Opioid receptors antagonists(Opioid receptors antagonists), κ opioid receptor agonists(Kappa opioid receptor agonists), μ opioid receptor antagonists(Mu opioid receptor antagonists)

Therapeutic Areas

Other DiseasesSkin and Musculoskeletal Diseases

Active Indication

AlcoholismOpiate OverdosePruritus+ [1]

Inactive Indication

GamblingSmoking Cessation

Originator Organization

Baxter International, Inc.

Active Organization

Tharimmune, Inc.

H. Lundbeck A/S

Purdue Pharma LP

+ [6]

Inactive Organization

Somaxon Pharmaceuticals, Inc.Hikma Pharmaceuticals USA, Inc.

Drug Highest PhaseApproved

First Approval Date

US (17 Apr 1995),

Opiate Overdose

RegulationPriority Review (US), Fast Track (US)

Structure

Molecular FormulaC21H26ClNO3

InChIKeyGYWMRGWFQPSQLK-OPHZJPRHSA-N

CAS Registry58895-64-0

Clinical Trials associated with Nalmefene Hydrochloride

NCT06733519 / Not yet recruitingPhase 2

Evaluation of TH104 for Moderate to Severe Pruritus in Primary Biliary Cholangitis: a Double-blind, Randomized, Placebo-controlled, Phase 2a Study

A phase 2a, multicenter, randomized, double-blind, placebo-controlled study of TH104 in primary biliary cholangitis (PBC) participants with moderate to severe pruritus.

Start Date01 Mar 2025

Sponsor / Collaborator

Tharimmune, Inc.

NCT06408714 / RecruitingPhase 3IIT

Comparison of Nalmefene Hydrochloride Injection and Naloxone Hydrochloride Injection for the Treatment of Recurrent Respiratory Depression After Suspected Acute Opioid Overdose in the Emergency Department

The goal of this clinical trial is to compare naloxone to nalmefene for the treatment of opioid overdose in adults. The main questions it aims to answer are:
* Does nalmefene lower the number of doses of medicine participants need to treat opioid overdose?
* When participants are given nalmefene instead of naloxone, do they have fewer complications of opioid overdose such as being admitted to the hospital or having a breathing tube inserted?
Researchers will compare nalmefene to naloxone for the treatment of opioid overdose. Nalmefene and naloxone are both approved medicines to treat opioid overdose.
Participants who are brought to the emergency department after an opioid overdose will be given a dose of either nalmefene or naloxone if their breathing slows down again after an opioid overdose. Participants will:
* Stay in the emergency department for 8 hours after receiving a dose of nalmefene or naloxone.
* Receive a phone call 7 days after their emergency department to check on how they are doing.
Background information:
Naloxone (also known as Narcan) and nalmefene are opioid blocking medicines. When someone overdoses on an opioid, such as heroin or fentanyl, their breathing slows down or stops and they can die. By giving naloxone or nalmefene, the effect of the opioid can be blocked and the person can start breathing again. Naloxone is the most commonly used medicine to reverse an opioid overdose. The effect of naloxone lasts about an hour, and patients may need more than one dose of naloxone to keep them breathing. Sometimes patients overdose, get a dose of naloxone and wake up, and then some time later their breathing slows down again and they need another dose of naloxone. This can happen because the effect of the opioid they took lasts longer than the effect of the naloxone.
The effect of nalmefene lasts longer than naloxone, about four hours. If a person gets nalmefene, their opioid may wear off before the nalmefene wears off and they might not need any more doses of a reversal medicine. Both naloxone and nalmefene are approved medicines for treating opioid overdose.
Often, when a person overdoses on an opioid, someone gives them naloxone right away and then they are brought to the emergency department. In the emergency department, they are watched for several hours to make sure they don't stop breathing again when their naloxone wears off. If they do stop breathing again, they are given another dose of naloxone. In this study, participants will be given either nalmefene or naloxone if their breathing slows down while they are in the emergency department.

Start Date26 Aug 2024

Sponsor / Collaborator

The University of New Mexico

ChiCTR2400088347 / SuspendedPhase 4IIT

Application of different doses of nalmefene pre-injection in painless gastrointestinal enddoscopy

Start Date20 Aug 2024

Sponsor / Collaborator-

100 Clinical Results associated with Nalmefene Hydrochloride

100 Translational Medicine associated with Nalmefene Hydrochloride

100 Patents (Medical) associated with Nalmefene Hydrochloride

472

Literatures (Medical) associated with Nalmefene Hydrochloride

01 Nov 2024·HEPATOLOGY RESEARCH

Brief intervention for chronic liver disease patients with alcohol use disorder in a hepatology outpatient unit: Effects and limitations

Article

Author: Takahashi, Hirokazu ; Sakamoto, Naoya ; Namisaki, Tadashi ; Shiraki, Makoto ; Miyaaki, Hisamitsu ; Hisanaga, Takuro ; Eguchi, Yuichiro ; Nakao, Kazuhiko ; Nakai, Masato ; Hara, Nagisa ; Ohama, Hideko ; Takami, Taro ; Tada, Fujimasa ; Yoshiji, Hitoshi ; Hiraoka, Atsushi

Abstract:

Aim:

It is not uncommon to encounter outpatients in the hepatology department with harmful alcohol habits. When treating such chronic liver disease (CLD) patients, an adequate intervention method for harm reduction of alcohol use, such as brief intervention (BI) or BI and nalmefene, should be considered. This study aimed to elucidate the clinical effectiveness of BI for CLD patients affected by harmful alcohol use.

Methods:

From June 2021 to 2023, 123 Japanese CLD outpatients (hepatitis B virus : hepatitis C virus : alcoholic liver disease : others = 32:18:42:31) with an Alcohol Use Disorders Identification Test (AUDIT) score of ≥8 at the initial interview and a repeat interview with AUDIT 9 months later were enrolled. Clinical features related to patient behavior following the initial AUDIT interview were retrospectively evaluated, and compared between patients without and with BI treatment.

Results:

For the non‐BI and BI groups, baseline AUDIT score (median 10 [interquartile range (IQR) 9–13] vs. 12 [IQR 10–17], p = 0.016) and relative change in AUDIT score (median 0 [IQR −3 to 2] vs. −3 [IQR −7 to 0], p < 0.01) showed significant differences, whereas there was no significant difference between the groups for AUDIT score at the time of the second interview (p = 0.156). Following BI, significant improvements were observed for items 1, 2, 3, 4, 5, 8, and 10 of AUDIT (each p < 0.05).

Conclusion:

Patients with an alcohol use disorder as well as those with alcohol dependency who received BI showed a significant decline in AUDIT score, although the score of the follow‐up AUDIT indicated continued alcohol use disorder. In addition to BI, medication with nalmefene should be considered, based on individual factors.

01 Sep 2024·ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE

Should the French approval of baclofen for alcohol dependence be extended to abstinence maintenance?

Article

Author: Naassila, Mickael ; Franchitto, Nicolas ; Karila, Laurent ; Rolland, Benjamin ; Barrault, Camille

Ever since 2018 France has been the only country to approve the gamma aminobutyric acid type B (GABA-B) receptor agonist baclofen for alcohol dependence. This authorization follows a ten-year period of intensive off-label use during which baclofen was used in doses of up to 300 and even 400mg per day to support the gradual reduction of alcohol consumption in patients suffering from alcohol dependence. However, in international clinical trials, baclofen has mainly been studied to support the maintenance of abstinence. The French use of baclofen was therefore somewhat atypical as it paved the way for drug-supported approaches to reducing alcohol consumption, even before nalmefene was marketed. In line with this specific use of baclofen, approval was granted only for alcohol reduction support. However, a recent Cochrane systematic review and meta-analysis by Agabio et al. found significant efficacy only for abstinence maintenance, while no significant effect was found on alcohol reduction outcomes and no dose-response relationship was identified in the analyses. The safety of baclofen was judged to be good. Based on these substantial new results, the Société française d'alcoologie (SFA) now considers that baclofen should also be approved for the maintenance of abstinence. The extension of approval should not lead to the removal of the initial indication or the possibility of using high doses, as some patients have found this therapeutic regimen particularly useful for them. France, which has been a open skies national laboratory on the use of baclofen in alcohol dependence for over ten years, should let this original therapeutic option available to patients. However, it should update the regulatory framework defining the main conditions of access to treatment for patients based on the latest and highest scientific evidence.

