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    DRUG:

    CGX1321

    i
    Other names: CGX1321, CGX-1321, CGX 1321
    Company:
    Curegenix
    Drug class:
    Wnt signalling pathway inhibitor, PORCN inhibitor
    Related drugs:
    over2years
    Sequential modulation of the Wnt/β-catenin signaling pathway enhances tumor-intrinsic MHC I expression and tumor clearance. (PubMed, Gynecol Oncol)
    Wnt/β-catenin pathway modulation increases MHC I expression and promotes tumor leukocytic infiltration, facilitating a pro-immune TME associated with decreased tumor burden. This intervention overcomes common tumor immune-evasion mechanisms and may render ovarian tumors susceptible to immunotherapy.
    Journal • IO biomarker
    |
    CXCL10 (Chemokine (C-X-C motif) ligand 10) • DKK1 (dickkopf WNT signaling pathway inhibitor 1)
    |
    sirexatamab (DKN-01) • CGX1321
    almost3years
    CGX1321 in Subjects With Advanced Solid Tumors and CGX1321 With Pembrolizumab or Encorafenib + Cetuximab in Subjects With Advanced GI Tumors (Keynote 596) (clinicaltrials.gov)
    P1b, N=72, Recruiting, Curegenix Inc. | Trial completion date: Dec 2022 --> Mar 2023 | Trial primary completion date: Dec 2022 --> Mar 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    BRAF (B-raf proto-oncogene) • RNF43 (Ring Finger Protein 43) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • AXIN1 (Axin 1) • RSPO2 (R-Spondin 2) • RSPO3 (R-Spondin 3)
    |
    BRAF V600E • BRAF V600 • RNF43 mutation
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • Braftovi (encorafenib) • CGX1321
    4years
    Manipulating the Wnt/β-catenin signaling pathway to promote anti-tumor immune infiltration into the TME to sensitize ovarian cancer to ICB therapy. (PubMed, Gynecol Oncol)
    CGX-1321 significantly reduced tumor burden and enhanced CD8+ T cell levels in ovarian cancer, nevertheless the addition of DKN-01 or anti-PD-1 therapies did not enhance these effects of CGX-1321. Further investigation is needed to determine if CGX-1321 + DKN-01 combination treatment sensitizes pre-clinical ovarian cancer to ICB therapy.
    Journal
    |
    CD8 (cluster of differentiation 8)
    |
    sirexatamab (DKN-01) • CGX1321
    over4years
    [VIRTUAL] Utilizing porcupine (PORCN) and DKK1 inhibition to improve anti-tumor immunity in a murine model of ovarian cancer. (ASCO 2020)
    CGX-1321 decreased omental weight and ascites volume, while DKN-01 increased the cellular percentage of NK cells. Both DKN-01 and CGX-1321 increased CD8+ T cells. Wnt-inhibition is therapeutically promising in EOC, and the combination of a PORCN inhibitor with DKN-01 could improve the response to immune checkpoint blockage and further investigation is warranted.
    Preclinical
    |
    CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1)
    |
    sirexatamab (DKN-01) • CGX1321
    over4years
    Inhibiting WNT Ligand Production for Improved Immune Recognition in the Ovarian Tumor Microenvironment. (PubMed, Cancers (Basel))
    When CD8 T cells were depleted, CGX1321 treatment did not have the same magnitude of effect on tumor growth. Our investigation confirmed an increase in Wnt activity correlated with a decreased T-cell-inflamed environment; a relationship that was further supported in our pre-clinical model that suggests inhibiting the Wnt/β-catenin pathway was associated with decreased tumor growth and improved survival via a partial dependence on CD8 T cells.
    Journal
    |
    CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    CGX1321
    over4years
    Inhibition of PORCN in a p53-/- knockout syngeneic ovarian cancer model (SGO 2020)
    CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.
    Preclinical
    |
    CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    CGX1321
    over4years
    Inhibition of PORCN in a p53-/- knockout syngeneic ovarian cancer model (SGO 2020)
    CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.
    Preclinical
    |
    CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    CGX1321
    over4years
    Inhibition of PORCN in a p53-/- knockout syngeneic ovarian cancer model (SGO 2020)
    CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.
    Preclinical
    |
    CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    CGX1321
    over4years
    Inhibition of PORCN in a p53-/- knockout syngeneic ovarian cancer model (SGO 2020)
    CGX1321 treatment inhibited tumor growth in ID8p53-/--luciferase tagged tumors; this was not seen in ID8p53-/-nonluciferase-tagged mice. Immune changes in the TME were not significant in this model, but were not measured in the luciferase-tagged model. There was no difference in tumor burden in ID8p53-/- injected DC-intrinsic β-catenin absent model.
    Preclinical
    |
    CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    CGX1321