Our Technology
Technology Overview
The technology underlying Trefoil’s engineered FGF1, TTHX1114 builds on the well-known activities of naturally-occurring (native) FGF1 to enable its use as a pharmaceutical for corneal diseases. Native FGF1 is a potent stimulator of cell proliferation and migration, and has cell protective properties, all key attributes for its use in corneal disease treatment. The compound uniquely activates all seven forms of the FGF receptor, contributing to its potency. Although FGF1’s activities have been well known, the naturally-occurring molecule has an extremely short half-life, which rendered it unsuitable for use as a pharmaceutical.
History of Trefoil’s eFGF1
The company’s engineered FGF1, TTHX1114, is designed to increase the short half-life of the naturally occurring FGF1 molecule. The key innovation was the introduction of specific mutations into the FGF1 molecule to increase its stability while retaining its biological activities. TTHX1114 was developed by one of the company’s founders, Michael Blaber, PhD at Florida State University. Dr. Blaber, along with the company’s other scientific founders, Ralph Bradshaw, PhD, and Ken Thomas, PhD, are recognized leaders in FGF research. Each of the founders has devoted more than 25 years to FGF research. FGF1 was discovered in Dr. Bradshaw’s laboratory and Dr. Thomas was the first to purify FGF1, determine its amino acid sequence and determine its biological activity.
Trefoil has licensed patents from Florida State University covering TTHX1114 as well as its use in ophthalmic conditions. Trefoil supplemented these patents with filings on company-developed technology.
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Endothelial Disease
The inner surface of the cornea is lined with endothelial cells, which play a critical role in maintaining a clear cornea. Although the number of endothelial cells slowly decreases with age, in a number of disorders, such as Fuchs endothelial cell dystrophy (FECD) the loss is accelerated. When the cells decline to a critical level, the consequence is clouding of the cornea, diminished vision and potential blindness in severe cases.
Patients who undergo intraocular surgery, such as cataract surgery or the implantation of glaucoma drainage devices, experience a loss of endothelial cells. Those patients with fewer endothelial cells before surgery may experience prolonged and persistent edema (swelling of the cornea) following intraocular surgery. This condition may result in a less than optimal surgical outcome and in some cases may require treatment by corneal transplantation.
Trefoil is developing TTHX1114, an intracameral injectable form of its engineered FGF1, as the first pharmaceutical treatment for the treatment of endothelial cell compromise associated with FECD or surgically induced endothelial damage.
Epithelial Conditions with
Associated Ulceration
Sjögren's syndrome is an autoimmune disorder that affects the ocular surface and the lacrimal glands, resulting in dry eye. Reduced tear production compromises the ocular surface and the corneal epithelium becomes vulnerable to damage, infection, and chronic inflammation, potentially causing corneal thinning, scarring, and vision loss.
Activation of herpes viruses, which cause oral and genital sores as well as chickenpox and shingles, can also affect the eye. Ocular herpes (herpetic keratopathy) can produce corneal ulcers that blur vision and induce intense pain and inflammation. There are no treatments specifically for these ulcers.
Neurotrophic keratitis is a degenerative corneal disease caused by impairment of corneal sensory innervation. The loss of corneal sensation leads to a reduction in tear production, blink reflex, and epithelial cell turnover, predisposing the cornea to breakdown, persistent epithelial defects, and, ultimately, ulceration and perforation.
Trefoil is developing a topical formulation of TTHX1114 to accelerate corneal ulcer wound healing by stimulating epithelial cell growth thereby reducing complications such as pain and inflammation. TTHX1114 also has the potential to treat other types of corneal damage, such as chemical or burn injuries and other types of ulcers.
Recent Publications
Ralph A. Bradshaw: Scholar, leader, entrepreneur, Stahl, P.D. (2022), Ralph A. Bradshaw: Scholar, leader, entrepreneur. FASEB BioAdvances, 4: 691-693.
Cost Burden of Endothelial Keratoplasty in Fuchs Endothelial Dystrophy: Real-World Analysis of a Commercially Insured US Population (2014–2019), Deepinder K Dhaliwal, Viktor Chirikov, Jordana Schmier, Sanika Rege, Schalon Newton Dovepress (2022)
Proliferation of Human Corneal Endothelia in Organ Culture Stimulated by Wounding and the Engineered Human Fibroblast Growth Factor 1 Derivative TTHX1114, David Eveleth, Sarah Pizzuto, Jessica Weant, Jennifer Jenkins-Eveleth, and Ralph A. Bradshaw Journal of Ocular Pharmacology and Therapeutics Ahead of Print (2020)
