Alx418, a CD47 checkpoint inhibitor, has two FDA fast track qualifications

Alex oncology is a clinical stage immunooncology company dedicated to developing innovative therapies that block the checkpoint mechanism of CD47, which cancer cells use to evade the immune system Recently, the company announced that the U.S Food and Drug Administration (FDA) has awarded its leading candidate drug alx148 two fast channel qualification (FTD) for the first-line treatment of head and neck squamous cell carcinoma (HNSCC) patients, and the second-line treatment of HER2 positive gastric or gastroesophageal junction (gastric / GEJ) adenocarcinoma patients FTD aims to accelerate drug development and rapid review for critical diseases to address critical unmet medical needs in key areas The fast track qualification of experimental drugs means that pharmaceutical companies can interact with FDA more frequently in the R & D stage If they meet the relevant standards after submitting the listing application, they are qualified for accelerated approval and priority review, as well as rolling review The FDA grants alx148 FTD based on data from an open label, multicenter phase I clinical trial The data showed that the objective response rate (ORR) of alx418 combined with keytruda was 40% in HNSCC patients who had previously received platinum containing chemotherapy and had not received immunosuppressive checkpoint inhibitors (initial treatment of checkpoint inhibitors) In addition, in patients with gastric / GEJ cancer who had previously been treated with at least one anti HER2 regimen, the orr of the combination of alx418 and trastuzumab was 21% Dr Sophia Randolph, chief medical officer of alx oncology, said: "the FDA granted alx148 fast track qualification, which is an important recognition of the efficacy data in the company's phase I clinical trials This qualification reflects an important progress of alx148 in the treatment of HNSCC and HER2 positive gastric / GEJ cancer patients We are encouraged by the preliminary data from phase I clinical trials We look forward to working closely with FDA to develop alx148 for cancer patients " CD47 is a kind of glycoprotein widely expressed on the surface of many kinds of cancer cells It can release the signal of "don't eat me" through the connection with SIRP α on the surface of tumor phagocytes and prevent macrophages from phagocytosis Alx148 is a new generation of CD47 myeloid checkpoint inhibitor, which is a fusion protein for intravenous infusion It consists of two engineering high affinity CD47 binding domains of SIRP α connected to an inactive Fc domain of human immunoglobulin Compared with the natural SIRP α, the affinity of alx148 to CD47 was significantly improved The key features of alx418 include: (1) alx418 binds to CD47 with high affinity and inhibits the cd47-sirp α signal pathway; (2) the Fc domain of alx418 is inactivated by engineering mutation, eliminating the binding effect on FC γ receptor, minimizing the hematological toxicity observed by other CD47 blockers; (3) the molecular weight of alx418 is half of the antibody, so it can achieve linear pharmacokinetics, The complete target occupancy of CD47 was achieved at about half of the dose of anti-CD47 antibody The mechanism of alx418 is as follows: (1) macrophage phagocytosis is regulated by cd47-sirp α signal (an inhibitory signal) and Fc receptor (an active signal) The combination of alx418 (blocking CD47) and anticancer antibody (binding Fc receptor) can activate macrophages to the greatest extent and eliminate tumor cells; (2) alx418 can increase inflammatory M1 tumor related macrophages (TA) M) (3) alx418 can activate dendritic cells (DC) and enhance the cross activation of T cells, including CD8 + cytotoxic T cells In preclinical model, alx418 can block CD47 and enhance the activity of checkpoint inhibitors and anti-cancer targeted antibodies safely through FC dependent and independent mechanisms Therefore, alx418 can bridge innate and adaptive immunity to activate various types of immune cells against cancer At present, ALX148 is undergoing clinical development in a wide range of tumor types to maximize the potential of anti-cancer treatment.