E-602 / Palleon Pharma, Fosun Pharma - LARVOL DELTA

Glycan Mediated Immune Regulation With a Bi-Sialidase Fusion Protein (GLIMMER-01) (clinicaltrials.gov) - P1/2 | N=69 | Completed | Sponsor: Palleon Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | N=273 ➔ 69 | Trial completion date: Jun 2025 ➔ Oct 2024 | Trial primary completion date: Jun 2025 ➔ Oct 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Urothelial Cancer

Palleon Pharmaceuticals Announces NMPA IND Clearance to Proceed with Phase 2 Clinical Trial of E-602 (HLX79), a First-In-Class Treatment for Autoimmune Diseases (Businesswire) - "Palleon Pharmaceuticals...today announced that the China National Medical Products Administration (NMPA) has cleared Shanghai Henlius Biotech’s Investigational New Drug (IND) application for a Phase 2 clinical trial of Palleon’s first-in-class human sialidase enzyme therapeutic, E-602 (HLX79), in combination with Henlius’ self-developed HANLIKANG (rituximab biosimilar) in patients with active glomerulonephritis, including lupus nephritis (LN)."

New P2 trial • Glomerulonephritis • Lupus Nephritis

Henlius Announces China’s NMPA Approval of Phase 2 Clinical Trial for HLX79 Plus HANLIKANG in Active Glomerulonephritis [Google translation] (Henlius Press Release) - "Shanghai Henlius Biotech...announced that the National Medical Products Administration (NMPA) has approved the investigational new drug (IND) application for a phase 2 clinical trial for the potential first-in-class human sialidase enzyme therapeutic, HLX79 (E-602), in combination with Henlius’ self-developed HANLIKANG (rituximab) in patients with active glomerulonephritis....Glomerulonephritis can be classified into primary forms (e.g., membranous nephropathy [MN], focal segmental glomerulosclerosis [FSGS]) and secondary forms (e.g., lupus nephritis [LN], anti-neutrophilic cytoplasmic antibodies [ANCA]-associated vasculitis [AAV]), representing the leading cause of ESRD in China."

New P2 trial • ANCA Vasculitis • Glomerulonephritis • Lupus Nephritis

Palleon Pharmaceuticals and Henlius Collaborate to Advance Glycan Editing as a Treatment for Autoimmune Diseases (Businesswire) - "Palleon Pharmaceuticals...today announced a collaboration and license agreement with Shanghai Henlius Biotech, Inc. (2696.HK) to develop and commercialize Palleon’s first-in-class human sialidase enzyme therapeutic, E-602, in combination with Henlius’ self-developed HANLIKANG (rituximab) in patients with autoimmune diseases, including lupus nephritis (LN)....Under the terms of the agreement, Henlius received an exclusive China license to Palleon’s E-602. Palleon is eligible to receive up to $95.3 million in certain predetermined development and commercial milestones, in addition to royalties upon E-602 commercialization in China."

Licensing / partnership • Immunology • Lupus Nephritis

GLIMMER-01: phase 1/2 trial of a first-in-class bi-sialidase (E-602) in combination with cemiplimab in patients with PD-(L)1-resistant solid tumors (SITC 2024) - P1/2 | "Next generation sialidase therapeutics with longer half-life are in development. Ethics Approval The study obtained ethics approval from institutional or central IRBs affiliated with each institution."

Clinical • Combination therapy • P1/2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD163 • CD8

Palleon Pharmaceuticals Presents Results from the Phase 1/2 GLIMMER-01 Trial of E-602 in Combination with Cemiplimab in Patients with Solid Tumors at the Society for Immunotherapy of Cancer (SITC) Annual Meeting (Businesswire) - P1/2 | N=273 | GLIMMER-01 (NCT05259696) | Sponsor: Palleon Pharmaceuticals, Inc. | "In the Phase 1/2 study, 21 patients with anti-PD(L)-1-resistant melanoma, non-small cell lung cancer and esophagogastric junction cancer, defined according to the SITC consensus definition for resistance to immunotherapy, were treated with E-602 in combination with cemiplimab....The combination was generally well-tolerated, with no dose-limiting toxicities observed. Patients with tumor hypersialylation trended toward better clinical outcomes compared to those lacking hypersialylation, including a confirmed partial response achieved in one anti-PD-1 resistant melanoma patient, and disease stabilization achieved in another six patients. All patients lacking hypersialylation showed disease progression."

