GRWD5769 / GreyWolf Therapeutics - LARVOL DELTA

A Phase 1 Study in Healthy Adult Participants to Evaluate the Bioavailability of GRWD5769 Tablets Relative to Capsules and the Effect of Food (ANZCTR) - P1 | N=18 | Recruiting | Sponsor: Greywolf Therapeutics | Not yet recruiting ➔ Recruiting | Initiation date: Aug 2026

Enrollment open • Trial initiation date • Oncology

EMITT-1: Final clinical, PK & PD data from dose escalation and selection of recommended dose for expansion cohorts in a phase I study of GRWD5769 (a first-in-class ERAP1i) in patients with solid malignancies (ESMO 2025) - P1/2 | "Methods Patients with advanced solid malignancies were treated with GRWD5769 in monotherapy or cemiplimab combination DE cohorts at doses of 25-800 mg BID. Early evidence of clinical activity supports further exploration in tumor specific EC. 1 Abstract 2589, ASCO 2024."

Clinical • P1 data • PK/PD data • Colorectal Cancer • Oncology • Solid Tumor

EMITT-1: Clinical and pharmacodynamic activity with the oral ERAP1 inhibitor GRWD5769 and cemiplimab in 6 completed phase 1b expansion cohorts in solid tumors with anti–PD-1 resistance or MSS-CRC. (ASCO 2026) - P1/2 | "GRWD5769 with cemiplimab demonstrated broad, durable activity across all 6 phase 1b expansion cohorts in pts with ≥2 prior lines of therapy and secondary anti-PD-1 resistance, or MSS-CRC. Translational analyses suggest that GRWD5769 exerts a dual mechanism of action, both reprogramming antigen-experienced T cells and inducing de novo T cell responses, in keeping with its potential to address both primary and secondary resistance to anti-PD-1 therapy. Based on the efficacy and tolerability of the combination, stage 2 cohort expansions are now ongoing, to inform a randomized Phase 2 study."

Clinical • P1 data • PK/PD data • Colorectal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

GRWD5769-ST-01: A Modular, Multi-part, Multi-arm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of GRWD5769 Alone and in Combination with Anticancer Treatments in Patients with Solid Malignancies (clinicaltrialsregister.eu) - P1/2 | N=175 | Recruiting | Sponsor: Grey Wolf Therapeutics Limited | N=130 ➔ 175

Enrollment change • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TMB

Combos New and Old Counter PD-(L)1 Resistance, Treat Rare Cancers. (PubMed, Cancer Discov) - "The ERAP1 inhibitor GRWD5769 combined with cemiplimab, a PD-1 inhibitor, has shown preliminary promise in overcoming resistance to PD-(L)1 blockade by targeting antigen processing. Another resistance-mitigating strategy is potentially IOS-1002, an antagonist of two immunosuppressive receptors, LILRB1/2 and KIR3DL1, combined with anti-PD-1 pembrolizumab. As well, an update on the recently published DART (NCI/SWOG S1609) study indicates that the classic combination of ipilimumab with nivolumab may benefit even more rare cancers, including gestational trophoblastic neoplasia."

Journal • Gestational Trophoblastic Neoplasia • Oncology • KIR3DL1 • LILRB1

EMITT-1 Study: GRWD5769 Plus Cemiplimab in Anti-PD-1-Resistant Solid Tumors and MSS Colorectal Cancer (OncoDaily) - "All six cohorts were fully recruited, with a total of 81 patients included in this interim analysis. Median follow-up was 6.0 months. Clinical activity was observed across all completed cohorts. Key efficacy findings included: ORR ranging from 13% to 46%; Durable clinical benefit observed across multiple tumor types; Median PFS varied across cohorts; Median PFS reached 8.2 months in patients with MSS colorectal cancer without liver metastases."

P1 data • Cervical Cancer • Colorectal Cancer • Hepatocellular Cancer • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

High-sensitivity HLA-I immunopeptidome profiling from limited clinical PBMC samples (AACR 2026) - "Peripheral blood mononuclear cells (PBMCs) offer a minimally invasive and clinically accessible matrix for such analyses, enabling serial sampling and longitudinal monitoring in clinical trials.Application of the immunopeptidomics profiling (IMPX) to PBMC samples has demonstrated clinical relevance, as exemplified by its use in the GRWD5769 trial where pharmacodynamic modulation of the immunopeptidome was observed in patients treated with an ERAP1 inhibitor (ESMO 2024, ASCO 2025)...Following optimization of both the biochemical and computational pipelines, up to 2,300 HLA class I-associated peptides were confidently quantified from as few as 1 million PBMCs. When 5 million PBMCs were used as input, more than 9,500 unique HLA-bound peptides were identified.In summary, this high-sensitivity, optimized immunopeptidomics platform enables comprehensive class I HLA profiling from minimal PBMC input, supporting its translational application as a pharmacodynamic readout in..."

