Efficacy, Safety and Tolerability of BAF312 Compared to Placebo in Patients With Intracerebral Hemorrhage (ICH).

This is the first trial of BAF312 in ICH patients to study efficacy, safety, and
tolerability, compared to placebo. BAF312 is a drug that could potentially limit brain
inflammation after ICH, and thereby improve neurological outcome for stroke patients.

In this study, ICH patients meeting study criteria will be randomized at 1:1 ratio into
either active or placebo group. The first i.v. treatment must starts within 24 hours of ICH
event. Participating patients will also be followed up for additional 76 days after treatment
on neurological and safety conditions in 3 clinic visits.

BAF312 treatment includes the following identified risks: transient effects on heart rate and
rhythm (bradyarrhythmia and 2nd degree AV block) at treatment initiation that are completely
avoided by initial up-titration; liver enzyme elevation; lymphopenia due to lymphocyte
redistribution (expected effect of BAF312); macular edema; and varicella zoster (VZV)
infection.

Inclusion Criteria:

ICH patients eligible for inclusion in this study must fulfill all of the following
criteria:

1. Male or female patients aged 18 to 85 years (inclusive).

2. Written informed consent obtained before any study assessment is performed. If the
patient is not able to give the informed consent personally, consent by a relative or
legal representative is acceptable.

3. Spontaneous, supratentorial intracerebral hemorrhage in deep brain structures
(putamen, thalamus, caudate, and associated deep white matter tracts) with a volume ≥
10 mL but ≤ 45 mL (calculated by the ABC/2 method, after Kothari et al 1996)
determined by routine clinical MRI or CT.

4. Patients with the onset of ICH witnessed and/or last seen healthy no longer than 24
hrs previously.

5. Patients with Glasgow Coma Scale (GCS) best motor score no less than 6.

Exclusion Criteria:

ICH patients fulfilling any of the following criteria are not eligible for inclusion in
this study:

1. Use of other investigational drugs within 5 half-lives of enrollment, or until the
expected pharmacodynamic effect has returned to baseline (for biologics), whichever is
longer.

2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
classes (e.g., fingolimod).

3. Current use of concomitant medications with potent CYP2C9/3A4 inhibitory or induction
potential.

4. Necessity for mechanical ventilation at screening.

5. Infratentorial (midbrain, pons, medulla, or cerebellum) or superficial cortical
(lobar) ICH.

6. Candidates for surgical hematoma evacuation or other urgent surgical intervention
(i.e., surgical relief of increased intracranial pressure) on initial presentation. If
during the treatment period surgical hematoma evacuation or surgical intervention to
lower intracranial pressure becomes indicated, the investigational treatment should be
stopped.

7. Patients with intraventricular hemorrhage (IVH) having a Graeb score of >3 on initial
presentation. Patients must not have blood in the 4th ventricle and may only have
blood in the 3rd ventricle in the absence of ventricular expansion. Trace or mild
hemorrhage in either or both lateral ventricles is permitted. Patients with
hydrocephalus determined radiologically on initial presentation are excluded
regardless of Graeb score.

8. Secondary ICH due to:

- aneurysm

- brain tumor

- arteriovenous malformation

- thrombocytopenia, defined as platelet count of <150,000/µl

- known history of coagulopathy

- acute sepsis

- traumatic brain injury (TBI)

- disseminated intravascular coagulation (DIC)

9. Prior disability due to other disease compromising mRS evaluation, thereby interfering
with the primary outcome, operationally defined as an estimated mRS score (by history)
of ≥ 3 before ICH for patients less than or equal to 80 years of age. For ICH patients
81-85 years of age, estimated mRS by history prior to ICH must be less than or equal
to 1 (no significant disability despite symptoms).

10. Preexisting unstable epilepsy.

11. Patients with active systemic bacterial, viral or fungal infections.

12. Concomitant drug-related exclusion criteria:

- Intravenous immunoglobulin, immunosuppressive and/or chemotherapeutic
medications.

- Moderate immunosuppressives (e.g. azathioprine, methotrexate) and/or fingolimod
within 2 months prior to randomization.

- Stronger immunosuppressives (e.g. cyclophosphamide, immunosuppressive mAb) within
(minimally) 6 months prior to randomization, or longer with long-lasting
immunosuppressive medications as determined by the investigator.

13. Cardiovascular exclusion criteria:

- Cardiac conduction or rhythm disorders including sinus arrest or sino-atrial
block, heart rate <50 bpm, sick-sinus syndrome, Mobitz Type II second degree AV
block or higher grade AV block, or preexisting atrial fibrillation (either by
history or observed at screening).

- PR interval >220 msec. Long QT syndrome or QTcF prolongation >450 msec in males
or >470 msec in females on screening electrocardiogram (ECG).

- Patients receiving treatment with QT-prolonging drugs having a long half-life
(e.g., amiodarone).

14. Any of the following abnormal laboratory values prior to randomization:

- White blood cell (WBC) count < 2,000/μl (< 2.0 x 109/L)

- Lymphocyte count < 800/μl (< 0.8 x 109/L)

15. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test.

16. Patients with any other medically unstable condition or serious laboratory abnormality
as determined by the investigator.