HONG KONG, December 11, 2022 /PRNewswire/ — Akeso Inc. (9926. HK) (“Akeso”) announced today that the Journal for Immunotherapy of Cancer (JITC), a BMJ oncology journal, has published the mechanism of action of its Ligufalimab (AK117). The title of the article is “Ligufalimab, a novel non-hemagglutination-free anti-CD47 antibody that shows both monotherapy and combination antitumor activity”. The results showed promising antitumor efficacy and a favorable safety profile of AK117. The unique mechanism of action of AK117 was also announced at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2021).
AK117 is a new humanized IgG4 anti-CD47 antibody without hemagglutination effect developed by Akeso Independently. AK117 promotes tumor cell phagocytosis and improves antitumor efficacy without the need for a lower starting dose to prevent anemia. This article comprehensively elaborates the safety breakthrough and antitumor activity of AK117 as a new generation CD47 monoclonal antibody alone or in combination from a mechanistic point of view. AK117 is expected to lead to better efficacy and safety in clinical practice and expansion of indications.
The JITC publication includes the following findings:
- AK117 that specifically binds human CD47 with high affinity and blocks the interaction of SIRPα with CD47
AK117 can specifically bind human CD47 with high affinity. And AK117 effectively blocked CD47-SIRPα interaction on the surface of tumor cells, and the blocking activity of AK117 was comparable to that of Hu5F9-G4.
- AK117 does not induce agglutination of red blood cells associated with binding epitopes
CD47 is ubiquitously expressed on various human cells, including erythrocytes and platelets. The main adverse events associated with treatment with CD47-blocking antibodies are hematotoxicity, particularly hemagglutination and anemia. The hemagglutination test showed that AK117 did not induce erythrocyte hemagglutination even at concentrations up to 3000 nM, while Hu5F9-G4 induced erythrocyte hemagglutination at concentrations lower than 4.1 nM.
The different binding orientations of AK117 and Hu5F9-G4 on CD47 could be related to different epitopes of AK117 and Hu5F9-G4 binding. The AK117/CD47 complex formed a smaller angle, indicating that AK117 is unlikely to bind two cells simultaneously. However, the long distance between the two bound CD47 proteins is more permissive for Hu5F9-G4 to bind CD47 on two different cells, resulting in RBC agglutination.
- AK117 promotes phagocytosis of tumor cells and shows antitumor activity in a mouse model
AK117 induces tumor cell phagocytosis in a dose-dependent manner and improves antitumor efficacy, with activity similar to Hu5F9-G4. AK117 shows strong antitumor activity in a mouse model, and the antitumor activity of AK117 was significantly higher than that of Hu5F9-G4 at a dose of 0.02 mg/kg.
- AK117 shows potent antitumor activity of AK117, as monotherapy or in combination with AK112
The results showed that tumor growth was effectively inhibited in the monotherapy and combination therapy groups, and a dramatic inhibition effect was observed in the AK117 and AK112 combination group with statistically significant differences, and no obvious loss of mice body was found in all groups.
- AK117 shows a favorable safety profile in non-human primates compared to Hu5F9-G4.
Toxicological evaluation of AK117 was performed in cynomolgus monkeys. AK117 did not induce hemagglutination of red blood cells in cynomolgus monkeys. Compared with Hu5F9-G4, AK117 caused less anemia and recovered rapidly with greater safety.
Based on preclinical data and early clinical results, a number of phase IB/II clinical studies of AK117 in combination with different agents for the treatment of a range of cancer types are underway ( NCT04900350, NCT04980885, NCT05227664, NCT05229497, NCT05214482, NCT05235542, NCT05382442).
SOURCE Akeso, Inc.