This study is recruiting participants who are experiencing a first episode of psychosis and who have certain genetic factors that may make them respond better to certain medications that are used to treat people with psychosis.

开始日期2025-07-30

申办/合作机构

Northwell Health, Inc.

[+1]

NCT05603104

/ Recruiting临床3期IIT

A Randomised, Controlled Trial to Investigate the Effect of an Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.

Schizophrenia, bipolar and major depressive disorders collectively affect over 10 million people across the EU and are associated with annual healthcare and societal costs in excess of 100 billion Euros. When diagnosed with one of these disorders, patients are prescribed psychotropic medication such as antidepressants, mood stabilisers or antipsychotics. It is unknown whether this first-line treatment will be successful. After this first-line treatment fails, usually a second-line treatment is initiated, and when this is not successful either a third-line treatment is initiated. Third-line treatments are quite successful, especially when compared to second-line treatments. The research question is whether the third-line treatments (early-intensified treatments) would be more efficacious than the current second-line treatments (treatment as usual) for schizophrenia, bipolar and major depressive disorders. If this is indeed the case, this could lead to the prevention of unnecessary trials of ineffective treatments and adaptations of worldwide guidelines as well as a reduction of healthcare and societal costs.

开始日期2025-04-30

申办/合作机构

Universität Leipzig

CTRI/2024/10/074933

/ Not yet recruiting临床1期

A multicentre, open label, balanced, randomized, two-treatment, two-period, two-sequence, multiple dose, steady state, crossover oral bioequivalence study of Clozapine Orally Disintegrating Tablets 100 mg (Test) of Alkem laboratories Ltd., India with Clozapine Orally Disintegrating Tablets 100 mg (Reference) of Teva Pharmaceuticals USA, Inc., North Wales, PA 19454 in patients with Schizophrenia under fasting conditions. - NIL

开始日期2024-10-23

申办/合作机构

Alkem Laboratories Ltd.

100 项与氯氮平相关的临床结果

登录后查看更多信息

100 项与氯氮平相关的转化医学

登录后查看更多信息

100 项与氯氮平相关的专利（医药）

登录后查看更多信息

18,048

项与氯氮平相关的文献（医药）

2025-08-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Letter to Editor: Critical commentary on the study of Siddig et al: Pharmacovigilance of drug-drug interactions: A pharmacokinetic study on the combined oral administration of lurasidone and clozapine in rats by using LC-MS/MS

Letter

作者: Juřica, Jan

2025-08-01·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Clozapine blunts mitochondrial biogenesis in differentiating adipocytes: The increased ATP demand is met via stimulation of electron transport chain expression and activity in residual mitochondria

Article

作者: Montanari, Mariele ; Battistelli, Michela ; Bagherlou, Nazanin ; De Matteis, Rita ; Spina, Andrea ; Cantoni, Orazio ; Guidarelli, Andrea ; Cerioni, Liana ; Fiorani, Mara ; Papa, Stefano ; Canonico, Barbara ; Coppo, Lucia ; Buffi, Gloria

Clozapine (CLZ), a second-generation antipsychotic, is associated with an elevated risk of metabolic syndrome, the underlying mechanism of which remains poorly understood. We recently showed that CLZ inhibits lipid accumulation and CAAT/enhancer-binding protein β and peroxisome proliferator-activated receptor γ expression in early differentiating SW872 liposarcoma cells. Additionally, while not affecting viability, CLZ disrupts the cellular redox state of these cells by inhibiting NADPH oxidase-dependent ROS formation, thereby leading to nuclear factor (erythroid-derived2)-like 2 downregulation, reduced antioxidant defence and increased mitochondrial ROS emission. We confirmed and extended these results by showing that, under the same conditions, CLZ reduces the size of the lipid droplets, inhibits the otherwise increased expression of transcription factors regulating mitochondrial biogenesis, as peroxisome proliferator-activated receptor γ coactivator 1-α, and prevents the increase in mitochondrial DNA and mass. Consistently, decreased expression of mitochondrial proteins as thioredoxin 2, 2-oxoglutarate/malate carrier, and translocase of outer mitochondrial membrane 20 was also observed. However, the expression of various components of the electron transport chain was unexpectedly increased, and this event was accompanied by enhanced mitochondrial dehydrogenase activity, coupled oxygen consumption, mitochondrial membrane potential, ATP synthesis and ROS production. Moreover, residual mitochondria appeared remarkably enlarged and functional, with dense and organized cristae and uniform electron density. Thus, early adipocytes differentiated with or without CLZ meet the increased ATP demand by switching from glycolysis to oxidative phosphorylation, respectively via enhanced mitochondrial biogenesis, and increased activity of residual mitochondria.

2025-07-01·JOURNAL OF HAZARDOUS MATERIALS

Screening and risk assessment of priority organic micropollutants for control in reclaimed water in China

Article

作者: Wang, Zijian ; Meng, Qingling ; Sun, Kaicheng ; Wen, Zhao ; Xue, Honghai

Organic micropollutants (OMPs) in reclaimed water have been frequently detected over the past decades, posing significant risks to ecosystems and human health. Given the complexity of these pollutants and the differences in their risk and toxicity, current assessments remain incomplete. This study conducted a large-scale investigation of OMPs in reclaimed water across China and developed a comprehensive multi-criteria integrated scoring method based on OMP toxicity and exposure potential. This method aims to protect aquatic organisms and human health by screening and prioritizing OMPs in reclaimed water, classifying their priority levels, and creating a prioritized control list. The study quantified OMP exposure potential, environmental persistence, bioaccumulation, and impacts on ecology and human health. The survey detected 369 OMPs from 11 chemical classes, with 325 compounds passing pre-selection. According to the prioritization scheme, 29 OMPs were identified as high priority, 171 as medium priority, and 125 as low priority. The BPs and Other Industrial Chemicals categories had the highest average maximum concentrations, followed by HPCCs and PAEs. High-priority pollutants were dominated by PAHs and PCBs, each comprising 31.03 %. Medium- and low-priority groups were mainly composed of Pesticides. PAHs and PCBs showed higher risk quotients, indicating significant ecological risks, while PCB 126, BaP, and PFOA exhibited high toxicity and potential health risks. This study provides valuable information for controlling priority pollutants in Chinese reclaimed water and establishes a foundation for OMP risk management. Future research should intensify monitoring to ensure the safe and sustainable use of water resources.

