Stemline Therapeutics, Inc.

Transcription

1 Stemline Therapeutics, Inc. NAAQ: STML Corporate Presentation October 08

2 ForwardLooking Statements This presentation includes statements that are, or may be deemed, forwardlooking statements. In some cases, these forwardlooking statements can be identified by the use of forwardlooking 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 forwardlooking 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 ForwardLooking Statements and the factors described in the Risk Factors sections of our reports on Form 0K and Form 0Q filed with the Securities and Exchange Commission to better understand the risks and uncertainties inherent in our business.

3 Stemline Objectives Goal is to become a leading commercial stage biotechnology company ELZONRIS (Tagraxofusp; SL40): Novel CDtargeted therapy Secure approval then launch in st CD+ indication (BPDCN) PDUFA date //9; Priority Review and Breakthrough Therapy Secure approval in nd and rd indications Initiate pivotal trials in ~H9 and beyond Pursue registrational paths in additional indications Other pipeline candidates SL70 SL80 Immunotherapeutic XPO inhibitor Secondline glioblastoma (GBM) Heavily pretreated solid tumors Phase Phase Ø Provide updates 4Q8 (ESMO) Ø Provide updates 4Q8 (ESMO, SNO) Abbreviations: BPDCN = blastic plasmacytoid dendritic cell neoplasm

4 ELZONRIS Market Opportunity Indications beyond heme e.g., solid tumors, autoimmune rd indication and beyond e.g., MF Multiple possibilities: AML, MM, ALL, CML, HL, HCL, CLL, NHL, MCL, et al nd indication e.g., CMML BPDCN Initial US label Ø Then full Universe (US and EU) 4

5 Highlights and Key Priorities ü Launch disease awareness and market shaping campaigns ü Complete BLA submission ü BLA accepted and granted Priority Review ü Meet with Rapporteurs and EMA re MAA filing q Secure US approval (PDUFA date: Feb., 09) q Launch successfully in US, if approved q Submit MAA (~Q9) and secure EU approval q Initiate pivotal trial in next indications (~H9 and thereafter) Other Pipeline Candidates: SL70 & SL80 ü Present Phase data for SL70 (immunotherapy) in nd line glioblastoma patients at ASCO 08 ü Present Phase data for SL80 (XPO inhibitor) in advanced solid tumor patients at ASCO 08 q Present additional updates in 4Q8 at major meetings (e.g. ESMO, SNO) 5

6

7 ELZONRIS and CD Targeting Opportunities ELZONRIS is a targeted therapy directed to CD CD expression landscape ELZONRIS SL40 BPDCN Truncated diphtheria toxin payload IL ILR/CD Cancer cell CMML MF Heme: AML, MM, ALL, CML, HL, HCL, CLL, NHL, MCL, et al NonHeme: Solid tumors Autoimmune 7

8 BPDCN Overview and Opportunity Highly aggressive hematologic malignancy plasmacytoid dendritic cell (pdc) origin Diagnostic signature: CD / CD4 / CD56 Memorable, consecutively, as: 456 High CD expression Middle agedelderly; male predominance Previously considered a lymphoma then a leukemia, now classified as unique entity Bone marrow and skin involvement, lymph nodes and viscera as well Poor prognosis Median OS of 84 months from diagnosis Skin CD Unmet medical need No approved therapies or standard of care Bone marrow CD Riaz et al. Cancer Control, 04; Pagano et al. Haematologica, 0; Pemmaraju. Curr Hematol Malig Rep, 07; Bueno et al., Haematologica 004; Wang et al. Haematologica 0. 8

9 Multiple Opportunities for Growth within BPDCN Universe ~,600,00 addressable patients BPDCN Signature BPDCN (EU) Similar patient size to US Filing Targeted in Q9 Maintenance Therapy (postsct) (0%) x (6%) x new AML cases (EHA, 06) Potential upside BPDCN (US) ~45% firstline BPDCN patients on ELZONRIS bridged to SCT Study Design In Process 9

10 Safety and Tolerability Across All ELZONRIS Trials Most Common Adverse Events (AEs) (>5% TreatmentRelated AEs, TRAEs) Preferred Term All Grades n (%) TRAEs n (%) TRAEs All AEs Gr Gr Gr 4 Gr 5 ALT increased 65 (4.9%) 80 (54.%) (0.9%) 4 (.0%) 0 (0.0%) 0 (0.0%) AST increased 65 (4.9%) 74 (50.0%) 0 (0.%) (0.9%) 4 (.7%) 0 (0.0%) Hypoalbuminaemia 65 (4.9%) 7 (49.%) 64 (4.%) (0.7%) 0 (0.0%) 0 (0.0%) Thrombocytopenia 9 (6.4%) 48 (.4%) 7 (4.7%) 8 (5.4%) 4 (6.%) 0 (0.0%) Nausea 8 (5.7%) 70 (47.%) 7 (5.0%) (0.7%) 0 (0.0%) 0 (0.0%) Pyrexia (.%) 60 (40.5%) (.%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Fatigue 0 (0.%) 67 (45.%) 6 (7.6%) 4 (.7%) 0 (0.0%) 0 (0.0%) Weight increased 8 (8.9%) 4 (8.4%) 8 (8.9%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Chills 6 (7.6%) 40 (7.0%) 5 (6.9%) (0.7%) 0 (0.0%) 0 (0.0%) Capillary leak syndrome (CLS) 5 (6.9%) 5 (6.9%) 6 (0.8%) 5 (.4%) (.0%) (0.7%) Hypotension (5.5%) 6 (4.%) 7 (.5%) 5 (.4%) (0.7%) 0 (0.0%) Oedema peripheral (4.9%) 57 (8.5%) (4.%) (0.7%) 0 (0.0%) 0 (0.0%) All clinical trials with ELZONRIS at ug/kg/day (n=48 patients) 0.7% (/48) for all trials (µg/kg/day) and.6% (/8) for all trials (all doses) were grade 5. A myocardial infarction, grade 5, was also reported in a patient who experienced a grade 4 CLS 0

11 ELZONRIS: Clinical Outcomes in BPDCN Response Rates In treatmentnaïve patients at ug/kg/day: 7% (/9) CR + CRc rate 90% (6/9) ORR 45% (/9) bridged to stem cell transplant Median duration of CR + CRc has not been reached (range, months) Overall Survival Ø Median OS: Not reached Ø Longterm survivors Ø Median follow up:.8 months ( months) Study Overview Largest prospectively designed study in BPDCN Enrolled 9 treatmentnaïve and 5 previouslytreated patients with BPDCN Primary endpoint : CR + CRc Secondary endpoints: ORR, OS, PFS CR = complete response; CRc = clinical complete response, defined as complete response with minimal residl skin abnormality not indicative of active disease; ORR = overall response rate; OS = overall survival; PFS = progressionfree survival. In Stage, the pivotal, confirmatory cohort

12 ELZONRIS: Prelaunch Activities

13 Critical Elements of ELZONRIS Launch Prepare the Product Prepare the Market Prepare the Organization Collect comprehensive. Stakeholder insights to inform product strategy Generate meaningful evidence that translates to clinical practice Prepare for and secure regulatory approval Establish effective value proposition and messages that resonate Maximize commercial lifecycle potential Understand market to define success factors & implications for launch Build advocacy with stakeholders to drive adoption & to limit barriers Energize effective customeroriented commercial team Achieve organizational alignment on success requirements and strategy Implement optimal supply chain Create infrastructure and processes to enable seamless execution HTA Planning Clinical Trial Strategy Registration Package Target Product Profile Geographic Sequencing Market Definition & Landscaping Unbranded Campaign & Communication Commercial Model Design Franchise Integration Manufacturing Strategy Launch Governance Physician Awareness, Trial, Usage Winning Label Design Trade Name Registration Positioning Lifecycle Planning Competitive Intelligence KOL Identification & Planning CustomerFacing Team Design Revenue Forecasting Demand Planning & Forecasting ERP Platform Update & Integration Patient Affordability & Unmet Needs Registration Trial Design Advisory Committee Meetings Targeted Messaging Formulation Strategy Key Stakeholder Mapping Congress/ Symposia Planning & Exec. Incentive Compensation Planning Integrated Launch Planning Trade & Distribution Strategy CRM System Payer Market Access Requirements Phase b Trial Design Label Negotiation Pricing Strategy Diagnostic Strategy Public Policy Analysis Publication Planning & Exec. Field Team Hiring & Onboarding Launch Risk Mitigation Planning Packaging Performance Reporting System Pharmacist Perspectives PostMarketing Surveillance Risk Management Payer Value Proposition Patient Adherence Strategy Patient Journey Patient Advocacy Plan. & Engagement Key Account Segmentation Launch Budgeting Contracting & Tendering Strategy TeamUp Design Caregiver Analysis Comparative Effectiveness Research Pharmacovigilance Branding Partner Identification & Licensing Strategic Segmentation MSL Engagement Planning Targeting & Call Planning Key Performance Indicators Patient Support Hub SiteofCare Analysis Investigator Initiated Studies Branded Campaign & Communication Market Access Landscaping Medical Education Field Team Training Promotion Mix Optimization MarketLevel CSFs Investor Relations Public Relations Sampling Patient Access Programs

14 BPDCN and CD Awareness and Market Shaping BPDCNinfo.com Launched at ASH 07 Build awareness of CD testing Presence at key hematology, oncology, pathology and dermatology conferences Print and campaign targeting HCPs International, national and regional conference presence: ASH 07 ONS Congress ASCO EHA USCAP 4 ECP 08 ASCP CAP ESMO ASH 08

15 Key Commercial Launch Deliverables Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec SL40 Brand Name Development MD Treatment Flow/Patient Journey BPDCN Incidence & Patient Segmentation BPDCN Misdiagnosis Research Access & Reimbursement Strategy Mechanism of Action Video SL40 International Nonproprietary Name (INN) Logo Development BPDCN/SL40 Brand Lexicon PL / HUB Selection Sales Force Sizing, Targeting & Alignment Sales Training Program Development Distribution/Channel Strategy Agency of Record Selection Disease Awareness Campaign Development & Testing Patient Assistance Program EHA Advisory Board 5

