New Trefoil Therapeutics’ Data Presented at ARVO Demonstrate that TTHX1114 Controls Edema in At-Risk Patients Undergoing Cataract Surgery

Trefoil Therapeutics announced a series of data presentations demonstrating the potential use of TTHX1114 to protect endothelial cells at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in New Orleans. The company also announced the completion of the phase 1 epithelial study designed to assess the safety and dosing profile of TTHX1114 in a topical eye drop formulation for epithelial conditions.

David Eveleth, PhD, President and CEO of Trefoil Therapeutics, presented a data update from the Phase 2 STORM study, which evaluated the potential use of TTHX1114 as a way to protect endothelial cells from damage due to cataract surgery in Fuchs endothelial corneal dystrophy (FECD) patients undergoing Descemet Stripping Only (DSO).

New findings included:

• Across all patients, TTHX1114 produced a dose-dependent response in resolution of corneal edema and improvement of best corrected visual acuity (BCVA) following surgery
• The proportion of patients with complete resolution of corneal edema in the high-dose groups at 28 days after surgery was similar in patients with DSO vs. those with DSO and cataract surgery (25.9% vs 17.4%)
• The proportion of patients recovering adequate BCVA (seeing 69 letters or better) was also similar between these groups, with 58% of the DSO only patients vs. 61% of the DSO and cataract surgery patients at 28 days after surgery

“Corneal endothelial diseases, like FECD, affect millions of Americans, and today there are limited treatment options. Therefore, it is imperative that we continue to explore new therapies to allow these patients to retain functional vision. It is exciting to see TTHX1114 perform well in controlling post-surgical edema in at-risk patients undergoing cataract surgery,” said Mr. Eveleth.

In the poster presentation “Factors affecting recovery following Descemet Stripping Only (DSO) with TTHX1114,” recovery following DSO was evaluated in relation to three variables. Smaller descemetorhexis (surgical removal of Descemet membrane) size was associated with faster recovery while comorbid diabetes appeared to delay recovery. However, visual outcomes for patients undergoing DSO did not appear to be adversely affected by concurrent cataract surgery.

The poster presentation “The engineered fibroblast growth factor TTHX1114 mediates enrichment of proliferative and wound healing pathways in wounded human corneal endothelium,” followed up on Trefoil’s publication earlier this year demonstrating that TTHX1114 accelerates wound healing in the corneal endothelium. RNA-sequencing analysis was performed to identify changes in gene expression and pathway enrichment resulting from treatment with TTHX1114. These results confirmed that treatment of wounded corneal endothelium with TTHX1114 generates a statistically significant shift in gene expression, and specifically produces a response in fibroblast growth factor (FGF) signaling, potentially connected to the previously reported 2.5 times greater wound healing in treated corneas.

Protecting the corneal endothelium from further damage due to oxidative stress is beneficial for FECD patients and cataract patients as the two are closely linked. In the poster presentation, “TTHX1114 protects and rescues primary rabbit corneal endothelial cells from oxidative stress,” data show that TTHX1114 protects and rescues rabbit corneal endothelial cell viability against tBHP induced oxidative stress, supporting TTHX1114 as a promising approach to mitigate endothelial damage.

The abstracts are available at the ARVO 2023 program here.