EP0089 / Genome & Company, Ellipses Pharma - LARVOL DELTA

A phase I/IIa study to evaluate the safety and tolerability, activity and PK of a potential novel CNTN4-targeted checkpoint inhibitor, EP0089, in patients with advanced solid tumors (AACR-NCI-EORTC 2025) - P1/2 | "The study is being conducted in the Republic of Korea, Australia and United States and later in Europe. Target recruitment is approximately 190 patients."

Checkpoint inhibition • Clinical • IO biomarker • Late-breaking abstract • Metastases • P1/2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Melanoma • Oncology • Solid Tumor • APP • CD4 • CD8 • CNTN

GENA104-101: A First-in-human Study of GENA-104A16 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Genome & Company | N=80 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Solid Tumor

A Study to Evaluate the Safety and Tolerability of EP0089 (clinicaltrials.gov) - P1/2 | N=190 | Not yet recruiting | Sponsor: Ellipses Pharma

New P1/2 trial • Oncology • Solid Tumor

Targeting CNTN4 with exatecan-based antibody-drug conjugate for the treatment of solid tumors (AACR 2025) - "This ADC utilizes GENA-104A16.hIgG1 (A16.1), an anti-CNTN4 antibody with reduced effector function of human IgG1, conjugated via cysteine-maleimide linkage to linker including hydrophilic moiety and the topoisomerase I inhibitor (exatecan) with high drug-to-antibody ratio (DAR)(A16.1-Exa). To evaluate its potential, the internalization performance of A16.1 was compared with trastuzumab (anti-HER2) using SK-BR3 cells engineered to overexpress CNTN4, which exhibited a higher HER2 target count than CNTN4 target count...The treatment showed strong anti-tumor activity, leading to tumor regression. Future studies will expand the PDX models and optimize the therapeutic potential of exatecan conjugates to advance the development of CNTN4-targeted therapies, offering a promising approach for treating diverse cancers."

Fibrosarcoma • Melanoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • ACTN4 • APP • CNTN

Immunostimulatory effects of GENA-104A16, a monoclonal anti-CNTN4 antibody, on tumor-infiltrating lymphocytes in a colon cancer liver metastasis model (AACR 2025) - "One day later, mice were treated with either isotype control (n=10), GENA-104A16 (n=10), or atezolizumab (n=9) via intraperitoneal injection (3 mg/kg) on a q3d schedule. Our findings demonstrate a significant increase in CD4+ and CD8+ TILs following treatment with GENA-104A16 in a clinically relevant model, suggesting a potential for enhanced anti-tumor immunity. These results support the clinical evaluation of GENA-104A16 and underscore the potential of TILs quantified by an AI-powered IHC analyzer as a predictive biomarker for its therapeutic efficacy."

IO biomarker • Tumor-infiltrating lymphocyte • Colon Cancer • Colorectal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • APP • CD4 • CD8

Ellipses In-Licences First in Class Novel Immuno-Oncology Agent With Potential as a Next Generation Checkpoint Inhibitor (Businesswire) - "Ellipses Pharma Limited...announced today it is to develop a next-generation immuno-oncology drug which could address the needs of cancer patients who do not respond to existing checkpoint inhibitors. Ellipses has agreed to in-license global rights to ‘GENA-104’, a first-in-class immuno-oncology monoclonal antibody that targets CNTN4, a recently discovered checkpoint protein that is highly expressed in a wide range of tumour types....Under the agreement with Genome, Ellipses will take responsibility for all future clinical development of GENA-104 under the identifier EP0089....A Phase 1 IND for EP0089 was approved by the South Korean Ministry of Food and Drug Safety in January 2024. Ellipses expects to initiate a Phase 1 clinical trial in South Korea during 2025 with expansion of involvement to the US and Europe following the relevant regulatory approvals."

Licensing / partnership • New P1 trial • Oncology

Contactin-4 suppresses antitumor T cell responses by engaging amyloid precursor protein. (PubMed, Sci Immunol) - "We developed an anti-CNTN4 antibody (GENA-104A16) and an anti-APP antibody (5A7) that blocked the binding between CNTN4 and APP...Furthermore, elevated CNTN4 levels were associated with poor prognosis and negatively correlated with various cytotoxic immune-related markers. These results suggest that CNTN4-APP is an inhibitory checkpoint in T cells and represents a promising therapeutic strategy for cancer immunotherapy."

IO biomarker • Journal • Oncology • APP • CNTN

Genome & Company “GENA-104 will achieve technology export results with multinational pharmaceutical companies” [KIW2024] [Google translation] (Hankyung) - "Hong Yoo- seok, CEO of Genome & Company, at the ‘Korea Investment Week (KIW) 2024’ held at the Conrad Hotel in Yeouido-dong, Seoul on the 9th. 'There is a demand from multinational pharmaceutical companies to acquire the rights to GENA-104 and conduct clinical trials directly.'....'We are currently discussing signing a contract with a multinational pharmaceutical company that can conduct phase 1 and 2 clinical trials of CNTN4 well.'"

Licensing / partnership • Oncology • Solid Tumor

Association between the CNTN4 expression and responsiveness to pembrolizumab in gastric cancer (AACR 2024) - "Hazard ratio = 3.303 [95% CI = 1.647-6.624], P = 0.0008).Together, we suggest that CNTN4 is a potential ICP candidate for gastric cancer patients unfavorable to pembrolizumab treatment. The anti-CNTN4 antibody GENA-104A16 is under the IND submission stage for clinical studies."

IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CXCL9 • GZMA • IFNG • PD-L1

CNTN4 as a novel target for solid cancer with antibody-drug conjugate (AACR 2024) - "Furthermore, treating MMAF conjugate of GENA-104A16 showed promising efficacy in the Pan02 pancreatic orthotopic mouse model and the patient-derived xenograft model. These results suggest that CNTN4 could be a highly potential ADC target that could expand the options for cancer treatment strategies."

Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • APP • CNTN

A First-in-human Study of GENA-104A16 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Genome & Company

New P1 trial • Oncology • Solid Tumor

Activation of transcription factors, p65 and NFATc1, mediated by WNT5a, induces up-regulation of novel immune checkpoint CNTN4 expression (AACR 2023) - "Therefore, we constructed B16F10 murine melanoma cells overexpressing WNT5a (B16F10/WNT5a) to assess the anti-tumor efficacy by administering GENA-104A16, the anti-CNTN4 humanized monoclonal antibody, in the syngeneic mice model with increased expression of CNTN4 induced by WNT5a, and in vivo efficacy by treatment of GENA-104A16 is under assessment in the B16F10/WNT5a syngeneic mice model. Through the investigation, we expect to support the rationale and strategy for a combination therapy approach of GENA-104A16 for non-responding patients to immunotherapy."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • APP • CNTN • NFATC1 • RELA • WNT5A • WNT7B

Novel immune checkpoint inhibitor: In vivo and in vitro efficacy of anti-CNTN4 antibody, GENA-104A16 in the models with increased CNTN4 expression (AACR 2023) - "And the expression level of CNTN4 on tumors was essential for the anti-tumor activity of GENA-104A16. Therefore, the expression of CNTN4 could be a potential biomarker for monitoring clinical responses to anti-CNTN4 therapy."

Checkpoint inhibition • IO biomarker • Preclinical • Gallbladder Cancer • Melanoma • Oncology • Osteosarcoma • Pancreatic Cancer • Sarcoma • Solid Tumor • APP • CD4 • CD8 • CNTN • IFNG • TNFA