A Phase 1 Dose-Escalation Study Evaluating the Safety, Tolerability, and Pharmacokinetics of TTHX1114(NM141) Ophthalmic Solution In Healthy Adult Volunteers

Dose escalation 3+3 design with accelerated titration 4 dose levels

Start Date06 Dec 2022

Sponsor / Collaborator

Trefoil Therapeutics, Inc.Startup

NCT04812067 / CompletedPhase 2

A Phase 2 Clinical Trial to Assess the Safety and Observe the Potential Benefit of TTHX1114 Delivered Via Intra-Cameral (IC) Injection

Expanded access, open label study at a single dose level in patients with CED that in the opinion of the investigators might benefit from TTHX1114

Start Date30 Nov 2021

Sponsor / Collaborator

Trefoil Therapeutics, Inc.Startup

NCT04676737 / CompletedPhase 2

Phase 2 Study To Determine the Safety and Efficacy of TTHX1114(NM141) on the Regeneration and Migration of Corneal Endothelial Cells in Patients Undergoing DWEK/DSO

Open label, single-treatment, with a concurrent non-treatment control

Start Date01 Feb 2021

Sponsor / Collaborator

Trefoil Therapeutics, Inc.Startup

100 Clinical Results associated with TTHX-1114

100 Translational Medicine associated with TTHX-1114

100 Patents (Medical) associated with TTHX-1114

Literatures (Medical) associated with TTHX-1114

01 Feb 2023·Cornea

Acceleration of Regeneration of the Corneal Endothelial Layer After Descemet Stripping Induced by the Engineered FGF TTHX1114 in Human Corneas in Organ Culture

Article

Author: Eveleth, David ; Weant, Jessica ; Pizzuto, Sarah ; Duffey, Grace

Purpose:Descemet stripping only (DSO, descemetorhexis without endothelial keratoplasty) is increasing in clinical use but can impose long recovery times. The objective of this research was to determine whether TTHX1114, an engineered analog of FGF1, could accelerate healing in corneas after DSO.Methods:Corneas obtained from eye banks were placed into suspension culture and subjected to DSO with a procedure comparable with that used clinically. The healing of the stripped area and the regeneration of the corneal endothelial cell (CEC) layer were evaluated intermittently for 14 days using trypan blue staining, alizarin red staining, and immunohistochemistry.Results:Corneas subjected to DSO showed about 30% of the stripped area healed after 14 days in culture while those treated with TTHX1114 healed 81%. The healed area was similar in both normal corneas and corneas judged by the eye banks to be dystrophic. The regeneration of the endothelial layer in the stripped area was substantially more complete in TTHX1114-treated corneas, most of which demonstrated a contiguous monolayer of CECs expressing ZO-1 at the cell–cell junctions. In corneas not subject to DSO, incorporation of EdU, a marker of proliferation, was stimulated by TTHX1114 treatment.Conclusions: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.

28 Jul 2021·Growth FactorsQ4 · BIOLOGY

Regenerative responses of rabbit corneal endothelial cells to stimulation by fibroblast growth factor 1 (FGF1) derivatives, TTHX1001 and TTHX1114

Q4 · BIOLOGY

Article

Author: Bradshaw, Ralph A. ; Dong, Hui ; Blaber, Michael ; Alimardanov, Asaf ; Broadt, Trevor ; Jenkins-Eveleth, Jennifer ; Weant, Jessica ; Yang, Xiaoyi ; Vyas, Vinay ; Eveleth, David D. ; Subramaniam, Amuthakannan ; Ornitz, David M. ; Li, Ling

Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC₅₀ ranges (3.3-24 vs.1.9-16. ng/mL) and, in organ culture, chemically lesioned corneas regained half of the lost endothelial layer in three days after treatment with the FGF1 derivatives as compared to controls. In vivo, following cryolesioning, the CEC monolayer, as judged by specular microscopy, regenerated 10-11 days faster when treated with TTHX1001. 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.

01 Nov 2020·Journal of Ocular Pharmacology and TherapeuticsQ4 · MEDICINE

Proliferation of Human Corneal Endothelia in Organ Culture Stimulated by Wounding and the Engineered Human Fibroblast Growth Factor 1 Derivative TTHX1114

Q4 · MEDICINE

Article

Author: Eveleth, David ; Bradshaw, Ralph A. ; Weant, Jessica ; Jenkins-Eveleth, Jennifer ; Pizzuto, Sarah

Purpose: Corneal endothelial dystrophies are characterized by endothelial cell loss and dysfunction. Recent evidence suggests that corneal endothelial cells (CECs) can regenerate although they do not do so under normal conditions. This work sought to test whether CECs can be stimulated to proliferate in organ culture by wounding and/or by treatment with the engineered human fibroblast growth factor 1 (FGF1) derivative TTHX1114. Methods: Human donor corneas obtained from eye banks were maintained in organ culture in the presence or absence of TTHX1114. Wounds in the corneas were created by quartering the corneas. The CEC monolayer was identified as a regular layer by Hoechst staining of the nuclear DNA with cell outlines delineated by immunohistochemical identification of ZO-1. Nuclei and nuclei incorporating 5-ethynyl-2'-deoxyuridine (EdU) were counted using ImageJ. Results: CECs in normal corneas in undisturbed monolayers had low, but measurable, rates of proliferation. CECs at the edge of a wound had higher rates of proliferation, probably due to the release of contact inhibition. TTHX1114 increased proliferation at wound edges. After 7 days of culture, proliferating CECs formed contiguous groups of labeled cells that did not migrate away from one another. TTHX1114-treated cells, including the EdU labeled proliferating cells, retained normal morphology, including cell/cell junction ZO-1 staining. Conclusions: Proliferation of CECs in organ-cultured corneas is low, but can be stimulated by wounding or by the administration of TTHX1114 with the effects of each being additive. The CEC monolayer appears to have a population of progenitor cells that are susceptible to stimulation.

News (Medical) associated with TTHX-1114

08 May 2023

·www.biospace.com

Trefoil Therapeutics’ Lead Investigational Candidate TTHX1114 Improves Rate of Visual Recovery after Descemet Stripping Only (DSO) in Phase 2 STORM Data Presented at ASCRS Annual Meeting

