1. The nab-Paclitaxel Difference

2. The nab-Paclitaxel Difference
Technology
MoA
Tumor uptake
Selectivity for tumor vs healthy tissue
Efficacy
Safety

3. nab-Paclitaxel individual molecule nab-Paclitaxel complex
nab-Paclitaxel is The First Tumor-Targeted Nanomedicine to Leverage the Natural Transport Properties of Albumin
nab-Paclitaxel individual molecule
nab-Paclitaxel complex
4–14 nm in size3,4
Albumin
Paclitaxel
130 nm in size1,2
A single molecule of albumin can bind up to 6 or 7 molecules of paclitaxel5
Desai et al. SABCS [Abstract 1071].
Kratz et al. J Control Release. 2008;132(3):
Peters, Jr. Adv Protein Chem. 1985;37:
Desai. Drug Delivery Report. 2008;Winter 2007/2008(16):35-41.
Paal et al. Eur J Biochem. 2001;268:

4. The MOA of nab-Paclitaxel Differs From That of Conventional Paclitaxel1-5
In vitro data that binding to endothelial cells is 9.9-fold higher for nab-paclitaxel vs conventional paclitaxel5
In vitro data that Cremophor EL at physiological levels blocks the binding of paclitaxel to albumin5
In vitro data that transcytosis of nab-paclitaxel is over 4-fold higher than that of conventional paclitaxel5
Unlike conventional paclitaxel, availability of active drug
not limited by entrapment in micelles with nab-paclitaxel1-4
Preclinical data that nab-paclitaxel accumulation in tumors is 33% higher than that of conventional paclitaxel5
Endothelial cells
nab-Paclitaxel
Dissolution
Binding
Transcytosis
Tumor uptake
Conventional Paclitaxel
Gardner et al. Clin Cancer Res. 2008;14(13):
Hamad & Moghimi. Expert Opin Drug Deliv. 2008;5:205–219.
Sparreboom et al. Cancer Res. 1999;59(7):
Van Tellingen et al. Br J Cancer. 1999;81(2):
Desai et al. Clin Cancer Res. 2006;12:
Albumin
Paclitaxel
Albumin receptor
SPARC and other extracellular matrix albumin-binding proteins
Cremophor solvent micelles
Tumor cells
Investigation of the functional importance of SPARC with respect to nab-paclitaxel is ongoing.
MoA, mechanism of action; SPARC, Secreted Protein Acidic and Rich in Cysteine.
References in slide notes.

5. Tumor AUC nab-Paclitaxel = 1.33 × Conv Paclitaxel P < .0001 ANOVA
At the Same Dose and Same Duration, Tumor Uptake is 33% Higher for nab-Paclitaxel1 8 7
nab-Paclitaxel
Conv Paclitaxel 6
Concentration
(µg paclitaxel/g) 5 4
Tumor AUC nab-Paclitaxel = 1.33 × Conv Paclitaxel P < ANOVA 3 2
0.01
0.1 1 10
100
Hours
Dose of both nab-paclitaxel and conventional paclitaxel = 20 mg/kg dose of paclitaxel; experiments in human breast tumor xenografts in nude mice.
ANOVA, analysis of variance; AUC, area under the curve;
conv, conventional.
1. Desai et al. Clin Cancer Res. 2006;12:

6. nab-Paclitaxel Demonstrates Greater Tumor Selectivity1,2
nab-Paclitaxel demonstrates greater tumor selectivity compared with conventional paclitaxel in this preclinical model1,2
1.5
nab-Paclitaxel
>
Conv paclitaxel
1.0 =
nab-Paclitaxel
Conv paclitaxel
Relative concentration (nab-Paclitaxel/Conventional paclitaxel)
<
nab-Paclitaxel
Conv paclitaxel
0.5
Tumor
Muscle
Heart
Kidney
Lung
Spleen
Blood
Comparative tissue distribution (ratio) of radiolabeled drug in mice bearing human breast tumor xenografts 1 hour after dose1,2
Hawkins et al. AACR Poster 1189.
Scheff . Community Oncol. 2008;5(7 suppl 8):7-13.
conv, conventional.

7. nab-Paclitaxel Clinical Data
Approved indication in the EU (SmPC): Treatment of metastatic breast cancer in adult patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated

8. Probability of Survival
Overall Survival is Increased With nab-Paclitaxel1,3 OS Results in MBC from CA 024 (Phase II) & CA 012 (Phase III)
CA 024,1,2 Phase II, first-line mBCa,b
CA 012,3,4 Phase III, > first-line MBC
nab-Paclitaxel 150 mg/m2 qw 3/4 (n = 74)
Conventional paclitaxel 175 mg/m2 q3w (n = 136)
nab-Paclitaxel 260 mg/m2 q3w (n = 131)
Docetaxel 100 mg/m2 q3w (n = 74)
1.00
1.00
0.75
0.50
0.25 10 20 30
10.7
13.0
+2.3
0.75
0.50
0.25 10 20 30 40
Probability of Survival
Months
26.6
33.8
+7.2
Probability of Survival
Months
HR = 0.688,1 P = NS
HR = 0.726,5 P =
anab-Paclitaxel 300 mg/m2 q3w and 100 mg/m2 qw 3/4 arms not shown.
bOS calculated when 58% of patients had died.
Gradishar et al. ASCO Breast Cancer Symposium [Abstract 275].
Gradishar et al. J Clin Oncol. 2009;27(22):
Gradishar et al. J Clin Oncol. 2005;23:
Abraxane® European SmPC; log-rank test.
Celgene Corporation; Data on file.
HR, hazard ratio; NS, not statistically significant; OS, overall survival; q3w, every 3 weeks; qw 3/4, first 3 of 4 weeks.

9. nab-Paclitaxel Demonstrates Antitumor Activity Where Conventional Taxanes have Failed1-4
In patients with MBC
Phase II study:1,2 patients with prior taxane exposure had a 43% response rate to nab-paclitaxel
Phase II study:3 nab-paclitaxel showed efficacy (ORR 14–16%, DCR 26–37%) and was well-tolerated in taxane refractory patients
Phase I study: 4 photographs illustrating reduction of breast lesions in a 62-year-old NSCLC patient following treatment with nab-paclitaxel
Patient did not respond to conventional paclitaxel
Following nab-paclitaxel treatment
Ibrahim et al. J Clin Oncol. 2005;23:
Ibrahim et al. ASCO 2002 [Abstract 209].
Blum et al. Clin Breast Cancer. 2007;7(11):
Campbell et al. ASCO 2002 [Abstract 403].
DCR, disease control rate; NSCLC, non-small cell lung cancer; ORR, overall response rate.

10. nab-Paclitaxel has a Different Tolerability Profile vs Conventional Paclitaxel in Patients with MBC1-4 CA 012 Phase III Trial
Selected adverse events, %
nab-Paclitaxel
260 mg/m2 q3w
(n = 226)
Conv paclitaxel
175 mg/m2 q3w (n = 222)
P-value
Grade 3
Grade 4
Hematologic
Neutropenia 25 9 32 22
< .001
Thrombocytopenia
Anemia
Febrile neutropenia
< 1 NS
Non-hematologic
Sensory neuropathy 10 2
Fatigue
Myalgia
Vomiting
Edema
Hypersensitivity 8 7 3 1
.002
Median time to improvement of SN to grade ≤ 2 (days)
223
793
.0284
Table adapted from Davidson 20101
Davidson. EJC Supplements. 2010;8(1):11-18.
Gradishar et al. J Clin Oncol. 2005;23(31):
Cortes et al. EJC Supplements. 2010;8(1):1-10.
Celgene Corporation. Data on file [CA 012 CSR].
conv, conventional; NS, not statistically significant; SN, sensory neuropathy. 10

11. nab-Paclitaxel is different from conventional paclitaxel because …
…it leverages albumin to target1 and delivers more drug to the tumor,2 resulting in higher ORR and OS3
Lammers et al. Br J Cancer. 2008:99;
Desai et al. Clin Cancer Res. 2006;12:
Gradishar et al. J Clin Oncol. 2005;23(31):
ORR, overall response rate; OS, overall survival.

12. Back-ups

13. Probability of Survival
Overall Survival is Increased With nab-Paclitaxel1 CA 024 Randomized Phase II Trial, First-Line MBC Patients Receiving nab-Paclitaxel qw 3/4 at 150 mg/m2 or Standard Docetaxela,b
1.00
0.75
0.50
0.25 10 20 30 40 50
Probability of Survival
Months
nab-Paclitaxel 150 mg/m2 qw 3/4 (n = 74)
Docetaxel 100 mg/m2 q3w (n = 74)
26.6
33.8
HR = 0.688
+7.2
The 150 mg/m2 qw nab-paclitaxel arm demonstrated a numerically longer OS versus docetaxel (not statistically significant)
anab-Paclitaxel 300 mg/m2 q3w and 100 mg/m2 qw 3/4 arms not shown.
bOS calculated when 58% of patients had died.
HR, hazard ratio; OS, overall survival; qw, weekly; q3w first 3 of 4 weeks.
Gradishar et al. ASCO Breast Cancer Symposium [Abstract 275].
Gradishar et al. J Clin Oncol. 2009;27(22):

14. Probability of Survival
Overall Survival is Longer With nab-Paclitaxel1 CA 012 Randomized Phase III Trial, > First-Line MBC Patients Receiving nab-Paclitaxel or Conventional Paclitaxel
1.00
0.75
0.50
0.25 10 20 30
10.7
13.0
+2.3
Conventional paclitaxel 175 mg/m2 q3w (n = 136)
nab-Paclitaxel 260 mg/m2 q3w (n = 131)
HR = 0.73, P = 0.024
Probability of Survival
Months
HR, hazard ratio; OS, overall survival; q3w, every 3 weeks; qw 3/4, first 3 of 4 weeks.
Gradishar et al. J Clin Oncol. 2005;23:

15. nab-Paclitaxel is different from conventional paclitaxel because …
…it leverages albumin to target1 and delivers more drug to the tumor,2 allowing for greater clinical efficacy3
…it targets tumors,4 achieves higher tumor uptake,2 and produces superior clinical efficacy3
Lammers et al. Br J Cancer. 2008:99;
Desai et al. Clin Cancer Res. 2006;12:
Gradishar et al. J Clin Oncol. 2005;23(31):
Scheff . Community Oncol. 2008;5(7 suppl 8):7-13.
ORR, overall response rate; OS, overall survival.