01 Sep 2024·Drug and alcohol dependence reports

Synthetic opioids have disrupted conventional wisdom for treating opioid overdose

Article

Author: Heidbreder, Christian ; Skolnick, Phil ; Paavola, Jordan

More than 90 % of opioid overdose deaths in North America are now caused by synthetic opioids, and while they are not as prevalent in the European illicit drug market, there are indications that they may become so in the near future. Multiple publications have argued that neither higher doses of naloxone nor more potent opioid receptor antagonists are needed to reverse a synthetic opioid overdose. However, the unique physicochemical properties of synthetic opioids result in a very rapid onset of respiratory depression compared to opium-based molecules, reducing the margin of opportunity to reverse an overdose. While intravenous administration rapidly delivers the high naloxone concentrations needed to reverse a synthetic opioid overdose, this option is often unavailable to first responders. A translational mechanistic model of opioid overdose developed by the FDA's Division of Applied Regulatory Science provides an unbiased approach to evaluate the effectiveness of overdose reversal strategies. Reports using this model demonstrated the naloxone tools (2 mg intramuscular and 4 mg intranasal) used by many first responders can result in an unacceptable loss of life following a synthetic opioid (fentanyl, carfentanil) overdose. Moreover, sequential (2.5 minutes between doses) administration of up to four doses of intranasal naloxone was no more effective at reducing the incidence of cardiac arrest (a surrogate endpoint for lethality) than a single dose, suggesting that attempts at titration may not provide the rapid absorption required to reverse a synthetic opioid overdose. This model was also used to compare the effectiveness of intranasal naloxone to intranasal nalmefene, a recently FDA-approved opioid receptor antagonist with a more rapid absorption and a higher affinity at mu-opioid receptors compared to intranasal naloxone. Intranasal nalmefene resulted in large and clinically meaningful reductions in the incidence of cardiac arrest compared to intranasal naloxone. Furthermore, simultaneous administration of four doses of intranasal naloxone was needed to reduce the incidence of cardiac arrest to levels approaching those produced by a single dose of intranasal nalmefene. These data are consistent with evidence that synthetics have indeed disrupted conventional wisdom in the treatment of opioid overdose.

News (Medical) associated with Nalmefene Hydrochloride

16 Dec 2024

·www.accesswire.com

Tharimmune Announces Phase 2 Study Plan for TH104 in Patients With Moderate-to-Severe Pruritus Associated With Primary Biliary Cholangitis and Provides a Business Update

BRIDGEWATER, NJ / ACCESSWIRE / December 16, 2024 / Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company committed to pioneering therapies in immunology and inflammation, today announced plans for initiating a Phase 2 study evaluating TH104 in patients suffering from moderate-to-severe pruritus (severe itching) associated with primary biliary cholangitis (PBC), a rare and chronic liver disease, and also provided a corporate update. The launch of this clinical trial, expected in 2025, follows favorable results from Tharimmune's Phase 1 study with TH104, recent regulatory feedback from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), as well as progress on manufacturing clinical study supply.Business Update and 2024 Corporate HighlightsThroughout 2024 Tharimmune achieved significant milestones across three key areas. These accomplishments reflect progress in advancing innovative therapies in inflammation and immunology, with a focus on improving patient outcomes in areas of high unmet need.Manufacturing, Clinical and Regulatory ProgressValidation and batches of manufacturing supply of TH104 for Phase 2 clinical study are on track for year-end.Announced positive results from a Phase 1 clinical trial of TH104 in healthy subjects, demonstrating a favorable pharmacokinetic profile and a mild side-effect profile.Received positive regulatory feedback from the FDA and EMA for the TH104 clinical program, providing guidance on the Phase 2 trial design.Granted a patent from the European Patent Office covering therapeutics created for carrying antibody and peptide therapies, representing a novel solution and addressing critical challenges with stability and absorption.Medical and Scientific Community EngagementParticipated in key industry conferences to present new clinical data and engage with the scientific community.Presented favorable clinical data at the American College of Gastroenterology (ACG) Annual Scientific Meeting, reinforcing the safety profile of TH104 with no unexpected treatment-emergent adverse events.Shared positive clinical data at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®, highlighting a significant correlation between blood levels and symptom relief in patients treated with TH104.Corporate AchievementsEntered into a licensing agreement with Intract Pharma, aiming to expand Tharimmune's product pipeline to develop oral biologics including an oral formulation of infliximab.Entered into a licensing agreement with OmniAb, accessing their antibody discovery technology platform to enhance Tharimmune's early-stage immunology pipeline.Appointed David Jones, Professor of Liver Immunology at Newcastle University in England and renowned scientist with extensive expertise in hepatic pathologies and PBC, to Tharimmune's Scientific Advisory Board.Completed private placement financings, raising more than $4 million to support clinical development and working capital, including TH104 development program.TH104 Phase 2 Clinical StudyThe multicenter, randomized, double-blind, placebo-controlled Phase 2 trial is designed to assess the safety, tolerability and efficacy of TH104 in reducing itch in PBC patients with moderate-to-severe pruritus, a condition that significantly impacts daily lives and remains an area of unmet medical need. The study plans to enroll approximately 40 patients at sites in the U.S., Europe and the UK. Patients will receive escalating doses of TH104 in a nine-week study that includes treatment and observation periods, with efficacy measured by changes in patient-reported itch scores utilizing the Worst-Itch Numerical Rating Scale (WI-NRS), a relevant clinical outcome assessment for pruritus, as well as other quality-of-life metrics. Additional information on the Phase 2 study is available on ClinicalTrials.gov (NCT06733519)."Following feedback from global regulators including guidance on a future Phase 3 program, we are delighted to advance TH104 into this Phase 2 clinical trial planned for 2025, marking a critical milestone in our efforts to address the debilitating effects of chronic pruritus. Our focus on innovative delivery mechanisms that target the opioid receptors involved in the body's itch circuitry underscores the favorable data collected thus far in clinical development. We plan to report preliminary results from this Phase 2 trial in late 2025," said Randy Milby, Chairman and CEO of Tharimmune.Board of Directors ExpansionAdditionally, Tharimmune announced the appointment of Sanam Parikh to its Board of Directors, expanding the size of its Board to six Directors. Mr. Parikh brings to Tharimmune significant experience in clinical trial management, regulatory submissions and operational oversight.Mr. Parikh has managed clinical studies across various global sites, overseeing CRO partnerships and site management to ensure compliance with complex regulatory standards. His experience includes site feasibility, budget negotiation, contract management and regulatory interactions, with particular expertise working under FDA and EMA guidelines. Earlier in his career, Mr. Parikh was an associate clinical project manager in oncology at Clario, and held various research laboratory positions prior to that."Sanam is an emerging leader in preclinical and clinical study management. His background in oncology-focused clinical operations along with a proven record in managing critical aspects of trial execution will significantly bolster our capabilities," added Mr. Milby. "Furthermore, his in-depth knowledge of clinical operations and his focus on ensuring study integrity from preclinical work through to regulatory submissions aligns with our strategic goals as we continue to develop and validate our oncology-focused product pipeline."Mr. Parikh holds a Master's in Public Health with a focus on Urban Public Health from Rutgers University, and a Bachelor's in Biology from the New Jersey Institute of Technology.About TH104TH104 is embedded with nalmefene onto a proprietary transdermal buccal film that easily adheres to the inside of the mouth. This endows TH104 with key features making it an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions. The molecule has a dual mechanism of action affecting both the µ-opioid receptor and the kappa-opioid receptor, as well as potentially inhibiting IL-17 inflammatory cytokine expression. These opioid receptors when stimulated and/or inhibited by the body's natural ligands have been known to be involved in the body's itch circuitry.About Pruritus and Primary Biliary CholangitisAccording to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC is a rare and chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the buildup of bile, resulting in liver damage. Pruritus is a common condition associated with PBC, affecting up to 75% of individuals at some point during their disease course. It has a debilitating impact on health-related quality of life with limited treatment options.Published survey data of PBC respondents suffering from pruritus described their itch as "bugs crawling under the skin." More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.About TharimmuneTharimmune, Inc. is a clinical-stage biotechnology company developing a diverse portfolio of 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 with no known cure. The expanded pipeline includes TH023, an oral TNF-alpha inhibitor, offering a new approach to treating autoimmune diseases. Tharimmune is also advancing early-stage multi-specific biologics targeting unique epitopes against multiple solid tumors. The company has a license agreement with OmniAb, Inc. to access their antibody discovery technology for targeting specified disease markers. For more information, please visit: www.tharimmune.com.Forward Looking StatementsCertain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, contained in this press release, including statements regarding the timing and design of Tharimmune's future Phase 2 trial, Tharimmune's strategy, future operations, future financial position, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "continue," "could," "depends," "estimate," "expect," "intend," "may," "ongoing," "plan," "potential," "predict," "project," "target," "should," "will," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements. Factors that may cause such differences, include, but are not limited to, those discussed under Risk Factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023 and other periodic reports filed by the Company from time to time with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views as of the date of this release. Subsequent events and developments may cause the Company's views to change; however, the Company does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this release.ContactsTharimmune, Inc.[email protected]Alliance Advisors IRTirth T. Patel[email protected]212-201-6614SOURCE: Tharimmune, Inc.

Phase 2Phase 1License out/inExecutive ChangeClinical Result

06 Dec 2024

·www.accesswire.com

Tharimmune Announces $2.02 Million Private Placement to Advance Development Programs

BRIDGEWATER, NJ / ACCESSWIRE / December 6, 2024 / Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company committed to pioneering therapies in immunology and inflammation, today announced it has entered into a securities purchase agreement to raise gross proceeds of approximately $2.02 million through a private placement.The agreement includes the issuance of 961,446 shares of common stock (or common stock equivalents) and warrants to purchase up to an additional 480,723 shares of common stock. Each share (or common stock equivalent) is priced at $2.10 and is accompanied by a warrant. The warrants will have an exercise price of $2.031 per share, becoming exercisable six months after issuance and expiring five and one-half years from the date of issuance. The closing of this transaction is expected on or about December 9, 2024, subject to customary closing conditions.Strategic Investors and Placement DetailsThe financing was led by Gravitas Capital and SDS Capital Group, alongside other biotechnology-focused private investors. President Street Global served as the exclusive placement agent for the offering, ensuring seamless execution of the transaction.After deducting placement agent fees and other offering-related expenses, the Company intends to allocate the net proceeds toward clinical development, including advancing its flagship TH104 development program, as well as general working capital.Advancing Innovation in BiotechnologyThis financing reinforces Tharimmune's commitment to advancing its portfolio of therapeutic candidates. TH104, the Company's lead clinical asset, is designed to address chronic pruritus associated with primary biliary cholangitis (PBC), a rare and challenging autoimmune liver disease.Regulatory DetailsThe securities in this private placement were offered under Section 4(a)(2) of the Securities Act of 1933, as amended, and Regulation D thereunder. The shares of common stock and underlying warrants are not registered under the Securities Act or state securities laws. The Company has agreed to file a resale registration statement covering these securities to enable their future trading upon registration or qualification under applicable laws.About TharimmuneTharimmune, Inc. is a clinical-stage biotechnology company focused on developing innovative therapies in immunology, inflammation, and oncology. The Company's lead product candidate, TH104, leverages a unique transdermal buccal film technology designed to address inflammatory conditions, including pruritus associated with PBC. Tharimmune is also advancing TH023, an oral TNF-alpha inhibitor, and exploring novel multi-specific biologics targeting solid tumors. Through a licensing agreement with OmniAb, Inc., the Company harnesses cutting-edge antibody discovery platforms to target specified disease markers. Learn more at www.tharimmune.com.Forward-Looking StatementsCertain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, contained in this press release, including statements regarding the timing and design of Tharimmune's future Phase 2 trial, Tharimmune's strategy, future operations, future financial position, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "continue," "could," "depends," "estimate," "expect," "intend," "may," "ongoing," "plan," "potential," "predict," "project," "target," "should," "will," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements. Factors that may cause such differences, include, but are not limited to, those discussed under Risk Factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023 and other periodic reports filed by the Company from time to time with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views as of the date of this release. Subsequent events and developments may cause the Company's views to change; however, the Company does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this release.Contact InformationTharimmune, Inc.[email protected]Alliance Advisors IRTirth T. Patel[email protected]212-201-6614SOURCE: Tharimmune, Inc.