16 BPDCN Awareness Impressions By Audience ~.8 million impressions to be delivered in 08 6

17 Market Expansion Opportunities (Beyond BPDCN)

18 Chronic Myelomonocytic Leukemia (CMML) Myelofibrosis (MF)

19 Chronic Myelomonocytic Leukemia (CMML) Overview Aggressive myeloid malignancy Monocytosis in peripheral blood CD in key disease compartments Spleen Median age 776; male predominance Despite available treatments, CMML carries a poor prognosis: CD+ 46 month median OS in firstline Bone marrow 67 month median OS in previouslytreated Splenomegaly is associated with more advanced disease, morbidity and poor prognosis (even in the firstline setting) CD+ Targeting CD with ELZONRIS offers a novel potential therapeutic option Loghavi, 08; Patnaik, 06; Pophali, 08; Orazi, 008; Solary, 07 9

20 CMML Response Criteria Historically, some MDS trials including patients with CMML have measured response via the IWG response criteria for MDS because dysplastic cases of CMML clinically behave similarly to myelodysplasia with primarily hematopoietic insufficiency and without organomegaly or severe constitutional symptoms However, the effects of the therapy on the myeloproliferative aspects of the disease were not captured with this approach because more proliferative cases of CMML are characterized by myeloproliferative features of leukocytosis, organomegaly, and considerable constitutional symptoms clinical features gauged less discernibly with IWG criteria for MDS Consortium proposed expanding response criteria to capture proliferative features Including spleen response, independent of other sites, as a measure of clinical benefit 0

21 ELZONRIS in CMML Patients: EHA 8 Age/Sex Prior Baseline Therapies WBC (0 9 /L) Best bone marrow (BM) response Best Spleen Response Response rate Responders Evalble 69/M % (5 0) 70/M % (4 0) 77/F % (0 0) 78/M NA 00% ( 0) 64/F % ( 0) 4/M % (0 0) 64/M % ( 4) 70/M 7. 8 NA % (4 ) 60/M No baseline splenomegaly 7/F No baseline splenomegaly 80/M No baseline splenomegaly 78/M.7 9 No baseline splenomegaly 60/M. NA No baseline splenomegaly 64/M. 6 No baseline splenomegaly 6/F.9 No baseline disease No baseline splenomegaly 7/M 8.5 No baseline disease No baseline splenomegaly Spleen responses All size reductions 00% % size reduction 75% % size reduction, baseline 5cm 60% 5 00% (8/8) spleen responses in evalble patients 75% (6/8) had reduction of 50% 60% (/5) with baseline 5cm had reduction 50% Bone marrow complete responses (BMCRs) Baseline BM blasts % to best BM blasts % Spleen size by physical examination [% reduction (pre > post cm palpable below left costal margin)] Baseline BM blasts 5%

22 ELZONRIS and CMML: Summary and Next Steps ELZONRIS has demonstrated single agent activity in patients with relapsed/refractory CMML Including in the poorprognosis, proliferative patients with splenomegaly Multiple spleen responses 00% (8/8) of evalble patients had reduction in baseline splenomegaly 75% had reduction by 50% 60% with baseline spleen size 5cm had reduction by 50% Complete responses in the bone marrow Patient enrollment and follow up continues; further updates in 4Q8 at ASH Based on these encouraging signals, the opportunity, and ongoing interactions with thought leaders, Stemline is finalizing formulation of a registrational trial (or cohort) which we expect to initiate ~H9

23 Myelofibrosis (MF) EHA 8 Pt Line Prior Tx Platelets (baseline, 0^9/L) 0 JAKi 9 7 JAKi 7 4 JAKi 8 PST; investig. agent 77 JAKi; lenalidomide 56 6 JAKi 59 5 JAKi; invest. agents 6 JAKi; prep for SCT 5 JAKi 78 JAKi 9 4 PST 9 8 JAKi Spleen Responders 00% (5cm à 0cm) 47% (9cm à 0cm) 46% (5cm à 9cm) % (0cm à 0cm) 9% (7cm à cm) 9% (4cm à 0cm) 9 PST Not evalble 5 JAKi; HMA, hydrea 5 No splenomegaly PST 56 No splenomegaly Spleen responses Patients with baseline splenomegaly ( 5cm BCM) BCM = below costal margin (by physical exam) Response rate 50% (6/) spleen responses Responders Evalble Reductions 9% 50% 6 Reductions % % 4 Reductions 5% 5% All 6 had reductions of at least 9% in spleen size % (4/) with baseline 5cm had reduction of % 5% (/) with baseline 5cm had reduction of 5% JAKi = JAK inhibitor; HMA = hypomethylating agent; SCT = stem cell transplant; PST = prior systemic therapy; N/E = not evalble Measured by palpation (cm below costal margin)

24 ELZONRIS and MF: Summary and Next Steps ELZONRIS has demonstrated single agent activity in patients with relapsed/refractory MF 50% of evalble patients, with baseline spleen size 5cm, had reduction in baseline splenomegaly % had reduction by % 5% had reduction by 5% Patient enrollment and follow up continues; further updates in 4Q8 at ASH ELZONRIS may offer a novel therapeutic approach in MF Based on these encouraging results, next steps for the program are being evalted including single agent, combination, and registrationdirected trials in patients with relapsed/refractory MF 4

25 SL80

26 SL80: Overview and Rationale SL80 Novel, oral, small molecule inhibitor of XPO (Exportin ) XPO Target Key nuclear transport oncogene Overexpressed by variety of solid and liquid cancers Clinicallyvalidated target in multiple cancer types SL80: Novel and Differentiated Novel molecular structure Reversibly inhibits XPO Potential for safety and therapeutic window benefit Phase Trial Patients with advanced solid tumors Data presented at ASCO 08 Dose escalation; enrollment ongoing 6

27 SL80: Study Design and Demographics Stage (Doseescalation) Enrollment Ongoing Advanced solid tumors SL80 orally administered Dose escalation (mg/day) o 5, 0, 0, 0, and by 5 mg increments thereafter D4 and D8 of a day cycle Standard x design Endpoints Safety and tolerability DLT and MTD ORR, DCR, DoR, PFS and OS Six sites in the US DLT = doselimiting toxicity; ORR = overall response rate; DCR = disease control rate; DoR = duration of response; PFS = progressionfree survival; OS = overall survival; MTD = maximum tolerated dose; CR = complete response Age, years Median [range] 64 [976] Gender [n, (%)] Female 8 (5) Lines of therapy prior to the study [n, (%)]* st Line (9) nd Line 7 () rd Line 6 (8) 4 th Line 8 (5) Cancer diagnosis GI (7) Breast 4 () Lung (9) Other 5 (4) ECOG performance status [n, (%)] 0 0 (8) (66) (6) Followup time on study, months Median [range].4 [0. 0.8] * One patient did not have their systemic therapy history available 7 Heavily pretreated patients: 7% patients were rd line or greater Wide spectrum of solid tumors, including GI, breast, lung, neuroendocrine, ovarian, et al

28 Safety and Tolerability ASCO 8 Treatment Related Adverse Events (AEs) (n=5) Most Common Treatment Related Adverse Events (TRAEs, 5%) All Grades n (%) TRAEs n (%) Preferred Term TRAEs All AEs G & G G4 G5 Nausea 9 (54.) 0 (57.) 6 (45.7) (8.6) No DLT s reported No MTD Dose escalation ongoing Enrolling th cohort (65 mg/day) Vomiting (7.) 0 (57.) (4.) (.9) Fatigue 0 (8.6) 4 (40.0) 0 (8.6) Diarrhea 8 (.9) (4.) 6 (7.) (5.7) Decreased appetite 7 (0.0) 0 (8.6) 7 (0.0) As of 0Apr8. Investigatorassessed data; unaudited Additionally, there was a one grade TRAE of acute kidney injury reported at 0 mg/day dose level and one grade TRAE of neutropenia reported at 0 mg/day dose level 8

29 Best Response ASCO 8 Dose Tumor Histology Best Response No. of lesions Sum of target lesions (measurable) Screening (mm) Best Response (mm) % Δ of target lesions Time to Best Response Last dose received 0 mg Neuroendo 44 5 % C C6 0 mg GI adenocarcinoma % C4 C7 40 mg BCC % C C4 40 mg Breast % C6 C6 5 mg NSCLC 7 4% C C 55 mg Paraganglioma % C C 5 mg CRC % C C6 5 mg Biliary 8.4 n/a n/a C4 0 mg SCC C C4 40 mg Mesothelioma % C C 45 mg GI Adeno % C C4 As of 0Apr08. Investigatorassessed data; unaudited = stable disease; () = reduction; (+) = increase Patient with KRAS mutation present at screening 9

30 Best Response and Treatment Duration ASCO 8 Cancer Type BCC Neuroendo GI Adeno Breast CRC Neuroendo Small Bowel Biliary Paraganglioma GI Adeno SCC CRC GI Adeno Breast SCC NSCLC Mesothelioma NSCLC Breast CRC Ovarian LMS Pancreas CRC ACC Parotid NSCLC Ovarian Neuroendo ACC Head & Neck Breast Bladder Pancreas CRC Appendix Renal Line of Therapy * u d u a u b u d u d u d u b u e u a u a u a u a u a u a u a u a u d u a u a u a u a u a u a u a u c u b u a u a u d u a u a u a u a u a u b u c u d u e Ongoing, receiving SL80 In addition (not shown): recently enrolled patients (0 th cohort: 60 mg) are receiving SL80, ongoing 55 mg cohort 50 mg cohort 45 mg cohort 40 mg cohort 5 mg cohort 0 mg cohort 0 mg cohort 0 mg cohort 5 mg cohort u a Discontinued, disease progression Discontinued, PI decision Discontinued, patient death, unrelated to SL80 Discontinued, consent withdrawn Discontinued, AE As of April 0, 08. Investigatorassessed data; unaudited. Time from CD to end of treatment or ongoing Months * One patient did not have their systemic therapy history available 0

31 SL80: Trial Status and Next Steps ASCO 08 #560 Next Steps Interim Results from a Phase Trial of SL80, a Novel XPO Inhibitor, in Patients with Advanced Solid Tumors J. Wang, J. Nemunaitis, E.G. Chiorean, P. Lorusso4, K. Courtney5, D. Qi6, A. Olguin6, J. Bullington6, M. Sardone6, V. Dunn6, S. Shemesh6, J. Chen6, C. Brooks6, T.M. Bauer7 Florida Dose escalation continues Cancer Specialists, Sarasota, FL; Mary Crowley Cancer Research Center, Dallas, TX; University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA; 4 Yale Cancer Center, New Haven, CT; 5 University of Texas Southwestern Medical Center, Dallas, TX; 6 Stemline Therapeutics, New York, NY; 7 Tennessee Oncology, Nashville, TN Introduction and Highlights cohort (65 mg/day) enrolling Dose escalation ongoing; 0th cohort (60 mg/day) currently enrolling Multiple cases of stable disease () in a heavily pretreated solid tumor patient population Pharmacokinetic (PK) analyses suggest dosedependent increases in exposure; studies ongoing Ideal therapeutic dose not yet determined as dose escalation continues Further updates expected this year Further updates expected later this year Background SL80 Background SL80 is an orally administered, novel small molecule XPO (Exportin ) inhibitor XPO is a key nuclear transport oncogene overexpressed in a variety of cancers Inhibition of XPO has been clinically validated in multiple cancer types SL80 demonstrated potent in vitro and in vivo activity against a wide array of solid and hematologic cancer models SL80 reversibly inhibits XPO offering the potential for a favorable therapeutic window A Phase trial of SL80 monotherapy in patients with advanced solid tumors is underway (NCT#066787) Results from the ongoing dose escalation trial are reported here XPO Background XPO is the key mediator of nuclearcytoplasmic transport and is involved with the export of more than 00 nuclear proteins, including: tumor suppressor proteins (p5, APC, Rb, BRCA, FOXO family proteins) cell cycle inhibitors (p/cip, p7/kip) transcription factors (ATF) oncogenic proteins (CIPA, Erk) immune response regulators (IkBa) molecular chaperone proteins (hsp90), XPO also exports specific subsets of messenger ribonucleic acid (mrna) via export adaptor proteins Mislocalization of a nuclear protein into the cytoplasm can render it ineffective as a tumor suppressor4 XPO is overexpressed in various solid tumors, including breast, cervical, ovarian, and pancreatic cancers, glioma, and osteosarcoma, as well as hematologic malignancies, including acute myeloid leukemia, chronic lymphocytic leukemia, multiple myeloma, and lymphoma,5 XPO overexpression has been associated with poor prognosis, including being correlated with tumor grade, size, metastases, resistance to chemotherapy, as well as shorter progressionfree survival (PFS) and overall survival (OS) Sum of target lesions (measurable) Dose Select exclusion criteria Persistent clinically significant ( G) toxicities from prior anticancer therapies (excluding G chemotherapyrelated neuropathy, and G lab abnormalities if not associated with symptoms and not considered clinically significant by PI) Chemotherapy, externalbeam radiation or other systemic anticancer therapy within prior 8 days to first dose Prior treatment with SL80 or another drug that inhibits XPO/CRM pathway Active secondary malignancy that may confound assessment of study endpoints Clinically significant cardiovascular disease, uncontrolled clinically significant pulmonary disease, suspected brain or leptomeningeal metastases Immunosuppressive therapy for a prior organ transplant Uncontrolled intercurrent illness Infection with HIV or chronic Hep B or Hep C Demographics Age, years Median [range] 64 [976] Gender [n, (%)] Female 8 (5) Lines of therapy prior to the study [n, (%)]* st Line (9) nd Line 7 () rd Line 6 (8) 4th Line 8 (5) RAS mutation [n, (%)] KRAS mutation: Yes 5 (4) No 9 (6) Unknown 9 (54) Other mutation: (6) ECOG performance status [n, (%)] 0 0 (8) (66) (6) Followup time on study, months Median [range].4 [0. 0.8] Cancer Diagnosis Colorectal cancer (CRC) Breast cancer Nonsmall cell lung cancer (NSCLC) GI adenocarcinoma (GI Adeno) Neuroendocrine (Neuroendo) Pancreatic cancer Adenoid Cystic Carcinoma (ACC) Ovarian carcinoma Sqmous cell carcinoma (SCC) Biliary Renal Bladder Basal cell carcinoma (BCC) Small bowel Mesothelioma (Mesoth) Leiomyosarcoma (LMS) Appendix carcinoma Paraganglioma n 5 4 Most Common Treatment Related Adverse Events (TRAEs, 5%) All Grades n (%) TRAEs n (%) TRAEs All AEs G & G G4 G5 Nausea 9 (54.) 0 (57.) 6 (45.7) (8.6) Vomiting (7.) 0 (57.) (4.) (.9) 0 (8.6) 4 (40.0) Fatigue Diarrhea Decreased appetite % C4 C7 BCC % C C4 Breast (8.6) 8 (.9) (4.) 6 (7.) (5.7) 7 (0.0) 0 (8.6) 7 (0.0) Nausea N Study Design Stage (Dose escalation) Enrollment Ongoing Advanced solid tumors SL80 orally administered Dose escalation (mg/day) o 5, 0, 0, 0, and by 5 mg increments thereafter D4 and D8 of a day cycle Standard x design Primary endpoints: o Safety and tolerability o DLT and MTD Stage (Expansion) Not started yet 5 mg 0 mg 0 mg 6 0 mg 5 mg 5 40 mg 4 45 mg 50 mg 4 55 mg 4 0% C6 C6 5 mg NSCLC 7 4% C C Paraganglioma % C C 5 mg CRC % C 5 mg Biliary 8.4 n/a n/a C4 0 mg SCC C C4 40 mg Mesothelioma % C C 45 mg GI adenocarcinoma % C C4 0 0 Line of Therapy * ub ud ue ud ub ud ud ub uc ud ue ud ub Dose and regimen selected from Stage Primary endpoints: o ORR o Safety profile Decreased appetite 0 Secondary endpoints: mg cohort 50 mg cohort 45 mg cohort 40 mg cohort 5 mg cohort 0 mg cohort 0 mg cohort 0 mg cohort 5 mg cohort Discontinued, disease progression Discontinued, PI decision Discontinued, patient death, unrelated to SL80 Discontinued, consent withdrawn Discontinued, AE Safety Manageable safety and tolerability profile observed during dose escalation No modification of dosing schedule required thus far No DLT or MTD has been reached up to 55 mg/day Most common TRAEs were grade, with no grade 4 or 5 toxicity reported Pharmacokinetics Dosedependent increases in exposure observed Study Status Dose escalation continues, tenth cohort (60 mg/day) currently enrolling Manageable safety and tolerability profile demonstrated thus far Achievement of multiple cases of stable disease, including with tumor reductions, in some patients with heavily pretreated solid tumors As of April 0, 08. Investigatorassessed data; unaudited. from CD to end of treatment or ongoing * One patient did not have their systemic therapy history available Takeaways and Next Steps Time Phase trial of SL80, a novel XPO inhibitor, in heavily pretreated patients with solid tumors Manageable safety and tolerability profile, largely grade adverse events (AEs), to date 0 No dose limiting toxicity (DLT) or maximum tolerated dose (MTD) reached Representative target lesion response Pharmacokinetic (PK) analyses suggest dosedependent increases in exposure; studies ongoing 4 0 Ideal therapeutic dose not yet determined as dose escalation continues year old female with metastatic stage IV basal cell carcinoma (BCC) in the head and neck region. Prior therapies included vismodegib and an experimental anticd40 therapy Achieved stable disease () while receiving SL80; CT scans (day of cycle vs baseline) indicated a reduction in target lesions of 4% (47.5 à 4 mm) Given favorable data profile thus far with SL80, coupled with clinical validation of the XPO target, additional SL80 trials, including in hematologic cancers and combination studies, planned Dose (mg/day) n Cohort Dose (mg/day) n enrolling No DLT s reported No MTD Dose escalation ongoing Currently enrolling 0th cohort (60 mg/day) o Pharmacokinetics o Efficacy (ORR, DCR, DoR, PFS and OS) Efficacy Ideal therapeutic dose not yet determined as dose escalation continues Stable disease () achieved in 6% (9/5) of patients in a heavily pretreated (7% rd line or greater) patient population Five patients had over months, including BCC patient with over 0 months duration % disease shrinkage noted in one patient with heavily pretreated neuroendocrine tumor One additional patient ( prior lines of therapy) receiving SL80 for months, ongoing Ongoing, receiving SL80 In addition (not shown): recently enrolled patients (0th cohort: 60 mg) are receiving SL80, ongoing ud Cohort SL80 orally administered Abbreviations: DLT = doselimiting toxicity; ORR = overall response rate; DCR = disease control rate; DoR = duration of response; PFS = progressionfree survival; OS = overall survival; MTD = maximum tolerated dose; CR = complete response Summary uc Months Diarrhea C6 Representative Patient CT Scans Dose escalation ongoing; 0th cohort (60 mg/day) currently enrolling Multiple cases of stable disease () in a heavily pretreated solid tumor patient population Further updates expected this year Durable for 4 cycles ~0 patients per cohort o CR, DoR, PFS, OS C6 Diseasespecific cohorts (up to 4 cohorts) Secondary endpoints: Fatigue C 55 mg 0 G G G G G G G4 G5 Tot G G4 G5 Tot G G4 G5 Tot G G4 G5 Tot G G4 G5 Tot Vomiting 9.9 % Last dose received Neuroendo 5 5 Time to Best Response GI adenocarcinoma TRAEs by dose level (n=5 patients) Dose level 44 % Δ of target lesions 0 mg 40 mg Best Screening Response (mm) (mm) Treatment Duration Treatment Related Adverse Events (AEs) (n=5 patients) Preferred Term No. of lesions 0 mg BCC Neuroendo GI Adeno Breast CRC Neuroendo Small Bowel Biliary Paraganglioma GI Adeno SCC CRC GI Adeno Breast SCC NSCLC Mesothelioma NSCLC Breast CRC Ovarian LMS Pancreas CRC ACC Parotid NSCLC Ovarian Neuroendo ACC Head & Neck Breast Bladder Pancreas CRC Appendix Renal Safety and Tolerability SL80 is a reversible XPO inhibitor; Potential for improved safety profile / therapeutic window Potent preclinical in vitro and vivo activity against multiple cancer types Best Response 40 mg Cancer Type * One patient did not have their systemic therapy history available Mechanism of Action and Preclinical Rationale Tumor Histology As of 0Apr08. Investigatorassessed data; unaudited = stable disease; () = reduction; (+) = increase Patient with KRAS mutation present at screening Heavily pretreated patients: 7% patients were rd line or greater Wide spectrum of solid tumors, including GI, breast, lung, neuroendocrine, ovarian, et al Pharmacokinetics Pharmacokinetic (PK) analyses suggest dosedependent increases in SL80 exposure Advanced (metastatic or locally advanced and unresectable) relapsed or refractory solid tumors with histologic evidence Measurable disease and evalble by RECIST. ECOG PS of 0 Adeqte organ function, including: Creatinine.5x ULN, albumin.5 g/dl, bilirubin.5x ULN, AST/ALT.5x ULN ( 5x for hepatic metastases), prothrombin time.5x ULN (and partial thromboplastin time.5xuln) Adeqte hematologic function, including: ANC.5x09/L, Hgb 8 g/dl (w/o RBC transfusions within prior 4 days), platelet count 00x09/L (w/o platelet transfusions within prior 4 days) Given favorable data profile thus far with SL80, coupled with clinical validation of the XPO target, additional SL80 trials, including in hematologic cancers and combination studies, planned Best Response Select inclusion criteria Manageable safety and tolerability profile, largely grade adverse events (AEs), to date No dose limiting toxicity (DLT) or maximum tolerated dose (MTD) reached th Inclusion / Exclusion Criteria Phase trial of SL80, a novel XPO inhibitor, in heavily pretreated patients with solid tumors As of 0Apr8. Investigatorassessed data; unaudited Additionally, there was a one grade TRAE of acute kidney injury reported at 0 mg/day dose level and one grade TRAE of neutropenia reported at 0 mg/day dose level References Turner et al. Biochemical pharmacology 0; 8(): 0 Tan et al. American journal of physiology Renal physiology 04; 07(): F7986 Siddiqui et al. WIREs RNA 0; :5 Hung et al. Journal of cell science 0; 4(Pt 0): 89 Senapedis et al. Seminars in cancer biology 04; 7:7486 Disclosures: Qi: Stemline employment, equity ownership; Olguin: Stemline employment, equity ownership; Bullington: Stemline employment, equity ownership; Sardone: Stemline employment, equity ownership; Dunn: Stemline employment, equity ownership; Shemesh: Stemline employment, equity ownership; Chen: Stemline employment, equity ownership; Brooks: Stemline employment, equity ownership Disclaimer: Copies of this poster obtained through Quick Response (QR) Code are for personal use only and may not be reproduced without permission from ASCO and the author of this poster.

32 SL70

33 SL70: Background SL70 is an offtheshelf, systemicallydelivered (subcutaneous) immunotherapy Short synthetic peptides, some mutated, to generate antigen specific CD8 + T cell response Coadministered with immunostimulants Targets (ILRa, Ephrin A, Survivin) overexpressed on glioblastoma (GBM) Overexpression of SL70 targets on GBM Normal brain GBM targets: ILRa, Survivin, Ephrin A GBM Mechanism of Action Directs T cells to GBM T cell response/inflammation in brain biopsy postsystemic therapy (earlier version of SL70) Abundant CD8 + T cells Survivin EphA ILRa Numerous CD68 + macrophages Adapted from Uematsu, MJ. Neurooncol, 005 and Wykosky, J. Clin Cancer Res, 008 JCO, 0; ASCO, 0

34 SL70: Phase Trial Design and Demographics Stage (single agent) SL70, with immunostimulants (GMCSF + imiquimod) Stage (Combination) SL70 + bevacizumab, with immunostimulants (polyiclc) Eligibility: Secondline GBM Stage Eligibility: Secondline GBM Stage SL70 GMCSF + Imiquimod MRI MRI SL70 polyiclc Bevacizumab MRI MRI Week: Week: After week : SL70 / GMCSF / imiquimod every 4 weeks thereafter until disease progression After week : SL70 / polyiclc every 4 weeks and bevacizumab (as per label) every weeks thereafter until disease progression *Previous ISTs (~70+ patients) with earlier version of SL70, multiple administration regimens/schedules, demonstrated tolerability with activity (major responses) in some adults and children with malignant high grade gliomas, including GBM and pediatric brainstem nonbrain stem gliomas Age, years Stage Stage Total (n=46) (n=8) (n=74) Median [range] 54 [47] 60 [679] 57 [479] Gender [n, (%)] Male 0 (65.) 8 (64.) 48 (64.9) KPS score at screening [n, (%)] 00 6 (.0) 5 (7.9) (4.9) 90 (50.0) 8 (8.6) (4.9) 80 (8.) 9 (.) (9.7) 70 4 (8.7) 6 (.4) 0 (.5) Followup time, months Median [range] 0.9 [0.79.7] 0.8 [.09.] 0.9 [0.79.7] Stage Stage Total (n=46) (n=8) (n=74) Disease related genotype MGMT promoter methylation status: Methylated / Hypermethylated 7 (5.) 0 (5.7) 7 (.0) Unmethylated 9 (9.6) 0 (5.7) 9 (5.7) Unknown 0 (65.) 8 (8.6) 8 (5.) IDH mutation status: Mutation present (4.) (7.) 4 (5.4) No mutation 6 (4.8) 7 (60.7) (44.6) Unknown 8 (60.9) 9 (.) 7 (50.0) 4 Stage Stage Total (n=46) (n=8) (n=74) Surgery at recurrence [n, (%)] Complete resection 6 (56.5) 0 (7.4) 46 (6.) Partial resection 6 (4.8) 7 (5.0) (.) No surgery at recurrence 4 (8.7) (.6) 5 (6.7) Prior GBM anticancer therapies [n, (%)] TMZ based therapy 40 (86.9) 6 (9.9) 66 (89.) Gliadel wafer (.) 0 (.4) Investigational agent / Other (6.5) (7.) 5 (6.7) Not specified (4.) 0 (.7)

