Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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. 2 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 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 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 6 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 7 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 9 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 10 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 12 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 14 14 The potential to treat AR+/ER+ metastatic breast cancer GTx-024 Selective AR agonist Treat AR+ metastatic breast cancer 15 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 16 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 18 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 19 19 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%) 26 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%) 28 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) 29 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 33 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