μ opioid receptor

Full year 2023 total revenues of $464.4 million, compared to $250.3 million in 2022 Full year 2023 CAPLYTA net product sales were $462.2 million, representing year-over-year growth of 86%. CAPLYTA fourth quarter 2023 net product sales grew to $131.5 million, a 50% increase over the same period in 2022 In 2023, CAPLYTA total prescriptions achieved strong year-over-year growth of 85% CAPLYTA 2024 net product sales guidance of $645 to $675 million NEW YORK, Feb. 22, 2024 (GLOBE NEWSWIRE) -- Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, today announced its financial results for the fourth quarter ended December 31, 2023 and provided a corporate update. “I am very proud of our accomplishments in 2023, including the continued strong uptake of CAPLYTA. In the year ahead, we are focused on continuing CAPLYTA’s momentum and advancing our pipeline. We look forward to the upcoming CAPLYTA Phase 3 read outs in adjunctive MDD and the potential to help a growing number of patients,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. FINANCIAL HIGHLIGHTS: Net product sales of CAPLYTA were $462.2 million for the full year 2023. This represents an increase of 86% compared to 2022. This growth was fueled by strong underlying prescription demand which grew 85% year-over-year in 2023. For the fourth quarter 2023, CAPLYTA net product sales reached $131.5 million representing a 50% increase over the fourth quarter of 2022.Net loss for the year ended December 31, 2023 was $139.7 million or $1.46 per share (basic and diluted) compared to a net loss of $256.3 million or $2.72 per share (basic and diluted) for the year ended December 31, 2022. Net loss for the fourth quarter of 2023 was $28.6 million compared to a net loss of $44.0 million for the same period in 2022.Selling, general and administrative (SG&A) expenses were $409.9 million for the year ended December 31, 2023, compared to $358.8 million for the year ended December 31, 2022. This increase is primarily due to an increase in commercialization, marketing and advertising costs. Research and development (R&D) expenses were $180.1 million for the year ended December 31, 2023, compared to $134.7 million for the year ended December 31, 2022. This increase is primarily due to higher lumateperone clinical and non-clinical project costs, and higher non-lumateperone project costs, including the ITI-1284, ITI-214, and ITI-333 programs.Cash, cash equivalents, restricted cash and investment securities totaled $499.7 million at December 31, 2023, compared to $593.7 million at December 31, 2022. Full Year 2024 Financial Outlook: CAPLYTA 2024 net product sales are expected to be $645 to $675 million.SG&A expenses for the full year 2024 are expected to be $450 to $480 million, including approximately $42.5 million of non-cash, share-based compensation expense. SG&A guidance reflects our commitment to continue to effectively and efficiently support CAPLYTA commercialization through investments in our sales and marketing activities.R&D expenses for the full year 2024 are expected to be $215 to $240 million, including approximately $20 million of non-cash, share-based compensation expense. Our R&D guidance reflects investments to support our broad pipeline. In 2024, we anticipate that a large portion of our total R&D expenditures will be related to our lumateperone development programs as we continue to explore the use of lumateperone in additional patient populations. 2024 Guidance(in $ millions) low highCAPLYTA Net Product Sales (GAAP)$645 $675SG&A expenses (GAAP)$450 $480R&D expenses (GAAP)$215 $240 COMMERCIAL HIGHLIGHTS Successfully continued the launch of CAPLYTA for the treatment of bipolar depression in adults. In 2023, CAPLYTA strong prescription demand continued with 85% total prescription growth over 2022. In the fourth quarter, total prescriptions of CAPLYTA increased 55% over the same period in 2022, and 10% sequentially over the third quarter of 2023. In 2023, we continued to improve market access for CAPLYTA across all three major channels. Our market access for CAPLYTA covers approximately 90% of commercially insured lives and greater than 99% of the Medicare Part D and Medicaid lives.Our LytaLink patient and prescriber support program continues to be very effective in supporting patient access to CAPLYTA. CLINICAL HIGHLIGHTS Lumateperone: Adjunctive MDD program: Studies 501, 502 and 505 are our global Phase 3 clinical trials evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of major depressive disorder. Study 501 is fully enrolled and most patients have completed treatment. We allowed the small