PITTSBURGH—Clinical-stage biopharmaceutical company Noveome Biotherapeutics Inc. announced early in the first quarter of 2021 that preclinical data regarding the neuroprotective potential of fractionated and unfractionated ST266 had been published in PLOS ONE. The results appeared in a paper titled “Mechanism of Neuroprotection Mediated by ST266 Requires full Complement of Proteins Secreted by Amnion-derived Multipotent Progenitor Cells.”
This work was conducted in the lab of Dr. Kenneth S. Shindler, an associate professor of ophthalmology and neurology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
“ST266 is a complex mixture of hundreds of large and small biomolecules secreted by a novel population of cells created by the proprietary culturing of amnion-derived epithelial cells collected from donated full-term placentas,” Larry Brown, chief scientific officer and vice president of R&D at Noveome, tells DDN. “This “cocktail” of biomolecules is known as a secretome. ST266 has many of the same properties as stem cells and other cell types, but it is cell-free, thus eliminating the unwanted variables associated with cell therapies.”
The company notes on its website that “ST266 is a first-of-its-kind, multitargeted, noncellular platform biologic with the potential to improve patients’ outcomes across a range of challenging diseases and conditions in ophthalmology, neurology, dermatology—and more.”
“Noveome has shown that when ST266 is administered using the intranasal nose to brain route, it can attenuate visual dysfunction, prevent retinal ganglion cell loss, and reduce both inflammation and demyelination of optic nerves six weeks after induction of EAE in mice,” stated Brown. “In this study, we wanted to determine how specific molecular weight protein ranges impact neuroprotective activity.”
The paper looked at neuroprotective and myelin-protective effects of ST266 in both unfractionated and fractionated formats, specifically a <30kDa fraction and a <50kDa fraction. Working in an experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis, researchers assessed retinal ganglion cell (RGC) survival in isolated retinas as well as inflammation and demyelination in optic nerves, while Schwann cell proliferation was assessed in vitro.
Their work showed that the full complement of the ST266 secretome was needed for optimal benefit. While the <50kDa molecular weight ST266 fraction significantly improved optic nerve demyelination, it only showed a trend toward improved RGC survival, while the full complement led to significantly improved RGC survival and reduced optic nerve demyelination in EAE mice. Similarly, the <30kDa and the <50kDa fractions resulted in increased Schwann cell proliferation in vitro, but fell short of the efficacy of full complement ST266.
Noveome stated that the results support intranasal nose to brain and eye delivery of ST266 as a potential therapy for optic neuritis.
“We ‘bypass (or circumvent)’ the blood-brain barrier rather than penetrate it,” Brown explains. “ST266 is administered using a novel delivery device that targets the cribriform plate at the superior aspect of the nasal cavity. Olfactory nerve fibers penetrate through holes in the cribriform plate to reach the nasal cavity. ST266 appears to travel along those nerve fibers into the brain and eye, effectively bypassing the blood-brain barrier. Considering that ST266 is a complex mixture of large molecular weight proteins, it is truly remarkable that it can be delivered in this manner and be effective. Noveome is currently conducting a Phase 1 clinical trial evaluating the safety of ST266 in glaucoma suspect patients. Thus far, we have not observed any safety concerns.”
“We absolutely believe there will be enormous interest in using the noninvasive intranasal delivery route for treating ‘back of the eye’ ophthalmic diseases such as wAMD and diabetic retinopathy rather than repeated intravitreal injections. Even if intranasal ST266 just reduced the number of injections necessary, that would be a win for patients,” he adds.
According to Brown, Noveome is currently evaluating ST266 in two indication categories: ophthalmology and anti-inflammation. Specifically, the company is exploring a front of the eye condition (persistent corneal epithelial defects), a back of the eye condition (glaucoma suspects/optic neuritis), and retinal diseases (i.e. wet age-related macular degeneration and diabetic retinopathy). Noveome’s anti-inflammation focus is in aiming to treat the cytokine storm seen in COVID-19 infections and/or bacterial infections.
As for the next step for the ST266, Brown reports that “Upon completion of the Phase 1 safety trial, we will select a specific back of the eye indication to determine efficacy of intranasal ST266 in Phase 2 trials. With respect to fractionating ST266, we will continue fractionating and testing in different animal models to better understand the mechanisms of action this complex product possesses. Based on promising preclinical data, we also have plans to evaluate intranasal ST266 in traumatic brain injury such as concussion and related injuries.”