项与氯氮平相关的新闻（医药）

2025-05-12

·Business Wire

Newron Announces Approval for Pivotal Phase III ENIGMA-TRS Program With Evenamide as Add-on Therapy in Patients With Treatment-resistant Schizophrenia (TRS)

MILAN & MORRISTOWN, N.J.--(BUSINESS WIRE)--Newron Pharmaceuticals S.p.A. (“Newron”) (SIX: NWRN, XETRA: NP5), a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system, today announced the approval for its pivotal ENIGMA-TRS Phase III development program evaluating evenamide as an add-on therapy to current antipsychotics, including clozapine, in patients with treatment-resistant schizophrenia (TRS). Newron today announced the approval for its pivotal ENIGMA-TRS Phase III development program evaluating evenamide as an add-on therapy to current antipsychotics, including clozapine, in patients with treatment-resistant schizophrenia (TRS). The ENIGMA-TRS Phase III development program consists of two pivotal studies, ENIGMA-TRS 1 and ENIGMA-TRS 2. The two studies are expected to meet the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) specified regulatory requirements for submission of the registration dossier for evenamide in major territories, including the US and Europe. ENIGMA-TRS 1 is an international, 52-week, randomized, double-blind, placebo-controlled Phase III study evaluating the efficacy, tolerability, and safety of the 15mg BID and 30mg BID therapeutic doses of evenamide compared to placebo. Patients on second-generation anti-psychotics (SGAs), including clozapine, will meet Treatment Response and Resistance Psychosis (TRRIP) international consensus criteria for TRS. ENIGMA-TRS 1 will enroll at least 600 patients at study centers in Europe, Asia, Latin America and Canada. Patients will undergo a 42-day screening period, during which their TRS diagnosis, antipsychotic plasma levels (background medication), and conformance to protocol selection criteria will be evaluated by an Independent Eligibility Assessment Committee (IEAC) of three leading international schizophrenia experts. The primary assessment of efficacy and safety will be performed 12 weeks after randomization to treatment. The study will continue double-blind and placebo-controlled until the 52-week (i.e. one year) time point. Enrolment to the study will start imminently. The 12-week results from the study are expected in Q4 2026. ENIGMA-TRS 2, approved by the US Food and Drug Administration (FDA), will be performed at centers in the US and selected additional countries and will include at least 400 patients in a 12-week, randomized, double-blind, placebo-controlled Phase III study, designed to evaluate the efficacy, tolerability, and safety of the 15mg BID dose of evenamide. Patients will meet selection criteria and be reviewed by the above-mentioned IEAC. The analysis for determination of efficacy and safety will be performed after patients complete 12 weeks of participation in the trial. US investigational centers are expected to initiate the study within the next three months. Stephen Marder, MD, Distinguished Professor of Psychiatry, Semel Institute of Neuroscience & Human Behavior, and Director, Section on Psychosis, UCLA Neuropsychiatric Institute, commented: “The imminent initiation of ENIGMA-TRS 1 study of evenamide is a significant milestone in the search for new medications to treat this devastating condition. Evenamide’s modulation of glutamate, good tolerability, and efficacy in studies performed to date, both in patients who are poor responders or treatment resistant to SGAs, suggests its therapeutic potential in patients with TRS. The field eagerly looks forward for results from this landmark trial.” Jean-Pierre Lindenmayer, MD, Director of Research, Psychopharmacology Research Unit - Nathan Kline Institute for Psychiatric Research at Manhattan Psychiatric Center, added: “Evenamide’s selectivity for sodium channels and consequent modulation of glutamate, the demonstration of its efficacy in multiple animal models of psychosis as well as the MAM model of neurodevelopmental abnormalities, suggests promising results in patients with TRS. Completed studies in inadequate responders to SGAs and the results of a one-year study in patients with TRS predict therapeutic benefit of evenamide in TRS patients. Evenamide has the potential to fill a wide gap in our treatment for patients with incomplete response to SGAs, including clozapine. I look forward to participating to the ENIGMA-TRS 2 trial as a study center.” Ravi Anand, MD, Chief Medical Officer of Newron, stated: “Newron greatly appreciates the regulatory approval of the ENIGMA-TRS trials. The positive results of evenamide observed in clinical studies and demonstrated in disease models have led to high enthusiasm in investigators to participate in this landmark program.” The Phase III ENIGMA-TRS clinical trials are part of Newron’s development program for evenamide, targeting patients with schizophrenia experiencing worsening of psychosis on therapeutic doses of current antipsychotics, as well as treatment-resistant patients, which together account for the vast majority of patients suffering from schizophrenia. Results from previous Phase II (study 014/015) and Phase III (study 008A) studies have demonstrated evenamide’s significant and increasing efficacy as an add-on therapy on multiple measures of psychopathology in patients with TRS and inadequate responders, respectively. These results also confirmed a favorable safety and tolerability profile, adding to the growing evidence that evenamide’s glutamatergic inhibition mechanism of action offers an innovative therapeutic option to schizophrenia patients who are not benefiting from current antipsychotic treatments. Newron has entered into licensing agreements with EA Pharma, a subsidiary of Eisai, in Japan and other designated territories, and with Myung In Pharm in South Korea, to develop, manufacture and commercialize evenamide in the respective territories. Under the terms of the agreements, Newron will receive up to a maximum total of EUR 117 million, including an upfront payment of EUR 44 million, financial contributions to the Phase III ENIGMA-TRS program, milestone payments, and tiered royalties up to a double-digit percentage of net sales for evenamide, from EA Pharma; Myung In Pharm will contribute 10% of the total patient population to be enrolled into Newron’s upcoming Phase III ENIGMA-TRS trial and cover the costs related to this population. Newron is actively exploring additional partnerships for the global development and commercialization of evenamide. About schizophrenia Approximately 25 million people worldwide are affected by schizophrenia. Despite more than 60 different types of atypical and typical antipsychotics used to treat schizophrenia globally, a considerable number of patients remain severely ill or resistant to treatment. Overall, 30-50% of patients do not respond to the available medications and are defined as treatment resistant. In addition to the patients with treatment-resistant schizophrenia (TRS), another 20-30% are described as “poor responders to anti-psychotic medication”, even if not meeting the criteria for TRS. New findings indicate that patients with TRS have abnormalities in the glutamatergic system, but not in dopaminergic transmission, so there is a significant unmet medical need for treatments with a glutamatergic mechanism of action, efficacious both in TRS patients and in those who are poor responders to the current treatments. About evenamide Evenamide is the first new chemical entity that has demonstrated significant benefits in this difficult-to-treat patient population, as seen in the potentially pivotal Phase III study 008A trial, as an add-on treatment to second generation anti-psychotics including clozapine, in 291 poorly responding patients with chronic schizophrenia. The primary endpoint, the Positive and Negative Syndrome Scale (PANSS)1, and the key secondary endpoint, the Clinical Global Impressions Scale – Severity (CGI-S), were met and showed statistical significance compared to placebo. Importantly, evenamide treatment was associated with statistically significant increases in the proportion of patients who experienced “clinically meaningful benefit” on the outcome variables. Evenamide was extremely well tolerated, without any of the usual side effects of available anti-psychotics. About Newron Pharmaceuticals Newron (SIX: NWRN, XETRA: NP5) is a biopharmaceutical company focused on developing novel therapies for patients with diseases of the central and peripheral nervous system. Headquartered in Bresso, near Milan, Italy, Newron is advancing its lead compound, evenamide, a first-in-class glutamate modulator, which has the potential to be the first add-on therapy for treatment-resistant schizophrenia (TRS) and for poorly responding patients with schizophrenia. Evenamide is currently in Phase III development and clinical trial results to date demonstrate the benefits of this drug candidate in the TRS patient population, with significant improvements across key efficacy measures increasing over time, as well as a favourable safety profile, which is uncommon for available antipsychotic medications. Newron has signed development and commercialization agreements for evenamide with EA Pharma (a subsidiary of Eisai) for Japan and other Asian territories, as well as Myung In Pharm for South Korea. Newron has a proven track record in bringing CNS therapies to market. Its Parkinson’s disease treatment, Xadago® (safinamide), is approved in over 20 markets, including the USA, UK, EU, Switzerland, and Japan, and commercialized in partnerships with Zambon and Meiji Seika. For more information, please visit: www.newron.com Important Notices This document contains forward-looking statements, including (without limitation) about (1) Newron’s ability to develop and expand its business, successfully complete development of its current product candidates, the timing of commencement of various clinical trials and receipt of data and current and future collaborations for the development and commercialization of its product candidates, (2) the market for drugs to treat CNS diseases and pain conditions, (3) Newron’s financial resources, and (4) assumptions underlying any such statements. In some cases, these statements and assumptions can be identified by the fact that they use words such as “will”, “anticipate”, “estimate”, “expect”, “project”, “intend”, “plan”, “believe”, “target”, and other words and terms of similar meaning. All statements, other than historical facts, contained herein regarding Newron's strategy, goals, plans, future financial position, projected revenues and costs and prospects are forward-looking statements. By their very nature, such statements and assumptions involve inherent risks and uncertainties, both general and specific, and risks exist that predictions, forecasts, projections and other outcomes described, assumed or implied therein will not be achieved. Future events and actual results could differ materially from those set out in, contemplated by or underlying the forward-looking statements due to a number of important factors. These factors include (without limitation) (1) uncertainties in the discovery, development or marketing of products, including without limitation difficulties in enrolling clinical trials, negative results of clinical trials or research projects or unexpected side effects, (2) delay or inability in obtaining regulatory approvals or bringing products to market, (3) future market acceptance of products, (4) loss of or inability to obtain adequate protection for intellectual property rights, (5) inability to raise additional funds, (6) success of existing and entry into future collaborations and licensing agreements, (7) litigation, (8) loss of key executive or other employees, (9) adverse publicity and news coverage, and (10) competition, regulatory, legislative and judicial developments or changes in market and/or overall economic conditions. Newron may not actually achieve the plans, intentions or expectations disclosed in forward-looking statements and assumptions underlying any such statements may prove wrong. Investors should therefore not place undue reliance on them. There can be no assurance that actual results of Newron's research programs, development activities, commercialization plans, collaborations and operations will not differ materially from the expectations set out in such forward-looking statements or underlying assumptions. Newron does not undertake any obligation to publicly update or revise forward-looking statements except as may be required by applicable regulations of the SIX Swiss Exchange or the Dusseldorf Stock Exchange where the shares of Newron are listed. This document does not contain or constitute an offer or invitation to purchase or subscribe for any securities of Newron and no part of it shall form the basis of or be relied upon in connection with any contract or commitment whatsoever. ______________________________ 1 Positive and Negative Syndrome Scale (PANSS) is widely used in clinical trials of schizophrenia and is considered the “gold standard” for assessment of antipsychotic treatment efficacy (Innvo Clin Neurosci, 2017: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC5788255/)

临床3期引进/卖出临床结果临床2期上市批准

2025-05-08

·hlstherapeutics.com

HLS Therapeutics Announces Q1 2025 Financial Results

Total Product revenue grew 5% compared to Q1 2024, with growth across both the US and Canada Canadian Product revenue grew 13% (in local currency) compared to Q1 2024, driven by 34% year-over-year growth in Vascepa net sales Adjusted EBITDA grew 41% (or 78% excluding royalty revenue) compared to Q1 2024 HLS expands Cardiovascular portfolio by securing Canadian rights to NEXLETOL® and NEXLIZET® from Esperion Therapeutics TORONTO, May 8, 2025 /CNW/ - HLS Therapeutics Inc. ("HLS" or the "Company") (TSX: HLS), a pharmaceutical company focused on addressing unmet needs in the treatment of psychiatric disorders and cardiovascular disease, announces its financial results for the three months ended March 31, 2025. All amounts are in thousands of United States ("U.S.") dollars unless otherwise stated. Q1 2025 FINANCIAL HIGHLIGHTS (comparisons are to Q1 2024) Revenue was $12.6 million, Adjusted EBITDA1 was $3.8 million and cash from operations was $3.5 million, compared to $12.5 million, $2.7 million and $0.8 million, respectively. Revenue for Vascepa increased 34% in local currency. Revenue for Clozaril Canada increased 1% in local currency. Revenue for Clozaril US increased 3%. Excluding cost of sales, operating expenses decreased 20%. Vascepa made a slightly positive contribution to Adjusted EBITDA in Q1 2025, compared to a negative $1.6 million contribution in Q1 2024. OTHER CORPORATE HIGHLIGHTS Announced an agreement with Esperion Therapeutics Inc. (NASDAQ:ESPR) to in-license and commercialize NEXLETOL2 and NEXLIZET2 in Canada. See full press release details here. Launched Normal Course Issuer Bid. Christine Elliott, ex-Minister of Health in Ontario, joined the Board of Directors. "Our Q1 financial results demonstrated solid execution across the business, with product revenues and Adjusted EBITDA growing in line with expectations. We also made progress in building the foundation for future growth by expanding our product portfolio," said Craig Millian, CEO at HLS. "Product revenue in Canada increased by 13% in local currency, driven by growth in both Vascepa and Clozaril, while Clozaril sales in the U.S. rose by 3%. Our focus on operational efficiencies led to a 20% reduction in operating expenses, resulting in a 41% increase in Adjusted EBITDA, or 78% when excluding passive royalty revenue." "The strengthening of our financial position has created new opportunities to enhance shareholder value. We initiated a share buyback program in Q1 while continuing to pursue strategic growth opportunities such as portfolio expansion. Today's announcement of our agreement with Esperion Therapeutics to in-license NEXLETOL and NEXLIZET for the Canadian market reflects this balanced approach to capital allocation." "These promising therapies are strategically aligned with our portfolio, complementing Vascepa and leveraging our established cardiovascular infrastructure in the Canadian market, which will minimize incremental costs. The products address significant unmet medical needs and represent a substantial growth opportunity. In Q4 2024, Esperion submitted New Drug Submissions to Health Canada for NEXLETOL and NEXLIZET, with approval expected by late 2025 and preparations in progress for commercial launch in early 2026." Q1 2025 FINANCIAL REVIEW The Company's Management's Discussion and Analysis and Consolidated Financial Statements for the three months ended March 31, 2025, are available at the Company's website and at its profile at SEDAR+. Revenue Three months ended March 31, 2025 2024 Product sales Canada 9,708 9,154 United States 2,718 2,642 12,426 11,796 Royalty revenue 197 677 12,623 12,473 Revenue for the three months ended March 31, 2025, increased 1%, due to growth of the Company's marketed products and was offset, in part, by lower royalty revenues and FX rate fluctuations. Excluding royalties, Q1 2025 revenue for the Company's marketed products (Vascepa and Clozaril) increased 5% from Q1 2024. Product sales – Canada 000's of CAD Three months ended March 31, 2025 2024 % change Clozaril 7,929 7,865 0.8 % Vascepa 5,978 4,471 33.7 % Other 32 13 13,939 12,349 12.9 % For the three months ended March 31, 2025, Canadian sales of Vascepa and Clozaril increased 13% in local currency compared to Q1 2024, driven primarily by the 34% growth of Vascepa. However, when converted to U.S. dollars, the growth was only 6% due to the decline in the CAD/USD exchange rate. Product Sales – United States In the U.S. market, Clozaril revenue for the three months ended March 31, 2025, increased 3% compared to Q1 2024. Royalty revenues As expected, royalty revenues for the three months ended March 31, 2025, were down 71% compared to Q1 2024. Following the sale of the Xenpozyme royalty interest in Q2 2024, HLS has one remaining royalty interest which generated $0.2 million in revenue in Q1 2025. Operating Expenses Three months ended March 31, 2025 2024 Cost of product sales 2,398 1,774 Selling and marketing 2,830 4,526 Medical, regulatory and patient support 1,436 1,265 General and administrative 2,139 2,201 8,803 9,766 Cost of product sales was up for the three months ended March 31, 2025, due primarily to higher Vascepa sales volumes. Operating expenses in Q1 2025, excluding cost of product sales, decreased by 20% compared to Q1 2024, primarily due to lower selling and marketing expenses following the Company's discontinuation of co-promotional activities with its marketing partner in August 2024. While selling and marketing expenses will remain below 2024 levels throughout the year, quarterly expenses are expected to be moderately higher for the remainder of 2025 than in Q1. This difference is due to Q1 2025 benefiting from several staff vacancies and a one-time vendor credit, neither of which are expected to recur in upcoming quarters. Adjusted EBITDA1 Three months ended March 31, 2025 2024 Net loss for the period (4,436) (6,106) Stock-based compensation 651 256 Amortization and depreciation 5,360 5,919 Finance and related costs, net 1,972 2,667 Other costs 296 — Income tax recovery (23) (29) Adjusted EBITDA 3,820 2,707 Adjusted EBITDA for the three months ended March 31, 2025, increased 41% primarily due to the growth in the Company's marketed products and ongoing focus on cost management, and was partially offset by the previously mentioned decline in royalty revenue. Excluding royalty revenue, Adjusted EBITDA for Q1 2025 would have been $3.6 million compared to $2.0 million in Q1 2024, representing an increase of 78%. The direct brand contribution from Clozaril to Adjusted EBITDA in Q1 2025 was $5.9 million, compared to $6.1 million in Q1 2024. Vascepa achieved a slightly positive direct brand contribution to Adjusted EBITDA in Q1 2025, compared to a brand loss of $1.6 million in Q1 2024. This was the second consecutive quarter of a positive contribution from Vascepa to Adjusted EBITDA. Net LossNet loss for the three months ended March 31, 2025, was ($4.4) million, or ($0.14) per share, compared to a net loss of ($6.1) million, or ($0.19) per share, in Q1 2024. Net loss improved in Q1 2025 due primarily to higher revenue from marketed products, lower operating expenses and lower amortization and depreciation expenses, which were offset, in part, by lower royalty revenue. Cash from Operations and Financial PositionCash generated from operations for the three months ended March 31, 2025, was $3.5 million compared to $0.8 million in Q1 2024. Cash was $17.7 million at March 31, 2025, compared to $17.5 million at December 31, 2024. Total borrowings under the credit agreement at March 31, 2025, were $64.5 million compared to $67.4 million at December 31, 2024, and $86.4 million at March 31, 2024. During Q1 2025, HLS made principal payments on its term loan totaling $3.0 million and spent $0.2 million to purchase shares for cancellation under its Normal Course Issuer Bid, which was launched on March 17, 2025. 2025 OUTLOOKRevenue projections for the Company's Canadian product portfolio are denominated in local currency to account for ongoing FX rate fluctuations. Importantly, the 2025 guidance fully incorporates all anticipated financial impacts from pre-launch activities related to the newly in-licensed NEXLETOL and NEXLIZET. 2025 financial targets are unchanged and as follows: Vascepa revenue of C$26.5-28.5 million (18-26% growth) Canada Clozaril sales of C$35.5-36 million (flat year-over-year) U.S. Clozaril sales of $12-12.3 million (2-4% decline) Royalty revenue of $0.6-0.75 million (50-60% decline) Consolidated Adjusted EBITDA of $19.5-20.5 million (17-23% growth) Future results could be impacted by continued exchange rate volatility. Q1 2025 CONFERENCE CALLHLS will hold a conference call today at 8:30 am Eastern Time to discuss its Q1 2025 financial results. The call will be hosted by Mr. Craig Millian, CEO, Mr. John Hanna, CFO and Mr. Brian Walsh, CCO. To view the slides that accompany management's discussion, please use the webcast link. CONFERENCE ID: 41562 DATE: Thursday, May 8, 2025 TIME: 8:30 a.m. ET WEBCAST LINK: https://app.webinar.net/EpY5Lzpk6d8 TRADITIONAL DIAL-IN NUMBER: 1-888-699-1199 or 1-416-945-7677 RAPIDCONNECT: To instantly join the conference call by phone, please use the following URL to easily register and be connected into the conference call automatically: https://emportal.ink/43us1qX TAPED REPLAY: 1-888-660-6345 or 1-646-517-4150 REPLAY CODE: 41562# The taped replay will be available for 14 days and the archived webcast will be available for 365 days. A link to the live audio webcast of the conference call will also be available on the events page of the investors section of HLS Therapeutics' website at www.hlstherapeutics.com. Please connect at least 15 minutes before the conference call to ensure enough time for any software download required to hear the webcast. ABOUT HLS THERAPEUTICS INC.Formed in 2015, HLS is a pharmaceutical company focused on the acquisition and commercialization of late-stage development, commercial stage promoted and established branded pharmaceutical products in the North American markets. HLS's focus is on products targeting the central nervous system and cardiovascular therapeutic areas. HLS's management team is composed of seasoned pharmaceutical executives with a strong track record of success in these therapeutic areas and at managing products in each of these lifecycle stages. For more information visit: www.hlstherapeutics.com 1CAUTIONARY NOTE REGARDING NON-IFRS MEASURESThis press release refers to certain non-IFRS measures. These measures are not recognized measures under IFRS, do not have a standardized meaning prescribed by IFRS and are therefore unlikely to be comparable to similar measures presented by other companies. Rather, these measures are provided as additional information to complement those IFRS measures by providing further understanding of HLS's results of operations from management's perspective. Accordingly, they should not be considered in isolation nor as a substitute for analysis of HLS's financial information reported under IFRS. HLS uses non-IFRS measures to provide investors with supplemental measures of its operating performance and thus highlight trends in its core business that may not otherwise be apparent when relying solely on IFRS financial measures. HLS also believes that securities analysts, investors and other interested parties frequently use non-IFRS measures in the evaluation of issuers. HLS's management also uses non-IFRS measures in order to facilitate operating performance comparisons from period to period, prepare annual operating budgets and assess HLS's ability to meet its future debt service, capital expenditure and working capital requirements. In particular, management uses Adjusted EBITDA as a measure of HLS's performance. To reconcile net income (loss) for the period with Adjusted EBITDA, each of (i) "stock-based compensation", (ii) "amortization and depreciation", (iii) "finance and related costs, net", (iv) "other costs (income)", and (v) "income tax expense (recovery)" appearing in the Consolidated Statement of Net Income (Loss) are added to net income (loss) for the period to determine Adjusted EBITDA. Adjusted EBITDA does not have any standardized meaning prescribed by IFRS and is not necessarily comparable to similar measures presented by other companies. Adjusted EBITDA should not be considered in isolation or as a substitute for net income (loss) prepared in accordance with IFRS as issued by the IASB. REFERENCES 2: NEXLETOL® (bempedoic acid) and NEXLIZET® (bempedoic acid and ezetimibe) are the commercial brand names in the U.S. The brand names in