An Open-label, Randomized, Multi-Center Study to Evaluate the Efficacy and Safety of Induction Treatment with Melphalan/HDS Followed by Consolidation Treatment with Trifluridine-Tipiracil Plus Bevacizumab Versus Trifluridine-Tipiracil Plus Bevacizumab Alone in Patients with Refractory Metastatic Colorectal Cancer with Liver Dominant Disease

The goal of this clinical trial is to learn if using a liver-directed therapy with high dose chemotherapy followed by approved cancer treatment to treat patients with colorectal cancer that has spread to the liver is safe and tolerable. The clinical trial will also learn if the liver-directed therapy with high dose chemotherapy works on the disease in the liver. Investigators will compare the use of the liver-directed therapy with high dose chemotherapy followed by approved cancer treatment or approved cancer treatment alone.
Participants will:
* Undergo up to two liver-directed therapy with high dose chemotherapy procedures followed by approved cancer treatment or take approved cancer treatment alone
* Visit clinic at least every two weeks for checkups and tests
* Complete scans approximately every two months

Start Date01 May 2025

Sponsor / Collaborator

Delcath Systems, Inc.

NCT05251636 / Not yet recruitingPhase 3

A Double-Masked, Multi-center, Active Controlled Safety and Efficacy Study of Adjunct Episcleral Brachytherapy for Polypoid Choroidal Vasculopathy

This study is investigating the use of episcleral brachytherapy (ESB) adjunct to aflibercept compared to aflibercept monotherapy for the treatment of polyploid choroidal vasculopathy (PCV) in patients experiencing an inadequate response to anti-VEGF monotherapy.

Start Date01 Mar 2025

Sponsor / Collaborator

Salutaris Medical Devices, Inc.

NCT06567314 / Not yet recruitingPhase 2IIT

Phase 2 Study of Ivonescimab in Patients With Cutaneous Squamous Cell Carcinoma

To learn if ivonescimab can help to control advanced cSCC. The safety and effects of ivonescimab will also be studied.

Start Date28 Feb 2025

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

100 Clinical Results associated with VEGF-A

100 Translational Medicine associated with VEGF-A

0 Patents (Medical) associated with VEGF-A

14,080

Literatures (Medical) associated with VEGF-A

01 Feb 2025·Neural Regeneration Research

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Article

Author: Tse, Dennis Yan-yin ; Abokyi, Samuel

Retinal aging has been recognized as a significant risk factor for various retinal disorders, including diabetic retinopathy, age-related macular degeneration, and glaucoma, following a growing understanding of the molecular underpinnings of their development. This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches, focusing on the activation of transcription factor EB. Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies, such as exercise, calorie restriction, rapamycin, and metformin, in patients and animal models of these common retinal diseases. The review critically assesses the role of transcription factor EB in retinal biology during aging, its neuroprotective effects, and its therapeutic potential for retinal disorders. The impact of transcription factor EB on retinal aging is cell-specific, influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways. In vascular endothelial cells, transcription factor EB controls important processes, including endothelial cell proliferation, endothelial tube formation, and nitric oxide levels, thereby influencing the inner blood-retinal barrier, angiogenesis, and retinal microvasculature. Additionally, transcription factor EB affects vascular smooth muscle cells, inhibiting vascular calcification and atherogenesis. In retinal pigment epithelial cells, transcription factor EB modulates functions such as autophagy, lysosomal dynamics, and clearance of the aging pigment lipofuscin, thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization. These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis, neuronal synapse plasticity, energy metabolism, microvasculature, and inflammation, ultimately offering protection against retinal aging and diseases. The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases. Therefore, it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

01 Jan 2025·JOURNAL OF ETHNOPHARMACOLOGY

A TCM formula assists temozolomide in anti-melanoma therapy by suppressing the STAT3 signaling pathway

Article

Author: Zhang, Hong ; Yuan, Wang ; Ye, Li ; Yuxi, Liu ; Yang, Liu ; Tingting, Huang ; Kaihua, Long ; Hong, Zhang ; Lu, Wang

ETHNOPHARMACOLOGICAL RELEVANCE:

Temozolomide (TMZ) is a first-line therapeutic medication for melanoma. Nonetheless, it exhibits a relatively elevated toxicity profile, and falls short in terms of both effectiveness and median survival rate. Clinical research has demonstrated that the integration of traditional Chinese medicine (TCM) with chemotherapy in the treatment of melanoma can enhance efficacy and reduce toxicity. A TCM formula (SLE) containing Lonicera japonica Thunb. and Robinia pseudoacacia L. has shown anti-melanoma properties through the inhibition of STAT3 phosphorylation. In the genesis and advancement of melanoma, the STAT3 signaling pathway is essential.