Clinical • Oncology

GRWD5769-ST-01: A Modular, Multi-part, Multi-arm, Open-label, Phase I/II Study to Evaluate the Safety and Tolerability of GRWD5769 Alone and in Combination with Anticancer Treatments in Patients with Solid Malignancies (clinicaltrialsregister.eu) - P1/2 | N=130 | Recruiting | Sponsor: Grey Wolf Therapeutics Limited | N=65 ➔ 130

Enrollment change • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TMB

A clinical trial to determine the safety and tolerability of GRWD5769 in patients with solid malignancies. (ANZCTR) - P1 | N=60 | Active, not recruiting | Sponsor: Grey Wolf Therapeutics Pty Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Neutropenia • Oncology • Solid Tumor

EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial - 1) (clinicaltrials.gov) - P1/2 | N=288 | Recruiting | Sponsor: Grey Wolf Therapeutics

New P1/2 trial • Oncology • Solid Tumor

A clinical trial to determine the safety and tolerability of GRWD5769 in combination with anticancer treatments in patients with solid malignancies. (ANZCTR) - P1/2 | N=168 | Recruiting | Sponsor: Grey Wolf Therapeutics Pty Ltd | Phase classification: P1 ➔ P1/2 | N=36 ➔ 168

Enrollment change • Phase classification • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A clinical trial to determine the safety and tolerability of GRWD5769 in combination with anticancer treatments in patients with solid malignancies. (ANZCTR) - P1 | N=36 | Recruiting | Sponsor: Grey Wolf Therapeutics Pty Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A clinical trial to determine the safety and tolerability of GRWD5769 in patients with solid malignancies. (ANZCTR) - P1 | N=60 | Recruiting | Sponsor: Grey Wolf Therapeutics Pty Ltd | N=36 ➔ 60

Enrollment change • Neutropenia • Oncology • Solid Tumor

EMITT-1: Proof-of-mechanism immunopeptidome (ImPD) effects at target PK exposure, in a phase 1 study of GRWD5769 (a first-in-class inhibitor of Endoplasmic Reticulum Aminopeptidase 1 [ERAP1]) in patients with solid malignancies. (ASCO 2024) - "GRWD5769 has been well tolerated at doses up to 100 mg BID. PK / PD data support dose-dependent target engagement of ERAP1. Proof of mechanism has been achieved for this first-in-class therapy, and this is the first demonstration that the human ImPD can be manipulated pharmacologically in cancer patients."

Clinical • P1 data • Infectious Disease • Nephrology • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor

Grey Wolf Therapeutics to Present First Clinical Data for GRWD5769, a First-in-Class ERAP1 Inhibitor, at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - "Grey Wolf Therapeutics...announced that the first clinical data for the company's lead immuno-oncology candidate, GRWD5769, will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The presented findings will consist of initial data from the company's ongoing Phase 1/2 clinical trial of the first-in-class ERAP1 inhibitor in a range of solid tumour types."

P1/2 data • Oncology • Solid Tumor

Grey Wolf Therapeutics Presents First Clinical Data for GRWD5769, a First-in-Class ERAP1 Inhibitor, at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - P1/2 | N=12 | EMITT-1 (ACTRN12623000108617) | "GRWD5769 was well tolerated, with predictable pharmacokinetics following repeat oral administration in all dose cohorts (up to 200 mg BID). Dose-dependent target engagement as evidenced by modulation of the immunopeptidome. Clinical proof-of-mechanism, confirming the expected mechanistic effects of ERAP1 inhibition and consistent with those seen in preclinical models. Initial, early efficacy assessments demonstrating stable disease achieved by a number of patients, some of whom have remained on treatment for nearly a year."

P1/2 data • Oncology • Solid Tumor

Grey Wolf Therapeutics Closes Oversubscribed $50 Million Series B Financing Expansion, Led by ICG Life Sciences Team, to Accelerate and Expand First-of-its-Kind Antigen Modulation Technology (PRNewswire) - "Grey Wolf Therapeutics...announced the closing of an oversubscribed $50 million Series B financing expansion, bringing the total amount of Series B funds raised to $99 million...Proceeds from the round will be leveraged to broaden the scope of the company's ongoing Phase 1/2 clinical trial of its lead immuno-oncology candidate, GRWD5769, in a range of solid tumour types. The funding also enables the company to expand research and development (R&D) for its versatile antigen modulation approach into treatments for autoimmune disease indications....Initial data on the ongoing adaptive Phase 1/2 trial of the lead asset GRWD5769, a first-in-class ERAP1 inhibitor will be presented at the upcoming 2024 American Society of Clinical Oncology (ASCO) annual meeting. A second ERAP1 inhibitor focussed on autoimmune disease is being advanced through IND-enabling studies with the goal of entering the clinic in 2025."

