Open Label Study of KRN23 on Osteomalacia in Adults With X-linked Hypophosphatemia (XLH)

Inclusion Criteria:

1. Male or female, aged 18 - 65 years, inclusive

2. Diagnosis of XLH supported by classic clinical features of adult XLH (such as short
stature or bowed legs), and at least one of the following at Screening:

- Documented phosphate regulating gene with homology to endopeptidases located on
the X chromosome (PHEX) PHEX mutation in either the patient or in a directly
related family member with appropriate X-linked inheritance

- Serum intact FGF23 (iFGF23) level > 30 pg/mL by Kainos assay

3. Biochemical findings consistent with XLH based on overnight fasting (min. 8 hours):

- Serum phosphorus < 2.5 mg/dL at Screening

- Ratio of renal tubular maximum phosphate reabsorption rate to glomerular
filtration rate (TmP/GFR) < 2.5 mg/dL at Screening

4. Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥ 4
on the Brief Pain Inventory question 3 (BPI-Q3, Worst Pain) at Screening. (Skeletal
pain that, in the opinion of the investigator, is attributed solely to causes other
than XLH/osteomalacia—for example, back pain or joint pain in the presence of severe
osteoarthritis by radiograph in that anatomical location—in the absence of any
skeletal pain likely attributed to XLH/osteomalacia should not be considered for
eligibility)

5. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney
Disease Epidemiology Collaboration [CKD-EPI] equation) or estimated glomerular
filtration rate (eGFR) eGFR of 45 to <60 mL/min at Screening with confirmation that
the renal insufficiency is not due to nephrocalcinosis

6. Provide written informed consent after the nature of the study has been explained, and
prior to any research-related procedures. If the subject in a minor, provide written
assent and have a legally authorized representative willing and able to provide
written informed consent, after the nature of the study has been explained, and prior
to any research-related procedures

7. Willing to provide access to prior medical records for the collection of biochemical
and radiographic data and disease history

8. Females of child-bearing potential must have a negative urine pregnancy test at
Screening and be willing to have additional pregnancy tests during the study. Females
considered not to be of childbearing potential include those who have been in
menopause for at least two years prior to Screening, or have had tubal ligation at
least one year prior to Screening, or have had a total hysterectomy or bilateral
salpingo-oophorectomy.

9. Participants of child‐bearing potential or with partners of child-bearing potential
who have not undergone a total hysterectomy or a bilateral salpingo‐oophorectomy and
are sexually active must consent to use two effective methods of contraception as
determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal
contraceptives, vaginal ring, intrauterine device, physical double-barrier methods,
surgical hysterectomy, vasectomy, tubal ligation, or true abstinence) from the period
following the signing of the informed consent through 12 weeks after last dose of
study drug

10. Must, in the opinion of the investigator, be willing and able to complete all aspects
of the study, adhere to the study visit schedule and comply with the assessments

Exclusion Criteria:

1. Use of any pharmacologic vitamin D metabolite or analog (e.g. calcitriol,
doxercalciferol, and paricalcitol) within the 2 years before Screening

2. Use of oral phosphate within 2 years before Screening

3. Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior
to Screening

4. Use of bisphosphonates in the 2 years prior to Screening

5. Use of denosumab in the 6 months prior to Screening

6. Use of teriparatide in the 2 months prior to Screening

7. Chronic use of systemic corticosteroids defined as more than 10 days in the 2 months
prior to Screening

8. Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening

9. Serum intact parathyroid hormone (iPTH) ≥ 2.5 times the upper limit of normal (ULN) at
Screening

10. Use of medication to suppress parathyroid hormone (PTH) (cinacalcet for example)
within 60 days prior to Screening

11. Prothrombin time/Partial thromboplastin time (PT/PTT) outside the normal range at
Screening

12. Evidence of any disease or use of anticoagulant medication (such as warfarin, heparin,
direct thrombin inhibitors, or Xa inhibitors (xabans) that, in the opinion of the
investigator, cannot be discontinued) that may increase the risk of bleeding during
the biopsy procedure

13. Pregnant or breastfeeding at Screening or planning to become pregnant (self or
partner) at any time during the study

14. Unable or unwilling to withhold prohibited medications throughout the study

15. Documented dependence on narcotics

16. Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to
Screening

17. Use of investigational product or investigational medical device within 30 days prior
to Screening, or requirement for any investigational agent prior to completion of all
scheduled study assessments.

OR, in Japan, use of any investigational product or investigational medical device
within 4 months prior to Screening, or requirement for any investigational agent prior
to completion of all scheduled study assessments.

18. Presence or history of any hypersensitivity, allergic or anaphylactic reactions to any
monoclonal antibody or KRN23 excipients that, in the judgment of the investigator,
places the subject at increased risk for adverse effects

19. History of allergic reaction or adverse reactions to tetracycline or demeclocycline

20. Prior history of positive test for human immunodeficiency virus antibody, hepatitis B
surface antigen, and/or hepatitis C antibody

21. History of recurrent infection (other than dental abscesses, which are known to be
associated with XLH) or predisposition to infection, or of known immunodeficiency

22. Presence of malignant neoplasm (except basal cell carcinoma)

23. Presence of a concurrent disease or condition that would interfere with study
participation or affect safety

24. Presence or history of any condition that, in the view of the investigator, places the
subject at high risk of poor treatment compliance or of not completing the study