As a result of ableism, people with disabilities (PWD) experience diagnostic overshadowing-attributing symptoms to disability rather than a potentially new or co-morbid condition. the goal of this researh is to identify and create understanding of what underlies and contributes to diagnostic overshadowing. The investigators plan to develop ways to reduce it, specifically ways to identify people with disabilities at risk of diagnostic overshadowing/diagnostic error. The investigators will also develop education programs and decision supports targeted to healthcare professionals. If it is effective, ways to reduce diagnostic overshadowing/diagnostic error will have been developed among people with disabilities.

Start Date01 Jan 2025

Sponsor / Collaborator

Rush University Medical Center

[+2]

KCT0009610 / Not yet recruitingPhase 4IIT

A single-arm, open-label study evaluating safety and efficacy of switching treatment to Enped tab (entecavir) in patients with chronic hepatitis B treated with Baraclude tab (ETV)

Start Date12 Aug 2024

Sponsor / Collaborator

GangNeung Asan Hospital

NCT06296147 / RecruitingNot ApplicableIIT

A Randomized, Controlled Trial: Impact on Patient Experience in Patients Assigned to Virtual Reality Headset; Aromatherapy Patch; Virtual Reality + Aromatherapy; or Standard of Care for Transperineal Prostate Biopsy

The purpose of this study is to evaluate if a VR headset and/or aromatherapy can be used to reduce patient pain, anxiety, and embarrassment during a transperineal biopsy (TPBx) compared to standard of care (SOC). The primary objective is to evaluate differences in self-reported pain, fear, or embarrassment during and after the procedure between the VR Group, Aromatherapy Group, VR+Aromatherapy Group, and the Control group.

Start Date20 May 2024

Sponsor / Collaborator

University of Pittsburgh

100 Clinical Results associated with Entecavir

100 Translational Medicine associated with Entecavir

100 Patents (Medical) associated with Entecavir

3,097

Literatures (Medical) associated with Entecavir

01 Dec 2025·CHILDS NERVOUS SYSTEM

Clinical and radiologic criteria to predict endoscopic third ventriculostomy success in non-communicating pediatric hydrocephalus

Article

Author: Pennacchietti, Valentina ; Thomale, Ulrich-W ; Tietze, Anna ; Cohrs, Gesa ; Schaumann, Andreas ; Tatoshvili, Davit ; Schulz, Matthias

Abstract:

Objective:

Endoscopic third ventriculocisternostomy (ETV) became the relevant treatment option for non-communicating pediatric hydrocephalus. ETV success was predicted in relation to age, diagnosis, and previous shunt implantation. Radiological factors are usually taken for indication decision-making. The aim of this study is to investigate radiological signs of non-communicating hydrocephalus for ETV success in a single-center retrospective analysis.

Patients and methods:

ETV interventions were collected from a 10-year period (2010–2019) from our institution. Clinical patient characteristics such as prematurity, age, diagnosis, and previous shunt treatment and follow-up in terms of possible shunt implantation or revision surgeries were investigated. Radiological data was retrieved from the in-house PACS system to analyze preoperative signs for noncommunicating hydrocephalus such as ventricular size, pressure gradients at the third ventricle, and any signs of obstruction from internal towards external cerebral spinal fluid communication. Fisher’s test was used to demonstrate the significance of each individual predictor. A multivariable model was built using the backward elimination method with multiple logistic regression.

Results:

From 136 ETV interventions, 95 met the inclusion criteria (age < 18 years; > 6-month follow-up; MR image data availability, treatment goal for shunt independence). In chi-square statistical evaluation of single parameters age > 6 months (OR 32.5; 95% CI 4.8–364), ventricular width (FOHR < 0.56; OR 6.1; 95% CI 2.2–16.3) and non-post-hemorrhagic hydrocephalus as underlying diagnosis (OR 13.1; 95% CI 1.9–163) showed significant increased odds ratio for shunt independence during follow-up. Logistic regression analysis for multiple parameters showed age > 6 months (OR 29.3; 95% CI 4.1–606) together with outward bulged lamina terminalis (OR 4.6; 95% CI 1.2–19.6), smaller FOHR (continuous parameter; OR 2.83 × 10−5; 95% CI 4.7 × 10−9–0.045), and non-4th-ventricular-outlet obstruction (4thVOO; OR 0.31; 95% CI 0.09–1.02) as significant factors for ETV success.

Conclusion:

ETV has become a relevant treatment for non-communicating hydrocephalus, with typical MR image characteristics. Analyzing radiological markers as predictors for success smaller ventricular width and outward displaced lamina terminalis was relevant in combination with age > 6 months. Since the analysis is based on single-center experience, a larger cohort of patients with a multi-center approach should further investigate the combined clinical and radiological criteria.

