TTHX1114 intracameral injection / Trefoil Therapeutics - LARVOL DELTA

TTHX1114 Guards Against Ferroptosis in Primary Rabbit Corneal Endothelial Cells (ARVO 2024) - "By reducing cell loss and DNA breakage; perturbing ferroptotic processes; and upregulating cell survival, proliferation, and anti-ferroptosis genes, a pre/post treatment with 50ng/mL TTHX is ideal for maximizing protection and rescue of pRCEnCs from oxidative stress and cell death."

Preclinical • Cataract • Ophthalmology • ACSL4 • HMOX1 • SLC7A11 • TJP1

TTHX1114 Rescues Cells Against DNA damage and Cell Loss in Primary Rabbit Corneal Endothelial Cells (ARVO 2024) - "A pre and / or post treatment with 50 ng/mL TTHX after an oxidative stress insult that results in 10-40% cell loss is sufficient for protecting and rescuing pRCEnCs from DNA damage and cell death"

Preclinical • Cataract • Ophthalmology • FGF1 • TJP1

TTHX1114(NM141) in Combination With DWEK/DSO (clinicaltrials.gov) - P2 | N=49 | Completed | Sponsor: Trefoil Therapeutics, Inc. | Active, not recruiting ➔ Completed | Trial primary completion date: Mar 2022 ➔ Nov 2022

Combination therapy • Trial completion • Trial primary completion date • Ophthalmology

OPTIC: A Safety and Efficacy Trial of TTHX1114 in People With CED (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: Trefoil Therapeutics, Inc. | Enrolling by invitation ➔ Completed | N=24 ➔ 41 | Trial primary completion date: Nov 2023 ➔ Aug 2023

Enrollment change • Trial completion • Trial primary completion date

TTHX1114 Protects Primary Rabbit Corneal Endothelial Cells from Oxidative Stress (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Oxidative stress • Preclinical • Cataract • Ophthalmology

The engineered fibroblast growth factor TTHX1114 mediates enrichment of proliferative and wound healing pathways in wounded human corneal endothelium (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • DUSP6 • PLA2G2A

Protection of endothelial cells by TTHX1114 in patients with Fuchs endothelial corneal dystrophy (FECD) undergoing Descemet’s Stripping Only (DSO) in combination with cataract surgery: evidence from the STORM study (ARVO 2023) - "These data support the potential use of TTHX1114 for the control of postsurgical edema in high risk patients undergoing cataract surgery Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Clinical • Combination therapy • Surgery • Cataract • Ophthalmology

A Phase 2 Study of an Engineered Fibroblast Growth Factor (FGF) to Accelerate Visual Recovery after Descemet Stripping Only (DSO) (ASCRS-ASOA 2023) - "Purpose This open label, non-randomized, study was designed to evaluate the safety and efficacy of TTHX1114 (an engineered FGF1) delivered as an intracameral injection as an adjunct to DSO with and without combination cataract surgery.Efficacy measurements included best-corrected visual acuity (BCVA) and central corneal thickness (CCT)MethodsSubjects were assigned to treatment at the discretion of the Investigator which included 3 active dose regimens (low-dose repeat administration [Group 2], high-dose single-administration [Group 3], high-dose repeat administration [Group 4]).BCVA Responder was defined as an eye achieving 20/40 or better post-DSO.CCT Responder was defined as an eye with a post-DSO CCT measurement less than pre-DSO.A dose effect was seen between the low-dose (Group 2) and the high-dose groups (Groups 3 and 4) in both BCVA and CCT.Efficacy was similar in Groups 3 and 4; all eyes in these groups were pooled (52 eyes) to evaluate the effect of covariates..."

P2 data • Cataract • Diabetes • Metabolic Disorders • Ophthalmology • FGF

Acceleration of Regeneration of the Corneal Endothelial Layer After Descemet Stripping Induced by the Engineered FGF TTHX1114 in Human Corneas in Organ Culture. (PubMed, Cornea) - "The corneal organ culture model recapitulated clinical observations of DSO, only with much more rapid recovery. Within the immediate postsurgical time frame of 2 weeks, treatment with TTHX1114 stimulated near-total regeneration of the CEC layer, suggesting that TTHX1114 may be useful as an adjunct to DSO."

Journal • Ophthalmology • Transplantation • FGF • TJP1

A Human Corneal Organ Culture Model of Descemet's Stripping Only with Accelerated Healing Stimulated by Engineered Fibroblast Growth Factor 1. (PubMed, J Vis Exp) - "Using this approach to evaluate the efficacy of the human engineered FGF1 (NM141), we found that treatment accelerated healing via stimulation of migration and proliferation of CECs. This finding was confirmed in 11 pairs of human corneas with signs of dystrophy reported by the eye banks in order to verify that these results can be replicated in patients with Fuchs' Dystrophy, as the target population of the DSO procedure."

Journal • Ophthalmology • Transplantation

A Phase 1/ Phase 2 Study Evaluating the Safety and Efficacy of TTHX1114 on the Regeneration of Corneal Endothelial Cells in Patients with Corneal Endothelial Dystrophy (ARVO 2022) - "Standard ocular assessments were sufficient to assess the safety and tolerability of TTHX1114 and an injection volume of 10mcL which appeared to be safe and well-tolerated. The MTD was not exceeded and the RP2D was determined to be 10ng/10mcL delivered by IC injection. The study was originally designed to also obtain a preliminary estimate of efficacy by assessment of CEC densities but this was confounded by the presence of guttae and the inability to reproducibly image the same geographic location at subsequent visits."

Clinical • P1 data • P2 data • Ophthalmology

TTHX1114(NM141) in Combination With DWEK/DSO (clinicaltrials.gov) - P2; N=40; Active, not recruiting; Sponsor: Trefoil Therapeutics, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2021 ➔ Mar 2022

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Ophthalmology

OPTIC: A Safety and Efficacy Trial of TTHX1114 in People With CED (clinicaltrials.gov) - P2; N=24; Enrolling by invitation; Sponsor: Trefoil Therapeutics, Inc.; Recruiting ➔ Enrolling by invitation

Enrollment status

Regenerative responses of rabbit corneal endothelial cells to stimulation by fibroblast growth factor 1 (FGF1) derivatives, TTHX1001 and TTHX1114. (PubMed, Growth Factors) - "Over two weeks, all treated eyes showed clearing of opacity about twice that of untreated controls. In all three rabbit models, both FGF1 derivatives were effective in inducing CEC proliferation over control conditions, supporting the prediction that these stabilised FGF1 derivatives can potentially regenerate corneal endothelial deficits in humans."

Journal • Preclinical