- |||||||||| GRWD5769 / GreyWolf Therapeutics
High-sensitivity HLA-I immunopeptidome profiling from limited clinical PBMC samples (Section 6) - Mar 17, 2026 - Abstract #AACR2026AACR_7594;
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 studies.
- |||||||||| GRWD5769 / GreyWolf Therapeutics
Enrollment closed: EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial (EUDRACT) - Aug 8, 2025
P1, N=60, Active, not recruiting,
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 studies. Recruiting --> Active, not recruiting
- |||||||||| ERAP2 inhibitor / Grey Wolf Therap
Development of first-in-class ERAP2 inhibitors to modulate the cancer immunopeptidome (Exhibit Hall B) - Sep 27, 2023 - Abstract #SITC2023SITC_510;
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.
- |||||||||| GRWD5769 / GreyWolf Therapeutics
Trial initiation date: EMITT-1 (ERAP Mediated Immunopeptidome Targeting Trial (EUDRACT) - Sep 1, 2023
P1, N=36, Recruiting,
Current efforts are focused on optimizing our lead FIC ERAP2 inhibitors and validating ERAP2 inhibition in human and mouse cancer models. Initiation date: Mar 2000 --> Mar 2023
- |||||||||| GRWD5769 / Grey Wolf Therap
GRWD5769: A first-in-class inhibitor of ERAP1, generating novel cancer antigens to drive de novo anti-tumor T cell responses (Valencia A - Convention Center) - Mar 14, 2023 - Abstract #AACR2023AACR_5599;
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.
- |||||||||| ERAP1 inhibitor / Grey Wolf Therap
First-in-class inhibitors of ERAP1 alter the HLA-I-restricted cancer immunopeptidome leading to the generation of novel peptides presented for immune recognition (Section 34) - Mar 9, 2022 - Abstract #AACR2022AACR_5831;
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.
- |||||||||| ERAP1 inhibitor / Grey Wolf Therap
A small molecule approach to drive novel neoantigen generation: First-in-class inhibitors of ERAP1 generate novel neoantigens driving anti-tumor effects (Section 38) - Mar 9, 2022 - Abstract #AACR2022AACR_4153;
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.
- |||||||||| ERAP1 modulator / Grey Wolf Therap
[VIRTUAL] First in class inhibitors of ERAP1 have the potential to be a transformative immunotherapy in oncology () - Mar 11, 2021 - Abstract #AACR2021AACR_1262;
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.
- |||||||||| ERAP1 modulator / Grey Wolf Therap
[VIRTUAL] Potent oral ERAP1 inhibitors modify the immunopeptidome in vivo and are novel immunotherapy agents (Virtual Meeting II: E-Posters) - May 16, 2020 - Abstract #AACRII2020AACR-II_274;
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.
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