Not listed
PRECISION NEXT-GENERATION RADIOIMMUNOTHERAPIES TO CURE NON-HODGKIN LYMPHOMA - PROGRESS HAS BEEN MADE OVER THE LAST DECADES IN THE TREATMENT OF NON-HODGKIN LYMPHOMA (NHL) WITH SEVERAL THERAPIES RECENTLY FDA-APPROVED, INCLUDING CD19 CAR-T CELLS, BISPECIFIC ANTIBODIES TARGETING CD20 AND CD3, AND ANTI-CD79B ANTIBODY-DRUG CONJUGATES (ADC) BUT OVER 20,000 PEOPLE WILL DIE OF NHL IN THE US IN 2024. THERE REMAINS A CRITICAL UNMET NEED FOR INNOVATIVE, ACTIVE AND ACCESSIBLE THERAPIES OF NHL. RADIOIMMUNOTHERAPIES (RITS) TARGETING CD20 (ZEVALIN® AND BEXXAR®) RECEIVED FDA APPROVAL TWO DECADES AGO IN FOLLICULAR AND SOME TRANSFORMED B-CELL LYMPHOMAS. THESE FIRST-GENERATION RITS USED IMMUNOGENIC MURINE ANTIBODIES AND WERE ONLY ADMINISTERED IN A SINGLE DOSE IN NON-MYELOABLATIVE REGIMENS. WHILE SAFE, WELL-TOLERATED, AND ACTIVE, THESE TREATMENTS WERE NOT MAJOR COMMERCIAL SUCCESSES FOR SEVERAL REASONS, INCLUDING ECONOMICS. ALSO, 131I AND 90Y ARE SUBOPTIMAL DUE TO UNFAVORABLE HIGH-ENERGY Γ-EMISSIONS OR A LONG Β-PARTICLE PATH LENGTH POORLY SUITED TO LOW-BURDEN RESIDUAL DISEASE, RESPECTIVELY. GIVEN THE CONTINUED UNMET MEDICAL NEEDS, ADDITIONAL TREATMENT APPROACHES MUST BE OBTAINED FOR NHL. TO ADDRESS THESE UNMET NEEDS, WE WILL DEVELOP PRECISION NEXT-GENERATION RIT FOR NHL THAT WE ANTICIPATE WILL RESULT IN MORE CURES. OUR STUDIES DRAW ON OUR EXTENSIVE EXPERIENCE IN FIRST-GENERATION NHL RADIOIMMUNOTHERAPY (OF WHICH THE PI WAS AN INVENTOR) AND OUR RECENT EXCITING PRECLINICAL WORK WITH NEXT-GENERATION FULLY-HUMAN ANTI-CD20 RITS. WE WILL DEVELOP AND EVALUATE NOVEL, PRECISION RADIOPHARMACEUTICAL THERAPIES FOR NHL USING PRECLINICAL MODELS. IN AIM 1), NEXT-GENERATION ANTI-CD20 RADIOIMMUNOTHERAPIES FOR NHL WILL BE EVALUATED USING SINGLE AGENT AND COMBINED Β-(LU177) AND Α-PARTICLE-(AC225)-EMITTING LABELED OFATUMUMAB IN DISSEMINATED AND SOLID TUMOR MURINE MODELS. THESE STUDIES WILL DETERMINE HOW TO BEST UTILIZE THESE Α- AND Β-PARTICLE EMITTING RIT AS SINGLE AGENTS WITH SINGLE OR MULTIPLE DOSES, OR IN COMBINATION TO CURE LYMPHOMA. IN AIM 2), NEW Α-PARTICLE ANTI-CD20 RITS WILL BE DEVELOPED AND ASSESSED, EVALUATING BOTH SHORT- LIVED HIGHER DOSE-RATE (PB212, T½ 10.6 HR) AND LONG-LIVED, LOWER DOSE-RATE (TH227, T½ 18.7 D) Α-PARTICLE- EMITTERS FOR NHL RIT IN MOUSE