Stemline Therapeutics, Inc. NASDAQ: STML Corporate Presentation September 2015
Forward-Looking Statements This presentation includes statements that are, or may be deemed, forwardlooking statements. In some cases, these forward-looking statements can be identified by the use of forward-looking terminology, including the terms believes, potentially, estimates, anticipates, expects, plans, intends, may, could, might, will, should, approximately or, in each case, their negative or other variations thereon or comparable terminology, although not all forward-looking statements contain these words. They appear in a number of places throughout this presentation and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations. You should read carefully our Special Cautionary Notice Regarding Forward- Looking Statements and the factors described in the Risk Factors sections of our reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission to better understand the risks and uncertainties inherent in our business. 2
Mission To build a leading biopharmaceutical company focused on greatly improving the lives of cancer patients by developing and commercializing innovative drugs that target cancer stem cells (CSCs) and tumor bulk. 3
Corporate Overview SL-401 clinical trials in multiple indications - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) pivotal trial Lead-in stage completed Phase 2 expansion stage underway - AML in complete remission (CR) with minimal residual disease (MRD) - High-risk myeloproliferative neoplasms (MPN) of unmet medical need SL-701 in advanced brain cancer - Phase 2 in adult second-line glioblastoma (GBM) SL-801 XPO1 inhibitor - IND filing expected 2H15 - Clinical trials in solid and hematologic cancers to follow 4
SL-401 Pivotal Program in BPDCN Phase 2 expansion stage in BPDCN open - 12 µg/kg/day for 5 days, every 3 weeks - 7 sites open, ramping up to 35+ sites in North America and Europe Lead-in stage completed ü Enrolled patients with either BPDCN or AML (n=15) ü Administered multiple cycles: 7, 9, or 12 µg/kg/day for 5 days, every 3 weeks ü Established dose and regimen for expansion stage ü Side effect profile similar to previous study: vascular leak and transaminitis ü No cumulative side effects observed to date with multiple cycles ü Major responses, including CRs, in BPDCN 5
Pipeline Program Target IND Lead-in Phase 2 Completed BPDCN (r / r) Open Open AML (in CR, MRD+) SL-401 IL-3R Open Mastocytosis Hypereosinophilic syndrome Myelofibrosis Chronic myelomonocytic leukemia Anticipated Myeloma (r / r) SL-701 IL-13Rα2 EphA2 Survivin Adult GBM (2 nd line) SL-801 XPO1 SL-501, SL-101 IL-3R BPDCN, blastic plasmacytoid dendritic cell neoplasm; AML, acute myeloid leukemia; r / r, relapsed / refractory; CR, complete response; MRD, minimal residual disease; GBM, glioblastoma multiforme 6
Our Differentiated Approach: Target Both Tumor Bulk and Cancer Stem Cells Conventional Approach Target Tumor Bulk Only Tumor Only tumor bulk targeted (CSCs survive) CSCs drive tumor regrowth Tumor relapse Cancer stem cells (CSCs) Tumor bulk Both tumor bulk and CSCs targeted Stemline s Approach Target Both Tumor Bulk and CSCs Cancer controlled / eliminated Improved long-term outcome 7
SL-401
SL-401 Target: Interleukin-3 Receptor (IL-3R) IL-3R is overexpressed on CSCs and/or tumor bulk across heme cancers - AML, chronic myeloid leukemia (CML), acute lymphoid leukemia (ALL) - Myelodysplastic syndrome (MDS) - Hodgkin s and certain non-hodgkin s lymphomas (NHL) - Multiple myeloma - BPDCN and other rare hematologic malignancies of unmet medical need IL-3R overexpression on tumor bulk IL-3R overexpression on CSCs AML tumor bulk Diffusely IL-3R+ Normal marrow Low IL-3R AML CSCs Uniformly IL-3R+ Normal stem cells Negative for IL-3R IL-3R IL-3R Jordan, C. Leukemia, 2000 9
