Evaluation of Safety, Tolerability, and PK of VX15/2503 In Patients With MS

VX15/2503-N-101 is a single ascending dose-escalation, randomized, double-blinded,
placebo-controlled study to evaluate the safety and tolerability of IV-administered
VX15/2503 in patients with multiple sclerosis. This will be accomplished by using a dose
escalation procedure starting at a low dose of VX15/2503 and will continue based on
predefined parameters until the maximum tolerated dose is identified. Patients will be
randomized at a 4:1 ratio to receive VX15/2503 to placebo. The patients and the study team
will be blinded to the treatment that each patient receives.

The study drug, VX15/2503, is a humanized monoclonal antibody that binds to the semaphorin
4D (SEMA4D; CD100) antigen. Experimental evidence suggest that antibody neutralization of
SEMA4D may represent a new therapeutic strategy for treating multiple sclerosis.

Inclusion Criteria:

- Patients 18-60 years of age who have been diagnosed with MS for at least 1 year as
defined by the 2010 revisions to the McDonald criteria

- Has an EDSS score of 0 to 6.5 inclusive at screening

- Has a body mass index of 18 to 32 kg/m2

- Is willing to undergo and has no contraindications to brain MRI

- Willing to use a medically acceptable method of contraception throughout the study
period and for 6 months after the dose of VX15/2503, unless patient is surgically
sterile or postmenopausal. Women of childbearing potential must have started using
adequate contraception at least 2 months before the Day 1 visit.

- Male patients must agree to defer from donating sperm for 6 months after VX15/2503
administration

- Women of childbearing potential must have a negative serum pregnancy test at
screening, which will be confirmed at baseline using a urine test before
administration of VX15/2503

- Is willing to forego other forms of experimental treatment during the study

Exclusion Criteria:

- Had an MS relapse that did not stabilize within the 30 days before the start of
screening.

- Has any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic,
metabolic, urologic/gynecologic, pulmonary, neurologic, psychiatric, or renal
conditions; has a history of relevant clinically significant allergic or anaphylactic
reactions; or has any other clinically significant major disease that, as assessed by
the investigator, would pose a risk to patient safety or interfere with the study
evaluations, procedures, or completion

- Has any clinically significant laboratory value outside the normal range for MS
patients at screening, or has abnormal hematologic, renal, or hepatic function based
on laboratory tests

- Is a pregnant or breastfeeding woman

- Has received treatment with any MS disease-modifying therapy other than interferon
beta or glatiramer acetate within 3 months prior to dosing

- Has been treated with natalizumab, daclizumab, or fingolimod for any indication
within 6 months prior to dosing

- Has had any prior treatment with alemtuzumab, rituximab, mitoxantrone, total lymphoid
irradiation, bone marrow transplantation, or T cell or T cell receptor vaccination

- Has received any experimental agent within 6 months prior to dosing, or within a
period equivalent to 5 half-lives of the agent (whichever is longer); or is currently
involved in any other research study

- Has undergone any major surgical procedure within the 4 weeks prior to dosing

- Has a history of congestive heart failure (New York Heart Association Class III to
IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional
intervention, or myocardial infarction within 6 months prior to dosing

- Has a clinically significant ECG finding at screening

- Has a known or suspected human immunodeficiency virus (HIV) or hepatitis B or
hepatitis C infection

- Has a known or suspected allergy to Gd or other contraindication to brain MRI

- Has a history of an opportunistic infection or a history of acute infection requiring
systemic antibiotics, antivirals, or antifungals within 6 weeks prior to dosing
(antiinfective therapy must have been completed at least 4 weeks prior to dosing)

- Has any other intercurrent illness or condition, including alcohol or drug dependence
as determined by the investigator, which could impact the patient's compliance with
or ability to complete the study

- History of seizure disorder or unexplained blackouts or history of seizure within 3
months of screening

- History of suicidal ideation within 3 months prior to screening, episode of severe
depression within 3 months prior to screening

- Has a sensitivity to VX15/2503 or the ingredients or excipients of VX15/2503, or
known or suspected sensitivity to mammalian cell-derived products

- Has donated or lost more than 1 unit of blood in the 60 days prior to screening