Our Technology

Technology Overview

The technology underlying Trefoil’s engineered FGF-1, TTHX1114 builds on the well-known activities of naturally-occurring (native) FGF-1 to enable its use as a pharmaceutical for corneal diseases. Native FGF-1 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 FGF-1’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 eFGF-1

The company’s engineered FGF-1, TTHX1114, is designed to increase the half-life of the naturally-occurring FGF-1 molecule. The key innovation was the introduction of specific mutations into the FGF-1 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. FGF-1 was discovered in Dr. Bradshaw’s laboratory and Dr. Thomas was the first to purify FGF-1, determine its amino acid sequence and determine its mitogenic and biological activities.

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.

Polymorphic structure of normal cells (Illustrated)

Irregular diseased cells
(Illustrated)

Healthy endothelial cells
(Fluorescence microscopy)

Cells with Fuchs’ dystrophy
(Fluorescence microscopy)

Endothelial Disease

The interior surface of the cornea is lined with endothelial cells, which play a critical role in ensuring the cornea is clear by maintaining the eye in a state of relative dehydration. Although the number of endothelial cells slowly decrease with aging, in a number of disorders, such as Fuchs Endothelial Cell Dystrophy (FECD), the loss is accelerated. The consequence is clouding of the cornea, diminished vision and potential blindness in severe cases. Trefoil is developing TTHX1114, an intracameral injectable form of its engineered FGF-1, as the first pharmaceutical treatment for FECD to regenerate lost corneal endothelial cells and help restore lost vision.

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Corneal Ulcers

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. 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 potential to treat other types of corneal damage, such as chemical burns or burn injuries and other types of ulcers.

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Recent Publications

A Bell-Shaped Dose Response of Topical FGF-1 in Dermal Wound Healing of Aged Female BALB/cByJ Mice, Hagerott, B.N., Blumstein, A.J., McGarry, L.E., Cohen, H.M., Tenorio, C.A., Powell, B.D., Nagy, T. and Blaber, M. Journal of Proteins and Proteomics (2020)

Fine-sampled Photographic Quantitation of Dermal Wound Healing Senescence in Aged BALB/cByJ Mice and Therapeutic Intervention with FGF-1, Mellers, A., Tenorio, C.A., Lacatusu, D., Powell, B., Patel, B., Harper, K.M. and Blaber, M. Advances in Wound Care 7, 409-418 (2018)

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