GRWD5769 / GreyWolf Therapeutics - LARVOL DELTA

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

First-in-class inhibitors of ERAP1 alter the HLA-I-restricted cancer immunopeptidome leading to the generation of novel peptides presented for immune recognition (AACR 2022) - "Importantly, we demonstrate that the degree of bias towards longer HLA-I-bound ligands uniquely presented following ERAP1 inhibition was governed by both ERAP1 and HLA-I haplotypes. Such dramatic changes in the peptide repertoire presented for immune recognition have the potential to enhance anti-tumoural immunogenicity through T cell recognition of a novel cancer immunopeptidome, and, in addition to global shifts in the peptide length distributions, unique peptides presented for immune recognition during ERAP1 inhibition may be used as biomarkers for monitoring activity of this novel therapeutic approach in the clinic."

Oncology • CD8

A small molecule approach to drive novel neoantigen generation: First-in-class inhibitors of ERAP1 generate novel neoantigens driving anti-tumor effects (AACR 2022) - "Grey Wolf are developing inhibitors of endoplasmic reticulum aminopeptidases (ERAP1 and ERAP2) to generate novel neoantigens. Importantly, ERAP1 inhibitors are well tolerated in mouse, rat, and non-human primates, which aligns with the observations that increases in T cell effects are tumor specific and not observed in peripheral tissue. Our investigation of the effects of ERAP1 inhibitors in mouse tumor models and ex vivo primary human T cell co-cultures have provided proof of mechanism and proof of principle biomarkers that will be used to explore the effects of GRWD5769 during Phase 1 clinical development in the second half of 2022."

IO biomarker • Tumor-specific neoantigens • Oncology • TMB

First-in-class inhibitors of ERAP1 alter the immunopeptidome of cancer, driving a differentiated T cell response leading to tumor growth inhibition (SITC 2021) - "Conclusions Grey Wolf Therapeutics ERAP1 inhibitors significantly modify the immunopeptidome and combination with anti PD-1 leads to significant TCR repertoire change, T cell infiltration and tumor growth inhibition in syngeneic mouse tumor models. These data provide the foundation from which we will explore the potential of our first-in-class ERAP1 inhibitor development candidate in the clinic, as well as identifying useful biomarkers to demonstrate desired biological activity."

IO biomarker • Oncology • CD8 • TMB

Grey Wolf Therapeutics to Present Preclinical Data on First-in-Class ERAP1 Inhibitors at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (PRNewswire) - "Grey Wolf Therapeutics...announced that preclinical in vivo data on the company's first-in-class inhibitors of ERAP1 will be presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). Presented findings will highlight the ability of the company's novel ERAP1 inhibitors to significantly increase the diversity of T cell receptors in the tumor, drive synergistic upregulation of translationally relevant immune markers that have been shown to correlate with patient response to checkpoint inhibition, and trigger significantly greater T cell infiltration into tumors in preclinical models. Additionally, the presentation will showcase significant tumor growth inhibition in syngeneic mouse tumor models following combination of ERAP1 inhibition with an anti-PD-1 antibody. The SITC conference is being held November 10-14, 2021 in Washington, D.C., as well as virtually."

Preclinical • Oncology

[VIRTUAL] First in class inhibitors of ERAP1 have the potential to be a transformative immunotherapy in oncology (AACR 2021) - "Extensive assessment of the potential of ERAP1 inhibitors to enhance tumor immune responses in combination with additional therapies (e.g. chemotherapy and radiotherapy), across different tumor microenvironments, is ongoing. These data provide the foundation from which we plan to explore the potential of our first-in-class ERAP1 inhibitor development candidate in the clinic."

IO biomarker • Oncology • CD8 • TMB

[VIRTUAL] Immunopeptidome changes mediated by a novel ERAP1 inhibitor leads to tumor growth inhibition. (SITC 2020) - "Combination of these inhibitors with anti PD-1 leads to significant T cell infiltration and tumor growth inhibition. Thus, ERAP1 mediated modulation of the immunopeptidome has the potential to drive anti tumor T cell responses and be a transformative immunotherapy."

IO Biomarker • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • MSI • TMB • Tyrosinase

[VIRTUAL] Immunopeptidome changes mediated by a novel ERAP1 inhibitor leads to tumor growth inhibition. (SITC 2020) - "Combination of these inhibitors with anti PD-1 leads to significant T cell infiltration and tumor growth inhibition. Thus, ERAP1 mediated modulation of the immunopeptidome has the potential to drive anti tumor T cell responses and be a transformative immunotherapy."

IO Biomarker • Melanoma • Oncology • Solid Tumor • CD8 • IFNG • MSI • TMB • Tyrosinase

[VIRTURL] Immunopeptidome changes mediated by a novel ERAP1 inhibitor leads to tumor growth inhibition (SITC 2020) - No abstract available

Oncology

[VIRTUAL] Potent oral ERAP1 inhibitors modify the immunopeptidome in vivo and are novel immunotherapy agents (AACR-II 2020) - "The immunogenic potential of these novel cancer associated antigens has been confirmed by the ability to stimulate IFNγ production in naïve T cells and suggests responses to these antigens could reinvigorate anti-tumor responses. Extensive assessment of mouse and human CD8 T cells responses is ongoing, in order to characterise and select Grey Wolf Therapeutics’ first lead ERAP1 inhibitor for use as monotherapy or in combination with other immunotherapies such as checkpoint blockade."

IO Biomarker • Preclinical • Oncology • CD8 • IFNG • TMB