Determination of the Claudin 6 Status Using the BioNTech Diagnostics CLAUDENTIFY® 6 IHC-Assay for the BNT142-01 study (Clinical Trial)

The scope of the Clinical Performance Study (CPS) is to investigate the
clinical performance of the CLAUDENTIFY® 6 IHC Assay, to determine Claudin 6
protein expression levels in formalin fixed, paraffin embedded (FFPE)
neoplastic tissue samples in advanced ovarian, lung, or testicular cancer. The
CLAUDENTIFY®6 IHC assay uses an immunohistochemistry (IHC) procedure for the
detection of Claudin 6 protein expression in freshly collected or archived FFPE
neoplastic tissue. A valid test result will be used as one of the
inclusion/exclusion criteria to determine patient eligibility for the BNT142-01
clinical trial.
Cancer is the second leading cause of death globally and in 2020 was estimated
to be responsible for 10 million deaths.1 In general, once a solid tumor has
metastasized, with a few exceptions such as germ cell and some carcinoid
tumors, 5-year survival rarely exceeds 25%.

To use the CE-marked CLAUDENTIFY®6 IHC-Assay as a pre-screening test to
determine Claudin 6 protein expression in patients with histological or
cytological documentation of a solid tumor that is metastatic or unresectable
provided as a pathology report.
Results of the test will be used as one of the inclusion/exclusion criteria to
determine patient eligibility for BioNTech*s clinical trial BNT142-01.

This is a device for performance study using the CLAUDENTIFY®6 IHC-Assay in
patients with advanced/metastatic ovarian (including fallopian tube and
peritoneal), non-squamous NSCLC, endometrial, or testicular cancer, for
inclusion in BioNTech*s BNT142-01 clinical trial.

Specimen Collection (FFPE tumor tissue)
1. FFPE tumor tissue from the surgical resection collected from the clinical
sites.
2. Specimens shipped to the clinical testing laboratory, at ambient temperature.

Specimen processing
1. Specimens are processed as per the CLAUDENTIFY®6 IHC-Assay Instructions for
Use.
a. Refer to the Instructions for Use: CLAUDENTIFY®6 IHC-Assay, Ref 90060
b. Refer to SOP-030-230, *CLDN6 Diagnostic Immunohistochemistry according to
CLAUDENTIFY 6 Histology Kit.*

Stained Specimen Scoring
1. For the assessment of Claudin 6 staining, the membrane staining intensity is
evaluated and documented. Staining intensities are classified in scores from 0,
1+, 2+ and 3+.
2. Human normal tissue and tumor cells of cancer tissues should always show a
staining intensity <= 1+ when stained with the Negative Control Reagent (NCR).
Unspecific staining (background) might arise especially on erythrocytes/lumen
of vessels, plasma cells, immune cells, oedema, or mucoid structures. Intensity
of such signals should be <= 2+. The positive control containing formalin-fixed,
paraffin-embedded fetal rabbit kidney tissue should always show a staining
intensity >= 2+ of cells near the renal capsule and of the Bowman capsule when
stained with the anti-human Claudin 6 monoclonal antibody. Other structures
might show varying staining intensities from 0 to 2+ or 3+.

Reported Data Results Used in BNT142-01.

The CLAUDENTIFY®6 IHC assay uses an immunohistochemistry (IHC) procedure for
the detection of Claudin 6 protein expression in freshly collected or archived
FFPE neoplastic tissue.

Risk of Laboratory Test Procedure:
Tumor sample will be tested with the IVD test at the BioNTech SE central
testing laboratory. The test itself cannot harm the subject, as the subject
will never be in contact with it. If the amount and quality of the tissue is
not sufficient, the doctor may request a new biopsy to be collected to take
part in the research (MAIN study BNT142-01). Preferably the subject's stored
tumor tissue is used for this test used in the IVD study; however, if a new
biopsy is collected, that may be used in the IVD study.

Risk of a false positive test result:
There is a risk that the IVD test will give a so-called *false positive* test
result. False positive means that the IVD test result does not correctly show
the presence of the CLDN6 protein.