Stemline Therapeutics, Inc.

Transcription

1 Stemline Therapeutics, Inc. NASDAQ: STML Jefferies 2016 Healthcare Conference June 8, 2016

2 Forward-Looking Statements This presentation includes statements that are, or may be deemed, forward-looking 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

3 Mission To build a leading biopharmaceutical company focused on greatly improving the lives of cancer patients by developing and commercializing innovative oncology therapeutics. 3

4 Corporate Overview SL Robust Phase 2 BPDCN data delivered via oral presentation at ASCO, June 4, patients enrolled 89% (17/19) overall response rate (ORR) (all lines/all doses) - 100% (12/12) ORR in first-line (all doses): 9 CR, 2 CRc - >50% (5/7) ORR in relapsed/refractory (R/R) BPDCN: 1 CR, 1 CRc Response duration data, PFS, OS maturing Encouraging trends to date Ongoing regulatory interactions regarding potential approval pathways in first-line and R/R Launched multi-faceted BPDCN awareness campaign to build foundation for commercialization SL Additional Phase 2 trials enrolling across multiple indications Acute myeloid leukemia (AML) in CR with minimal residual disease (MRD) High risk myeloproliferative neoplasms (MPN) Relapsed/refractory multiple myeloma - SL-401 in combination with pomalidomide SL novel XPO1 inhibitor - Phase 1 in advanced solid tumors, enrolling SL immunotherapy - Phase 2 in second-line GBM, enrolling Sufficient cash to fund through major clinical and regulatory milestones BPDCN=blastic plasmacytoid dendritic cell neoplasm; ORR=overall response rate; CR=complete response; CRc=Clinical complete response (CR in non-skin organs with gross reduction in cutaneous lesions and residual microscopic skin disease); PFS=progression free survival; OS=overall survival; GBM=glioblastoma 4

5 Clinical Pipeline Overview Program Target IND Lead-in/dose escalation Phase 2 BPDCN Enrolling AML (r/r) Enrolling SL-401 IL-3R AML (in CR, MRD+) Enrolling MPN Enrolling Myeloma Enrolling SL-801 XPO1 Advanced solid tumors Advanced heme tumors Planned Enrolling SL-701 IL-13Rα2 EphA2 Survivin Adult GBM (2 nd line) Enrolling BPDCN = blastic plasmacytoid dendritic cell neoplasm; AML = acute myeloid leukemia; r/r = relapsed/refractory; CR = complete response; MRD = minimal residual disease; MPN = myeloproliferative neoplasms; GBM = glioblastoma multiforme 5

6 SL BPDCN

7 SL-401 Highlights BPDCN clinical data continues to be robust in both first-line and R/R Regulatory interactions ongoing regarding approval strategies in both first-line and R/R We believe the global BPDCN commercial opportunity is meaningful and greater than initially appreciated, based on: Enrollment trends, physician/patient inquiries, publications, high profile conference participation, Leukemia & Lymphoma Society outreach, and social media efforts (e.g. #BPDCN on Twitter) Kick-off of Stemline awareness campaign, including medical education initiative and launch of BPDCN patient resource website: Significant upside potential in additional IL-3R+/CD123+ malignancies Multiple single agent and combination trials enrolling (AML, myeloproliferative neoplasms, myeloma) Opportunities in additional leukemias and lymphomas 7

8 BPDCN Overview BPDCN skin lesions BPDCN background Highly aggressive hematologic malignancy derived from plasmacytoid dendritic cells (pdc) with poor prognosis Median OS ~12 months (range: 8-15) from diagnosis Diagnosis World Health Organization (WHO) formalized diagnostic criteria (2008) - CD4, CD56, CD123, TCL-1, other pdc markers Presentation and course BPDCN bone marrow Primary sites: skin and bone marrow Secondary sites: lymph nodes, other viscera, CNS Often rapidly degenerates with bone marrow failure H&E Unmet medical need No approved therapies, standard of care or effective treatments Current recommendations are clinical trials for both firstline and R/R BPDCN Riaz et al. Cancer Control, 2014; Pagano et al. Haematologica, CD4 CD56 TCL1 CD123

9 BPDCN Historical Outcomes 46-50% CR rate in first-line BPDCN - Largest primary series (n 30 patients) since establishment of WHO diagnostic criteria for BPDCN - Weighted average basis CR rate Early death rates Source n Response criteria Pemmaraju, AML 51% Not reported Poret, Not reported 43% Not reported Martin-Martin, Not reported 55-72% High early death rate (26%) Pagano, AML 37-41% High death rate (17%) during induction therapy Dalle, Not reported 47% Not reported For published primary series (n 10 patients), the CR rate is 46-56% in first-line BPDCN on a weighted average basis Median OS: ~12 months Range: 8-15 months from diagnosis Percent survival OS (months) Pagano, Haematologica,

10 SL-401: Novel Targeted Therapy Directed to the IL-3 Receptor (IL-3R / CD123) IL-3Rα (CD123) overexpressed on BPDCN and many other hematologic cancers SL-401 SL-401 is a targeted therapy directed to the IL-3R/ CD123 SL-401 is highly potent against BPDCN cells in vitro and in vivo Truncated diphtheria toxin payload IL-3 IL-3R/CD123 Cancer cell In previous Phase 1/2 investigator-sponsored trial (Frankel, et al. Blood, 2014), with only a single cycle of SL-401 BPDCN skin biopsy (IHC) SL-401 fm IC 50 against BPDCN cells - 78% (7/9) ORR: 5 CR, 2 PR 2 CR in first-line 1 alive at 36+ months 3 CR in relapsed/refractory 3 survived >12 months (including 1 who survived 30+ months) CD123 % viable SL-401 (fm) 10

11 Trial Design and Eligibility Criteria (NCT ) Lead-in (Stage 1) - Completed BPDCN (n=9); R/R AML (n=14) SL-401 daily IV infusion for 5 days At 7, 9, 12, or 16 µg/kg/day for 5 doses Repeated every 21 days Expansion (Stage 2) - Ongoing BPDCN (n=15; ongoing) SL-401 daily IV infusion for 5 days At recommended Stage 1 dose (12 µg/kg/day) for 5 doses Repeated every 21 days Select inclusion criteria BPDCN: first-line or R/R (Stages 1 and 2) AML: R/R (Stage 1) Age 18; ECOG PS 0-2 Adequate organ function including: LVEF LLN, creatinine 1.5mg/dL, albumin 3.2 g/dl, bilirubin 1.5 mg/dl, AST/ALT 2.5x ULN 11

12 Demographics and Baseline Disease (n=23*) Age, years Median [range] 69 [29 83] Gender [n, (%)] Male 18 (78) Baseline sites of disease [n, (%)] Cutaneous 20 (87) Bone marrow 10 (44) Extramedullary (non-cutaneous) Follow-up time on study, months 10 (44) Median [range] 3 [ ] Line of Therapy [n, (%)] 1 st line 15 (65) Relapsed / refractory (R/R)* 8 (35) 2 nd line 6 (75) CHOP 4 (67) Ara-C/anthracycline 1 (17) Hyper-CVAD 1 (17) > 2 nd line 2 (25) CHOP; Ara-C/ anthracycline; Hyper- CVAD Investigational agent; CHOP 1 (50) 1 (50) * Excludes one 15 year old compassionate use patient 12

13 BPDCN Disease Measurements Developed by STML Investigators Site of disease Assessment tool Criteria Key Reference Primary Skin mswat/ biopsy mswat calculation* and pathology Olsen, % 0.5% 1% 1% Bone Marrow (BM) BM aspirate/biopsy, peripheral blood counts AML Cheson, % Secondary** Lymph nodes, viscera CT or PET/CT NHL Cheson, 2014 *CR includes clinical CR (CRc) = CR in non-skin organs with gross reduction in cutaneous lesions and residual microscopic skin disease **Assessed at baseline and thereafter as necessary 13 Illustration of mswat surface area assessment

14 SL-401 Adverse Events Most common side effects were transient transaminase elevation and hypoalbuminemia; not dose limiting Since implementation of safety precautions in lead-in (Stage 1), severe CLS not observed in BPDCN No dose reductions required in any patients to date, including middle-aged/elderly No cumulative side effects with multiple cycles Data, to date, indicate that SL-401 is more tolerable, especially in middle-aged/elderly, than combination chemotherapy previously used in BPDCN Most Common Adverse Events ( 15% treatment-related adverse effects, TRAEs ) All Grades (%) Grade 3 (%) TRAEs All AEs TRAEs All AEs Transaminase elevation Hypoalbuminemia Chills Pyrexia Nausea Fatigue Thrombocytopenia Hypotension Weight increased Capillary leak syndrome (CLS) Anemia Decreased appetite Edema peripheral Two Stage 1 patients had Grade >2 CLS: Grade 5 (7 µg/kg) and Grade 4 (12 µg/kg). No Stage 2 BPDCN patients had Grade >2 CLS 14

15 SL-401: Summary of Clinical Activity High response rates 89% (17/19) ORR in BPDCN (all lines/all doses) 100% (12/12) ORR in first-line BPDCN (all doses) 100% (10/10) CR/CRc rate in first-line BPDCN (12 ug/kg) >50% (5/7) ORR in R/R: 1 CR, 1 CRc Rapid onset of action with multi-cycle efficacy 69% responses after 1 cycle; 31% after 2-3 cycles 3 PRs improved to CR/CRc over multiple cycles Response duration data maturing, promising 75% (9/12) first-line (12 ug/kg) progression-free ( mos) - 5 receiving SL-401 therapy ( mos; cycles) - 4 bridged to SCT; remain in remission ( mos postfirst SL-401 dose; months post-sct) 43% (3/7) of R/R BPDCN patients progression-free, receiving ongoing SL-401 ( mos) While early, PFS and OS trending favorably Line of Therapy All lines First-line First-line Relapsed/ Refractory 1 Dose Group All Doses All Doses 12 ug/kg 12 ug/kg n (total) n (evaluable) ORR 89% 100% 100% 71% CR/CRc, n (rate) 13 (68%) 11 (92%) 10 (100%) 2 (29%) PR SCT, n (autosct n=3; allosct n=1) Includes one patient treated on a compassionate use basis 2 Includes 4 patients were recently treated with SL-401 and response assessment is pending ORR=overall response rate; CR=complete response; CRc=clinical complete response; PR=partial response; SCT=stem cell transplant 15

16 Bone Marrow Responses Bone marrow blast count best responses with SL-401 for all evaluable BPDCN patients with blast counts > 5% at screening (n=10) Representative bone marrow response Pretreatment Post-cycle 2 60% 50% First-line R/R H&E Absolute % blasts 40% 30% 20% IHC (CD56) 62 year old female with extensive BPDCN involving skin, bone marrow, lymph nodes, viscera (spleen, eyelids, gums) 10% Received 4 cycles of SL-401 and achieved a CR 0% Screening Best response Bone marrow biopsy (pretreatment and end of cycle 2) shows clearance of CD56+ BPDCN cells 16

17 Best Response and Treatment Outcomes for All BPDCN Patients (n=24) Individual patients PR NE CR CRc CR CR CR CR CR CR PR CR CRc CR CR PR CRc PR u u u u u u u u u Auto Allo Auto Auto First-line (12 µg/kg/day SL-401) First-line (7 µg/kg/day SL-401) R/R (12 µg/kg/day SL-401) Stem cell transplant (SCT) u Disease recurrence / progression Ongoing Months 17

18 Best Response and Treatment Outcomes for First-line BPDCN Patients Treated at 12 µg/kg/day (n=12) CR Auto CRc Auto CR CR Auto Individual patients CR CR CR CRc CR CR u Allo u First-line (12 µg/kg/day SL-401) Stem cell transplant (SCT) u Disease recurrence / progression Ongoing Months 18

19 PFS and OS in First-line BPDCN (12 µg/kg/day SL-401) Progression-Free Survival N=12 1L BPDCN (n=12) [12 ug/day] Progression-Free Survival Overall Overall Survival N=12 1L BPDCN (n=12) [12 ug/day] PFS Probability Survival Probability PFS (months) Survival Time (months) 19

20 SL-401 Next Steps Given robust clinical data in first-line and R/R BPDCN, we are seeking a registration path in both indications BPDCN clear unmet medical need; new standard of care emerging - Recent review papers recommend patients seek out clinical trials in all-lines - Physicians opting for SL-401 in upfront setting; Essentially no other viable options in R/R Regulatory interactions ongoing regarding approval strategies in both first-line and R/R We believe the global commercial BPDCN opportunity in BPDCN is meaningful and greater than initially appreciated; Launched effort to build disease awareness Significant upside potential for SL-401 in additional IL-3R+/CD123+ malignancies Sufficient cash to fund through key clinical and regulatory milestones for SL-401 and entire pipeline 20

21 SL-401 Market Expansion Opportunities (AML, MPN, Myeloma)

22 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 Buchner, T. JCO, 2012; Freeman, S. D. JCO, 2013; Jorgensen, J. L. Clin Lymphoma Myeloma Leuk, 2011; Konopleva, M. (unpublished) 22 CD45 CD34

