ReplagalTM

1
Transkaryotic Therapies, Inc.
ReplagalTM Gene Activated Human aGalactosidase
2
Milestones

• Application Received June 16, 2000
• 1st Complete Response (CR) Letter December 22,
  2000
• TKTs Response to 1st CR Letter May 24, 2002
• 2nd CR Letter November 22, 2002

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ReplagalTMDrug Substance

• Gene activated Human alpha galactosidase
• Homodimer comprised of two approximately 50 kDa
  subunits
• Produced in a continuous human cell line
• Identical amino acid sequence to endogenous
  protein
• Three N-linked glycosylation sites
• Well characterized molecule
• No outstanding Drug Substance issues

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ReplagalTMDrug Product

• Sterile solution intended for intravenous
  administration
• Each vial of Drug Product contains
• 3.5 mg alpha galactosidase
• 12 mg sodium phosphate USP
• 0.8 mg polysorbate 20 USP
• 31 mg sodium chloride USP
• Isotonic
• pH 5.4 6.6
• No outstanding Drug Product issues

5
FDA Review Committee
Product Clinical Blair Fraser,
Ph.D. Dwaine Rieves, M.D. John Hill,
Ph.D. Marc Walton, M.D., Ph.D. Barry Cherney,
Ph.D. Gary Kikuchi, Ph.D. Pharm/Tox Rona
LeBlanc, Ph.D. Mercedes Serabian, M.S.,
DABT Ralph Bernstein, Ph.D. Clinical
Pharm Biostatistics Martin Green,
Ph.D. Ghanshyam Gupta, Ph.D. Biomonitoring
Facility Debra Bower, MT (ASCP) Daniel
Kearns John Eltermann, R.Ph., M.S. Reg.
Coordinators Bradley Glasscock, Pharm
D. Katherine Needleman, M.S. Jeanne
Delasko, RN, MS Mike Harlow, B.S.