infliximab oral (TH023) / Celltrion, Tharimmune, Intract Pharma - LARVOL DELTA

Tharimmune Issues Comprehensive Corporate Update including Lead TH104 as Critical National Security Solution Against Weaponized Fentanyl and TH023 Poised to Revolutionize Oral Antibody Delivery (ACCESS Newswire) - "The Company has strengthened its financial position by successfully completing several equity financings and securing approximately $5.47 million in gross proceeds before deducting placement and legal fees, during the latter part of the second quarter and continuing into the third quarter of this year...We believe these proceeds will strategically accelerate the advancement of TH104, recognizing its paramount importance as a swiftly progressing national security asset, in addition to supporting general corporate purposes vital for the Company's continued growth and operational efficiency...Future Development: Building on these promising preclinical results, Tharimmune plans to optimize TH023's formulation and dosing regimen and prepare for a first-in-human clinical trial within the next 12 months, marking a significant step towards bringing this transformative therapy to patients."

Financing • New trial • Immunology • Inflammation • Inflammatory Bowel Disease • Pruritus

Tharimmune Announces Positive Results for Novel Oral Monoclonal Antibody TH023 Targeting Tumor Necrosis Factor-alpha (ACCESSWIRE) - "Tharimmune...announced positive preclinical results for its novel oral antibody, TH023. In a murine model, a proprietary protease enzyme stabilized platform demonstrated successful delivery of infliximab...in serum with concentrations detected being significantly higher than the standard serum trough concentration needed for antibody efficacy in immunology indications via injection (~3-5µg/ml).....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 (PK) profile for targeting both local gastrointestinal (GI) diseases such as inflammatory bowel disease..."

Preclinical • Inflammatory Bowel Disease

Network Meta-analysis to Evaluate the Comparative Efficacy of Advanced Therapies as First-Line Treatment for Maintenance Treatment of Adult Patients With Moderate to Severe Crohn's Disease (AIBD 2024) - "Background: Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn's disease (CD)... Eligible studies, identified by systematic literature review (PROSPERO no: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate to severe CD who responded to induction therapy... In this updated NMA, SC infliximab 120 mg Q2W demonstrated a favorable profile in achieving clinical remission and endoscopic response when administered as a first-line advanced therapy for maintenance treatment of patients with moderate to severe CD."

Metastases • Retrospective data • Crohn's disease • Immunology • Inflammatory Bowel Disease

DIRECTCD: InDuctIon TREatment with SubCuTaneous Infliximab for Crohn's Disease (clinicaltrials.gov) - P3 | N=158 | Recruiting | Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Trial completion date: Jul 2024 ➔ Dec 2025 | Trial primary completion date: Jan 2024 ➔ Jun 2025

Monotherapy • Trial completion date • Trial primary completion date • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease

TWO YEAR RESULTS OF SUBCUTANEOUS INFLIXIMAB (CT-P13 SC) DOSE ESCALATION THERAPY AS AN OPTION FOR MANAGING LOSS OF RESPONSE IN INFLAMMATORY BOWEL DISEASE – FROM LIBERTY-UC AND LIBERTY-CD STUDY (UEGW 2024) - "DE of CT-P13 SC from 120 mg to 240 mg Q2W following IV induction in patients who initially respond but subsequently lose response, shows clinical efficacy over an extended observation period of 102 weeks. Safety profiles were generally comparable between patients with or without DE, and no new safety concerns were found after DE as well in long term treatment."

Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Pain

NETWORK META-ANALYSIS TO EVALUATE THE COMPARATIVE EFFICACY OF ADVANCED THERAPIES AS FIRST LINE FOR MAINTENANCE TREATMENT OF ADULT PATIENTS WITH MODERATE-TO-SEVERE CROHN’S DISEASE (DDW 2024) - "Background Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn's disease (CD)...: CRD4 0 341375 ) evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab SC adalimumab IV or SC vedolizumab SC ustekinumab SC risankizumab or oral upadacitinib in patients with moderate-to-severe CD who responded to induction therapy...Barberio B et al . Gut 0 3;7 : 64-74."

