Project Summary/Abstract Cell expansion is a critical step for cell therapy, hindered by expensive and complex bioreactor requirements to yield sufficient cell numbers for adequate dosing and requiring expensive regents to enhance functionality for increased clinical success. To support the use of patient cells within the cell therapy workflow, there is a need for bioreactors designed for expanding patient cells from an initial iPS clonal population to clinically relevant cell doses. These reactors must also be suitable for cGMP processes and economically efficient to enable their utility within the healthcare system. Overall, there is a need for clinically relevant cell expansion technologies that are robust and efficient enough to enable the realization of autologous cell therapy workflows as a viable treatment option for all. Thus, the unmet need we will address is providing a bioreactor-based workflow for the efficient translation of patient cells into high-quality iPS cell based therapeutics in a patient-specific manner – benefiting drug developers, patients, clinicians, and the healthcare economy. Our universal approach to cell expansion (OnXpansion) uses a defined serum-free media and relies on controlled aggregation for enhanced paracrine signaling and cell-cell contact, enhanced nutrient delivery via low-shear perfusion, and organotypic tissue niches to generate thousands of identical spheroid tissues that can be further scaled to yield adequate cell numbers for cell therapy at both reduced costs and manual labor. Our approach to translating this technology center around de-risking its utility for precision medicine and increasing its suitability and handling within the intended customer workflows. Our bioreactor products are efficient (cost, time, labor), easy to use, automated, reliable, robust, physiologically relevant, and clinically predictive. The large unmet need and low barrier for entry positions Link favorably against competitors. Overall, Link’s products are designed to enable a reliable and robust precision medicine workflow that is efficient and of high biological fidelity, thereby enabling a future where cell therapy is more accessible to the patient, via decreased costs, and the provider, via simplified workflows.

Narrative In this Phase I SBIR, Link Biosystems, Inc. Overall, the Phase I is designed to demonstrate the feasibility of our OnXpansion technology to enable iPS culture and expansion of enhanced quality and efficiency to enable the realization of autologous cell therapy workflows. The OnXpansion bioreactor is user-friendly/automated, robust, and generates iPS cells of high purity and viability. In the Phase II portion of the proposed SBIR, we will further streamline and deeply characterize OnXpansions utility to directly provide a closed, automated process for the manufacturing of patient iPS cells at scale and derisk it’s utilization as a cGMP compliant bioreactor technology for the efficient generation of patient iPS cells at clinically relevant within academic research centers and companies offering cell therapy products.