ligufalimab (AK117) / Akesobio - LARVOL DELTA

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 | "Clinical Trial Registration Number: NCT06508606 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

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

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

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

Akeso Announces First Patient Enrollment in Phase 3 Trial of Ivonescimab Combined with Ligufalimab (CD47) for First-Line Treatment of Head and Neck Squamous Cell Carcinoma (HNSCC), Compared to Pembrolizumab (PRNewswire) - "Akeso Biopharma...is pleased to announce the enrollment of the first patient in its randomized, controlled, multicenter Phase III clinical study (AK117-302) for head and neck squamous cell carcinoma. This trial evaluates the innovative PD-1/VEGF bispecific antibody ivonescimab in combination with Akeso's next-generation CD47 monoclonal antibody ligufalimab (AK117) against pembrolizumab for the first-line treatment of PD-L1 positive (CPS≥1) recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC)."

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

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 | Not yet recruiting | Sponsor: Akeso

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

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

Combination therapy • Monotherapy • New P1/2 trial • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

A novel anti-CD47 antibody with therapeutic potential for NK/T-cell lymphoma. (PubMed, Hum Vaccin Immunother) - "In addition, in vivo experiments showed that the anti-CD47 mAb AK117 significantly inhibited the growth of subcutaneous xenograft tumors in SCID mice compared to the control antibody IgG. Our results indicate that targeting CD47 monoclonal antibodies is a potential therapeutic strategy for NKTCL."

IO biomarker • Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD47

Akeso Published Ivonescimab plus Ligufalimab as First-Line Treatment for PD-L1-Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma at ESMO 2024 (PRNewswire) - P1b/2 | N=114 | NCT05229497 | Sponsor: Akeso | "The objective response rate (ORR) for ivonescimab monotherapy group is 30%, while the ORR increases to 60% in ivonescimab plus ligufalimab group. The disease control rate (DCR) is 80% for ivonescimab monotherapy group improves to 90% with ligufalimab...The ORR for ivonescimab monotherapy and the combination of ivonescimab plus ligufalimab was to 40% and 65%, respectively. The median progression-free survival (mPFS) for ivonescimab monotherapy group was 5.0 months, with the 6-month PFS rate not yet reached. For the combination with ligufalimab group, the mPFS was 7.1 months, with a 6-month PFS rate of 71.8%. The safety profile of the ivonescimab for first-line treatment of PD-L1-positive R/M HNSCC was manageable, with no treatment-related adverse events (TRAE) leading to drug discontinuation or death in both the ivonescimab monotherapy and the ivonescimab plus ligufalimab groups."

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

Evaluation of the safety and efficacy of ivonescimab in combination with ligufalimab as first-line (1L) treatment for PD-L1 positive recurrent/metastasis head and neck squamous cell carcinoma (R/M HNSCC) (ESMO 2024) - P1/2 | "Ivonescimab with or without ligufalimab showed promising anti-tumor activity in pts with PD-L1 positive R/M HNSCC with a favorable safety profile."

Clinical • Combination therapy • IO biomarker • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

The efficacy and safety of ivonescimab with or without ligufalimab in combination with FOLFOXIRI as first-line (1L) treatment for metastatic colorectal cancer (mCRC) (ESMO 2024) - P2 | "Background: FOLFOXIRI plus bevacizumab is the standard 1L treatment for mCRC... Ivonescimab with or without ligufalimab in combination with FOLFOXIRI showed promising efficacy and tolerable safety as 1L treatment in pts with mCRC."

Clinical • Combination therapy • IO biomarker • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • KRAS

The world’s first CD47 solid tumor phase III: Kangfang Biopharma AK112+AK117 vs. K drug [Google translation] (bydrug.pharmcube.com) - "On September 11, the Drug Clinical Trial Registration and Information Disclosure Platform showed that Kangfang Biopharma launched a head-to-head Phase III study of AK112 (ivonescimab) combined with AK117 (Lefalimab/Ligufalimab) versus Pembrolizumab (K drug) for the treatment of head and neck squamous cell carcinoma."

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

Akeso to Present Data from 13 Clinical Studies at ESMO 2024, Featuring its Internally Developed Cadonilimab, Ivonescimab, Ligufalimab, and other I/O Antibodies (PRNewswire) - "Akeso...will showcase promising results from 13 clinical studies on its internally developed PD-1/CTLA-4 bispecific antibody cadonilimab, PD-1/VEGF bispecific antibody ivonescimab, next-generation CD47 monoclonal antibody ligufalimab, and commercially available PD-1 monoclonal antibody penpulimab at the ESMO Congress 2024 from September 13th to 17th (CEST). These studies span advanced colorectal cancer, triple-negative breast cancer, head and neck squamous cell carcinoma, hepatocellular carcinoma, nasopharyngeal carcinoma, gynecological malignancies, gastric cancer, esophageal squamous cell carcinoma, and biliary tract malignancies."

Clinical data • Biliary Tract Cancer • Colorectal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gynecologic Cancers • Hepatocellular Cancer • Nasopharyngeal Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

First Patient Enrolled in the US Phase 2 Combination Therapy of Akeso's Ligufalimab with Azacitidine for Myelodysplastic Syndrome (PRNewswire) - "Akeso has announced the completion of the first patient enrollment in the US for the phase II clinical trial of its innovative CD47 monoclonal antibody, ligufalimab (AK117), in combination with azacitidine for patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS). Preliminary studies show that combining AK117 with azacitidine for treating MDS is safe and significantly effective. In response to the urgent need for new therapies among global MDS patients and the evolving market landscape, Akeso has launched an international multicenter Phase II clinical trial. This initiative aims to expedite AK117's global approval and commercialization process."

Enrollment open • Myelodysplastic Syndrome

First Patient Enrolled in the US Phase 2 Combination Therapy of Akeso’s Ligufalimab with Azacitidine for Myelodysplastic Syndrome (PRNewswire) - "Akeso has announced the completion of the first patient enrollment in the US for the phase II clinical trial of its innovative CD47 monoclonal antibody, ligufalimab (AK117), in combination with azacitidine for patients with newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS)."

Enrollment status • Myelodysplastic Syndrome