MAD Study to Assess the Safety, Tolerability, PKs and Efficacy of YJ001 for Spray Use in Patients With DPNP

Inclusion Criteria:

• Male or female, between the ages of 18 to 80 years at screening, both inclusive.

• Subjects voluntarily consenting for participation in the study and having signedinformed consent document. Subjects are required to understand verbal and/or writtenEnglish or any other language in which a certified translation of the informedconsent is available.

• Body mass index (BMI) between 19 to 42 kg/m2 (both inclusive) at screening,calculated as weight (kg)/height2 (m2). Subjects must have two feet. Each foot musthave five digits. Each foot must have at least total surface area of 450 cm2measured from below the ankle to the toes including both dorsum and plantar areas.

• The subject is diagnosed with Type 1 or Type 2 diabetes, and has a history of DPNPfor at least 3 months based on participant report or medical history.

• The subject should have a glycemic control that has been optimized and has beenstable for at least 3 months prior to randomization. The subject has used a stableregimen of antidiabetic agents (oral) and/or insulin for at least 3 months beforescreening.

• Glycated hemoglobin (HbA1c) ≤ 10% at screening.

• Participants who have a weekly mean score of at least 4 based upon the daily meanscores using 11-point Numeric Rating Scale (NRS) in the daily diary (rated twicedaily, once in the morning and the other in the evening) from Day -7 through Day 1 (should be calculated from records 7 days immediately prior to study drugadministration).

• Males must not donate sperm until 90 days after last dose of study drug and must bewilling to use a condom during heterosexual activity for up to 90 days after theapplication of the study drug.

• Females must be either postmenopausal for at least 1 year, surgically sterile (bilateral tubal ligation [including clip, cauterization methods and coil],bilateral oophorectomy or hysterectomy, and needs to be confirmedfollicle-stimulating hormone [FSH] level >40 IU/L), or of childbearingpotential either practicing true abstinence or practicing 2 effective means ofcontraception for at least 4 weeks prior to randomization, and until 28 days afterstudy drug administration:

1. Intrauterine device (IUD) or IUD hormone-releasing system.

2. Combined estrogen and progestogen containing hormonal contraception (oral,intravaginal, or transdermal) associated with inhibition of ovulation.

3. Progesterone-only hormonal contraception (oral, injectable, implantable)associated with inhibition of ovulation.

4. Intrauterine hormone-releasing system.

5. Double-barrier method (condoms, contraceptive sponge, diaphragm, or vaginalring with spermicide).

• Able and willing to comply with all study requirements.

Exclusion Criteria:

• Current participation in another investigational drug or device study or treatedwith an investigational drug within 30 days or 5 half-lives, whichever is longer,before dosing.

• History of clinically significant drug, food allergy, skin allergy, or sensitivityto drugs of the same class (e.g., 5-aminosalicylic acid, sulfasalazine, andsalicylates) or known hypersensitivity to YJ001 or any of its components.

• History of asthma. Adults with history of benign (resolved) childhood asthma may beincluded.

• Any subject who suffers severe peripheral vascular disease (e.g., intermittentclaudication) at screening, and is not suitable to be involved in the study as perinvestigator evaluation.

• Any subject who suffers severe cardiovascular and cerebrovascular disease (e.g.,severe arrhythmia, heart failure, myocardial infarction, unstable angina pectoris,atherosclerosis, stroke, sequela of stroke, etc.), severe gastrointestinal tractdisease or other serious disease (e.g., cancer) which, in the opinion of theInvestigator, would prevent the subject from fully participating in the study.

• Any subject who suffers chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or multifocal motor neuropathy (MMN).

• Any subject who has a history of moderate to severe depression, obvious neurologicalor mental disorder not related to neuropathic pain but may interfere with rating ofpain, as well as poly neuropathy, numbness, feeling of pins and needles and weaknessin extremities, other serious pain cannot be clearly differentiated from orconditions that may interfere with rating of neuropathic pain. Subjects withweakness but w/o sensory complaints may be included.

• Any other medical, psychological, or social condition which, in the opinion of theInvestigator, would prevent the subject from fully participating in the study, wouldrepresent a concern for study compliance, or would constitute a safety concern tothe subject.

• Any subject who has suffered one or more severe hypoglycemia event (defined asneurofunctional hypoglycemia that needs third-party assistance) within 6 monthsprior to screening.

• Pain scores < 3 on the NRS over twice during the one-week run-in period.

• Any subject with unstable or poorly controlled abnormality in blood pressure orlipid (blood pressure ≥ 160 mmHg/95 mmHg, total cholesterol ≥ 6.2 mmol/L, and/ortriglyceride ≥ 6.3 mmol/L) at screening.

• Any subject with abnormal renal function, estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m2.

eGFR=186×Scr^-1.154×Age^-0.203×(0.742 for Female)

• Any subject with abnormal liver function, liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) greater than 2 times upper limit ofnormal.

• Consumed 8 units or more of alcoholic beverages per week for women or 15 units ormore of alcoholic beverages per week for men at any time in the 6 months beforedosing (1 unit of ethanol is equivalent to 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of spirits) or history of drug or alcohol abuse within the 6 monthsbefore dosing or evidence of such abuse as indicated by inquiry, medical history orthe laboratory assays conducted during screening. Any subject who has past historyof heavy drinking or alcoholism.

• Any subject who consumes more than 5 cigarettes per day within 30 days before studydrug dosing or who cannot stop using any tobacco- or nicotine-containing productduring the duration of the trial.

• Positive screening or check-in alcohol/drugs of abuse/cotinine screen.

• Positive test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Screening. SARS-CoV-2 testing will be either antigen, nasopharyngeal (NP) or nasal swab polymerase chain reaction (PCR) performed at Day -1, and inaccordance with Centers for Disease Control and Prevention (CDC), FDA and localhealth authorities at the time of enrollment for this study. Participants notwilling to comply with the investigational site's Coronavirus Disease 2019 (COVID

19. policy.

• Female volunteers who are pregnant or lactating.

• Have a significant acute illness within 7 days prior to study drug administration orhave had a major illness or hospitalization within 1 month prior to study drugadministration.

• Systemic or topical use of aspirin or salicylic acid containing products orsulfasalazine/salicylic acid derivatives within 14 days of study drug dosing.

• Use of other prescription and non-prescription medications (with the exception ofpermitted concomitant medications, oral contraceptives, combined estrogen andprogestogen containing hormonal contraception and progestogen-only hormonalcontraception), such as blood thinners, or sucralfate or herbal preparations within 14 days or 5 half-lives (whichever is longer) before study drug dosing, or use of anover-the-counter medication, vitamins, or supplements (including fish liver oils)within 14 days before study drug dosing.

• Positive screen on Hepatitis B, Hepatitis C, or Human immunodeficiency virus (HIV)at the time of screening evaluations.

• History of blood donation of more than 500 mL in the last 2 months prior toscreening.

• History or evidence of poor venous access.

• History of bleeding disorders.

• Any subject with foot ulcers and/or pedal oedema. Presence of skin disorders,tattoos, skin breakdown, or other skin conditions on either foot that may interferewith the objectives of the study (as per investigator evaluation).

• Use of any kind of topical lotions, sunscreen, heating pads/cooling pads on feet forat least 24 hours before study drug is administered and until End-of-Study.

• An employee of the study center or Sponsor or family member of a study centeremployee

• Unwilling to stay in the clinical unit for the required duration as per the protocolor consume the standard meal to be provided as per the protocol.

• Any subject considering or scheduled to undergo any surgical procedure fromscreening to at least 7 days post dose.