κ opioid receptor x μ opioid receptor

PDUFA date set for February 7, 2025 If approved by the FDA, label would expand to include alternative injection sites in the thigh, buttock and back of the arm for induction and maintenance as well as rapid induction one hour after a single transmucosal buprenorphine dose; both of which address significant patient and healthcare provider unmet needs. RICHMOND, Va., Oct. 7, 2024 /PRNewswire/ -- Indivior PLC (Nasdaq/LSE: INDV) today announced the Prior Approval Supplement (PAS) for SUBLOCADE® (buprenorphine extended-release) injection submitted by Indivior, Inc. has been granted Priority Review designation by the U.S. Food and Drug Administration (FDA). The Prescription Drug User Fee Act (PDUFA) action date for this submission is set for February 7, 2025. SUBLOCADE, Indivior's monthly injectable formulation of buprenorphine for the treatment of moderate to severe opioid use disorder (OUD), is the foundation of Indivior's portfolio of innovative treatments aimed at transforming how the chronic condition of OUD is managed. This PAS seeks to further expand treatment options via two proposed updates to the SUBLOCADE label, including: Alternative Injection Sites: Expands from the current subcutaneous abdominal injection site to also include the thigh, buttock, and back of the upper arm subcutaneously for induction and maintenance. Rapid Induction Protocol: Reduces treatment induction time from the current 7-day minimum on transmucosal buprenorphine (TM BUP) to a single dose of TM BUP with 1-hour observation period to confirm tolerability. Allows for the second 300 mg dose to be administered as early as one week after the initial 300 mg injection, based on patient needs. Indivior's PAS included comprehensive data which we believe demonstrate the efficacy and safety of the new rapid induction protocol and SUBLOCADE's pharmacokinetic profile following injection at alternative sites. These updates are expected to enhance the patient experience and expand treatment access especially for those patients who, similar to the study participants, have long-term opioid use including fentanyl. A Priority Review designation means that the FDA's goal is to take action on an application within 6 months (compared to 10 months under standard review) and, if approved, would translate into significant improvements in OUD treatment with SUBLOCADE. About SUBLOCADE® SUBLOCADE ® (buprenorphine extended-release) injection, for subcutaneous use, CIII INDICATION AND HIGHLIGHTED SAFETY INFORMATION INDICATION SUBLOCADE is indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a buprenorphine-containing product, followed by dose adjustment for a minimum of 7 days. SUBLOCADE should be used as part of a complete treatment plan that includes counseling and psychosocial support. HIGHLIGHTED SAFETY INFORMATION WARNING: RISK OF SERIOUS HARM OR DEATH WITH INTRAVENOUS ADMINISTRATION; SUBLOCADE RISK EVALUATION AND MITIGATION STRATEGY Serious harm or death could result if administered intravenously. SUBLOCADE forms a solid mass upon contact with body fluids and may cause occlusion, local tissue damage, and thrombo-embolic events, including life threatening pulmonary emboli, if administered intravenously. Because of the risk of serious harm or death that could result from intravenous self-administration, SUBLOCADE is only available through a restricted program called the SUBLOCADE REMS Program. Healthcare settings and pharmacies that order and dispense SUBLOCADE must be certified in this program and comply with the REMS requirements. CONTRAINDICATIONS SUBLOCADE should not be administered to patients who have been shown to be hypersensitive to buprenorphine or any component of Indivior's proprietary buprenorphine gel depot delivery system. WARNINGS AND PRECAUTIONS Addiction, Abuse, and Misuse: SUBLOCADE contains buprenorphine, a Schedule III controlled substance that can be abused in a manner similar to other opioids. Monitor patients for conditions indicative of diversion or progression of opioid dependence and addictive behaviors. Respiratory Depression: Life threatening respiratory depression and death have occurred in association with buprenorphine. Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with SUBLOCADE. Opioids can cause sleep-related breathing disorders e.g., central sleep apnea (CSA), sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. Consider decreasing the opioid using best practices for opioid taper if CSA occurs. Strongly consider prescribing naloxone at SUBLOCADE initiation or renewal because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose. Educate patients and caregivers on how to recognize respiratory depression and how to treat with naloxone if prescribed. Risk of Serious Injection Site Reactions: The most common injection site reactions are pain, erythema and pruritus with some involving abscess, ulceration, and necrosis. The likelihood of serious injection site reactions may increase with inadvertent intramuscular or intradermal administration. Neonatal Opioid Withdrawal Syndrome: Neonatal opioid withdrawal syndrome is an expected and treatable outcome of prolonged use of opioids during pregnancy. Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off the opioid. Risk of Opioid Withdrawal With Abrupt Discontinuation: If treatment with SUBLOCADE is discontinued, monitor patients for several months for withdrawal and treat appropriately. Risk of Hepatitis, Hepatic Events: Monitor liver function tests prior to and during treatment. Risk of Withdrawal in Patients Dependent on Full Agonist Opioids: Verify that patient is clinically stable on transmucosal buprenorphine before injecting SUBLOCADE. Treatment of Emergent Acute Pain: Treat pain with a non-opioid analgesic whenever possible. If opioid therapy is required, monitor patients closely because higher doses may be required for analgesic effect. ADVERSE REACTIONS Adverse reactions commonly associated with SUBLOCADE (in ≥5% of subjects) were constipation, headache, nausea, injection site pruritus, vomiting, increased hepatic enzymes, fatigue, and injection site pain. For more information about SUBLOCADE, the full Prescribing information including BOXED WARNING, and Medication Guide, visit . About Opioid Use Disorder (OUD) Opioid Use Disorder (OUD) is a chronic disease in which people develop a pattern of using opioids that can lead to negative consequences.1 OUD may affect the parts of the brain that are necessary for life-sustaining functions.1,2 Important Cautionary Note Regarding Forward-Looking Statements This news release contains certain statements that are forward-looking. Forward-looking statements include, among other things, express and implied statements regarding: whether the FDA will approve the PAS which would allow us to update our label; the safety and efficacy of the new rapid induction protocol and alternative injection sites; enhanced patient experience, and expanded patient access and other statements containing the words "believe," "anticipate," "plan," "expect," "intend," "estimate," "forecast," "strategy," "target," "guidance," "outlook," "potential," "project," "priority," "may," "will," "should," "would," "could," "can," "outlook," "guidance," the negatives thereof, and variations thereon and similar expressions. By their nature, forward-looking statements involve risks and uncertainties as they relate to events or circumstances that may or may not occur in the future. Actual results may differ materially from those because they relate to future events. Various factors may cause differences between Indivior's expectations and actual results, including, among others, the fact that the regulatory approval process is uncertain and may prevent us from obtaining approvals for some or all of our product candidate; the FDA or other regulatory agencies may not agree with our regulatory approval strategies or components of our filings for our products and may not approve, or may delay the approval of, our products; and the risks described in our most recent annual report on Form 20-F beginning on page 9 as filed with the U.S. SEC and in subsequent releases. Forward-looking statements speak only as of the date that they are made and should be regarded solely as our current plans, estimates and beliefs. Except as required by law, we do not undertake and specifically decline any obligation to update, republish or revise forward-looking statements to reflect future events or circumstances or to reflect the occurrences of unanticipated events. About Indivior Indivior is a global pharmaceutical company working to help change patients' lives by developing medicines to treat substance use disorders (SUD), overdose and serious mental illnesses. Our vision is that all patients around the world will have access to evidence-based treatment for the chronic conditions and co-occurring disorders of SUD. Indivior is dedicated to transforming SUD from a global human crisis to a recognized and treated chronic disease. Building on its global portfolio of OUD treatments, Indivior has a pipeline of product candidates designed to both expand on its heritage in this category and potentially address other chronic conditions and co-occurring disorders of SUD. Headquartered in the United States in Richmond, VA, Indivior employs over 1,000 individuals globally and its portfolio of products is available in over 30 countries worldwide. Visit to learn more. Connect with Indivior on LinkedIn by visiting . References National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on Medication-Assisted Treatment for Opioid Use Disorder, Mancher, M., & Leshner, A. I. (Eds.). (2019). Medications for Opioid Use Disorder Save Lives. National Academies Press (US). Accessed October 30, 2023, from NIDA. 2022, March 22. Drugs and the Brain. Accessed October 30,2023, from SOURCE Indivior PLC WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

