5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), DRDs antagonists(Dopamine receptors antagonists), GABAA receptor antagonists(Gamma-aminobutyric acid A receptor antagonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Schizoaffective disorderSchizophrenia, Treatment-ResistantSchizophrenia+ [2]

Inactive Indication

AgranulocytosisSeizures

Originator Organization

HLS Therapeutics, Inc.

Active Organization

United Heritage Life Insurance Co.

AA Pharma, Inc.Douglas Pharmaceuticals America Ltd.

+ [3]

Inactive Organization

Jazz Pharmaceuticals Ireland Ltd.

Novartis AG

License Organization-

Drug Highest PhaseApproved

First Approval Date

China (01 Jan 1985),

Psychotic Disorders

Regulation-

Structure/Sequence

Molecular FormulaC18H19ClN4

InChIKeyQZUDBNBUXVUHMW-UHFFFAOYSA-N

CAS Registry5786-21-0

140

Clinical Trials associated with Clozapine

NCT06969755

/ Not yet recruitingPhase 4IIT

Biomarkers to Enhance Early Schizophrenia Treatment

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.

Start Date30 Jul 2025

Sponsor / Collaborator

Northwell Health, Inc.

[+1]

NCT05603104

/ RecruitingPhase 3IIT

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.

Start Date30 Apr 2025

Sponsor / Collaborator

Universität Leipzig

CTRI/2024/10/074933

/ Not yet recruitingPhase 1

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

Start Date23 Oct 2024

Sponsor / Collaborator

Alkem Laboratories Ltd.

100 Clinical Results associated with Clozapine

100 Translational Medicine associated with Clozapine

100 Patents (Medical) associated with Clozapine

18,039

Literatures (Medical) associated with Clozapine

01 Aug 2025·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

Author: Juřica, Jan

01 Aug 2025·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

Author: 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.

01 Jul 2025·PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

The dosage-dependent effects of cevimeline in preventing clozapine-induced dyslipidaemia in female rats

Article

Author: Lian, Jiamei ; Deng, Chao ; Pan, Bo

Clozapine is the most effective second-generation antipsychotic drug, especially for the therapy of treatment-resistant schizophrenia. However, it is associated with metabolic side-effects. Clozapine has a high antagonistic affinity to muscarinic M3 receptors, which has been reported to play a significant role in these side-effects. This study aimed to investigate whether co-administration of cevimeline (an M3 receptor agonist) could prevent the metabolic disorders induced by clozapine. Female Sprague Dawley rats were treated orally with clozapine (20 mg/kg, 3 times daily) and/or cevimeline at three dosages (3, 6, 9 mg/kg, 3 times daily), or a vehicle for two weeks. Body weight gain, food/water intake, and temperature were recorded. Open field tests were performed to assess motor activity. Clozapine only treatment significantly decreased body weight gain, feeding efficiency, perirenal, periovary, inguinal, total white fat mass, and NEFA levels. The reduction in body weight gain and feeding efficiency caused by clozapine was partially reversed by co-treatment with 3 or 6 mg/kg cevimeline. Clozapine also significantly increased the liver mass, LDL, and HDL level, which were reversed by the co-treatment with cevimeline at all tested dosages. These results support further clinical trials to evaluate cevimeline's potential in controlling clozapine-induced dyslipidemia.

News (Medical) associated with Clozapine

12 May 2025

·www.businesswire.com

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/)

Phase 3License out/inClinical ResultPhase 2Drug Approval

08 May 2025

·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.

Financial StatementLicense out/inDrug Approval

08 Apr 2025

·www.prnewswire.com

Gedeon Richter: Cariprazine shows effectiveness in the treatment of mental health disorders with combined substance use disorder

BUDAPEST, Hungary, April 8, 2025 /PRNewswire/ -- At the 33rd Annual Meeting of the European Psychiatric Association (EPA; 5-8th April, Madrid), new analyses of cariprazine studies were presented by Gedeon Richter Plc. The scientific posters showed that cariprazine seems to be an appropriate treatment option for a difficult-to-treat patient population, schizophrenia patients with multiple psychotic episodes and cannabis use disorder. Three further scientific posters were presented, and a joint session with partner company Recordati was organized focusing on the advantages of treatment with third generation antipsychotics. Finally, a novel transdiagnostic scale for quantifying and visualizing the severity of symptoms in patients with different psychiatric conditions was also shown at EPA. The first scientific poster evaluated the effectiveness of cariprazine in dual schizophrenia patients with multiple schizophrenia episodes and cannabis use disorder. The results of the 6-month observational study showed that cariprazine seems to be an effective treatment option for this patient population. The second poster showed that the sex of patients does not seem to significantly influence risk of relapse, and that cariprazine decreases the risk of relapse compared to placebo in both males and females. The third poster evaluated the progression and treatment of negative symptoms in female patients during their hospital-stay. Importantly, results indicated cariprazine to be the first choice of medication both as mono- and polytherapy, resulting in significant decrease of negative symptoms during hospitalization. Finally, the fourth poster collected all available evidence on cariprazine-clozapine augmentation strategy, showing that it appears to be promising for treatment-resistant schizophrenia, particularly for negative symptoms with favorable safety outcomes. In addition, Richter and Recordati organized a scientific symposium titled " Partial activity, full impact: innovations in schizophrenia treatment", where experts discussed the potential of dopamine receptor partial agonists and the importance of understanding the mechanism of action to differentiate and personalize therapies. On the 4th of April, during a Scientific Event involving around 100 doctors, the importance of utilizing measurement-based care in everyday psychiatric practice was highlighted: Professor Christoph U. Correll and an expert from Gedeon Richter presented a novel transdiagnostic scale for quantifying-visualizing symptom severity in patients with different psychiatric conditions. Cariprazine is available in 67 countries globally, and the number of total patients treated from launch in Europe and US is around 1.700.000 (different indications). About Richter About Recordati About Cariprazine Media-contact: Zsuzsa Beke, Head of PR, [email protected] WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultClinical Study

100 Deals associated with Clozapine

External Link

KEGG	Wiki	ATC	Drug Bank
D00283	Clozapine	N05AH02	DB00363

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Schizoaffective disorder	United States	Douglas Pharmaceuticals America Ltd.	06 Feb 2013
Schizophrenia, Treatment-Resistant	United States	Douglas Pharmaceuticals America Ltd.	06 Feb 2013
Agranulocytosis	United States	Jazz Pharmaceuticals Ireland Ltd.	10 Feb 2004
Seizures	United States	Jazz Pharmaceuticals Ireland Ltd.	10 Feb 2004
Schizophrenia	United States	United Heritage Life Insurance Co.	26 Sep 1989
Self-Injurious Behavior	United States	United Heritage Life Insurance Co.	26 Sep 1989
Psychotic Disorders	China	Jiangsu Yixing Qianjin Pharmacy Factory	01 Jan 1985

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02404155 (BEN, CTgov)	Not Applicable	Balkan Nephropathy \| Schizophrenia	274	Clozapine	pwsacszlej(ljktzmdttf) = wvhuujklmi kwihifzjvv (kvtxxmgfbf, 1271.5) View more	-	31 Jan 2023
ENDO2021	Not Applicable	Glutamic Acid Decarboxylase Autoantibodies \| Zinc Transporter 8 Antibody \| IA-2 ... View more	-	Clozapine	iubqgtwoif(szmgxeyqeu) = zceuftxtkl intdpuzaed (hadhulhqay ) View more	Positive	03 May 2021
NCT01639872 (CLOCS, CTgov)	Phase 4	Marijuana Abuse \| Schizophrenia \| Cannabis withdrawal	49	Clozapine (Clozapine)	flhanydlke = kloewdatjg mgtnzllatz (sjguzedxmr, bgxoowbevn - qlxhtlgimv) View more	-	26 Dec 2019
				Risperidone (Risperidone)	flhanydlke = rcrcymteac mgtnzllatz (sjguzedxmr, bmzndqrfxq - riceduzigt) View more
NCT00981526 (CTgov)	Phase 4	Schizoaffective disorder \| Schizophrenia	66	Olanzapine+Telmisartan+Clozapine (A: Telmisartan)	mhdtxstuyv(wxqtgylfgs) = nkacrcfgsc coumbmarhb (gqaxqflrfl, 1.4262) View more	-	19 Jun 2018
				Placebo+Olanzapine+Clozapine (B: Placebo)	mhdtxstuyv(wxqtgylfgs) = chgspfvhdk coumbmarhb (gqaxqflrfl, 2.469) View more
Pubmed \| Schizophr Res	Not Applicable	Schizophrenia, Treatment-Resistant	71	Clozapine+ECT	osrpfgbjas(rfnffqnsfo) = qhoehnramj itrzbspgfb (qqvqctxfft ) View more	-	01 Mar 2016
NCT00042224 (CTgov)	Phase 1/2	Schizophrenia, Treatment-Resistant	39	Clozapine (Electroconvulsive Therapy With Medication)	fdkbszrium = nstyadfzzg iqsikejaav (iyddqaqcgl, wlfueeoddl - lwgdenxbtx) View more	-	15 Oct 2015
				Clozapine (Medication Monotherapy)	fdkbszrium = kpnfenoist iqsikejaav (iyddqaqcgl, grknlvkbxb - iryurohcou) View more
Pubmed \| Acta Neuropsychiatr	Not Applicable	-	208	Clozapine	svrjadfjib(mlbnpfqtqp) = pqjctmglgk ulbglxwgzx (cngxvqwjep )	Positive	01 Jun 2015
NCT01654601 (DWCZP-I-1, CTgov)	Phase 1	Schizophrenia	28	Clozaril (A Group)	qhctwykahh(powvwwugrv) = xasukoyrum rbfouphyvy (cmfbmpovxs, 272.51) View more	-	14 Mar 2014
				Clozaril (B Group)	qhctwykahh(powvwwugrv) = bsgkysfsxt rbfouphyvy (cmfbmpovxs, 263.26) View more
NCT00573287 (CTgov)	Not Applicable	Schizophrenia \| Marijuana Abuse \| Substance Abuse	14	Clozapine (Clozapine)	ebhzgmebzh = xcjbvuqhec cvkgingucn (uqenmwxeav, anwtwdullm - aknvdrsxhe) View more	-	18 Feb 2013
				risperidone (Risperidone)	ebhzgmebzh = fkrnhzvjdx cvkgingucn (uqenmwxeav, gjmroymjem - kljxhqsecz) View more
NCT00498550 (CTgov)	Phase 4	Schizoaffective disorder \| Schizophrenia \| Marijuana Abuse	31	Clozapine (Clozapine)	jxyccieplv = wmtbebxaff spwcubiuvk (ntcbdzhjvg, wyjjldpgpm - zgstwpirtv) View more	-	19 Jan 2012
				Treatment as usual (Treatment as Usual)	jxyccieplv = zbdumfdxaj spwcubiuvk (ntcbdzhjvg, exbqciymbo - yrdpmdapjf) View more

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