Stemline Therapeutics, Inc. NASDAQ: STML

Jefferies 2015 Healthcare Conference June 2015

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.

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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.

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Corporate Overview Multiple clinical trials - SL-401

• 3 trials across 7 indications - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) pivotal trial;

Top-line results from lead-in stage reported, pivotal trial ongoing - Early and late stage acute myeloid leukemia (AML) - Four high-risk myeloproliferative neoplasms (MPNs)

- SL-701 • Adult second-line glioblastoma (GBM)

Preclinical pipeline nearing IND - SL-801

• Oral small molecule reversible inhibitor of Exportin-1 (XPO1) • Broad preclinical activity in a wide array of tumor types • Advancing toward clinic for solid and hematologic malignancies

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BPDCN, blastic plasmacytoid dendritic cell neoplasm; AML, acute myeloid leukemia; r / r, relapsed / refractory; CR, complete response; MRD, minimal residual disease; GBM, glioblastoma multiforme

Pipeline Program Target Phase 2

Adult GBM (2nd line)

SL-401

SL-701

IND

SL-801

SL-501, SL-101

AML (r / r)

BPDCN (r / r) – Pivotal trial

AML (in 1st CR, MRD+)

Mastocytosis

Hypereosinophilic syndrome

Myelofibrosis

Chronic myelomonocytic leukemia

Myeloma (r / r)

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IL-3R

IL-13Rα2 EphA2

Survivin

IL-3R

Anticipated

Lead-in

XPO1

6

Management

Ivan Bergstein, M.D. – Chief Executive Officer - Founded Stemline, served as CEO since inception, advanced company from concept

to clinical stage public company - Pioneer in the therapeutic targeting of cancer stem cells; filed early CSC patents - Key member of team that built Access Oncology, Inc.; company acquired by Keryx

Biopharmaceuticals (Nasdaq: KERX)

Eric Rowinsky, M.D. – Chief Medical Officer and Head of R&D - Former Chief Medical Officer of ImClone Systems, Inc. - Led FDA approval of Erbitux® for head and neck and colorectal cancers and played

integral roles in developing and registering many anticancer therapeutics - Board of directors (Biogen, others)

Ken Hoberman – Chief Operating Officer - Former VP of Corporate Development, Keryx Biopharmaceuticals - Led multiple business development transactions and financings - Originated, in-licensed, and developed Auryxia™ (FDA approved Sept ’14)

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Our Differentiated Approach: Target Both Tumor Bulk and Cancer Stem Cells

Tumor bulk

Cancer stem cells (CSCs)

Tumor

Both tumor bulk and CSCs targeted

Improved long-term outcome

Stemline’s Approach Target Both Tumor Bulk and CSCs

Cancer controlled / eliminated

Only tumor bulk targeted (CSCs survive)

CSCs drive tumor regrowth

Conventional Approach Target Tumor Bulk Only

Tumor relapse

SL-401

SL-401 Target: Interleukin-3 Receptor (IL-3R)

Jordan, C. Leukemia, 2000

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

AML tumor bulk Diffusely IL-3R+

Normal marrow Low IL-3R

IL-3

R

AML CSCs Uniformly IL-3R+

IL-3R overexpression on tumor bulk IL-3R overexpression on CSCs

IL-3

R

Normal stem cells Negative for IL-3R

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SL-401 Targeted Therapy

Payload ideally suited to kill both tumor bulk and CSCs

SL-401 kills both rapidly dividing tumor bulk and slow-growing 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

IL-3

Tumor bulk cell

Normal stem cell

Cancer stem cell

IL-3R IL-3R

IL-3R

Truncated diphtheria

toxin payload

SL-401

SL-401 spares normal stem cells, which do not express IL-3R

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SL-401 Overview

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Novel targeted therapy directed to IL-3R on tumor bulk and CSCs

Single cycle activity observed in previous Phase 1/2 trial - High overall response rate (ORR), with multiples CRs, in BPDCN - Durable CRs and overall survival (OS) signal in heavily pretreated AML

Orphan Drug designation in BPDCN and AML

Pivotal trial in BPDCN in progress (multi-cycle schedule) - Lead-in stage confirms safety and efficacy of previous study; trial ongoing

Accelerated approval opportunities with market expansion potential - BPDCN and rare IL-3R+ malignancies (studies underway) - AML (studies underway), myeloma, additional leukemias and lymphomas

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

SL-401 concentration, fM

% V

iabi

lity

ASH, 2013; Mraz-Gernhard, S. JCO, 2001; Tecchio, C. The Oncologist, 2009

SL-401: Highly potent (femtomolar IC50) against BPDCN

IL-3R is highly overexpressed (IHC of BPDCN skin lesion)

IL-3R (CD123)

BPDCN skin lesions

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Robust Activity in Prior Phase 1/2 Trial with Single Cycle of SL-401 Supports Pivotal Program in BPDCN

Published in Blood, July 2014 (Blood 124: 385–392, 2014) - Overall response rate: 78% (7/9); 5 CRs and 2 PRs - Median response duration: 5 mo

74-year old male CR 3+ months (ongoing)

Pre-SL-401

Post-SL-401

40-year old male CR 5 months

70-year old male CR 7+ months (ongoing)

Skin (photo) Bone marrow: IL-3R Lymph Nodes (PET/CT)

Blood publication accompanied by editorial from a senior NIH investigator - “… the community should rejoice in the publication of a study reporting on major patient

responses in a disease that is very difficult to treat with existing agents.”

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BPDCN Pivotal Trial (Multi-cycle SL-401)

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Stage 1: Lead-in (Top-line Results)

• 15 patients with either BPDCN or AML treated to date at 7 sites

• 3 doses (7, 9, 12 µg/kg/day); multi-cycle • Side effects similar to previous study:

vascular leak and transaminitis • No cumulative side effects observed

• 10 pts >2 cycles, 4 pts >5 cycles • Anti-tumor activity to date

• Major responses, including CRs, in 3/5 BPDCN pts at 12 µg/kg/day;

Patients remain on study • Major objective responses also

observed at lower doses

• Single arm, open label • > 1 prior treatment • 40-45 patients at 12 µg/kg/day • Multi-cycle • Primary endpoint: overall response

rate (ORR) • 7 (open) + approx. 20 new sites

Stage 2: BPDCN Expansion

SL-401: Opportunities in Other Rare IL-3R+ Cancers

ASH, 2014; ASH 2013

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 Venkastaraman. Am J Clin Pathol, 2011; Munoz. Haematologica, 2001; Shao. Leuk Res, 2013

IL-3R expression on rare cancers

IL-3R expression SL-401 activity

EOL-1 (CEL) IC50=1 pM

EOL-1 (CEL)

IL-3R+ 98.3%

Coun

t IL-3R+ 98.3%

IL-3R expression SL-401 activity

FITC

CD12

3

MoT (HCL) MoB (HCL) IC50 low nM

Chronic eosinophilic leukemia (CEL) Hairy cell leukemia (HCL)

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SL-401: Opportunities in Other Rare IL-3R+ Cancers

Current STML trial could be foundation for pivotal trials in 4 additional IL3R+ malignancies (SM, HES, MF, CMML)

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Myeloproliferative Neoplasm (MPN) Trial

Stage 1: Lead-in • Four types of high-risk MPNs* • 3 doses (7, 9, 12 µg/kg/day) • Multi-cycle • 5-10 sites

• 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) • 15-20 sites

Stage 2: Expansion

*Mastocytosis, Hypereosinophilic syndrome, Myelofibrosis, and Chronic myelomonocytic leukemia

Rationale for SL-401 in AML (1st CR, MRD+)

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Majority of AML patients in 1st CR will relapse

Rel

apse

-free

sur

viva

l

MRD is a predictor of 1st relapse

MRD+

MRD-

MRD is CSC-rich MRD is IL-3R+

CD

38

Normal AML MRD, 0.1%

CD34

SSC

CD45

IL-3

R

CD34

Standard treatment

Study B Study C

Study E Study D

Study A

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

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Stage 1: Lead-in • AML in 1st CR, MRD+ • 3 doses (7, 9, 12 µg/kg/day) • Multi-cycle • 5-10 sites

• AML in 1st CR, MRD+ • 25-30 patients • Single-arm, open label • Multi-cycle • Primary endpoint: Conversion of

MRD+ to MRD-, disease free survival • 15-20 sites

Stage 2: Expansion

AML in 1st CR, MRD+ Trial

SL-401: Activity in Myeloma via a Novel Mechanism

0

0.2

0.4

0.6

0.8

1

0 0.2 0.4 0.6 0.8 1

Fractional Effect (Fa)

Co

mb

inat

ion

In

dex

(C

I)

1-9

Antagonism

Synergism

0

0.2

0.4

0.6

0.8

1

0 0.2 0.4 0.6 0.8 1

Fractional Effect (Fa)

Co

mb

inat

ion

In

dex

(C

I)

1-9

Antagonism

Synergism

0

0.2

0.4

0.6

0.8

1

0 0.2 0.4 0.6 0.8 1

Fractional Effect (Fa)

Com

bina

tion

Inde

x (C

I)