MONMOUTH JUNCTION, N.J.--( BUSINESS WIRE )--Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company focused on attention deficit hyperactivity disorder (ADHD), pain, addiction and neurological disorders, today announced that the company will present data from its first-in-class, late-stage investigational pain therapy with a novel mechanism of action, cebranopadol, at the upcoming International Association for the Study of Pain (IASP) 2024 World Congress on Pain, taking place August 5-9, 2024, in Amsterdam. “I am inspired to see the rise in interest, funding and research into the development of novel treatment options for the millions of people who suffer daily from debilitating pain that impacts their quality of life,” said Ketan Mehta, founder and CEO at Tris Pharma. “Our team has been working with urgency to advance cebranopadol, a first-in-class investigational pain therapy with a novel mechanism of action, through clinical studies with the goal of offering physicians an effective treatment option that they can confidently prescribe and patients feel is safe. We look forward to collaborating with the pain community at IASP 2024 and sharing our latest findings.” Cebranopadol is the first and only dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist in development to treat moderate-to-severe pain. Dual-NMR agonist compounds have the potential to deliver gold-standard pain relief with a strong safety profile because they mimic the body’s natural pain-modulation processes by synergizing the analgesic and safety characteristics of the NOP receptor with the analgesic advantages of the MOP receptor. Tris Pharma plans to share important news regarding its Phase 3 clinical trials in the near future. Symposium Highlighting Novel Pain Mechanism Tris Pharma will host a symposium featuring a series of presentations focused on dual-NMR agonists, a promising new mechanism of action in treating pain, and its potential to overcome the shortfalls of opioids for moderate-to-severe pain. The symposium will be presented as part of the congress by leading scientists with extensive experience in the research and development of novel pain therapies. Details of the symposium are as follows: Symposium: Break the Mold in Pain Biology: The Promise of a New Mechanism that May Overcome the Shortfalls of Current Moderate to Severe Pain Medications Presenters: Charles E. Argoff, MD, Albany Medical College; Roberto Ciccocioppo, PhD, University of Camerino; Jeffrey Gudin, MD, University of Miami Miller School of Medicine Location: RAI Amsterdam Convention Centre, Elicium I Date and Time: August 6, 12:45 – 1:45 p.m. CEST At IASP 2024 Tris Pharma will be present at Booth #316 where company executives will be available to provide additional information and data presented at the congress. About Cebranopadol (TRN-228) Cebranopadol is the first and only investigational dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). Cebranopadol offers a first of its kind and novel mechanism of action that takes advantage of the inherent properties of the NOP receptor, which has demonstrated both the potential to lessen the risk of misuse while still providing effective pain relief, and the potential to block drugs of abuse from producing drug-seeking behaviors. The FDA has granted Fast Track Designation to cebranopadol for chronic low back pain. Cebranopadol’s profile has been well-characterized in pain management studies, and if approved, it could become the first and only pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with significantly less risk for misuse or risk of physical dependence, addiction or overdose. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain and neurological disorders, including addiction and diseases of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @ TrisPharma .

Pharmacokinetic pro oral transmucosal delivery of TH104 was comparable to intravenous delivery of reference drug Positive safety/tolerability achieved with TH104 reporting a mild side-effect pro > Planning for Phase 2 trial for moderate-to-severe chronic pruritus in primary biliary cholangitis (PBC) is ongoing and on track to initiate in 2024 BRIDGEWATER, NJ / ACCESSWIRE / June 10, 2024 / Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates for inflammation and immunology, reports positive results from its Phase 1 clinical trial with TH104, a proprietary transmucosal buccal film embedded with the approved, active compound nalmefene that easily adheres inside of the mouth on the cheek and biodegrades within minutes. Results in healthy subjects demonstrated consistent pharmacokinetic (PK) profiles across buccal and intravenous routes of administration with a comparable safety and tolerability pro routes of administration. "We are pleased with the results of our Phase 1 trial of TH104, and our expectations for a predictable kinetic pro demonstrating excellent safety and tolerability by transmucosal administration have been met. With these results, we look forward to advancing TH104 to a Phase 2 trial this year," said Randy Milby, Chief Executive Officer of Tharimmune. "We would like to thank the volunteers for participating in this trial where the data generated are a critical step forward to continue our momentum and remain on track to advance the development of this important program." TH104, the Company's lead clinical asset, is designed to avoid the