01 Jan 2025·Liver International

Safety, Pharmacokinetics and Antiviral Efficacy of Capsid Assembly Modulator Freethiadine in Healthy Volunteers and Chronic Hepatitis B Patients

Article

Author: Liu, Jingrui ; He, Qingwei ; Chen, Yujie ; Wu, Min ; Zhuang, Yulei ; Sun, Jixuan ; Niu, Junqi ; Zhang, Yingjun ; Ding, Yanhua ; Zhu, Jing ; Chen, Yunfu ; Zhu, Xiaoxue ; Xu, Jia ; Li, Cuiyun ; Li, Xiaojiao ; Luo, Lin ; Zhang, Hong

ABSTRACT:

Background and Aims:

Freethiadine is a novel hepatitis B virus capsid assembly modulator. Herein, we report the safety, tolerability, pharmacokinetics and 28‐day antiviral activities of freethiadine.

Methods:

The study consisted of two parts. Part 1 involved a single‐ascending‐dose, a multiple‐ascending‐dose and a food effect study. Part 2 was a double‐blind, double‐dummy, randomised, entecavir‐controlled, multi‐dose escalation study in chronic hepatitis B (CHB) patients.

Results:

A total of 88 healthy subjects and 40 patients with CHB were enrolled in this study. Freethiadine was well tolerated by both healthy subjects and patients. Among freethiadine‐treated patients with CHB, the most common drug‐related adverse event was alanine aminotransferase elevation (28.1%) (mostly grade 1 or 2). Both HEC160208 and its active metabolite, HEC142106, were rapidly absorbed and eliminated in plasma. Food intake did not significantly influence the exposure of either analyte. Following 28 days of treatment, the mean maximum HBV DNA declines from baseline were −2.76, −3.47, −3.56, −2.89 and −2.55 log10 IU/mL for the 100 mg BID, 200 mg QD, 200 mg BID and 300 mg QD of freethiadine or entecavir control cohorts, respectively; simultaneously, the mean maximum pregenomic RNA (pgRNA) declines from baseline were −1.69, −2.26, −2.07, −1.47 and −0.06 log10 copies/mL, respectively.

Conclusions:

Freethiadine has an acceptable safety profile and favourable antiviral activity in patients with CHB. These results support further investigations of freethiadine for the treatment of chronic HBV infection.

Trial Registration:

www.clinicaltrials.gov identifier NCT05391360; www.chinadrugtrials.org.cn identifier CTR20212114

01 Jan 2025·Hepatology (Baltimore, Md.)

Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN Trials

Article

Author: Gehring, Adam J. ; Feld, Joshua B. ; Feld, Jordan J. ; Perrillo, Robert P. ; Salimzadeh, Loghman ; Janssen, Harry L.A. ; Lin, Hsing-Hua Sylvia ; Zahoor, Muhammad Atif ; Schwarz, Kathleen B. ; Chung, Raymond T. ; Mosa, Alexander I.

Background & Aims::

Pegylated interferon-α (PegIFNα) is of limited utility during immunotolerant or immune active phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some patients receiving treatment are associated with limited/no virological responses. The study aimed to determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies.

Approach & Results::

Pre-treatment, on-treatment, and post-treatment sera from 61 immunotolerant trial participants on PegIFNα/entecavir therapy and 88 immune active trial participants on PegIFNα/tenofovir therapy were screened for anti-IFNα antibodies by indirect ELISA. The neutralization capacity of antibodies was measured by preincubation of sera±recombinant human IFNα added to Huh7 cells with the measurement of interferon-stimulated gene (ISG)-induction by qPCR. Correlations between serum-induced ISG inhibition, presence, and titer of anti-IFNα antibodies and virological responses were evaluated. Preincubation of on-treatment serum from 26 immunotolerant (43%) and 13 immune active (15%) participants with recombinant-human IFNα markedly blunted ISG-induction in Huh7 cells. The degree of ISG inhibition correlated with IFNα antibody titer (p < 0.0001; r = 0.87). On-treatment development of anti-IFNα neutralizing antibodies (nAbs) was associated with reduced quantitative HBsAg and qHBeAg declines (p < 0.05) and inhibited IFNα bioactivity to 240 weeks after PegIFNα cessation. Children developed anti-IFNα nAbs more frequently than adults (p = 0.004) but nAbs in children had less impact on virological responses.

Conclusions::

The development of anti-IFNα nAbs during PegIFNα treatment diminishes responses to antiviral therapy. Understanding how and why anti-IFNα antibodies develop may allow for the optimization of IFN-based therapy, which is critical given its renewed use in HBV-cure strategies.

News (Medical) associated with Entecavir

06 Nov 2024

·www.globenewswire.com

Denali Therapeutics Reports Third Quarter 2024 Financial Results and Business Highlights

SOUTH SAN FRANCISCO, Calif., Nov. 06, 2024 (GLOBE NEWSWIRE) -- Denali Therapeutics Inc. (Nasdaq: DNLI) today reported financial results for the third quarter ended September 30, 2024, and provided business highlights. "As leaders in pioneering a new class of therapeutics that cross the blood-brain barrier, we are making significant progress across our Transport Vehicle (TV)-enabled portfolio,” said Ryan Watts, Ph.D., Chief Executive Officer of Denali Therapeutics. “Within our Enzyme TV (ETV) franchise, we are on track to file for accelerated approval of tividenofusp alfa in MPS II in early 2025 after a successful meeting with the FDA in the third quarter. Today, we are also pleased to share that preliminary data from our Phase 1/2 study of DNL126 in MPS IIIA demonstrate a robust reduction from baseline in CSF heparan sulfate levels, including normalization. Based on these data and a positive regulatory environment, we recently expanded the study to support a potential accelerated path. In addition, our recent preclinical publication on our oligonucleotide TV (OTV) technology in Science Translational Medicine, which describes broad and deep brain biodistribution of oligonucleotides following systemic administration of OTV, demonstrates the power and potential of our TV platform to transform the way we treat brain diseases.” Third Quarter 2024 and Recent Program Updates Late-stage and mid-stage clinical programs Tividenofusp alfa (DNL310): Enzyme Transport Vehicle (ETV)-enabled, iduronate-2-sulfatase (IDS) replacement therapy in development for MPS II (Hunter syndrome) In September, announced the outcome of a successful meeting with the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA) providing a path to filing a biologics license application (BLA) for accelerated approval and subsequent conversion to full approval for tividenofusp alfa (DNL310) for the treatment of MPS II. Agreement was reached that cerebrospinal fluid heparan sulfate (CSF HS) is reasonably likely to predict clinical benefit and can be used as a surrogate endpoint to support accelerated approval for tividenofusp alfa in MPS II. Denali intends to submit the BLA under the accelerated approval pathway in early 2025.In September, presented new interim data from the Phase 1/2 study at the Society for the Study of Inborn Errors of Metabolism (SSIEM 2024), including data from additional study participants (N=37) and longer duration of treatment with tividenofusp alfa (up to Week 129) as well as new analyses on biomarkers and clinical outcomes.COMPASS, the global Phase 2/3 study, is expected to complete enrollment in 2024. DNL343: eIF2B activator in development for the treatment of amyotrophic lateral sclerosis (ALS) DNL343 is being evaluated in Regimen G (DNL343) of the Phase 2/3 HEALEY ALS Platform Trial conducted by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) in collaboration with the Northeast ALS Consortium (NEALS). Enrollment in Regimen G is complete. SAR443820/DNL788: CNS-penetrant RIPK1 inhibitor In October, Denali was informed by its strategic partner Sanofi that the K2 Phase 2 study evaluating the safety and efficacy of oditrasertib (SAR443820/DNL788) on serum neurofilament light chain levels in participants with multiple sclerosis was discontinued based on not meeting the primary and key secondary endpoints. BIIB122/DNL151: LRRK2 inhibitor in development for the treatment of Parkinson’s disease (PD) Biogen is conducting the ongoing global Phase 2b LUMA study of BIIB122 in participants with early-stage Parkinson’s disease.Denali has initiated screening of participants for the global Phase 2a study to evaluate safety and biomarkers associated with BIIB122 in participants with Parkinson’s disease and confirmed pathogenic variants of LRRK2. This study is being funded under the Collaboration and Development Funding Agreement with a third party. Eclitasertib (SAR443122/DNL758): Peripheral RIPK1 inhibitor in development for the treatment of ulcerative colitis (UC) Sanofi is conducting the ongoing Phase 2 study of SAR443122/DNL758 in participants with UC. Early-stage clinical and preclinical programs DNL126: ETV-enabled N-sulfoglucosamine sulfohydrolase (SGSH) replacement therapy in development for the treatment of MPS IIIA (Sanfilippo syndrome Type A) Denali today announced that preliminary data from up to 25 weeks of dosing in the ongoing open-label Phase 1/2 study in MPS IIIA participants demonstrate a significant reduction in CSF HS levels from baseline, including normalization. The safety profile supports continued development. The most frequent treatment emergent adverse events were infusion related reactions of mild and moderate severity in all participants. There was one serious adverse event considered by the investigator not related to drug. Denali plans to present the data at a future medical meeting.Based on the preliminary Phase 1/2 results and a positive regulatory environment, Denali recently expanded the study and continues to assess the development plans including an accelerated approval path.DNL126 was selected in June 2024 for the FDA's Support for clinical Trials Advancing Rare disease Therapeutics (START) program to accelerate the development of rare disease therapeutics, and collaborative engagement has commenced to support progress to a pre-BLA meeting. TAK-594/DNL593: Protein Transport Vehicle (PTV)-enabled progranulin (PGRN) replacement therapy in development for the treatment of frontotemporal dementia-granulin (FTD-GRN) Screening of participants for Cohort B2 in the Phase 1/2 study is ongoing. Oligonucleotide Transport Vehicle (OTV) platform Denali is advancing OTV:MAPT, targeting tau for Alzheimer’s disease, and OTV:SNCA, targeting alpha-synuclein for Parkinson’s disease, in the investigational new drug (IND)-enabling stage of development.In August, announced publication of nonclinical data in the August 14, 2024 issue of Science Translational Medicine (link) demonstrating the ability of the OTV platform to achieve broad biodistribution of antisense oligonucleotides (ASOs) in the central nervous system and skeletal and cardiac muscle following intravenous administration. Antibody Transport Vehicle Amyloid beta (ATV:Abeta) program Denali is working to develop the next generation of anti-amyloid beta therapeutics with ATV:Abeta, which is designed to increase exposure of the therapeutic antibody and achieve broad biodistribution in the brain with the potential for improved efficacy and safety. Preclinical data demonstrated potential for a wider therapeutic window compared to a standard antibody, with superior plaque decoration and reduction and very low rates of amyloid related imaging abnormalities (ARIA). These data are included in a manuscript posted on bioRxiv (link).Denali plans to advance a TfR-targeting ATV:Abeta molecule as well as a CD98hc-targeting ATV:Abeta molecule into development for Alzheimer's disease. Discovery programs Denali applies its deep scientific expertise in neurodegeneration biology and the BBB to discover and develop medicines and platforms with the focus on programs enabled by the TV technology and targeting neurodegenerative disease, including Alzheimer’s and Parkinson’s, and lysosomal storage diseases. 2024 Guidance on Operating Expenses Cash, cash equivalents, and marketable securities were approximately $1.28 billion as of September 30, 2024. Denali is providing updated guidance on cash operating expenses for the full year 2024 and now anticipates an increase of approximately 5-10% compared to 2023, which is an increase from previous guidance of equal to or less than full year 2023 cash operating expenses. This updated guidance is associated with increased activities to support filing of a BLA in early 2025 and commercial readiness for tividenofusp alfa in MPS II, and to accelerate the development of additional therapeutic programs in Denali's TV platform portfolio. Participation in Upcoming Investor Conferences UBS Global Healthcare Conference, November 11-14B. Riley Securities’ Next-Gen Tissue Delivery Modalities Virtual Summit, November 14Stifel 2024 Healthcare Conference, November 18-19Jefferies London Healthcare Conference, November 19-217th Annual Evercore ISI HealthCONx Conference, December 3-5 Third Quarter 2024 Financial Results Net losses were $107.2 million and $99.4 million for the three months ended September 30, 2024 and 2023, respectively. There was no collaboration revenue for the quarter ended September 30, 2024, compared to $1.3 million for the quarter ended September 30, 2023. The decrease in collaboration revenue was primarily due to activities under the Biogen Collaboration Agreement. Total research and development expenses were $98.2 million for the quarter ended September 30, 2024, compared to $89.7 million for the quarter ended September 30, 2023. The increase of approximately $8.5 million for the quarter ended September 30, 2024 was primarily attributable to increases in costs in various clinical stage programs, including ETV:IDS, eIF2B, ETV:SGSH, and LRRK2 reflecting the continued progress of these programs in clinical trials, and increases in TV platform and other program external expenses, reflecting continued investment in TV-enabled product candidates. These increases were partially offset by a decrease in personnel and external expenses associated with the divestiture of Denali’s preclinical small molecule programs. General and administrative expenses were $24.9 million for the quarter ended September 30, 2024, and $25.3 million for the same period in 2023. About Denali Therapeutics Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for the treatment of neurodegenerative diseases and lysosomal storage diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB, and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit www.denalitherapeutics.com. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding expectations regarding Denali’s TV technology platform; statements made by Denali’s Chief Executive Officer; plans, timelines, and expectations regarding DNL310 and the ongoing Phase 2/3 COMPASS and Phase 1/2 studies, the timing and likelihood of accelerated approval, and the timing and availability of program updates; plans and timelines regarding DNL343, including the timing and availability of data from the Phase 2/3 HEALEY ALS Platform Trial; plans, timelines, and expectations of both Denali and Sanofi regarding DNL788; plans, timelines, and expectations regarding DNL151, including with respect to the ongoing LUMA study as well as enrollment and timing of the proposed Phase 2a study in PD patients with LRRK2 mutations; expectations regarding DNL758, including the ongoing Phase 2 study in patients with UC; plans, timelines, and expectations related to DNL126, including the timing and availability of data in the ongoing Phase 1/2 study and the timing and likelihood of regulatory approval; plans, timelines, and expectations of both Denali and Takeda regarding DNL593 and the ongoing Phase 1/2 study; plans, timelines, and expectations regarding the advancement of OTV:MAPT and OTV:SNCA towards clinical development; plans, timelines, and expectations regarding the ATV:Abeta program, including its therapeutic potential and the clinical advancement of ATV:Abeta molecules; plans and expectations for Denali's preclinical programs; Denali's future operating expenses and anticipated cash runway; and Denali's participation in upcoming investor conferences. All drugs currently being developed by Denali are investigational and have not received regulatory approval for any indication. Actual results are subject to risks and uncertainties and may differ materially from those indicated by these forward-looking statements as a result of these risks and uncertainties, including but not limited to, risks related to: any and all risks to Denali’s business and operations caused by adverse economic conditions; risk of the occurrence of any event, change, or other circumstance that could give rise to the termination of Denali’s agreements with Sanofi, Takeda, or Biogen, or any of Denali’s other collaboration agreements; Denali’s transition to a late-stage clinical drug development company; Denali’s and its collaborators’ ability to complete the development and, if approved, commercialization of its product candidates; Denali’s and its collaborators’ ability to enroll patients in its ongoing and future clinical trials; Denali’s reliance on third parties for the manufacture and supply of its product candidates for clinical trials; Denali’s dependence on successful development of its blood-brain barrier platform technology and its programs and product candidates; Denali’s and its collaborators' ability to conduct or complete clinical trials on expected timelines; the risk that preclinical profiles of Denali’s product candidates may not translate in clinical trials; the potential for clinical trials to differ from preclinical, early clinical, preliminary or expected results; the risk of significant adverse events, toxicities or other undesirable side effects; the uncertainty that product candidates will receive regulatory approval necessary to be commercialized; Denali’s ability to continue to create a pipeline of product candidates or develop commercially successful products; developments relating to Denali's competitors and its industry, including competing product candidates and therapies; Denali’s ability to obtain, maintain, or protect intellectual property rights related to its product candidates; implementation of Denali’s strategic plans for its business, product candidates, and blood-brain barrier platform technology; Denali's ability to obtain additional capital to finance its operations, as needed; Denali's ability to accurately forecast future financial results in the current environment; and other risks and uncertainties, including those described in Denali's most recent Annual and Quarterly Reports on Forms 10-K and 10-Q filed with the Securities and Exchange Commission (SEC) on February 28, 2024 and August 1, 2024, respectively, and Denali’s future reports to be filed with the SEC. Denali does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results, or to make changes in Denali’s expectations, except as required by law. Denali Therapeutics Inc.Condensed Consolidated Statements of Operations(Unaudited)(In thousands, except share and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Collaboration revenue: Collaboration revenue from customers(1)$— $1,267 $— $330,531 Other collaboration revenue — — — — Total collaboration revenue — 1,267 — 330,531 Operating expenses: Research and development(2) 98,238 89,737 296,653 316,073 General and administrative 24,949 25,325 75,379 78,585 Total operating expenses 123,187 115,062 372,032 394,658 Gain from divestiture of small molecule programs — — 14,537 — Loss from operations (123,187) (113,795) (357,495) (64,127)Interest and other income, net 15,995 14,442 49,475 38,376 Net loss$(107,192) $(99,353) $(308,020) $(25,751)Net loss per share, basic and diluted$(0.63) $(0.72) $(1.89) $(0.19)Weighted average number of shares outstanding, basic and diluted 169,456,988 137,644,534 162,589,325 137,076,199 __________________________________________________ (1) Includes related-party collaboration revenue from customers of $1.3 million and $295.5 million for the three and nine months ended September 30, 2023, respectively.(2) Includes expenses for cost sharing payments due to a related party of $3.4 million and $14.5 million for the three and nine months ended September 30, 2023, respectively. Denali Therapeutics Inc.Condensed Consolidated Balance Sheets(Unaudited)(In thousands) September 30, 2024 December 31, 2023Assets Current assets: Cash and cash equivalents$90,636 $127,106Short-term marketable securities 745,923 907,405Prepaid expenses and other current assets 32,280 29,626Total current assets 868,839 1,064,137Long-term marketable securities 445,463 —Property and equipment, net 50,822 45,589Operating lease right-of-use asset 23,717 26,048Finance lease right-of-use asset 38,685 —Other non-current assets 26,487 18,143Total assets$1,454,013 $1,153,917Liabilities and stockholders' equity Current liabilities: Accounts payable$9,594 $9,483Accrued clinical and other research & development costs 23,923 19,035Accrued manufacturing costs 9,568 15,462Accrued compensation 14,874 21,590Operating lease liability, current 8,036 7,260Deferred research and development funding liability, current 16,269 —Other accrued costs and current liabilities 4,829 5,152Total current liabilities 87,093 77,982Operating lease liability, less current portion 38,850 44,981Finance lease liability, less current portion 5,631 —Deferred research funding and development liability, less current portion 3,944 —Total liabilities 135,518 122,963Total stockholders' equity 1,318,495 1,030,954Total liabilities and stockholders’ equity$1,454,013 $1,153,917 Investor Contact:Laura Hansen, Ph.D.Vice President, Investor Relationshansen@dnli.com(650) 452-2747 Media Contact:Rich AllanFGS Global Rich.Allan@fgsglobal.com(503) 851-0807