number of patients who were in screening when we reached our previously determined enrollment target to continue and be randomized to the double-blind treatment phase of the study. As a result, we expect to report topline results from Study 501 in April of this year. In addition, we expect to report topline results from Study 502 late in the second quarter of this year. Subject to those results, we continue to anticipate filing a supplemental New Drug Application with the FDA in the second half of 2024. Mixed Features program: In 2023, we reported robust positive results from Study 403, our clinical trial evaluating lumateperone in patients with major depressive disorder exhibiting mixed features and patients with bipolar depression exhibiting mixed features In this study, lumateperone 42 mg was statistically significant on the primary endpoint of symptom reduction on the Montgomery Asberg Depression Rating Scale (MADRS) for the combined mixed features patient population of MDD and bipolar depression and the individual patient populations of MDD with mixed features and bipolar depression with mixed features. The robust effect sizes ranged from 0.64 to 0.67. Lumateperone was generally safe and well tolerated, with a side effect profile consistent with prior trials. There were no notable changes in weight, body mass index or waist circumference and no clinically relevant changes in metabolic parameters. Last year, we presented results from Study 403 at several medical conferences including the Psych Congress, the European College of Neuropsychopharmacology Congress and the American College of Neuropsychopharmacology annual meeting. Lumateperone pediatric program: We have commenced our lumateperone pediatric program. This program includes an open-label safety study in schizophrenia and bipolar disorder; a double-blind, placebo-controlled study in bipolar depression and two double-blind, placebo-controlled studies in irritability associated with autism spectrum disorder. The patient enrollment in the open-label safety study has commenced. Lumateperone Long Acting Injectable (LAI) formulation: The goal of the program is to develop LAI formulations that are effective, safe, and well-tolerated with treatment durations of one month or longer. For our first LAI formulation, we have completed the pre-clinical development and conducted a Phase 1 single ascending dose study. We expect to initiate a Phase 1 single ascending dose study with four additional formulations in the first half of 2024. Other pipeline programs: ITI-1284-ODT-SL program: ITI-1284 is a deuterated form of lumateperone, a new chemical entity formulated as an oral disintegrating tablet for sublingual administration. In 2023, we advanced several Phase 1 studies. We have initiated Phase 2 programs evaluating ITI-1284 in generalized anxiety disorder (GAD), psychosis in Alzheimer’s disease, and agitation in Alzheimer’s disease and anticipate commencing patient enrollment in the first half of 2024. Phosphodiesterase type I inhibitor (PDE1) program: Our portfolio of PDE1 inhibitors continues to advance clinical development. Lenrispodun (ITI-214) Parkinson’s disease (PD) program: Patient enrollment in our Phase 2 clinical trial is ongoing. The objective of this study is to evaluate improvements in motor symptoms in patients with PD. Changes in cognition and inflammatory biomarkers are also being assessed. We expect to complete patient enrollment in late 2024 with topline results anticipated in the first half of 2025. ITI-1020 cancer immunotherapy program: Our Phase 1 single ascending dose study in healthy volunteers is progressing. The objective of this study is to evaluate pharmacokinetics, safety, and tolerability of different doses of ITI-1020. ITI-333 program: ITI-333, a 5-HT2A receptor antagonist and μ-opioid receptor partial agonist, provides potential utility in the treatment of opioid use disorder and pain. A multiple ascending dose study and a positron emission tomography (PET) study are both ongoing. ITI-1500 Non-Hallucinogenic Psychedelic Program: In 2023, we introduced the ITI-1500 program. This program is focused on the development of novel non-hallucinogenic psychedelics for the treatment of mood, anxiety and other neuropsychiatric disorders without the liabilities of known psychedelics, including the hallucinogenic potential and risk for cardiac valvular pathologies. Our lead product candidate in this program, ITI-1549, is advancing through IND enabling studies and is expected to enter human testing in late 2024 or early 2025. Conference Call and Webcast Details The Company will host a live conference