Single-Center Study Evaluating Systemic Exposure and Safety of KX2-391 Ointment 1% on the Face or Balding Scalp in Subjects With Actinic Keratosis

This study will be a open-label, single center, pharmacokinetic, and safety study of KX2-391
Ointment administered topically to the face or balding scalp of subjects with actinic
keratosis.

The study consists of Screening, Treatment, and Follow-up Periods. Eligible subjects will
receive 5 consecutive days of topical treatment, to be applied at the same location. Activity
(lesion counts) and safety evaluations will be performed.

Inclusion Criteria:

1. Males and females ≥18 years old.

2. Able to comprehend and are willing to sign an informed consent form (ICF).

3. At least 5 clinically typical, visible, and discrete AKs on 25 cm2 of the face or
balding scalp.

4. Subjects who, in the judgment of the Investigator, are in good general health based
on:

1. Medical history

2. Physical examination (PE) findings

3. ECG, clinical chemistry, hematology, and urinalysis results.

5. In the case of a female of childbearing potential, TKL will initiate two forms of
birth control at Screening and that at least one had to be in place for 30 days prior
(oral/implant/injectable/transdermal contraceptives, intrauterine device (IUD), condom
with spermicide, diaphragm with spermicide, abstinence, partner's vasectomy, tubal
ligation). Abstinence or vasectomies are acceptable if the female subject agrees to
implement one of the other acceptable methods of birth control if her
lifestyle/partner changes;

6. Females of childbearing potential, must agree to continue to use two methods of birth
control for 30 days following the last dose of study treatment;

7. In the case of a female of childbearing potential, has a negative urine pregnancy test
(UPT) on Day 1 prior to randomization and are willing to submit to a UPT at the end of
study (EOS);

8. In the case of 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;

9. In the case of a female of non-childbearing potential, has had a hysterectomy or is
postmenopausal (at least 2 years with no menses prior to enrollment);

10. 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;

11. Willing to avoid direct sun or ultraviolet (UV) light exposure to the face or scalp.

Exclusion Criteria:

1. Clinically atypical and/or rapidly changing AK lesions on the treatment area, e.g.,
hypertrophic, hyperkeratotic, recalcitrant disease (had cryosurgery on two previous
occasions) and/or cutaneous horn.

2. Location of the treatment area:

1. Within 5 cm of an incompletely healed wound

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

3. Been previously treated with KX2-391 ointment.

4. Has QTcF >450 ms for males and 470 ms for females or other relevant pathological
changes in the ECG, in the opinion of the Investigation, at Screening.

5. Anticipated need for in-patient hospitalization or in-patient surgery during the
study.

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

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

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

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

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

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

1. Treatment with immunomodulators (e.g., azathioprine), cytotoxic drugs (e.g.,
cyclophosphamide, vinblastine, chlorambucil, methotrexate) or
interferons/interferon inducers

2. Treatment with systemic medications that suppress the immune system (e.g.,
cyclosporine, prednisone, methotrexate, alefacept, infliximab)

3. Therapy/treatment with UVA or UVB.

9. Use of systemic retinoids (e.g., isotretinoin, acitretin, bexarotene) within 6 months
prior to the Screening visit.

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

11. A skin disease (e.g., atopic dermatitis, psoriasis, eczema) or condition (e.g.,
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.

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

13. Females who are pregnant or nursing.

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