ligufalimab (AK117) / Akesobio - LARVOL DELTA

ILLUMINE: Study Comparing Ivonescimab Alone or Ivonescimab in Combination With Ligufalimab Versus Pembrolizumab for the Treatment of SCCHN (clinicaltrials.gov) - P3 | N=780 | Not yet recruiting | Sponsor: Groupe Oncologie Radiotherapie Tete et Cou

New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A Study of Ivonescimab in First-Line ES-SCLC (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Akeso

New P2 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Phase 1b Study Evaluating the Safety and Efficacy of AK117 (anti-CD47 monoclonal antibody) in Combination with Azacitidine in Patients with Treatment-Naïve Acute Myeloid Leukemia (ASH 2023) - "The combination of AK117 and AZA exhibited a manageable safety profile with a low incidence of anemia, and demonstrated promising efficacy as a first-line treatment in AML patients who were unable to undergo intensive chemotherapy."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Anemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

AK117 (anti-CD47 monoclonal antibody) in Combination with Azacitidine for Newly Diagnosed Higher Risk Myelodysplastic Syndrome (HR-MDS): AK117-103 Phase 1b Results (ASH 2023) - "AK117 in combination with AZA was well tolerated with low incidence of anemia and demonstrated promising efficacy in patients with newly diagnosed HR-MDS."

Combination therapy • P1 data • Anemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Trial in Progress: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 2 Study of AK117/Placebo in Combination with Azacitidine in Patients with Newly Diagnosed Higher-Risk Myelodysplastic Syndromes (AK117-205) (ASH 2024) - P2 | "Additionally, unlike the first generation anti-CD47 agents such as magrolimab, AK117 does not cause red blood cell agglutination and on-target anemia. Stratification factors will be based on IPSS-R scores : ≤4.5, >4.5-6, and >6.The primary endpoint is complete remission rate (CRR) assessed by investigators based on 2023 International Working Group (IWG 2023) response criteria (Zeidan A et al, Blood, 2023), and to determine the optimal dose of AK117 for future confirmatory trials (can expand this Phase 2 trial to a Phase 3 trial). Key secondary endpoints include overall response rate (ORR), duration of response (DoR), event-free survival (EFS), overall survival (OS), rate and duration of transfusion independence (TI), time to transformation to acute myeloid leukemia (AML), safety assessed by incidence and severity of adverse events (AEs), pharmacokinetics (PK) and immunogenicity."

Clinical • Combination therapy • P2 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • SIRPA

AK112-206: A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=254 | Active, not recruiting | Sponsor: Akeso | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor

…Patient enrollment has been completed in a randomized, double-blind, multicenter Phase II study assessing ligufalimab combined with azacitidine in higher-risk myelodysplastic syndromes (HR-MDS). (PRNewswire)

Enrollment closed • Myelodysplastic Syndrome

Anti-CD47 drug interference in pre-transfusion testing can be overcome by antigen masking. (PubMed, Transfusion) - "These findings emphasize the need for awareness and adaptation in immunohematology practices as anti-CD47 drugs continue to advance in clinical development, and highlight the utility of antigen masking strategies to enhance the safe administration of blood products to treated patients."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD47 • SIRPA

Akeso's Ligufalimab (CD47 mAb) Receives FDA Orphan Drug Designation for Acute Myeloid Leukemia (AML) (PRNewswire) - "Clinical trials have demonstrated that ligufalimab combined with azacitidine shows a favorable safety profile and promising efficacy in first-line AML treatment."

Orphan drug • Acute Myelogenous Leukemia

Akeso Announces First Patient Enrollment in Phase III Trial of Ivonescimab for Pancreatic Cancer (PRNewswire) - "Akeso...is pleased to announce that the first patient has been enrolled in the pivotal/registration Phase III clinical trial (AK112-310/HARMONi-GI2) of ivonescimab, a first-in-class PD-1/VEGF bispecific antibody developed by the company. The trial is investigating ivonescimab in combination with chemotherapy, with or without ligufalimab (CD47 monoclonal antibody), for the first-line treatment of metastatic pancreatic cancer."

Trial status • Pancreatic Cancer

TRIAL IN PROGRESS: AN INTERNATIONAL, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER PHASE 2 STUDY OF AK117/PLACEBO IN COMBINATION WITH AZACITIDINE IN PATIENTS WITH NEWLY DIAGNOSED HIGHER-RISK MYELODYSPLASTIC SYNDROMES (AK117-205) (EHA 2025) - P2 | "Additionally, unlike the first generation anti-CD47 agents such as magrolimab, AK117 does not cause red blood cell agglutination and on-target anemia. The primary objective of the study is to determine the optimal dose of AK117 for future confirmatory trials. Assuming the CR rates are 50%, 35%, and 20% for the 30mg/kg (the assumed superior dose), 20mg/kg, and the control group, respectively, with 30 patients per group, the power to detect a statistically significant difference between the superior dose and the control is 84% at a 1-sided alpha level of 10%; the probability of selecting the superior dose is 86%; the probability of mistakenly selecting the inferior dose is 14%.Key secondary endpoints include overall response rate (ORR), duration of response (DoR), event-free survival (EFS), and overall survival (OS)."

