Providing GMP-grade Terbium-161 as a therapeutic option for US academic institution - Abstract In nuclear medicine, radiotherapeutic drugs are advantageous in delivering targeted radiation to tumor cells non- invasively and with high efficacy, especially in cases where antibody-drug conjugates (ADCs) may not achieve desired outcomes due to drug resistance or insufficient intracellular drug release. For instance, Lutetium-177 labeled radiotherapeutic drugs (e.g., Lutathera and Pluvicto) have provided novel treatments for thousands of patients across the US. Despite their benefits, these drugs present challenges in delivering radiation to promising targets with superior selectivity, but inferior expression levels in primary and metastatic lesions (e.g., DLL3 due to its exceptionally selectively expressing < 5,000 copies per tumor cell). These challenges are primarily due to Lutetium-177’s low linear energy transfer (LET) emissions which deposit energy over a relatively long track length, resulting in less efficient damage to targeted cells. To address this issue, Serva Energy (Serva) proposes Terbium-161 is a viable solution to serve as an alternative to Lutetium-177 given its combined high energy beta emission and high energy Auger emission properties. Additionally, Terbium-161 does not have any daughter isotopes (which potentially could cause long-term off-target toxicity), can be produced in scale, and the generation of non-carrier added material is possible. The Auger component of Terbium-161 may also unlock further, precision-targeted cytotoxic effects, further improving the already impressive therapeutic breadth of radiotherapeutics. Thus herein this Direct to Phase II Serva proposes to (1) optimize non-carrier added process optimization for Terbium-161 production, (2) pursue purification and GMP-production efforts of Terbium-161, and (3) demonstrate its efficacy in an in vivo mouse prostate model. These efforts will be performed in collaboration with Evergreen Theragnostics (subcontractor; Springfield, NJ). Here, Serva will develop and optimize a strategy to scale up production for Good Manufacturing Practices (GMP) compliance, as well as develop standard operating procedures (SOP). Evergreen will oversee quality assurance and quality control (QA/QC) procedures development (Aim 2) and will spearhead mouse studies (Aim 3). Together under the guidance of Evergreen, Serva will prepare and submit the Drug Master File (DMF) to the FDA for Terbium-161 to be approved as a radiotherapeutic drug. These technical efforts are aligned with our commercialization goals since this would enable Serva to become a leader in the industry which would provide the company with a competitive advantage to attract partnerships and collaborations from pharmaceutical companies, industry, and academia. If successful, we will have the ability to make Terbium-161 readily accessible for radiotherapeutic treatments, preclinical and clinical, across the scientific community in the United States.
