A Study to Evaluate Safety and Efficacy of a New Formulation of Recombinant Human Nerve Growth Factor (rhNGF) Eye Drop Solution in Patients With Dry Eye Disease

Inclusion Criteria:

• Male or female aged ≥18 years of any race/ethnicity and eye color.

• A diagnosis of dry eye disease at least 6 months before enrollment (current use orrecommended use of artificial tears for the treatment of dry eye).

• Moderate-to-severe dry eye characterized by the following clinical features:

1. Symptoms Assessment in Dry Eye (SANDE) questionnaire global score ≥50, and

2. Schirmer-I test without anesthesia >2 mm and <10 mm/5 minutes, and

3. Total corneal fluorescein staining grade ≥3 (NEI scale) and/or totalconjunctival lissamine green staining score ≥3 assessed by the NEI gradingsystem, and

4. Fluorescein tear film break-up time (fTBUT) < 10 seconds The same eye must havefulfilled all the above criteria.

• Best corrected distance visual acuity (BCDVA) score on ETDRS chart of ≥0.1 decimalunits (≤1.0 logMAR) in each eye at the time of study enrollment

• Negative pregnancy test in females of childbearing potential.

• Only participants who satisfy all informed consent requirements will be included inthe study; the participant and/or his/her legal representative must have read,signed, and dated the informed consent document before any study-related proceduresare performed; the informed consent form signed by participants and/or legalrepresentatives must have been approved by the Institutional Review Board (IRB) forthe current study.

• Have the ability and willingness to comply with study procedures.

Exclusion Criteria:

• Inability to speak and understand the local language sufficiently to understand thenature of the study, to provide written informed consent, and to allow thecompletion of all study assessments.

• Evidence of an active ocular infection in either eye.

• Presence of any other ocular disorder or condition requiring topical ocularmedication during the entire duration of the study.

• Possibility of the need for ocular surgery at the time of inclusion in the study oranticipated ocular surgery expected during the participation in the study

• History of severe systemic allergy or severe ocular allergy [including seasonalconjunctivitis, AKC (Atopic KeratoConjunctivitis), VKC (VernalKeratoConjunctivitis)] or chronic conjunctivitis and/or keratitis other than dryeye.

• Ocular scarring due to irradiation, alkali burns, Stevens-Johnson syndrome andocular cicatricial pemphigoid.

• Destruction of conjunctival goblet cells such as in Vitamin A deficiency.

• Severe blepharitis or obvious inflammation of the lid margin.

• Intraocular inflammation defined as Tyndall score >0.

• Medical history of tumor malignancy in the previous 3 years

• Systemic disease not stabilized within 1 month before the screening visit (e.g.,diabetes with glycemia out of range, thyroid malfunction) or judged by theinvestigator to be incompatible with the study (e.g., current systemic infections)or with a condition incompatible with the frequent assessment required by the study.

• History of a serious adverse reaction or significant hypersensitivity to any drug orchemically related compounds or had a clinically significant allergy to drugs,foods, topical anesthetic eye drop or other local anesthetics or other materials,including ocular vital dyes, tropicamide eye drops, commercial artificial tears.

• Known or suspected allergy to component(s) of the new rhNGF formulation.

• Fertile patients (i.e., not surgically sterilized, or postmenopausal women for atleast 1 year) are excluded from participation in the study if they do not practiceabstinence from heterosexual intercourse as per usual and customary lifestyle, orare unwilling to use an acceptable form of contraception such as condom withspermicidal cream or jelly for males, or for females if they meet any one of thefollowing conditions:

1. Currently pregnant (positive urine pregnancy test at screening or baselinevisits) or planning to become pregnant during the duration of the treatmentphase of the clinical trial.

2. Participant is breastfeeding.

3. Unwilling to use birth control measures such as mechanical barrier methods (spermicide in conjunction with a barrier such as a condom or diaphragm orintrauterine device) during the entire course of and 30 days after the studytreatment period, or,

4. Unwilling to continue to use highly effective birth control measures such ashormonal contraceptives (oral, implanted, transdermal, or injected) during theentire course of and 30 days after the study treatment period.

• Any concurrent medical condition that, in the judgment of the principalinvestigator, might interfere with the conduct of the study, confound theinterpretation of the study results, or endanger the participant's well-being.

• Contact lenses or punctum plug use in either eye during the washout, treatment, andfollow-up phases of the study (previous use is not an exclusion criteria but must beremoved and discontinued at the Screening visit).

• Medical history of drug addiction or alcohol abuse (>1 drink /day for women and >2drinks /day for men following USDA dietary Guidelines 2020-2025).

• Any prior ocular surgery including but not limited to amniotic membrane transplant,refractive [PTK (Excimer Laser Phototherapeutic Keratectomy) / LASIK (Laser-AssistedIn Situ Keratomileusis) / Epi-LASIK (Epithelial Laser In Situ Keratomileusis) /LASEK (Laser-Assisted Subepithelial Keratectomy) / SMILE (Small Incision LenticuleExtraction)], palpebral, cataract surgery, trabeculectomy, vitrectomy andPan-Retinal Photocoagulation (PRP) within 90 days before the screening visit.

• Participation in a clinical trial with a new active substance, including medicaldevices, during the previous 60 days.

• Participation in another clinical trial study at the same time as the present study.