CDR404 / CDR-Life - LARVOL DELTA

First-in-human evaluation of CDR404, a MAGE-A4–targeted T cell engager, in ovarian cancer: Initial pharmacodynamic and clinical activity (ESMO-IO 2025) - P1 | "Expression in 70% of HGSOC across HRD and HRP tumours underscores its relevance as a therapeutic target. These findings support the development of CDR404 as a novel immunotherapy in HGSOC with planned expansion into late-line combinations and second-line platinum-sensitive disease.Clinical trial identification NCT06402201.Legal entity responsible for the study CDR-Life Inc."

Clinical • First-in-human • IO biomarker • P1 data • PK/PD data • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • HLA-A • HRD • MAGEA4 • MUC16

Hallmarks of pharmacodynamic activity of CDR404, a new antibody-derived T cell engager (TCE) targeted against MAGE-A4+ solid tumors in HLA-A*02:01+ patients (AACR-NCI-EORTC 2025) - P1 | "Integrated PK-PD data including changes in ctDNA levels will be presented for OC and other solid tumors at the conference. In conclusion, early patient data from the CDR404-001 trial confirms that the first M-gager® in the clinic shows all 4 canonical PD hallmarks for a TCE and has emerging favorable immunological safety."

Clinical • PK/PD data • Oncology • Ovarian Cancer • Solid Tumor • CD8 • HLA-A • MAGEA4 • MUC16

CDR609: A First-in-Class LGR5-targeted T Cell Engager for treatment of Colorectal Cancer and other solid tumors (AACR-NCI-EORTC 2025) - P1 | "CDR609 is a first-in-class T cell engager (TCE) for the treatment of LGR5-expressing solid tumors, based on the same M-gager® format as CDR404 (Phase I, NCT06402201). CDR609 also shows high specificity for LGR5, and an overall safe profile in the presence of normal human cells. Future studies will include in vivo efficacy testing and a broader range of cellular assays using ex vivo patient-derived tissues and cultured cells as part of the preclinical studies that will be included in the IND application."

IO biomarker • Colorectal Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • CD69 • CD8 • GZMB • IFNG • IL2RA • LGR5

CDR-Life Presents Early Clinical Data Demonstrating Pharmacodynamic Activity of CDR404, a Novel Antibody-Derived T Cell Engager Targeting MAGE-A4+ Solid Tumors (Businesswire) - "The data presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....At initial dose levels of 100–200 μg, CDR404 triggered the full cascade of immune activation associated with effective TCE therapy....Notably, repeated dosing did not induce PD-1–mediated T cell exhaustion, suggesting sustained biological activity. In one patient, a transient tumor flare followed by stabilization was observed, which is consistent with tumor infiltration by cytotoxic T cells."

P1 data • Solid Tumor

Durable and potent in vitro T cell activity with repeated exposure to CDR404, a potential best-in-class T cell engager targeting MAGE-A4 (AACR 2025) - P1 | "Since upregulation of PD-1 is an obligate immunosuppressive brake to T cell activation, we additionally investigated the in vitro killing activity of a CDR404 and Pembrolizumab combination compared to CDR404 alone. In conclusion, these results demonstrate the potential of CDR404 to achieve improved efficacy and more durable responses for HLA-A*02:01+ patients with MAGE-A4+ tumors. The combination with an anti-PD-1 therapy may have additive anti-tumor activity in patients, and could potentially allow a transition into earlier, anti-PD-1/PD-L1 containing lines of treatment for multiple solid cancers including NSCLC, thus benefiting a larger patient population."

IO biomarker • Preclinical • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD69 • HLA-A • IL2RA • MAGEA4

Key Findings for CDR404 in MAGE-A4-Positive Tumors (Abstract #3494) (Businesswire) - "Superior Potency and Durability: CDR404 showed more potent killing of MAGE-A4-positive cancer cell lines across multiple indications, even at low effector-to-target cell ratios which mimic a 'cold' tumor environment, compared to a TCR-based competitor; Enhanced T Cell Fitness: After multiple rounds of serial killing, T cells exposed to CDR404 maintained significantly better fitness, with lower levels of crucial T cell exhaustion markers compared to the TCR-based approach; Favorable Cytokine Profile: CDR404 demonstrated a more favorable cytokine release profile, potentially offering safety advantages in the clinical setting; Effective Across Multiple Cancer Types: CDR404 showed strong activity against MAGE-A4-positive tumor cells from different cancer types, including lung adenocarcinoma and squamous cell carcinoma, and melanomas....Dose escalation is ongoing and patient data from the early stages of the Phase 1 trial will be reported later this year."