TUMOR MODELS. COMPARATIVE EVALUATION OF MULTIPLE Α-PARTICLE RITS IS NOVEL, SIGNIFICANT, AND CLINICALLY RELEVANT. IN AIM 3), A HIGHLY-INNOVATIVE APPROACH OF COMBINED DUAL-TARGETED THERAPY FOR NHL WILL BE DEVELOPED AND EVALUATED FOR MECHANISM AND FOR THERAPEUTIC EFFICACY, USING AN ANTI-CD79B ANTIBODY-DRUG CONJUGATE, POLIVY®, AS A RADIOSENSITIZER FOR CD20-TARGETED RIT. THIS IMPORTANT, SELECTIVE AND NOVEL DUAL- TARGETED APPROACH, WITH MECHANISTIC STUDIES AND THERAPEUTIC STUDIES, SHOULD IMPROVE LYMPHOMA CURABILITY AND IS EXPECTED TO BE BROADLY GENERALIZABLE TO OTHER TUMOR TYPES. TOGETHER, WE EXPECT OUR PRECISION, NEXT-GENERATION RIT APPROACHES TO LEAD TO HUMAN TRANSLATION, FACILITATING MORE CURES OF PATIENTS WITH OTHERWISE INCURABLE NHL.
$0 2/12/25 Not listed
PRECISION NEXT-GENERATION RADIOIMMUNOTHERAPIES TO CURE NON-HODGKIN LYMPHOMA - PROGRESS HAS BEEN MADE OVER THE LAST DECADES IN THE TREATMENT OF NON-HODGKIN LYMPHOMA (NHL) WITH SEVERAL THERAPIES RECENTLY FDA-APPROVED, INCLUDING CD19 CAR-T CELLS, BISPECIFIC ANTIBODIES TARGETING CD20 AND CD3, AND ANTI-CD79B ANTIBODY-DRUG CONJUGATES (ADC) BUT OVER 20,000 PEOPLE WILL DIE OF NHL IN THE US IN 2024. THERE REMAINS A CRITICAL UNMET NEED FOR INNOVATIVE, ACTIVE AND ACCESSIBLE THERAPIES OF NHL. RADIOIMMUNOTHERAPIES (RITS) TARGETING CD20 (ZEVALIN® AND BEXXAR®) RECEIVED FDA APPROVAL TWO DECADES AGO IN FOLLICULAR AND SOME TRANSFORMED B-CELL LYMPHOMAS. THESE FIRST-GENERATION RITS USED IMMUNOGENIC MURINE ANTIBODIES AND WERE ONLY ADMINISTERED IN A SINGLE DOSE IN NON-MYELOABLATIVE REGIMENS. WHILE SAFE, WELL-TOLERATED, AND ACTIVE, THESE TREATMENTS WERE NOT MAJOR COMMERCIAL SUCCESSES FOR SEVERAL REASONS, INCLUDING ECONOMICS. ALSO, 131I AND 90Y ARE SUBOPTIMAL DUE TO UNFAVORABLE HIGH-ENERGY Γ-EMISSIONS OR A LONG Β-PARTICLE PATH LENGTH POORLY SUITED TO LOW-BURDEN RESIDUAL DISEASE, RESPECTIVELY. GIVEN THE CONTINUED UNMET MEDICAL NEEDS, ADDITIONAL TREATMENT APPROACHES MUST BE OBTAINED FOR NHL. TO ADDRESS THESE UNMET NEEDS, WE WILL DEVELOP PRECISION NEXT-GENERATION RIT FOR NHL THAT WE ANTICIPATE WILL RESULT IN MORE CURES. OUR STUDIES DRAW ON OUR EXTENSIVE EXPERIENCE IN FIRST-GENERATION NHL RADIOIMMUNOTHERAPY (OF WHICH THE PI WAS AN INVENTOR) AND OUR RECENT EXCITING PRECLINICAL WORK WITH NEXT-GENERATION FULLY-HUMAN