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Glycopyrrolate

Larry Dillaha, M.D.Executive Vice President

Chief Medical Officer

for the treatment of chronic moderate-severe drooling in pediatric patients

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Cerebral Palsy (CP) Cerebral Palsy (CP) Definition:

A group of motor impairments manifested as various physical and mental disorders caused by injury to the brain.

Common symptoms:Uncontrolled reflex movementsSpasticity affecting different parts of the bodyMental retardationSeizure disordersVision impairmentsAuditory impairmentsDrooling

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Impact of CPImpact of CP

800,000 patients in US

$920,0001 total lifetime cost of care

Patients need around-the-clock care

Frequent doctor and hospital visits

Shortened life expectancy

1: United CP

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SalivaSaliva

FunctionsProtectiveSwallowingDigestionSpeaking

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DroolingDroolingDefinition - unintentional loss of saliva from the mouth

Sialorrhea - increase in salivary flow

Anatomy - 3 pairs of major salivary glandsParotid Submandibular – 70%Sublingual

Oral PhaseInability to close the mouthPoor head controlAbnormal tongue controlReduced intra-oral sensation

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Pediatric DroolingPediatric Drooling

Drooling is normal in growing children, up to the age of 18 months

Drooling beyond the age of 4 is considered abnormal

Drooling frequently persists in children with CP

Parents of more than 1400 patients with CP stated:– Drooling is sometimes a problem 'requiring a bib' (34%)

– Drooling is often a problem 'requiring daily clothing changes' (16%)1

1:Bachrach SJ, et al. Use of glycopyrrolate and other anticholinergic medications for sialorrhea in children with cerebral palsy. Clin. Pediatr. (Phila)

1998;37:485-90.

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Complications of Severe DroolingComplications of Severe Drooling

Chronically irritated, chapped, or macerated skin cheilitis 67%

Pooling of saliva in mouthLeaking of saliva into the hypopharynx– Congested breathing– Loud rattle in the throat

Unrecognized aspirationRecurrent silent pneumoniaAnxiety and refusal to swallow

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Limited Success with Current Drooling TreatmentsLimited Success with Current Drooling Treatments

Oral motor training

Behavioral therapy

Radiotherapy

Surgical Therapy

Pharmacological therapy

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Orphan Drug DesignationOrphan Drug Designation

Granted by the FDA in June 2006– Pediatric patients with chronic moderate-

to-severe drooling

7 years marketing exclusivity after product launchTax credits for development

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Development of Orphan Drug IndicationDevelopment of Orphan Drug Indication

Development of new liquid formulation

Created a caregiver manual

Dose titration study

Generate safety data for NDA filing

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Glycopyrrolate HistoryGlycopyrrolate HistoryApproved in U.S. for more than 40 years

Anticholinergic agentglycopyrrolate inhibits the action of acetylcholine

Adjunctive therapy in treatment of peptic ulcersOnly Approved Indication in U.S.

Available only in tablets and injectable liquid

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Many Other Current UsesMany Other Current Uses

Gastrointestinal

Hyperhidrosis

Meniere’s Disease

Dermal Conditions

Anesthesia

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Day - 8 to 0

Visit 3Day 1 Visit 4

Week 2

Visit 5Week 4

Visit 6Week 6

Visit 7Week 8

Efficacy Study Design Efficacy Study Design Screening

Visit 1Day - 21 to

Day -9

Baseline

TreatmentDose Titration

Randomized, DB, Placebo controlled

Post Titration

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Efficacy AssessmentsEfficacy AssessmentsEfficacy will be assessed by:

Modified Teacher’s Drooling Scale (mTDS)

Visual analog scale (VAS) performed at the end of the day on thesame days as the mTDS

Rate today’s overall extent of drooling by placing a mark on the line below:

Normal Extremely wet

Global assessment by parent/caregiver and Investigator

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Safety Study DesignSafety Study DesignTwenty-four week, multi-center (26 sites), open-label

100 patients complete 24 weeks of oral Glycopyrrolate Liquid treatment

Patient population: – 3 - 18 years of age– Cerebral Palsy – MR– Other neurological conditions

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6 Month Safety Study6 Month Safety Study

Visit 8EXIT VISITWeek 24

Visit 2Day 1 Visit 3

Week 4 Visit 4Week 8 Visit 5

Week 12 Visit 6Week 16 Visit 7

Week 20

Screening

Day -14 to Day -3

Baseline

Day -2 and -1

TreatmentDose Titration

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Safety AssessmentsSafety Assessments

Description and tabulation of all AEs;

Physical examinations (PEs) at screening and Week 24;

ECGs

Clinical laboratory evaluations

Behavioral and safety-related data recorded by parents/caregivers

– Twice weekly for the first month of the study

– Once a week from Week 4 to the end of study (Week 24)

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Glycopyrrolate Clinical TimelineGlycopyrrolate Clinical TimelineApr

il 200

7Oct

2007

Completed pivotal phase III patient enrollment

Began patient pivotal phase III enrollment

File with NDA

Mid 20

08

1st ha

lf 200

8

Final Results

2020

Thank YouThank You

NASDAQ Symbol: SCRX