A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on AK on Face or Scalp (AK004)

This study will be a double-blinded, multicenter, activity, and safety study of KX2-391
Ointment administered topically to the face or scalp of subjects with actinic keratosis.

The study consists of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods.
Eligible subjects will receive X consecutive days of topical treatment, to be applied at the
study site. Activity (lesion counts) and safety evaluations will be performed.

Inclusion Criteria

1. Males and females ≥18 years old

2. A defined area on the face or scalp contains 4 to 8 clinically typical, visible, and
discrete AK lesions

3. Subjects who in the judgment of the Investigator, are in good general health

4. Females must be postmenopausal (>45 years of age with at least 12 months of
amenorrhea), surgically sterile (by hysterectomy, bilateral oophorectomy, or tubal
ligation); or, if of childbearing potential, must be using highly effective
contraception for at least 30 days or 1 menstrual cycle, whichever is longer, prior to
study treatment and must agree to continue to use highly effective contraception for
at least 30 days following their last dose of study treatment. Highly effective
contraception includes oral hormonal contraceptives, hormonal contraceptive implant,
injection or patch, intrauterine device or complete abstinence from sexual
intercourse.

5. Sexually active males who have not had a vasectomy, and whose partner is
reproductively capable, must agree to use barrier contraception from Screening through
90 days after their last dose of study treatment.

6. All subjects must agree not to donate sperm or eggs or attempt conception from
Screening through 90 days following their last dose of study treatment

7. Willing to avoid excessive sun or UV exposure

8. Able to comprehend and are willing to sign the informed consent form (ICF).

Exclusion Criteria

1. Clinically atypical and/or rapidly changing AK lesions on the treatment area

2. Location of the selected area is:

- On any location other than the face or scalp

- Within 5 cm of an incompletely healed wound

- Within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma
(SCC)

3. Been previously treated with KX2-391 Ointment

4. Anticipated need for in-patient hospitalization or in-patient surgery from Day 1 to
Day 57

5. Treatment with 5-fluorouracil (5-FU), imiquimod, ingenol mebutate, diclofenac,
photodynamic therapy, or other treatments for AK within the treatment area or within 2
cm of the treatment area, within 8 weeks prior to the Screening visit

6. Use of the following therapies and/or medications within 2 weeks prior to the
Screening visit:

- Cosmetic or therapeutic procedures (eg, use of liquid nitrogen, surgical
excision, curettage, dermabrasion, medium or greater depth chemical peel, laser
resurfacing) within the treatment area or within 2 cm of the selected treatment
area

- Acid-containing therapeutic products (eg, salicylic acid or fruit acids, such as
alpha- and beta-hydroxyl acids and glycolic acids), topical retinoids, or light
chemical peels within the treatment area or within 2 cm of the selected treatment
area

- Topical salves (non-medicated/non-irritant lotion and cream are acceptable) or
topical steroids within the treatment area or within 2 cm of the selected
treatment area; artificial tanners within the treatment area or within 5 cm of
the selected treatment area

7. Use of the following therapies and/or medications within 4 weeks prior to the
Screening visit:

- Treatment with immunomodulators (eg, azathioprine), cytotoxic drugs (eg,
cyclophosphamide, vinblastine, chlorambucil, methotrexate) or
interferons/interferon inducers

- Treatment with systemic medications that suppress the immune system (eg,
cyclosporine, prednisone, methotrexate, alefacept, infliximab)

8. Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene) within 6 months
prior to the Screening visit

9. A history of sensitivity and/or allergy to any of the ingredients in the study
medication

10. 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 unacceptable risk by study
participation

11. Other significant uncontrolled or unstable medical diseases or conditions that, in the
opinion of the Investigator, would expose the subject to unacceptable risk by study
participation

12. Females who are pregnant or nursing

13. Participated in an investigational drug trial during which an investigational study
medication was administered within 30 days or 5 half-lives of the investigational
product, whichever is longer, before dosing