AIM OF THE STUDY:

The aim of this study was to evaluate the effect of SLE combined with TMZ (SLE/TMZ) in inhibiting melanoma, and to explore the contribution of inhibiting the STAT3 signaling pathway in this effect.

MATERIALS AND METHODS:

Both A375 cells and B16F10 tumor-bearing mice were used for in vitro and in vivo experiments, respectively. In vitro assays included CCK8, crystal violet staining, flow cytometry, qRT-PCR, and Western blotting. Animal experiment indicators included tumor volume, tumor weight, mouse weight, and the proportion of mouse immune cells.

RESULTS:

SLE/TMZ inhibited the proliferation and growth of A375 cells, and also induced apoptosis. Additionally, SLE/TMZ synergistically inhibited tumor growth in the B16F10 melanoma mouse model and had immunomodulatory effects, increasing the proportion of Th, Tc, and NK cells and decreasing the proportion of MDSCs in the spleen of melanoma-bearing mice. qRT-PCR and Western blotting results confirmed that SLE/TMZ inhibited STAT3 phosphorylation and regulated its downstream factors, including Bcl2, Mcl1, CCND1, MYC, MMP2, MMP9, VEGFA, and FGF2. The inhibitory effect of SLE/TMZ on melanoma cell growth was considerably lessened when STAT3 was overexpressed at the cellular level.

CONCLUSION:

Synergistic anti-melanoma effects of SLE/TMZ have been observed in animal and cellular models. One of the mechanisms of SLE/TMZ that underlies its anti-melanoma actions is inhibition of the STAT3 pathway. This work offers pre-clinical pharmacological backing for the advancement of SLE as a therapeutic agent to be used in conjunction with TMZ for the treatment of melanoma.

01 Jan 2025·ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER

Relationship between autophagy and NLRP3 inflammasome during articular cartilage degradation in oestrogen-deficient rats with streptozotocin-induced diabetes

Article

Author: de Jesus Simões, Manuel ; Cerri, Paulo Sérgio ; da Silva Sasso, Gisela Rodrigues ; Sasso, Gisela Rodrigues da Silva ; Sasso-Cerri, Estela ; Florencio-Silva, Rinaldo ; Gil, Cristiane Damas

BACKGROUND:

Estrogen deficiency and Diabetes mellitus (DM) cause joint tissue deterioration, although the mechanisms are uncertain. This study evaluated the immunoexpression of autophagy and NLRP3-inflammasome markers, in rat articular cartilage with estrogen deficiency and DM.

METHODS:

Twenty rats were sham-operated (SHAM) or ovariectomized (OVX) and equally allocated into four groups: SHAM and OVX groups administered with vehicle solution; SHAM and OVX groups treated with 60 mg/kg/body weight of streptozotocin, intraperitoneally, to induce DM (SHAM-DM and OVX-DM groups). After seven weeks, the rats were euthanized, and their joint knees were processed for paraffin embedding. Sections were stained with haematoxylin-eosin, toluidine blue, safranin-O/fast-green or subjected to picrosirius-red-polarisation method; immunohistochemistry to detect beclin-1 and microtubule-associated protein 1B-light chain 3 (autophagy markers), NLRP3 and interleukin-1β (IL-1β) (inflammasome activation markers), along with matrix metalloproteinase-9 (MMP-9), Nuclear factor-kappa B (NFκB), and Vascular endothelial growth factor A (VEGF-A) were performed.

