THR-687 / Oxurion - LARVOL DELTA

RNA-seq suggests integrins as a potential therapeutic target in epiretinal membrane pathogenesis (ARVO 2024) - "The identification of upregulation of integrins α-1, α-3, α-11 and β-4 in epiretinal membranes is a new and exciting finding. Integrins have a critical role in linking the cell and extracellular matrix and play a role in cell migration and transition from quiescent to proliferative states. Anti-integrin therapies, including risuteganib, THR-687 and SF-0166 are being investigated for use in retinovascular diseases including diabetic macular oedema and age-related macular degeneration, but this study suggests that epiretinal membrane is another possible indication for these therapies."

Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Macular Edema • Ophthalmology • Retinal Disorders

Revealing the structural and molecular interaction landscape of the favipiravir-RTP and SARS-CoV-2 RdRp complex through integrative bioinformatics: Insights for developing potent drugs targeting SARS-CoV-2 and other viruses. (PubMed, J Infect Public Health) - "The results revealed the structural and molecular interaction landscape of the binding mode of favipiravir with the nsp7-nsp8-nsp12-RNA SARS-CoV-2 RdRp complex. Our findings can help future researchers in understanding the mechanism underlying viral action and guide the design of nucleotide analogs that mimic favipiravir and exhibit greater potency as antiviral drugs against SARS-CoV-2 and other infectious viruses. Thus, our work can help in preparing for future epidemics and pandemics."

Journal • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases

INTEGRAL: A Study to Evaluate THR-687 Treatment for Diabetic Macular Oedema. (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: Oxurion | N=303 ➔ 16 | Trial completion date: Aug 2023 ➔ Jun 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2023 ➔ Jun 2022; Based on data obtained in Part A, there was insufficient evidence of efficacy on the key outcome measures. As a result, the study was not advanced to Part B.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Macular Edema • Metabolic Disorders • Ophthalmology • Retinal Disorders

THR-687, a Potent and Highly Selective RGD Integrin Inhibitor in Development for the Treatment of Diabetic Macular Edema (Macula 2022) - "Both preclinical and early clinical data support the continued development of THR-687 as a potential first line treatment for patients with CI-DME. Safety data and the selected dose level for Part B of the study will be presented at the Annual Meeting. Pre-Recorded"

Diabetes • Diabetic Macular Edema • Immunology • Inflammation • Metabolic Disorders • Ophthalmology

INTEGRAL: A Study to Evaluate THR-687 Treatment for Diabetic Macular Oedema. (clinicaltrials.gov) - P2 | N=303 | Active, not recruiting | Sponsor: Oxurion | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Macular Edema • Metabolic Disorders • Ophthalmology • Retinal Disorders

THR-687, a potent pan-RGD integrin antagonist, protects against retinal vascular permeability, inflammation and reactive gliosis in the diabetic rat (ARVO 2022) - P2 | "RGD-integrin antagonism using THR-687 potently inhibits vascular permeability, inflammation and gliosis induced by STZ in the diabetic rat retina. Given its broad mode of action, THR-687 is a promising drug candidate for the treatment of vision-threatening retinal pathologies and is currently in a phase 2 clinical trial in diabetic macular edema patients (INTEGRAL - NCT05063734)."

Preclinical • Diabetic Macular Edema • Ophthalmology • Retinal Disorders • VIM

Current Clinical Trials in Diabetic Macular Edema: Various therapies are in development (Retin Physician) - "Diabetic macular edema (DME) represents a leading causes of irreversible legal blindness in the industrialized world. Therapeutically, corticosteroids were utilized early in the treatment of DME. Intravitreal (IVT) corticosteroids, which reduce inflammatory cytokines and act on several pathogenic pathways in DME, have proven effective for the management of DME, supplementing focal laser."

Online posting

A study to evaluate THR-687 treatment for diabetic macular oedema Štúdia hodnotiaca liečbu diabetického makulárneho edému s THR-687 (clinicaltrialsregister.eu) - P2; N=303; Ongoing; Sponsor: Oxurion NV

Clinical • New P2 trial • Diabetes • Diabetic Macular Edema • Macular Edema • Metabolic Disorders • Ophthalmology

A Phase 1 Study of THR-687, an RGD Integrin Antagonist, for the Treatment of Diabetic Macular Edema (DME) in Patients Previously Responsive to anti-VEGF Agents or Corticosteroids (EURETINA 2021) - "This first-in-human study with THR-687 evaluated the safety and the preliminary efficacy in the treatment of subjects with CI-DME who had previously been treated with and had a history of response to anti-VEGF agents or corticosteroids. At all dose levels tested, a single IVT injection of THR-687 was safe and well tolerated...Both the safety and the efficacy results following a single injection of THR-687 are promising. The upcoming Phase 2 study is planned to further assess the efficacy and safety of THR-687 with multiple IVT injections in patients who had not yet received treatment for their CI-DME (treatment naïve patients)."

INTEGRAL: A Study to Evaluate THR-687 Treatment for Diabetic Macular Oedema. (clinicaltrials.gov) - P2; N=303; Recruiting; Sponsor: Oxurion

Clinical • New P2 trial • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Macular Edema • Metabolic Disorders • Ophthalmology • Retinal Disorders

Oxurion NV - Publication of Positive Phase 1 Clinical Data evaluating THR-687 for Treatment of DME in Ophthalmology Science, the American Academy of Ophthalmology Journal - "Very excited to see our positive phase 1 data with THR-687, a novel, highly selective pan-RGD integrin antagonist, published in Ophthalmology Science, the American Academy of Ophthalmology Journal! #THR687 offers an an exciting new mechanism of action to help patients with DME and wetAMD! Thank you...Pravin Dugel MD, raj maturi MD for making this happen."

Announcement

Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687. (PubMed, J Pharmacokinet Pharmacodyn) - "We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure."

Journal • PK/PD data • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

[VIRTUAL] OXURION NV (BIO 2021) - "Oxurion is aiming to build global franchise in treatment of retinal vascular disorders based on the successful development of its two novel therapeutics: - THR-149, a plasma kallikrein inhibitor being developed as potential new standard of care for the 40% of DME patients who respond sub-optimally to anti-VEGF therapy. Positive topline results in a Ph1 clinical study assessing THR-687 as treatment for DME were announced in 2020. THR-687 expected to enter a Phase 2 clinical trial in mid-20"

Age-related Macular Degeneration • Complement-mediated Rare Disorders • Diabetes • Diabetic Macular Edema • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

DME trial results are positive for intravitreal integrin antagonist (Ophthalmology Times) - P1, N=12; NCT03666923; Sponsor: ThromboGenics; '"Multiple challenges remain in the management of DME with unmet needs to improve treatment outcomes, speed of treatment benefit, and the duration of response,' said Maturi...'Unlike anti-VEGF agents, integrin antagonists have a broader biologic effect because integrins contribute to the activation of multiple growth factor receptors and are involved in multiple processes resulting in pathological angiogenesis and vascular leakage.'"

Media quote

[VIRTUAL] PA052: A Phase 1 Study of THR-687, an Integrin Antagonist, for the Treatment of DME (AAO 2020) - "Conclusion The safety / efficacy of THR-687 in this first-in-human study following a single injection are promising. A Phase 2 study is planned to further assess efficacy of THR-687 with multiple injections."

P1 data • Diabetic Macular Edema • Ophthalmology

"$BCYC OXURION NV Confirms New Patents for THR-687 Issued by European and US Patent Offices https://t.co/ABALnAhZrZ" (@otcdynamics)

[VIRTUAL] THR-687, a potent pan-RGD integrin antagonist, holds promise as next-generation therapy for diabetic macular edema (EURETINA 2020) - "THR-687, a pan-RGD integrin antagonist, potently inhibits retinal vascular permeability, inflammation, pericyte loss and gliosis induced by diabetes in the STZ rat. Given its multifaceted mode of action and broad therapeutic potential, THR-687 is a promising drug candidate for the treatment of vision-threatening retinal pathologies such as DR and DME."

Age-related Macular Degeneration • CNS Disorders • Complement-mediated Rare Disorders • Diabetic Macular Edema • Diabetic Retinopathy • Fibrosis • Immunology • Inflammation • Macular Degeneration • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • ITGAM • PDGFRB • VIM

Intermolecular interaction among Remdesivir, RNA and RNA-dependent RNA polymerase of SARS-CoV-2 analyzed by fragment molecular orbital calculation. (PubMed, J Mol Graph Model) - "Moreover, stable OH/π interaction is also formed with Thr687 of the RdRp. We quantitatively revealed the exhaustive interaction within the complex among Remdesivir, template-primer-RNA, RdRp and co-factors, and published the results in the FMODB database."

Journal • Infectious Disease • Novel Coronavirus Disease

Anti-Integrin therapy for retinovascular diseases. (PubMed, Expert Opin Investig Drugs) - "Clinical candidates include risuteganib, THR-687, SF-0166, which have shown promise in treating diabetic macular edema (DME) and non-neovascular AMD in early clinical studies. Preclinical candidates include SB-267268, JNJ-26076713, Cilengitide and Lebecetin, which exhibit a decrease in retinal permeability, angiogenesis and/or choroidal neovascularization (CNV)...Anti-integrin agents tackle the multi-factorial nature of DR and AMD and show promise as injectable and topical agents in preclinical and early clinical studies. Integrin inhibition has potential to serve as primary therapy, adjunctive therapy to anti-vascular endothelial growth factor agents, or secondary therapy in refractory cases."

Journal • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Diabetic Macular Edema • Diabetic Retinopathy • Fibrosis • Gene Therapies • Immunology • Ophthalmology • Retinal Disorders

Oxurion NV – expert presentation of positive topline data from a phase 1 study evaluating THR-687 for the treatment of DME,at Angiogenesis, Exudation, and Degeneration 2020 Conference (GlobeNewswire) - "Oxurion...today announces that further positive topline data from a Phase 1 study with THR-687, a novel, potent, pan-RGD integrin antagonist for the treatment of Diabetic Macular Edema (DME) was presented by Arshad Khanani, M.D., M.A., Director of Clinical Research at Sierra Eye Associates, Reno, Nevada, US at the Angiogenesis, Exudation, and Degeneration 2020 conference on February 8, 2020, in Miami, US."

P1 data

Oxurion NV – Additional topline data from positive phase 1 trial with THR-687 in patients with diabetic macular edema (DME) to be presented at the upcoming Angiogenesis, Exudation, and Degeneration 2020 Conference (GlobeNewswire) - "Oxurion NV...today announces that a presentation of further data from a Phase 1 study with THR-687 in patients with diabetic macular edema (DME) will be given at the Angiogenesis, Exudation, and Degeneration 2020 conference being held on February 8, 2020, in Miami, US....THR-687 is expected to enter a Phase 2 clinical trial in H2 2020."

New P2 trial • P1 data

A Study to Evaluate the Safety of THR-687 in Subjects With Diabetic Macular Edema (DME) (clinicaltrials.gov) - P1; N=12; Completed; Sponsor: ThromboGenics; Recruiting ➔ Completed

Clinical • Trial completion

Newly added product (GlobeNewswire) - P1, DME, Ophthalmology

Pipeline update