Transaction Description:
COMBINATION OF CB101 AND RADIATION THERAPY IN HEAD AND NECK SQUAMOUS CELL CARCINOMA - CUREBIOTECH, INC., FOA # PA-21-262 APPLICATION NUMBER 1121483 PROJECT SUMMARY HEAD AND NECK SQUAMOUS CELL CARCINOMA (HNSCC) IS THE SEVENTH LEADING CAUSE OF CANCER-RELATED MORTALITY IN THE WORLD. RADIATION THERAPY (RT) IS ROUTINELY USED FOR PATIENTS WITH LOCOREGIONALLY ADVANCED DISEASE. THE HISTORICAL 5-YEAR OVERALL SURVIVAL RATES FOR LOCALLY ADVANCED HNSCC AFTER TREATMENT WITH SURGERY, CHEMOTHERAPY, AND RT IS ~50%. MANY OF THESE PATIENTS RELAPSE AFTER INITIAL THERAPY AND/OR DEVELOP METASTATIC DISEASE, AND THE PROGNOSIS FOR THESE PATIENTS REMAINS POOR, WITH A MEDIAN SURVIVAL BETWEEN 6 TO 12 MONTHS. IMMUNOTHERAPY WITH ANTI-PD-1 ANTIBODIES YIELDS A RESPONSE RATE LESS THAN 20%. HENCE, THERE IS A PRESSING CLINICAL NEED TO DEVELOP ALTERNATIVE APPROACHES FOR PATIENTS WITH RELAPSED AND/OR METASTATIC HNSCC. CUREBIOTECH INC. IS A PRECLINICAL STAGE BIOTECH COMPANY THAT FOCUSES ON TOLL-LIKE RECEPTOR 7/8 AGONIST, RESIQUIMOD. RESIQUIMOD IS MORE POTENT AND HAS BETTER BIOAVAILABILITY THAN IMIQUIMOD, AN FDA APPROVED IMMUNE MODULATING DRUG. CUREBIOTECH HAS DEVELOPED AN INNOVATIVE INTRATUMORAL CONTROLLED RELEASE FORMULATION OF RESIQUIMOD, CB101, WHICH SEQUESTERS THE DRUG TO A LOCAL SITE USING A POLYMER MATRIX, WITH THE AIM OF AVOIDING SYSTEMIC ADVERSE IMMUNE RESPONSE. IT SHOWED SUPERIOR TREATMENT EFFICACY OVER UNFORMULATED RESIQUIMOD IN MULTIPLE PRECLINICAL MODELS. LOCALLY ADVANCED OR RELAPSED HNSCC IS EASILY ACCESSIBLE FOR INTRATUMORAL INJECTION OF CB101. WE POSTULATE THAT CB101 WILL SIGNIFICANTLY AUGMENT THE RESPONSE OF CANCERS TO RT VIA MODULATING THE TUMOR MICROENVIRONMENT (TME). IN AIM 1, WE WILL OPTIMIZE DOSE AND TREATMENT SCHEDULE OF CB101 AND RT IN HNSCC PRE-CLINICAL MODELS. SINCE RT MAY INCREASE PD-L1 EXPRESSION ON TUMOR CELLS, IN AIM 2, WE WILL INVESTIGATE THE TREATMENT EFFICACY OF ANTI-PD-1 ANTIBODIES WITH CB101/RT COMBINATION. WE EXPECT THAT LOWER DOSES OF RT WITH CB101 MAY YIELD THE SAME OR BETTER RESULTS AS HIGHER DOSE RADIATION ALONE BUT WITH REDUCED TOXICITY, MAKING RT RESISTANT TUMORS SENSITIVE AND ENHANCING THE ABSCOPAL EFFECT OF RT. SUCCESSFUL COMPLETION OF THESE AIMS WILL HAVE A DIRECT IMPACT ON THE DESIGN OF FUTURE CLINICAL TRIALS. WE HAVE THE SCIENTIFIC AND PERSONNEL CAPABILITY TO ACHIEVE THESE AIMS QUICKLY AND METICULOUSLY. THE DATA GENERATED IN THIS PROJECT WILL BE INCLUDED IN AN IND APPLICATION OF A PHASE I CLINICAL TRIAL OF CB101/RT IN HNSCC PATIENTS TO THE FDA.