ANTI-CD20 RITS. WE WILL DEVELOP AND EVALUATE NOVEL, PRECISION RADIOPHARMACEUTICAL THERAPIES FOR NHL USING PRECLINICAL MODELS. IN AIM 1), NEXT-GENERATION ANTI-CD20 RADIOIMMUNOTHERAPIES FOR NHL WILL BE EVALUATED USING SINGLE AGENT AND COMBINED Β-(LU177) AND Α-PARTICLE-(AC225)-EMITTING LABELED OFATUMUMAB IN DISSEMINATED AND SOLID TUMOR MURINE MODELS. THESE STUDIES WILL DETERMINE HOW TO BEST UTILIZE THESE Α- AND Β-PARTICLE EMITTING RIT AS SINGLE AGENTS WITH SINGLE OR MULTIPLE DOSES, OR IN COMBINATION TO CURE LYMPHOMA. IN AIM 2), NEW Α-PARTICLE ANTI-CD20 RITS WILL BE DEVELOPED AND ASSESSED, EVALUATING BOTH SHORT- LIVED HIGHER DOSE-RATE (PB212, T½ 10.6 HR) AND LONG-LIVED, LOWER DOSE-RATE (TH227, T½ 18.7 D) Α-PARTICLE- EMITTERS FOR NHL RIT IN MOUSE TUMOR MODELS. COMPARATIVE EVALUATION OF MULTIPLE Α-PARTICLE RITS IS NOVEL, SIGNIFICANT, AND CLINICALLY RELEVANT. IN AIM 3), A HIGHLY-INNOVATIVE APPROACH OF COMBINED DUAL-TARGETED THERAPY FOR NHL WILL BE DEVELOPED AND EVALUATED FOR MECHANISM AND FOR THERAPEUTIC EFFICACY, USING AN ANTI-CD79B ANTIBODY-DRUG CONJUGATE, POLIVY®, AS A RADIOSENSITIZER FOR CD20-TARGETED RIT. THIS IMPORTANT, SELECTIVE AND NOVEL DUAL- TARGETED APPROACH, WITH MECHANISTIC STUDIES AND THERAPEUTIC STUDIES, SHOULD IMPROVE LYMPHOMA CURABILITY AND IS EXPECTED TO BE BROADLY GENERALIZABLE TO OTHER TUMOR TYPES. TOGETHER, WE EXPECT OUR PRECISION, NEXT-GENERATION RIT APPROACHES TO LEAD TO HUMAN TRANSLATION, FACILITATING MORE CURES OF PATIENTS WITH OTHERWISE INCURABLE NHL.
$641.5k 12/5/24 Not listed
PRECISION NEXT-GENERATION RADIOIMMUNOTHERAPIES TO CURE NON-HODGKIN LYMPHOMA - PROGRESS HAS BEEN MADE OVER THE LAST DECADES IN THE TREATMENT OF NON-HODGKIN LYMPHOMA (NHL) WITH SEVERAL THERAPIES RECENTLY FDA-APPROVED, INCLUDING CD19 CAR-T CELLS, BISPECIFIC ANTIBODIES TARGETING CD20 AND CD3, AND ANTI-CD79B ANTIBODY-DRUG CONJUGATES (ADC) BUT OVER 20,000 PEOPLE WILL DIE OF NHL IN THE US IN 2024. THERE REMAINS A CRITICAL UNMET NEED FOR INNOVATIVE, ACTIVE AND ACCESSIBLE THERAPIES OF NHL. RADIOIMMUNOTHERAPIES (RITS) TARGETING CD20 (ZEVALIN® AND BEXXAR®) RECEIVED FDA APPROVAL TWO DECADES AGO IN FOLLICULAR AND SOME TRANSFORMED B-CELL LYMPHOMAS. THESE FIRST-GENERATION RITS USED IMMUNOGENIC MURINE ANTIBODIES AND WERE ONLY ADMINISTERED IN A SINGLE DOSE