License out/inPhase 2Immunotherapy

18 Nov 2024

·www.accesswire.com

Tharimmune Presents Positive Clinical Data at AASLD the Liver Meeting(R) to Support TH104 for Chronic Pruritus in Chronic Liver Disease

Significant correlation shown between blood levels and symptom relief; TH104 was well tolerated with no unexpected treatment-emergent adverse eventsPhase 2 preliminary data for chronic pruritus in primary biliary cholangitis expected in 2025BRIDGEWATER, NJ / ACCESSWIRE / November 18, 2024 / Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation and immunology, presented new TH104 clinical data at the American Association for the Study of Liver Disease (AASLD) The Liver Meeting® 2024, underway in San Diego from November 15-19. The Phase 1 trial was a single-dose, single-center, open-label, randomized study of TH104 transmucosal buccal film conducted in two cohorts of patients with chronic liver disease (CLD), with the primary outcome of safety and tolerability."This presentation at The Liver Meeting expands the audience for encouraging Phase 1 data with our lead candidate TH104," said Randy Milby, CEO of Tharimmune. "We look forward to initiating a Phase 2 multiple-ascending dose trial in the coming months to evaluate TH104 in chronic pruritus in primary biliary cholangitis (PBC) patients, with topline data expected in 2025. In the meantime, we continue to engage with both U.S. and EU regulatory authorities."Data presented at The Liver Meeting include adverse events (AEs) as well as an assessment of patients' relief of pruritus symptom scores when correlated to pharmacokinetics (PK) of TH104. Patients with cholestatic liver disease and a known history of persistent generalized pruritus for at least 4 weeks prior to screening were included. After an overnight fast of 10 hours, subjects received a single low dose of TH104. Serial blood samples for PK analysis were taken, and patients were monitored for itch severity scores utilizing the Worst-Itch Numerical Rating Scale (WI-NRS), a relevant clinical outcome assessment for pruritus in chronic liver disease, and for itch intensity over a 24-hour period.Pruritus is common in most liver diseases and the WI-NRS is a validated numerical rating scale displaying 11 numbers ranging from 0, representing "no itch," to 10, representing "worst imaginable itch," and patients are asked to pick the number corresponding to the intensity of their pruritus. Results from multiple large studies support the usefulness and validity of WI-NRS for evaluating change over time in clinical trials. Pearson's correlation coefficient (r) was used to assess the correlation between TH104 concentration (ng/ml) Area Under the Curve (AUC) and the change in WI-NRS score 48 hours after dosing.This study screened 19 patients and 12 were enrolled with two types of CLD categorized as Child-Pugh A (cohort A) and Child-Pugh B (cohort B). The Child-Pugh score is a system for assessing the prognosis and necessity of transplant in CLD that provides a forecast of the increasing severity of a patient's liver disease and expected survival rate. The score is determined by scoring clinical measures of liver disease and the possibility of eventual liver failure, with Class A indicating mild liver disease and Class B indicating moderate liver disease with one-to-five-year survival rates of 95% and 75%, respectively. There were no patients enrolled in this study with the most severe Child-Pugh C classification.The correlation coefficient between TH104 AUC and change in itch, r, was 0.7060, with a p-value of 0.0103 and a 95% confidence interval for r of 0.2220 to 0.9108.Change in Itch Score vs. Pharmacokinetics of TH104 The mean baseline WI-NRS scores in Groups A and B were 4.33 and 6.17, respectively, translating to moderate-to-severe chronic pruritus at the start of the study. The mean baseline itch score for all 12 subjects was 5.25. At one-hour post-dosing with TH104, Group A and Group B had a mean decline in WI-NRS scores of 26.8% and 19.0%, respectively, and continued to decline two hours post-dose by 42.3% and 21.7%, respectively. Both cohorts continued to improve in mean itch scores at the four-hour and eight-hour time points, including the combined total subjects. At 24-hours post dosing, Group A and Group B achieved a mean decline of 30.7% and 35.2%, respectively, in pruritus scores. The mean reduction in itch scores for all 12 subjects 24 hours after a single dose of TH104 was 33.3%.WI-NRS score over time A total of two AEs (headache) were reported in two subjects over the course of the study. These AEs were mild and possibly related to study drug, with no serious adverse events reported. There were no deaths or other significant adverse events reported during the entire study. There were no new adverse events during the study, with events correlated with previous studies and a safety profile consistent with the literature for the active ingredient in TH104.About TH104TH104 is embedded with nalmefene onto a proprietary transdermal buccal film that easily adheres to the inside of the mouth. This endows TH104 with key features making it an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions. The molecule has a dual mechanism of action affecting both the µ-opioid receptor and the kappa-opioid receptor, as well as potentially inhibiting IL-17 inflammatory cytokine expression. These opioid receptors when stimulated and/or inhibited by the body's natural ligands have been known to be involved in the body's itch circuitry.About Pruritus and Primary Biliary CholangitisAccording to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC is a chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the buildup of bile, resulting in liver damage. The disease, believed to be an autoimmune condition, affects an estimated 58 out of every 100,000 U.S. women and about 15 out of every 100,000 U.S. men. Pruritus is one of the most common conditions associated with PBC, affecting up to 75% of individuals at some point during their disease course. It has a negative impact on health-related quality of life with limited treatment options.Published survey data of PBC respondents suffering from pruritus described their itch as "bugs crawling under the skin." More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.About TharimmuneTharimmune, Inc. is a clinical-stage biotechnology company developing a diverse portfolio of 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 with no known cure. The expanded pipeline includes TH023, an oral TNF-alpha inhibitor, offering a new approach to treating autoimmune diseases. Tharimmune is also advancing early-stage multi-specific biologics targeting unique epitopes against multiple solid tumors. The company has a license agreement with OmniAb, Inc. to access their antibody discovery technology for targeting specified disease markers. For more information, please visit: www.tharimmune.com.Forward Looking StatementsCertain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, contained in this press release, including statements regarding the timing and design of Tharimmune's future Phase 2 trial, Tharimmune's strategy, future operations, future financial position, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "continue," "could," "depends," "estimate," "expect," "intend," "may," "ongoing," "plan," "potential," "predict," "project," "target," "should," "will," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements. Factors that may cause such differences, include, but are not limited to, those discussed under Risk Factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023 and other periodic reports filed by the Company from time to time with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views as of the date of this release. Subsequent events and developments may cause the Company's views to change; however, the Company does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by applicable law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this release.ContactsTharimmune, Inc.[email protected]Alliance Advisors IRTirth T. Patel[email protected]212-201-6614Contact InformationTirth Patel Alliance Advisors IR[email protected]1-212-201-6614Related ImagesChange in Itch Score vs. Pharmacokinetics of TH104WI-NRS score over timeSOURCE: Tharimmune, Inc.

