A Clinical Trial to Evaluate the Safety and Efficacy of RP-L201 in Subjects With Leukocyte Adhesion Deficiency-I

This is a pediatric non-randomized open-label Phase I/II clinical trial. The Phase I portion
will include a safety evaluation and preliminary assessment of the efficacy of hematopoietic
gene therapy consisting of autologous CD34+ enriched cells transduced with a lentiviral
vector carrying the ITGB2 gene in subjects with severe LAD-I. CD34+ cells will be transduced
ex vivo with the therapeutic vector followed by cryopreservation. If the number of CD34+
cells that are available for infusion is at least 2x10e6 total CD34+ clells/kg, subjects will
undergo myeloablative conditioning with intravenous busulfan. Subjects will then receive
infusion of gene-corrected hematopoietic cells approximately 24 hours following the final
busulfan dose.

The active agent is a self-inactivating lentiviral vector carrying the therapeutic ITGB2
gene, encoding for the human CD18 receptor (β2 integrin subunit). The therapeutic product is
the subject's autologous hematopoietic stem cells that have been transduced with the
lentiviral vector.

Inclusion Criteria:

- A confirmed diagnosis of severe LAD-I as demonstrated by flow cytometry indicating
CD18 expression on <2% neutrophils (polymorphonuclear neutrophils (PMNs)). Subjects in
which CD18+ PMNs are >2% will be considered eligible with <2% CD11a or CD11b
expressing PMNs and if there is a documented ITGB2 mutation and clinical history
consistent with LAD-I (or known family history).

- At least one (1) prior significant bacterial or fungal infection US NCI CTCAE, v5.0,
Grade ≥2). This criterion is not required for subjects with documented family history
who meet the above inclusion criteria.

- Age ≥3 months.

- Considered to be an appropriate candidate for autologous transplantation of
hematopoietic stem cells.

- A competent custodial parent with legal capacity to execute an institutional review
board (IRB)/ethics committee (EC)-approved consent form must be available to
participate in the consent process. (Informed assent will be sought from capable
subjects, in accordance with the directive of the IRB/EC and with local requirements).

- Ability to comply with trial procedures including investigational therapy and
follow-up evaluations.

Exclusion Criteria:

- Availability of a medically-eligible human leukocyte antigen (HLA)-identical sibling
donor transplant. Subjects may not be included in this trial as an alternative to a
clinically-indicated and feasible HLA-matched sibling donor hematopoietic stem cell
transplant. If an HLA-identical sibling is identified, but mobilized peripheral blood
or bone marrow hematopoietic stem cell collection is not feasible (for example: donor
is in utero, is a newborn from whom cord blood was not collected, or is unable to
undergo donation procedure because of medical impairments), then inclusion may be
permitted per Investigator discretion.

- Hepatic dysfunction as defined by either:

- Bilirubin >1.5× the upper limit of normal (ULN) or

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5×ULN.

- Renal dysfunction as defined by either Grade 3 or higher abnormalities in serum
sodium, potassium, calcium, magnesium or phosphate as defined by NCI CTCAE v5.0, or
the requirement for either peritoneal dialysis or hemodialysis.

- Pulmonary dysfunction as defined by either:

- Need for supplemental oxygen during the prior 2 weeks (in absence of acute
infection).

- Oxygen saturation (by pulse oximetry) <90%.

- Evidence of active metastatic or locoregionally advanced malignancy (including
hematologic malignancy) for which survival is anticipated to be less than 3 years.

- Serious infections with persistent bloodstream pathogens at time of trial entry.
(Subjects with active infections (e.g., unresolved ulcerative lesions, skin or oral
infections) are permitted as long as appropriate antibiotic therapy has been (or is
being) administered).

- Any medical or other contraindication for both leukapheresis and bone marrow harvest
procedure, as determined by the treating Investigator.

- Any medical or other contraindication for the administration of conditioning therapy,
as determined by the treating Investigator.

- Significant medical conditions, including documented human immunodeficiency virus
(HIV) infection, poorly-controlled diabetes, poorly-controlled hypertension,
poorly-controlled cardiac arrhythmia or congestive heart failure; or arterial
thromboembolic events (including stroke or myocardial infarction) within the 6 prior
months.

- Any medical or psychiatric condition that in the opinion of the Investigator renders
the subject unfit for trial participation or at higher than acceptable risk for
participation.