Safe harbor
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.
1
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

Input from with FDA, MHRA and MPA on our Phase III clinical development plan

Currently enrolling two pivotal Phase III clinical trials in non-small cell lung cancer
(NSCLC) patients - topline results expected 1H 2013

DSMB reviewed safety data in May 2012 and October 2012 and agreed trial
could continue as planned
Capesaris (GTx-758), an oral selective ER alpha agonist, for secondary
hormonal treatment of advanced prostate cancer:

Eight clinical trials conducted to date involving approximately 500 subjects

FDA removed its Clinical Hold on Capesaris IND in May 2012

Phase II 712 clinical trial evaluating Capesaris® (GTx-758) for secondary
hormonal treatment in men with metastatic castration resistant prostate cancer
started 3Q2012
2
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
4
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
5
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
6
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%
Physical Function
1.5
25
1.1
Placebo
Enobosarm
1
% change from baseline
Change from baseline (kg)
Lean Body Mass
0.5
0
-0.5
-1
-0.84
N=31
-1.5
placebo
1 mg
3 mg
P=0.198
Placebo
Enobosarm
17.6
15
10
5
0
-5
-10
-15
-14.7
N=31
-20
P=0.051
Placebo
(n=21)
1 mg
(n=21)
3mg
(n=19)
Deaths
6 (29%)
8 (38%)
3 (16%)
SAE
10 (48%)
10 (48%)
6 (32%)
Steiner, et al. J Clin Oncol. 2011;29:15s(suppl;abstr 9022).
20
Reported incidence of tumor progression similar
across groups. The most common AEs were fatigue,
anemia, nausea and diarrhea.
7
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
8
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 LBM; (2) at least 10% improvement in 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
@ 3 months
• Durability of effect
@ 5 months
• Overall survival
Enobosarm
150 patients
3 mg
platinum +
taxane
Other endpoints
Placebo
•QoL – FAACT,
150 patients
FACIT fatigue scales
•Healthcare resource
utilization
•Adherence to
chemo plans
•Tolerance to chemo
Enobosarm
150 patients
3 mg
platinum +
non taxane
Placebo
Input from with FDA, MHRA (U.K.)
and MPA (Sweden) on Phase III
clinical development plans
150 patients
NSCLC-Stage III/IV
Ad Hoc Phase IIb Responders
Analysis
Placebo
Enobosarm
Physical Function
33%
69%
Lean Body Mass
33%
63%
9
Enobosarm
Anticipated clinical development plan
2011
1Q
2Q
3Q
2012
4Q
1Q
2Q
3Q
2013
4Q
1Q
2Q
2014
3Q
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)
10
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 - 222,500 new cases and 157,300 deaths in 2010

50% present with advanced disease
•
Indication being pursued is prevention and treatment
of muscle wasting in patients with NSCLC
•
In US, 170,000+ advanced NSCLC patients initiate chemotherapy each year
•
Currently, several drugs treating cancer related symptoms
are priced between $30 and $50 per day
•
GTx estimates muscle wasting in patients with NSCLC
could be a $750 million opportunity in US alone
11
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
NSCLC
= 207 K
Stage III-IV
NSCLC
= 161 K (78% of NSCLC)
Muscle hyperK+
Wasting Rates
~50% or higher
(81 K)
5 EU
NSCLC
= 186 K
Stage III-IV
NSCLC
= 148 K (79% of NSCLC)
Muscle
Wasting
hyperK+
Rates
~50% or higher
(74 K)
Source: Datamonitor 2011; projected market size in 2012, US and EU Qualitative market research
12
Enobosarm
Large market opportunity
Oncologists believe that muscle wasting has a high to medium impact on a NSCLC patient’s
physical activity, QoL, weight loss, ability to tolerate chemotherapy and ultimately on survival
Level of Impact from Muscle
wasting
US
Parameter
Level of Impact from Muscle
wasting
France, Germany, Italy, Spain,
UK
High
Medium
Low
High
Medium
Low
Physical Activity
70%
20%
10%
84%
16%
0%
Quality of life
60%
30%
10%
68%
32%
0%
Weight Loss
70%
20%
10%
40%
44%
16%
Ability to tolerate
chemotherapy
55%
36%
9%
68%
24%
8%
Survival
44%
44%
11%
60%
36%
4%
Hospitalizations
22%
22%
56%
20%
64%
16%
Source: US and EU Qualitative market research
GTx-024 Commercial Assessment & Forecast – May 2012
13
Enobosarm
Large market opportunity
There is a high level of interest in treatments for muscle wasting, but very little
awareness of specific drugs in clinical development
Only 30% of US oncologists
and 20% of European
oncologists had any awareness
of products in development for
muscle wasting
•
Oncologists in both the US and
the EU expressed a high level
of interest for new treatments
for the management of muscle
wasting
High
Need
Extremely
Extremely
interested
interested
Not interested
at all
•
US
5 EU
(N=16) (N=24)
No need
at all
US
Quant
(N=150)
Source: US Oncologist Quantitative and US and 5 EU Qualitative market research
GTx-024 Commercial Assessment & Forecast – May 2012
14
Enobosarm
Intellectual property
•
79 enobosarm composition of matter and method of use patent
applications approved or pending in U.S. and rest of world with
expiration dates in 2024
•
As a new chemical entity, issued patents should be eligible for patent
term extension of up to 5 years (2029)
•
GTx has 350 patents approved or pending worldwide for all SARMs
including enobosarm
15
®
Capesaris
(GTx-758)
Selective ERα agonist for the treatment of
advanced prostate cancer
Evolving treatment paradigm
Advanced prostate cancer
Advanced Prostate Cancer
Castration Resistant Prostate Cancer (CRPC)
Hormone
sensitive
Primary hormone
therapy
(LHRH agonists
or antagonists)
Capesaris*
*Potential for future
development
First
Secondary
Hormone Tx
Capesaris
Enzalutamide
Italicized- not approved
Second
Secondary
Hormone Tx
Capesaris
Enzalutamide
Third
Secondary
Hormone Tx
Abiraterone +
Prednisone
Capesaris
Chemotherapy
Docetaxel
Post
Chemotherapy
Enzalutamide
Abiraterone/
Prednisone
Cabazitaxel
Market
750,000
patients
100,000
patients/year
15,000
patients/year
17
Multiple potential mechanisms of action for a
selective ERα agonist to treat prostate cancer
18
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
19
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
20
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
21
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
22
22
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
23
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
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)
25
Capesaris
Intellectual Property
•
20 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 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
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
27
28