Tharimmune, Inc. (Nasdaq: THAR) has announced promising preclinical results for TH023, its novel oral formulation of infliximab targeting tumor necrosis factor-alpha (TNF-α). The study demonstrated successful delivery of the monoclonal antibody through a proprietary protease enzyme stabilized platform, achieving serum concentrations significantly higher than the standard trough concentration needed for efficacy in immunology indications via injection (approximately 3-5μg/ml).
The breakthrough represents a significant advancement toward developing a more convenient alternative to current infliximab treatments, which require intravenous infusion or subcutaneous injection. Infliximab is widely used to treat several chronic inflammatory conditions, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, and psoriasis.
Key Preclinical Findings
The preclinical evaluation revealed several important achievements for the oral delivery platform:
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Enzymatic protection of infliximab against human colon enzymes was demonstrated ex vivo using fresh fecal samples from healthy subjects through the Soteria® platform, a proprietary formulation of natural amino acids.
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Successful delivery of TH023 was achieved in vivo into both local colonic tissue and systemic circulation following intra-duodenal once-daily dosing for one week in a healthy mouse model.
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The mechanism of antibody transcytosis in the gastrointestinal tract was shown to involve both passive transport and active transport mediated by the neonatal fragment crystallizable receptor (FcRn), which is highly expressed in distal intestinal epithelial cells.
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Tissue penetration of infliximab using the enzyme stabilization platform proved superior to traditional permeation enhancers like sodium N-(8-[2-hydroxylbenzoyl] amino) caprylate (SNAC), which is used in GLP-1 peptides such as semaglutide.
"We are extremely encouraged by these results, which validate the potential of our partnership with Intract and the platform to deliver complex biologic molecules like infliximab orally," said Randy Milby, CEO of Tharimmune. "This represents a potential major milestone in our mission to develop more patient-friendly and accessible treatment options for chronic inflammatory diseases, addressing a multi-billion dollar market. These findings provide a strong foundation for further development into clinical trials."
Dual-Action Delivery System
The data demonstrates the potential of Tharimmune's delivery platform to enable both local delivery of the antibody precisely in the large intestinal tissue through enzymatic stabilization and systemic circulation. This dual-action pharmacokinetic profile makes it potentially ideal for targeting both local gastrointestinal diseases such as inflammatory bowel disease (IBD) and systemic inflammatory conditions.
The company's approach leverages technology from its partnership with Intract Pharma, announced last year. Tharimmune licensed global development and commercialization rights (outside South Korea) to Intract Pharma's Soteria® and Phloral® delivery platforms, along with an existing supply agreement for infliximab to be used in the oral product development program.
Addressing Market Needs and Patient Burden
Infliximab, including biosimilars, generated approximately $6.3 billion in global sales in 2022, with experts projecting the market could reach $9 billion within a decade. However, current administration routes require frequent healthcare facility visits, creating significant patient burden and healthcare costs.
An oral formulation of infliximab could potentially:
- Improve patient convenience and treatment adherence by eliminating the need for injections or infusions
- Reduce clinic visits and specialized nursing care, potentially lowering overall treatment costs
- Expand accessibility to patients in areas with limited access to infusion centers
Development Timeline
Tharimmune plans to optimize the formulation and dosing regimen of TH023 and prepare for first-in-human clinical trials within the next 12 months. The company aims to capture a portion of the existing and growing infliximab market by offering a differentiated, patient-preferred oral option.
Technical Advantages Over Existing Approaches
The study demonstrated that standard off-the-shelf oral peptide delivery technologies are not suitable for oral delivery of antibodies. Two other permeation enhancer technologies tested (sodium caprate and labrasol) also showed unsuitable results for oral delivery, further supporting the company's proprietary TH023 formulation approach.
By leveraging Intract's platform, Tharimmune aims to enhance the effectiveness of TNF-α inhibitors through precision delivery that maximizes proteolytic stabilization and tissue permeation. This novel approach offers significant potential for directly addressing inflammatory conditions within the GI tract and systemic inflammatory disorders where TNF-α plays a critical role in disease progression.
About Tharimmune
Tharimmune is a clinical-stage biotechnology company developing therapeutic candidates in immunology, inflammation, and oncology. Its lead clinical asset, TH104, aims to suppress chronic pruritus associated with primary biliary cholangitis (PBC), a rare autoimmune liver disease. The expanded pipeline includes TH023 and early-stage multispecific biologics targeting unique epitopes against multiple solid tumors through its proprietary EpiClick™ Technology.
