The diverse biologic properties and modes of administration of ST266 enable exceptionally broad therapeutic utility for ophthalmic indications. ST266 can be safely and effectively delivered to both the front of the eye and the back of the eye, thus enabling us to take full advantage of its anti-inflammatory and neuroprotective properties. In addition, the broad range of delivery options enable the use of ST266 for a number of inflammatory conditions.
Wounds of the corneal surface of the eye usually heal within a week. PEDs are corneal wounds caused by infection, trauma, surgery or other conditions that are slow to heal—often as a result of a patient’s concomitant diabetes or an underlying immune deficiency. PEDs can lead to blindness.
PED is estimated to affect up to 100,000 patients in the U.S. (source: Wirostko, et al. 2015). It is considered an orphan drug indication. Currently, there is no FDA-approved drug that has been adopted as standard of care for healing PEDs.
Preclinical studies have shown that ST266 reduces eye inflammation in damaged corneas and enhances re-epithelialization by cells that form the cornea. Noveome announced positive data for its Phase 2 clinical trial in PED in June of 2020, and plans to initiate a Phase 2b trial by the end of 2021.
Optic neuritis is an inflammatory disease of the optic nerve and is frequently the presenting sign of multiple sclerosis. These patients commonly experience pain on eye movement and then suddenly have a major loss in visual acuity, usually in one eye. The blindness often resolves in 6-8 weeks. Six months after the episode of blindness, more than half of the patients have some visual changes, including deficits in color vision, contrast sensitivity, and light brightness. The current treatment is steroids, which reduce the period of visual acuity loss but have little or no effect on the preventing damage to contrast vision.
Over time, relapses of this inflammation can lead to vision loss and potentially permanent blindness due to damaged optic nerve cells. In preclinical studies using a model which mimics optic neuritis and multiple sclerosis, ST266 administered by intranasal delivery has been shown to restore vision when given even as late as 2 to 3 weeks after the disease has been induced (Khan, et al. 2017, Khan, et al. 2019). These findings offer hope for preservation of vision in patients with optic neuritis and other optic nerve and retinal diseases.
Glaucoma is a progressive disease of the optic nerve in which elevated intraocular pressure damages the retinal ganglion cells resulting in irreversible vision loss and ultimately blindness. It affects approximately 77 million patients worldwide. Currently approved treatments for glaucoma reduce intraocular hypertension but do not treat the underlying optic nerve degeneration.
In preclinical studies, ST266 has been shown to be neuroprotective and to resuscitate damaged and diseased retinal ganglion cells, offering the possibility of a novel treatment for glaucoma. Noveome is currently conducting a Phase I clinical trial testing the safety of intranasally delivered ST266 in glaucoma suspect patients. This Phase I will enable Phase 2 studies in a number of ophthalmologic conditions such as glaucoma, macular degeneration, and diabetic neuropathy.
NEC is a leading cause of death in infants born prematurely (before 37 weeks of pregnancy) or born with a low birth weight (less than 5.5 pounds). NEC may be linked to a reduced exposure to amniotic fluid as a result of premature birth (Hackam, D.J. and Sodhi, C.P., 2018). There is no cure for this disease, and no change in its mortality rate in 30 years. Moreover, the population at greatest risk for NEC continues to increase, as technological advances have improved the neonatal care of very low birth weight infants.
Approximately 480,000 infants are born preterm each year in the U.S.—all at increased risk for NEC. The percentage of very low birth weight infants who develop NEC remains steady at about 7% (source: www.nichd.nih.gov).
Because ST266 is made from selected and cultured amnion epithelial cells, it may provide many of the same benefits as amniotic fluid. Preclinical studies are underway to investigate the potential role of ST266 in helping prevent NEC and/or accelerate its recovery.
The body’s response to COVID-19 infection can be a dangerous inflammatory overreaction known as a “cytokine storm,” that can lead to acute lung injury, fibrosis, multiple organ failure and death.1-4 Controlling the cytokine storm triggered by COVID-19 is critical to lowering mortality, especially in the elderly and those with chronic conditions such as diabetes, acute respiratory distress syndrome, hypertension and cardiovascular disease.2
Noveome believes that its lead biologic drug candidate, ST266, has the potential to prevent or significantly reduce the life-threatening cytokine storm observed in severely ill COVID-19 patients. ST266 has been shown to be safe and effective in numerous preclinical studies.
For example, preclinical studies in an acute systemic inflammation model demonstrated that ST266 was able to significantly reduce multiple inflammatory cytokines when administered systemically. The data from other preclinical studies demonstrate that ST266 can significantly reduce the cytokine-mediated inflammatory response in several indications.
In clinical trials, 253 patients have been administered ST266 by topical dermal, topical oral, topical ocular or targeted intranasal delivery with no reported drug-related serious adverse events.
In clinical studies, topically applied ST266’s anti-inflammatory and healing activity has been demonstrated in UV light burns, radiation burns, gingivitis, and was shown to be beneficial in healing Persistent Corneal Epithelial Defects, and plans to initiate a Phase 2b trial by the end of 2021.