Phase 2Financial StatementAccelerated Approval

22 Oct 2024

·www.globenewswire.com

Gyre Therapeutics Announces Last Patient Completed Pivotal Phase 3 Trial Evaluating F351 for CHB-Associated Liver Fibrosis

SAN DIEGO, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Gyre Therapeutics, Inc. (“Gyre”) (Nasdaq: GYRE), a self-sustainable, commercial-stage biotechnology company with clinical development programs focusing on a variety of chronic organ diseases, today announced that the last patient in Gyre Pharmaceuticals’ pivotal Phase 3 trial in the People’s Republic of China (“PRC”) evaluating F351 (hydronidone) for Chronic Hepatitis B (“CHB”)-associated liver fibrosis has completed the 52-week study. Gyre Pharmaceuticals expects to report topline data from this trial by the first quarter of 2025. “The final patient completing our pivotal F351 Phase 3 trial marks an important milestone for Gyre and our development pipeline. We are grateful to the patients, researchers, trial investigators, and various teams who supported this trial and look forward to sharing data in the first quarter of 2025,” said Han Ying, Ph.D., CEO of Gyre Therapeutics. “Furthermore, we are excited to potentially use these results to spur initiation of our Phase 2 clinical trial in the United States evaluating F351 for Metabolic Dysfunction-Associated Steatohepatitis (“MASH”)-associated fibrosis in 2025.” The randomized, double-blind, placebo-controlled, multicenter Phase 3 trial (NCT05115942) enrolled 248 patients across 39 clinical research hospitals in the PRC. Patients were randomized 1:1 to receive either F351 or placebo in addition to entecavir antiviral basic therapy for CHB. The primary endpoint is a decrease in liver fibrosis (as measured by the Ishak Scoring System) by at least one stage after 52 weeks of treatment relative to baseline. China’s National Medical Products Administration (“NMPA”) designated F351 as a “Breakthrough Therapy” in 2021. About Hydronidone (F351) F351 is a structural analogue of the approved anti-fibrotic drug Pirfenidone (approved in the PRC for the treatment of idiopathic pulmonary fibrosis) and has been shown to inhibit in vitro both p38γ kinase activity and TGF-β1-induced excessive collagen synthesis in hepatic stellate cells (“HSCs”), which are recognized as critical event in the development and progression of fibrosis in the liver. This is further supported by its anti-proliferative effects on the HSCs in the liver. In vitro anti-fibrotic effects of F351 were also confirmed in several established in vivo models of liver fibrosis, such as CCI4-induced liver fibrosis mouse model, DMN-induced liver fibrosis rat model, and HSA-induced liver rat model, as well as mouse model of MASH fibrosis (CCI4+Western High Fat Diet). About Gyre Therapeutics Gyre Therapeutics is a biopharmaceutical company headquartered in San Diego, CA, with a primary focus on the development and commercialization of F351 (Hydronidone) for the treatment of MASH-associated fibrosis in the U.S. Gyre’s development strategy for F351 in MASH is based on the Company’s experience in MASH rodent model mechanistic studies and CHB-induced liver fibrosis clinical studies. Gyre is also advancing a diverse pipeline in the PRC through its indirect controlling interest in Gyre Pharmaceuticals, including ETUARY therapeutic expansions, F573, F528, and F230. About Gyre Pharmaceuticals Gyre Pharmaceuticals is a commercial-stage biopharmaceutical company committed to the research, development, manufacturing and commercialization of innovative drugs for organ fibrosis. Its flagship product, ETUARY (Pirfenidone capsule), was the first approved treatment for IPF in the PRC in 2011 and has maintained a prominent market share (2023 net sales of $112.1 million). In addition, Gyre Pharmaceuticals is evaluating F351 in a Phase 3 clinical trial in CHB-associated liver fibrosis in the PRC, which is expected to readout topline data by the first quarter of 2025. F351 received Breakthrough Therapy designation by the National Medical Products Administration’s Center for Drug Evaluation in March 2021. Gyre Pharmaceuticals is also developing treatments for COPD, PAH and ALF/ACLF. In October 2023, Gyre Therapeutics acquired an indirect majority interest in Gyre Pharmaceuticals (also known as Beijing Continent Pharmaceuticals Co., Ltd.). Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, which statements are subject to substantial risks and uncertainties and are based on estimates and assumptions. All statements, other than statements of historical facts included in this press release, are forward-looking statements, including statements concerning: the expectations regarding Gyre’s research and development efforts, timing of expected clinical readouts, including timing of topline data from Gyre Pharmaceuticals’ Phase 3 clinical trial evaluating F351 for the treatment of CHB-associated liver fibrosis in the PRC, and the initiation of Gyre’s Phase 2 trial in the U.S. for F351. In some cases, you can identify forward-looking statements by terms such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “plan” or the negative of these terms, and similar expressions intended to identify forward-looking statements. These statements reflect our plans, estimates, and expectations, as of the date of this press release. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the forward-looking statements expressed or implied in this press release. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation: Gyre’s ability to execute on its clinical development strategies; positive results from a clinical trial may not necessarily be predictive of the results of future or ongoing clinical trials; the timing or likelihood of regulatory filings and approvals; competition from competing products; the impact of general economic, health, industrial or political conditions in the United States or internationally; the sufficiency of Gyre’s capital resources and its ability to raise additional capital. Additional risks and factors are identified under “Risk Factors” in Gyre’s Annual Report on Form 10-K for the year ended December 31, 2023 filed on March 27, 2024 and in other filings with the Securities and Exchange Commission. Gyre expressly disclaims any obligation to update any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law. For Investors:Stephen Jasperstephen@gilmartinir.com

Phase 2Phase 3Breakthrough TherapyDrug ApprovalClinical Result

22 Jul 2024

·www.globenewswire.com

Aligos Therapeutics Announces Clinical Collaboration with Xiamen Amoytop Biotech Co., Ltd.

