nalmefene (TH-104) / Tharimmune - LARVOL DELTA

Tharimmune Receives Positive FDA Feedback for TH104 Prophylaxis Program Against Respiratory Depression from Fentanyl and Ultrapotent Opioids (PRNewswire) - "In a formal Type D meeting with the FDA, Tharimmune presented its initial pharmacokinetic simulation results, and the plan for a more detailed pharmacokinetic modeling, for FDA review...Rhe FDA's feedback further de-risks the TH104 program and aligns with Tharimmune's development strategy for the planned 505(b)(2) New Drug Application (NDA) submission...In parallel with this regulatory clarity, the Company is on track to initiate a comprehensive Chemistry, Manufacturing, and Controls...The key findings from the simulation analysis demonstrated: Rapid Onset: A conservative nalmefene concentration target—representing the threshold effect for protection from respiratory depression—was projected to be achieved in approximately 30 minutes post-dose; Sustained Protection....Potential Superiority..."

FDA event • Depression

Comparison of the Pharmacokinetics of TH 104, Buccal Nalmefene, in Healthy Subjects and Patients With Cholestatic Liver Disease (ACG 2025) - "For healthy subjects, the Cmax and Tmax were 0.66 ng/mL (SD 0.18) and 2.23 hours (SD 0.92). For patients with cholestatic liver disease, the Cmax and Tmax were 0.73 ng/mL (SD 0.37) and 2.16 hours (SD 0.83). For healthy subjects, the mean AUC was 7.16 ng*hour/mL (SD 2.15 ) with 95% CI of 6.15 to 8.16."

Clinical • PK/PD data • Cholestasis • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus • NANOG

CORRELATION BETWEEN OPIOID LIGANDS AND RESPONSE TO OPIOID ANTAGONIST IN CHOLESTATIC PATIENTS WITH PRURITUS (AASLD 2025) - "In our recent work, we showed that nalmefene—a Mu and delta opioid receptor antagonist and kappa receptor agonist—reduced pruritus intensity in individuals with cholestatic liver disease...ELISA kits (Qayeebio, China) were used to test the following ligands: Dynorphin (Kappa agonist), Beta-Endorphin (Mu agonist), Met-Enkephalin and Leu-Enkephalin (Mu and Kappa agonists)... Leu-Enkephalin is an endogenous opioid peptide that primarily acts on delta-opioid receptors but also interacts with mu-opioid receptors. Previous studies, such as Dull (2021), found no correlation between endogenous opioid ligand levels and pruritus severity in cholestatic liver disease. Our findings represent the first reported association between Leu-enkephalin levels and itch reduction following treatment with an opioid antagonist, and suggest a potential role for delta opioid receptors in cholestatic pruritus (Smith KM, 2023)."

Clinical • Cholestasis • Dermatology • Hepatology • Pruritus • PENK

TH104 for the Treatment of Pruritus in Primary Biliary Cholangitis (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Tharimmune Inc | Trial completion date: Apr 2026 ➔ Jun 2027 | Initiation date: Mar 2025 ➔ Jun 2026 | Trial primary completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Trial initiation date • Trial primary completion date • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Tharimmune Secures Key Global Patents for TH-104, Laying Foundation for Broader Indications Following Initial Development as a National Security Medical Countermeasure Against Weaponized Fentanyl (Yahoo Finance) - "The new patents, recently granted and allowed across key global markets, will enable the Company's long-term strategy of pursuing broader indications for the technology, beginning with its lead program as a critical medical countermeasure for military and first responders against high-potency opioids....The granted and allowed patents include: United States (US) Application No. 17/285,971 (Allowed); Japan (JP) Patent No. 7603583 (Granted); Mexico (MX) Patent No. 422769 (Granted); Australia (AU) Patent Application No. 2019361980 (Allowed)."

Patent • Immunology

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

THE PHARMACOKINETICS OF TH104, BUCCAL NALMEFENE, IN HEALTHY SUBJECTS (DDW 2025) - "Both drugs showed early phase 2 metabolism (glucuronidation), but TH104 showed a delayed phase 1 metabolism. As phase 1 metabolism are primarily catalyzed by cytochrome P450 enzymes, whereas phase 2 metabolism is through enzymatic conjugation reactions, this difference in metabolism may represent an advantage for TH104 formulation in patients with liver disease."

