Exploratory Study to Assess Clinical Response to Gilenya® (Fingolimod) in Hispanics With RRMS

The primary objective of this study is to determine the success of Gilenya® (fingolimod)
treatment in patients with MS of Hispanic descent relative to their ancestral background.
Therapeutic success will be determined by annualized relapse rate (ARR; defined as the number
of relapses divided by the person years followed) after initiation of treatment with Gilenya®
(fingolimod)in comparison to the relapse rate in the previous 12 months. This will be
determined based on medical chart extraction, in-person assessment and regular clinical
follow-up.

A secondary objective of this study is to investigate whether the efficacy of Gilenya®
(fingolimod) is superior or equal in HW which have higher loads of Amerindian versus
Caucasian background with opticospinal MS (OSMS-NMO neg) versus classical MS (CMS) in the
first 12 months using radiological and clinical parameters. The following measures will be
obtained:

1. Number of relapse-free patients over the investigational period

2. Site of relapse defined as brain or spinal cord.

3. Sustained Disability progression will be defined as a one point (1) increase from
baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5)
increase in patients with baseline EDSS score of 5-5.5 or above after 3 months.

4. MRI changes as described as number of new T2 lesions and number of Gd-enhancing lesions
after 12 months from baseline.

Inclusion Criteria:

- Clinically definite multiple sclerosis defined by McDonald Criteria (8) with a score
of 0 to 5.5 on the Expanded Disability Status Scale (EDSS)(9). Inclusion will also be
determined by PI if clinically indicated. Relapsing remitting form of MS.

- Between 18-65 years of age (This age range is selected so as to capture the vast
majority of patients who are seen in the clinics with a confirmed diagnosed of MS.
This age range also allows for exclusion of co-morbid conditions that may be
associated with aging as well as pediatric cases where their disease characteristics
have been shown to be different).

- Ability to understand and sign the IRB-approved informed consent form prior to the
performance of any study-specific procedures and is willing to comply with the
required scheduling and assessments of the protocol.

- Women of childbearing potential must have a negative urine pregnancy test at the
Screening Visit and must be willing to practice a reliable birth-control method.

- Patient must be willing to discontinue and remain free from concomitant
immunosuppressive or additional immunomodulatory treatment (including IFNβ1a, 1b,
natalizumab and GA) for the duration of the study.

- Willing to answer a series of questions about disease, ancestry, residence history,
socioeconomic status and ethnic background.

- Willing to donate 50cc of blood for genetic admixture and immunological testing on
three occasions (O months, 6 months, 12 months).

- Willing to undergo MRI as standard of care at a 1.5 Tesla magnet strength at least.

Exclusion Criteria:

- Inability to understand nature of the study.

- Lack of a definite diagnosis of Multiple Sclerosis such as clinical isolated syndrome
will be excluded.

- NMO Antibody positive.

- Primary progressive or secondary progressive MS.

- Inability to undergo an MRI study or receive contrast agent and GFR<30.

- Considered by the Investigator to be immunocompromised, based on medical history,
physical examination, or laboratory testing or due to prior immunosuppressive
treatment.

- Lack of Varicella immunity.

- History of, or available abnormal laboratory results indicative of, any significant
cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic,
pulmonary, gastrointestinal, dermatologic, psychiatric (including major depression),
renal, and/or other major disease.

- History of malignancy (subjects with basal cell carcinoma that has been completely
excised prior to study entry remain eligible).

- Known history of human immunodeficiency virus infection, hematological malignancy, or
organ transplantation, history of severe allergic or anaphylactic reactions or known
drug hypersensitivity.

- Prior treatment history with the interferons, glatiramer acetate or natalizumab will
be acceptable after drug clearance of 1 month. 1 month has been selected due to
clinical experience of possible disease breakthrough if longer period is performed.