Clinical • Combination therapy • P2 data • Anemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • SIRPA

A phase II study of AK117 combined with cetuximab or AK104 in the treatment of recurrent or metastatic head and neck squamous cell carcinoma after the failure of PD-1 (L1) inhibitors and/or platinum-based therapy. (ASCO 2025) - P2 | "Funded by Akeso, Inc Clinical Trial Registration Number: NCT06508606 Background: The administration of first-line pembrolizumab monotherapy or pembrolizumab combined chemotherapy has been shown to improve survival among patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The primary endpoints are incidence of adverse events and overall survival. Secondary endpoints are objective response rate, progression free survival, disease control rate, and duration of response."

Metastases • P2 data • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CTLA4

A Phase III Study of Ivonescimab + Chemo With/Without AK117 vs Chemo in Metastatic Pancreatic Cancer (clinicaltrials.gov) - P3 | N=999 | Not yet recruiting | Sponsor: Akeso

New P3 trial • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

AK117-203: A Study of AK117/AK112 in Metastatic Triple-Negative Breast Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Akeso | N=80 ➔ 120 | Trial completion date: Oct 2023 ➔ Dec 2026 | Trial primary completion date: Jan 2023 ➔ Jul 2025

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

AK117-202: A Study of AK112 in Advanced Malignant Tumors (clinicaltrials.gov) - P1/2 | N=250 | Active, not recruiting | Sponsor: Akeso | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2025 ➔ Jun 2026 | Trial primary completion date: Aug 2024 ➔ May 2025

Enrollment closed • Trial completion date • Trial primary completion date • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor

AK117-104: A Trial of AK117 (Anti-CD47 Antibody) in Patients With Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=68 | Active, not recruiting | Sponsor: Akeso | Recruiting ➔ Active, not recruiting | N=160 ➔ 68 | Trial completion date: Jul 2024 ➔ Dec 2025 | Trial primary completion date: Jul 2023 ➔ Sep 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

AK117-103: A Trial of AK117 (Anti-CD47) in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=136 | Active, not recruiting | Sponsor: Akeso | Recruiting ➔ Active, not recruiting | Trial completion date: May 2024 ➔ Dec 2025 | Trial primary completion date: May 2023 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

AK112-206: A Study of AK112 With or Without AK117 in Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=254 | Recruiting | Sponsor: Akeso | N=104 ➔ 254 | Trial completion date: Dec 2026 ➔ Aug 2028 | Trial primary completion date: Dec 2024 ➔ May 2026

Enrollment change • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

Ligufalimab and Cadonilimab in Advanced Liver Cancers (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

A Study of AK129 With or Without AK117 in PD(L)1-refractory Classic Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: Akeso | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2024 ➔ Jan 2025

Enrollment open • Trial initiation date • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Akeso to Share Global Strategy for New Drug Development at the 43rd J.P. Morgan Healthcare Conference (PRNewswire) - "Akeso, Inc...is pleased to announce its participation in the upcoming 43rd Annual J.P. Morgan Healthcare Conference, taking place on January 13, 2025, in San Francisco, California. The company's founder, chairwoman, president, and CEO, Dr. Michelle Xia will share the latest developments and plans for its globally leading programs, including ivonescimab (PD-1/VEGF bispecific antibody), cadonilimab (PD-1/CTLA-4 bispecific antibody), and ligufalimab (CD47 monoclonal antibody), as well as more cutting-edge multispecific antibody pipeline assets."

Pipeline update • Hematological Malignancies • Solid Tumor

A Randomized, Controlled, Multicenter Phase 3 Study of AK112 in Combination With AK117 Versus Pembrolizumab as First Line Treatment for a Programmed Cell Death-ligand 1 (PD-L1) Positive Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (ChiCTR) - P3 | N=510 | Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Union Hospital, Tongji Medical College, Huazhong University of

New P3 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Ligufalimab and Cadonilimab in Advanced Liver Cancers (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: University of Texas Southwestern Medical Center

New P2 trial • Biliary Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor

A Phase 3 Study of AK112 Plus AK117 Versus Pembrolizumab in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (clinicaltrials.gov) - P3 | N=510 | Recruiting | Sponsor: Akeso | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

AK132, a first-in-class asymmetric Claudin18.2/CD47 bispecific antibody for cancer immunotherapy (SITC 2024) - "Mice were treated with Isotype control antibody, AK117 (a bivalent CD47 antibody with IgG4 backbone; 20 mg/kg), anti-CLDN8.2 (a bivalent CLDN18.2 antibody with IgG1 backbone; 20 mg/kg) and AK132 (1.9 mg/kg; 5.7 mg/kg; 17 mg/kg) via i.p. injection...Conclusions AK132, an asymmetric CLDN18.2/CD47 bispecific antibody, has ADCC, ADCP and CDC effects on tumor cells but not on RBCs. It shows great anti-tumor efficacy with better safety, supporting its clinical development for the treatment of human cancers."

Colon Cancer • Colorectal Cancer • Gastric Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD47 • CLDN18 • CLDN8