Phase II year
2017
(last award dollars: 2018)
Phase II Amount
$2,096,994
Macular edema (ME) and diabetic macular edema (DME), which affects at least 2 million people in the US, are leading causes of blindness in people between the ages of 20-74. The major problem in these diseases is a leaky vasculature, which results in pooling of blood around the retina. This blood can cause occlusion of vision as well as swelling and increased ocular pressure and detachment of the retina. The effective therapies approved to date for these conditions are proteins that are injected intravitreally to bind to VEGF to blocks its activity. Although these drugs are efficacious for some, a significant number of ME patients are unable to gain significant improvements to visual acuity using these drugs. In addition, drugs in this space have also proven to be effective for NVAMD, a $4.5 billion/year market. Our peptide drug AXT107 inhibits signaling of not only VEGF but also of growth factors PDGF, HGF, and IGF-1. Thus, it could serve as an anti-VEGF monotherapy in patients in whom VEGF is the primary driver of disease but it could also successfully treat patients in whom these other factors contribute to disease. AXT107 could also have advantages over the next generation combination therapy of Fovista, an anti-PDGF aptamer, with Eylea or Lucentis. Specifically because AXT107 inhibits PDGF and VEGF simultaneously, even as a monotherapy it could be as efficacious as the combination while avoiding the dual injection and the associated complications. AsclepiX Therapeutics LLC represents the next generation of drug development technology. We use bioinformatics and systems biology methods to design classes of short biomimetic anti-angiogenic and anti- permeability peptides. In addition, we also have technology to prolong the efficacy of our peptide agents through long-lasting biodegradable nano- and microparticles as may be needed. Although he have demonstrated efficacy of our novel lead agent, including in gold standard head-to-head models in the mouse and rabbit vs. the leading FDA-approved agents, we have not yet conducted the IND enabling GLP toxicity studies needed in two species to enable the filing of an IND for subsequent FDA approval. This Phase II SBIR Proposal would provide the funding necessary to move this technology from promising pre-clinical research to a patientÂ’s bedside and the beginning of clinical trials. This proposal is to optimize the excipients and formulation for our novel biomimetic peptide drug, determine its local toxicity and biodistribution when administered intravitreally, and determine its potential toxicity when administered at various doses systemically. We believe that our Phase II program will lead to the approval of an IND for a novel safe and effective peptide agent for treating macular edema. This drug has the potential to improve the vision of millions of Americans and may be impactful in multiple ocular diseases.
Public Health Relevance Statement: Project Narrative There is a large medical need for drugs for the treatment of macular edema. We have identified a promising peptide therapeutic that has shown remarkable activity in animal models of the human disease. Here we propose IND-enabling safety studies on our drug. If these studies show that our drug is safe in animals, the next stage will be a Phase I clinical trial to determine safety in people.
Project Terms: Affect; Age; American; angiogenesis; Angiogenic Factor; Animal Model; Animals; aptamer; bevacizumab; Binding; Biodistribution; Bioinformatics; Biomimetics; Blindness; Blood; Blood Vessels; Choroidal Neovascularization; Clinical; Clinical Trials; Combined Modality Therapy; Data; design; Development; diabetic; Disease; Dose; drug development; Drug Kinetics; Drug or chemical Tissue Distribution; Drug usage; Edema; effective therapy; Endothelial Cells; Ensure; Event; Excipients; Extravasation; Eye; FDA approved; Fibroblasts; Formulation; Funding; Future; Gold; Growth Factor; Head; human disease; Hypoxia; improved; inhibitor/antagonist; Injectable; Injection of therapeutic agent; Insulin-Dependent Diabetes Mellitus; Insulin-Like Growth Factor I; intravitreal injection; Lead; Lucentis; macular edema; Medical; Methods; Modeling; Mus; nano; neovascular; neovascularization; New Zealand; next generation; Non-Insulin-Dependent Diabetes Mellitus; novel; Oryctolagus cuniculus; overexpression; Patients; peptide drug; Peptides; Permeability; Pharmaceutical Preparations; Pharmacotherapy; Phase; Phase I Clinical Trials; Plasma; Platelet-Derived Growth Factor; Play; pre-clinical; pre-clinical research; pressure; programs; Proteins; Recovery; research clinical testing; Retina; Retinal Detachment; Retinal Neovascularization; Retinal Vein Occlusion; Role; Safety; safety study; Secondary to; Signal Transduction; Small Business Innovation Research Grant; Source; Swelling; Systems Biology; Technology; technology development; Testing; Therapeutic; Toxic effect; Toxicology; Up-Regulation; Vascular Endothelial Growth Factors; Vision; Visual Acuity; Water; Work
