The SynthNode Paradigm: Reimagining CAR T Cell Therapy for Improved Patient Outcomes

PROJECT SUMMARY CAR T cell therapy is a transformative approach in cancer treatment, particularly for treating lymphoma and myeloma, with emerging applications in solid tumors and non-cancer conditions such as lupus. Despite the remarkable success of CAR T cell therapy, widespread adoption has been hampered by the complex, labor- intensive, and costly production process that exists today. Delays in CAR T cell manufacturing can be detrimental, particularly for patients with rapidly progressing diseases. Approximately 20% of eligible patients are deprived of CAR T therapy due to production constraints that can delay therapy and compromise the potency and quality of the cell therapy product. Moreover, 40%–60% of patients who receive treatment eventually experience relapse in part due to poor CAR T cell persistence and expansion. Persistence Therapeutics Inc. is introducing a potentially revolutionary CAR T cell therapy approach called SynthNode. This implantable device, SynthNode, is the size of a dime and mimics the function of a synthetic lymph node, producing potent antigen- specific cells that durably persist for patient benefit. This solution is not only cost-effective and simpler to manufacture, but also produces CAR T cells with markedly enhanced potency and efficacy in eliminating tumors. By addressing the primary obstacles of cellular immunotherapy, this method promises to extend the accessibility and effectiveness of such treatments, even in resource-constrained environments. Furthermore, the use of biomaterial scaffolds represents a significant advancement in the field, offering a scalable and practical solution to the challenges faced by current CAR T cell manufacturing protocols. This fast-track Phase I/II proposal outlines a comprehensive plan of complete prototyping, non-GLP toxicology and large-animal efficacy testing, poising Persistence for an IDE-filing in 2027. The proposal is structured into two phases. Phase I focuses on optimizing SynthNode resulting in a design-locked formulation and determining the shelf life and in-use stability of the final formulation. Phase II focuses on scaling up SynthNode production, conducting a biocompatibility study per FDA standards, and performing large animal studies to ensure safety and efficacy at clinically relevant doses. With the completion of Phase II, the company will be ready to launch GLP toxicology studies for an Investigational Device Exemption (IDE) filing and first in human trials in 2028. This proposal addresses the urgent need for innovative solutions to enhance CAR T cell therapy and presents a clear, focused strategy to bring SynthNode from proof-of-concept animal studies to the clinic. Through meticulous planning, collaboration with manufacturing and regulatory experts, and a commitment to rigorous scientific investigation, Persistence Therapeutics Inc. is poised to make a significant impact on the future of cancer treatment.