Canada to be confirmed upon approval by Health Canada. FORWARD LOOKING INFORMATIONThis release includes forward-looking statements regarding HLS and its business. Such statements are based on the current expectations and views of future events of HLS's management. In some cases the forward-looking statements can be identified by words or phrases such as "may", "will", "expect", "plan", "anticipate", "intend", "potential", "estimate", "believe" or the negative of these terms, or other similar expressions intended to identify forward-looking statements, including, among others, statements with respect to HLS's pursuit of additional product and pipeline opportunities in certain therapeutic markets, statements regarding growth opportunities, expectations regarding financial performance, and the NCIB and ASPP. The forward-looking events and circumstances discussed in this release may not occur and could differ materially as a result of known and unknown risk factors and uncertainties affecting HLS, including risks relating to the specialty pharmaceutical industry, risks related to the regulatory approval process, economic factors and many other factors beyond the control of HLS. Forward-looking statements and information by their nature are based on assumptions and involve known and unknown risks, uncertainties and other factors which may cause HLS's actual results, performance or achievements, or industry results, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statement or information. Accordingly, readers should not place undue reliance on any forward-looking statements or information. A discussion of the material risks and assumptions associated with this release can be found in the Company's Annual Information Form dated March 12, 2025, and Management's Discussion and Analysis dated May 7, 2025, both of which have been filed on SEDAR+ and can be accessed at www.sedarplus.ca. Accordingly, readers should not place undue reliance on any forward-looking statements or information. Except as required by applicable securities laws, forward-looking statements speak only as of the date on which they are made and HLS undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, or otherwise. HLS THERAPEUTICS INC. CONSOLIDATED STATEMENTS OF FINANCIAL POSITION Unaudited [in thousands of U.S. dollars] As at As at March 31, 2025 December 31, 2024 ASSETS Current Cash 17,734 17,456 Accounts receivable 7,732 7,454 Inventories 7,483 9,058 Income taxes recoverable 71 71 Other current assets 1,048 1,361 Total current assets 34,068 35,400 Property, plant and equipment 972 997 Intangible assets 117,177 122,122 Deferred tax asset 1,200 857 Other non-current assets 530 528 Total assets 153,947 159,904 LIABILITIES AND SHAREHOLDERS' EQUITY Current Accounts payable and accrued liabilities 8,682 8,709 Provisions 8,561 8,367 Debt and other liabilities 6,203 5,317 Income taxes payable 394 152 Total current liabilities 23,840 22,545 Debt and other liabilities 59,181 61,944 Deferred tax liability 4,128 4,074 Total liabilities 87,149 88,563 Shareholders' equity Share capital 260,136 260,595 Contributed surplus 14,893 15,136 Accumulated other comprehensive loss (9,898) (10,210) Deficit (198,333) (194,180) Total shareholders' equity 66,798 71,341 Total liabilities and shareholders' equity 153,947 159,904 HLS THERAPEUTICS INC. CONSOLIDATED STATEMENTS OF LOSS Unaudited [in thousands of U.S. dollars, except per share amounts] Three months ended March 31, 2025 2024 Revenue 12,623 12,473 Expenses Cost of product sales 2,398 1,774 Selling and marketing 2,830 4,526 Medical, regulatory and patient support 1,436 1,265 General and administrative 2,139 2,201 Stock-based compensation 651 256 Amortization and depreciation 5,360 5,919 Finance and related costs, net 1,972 2,667 Other costs 296 — Loss before income taxes (4,459) (6,135) Income tax recovery (23) (29) Net loss for the period (4,436) (6,106) Net loss per share: Basic and diluted $(0.14) $(0.19) HLS THERAPEUTICS INC. CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS Unaudited [in thousands of U.S. dollars] Three months ended March 31, 2025 2024 Net loss for the period (4,436) (6,106) Item that may be reclassified subsequently to net loss Unrealized foreign currency translation adjustment 312 (2,373) Comprehensive loss for the period (4,124) (8,479) HLS THERAPEUTICS INC. INTERIM CONSOLIDATED STATEMENTS OF CHANGES IN SHAREHOLDERS' EQUITY Unaudited [in thousands of U.S. dollars] Share capital Contributed surplus Accumulated other comprehensive loss Deficit Total Balance, December 31, 2024 260,595 15,136 (10,210) (194,180) 71,341 Shares repurchased (459) — — 283 (176) Change in share purchase obligation — (495) — — (495) Stock option expense — 252 — — 252 Net loss for the period — — — (4,436) (4,436) Unrealized foreign currency translation adjustment — — 312 — 312 Balance, March 31, 2025 260,136 14,893 (9,898) (198,333) 66,798 Balance, December 31, 2023 262,127 13,865 (2,838) (175,457) 97,697 Shares repurchased (768) — — 485 (283) Stock option expense — 131 — — 131 Net loss for the period — — — (6,106) (6,106) Unrealized foreign currency translation adjustment — — (2,373) — (2,373) Balance, March 31, 2024 261,359 13,996 (5,211) (181,078) 89,066 HLS THERAPEUTICS INC. INTERIM CONSOLIDATED STATEMENTS OF CASH FLOWS Unaudited [in thousands of U.S. dollars] Three months ended March 31, 2025 2024 OPERATING ACTIVITIES Net loss for the period (4,436) (6,106) Adjustments to reconcile net loss to cash provided by operating activities Stock-based compensation 651 256 Amortization and depreciation 5,360 5,919 Accreted interest 308 282 Fair value adjustment on financial assets and liabilities — 187 Deferred income taxes (289) (61) Net change in non-cash working capital balances related to operations 1,949 301 Cash provided by operating activities 3,543 778 INVESTING ACTIVITIES Additions to property, plant and equipment (21) (2) Cash used in investing activities (21) (2) FINANCING ACTIVITIES Shares repurchased (176) (283) Repayment of credit agreement borrowing (2,960) (2,075) Debt costs — (533) Lease payments (143) (143) Cash used in financing activities (3,279) (3,034) Net increase (decrease) in cash during the period 243 (2,258) Foreign currency translation 35 (251) Cash, beginning of period 17,456 21,952 Cash, end of period 17,734 19,443 SOURCE HLS Therapeutics Inc.