IN NON-MYELOABLATIVE REGIMENS. WHILE SAFE, WELL-TOLERATED, AND ACTIVE, THESE TREATMENTS WERE NOT MAJOR COMMERCIAL SUCCESSES FOR SEVERAL REASONS, INCLUDING ECONOMICS. ALSO, 131I AND 90Y ARE SUBOPTIMAL DUE TO UNFAVORABLE HIGH-ENERGY Γ-EMISSIONS OR A LONG Β-PARTICLE PATH LENGTH POORLY SUITED TO LOW-BURDEN RESIDUAL DISEASE, RESPECTIVELY. GIVEN THE CONTINUED UNMET MEDICAL NEEDS, ADDITIONAL TREATMENT APPROACHES MUST BE OBTAINED FOR NHL. TO ADDRESS THESE UNMET NEEDS, WE WILL DEVELOP PRECISION NEXT-GENERATION RIT FOR NHL THAT WE ANTICIPATE WILL RESULT IN MORE CURES. OUR STUDIES DRAW ON OUR EXTENSIVE EXPERIENCE IN FIRST-GENERATION NHL RADIOIMMUNOTHERAPY (OF WHICH THE PI WAS AN INVENTOR) AND OUR RECENT EXCITING PRECLINICAL WORK WITH NEXT-GENERATION FULLY-HUMAN ANTI-CD20 RITS. WE WILL DEVELOP AND EVALUATE NOVEL, PRECISION RADIOPHARMACEUTICAL THERAPIES FOR NHL USING PRECLINICAL MODELS. IN AIM 1), NEXT-GENERATION ANTI-CD20 RADIOIMMUNOTHERAPIES FOR NHL WILL BE EVALUATED USING SINGLE AGENT AND COMBINED Β-(LU177) AND Α-PARTICLE-(AC225)-EMITTING LABELED OFATUMUMAB IN DISSEMINATED AND SOLID TUMOR MURINE MODELS. THESE STUDIES WILL DETERMINE HOW TO BEST UTILIZE THESE Α- AND Β-PARTICLE EMITTING RIT AS SINGLE AGENTS WITH SINGLE OR MULTIPLE DOSES, OR IN COMBINATION TO CURE LYMPHOMA. IN AIM 2), NEW Α-PARTICLE ANTI-CD20 RITS WILL BE DEVELOPED AND ASSESSED, EVALUATING BOTH SHORT- LIVED HIGHER DOSE-RATE (PB212, T½ 10.6 HR) AND LONG-LIVED, LOWER DOSE-RATE (TH227, T½ 18.7 D) Α-PARTICLE- EMITTERS FOR NHL RIT IN MOUSE TUMOR MODELS. COMPARATIVE EVALUATION OF MULTIPLE Α-PARTICLE RITS IS NOVEL, SIGNIFICANT, AND CLINICALLY RELEVANT. IN AIM 3), A HIGHLY-INNOVATIVE APPROACH OF COMBINED DUAL-TARGETED THERAPY FOR NHL WILL BE DEVELOPED AND EVALUATED FOR MECHANISM AND FOR THERAPEUTIC EFFICACY, USING AN ANTI-CD79B ANTIBODY-DRUG CONJUGATE, POLIVY®, AS A RADIOSENSITIZER FOR CD20-TARGETED RIT. THIS IMPORTANT, SELECTIVE AND NOVEL DUAL- TARGETED APPROACH, WITH MECHANISTIC STUDIES AND THERAPEUTIC STUDIES, SHOULD IMPROVE LYMPHOMA CURABILITY AND IS EXPECTED TO BE BROADLY GENERALIZABLE TO OTHER TUMOR TYPES. TOGETHER, WE EXPECT OUR PRECISION, NEXT-GENERATION RIT APPROACHES TO LEAD TO HUMAN TRANSLATION, FACILITATING MORE CURES OF PATIENTS WITH OTHERWISE INCURABLE NHL.
$641.5k 12/5/24