Digging deep in the retina pipeline
While Novartis’ recently approved Beovu soaked up a lot of the buzz in the retina space at the American Academy of Ophthalmology, reports of early phase research at OIS@AAO may provide a glimpse of what will be the buzz five or 10 years from now, if not sooner. They include a fully degradable implant to extend the release of drugs inside the eye, a wearable visual aid that uses augmented reality and eye tracking, an implantable cell therapy, and a daily drop with neuroprotective properties. Here’s a look at the four technologies.
Degradable, nonpolymeric implant
IBE-814 is a fully degradable, nonpolymeric implant that releases dexamethasone to treat posterior inflammation. Thomas P. Reeves, president and CEO of Interface Biologics, described it as a dexamethasone prodrug cylinder delivered via a 30-gaugue needle. The goal is to deliver a low dose of the steroid for approximately six months, with the potential to extend time between anti-VEGF treatments. “It delivers 70 ug vs. 700 ug of dexamethasone for the leading implant,” Reeves said.
In preclinical rabbit studies, IBE-814 exhibited zero-order drug release and sustained inhibition of vascular leakage induced by vascular endothelial growth factor. The company has initiated toxicology studies and anticipates started a Phase 2 clinical trial of patients with diabetic macular edema and retinal vein occlusion in Q3 2020, Reeves said. The trial will enroll 50 patients, with an interim readout due in Q4 2020.
Interface is also exploring programs with the IBE-1119 intravitreal implant in wet age-related macular degeneration and the IBE-1212 intravitreal implant in dry AMD, Reeves said. The company is raising a $25 million Series A round to fund the Phase 2 trial for IBE-814.
Augmented reality vision aide
Ocutrx Vision Technologies is developing the Oculenz augmented reality device for people with AMD. It’s a wraparound headpiece that looks like safety glasses with a white strip across the top front that holds the electronic components. It weighs less than 200 grams, said Ocutrx consultant Linda A. Lam, MD, MBA, of the University of Southern California Keck School of Medicine.
Oculenz projects 200 frames per second with a resolution of 60 pixels per degree and a field of view of 117 degrees. Its magnification range is from 1x to 10x.
The electronics include an on-board visual field test, a computer to mediate reality and integrated eye-tracking to, in essence, fill in the details of the scotoma, or patient’s blind spot, by projecting the image onto viable retina. Integrated calibration tools perform static and dynamic visual-field testing to monitor the scotoma size, customize the view to the scotoma size, and use object recognition of the entire field and voice feedback, Dr. Lam said.
She explained that augmented reality overlays computer-generated graphics and animation on real-world situations and environments, whereas virtual reality devices recreate real-life environment and provide an immersive experience for simulated reality.
In a beta test of five patients with AMD, best-corrected visual acuity improved from <20/200 without Oculenz to 20/63, on average, with the device, Dr. Lam reported. Mean characters per second improved from 0.96 logMAR with near or no correction to 0.61 and 0.58 logMAR with the device.
Cell therapy implant
Renexus is an encapsulated cell therapy (ECT), an implantable device that releases the neurotrophic factor CNTF, which has been shown to protect against progressive photoreceptor loss. Neurotech CEO Rich Small noted that CNTF has been shown to promote neuron survival in the ellipsoid zone of the retina for macular telangiectasia (MacTel) and in retinal ganglion cells for glaucoma.
Twenty-four-month Phase 2 trial results in MacTel showed Renexus was well tolerated and achieved statistically significant reduction in the rate of change in the MacTel ellipsoid zone (p=0.03), Small said. The trial involved 67 patients. Now Neurotech is enrolling two 112-patient Phase 3 trials to follow MacTel patients over 24 months.
Small said next steps include internally preparing the biologics license application to the Food and Drug Administration. In the meantime, Neurotech is also pursuing a Renexus Phase 2 trial in glaucoma.
Privately owned Neurotech is supported by the Lowy Family Group, the international investment business of the Lowy family, and the Lowy Medical Research Institute is collaborating with Neurotech in the MacTel Program.
Small-molecule eye drop
GAL-101 is a novel small-molecule drop for neuroprotection and functional improvement in dry AMD and glaucoma that’s ready for Phase 2 study, said Galimedix chief scientific officer Hermann Russ, MD, PhD. GAL-101 works by binding to the amyloid ß oligomers known to attack retinal ganglion and pigment epithelium cells, causing neurodegeneration. “GAL-101 attenuates amyloid ß toxicity,” Dr. Russ said. Mouse studies showed GAL-101 reduced toxic retinal amyloid ß and complement C3b response in AMD, he said. In a primate model, 1 µm of GAL-101 was detected in the retina five minutes after application.
The Phase 1 glaucoma trial showed an excellent safety profile, and now the company is planning Phase 2 trials in dry AMD and glaucoma, Dr. Russ said, with enrollment to start in Q2 2020. The company is in the process of raising $5 million to cover completion of the investigational new drug submission, then plans to raise an additional $15 million for the Phase 2 trials, he said.
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