财报引进/卖出上市批准

2025-04-23

·药时代

35年来首款新型精神分裂症药物，折戟辅助治疗

2025年4月22日，BMS宣布旗下重磅精神分裂症药物Cobenfy，在一项关键Ⅲ期临床试验（ARISE研究）中未能达到主要终点。Cobenfy是一种毒蕈碱乙酰胆碱受体激动剂的复方制剂（xanomeline/氯噻平复方制剂），该药物并非BMS原研，是BMS于2023年12月豪掷140亿美元收购Karuna Therapeutics后所得。2024年9月，FDA批准Cobenfy用于口服治疗成人精神分裂症。该药物成为全球首款用于治疗精神分裂症的毒蕈碱激动剂，也是近35年来首个获批的全新机制精神分裂症药物，上一款获批的药物还是Clozaril（氯氮平）。因此，在Evaluate2024年预测的全球前十大最有价值的管线中，Cobenfy赫然在列，并预计该药物2030年的销售额可达到25亿美元。事实也确实如此，在2024年第四季度，Cobenfy上市初期两个月，销售额达到了为1000万美元。BMS首席商业官Adam Lenkowsky也十分看好该产品潜力称，“Cobenfy的推出有一个强劲的开端。”然而，就是这款140亿美元天价买来的重磅药物、35年后的第一款、被业内评为全球最有价值的管线之一，却折戟在了作为非典型抗精神病药物的辅助疗法的三期临床试验之中。ARISE研究旨在评估Cobenfy联合非典型抗精神病药（如奥氮平、喹硫平等）的疗效，对照组为安慰剂联合非典型抗精神病药，主要终点为第6周时PANSS（阳性与阴性症状量表）总评分较基线的变化。结果显示，Cobenfy联合治疗组患者的PANSS总分较安慰剂组平均降低2.0分（P=0.11），未达到统计学显著性阈值。尽管主要终点失败，但事后亚组分析显示，以非利培酮（risperidone）为背景治疗的患者对Cobenfy的反应显著优于安慰剂组。BMS首席医学官Samit Hirawat博士指出，精神分裂症辅助治疗研发面临多重挑战：患者反应差异大、试验设计严苛，且需证明超越现有药物的增量疗效。尽管此次试验的主要终点未达统计学显著性，但我们需要完成全部数据分析，并计划下一步行动。正如Samit Hirawat博士所述，历史上关于精神分裂症药物的开发，确实困难重重。emraclidine的失败便是最好的案例。2024年，AbbVie以87亿美元天价收购Cerevel Therapeutics后，获得了旗下精神分裂症药物emraclidine。然而时隔仅百天，AbbVie便宣布Emraclidine在两项II期临床试验中未能达到预期效果，精神分裂症是全球致残率最高的疾病之一，据流行病学调查显示，该疾病影响了全球近1%的人口。然而庞大疾病人口基数，并未得到更好的控制。据悉目前常用治疗药物仍是以氯氮平、奥氮平、喹硫平为主的第二代抗精神病药物。此类药物虽较第一代抗精神病药物（氯丙嗪、氟哌啶醇和奋乃静等），可在阴性症状方面有更好的治疗效果，且相对减少了锥体外系的不良反应。但此类药物药物引发的代谢综合征、高泌乳素血症等耐受性问题仍有待解决。至于辅助治疗药物，跟不用说，更是只有慢性炎症的抗炎药、有助于改善精神症状评分的维生素D、叶酸等营养补充剂等。目前，中国现行的《精神分裂症防治指南（第二版）》上次更新时间仍是十年前，这在肿瘤领域几乎是不可想象的。基于如此庞大的蓝海市场，Cobenfy的市场价值可见一斑。小结因此，BMS十分重视Cobenfy。仅2025年，BMS就计划启动7项3期临床研究，涵盖了阿尔茨海默病躁动、阿尔茨海默病认知障碍和双相I型障碍等适应症。在BMS的计划中，每年都会有Cobenfy重要的临床数据读出。此外，值得一提的是，再鼎医药（持有Cobenfy大中华区权益）已于2024年底提交该药的上市申请。2025年1月，NMPA受理了Cobenfy用于治疗成人精神分裂症的新药上市申请。同时，再鼎医药称Cobenfy在“2028年20亿美元营收”愿景中扮演重要的支柱角色。只是此次辅助适应症受挫，是否只是一个“偶然”，是否会对中国获批带来影响，药时代将持续关注。参考资料：1.BMS官网2.当我们谈论KarXT时我们在谈论什么？（雪球）3.精神分裂症新药：变局与竞争（博药）4.其他公开资料图片来源：pixabayFDA新局长上任后，第一枪打响！2025-04-22「新环境下中国新药研发、临床与出海研讨会暨第二届金赛药业研发日」直播预约通道开启！诚邀观看！2025-04-21FDA局长：药企员工不能成为专家咨询委员会正式成员！2025-04-19版权声明/免责声明本文为原创文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，查看更多精彩!

临床3期临床结果并购引进/卖出临床成功

100 项与氯氮平相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D00283	氯氮平	N05AH02	DB00363

