An Open-label Treatment Protocol for VTS-270 in Patients With Neurologic Manifestations of NPC

This is a prospective, open-label, treatment protocol to provide expanded access to VTS-270
to eligible Niemann-Pick type C disease (NPC) patients. Eligible patients will receive
VTS-270 via intrathecal (IT) lumbar puncture (LP) every 2 weeks, and assessments of safety
and exploratory efficacy measures will be performed at prescribed intervals. Patients who
have not previously been treated with VTS-270 will start at a dose of 900 mg, and patients
who have been previously receiving VTS-270 will receive their current stable dose of VTS-270.
Treatment will continue until the clinician considers VTS-270 to be no longer beneficial, the
patient withdraws from the treatment protocol, VTS-270 receives marketing authorization in
the US, or the development program is discontinued. Patients participating in this treatment
protocol should not expect additional access to VTS-270 beyond this treatment protocol.

Inclusion Criteria:

1. Patient is male or female and at least 4 years of age at time of screening.

2. Patient has a confirmed diagnosis of NPC.

3. Patient or parent/guardian must provide written informed consent to participate in the
treatment protocol. In addition to parental consent, assent to participate must also
be sought from minor children.

4. Patient has the ability to undergo LP and IT drug administration.

5. If taking miglustat (Zavesca®), must have been on a stable dose for the past 6 weeks
and be willing to remain on a stable dose for the duration of participation in the
treatment protocol. Alternatively, patients may elect to discontinue miglustat use and
be eligible for entry into the treatment protocol after undergoing a minimum 6-week
washout period prior to study Day 1.

6. If a patient has a history of seizures, the condition must be adequately controlled,
i.e., the pattern of seizure activity must be stable and the patient must be on a
stable dose and regimen of antiepileptic medication during the 1 month prior to
screening, with no change in dose or regimen up to and including the day of the first
dose of VTS-270 (Day 1).

7. Patients not currently receiving VTS-270 agree to discontinue any other
investigational treatment for at least 1 month prior to first dose of VTS-270 (Day 1).

8. Patients who are females of childbearing potential (not surgically sterile) must use a
medically acceptable method of contraception and must agree to continue use of this
method for the duration of the treatment protocol and for 30 days after participation
in the treatment protocol. Acceptable methods of contraception include barrier method
with spermicide, intrauterine device, steroidal contraceptive in conjunction with a
barrier method, abstinence, or same-sex partner.

9. Patient or parent/guardian must possess the ability, in the clinician's opinion, to
understand and comply with treatment protocol requirements, including clinical outcome
measurements and instructions, for the entire duration of the treatment protocol.

10. Caregiver, parent, guardian, or responsible adult must be able and willing to
accompany the patient to treatment protocol visits.

Exclusion Criteria:

1. Patient weighs less than 15 kg.

2. Patient has uncontrolled psychosis.

3. Patient has a history of hypersensitivity reactions to any product containing HP-β-CD
or has a history of hypersensitivity reactions or allergy to anesthesia/sedation.

4. Patient has received treatment with any investigational product (other than VTS-270)
within 1 month prior to Day 1 of treatment.

5. Patient is a female who is pregnant or nursing.

6. Patient has suspected infection of the CNS or any systemic infection.

7. Patient has a spinal deformity that, in the opinion of the clinician, could impact the
ability to perform repeated LPs.

8. Patient, in the opinion of the clinician, has a serious skin infection in the lumbar
region within 2 months of entry into the treatment protocol.

9. Patient has neutropenia, defined as an absolute neutrophil count of less than 1.0 ×
109/L.

10. Patient has thrombocytopenia (platelet count of less than 75 × 109/L).

11. Patient has an activated partial thromboplastin time (aPTT) or prothrombin time (PT)
prolonged by greater than 1.5 times the upper limit of normal (ULN) or a known history
of a bleeding disorder.

12. Patient has evidence of obstructive hydrocephalus or normal pressure hydrocephalus.

13. Patient has recently used anticoagulants (in past 2 weeks prior to first dose of
VTS-270 [Day 1].

14. Patient, in the opinion of the clinician, is unable to comply with the treatment
protocol or has a medical condition (e.g., cardiovascular, respiratory, hematologic,
neurologic, renal) that would potentially increase the risk of participation