Financing • New trial • P1/2 data • Immunology • Oncology • Solid Tumor

Development of first-in-class ERAP2 inhibitors to modulate the cancer immunopeptidome (SITC 2023) - "We have previously described the preclinical development of the First-in-Class (FIC) ERAP1 inhibitor, GRWD5769, which has now entered Phase I clinical trials. Conclusions ERAP2 is a genetically-validated target for human cancer and member of an emerging category of therapeutic targets in the antigen presentation pathway that can alter the visibility of cancer through generation of novel cancer antigens. Current efforts are focused on optimizing our lead FIC ERAP2 inhibitors and validating ERAP2 inhibition in human and mouse cancer models."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A clinical trial to determine the safety and tolerability of GRWD5769 in combination with anticancer treatments in patients with solid malignancies. (ANZCTR) - P1 | N=36 | Not yet recruiting | Sponsor: Grey Wolf Therapeutics Pty Ltd

Combination therapy • New P1 trial • Neutropenia • Oncology • Solid Tumor • PD-L1

A clinical trial to determine the safety and tolerability of GRWD5769 in patients with solid malignancies. (ANZCTR) - P1 | N=36 | Recruiting | Sponsor: Grey Wolf Therapeutics Pty Ltd | Initiation date: Mar 2000 ➔ Mar 2023

Trial initiation date • Neutropenia • Oncology • Solid Tumor • PD-L1

GRWD5769: A first-in-class inhibitor of ERAP1, generating novel cancer antigens to drive de novo anti-tumor T cell responses (AACR 2023) - "In conclusion, the first-in-class, ERAP1 inhibitor clinical candidate, GRWD5769, drives novel anti-tumor T cell responses through neoantigen creation and circumventing T cell exhaustion. GRWD5769 has demonstrated a good safety profile in GLP toxicology studies and robust proof of mechanism and proof of principle biomarkers have been developed to provide a clear path to establish the activity and efficacy of GRWD5769 in patients in 2023."

IO biomarker • Tumor mutational burden • Oncology • TMB

Grey Wolf Therapeutics Announces Dosing of First Patient in Phase 1/2 Clinical Study of GRWD5769 in Patients with Advanced Solid Tumours (PRNewswire) - "Grey Wolf Therapeutics...announced dosing of the first patient in the initial monotherapy module of an adaptive Phase 1/2 clinical trial evaluating GRWD5769, the company's investigational first-in-class ERAP1 inhibitor. The trial, named EMITT-1 (ERAP Mediated Immunopeptide Targeting Trial – 1), is a modular multi-part, multi-arm open-label study designed to evaluate the safety, tolerability, preliminary efficacy and pharmacokinetics of GRWD5769 alone and in combination with Regeneron's PD-1 inhibitor Libtayo^® (cemiplimab) in patients with advanced solid tumours."

Trial status • Oncology • Solid Tumor

Grey Wolf Therapeutics Closes Oversubscribed $49 Million Series B Financing to Advance First-of-its-Kind Neoantigen Creation Approaches (PRNewswire) - "Grey Wolf Therapeutics...announced the closing of an oversubscribed $49 million Series B financing....During the first half of 2023, the company intends to initiate an adaptive Phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of GRWD5769, including a planned combination with the PD-1 inhibitor Libtayo^® (cemiplimab), in a range of solid tumour types. Additionally, the company will direct a portion of the Series B proceeds to follow-on programs including efforts focused on ERAP2 inhibition and the identification of entirely novel cancer antigens that can be targeted with MHC Class I directed therapies, such as soluble T cell receptor (TCR) and TCR mimic bispecifics."

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

GRWD5769: A first-in-class inhibitor of ERAP1, generating novel cancer antigens to drive de novo anti-tumor T cell responses. (SITC 2022) - "GRWD5769 has completed GLP toxicology studies, has a very good safety profile and clear path forward to first patient dosed. Extensive biomarker development has resulted in development of proof of mechanism and proof of principle biomarkers that will be used to establish the activity and efficacy of GRWD5769 in patients in 2023."

IO biomarker • Oncology • TMB

Grey Wolf Therapeutics Announces Clinical Supply Agreement with Regeneron for Trial Evaluating GRWD5769 in Combination with Libtayo (cemiplimab) (PRNewswire) - "Grey Wolf Therapeutics...announced it has entered into a clinical supply agreement with Regeneron for their PD-1 inhibitor Libtayo® (cemiplimab). The agreement relates to Grey Wolf's planned Phase 1/2 clinical trial evaluating the safety, tolerability and efficacy of their lead development candidate GRWD5769 (an investigational first-in-class ERAP1 inhibitor), including in combination with Libtayo®, in a range of solid tumour types. The study is expected to begin in the first half of 2023. In both the GRWD5769 monotherapy and GRWD5769/Libtayo® combination modules of the trial...such as head and neck squamous cell carcinoma, cervical cancer, and hepatocellular carcinoma as Grey Wolf's analysis of patient data suggests these could be particularly sensitive to GRWD5769."

Licensing / partnership • New P1/2 trial • Cervical Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck