Transcript Phase 3 studies of enobosarm

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 12, 2013. We expressly disclaim any obligation to
release publicly any updates to forward-looking statements
made during the course of this presentation.
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2
Overview

Three late stage clinical programs
 Enobosarm 3 mg (Ostarine ®; GTx-024), an oral SARM, for the prevention and treatment of
muscle wasting in patients with non-small cell lung cancer:
 13 clinical trials completed to date involving approximately 1325 subjects
 Completed two pivotal Phase 3 clinical trials with approximately 650 non-small cell lung cancer
(NSCLC) patients
 Met with FDA February 2014- may move forward with additional Phase 3 program
 Met with national authorities from 2 EMA member countries January 2014- will file MAA in
Europe by Q1 2015
 Enobosarm 9 mg (Ostarine ®; GTx-024), an oral SARM, for the treatment of advanced AR and
ER positive breast cancer:
 Phase 2 open label, dose finding clinical trial fully enrolled 22 patients- data expected Q3 2014
 Capesaris®(GTx-758), an oral selective ER alpha agonist, for secondary hormonal treatment
of advanced prostate cancer:
3
 Eight clinical trials conducted to date involving approximately 500 subjects
 Phase 2 G200712 open label, dose finding clinical trial for secondary hormonal treatment in men
with castration resistant prostate cancer (CRPC)- completed enrollment of 125mg arm with
metastatic CRPC and now enrolling 250mg arm with nonmetastatic and metastatic CRPC
 Met with FDA on Nov 14, 2013 for Capesaris® for the indication of first secondary hormonal
therapy for nmCRPC
Enobosarm (Ostarine®; GTx-024)
Selective Androgen Receptor Modulator (SARM)
for the prevention and treatment of muscle wasting
4
Cancer induced muscle wasting is a serious
unmet medical need
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5
Cancer induced wasting begins early in the
course of malignancy
At diagnosis,46.8% of lung cancer patients have
severe muscle wasting
After diagnosis, an additional 65% of lung
cancer patients will experience muscle wasting
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Physical functional limitation is a strong
predictor of all-cause mortality
57% of cancer patients with muscle wasting
exhibit physical function limitations
88% of lung cancer survivors experience
physical function limitations
Baracos VE, et al. Am J Clin Nutr. 2010;91(4):1133S-1137S. Baracos VE. 2011 data on file. Bruera E. BMJ. 1997;315(7117)1219-22.
Schootman M, et al. Cancer. 2009;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.
US and Europe: Control for negative or positive effects of
chemotherapy
Endpoints
Add-on, placebo-controlled trials
New study design slide
G300504
G300505
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Efficacy summary of 3 clinical trials
For FDA, did not meet pre-specified responder analysis of all coprimary endpoints
of LBM and SCP less than 0.05; however, for EMA:
Study
(Duration)
Phase 3 G300504
(20 weeks)
Positive study
Phase 3 G300505
(20 weeks)
Supportive study
Day 84
Day 84
Placebo
1 mg
3 mg
SCP
(p-values)
0.0147
0.8877
0.11
0.0008
0.0006
LBM
(p-values)
0.0002
0.0111
0.88
0.0012
0.046
NSCLC
Chemo controlled:
Chemo+Taxane
NSCLC
Chemo controlled:
Platinum+Nontaxane
Multiple cancer types
Chemo not controlled
321
320
159
Continuous
variable
analyses
Population
type
N

Phase 2B G200502
(16 weeks)
Supportive study
Anaemia observed in G300505 patients prevented improvement in LBM from being translated to benefit on
physical function
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Differences in selected AEs between the trials
G300504
(Platinum+Taxane)
Adverse Event
8
G300505
(Platinum+Nontaxane)
Placebo
GTx-024
Placebo
GTx-024
Anemia
27.3%
28.8%
47.9%
50.9%
Neutropenia
18.6%
12.5%
33.9%
30.9%
Leukopenia
3.1%
3.8%
17.0%
15.8%
Thrombocytopenia
5.6%
3.8%
17.6%
18.8%
Nausea
32.3%
35.6%
44.2%
44.8%
Vomiting
16.1%
18.1%
29.1%
27.3%
Constipation
4.3%
8.1%
15.2%
12.7%
Asthenia
12.4%
20.6%
16.4%
15.2%
Decreased appetite
16.8%
6.9%
17.0%
19.4%
Arthralgia
13.7%
16.9%
2.4%
1.8%
Alopecia
32.3%
33.8%
10.3%
10.9%
Tables 14.5.4 (10% or greater) and 14.5.2 (all TEAEs)
Interim pooled survival analysis
Interim analysis
performed at 277
deaths (62% of
expected deaths)
Final analysis will
be performed at 450
deaths
Placebo 10.9 months
GTx-024 3 mg 11.2 months
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Conclusions

Phase 3 G300504-Platinum+taxane is a positive study using continuous variable analysis
 Declines in both lean body mass and stair climb power were observed in placebo group
 Statistical and clinically meaningful differences between GTx-024 and placebo were
observed for both lean body mass (muscle) and stair climb test (physical function)

Phase 3 G300505-Platinum+nontaxane is a supportive study using continuous variable analysis
 Declines in lean body mass and stair climb power were observed in placebo group
 Statistically and clinically meaningful differences between GTx-024 and placebo were
observed for lean body mass (muscle)
 Different populations and chemotherapy side effects (anemia & vomiting) appear to explain
physical function responses

GTx-024 was very well tolerated in both trials
 Minor differences in AEs between enobosarm and placebo add on groups were observed
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Conclusions
(continued)
•
The apparent correlation between maintaining or increasing lean body mass and increased
survival adds support for enobosarm treatment in NSCLC patients
• Enobosarm maintains and builds muscle better than chemotherapy alone

Totality of the data from these two Phase 3 studies and the Phase 2b G200502 study support
the efficacy and safety of GTx-024 (enobosarm) for the indication of Prevention and treatment of
muscle wasting in patients with advanced NSCLC treated with platinum plus taxane
chemotherapy
11
Next steps
 Met with FDA February 2014
 GTx may move forward after we agree upon design and complete Phase 3
program
 Met with national authorities in EMA in January 2014
 Can file MAA with completed single positive Phase 3 clinical study and
Phase 3 supportive clinical study for the indication of prevention and
treatment of muscle wasting in non small cell lung cancer patients on
taxanes
 Standard EMA guidance requires:
 Phase 1 DDI and Phase 1 QT study for drug labeling will be completed by Q3
2014
 Completed Phase 1s: renal impairment study, hepatic impairment study, and
mass balance study
 Pediatric investigational plan to be agreed upon by Q4 2014
 MAA will be filed by Q1 2015
 Meet with Japanese regulatory – PMDA in 2H 2014
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Enobosarm offers benefit in clinical practice
US Commercial Perspective
2nd and 3rd line chemotherapy market
1st line chemotherapy market
Stage III/IV NSCLC
First line chemotherapy
177,000 per year
Nonsquamous (2/3)
118,000
Taxane +Avastin
~50% eligible
59,000
Assume 1/2
receive Avastin
30,000
Squamous (1/3)
59,000
Taxane or non-taxane
(non Avastin eligible)
59,000
Assume 1/3
receive taxane
20,000
50,000 patients per year
13
Stage III/IV NSCLC
177,000 per year
2013 Thomson Reuters Spotlight on NSCLC
2nd line chemotherapy
123,000 (70%)
3rd line chemotherapy
53,000 (30%)
Assume 1/2
receive taxane
62,000
Assume 1/2
receive taxane
26,000
Taxane or non-taxane
59,000
Assume 1/3
receive taxane
20,000
20,000 patients per year
158,000 patient per year
88,000 patients per year
Potential new indications for enobosarm/SARMs
Muscle wasting
End stage renal
disease
Cardiac cachexia
AR
Breast
Cancer
Phase 2
(ongoing
Endometriosis
Anabolic agent
Osteoporosis:
PMO
Male osteoporosis
Glucocorticoid induced
COPD
Rehab- hip &
knee replacement
Enobosarm
(or other SARM)
Muscular
dystrophy
Dry eyes-
Glucocorticoids
wasting
Stroke
Animal health
MTA with Intervet for
swine and cattle
Female sexual
dysfunction
Male
Hypogonadism
Drops formulaton
Gel formulation
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The potential to treat AR+/ER+ metastatic
breast cancer
GTx-024
Selective AR agonist
Treat AR+
metastatic breast cancer
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AR+/ER+ metastatic breast cancer
Summary
•Androgens are effective in the treatment of metastatic breast cancer
•Androgens that have been used include androstenedione, testosterone,
medroxyprogesterone, DHEA/DHEAS, fluoxymesterone, and mibolerone
•Regression and overall response rates in unknown receptor status patients have
been reported between 20-44% with pain relief and increase in well being
•Concerns
•Side effects in women, especially virilization, limits the use of androgens
•Possibility of some androgens being aromatized to estrogens
•Targeting the AR in patients with AR+ metastatic breast cancer who have
responded, but then failed other hormone therapy with a SARM like enobosarm
may potentially provide at least similar response rates as seen with androgens
without the unwanted side effects
•Finding a biomarker like increased serum PSA to determine PSA response will
also facilitate clinical development
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Phase 2, open label, study of the effect of GTx-024 9 mg oral daily in
women with AR+/ER+ metastatic breast cancer who previously
responded to hormonal therapy
Subjects
•Progressing metastatic breast cancer
•Response on at least one previous hormone therapy
Primary endpoint
Clinical benefit response
(CR, PR, and
stable disease for 6 months in AR+ subjects)
GTx-024
9 mg PO qD
22 patients
17
6 months
•
•
•
•
•
Lead PI- Dr. Beth Overmoyer- Dana Farber
9 clinical sites in US and fully enrolled 22 patients
Well tolerated
Although trial is ongoing, already met goal to see 3 clinical
benefit responses in 14 AR+ patients
Data expected Q3 2014
AR+/ER+ metastatic breast cancer
•Regulatory pathway
•Unmet medical need with no established targeted therapy
•Potential for Orphan drug status
•Plan to meet with FDA 2H 2014
•Large market
•50,000 women with metastatic breast cancer breast cancer in US
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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, Europe and
Japan
•
As a new chemical entity, issued patents should be eligible for patent term
extension of up to 5 years (2029)
•
GTx has 345 patents issued, approved or pending worldwide for all
SARMs, including enobosarm
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Capesaris® (GTx-758)
Selective ERα agonist for the treatment of
advanced prostate cancer
Multiple potential mechanisms of action for a selective
ERα agonist to treat prostate cancer
21
Androgen deprivation therapy has estrogen
deficiency side effects
22
Phase 2, open label, dose finding, G200712 clinical study
of secondary hormonal treatment in men with
nonmetastatic and metastatic CRPC
Subjects:
• mCRPC
• nmCRPC
• Maintain ADT
GTx-758
125 mg
Sequential
enrollment
Primary Endpoint:
• Serum PSA response
Secondary Endpoints:
•
•
•
•
•
•
PSA progression
Tumor progression
Free T and SHBG
Adrenal (DHEA&DHEAS)
Estrogen deficiency side effects
SRE
38 patients with metastatic CRPC –fully enrolled
GTx-758
250 mg
Day 0
38 patients with metastatic and nonmetastatic CRPC- enrolling
Day 90
23
Free testosterone levels at day 90 at 125mg dose
DAY OF VISIT
STANDARD
PMEAN DEVIATION VALUE
N
RANGE
MEDIAN
DAY 1 (Baseline)
33
(0.20, 4.60)
0.80
1.17
0.90
.
DAY 90
20
(0.30, 1.20)
0.45
0.57
0.31
.
CHANGE FROM BASELINE TO DAY 90
20
(-3.90, 0.30)
-0.50
-0.74
0.98
0.0002
% CHANGE FROM BASELINE TO DAY 90
20
(-84.80, 150.00)
-57.14
-34.59
54.53
0.0035
24
GTx-758 treatment lowers PSA levels in mCRPC
Maximum decrease in 125mg treated patients by day 90
N=31
25
Phase 2 G200712 study
Central RECIST 1.1 analysis in 125 mg cohort
Comparison of baseline and Day 90 reads
