Open Label Trial Assessing Safety and Efficacy of Burosumab (KRN23), in a Patient With ENS and Hypophosphatemic Rickets

1.1 Primary Objective

The effect of KRN23 treatment on normalizing age-adjusted serum phosphorous levels in a
single pediatric patient with Epidermal Nevus Syndrome associated hypophosphatemic rickets

1.2 Secondary Objectives

1. The PD profile of KRN23 as assessed by changes from baseline over time 1,25(OH)2D, iPTH,
Serum Calcium, TRP and TmP/GFR (the ratio of renal tubular maximum phosphate
reabsorption rate to glomerular filtration rate)

2. Changes in underlying skeletal disease/rickets as assessed by standard radiographs
utilizing the Radiographic Global Impression of Change (RGI-C) rating scales

3. Effects of KRN23 on biochemical markers of bone turnover that reflect rickets severity,
alkaline phosphatase (ALP)

4. Walking ability as assessed by 6-Minute Walk Test (6MWT)

5. Patient/parent-Reported Outcomes as assessed by PROMIS and FPS-R rating scales

1.3 Exploratory Objective

1. Dual-energy X-ray absorptiometry (DXA)

1.4 Safety Objective Assess the safety of KRN23 administration in a single patient with
ENS-associated hypophosphatemic rickets, based on adverse events (AEs), laboratory
assessments, cardiac imaging and renal ultrasound.

Inclusion Criteria:

1. Patient has confirmed ENS by physician diagnosis

2. Patient has confirmed FGF23 elevations in the context of low serum phosphorous < 4.1
mg/dL

3. Patient able to tolerate KRN23 treatment

4. Have a corrected serum calcium level < 10.8mg/dL

5. Have an eGFR >60 ml/min

6. Must be willing in the opinion of the investigator, to comply with study procedures
and schedule

7. Provide written informed consent by a parent after the study has been explained and
prior to any research related procedures begin

Exclusion Criteria:

1. Concomitant use of active vitamin D (i.e calcitriol) and/or exogenous phosphate
supplementation. Patient will be allowed OTC Vitamin D should levels drop below <20
ng/ml

2. The use or enrollment in studies using other investigational therapies including other
monoclonal antibodies

3. Subject and their parent not willing or not able to give written informed consent

4. In the Investigators opinion, the patient may not be able to meet all the requirements
for study participation

5. Patient has a history of hypersensitivity to KRN23 excipients that in the opinion of
the investigator, places the patient at an increased risk of adverse effects

6. Patient has a condition that in the opinion of the investigator could present a
concern for subject safety or data interpretation.