研发状态

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
分裂情感性障碍	美国	Douglas Pharmaceuticals America Ltd.	2013-02-06
精神分裂症，难治性	美国	Douglas Pharmaceuticals America Ltd.	2013-02-06
粒细胞减少症	美国	Jazz Pharmaceuticals Ireland Ltd.	2004-02-10
癫痫发作	美国	Jazz Pharmaceuticals Ireland Ltd.	2004-02-10
精神分裂症	美国	United Heritage Life Insurance Co.	1989-09-26
自残行为	美国	United Heritage Life Insurance Co.	1989-09-26
精神障碍	中国	江苏瑞年前进制药有限公司	1985-01-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02404155 (BEN, CTgov)	N/A	巴尔干肾病 \| 精神分裂症	274	Clozapine	齋淵夢衊網窪繭簾襯醖(鹹衊鑰願選願顧顧壓餘) = 膚簾選齋壓夢鏇廠鹹範艱艱壓窪淵鑰衊窪衊鑰 (構糧壓醖蓋鬱膚憲淵鬱, 1271.5) 更多	-	2023-01-31
ENDO2021	N/A	Glutamic Acid Decarboxylase Autoantibodies \| Zinc Transporter 8 Antibody \| IA-2 ... 更多	-	Clozapine	鑰膚壓廠鏇選鑰鑰廠觸(襯鹽遞網鬱鹽憲簾顧夢) = 淵衊餘蓋積構艱願製鏇壓鹹構鏇襯膚齋網蓋選 (積鏇醖蓋築顧築膚醖衊 ) 更多	积极	2021-05-03
NCT01639872 (CLOCS, CTgov)	临床4期	大麻滥用 \| 精神分裂症 \| 大麻戒断	49	Clozapine (Clozapine)	艱範積鏇艱鬱鏇願選艱 = 鏇壓艱艱積繭蓋鏇顧簾積淵獵醖顧鹹獵選簾鹽 (製糧範範齋窪衊蓋餘觸, 選齋糧鬱鏇製壓製選鑰 ~ 齋衊壓鏇鏇築構醖廠觸) 更多	-	2019-12-26
				Risperidone (Risperidone)	艱範積鏇艱鬱鏇願選艱 = 選窪鬱網鬱鬱製願蓋積積淵獵醖顧鹹獵選簾鹽 (製糧範範齋窪衊蓋餘觸, 廠餘鑰艱夢築糧淵範遞 ~ 選鏇構繭衊餘觸壓鬱鑰) 更多
NCT00981526 (CTgov)	临床4期	分裂情感性障碍 \| 精神分裂症	66	Olanzapine+Telmisartan+Clozapine (A: Telmisartan)	鑰襯構憲襯選齋鏇憲蓋(獵構範糧願遞蓋齋繭選) = 願窪構蓋簾窪壓繭構夢廠獵選齋繭衊醖獵衊齋 (齋糧餘製鏇醖襯鹽構餘, 1.4262) 更多	-	2018-06-19
				Placebo+Olanzapine+Clozapine (B: Placebo)	鑰襯構憲襯選齋鏇憲蓋(獵構範糧願遞蓋齋繭選) = 築鑰觸鏇遞襯廠遞醖顧廠獵選齋繭衊醖獵衊齋 (齋糧餘製鏇醖襯鹽構餘, 2.469) 更多
Pubmed \| Schizophr Res	N/A	精神分裂症，难治性	71	Clozapine+ECT	鹽遞願壓鬱齋糧範觸憲(衊選糧醖淵艱鬱壓憲壓) = 繭築鑰壓鹽築窪壓獵觸願鑰窪餘範壓壓糧窪繭 (襯糧蓋網構夢築築夢蓋 ) 更多	-	2016-03-01
NCT00042224 (CTgov)	临床1/2期	精神分裂症，难治性	39	Clozapine (Electroconvulsive Therapy With Medication)	製繭壓觸積繭繭壓醖鑰 = 獵構積鹽觸鑰製襯範壓選鹹遞獵憲鏇鹹憲鹹襯 (壓鏇蓋選製窪鹹醖衊夢, 憲壓選廠糧鑰獵艱築遞 ~ 廠壓範築餘醖遞築願夢) 更多	-	2015-10-15
				Clozapine (Medication Monotherapy)	製繭壓觸積繭繭壓醖鑰 = 範鏇鬱夢繭淵繭膚積簾選鹹遞獵憲鏇鹹憲鹹襯 (壓鏇蓋選製窪鹹醖衊夢, 築網範廠鏇糧觸製夢網 ~ 艱膚窪壓窪淵網顧齋廠) 更多
Pubmed \| Acta Neuropsychiatr	N/A	-	208	Clozapine	廠衊繭淵壓製壓構獵簾(繭築蓋衊衊糧齋壓淵築) = 餘獵獵積選壓簾遞窪願膚廠襯糧鬱繭蓋築廠繭 (選願衊鬱淵製獵夢醖築 )	积极	2015-06-01
NCT01654601 (DWCZP-I-1, CTgov)	临床1期	精神分裂症	28	Clozaril (A Group)	蓋艱繭窪窪選積艱蓋選(顧願顧餘築醖觸膚艱糧) = 襯衊範構窪選積夢窪選構糧範選獵範鹽簾願艱 (鏇糧蓋獵淵鑰衊淵鏇顧, 272.51) 更多	-	2014-03-14
				Clozaril (B Group)	蓋艱繭窪窪選積艱蓋選(顧願顧餘築醖觸膚艱糧) = 壓簾艱選構糧壓製積壓構糧範選獵範鹽簾願艱 (鏇糧蓋獵淵鑰衊淵鏇顧, 263.26) 更多
NCT00573287 (CTgov)	N/A	精神分裂症 \| 大麻滥用 \| 物质滥用	14	Clozapine (Clozapine)	範廠鬱醖膚憲膚襯襯壓 = 遞蓋鏇選壓糧膚淵願繭選觸願顧蓋窪築淵選鏇 (鹽顧鏇網選淵齋範醖繭, 構膚繭積衊選鏇獵構窪 ~ 繭構廠構願鑰鬱選壓廠) 更多	-	2013-02-18
				risperidone (Risperidone)	範廠鬱醖膚憲膚襯襯壓 = 網願蓋觸壓獵遞壓網築選觸願顧蓋窪築淵選鏇 (鹽顧鏇網選淵齋範醖繭, 鬱鑰壓繭積醖廠鹽餘淵 ~ 選觸鹹齋廠窪壓廠獵窪) 更多
NCT00498550 (CTgov)	临床4期	分裂情感性障碍 \| 精神分裂症 \| 大麻滥用	31	Clozapine (Clozapine)	鑰糧獵積廠鹹醖繭窪廠 = 蓋獵簾憲夢鏇築窪簾繭膚繭膚廠選襯範築鑰積 (築齋構構遞顧繭積廠鏇, 襯夢壓蓋積積鑰糧簾鹽 ~ 窪夢範構醖製遞廠鑰襯) 更多	-	2012-01-19
				Treatment as usual (Treatment as Usual)	鑰糧獵積廠鹹醖繭窪廠 = 鹽範鏇繭廠醖醖鑰艱窪膚繭膚廠選襯範築鑰積 (築齋構構遞顧繭積廠鏇, 窪衊積鏇夢艱構衊糧膚 ~ 醖窪顧糧衊淵餘膚鬱醖) 更多