Center, Birmingham, AL; 4 Northwestern Brain Tumor Institute, Chicago, IL; 5 Baylor University Medical Center, Dallas, TX; 6

Transcription

1 Phase 2 trial of SL-701, a novel immnotherapy comprised of synthetic short peptides against GBM targets IL-13Rα2, EphA2, and Srvivin, in adlts with second-line recrrent GBM: Interim reslts David A. Reardon 1, David Peereboom 2, L. Brt Nabors 3, Karen Fink 5, Srasak Phphanich 6, Tom Mikkelsen 7, Erin Dnbar 8, Michael Badrddoja 9, David Schiff 10, Frank Lieberman 11, David Tran 12, Michael Schlder 13, Nicholas Btowski 14, Lynn Ashby 15, Christopher Moertel 16, Fabio Iwamoto 17, Jonathan Sherman 18, Janice Chen 19, Peter McDonald 19, Enriqe Porados 19, Chris Brooks 19, Shay Shemesh 19, Jeff Raizer 4 1 Dana-Farber Cancer Center, Boston, MA; 2 Cleveland Clinic Fondation, Cleveland, OH; 3 University of Alabama Cancer Center, Birmingham, AL; 4 Northwestern Brain Tmor Institte, Chicago, IL; 5 Baylor University Medical Center, Dallas, TX; 6 Cedars-Sinai Medical Center, Los Angeles, CA; 7 Henry Ford Hospital, Detroit, MI; 8 Piedmont Brain Tmor Center, Atlanta, GA; 9 Center for Nerosciences, Tcson, AZ; 10 University of Virginia, Charlottesville, VA; 11 University of Pittsbrgh, Pittsbrgh, PA; 12 University of Florida, Gainesville, FL; 13 North Shore University Hospital, Manhasset, NY; 14 UC San Francisco, San Francisco, CA; 15 Barrow Nerological Institte, Phoenix, AZ; 16 University of Minnesota, Minneapolis, MN; 17 Colmbia University Medical Center, New York, NY; 18 George Washington University, Washington, DC; 19 Stemline Therapetics, Inc., New York, NY

2 SL-701 Backgrond SL-701 is a sbctaneosly-delivered immnotherapy Comprised of short synthetic peptides engineered to generate T cell response against GBM Co-administered with immnostimlants GBM targets: IL-13Ra2, Srvivin, Ephrin A2 Mechanism of Action SL-701 (sbctaneosly administered) Immnostimlants co-administered Overexpression of SL-701 targets on GBM GBM IL-13Ra2 Normal brain Antigen presentation GBM cells Immne activation Directs T cells to GBM Inflammatory response in post-therapy brain biopsy Abndant CD8+ T cells CD8+ T cell EphA2 Dendritic cell Tmor cell killing Srvivin YYYY CD8+ T cell CD8+ T cell activation CD8+ T cell Nmeros CD68+ macrophages CD8+ T cell Adapted from Uemats, MJ. Nerooncol, 2005 and Wykosky, J. Clin Cancer Res, 2008 CD8+ T cell CD8+ T cell CD8+ T cell proliferation and differentiation 2 From: JCO, 2011; ASCO, 2011

3 SL-701 Clinical Trials Smmary Previos Phase 1/2 Trial for safety; completed - Earlier version of SL poly-iclc (T cell and NK cell activator) - Safe and well-tolerated - Single-agent activity (major responses in relapsed/refractory GBM) (JCO, 2011; ASCO, 2011 Poster#2506; AACR, 2012 Poster#LB-135) Phase 2 Trial (STML ), Stage 1 (single agent proof-of-concept); completed - SL GM-CSF + Imiqimod - Single agent activity observed in second-line GBM Ø Bevacizmab and poly-iclc introdced in combination stdy (Stage 2) to potentially enhance immne activity & optimize long-term anti-tmor effect of SL-701 (i.e. srvival) Phase 2 Trial (STML ), Stage 2 (combination stdy); ongoing - SL poly-iclc + bevacizmab Major responses observed in second-line GBM Overall srvival trending favorably, median not reached PR=partial response; SD=stable disease 3

4 SL-701: Phase 2 Trial Design (STML ) Eligibility: Second-line GBM Stage 1 SL-701 GM-CSF + Imiqimod MRI MRI Week: After week 22: SL-701 / GM-CSF / imiqimod every 4 weeks thereafter ntil disease progression Eligibility: Second-line GBM Stage 2 SL-701 poly-iclc Bevacizmab MRI MRI Week: After week 22: SL-701 / poly-iclc every 4 weeks and bevacizmab (as per label) every 2 weeks thereafter ntil disease progression 4