call and webcast today at 8:30 AM Eastern Time to discuss the Company’s financial results and provide a corporate update. To attend the live conference call by phone, please use this registration link (https://register.vevent.com/register/BI4a916e3aa80448ae8e675216382f1cf2). All participants must use the link to complete the online registration process in advance of the conference call. The live and archived webcast can be accessed under "Events & Presentations" in the Investors section of the Company's website at www.intracellulartherapies.com. Please log in approximately 5-10 minutes prior to the event to register and to download and install any necessary software. CAPLYTA® (lumateperone) is indicated in adults for the treatment of schizophrenia and for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. Important Safety Information Boxed Warnings: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. All antidepressant-treated patients should be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of CAPLYTA have not been established in pediatric patients. Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria. Warnings & Precautions: Antipsychotic drugs have been reported to cause: Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.Potential for Cognitive and Motor Impairment. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration. Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers. Dose reduction is recommended for concomitant use with strong CYP3A4 inhibitors or moderate CYP3A4 inhibitors. Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Dose reduction is recommended for patients with moderate or severe hepatic impairment. Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation, dizziness, nausea, and dry mouth. CAPLYTA is available in 10.5 mg, 21 mg, and 42 mg capsules. Please click here to see full Prescribing Information including Boxed Warning. About CAPLYTA (lumateperone) CAPLYTA 42 mg is an oral, once daily atypical antipsychotic approved in adults for the treatment of schizophrenia and the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. While the mechanism of action of CAPLYTA is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors. Lumateperone is being studied for the treatment of major depressive disorder, and other neuropsychiatric and neurological disorders. Lumateperone is not FDA-approved for these disorders. About Intra-Cellular Therapies Intra-Cellular Therapies is a biopharmaceutical company founded on Nobel prize-winning research that allows us to understand how therapies affect the inner-workings of cells in the body. The company leverages this intracellular approach to develop innovative treatments for people living with complex psychiatric and neurologic diseases. For more information, please visit www.intracellulartherapies.com. Forward-Looking Statements This news release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, our financial and operating performance, including our future revenues and expenses; our expectations regarding the commercialization of CAPLYTA; our plans to conduct clinical or non-clinical trials and the timing of developments with respect to those trials, including enrollment, initiation or completion of clinical conduct, or the availability of results; plans to make regulatory submissions to the FDA and the timing of such submissions; whether clinical trial results will be predictive of future real-world results; whether CAPLYTA will serve an unmet need; the goals of our development programs; our beliefs about the potential utility of our product candidates; and development efforts and plans under the caption “About Intra-Cellular Therapies.” All such forward-looking statements are based on management's present expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, the following: there are no guarantees that CAPLYTA will be commercially successful; we may encounter issues, delays or other challenges in commercializing CAPLYTA; whether CAPLYTA receives adequate reimbursement from third-party payors; the degree to which CAPLYTA receives acceptance from patients and physicians for its approved indications; challenges associated with execution of our sales activities, which in each case could limit the potential of our product; results achieved in CAPLYTA in the treatment of schizophrenia and bipolar depression following commercial launch of the product may be different than observed in clinical trials, and may vary among patients; challenges associated with supply and manufacturing activities, which in each case could limit our sales and the availability of our product; risks