ICAAC September 28, 2006, San Francisco

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ICAAC September 28, 2006, San Francisco

• Anthim Phase 1 Study AH-101
• V. Strout, L. Casey, L. Nardone, K. Curtis, G.
  DAlia, G. Apseloff, J. Lazar

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AH-101 Phase I Study Title

• Randomized, Placebo-Controlled, Double Blind,
  Dose-Escalation Phase I Study of the Safety,
  Tolerability and Pharmacokinetics of a Single
  Intravenous Dose of Anthim (ETI-204) and Its
  Potential Interaction with Ciprofloxacin

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Anthim AH-101 Phase 1 Study

• Anthrax Protective Antigen (PA) combines with
  Lethal Factor (LF) and Edema Factor (EF) to form
  Lethal Toxin and Edema Toxin which destroy
  lymphatic tissue and leukocytes
• Anthim prevents this by binding to PA before it
  can fuse with cell membranes and transport LF and
  EF into the cell
• Anthim is an affinity enhanced, de-immunized IgG1
  ? class Mab developed with DoD and NIAID funding

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Anthim Animal Efficacy

• Anthim being developed under FDA Animal Rule
• Anthim protects rabbits against anthrax spore
  challenge when administered pre or post-exposure
  at a 4 mg/kg dose
• Anthim protection can be achieved by IV or IM
  administration with or without ciprofloxacin

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Study Design

• Primary Objectives
• Safety and tolerability of Anthim following IV
  administration, /- ciprofloxacin
• Secondary Objectives
• Pharmacokinetics of Anthim and ciprofloxacin and
  potential interactions

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Study Design

• Part I
• 19 mg 6 Anthim, 2 PBO, M/F
• 57 mg 6 Anthim, 2 PBO, M/F
• 114 mg 6 Anthim, 2 PBO, M/F
• 24 subjects total
• Part II
• 114 mg Anthim or PBO, /- 500 mg BID
  ciprofloxacin for 14 days, 6 subjects per group,
  12 subjects total

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Study Design

• Methods
• Subjects were followed for 42 days after a single
  IV injection
• Safety assessed by PE, ECG and lab measures
• Anthim levels measured by ELISA
• Immune response to Anthim by Biacore assay
• Ciprofloxacin by LC/MS/MS

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Demographics

• Mean Group Ages 30-38 18 min, 50 max
• Gender 64 M, 36 F
• Race 28 Caucasian, 6 Black, 2 Asian,1 Other
• Mean Group BMI 24.5-28.6 19.6 min, 34.9 max
• All subjects completed study

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Safety Results

• Treatment Emergent AEs 24 of 36 subjects
• Grade 1 or 2 n 22
• Grade 3 n2 (unrelated URI, nausea)
• Grade 4 n0 , no SAE
• All resolved
• Treatment Related AEs 11 of 36, all Grade1 or 2
• 7 Headaches (5 in Part 2)
• 2 Nausea, 1 Influenza like illness
• 1 Detected Immune responseno clinical symptoms

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Safety Results
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Safety Results

• No significant changes in lab values
• No dose relationship
• No abnormal physical exam results
• No clinically significant ECG changes

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AH-101

• Pharmacokinetics Data

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Anthim Plasma Conc. Part 1
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Anthim Half Life Part 1
Half life 16 days
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Anthim C max Part 1
C max 35 ug/mL
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Anthim AUCinf Part 1
Exposure is dose proportional
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Anthim Vol. of Dist Part 1
Confined to central compartment
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Anthim Clearance Part 1
Not dose-dependent
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Anthim AUCinf Part 2
AUC not affected by Cipro
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Anthim Half Life Part 2
Half life not affected by Cipro
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Ciprofloxacin AUC 0-12 Hrs. Part 2
AUC not affected by ETI-204
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Ciprofloxacin Half Life 0-12 Hrs Part 2
Half life not affected by ETI-204
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Ciprofloxacin Conc. 168 Hrs Part 2
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AH-101 Study Conclusions

• Anthim is safe and well tolerated with or without
  ciprofloxacin
• No safety concerns in Part 1 or Part 2 no renal,
  hepatic, cardiac or immune toxicitywas seen
• No clinically significant changes in lab values
• Anthim Cmax and AUC are dose proportional
• Anthim has a long half life of 16 days and there
  is no apparent PK interaction with ciprofloxacin