HONG KONG – China has approved the fourth homegrown CD47 antibody to start clinical trials, intensifying the local CD47 race. Chinese biologics developer I-Mab Biopharma (Shanghai) Co. Ltd. said it received the go-ahead for the clinical study of TJC-4, its differentiated fully human CD47 monoclonal antibody for treating advanced malignant tumors.

This is the second IND approval for TJC-4; the first came from the U.S. FDA in January. Weimin Tang, executive vice president of global business development at I-Mab, told BioWorld that dosing of the first patient cohort at 1 mg/kg has been completed and no major hematological safety concerns have been identified so far.

"In China, we have just received the approval for initiating clinical trials. We plan to explore multiple indications by either monotherapy or combination therapies in patients with hematological or solid tumors," he said.

"We are developing our proprietary CD47 antibody, TJC-4, rapidly in the U.S. and China. Our strategy is to simultaneously develop TJC-4 globally for maximal efficiency and early commercialization."

Calling TJC-4 "a potential global best-in-class" CD47 antibody, Tang said it is "designed to avoid inherent hematologic toxicity commonly found in this class of drug candidates. The key differentiation of TJC-4 stems from its unique property to interact with a rare epitope selected from initial antibody screen. TJC-4 binds minimally to red blood cells while maintaining high tumor-killing property.

"TJC-4 does not cause hematologic toxicity in nonhuman primates," he added.

CD47 has emerged as another key target in the immuno-oncology field, following the much-studied PD-1 and PD-L1 receptors. CD47 is dubbed as the "don't eat me" protein, and it binds to the SIRP-alpha receptor on macrophages. The idea is that by blocking the CD47-SIRP-alpha signaling pathway, the "don't eat me" signal will be switched off and macrophages will then swallow the tumor cells.

CD47 race at home and abroad

So far, there are no approved anti-CD47 therapies globally.

But at least six Chinese biotech companies are known to be developing CD47 antibodies, with four in clinical stages already, including I-Mab's TJC-4. The Chinese regulators are granting IND approvals faster to intensify the race.

In June 2018, Chinese biotech giant Jiangsu Hengrui Medicine Co. Ltd. had its SHR-1603 approved for clinical trials in China, making it the first domestic player to obtain the approval. But the phase I study was withheld. Tang suggested the delay was "likely because of the hematologic adverse events."

Three months later, Innovent Biologics Inc., of Suzhou, China, received an IND greenlight for its IBI-188. It plans to launch several clinical trials to explore IBI-188's potential in treating multiple tumor types, including non-Hodgkin lymphoma and ovarian cancer. (See BioWorld, Sept. 13, 2018.)

In May, Shanghai-based Immuneonco Biopharmaceuticals (Shanghai) Co. Ltd. said its drug candidate, IMM-01, was granted IND approval in China to investigate its efficacy for leukemia. It took the company only 39 working days to receive that approval.

Outside of China, other players advancing CD47-targeting drugs include Canadian firm Trillium Therapeutics Inc., the aptly named Forty Seven Inc., of Menlo Park, Calif., and biopharma powerhouse Celgene Corp. (See BioWorld, May 8, 2018.)

Of all the CD47 antibodies under development, only Forty Seven's Hu5F9 is in phase II testing; the others are still in phase I.

Since China now accepts overseas clinical data, companies that have already started clinical trials in the U.S. may benefit from that policy to speed up their development programs in China. Innovent, which conducts clinical trials on IBI-188 at home and abroad simultaneously, plans to do so.

Two more Chinese players are also known to be studying CD47-targeting therapies. Tasly Biopharmaceuticals Co. Ltd. has SY-102 for leukemia and solid tumors in the preclinical stage, as revealed in its prospectus filed with the Hong Kong Stock Exchange last month. Genrix (Shanghai) Biopharmaceutical Co. Ltd., meanwhile, has filed a patent application for a CD47 antibody.

Expanding pipeline

Beyond the CD47 front, I-Mab is working to expand its innovative drug pipeline. Last week, it in-licensed the greater China rights to an anti-B7-H3 monoclonal antibody known as enoblituzumab. B7-H3 is a target for which no agent is currently approved. (See BioWorld, July 12, 2019.)

The initial focus will be on squamous cell carcinoma of the head and neck, the most common type of head and neck cancer that is treated by cetuximab, the only approved drug in China.

"By acquiring the greater China rights of enoblituzumab, we hope to strengthen our clinical stage pipeline of innovative immune-oncology investigational drugs, including antibodies targeting CD47 and CD73," Jielun Zhu, chief financial officer at I-Mab, told BioWorld.

"As the only conventional B7-H3 antibody in clinical development worldwide, enoblituzumab has the potential to be a first-in-class anticancer immunotherapy for a variety of solid tumors that overexpress B7-H3," he added.

I-Mab will also see how it can combine enoblituzumab with other drug candidates in its pipeline to maximize its value, as so far enoblituzumab has already shown promising therapeutic potential in combination with PD-1 inhibitors.

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