Clinical ResultPhase 1AACRPhase 2

100 Deals associated with Nalmefene Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D02104	Nalmefene Hydrochloride	N07BB05	DB06230

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Alcoholism	EU	H. Lundbeck A/S	24 Feb 2013
Alcoholism	IS	H. Lundbeck A/S	24 Feb 2013
Alcoholism	LI	H. Lundbeck A/S	24 Feb 2013
Alcoholism	NO	H. Lundbeck A/S	24 Feb 2013
Opiate Overdose	US	Hikma Pharmaceuticals USA, Inc.	17 Apr 1995

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Gambling	Phase 3	-	Somaxon Pharmaceuticals, Inc.	01 Aug 2005
Pruritus	Phase 2	-	Avior Bio, Inc.Startup	24 Mar 2022
Smoking Cessation	Phase 2	US	Somaxon Pharmaceuticals, Inc.	01 Sep 2005
Opioid-Related Disorders	Phase 1	US	Titan Pharmaceuticals, Inc.	05 Jul 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06198686 (Company_Website) Manual	Phase 1	Pruritus	12	TH104	bejkxlzgch(cdlkxsnwjr) = None nckyykpbpe (athsmjfgcr )	Positive	18 Nov 2024
Company_Website Manual	Phase 1	Chronic liver disease	12	TH104 (Child-Pugh A)	shojjdvgnz(sqbndncdlt) = lmlvkodgdq nuzuzyuqfa (osxfupkdnv ) View more	Positive	28 Oct 2024
				TH104 (Child-Pugh B)	shojjdvgnz(sqbndncdlt) = dhwczsjfva nuzuzyuqfa (osxfupkdnv ) View more
NCT04759768 (CTgov)	Phase 1	-	68	Nalmefene Hydrochloride (Intranasal Nalmefene)	tukipsfhhw(ibqxveoaav) = ijlhknbtoo fvtaapxjpi (fujxtanmph, mmwaucfaie - htwwrbwlqw) View more	-	13 Aug 2024
				Nalmefene (Intramuscular Nalmefene)	tukipsfhhw(ibqxveoaav) = kmroohwbyk fvtaapxjpi (fujxtanmph, ubcebsshmt - noskjsfpgy) View more
NCT05219669 (CTgov)	Phase 1	Opiate Overdose	24	Nalmefene Hydrochloride (Intranasal Nalmefene 1 Spray in 1 Nostril)	hyejbfwuay(eqxhyzqcnr) = mxplsxshmn yecizojuby (ljnxcyjsjf, mrrkhgtfxc - jyrrmnprou) View more	-	05 Aug 2024
				Nalmefene Hydrochloride (Intranasal Nalmefene 2 Sprays in 1 Nostril)	hyejbfwuay(eqxhyzqcnr) = rpfbhifjwv yecizojuby (ljnxcyjsjf, splciykbpb - rtjwifxqwl) View more
Biospace Manual	Phase 1	Chronic liver disease	12	TH104	ffidjasfax(kcoablpswi) = guswyldfsc huedarotvx (pzvnvgvtrn ) View more	Positive	11 Dec 2023
				TH104 (Child-Pugh A)	ffidjasfax(kcoablpswi) = whsrnlhcxc huedarotvx (pzvnvgvtrn ) View more
Biospace Manual	Phase 1	Cholestatic pruritus	-	TH104	ceqrjprbfi(sgyuttsbkq) = The Cmax and AUC0-∞ of TH104 was observed to be higher than the tablet product because of a possible reduced presystemic metabolism in the lower GI and liver, which is potentially advantageous for patients with an impaired liver. The half-life and Tmax was observed to be similar for both products. bcrgkbvljt (dvrnlyekiq ) View more	Positive	27 Nov 2023
NCT03278886 (PETER PAIN, CTgov)	Phase 1/2	Pain \| Inflammation \| HIV Infections ... View more	11	Low dose naltrexone (Low Dose Naltrexone)	axijjqcpqk(qttrhepqfe) = dnelyeihjb ginlsuctyq (fsgsvxzske, puzvchqrkm - kxlcbvkipn) View more	-	03 Aug 2020
				Nalmefene (Nalmefene)	axijjqcpqk(qttrhepqfe) = pskcdwldko ginlsuctyq (fsgsvxzske, djwlmyjebo - knqhvgnpyf) View more
NCT02382276 (CTgov)	Phase 3	Alcoholism	405	Nalmefene (Nalmefene 20 mg in the lead-in Study)	ovafnbohgg(lxftcqqntr) = zmtybruwkk wwkigdpzlh (apryawiuej, thdfvcqufd - nczabnjshe) View more	-	20 Jul 2020
				Nalmefene (Nalmefene 10 mg in the lead-in Study)	ovafnbohgg(lxftcqqntr) = msgffbnzrv wwkigdpzlh (apryawiuej, ypjkjmrcim - slhemlslbn) View more
NCT02364947 (CTgov)	Phase 3	Alcoholism	678	Nalmefene hydrochloride (Nalmefene Hydrochloride 20 mg)	tdbayjbxvu(cifrdaghma) = mcdqxjpoth bnetzihsms (zxnrebljos, mozrvxfitg - kdknencsra) View more	-	30 Sep 2019
				Nalmefene hydrochloride (Nalmefene Hydrochloride 10 mg)	tdbayjbxvu(cifrdaghma) = yotnkcpkii bnetzihsms (zxnrebljos, aswiviitok - krvhglbvez) View more
NCT02679469 (CTgov)	Phase 1	Alcoholism	7	nalmefene hydrochloride 10 mg	hdbdbwowzo(bhvsnmlvqd) = tbnujspgbb ntlxqqnqpx (niantaooak, bejoztmoiw - bzhphosqbj) View more	-	18 Apr 2017

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