23 AML in CR, MRD+ Trial AML in Stage CR 1 (Lead-in) - Enrolling ~9-12 patients AML in CR 7, 9, or 12 ug/kg/day for 5 days, every ~ patients weeks ~15 7, 9, sites or 12 in µg/kg/day North America for 5 days, every 4 weeks ~15 sites in North America AML in CR, MRD+ Stage 2 (Expansion) ~15-20 patients AML in CR, MRD+ At dose defined by Stage 1 ~15-20 patients Endpoints At dose defined by Stage 1 - MRD+ to MRD- conversion Endpoints - CR durability - MRD+ to MRD- conversion - CR durability Updates expected 2H16 23

24 Rationale for SL-401 in MPN (Mastocytosis, Eosinophilic syndrome, Myelofibrosis, CMML) IL-3R expression on mastocytosis Systemic mastocytosis IL-3R (CD123+) pdc proliferation in microenviroment All types 64% (37/58) 76% (44/58) Aggressive (ASM) 100% (10/10) 90% (9/10) SL-401: Opportunities in Other Rare IL-3R+ Cancers Indolent (ISM) 61% (14/23) 87% (20/23) With associated heme malignancy (SM-AHN) 57% (13/23) 65% (15/23) Mast cell leukemia (MCL) 0% (0/2) 0% (0/2) IL-3R expression on eosinophilic leukemia and potent SL-401 anti-tumor activity IL-3R (CD123) expression by CMML correlates with poor prognosis Count IL-3R expression EOL-1 (CEL) IL-3R+ 98.3% IL-3R+ 98.3% SL-401 activity EOL-1 (CEL) IC 50 =1 pm Pardanani. Leukemia, 2015; ASH,

25 MPN Trial AML in Stage CR 1 (Lead-in) - Enrolling ~9-12 patients 4 types of high-risk MPN* 7, 9, or 12 ug/kg/day for 5 days, every ~ patients weeks ~15 7, 9, sites or 12 in µg/kg/day North America for 3 days, every 3 weeks sites in North America AML in CR, MRD+ Stage 2 (Expansion) ~15-20 patients 4 types of high-risk MPN At dose defined by Stage 1-4 arms (1 arm for each indication Endpoints ~15-20 patients each arm, with expansion - MRD+ to MRD- conversion flexibility (Simon 2-stage) - CR durability At dose defined by Stage 1 Endpoints: ORR, CR, response duration Updates expected 2H16 * 4 types of high-risk myeloproliferative neoplasms (MPN) Mastocytosis Eosinophilic syndrome Myelofibrosis Chronic myelomonocytic leukemia (CMML) 25

26 Rationale for SL-401 in Myeloma pdcs are elevated in myeloma bone marrow pdcs and MM cells direct contact in vivo pdcs potentiate MM cell growth MM patient BM biopsy SL-401 inhibits pdc-induced MM cell growth in vivo SL-401 is synergistic with pomalidomide Tumor volume (mm 3 ) ASCO, 2014; Chauhan. Cancer Cell, 2009 Collaboration with Dana-Farber 26

27 Myeloma Trial: SL Pomalidomide First combination study for SL-401 AML in Stage CR 1 (Lead-in) - Enrolling ~9-12 patients (r/r) myeloma (2+ prior therapies) 7, 9, or 12 ug/kg/day for 5 days, every ~ weeks patients ~15 SL-401 sites (7, in 9, North 12 America µg/kg/day for 5 days) every 4 weeks - Cycle 1: SL Cycles 2 + : SL pomalidomide (POM) and dexamethasone (DEX) ~5 sites in North America AML in CR, MRD+ Stage 2 (Expansion) ~15-20 patients (r/r) myeloma (2+ prior therapies) At dose defined by Stage 1 14 patients Endpoints - At MRD+ dose to defined MRD- conversion by Stage 1 Endpoints: ORR, clinical benefit rate, - CR durability response duration, PFS and OS 27

28 SL-801

29 SL-801 Overview SL-801 Background Orally administered, novel small molecule inhibitor of XPO1 (Exportin 1) Clinically-Validated Mechanism of Action / Potential for Differentiation XPO1 is a key nuclear transport oncogene Clinically-validated target in multiple cancer types SL-801 reversibly inhibits XPO1 in low nanomolar range; may offer improved therapeutic window benefits Status Phase 1 Enrolling Patients 1. XPO1 recognizes cargo proteins through nuclear export sequences and bind cargos in nucleus. 2. Ternary complex transported through nuclear pore complex and into cytoplasm where cargo released. 3. XPO1 and Ran subsequently recycled into nucleus where process is repeated. Phase 1 trial advanced solid tumors underway (1 st cohort cleared) Phase 1 trial in advanced hematologic cancers planned Strong IP Protection Composition of matter patent to

30 SL-801: Reversible and Potent XPO1 Inhibitor SL-801 is a reversible inhibitor of XPO1 SL-801 has potent in vitro activity against multiple solid and hematologic cancers 100nM SL-801-biotin 0.5nM Leptomycin-biotin XPO1 Biotin GI 50 (µm) 0.01 XPO1 Actin Sakakibara, Blood, 2011; ASH

31 SL-801: Anti-Tumor Activity in Animal Models SL-801 demonstrates potent anti-tumor activity in animal models, across wide array of solid and hematologic cancers NCI-H226 non-small cell lung cancer 22RV prostate carcinoma MM.1S multiple myeloma Vehicle, qd (d1-5,8-12,15-19) SL-801, mg/kg, qd (d1-5,8-12,15-19) SL-801, 125 mg/kg, qd (d1,3,5,8,10,12,15,17,19) 1200 Vehicle, qd (d1,3,5,8,10,12,15,17,19) SL-801, 125 mg/kg, qd (d1,3,5,8,10,12,15,17,19) SL-801, 125 mg/kg, qd (d1,8,15) SL-801, 250 mg/kg, qd (d1,8,15) Vehicle, qd (d1,3,5,8,10,12) SL-801, 125 mg/kg, qd (d1,3,5,8,10,12) SL-801, 125 mg/kg, qd (d1,8,15) Tumor volume (mm 3 ) * *** Tumor volume (mm 3 ) *** *** Survival rate (%) *** *** Days after first treatment Days after first treatment Days after first treatment *, p < 0.05; **, p < 0.01; ***, p <

32 AML in CR, MRD+ AML in CR Multicenter, Dose Escalation (Standard 3+3 design) ~15-20 patients ~9-12 patients Advanced solid tumors At dose defined by Stage 1 7, 9, or ug/kg/day patients for 5 with days, advanced solid tumors every 4 weeks Endpoints Dose escalation: starting at 5 mg oral tablet/day ~15 sites in North America - MRD+ to MRD- conversion - 4 days on/3 days off x 2 weeks (for 21 day cycle) - CR durability Evaluate safety Signal detection for subsequent Phase 2 disease-directed trials Endpoints - Safety, maximum tolerated dose (MTD) determination - ORR, disease control, duration of response, PFS, OS 5 sites in U.S. SL-801 Clinical Development Plan Phase 1 in advanced solid tumors underway First dosing cohort cleared Updates expected 2H16 Phase 1 in advanced hematologic cancers planned 32

33 SL-701

34 SL-701 Background Immunotherapy designed to elicit anti-tumor immune response Pre-therapy (baseline) Nine weeks post-therapy shows tumor shrinkage Off-the-shelf, subcutaneously-administered peptides Synthetically-designed to elicit immune response against targets overexpressed on GBM - IL-3Rα2, EphA2, Survivin 3 completed Phase 1/2 investigator-sponsored trials (n~70 patients) Adults and children with high grade gliomas Earlier version of SL-701, several administration methods Immunostimulant adjuvant: poly-iclc, a toll-like receptor 3 (TLR3) agonist that activates NK cells and CD8+ T cells Multiple major objective responses in adults and children Orphan drug designation in glioma Post-therapy brain biopsy Reactive gliosis 34 Numerous CD68+ macrophages Abundant CD8+ T cells Inflammatory response, including abundant cytotoxic (CD8+) T cells, in region of brain tumor in setting of regression post-therapy

35 SL-701 Corporate-Sponsored Clinical Development Phase 2 trial in adult second-line GBM - enrolling patients Stage 1 (completed): SL adjuvants (GM-CSF and Imiquimod) - Patients continue to be followed Stage 2 (enrolling): SL adjuvant (poly-iclc) + bevacizumab - Patients currently enrolling Trial updates expected this year 35

36 Financial Summary

37 Financial Summary As of March 31 st, 2016 Cash, Cash Equivalents and Investments (mm) $87.8 Debt $ 0.0 Shares Outstanding (mm) ~

38 Stemline Therapeutics, Inc. NASDAQ: STML Jefferies 2016 Healthcare Conference June 8, 2016