HuL001 / HuniLife Biotech - LARVOL DELTA

Targeting ENO1 reprograms macrophage polarization to trigger antitumor immunity and improves the therapeutic effect of radiotherapy. (PubMed, Cell Death Dis) - "Targeting surface ENO1 with HuL001, a first-in-class humanized antibody, significantly reduced glycolysis, decreased extracellular lactate accumulation, reprogrammed macrophage polarization and inhibited tumor growth and distant metastasis. Moreover, targeting surface ENO1 significantly increased the therapeutic response to radiotherapy and delayed tumor regrowth by increasing antitumoral M1 macrophages and cytotoxic CD8+ T cells infiltration within TME. These results indicated that targeting surface ENO1 remodeled the tumor microenvironment and provided better therapeutic effects to radiotherapy in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC)."

Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • ENO1 • SMAD3

Study of HuL001 in Relapsed/Refractory Multiple Myeloma Patients (clinicaltrials.gov) - P1/2 | N=21 | Enrolling by invitation | Sponsor: HuniLife Biotechnology, Inc.

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Novel Therapeutic Approach Using ENO1-specific CAR-NK Cells to Target KRAS-Mutated Cancers (ASTRO 2025) - "We further developed ENO1-specific CAR-NK cells with a novel therapeutic ENO1 antibody (HuL001)... These results showed that ENO1 served as an ideal surrogate cell surface target for KRAS mutated cancers. ENO1-specific CAR-NK when in combination with RT overcome the resistant nature of KRAS-mutated cancers. This approach can be applied to patients who currently have very limited therapeutic options."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ENO1 • KRAS

A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Immunogenicity of HuL001 (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: HuniLife Biotechnology, Inc. | Recruiting ➔ Completed

Trial completion • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Targeting ENO1 to tilt the immunometabolic balance in the tumor microenvironment of KRAS-mutated colorectal cancer to improve therapeutic efficacy (AACR 2025) - P1 | "While adagrasib is approved for KRAS G12C-mutated CRC (about 3% of cases), effective therapies for the more common KRAS G12D and G12V mutations remain unavailable. This is the first study to demonstrate that targeting ENO1 can simultaneously overcome the immunosuppressive TME and enhance radiotherapy efficacy in KRAS-mutated CRC. These findings support further clinical evaluation of this immunometabolic strategy, with a phase I/II trial underway to assess HuL001's therapeutic potential."

Biomarker • Clinical • Late-breaking abstract • Tumor microenvironment • Colorectal Cancer • Oncology • Solid Tumor • CD8 • ENO1 • KRAS

Extracellular enolase-1 drives cancer-associated fibroblast differentiation in the tumor microenvironment to enhance tumor growth of multiple myeloma: Development of the therapeutic antibody, HuL001 (AACR 2025) - P1 | "In vivo, blocking ENO1 with HuL001 inhibited CAF-mediated tumor progression and enhanced lenalidomide efficacy in bortezomib (BTZ)-resistant MM xenograft model, probably by altering the TME and its interaction with MM cells. This is the first study to demonstrate that targeting extracellular ENO1 could reprogram the TME via inhibiting CAF to suppresses MM progression and overcome BTZ resistance. Given the satisfactory safety profile of ENO1 antibody (HuL001), these findings further support the ongoing clinical investigations of ENO1 as a therapeutic target to advance MM treatments."

Biomarker • Late-breaking abstract • Tumor microenvironment • Hematological Malignancies • Multiple Myeloma • Oncology • ENO1 • HIF1A • IL6 • TGFB1

Tilting Immunometabolic Balance of Tumor Microenvironment by Targeting ENO1 in KRAS-Mutated Colorectal and Pancreatic Cancers (ASTRO 2024) - P1 | "We then characterized whether targeting ENO1 by a novel therapeutic GMP-compliant ENO1 antibody (HuL001), which has completed a phase 1 safety, tolerability, pharmacokinetics and immunogenicity study in healthy subjects (NCT04540770), could affect the metabolic balance and remodeling TME +/- radiotherapy... These results showed that oncogenic KRAS triggered surface translocation of ENO1 leading to lactate accumulation in TME. Targeting surface ENO1 not only inhibits cancer invasion/metastasis via blocking plasminogen receptor but also improved therapeutic effect by tilting immunometabolic balance of TME. We are in the process of initiating a phase I/II clinical trial to validate the dosing and efficacy of this immunometabolic approach in KRAS-mutated cancers."

Biomarker • Tumor microenvironment • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • ENO1 • KRAS

A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Immunogenicity of HuL001 (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: HuniLife Biotechnology, Inc. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Oct 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Phase 1 Single and Multiple Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Immunogenicity of HuL001 in Healthy Volunteers and Multiple Sclerosis Subjects (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: HuniLife Biotechnology, Inc.; Not yet recruiting ➔ Recruiting; Trial primary completion date: Jun 2022 ➔ Oct 2022

Clinical • Enrollment open • Trial primary completion date • CNS Disorders • Multiple Sclerosis • MRI

A Phase 1 Single and Multiple Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Immunogenicity of HuL001 in Healthy Volunteers and Multiple Sclerosis Subjects (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: HuniLife Biotechnology, Inc.

Clinical • New P1 trial • CNS Disorders • Multiple Sclerosis