Additional data from the STORM study demonstrate vision quality to be a major driver of the patient decision to undergo surgery SAN DIEGO--(BUSINESS WIRE)-- Trefoil Therapeutics, a clinical-stage biotechnology company focused on developing novel new therapeutic agents to treat corneal diseases, today announced that TTHX1114 was found to improve the rate of visual recovery and corneal deturgescence (state of relative dehydration maintained by the normal cornea that is necessary for transparency) after Descemet Stripping Only (DSO) in a dose-responsive manner in the Phase 2 STORM study. A separate STORM analysis assessed visual morbidity in patients with Fuchs endothelial corneal dystrophy (FECD) prior to surgery using the V-Fuchs Questionnaire (V-FUCHS). The data were presented at the American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting in San Diego. Brandon J. Baartman, M.D., lead surgeon, Vance Thompson Vision (Omaha, NE), presented data from the Phase 2 STORM study designed to evaluate the safety and efficacy of TTHX1114, an engineered form of Fibroblast Growth Factor (FGF1), delivered as an intracameral injection as an adjunct to DSO (with or without combination cataract surgery). The study results showed TTHX1114 improved best-corrected visual acuity (BCVA) and central corneal thickness (CCT) after DSO in the 49 subjects/64 eyes. Faster recovery was associated with smaller descemetorhexis (surgical removal of Descemet membrane), while comorbid diabetes appeared to delay recovery. No significant differences were noticed in the recovery of subjects undergoing combination cataract surgery compared to those undergoing DSO alone. “Our increasing body of clinical evidence continues to support our hypothesis that FGF1 leverages the inherent regenerative properties of corneal endothelial and epithelial cells with TTHX1114 to restore vision. We are excited to continue to build on our research demonstrating the safety and efficacy of TTHX1114 in scenarios where patients with endothelial compromise undergo ocular surgery,” said David Eveleth, Ph.D., President and CEO of Trefoil Therapeutics. Russell Swan, M.D., presented “Assessing Visual Morbidity in Patients with FECD Prior to Surgery Using the V-Fuchs Questionnaire.” In this study data from the Phase 2 STORM study was utilized to assess the baseline characteristics of subjects and identify quality of vision characteristics that may motivate patients to seek DSO surgery. Despite baseline assessments showing reasonably good vision, even in the presence of disease, results from the V-FUCHS suggest moderate vision interference in daily activities, difficulty in seeing fine details, and issues with glare and halos, particularly at night. The V-FUCHS questionnaire is a 15 item, two domain self-report measure of vision function developed by Mayo Clinic. “Vision function from the perspective of the patient is an important consideration as quantitative measures of vision often do not capture the totality of how quality of vision affects daily activities. This indicates a need for providers to consider the lifestyle and visual requirements for patients and how quality of life may be impaired by corneal diseases when discussing treatment options,” said Dr. Eveleth. “Protection of the corneal endothelium in patients with Fuchs dystrophy undergoing surgery represents a significant unmet medical need,” said Mark Packer, M.D., Chief Medical Officer of Trefoil Therapeutics. “There is now a promising therapeutic agent that speeds recovery of the endothelium following surgery. TTHX1114 provides hope that patients at risk of corneal decompensation may maintain good vision and avoid the risks of corneal transplantation.” The abstracts can be found online here. All educational content of the ASCRS Annual Meeting is planned by its program committee, and ASCRS does not endorse, promote, approve, or recommend the use of any products, devices, or services. About TTHX1114 TTHX1114 is an investigational engineered variant of the naturally occurring molecule Fibroblast Growth Factor-1 (FGF1), which stimulates corneal endothelial and epithelial cell proliferation and migration as well as protecting these cells from stress and injury. Trefoil is conducting clinical trials for TTHX1114 as an intracameral injection in patients susceptible to corneal edema due to endothelial damage, including Fuchs endothelial corneal dystrophy (FECD) and other corneal endothelial dystrophies (CED) and patients with other risk factors undergoing ocular surgeries. The drug is aimed at protecting and regenerating corneal endothelial cells lost due to disease and thereby improving vision. Trefoil is also developing a topical formulation of TTHX1114 which stimulates corneal epithelial cell growth, potentially reducing common complications associated with ulcerative corneal conditions, such as pain, inflammation, and loss of vision due to corneal scarring. The Phase 1 safety study for the topical product was completed in April 2023. About Trefoil Therapeutics San Diego-based Trefoil Therapeutics is a clinical-stage biotechnology company focused on leveraging its engineered FGF1 protein technology platform to develop first-in-class pharmacologic treatments for serious corneal endothelial diseases and epithelial disorders. Trefoil’s lead product candidate is TTHX1114, an investigational engineered form of naturally occurring FGF1 designed to stimulate corneal cell protection, proliferation and migration, which will treat a number of corneal conditions. The technology underlying Trefoil’s platform was developed by co-founders Michael Blaber, Ph.D., and David Eveleth, Ph.D., and is licensed from Florida State University. Trefoil investors include Bios Partners, Hatteras Venture Partners, Access Biotechnology, Solasta Ventures, InFocus Capital Partners, Correlation Ventures, ExSight Ventures and FemHealth Ventures. Learn more at . Safe Harbor Statement The clinical research discussed in this press release is preliminary and the outcome of such studies may not be predictive of the outcome of later clinical trials. Future clinical trial results may not demonstrate safety and efficacy sufficient to obtain regulatory approval related to the clinical research findings discussed in this press release.

Clinical ResultPhase 2Phase 1

25 Apr 2023

·www.businesswire.com

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

SAN DIEGO--( BUSINESS WIRE )-- Trefoil Therapeutics , a clinical-stage biotechnology company focused on developing novel new therapeutic agents to treat corneal diseases, today 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, Ph.D., 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 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 . About TTHX1114 TTHX1114 is an investigational engineered variant of the naturally occurring molecule Fibroblast Growth Factor-1 (FGF1), which stimulates corneal endothelial and epithelial cell proliferation and migration as well as protecting these cells from stress and injury. Trefoil is conducting clinical trials for TTHX1114 as an intracameral injection in patients susceptible to corneal edema due to endothelial damage, including FECD and other corneal endothelial dystrophies (CED) and patients with other risk factors undergoing ocular surgeries. The drug is aimed at protecting and regenerating corneal endothelial cells lost due to disease and thereby improving vision. The topical formulation of TTHX1114 is designed to accelerate corneal ulcer wound healing by stimulating corneal epithelial cell growth, potentially reducing common complications associated with corneal ulcers, such as pain, inflammation, and loss of vision due to corneal scarring. The Phase 1 safety study for the topical product was completed in March of 2023. About Trefoil Therapeutics San Diego-based Trefoil Therapeutics is a clinical-stage biotechnology company focused on leveraging its engineered FGF1 protein technology platform to develop first-in-class pharmacologic treatments for serious corneal endothelial diseases and epithelial disorders. Trefoil’s lead product candidate is TTHX1114, an investigational engineered form of naturally occurring FGF1 designed to stimulate corneal cell protection, proliferation and migration, thereby reversing vision loss. The technology underlying Trefoil’s platform was developed by co-founders Michael Blaber, Ph.D., and David Eveleth, Ph.D., and is licensed from Florida State University. Trefoil investors include Bios Partners, Hatteras Venture Partners, Access Biotechnology, Solasta Ventures, InFocus Capital Partners, Correlation Ventures, ExSight Ventures and FemHealth Ventures. Learn more at www.trefoiltherapeutics.com . Safe Harbor Statement The clinical research discussed in this press release is preliminary and the outcome of such studies may not be predictive of the outcome of later clinical trials. Future clinical trial results may not demonstrate safety and efficacy sufficient to obtain regulatory approval related to the clinical research findings discussed in this press release.

