Innovent Biologics has started dosing participants in the Phase Ia/Ib CIBI322A101 clinical trial of IBI322 to treat advanced malignancies in China.

IBI322 is a recombinant anti-CD47/PD-L1 bispecific antibody designed to inhibit the PD-1/PD-L1 and CD47/ SIRP-α pathways.

In pre-clinical studies, the drug candidate was able to effectively block CD47–SIRP-α interactions and trigger macrophages to phagocytize CD47 expressed tumour cells. This demonstrates the candidate’s anti-CD47 mechanism.

IBI322’s anti-PD-L1 mechanism involves the effective inhibition of the binding of PD-1 to PD-L1 and activation CD4+T lymphocyte.

As PD-L1 is expressed on tumour cells, the drug candidate is expected to selectively attach to tumour cells more potently compared to an anti-CD47 monoclonal antibody.

Innovent added that this selective attachment decreases the possibility of binding to CD47 on red blood cells, mitigating the toxicity related to anti-CD47 antibodies.

The Phase Ia/Ib trial will assess the safety, tolerability and initial anti-tumour efficacy of IBI322 in patients with advanced malignancies who did not have adequate response to standard therapy.

IBI322 obtained an investigational new drug (IND) approval from the China National Medical Products Administration (NMPA) and the US Food and Drug Administration (FDA).

Innovent Biologics vice-president and Oncology Strategy and Medical Sciences head Dr Hui Zhou said: “The preliminary results showed that IBI322 had higher efficacy in vivo, tumour-rich distribution and better safety than the single-specific anti-CD47 antibody.

“Bispecific monoclonal antibody could bring a lower-cost solution to patients compared with a combination of monoclonal antibody therapies. Therefore, the development of the anti-CD47/PD-L1 bispecific antibody will provide patients with a novel, comprehensive, effective and cost-saving treatment regimen.”

In November last year, Innovent dosed the first patient in a Phase I study of IBI315, a recombinant fully human IgG1 bispecific antibody that targets programmed cell death receptor-1 (PD-1) and human epidermal growth factor receptor 2 (HER2) simultaneously.