our clinical plan to the CDE, including the planned Taiwan trials. Once we completed an abbreviated animal pharmacokinetic study requested by CDE to bridge the chemistry, manufacturing and control [CMC], we received their endorsement to begin clinical studies in China," said Shen.

Parallel tracks

That parallel track has worked out well for I-Mab, enabling a seamless link between its studies in Taiwan and mainland China. In addition, the data from Taiwan will be part of the overall data package for the BLA submission in the mainland as well.

"It is believed that TJ-202/MOR-202 recruits cells of the body's immune system to kill the tumor through antibody-dependent cellular cytotoxicity [ADCC] and antibody-dependent cellular phagocytosis [ADCP], while sparing the complement-dependent cytotoxicity [CDC]," said Shen.

I-Mab has said that distinction in the mechanism of action (i.e. ADCC/ADCP vs. CDC) may result in an improved safety profile for its antibody, as it has observed significantly fewer injection site reactions compared to other drugs currently on the market or in development.

TJ-202/MOR-202 is one of the more advanced products in I-Mab's pipeline and could be one of its first products to reach the market.

It was initially developed as a third-line treatment in patients with relapsed or refractory MM.

"If we continue to see a clear benefit-versus-risk profile with these clinical studies, we anticipate being in a position to possibly submit a BLA in 2H 2021 in our first indication, with potential approval in 2022 subject to feedback from the NMPA," Shen told BioWorld.

"We are also pursuing second-line treatment for TJ-202/MOR-202 in combination with LEN and DEX in patients with relapsed or refractory MM who received at least one prior line of treatment." She said she anticipates completing that phase III study and submitting the BLA in 2023, with potential approval in 2024.

I-Mab also scored an IND recently for its CD73 antibody in mainland China. It got the go-ahead for a phase I/II trial of TJD-5 in patients with advanced solid tumors. (See BioWorld, Oct. 9, 2019.)

"I-Mab has a robust pipeline of eight clinical-stage biologics with novel and highly differentiated profiles. We are making steady progress executing our clinical development plans for those assets," Jielun Zhu, chief financial officer of I-Mab, told BioWorld.

"In addition to clinical assets, we also boast a preclinical pipeline with nine cutting-edge candidates consisting of two next-generation MAbs and seven uniquely bioengineered bispecific antibodies. We are working hard to get them through IND and into clinical development in the U.S. in the near term," Zhu added.

The company is also in an advanced planning stage for its own manufacturing facility in China.

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