RESULTS:

Deterioration of articular cartilage and subchondral bone were greater in SHAM-DM and OVX-DM groups. Higher percentages of immunolabeled chondrocytes to NLRP3, IL-1β, MMP-9, NFκB, and VEGF-A, as well as lower percentages of chondrocytes immunolabeled to autophagy markers, were noticed in estrogen-deficient and diabetic groups. These differences were greater in the OVX-DM group. Percentages of immunolabeled chondrocytes showed negative correlation between autophagy markers v.s IL-1β, NLRP-3, MMP-9, NFκB, and VEGF-A, along with positive correlation between VEGF-A vs. MMP-9, NFκB, IL-1β, and NLRP3, and MMP-9 vs. NFκB.

CONCLUSIONS:

In conclusion, autophagy reduction and NLRP3 inflammasome activation in chondrocytes may be implicated in articular cartilage degradation, under estrogen-deficient and DM conditions. Moreover, the combination of estrogen deficiency and DM may potentiate those effects.

250

News (Medical) associated with VEGF-A

30 Sep 2024

·www.globenewswire.com

Opthea to Participate in the UBS Virtual Ophthalmology Day 2024

MELBOURNE, Australia and PRINCETON, N.J., Sept. 30, 2024 (GLOBE NEWSWIRE) -- Opthea Limited (ASX/NASDAQ: OPT, “Opthea”, the “Company”), a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD), today announced that management will participate in a fireside chat and be available for one-on-one investor meetings at the UBS Virtual Ophthalmology Day 2024 being held on October 2, 2024. UBS Virtual Ophthalmology Day 2024 Fireside chat: Wednesday, October 2, 2024, 4:00 PM ETPresenter:Frederic Guerard, PharmD, CEOWebcast link:https://kvgo.com/ubs/opthea-ltd-oct-2024 The webcast can also be accessed under “Events & Presentations” in the Investor Relations section of the Company’s website, www.opthea.com. About Opthea Opthea (ASX/NASDAQ:OPT) is a biopharmaceutical company developing novel therapies to address the unmet needs in the treatment of highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME). Opthea’s lead product candidate, sozinibercept, is being evaluated in two fully enrolled pivotal Phase 3 clinical trials (COAST, NCT04757636, and ShORe, NCT04757610) for use in combination with standard-of-care anti-VEGF-A monotherapies to improve the overall efficacy and deliver superior vision gains compared to standard-of-care anti-VEGF-A agents alone. To learn more, visit our website at www.opthea.com and follow us on X and LinkedIn. Investor Inquiries PJ Kelleher LifeSci Advisors, LLC Email: pkelleher@lifesciadvisors.com Phone: 617-430-7579 Media Inquiries Silvana Guerci-Lena NorthStream Global Partners Email: silvana@nsgpllc.com Join our email database to receive program updates: Tel: +61 (0) 3 9826 0399, Email: info@opthea.com Web: www.opthea.com Source: Opthea Limited

Phase 3

23 Sep 2024

·www.globenewswire.com

Opthea Joins the S&P/ASX 300 Index

MELBOURNE, Australia and PRINCETON, N.J., Sept. 23, 2024 (GLOBE NEWSWIRE) -- Opthea Limited (ASX/NASDAQ: OPT, “Opthea”, the “Company”), a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD), today announced that the Company joins the S&P/ASX 300 Index, effective Monday, September 23, 2024, prior to market open in Australia. “Opthea’s addition to the S&P/ASX 300 Index reflects the Company’s strengthened balance sheet with proceeds from the recent financing completed in July 2024. We also reached a significant milestone by completing enrollment of close to 2,000 patients in the sozinibercept Phase 3 wet AMD program,” said Frederic Guerard, PharmD, Chief Executive Officer of Opthea. “We believe our inclusion in the S&P/ASX 300 Index may further diversify the Company’s institutional shareholder base as we progress our Phase 3 pivotal program to anticipated topline data readouts of COAST in early Q2 calendar year 2025 and ShORe in mid calendar year 2025 and prepare the organization for a potential US FDA approval and launch.” The S&P/ASX indices measure the performance of ASX-listed companies across various sizes, industries, themes, and strategies. Each index is designed to represent a certain segment of the Australian equities market. The S&P/ASX 300 index, which is rebalanced semi-annually in March and September, measures the performance of 300 of Australia’s largest securities listed on the ASX by float-adjusted market capitalization. The index includes the large-cap, mid-cap, and small-cap components of the S&P/ASX index family. About Opthea Opthea (ASX/NASDAQ:OPT) is a biopharmaceutical company developing novel therapies to address the unmet need in the treatment of highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME). Opthea’s lead product candidate, sozinibercept, is being evaluated in two fully enrolled pivotal Phase 3 clinical trials (COAST, NCT04757636, and ShORe, NCT04757610) for use in combination with standard-of-care anti-VEGF-A monotherapies to improve overall efficacy and deliver superior vision gains compared to standard-of-care anti-VEGF-A agents. To learn more, visit our website at www.opthea.com and follow us on X and LinkedIn. Inherent risks of Investment in Biotechnology Companies There are a number of inherent risks associated with the development of pharmaceutical products to a marketable stage. The lengthy clinical trial process is designed to assess the safety and efficacy of a drug prior to commercialization and a significant proportion of drugs fail one or both of these criteria. Other risks include uncertainty of patent protection and proprietary rights, whether patent applications and issued patents will offer adequate protection to enable product development, the obtaining of necessary drug regulatory authority approvals and difficulties caused by the rapid advancements in technology. Companies such as Opthea are dependent on the success of their research and development projects and on the ability to attract funding to support these activities. Investment in research and development projects cannot be assessed on the same fundamentals as trading and manufacturing enterprises. Therefore, investment in companies specializing in drug development must be regarded as highly speculative. Opthea strongly recommends that professional investment advice be sought prior to such investments. Forward-Looking Statements This ASX announcement contains certain forward-looking statements, including within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. The words “expect”, “believe,” “should”, “could”, “may”, “will”, “plan” and other similar expressions are intended to identify forward-looking statements. Forward-looking statements in this ASX announcement include statements regarding the potential for sozinibercept to treat highly prevalent and progressive retinal diseases, including wet AMD, the expected timing for top-line data for Opthea’s Phase 3 clinical trials of sozinibercept, the potential US FDA approval and launch of sozinibercept and the expectation that the inclusion of the Company in the S&P/ASX 300 Index may further diversify the Company’s institutional shareholder base. Forward-looking statements, opinions and estimates provided in this ASX announcement are based on assumptions and contingencies which are subject to change without notice, as are statements about market and industry trends, which are based on interpretations of current conditions. Forward-looking statements are provided as a general guide only and should not be relied upon as an indication or guarantee of future performance. They involve known and unknown risks and uncertainties and other factors, many of which are beyond the control of Opthea and its directors and management and may involve significant elements of subjective judgment and assumptions as to future events that may or may not be correct. These statements may be affected by a range of variables which could cause actual results or trends to differ materially, including but not limited to future capital requirements, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, ongoing clinical studies to demonstrate sozinibercept’s safety, tolerability and therapeutic efficacy, analysis of data from Opthea’s Phase 3 clinical trials, clinical research organization and labor costs, intellectual property protections, and other factors that are of a general nature which may affect the future operating and financial performance of the Company, including risk factors set forth in Opthea’s Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (the “SEC”) on August 30, 2024, and other future filings with the SEC. Actual results, performance or achievement may vary materially from any projections and forward-looking statements and the assumptions on which those statements are based. Subject to any continuing obligations under applicable law or any relevant ASX listing rules, Opthea disclaims any obligation or undertaking to provide any updates or revisions to any forward-looking statements in this ASX announcement to reflect any change in expectations in relation to any forward-looking statements or any change in events, conditions or circumstances on which any such statement is based, except as otherwise required by applicable law. Authorized for release to ASX by Frederic Guerard, CEO. Investor Inquiries PJ KelleherLifeSci Advisors, LLCEmail: pkelleher@lifesciadvisors.com Phone: 617-430-7579 Media Inquiries Silvana Guerci-LenaNorthStream Global PartnersEmail: silvana@nsgpllc.com Join our email database to receive program updates:Tel: +61 (0) 3 9826 0399, Email: info@opthea.com Web: www.opthea.com Source: Opthea Limited

Phase 3

18 Sep 2024

·www.globenewswire.com

Opthea Announces Completion of Drug Substance PPQ Campaign Validating Manufacturing Process of Sozinibercept

Three consecutive commercial-scale batches successfully produced Major milestone for potential BLA filing of sozinibercept in wet AMD Progress update of drug product PPQ campaign expected in early 2025 MELBOURNE, Australia and PRINCETON, N.J., Sept. 18, 2024 (GLOBE NEWSWIRE) -- Opthea Limited (ASX/NASDAQ: OPT, “Opthea”, the “Company”), a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD), today announced the completion of its drug substance Process Performance Qualification (PPQ) campaign for sozinibercept. The PPQ campaign consisted of the production of three successful consecutive commercial-scale drug substance batches required for the validation of Opthea’s manufacturing process. The batches have been produced following an extensive manufacturing process development program. “The successful completion of the drug substance PPQ campaign is an important step towards de-risking the program and a potential biologics license application (BLA) filing of sozinibercept in wet AMD,” commented Fred Guerard, PharmD, Chief Executive Officer of Opthea. “While we continue to advance our two fully enrolled, pivotal Phase 3 trials of sozinibercept in wet AMD, we now have demonstrated our ability to consistently manufacture quality drug substance at commercial scale, which will serve as a key component of our BLA Chemistry, Manufacturing and Controls (CMC) module.” “In achieving this commercialization milestone, we believe Opthea is well positioned to supply both our planned drug product PPQ campaign, as well as our initial launch materials,” concluded Mark O’Neill, Vice President, Technical Operations, Opthea. “We expect to share a progress update of our drug product PPQ campaign in early 2025.” About Opthea Opthea (ASX/NASDAQ:OPT) is a biopharmaceutical company developing novel therapies to address the unmet need in the treatment of highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME). Opthea’s lead product candidate, sozinibercept, is being evaluated in two fully enrolled pivotal Phase 3 clinical trials (COAST, NCT04757636, and ShORe, NCT04757610) for use in combination with standard-of-care anti-VEGF-A monotherapies to improve overall efficacy and deliver superior vision gains compared to standard-of-care anti-VEGF-A agents. To learn more, visit our website at www.opthea.com and follow us on X and LinkedIn. Forward Looking Statements This ASX announcement contains certain forward-looking statements, including within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. The words “expect”, “believe”, “should”, “could”, “may”, “will”, “plan” and other similar expressions are intended to identify forward-looking statements. Forward-looking statements in this ASX announcement include statements regarding the Company’s continued efforts to advance its BLA preparations for FDA approval, the Company’s commercialization potential and timing of the progress update of the Company’s drug product PPQ campaign. Forward-looking statements, opinions and estimates provided in this ASX announcement are based on assumptions and contingencies which are subject to change without notice, as are statements about market and industry trends, which are based on interpretations of current conditions. Forward-looking statements are provided as a general guide only and should not be relied upon as an indication or guarantee of future performance. They involve known and unknown risks and uncertainties and other factors, many of which are beyond the control of Opthea and its directors and management and may involve significant elements of subjective judgment and assumptions as to future events that may or may not be correct. These statements may be affected by a range of variables which could cause actual results or trends to differ materially, including but not limited to future capital requirements, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, ongoing clinical studies to demonstrate sozinibercept safety, tolerability and therapeutic efficacy, clinical research organization and labor costs, intellectual property protections, and other factors that are of a general nature which may affect the future operating and financial performance of the Company including risk factors set forth in Opthea’s Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (the “SEC”) on August 30, 2024, and other future filings with the SEC. Actual results, performance or achievement may vary materially from any projections and forward-looking statements and the assumptions on which those statements are based. Subject to any continuing obligations under applicable law or any relevant ASX listing rules, Opthea disclaims any obligation or undertaking to provide any updates or revisions to any forward-looking statements in this ASX announcement to reflect any change in expectations in relation to any forward-looking statements or any change in events, conditions or circumstances on which any such statement is based, except as otherwise required by applicable law. Authorized for release to ASX by Frederic Guerard, CEO Investor Inquiries PJ Kelleher LifeSci Advisors, LLC Email: pjkelleher@lifesciadvisors.com Phone: 617-430-7579 Media Inquiries Silvana Guerci-Lena NorthStream Global Partners Email: silvana@nsgpllc.com Join our email database to receive program updates:Tel: +61 (0) 3 9826 0399, Email: info@opthea.com Web: www.opthea.comSource: Opthea Limited

Phase 3

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

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