ATPS-49RESULTS OF A PHASE 0 CLINICAL TRIAL IN CANINE BRAIN CANCER EVALUATING SAFETY AND ACTIVITY OF OMX-4.80P, A PROTEIN OXYGEN CARRIER IND CANDIDATE FOR TREATMENT OF GLIOBLASTOMA

BACKGROUND: Hypoxia in solid tumors blunts the tumor cytotoxicity of radiotherapy (RT) and is a major independent predictor of poor patient outcomes in glioblastoma (GB). To increase tumor oxygenation, Omniox has engineered a novel oxygen delivery protein, OMX-4.80P (OMX), tuned to release oxygen specifically in hypoxic tumor tissue. When given with radiotherapy, OMX significantly enhances RT efficacy in rodent tumor models. Since spontaneous canine brain cancers, including GB, share similarities with human brain cancers in terms of morphology, disease progression, and response to approved therapies, a Phase 0 clinical trial was conducted in patient dogs to assess OMX safety, PK/PD and signs of efficacy to inform human clinical strategy. METHODS: Dogs with presumed brain cancers (MRI) underwent either resection surgery with radiotherapy (Sx + RT) or stereotactic radiosurgery (SRS). In the Sx + RT group, OMX was administered once before surgery (4–48 hours pre-Sx) and twice weekly in conjunction with RT (20x2.5Gy). In the SRS group, OMX was dosed on 2 consecutive days in combination with SRS (3x8Gy). PK, CBC, blood chemistry, coagulation, and immune responses were assessed. Additionally, resected tumors were analyzed for OMX accumulation and hypoxia levels (ELISA, IHC). RESULTS: To date, 14 dogs have completed the trial (10 Sx, 5 Sx + RT, 4 SRS): Five dogs show no signs of tumor regrowth at 3 months and 2 dogs had no visible tumors at 6 months. OMX induced no dose-limiting adverse events and median T1/2 is 35h. Resected tumors show a strong correlation between OMX concentration in tumor tissue and reduced hypoxia with OMX penetrating deep into tumor tissue. CONCLUSIONS: When given in conjunction with RT regimens equivalent to human standard of care, OMX is safe and well-tolerated. Tumor tissue analysis suggests that OMX-4.80P decreases tumor hypoxia, thus supporting its further clinical development for the enhancement of radiotherapy efficacy in GB patients.