Biopharmaceutical development has gone well beyond the drugs themselves to mechanisms and platforms that aim to deliver those drugs more effectively and precisely than existing platforms, as nearly 800 attendees at the Ophthalmology Innovation Summit in Chicago heard during the BioPharma Showcase.
Read the key takeaways below on the companies that presented, and watch the video presentations.
Publicly traded Aerie Pharmaceuticals Inc. has two Rho kinase inhibitors, or ROCK inhibitors, in development. CEO Vicente Anido, Jr, PhD reported Rhopressa which is in Phase III studies, and, Roclatan a Rhopressa-latanoprost combination that is entering a Phase III trial. ROCK inhibitors have been known to improve aqueous outflow through the trabecular meshwork and, possibly, improve blood flow to the optic nerve and delay ocular cell death in glaucoma.
Vicken Karageozian, MD, Co-Founder and CTO of Allegro Opthalmics LLC, updated the OIS audience on the clinical trial progress of Luminate, a first-in-class integrin peptide therapy that treats vitreo-retinal diseases by utilizing two mechanisms of action, anti-angiogenesis and vitreolysis. The company just initiated a Phase II study of the drug as a treatment of diabetic macular edema (DME). The company is close to reporting a data lock in a Phase II trial against vitreomacular traction (VMT).
Aly1337 is a novel, small-molecule multi-kinase inhibitor that Allysta Pharmaceuticals Inc. is developing to treat glaucoma, said Henry Hsu, MD, Founder and CEO. Kinase, particularly Rho kinase, plays a key role in preventing aqueous outflow through the trabecular meshwork, thus contributing to increasing intraocular pressure. Among the kinases Aly1337 targets is kinase LRRK2, which, according to Dr. Hsu, has not been previously described as active in glaucoma.
Thomas W. Chalberg, PhD presented an update on Avalanche Biotechnologies Inc.’s pipeline of products emerging from its integrated gene therapy discovery, development, and manufacturing platform, Ocular BioFactory. Avalanche’s lead product, AVA-101, is undergoing Phase IIa clinical trials for wet AMD; the company could submit an investigational new drug application in the second half of 2015. Avalanche is testing the compound against diabetic macular edema (DME) and retinal vein occlusions as well. It also has entered into a partnership with Regeneron to pursue multiple applications of its AVA-311 preclinical product.
GrayBug LLC, meanwhile, is conducting preclinical work on its microparticle anti-VEGF compound GB-102, an extended-release injectable for wet AMD. The platform encapsulates the active drug ingredient in microparticles that degrade over time once injected into the eye, to gradually release the agent. In mouse studies, GB-102 has been shown to prolong suppression of choroidal neovascularization 4.5 times longer than ranibizumab alone, President and CEO Michael O’Rourke said, potentially extending the interval between anti-VEGF injections from every one to two months to every four to six months. The company is also doing early work in glaucoma and other areas, O’Rourke said.
Kala Pharmaceutical Inc. is moving its proprietary Loteprednol Etabonate Mucus Penetrating Particle (LE-MPP) platform through a host of trials, Interim President and CBO Charlie McDermott reported. Animal investigations showed that LE-MPP retained approximately 10 times the concentration of the agent on the ocular surface at one hour than either loteprednol etabonate nanoparticle or suspension alone, McDermott said. Additionally, early animal studies of topical dosing of 1% LE-MPP showed concentrations in the retina after two hours, supporting the rationale for a DME trial, McDermott added.
Ed Timm, President and CEO of Mobius Therapeutics LLC, provided an update on the investigations into extending the company’s Mitosol platform, presently used to administer mitomycin-C in ab externo glaucoma surgery. Mitosol avoids the issues of sterility and stability of mitomycin-C made in compounding pharmacies. Mobius is investigating the use of the platform in refractive surgery.
MC2 Biotek Group’s Co-Founder and President Jesper J. Lange updated attendees on the company’s PAD technology, which may make existing drugs easier to use. The company’s lead product PADciclo is beginning Phase II testing against dry eye. MC2 Biotek has a collaboration with Moorfield Pharmaceuticals (part of Moorfield Eye Hospital) to develop a cyclosporine formulation that could be used once a day instead of twice a day.
Novaliq GmbH is using semifluorinated alkanes to improve solubility of topical agents like cyclosporin and latanoprost on the ocular surface, according to CEO Bernhard Günther. Its CyclASol and TacroSol compounds, which are ready for Phase II studies, pair with cyclosporine for dry eye and tacrolimus for uveitis, respectively, said Günther. Novaliq also has in development other formulations for post-cataract pain and mild and moderate dry eye. Its OTC platform for dry eye, NovaTears, received the CE Mark in 2014, and Günther expects the company to receive the CE Mark designation for NovaTears Omega3 in 2015.
CEO David R. Guyer, MD reports that Phase III clinical trials of Ophthotech Corp.’s Fovista, a first-in-class anti-PDGF agent for wet AMD combination therapy, are on track. The company expects to receive top-line data in 2016. Meanwhile, Ophthotech is partnering with Novartis to sell Fovista outside the US. The deal could be worth $1 billion if all up-front and milestone payments are made.
ONL Therapeutics Inc. is developing Met12, a small peptide inhibitor that uses a novel mechanism to attack Fas receptor apoptosis, which has a key role in retinal detachment and AMD, CEO John Freshley reported. The drug targets the pathway activated in Fas-mediated apoptosis, Freshley said. Fas is an antigen encoded to the tumor necrosis factor receptor superfamily member 6 (TNFRSF6) gene.
Panoptes Pharma GmbH is developing PP-001, a dihydroorotate dehydrogenase (DHODH) inhibitor for local treatments in ocular disease, Co-Founder and CEO Franz Obermayr, PhD told the OIS gathering. Preclinical investigation is focusing on use for intravitreal and oral administration for posterior uveitis, but Panoptes is also researching topical applications for anterior uveitis, dry eye, and viral conjunctivitis, said Obermayr. The DHODH inhibitor disrupts T-cell proliferation and selectively inhibits key activators of disease pathways, including VEGF.
Clinicians have few treatment options for dry AMD, but Translatum Medicus Inc. is working on an agent, TMi-018, for such an indication. President and CSO Shelley Boyd, MD, FRCSC explained the company has reverse engineered an animal model to mimic the disease so investigators can test treatments. TMi-018 is a first-in-class transcriptional modulator that is already demonstrated safety in Phase II and III trials for autoimmune disease.
Monoclonal antibody company Xoma Corp. shared its new strategy of developing an internal pipeline of potential therapeutics. The company’s lead molecule is gevokizumab, a monoclonal antibody directed at the interleukin-1 beta, an important cytokine involved in multiple diseases where inflammation is a key component. Paul Rubin, MD, Senior Vice President, Research and Development and CMO, says the company has multiple, ongoing trials for Behcet’s uveitis, scleritis, and other ophthalmology conditions.