Attached files
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| 8-K - FORM 8-K - ENDOCYTE INC | d269305d8k.htm |
| EX-99.1 - PRESS RELEASE - ENDOCYTE INC | d269305dex991.htm |
 Endocyte Inc.
Supplemental PRECEDENT Trial Analysis
December 13, 2011
Exhibit 99.2 |
 Forward-Looking Statements
During the course of this presentation, we will make forward-looking statements
regarding future events and our future performance.
The
words
“believe”,
“anticipate”,
“expect”,
“estimate”,
“intend”,
“plan”,
“may”,
“will”
and
other
similar
expressions generally identify forward-looking statements. In addition, any
statements that refer to expectations, projections or
other
characterizations
of
future
events
or
circumstances
are
forward-looking
statements.
Forward-looking
statements
entail various significant risks and uncertainties that could cause our actual
results to differ materially from those expressed in such forward-looking
statements. You are cautioned not to place undue reliance on these forward-looking statements,
which speak only as of the date hereof. We do not intend to update any of the
information contained in any forward-looking statement, except as
required by law. More information about the risks and uncertainties
faced by Endocyte, Inc. is contained in the company’s periodic reports
filed with the Securities and Exchange Commission. Endocyte, Inc. disclaims any
intention or obligation to update or revise any forward-looking
statements, whether as a result of new information, future events or otherwise. |
 PRECEDENT Trial Supplemental Analysis
2
Purpose
Results
Validate EC20 to select FR
positive patients
Validated (inter-reader
agreement 85%)
Test robustness of PFS
primary endpoint
(investigator assessed)
PFS robust (no evidence of
bias)
Confirmed PFS results in
FR(++) group
Update OS analysis (102
events)
OS underpowered and
inconclusive |
 FR
Positive Platinum-Resistant Ovarian Cancer Is an Attractive Patient
Population for Drug Approvals •
Platinum-resistant ovarian cancer overall
survival 12.7 months
•
Current drugs don’t delay progression or extend survival
and have toxicities that reduce quality of life
3
n= 149 patients
Platinum resistant
ovarian cancer patients
(failed first or second
platinum therapy < 6
months)
EC145 + PLD
PLD only
EC20 Scan
EC145= 2.5mg TIW wks 1, 3
PLD=50
mg/m
2
(IBW) every 28 days
PLD= 50
mg/m
2
(IBW) every 28 days |
 EC20
Validates Reader Agreement
FR(+) >
1 positive lesion
87%
FR(++) all lesions positive
85%
Independent reader study validates EC20 to select FR positive patients
for phase 3 study
Targeted >70% agreement
4 |
 Investigator PFS Assessment Passed
Standard Battery of Tests for Robustness
5
Test for Imbalances
Pass / Fail
Results
Patient populations
Pass
Adjusted for imbalances in patient prognostic
factors (e.g. performance status)
HR 0.597*
Study discontinuance
Pass
Treat discontinuance as event
HR 0.610*
Clinical progressions
Pass
Censor clinical progression
HR 0.601*
Off-schedule assessments
Pass
Off-schedule assessments
4.6% equal in both arms
Investigator delays calling
progression in treatment arm
versus control arm
**
Pass
IRC called progression earlier less often in
treatment arm
(Treatment 38% versus Control 43%).