Amoytop to sponsor a Phase 1b exploratory clinical study evaluating the efficacy and safety of ALG-000184 in combination with PEGBING® (Mipeginterferon alfa-2b) in CHB patients SOUTH SAN FRANCISCO, Calif., July 22, 2024 (GLOBE NEWSWIRE) -- Aligos Therapeutics, Inc. (Nasdaq: ALGS, “Aligos”), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in liver and viral diseases, today announced that it has entered into a clinical trial collaboration agreement with Xiamen Amoytop Biotech Co., Ltd. (“Amoytop”). Under the terms of the agreement, Amoytop will sponsor and perform a Phase 1b exploratory clinical study evaluating the efficacy and safety of ALG-000184 in combination with PEGBING® (Mipeginterferon alfa-2b) in chronic hepatitis B (CHB) patients in China. The clinical study is expected to begin after approval by the National Medical Products Administration in China. “We are pleased to build on our existing relationship with Amoytop, as they have proven to be a valuable partner,” stated Lawrence Blatt, Ph.D., MBA, Chairman, President, and Chief Executive Officer at Aligos Therapeutics. “We look forward to initiating this exploratory study to evaluate the combination of ALG-000184 with PEGBING®, one of the approved drugs for CHB patients in China, to assess the potential benefits of a combinatory approach.” ALG-000184 is a potent best/first-in-class oral small molecule capsid assembly modulator (CAM-E) being developed for CHB. It is designed to exploit the dual role of CAMs by disrupting hepatitis B cccDNA levels and its derived transcripts by reducing expression of viral markers such as DNA, RNA, and the relevant antigens (HBsAg, HBeAg, HBcrAg). Phase 1a studies have demonstrated after single and multiple daily doses that ALG-000184 was well-tolerated, with no safety signals observed, and demonstrated linear pharmacokinetics (PK) and excellent antiviral activity. In longer term Phase 1b studies of ALG-000184 300mg x ≤96 weeks ± entecavir (ETV), ALG-000184 monotherapy has demonstrated best-in-class reductions in HBV DNA, RNA, HBsAg, HBeAg, and HBcrAg without viral breakthrough to date. PEGBING®, independently developed by Amoytop, is the world's first 40kD pegylated interferon α-2b injection. With dual effects of inhibiting viral replication and enhancing immunity, PEGBING® is mainly used in the clinical treatment of viral hepatitis and is the first-line drug for the antiviral treatment of chronic hepatitis B, which plays an important role in improving the clinical cure rate of hepatitis B and reducing the risk of liver cancer. “We are pleased to deepen our cooperation in the field of liver disease treatment and look forward to working together to provide a new treatment solution for patients in need,” said Sun Li, Chairman and Chief Executive Officer at Amoytop. “Amoytop is committed to further optimizing the chronic hepatitis B combination treatment pathway and hopes that the cooperation will lead to better clinical value drugs and drug combinations.” The Phase 1b study will be a randomized, double blinded, active controlled study to evaluate the safety, pharmacokinetics, and antiviral activity of oral once daily doses of 300 mg ALG-000184 + PEGBING® + entecavir (ETV) compared with 300 mg ALG-000184 + ETV or PEGBING® + ETV in treatment naïve or currently-not-treated HBeAg-positive and nucleos(t)ide analog (NA) suppressed HBeAg-negative subjects with CHB for 48 weeks. About Aligos Aligos Therapeutics, Inc. is a clinical stage biopharmaceutical company that was founded in 2018 with the mission to become a world leader in the treatment of liver and viral diseases. Aligos’ strategy is to harness the deep expertise and decades of drug development experience its team has in liver and viral diseases to discover and develop potentially best-in-class therapeutics for metabolic dysfunction-associated steatohepatitis (MASH) and viruses with high unmet medical need such as hepatitis B and coronaviruses. For more information, please visit www.aligos.com or follow us on LinkedIn or X. About Xiamen Amoytop Biotech Co., Ltd. Xiamen Amoytop Biotech Co., Ltd. is an innovative biopharmaceutical company and a listed company on the Science and Technology Innovation Board (SSE STAR Market) in China, specializing in R&D, manufacturing and marketing of regular and long-acting recombinant protein drugs. Focusing on the R&D of immune-related cytokine medicines, Amoytop is committed to becoming a leader in solving cytokine medicine-based systemic immune problems, providing better solutions for major diseases (such as viral hepatitis, malignant tumors) and immunotherapy. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered “forward-looking statements,” including, without limitation, statements regarding Aligos’ financial results and performance as well as research and development activities, including regulatory status and the timing of announcements and updates relating to our regulatory filings and clinical trials. Such forward-looking statements are subject to substantial risks and uncertainties that could cause our development programs, future results, performance, or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties inherent in the drug development process, including Aligos’ clinical stage of development, the process of designing and conducting clinical trials, the regulatory approval processes, and other matters that could affect the sufficiency of Aligos’ capital resources to fund operations. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Aligos in general, see Aligos’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on May 7, 2024 and its future periodic reports to be filed or submitted with the Securities and Exchange Commission. Except as required by law, Aligos undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events. Aligos Therapeutics Investor Contact Jordyn TaraziVice President, Investor Relations & Corporate Communications+1 (650) 910-0427jtarazi@aligos.com Media Contact Michael FitzhughLifeSci Communicationsmfitzhugh@lifescicomms.com Xiamen Amoytop Biotech Co., Ltd. Investor Contact Liu Peiyu联系电话：86592-6889118邮箱：ir@amoytop.com Media Contact Wu Xueyan联系电话：86592-6889127邮箱：wxy@amoytop.com

Phase 1License out/inPhase 2

100 Deals associated with Entecavir

External Link

KEGG	Wiki	ATC	Drug Bank
D04008	Entecavir	J05AF10	DB00442

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hepatitis B, Chronic	US	Bristol Myers Squibb Co.	29 Mar 2005