Metastases • Retrospective data • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Oncology

SUPER-RESPONDERS IN PATIENTS WITH MODERATE-TO-SEVERE CROHN’S DISEASE TREATED WITH SUBCUTANEOUS INFLIXIMAB MAINTENANCE THERAPY: A POST HOC ANALYSIS OF THE LIBERTY-CD STUDY (DDW 2024) - P3 | "Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long-term outcomes with substantial individual benefit (comprehensive disease control). Baseline characteristics and TLI were associated with super-response."

Clinical • Retrospective data • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • Pain

Network meta-analysis to evaluate the comparative efficacy of advanced therapies as first line for maintenance treatment of adult patients with moderate-to-severe Crohn’s disease (ECCO-IBD 2024) - "Background Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn’s disease (CD)...Methods Eligible studies, identified by systematic literature review (PROSPERO no.: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate-to-severe CD who responded to induction therapy...2 Barberio B et al . Gut 2023;72:264–74."

Metastases • Retrospective data • Crohn's disease • Immunology • Inflammatory Bowel Disease

Super-responders in patients with moderate-to-severe Crohn’s disease treated with subcutaneous infliximab maintenance therapy: A post hoc analysis of the LIBERTY-CD study (ECCO-IBD 2024) - P3 | "Super-responders with rapid and sustained improvements during SC IFX therapy had a higher likelihood of achieving desirable long‑term outcomes, with substantial individual benefit (CDC). Baseline characteristics and TLI were associated with super-response."

Clinical • Retrospective data • Crohn's disease • Immunology • Inflammatory Bowel Disease

EFFICACY, SAFETY AND IMMUNOGENICITY OF SUBCUTANEOUS INFLIXIMAB (CT-P13 SC) MONOTHERAPY VERSUS COMBINATION THERAPY WITH IMMUNOSUPPRESSANTS – POST HOC ANALYSIS OF LIBERTY-CD STUDY AND LIBERTY-UC STUDY (UEGW 2023) - "IS (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) were allowed if patients maintained stable doses at least 8 weeks prior to W0, and stable doses were maintained up to W54. No statistical differences in efficacy outcomes at W54 were observed between monotherapy and combination therapy in CD and UC patients. Concomitant IS use was associated with less ADA formation, whereas more infections are seen for combination therapy during maintenance period in CD and UC patients. The overall safety profile during maintenance period was otherwise comparable between monotherapy and combination therapy in CD and UC patients."

Clinical • Combination therapy • Monotherapy • Retrospective data • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammatory Bowel Disease • Ulcerative Colitis

Opinion: Embrace the Era of Next-Generation Biologics (Center for Biosimilars) - "Several real-world studies conducted in Europe demonstrate the safety of switching...One long-term observational, prospective cohort study conducted in Germany showed that switching 148 patients with IBD (96 with CD, 52 with UC) from reference infliximab to a biosimilar did not lead to any increase in disease activity....Real-world data on US veteran patients with IBD revealed that a single switch from reference to biosimilar infliximab...did not lead to any significant safety issues....In another real-world study conducted by Cleveland Clinic, patients were randomized to switch to infliximab biosimilar or continue on reference infliximab....No significant difference in the use of corticosteroid taper...between these 2 groups."

Review • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Celltrion partners with Intract to develop oral infliximab (Bioworld) - "Under the agreement signed between Celltrion Group (which includes Celltrion Inc. and Celltrion Healthcare Co. Ltd.) and Intract, of London, on Aug. 20, 'Celltrion will supply the drug material through clinical evaluation and into the market, while Intract will be responsible for performing clinical studies'...Phase IB/IIa trials targeting patients suffering from inflammatory bowel disease are scheduled to begin in the third quarter of 2021."

Licensing / partnership • New P1/2 trial • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis