A multinational, multicenter, open-label, single-assignment extension of the MS-LAQ-301 (ALLEGRO) study, to evaluate the long-term safety, tolerability and effect on disease course of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis

Laquinimod is a novel synthetic compound with high bioavailability, which is
currently being developed as an oral formulation for Relapsing Remitting
Multiple Sclerosis and Crohn's Disease.
Laquinimod relates to a predecessor compound, roquinimex (Linomide).Roquinimex
demonstrated clinical efficacy in Ms patients in Phase II studies. Serious
cardiopulmonary toxicities which occurred during Phase III trials led to early
termination of these trials. Extensive research of laquinimod shopws much less
clinical symtoms and signs of inflammation/toxicity.

Laquinimod is already been examined in 8 Phase I studies, 3 Phase II/IIb
studies in MS, an ongoing longterm open-label extension of the Phase IIb study
and 2 ongoing clinical Phase II studies in MS. In addition, a Phase II clinical
trial in Crohn's Disease patients has been initiated recently.

To make laquinimod 0.6 mg available for all subjects who completed the
placebo-controlled MS-LAQ-301 study according to the protocol and to evaluate
the long-term safety, tolerability and effect on disease course of daily oral
laquinimod 0.6 mg in subjects with relapsing multiple sclerosis.

This is a multinational, multicenter, open-label, single-assignment extension
of the MS-LAQ-301 study, to evaluate the long-term safety, tolerability and
effect on disease course of daily oral laquinimod 0.6 mg in subjects with
relapsing multiple sclerosis.

Eligible subjects will be treated with laquinimod 0.6 mg capsules once daily.
Subjects completing the full-duration of the double-blind MS-LAQ-301 study
(completion of Termination visit) according to the MS-LAQ-301 protocol will be
offered the opportunity to enter the MS-LAQ-301E study. In this open-label
study, the subjects will be treated with laquinimod 0.6 mg (regardless of their
initial treatment assignment during the MS-LAQ-301 study) until laquinimod 0.6
mg is commercially available for the treatment of MS patients or until its
development for MS is stopped.

Scheduled in-clinic visits will be conducted at Baseline (Month 0E) (the
Termination visit of MS-LAQ-301 will serve as the baseline visit of
MS-LAQ-301E) and at months 1E, 2E, 3E, 6E and every 6 months thereafter, until
Termination/Early discontinuation.
The following assessments will be performed at the specified time points: Vital
signs,weight,height, physical- and neurological examinations, bloodwithdrawl
and urinetests ( including pregnancy test), ECG's. The Sponsor may decide to
perform a Magnetic Resonance imaging (MRI) scan at Termination/early
discontinuation visit for all subjects.
Starting from Visit Month 6E, all subjects will be regularly contacted by
telephone every 3 months between the scheduled visits and asked a general
question regarding their well-being. In addition: women of child-bearing
potential will be contacted by phone for the monthly home pregnancy urine
test call.

For purposes of neurological/medical assessments, the study will be divided
into 2 periods:
Period 1: in which all subjects will continue to be evaluated by 2 distinct
physicians - a Treating and an Examining Neurologists/ Physician (as in the
MS-LAQ-301 study).
Period 2: in which all subjects will be assessed by a single Study Physician/
Neurologist.
The Sponsor will inform the sites when to change from Period 1 to Period 2.

All patients receive once daily 0.6 mg Laquinimod.
The allowed treatment for a relapse will be intravenous Methylprednisolone 1
g/day for up to 5 consecutive days.

During the first year of the study:physical examination: 3x/ ECG 3x/
bloodwithdrawl and urine test 6x/ home pregnancy test 7x/ neurological tests
3x/ MFIS 3x.
Followed by: every year: physical examination 2x/ ecg 2x/ bloodwithdrawl and
urinetest 2x/ home pregnancy test 10x/ neurological examination 2x/ MFIS 2x

Most common reported adverse events as a result of laquinimod: backpain,
stomach ache,chestpain, difficulties with falling into sleep or stayng asleep,
cystitis, vaginal fungal infections and anxiety.
Laquinimod may cause elevation of liver enzymes, usually within the first few
months of treatment. In the majority of cases the abnormality was temporary and
resolved on its own without any treatment and without stopping the study drug.
In a few other cases laquinimod was stopped and liver enzymes returned to
normal.