Stemline Therapeutics
Annual Report 2015

Plain-text annual report

Table of Contents UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549 FORM 10-K xx ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2015 OR oo TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF1934 For the transition period from to . Commission File Number: 001-35619 STEMLINE THERAPEUTICS, INC.(Exact name of registrant as specified in its charter) Delaware45-0522567(State or other jurisdiction of incorporation or organization)(I.R.S. Employer Identification Number) 750 Lexington AvenueEleventh FloorNew York, New York 10022(Address of principal executive offices, including zip code) (646)-502-2311(Registrant’s telephone number, including area code) Securities registered pursuant to Section 12(b) of the Act: Common Stock, par value $0.0001 per shareNASDAQ Capital Market(Title of Class)(Name of Each Exchange on Which Registered) Securities registered pursuant to Section 12(g) of the Act: None Indicate by check mark whether the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. o Yes x No Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. o Yes x No Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filingrequirements for the past 90 days. xYes o No Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Website, if any, every Interactive Data Filerequired to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorterperiod that the registrant was required to submit and post such files). xYes o No Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K (§229.405 of this chapter) is not contained herein, andwill not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K. o Yes x No Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. Seethe definitions of “large accelerated filer,” “accelerated filer,” and “smaller reporting company” in Rule 12b-2 of the Exchange Act. (Check One): Large-accelerated filer oAccelerated filer x Non-accelerated filer oSmaller reporting company o(Do not check if a smaller reporting company) Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). o Yes x No The aggregate market value of voting common stock held by non-affiliates of the registrant (assuming, for purposes of this calculation, withoutconceding, that all executive officers and directors are “affiliates”) was $ 183,407,602 as of June 30, 2015, based on the closing sale price of such stock asreported on the NASDAQ Capital Market. There were 19,005,263 shares of the registrant’s common stock outstanding as of March 14, 2016. DOCUMENTS INCORPORATED BY REFERENCE Portions of the registrant’s Proxy Statement for the 2015 Annual Meeting of Stockholders are incorporated by reference in Part III of this Annual Reporton Form 10-K. Table of Contents TABLE OF CONTENTS Part I3Item 1. Business3Item 1A. Risk Factors29Item 1B. Unresolved Staff Comments53Item 2. Properties54Item 3. Legal Proceedings54Item 4. Mine Safety Disclosures54Part II55Item 5. Market for the Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities55Item 6. Selected Financial Data56Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations57Item 7A. Quantitative and Qualitative Disclosures About Market Risk66Item 8. Financial Statements and Supplementary Data66Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure66Item 9A. Controls and Procedures67Item 9B. Other Information67Part III68Item 10. Directors, Executive Officers and Corporate Governance68Item 11. Executive Compensation68Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters68Item 13. Certain Relationships and Related Transactions and Director Independence68Item 14. Principal Accounting Fees and Services68Part IV69Item 15. Exhibits, Financial Statements Schedules69Signatures This Annual Report on Form 10-K contains trademarks and trade names of Stemline Therapeutics, Inc., including our name and logo. All other trademarks,service marks, or trade names referenced in this Annual Report on Form 10-K are the property of their respective owners. 1Table of Contents SPECIAL CAUTIONARY NOTICE REGARDING FORWARD-LOOKING STATEMENTS This annual report on Form 10-K (“Form 10-K”) 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,” “estimates,” “anticipates,” “expects,”“plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “approximately” or, in each case, their negative or other variations thereon or comparableterminology, although not all forward-looking statements contain these words. They appear in a number of places throughout this Form 10-K and includestatements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, our ongoing and planneddiscovery and development of drug candidates, the strength and breadth of our intellectual property, our ongoing and planned preclinical studies andclinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for our product candidates, the degree ofclinical utility of our product candidates, particularly in specific patient populations, expectations regarding clinical trial data, our results of operations,financial condition, liquidity, prospects, growth and strategies, the length of time that we will be able to continue to fund our operating expenses and capitalexpenditures, our expected financing needs and sources of financing, the industry in which we operate and the trends that may affect the industry or us. By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics, and healthcare, regulatoryand scientific developments and depend on the economic circumstances that may or may not occur in the future or may occur on longer or shorter timelinesthan anticipated. Although we believe that we have a reasonable basis for each forward-looking statement contained in this Form 10-K, we caution you thatforward-looking statements are not guarantees of future performance and that our actual results of operations, financial condition and liquidity, and thedevelopment of the industry in which we operate may differ materially from the forward-looking statements contained in this Form 10-K. In addition, even ifour results of operations, financial condition and liquidity, and the development of the industry in which we operate are consistent with the forward-lookingstatements contained in this Form 10-K, they may not be predictive of results or developments in future periods. Some of the factors that we believe could cause actual results to differ from those anticipated or predicted include: · the success and timing of our clinical trials, including patient accrual;· our ability to obtain and maintain regulatory approval and/or reimbursement of our product candidates for marketing;· our ability to obtain the appropriate labeling of our products under any regulatory approval;· our plans to develop and commercialize our products;· the successful development and implementation of our sales and marketing campaigns;· the loss of key scientific or management personnel;· the size and growth of the potential markets for our product candidates and our ability to serve those markets;· our ability to successfully compete in the potential markets for our product candidates, if commercialized;· regulatory developments in the United States and foreign countries;· the rate and degree of market acceptance of any of our product candidates;· new products, product candidates or new uses for existing products or technologies introduced or announced by our competitors and the timing ofthese introductions or announcements;· market conditions in the pharmaceutical and biotechnology sectors;· our available cash;· the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for additional financing;· our ability to obtain additional funding;· our ability to obtain and maintain intellectual property protection for our product candidates;· our ability to maintain the license agreements for SL-401, SL-701, SL-801 and our other in-licensed product candidates;· the success and timing of our preclinical studies including IND enabling studies;· the ability of our product candidates to successfully perform in clinical trials;· our ability to obtain and maintain approval of our product candidates for trial initiation;· our ability to manufacture and the performance of third-party manufacturers;· the performance of our clinical research organizations, clinical trial sponsors and clinical trial investigators; and· our ability to successfully implement our strategy. Any forward-looking statements that we make in this Form 10-K speak only as of the date of such statement, and we undertake no obligation to update suchstatements to reflect events or circumstances after the date of this Form 10-K. You should also read carefully the factors described in the “Risk Factors”section of this Form 10-K to better understand the risks and uncertainties inherent in our business and underlying any forward-looking statements. As a resultof these factors, we cannot assure you that the forward-looking statements in this Form 10-K will prove to be accurate. This Form 10-K includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studiesconducted by third-parties. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtainedfrom sources believed to be reliable, although they do not guarantee the accuracy or 2Table of Contents completeness of such information. While we believe these industry publications and third-party research, surveys and studies are reliable, we have notindependently verified such data. We qualify all of our forward-looking statements by these cautionary statements. In addition, with respect to all of our forward-looking statements, we claimthe protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Part I Unless the context requires otherwise, references in this report to “Stemline,” “Company,” “we,” “us” and “our” refer to Stemline Therapeutics, Inc. Item 1. Business Overview We are a clinical stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing proprietary oncology therapeutics.We are currently developing three clinical stage product candidates: SL-401, SL-701, and SL-801. SL-401 is a targeted therapy directed to the interleukin-3 receptor, or IL-3R (CD123), present on a wide range of hematologic cancers. SL-401 is beingadvanced through a Phase 2 registration-directed clinical trial in patients with blastic plasmacytoid dendritic cell neoplasm, or BPDCN. Data from the initialstage of this ongoing trial demonstrated a high overall response rate, or ORR, with multiple complete responses, or CRs. Patients continue to be followed foroverall response, response duration, progression free survival, or PFS, and overall survival, or OS. New patients are also enrolling into the study. We believethat results from this trial could potentially support registration in the United States. Clinical studies with SL-401 are also open in additional malignanciesincluding acute myeloid leukemia, or AML, in CR with minimal residual disease, or MRD, and high-risk myeloproliferative neoplasms, or MPNs. SL-701 is an immunotherapy designed to activate the immune system to attack tumors. SL-701 is comprised of three short synthetic tumor-specific peptides,two of which are mutant and selected for potentially enhanced immune effects, that are designed to direct the immune system to their corresponding cellsurface targets overexpressed on tumors including glioblastoma multiforme, or GBM. SL-701 in combination with bevacizumab (Avastin) and animmunostimulant is currently being advanced through a Phase 2 trial in adult patients with second-line GBM. SL-801 is a novel, oral, small molecule, reversible inhibitor of Exportin-1, or XPO1, a key nuclear transport protein. SL-801 has demonstrated potentpreclinical in vitro and in vivo antitumor activity against a wide array of solid and hematologic cancers. We recently opened an investigational new drug, orIND, for SL-801 and are advancing SL-801 into a Phase 1 clinical trial in patients with advanced cancers. Our Company We were incorporated under the laws of the State of Delaware in August 2003. Our principal executive office is located at 750 Lexington Avenue, EleventhFloor, New York, New York 10022 and our telephone number is (646) 502-2311. Our website address is www.stemline.com. The information set forth on our website is not a part of this report. We will make available free of charge throughour website our annual reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, and any amendments to these reports, as soonas reasonably practicable after we electronically file such material with, or furnish such material to, the Securities and Exchange Commission, or SEC. We arenot including the information on our website as a part of, nor incorporating it by reference into, this report. You may read and copy any materials we file atthe SEC’s Public Reference Room at 100 F Street, N.E., Washington, D.C. 20549. You may obtain information on the operation of the Public ReferenceRoom by calling the SEC at 1-800-SEC-0330. Additionally, the SEC maintains a website that contains annual, quarterly, and current reports, proxystatements, and other information that issuers (including us) file electronically with the SEC. The SEC’s website address is http://www.sec.gov/. Management We are led by a team with extensive experience in managing biopharmaceutical companies and in oncology drug development, including: · Ivan Bergstein, M.D. — Chairman, Chief Executive Officer and President. Dr. Bergstein is Chief Executive Officer and Founder of StemlineTherapeutics. He led Stemline through multiple private financings and ultimately its successful IPO and subsequent follow-on offerings, raisingover $165 million as a public company. Dr. Bergstein’s early and broad intellectual property founded and positioned Stemline with deepdomain expertise and a competitive advantage in the rapidly emerging cancer stem cell, or CSC, field of oncology. He then went on to managethe company’s evolution from 3®Table of Contents early-stage research and development to current late clinical stage. Prior to founding Stemline, Dr. Bergstein was Medical Director of AccessOncology, Inc., a clinical stage oncology-focused biotechnology company where he was a key member of a small team responsible for theacquisition and development of the company’s clinical stage assets and ultimately the sale of the company to Keryx Biopharmaceuticals, Inc.(Nasdaq: KERX). Previously, he was a senior biopharmaceuticals analyst at a Wall Street-based firm that advised funds on investmentopportunities in public companies with late clinical stage assets. He received a BA in mathematics from the University of Pennsylvania and waselected to the Pi Mu Epsilon National Mathematics Honor Society, an MD from the Mount Sinai School of Medicine where he was elected tothe Alpha Omega Alpha Honor Medical Society, received the Merck Award for Clinical Excellence, and subsequently completed an internshipin general surgery. He then became the Jerome A. Urban Post-Doctoral Research Fellow at the Cornell University Medical College where hestudied and published work relating to Wnt genes in human breast cancer. He then went on to complete an internal medicine residency andhematology-oncology fellowship at the New York Presbyterian Hospital—Weill Medical College of Cornell University where he studied andpublished work on gene therapy manipulations of the sonic hedgehog pathway. He currently holds a voluntary faculty position at the New YorkPresbyterian Hospital — Weill Medical College of Cornell University. · Kenneth Hoberman — Chief Operating Officer. Mr. Hoberman has extensive financial, accounting, investor relations, corporate governance andbusiness development experience including M&A, strategic alliances and partnerships both domestic and international. His operationalexpertise includes regulatory oversight, human resources, manufacturing and clinical development. He was previously Vice President ofCorporate and Business Development of Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX), where he was instrumental in the success of thecompany. He also helped secure multiple sources of capital including over $200 million in equity investments through public and privateofferings. He also initiated and executed a $100 million strategic alliance and originated, negotiated and closed dozens of licensing andoperational contracts, helping to grow the company’s market capitalization to over $1 billion. He also led the team that originated, in-licensed,and developed Auryxia™ which was approved by the FDA in September 2014. He is on the Board of Directors of TG Therapeutics, Inc.(Nasdaq: TGTX). He received a B.S.B.A. in Finance from Boston University and completed post-baccalaureate studies at Columbia University. · David Gionco — Vice President of Finance and Chief Accounting Officer. Mr. Gionco was previously Vice President, Chief Financial Officerand Chief Accounting Officer of Savient Pharmaceuticals, Inc. where he oversaw the finance function for the organization and was instrumentalin helping to grow the company, raising over $350 million. Prior to this, Mr. Gionco held audit, corporate accounting, financial planning,finance and controller roles at companies including Merck & Co., Inc. (“Merck”) and, previously, Medco Health Solutions, Inc., which wasacquired by Merck during his tenure. At Merck, Mr. Gionco held various financial and accounting positions of increasing responsibility.Mr. Gionco also held senior financial positions at Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX) and Odyssey Pharmaceuticals, Inc. (asubsidiary of Pliva, Inc., now Teva Pharmaceutical Industries Ltd. (NYSE: TEVA)). Mr. Gionco previously had 7 years of financial auditingexperience with a major public accounting firm. Mr. Gionco holds a B.S. in Accounting from Fairleigh Dickinson University and an MBA inFinance from Rutgers University. Mr. Gionco is a Certified Public Accountant in the State of New York. Strategy Our goal is to build a leading biopharmaceutical company focused on improving the lives of cancer patients by developing and commercializing innovativeoncology therapeutics. The fundamental components of our business strategy to achieve this goal include the following: · Develop and commercialize SL-401 in multiple cancers. We have advanced SL-401 into a potentially pivotal Phase 2 trial of patients withblastic plasmacytoid dendritic cell neoplasm, or BPDCN. We have also opened Phase 1/2 clinical trials, and are enrolling patients, in additionalindications including 1) acute myeloid leukemia, or AML, in complete remission, or CR, with minimum residual disease, or MRD, and 2)myeloproliferative neoplasms, or MPNs, that include mastocytosis, hypereosinophilic syndrome, myelofibrosis, and chronic myelomonocyticleukemia. We also intend to pursue additional indications including multiple myeloma. · Develop and commercialize SL-701 in brain cancer. We have advanced SL-701 into a Phase 2 trial in adult patients with second-lineglioblastoma multiforme, or GBM. Patients are currently enrolling into the study and being treated with SL-701 in combination withbevacizumab (Avastin) and an immunostimulant. · Develop and commercialize SL-801 in multiple cancer types. We have opened an IND and are advancing SL-801 into a Phase 1 trial in patientswith advanced solid cancers and also may pursue its development in hematologic cancers in the future. 4®Table of Contents · Develop commercialization capabilities in North America and Europe. It is our intention to build out a commercial infrastructure to marketand sell our product candidates if and when they attain marketing approval in the United States, Canada, and potentially Europe. However, wewill remain opportunistic in seeking strategic partnerships in these and other territories when advantageous to us. SL-401 Overview SL-401 is a targeted therapy directed to the interleukin-3 receptor, or IL-3R (CD123). IL-3R is overexpressed on multiple cancers including acute myeloidleukemia, or AML, chronic myeloid leukemia, or CML, myelodysplastic syndrome, or MDS, certain lymphomas including Hodgkin’s disease, multiplemyeloma, or MM, blastic plasmacytoid dendritic cell neoplasm, or BPDCN, certain myeloproliferative neoplasms, or MPNs, and other malignancies. Previously, SL-401 was evaluated in an investigator sponsored Phase 1/2 clinical trial in patients with advanced hematologic cancers; a trial which has sincecompleted. In this trial, SL-401 administered over a single, five-day, cycle demonstrated anti-tumor activity, including multiple CRs, in both BPDCN andrelapsed or refractory AML (Frankel et al. Blood 124, 2014; ASH 2013 Poster #2682; ASH 2015 Poster #3795). We are currently advancing SL-401 through a potentially pivotal corporate-sponsored Phase 2 clinical trial in patients with blastic plasmacytoid dendriticcell neoplasm, or BPDCN. We are also currently advancing SL-401 through clinical trials in additional IL-3R expressing malignancies including acutemyeloid leukemia, or AML, in CR with minimal residual disease, or MRD, and high-risk myeloproliferative neoplasms, or MPNs. Design of SL-401 and mechanism of action SL-401 is a novel biologic targeted therapy directed to the IL-3R (CD123). SL-401 consists of IL-3 recombinantly fused to a truncated diphtheria toxinpayload. Mechanistically, the IL-3 domain of SL-401 directs its cytotoxic payload to IL-3R+ cells. SL-401 is then internalized by target cells, leading tointracellular release of the payload, inhibition of protein synthesis and cell death, or apoptosis. Given this novel mechanism of action, there is a potential todevelop SL-401 not only as a single agent but also in combination with other therapies. IL-3R is normally expressed on certain maturing hematopoietic cells, including maturing myeloid cells, B cells, dendritic cells, mast cells, basophils andeosinophils, and appears to be involved in cell maturation, differentiation, and survival. Importantly, IL-3R is not expressed to a significant degree on normalhematopoietic stem cells. IL-3R is, however, overexpressed on multiple hematological malignancies including AML, BPDCN, MDS, CML, B cell acutelymphoid leukemia, Hodgkin’s and certain aggressive non-Hodgkin’s lymphomas, hairy cell leukemia, and certain myeloproliferative neoplasms. In additionto expression on tumor bulk, IL-3R expression has been reported on the cancer stem cells, or CSCs, of multiple hematologic cancers including AML, CML,MDS, and potentially T-cell acute lymphoid leukemia. Elevated IL-3R expression has been correlated with poor patient prognosis. For example, as describedby Vergez in Haematologica in 2011, a higher percentage of IL-3R-expressing, or IL-3R+, CSCs within a patient’s entire tumor correlates with poor outcome.In particular, AML patients with IL-3R+ CSCs that comprise greater than or equal to 1% of their entire leukemia were found to have a worse prognosis thanpatients with IL-3R+ CSCs that comprise less than 1% of their entire leukemia. SL-401 preclinical activity SL-401 has demonstrated preclinical in vitro and in vivo activity against a wide range of hematologic cancer types. In AML, SL-401 is highly active againstboth leukemia blasts (i.e., tumor bulk) and CSCs of a variety of human leukemia cell lines and primary leukemia cells from patients. In particular, SL-401demonstrated potent cytotoxicity against leukemic cells in vitro in a dose-dependent fashion with concentrations that inhibit the growth of fifty percent(50%) of cells, or an IC, in the low picomolar range. Notably, normal bone marrow stem cells were relatively insensitive to SL-401. SL-401 also exhibitedanti-CSC activity. In particular, SL-401 inhibited AML colony formation, an assay for stem cell activity, compared with normal human bone marrow. Asfurther validation of an anti-CSC effect, SL-401 reduced the incorporation and growth (i.e., tumorigenicity) of AML cells, relative to normal human bonemarrow, when treated ex vivo and reimplanted into immunodeficient mice—indicating activity at the level of the CSC. In addition, SL-401 prolonged thesurvival of mice implanted with human leukemia xenografts compared with untreated mice. In addition, SL-401 demonstrated very high potency against BPDCN cells from patients, with an IC in the femtomolar (10 molar) range. SL-401 has alsodemonstrated preclinical activity against a variety of additional hematologic cancers including certain rare IL-3R+ malignancies such as chroniceosinophilic leukemia, where it produced IC values in the low single-digit picomolar (10 molar) 55050-1550-12Table of Contents range. SL-401 has also shown potent in vitro anti-leukemia activity against CML tumor bulk and CML CSCs, and increased survival in mouse models ofhuman CML taken from patients who were resistant to tyrosine kinase inhibitors, or TKIs. SL-401 has also been shown to possess a synergistic anti-CMLeffect when used in combination with certain TKIs. SL-401 has also demonstrated potent in vitro anti-tumor activity against several lymphoid cancer types,including lymphoid leukemia (e.g. T cell acute lymphoid leukemia, or T-ALL), Hodgkin’s and non-Hodgkin’s lymphoma, and multiple myeloma, or MM.Interestingly, SL-401 appears to have both a direct as well as an indirect anti-MM effect, the latter seemingly caused by SL-401’s ability to target IL-3R+hyperproliferative dendritic cells (the cells of origin of BPDCN) that appear to provide a novel immune-associated growth stimulus to their neighboring MMcells. This is notable for several reasons including the drug’s novel mechanism of anti-MM action as well as linking the MM and BPDCN diseases via acommon plasmacytoid dendritic cell, and IL-3R, target. SL-401 has also been shown to have a synergistic effect against MM when combined with existingtherapies including pomalidomide (Pomalyst), lenalidomide (Revlimid) and bortezomib (Velcade). We believe these findings warrant clinicalinvestigation of SL-401 in multiple myeloma. Potentially pivotal Phase 2 clinical trial of SL-401 in BPDCN Our ongoing potentially pivotal Phase 2 trial of SL-401 in BPDCN is a single arm, open-label, multicenter study. This trial consists of a lead-in, doseescalation stage that included BPDCN and relapsed refractory AML patients (Stage 1) and a subsequent expansion stage that is enrolling BPDCN patients(Stage 2) that utilizes the optimal dose and regimen identified in Stage 1. Stage 1 of the trial has been completed, and patients are currently being enrolledinto Stage 2. This trial is designed to generate sufficient safety and efficacy data to support potential registration in BPDCN. In December 2015, we reported initial data from Stage 1 and the ongoing expansion stage (Stage 2) of this trial at the 2015 American Society of Hematology(ASH) Annual Meeting. Twenty nine patients (15 BPDCN, 14 relapsed/refractory AML) including one compassionate use patient were enrolled in theongoing study. This includes 6 BPDCN patients in Stage 2. The median age of BPDCN patients was 70.5 years (range 45-88) plus one compassionate usepatient age 15 years. The data demonstrated that multiple consecutive cycles of SL-401 produced an 86% (12/14) overall response rate, or ORR, in BPDCNpatients, with a 100% (9/9) ORR in first-line BPDCN patients and a 60% (3/5) ORR in relapsed/refractory BPDCN patients. Additionally, we reported fourcomplete responses (CR) and four clinical complete responses (CRc). CRc is defined as a CR in all non-skin organ systems affected by disease, includingbone marrow, with marked clearance of gross skin lesions but with residual microscopic-only disease detected by biopsy. Interim data reported at ASH 2015 indicated that of nine evaluable BPDCN responders treated at 12 ug/kg/day, five were in remission and receiving SL-401therapy, and two were successfully bridged to stem cell transplant (SCT). In terms of safety, multiple consecutive cycles of SL-401 dosed up to 12 ug/kg/day demonstrated a manageable safety and tolerability profile, with noevidence of cumulative side effects over multiple cycles. Additionally, we developed dosing and safety parameters during the lead-in stage of the study thatwere designed to minimize the risk of severe capillary leak syndrome (CLS). Since implementation of these measures, severe CLS has not been observed atdoses up to 12 ug/kg/day. Most common treatment related adverse events, all grades, were transaminase elevation (64%) and hypoalbuminemia (46%).Thrombocytopenia was also noted (25%). The tables below summarize efficacy and safety presented at ASH 2015 from the lead-in (Stage 1) and initial expansion stage (Stage 2) of the ongoing Phase2 trial in BPDCN. Table 1. Overview of SL-401 Clinical Activity in BPDCN Presented at ASH 2015 Major objective responses· 86% (12/14) ORR in BPDCN (all lines)· 100% (9/9) ORR in first-line BPDCN; 100% (7/7) ORR in first-line BPDCN at 12 ug/kg/day· 60% (3/5) ORR in relapsed/refractory (r/r) BPDCN Setting All lines All lines First-line First-line r/r Dose Group All doses μ All Doses μ μ n (total)15121075n (evaluable for response)1412975CR4343—CRc4444—PR431—3Major responses (CR+CRc+PR)1210973CR (%)29%25%44%43%—CR+CRc (%)57%58%89%100%—ORR (%)86%83%100%100%60% 6®®®12 g/kg12 g/kg12 g/kgTable of Contents Table 2. Overview of SL-401 Safety in BPDCN Most common adverse events (AEs) (>15%; treatment-related) Treatment-related AEs All AEs All grades grade >=3 All grades grade >=3 Transaminase elevation64%43%71%43%Hypoalbuminemia46%0%54%4%Pyrexia39%0%54%7%Nausea36%0%46%0%Fatigue32%4%43%7%Anemia29%25%39%29%Thrombocytopenia25%21%29%25%Chills25%0%29%0%Decreased appetite25%0%25%0%Hypotension21%0%29%7%Edema peripheral21%0%25%0%Weight increased18%0%25%0%Lymphopenia18%14%18%14%Capillary leak syndrome (CLS)18%11%18%11% Dose levels, DLTs, and adjustments made in Lead-in (Stage 1) · Cohort 1 (7 ug/kg/day): grade 5 CLS (BPDCN); cohort expanded to 6 patients and cleared· Cohort 2 (9 ug/kg/day): no DLTs (n=3 patients); cohort cleared· Cohort 3 (12 ug/kg/day): grade 4 CLS (BPDCN); cohort expanded to 6 patients and cleared Since implementation of the following safety precautions, severe CLS has not been observed at doses up to 12 ug/kg/ day (n >10 patients): normalcardiac ejection fraction (LVEF) required at study entry; albumin of >3.2 g/dL required at study entry; if weight gain >1.5 kg from prior day, SL-401held for > 1 day until stable; if albumin reduction to <3.0 g/dL or absolute reduction of 1.0 g/dL from pre-cycle baseline, SL-401 withheld forremainder of cycle (but may resume at next cycle); if transaminase elevation >5x ULN, SL-401 withheld for remainder of cycle (but may resume atnext cycle). · Cohort 4 (16 ug/kg/day): grade 5 suspected CLS (AML r/r); cohort expanded to 6 patients· Cohort 4 (16 ug/kg/day): grade 3 infusion reaction (AML r/r); DLT in AML (r/r) in this cohort Dose and schedule determined for expansion (Stage 2) · BPDCN: 12 ug/kg/day (MTD not reached)· AML (r/r): 12 ug/kg/day (MTD) No cumulative side effects observed at, or below, 12 ug/kg/day after multiple consecutive cycles of SL-401 Abbreviations: MTD=maximum tolerated dose; DLT=dose limiting toxicity 7aTable of Contents Patient enrollment in the SL-401 potentially pivotal Phase 2 trial in BPDCN is ongoing and data from the trial continue to mature. Patients are beingfollowed for, among other parameters, ORR, response duration, PFS and OS. SL-401 has been granted Orphan Drug designation from the FDA and the European Medicines Agency (EMA) for the treatment of BPDCN and AML. TheFDA awarded Orphan Drug status to SL-401 for the treatment of AML in February 2011 and for BPDCN in June 2013. The EMA awarded Orphan Drug statusto SL-401 for the treatment of AML in September 2015 and for BPDCN in November 2015. SL-401 Clinical Trials in Additional Indications AML in complete remission, or CR, with minimal residual disease, or MRD: SL-401 is currently being advanced through a clinical trial in AML in CR withMRD. Historically, chemotherapy has been effective in inducing CRs in early stage AML patients but response durability and relapse rates have beensuboptimal (Buchner in Journal of Clinical Oncology, 2012). Recent work has identified the presence of microscopic disease, or minimal residual disease, orMRD, in the bone marrow of