SL-401 Targeted Therapy Payload ideally suited to kill both tumor bulk and CSCs SL-401 Truncated diphtheria toxin payload IL-3 IL-3R IL-3R Tumor bulk cell Cancer stem cell SL-401 kills both rapidly dividing tumor bulk and slowgrowing CSCs (payload not cell-cycle dependent) SL-401 avoids many drug resistance mechanisms, including multi-drug resistance pumps present on tumor bulk and at high levels on CSCs Normal stem cell SL-401 spares normal stem cells, which do not express IL-3R 10
SL-401 Overview Novel targeted therapy directed to IL-3R on tumor bulk and CSCs Single cycle activity observed in previous Phase 1/2 trial - Major objective responses, including CRs, in BPDCN - Overall survival (OS) signal and CRs in heavily pretreated AML Orphan Drug designation in BPDCN and AML Pivotal trial in BPDCN (multi-cycle schedule) - Lead-in stage completed Established dose and schedule Safety profile in-line with previous Phase 1/2 trial Major objective responses, including CRs - Phase 2 expansion stage underway Opportunities for accelerated approval and market expansion - BPDCN and other rare IL-3R+ malignancies (open) - AML/MRD (open), myeloma (anticipated), others 11
SL-401 Phase 1/2 Trial Completed Trial design - Multi-center Phase 1/2 trial Single-cycle, 4-22 µg/kg/day - Advanced hematologic cancer patients (n = 86) Results 59 AML (relapsed or refractory), 11 AML (unfit for chemo), 7 MDS (refractory, high risk), 9 BPDCN - Active doses: 7, 9.4, 12.5, 16.6 (MTD) µg/kg/day - Regimen: Daily for 5 days (single-cycle) - Side effect profile Transaminitis, hypoalbuminemia and edema (capillary leak), thrombocytopenia, fever, chills - Single agent activity Major objective responses, with CRs, in BPDCN Overall survival (OS) signal and CRs in heavily pretreated AML 12
BPDCN Disease and Rationale for SL-401 Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy and represents a significant unmet medical need - Previous names: blastic NK cell lymphoma; agranular CD4+/CD56+ hematodermic neoplasm - Malignancy of plasmacytoid dendritic cells (pdcs) (World Health Organization, 2008) - Highly aggressive cancer that involves skin, bone marrow, blood, lymph nodes, spleen; often enters terminal leukemic phase - Poor prognosis, no standard of care, traditional cancer therapy ineffective Rationale for SL-401: Elevated target expression & robust preclinical activity BPDCN skin lesions IL-3R is highly overexpressed (IHC of BPDCN skin lesion) SL-401: Highly potent (femtomolar IC 50 ) against BPDCN % Viability IL- 3R (CD123) SL-401 concentration, fm ASH, 2013; Mraz-Gernhard, S. JCO, 2001; Tecchio, C. The Oncologist, 2009 13
Robust Activity in Prior Phase 1/2 Trial with Single Cycle of SL-401 Supports Pivotal Program in BPDCN Major objective responses, including CRs, in BPDCN patients (Blood 124: 385 392, 2014) - Overall response rate (ORR): 78% (7/9); 5 CRs and 2 PRs - Median response duration: 5 months Skin (photo) Bone marrow: IL-3R Lymph Nodes (PET/CT) Pre-SL-401 Post-SL-401 70-year old male CR 7+ months (ongoing) 40-year old male CR 5 months 14 74-year old male CR 3+ months (ongoing)
BPDCN Pivotal Program (Multi-cycle SL-401) Lead-in stage completed ü Enrolled patients with either BPDCN or AML (n=15) ü Administered multiple cycles: 7, 9, or 12 µg/kg/day for 5 days, every 3 weeks ü Established dose and regimen for expansion stage ü Side effect profile similar to previous study: vascular leak and transaminitis ü No cumulative side effects observed to date with multiple cycles ü Major responses, including CRs, in BPDCN Phase 2 expansion stage in BPDCN open - 12 µg/kg/day for 5 days, every 3 weeks - 7 sites open, ramping up to 35+ sites in North America and Europe 15
SL-401: Opportunities in Other Rare IL-3R+ Cancers Chronic eosinophilic leukemia (CEL) Hairy cell leukemia (HCL) IL-3R expression SL-401 activity IL-3R expression SL-401 activity Count EOL-1 (CEL) IL-3R+ 98.3% IL-3R+ 98.3% EOL-1 (CEL) IC 50 =1 pm SL-401: Opportunities in Other Rare IL-3R+ Cancers CD123 MoT (HCL) MoB (HCL) IC 50 low nm Indication Reference Systemic mastocytosis (SM) Teodosio. J Allergy Clin Immunol, 2010 Hypereosinophilic syndrome (HES) Brooks. Blood, 2013 Myelofibrosis (MF) Pardanani. ASH, 2014 Chronic Myelomonocytic Leukemia (CMML) Orazi. Mod Pathol, 2006 Hairy Cell Leukemia FITC IL-3R expression on rare cancers Venkastaraman. Am J Clin Pathol, 2011; Munoz. Haematologica, 2001; Shao. Leuk Res, 2013 ASH, 2014; ASH 2013 16
Myeloproliferative Neoplasm (MPN) Trial Stage 1: Lead-in (open) Four types of high-risk MPNs* 7, 9, or 12 µg/kg/day for 3 days, every 3-4 weeks Multi-cycle ~15-18 sites in North America *Mastocytosis, Hypereosinophilic syndrome, Myelofibrosis, and Chronic myelomonocytic leukemia Stage 2: Expansion Four separate arms (one arm for each indication*) 15-20 patients each arm Single-arm, open label Multi-cycle Primary endpoint: overall response rate (ORR) 17
Rationale for SL-401 in AML (in CR, MRD+) Majority of AML patients in 1 st CR will relapse MRD is a predictor of 1 st relapse Relapse-free survival Standard treatment Study A Study B Study C Study D Study E MRD+ MRD- MRD is CSC-rich Normal AML MRD, 0.1% MRD is IL-3R+ CD38 SSC IL-3R CD34 CD45 CD34 Buchner, T. JCO, 2012; Freeman, S. D. JCO, 2013; Jorgensen, J. L. Clin Lymphoma Myeloma Leuk, 2011; Konopleva, M. (unpublished) 18
AML in CR, MRD+ Trial Stage 1: Lead-in (open) AML in CR, MRD+ 7, 9, or 12 µg/kg/day for 5 days, every 4 weeks Multi-cycle ~13-15 sites in North America AML in CR, MRD+ 25-30 patients Single-arm, open label Multi-cycle Stage 2: Expansion Primary endpoint: Conversion of MRD+ to MRD-, disease free survival 19
SL-401: Activity in Myeloma via a Novel Mechanism SL-401 is active against myeloma as a monotherapy via a unique mechanism IL-3R+ pdcs are elevated in myeloma (MM) pdcs potentiate MM growth SL-401 is active against refractory MM pdc-induced growth (fold change) 0 10-12 10-11 10-10 10-8 SL-401 [M] SL-401 is synergistic with existing therapies Pomalidomide Bortezomib Lenalidomide Combination Index (CI) 1 0.8 0.6 0.4 0.2 1 2 Antagonism Synergism 3 4 5 6 Combination Index (CI) 1 0.8 0.6 0.4 0.2 Antagonism Synergism 1-9 0 0 0.2 0.4 0.6 0.8 1 Fractional Effect (Fa) 0 0 0.2 0.4 0.6 0.8 1 Fractional Effect (Fa) ASCO, 2014; Chauhan. Cancer Cell, 2009 Collaboration with Dana-Farber 20
Myeloma Trial (SL-401 + Pomalidomide) Stage 1: Lead-in Pomalidomide (POM)- indicated myeloma patients One cycle of SL-401 followed by combination SL-401+POM/ Dex (in escalating doses of SL-401) for 5 days, every 3 weeks Multi-cycle Pomalidomide (POM)-indicated myeloma patients Single-arm, open label Multi-cycle Stage 2: Expansion Primary endpoint: ORR, PFS 21
Next Generation IL-3R Targeted Therapies
