EGL-001 / Egle Therap - LARVOL DELTA

First-in-Human Phase I/II study of EGL-001: Initial Clinical Evaluation of a Novel Therapy for Selected Advanced or Metastatic Solid Tumors [WITHDRAWN] (ESMO 2025) - No abstract available

Clinical • First-in-human • Metastases • P1/2 data • Oncology • Solid Tumor

EGL-121, a first-in-human phase 1/2 trial of EGL-001 in adult patients with selected advanced and/or metastatic solid tumors. (ASCO 2025) - P1/2 | "The study consists of a Part 1 (Phase 1) dose escalation of EGL-001 administered as a single agent (from 0.3 mg/kg to 12 mg/kg), and in combination with pembrolizumab treatment, according to a BOIN design, followed by a Part 2 (Phase 2) dose expansion of EGL‑001 administered at the selected doses as monotherapy and/or in combination therapy with anti-PD(L)1...As of January 2025, the first 3 Cohorts of EGL-001 (0.03, 0.1, 0.3 mg/kg) have been completed. EGL-001 was well tolerated with no DLTs reported."

Clinical • Metastases • P1/2 data • Oncology • Solid Tumor • CD80 • FCGR2A • IL2 • IL2RA

Egle Therapeutics to Present Clinical Trial Progress Poster on Phase I/II EGL-121 Study for EGL-001 at 2025 ASCO Annual Meeting (Eagle Pharmaceuticals Press Release) - "The poster presentation will detail development progress for EGL-001, a novel therapeutic agent with first-in-class potential. EGL-001 is designed to provide checkpoint inhibition by antagonizing the CTLA-4-CD80/86 interaction while selectively depleting intratumoral Tregs by downregulating CD25 and inhibiting IL-2 signaling specifically within these cells."

Trial status • Solid Tumor

Preferential tumor uptake and retention of EGL-001, an anti-CTLA4-IL2 mutein fusion antibody achieving selective tumor Treg depletion (Businesswire) - "Egle Therapeutics unveils preclinical biodistribution data on EGL-001, a novel anti-CTLA4-IL2 mutein fusion antibody designed to selectively deplete tumor-infiltrating regulatory T cells (Tregs). EGL-001 mode of action combines competitive inhibition of IL-2 signaling and potent downregulation of surface CD25, leading to induction of Treg apoptosis....In vivo EGL-001 preferentially bound to the surface of Tregs due to their high CTLA-4 and CD25 expression and depleted them from the tumor microenvironment without affecting other immune cells. In a biodistribution study, EGL-001 accumulated and persisted in tumors while rapidly clearing from healthy tissues."

Preclinical • Solid Tumor

Preferential tumor uptake and retention of EGL-001, an anti-CTLA4 -IL2 mutein fusion antibody achieving selective tumor Treg depletion (AACR 2025) - P1/2 | "Preclinical studies have demonstrated that EGL-001 exhibits potent anti-tumor activity by depleting Tregs and reactivating anti-tumor immunity. The current data indicates that EGL-001 preferentially acts within the TME, a phenomenon attributed to the strong overexpression of CTLA-4 and CD25 by tumor-associated Tregs compared to other Treg populations. This unique tumor selectivity sets EGL-001 apart from other Treg-targeting agents, presenting a promising strategy to overcome resistance to immune checkpoint blockade."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • CD80 • IL2 • IL2RA • STAT5

Preferential tumor retention of EGL-001, a CTLA-4/CD25 antagonist fusion protein, to selectively deplete tumor Tregs and minimize peripheral toxicities: towards a first-in-human clinical study (SITC 2024) - "EGL-001 was well tolerated at all tested dose levels in monkeys and, due to its rapid peripheral clearance, did not induce the lymph node and spleen hyperplasia reported with similar doses of ipilimumab.1 Modeling with allometric scaling predicted that clinical doses of EGL-001 below those inducing toxicity with anti-CTLA-4 agents would be pharmacologically active. 2017090512285386). Egle Therapeutics has submitted an initial Clinical Trial Application, which involves France and Spain under reference number 2024-512921-10-00."

Clinical • IO biomarker • P1 data • Oncology • Solid Tumor • CD8 • CTLA4 • IL2RA • ISG20

Egle Therapeutics to Share Preclinical Efficacy Data for EGL-001, a CTLA-4/CD25 Antagonist Fusion Protein at the Society for Immunotherapy of Cancer Meeting (Businesswire) - "Egle Therapeutics...will present at the Society for Immunotherapy of Cancer Meeting taking place in Houston, Texas from November 6th to 10th, 2024....The data showcases EGL-001's potential as single-agent and to enhance the effectiveness of immune checkpoint blockade therapies by depleting tumor-associated Tregs, leading to increased CD8+ T cell activation and anti-tumor responses in preclinical models .The SITC presentation will include key findings from studies in mouse models and cynomolgus monkeys, demonstrating the safety, tolerability, and efficacy of EGL-001, as well as its preferential tumor accumulation and rapid clearance from peripheral organs. These promising results leading Egle Therapeutics to conduct a first-in-human open-label, phase I/II trial evaluating the safety, tolerability, PK and preliminary activity of EGL-001 in patients with selected solid tumors, with the goal to address the critical need for more effective immunotherapies in cancer treatment."

Preclinical • Oncology

First-in-human Trial of EGL-001 in Patients with Selected Advanced And/or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Egle Therapeutics

New P1/2 trial • Oncology • Solid Tumor

EGL-001 is a novel immunocytokine designed to specifically target and disarm T regulatory cells in the tumor microenvironment (AACR 2024) - "Accordingly, EGL-001 induces anti-tumor responses in mice in combination with anti-PD1 therapy.Conclusions EGL-001 is an ICK with a novel and unique mechanism of action combining ICB and Treg selective IL-2 starvation, designed to specifically disarm and deplete tumor-associated Tregs. Based on our preclinical data, EGL-001 is being developed as a cancer immunotherapeutic to improve patients' response to ICB and counteract ICB resistance."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • CD80 • IL2RA

Egle Therapeutics to present novel immunocytokine preclinical data for EGL-001 with poster presentation at the 2024 AACR Annual Meeting (Businesswire) - "Egle Therapeutics...will present a poster at the American Association for Cancer Research Annual Meeting (AACR) 2024 being held on April 5-10, 2024. In the poster, entitled 'EGL-001 is a novel immunocytokine designed to specifically target and disarm T regulatory cells in the tumor microenvironment'. Egle scientists present evidence that EGL-001, a CTLA-4 targeted IL-2 dominant negative mutein, selectively binds to T regulatory (Treg) cells and inhibits Treg IL-2 signaling."

Preclinical • Oncology