12

3

4

56

SynergismAntagonism

0

0.2

0.4

0.6

0.8

1

0 0.2 0.4 0.6 0.8 1

Fractional Effect (Fa)

Com

bina

tion

Inde

x (C

I)

12

3

4

56

SynergismAntagonism

Lenalidomide

SL-401 is active against myeloma as a monotherapy via a unique mechanism

Bortezomib

IL-3R+ pDCs are elevated in myeloma (MM)

SL-401 is active against refractory MM

pDC

-indu

ced

grow

th

(fold

cha

nge)

SL-401 [M] 10-12 10-10 10-8 10-11 0

Pomalidomide

ASCO, 2014; Chauhan. Cancer Cell, 2009 Collaboration with Dana-Farber

SL-401 is synergistic with existing therapies

pDCs potentiate MM growth

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Next Generation IL-3R Targeted Therapies

SL-501: Potent Activity Against AML and CML

Adapted from: Testa, U. Blood, 2005; Hogge, D. E. Clin Cancer Res, 2006; Brooks, C.L. AACR, 2014; Frolova, O. Br J Haematol, 2014

Variant of SL-401 (alteration in IL-3 sequence) High affinity for IL-3R Elevated potency in vitro and in vivo

CML

0 5 50 250 0 50 250

SL-501 is active against TKI-resistant and

-sensitive cell lines Control SL-501

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 induces apoptosis of IL-3R+ CML CSCs

Control SL-501

SL-501 prolongs survival of mice engrafted with CML blast crisis xenografts

SL-501 is highly active against both primary AML leukemic blasts and AML CSCs

0

20

40

60

80

100

120

0.02 0.09 0.87 4.33

Mea

n %

kill

AML-

CFC

SL-501 (nMl)

% a

popt

otic

cel

ls

0.01 0.1 1 10 100

SL-501 (nM)

SL-501 inhibits AML engraftment in immunocompromised mice

AML

1

0 0.09 0.87 4.33 0 0.02 0.09

Patient 5 Patient 6 Patient 9

0.1

1

10

100

% C

D45

+ AM

L ce

lls in

m

ouse

mar

row

< 0.

1%

< 0.

1%

< 0.

1%

< 0.

1%

SL-501 (nM): 0 0.09 0.87 4.33 0.87

Amino acid substitution at position 116

IL-3

Truncated diphtheria

toxin payload

21

s

s IL-3Rα (CD123) overexpressing pDCs in diseased tissues

Systemic lupus erythematosus (SLE)

Skin lesion from lupus patient Epidermis Dermis

Mor

phea

N

on-le

sion

al

CD

123

BDCA2

Scleroderma Psoriasis

Beyond Oncology: IL-3R-Targeted Therapies in Autoimmune Diseases

Vermi, W. Immunobiology, 2009; Ghoreishi, M. Exp Dermatol, 2012; Nestle, F. JEM, 2005; Rowland, S. L. JEM, 2014; Boyman, O. JEM, 2004

Blockade or removal of IL-3R+ pDCs improves autoimmune disease pathology in mouse models

SLE Blockade of pDC function inhibits development of skin lesions in xenograft model of human psoriasis

+ pDCs - pDCs

IgG

C

3

Immune complex deposition in kidneys (G=glomeruli)

Removal of pDCs in SLE-prone mice reverses disease pathology

Psoriasis

Representative normal skin graft

Representative psoriatic skin graft

isotype anti-BDCA-2

Papi

llom

atos

is in

dex

Anti-pDC antibody blocks development of psoriasis

CD123 staining CD123 staining

Nor

mal

ized

sig

nal

pDCs: + - + -

Circulating autoantibodies

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SL-701

SL-701 Overview

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Immunotherapy that activates immune system to attack multiple targets present on tumor bulk and CSCs

Earlier version demonstrated clinical activity, including durable CRs and PRs, in adults and children with advanced brain cancer

Multi-center trial in adult patients with second-line glioblastoma (GBM)

Orphan drug designation for glioma

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SL-701: Targets Overexpressed on GBM Relative to Normal Tissue

0

20

40

60

80

100

Normalbrain

A AA GBM

NoneWeakModerateStrong

% o

f sam

ples

9 16 13 46

Staining intensity

0

20

40

60

80

100

Normalbrain

A AA GBM

NoneWeakModerateStrong

Staining intensity

% o

f sam

ples

0

20

40

60

80

100

2 3 4

0-25%25-50%50-75%75-100%

% of positive-staining cells

% o

f sam

ples

A AA GBM 9 12 8

Adapted from: Uematsu. J Neurooncol, 2005; Wykosky. Clin Cancer Res, 2008

n = 9 16 13 46 n = n =

Normal brain Anaplastic

astrocytoma (AA)

Low-grade astrocytoma (A)

Normal brain Anaplastic

astrocytoma (AA)

GBM Low-grade astrocytoma (A)

Normal brain Anaplastic

astrocytoma (AA)

GBM Low-grade astrocytoma (A)

GBM

IL-13Rα2 EphA2 Survivin

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SL-701: Induction of Immune Response in Brain with SL-701 is Associated with Tumor Regression

Reactive gliosis Numerous CD68+ macrophages

Abundant CD8+ T cells

• Inflammatory response, including abundant cytotoxic (CD8+) T cells, in brain tissue

• Indicative of immune response against the brain tumor

Pre-therapy (baseline)

Nine weeks post-therapy shows tumor shrinkage

Post-therapy brain biopsy

JCO, 2011

SL-701: Major Objective Responses

Adult 2nd-line GBM

Baseline CR

Pediatric radiation-resistant HGG

Baseline PR

Durable CR (> 23 month duration)

Durable PR (15 month duration)

Study GBM and other non-brainstem HGG (n=26)

ORR Response duration (median)

CR

Immuno- therapy

Adult GBM (>2nd-line)1 23% (3/13)

7-15 months

1

Adult AG (>2nd-line) 22% (2/9) 1

Pediatric non-brainstem HGG (post-chemo/XRT) 25% (1/4) 0

Avastin® GBM (2nd-line) 19.6%-25.9 % 3.9-4.2 months 0

Results in line with historical precedent for accelerated approval

12nd-line (n=5); 3rd-line (n=6); 4th-line (n=2)

AACR, 2012; Okada. JCO, 2011; Cohen. The Oncologist, 2009 27

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SL-701: Overall Survival Signal in Adult ≥ 2nd-Line High Grade Glioma

GBM AG Immunotherapy Historical Immunotherapy Historical

Median OS 13 mo 5-7 mo >22 mo 9-11 mo

6 month OS 80% 38-55% 85% 66%

12 month OS 55% 14-25% 76% 44-47%

Kaplan-Meier Plot of Overall Survival > 2nd line adult high grade glioma

(n = 22 patients) Pe

rcen

t Ove

rall

Surv

ival

0

25

50

75

100

0 10 20 30 40

Glioblastoma (GBM), n=13

Anaplastic glioma (AG), n=9

Months

Okada. JCO, 2011

SL-701 Trial Design

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Adults with glioblastoma multiforme (GBM), first recurrence

80-100 patients

Co-primary endpoints

– Objective response rate and overall survival

2 Arms

– SL-701 versus SL-701 + bevacizumab (new arm)

– Rationale for addition of new arm – Bevacizumab is standard of care in recurrent GBM – Bevacizumab decreases rate of radiographic disease progression – No apparent overlapping toxicities – Clinical validation emerging that VEGF may suppress immune stimulation and

thus may combine well with immunotherapy approaches

SL-801

Nucleus

Cytoplasm

XPO1

RanGTP

Cargo

XPO1 Cargo

RanGTP

RanGDP

Cargo Pi

XPO1

Nuclear pore complex

SL-801 Target: XPO1 Nuclear Transport

XPO1/CRM-1 controls key cellular processes by regulating nuclear-cytoplasmic transport of proteins & RNA - Tumor suppressor and activators

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

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SL-801: Novel Oral Small Molecule XPO1 Inhibitor

Composition of matter patents IND filing expected this year Clinical and regulatory paths in solid and liquid tumors

Reversible inhibitor of the key nuclear transport protein XPO1 - Potential for broad therapeutic window, flexible dosing and scheduling XPO1 recently shown to be a clinically relevant target Preclinical activity, including safety and efficacy in animal models, across wide array of solid and hematologic cancers

Sakakibara, K. Blood, 2011

NCI-H226 lung cancer

Tum

or v

olum

e (m

m3 )

Days post-treatment

s s Pe

rcen

t Sur

viva

l

Days post-treatment

MM.1S Myeloma

s s

Control

SL-801 125 mg/kg po day 1, 8-15

SL-801 125 mg/kg po day 1,3,5,8,10,12

SL-801 125 mg/kg po day 1,3,5,8,10,12,15,17,19

Control

SL-801 31.25 mg/kg po day 1-5,8-12,15-19

SL-801 250 mg/kg po day 1

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Financial Summary

Financial Summary

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As of March 31st, 2015

Cash, Cash Equivalents and Investments (mm) $115.8

Shares Outstanding (mm) ~ 17.9

Stemline Therapeutics, Inc. NASDAQ: STML

Jefferies 2015 Healthcare Conference June 2015