5 SL-701: Demographics and Baseline Disease Stage 1 (n=46) Stage 2 (n=28) Age, years Median [range] 56 [25-73] 60 [26-79] Gender [n, (%)] Male 36 (65) 18 (64) Time from initial diagnosis, months Median [range] 14.4 [ ] 11.2 [ ] IDH1 mtation [n,(%)] Mtation 2 (4) 2 (7) No mtation 16 (35) 17 (61) Unknown / not available 28 (61) 9 (32) KPS score at screening Median [range] 90% [70-100] 80% [70-100] Dration on treatment, months Median [range] 1.9 [ ] 3.1 [ ] Salvage srgeries [n, (%)] Gross Total Resection (GTR) 15 (33) 6 (21) Sb Total Resection (STR) 10 (22) 3 (11) Non-srgical anti-gbm therapies [n, (%)] Stpp protocol for GBM 42 (91) 26 (93) TMZ chemotherapy 40 (87) 24 (86) Investigational agent 1 (2) 0 Other (Gliadel wafer, Nivolmab, Vorinostat) 1 (2) 2 (7) Radiotherapy only 1 (2) 1 (4) 5

6 SL-701: Adverse Events Most common adverse events ( 15% treatment-related adverse effects, TRAEs) Stage 1 (N=46) All Grades (% of patients) Grade 3 (% of patients) TRAEs All AEs TRAEs All AEs Injection site disorders Fatige Headache Stage 2 (N=28) All Grades (% of patients) Grade 3 (% of patients) TRAEs All AEs TRAEs All AEs Injection site disorders Fatige Nasea Incldes: injection site celllitis, erythema, indration, pain, prrits, rash, swelling and general reaction 2 Incldes: injection site erythema, hemorrhage, infection, pain, prrits, rash and general reaction 6

7 SL-701: Efficacy Reslts Stage 1 (single agent proof-of-concept) - 1 PR of 13 + months dration, ongoing - 2 SDs of 18 + and 20 + months dration, both ongoing Stage 2 (combination stdy) - 7 responses (2 CR, 5 PR) 4 confirmed with 2 nd response assessment 2 with pending 2 nd response assessment 1 progressed prior to 2 nd response assessment - 28 patients enrolled; 21 patients crrently evalable, which excldes: 4 with pending 1 st response assessment 3 with pending 2 nd response assessment (SD at 1 st assessment) Dration of Response: months, ongoing Stage 1 PR Stage 2 PR CR PR PR 1 CR PR PR PR Confirmed (with 2 nd response assessment) 2 nd response assessment pending Discontined, progression Ongoing 1 PR (confirmed) converted to CR (pending 2 nd response assessment Time (months)

8 SL-701: Stage 2 Overall and Progression Free Srvival (n=28) Srvival PFS probability Probability Median follow-p: 4.1 months ( ) OS Median =5.6, n= Time (months) Srvival OS probability Probability Median not reached, n= PFS Time (months)

9 SL-701: Major Responder, Single Agent (Stage 1) Stage 1 (single agent) 30 yr male, grade IV GBM, KPS 90% Prior treatment: 2 resections + Stpp SL-701 for 23 + months (ongoing) - PR after 11 months (confirmed by 2 nd assessment) Patient contines to receive SL-701 on stdy in remission Pre-SL months of SL months of SL-701 9

10 SL-701: Major Responders, Combination (Stage 2) Stage 2 (combination stdy) 51 yr male, grade IV GBM, KPS 90% Prior treatment: 2 resections + Stpp SL-701 for 6 + months (ongoing) - PR after 2 months (confirmed by 2 nd assessment); sbseqently converted to CR (2 nd assessment pending) Patient contines to receive SL-701 on stdy in remission Pre-SL months of SL-701 Stage 2 (combination stdy) 60 yr male, grade IV GBM, KPS 90% Prior treatment: 1 resections + Stpp + Veliparib SL-701 for 10 + months (ongoing) - CR after 4 months (confirmed by 2 nd assessment) Patient contines to receive SL-701 on stdy in remission Pre-SL months of SL months of SL-701

11 SL-701: Phase 2 Trial Smmary and Conclsions SL-701 is safe and well-tolerated as both a single agent and in combination with bevacizmab SL-701 has demonstrated clinical activity, inclding major responses, in relapsed/refractory GBM when sed either alone or in combination with bevacizmab Key efficacy otcomes observed in the Phase 2 (STML ) trial: - Major objective responses - Response dration encoraging, with 4 responses of 6 + months in dration, all ongoing - Overall srvival data matring and appear promising; median not reached Patients contine to be followed for response and srvival, and additional clinical data pdates are expected next year, as well as immnocorrelative analyses Next steps inclde a potential Phase 3 pivotal trial and evalation of additional combination regimens 11

12 Acknowledgements We wold like to thank investigators, co-investigators, and stdy teams at each participating center: Dana-Farber Cancer Center Cleveland Clinic Fondation University of Alabama Cancer Center Northwestern Brain Tmor Institte Baylor University Medical Center Cedars-Sinai Medical Center Henry Ford Hospital Piedmont Brain Tmor Center Center for Nerosciences University of Virginia University of Pittsbrgh University of Florida North Shore University Hospital UC San Francisco Barrow Nerological Institte University of Minnesota Colmbia University Medical Center George Washington University This stdy is sponsored by Stemline Therapetics, Inc