HONG KONG – Amid renewed interest in CD47 as an immuno-oncology target, Innovent Biologics Inc., of Suzhou, China, has received IND approval in China to start clinical trials of its monoclonal antibody (MAb), IBI-188. To further get ahead in the anti-CD47 race, Innovent will conduct clinical trials on IBI-188 at home and abroad simultaneously.

"We will start clinical development in both China and the U.S., starting with [a] dose-escalation [study]," Michael Yu, CEO of Innovent, told BioWorld Asia.

There will be several clinical trials to explore IBI-188's potential in treating multiple tumor types, including non-Hodgkin's lymphoma and ovarian cancer.

CD47 has emerged as another key target in the I-O field, following the much-studied PD-1 and PD-L1 receptors. Dubbed as the "don't eat me" protein, CD47 binds to the SIRP-alpha receptor on macrophages. 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.

There are only a few anti-CD47 antibodies in early clinical stage. In July, Chinese peer Jiangsu Hengrui Medicine Co. Ltd. had its anti-CD47 agent SHR-1603 approved for clinical trials by China's National Medical Products Administration (NMPA, formerly the CFDA). Three more similar drugs developed by Chinese drugmakers are waiting for their IND approvals.

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.)

Innovent has a global development plan for IBI-188. As China now accepts overseas clinical data, the company plans to submit the data from its U.S. clinical trials to advance IBI-188 to the finish line faster.

In addition to its use as a monotherapy, IBI-188 offers the potential for use in combination. "Emerging data suggest that [a] CD47 antibody in combination with other treatments, including anti-PD-1 monoclonal antibodies, could result in higher levels of antitumor efficacy," said Kerry Blanchard, chief scientific officer of Innovent.

The latest IND approval is the fourth received by the company from the NMPA, following regulatory clearances to move into the clinic with anti-CTLA-4 MAb IBI-310, anti-RANKL MAb IBI-307 and anti-OX40 MAb IBI-101.

Earlier this week, the company said it dosed the first patient in a phase III trial of its PD-1 antibody, IBI-308 (sintilimab), for treating first-line nonsquamous non-small-cell lung cancer (NSCLC). If successful, that trial could lead to a second NDA for the drug.

In April, Innovent applied for marketing approval for IBI-308 in China for treating relapsed or refractory classical Hodgkin lymphoma. The application was granted priority review status by the NMPA.

IBI-308 is also being studied in phase III trials in other indications, including relapsed or refractory classical Hodgkin lymphoma, lung cancer, esophageal cancers and gastric cancer.

Currently, two PD-1 inhibitors have been approved in the Chinese market, but both are foreign-bred. Opdivo (nivolumab) from Bristol-Myers Squibb Co. and Keytruda (pembrolizumab) from Merck & Co. Inc. won NMPA nods in June and July, respectively, part of China's effort to introduce PD-1/PD-L1 antibodies faster. The NMPA issued the NDA submission guidelines for immunotherapy antibodies in February. (See BioWorld, Feb. 15, 2018.)

While the approval of Opdivo has opened the door to the Chinese market for foreign drugmakers, domestic players are now vying to score the first home-grown PD-1/PD-L1 antibody win.

Besides Innovent's IBI-308, Beigene Ltd.'s BGB-A317 (tislelizumab), Hengrui's SHR-1210 (camrelizumab) and Shanghai Junshi Biosciences Co. Ltd.'s JS-001 are also waiting for marketing approval.

IBI-308's main competitor is Beigene's BGB-A317, which the company aims to market before the end of the year for treating the same indication, classical Hodgkin lymphoma. Its NDA was filed in late August, four months after IBI-308's.

Industry consultant Frost and Sullivan projected anti-PD-1 treatments will balloon in China, from $5.8 billion in the coming four years to $12.1 billion by 2025.

Innovent's drug is partnered with Eli Lilly and Co., as part of one of the largest Sino-foreign partnerships in the biotech sector, inked in 2015. (See BioWorld Today, Oct. 12, 2015.)

"We have developed IBI-308 together with Eli Lilly and have been working on multiple first-in-class bispecific antibodies," said Yu.

In June, Innovent filed an IPO to the Hong Kong Stock Exchange, which revealed the company has a pipeline of 17 antibody drug candidates.

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