* P-value <0.05
** # Patients IRC PFS date Less than investigator / total # patients with
> 1 CT scan |
 As
Expected Treatment Arm Median Decreased More Than Control Arm
6
Note:
#
of
patients
with
>
1
follow
up
CT
scan
–
EC145/PLD
33
and
PLD
11 |
 Investigator and IRC PFS Results
7
FR(++) results are statistically significant and clinically
meaningful in both analyses |
 PFS
Conclusions •
Primary endpoint (investigator assessed PFS) is robust and
unbiased
•
IRC confirmed statistically significant and clinically meaningful
results in FR(++) group
•
Greater confidence that phase 2 results can be repeated in
phase 3 (blinded) confirmatory study
8 |
 Historical PLD Phase 3 Trials in Platinum
Resistant Ovarian Cancer
9
Study
Drug
N
OS
Gordon et al. (2004)
PLD
130
8.3
Topotecan
128
9.5
Mutch et al. (2007)
PLD
99
13.5
Gemcitabine
96
12.7
Ferrandina et al. (2008)
PLD
76
12.7
Gemcitabine
77
11.5
Vergote et al. (2009)
PLD or Topotecan
229
13.5
Canfosfamide
232
8.5
Monk et al. (2010)
PLD
115
12.4
PLD + trabectedin
113
14.2
Colombo et al. (2010)
PLD
417
12.7
Patupilone
412
13.2
Historical Median Overall Survival of 12.7 months (8.3 -
13.5 months) |
 Overall Survival Underpowered and
Indeterminate
Overall Survival
ITT
n=149
FR(++)
n=38
EC145/PLD
PLD
EC145/PLD
PLD
Median (months)
14.1
16.9
14.0
16.4
Hazard Ratio (95% CI)
1.099 (0.722, 1.673)
1.420
(0.631, 3.194)
6-month Survival Rate
81%
70%
73%
60%
12-month Survival Rate
62%
63%
64%
53%
10
•
ITT OS hazard ratio is 1.0. Higher in FR(++) group
•
PLD arm much longer than historical (16.9 versus 12.7 months)
•
EC145/PLD arm median OS is longer than historical and early survival rates
favor EC145/PLD |
 2:1
Randomization Introduced Greater Variability in Control Arm OS Curve
Months
ITT Patient Population
EC145 + PLD (n=100)
PLD Alone (n=49)
PRECEDENT PLD control survival is more than 4 months longer than
historic
11
EC145/PLD
Median
PLD
Median |
 Imbalance in PFI and Post-Trial Platinum
Therapy May Have Confounded OS Results
% of Patients
ITT
FR(++)
EC145/PLD
PLD
EC145/PLD
PLD
>
3 months platinum free interval*
56%
76%
57%
73%
Received post-study chemotherapy
70%
71%
65%
80%
Platinum
18%
33%
17%
27%
Topotecan
34%
31%
44%
33%
Gemcitabine
27%
37%
22%
33%
Paclitaxel/Docetaxel
24%
29%
30%
40%
Bevacizumab
18%
14%
22%
20%
12
* Last platinum dose to progression |
 OS
Exploratory Analysis Overall Survival Hazard Ratio
Population
(events by arm)
N
(1)
Unadjusted Analysis
Adjusted Analysis
(2)
ITT (events: 70/32)
149
1.099
0.928
FR(++) (events: 18/10)
38
1.420
0.495
1.
EC20 scan assessment available for 94 of 149 patients.
2.
Results from Cox proportional hazards model with age, platinum failure, CA-125
level, geography, tumor size, months since last platinum
treatment,
and
ECOG
as
baseline
factors
included
in
the
model.
13
Adjusting OS results based on PFS prognostic factors improve OS
results particularly in FR(++) group |
 Overall Survival Conclusions
•
Underpowered, particularly in the control arm (49 patients)
•
Control arm curve median is significantly longer than in
historical PLD trials
•
Imbalance in platinum free interval and post platinum
therapy may have impacted results
•
Results inconclusive
14 |
 Implications for Phase 3 Study
•
Validation of EC20 allows
us to focus on FR(++)
population
•
Higher confidence that
phase 2 results repeated in
phase 3 study
•
Primary endpoint of phase
3 on blinded investigator
reads
•
Include platinum free
interval in stratification
•
1:1 Randomization
15
FR(++) Population
EC145/PLD
PLD
Investigator Assessment
PFS Median (months)
5.5
1.5
PFS Hazard Ratio
0.381 (p=0.0134)
IRC Assessment
PFS Median (months)
4.0
1.5
PFS Hazard Ratio
0.465 (p=0.0498)
Overall response rate
(1)
17.4%
6.7%
Median OS (months)
14.0
16.4
OS Hazard ratio (unadjusted)
1.420
OS Hazard ratio (adjusted)
(2)
0.495
1.
Response confirmed by follow-up CT scan.
2.
Results from Cox proportional hazards model with age, platinum failure, CA-125
level, geography, tumor size, months since last platinum treatment, and ECOG
as baseline factors included in the model. |
 Questions & Answers |