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Chronic Disease	Phase 3	US	Bristol Myers Squibb Co.	01 Dec 2004
Chronic Disease	Phase 3	CA	Bristol Myers Squibb Co.	01 Dec 2004
Chronic Disease	Phase 3	HK	Bristol Myers Squibb Co.	01 Dec 2004
Chronic Disease	Phase 3	ID	Bristol Myers Squibb Co.	01 Dec 2004
Chronic Disease	Phase 3	PH	Bristol Myers Squibb Co.	01 Dec 2004
Chronic Disease	Phase 3	SG	Bristol Myers Squibb Co.	01 Dec 2004
Chronic Disease	Phase 3	TW	Bristol Myers Squibb Co.	01 Dec 2004
Chronic Disease	Phase 3	TH	Bristol Myers Squibb Co.	01 Dec 2004
Hepatitis B	Phase 3	US	Bristol Myers Squibb Co.	01 Sep 2002
Viremia	Phase 3	US	Bristol Myers Squibb Co.	01 Sep 2002

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04536337 (ALG-000184-201, EASL2024) Manual	Phase 1	Hepatitis B, Chronic	22	ALG-000184 + ETV	egzcqdsorc(asjgmklnmh) = In a multiple regression model, baseline HBsAg (< or ≥4 log10 IU/ ml) and steady state plasma ALG-001075 exposure (AUC or Ctrough) statistically significantly predicted change from baseline in HBsAg at week 24 (p < 0.00018, R2 = 0.65). paszvdaroh (rqogqudzor ) View more	Positive	01 Jun 2024
				ALG-000184
NCT04536337 (ALG-000184-201, EASL2024) Manual	Phase 1	Hepatitis B, Chronic	22	ALG-000184 + Entecavir	zfdzofobak(nhtenlrxcz) = vdewpgrqjo zagmeickzt (wzvqpvflml, 0.4) View more	Positive	01 Jun 2024
				ALG-000184	-
NCT03887702 (CTgov)	Phase 3	Hepatitis B \| Malignant Solid Neoplasm	4	Tenofovir Alafenamide+Tenofovir Disoproxil Fumarate+Entecavir (Arm 1 (TAF, TDF, Entecavir: Prophylactic))	jrujmadggh(vgyxskkotg) = nnixlvllcy mccjemvrww (gfensdqjne, ekspwvqoix - cjznswxlan) View more	-	20 May 2024
				Tenofovir Alafenamide+Tenofovir Disoproxil Fumarate+Entecavir (Arm 2 (TAF, TDF, Entecavir: Upon Indication))	jrujmadggh(vgyxskkotg) = moneinnsop mccjemvrww (gfensdqjne, bdfrkmcvon - atrdinugci) View more
NCT03083821 (CTgov)	Phase 1	Hepatitis B	6	Baraclude	rxtubgalbt(wrrcrwhstm) = otutrzbtys zokyvplfsc (laevnutkjt, rsxaaokqog - dsrtgdsfgo) View more	-	18 Nov 2023
AASLD2023	Not Applicable	Hepatitis B	194	Entecavir	hjgwqwarhy(mkclhmaujx) = rkungflfpi eqqdgzxtxy (nxfhdvmvlu, 18.0 - 31.0) View more	-	10 Nov 2023
AASLD2023	Not Applicable	Decompensated cirrhosis of liver	283	Entecavir	pzbxgdvsds(fyobtollyo) = hmvsflveso pfvglqixmx (eukmlgxlfd ) View more	-	10 Nov 2023
				Entecavir	pzbxgdvsds(fyobtollyo) = dkncxnpitn pfvglqixmx (eukmlgxlfd ) View more
AASLD2023	Not Applicable	Hepatitis B, Chronic	-	Entecavir (ETV)	mvcclejmrb(lmeibwwcee) = felkyicira vyqsqezfpu (jdhwaakrnh )	-	10 Nov 2023
				Tenofovir alafenamide (TAF)	mvcclejmrb(lmeibwwcee) = ukbdadxzwp vyqsqezfpu (jdhwaakrnh )
AASLD2023	Not Applicable	Hepatitis B, Chronic	268	Entecavir	bbtktonhqk(ockttivvsx) = sqaszcublr jedxvkxhvf (rjpqcpxitn ) View more	-	10 Nov 2023
				Tenofovir alafenamide	bbtktonhqk(ockttivvsx) = kccnsvbjed jedxvkxhvf (rjpqcpxitn ) View more
NCT04781647 (CTgov)	Phase 2	Hepatitis B, Chronic	54	ETV+ABI-H0731 (ABI-H0731 + ETV)	tdcqeoyawg(iccbrmjyin) = elirioxszg jcqnptmgop (awukodidiu, dckjzpgpkr - ckigyvtsxm) View more	-	06 Oct 2023
				Peg-IFNα+ETV+ABI-H0731 (ABI-H0731 + ETV + Peg-IFNα)	tdcqeoyawg(iccbrmjyin) = nmfyplthbw jcqnptmgop (awukodidiu, ppjpgoiwde - ckkjvjxxvx) View more

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