Clinical ResultPhase 1Phase 2

18 Apr 2023

·www.biospace.com

Trefoil Therapeutics Announces TTHX1114 Data Presentations at the Annual Association for Research in Vision and Ophthalmology (ARVO) Meeting

SAN DIEGO--(BUSINESS WIRE)-- Trefoil Therapeutics, a clinical-stage biotechnology company focused on restoring sight to people with corneal diseases, today announced multiple presentations providing evidence for clinical and preclinical efficacy of the company’s investigational medicine TTHX1114 for improving visual outcomes and protection against corneal endothelial damage at the Annual Association for Research in Vision and Ophthalmology (ARVO) Meeting in New Orleans, April 23-27, 2023. “We aim to address an unmet clinical need with TTHX1114 by offering the potential to restore vision by stimulating and protecting the cornea’s own endothelial cells,” said David Eveleth, Ph.D., President and CEO of Trefoil Therapeutics. “We're excited to share the growing body of research that supports TTHX1114 as an important and unique approach to corneal disease.” The details of the presentations are as follows (all times local, CT): 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 Presenter: David Eveleth Location: Room 244 Date and Time: Monday, April 24, 2023; 11:30-11:45 am The engineered fibroblast growth factor TTHX1114 mediates enrichment of proliferative and wound healing pathways in wounded human corneal endothelium Poster Number: 618 - B0255 Date and Time: Sunday, April 23, 2023; 12:00-1:45 pm Factors Affecting Recovery Following Descemet Stripping Only (DSO) with TTHX1114 Poster Number: 631 - B0268 Date and Time: Sunday, April 23, 2023; 12:00-1:45 pm TTHX1114 Protects Primary Rabbit Corneal Endothelial Cells from Oxidative Stress Poster Number: 621 - B0258 Date and Time: Sunday, April 23, 2023; 12:00-1:45 pm David Eveleth will be a panelist in a symposium titled “Emerging Therapeutics to Maintain Corneal Health” on April 25, 2023, from 8:45-10:30 am in the La Nouvelle C room. His topic will be: The Role of Fibroblast Growth Factor derivatives in corneal endothelial regeneration which will be presented from 9:13-9:27 am. Trefoil will also be present at booth #1156. About TTHX1114 TTHX1114 is an investigational engineered variant of the naturally occurring molecule Fibroblast Growth Factor-1 (FGF1), which stimulates cell proliferation and migration as well as protecting cells from stress and injury. Trefoil is conducting clinical trials for TTHX1114 as an intracameral injection into the eye for patients susceptible to corneal edema due to endothelial damage, including Fuchs Endothelial Corneal Dystrophy (FECD) and other corneal endothelial dystrophies (CED) and patients with other risk factors undergoing ocular surgeries. The drug is aimed at protecting and regenerating corneal endothelial cells lost due to disease and thereby improving vision. The topical formulation of TTHX1114 is designed to accelerate corneal ulcer wound healing by stimulating epithelial cell growth, potentially reducing common complications associated with corneal ulcers, such as pain, inflammation, and loss of vision due to corneal scarring. The Phase 1 safety study for the topical product was completed in March of 2023. About Trefoil Therapeutics San Diego-based Trefoil Therapeutics is a clinical-stage biotechnology company focused on leveraging its engineered FGF1 protein technology platform to develop first-in-class pharmacologic treatments for serious corneal endothelial diseases and epithelial disorders. Trefoil’s lead product candidate is TTHX1114, an investigational engineered form of naturally occurring FGF1 designed to stimulate corneal cell protection, proliferation and migration, thereby reversing vision loss. The technology underlying Trefoil’s platform was developed by co-founders Michael Blaber, Ph.D., and David Eveleth, Ph.D., and is licensed from Florida State University. Trefoil investors include Bios Partners, Hatteras Venture Partners, Access Biotechnology, Solasta Ventures, InFocus Capital Partners, Correlation Ventures, ExSight Ventures and FemHealth Ventures. Learn more at . Safe Harbor Statement The clinical research discussed in this press release is preliminary and the outcome of such studies may not be predictive of the outcome of later clinical trials. Future clinical trial results may not demonstrate safety and efficacy sufficient to obtain regulatory approval related to the clinical research findings discussed in this press release.

Phase 1

100 Deals associated with TTHX-1114

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Indication	Highest Phase	Country/Location	Organization	Date
Camurati-Engelmann Syndrome	Phase 2	US	Trefoil Therapeutics, Inc.Startup	30 Nov 2021
Corneal Endothelial Dystrophy Type 2	Phase 2	US	Trefoil Therapeutics, Inc.Startup	30 Nov 2021
Fuchs' Endothelial Dystrophy	Phase 2	US	Trefoil Therapeutics, Inc.Startup	01 Feb 2021
Bullous keratopathy	Phase 2	US	Trefoil Therapeutics, Inc.Startup	19 Aug 2020
Endothelial dysfunction	Phase 2	US	Trefoil Therapeutics, Inc.Startup	19 Aug 2020
Corneal epithelial defect	Phase 1	US	Trefoil Therapeutics, Inc.Startup	18 Jan 2023
Corneal epithelial degeneration	Phase 1	US	Trefoil Therapeutics, Inc.Startup	06 Dec 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04520321 (INTREPID, CTgov)	Phase 1/2	Corneal Endothelial Dystrophy Type 2 \| Bullous keratopathy \| Endothelial dysfunction \| Fuchs' Endothelial Dystrophy	22	Vehicle (placebo) (Vehicle (Placebo))	pxlqbahuqy(kygbmaqsuq) = cyqxjvwwhe tsmmhlnwph (poiagydvxu, hrquumtmcd - vjcgqokdgr) View more	-	30 Oct 2023
				TTHX1114(NM141) (Low Dose)	pxlqbahuqy(kygbmaqsuq) = vasaqnepoc tsmmhlnwph (poiagydvxu, mnnxqkxtrq - lxaohwbgqo) View more
TTHX-002 (ARVO2023)	Not Applicable	comorbid diabetes	50	TTHX1114	eossbosswx(yimqytzhla) = xikktmgght ccniimaqjs (xynvdeljbm ) View more	-	01 Jun 2023
STORM study (ARVO2023)	Phase 2	Fuchs' Endothelial Dystrophy	-	TTHX1114	(ppevdcgytd) = mabitniwjg bsgodneton (nbdyhbmorx )	-	23 Apr 2023
				TTHX1114	(ppevdcgytd) = dvqwbjpbtm bsgodneton (nbdyhbmorx )
NCT04676737 (STORM, Corporate Publications) Manual	Phase 2	Fuchs' Endothelial Dystrophy	40	TTHX1114	(yceqpkmjlz) = dgnzihftst jifbrnqjgs (kiaigpdtqw ) View more	Positive	29 Sep 2022
ARVO2022	Phase 1/2	Iridocorneal Endothelial Syndrome	22	TTHX1114 1ng	(ulyhdogilh) = 4 AEs were considered related to the IC injections procedure; these events were all mild, reported only in 1 subject each, and included conjunctival hemorrhage, eye irritation, foreign body sensation in eye, and photophobia yssrciqlfc (jaulooaajx )	-	01 May 2022
				TTHX1114 3ng
ARVO2021	Not Applicable	-	-	TTHX1114	ztkegvosgr(mfkyuwojgd) = tsbplsnuai ixwoznuxtz (bktpdwwryy )	-	01 Jun 2021
				engineered fibroblast growth factor TTHX1114	ztkegvosgr(mfkyuwojgd) = ijmnrwhsev ixwoznuxtz (bktpdwwryy )
ARVO2020	Not Applicable	Corneal Endothelial Cell Loss	-	TTHX1114	(mpconqpqsb) = nofsynlncl xaelrcrlnb (nxaeqrrcxy )	-	01 Jun 2020
				TTHX1114	(mpconqpqsb) = nayjecmspw xaelrcrlnb (nxaeqrrcxy )

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