Allogeneic mesenchymal stem cells (MSCs) were shown to improve functional outcomes in seven treated patients with severe COVID-19 pneumonia.5 However, this type of cell therapy is associated with numerous safety and practical hurdles, especially during an emergency pandemic.
Noveome’s ST266 presents a unique opportunity to administer a multi-targeted COVID-19 cytokine storm countermeasure with many of the advantages of cell therapy, but without the cells or the associated risks.6-11 In addition to COVID-19, ST266 has the potential to treat other severe, acute systemic inflammatory responses and resultant multiple organ injuries caused by other inflammatory conditions such as sepsis. In March, 2021 Noveome initiated a Phase I clinical trial to examine the safety of intravenously delivered ST266 in COVID-19 patients. The first patient was dosed in June, 2021.
1. Tisoncik, J. R. et al. Into the Eye of the Cytokine Storm. Microbiol. Mol. Biol. Rev. (2012). doi:10.1128/mmbr.05015-11
2. Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (2020). doi:10.1016/S0140-6736(20)30183-5
3. Rubenfeld, G. D. et al. Incidence and outcomes of acute lung injury. N. Engl. J. Med. (2005). doi:10.1056/NEJMoa050333
4. McDermott, J. E. et al. Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems. BMC Syst. Biol. (2011). doi:10.1186/1752-0509-5-190
5 Leng, Z. et al. Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. ChinaXiv (2020).
6. Deng-Bryant, Y. et al. Long-term administration of amnion-derived cellular cytokine suspension promotes functional recovery in a model of penetrating ballistic-like brain injury. J. Trauma Acute Care Surg. 73, S156-64 (2012).
7. Deng-Bryant, Y. et al. Treatment with amnion-derived cellular cytokine solution (ACCS) induces persistent motor improvement and ameliorates neuroinflammation in a rat model of penetrating ballistic-like brain injury. Restor. Neurol. Neurosci. 33, 189–203 (2015).
8. Grinblat, G. A. et al. RGC neuroprotection following optic nerve trauma mediated by intranasal delivery of amnion cell secretome. Investig. Ophthalmol. Vis. Sci. 59, 2470–2477 (2018).
9. Khan, R. S., Dine, K., Wessel, H., Brown, L. & Shindler, K. S. Effects of Varying Intranasal Treatment Regimens in ST266-Mediated Retinal Ganglion Cell Neuroprotection. J. Neuro-Ophthalmology (2019). doi:10.1097/WNO.0000000000000760
10. Brown, L. et al. ST266 Amnion Cell-derived Cytokine Secretomefor Treatment of Hemorrhagic Shock and Trauma. MHSRS-19-02489 (2019).
11. Khan, R. S. et al. Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model. Sci. Rep. 7, 41768 (2017).
Background: Traumatic brain injury (TBI) occurs when sudden trauma causes damage to the brain. Symptoms of TBI can be mild, moderate, or severe, depending on the extent of the damage. TBI is the leading cause of death and disability for people under the age of 45 years.
Noveome’s multi-factor product ST266 has been shown to be effective in animal models of TBI when administered intracranially. ST266 ameliorated microglial activation and axonal injury and demonstrated a strong capacity to modulate neuroinflammatory responses as well as demonstrating continued neuroprotective effects following TBI. Functionally, improved motor impairment in rodents was observed in the rotarod test as a sensitive indicator of recovery from trauma.
Noveome has conducted extensive targeted intranasal delivery studies with ST266 in three animal species. First, it was shown that intranasally administered 125I-ST266 deposited throughout the brain, on the optic nerve and in the vitreous of rats. Second, 125I-ST266 has been successfully delivered to the brain and ocular structures of non-human primates using a novel intranasal delivery device designed to maximize dosing to the brain. Third, it was shown that a single daily 6 µL drop of intranasally delivered ST266 effectively reversed the predominant neuropathological abnormalities that mimic optic neuritis in the mouse model of multiple sclerosis. ST266 was neuroprotective, reduced oxidative stress and promoted SIRT1-mediated mitochondrial cell restorative functions.
Thus, Noveome’s ST266 is a potentially effective biotherapeutic product that, coupled with targeted intranasal delivery, could be a promising means of treating TBI. Preliminary results indicate that ST266 may be safely administered intranasally. In February, 2021, Noveome announced a new collaboration with Walter Reed Army Institute of Research to further investigate and develop intranasally-delivered ST266 for the treatment of TBI.
Glaucoma is a progressive disease of the optic nerve in which elevated intraocular pressure damages the retinal ganglion cells resulting in irreversible vision loss and ultimately blindness. It affects approximately 77 million patients worldwide. Currently approved treatments for glaucoma reduce intraocular hypertension but do not treat the underlying optic nerve degeneration.
In preclinical studies, ST266 has been shown to be neuroprotective and to resuscitate damaged and diseased retinal ganglion cells, offering the possibility of a novel treatment for glaucoma. Noveome is currently conducting a Phase I clinical trial testing the safety of intranasally delivered ST266 in glaucoma suspect patients. This Phase I will enable Phase 2 studies in a number of ophthalmologic conditions such as glaucoma, macular degeneration, and diabetic neuropathy.