Target CD47: The fiery track attracts the crowds to compete and differentiated competition becomes increasingly obvious

After PD-1/L1 inhibitors, CD47 has become another popular target among immune checkpoint inhibitors.

01 CD47-SIRPα signal transduction

As an important "immune checkpoint" molecule of innate immunity, CD47 can play a role in cell migration, adhesion, proliferation and apoptosis

The strategy of targeting CD47-SIRPα signal transduction is to prevent the combination of the two and stop the "don't eat me" signal sent by cancer cells to macrophages

Anti-CD47 or SIRPɑ antibody can be used to induce macrophages to phagocytose tumor cells

02 Targeting CD47

CD47 monoclonal antibody was the first to enter clinical research and development

The killing power of macrophages induced by single drug on tumor is related to the selection of IgG subclass

There is another way that has not completely abandoned the potent ADCC effect of CD47 antibodies, and only uses the biological effects of CD47-SIRPα itself to release the anti-tumor potential of macrophages

Clinical stage CD47 antibody/fusion protein drugs

03 Targeting SIRPα

The main advantage of targeting SIRPα to block the CD47-SIRPα checkpoint is that SIRPα has limited tissue distribution and is not expressed on red blood cells.

Trillium and ALX Oncology lead the development of SIRPα fusion protein drugs.

Trillium develops two SIRPα fusion proteins of different IgG subtypes at the same time

Clinical stage SIRPα antibody/fusion protein drugs

04 differentiated competition

This field seems very crowded, but because of the differences in the development of technology, the development of them in different indications is also differentiated

Gilead’s magrolimab is clearly ahead of its competitors and is most likely to become the first CD47 antibody on the market

In August 2021, Pfizer announced the acquisition of Trillium Therapeutics for US$2.

It is difficult to draw conclusions due to the relatively small sample size, but CD47+CD20 does not seem to improve ORR

Is a single drug the best standard for evaluating CD47 antibody drugs? It is worth noting that although magrolimab and ALX148 monotherapy have poor efficacy, when combined with rituximab in the treatment of relapsed or refractory CD20-positive B-cell non-Hodgkin’s lymphoma, the ORR is 50% and respectively.

AXL’s SIRPα-Fc fusion protein ALX148 is the first drug to be used in combination and to be explored in solid tumors

ALX148 combined treatment phase I trial results

Preliminary results showed that in the HNSCC cohort, the ORR of 10 CPI-naïve second-line patients was 40% (n=4).

At present, there are also dual antibody strategies.

Clinical stage CD47 double anti-drugs