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 August 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 (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 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 will start 3Q2012 2
(Ostarine; GTx-024) Selective Androgen Receptor Modulator (SARM) for the prevention and treatment of muscle wasting in patients with lung cancer
Approximately 600 patients have participated in eight clinical trials SARM 2005 2006 2007 2008 2009 2010 2011 GTx GTx GTx GTx GTx Collaboration Collaboration GTx and Merck SARM Phase I SAD Phase I MAD Phase II POC chronic sarcopenia Phase IIb muscle wasting in cancer Phase I divided dose Phase Ib head to head chronic sarcopenia Phase Ib PK study Japanese women Phase I Formulation study 4
increased lean body mass and improved physical function in three efficacy clinical trials Phase IIb cancer cachexia trial: 159 subjects with cancer cachexia, 4 months tx Change from baseline (kg) 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 LEAN BODY MASS Placebo 3 mg Change from baseline (%) 30% 25% 20% 15% 10% 5% 0% 5% 10% PHYSICAL FUNCTION Placebo 3 mg Time STAIR CLIMB Power Phase II POC clinical trial: 120 elderly men and postmenopausal women, 3 months tx Change from baseline (kg) 0.2 1.4 1.2 1 0.8 0.6 0.4 0.2 0 0.2 Placebo 3 mg Change from baseline (%) 25% 20% 15% 10% 5% 0% 5% 10% 15% Placebo 3 mg Time STAIR CLIMB Power Phase Ib sarcopenia trial: 88 postmenopausal women, 3 months tx Change from baseline (kg) 1.6 1.4 1.2 0.8 0.4 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. 1 0.6 0.4 0.2 0 0.2 Placebo 3 mg Change from baseline (lbs) 40 30 20 10 0 10 20 Placebo 3 mg BILATERAL LEG PRESS 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: increased lean body mass & improved physical function in NSCLC Subset analysis: 61 NSCLC patients; mean % weight loss at entry was 9.7% Lean Body Mass Physical Function 1.5 Change from baseline (kg) 1 0.5 0-0.5-1 -1.5 Placebo 1.1-0.84 N=31 placebo 1 mg 3 mg P=0.198 % change from baseline Placebo -14.7 P=0.051 17.6 N=31 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. Steiner, et al. J Clin Oncol. 2011;29:15s(suppl;abstr 9022). 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 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 1 st 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 platinum + taxane platinum + non taxane 3 mg Placebo 3 mg Placebo Co-primary endpoints Lean body mass Physical function @ 3 months 150 patients 150 patients 150 patients 150 patients Secondary endpoints Durability of effect @ 5 months Overall survival Other endpoints QoL FAACT, FACIT fatigue scales Healthcare resource utilization Adherence to chemo plans Tolerance to chemo Input from with FDA, MHRA (U.K.) and MPA (Sweden) on Phase III clinical development plans Ad Hoc Phase IIb Responders Analysis NSCLC-Stage III/IV Placebo Physical Function 33% 69% Lean Body Mass 33% 63% 9
Anticipated clinical development plan 2011 2012 2013 2014 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q Phase III-POWER 1 3 mg vs placebo in 300 pts with NSCLC receiving platinum + taxane chemotherapy (5 month study) Phase III-POWER 2 3 mg vs placebo in 300 pts with NSCLC receiving platinum + non taxane chemotherapy (5 month study) NDA 10
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
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 12
Capesaris (GTx-758) Selective ERα agonist for the treatment of advanced prostate cancer
Evolving treatment paradigm Advanced prostate cancer Advanced Prostate Cancer Hormone sensitive Primary hormone therapy (LHRH agonists or antagonists) Capesaris* *Potential for future development Castration Resistant Prostate Cancer (CRPC) First Secondary Hormone Tx Capesaris Enzalutamide Second Secondary Hormone Tx Capesaris Enzalutamide Third Secondary Hormone Tx Abiraterone + Prednisone Capesaris Chemotherapy Docetaxel Post Chemotherapy Enzalutamide Abiraterone/ Prednisone Cabazitaxel Italicized- not approved Market 750,000 patients 100,000 patients/year 15,000 patients/year 14
Multiple potential mechanisms of action for a selective ERα agonist to treat prostate cancer 15
The relative amount of free T and T bound to albumin or SHBG in prostate cancer patients 100 Total testosterone % 50 0 Control Orchiectomy Estrogen Bioavailable Free testosterone Albumin bound testosterone SHBG bound testosterone Damber, JE et al, J. Endocrin. Invest, 6: 91-3, 1983 16
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) Castration rate greater than 90% for both arms Capesaris increased SHBG and decreased free T 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 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 17
Phase II, secondary hormonal therapy 707 clinical study in chemotherapy naive CRPC Inclusion/Exclusion Criteria: Serum PSA > 2ng/ml Castrate (total T <50ng/dl) ECOG 0-2 Maintain primary ADT Endpoints: Serum PSA response > 50% (Primary Endpoint) Serum PSA Progression (PSA > 2 & >25%) Serum free T and SHBG Bone and Soft Tissue metastases Capesaris 2000 mg PO q d 25 patients Day 90 Percent of baseline 0-10 -20-30 -40-50 -60-70 Serum PSA Response (N=7) Day 1 Day 15 Day 30 Day 60 1S001 1S003 2S001 5S001 5S003 5S004 5S002 Serum PSA responders (>50% reduction) Mean SHBG = 399% ± 85% -80-90 Days 18
Phase II, open label, 712 clinical study of secondary hormonal treatment in men with metastatic CRPC starts 3Q 2012 Subjects mcrpc Maintain ADT Primary Endpoint: Serum PSA response Secondary Endpoints: PSA progression Progression free survival Free T/SHBG Adrenal (DHEA&DHEAS) Estrogen deficiency side effects SRE GTx-758 125 mg 25 patients GTx-758 250 mg 25 patients GTx-758 500 mg 25 patients Day 0 Day 90 19
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 20
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) Robert Dreicer (Cleveland Clinic) Urology David Penson (Vanderbilt) Advocacy group Tom Kirk (Us TOO) * Confirmed participation
Capesaris Anticipated clinical development plan 2011 2012 2013 2014 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q Phase IIb 705 clinical study Maintenance dose finding Phase II 710 clinical study Loading dose finding Phase II 707 clinical study Secondary hormonal therapy in CRPC patients Phase II 712 clinical study Secondary hormonal therapy in mcrpc patients (lower doses) 22
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 mm Cash, cash equivalents and short term investments at June 30, 2012: $55.9 mm No debt, no warrants 24
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