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

Novartis Pharma KK

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

144

Clinical Trials associated with Clozapine

NCT07085195

/ Not yet recruitingEarly Phase 1IIT

A Clinical Study of the Safety and Efficacy of Chemogenetics Therapy in the Treatment of Parkinson's Disease

The investigators propose a gene therapy strategy using chemical genetic inhibition to intervene in the abnormal activity of the subthalamic nucleus in Parkinson's disease. The investigators design and construct a highly efficient therapeutic injection STP-001 (first drug), through the efficient adeno-associated virus capsid (AAV), neuronal promoter (hSyn), and chemical genetic effector element (hM4Di), and accurately inject the drug into the bilateral subthalamic nucleus, the core pathological nucleus of Parkinson's disease, through stereotactic technology. Combined with a very low dose of clozapine (the second drug), the abnormal activity of the subthalamic nucleus is precisely intervened to improve the core motor symptoms of Parkinson's disease.

Start Date01 Aug 2025

Sponsor / Collaborator

Ruijin Hospital

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]

ACTRN12625000567426

/ Not yet recruitingNot ApplicableIIT

The effect of a pharmacist-led intervention on medication adherence and the quality use of medicines in people using clozapine attending the Colombo south teaching hospital, Sri Lanka

Start Date04 Jun 2025

Sponsor / Collaborator

Griffith University

100 Clinical Results associated with Clozapine

100 Translational Medicine associated with Clozapine

100 Patents (Medical) associated with Clozapine

16,823

Literatures (Medical) associated with Clozapine

01 Nov 2025·JOURNAL OF AFFECTIVE DISORDERS

Relationship between regional prescriptions of lithium and clozapine and suicide mortality in children and adolescents in France between 2014 and 2019

Article

Author: Cohen, David ; Consoli, Angèle ; Guez, Edouard ; Benarous, Xavier ; Melchior, Maria ; Rojas-Chaves, Alejandro ; Van Der Waerden, Judith ; Pellerin, Hugues

INTRODUCTION:

The protective effect of lithium and clozapine against suicide risk was reported in adults but remains unclear in the pediatric population.

METHOD:

This cross-sectional ecological study utilized a combination of health registers to collect information on drug prescriptions (OPENMEDIC national health insurance database), mortality (CepiDC national mortality register), medical demography (CNOM data) and social disadvantage (INSEE data), extracting data on subjects aged 0 to 19 years living in France from 2014 to 2019. The relationships between the regional variabilities in lithium and clozapine dispensations and different death rates: by suicide and self-injury, by mental and behavioral disorders, and all causes.

RESULTS:

Dispensations of lithium and clozapine varied widely by region. Inter-regional variabilities in lithium and clozapine dispensations were associated with mortality by suicide and self-injury in simple regression models (respectively, β = -0.006, p = .032 and β - 0.0104, p = .009) but not for other causes of mortality. Both dispensations were strongly correlated with social deprivation scores and the density of adult psychiatrists. In robust and multiple regression models, the level of association with suicide and self-injury mortality remained significant for clozapine but not for lithium.

DISCUSSION:

Keeping in mind the limitations inherent to spatial study design, these preliminary findings are consistent with a possible antisuicide effect of clozapine in the pediatric population, while the effect of lithium is less clear. Even in the context of the French free-of-charge healthcare system, major spatial inequities exist in access to these medications for youths, partly underlaid by social disparities and medical demography.

01 Oct 2025·BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Harnessing integrated bioinformatics to identify new diagnostic and therapeutic strategies for heart failure

Article

Author: Wang, Ruilin ; Shang, Min ; Fu, Guosheng ; Sun, Shuo ; Huang, Chengchen ; Lai, Chaojie

