ORIC-613 / ORIC Pharma - LARVOL DELTA

ORIC-613, a potential first- and best-in-class, orally bioavailable, potent and selective PLK4 inhibitor with synthetic lethality in TRIM37 high cancer models (AACR 2024) - "Oral dosing of ORIC-613 resulted in tumor growth inhibition and regressions in TRIM37 high xenograft breast tumors with no body weight loss. In summary, ORIC-613 is a potential first- and best-in-class development candidate, with exquisite selectivity for PLK4, which demonstrates synthetic lethality in TRIM37 high tumors and has the potential to benefit these patients."

Preclinical • Synthetic lethality • Breast Cancer • CNS Tumor • Neuroblastoma • Oncology • Oral Cancer • Solid Tumor • CASP3 • CASP7 • PLK4 • TRIM37

ORIC Pharmaceuticals Presents Promising Preclinical Data on Two Programs at the 2023 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "ORIC PLK4 selective inhibitors show greater potency in TRIM37 high cancer cell lines relative to low TRIM37 low cell lines, whereas no differential was observed for non-selective inhibitors. Apoptotic cell death was observed solely in TRIM37 high cancer cells for ORIC PLK4 selective inhibitors, in contrast to non-selective inhibitors which did not show this synthetic lethality. Using a genetically engineered PLK4 cell line variant (PLK4 G95L) that prevents compound-mediated inhibition of PLK4, selective PLK4 inhibitors lose activity in TRIM37 high G95L cells, confirming on-target cell activity, compared with non-selective inhibitors whose cell potency is not dependent on PLK4 inhibition."

Clinical data • Oncology • Solid Tumor • PLK4 • TRIM37

Selective PLK4 inhibition demonstrates synthetic lethality in TRIM37 amplified neuroblastoma and breast cancer models while less selective inhibitors do not (AACR 2023) - "In cell viability assays, selective PLK4 inhibitors were potent in the parental G95 cells and lost activity in L95 cells, unlike less selective inhibitors whose potency did not depend on PLK4. Oral dosing of a selective PLK4 inhibitor resulted in tumor growth inhibition in TRIM37 high xenograft tumors with no body weight loss.In summary, we have discovered that highly selective small molecule inhibitors of PLK4 confirm the potential of the synthetic lethal impact in treating tumors with high levels of TRIM37."

Preclinical • Synthetic lethality • Breast Cancer • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • CASP3 • CASP7 • PLK1 • PLK4 • TRIM37

ORIC Pharmaceuticals Announces Multiple Presentations at the 2023 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "ORIC Pharmaceuticals...announced that two abstracts have been accepted for poster presentations at the 2023 American Association for Cancer Research (AACR) Annual Meeting taking place April 14-19, 2023, in Orlando, FL. The presentations will highlight: (i) preclinical biomarker results for ORIC-944, a potent and selective allosteric inhibitor of PRC2 currently in Phase 1 for patients with metastatic prostate cancer; and (ii) preclinical data from ORIC’s selective PLK4 inhibitor discovery program."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PRC2

Discovery of novel, highly selective inhibitors of PLK4 that demonstrate in vivo regressions in TRIM37 high xenografts (AACR 2022) - "Importantly, cell potency in TRIM37 high cancer cells was rescued with knockdown of TRIM37, illustrating that selective PLK4 inhibitors are synthetic lethal with TRIM37 amplification. Oral administration of ORIC PLK4 inhibitors resulted in regressions of TRIM37 high xenograft tumors, with corresponding PD effects and no body weight loss.In summary, we have discovered novel, potent, highly selective small molecule inhibitors of PLK4 that are orally bioavailable and confirmed the potential for this new target in treating tumors with high levels of TRIM37."

Preclinical • Breast Cancer • Neuroblastoma • Oncology • Solid Tumor • PLK1 • PLK4 • TRIM3

ORIC Pharmaceuticals Presents Promising Preclinical Data on Three Programs at the 2022 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "...'Preclinical data further demonstrate the potential of CD73 inhibitor ORIC-533 as a treatment for multiple myeloma, as well as the compelling brain penetrant properties of ORIC-114 with its high potency against exon 20 insertion mutations. We also introduced our highly selective inhibitors of PLK4 as a potential treatment for breast cancer by leveraging a synthetic lethal liability. We look forward to the continued advancement of these programs as well as ORIC-944, with initial data for our three clinical programs expected in the first half of 2023'."

Clinical data • Preclinical • Synthetic lethality • Breast Cancer • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer