Topical QR-313 in Recessive Dystrophic Epidermolysis Bullosa (RDEB) Due to Mutation(s) in Exon 73 of the COL7A1gene

This clinical trial will evaluate the safety and tolerability, proof of mechanism, systemic
exposure and preliminary efficacy following topical application of QR-313 to subjects with
confirmed RDEB with one or more pathogenic mutations in exon 73 in the COL7A1 gene.

Up to two Target Wound Areas (TWAs) per subject will be selected and randomized. Each TWA
will be treated with IMP for 4 weeks, either QR-313 or matching placebo. All subjects will
continue to be followed up for 8 weeks post last dose.

Subjects will be monitored through home visits and site visits. An imaging system will be
used to assess the target wound at all home and study site visits.

QR-313 is a 21-nucleotide antisense oligonucleotide (AON) designed to hybridize to a specific
sequence in the COL7A1 pre-messengerRNA (pre-mRNA).

Inclusion Criteria:

1. Male or female, ≥ 6 years of age at Screening with a clinical diagnosis of RDEB with
confirmation of at least one of the alleles of the COL7A1 gene containing one or more
pathogenic mutations in exon 73.

2. Have at least one TWA, ie, a skin area of 10 x 10 cm that shows no signs of local
infection, and contains a target wound that shows dynamic wound healing and complies
to the following additional criteria:

1. surface area of the target wound ranging from 5 to 60 cm2, located centrally in
the selected 10 x 10 cm TWA.

2. exposed sub-epidermal tissue to allow absorption of the IMP.

3. no suspicion of current squamous cell carcinoma (SCC) upon visual inspection.

Exclusion Criteria:

1. Pregnant or breast-feeding female

2. Hemoglobin level at Screening requiring transfusion. The subject may be rescreened
when the condition is considered stable.

3. Untreated carcinoma of the TWA or history of carcinoma within 5 years prior to
Screening, except adequately treated cutaneous squamous or basal cell carcinoma.

4. Life expectancy less than 6 months, as assessed by the Investigator

5. Current or known history of clinically significant hepatic or renal disease, that in
the opinion of the Investigator, could impact subject safety or study participation.

6. Treatment with any systemic immunomodulators, immunosuppressants or cytotoxic
chemotherapy within 2 months prior to the Baseline visit.

7. Use of any investigational drug or device within 28 days or 5 half-lives of the
Baseline visit, whichever is longer, or plans to participate in another study of a
drug or device during the study period. The washout of 5 half-lives does not apply to
gene and cell therapy.

8. Known hypersensitivity to oligonucleotide treatment or excipients of the IMP.