associated with our current and planned clinical trials; we may encounter unexpected safety or tolerability issues with CAPLYTA following commercial launch for the treatment of schizophrenia or bipolar depression or in ongoing or future trials and other development activities; our other product candidates may not be successful or may take longer and be more costly than anticipated; product candidates that appeared promising in earlier research and clinical trials may not demonstrate safety and/or efficacy in larger-scale or later clinical trials or in clinical trials for other indications; our proposals with respect to the regulatory path for our product candidates may not be acceptable to the FDA; our reliance on collaborative partners and other third parties for development of our product candidates; impacts on our business, including on the commercialization of CAPLYTA and our clinical trials, as a result of the COVID-19 pandemic, the conflicts in Ukraine and the Middle East, global economic uncertainty, inflation, higher interest rates or market disruptions; and the other risk factors detailed in our public filings with the Securities and Exchange Commission. All statements contained in this press release are made only as of the date of this press release, and we do not intend to update this information unless required by law. Contact: Intra-Cellular Therapies, Inc.Juan Sanchez, M.D. Vice President, Corporate Communications and Investor Relations646-440-9333 Burns McClellan, Inc.Cameron Radinoviccradinovic@burnsmc.com212-213-0006 INTRA-CELLULAR THERAPIES, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands except share and per share amounts) (Unaudited) (1) Three Months Ended December 31, Twelve Months Ended December 31, 2023 2022 2023 2022 Revenues Product sales, net$131,506 $87,433 $462,175 $249,132 Grant revenue 593 436 2,195 1,182 Total revenues, net 132,099 87,869 464,370 250,314 Operating expenses: Cost of product sales 10,702 6,788 33,745 20,443 Selling, general and administrative 104,720 94,631 409,864 358,782 Research and development 50,774 33,862 180,142 134,715 Total operating expenses 166,196 135,281 623,751 513,940 Loss from operations (34,097) (47,412) (159,381) (263,626)Interest income 5,966 3,386 20,343 7,376 Loss before provision for income taxes (28,131) (44,026) (139,038) (256,250)Income tax expense (448) — (636) (6)Net loss$(28,579) $(44,026) $(139,674) $(256,256)Net loss per common share: Basic & Diluted$(0.30) $(0.45) $(1.46) $(2.72)Weighted average number of common shares: Basic & Diluted 96,285,558 94,516,794 95,881,729 94,046,670 (1) The condensed consolidated statements of operations for the three and twelve months ended December 31, 2023 and 2022 have been derived from the financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements. INTRA-CELLULAR THERAPIES, INC. CONDENSED CONSOLIDATED BALANCE SHEETS(in thousands except share and per share amounts) (Unaudited) December 31,2023 December 31,2022Assets Current assets: Cash and cash equivalents$147,767 $148,615 Investment securities, available-for-sale 350,174 443,290 Restricted cash 1,750 1,750 Accounts receivable, net 114,018 75,189 Inventory 11,647 23,920 Prepaid expenses and other current assets 42,443 45,193 Total current assets 667,799 737,957 Property and equipment, net 1,654 1,913 Right of use assets, net 12,928 14,824 Inventory, non-current 38,621 — Other assets 7,293 86 Total assets$728,295 $754,780 Liabilities and stockholders’ equity Current liabilities: Accounts payable$11,452 $10,395 Accrued and other current liabilities 27,944 19,657 Accrued customer programs 53,173 25,621 Accrued employee benefits 27,364 22,996 Operating lease liabilities 3,612 4,567 Total current liabilities 123,545 83,236 Operating lease liabilities, non-current 13,326 15,474 Total liabilities 136,871 98,710 Stockholders’ equity: Common stock, $0.0001 par value: 175,000,000 shares authorized at December 31, 2023 and December 31, 2022, respectively; 96,379,811 and 94,829,794 shares issued and outstanding at December 31, 2023 and December 31, 2022, respectively 10 9 Additional paid-in capital 2,208,470 2,137,737 Accumulated deficit (1,617,160) (1,477,486)Accumulated comprehensive income (loss) 104 (4,190)Total stockholders’ equity 591,424 656,070 Total liabilities and stockholders’ equity$728,295 $754,780 The condensed consolidated balance sheets at December 31, 2023 and December 31, 2022 have been derived from the financial statements but do not include all of the information and footnotes required by accounting principles generally accepted in the United States for complete financial statements.

