Study of Patidegib Topical Gel, 2%, for the Reduction of Disease Burden of Persistently Developing Basal Cell Carcinomas (BCCs) in Subjects With Basal Cell Nevus Syndrome

An open-label, extension safety and tolerability study is planned for at least 12 months
duration following the end of this study. All participants who complete the Month 12 Exit
Visit having demonstrated adequate compliance with application of the Investigational Product
(IP) without major Protocol Deviations (PDs) during the study will be eligible for
participation in the extension study.

Inclusion Criteria:

1. The participant must be age at least 18 years of age at the Screening Visit.

2. The participant must provide written informed consent prior to any study procedures.

3. The participant must meet diagnostic criteria for the basal cell nevus (Gorlin)
syndrome including major criterion #3a plus 1 additional major criterion or plus 2
additional minor criteria listed below.

Major criteria:

1. >2 histologically confirmed BCCs or 1 for participant under age 20.

2. Odontogenic keratocysts of the jaw confirmed histologically.

3. ≥3 palmar and/or plantar pits seen at the Screening Visit.

4. Bilamellar calcification of the falx cerebri present at less than 20 years of
age.

5. Fused, bifid, or markedly splayed ribs.

6. First degree relative with BCNS.

7. Patched proteine 1 (PTCH1) mutation predicted to be of functional significance in
normal tissue.

Minor criteria:

1. Macrocephaly.

2. Congenital malformations including frontal bossing, cleft lip or palate, "coarse
face", moderate to severe hypertelorism.

3. Skeletal abnormalities detectable clinically: Sprengel deformity, marked pectus
deformity, or marked finger syndactyly.

4. Skeletal abnormalities detectable radiographically: bridging of the sella
turcica; vertebral abnormalities such as hemivertebrae, fusion or elongation of
the vertebral bodies; modeling defects of the hands and feet; flame shaped
lucencies of the hands or feet.

5. Ovarian fibroma.

6. Medulloblastoma (Modification of criteria of V Kimonis et al Am J Med Genet 69:
299-308, 1997).

4. The participant must have 10 (with at least 3 on the face) clinically typical BCCs
present within 24 months prior to Randomization (Baseline/Day 1). Additionally, the
subject must have at least 2 BCCs with longest diameter <5 mm present on the face
prior to Randomization (Baseline/Day 1).

5. The participant is willing to have blood collected to measure circulating drug levels.

6. The participant is willing to abstain from application of a non-study topical
medication (prescription or over the counter) to facial skin for the duration of the
trial except as prescribed by the Investigator. Moisturizers and emollients are
allowed. Participant will be encouraged to use their preferred sunscreen with an sun
protector factor (SPF) of at least 30 daily on all exposed skin sites.

7. If the participant is a woman of childbearing potential (WOCBP), she must be willing
to use complete abstinence from sexual intercourse and/or she and her partner must be
willing to use at least 2 highly-effective forms of birth control starting prior to
Baseline, through the duration of the study, and for 12 months after last application
of IP.

8. If the participant is a male with a female sex partner who is a WOCBP, the participant
must be willing to use condoms, even after a vasectomy, starting prior to Baseline,
through the duration of the study, and for at least 8 months after the last
application of IP.

9. The participant is willing for all facial BCCs to be evaluated and treatment
recommendations made only by the Investigator.

10. The participant is willing to forego treatment of facial BCCs with anything other than
the study IP except when the Investigator believes that delay of treatment of a facial
BCC potentially might compromise the health of the subject. During the trial the only
allowed form of treatment is surgical. Non-facial BCCs may be removed at the
discretion of the Investigator or Primary Skin Care Physician (PSCP).

Exclusion Criteria:

1. The subject has previously participated in a clinical trial evaluating patidegib
topical gel.

2. The participant has used topical treatment to the face or systemic therapies that
might interfere with the evaluation of the study IP. Among these are use of the
following:

1. Topical glucocorticoids of potency greater than 2.5% hydrocortisone or desonide
within the 30 days prior to the Screening Visit.

2. Retinoids (such as etretinate, isotretinoin, acetretin, tazarotene, tretinoic
acid, adapalene) systemically or topically, or >5% concentration of an alpha
hydroxy acid (such as glycolic acid, lactic acid) within the 3 months prior to
the Screening Visit.

3. 5-fluorouracil, imiquimod, diclofenac, or Ingenol mebutate (except as topical
treatment to discrete non-facial BCCs) systemically or topically to the skin
within the 3 months prior to the Screening Visit.

4. Systemic chemotherapy within 1 year prior to the Screening Visit.

5. Known inhibitors of the Hedgehog signaling pathway (such as vismodegib,
sonidegib, itraconazole) topically or systemically within 3 months prior to the
Screening Visit.

6. Photodynamic therapy (PDT) except to localized non-facial, individual BCCs within
3 months prior to the Screening Visit.

7. High-dose nicotinamide orally within 3 months prior to the Screening Visit.

3. The participant is known to have a hypersensitivity to any of the ingredients in the
study medication formulation.

4. The participant is unable or unwilling to make a good faith effort to return to the
study site for all study visits and tests.

5. The participant has uncontrolled systemic disease.

6. The participant has been treated for invasive cancer within the past 5 years excluding
non-melanoma skin cancer, Stage I cervical cancer, ductal carcinoma in situ of the
breast, or chronic lymphocytic leukemia (CLL) Stage 0.

7. The participant has current, recent (within five half-lives of the experimental drug
or if half-life not known, within the past 6 months prior to the Screening Visit), or
planned participation in an experimental drug study while enrolled in this study.

8. The participant is a WOCBP who is unwilling or unable to comply with pregnancy
prevention measures.

9. The participant is pregnant or breastfeeding.

10. The participant has any condition or situation which, in the Investigator's opinion,
may put the subject at significant risk, could confound the study results, or could
interfere significantly with the subject's participation in the study. This may
include a history of other skin conditions (such as severe facial eczema) or diseases,
metabolic dysfunction, physical examination findings, or clinical laboratory findings
giving reasonable suspicion of a disease or condition that contraindicates use of an
investigational drug or that might affect interpretation of the results of the study
or render the participant at high risk from treatment complications.