Ph 1, Single-Center, Safety, Tolerability & Pharmacokinetic Study of KX2 391 Ointment in Subj. w Actinic Keratosis

Inclusion Criteria:

1. Subject is at least 18 years old

2. Subject has a clinical diagnosis of stable, clinically typical AK

3. Subject has a treatment area on 1 dorsal forearm that in:

Cohort 1:

- Is one contiguous area

- Measures 25 cm2

- Contains 4 to 8 AK lesions that are clinically typical.

Cohort 2:

- Is one contiguous area

- Measures 100 cm2

- Contains 8 to 16 AK lesions that are clinically typical.

4. All women of childbearing potential (WOCBP) must be:

- Post-menopausal, defined as at least 50 years of age with amenorrhea for at least
18 months, or

- Surgically sterile, defined as having undergone a hysterectomy, bilateral
oophorectomy or tubal ligation, or otherwise incapable of pregnancy.

- Pre or perimenopausal and practicing a highly effective method of birth control,
including hormonal prescription, oral contraceptives, contraceptive injections,
contraceptive patch, and intrauterine device, for the duration of their
participation in the study. Abstinence and double-barrier methods do not qualify
as highly effective methods of birth control.

- All woman of child-bearing potential must have a negative serum pregnancy test at
screening and a negative urine pregnancy test on Day 1 (Visit 2) prior to
administration of KX2-391 Ointment dose.

Contraception

- Contraception must be consistently used for at least 3 months prior to screening
to 3 months after the last KX2-391 Ointment dose.

- Male Contraception: All men who are sexually active with female partners of child
bearing potential must agree to ensure their partners use highly effective
contraception and therefore will not father a child from screening to 3 months
after the last dose of study medication.

- Male and Female Contraception: All men and women subjects must agree to not
donate sperm or eggs or attempt conception from screening to 3 months after the
last KX2-391 Ointment dose.

5. Subject is, in the opinion of the investigator, in good general health based on
medical history, physical examination, electrocardiogram (ECG), and clinical
laboratory evaluations at screening.

6. Subject has clinically acceptable liver function at screening as demonstrated by:

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2x upper
limit of normal (ULN)

- Total bilirubin ≤ ULN

7. No other screening laboratory test, including CBC results, considered clinically
significant by the investigator

8. Subject is not lactating

9. Subject is willing and able to follow all study instructions and to attend all study
visits

10. Subject is able to comprehend and willing to sign an Informed Consent Form (ICF)

Exclusion Criteria:

1. Subject has clinically atypical and/or rapidly changing AK lesions on the treatment
area

2. Subject has current systemic malignancy

3. Subject has used any of the following systemic therapies within the specific period
before Visit 1:

- Retinoids; 180 days

- Glucocortico-steroids; 28 days

- Methotrexate or other anti-metabolites; 28 days

4. Subject has used any of the following topical therapies on the treatment area within
the specified period before Visit 1:

- Retinoids; 90 days

- Glucocortico-steroids; 14 days

5. Subject has had any of the following of the AK therapies on the treatment area:

Medical Therapies within 90 days (or until the site has healed, whichever is longer)
before Visit 1:

- Ingenol mebutate (eg, Picato)

- 5-fluorouracil (eg, 5-FU; Efudex)

- Imiquimod (eg, Aldara; Zyclara)

- Diclofenac with or without hyaluronic acid (eg, Solaraze)

- Moisturizer, emollients (12 hours prior to Visit 1)

Surgical Modalities on the treatment area within 30 days (or until the site has healed
following treatment, whichever is longer) before Visit 1:

- Cryotherapy

- Electrodesiccation

- Laser, light (eg, photodynamic therapy, intense pulsed light) or any other energy
based therapy

- Chemical peels (eg, tricholoracetic acid)

- Dermabrasion

- Surgical removal (eg, curettage, excision)

6. Subject currently has, or has experienced any of the following on the treatment area
within the specified period before Visit 1:

- A cutaneous malignancy; 180 days

- Sunburn; 28 days

- Body art (eg, tattoo, piercing); currently

- Excessive tan; currently

7. Subject has a history of sensitivity to any of the ingredients in the study
medications

8. Subject is chronically taking a known strong inhibitor of CYP3A4

9. Subject has a skin disease (eg, atopic dermatitis, psoriasis, eczema) or condition
(eg, scarring, open wounds) that, in the opinion of the investigator, might interfere
with the study conduct or evaluations, or which exposes the subject to an unacceptable
risk by study participation.

10. Subject has other significant uncontrolled or unstable medical diseases or conditions
that, in the opinion of the investigator, would expose the patient to unacceptable
risk from study participation.

11. Subject has participated in an investigational drug trial during which an
investigational study medication was administered within 30 days before Visit 1.