gersizangitide (AXT107) / Asclepix - LARVOL DELTA

AsclepiX Therapeutics Completes Enrollment in DISCOVER Trial for Neovascular Age-Related Macular Degeneration (nAMD) (GlobeNewswire) - "AsclepiX Therapeutics...announced the completion of enrollment into the DISCOVER trial (NCT05859776). Fifteen patients have completed enrollment in the trial for AXT107 (gersizangitide). The objectives of the trial are to evaluate the safety and tolerability of three dose strengths of AXT107 [125 µg (n=3), 250 µg (n=3), and 500 µg (n=9)] and to determine the bioactivity and duration of action when injected suprachoroidally....The trial was initiated in December 2023 to evaluate the safety, tolerability, and biologic activity of AXT107, with topline results expected in Q2 2025."

Enrollment closed • P1/2 data • Wet Age-related Macular Degeneration

DISCOVER: Safety and Bioactivity of AXT107 in Subjects With Neovascular Age-Related Macular Degeneration (nAMD) (clinicaltrials.gov) - P1/2 | N=15 | Active, not recruiting | Sponsor: AsclepiX Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

SHASTA: Safety and Bioactivity of AXT107 in Subjects With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=3 | Terminated | Sponsor: AsclepiX Therapeutics, Inc. | Completed ➔ Terminated; Adverse Events

Trial termination • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

CONGO: Safety and Bioactivity of AXT107 in Subjects With Diabetic Macular Edema (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: AsclepiX Therapeutics, Inc. | Completed ➔ Terminated; Adverse Events

Trial termination • Diabetic Macular Edema • Ophthalmology

DISCOVER: Safety and Bioactivity of AXT107 in Subjects With Neovascular Age-Related Macular Degeneration (nAMD) (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: AsclepiX Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

AsclepiX Therapeutics Raises $10 Million to Advance Phase 1/2a Clinical Study of AXT107 (GlobeNewswire) - "AsclepiX Therapeutics, Inc...announced today that it has secured a $10 million Series A-3 financing....'With the completion of this round, we are excited to embark into the next phase of our clinical development program,'...'The DISCOVER study, utilizing AXT107 microparticulate suspension, will evaluate the safety and tolerability of three doses of AXT107 in patients with wet AMD. We look forward to announcing the initiation of enrollment in early 2024.'"

Financing • Trial initiation date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Wet Age-related Macular Degeneration

DISCOVER: Safety and Bioactivity of AXT107 in Subjects With Neovascular Age-Related Macular Degeneration (nAMD) (clinicaltrials.gov) - P1/2 | N=15 | Not yet recruiting | Sponsor: AsclepiX Therapeutics, Inc.

New P1/2 trial • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Anti-angiogenic collagen IV-derived peptide target engagement with αβ and αβ in ocular neovascularization models. (PubMed, iScience) - "AXT107-integrin binding was demonstrated by ex vivo cross-linking/pull-down experiments. These data support the hypothesis that AXT107 therapeutic activity is mediated through binding αβ and αβ which are markedly upregulated on endothelial cells in NV providing selective targeting of diseased vessels which has therapeutic and safety benefits."

Journal

SHASTA: Safety and Bioactivity of AXT107 in Subjects With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=3 | Completed | Sponsor: AsclepiX Therapeutics, Inc. | Active, not recruiting ➔ Completed | N=18 ➔ 3

Enrollment change • Trial completion • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

CONGO: Safety and Bioactivity of AXT107 in Subjects With Diabetic Macular Edema (clinicaltrials.gov) - P1/2 | N=6 | Completed | Sponsor: AsclepiX Therapeutics, Inc. | Active, not recruiting ➔ Completed | N=18 ➔ 6

Enrollment change • Trial completion • Diabetic Macular Edema • Ophthalmology

CONGO: Safety and Bioactivity of AXT107 in Subjects With Diabetic Macular Edema (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: AsclepiX Therapeutics, Inc. | Trial completion date: Jul 2022 ➔ Oct 2022 | Trial primary completion date: Jul 2022 ➔ Oct 2022

Trial completion date • Trial primary completion date • Diabetic Macular Edema • Ophthalmology

SHASTA: Safety and Bioactivity of AXT107 in Subjects With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: AsclepiX Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

CONGO: Safety and Bioactivity of AXT107 in Subjects With Diabetic Macular Edema (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: AsclepiX Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetic Macular Edema • Ophthalmology

The emerging role of the angiopoietin-Tie pathway as therapeutic target for treating retinal diseases. (PubMed, Expert Opin Ther Targets) - "We analyzed the novel, emerging drugs (ARP- 1536, the coformulation of aflibercept and nesvacumab, AXT107 and AKB-9778) that target the Ang/Tie pathway. Further clinical trials are necessary to define the role of agents targeting Ang/Tie in future clinical practice. Among the investigational drugs targeting the Ang/Tie pathway, faricimab has shown promising results in phase II/III trials and in the near future may represent a viable treatment option for the management of exudative macular diseases."

Journal • Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Retinal Vein Occlusion • Wet Age-related Macular Degeneration

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

[VIRTUAL] AXT107 an Inhibitor of Neovascularization, Vascular Leakage, and Inflammation, Is Well-Tolerated and Could Potentially Be Dosed Once a Year to Treat Retinal Vascular Diseases (ARVO 2021) - "Multiple doses of a single injection of AXT107 injected intravitreally were found to be safe and well- tolerated in GLP safety studies over 9-months in two species. PK and ocular distribution studies in rabbit and minipig showed that AXT107 formed a gel upon intravitreal injection that stayed below the visual axis releasing AXT107 slowly over the course of the study with a half-life of 180 days. The released AXT107 was found to be present at efficacious levels in the retina and choroidal tissues."

Ophthalmology

SHASTA: Safety and Bioactivity of AXT107 in Subjects With Neovascular Age-Related Macular Degeneration (clinicaltrials.gov) - P1/2; N=18; Recruiting; Sponsor: AsclepiX Therapeutics, Inc.

Clinical • New P1/2 trial • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

[VIRTUAL] AXT107, a Gel Forming Peptide that Inhibits VEGFR2 Signaling and Activates Tie2 Signaling for the Treatment of Retinal Vascular Diseases (Macula 2021) - No abstract available

[VIRTUAL] AXT107, an Inhibitor of Integrins ?v?3 and ?5?1 that Blocks VEGF Signaling, Activates Tie2, and Suppresses Inflammation, Inhibits Ocular Neovascularization and Vascular Leakage (Macula 2021) - No abstract available

Immunology • Inflammation • Ocular Inflammation

Experimental drugs show the potential for vision-depriving eye conditions (Eminetra) - '"We expect injections of AXT107 into humans to be significantly longer effective than current treatments,' said lead investigator Dr. Peter Campochiaro...'Instead of injecting the eyes every 4-6 weeks, I hope the injection intervals will be several months,' he said. Drug tests in rabbits lasted only two months, but the drug appeared to be safe and effective, Campochiaro said. Researchers hope to begin their first human experimentation later this year. The Phase 1 trial will test the safety of people's drugs, but Campochiaro says more testing will be needed to see how effective it is."

Media quote

First patient dosed in AXT107 clinical trial for DME (Healio) - '"We are hopeful that AXT107’s unique mechanisms of action, as a peptide and intravitreal self-forming gel depot, will improve outcomes and decrease patient and caregiver burden for our DME patients,' Jeffrey Heier, MD...said in the release."

Media quote

CONGO: Safety and Bioactivity of AXT107 in Subjects With Diabetic Macular Edema (clinicaltrials.gov) - P1/2; N=18; Recruiting; Sponsor: AsclepiX Therapeutics, Inc.

Clinical • New P1/2 trial • Diabetic Macular Edema • Ophthalmology

The Tie2 signaling pathway in retinal vascular diseases: a novel therapeutic target in the eye. (PubMed, Int J Retina Vitreous) - "AXT107 is a collagen IV-derived synthetic peptide with a dual mechanism of action that involves suppression of VEGF signaling and activation of the Tie2 pathway; these actions are accomplished by AXT107 binding to and disrupting different integrin, leading to blockade of the VEGF receptor and rearrangement of cellular Tie2 rendering it susceptible to Ang2 agonism. Other Tie2 agonist compounds are also in development, including faricimab and razuprotafib. Tie2 activation only modestly impacts angiogenesis on its own but significantly potentiates VEGF suppression. Co-regulation of the VEGF and Tie2 signaling pathways has the potential to improve functional and structural outcomes in eyes with retinal vascular diseases."

Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Diabetic Macular Edema • Diabetic Retinopathy • Immune Modulation • Immunology • Inflammation • Macular Degeneration • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinal Vein Occlusion • Wet Age-related Macular Degeneration • ANGPT2

Video: Synthetic peptide may yield durable vision gains in retinal diseases (Healio) - "In this video from the virtual American Society of Retina Specialists meeting, Peter K. Kaiser, MD, discusses AXT107, a synthetic peptide designed to treat wet age-related macular degeneration and macular edema."

Video

Suppression of Ocular Vascular Inflammation through Peptide-Mediated Activation of Angiopoietin-Tie2 Signaling. (PubMed, Int J Mol Sci) - "AXT107 also decreased the levels of pro-inflammatory TNF receptor 1 (TNFR1) without affecting levels of the more protective TNFR2. These data suggest that AXT107 may provide multiple benefits in the treatment of retinal/choroidal and other vascular diseases by suppressing inflammation and promoting vascular stabilization."

Journal • Immunology • Ocular Inflammation • Ophthalmology • ANGPT2 • ICAM1 • TNFA • TNFRSF1B