liver's first-pass metabolism of oral formulations and, as such, may be a preferred product candidate for liver-related and other pruritogenic inflammatory conditions. The molecule has a dual mechanism of action that affects both the mu (μ-) and kappa opioid receptors. These extensively studied receptors, when stimulated and/or inhibited by the body's endogenous ligands, have been implicated in human itch circuitry for certain conditions, specifically cholestatic liver conditions. This Phase 1 trial is a single-dose, single-center, open-label, randomized 2-way crossover study comparing 16mg of TH104 with 1mg intravenous nalmefene administered under fasting conditions, with a 7-day washout period between doses. Twenty healthy subjects were enrolled to complete both doses of the crossover design. All 20 subjects completed TH104 buccal dosing, while 19 of 20 subjects also completed the intravenous dosing. The primary objective was to evaluate the absolute bioavailability of TH104, as well as to assess safety and tolerability. Findings from the study indicate that the primary endpoint of the absolute bioavailability (F) of TH104, or fraction (or percentage) of the administered dose absorbed into the systemic circulation compared to an equivalent intravenous dose of nalmefene, was 0.459 (45.9%). The median time to maximum concentration (Cmax) of TH104 was 2.0 hours, with rising concentrations beginning within minutes of dosing. The mean half-life (T1/2) as measured in the blood of subjects was 14 hours after a single buccal administration of TH104, compared to 9 hours for the 1mg intravenous dose of nalmefene. These data are consistent and within range of published findings of population PK data of nine Phase 1 studies of 243 subjects with extensive blood sampling.1. Furthermore, in the same analysis, receptor occupancy of oral dosing of nalmefene using a robust PK model for nalmefene was developed where a single 20mg dose showed μ-opioid receptor occupancy was simulated to be within or above 60-90% for up to 22-24 hours. The Company believes PK results from this Phase 1 trial show proportional kinetics consistent with published findings of oral and intravenous formulations of nalmefene including F, Cmax, T1/2 and potential receptor occupancy time, suggest TH104 could be developed for once-daily dosing in a target population of moderate-to-severe chronic pruritus in PBC patients. The Phase 1 trial also demonstrated that a 16mg dose of TH104 had a comparable safety and tolerability pro the FDA-approved 1mg dose of nalmefene intravenous formulation. Treatment emergent adverse events (TEAEs) were reported in 8 subjects (40.0%) in the TH104 group and 7 subjects (36.8%) in the intravenous group. All reported TEAEs were considered mild in severity. The most frequently reported TEAE for both TH104 and intravenous treatments was dizziness (4 subjects in the TH104 group; 7 subjects in the intravenous group). TEAEs reported in at least 2 subjects in any treatment group were nausea (3 subjects in each group) and somnolence (3 subjects in each group). There were no serious adverse events reported during this study. No subjects discontinued the study due to adverse events. No subjects exhibited abnormal results for the visual examinations of the buccal mucosa pre- or post-dosing with TH104 buccal film. The Company continues to have discussions with the FDA regarding its Phase 2 program and intends to initiate a clinical trial with TH104 in moderate-to-severe chronic pruritus in PBC patients in 2024. About TH104 TH104 is embedded with nalmefene onto a proprietary transmucosal buccal film which 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 and kappa opioid receptors. 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 Tharimmune Tharimmune, Inc. is a clinical-stage biotechnology company developing a portfolio of therapeutic candidates for inflammation and immunology. The Company's lead clinical-stage asset, TH104 is known to suppress chronic, debilitating pruritus or "uncontrollable itching" in PBC, a rare and orphan liver disease with no known cure. The Company's early-stage immunology pipeline includes novel multi-specific antibodies targeting unique epitopes with novel mechanisms of action against well-known, validated targets in multiple solid tumors, including PD-1, HER2 and HER3. Tharimmune has a license agreement with OmniAb, Inc. to access the company's antibody discovery technology platform against these and other specified targets. For more information please visit: . Forward Looking Statements Certain 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 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. References Kyhl, L. B., Shen, L., Faerch, K. U., Soegaard, B., Larsen, F., & Areberg, J. (2016). Population pharmacokinetics of nalmefene in healthy subjects in relation to μ-opioid receptor occupancy. British Journal of Clinical Pharmacology, 81(2), 290-300. Contacts: Tharimmune, Inc. ir@tharimmune.com LHA Investor Relations Tirth T. Patel tpatel@lhai.com 212-201-6614 SOURCE: Tharimmune, Inc. View the original press release on accesswire.com