SL-501: Potent Activity Against AML and CML Variant of SL-401 (alteration in IL-3 sequence) High affinity for IL-3R Elevated potency in vitro and in vivo Truncated diphtheria toxin payload IL-3 Amino acid substitution at position 116 % apoptotic cells SL-501 is highly active against both primary AML leukemic blasts and AML CSCs 0.01 0.1 1 10 100 SL-501 (nm) Mean % kill AML-CFC 120 100 80 60 40 20 0 0.02 0.09 0.87 4.33 SL-501 (nml) SL-501 inhibits AML engraftment in immunocompromised mice % CD45+ AML cells in mouse marrow 100 10 1 < 0.1% < 0.1% AML 0.1 SL-501 (nm): 0 0.09 0.87 4.33 0 0.02 0.09 0.87 0 0.09 0.87 4.33 < 0.1% < 0.1% SL-501 is active against TKI-resistant and -sensitive cell lines Control SL-501 CML SL-501 induces apoptosis of IL-3R+ CML CSCs Patient #1: CML, myeloid blast crisis Resistant to imatinib and dasatinib T315I mutation Patient #2: CML, lymphoid blast crisis Resistant to imatinib, dasatinib, INNO-46 Y253H mutation SL-501 prolongs survival of mice engrafted with CML blast crisis xenografts Control SL-501 0 1 5 50 250 0 50 250 Patient 5 Patient 6 Patient 9 Adapted from: Testa, U. Blood, 2005; Hogge, D. E. Clin Cancer Res, 2006; Brooks, C.L. AACR, 2014; Frolova, O. Br J Haematol, 2014 23
SL-701
SL-701 Background Immunotherapy directed to multiple tumor targets Orphan drug designation in glioma Previous investigator-sponsored Phase 1/2 trial Earlier version of SL-701 + immunostimulant adjuvant: poly-iclc, a toll-like receptor 3 (TLR3) agonist that activates NK cells and CD8+ T cells Major objective responses, including CRs, in advanced adult and pediatric brain cancer; some responses occurred late (>12 mos of therapy) Induction of immune response with SL-701 is associated with tumor regression Pretherapy (baseline) Nine weeks post-therapy shows tumor shrinkage Inflammatory response, including abundant cytotoxic (CD8 +) T cells, in brain tissue Indicative of immune response against the brain tumor Reactive gliosis Post-therapy brain biopsy Numerous CD68 + macrophages Abundant CD8 + T cells 25
SL-701 Next Steps Corporate-sponsored Phase 2 program Initial stage: SL-701 + different adjuvants: GM-CSF and Imiquimod Patients continue to be followed for PFS and OS Next stage: SL-701 + poly-iclc + bevacizumab Poly-ICLC: More closely replicate previous regimen Bevacizumab: Clinical support emerging that VEGF may suppress immune stimulation and thus VEGF inhibition may combine well with immunotherapeutic approaches 26
SL-801
SL-801 Target: XPO1 Nuclear Transport Pi Cargo XPO1/CRM-1 controls key cellular processes by regulating nuclearcytoplasmic transport of proteins & RNA RanGDP XPO1 - Tumor suppressor and activators Nuclear pore complex Cytoplasm Nucleus RanGTP Cargo XPO1 XPO1 RanGTP Cargo XPO1 overexpressed by a wide range of both solid and liquid cancers Cancer cells utilize nuclear transport machinery to sequester key regulatory proteins in the cytoplasm, leading to cell proliferation and resistance to apoptosis Inhibition of XPO1 leads to growth arrest and induction of apoptosis XPO1 is a clinically validated target in multiple tumor types 28
SL-801: Novel Oral Small Molecule XPO1 Inhibitor Reversible inhibitor of the key nuclear transport protein XPO1 - Potential for broad therapeutic window, flexible dosing and scheduling XPO1 is a clinically validated target in multiple tumor types Preclinical activity, including safety and efficacy in animal models, across wide array of solid and hematologic cancers Control NCI-H226 lung cancer SL-801 250 mg/kg po day 1 SL-801 31.25 mg/kg po day 1-5,8-12,15-19 SL-801 125 mg/kg po day 1,3,5,8,10,12,15,17,19 MM.1S Myeloma SL-801 125 mg/kg po day 1,3,5,8,10,12 SL-801 125 mg/kg po day 1, 8-15 Control Tumor volume (mm 3 ) s s Percent Survival s Days post-treatment Days post-treatment Composition of matter patents IND filing expected this year Clinical and regulatory paths in solid and liquid tumors Sakakibara, K. Blood, 2011 29
Financial Summary
Financial Summary As of June 30 th, 2015 Cash, Cash Equivalents and Investments (mm) $109.0 Shares Outstanding (mm) 18.0 31
Stemline Therapeutics, Inc. NASDAQ: STML Corporate Presentation September 2015