Sernova Corp. announced the presentation of preclinical data supporting the anticipated 2024 IND submission and planned Phase 1/2 clinical trial of Evotec SE's iPSC-derived ILCs in combination with Sernova's implantable Cell Pouch device for the treatment of patients with T1D. The objective of the partnership is to produce an off-the-shelf, commercially scalable cell therapy treatment, with human testing anticipated to begin in 2024.

The data were presented by Matthias Austen, PhD, SVP Cell Therapy at Evotec SE (Evotec), as an oral podium presentation at the 4th International Pancreas and Islet Transplant Association (IPITA) /Harvard Stem Cell Institute (HSCI) /Juvenile Diabetes Research Fund (JDRF) Summit, held from April 24-25, 2023 in Cambridge, Massachusetts. The presentation included an introduction to Evotec's proprietary GMP process for manufacturing iPSC-derived ILCs for use in Sernova's Cell Pouch, as well as encouraging results from multiple studies using a standard mouse model of T1D. Key findings: Evotec has developed a scalable GMP manufacturing workflow, starting from GMP-grade iPSCs to the final product of ILCs, yielding a high beta cell fraction with no post-implantation variability of cell composition.

Evotec ILCs are cryopreserved at a late-intermediate stage of differentiation allowing for a cost-effective large-scale manufacturing process to optimize both pre- and post-implantation durability, offering a major advantage over competing cell therapies in development. ILCs implanted to mouse kidney capsule demonstrated complete and durable normalization of glucose levels in a standard diabetic mouse model out to the pre-planned termination date at 320 days. ILCs implanted into Sernova's Cell Pouch demonstrated rapid normalization of glycemic control in the streptozotocin (STZ)-induced diabetic NSG (NOD.SCID.IL-2Rgammanull) mouse model.

Circulating C-peptide levels (a biomarker for insulin production) in mice implanted with the Cell Pouch and ILCs were equivalent after 6 weeks to those in mice that received 4000 IEQ human islets under the kidney capsule. Efficient glucose clearance and no hypoglycemia was demonstrated in an oral glucose tolerance test administered at 8 weeks post-implantation. Animals implanted with Cell Pouch and ILCs showed an identical glucose clearance time course compared to animals transplanted with 4000 IEQ human islets.

Upon explanation of the Cell Pouch with ILCs after the 32-week survival period, histological graft analyses showed the presence of all relevant islet cell types including insulin-producing beta cells, glucagon-producing alpha cells, and somatostatin-producing delta cells, indicating a favorable cell composition of the implanted ILCs. Histological graft analyses also revealed extensive intra-graft vascularization, likely contributing to the excellent endocrine cell survival with a high beta cell fraction, and consistent with the observed functional outcomes.