Calgary, Alberta--(News - February 20, 2024) - Marvel Biosciences Corp. (TSXV: MRVL) (OTCQB: MBCOF) and its wholly owned subsidiary, Marvel Biotechnology Inc. (collectively the "Company" or "Marvel"), is pleased to announce it has begun testing MB-204 in the Oprm1 mouse model of autism in collaboration with Dr. Julie Le Merrer and Dr. Jerome Becker at the iBrain Institute, Tours, France. "We are going to test the effect of acute dosing of MB-204 in one of the prototypic models of autism, the Oprm1 mouse, looking specifically at sociability and stereotypic behaviour in the Y-maze model after acute dosing", said Dr. Mark Williams, CSO of Marvel. "We have seen immediate effects of MB-204 after a single dose in mouse models of depression, which gives us confidence the drug could offer improvements in these autistic behaviours after a short course of therapy." "Autism is a very underserved medical condition that affects approximately 1 in 36 children", said Mr. Rod Matheson, CEO of Marvel, "and the social impact cost of autism in the US is expected to exceed $450B by 2025. There is an approved drug Daybue® for Rett's Syndrome as of 2023, a very specific form of autism that affects about 1 in 10,000 girls. Based on the pre-clinical evidence we believe MB-204 could treat multiple forms of autism including Rett's Syndrome. Pending positive data, we intend to approach many of the autism foundations and venture philanthropy groups to support the testing MB-204 in other models of autism including Rett's Syndrome". About Marvel Biosciences Corp. Marvel Biosciences Corp., and its wholly owned subsidiary, Marvel Biotechnology Inc., is a Calgary-based pre-clinical stage pharmaceutical development biotechnology company that utilizes a "drug redevelopment" approach to drug development. Historically, when a new class of drug is developed, it is optimized for a particular target, but typically only approved for a specific disease. Often, a new disease is identified which involves the same target, however, pending the remaining patent life, the originally approved drug may not have sufficient time left for it to be commercially viable to be developed for the new disease indication. Marvel develops new synthetic chemical derivatives of the original approved drug for the new disease indication. Patent protection is sought, as the new potential asset is developed by the Company. The Company believes the business model results in significantly less risk, cost and time to develop its assets compared to traditional biotechnology companies. Marvel Biotechnology Inc. has currently developed several new chemical entities, using synthetic chemical derivatives of known, off-patent drugs, that inhibit the A2a adenosine receptor with application to neurological diseases (depression & anxiety, Alzheimer's, ADHD), and the non-neurological conditions of cancer and non-alcoholic steatohepatitis. Marvel is also exploring additional undisclosed targets to expand its asset pipeline. Contact Information Marvel Biosciences Corp. J. Roderick (Rod) Matheson, Chief Executive Officer or Dr. Mark Williams, President and Chief Science Officer Tel: 403 770 2469 Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSXV) accepts responsibility for the adequacy or accuracy of this press release. All information contained in this news release with respect to the Company and its subsidiary, (collectively, the "Parties") were supplied by Marvel, respectively, for inclusion herein and each parties' directors and officers have relied on each other for any information concerning such Party. This news release may contain forward-looking statements and other statements that are not historical facts. Forward-looking statements are often identified by terms such as "will", "may", "should", "anticipate", "expects" and similar expressions. All statements other than statements of historical fact, included in this release, including, without limitation, statements regarding the future plans and objectives of the Company are forward-looking statements that involve risks and uncertainties. There can be no assurance that such statements will prove to be accurate and actual results and future events could differ materially from those anticipated in such statements. Important factors that could cause actual results to differ materially from the expectations of the Company and include other risks detailed from time to time in the filings made by the Company under securities regulations. The reader is cautioned that assumptions used in the preparation of any forward-looking information may prove to be incorrect. Events or circumstances may cause actual results to differ materially from those predicted, as a result of numerous known and unknown risks, uncertainties, and other factors, many of which are beyond the control of the Company. As a result, the Company cannot guarantee that the above events on the terms will occur and within the time disclosed herein or at all. The reader is cautioned not to place undue reliance on any forward-looking information. Such information, although considered reasonable by management at the time of preparation, may prove to be incorrect and actual results may differ materially from those anticipated. Forward-looking statements contained in this news release are expressly qualified by this cautionary statement. The forward-looking statements contained in this news release are made as of the date of this news release and the Company will update or revise publicly any of the included forward-looking statements as expressly required by Canadian securities law. To view the source version of this press release, please visit

Phase 1 clinical trial dosing of first patient complete; primary objective to assess safety/tolerability and absolute bioavailability of TH104 Phase 1 study expected to be completed in 1Q24 with topline readout in 2Q24 Company fully funded into 2025 with full readouts of Phase 1 and 2 in moderate-to-severe chronic pruritus in PBC expected in 4Q24/1Q25 BRIDGEWATER, NJ / ACCESSWIRE / February 5, 2024 / Tharimmune, Inc. (NASDAQ:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation & immunology announced today the first patient dosed in the Company's Phase 1 clinical trial with TH104, utilizing a proprietary oral thin film. TH104 is a proprietary transmucosal buccal film embedded with the approved, active compound nalmefene onto a thin film which easily adheres inside of the mouth on the cheek and biodegrades within minutes. Tharimmune's lead clinical-stage asset, TH104, is designed as an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions, by avoiding the first-pass metabolism usually in traditional oral formulations. The molecule has a dual mechanism of action affecting both the mu and kappa opioid receptors, while emerging data suggests inhibition of interleukin-17, a pro-inflammatory cytokine. The well-known mu and kappa receptors, when stimulated and/or inhibited by the body's endogenous ligands, have been implicated in the body's itch circuitry for certain conditions, specifically cholestatic or dysregulated bile acid-related liver conditions. The Phase 1 clinical trial currently recruiting is a pharmacokinetic bridging study in the U.S. designed as a single-dose, single-center, open-label, randomized 2-way crossover study of TH104 and an intravenous dose of nalmefene administered under fasting conditions, with a 7-day washout period between doses. Sixteen normal healthy volunteers are anticipated to participate and complete the study. The primary objective is to evaluate the absolute bioavailability of TH104 as well as assess safety and tolerability. Topline data is expected in 2Q24 with a full data readout shortly thereafter. "The dosing of the first patient in our Phase 1 study of TH104 marks the initiation of our vision of becoming a patient-focused clinical development organization," said Randy Milby, Chief Executive Officer of Tharimmune. "Along with the recently disclosed human studies conducted outside the US, and a focused effort to complete this ongoing trial, we are dedicated to advance TH104, which has the potential to bring meaningful patient benefit. We aim to continue our momentum in the clinic and remain on-track to initiate a Phase 2 program this year." Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease with debilitating symptoms, including pruritus or "unrelenting itching" and fatigue. Pruritus is a common clinical feature seen in liver diseases but particularly frequent in cholestatic liver disease. A recent study found that pruritus in PBC is under-treated in clinical practice in the United States. Current treatment options may only be partially effective or poorly tolerated and are not FDA-approved for cholestatic pruritus in patients with PBC, therefore effective solutions for this significant problem are a high unmet need. Multiple ex-US human studies have been completed with TH104 which showed reliable and predictable delivery of nalmefene in healthy subjects using our proprietary drug embedded transmucosal oral film applied to the inside of the cheek. Another previously disclosed study of an open-label trial using TH104 in chronic liver disease patients showed a 33.3% decline in 24-hour itch intensity when administered a single low-dose. Safety and tolerability in these studies were consistent with published studies in the literature with nalmefene, the active ingredient in TH104. The Company previously announced the closing of an $11 million public offering which it believes is sufficient to extend its cash runway into early 2025 for both clinical readouts of its lead program, TH104. Tharimmune plans to advance both its clinical and non-clinical programs and announce an R&D Day in 2Q24 to update stakeholders and patients. About TH104 TH104 is embedded with nalmefene onto a proprietary transdermal 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 receptor and the kappa opioid receptor as well as 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 Cholangitis According 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 which causes 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 symptoms 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 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/A for the year ended December 31, 2022 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. Investor Relations Contact ir@tharimmune.com SOURCE: Tharimmune, Inc. View the original press release on accesswire.com