AN OPEN-LABEL, SINGLE-ARM, PROOF-OF-CONCEPT STUDY TO EVALUATE THE SAFETY AND EFFICACY OF SINGLE AND MULTIPLE DOSES OF REGN1500 IN PATIENTS WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

Please refer to protocol, section 1.1 "lntroduction"

Please refer to protocol, section 1.2 "Rationale"

This is an open-label, single-arm study in patients with HoFH. The study
consists of 6 periods: a run-in (for patients whose background LMT has not been
stable prior to screening or who have undergone lipid-apheresis within 4 weeks
of screening), screening, a main study open-label treatment period, an
observation period and an open-label extension (OLE) treatment period, and an
OLE follow-up period.

Run-In:
Patients whose background medical LMT has not been stable for at least 4 weeks
(6 weeks for fibrates) prior to the screening visit (week -2) or who have
undergone lipid-apheresis within 4 weeks prior to the screening visit (week -2)
will enter a run-in period (4 weeks to stabilize LMT other than fibrates; 6
weeks to stabilize fibrate therapy, and 4 weeks to wash out of lipidapheresis
therapy).

Screening:
Patients who have been on a stable background medical LMT for at least 4 weeks
(6 weeks for fibrates) prior to the screening visit (week -2) or who have not
undergone lipid apheresis within 4 weeks prior to the screening visit (week -2)
will directly enter a 2-week screening period. Background (stable) lomitapide
is permitted, with sponsor approval prior to enrollment, in up to 4 patients.
Rescreening of patients may be permitted on a case-by-case basis, following a
full review and approval by the study medical monitor. Patients who are
determined to be eligible for rescreening must be reconsented and undergo all
screening evaluations.

Main Study Open-Label Treatment:
Patients who meet all inclusion criteria and none of the exclusion criteria
will be enrolled to receive a singel open-label dose of REGN1500 at 15 mg/kg IV
at week 2 (day 15).

Observation Period:
Patients will be followed for a period of 24 weeks (through week 26 [day 183])
after the last dose of study drug in the main study period.

Open-Label Extension Treatment Period:
Patients who meet the eligibility criteria for the OLE will be enrolled to
continue treatment. The OLE period will last approximately 4 years, from week
26 (day 183) through week 214 (day 1493). It is estimated that this
period will last either until REGN1500 is available commercially, or until the
program is terminated, whichever comes first. Patients who still meet
eligibility criteria will receive 4 weekly 300 mg subcutaneous (SC) doses of
REGN1500 starting at week 26 (day 183). They will then receive a 20 mg/kg
intravenous (IV) dose of REGN1500 at week 38 (day 267). Starting at week 58
(day 407), patients will receive a 20 mg/kg IV dose of REGN1500 every 12
weeks, through week 178 (day 1247).


Open-Label Extension Follow-up Period:
Patients will be followed for a period of 24 weeks (through week 214 [day 149])
after the last dose of study drug in the OLE treatment period.

Study Duration:
The maximum duration of the main study per patient is up to approximately 34
weeks (approximately 8.5 months): up to 8 weeks for run-in/screening, 2 weeks
for the open-label treatment period, and 24 weeks of follow-up in the
observation period. The planned duration of the OLE is up to an additional 4
years.

In the main portion of the study, eligible patients will be enrolled to receive
a single open-label dose of REGN1500 at 15 mg/kg IV at week 2 (day 15).
In the OLE potion of the study, patients will receive open label REGN1500 in
all of the following schedules:
* REGN1500 at 300 mg SC once weekly for 4 weeks starting at week 26 (day 183)
* REGN1500 at 20 mg/kg IV at week 38 (day 267)
* REGN1500 at 20 mg/kg IV every 12 weeks from week 58 (day 407) through week
178 (day 1247)

Please refer to IMPD, page 869 "Risk Benefit Assessment"