P1 data • Preclinical • Lung Adenocarcinoma • Melanoma • Squamous Cell Carcinoma

First-in-human study of CDR404, a novel bivalent and bispecific, antibody-derived, T cell engager in MAGE-A4-positive advanced solid cancers (SITC 2024) - P1 | "Ethics Approval The study was approved by the institutional review board at each site and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines of the International Conference on Harmonization. All patients provided written informed consent."

Metastases • P1 data • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • MAGEA4

CDR-Life Announces Pipeline Progress of M-gager Programs for Treatment of Solid Tumors (Businesswire) - "The first patient was dosed with CDR404, a novel, bispecific and bivalent antibody fragment-based T cell engager (TCE) targeting MAGE-A4, an intracellular cancer-specific protein that is cleaved into smaller peptide fragments and presented on HLA-A*02:01 molecules at the surface of cancer cells....CDR-Life has identified and characterized an antibody fragment-based TCE as a clinical candidate targeting PRAME called CDR813. This TCE binds potently and bivalently to an HLA-A*02-restricted PRAME peptide on the surface of cancer cells. Pre-clinical studies have shown that CDR813 has very favorable pharmacological and manufacturability properties with best-in-class potential for the clinic."

Preclinical • Trial status • Oncology • Solid Tumor • Squamous Cell Carcinoma

In silico tumor immune microenvironment (TiME) analysis of non-small cell lung cancer (NSCLC) to inform clinical development of CDR404: A first-of-its-kind MAGE-A4 targeted T-cell engager. (ASCO 2024) - "LUSC MAGE-A4HIGH tumors had a differentiated TiME profile. Our findings are consistent with an INFLAMLOWVASCLOW phenotype possibly indicative of an "immune desert" [Desbois et al 2020]. In contrast, LUAD MAGE-A4HIGH tumors had an INFLAMHIGHVASCLOW phenotype indicating that MAGE-A4 associations with TiME may be histology dependent in NSCLC."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • MAGEA4

First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: CDR-Life AG | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

CDR-Life Announces Initiation of CDR404 Phase 1 Trial for Treatment of Solid Tumors at ASCO (Businesswire) - "CDR-Life Inc. today announced the initiation of enrollment for the Phase 1 trial of CDR404, its lead program in development as a precision immunotherapy for solid tumors. CDR404 will be the focus of an abstract accepted for online presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, occurring May 31 - June 4 in Chicago, Illinois....The ASCO abstract presents findings from a study that assessed the biomarkers responsible for predicting the effectiveness of CDR404 in fighting non-small cell lung cancer (NSCLC) tumors."

Enrollment status • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First in Human Study of CDR404 in HLA-A*02:01 Participants With MAGE-A4 Expressing Solid Tumors (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: CDR-Life AG

New P1 trial • Oncology • Solid Tumor

CDR-Life Announces FDA Clearance of IND Application for CDR404 for Treatment of Solid Tumors (GlobeNewswire) - "CDR-Life Inc. today announced the clearance of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for CDR404, its lead program in development as a precision immunotherapy for solid tumors....The company anticipates initiating Phase 1 trial enrollment in the coming months."

IND • New P1 trial • Solid Tumor

CDR404, an antibody-based bispecific & bivalent T-cell engager targeted against MAGE-A4, for Squamous Non-Small Cell Lung Cancer (SQ-NSCLC) (SITC 2023) - "Conclusions The high MAGE-A4 expression levels and the highly specific anti-cancer cell activity of CDR404 make it a highly attractive immunotherapy for development post-progression on ICI for patients with HLA-A*02:01+ SQ-NSCLC. A multi-tumor phase 1 trial of CDR404, including SQ-NSCLC, is expected to begin in 2024 with prospective patient selection for both HLA-A*02:01 and tumor MAGE-A4."