P1/2 data • Esophageal Cancer • Gastric Cancer • Melanoma • Non Small Cell Lung Cancer

Glycan Mediated Immune Regulation With a Bi-Sialidase Fusion Protein (GLIMMER-01) (clinicaltrials.gov) - P1/2 | N=273 | Active, not recruiting | Sponsor: Palleon Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Urothelial Cancer

Stromal hypersialylation within colorectal tumors contributes to immunosuppression of T cell adaptive immunity in the tumor microenvironment (SITC 2023) - "We propose that targeting stromal cell sialylation and/or Siglec-Siglec ligand interactions changes the immune contexture in stromal-dense tumors and may represent an innovative strategy to enhance anti-tumor immunity in immunosuppressive TMEs. An engineered human sialidase is being evaluated in a FIH Phase 1/2 trial (NCT005259696) for patients of advanced solid tumors."

Biomarker • IO biomarker • Stroma • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CAFs • CD33 • CD8 • PD-1

Glycan Mediated Immune Regulation With a Bi-Sialidase Fusion Protein (GLIMMER-01) (clinicaltrials.gov) - P1/2 | N=267 | Recruiting | Sponsor: Palleon Pharmaceuticals, Inc.

Combination therapy • New P1/2 trial • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

GLIMMER-01 Beings Examination of E-602 Plus Cemiplimab in Advanced Cancers (Targeted Oncology) - "'The ability of the field to study hypersiaylation of tumor and immune cells has opened a new field of glyco-immunobiology. E-602 represents the first glyco-immune checkpoint inhibitor and the early safety as well as translational immunology associated with the treatment in patients with advanced cancer is promising,' Jason Luke, MD..."

Media quote

Palleon Pharmaceuticals Announces First Patient Dosed with E-602 in Combination with Cemiplimab in GLIMMER-01 Phase 1/2 Clinical Trial (Businesswire) - "Palleon Pharmaceuticals...today announced that the first patient has been dosed in the combination therapy cohort of the Phase 1/2 clinical trial for E-602, its lead candidate from the EAGLE (Enzyme Antibody Glyco-Ligand Editing) oncology platform. The GLIMMER-01 (Glycan-Mediated Immune Regulation) trial is designed to study E-602 as a monotherapy and in combination with cemiplimab (anti-PD-1) in patients with advanced cancers."

Trial status • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Skin Cancer • Solid Tumor • Thoracic Cancer • Urothelial Cancer

Engineering Human Neuraminidase as a Novel Cancer Immunotherapy to Enhance T Cell Immunity by Degrading Immunosuppressive Sialoglycans (PEGS 2023) - "We engineered a novel first-in-class drug candidate (Bi-Sialidase), consisting of an engineered human sialidase (Neu2) Fc fusion, to degrade immunosuppressive sialoglycans. Bi-Sialidase potentiates T cell immune response and demonstrates single-agent antitumor activity and a wide safety margin in preclinical animal models, offering a novel immunomodulatory approach to treat cancer."

Immune Modulation • Oncology

Initial results from a phase 1 dose escalation trial of E-602 shows efficacy in solid tumours (YouTube) - "Dr Jason Luke speaks to ecancer about the initial results from the GLIMMER-01 trial which is a phase 1 first-in-human dose escalation study which evaluated the safety, pharmacokinetics, pharmacodynamics, and anti-tumour activity of E-602 in patients with advanced cancers. E-602 is a first-in-class fusion protein of engineered human sialidase and a human IgG1 Fc region....Dr Luke concludes by exploring how these results could impact future trials regarding the treatment of solid tumours."

Video

Dr Luke on Initial Data From the GLIMMER-01 Trial of E-602 in Advanced Solid Tumors (OncLive) - P1 | N=40 | GLIMMER-01 (NCT05259696) | Palleon Pharmaceuticals, Inc. | "Jason Luke, MD...discusses initial results from the phase 1 GLIMMER-01 trial (NCT05259696) of E-602 in advanced solid tumors. E-602 is a first-in-class fusion protein consisting of an engineered human sialidase (Neu2) and a human IgG1 Fc region. Recently improved understanding of the impact of glycosylation patterns on tumor cell immunity provided the impetus for investigating this novel therapeutic class....These studies will confirm whether the pharmacodynamic effect of E-602 on certain immune subsets in peripheral blood is consistent with its activity preclinical mouse models."

P1 data • Video

GLIMMER-01: initial results from a phase 1 dose escalation trial of a first-in-class bi-sialidase (E-602) in solid tumors (AACR 2023) - "E-602 is tolerated at doses up to 30 mg/kg. Consistent with preclinical findings, dose-dependent desialylation and immune system activation were observed. Based on the observed tolerability and PD effects, the Phase 2 portion of the study to evaluate clinical activity of E-602 monotherapy in patients with checkpoint-inhibitor resistant NSCLC and melanoma will proceed."

P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD69 • CD8 • CXCL10 • IFNG • TNFA

Palleon Pharmaceuticals Presents Initial Phase 1 Results from the GLIMMER-01 Clinical Trial for E-602, the First Ever Glyco-Immune Checkpoint Inhibitor (Businesswire) - P1/2 | N=273 | GLIMMER-01 (NCT05259696) | Sponsor: Palleon Pharmaceuticals | "Palleon Pharmaceuticals...announced the initial Phase 1 results from the GLIMMER-01 trial of its lead EAGLE oncology platform program, E-602, at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, Florida....E-602 was found to be well tolerated across the entire dose range evaluated with no dose limiting toxicities."

P1 data • Oncology • Solid Tumor

A Phase 1/2 dose escalation/expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of E-602, a bi-sialidase fusion protein, in advanced cancer (GLIMMER-01) (SITC 2022) - "Phase 2 will include up to 3 disease indications, evaluating E-602 as monotherapy and/or in combination with an anti-PD-1 agent utilizing a Simon’s minimax 2-stage design. Pre and on-treatment biopsies to further explore the pharmacodynamic effects of E-602 are required for the Phase 1 backfill and Phase 2 participants."

Clinical • P1/2 data • PK/PD data • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer

Palleon to Present on Phase 1/2 E-602 Bi-Sialidase Trial Design at Society for Immunotherapy of Cancer (SITC) Annual Meeting (Businesswire) - "Palleon Pharmaceuticals...announced that it will present on GLIMMER-01, the ongoing Phase 1/2 Trial of its lead program E-602 Bi-Sialidase at the Society for Immunotherapy of Cancer’s 37th Annual Meeting taking place in Boston from November 8-12, 2022....The Trials-in-Progress poster will include the specifics of the GLIMMER-01 trial (NCT#05259696) which is designed to assess the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of E-602."

Clinical protocol • Bladder Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Skin Cancer • Solid Tumor • Thoracic Cancer • Urothelial Cancer

Development of PD-L1-targeted sialidase as a novel cancer immunotherapeutic approach (AACR 2022) - "Furthermore, we have shown that a tumor-targeted sialidase, a heterodimeric molecule consisting of one chain of sialidase-Fc and a second chain of a HER2-targeting antibody (trastuzumab), leads to more efficient desialylation of tumor cells than the non-targeted Bi-Sialidase and demonstrates antitumor activity in trastuzumab-resistant and low HER2-expressing tumor models...We generated a humanized anti-human PD-L1 antibody with comparable PD-1/PD-L1 blockade potency to the existing anti-PD-L1 drugs, atezolizumab and avelumab...Furthermore, the PD-L1-targeted sialidase demonstrated a dose-dependent tumor growth inhibition and modulation of immune cell infiltration. In conclusion, these results suggested that PD-L1-targeted sialidase offers a promising cancer immunotherapeutic approach, which simultaneously inhibits immunosuppressive sialoglycans and the PD-1/PD-L1 axis through targeted delivery of engineered human sialidase to PD-L1-expressing tumor cells and immune cells."

