1. R Hermann6, P Sportelli7, L Gardner7 and J Bendell8
Final Results of a Randomized Phase II Study of Perifosine in Combination with Capecitabine (P-CAP) vs. Placebo Plus Capecitabine (CAP) in Patients with 2nd or 3rd Line mCRC
Abstract # 3531
D Richards1, J Nemunaitis2, S Vukelja1, C Hagenstad3, L Campos4, J Letzer5,
R Hermann6, P Sportelli7, L Gardner7 and J Bendell8
(1) Texas Oncology, Tyler, TX, (2) Mary Crowley Cancer Research Center, Dallas, TX,
(3) Suburban Hematology/Oncology, Lawrenceville, GA, (4) Oncology Consultants, Houston, TX,
(5) Kalamazoo Hematology Oncology, Kalamazoo, MI, (6) Northwest Georgia Oncology, Marietta, GA,
(7) Keryx Biopharmaceuticals, Inc., NY, NY, (8) Sarah Cannon Research Institute, Nashville, TN 1

2. Perifosine Oral alkylphospholipid
Inhibition of multiple signal transduction pathways
AKT inhibition
NF-kB inhibition
Activation of apoptotic pathway via JNK
Selective tumor cell accumulation and potential disruption of membrane asymmetry 2

3. Potential Mechanisms of Action of Perifosine + Capecitabine
NF-kB Inhibition
Fluorouracil resistance associated with upregulation of NF-kB1
Inhibition of NF-kB pathway (proteasome inhibitors, mTOR inhibitors) augments fluorouracil anti-tumor effect2
Perifosine shown to inhibit NF-kB nuclear translocation and pathway activation3
Anti-angiogenic effects
Downstream inhibition of VEGF receptor signaling pathway
Anti-VEGF therapy potentially augments chemotherapy
Voboril, R., et al., Inhibition of NF-kappa B augments sensitivity to 5-fluorouracil/folinic acid in colon cancer. J Surg Res, (2)
Nakanishi, C. and M. Toi, Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nat Rev Cancer, (4)
Leleu, X., et al., Targeting NF-kappaB in Waldenstrom macroglobulinemia. Blood, (10) 3

4. Treatment Plan / Schema
Perifosine 50 mg PO QD
Capecitabine 825 mg/m2 BID d
Placebo PO QD
Patients with 2nd or 3rd line mCRC
No prior Rx with CAP in metastatic setting
Prior Rx with 5-FU or 5-FU based regimen
Cycle = 21 Days
Primary Objective:
To compare time to progression (TTP) of P-CAP vs. CAP as 2nd or 3rd line Rx
Secondary Objective:
To compare overall response rate (CR + PR) and overall survival
To evaluate the safety of P-CAP vs. CAP

5. Refractory to prior 5 – FU Rx
Patient Demographics
38 Patients Enrolled
Demographic
P-CAP
(n = 20)
CAP
(n = 18)
All Patients
(n = 38)
Median Age
65 (range 32 – 83)
65 (range 43 – 83)
65 (range 32-83)
Male / Female
14 / 6
9 / 9
23 / 15
Median Prior Rx
2 (range 1-4)
2 (range 2-5)
2 (range 1-5)
ECOG PS: 0/1
6 / 14
5 / 13
11 / 27
Refractory to prior 5 – FU Rx 14
70 % 13
72% 27
71%

6. 89% of patients were third line or greater
Prior Rx by Arm
PRIOR Rx
P-CAP
( n = 20)
CAP
(n = 18)
All Patients
N=38
FOLFIRI
18 (90%)
16 (89%)
34 (89%)
FOLFOX
15 (75%)
13 (72%)
28 (74%)
FOLFIRI & FOLFOX
13 (65%)
12 (67%)
25 (66%)
Bevacizumab
15 (83%)
30 (79%)
EGFR Antibody
9 (45%)
10 (56%)
19 (50%)
89% of patients were third line or greater

7. Most Common Grade 1 & 2 Adverse Events
Results: Safety ( n = 38 )
Most Common Grade 1 & 2 Adverse Events
Adverse Event
P-CAP (20 pts)
n (%)
CAP (18 pts)
Diarrhea
15 (75%)
5 (28%)
Fatigue
10 (50%)
6 (33%)
Nausea
9 (45%)
Musculoskeletal Pain
6 (30%)
3 (17%)
Hand & Foot
5 (25%)
4 (22%)
Mucositis
1 (6%)
Anorexia
2 (11%)
Anemia

8. Grade 3 & 4 Adverse Events: > 10%
Results: Safety ( n = 38 )
Grade 3 & 4 Adverse Events: > 10%
Adverse Event
P-CAP
(n=20)
CAP
(n=18)
Hand and Foot
6 (30%) 0%
Anemia
3 (15%)
Abdominal Pain
1 (5%)
2 (11%)
Fatigue
Bowel Obstruction
Median time to onset of Grade 3 / 4 Hand-Foot Syndrome for perifosine arm: 19 wks
Median time to onset of Hand-Foot Syndrome for CAP: 11 weeks

9. Results: Response All Evaluable: n = 35 5-FU Refractory: n = 25
35 / 38 Patients evaluable for efficacy
3 placebo patients not evaluable: 2 off for toxicity at d 14, 46; 1 off at d 4 for other disease
All Evaluable: n = 35
Group n CR
N (%) PR
Duration of Response
(months)
SD > 12 Weeks
SD or >*
P-CAP 20
1 (5%)
3 (15%)
CR: 34
11 (55%)
15 (75%)
PR: 21, 19, 11
CAP 15
1 (7%)
PR: 7
5 (33%)
6 (40%)
*p = 0.036
5-FU Refractory: n = 25
Group n PR
N (%)
Duration of Response
(months)
SD > 12 Weeks
SD or >*
P-CAP 14
1 (7%)
19 months
8 (57%)
9 (64%)
CAP 11 -
3 (27%)
*p = 0.066 9

10. Median Time to Progression (TTP)
ALL EVALUABLE PATIENTS
Median TTP: P-CAP:
28 weeks [95% CI (12, 48)]
Median TTP: CAP:
11 weeks [95% CI (9, 15.9)]
p-value =
Hazard ratio: 0.284
(0.127, 0.636)
5-FU REFRACTORY PATIENTS
Median TTP: P-CAP:
18 weeks [95% CI (12, 36)]
Median TTP: CAP:
10 weeks [95% CI (6.6, 11)]
p-value =
Hazard ratio: 0.186
(0.066, 0.521)

11. Median Overall Survival (OS)
ALL EVALUABLE PATIENTS
Median OS: P-CAP:
17.7 mos [95% CI (8.5, 24.6)]
Median OS: CAP:
10.9 mos [95% CI (5, 16.9)]
p-value =
Hazard ratio: 0.410
(0.193, 0.868)
5-FU REFRACTORY PATIENTS
Median OS: P-CAP:
15.1 mos [95% CI (7.3, 22.3)]
Median OS: CAP:
6.6 mos [95% CI (4.7, 11.7)]
p-value =
Hazard ratio: 0.313
(0.122, 0.802)

12. Randomized Phase II Conclusions
Although a small study, perifosine + capecitabine (P-CAP) appears to improve TTP, ORR and OS compared to placebo + capecitabine (CAP)
These results are also seen in the subset of patients with 5-FU refractory disease
P-CAP was well-tolerated compared to CAP alone
Increase in grade 3/4 hand-foot syndrome, anemia
A randomized ph III study comparing P-CAP to CAP in patients with refractory mCRC has been initiated (X-PECT Trial) 12

13. X-PECT Trial
RANDOMIZED, DOUBLE-BLIND, PHASE III TRIAL OF PERIFOSINE + CAPECITABINE (P-CAP) VERSUS PLACEBO + CAPECITABINE (CAP) IN PATIENTS WITH REFRACTORY METASTATIC COLORECTAL CANCER
Opened April 2010 13

14. Treatment / Schema Cycle = 21 Days Primary Endpoint: Overall Survival
Patients with refractory mCRC
No prior Rx with CAP in metastatic setting
Cycle = 21 Days
Primary Endpoint:
Overall Survival
Secondary Endpoints:
PFS, ORR, Safety
Randomized 1:1, Double-blind
N = ~430 patients
RECIST v 1.1
CTCAE v 4.0
*Phase I study perifosine + capecitabine with capecitabine at 1000 mg/m2 PO
BID days 1 – 14 showed safety and tolerability of combination
(ASCO 2010 Abstract # 51462) 14