PARP4 inhibitor / Ribon Therap - LARVOL DELTA

Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma. (PubMed, J Immunother Cancer) - "Although adaptive resistance mechanisms re-emerge, PARP14 inhibition combined with PD-1 blockade offers a promising strategy to enhance treatment outcomes and overcome ICI resistance in melanoma, as immune cells are primed for further therapeutic interventions that leverage the quiescent state."

IO biomarker • Journal • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor • IFNG

PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models. (PubMed, Nat Commun) - "Effector T cell infiltration is enhanced in tumours derived from cells pre-treated with IFNγ in immunocompetent female mice when PARP14 is pharmacologically inhibited or knocked down, while the presence of regulatory T cells is decreased, leading to restoration of α-PD-1 sensitivity. Finally, we determine that tumours which spontaneously relapse in immunocompetent female mice following α-PD-1 therapy upregulate IFNγ signalling and can also be re-sensitised upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance."

Checkpoint inhibition • IO biomarker • Journal • Preclinical • Melanoma • Oncology • Solid Tumor • IFNG

PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven adaptive resistance (AACR 2023) - "Knockdown or pharmacological inhibition of PARP14 increased effector T cell infiltration into tumors derived from cells pre-treated with IFNγ and decreased the presence of regulatory T cells, leading to restoration of α-PD-1 sensitivity. Finally, we determined that tumors which spontaneously relapsed following α-PD-1 therapy could be re-sensitized upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance."

Checkpoint inhibition • IO biomarker • Melanoma • Oncology • Solid Tumor • IFNG

The PARP14 inhibitor RBN-3143 suppresses skin inflammation in preclinical models (ISID 2023) - P1 | "For all disease features, RBN-3143 either equaled or outperformed treatment with dupilumab. RBN-3143 is well-tolerated in preclinical studies and is the first small molecule inhibitor of PARP14 to enter clinical trials. It is currently being tested in a Phase I study in normal healthy volunteers and patients with atopic dermatitis (NCT05215808)."

IO biomarker • Preclinical • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • STAT3 • STAT6