(15 subjects with central scan reads)
Partial Response
(PR)
1/15 (6.7%)
Stable Disease (SD)
12/15 (80.0%)
Progressive Disease
(PD)
1/15 (6.7%)
Not evaluable (NE)
1/15 (6.7%)
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Phase 2 G200712 study
An example of a metastasis response at the 125mg dose
Prestudy
Day 90
Reduction in “target lesion” – bladder mass from 43 x 35 mm to 33 x 30 mm
27
Amelioration of estrogen deficiency side effects
Bone turnover markers in 125mg treated patients
CTX
# of patients (%)
Bone specific alkaline phosphatase
Increased
Decreased
Unchanged
5/20 (25%)
12/20 (60%)
3/20 (15%)
# of patients (%)
Increased
Decreased
Unchanged
8/21 (38%)
11/21 (52%)
2/21 (10%)
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Individual subjects
Individual subjects
Phase 2 G200712 study
Most frequent adverse events (38 subjects) in the 125
mg cohort
Adverse Event
Frequency (%)
Gynecomastia
6 (15.8%)
Nipple pain
3 (7.9%)
Loss of appetite
3 (7.9%)
Bone pain
3 (7.9%)
Fatigue
3 (7.9%)
*VTE - 0
No drug related Serious AEs (SAE)
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Dual potential mechanisms of action for a GTx-758 to
treat prostate cancer and prevent metastases
Prostate cancer cells
•
•
•
•
Increases sex hormone binding globulin
Decreases free T, DHT, and certain adrenal androgens
Potential direct inhibitory effects on prostate growth
Net effects: suppresses prostate cancer
Bone
•
•
•
•
Acts like estrogen to promote bone
Decreases bone turnover markers
Prevent bone loss and fractures
Bone drugs, make the bone resistant to metastases
30
Evolving treatment options for advanced prostate
cancer
Advanced Prostate Cancer
Hormone
Sensitive
Primary hormone
therapy
(LHRH agonists
or antagonists)
Hormone
Sensitive
(suboptimal
castration)
Orchiectomy
Nonmetastatic
(nmCRPC)
PSA rise/
Progression
First
Secondary
Hormone Tx
GTx-758
ARN-509
Metastatic Castration Resistant Prostate Cancer (mCRPC)
Second
Secondary
Hormone Tx
(Prechemo)
=Approved
Enzalutamide
Abiraterone +
Prednisone
Chemotherapy
Hormone
Sensitive
(optimal
castration)
750,000
patients
Docetaxel
PSA rise/
Progression
Post
Chemotherapy
Enzalutamide
Abiraterone/
Prednisone
Cabazitaxel
Xofigo (radium 223)
100,000
patients
36,000
patients
Market
31
Capesaris
Intellectual Property
32
•
Approximately 47 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
Financial summary
•
Shares outstanding: 75.2 M*
•
Cash, cash equivalents and short-term investments
at $14.7 mm at December 31, 2013
•
March 2013 added $21mm*
•
*following closing of the PIPE
33
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Clinical programs- milestones

Three late stage clinical programs
 Enobosarm 3 mg (Ostarine ®; GTx-024), an oral SARM, for the prevention and treatment of
muscle wasting in patients with non-small cell lung cancer:
 Completed 2 Phase 3 clinical trials
 Met with FDA Q1 2014- may move forward with additional Phase 3 program
 Met with national authorities from 2 EMA member countries January 2014- plan to file MAA in
Europe by Q1 2015
 Plan to meet with Japanese regulatory
 Enobosarm 9 mg (Ostarine ®; GTx-024), an oral SARM, for the treatment of advanced AR
positive breast cancer:
 Phase 2 open label, dose finding clinical trial fully enrolled 22 patients
 Data expected Q3 2014
 Capesaris®(GTx-758), an oral selective ER alpha agonist, for secondary hormonal treatment
of advanced prostate cancer:
 Phase 2 G200712 open label, dose finding clinical trial for secondary hormonal treatment in men
with castration resistant prostate cancer (CRPC)- completed enrollment of 125mg arm with
metastatic CRPC and now enrolling 250mg arm with nonmetastatic and metastatic CRPC
 Data expected 2H 2014