Heart failure (HF) is a life-threatening condition that poses a significant challenge on public health, particularly among the elder populations. To develop new diagnostic and therapeutic strategies for HF, we analyzed large-scale transcriptome sequencing data from HF patients as an exploratory approach. We identified 18 HF-related genes and developed a robust scoring model for HF diagnosis, by applying two machine learning algorithms for data analysis. Meanwhile, we evaluated and compared the predictive abilities of three bioinformatics methods in identifying potential HF treatment drugs. Significantly, an unconventional network-based proximity analysis, integrating multidimensional drug target information, outperformed other methods in the assessment of predictive ability. To validate these findings, we tested several candidate drugs in a mouse model transitioning from acute myocardial infarction (MI) to chronic HF. Among the candidates, mirtazapine exhibited cardioprotective effects in both early (1-week) post-MI and chronic HF (4-week post-MI) settings, while cabergoline showed potential efficacy primarily in the early post-MI phase. Additionally, the screened triamterene, used as a positive control, exhibited protective effects in both early post-MI and chronic HF stages. Mechanistic studies revealed that growth factor receptor-bound protein 14 and Ras-related protein Rab-3A were critical to the observed cardioprotection. These findings provide valuable evidence and insights for exploring potential therapeutic agents for HF treatment.

01 Oct 2025·PSYCHIATRY RESEARCH

Polypharmacy in clozapine-treated patients: A retrospective analysis of 667 patients in Ottawa, Canada

Article

Author: Hsieh, TiChen ; Preobrazenski, Nicholas ; Owoeye, Olabisi ; Robertson, Carrie ; Thai, Helen

BACKGROUND:

Clozapine is the gold standard for treatment-resistant schizophrenia (TRS), yet only 40 % of patients respond. Clinicians often add other psychotropics despite limited evidence and possible harms. Canadian data on this practice remains sparse.

METHODS:

We retrospectively reviewed charts of 667 adults prescribed clozapine between 2017-2020 in Ottawa, Canada. Clozapine augmentation was defined as prescription of ≥1 other psychotropic medication. Descriptive statistics summarized medication class frequences; X² or Wilcoxon tests assessed associations with demographic and clinical variables.

RESULTS:

After excluding four charts without medication data, 550/663 patients (83 %) received at least one add-on class (median 2 classes, IQR 1-3). Anti-psychotics were the commonest add-ons with 354 patients (53.4 % of all; 64.4 % of the augmented group) receiving clozapine plus another antipsychotic, most often aripiprazole (n=83). Valproate/divalproex was the commonest add-on (n=115). Clozapine with Paliperidone was the most frequent two-drug combination (n=29). Augmentation was more frequent in schizoaffective disorder than schizophrenia (91 vs. 81 %, p=0.010), in older adults (median 46 vs. 38 yrs, p<0.001), in females (88 vs. 81 %, p=0.028), and in patients with respiratory disease (p=0.015) or diabetes (p=0.019). Residence in supported or inpatient housing was also associated with augmentation (p<0.001). Recent hospitalization, current smoking, and self-reported ethnicity showed no association with augmentation (p≥0.33).

CONCLUSIONS:

Clozapine polypharmacy is common in patients treated at this Canadian psychiatric hospital, with more than half of clozapine-treated patients receiving an additional antipsychotic. This high prevalence highlights a need for evidence-based guidelines and integrated monitoring to balance symptomatic benefit against additive pharmacologic risk in TRS.

News (Medical) associated with Clozapine

14 Aug 2025

·hlstherapeutics.com

HLS Therapeutics Announces Q2 2025 Financial Results

Adjusted EBITDA grew 21% in Q2 and 29% year-to-date Cash from operations grew 83% in Q2 and 147% year-to-date Made principal repayments on the Company's long-term debt totalling $8.5 million Expanded cardiovascular portfolio by licensing Canadian rights to NEXLETOL® and NEXLIZET® from Esperion Therapeutics TORONTO, Aug. 14, 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 and six months ended June 30, 2025 ("Q2 2025" and "year-to-date"). All amounts are in thousands of United States ("U.S.") dollars unless otherwise stated. Q2 & YEAR-TO-DATE 2025 FINANCIAL HIGHLIGHTS (comparisons are to the respective 2024 periods) Q2 2025 revenue was $14.2 million, Adjusted EBITDA1 was $5.2 million and cash from operations was $4.6 million, compared to $14.5 million, $4.3 million and $2.5 million, respectively. Year-to-date 2025 revenue was $26.8 million, Adjusted EBITDA was $9.0 million and cash from operations was $8.1 million, compared to $27 million, $7 million and $3.3 million, respectively. In local currency, combined Canadian product sales for Vascepa and Clozaril were flat in Q2 2025 and were up 6% year-to-date. US sales of Clozaril were up 1% in Q2 2025 and were up 2% year-to-date. Excluding cost of sales, operating expenses decreased 18% in Q2 2025 and 19% year-to-date. Vascepa made a positive contribution to Adjusted EBITDA in Q2 2025 for the third straight quarter. Q2 2025 CORPORATE HIGHLIGHTS Announced in-license agreement with Esperion Therapeutics Inc. (NASDAQ:ESPR) to commercialize NEXLETOL2 and NEXLIZET2 in Canada. Made principal repayments on the Company's long-term debt totalling $8.5 million. Repurchased $0.8 million of common stock in Q2 2025. Year-to-date, the Company has purchased $1.0 million of common stock at an average price of C$4.56 per share. "Our year-to-date results reflect continued execution on our key strategic priorities as we position the Company to resume its growth trajectory," said Craig Millian, Chief Executive Officer at HLS. "We remain on track to achieve full-year guidance, with strong underlying performance demonstrated by 29% year-to-date Adjusted EBITDA growth, robust cash flow generation, and continued balance sheet strengthening through significant debt repayments." "Looking ahead, we're excited to introduce NEXLETOL and NEXLIZET in Canada, addressing an important treatment need for at-risk Canadian patients. These medicines have the potential to more than double the size of our cardiovascular business and will further establish HLS as a leading Canadian-based company focused on cardiovascular risk reduction. With Health Canada approval expected by year-end and launch planned for Q2 2026, we believe HLS is well-positioned for our next phase of growth." Q2 & YEAR-TO-DATE 2025 FINANCIAL REVIEWThe Company's Management's Discussion and Analysis and Consolidated Financial Statements for the three and six months ended June 30, 2025, are available at the Company's website and at its profile at SEDAR+. Revenue Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Product sales Canada 10,521 10,637 20,229 19,791 United States 3,502 3,462 6,220 6,104 14,023 14,099 26,449 25,895 Royalty revenue 148 420 345 1,097 14,171 14,519 26,794 26,992 Revenue for Q2 2025 decreased 2%, due primarily to lower royalty revenues and FX rate fluctuations. Year-to-date 2025, revenue was essentially flat with 2% growth in product revenue being offset by a 69% drop in royalty revenue. Product sales – Canada 000's of CAD Three months ended June 30, Six months ended June 30, 2025 2024 % change 2025 2024 % change Clozaril 8,589 9,131 (5.9) % 16,518 16,996 (2.8) % Vascepa 5,884 5,407 8.8 % 11,862 9,878 20.1 % Other 76 14 108 27 14,549 14,552 0.0 % 28,488 26,901 5.9 % Canadian product sales in local currency were flat in Q2 2025 and up 6% year-to-date, compared to the same periods last year. The Q2 2024 period benefited from the timing of certain orders shifting from Q1 2024 because of the Easter holiday timing last year. For this reason, the Company views year-to-date revenue as a more relevant measure for the comparison of year-over-year revenue performance. Product Sales – United States In the U.S. market, Clozaril revenue for the three and six months ended June 30, 2025, increased 1% and 2%, respectively, compared to the same prior year periods. Royalty revenues As expected, following the sale of the Xenpozyme royalty interest in Q2 2024, royalty revenue has declined. Royalty revenue for the three and six months ended June 30, 2025, was down 65% and 69%, respectively, compared to the same periods last year. HLS has one remaining royalty interest which generated $0.15 million in revenue in Q2 2025. Operating Expenses Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Cost of product sales 2,505 2,303 4,903 4,077 Selling and marketing 3,046 4,561 5,876 9,087 Medical, regulatory and patient support 1,366 1,420 2,802 2,685 General and administrative 2,084 1,977 4,223 4,178 9,001 10,261 17,804 20,027 Cost of product sales increased for the three and six months ended June 30, 2025, due primarily to higher Vascepa sales volumes. Operating expenses in Q2 2025, excluding cost of product sales, decreased by 18% compared to Q2 2024, and by 19% for the year-to-date period. This was 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 selling and marketing expenses are expected to be moderately higher for the remainder of 2025 as several staff vacancies have now been filled. Adjusted EBITDA1 Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Net loss for the period (2,741) (5,682) (7,177) (11,788) Stock-based compensation 465 427 1,116 683 Amortization and depreciation 5,483 5,856 10,843 11,775 Finance and related costs, net 1,690 2,942 3,662 5,609 Other costs 31 (3,361) 327 (3,361) Income tax expense 242 4,076 219 4,047 Adjusted EBITDA 5,170 4,258 8,990 6,965 Adjusted EBITDA for the three and six months ended June 30, 2025, increased 21% and 29%, respectively, compared to the same periods last year. The increases were primarily due to steady performance from the Company's marketed products and the ongoing focus on cost management and were partially offset by FX fluctuations and the previously mentioned decline in royalty revenue. Excluding royalty revenue, Adjusted EBITDA for the three and six months ended June 30, 2025, would have increased 31% and 47%, respectively, compared to the same periods last year. In Q2 2025, the direct brand contribution from Clozaril to Adjusted EBITDA was $7.1 million, while the direct brand contribution from Vascepa to Adjusted EBITDA improved from negative $1.6 million in Q2 2024 to positive $0.1 million. Year-to-date, the direct brand contribution from Clozaril to Adjusted EBITDA was $12.9 million, while the direct brand contribution from Vascepa to Adjusted EBITDA improved from negative $3.2 million to positive $0.1 million. Net LossQ2 2025 net loss was ($2.7) million, or ($0.09) per share, compared to a net loss of ($5.7) million, or ($0.18) per share, in Q2 2024. Year-to-date net loss was ($7.2) million, or ($0.23) per share, compared to a net loss of ($11.8) million, or ($0.37) per share, in the same period last year. Net loss improved in both periods of 2025 due primarily to the previously noted factors that have positively impacted Adjusted EBITDA this year. Cash from Operations and Financial PositionCash generated from operations for the three and six months ended June 30, 2025, was $4.6 million and $8.1 million, compared to $2.5 million and $3.3 million in the same periods last year. This represents year-over-year increases of 83% and 147%, respectively. Total borrowings under the credit agreement at June 30, 2025, were $56.0 million compared to $67.4 million at December 31, 2024, and $84.9 million at June 30, 2024. This represents a reduction of 34% from June 30, 2024. During Q2 2025, HLS made principal payments on its term loan totaling $8.5 million and spent $0.8 million to purchase shares for cancellation under its Normal Course Issuer Bid. Year-to-date, HLS has made debt principal repayments of $11.4 million and under its share buyback program, has purchased 308,928 shares at a cost of $1 million since launching the buyback on March 17, 2025. Cash was $12.2 million at June 30, 2025, compared to $17.5 million at December 31, 2024. The decrease reflects the debt principal repayments, and the share buyback activity described previously, offset, in part, by the significant increase in cash from operations. 2025 OUTLOOKRevenue projections for the Company's Canadian product portfolio are denominated in local currency to account for ongoing FX rate fluctuations. 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. Q2 2025 CONFERENCE CALLHLS will hold a conference call today at 8:30 am Eastern Time to discuss its Q2 and year-to-date 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: 66543 DATE: Thursday, August 14, 2025 TIME: 8:30 a.m. ET WEBCAST LINK: https://app.webinar.net/Zo9wjb9V5KR 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/4kiYlSu TAPED REPLAY: 1-888-660-6345 or 1-289-819-1450 REPLAY CODE: 66543# 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. REFERENCES2: NEXLETOL® (bempedoic acid) and NEXLIZET® (bempedoic acid and ezetimibe) are the commercial brand names in the U.S. The brand names in Canada are 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 August 13, 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. INTERIM CONSOLIDATED STATEMENTS OF FINANCIAL POSITION Unaudited [in thousands of U.S. dollars] As at As at June 30, 2025 December 31, 2024 ASSETS Current Cash 12,153 17,456 Accounts receivable 8,968 7,454 Inventories 6,823 9,058 Income taxes recoverable 80 71 Other current assets 2,011 1,361 Total current assets 30,035 35,400 Property, plant and equipment 1,048 997 Intangible assets 116,047 122,122 Deferred tax asset 1,386 857 Other non-current assets 556 528 Total assets 149,072 159,904 LIABILITIES AND SHAREHOLDERS' EQUITY Current Accounts payable and accrued liabilities 8,339 8,709 Provisions 11,814 8,367 Debt and other liabilities 7,025 5,317 Income taxes payable 411 152 Total current liabilities 27,589 22,545 Debt and other liabilities 50,799 61,944 Deferred tax liability 4,125 4,074 Total liabilities 82,513 88,563 Shareholders' equity Share capital 258,063 260,595 Contributed surplus 14,788 15,136 Accumulated other comprehensive loss (6,458) (10,210) Deficit (199,834) (194,180) Total shareholders' equity 66,559 71,341 Total liabilities and shareholders' equity 149,072 159,904 HLS THERAPEUTICS INC. INTERIM CONSOLIDATED STATEMENTS OF LOSS Unaudited [in thousands of U.S. dollars, except per share amounts] Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Revenue 14,171 14,519 26,794 26,992 Expenses Cost of product sales 2,505 2,303 4,903 4,077 Selling and marketing 3,046 4,561 5,876 9,087 Medical, regulatory and patient support 1,366 1,420 2,802 2,685 General and administrative 2,084 1,977 4,223 4,178 Stock-based compensation 465 427 1,116 683 Amortization and depreciation 5,483 5,856 10,843 11,775 Finance and related costs, net 1,690 2,942 3,662 5,609 Other costs (income) 31 (3,361) 327 (3,361) Loss before income taxes (2,499) (1,606) (6,958) (7,741) Income tax expense 242 4,076 219 4,047 Net loss for the period (2,741) (5,682) (7,177) (11,788) Net loss per share: Basic and diluted $(0.09) $(0.18) $(0.23) $(0.37) HLS THERAPEUTICS INC. INTERIM CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS Unaudited [in thousands of U.S. dollars] Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 Net loss for the period (2,741) (5,682) (7,177) (11,788) Item that may be reclassified subsequently to net loss Unrealized foreign currency translation adjustment 3,440 (963) 3,752 (3,336) Comprehensive income (loss) for the period 699 (6,645) (3,425) (15,124) 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 as at December 31, 2024 260,595 15,136 (10,210) (194,180) 71,341 Shares repurchased (2,532) — — 1,523 (1,009) Change in share purchase obligation — (878) — — (878) Stock option expense — 530 — — 530 Net loss for the period — — — (7,177) (7,177) Unrealized foreign currency translation adjustment — — 3,752 — 3,752 Balance as at June 30, 2025 258,063 14,788 (6,458) (199,834) 66,559 Balance as at December 31, 2023 262,127 13,865 (2,838) (175,457) 97,697 Shares repurchased (1,532) — — 932 (600) Change in share purchase obligation — 300 — — 300 Stock option expense — 433 — — 433 Net loss for the period — — — (11,788) (11,788) Unrealized foreign currency translation adjustment — — (3,336) — (3,336) Balance as at June 30, 2024 260,595 14,598 (6,174) (186,313) 82,706 HLS THERAPEUTICS INC. INTERIM CONSOLIDATED STATEMENTS OF CASH FLOWS Unaudited [in thousands of U.S. dollars] Three months ended June 30, Six months ended June 30, 2025 2024 2025 2024 OPERATING ACTIVITIES Net loss for the period (2,741) (5,682) (7,177) (11,788) Adjustments to reconcile net loss to cash provided by operating activities Stock-based compensation 465 427 1,116 683 Amortization and depreciation 5,483 5,856 10,843 11,775 Gain on royalty sale — (3,381) — (3,381) Accreted interest expense 302 277 610 559 Fair value adjustment on financial assets and liabilities — 318 — 505 Deferred income taxes (189) 3,861 (478) 3,800 Net change in non-cash working capital balances related to operations 1,284 843 3,233 1,144 Cash provided by operating activities 4,604 2,519 8,147 3,297 INVESTING ACTIVITIES Intangible asset acquisition (1,000) — (1,000) — Additions to property, plant and equipment (87) — (108) (2) Proceeds from royalty sale — 13,250 — 13,250 Cash provided by (used in) investing activities (1,087) 13,250 (1,108) 13,248 FINANCING ACTIVITIES Shares repurchased (833) (317) (1,009) (600) Repayment of credit agreement borrowing (8,481) (1,493) (11,441) (3,568) Debt costs — (658) — (1,191) Lease payments (151) (112) (294) (255) Cash used in financing activities (9,465) (2,580) (12,744) (5,614) Net increase (decrease) in cash during the period (5,948) 13,189 (5,705) 10,931 Foreign currency translation 367 (117) 402 (368) Cash, beginning of period 17,734 19,443 17,456 21,952 Cash, end of period 12,153 32,515 12,153 32,515 SOURCE HLS Therapeutics Inc.

Financial Statement

16 Jun 2025

·www.einpresswire.com

S&PAA Launches New Education Series to Remove Barriers to Treatment & Recovery

S&PAA Launches Its First Curriculum in Partnership with AAPP to Advance Knowledge of Clozapine and Clozapine Management with Elimination of the REMS Program ALEXANDRIA, VA, UNITED STATES, June 16, 2025 / EINPresswire.com / -- Friday, the FDA announced the final steps in eliminating the Clozapine Risk Evaluation and Mitigation Strategy (REMS) regulations by modifying the labeling to reflect their February 24, 2025, decision to eliminate the REMS program. Terminating REMS is expected to help patients more easily access clozapine and marks a pivotal moment for schizophrenia treatment—but without swift and widespread education, patients may still face unnecessary barriers to accessing this important medication. To address this urgent gap, the Schizophrenia & Psychosis Action Alliance (S&PAA) announced today the upcoming development of “ A New Era in Clozapine Management ”, a set of clinical, evidence-based courses designed to provide rapid education and appropriate dispensing guidance for clozapine. The partnership is in collaboration with the American Association of Psychiatric Pharmacists (AAPP). The revocation of bloodwork monitoring and other administrative requirements is a direct result of S&PAA’s advocacy. Now, S&PAA has mobilized an education initiative to help clinicians lower treatment barriers by leveraging the increased flexibility in prescribing this medication for treatment-resistant schizophrenia. S&PAA Chief Executive Officer, Gordon Lavigne, said the advocacy that catalyzed this change represented the many voices from our community. “Navigating treatment for schizophrenia is incredibly challenging. We're thrilled to launch our first in a series of educational programs to address and access effective care and treatment outcomes.” Michelle Geier, a psychiatric pharmacist and President of AAPP, also weighed in. “Clozapine is a life-saving medication for those living with schizophrenia, but many clinicians have not received training on this medication nor managed and monitored patients on clozapine. This curriculum offering on clozapine is a huge step forward in ensuring that health care professionals have access to the information needed to save and improve patient lives.” However, confusion among prescribers and pharmacists could stall this progress. Many may hesitate to prescribe or dispense the medication due to lingering misconceptions about safety protocols and/or lack of experience with clozapine. Without clear guidance, outdated caution could continue to limit patient access—despite the FDA’s decisive action. The “A New Era in Clozapine Management” curriculum is an educational series developed in collaboration with AAPP. It builds on S&PAA’s broader educational mission, which includes comprehensive toolkits, national webinars, and many tailored resources to support everyone impacted by schizophrenia and psychosis—from individuals living with schizophrenia and related disorders to caregivers and the clinical professionals who support them. Launching in the fall, the community-sponsored modules will be available at no cost on the AAPP website and will be approved for pharmacy (ACPE) and medical credit (ACCME). Sign up now to stay tuned this summer for updates and opportunities to provide input. “There has never been a more important time to reintroduce clozapine with clarity and confidence,” said Michael Brisbin, an S&PAA advocate with lived experience of schizophrenia. “This medication put me on the path to recovery. Together, we’re closing the knowledge gap and opening doors to better care.” Erica Tingler Schizophrenia & Psychosis Action Alliance +1 330-697-3905 email us here Visit us on social media: LinkedIn Instagram Facebook YouTube X Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

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

100 Deals associated with Clozapine

External Link

KEGG	Wiki	ATC	Drug Bank
D00283	Clozapine	N05AH02	DB00363

R&D Status

10 top approved records.

to view more data

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

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02404155 (BEN, CTgov)	Not Applicable	Balkan Nephropathy \| Paranoid Schizophrenia \| Schizophrenia ... View more	274	Clozapine	vdjpfsiuir(otahtztovl) = nwgszhkfvj vgfnsbjcuj (igdivwsbps, 1271.5) View more	-	31 Jan 2023
NCT01639872 (CLOCS, CTgov)	Phase 4	Schizophrenia \| Marijuana Abuse	49	Clozapine (Clozapine)	pksouaqtqn = aqalrhzdss cqggjcfjkg (qdxqcfitdu, weuncwirea - xnzeppssym) View more	-	26 Dec 2019
				risperidone (Risperidone)	pksouaqtqn = mxpfzfkwuk cqggjcfjkg (qdxqcfitdu, nwrzgujuzw - edvyerqtej) View more
NCT00981526 (CTgov)	Phase 4	Schizoaffective disorder \| Schizophrenia	66	Olanzapine+Telmisartan+Clozapine (A: Telmisartan)	uavgyiruqb(ftjciheaiw) = zgxzgdwsab mmpwkbqgea (wtdnexrxgv, 1.4262) View more	-	19 Jun 2018
				Placebo+Olanzapine+Clozapine (B: Placebo)	uavgyiruqb(ftjciheaiw) = wapwtlwhyk mmpwkbqgea (wtdnexrxgv, 2.469) View more
Pubmed \| Schizophr Res	Not Applicable	Schizophrenia, Treatment-Resistant	71	Clozapine+ECT	vzaopyqulq(cfcljkrlmz) = hwglxfqlfw urgedpkodq (ajviyntpxl ) View more	-	01 Mar 2016
NCT00042224 (CTgov)	Phase 1/2	Schizophrenia, Treatment-Resistant	39	Clozapine (Electroconvulsive Therapy With Medication)	ymrdjhziob = iidxjhajtp yqxzybiqtc (ysuajxzabn, rosourafen - ejrwcdhxxy) View more	-	15 Oct 2015
				Clozapine (Medication Monotherapy)	ymrdjhziob = xinbotmgpy yqxzybiqtc (ysuajxzabn, ghxklxafae - ixusybpwmo) View more
NCT01654601 (DWCZP-I-1, CTgov)	Phase 1	Schizophrenia	28	Clozaril (A Group)	wbzwaxjiaz(abhzqtjybb) = tomqrrcoin ejtgtqotdl (etwhywzyei, 272.51) View more	-	14 Mar 2014
				Clozaril (B Group)	wbzwaxjiaz(abhzqtjybb) = dnkpwfqlsq ejtgtqotdl (etwhywzyei, 263.26) View more
NCT00573287 (CTgov)	Not Applicable	Schizophrenia \| Substance Abuse	14	Clozapine (Clozapine)	stnbietuik = yzzqxvqivf agxatnojxx (jcrklhscoi, pejhdfmlnh - uaeqlxdxvf) View more	-	18 Feb 2013
				risperidone (Risperidone)	stnbietuik = xqbibjgvhg agxatnojxx (jcrklhscoi, fejhasnfvq - xpgtlicbfc) View more
NCT00498550 (CTgov)	Phase 4	Schizoaffective disorder \| Schizophrenia \| Marijuana Abuse ... View more	31	Clozapine (Clozapine)	vlserebncp = ilnusxaffi prgtezuscd (oqhcuvsgac, yljnoeezzh - euhxedyhis) View more	-	19 Jan 2012
				Treatment as usual (Treatment as Usual)	vlserebncp = ogradfxxad prgtezuscd (oqhcuvsgac, vmgmvkbvgb - zvsmlbwikf) View more
NCT00001656 (CTgov)	Phase 4	Schizophrenia	25	Olanzapine (Olanzapine Group)	chkpbyiobv(pilouijdiq) = owzemjkxve axezanrnvt (zdpkpblmse, klnuvikcyb - jyvsefxgmt) View more	-	12 Apr 2011
				Clozapine (Clozapine Group)	chkpbyiobv(pilouijdiq) = ugbbhszrpk axezanrnvt (zdpkpblmse, rvpnxnvmhr - qrtunuxspy) View more
InterSePT (Pubmed)	Phase 3	Schizophrenia	980	Clozapine	edrirfnoif(jwzkoumula): hazard ratio = 0.76 (95% CI, 0.58 - 0.97)	Positive	01 Jan 2003
				Olanzapine

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis