Study to Evaluate the Safety and Efficacy of BF-200 ALA (Ameluz®) and BF-RhodoLED® in the Treatment of Superficial Basal Cell Carcinoma (sBCC) With Photodynamic Therapy (PDT).

The study will be conducted as randomized, double blind and vehicle-controlled ( 4:1 ratio of
verum (BF-200 ALA; Ameluz®) to vehicle (placebo)) clinical trial at 12 sites in the United
States of America (US). Each site should randomize between 10 and 20 subjects.

Each subject will complete a clinical observation period that will last for up to 7 months
(up to 4 weeks screening and pre-randomization period, and up to 6 months clinical
observation period) followed by a 5-year follow-up (FU) period after the completion of the
first PDT cycle.

The treatment of superficial BCC lesion(s) comprises of up to two PDT cycles each with two
PDT sessions one to two weeks apart of each other. 12 weeks after the first PDT of the first
cycle lesion(s) will be assessed clinically and only subjects with remaining BCC lesion(s)
will be retreated in the second PDT cycle starting the same day. For clinically completely
cleared subjects the clinical observation period of the study will end and these subjects
will enter the FU part of the study.

For each subject a Main Target Lesion will be defined that will be excised either 12 weeks
after the first PDT of the first cycle, if clinically cleared, or at the end of the clinical
observation period in order to histologically confirm the clinical assessment. Additional
Target Lesions will be assessed clinically, only. Randomization will be stratified by the
number of lesions (1 vs ≥2 Lesion(s)).

Definitions of complete responders comprise of:

1. Complete response of the Main Target Lesion which is assessed 12 weeks after the start
of the last PDT cycle that included treatment of the Main Target Lesion and is defined
as a Main Target Lesion that is completely clinically and histologically cleared.

2. In general, clinically complete responders are categorized 12 weeks after the start of
the last PDT cycle according to clinical assessment only and are defined as subjects
with all lesions (Main plus Additional Target Lesions) clinically cleared.

Verum and vehicle are indistinguishable. However, treatment is accompanied with typical
adverse events (AEs). In order to guarantee the blind status of the investigator assessing
efficacy after each PDT cycle, a second investigator or delegated person will perform drug
application and light treatment as well as all safety evaluations at visits where PDT is
applied and during the phone call 1 week after each PDT cycle, respectively. Both
investigators (delegated person(s)) are not entitled to exchange information about the study
outcome and side effects.

Inclusion Criteria:

- Willingness and ability to sign the informed consent form and Health Insurance
Portability and Accountability Act (HIPAA) form. A study-specific informed consent
form and a HIPAA form must be obtained in writing for all subjects prior to starting
any study procedures.

- Men or women ≥18 years of age.

- Presence of ≥1 naïve sBCC lesion in the treatment areas face/forehead, bald scalp,
extremities and/or neck/trunk, all of which are, according to the clinical judgement
of the investigator, likely to be histologically confirmed as sBCCs. Lesions should
not be within the embryonic fusion planes (H-zone), especially within 2 cm of the hair
zone or on the ears. In case of multiple lesions, one lesion is defined as Main Target
Lesion which will be excised at the end of the clinical observation period. Only
eligible naïve sBCCs, confirmed by histology taken at screening, are allowed to be
included in the study as Main or Additional Target Lesions. Thus, eligible sBCCs must
lack any histological evidence of aggressive growth patterns (e.g. severe squamous
metaplasia, infiltrative/desmoplastic features or basosquamous features). BCCs
assessed as non-naïve (e.g. previously treated or recurrent) or non-eligible by biopsy
taken at screening (and in a distance >5 cm from the next lesion included in the
study) should be excised by surgery or removed by cryotherapy in a timely manner.
Other treatments for these lesions are not allowed during the study.

- The diameter of each eligible lesion should be ≥ 0.6 cm, and the entire treatment
field must not exceed ~20 cm². The treatment field is defined as the field to which
IMP is applied, usually including the target lesions and margins surrounding the
lesions of up to 1 cm. For the Main Target Lesion, the maximal lesion size should be
such that surgical excision without a skin transplant is feasible according to the
investigator's judgement.

- Target BCC lesions must be discrete and located within 1-2 illumination areas (the
illumination area is defined by the effective illumination area of the BF-RhodoLED®
device with approximately 6 x 16 cm).

- Willingness to receive up to 4 PDTs within 3.5 months and excision of the Main Target
Lesion either at Visit 5, if clinically cleared, or at the end of the clinical
observation period 12 weeks after the start of the last PDT cycle (Visit 8),
irrespective of whether the treated Main Target Lesion was clinically cleared or not.