IO biomarker • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HLA-A • MAGEA4

Overcoming the dose-response prediction limitation from bench to clinic for T-cell engagers: using quantitative systems pharmacology (QSP) modelling in the development of CDR404 for solid tumors (SITC 2023) - "Conclusions QSP modeling is a powerful approach which guides the clinical trial design through integrating biophysics data, in vitro functional data, preclinical PK and MoA-related target biology. The developed QSP model will become an integrated part of the clinical development program and can be updated with emerging clinical data during the Phase 1 trial to facilitate discovery of a safe and therapeutic dose range for CDR404."

Lung Cancer • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • HLA-A • IFNG • MAGEA4

CDR-Life Presents Findings from Two Studies in Preparation of Phase 1 Trial with Immunotherapy CDR404 for Treatment of Solid Tumors at SITC 2023 (GlobeNewswire) - "SQ-NSCLC had the highest MAGE-A4 mRNA expression levels among solid cancers in the TCGA database. Immunohistochemistry showed positive MAGE-A4 staining in 28/50 SQ-NSCLC samples. Treatment with four different doses of CDR404 induced complete tumor regression in the in vivo SQ-NSCLC NCI-H1703 xenograft model."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CDR-Life Presents Findings from Two Studies in Preparation of Phase 1 Trial with Immunotherapy CDR404 for Treatment of Solid Tumors at SITC 2023 (GlobeNewswire) - "The QSP model builds a preliminary understanding of the relationship between MAGE-A4 expression and intra-tumor T-cell density in determining CDR404 anti-tumor activity. The QSP model predicted doses of CDR404 which might have the most favorable benefit-risk profile for patients in the Phase 1 trial."

Preclinical • Oncology • Solid Tumor

Applied BioMath, LLC Presents Quantitative Systems Pharmacology Model of T-cell Engagers for Solid Tumors at the Society for Immunotherapy of Cancer Annual Meeting (PRNewswire) - "Applied BioMath's poster describes a QSP model developed to support the first-in-human trial design for CDR404, a highly potent and highly specific antibody-based T-cell engager that binds bivalently to a MAGE-A4 peptide displayed on HLA-A*02:01 on cancer cells and monovalently to CD3 on T-cells. The QSP model will become an integrated part of the clinical development program and can be updated with emerging clinical data to facilitate discovery of a safe and therapeutic dose range for CDR404."

Preclinical • Oncology • Solid Tumor

Precise tumor & patient selection for CDR404: A bispecific & bivalent MAGE-A4 T cell engager (ESMO 2023) - P1/2 | "Lack of response reported in another MAGE-A4 TCE trial (NCT03973333) where tumor screening in ovarian cancer was absent confirms that IHC selection will be essential for RNALOW tumors. In this regard, we have identified E7O1U as a highly specific MAGE-A4 antibody for precise IHC patient selection in the CDR404 trial."

Clinical • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • MAGEA4

CDR-Life Presents Precise Tumor and Patient Selection for CDR404: First-of-its-Kind Dual MAGE-A4 T-cell Engager, at ESMO Congress 2023 (GlobeNewswire) - "CDR-Life Inc. presented findings on tumor target expression and precise patient selection for the upcoming Phase 1 trial of CDR404 (Abstract 200P)...which is presented on HLA-A*02:01 on the surface of cancer cells, at the ESMO Congress 2023, occurring October 20-24 in Madrid, Spain....High levels of MAGE-A4 expression are present in different-sized sub-groups across a wide range of solid cancers with high unmet medical needs including NSCLC (squamous and adenocarcinoma histology), head and neck squamous cell carcinoma, gynecological and bladder cancers....'We look forward to the continued progress of our innovative CDR404 T-cell engager program as we near the initiation of our Phase 1 trial, anticipated to begin in 2024.'"

New P1 trial • Preclinical • Bladder Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck