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This presentation and our remarks based upon it,
including responses to questions made during and
following the presentation, may include forward-looking
statements. Such statements are subject to the risks and
uncertainties we discuss in detail in our reports filed with
the Securities & Exchange Commission, including in our
quarterly report on Form 10-Q filed November 8, 2012.
We expressly disclaim any obligation to release publicly
any updates to forward-looking statements made during
the course of this presentation.
2
Two late stage clinical programs
•
•
Enobosarm (Ostarine; GTx-024), a SARM, for the prevention and treatment
of muscle wasting in patients with non-small cell lung cancer:

Eight clinical trials completed to date involving approximately 600 subjects

Granted fast track status January 2013

Enrollment completed 4Q 2012 for two pivotal Phase III clinical trials with
approximately 650 non-small cell lung cancer (NSCLC) patients – top line results
expected summer 2013

DSMB reviewed safety data in October 2012 and agreed trial could continue as
planned
Capesaris (GTx-758), an oral selective ER alpha agonist, for combination
primary ADT & secondary hormonal treatment of advanced prostate cancer:

Eight clinical trials conducted to date involving approximately 500 subjects

Phase II 712 clinical trial evaluating Capesaris® (GTx-758) for secondary
hormonal treatment in men with metastatic castration resistant prostate cancer
currently enrolling
3
Enobosarm (Ostarine; GTx-024)
Selective Androgen Receptor Modulator (SARM)
for the prevention and treatment of muscle wasting
in patients with lung cancer
Enobosarm
Approximately 600 patients have participated in eight clinical trials
2005
SARM
GTx
Enobosarm
Phase I SAD
GTx
Enobosarm
Phase I MAD
GTx
Enobosarm
Phase II POC chronic
sarcopenia
GTx
Enobosarm
Phase IIb muscle wasting
in cancer
GTx
Enobosarm
Phase I divided dose
Collaboration
Enobosarm and
Merck SARM
Phase Ib head to head
chronic sarcopenia
Collaboration
Enobosarm
Phase Ib PK study –
Japanese women
GTx
Enobosarm
Phase I Formulation study
2006
2007
2008
2009
2010
2011
5
Enobosarm increased lean body mass and improved
physical function in three efficacy clinical trials
159 subjects with cancer
cachexia, 4 months tx
1.4
1.2
LEAN BODY MASS
Placebo
Enobosarm 3 mg
1
0.8
0.6
0.4
0.2
PHYSICAL FUNCTION
Change from baseline (%)
Phase IIb cancer
cachexia trial:
Change from baseline (kg)
1.6
30%
25%
20%
Placebo
Enobosarm 3 mg
15%
10%
5%
0%
-5%
STAIR CLIMB
-10%
0
-0.2
120 elderly men and
postmenopausal women,
3 months tx
Change from baseline (kg)
Phase II POC clinical
trial:
1.2
1
Placebo
Enobosarm 3 mg
0.8
0.6
0.4
0.2
Change from baseline (%)
25%
1.4
20%
15%
Placebo
Enobosarm 3 mg
10%
5%
0%
-5%
-10%
0
STAIR CLIMB
-15%
88 postmenopausal women,
3 months tx
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
-0.2
-0.4
Placebo
Enobosarm 3 mg
Change from baseline (lbs)
Phase Ib sarcopenia
trial:
Change from baseline (kg)
-0.2
Morton, et al. AACR. 2009; abstract nr(9273). Steiner, et al. J Clin Oncol. 2010;28:7s(suppl;abstr 9147). Dalton, et al. J Cachexia
Sarcopenia Muscle. 2011;2:153-161. Marcantonio, et al. Endocrine Reviews. 2010;31(3):(suppl 1)S872.
40
30
Placebo
Enobosarm 3 mg
20
10
0
-10
BILATERAL LEG PRESS
-20
6
Muscle wasting is an important cancer related
symptom in patients with advanced NSCLC
•
At diagnosis, nearly 50% of advanced NSCLC patients have severe
muscle loss and approximately 70% of NSCLC patients will lose muscle
 88% have lower body functional limitations including the ability to climb stairs, lift
and carry 10 lbs, walk ¼ mile, and stoop, crouch or kneel
•
Performance status is a predictor of a patient’s ability to tolerate
chemotherapy, and poor performance status is a primary reason patients
are not offered treatment
 Performance status also predicts the likelihood of hospitalization, ability to
maintain independence, and survival
Baracos VE, et al. Am J Clin Nutr. 2010 Apr;91(4):1133S-1137S. Baracos VE. 2011 data on file. Bruera E. BMJ. 1997;315(7117)1219-22. Schootman M, et al.
Cancer. 2009 Nov 15;115(22):5329-38. Braithwaite D, et al. J Natl Cancer Inst. 2010;102(191):1468-77. Prado CMM, et al. The Lancet Oncology 2008;9(7):629-35.
7
Phase IIb clinical trial in cancer patients:
Enobosarm increased lean body mass & improved physical function in NSCLC
Subset analysis: 61 NSCLC patients
• Mean weight loss at entry was 9.7%
• Enobosarm treated patients had a mean 18% improvement in stair climb power from
baseline and 1.1 kg improvement in LBM
• No statistically significant improvements in physical function or LBM in placebo group
Ad Hoc Phase IIb Responders Analysis – NSCLC*
Endpoint
Placebo
Enobosarm
Physical Function
19%
42%
Lean Body Mass
24%
42%
*Based on ITT including 30% drop out rate
Safety- NSCLC
Placebo
(n=21)
1 mg
(n=21)
3mg
(n=19)
Deaths
6 (29%)
8 (38%)
3 (16%)
SAE
10 (48%)
10 (48%)
6 (32%)
•
Reported incidence of tumor progression similar
across groups
•
The most common AEs were fatigue, anemia,
nausea and diarrhea
8
Goals for the treatment of advanced stage NSCLC
with chemotherapy
•
Advanced NSCLC is incurable
•
With currently available platinum doublet therapies, median
survival is 8–11 months and the one year survival rate is 30-40% for
patients who maintain good physical function
Goals of Treatment
Enobosarm
Improve cancer related symptoms
Improve quality of life
Prolong survival
Goal met in clinical trials
Ability to meet goal to be determined
Ramalingam et al, Ca Cancer J Clin, 2011; 61: 91-112
9
International pivotal Phase III clinical trials: POWER 1 and 2
Indication: Prevention and treatment of muscle loss in patients with NSCLC
• Stage III/IV NSCLC patients initiating 1st line chemotherapy
• Co-primary endpoints (responders analysis): (1) no loss of lean body mass (LBM) by DEXA; (2) at least
10% improvement in Stair Climb Power (SCP)
• Each endpoint α=0.05, power >93%
• Assumes 30% drop out rate by 3 months
Co-primary endpoints
Secondary endpoints
•Lean body mass
•Physical function SCP
@ 3 months
• Durability of effect
@ 5 months
• Overall survival
Enobosarm
150 patients
3 mg
platinum +
taxane
Other endpoints
Placebo
150 patients
Enobosarm
150 patients
3 mg
platinum +
non taxane
Placebo
•QoL – FAACT,
FACIT fatigue scales
•Healthcare resource
utilization
•Adherence to
chemo plans
•Tolerance to chemo
150 patients
Input from FDA, MHRA (England) and MPA (Sweden) on Phase III clinical development plans and
Fast Track granted 1/13
10
Enobosarm
Anticipated clinical development plan
2011
1Q
2Q
3Q
2012
4Q
1Q
2Q
3Q
2013
4Q
1Q
2Q
3Q
2014
4Q
1Q
2Q
3Q
4Q
Phase III-POWER 1
Enobosarm 3 mg vs placebo in 300 pts
with NSCLC receiving platinum + taxane
chemotherapy (5 month study)
NDA
Phase III-POWER 2
Enobosarm 3 mg vs placebo in 300 pts
with NSCLC receiving platinum + non taxane
chemotherapy (5 month study)
First patient
enrolled
Last patient
out
11
Enobosarm
Steering Committee
•
Medical Oncology







•
Jeff Crawford (Duke University)
Richard Gralla (Quality of Life Research Associates)
Phil Bonomi (Rush University Medical Center)
Arti Huria(City of Hope)
Kavitha Ramchandran (Stanford University)
Carla Prado (Florida State University)
Aminah Jatoi (Mayo Clinic)
Advocacy
 Bonnie Addario (Bonnie J. Addario Foundation)
•
Other
 Simon Pickard (University of Illinois)
 Dave Cella (Northwestern)
12
Enobosarm
Large market opportunity
Stage III-IV NSCLC is the majority of NSCLC diagnosed and, based on perceptions of
oncologists, at least 50% of these patients have muscle wasting
United States
5 EU
NSCLC
NSCLC
207 K
186 K
Stage III-IV
NSCLC
161 K (78%)
hyperK+
Rates
Stage III-IV
NSCLC
148 K (79%)
hyperK+
Rates
Muscle Wasting
Muscle Wasting
81K (~50%)
74K (~50%)
Source: Datamonitor 2011; projected market size in 2012, US and EU Qualitative market research
13
Enobosarm
Large market opportunity
There is a high level of interest in treatments for muscle wasting
High
need
Extremely
Extremely
interested
interested
Not interested
at all
5.8
5.6
US
5 EU
(N=16)
(N=24)
5.9
No need
at all
US
Quant
(N=150)
Source: US Oncologist Quantitative and US and 5 EU Qualitative market research
14
Enobosarm
Large market opportunity- US Payors’ perspective*
•
Improvement in physical function and increase in muscle mass were
considered the two most favorable clinical attributes of enobosarm
•
All economic endpoints being evaluated are acceptable by the majority of
Payors

Hospitalizations, ER visits, mobility devices, home health services, and hospice
•
80% of Payors would cover enobosarm with or without restriction
•
At a monthly WAC of $1500 - $3000 the majority of Payors would cover
enobosarm as a Tier 3 with a prior authorization
*Based
on US Managed Healthcare Landscape and Assessment of Enobosarm, Managed Solutions, LLC April 2012
15
Enobosarm
Large market opportunity
•
Lung cancer is the most common malignancy

Worldwide - estimated 1.6 million new cases and 1.4 million deaths each year

United States – 226,160 new cases and 160,340 deaths in 2012

50% present with advanced disease

In US, 170,000+ advanced NSCLC patients initiate chemotherapy each year
•
Indication being pursued is prevention and treatment of muscle wasting in
patients with NSCLC, a cancer related symptom
•
Currently, several drugs treating cancer related symptoms are priced
between $30 and $50 per day
•

Xgeva (CTIBL and SRE) $55 per day

Zometa (CTIBL and SRE) $40 per day

Neulasta (neutropenia) $5600 per dose
GTx estimates muscle wasting indication in patients with NSCLC
could be a $750 million opportunity in US alone
16
Potential new indications for Enobosarm
Muscle wasting
End stage
renal disease
Cardiac
cachexia
AR
Breast
cancer
Anabolic agent
Osteoporosis:
PMO
Male osteoporosis
Glucocorticoid induced
COPD
Rehab- hip
replacement
Enobosarm
Animal health
(or other SARM)
Rehab- knee
replacement
Glucocorticoids
wasting
Stroke
Male
Hypogonadism
Dry eyesDrops
formulaton
Gel formulation
17
Enobosarm
Intellectual property
•
79 enobosarm composition of matter and method of use patent
applications issued, approved, or pending in U.S. and rest of world with
expiration dates in 2024.

Includes issued composition of matter and method patents in US and Japan
•
As a new chemical entity, issued patents should be eligible for patent
term extension of up to 5 years (2029)
•
GTx has 350 patents issued, approved or pending worldwide for all
SARMs including enobosarm
18
Capesaris® (GTx-758)
Selective ERα agonist for the treatment of
advanced prostate cancer
Evolving treatment paradigm
Advanced prostate cancer
Advanced Prostate Cancer
Primary ADT
Castration Resistant Prostate Cancer (CRPC)
Capesaris*
First
Secondary
Hormone Tx
(combination
ADT)
Capesaris
LHRH agents
Second
Secondary
Hormone Tx
Enzalutamide
*Potential for future
development
Red= approved
Third
Secondary
Hormone Tx
Abiraterone +
Prednisone
Chemotherapy
Docetaxel
Post
Chemotherapy
Enzalutamide
Abiraterone/
Prednisone
Cabazitaxel
Market
750,000
patients
100,000
patients/year
15,000
patients/year
20
Multiple potential mechanisms of action for a
selective ERα agonist to treat prostate cancer
21
The relative amount of free T and T bound to
albumin or SHBG in prostate cancer patients
Total testosterone %
100
50
Bioavailable
Free testosterone
Albumin bound testosterone
0
Control
Orchiectomy
Estrogen
SHBG bound testosterone
Damber, JE et al, J. Endocrin. Invest, 6: 91-3, 1983
22
Phase II studies in men with advanced prostate
cancer confirms the mechanism of action*
•
Phase II open label loading dose finding 705 clinical study in
advanced prostate cancer comparing1500mg BID and 1000mg BID
loading doses followed by 1000mg or 2000mg maintenance doses
(n=55)
•
•
•
Phase II open label maintenance dose finding 710 clinical study in
advanced prostate cancer comparing Lupron, Capesaris 1000mg
PO qd and Capesaris 2000mg PO qd (n=164)

2000mg Capesaris and Lupron arms
•
•
•
•
•
Castration rate greater than 90% for both arms
Capesaris increased SHBG and decreased free T
Maintained castration by Kaplan-Meier estimates >95.5%
Similar testosterone escapes
Capesaris increased SHBG and decreased free T
Improvement in hot flashes, bone turnover markers and insulin resistance
Safety- VTE incidence rate increased for Capesaris
*Studies terminated prior to completion
23
Phase II, secondary hormonal therapy 707 clinical
study in chemotherapy naive CRPC
Inclusion/Exclusion Criteria:
•
•
•
•
Endpoints:
•
•
•
•
Serum PSA > 2ng/ml
Castrate (total T <50ng/dl)
ECOG 0-2
Maintain primary ADT
Capesaris
2000 mg PO q d
Serum PSA response > 50% (Primary Endpoint)
Serum PSA Progression (PSA > 2 & >25%)
Serum free T and SHBG
Bone and Soft Tissue metastases
Day
90
25 patients
Serum PSA Response (N=7)
Percent of baseline
0
-10
Day 1
Day 15
Day 30
Day 60
1S001
1S003
2S001
5S001
5S003
5S004
5S002
-20
-30
-40
-50
-60
-70
Serum PSA responders (>50% reduction)
Mean SHBG =
399% ± 85%
-80
-90
Days
24
Phase II, open label, 712 clinical study of secondary
hormonal treatment in men with metastatic CRPC
started 3Q 2012
Subjects
Primary Endpoint:
Secondary Endpoints:
• mCRPC
• Maintain ADT
• Serum PSA response
•
•
•
•
•
•
GTx-758
25 patients
125 mg
30 d
GTx-758
250 mg
30 d
25 patients
GTx-758
500 mg
Day
0
PSA progression
Progression free survival
Free T/SHBG
Adrenal (DHEA&DHEAS)
Estrogen deficiency side effects
SRE
25 patients
Day
90
25
Efficacy should be maintained with lower
doses of Capesaris
Projected SHBG increases by dose and time*
Dose
Day 28
Day 60
Day 90
125 mg
270.6%
299.8%
394.0%
250 mg
311.9%
364.4%
448.4%
500mg
361.2%
429%
502.8%
*Based on Phase II 703/705 studies
(Data on file)
Dose
26
Capesaris
Steering Committee
•
Medical oncology






•
Evan Yu* (U Washington)
Johann DeBono* (Royal Marsden)
Dan Petrylak* (Columbia/ Yale)
Chuck Ryan* (UCSF)
Phil Kantoff* (Dana Farber Harvard)
Thomas Flaig* (U Colorado)
Urology
 Badri Konety (U Minnesota)
•
Advocacy group
 Tom Kirk (Us TOO)
* Confirmed participation
27
Capesaris
Anticipated clinical development plan
2011
1Q
2Q
2012
3Q
4Q
1Q
2Q
2013
3Q
4Q
1Q
2Q
3Q
2014
4Q
1Q
2Q
3Q
4Q
Phase IIb
705 clinical study
Maintenance dose finding
Phase II
710 clinical study
Loading dose finding
Phase II
Phase II
707 clinical study
Secondary hormonal
therapy in CRPC patients
712 clinical study
Secondary hormonal therapy in
mCRPC patients (lower doses)*
*Estimated based on projected enrollment
28
Capesaris
Intellectual Property
•
Approximately 43 composition of matter and method of use patent applications
and patents, which are either issued, allowed or pending in the US and rest of
world with expiration dates of January 2029 in the US (issued) and November
2026 in the ROW
•
As a chemical entity, issued US patent should be eligible for additional patent
term extension of up to 5 years (for a maximum term of November 2034), as
may be determined following FDA approval of Capesaris
29
Financial summary
•
Shares outstanding: 62.8 M
•
Cash, cash equivalents and short-term investments
at September 30, 2012: $47.3M
•
Cash and short-term investments increased in October 2012 from the
receipt of $19M in net cash proceeds from the sale of the rights to
Fareston
•
No debt, no warrants
30
Two late stage clinical programs: milestones
•
•
Enobosarm (Ostarine; GTx-024), a SARM, for the prevention and treatment
of muscle wasting in patients with non-small cell lung cancer:

Enrollment completed 4Q 2012 for two pivotal Phase III clinical trials in
approximately 650 non-small cell lung cancer (NSCLC) patients – top line results
expected summer 2013

Granted Fast Track designation January 2013
Capesaris (GTx-758), an oral selective ER alpha agonist, for combination
primary ADT & secondary hormonal treatment of advanced prostate cancer:

Currently enrolling Phase II 712 clinical trial evaluating Capesaris® (GTx-758) for
secondary hormonal treatment in men with metastatic castration resistant
prostate cancer
31