- Free of significant physical abnormalities (e.g. tattoos, dermatoses) within the
potential treatment field plus a 5 cm radius surrounding the target lesion(s) as they
may interfere with examination or final evaluation.

- Willingness to stop the use of moisturizers and any other cosmetics within the
treatment field plus a 5 cm radius surrounding the target lesion(s) 48 hours prior to
an office visit and 48 hours after each PDT session. Sunscreen will be allowed, but
should not be applied to the treatment field plus the 5 cm radius surrounding the
target lesion(s) within approximately 24 h prior to a clinical visit.

- Acceptance to abstain from extensive sunbathing and the use of a solarium during the
clinical observation period. Subjects with sunburn within treatment areas cannot be
included until fully recovered.

- Healthy subjects and subjects with clinically stable medical conditions, including,
but not limited to controlled hypertension, diabetes mellitus type II,
hypercholesterolemia, and osteoarthritis, will be permitted to be included in the
study if their medication is not prohibited by this protocol.

- Women of childbearing potential are permitted to participate in this study only if
they have a negative serum pregnancy test at screening and are willing to use a highly
effective method of contraception during the clinical observation period of the study.

Exclusion Criteria:

- History of hypersensitivity to 5-ALA or any ingredient of BF-200 ALA which includes
soybean phosphatidylcholine.

- Hypersensitivity to porphyrins.

- Current treatment with immunosuppression therapy.

- Presence of photodermatoses.

- Presence of porphyria.

- Presence of clinically significant inherited or acquired coagulation defect.

- Evidence of clinically significant (CS) unstable medical conditions, such as:

- Metastatic tumor or tumor with high probability of metastasis.

- Cardiovascular disease class III, IV (New York Heart Association [NYHA]).

- Immunosuppressive condition.

- Hematologic, hepatic, renal, neurologic, or endocrine condition.

- Collagen-vascular condition.

- Gastrointestinal condition.

- Clinically relevant cardiovascular, hepatic, renal, neurologic, endocrine, or other
major systemic diseases that complicate implementation of the protocol or
interpretation of the study results.

- Gorlin Syndrome or Xeroderma pigmentosum.

- Presence and/or physical treatment of skin tumors other than (naïve) sBCC (e.g.
malignant melanoma, squamous cell carcinoma (SCC), Bowen's disease, aggressive BCC or
nBCC diagnosed at the screening visit by clinical assessment) within a distance of ≤ 5
cm from the nearest target lesion within 4 weeks prior to PDT (Visit 2) until the end
of the clinical observation period. However, biopsied lesion(s) that were not
confirmed eligible at screening and which are located at a distance of > 5 cm from any
lesion(s) that will be included in the study can be surgically removed. Treatment by
PDT or topical medication during the course of the clinical observation period of the
study triggers exclusion of the subject.

- If lesion(s) are assessed as non-eligible by biopsy during initial screening and these
lesions are localized within a distance of 5 cm from an otherwise suitable lesion,
this suitable lesion must be excluded from the study.

- Αny AK lesions within the treatment field (lesion area including margin of 0.5 to 1.0
cm).

- Any topical medical treatment of AK, other non-melanoma skin cancers (NMSC), or
melanoma (except for IMP treatment of the target lesion(s)) starting 12 weeks prior to
Visit 2 (PDT-1) and lasting until the end of the clinical observation period.

- Any other topical medical treatment of the skin 12 weeks prior to Visit 2 (PDT-1)
until the end of the clinical observation period, with the exception of:

- Topical treatments with corticosteroids (allowed throughout the clinical
observation period of the study).

- Topical non-steroidal anti-inflammatory drugs (NSAIDs such as diclofenac)
(allowed throughout the clinical observation period of the study with the
restriction of 7 days prior to and 7 days after PDTs).

- Start of intake of medication with hypericin or systemically acting drugs with
phototoxic or photoallergic potential within 8 weeks prior to screening.

- Any of the systemic treatments listed below, within the designated period prior to PDT
and during the clinical observation period.

- Interferon - 6 weeks

- Immunomodulators or immunosuppressive therapies - 12 weeks

- Cytotoxic drugs - 6 months

- Investigational drugs - 8 weeks

- Drugs known to have major organ toxicity - 8 weeks

- Corticosteroids (oral or injectable) - 6 weeks

- MAL or ALA - 12 weeks

- Systemic treatment with NSAIDs is not to be used 7 days prior to and 7 days after PDT.
ASA (e.g. Aspirin®) up to 100 mg/ day, ibuprofen up to 200 mg/ day, and acetaminophen
(e.g. Tylenol®) is allowed during this period.

- Presence of tattoos, skin inflammation, wounds, etc. in the treatment field(s) plus a
5 cm radius surrounding the target lesion(s).