Clinical • PK/PD data • Dermatology • Gastroenterology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

Tharimmune Presents Positive Clinical Data Highlighting TH104 Metabolic Profile and Advances Program for Prophylaxis Against Ultrapotent Opioid Exposure Following FDA Feedback (ACCESSWIRE) - P1 | N=20 | NCT06198686 | Sponsor: Tharimmune Inc | "Key findings from the pharmacokinetic study...Buccal administration of TH104 resulted in slower absorption compared to IV administration; The ratio of the area under the curve (AUC) of nalmefene glucuronide, a metabolite, compared to nalmefene was significantly higher for TH104 versus IV administration; Pharmacokinetics of nalmefene sulfate and nornalmefene, 2 other metabolites, were significantly delayed with TH104 compared to IV administration; Both formulations showed early phase 2 metabolism (glucuronidation), but importantly, TH104 demonstrated delayed phase 1 metabolism, which is mainly catalyzed by enzymes such as cytochrome P450 oxidases in the liver...The FDA has indicated that no additional clinical trials appear to be necessary prior to the submission of a New Drug Application (NDA) for this indication, allowing Tharimmune to leverage existing safety and efficacy data for nalmefene along with the...

FDA event • P1 data • Immunology

Tharimmune Abstracts Accepted for Presentation at Upcoming DDW and EASL Conferences (ACCESSWIRE) - "Tharimmune, Inc...announced abstracts featuring clinical data on its lead drug candidate, TH104, have been accepted for presentation at the Digestive Disease Week (DDW) Annual Meeting and at the European Association for the Study of the Liver (EASL) International Liver Congress. Both conferences will take place in May 2025....The accepted abstracts detail recent clinical advancements and emerging data underscoring the potential of TH104 to address significant unmet medical needs in immunological and inflammatory disorders."

Clinical • Immunology • Primary Biliary Cholangitis • Pruritus

The metabolism of TH104; a new drug for the treatment of pruritus in primary biliary cholangitis (EASL 2025) - "Both drugs showed early phase 2 metabolism (glucuronidation), but TH104 showed a delayed phase 1 metabolism. As phase 1 metabolism are primarily catalyzed by cytochrome P450 enzymes, whereas phase 2 metabolism is through enzymatic conjugation reactions, this difference in metabolism may represent an advantage for TH104 formulation in patients with liver disease."

Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus

An Evaluation of The Absolute Bioavailability of TH104 (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Tharimmune Inc | Active, not recruiting ➔ Completed | Trial completion date: Apr 2024 ➔ Nov 2024

Trial completion • Trial completion date

Tharimmune Announces Positive FDA Feedback on NDA Path for TH104 for Prophylaxis of Respiratory and/or CNS Depression for Ultrapotent Opioid Exposure (ACCESSWIRE) - "Tharimmune...announced in addition to developing TH104 for the proposed indication of moderate-to-severe chronic pruritus in patients with primary biliary cholangitis ('PBC'), which utilizes an approved active ingredient, now formulated as a buccal film, Tharimmune is seeking to develop TH104 for the additional proposed indication of 'Temporary Prophylaxis of Respiratory and/or Nervous System Depression in Military Personnel and Chemical Incident Responders Entering an Area Contaminated with High-Potency Opioids', for which we have submitted a Pre-Investigational New Drug Application ('PIND'). With respect to our PIND for this additional proposed indication for TH104, Tharimmune recently received positive feedback from the U.S. Food and Drug Administration (FDA) regarding a regulatory pathway that will allow the Company to submit a 505(b)(2) New Drug Application (NDA) for TH104."

FDA event • Immunology • Primary Biliary Cholangitis

TH104 for the Treatment of Pruritus in Primary Biliary Cholangitis (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Tharimmune Inc

New P2 trial • Dermatology • Hepatology • Immunology • Primary Biliary Cholangitis • Pruritus