35 5 Disease Control, Including Major Responses Modified RANO Criteria (ITT) Stage Stage n (evalble/total) 46/46 8/8 Disease Control Rate (DCR), n (rate) Objective Response Rate (ORR), n (rate) 0 (%) (95% CI: 0.9, 6.4) (%) (95% CI: 0.,.) 5 (54%) (95% CI:.9, 7.5) 4 (4%) (95% CI: 4.0,.7) Complete response (CR), n (rate) 0 (0%) (7%) Partial Response (PR), n (rate) (%) (7%) Stable Disease (), n (rate) (8%) (79%) RANO = Revised Assessment in NeuroOncology; ITT = intent to treat; CI = confidence interval DCR is the proportion of patients who have a best response of CR, PR or documented on consecutive MRIs 4 weeks apart as judged by modified RANO criteria. ORR is the proportion of patients who have a best response of CR or PR documented on consecutive MRIs 4 weeks apart as judged by modified RANO criteria.

36 Overall Survival (OS) Stage Overall Survival Stage, N=46 Stage Overall Survival Stage, N=8 Survival Probability % month OS (OS) Survival Probability % month OS (OS) Time (months) OS = 44% (95% CI: 8.9, 58.9) Median OS =.0 months (95% CI: 8.,.0) Time (months) OS = 50% (95% CI: 0.6, 69.4) Median OS =.7 months (95% CI: 7., NE) Above calculations by ClopperPearson method NE = not estimable Historical OS: ~08% in trials of bevacizumab in patients with recurrent GBM (BRAIN, ReACT control arm, BELOB, CABARET, and NCI 64E) References: BELOB: Taal et. al., Lancet Oncol 04; BRAIN: Friedman et. al., JCO 009; ReACT: Celldex Presentation; CARBARET: Field et. al., Neuro Oncol. 05; NCI 64E FDA Briefing Documents 6

37 7 TargetSpecific CD8+ T Cell Immunophenotyping by Flow Cytometry Frequency of antigenspecific CD8+ T cells (%) Potential immunerelated biomarker 0.0

38 8 LongTerm Survivors Comprised Largely of TargetSpecific CD8+ T Cell Responders Overall Survival Stage Stage, N=8 (All patients) Stage (TargetSpecific CD8+ N=8T cell Responders) Survival Probability Tail comprised largely of patients with TargetSpecific T cell Response Survival Probability % OS Median OS not reached TargetSpecific CD8 + T cell Responders TargetSpecific CD8 + T cell Responders Time (months) Time (months)

39 Complete Responses (CRs) and High TargetSpecific CD8+ T cell Responses Patient Narrative 60 yearold male Grade IV GBM, KPS 90%, MGMT promoter methylated, nonmutated IDH Prior treatment: resections + Stupp + Veliparib Received SL70 + bevacizumab CR after 4 months Confirmed by nd assessment Targetspecific CD8+ T cells CR PreSL70 months of SL70 9 months of SL70 months of SL70 9

40 Complete Responses (CRs) and High TargetSpecific CD8+ T cell Responses Patient Narrative 5 yearold male Grade IV GBM, KPS 90%, MGMT promoter methylated Prior treatment: resections + Stupp Received SL70 + bevacizumab PR after months, confirmed by nd assessment Subsequently converted to CR, confirmed by nd assessment CR PR Targetspecific CD8+ T cells PreSL70 6 months of SL70 40

41 4 Conclusions and Next Steps Longterm survivors: 50% month OS with SL70 + bevacizumab Longterm survivors comprised largely of patients with targetspecific CD8+ Tcell responses 75% month OS, median OS not reached Indicates potential correlation of immunerelated biomarker with clinical outcome Major responses, including CRs, and durable stable diseases in secondline GBM Welltolerated, very manageable side effect profile Given the major unmet medical need in GBM and promising safety and efficacy data generated to date with SL70, Stemline is considering next steps to unlock value including leveraging potential immunerelated biomarker in registrationdirected trial designs

42 Milestones

43 Milestones Launch disease awareness campaign Complete BLA submission Acceptance of BLA by FDA; grant of Priority Review Meet with Rapporteurs and EMA o Present updated data at scientific meetings 4Q8 o Formulate registration strategy in additional indication(s) ~4Q8/Q9 o PDUFA Date 0//9 o Commercial launch, if approved o Potential MAA filing (EU) ~Q9 Other pipeline candidates o SL70: Data presentation at scientific meetings 4Q8 o SL80: Data presentation at scientific meetings 4Q8 4

44 Financial Summary

45 Financial Summary As of June 0, 08 Cash, Cash Equivalents and Investments (MM) $97. Debt $0.0 Shares Outstanding (MM)

46 Stemline Therapeutics, Inc. NAAQ: STML Corporate Presentation October 08