AMD3100 Clinical Overview Dr' Gary Calandra VP Clinical Development AnorMED Inc'

1
AMD3100 Clinical OverviewDr. Gary Calandra VP
Clinical Development AnorMED Inc.

• December 7, 2004

2
AMD3100 is being evaluated for use in combination
with G-CSF in stem cell mobilization for stem
cell transplantation in cancer patients

• Clinical data to date shows AMD3100
• Provides a rapid increase in the number of
  peripheral blood stem cells capable of
  engraftment.
• Increases the proportion of patients reaching a
  peripheral blood stem cell target.
• Reduces the number of apheresis sessions required
  for patients to reach a target number of
  peripheral blood stem cells.

3
AMD3100 Dosed in AM After 5 Days of G-CSF
Consistent and Predictable Mobilization of Stem
Cells
Time Curve Response
G-CSF (10 ?g/kg) x 5 days AMD3100 (240 ?g/kg) in
AM of Day 5
250
200
150
CD34 cells/?l
100
50
N3 Healthy Volunteers
0
0
5
10
15
20
time (hours) post-AMD3100 dose
4
AMD3100 Safety Database

• Data up to August 9, 2004.
• Includes studies 98-01, 1002, 1003, 1004, 1005,
  2001, 2101, 2102, 2103, 2104, and 2105.

5
Number of Patients Entered By Protocol
Phase I
6
AMD3100 Clinical Studies To Date
Previously Published 2101 Proof of principle10
NHL/15MM patients (ASH2003, NMDP 2004) 2102 Poor
mobilizers with MM No MM cells mobilized (ASCO
2004) ASH 2004 2103 NHL cells not mobilized (Dr.
Gazitt) 2104 AMD3100 works with
Chemo-mobilization (Dr. Dugan) 2105 10PM/8AM
schedule works in MM and NHL (Drs. Stiff and
Micallef) Allogeneic Studies A alone in donors.
(Dr. Devine) New Studies Pilot Study Hodgkins
Disease Pilot Study AMD3100 Alone in MM patients
7
Protocol AMD3100-2101
Design

• Myeloma or NHL 1st or 2nd CR or PR
• 13 16 days between mobilizations
• Central and local CD34 analysis

• 13-16 days between mobilizations
• Central and Local CD34 analysis

8
Mobilization Success of AMD3100 G-CSF vs. G-CSF
Alone
Note The total number of patients is lt 25
because one patient (02-750) had more cells and
more aphereses in the AG arm and therefore, does
not fall into any of the categories in the table.
In the same number of days of apheresis, this
patient collected 105 more cells on the G-Alone
arm.
9
AMD3100-2101 Conclusions

• AMD3100 is safe and well-tolerated in cancer
  patients.
• After 4-5 days of G-CSF administration, AMD3100
  produced a gt 3-fold median increase in the number
  of circulating CD34 cells.
• In comparative studies, more cells were
  consistently collected per apheresis with AG.
• The increase in cell mobilization allowed a
  transplantable cell dose to be collected in
  patients who failed to mobilize adequately with
  G-alone.
• Patients given AMD3100 with GCSF require fewer
  aphereses to reach their target cell goal than
  when given G-alone.
• Engraftment of AG mobilized cells occurs
  promptly and is durable.

10
Number of Patients Entered By Protocol
Phase II
11
Mobilization Procedures with A G

• In 2102, 2103, and in part 2104 and 2105
• Four days of G-CSF (10 ?g/kg)
• 10 PM dose of AMD3100 (240 ?g/kg)
• AM dose of G-CSF
• Apheresis 1 hr later
• Repeat procedures for up to a total of 5 days of
  apheresis

12
Mobilization Procedures with A G

• In 2101 and in part 2104
• Five days of G-CSF (10 ?g/kg)
• AM dose of AMD3100 (240 ?g/kg) on day 5
• Apheresis starting 6 hr later
• Repeat procedures for up to a total of 5 days of
  apheresis

13
AMD3100 Phase II Program Plans

• Studies 2101 through 2108 support broad use of
  AMD3100 in different mobilization regimens and in
  different cancer patient populations.
• Additional small studies will evaluate more
  resistant patients (3CR/PR ) to mobilization,
  Rituxan use in poor mobilizers, and pediatrics.
• Allogeneic data will accumulate over several
  years.
• Series of small studies will target a number
  transplant centers in US, EU and Canada. Likely
  over 20 different sites - Size (n20/study ),
  likely non-comparative.

14
AMD3100 Safety Summary

• No SAEs have been related to AMD3100
• There have been no unusual AEs except paresthesia
• There has been no pattern of severe AEs
• The AE profile of AMD3100 at dose and schedule is
  deemed acceptable for Phase III

15
Regulatory Overview

• FDA Meetings
• July 2003 Orphan Drug Status Granted
• April 2004 End Phase I Meeting
• Sept. 2004 End of Phase II Meeting
• Sept. 2004 Filed Phase III Protocols For SPA
• October 2004 European Orphan Drug Status
  Granted
• Dec. 2004 FDA SPA Agreement Reached

16
Phase III Studies
Randomized, double-blind,comparative trials of
AMD3100 plus G-CSF versus Placebo plus G-CSF

• Study 1 300 NHL Patients
• gt 5 million CD34 cells/kg patient weight in 4
  or less collections
• Study 2 300 MM Patients
• gt 6 million CD34 cells/kg patient weight in 2
  or less collections
• Design is based on Phase II studies and
  historical data from multiple centres using G-CSF
  alone mobilization

17
Safety Graft Durability

• Definition Patient is stable without requiring
  another hematopoietic progenitor cell infusion
• 100 days Required to file NDA
• 6 months Available for all at 120 day safety
  update
• 1 year some available at each time point above,
  and all will be supplied at end of study

18
Acknowledgements Introductions
Dr. John Dipersio and Dr. Steven Devine,
Washington University School of Medicine, St.
Louis, MO Dr. Michael Dugan, Indiana University,
IN Dr. Ivana Micallef, Rochester Mayo Clinic,
MN Dr. Patrick Stiff, Loyola University, IL Dr.
Neal Flomenberg, Thomas Jefferson University,
PA Dr, Guido Tricot, Myeloma Institute,
University of Arkansas, Little Rock, AR