Tharimmune announce preclinical TH023 results

Tharimmune (THAR) announced preclinical results for its novel oral antibody, TH023. In a murine model, a proprietary protease enzyme stabilized platform demonstrated successful delivery of infliximab, a tumor necrosis factor-alpha inhibitor, in serum with concentrations detected being significantly higher than the standard serum trough concentration needed for antibody efficacy in immunology indications via injection. These findings represent a significant step towards developing a more convenient and potentially patient-preferred alternative to currently available infliximab treatments, which are administered via intravenous infusion or subcutaneous injection. Key findings of the preclinical evaluation include demonstrating enzymatic protection of infliximab against human colon enzymes ex vivo using fresh fecal samples from healthy subjects utilizing the Soteria platform, a proprietary formulation of natural amino acids. Furthermore, successful delivery of TH023 in vivo into both local colonic tissue and systemic circulation was shown following intra-duodenal once-daily dosing for 1 week in a healthy mouse model at two doses of infliximab. This data shows the potential of the delivery platform to allow for both local delivery of the antibody precisely in the large intestinal tissue through enzymatic stabilization, as well as systemic circulation, which is an ideal pharmacokinetic profile for targeting both local gastrointestinal diseases such as inflammatory bowel disease as well as systemic inflammatory diseases. The mechanism by which the antibody transcytosis occurs in the GI tract was shown to be a combination of passive, as well as mediated via the neonatal fragment crystallizable receptor, highly expressed in distal intestinal epithelial cells enabling active transport. Additionally, the study demonstrated that tissue penetration of infliximab in combination with the enzyme stabilization platform was superior to a traditional permeation enhancer, sodium N-(8-(2-hydroxylbenzoyl) amino) caprylate, which has been used to enhance the absorption of GLP-1 peptides, such as semaglutide. Utilization of SNAC to protect infliximab from enzymatic degradation or permeation enhancement did not result in tissue or serum concentrations suggesting standard off-the-shelf oral peptide delivery technologies are not suitable for oral delivery of antibodies. Two other standard permeation enhancer technologies tested also showed unsitable results for oral delivery, further supporting the Company’s proprietary TH023 formulation.