Late-breaking abstract • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • PD-L1

Assessment of the safety, pharmacokinetics, and pharmacodynamics of a first-in-class cancer drug candidate E-602, a sialoglycan degrader, in non-human primates (AACR 2022) - "In conclusion, the PK and PD data have supported the selection of cynomolgus monkeys as the toxicity species to evaluate E-602’s safety profile. E-602 has demonstrated sustained PD effects of immune cell desialylation up to seven days postdose and a wide safety margin with NOAEL of 100 mg/kg in cynomolgus monkeys."

Clinical • Late-breaking abstract • PK/PD data • Oncology

Palleon Presents Preclinical Data on Lead Program E-602 and Novel Bifunctional PD-L1-Targeted Sialidase (Businesswire) - "Data presented from non-human primate studies of E-602 (formerly Bi-sialidase) indicate that E-602 exhibits sustained, dose-dependent pharmacodynamic effects on desialylation of immune cells and a wide safety margin. E-602 produced dose-dependent effects on desialylation of immune cells, such as T cells, monocytes, and dendritic cells, with the effect of T cell desialylation sustained for up to seven days post-dosing. E-602 was well tolerated with NOAEL (Non-Observable-Adverse-Effect-Level) determined to be 100 mg/kg."

Preclinical • Oncology • Solid Tumor

Palleon Pharmaceuticals to Present Preclinical Data on Lead Program E-602 and Novel Bifunctional PD-L1-Targeted Sialidase at AACR Annual Meeting (Businesswire) - "Palleon Pharmaceuticals...announced two poster presentations at the American Association for Cancer Research Annual Meeting....E-602 exhibits sustained, dose-dependent pharmacodynamic effects on desialylation of immune cells and a wide safety margin....Studies performed in a transgenic mouse model of colon cancer expressing PD-L1 found that the bifunctional PD-L1-targeted sialidase exhibited enhanced efficacy compared to E-602 and to an anti-PD-L1 antibody, as well as dose-dependent tumor growth inhibition and modulation of immune cell infiltration."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Palleon Pharmaceuticals Announces First Patient Dosed in Phase 1/2 Study of Lead Glyco-Immunology Drug Candidate for Oncology (Businesswire) - "Palleon Pharmaceuticals...announced dosing of the first patient in the company’s Phase 1/2 study of E-602 in patients with advanced cancers....The GLIMMER-01 trial (NCT05259696) is an open-label, dose-escalation, and dose-expansion study. It will evaluate safety, pharmacodynamic effects, and antitumor activity of E-602, both as a single agent and in combination with pembrolizumab (anti-PD-1). The study will enroll patients with previously treated non-small cell lung cancer, colorectal cancer, melanoma, pancreatic cancer, and ovarian cancer."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

Palleon Pharmaceuticals Announces IND Clearance for First-in-Class Cancer Immunotherapy Leveraging Glyco-Immunology (Businesswire) - "Palleon Pharmaceuticals...announced that the U.S. Food and Drug Administration has cleared the company’s investigational new drug (IND) application for its lead candidate E-602....E-602 is a first-in-class engineered human sialidase enzyme genetic fusion from Palleon’s EAGLE platform which is designed to desialylate both immune cells and tumor cells, potentiating an anti-tumor immune response. Palleon’s Phase 1/2 trial of E-602 is expected to begin enrolling patients with solid tumors refractory to standard of care in Q1 2022."

IND • New P1/2 trial • Oncology • Solid Tumor