many AML patients in CR after chemotherapy indicating that leukemic cells are often still present despite seemingly successfulstandard therapy (Hourigan in Nature Reviews Clinical Oncology, 2013). The presence of MRD in the bone marrows of such AML patients has beenassociated with a high risk of relapse and worse overall prognosis (Chen in Journal of Clinical Oncology, 2015; Freeman in Journal of Clinical Oncology,2013; Walter in Leukemia, 2015; Jorgensen in Clinical Lymphoma Myeloma and Leukemia, 2011; Terwijn in Journal of Clinical Oncology, 2013). Recentwork attempting to understand MRD has demonstrated a preponderance of immature cancer stem cell-like, or CSC-like, cells (Terwijn in PLoS One, 2014;Gerber in Blood, 2012) and IL-3R positivity (Roug in British Journal of Haematology, 2014; Konopleva unpublished), consistent with the view that IL-3R+AML CSCs comprise MRD, are not adequately eradicated by traditional therapies, and may be a key contributor to treatment failure and relapse. Theobjectives of this clinical study of SL-401 in AML patients in CR with MRD are to determine 1) safety and optimal dose in this indication, 2) SL-401’sability to convert MRD positivity to negativity, and 3) whether CR duration can be extended by SL-401 relative to historical data. This trial has a lead-indose escalation stage (Stage 1) and an expansion stage (Stage 2) and is currently enrolling patients in Stage 1. High risk myeloproliferative neoplasms, or MPN: SL-401 is currently being advanced through a clinical trial in advanced high-risk MPN. Certain high-riskMPNs, including systemic mastocytosis, advanced symptomatic hypereosinophilic disorder, myelofibrosis, and chronic myelomonocytic leukemia, mayderive from an IL-3R+ progenitor cell and express IL-3R (Pardanani in Leukemia, 2015; Brooks in Blood, 2013; Orazi in Modern Pathology, 2006). Webelieve that MPNs may represent a potential accelerated approval path for SL-401, similar to BPDCN, if robust clinical activity can be demonstrated. Theobjectives of this clinical study of SL-401 in MPN are to determine safety, dose and efficacy. This trial has a lead-in dose escalation stage (Stage 1) and anexpansion stage (Stage 2) and is currently enrolling patients in Stage 1. Multiple myeloma: SL-401 clinical trials are also currently planned in other indications including multiple myeloma. In previous studies, plasmacytoiddendritic cells, or pDCs, the cells which when malignant become BPDCN, were found to be present in large numbers in the bone marrow microenvironment ofpatients with multiple myeloma (Chauhan in Cancer Cell, 2009). These IL-3R+ pDCs were also found to possess growth-promoting interactions with theirneighboring myeloma cells, as well as additional interactions with immune effector T cells and natural killer, or NK, cells in the myeloma bone marrowmilieu (Ray in Leukemia, 2015). In preclinical studies, SL-401 has been shown to possess an anti-myeloma effect both directly against myeloma cells as wellas indirectly via inhibition of surrounding pDCs, a potentially novel immune-associated mechanism (Chauhan in Journal of Clinical Oncology, 2013;Chauhan in Journal of Clinical Oncology, 2014; Chauhan et al. Blood 2015). SL-401 has also demonstrated synergy with several standard anti-myelomaagents, including pomalidomide, in preclinical studies of myeloma (Ray in Blood, 2014). Clinical studies are currently planned with SL-401 in combinationwith pomalidomide in myeloma patients. Potential SL-401 Indications Blastic plasmacytoid dendritic cell neoplasm (BPDCN) BPDCN is an aggressive hematologic cancer that carries a poor prognosis. BPDCN had been previously classified as blastic NK cell lymphoma, agranularCD4+/CD56+ hematodermic neoplasm, and plasmacytoid dendritic cell cancer. In 2008, this disease was renamed BPDCN by the World Health Organization,or WHO, due to its derivation from plasmacytoid dendritic cells, which are specialized immune cells. BPDCN is a rare malignancy most commonly affectsmiddle-aged and older patients and is approximately three times more common in men than women. This malignancy typically presents with skin lesions, aswell as bone marrow involvement. BPDCN growth in the bone marrow results in decreased blood cell counts, which can lead to serious infections, fatigue,bleeding, and death. Although BPDCN responses have been reported with various combination chemotherapy regimens, overall prognosis remains poor.There are currently no approved therapies for BPDCN, and an optimal therapeutic regimen for BPDCN has not yet been established. 8Table of Contents Acute myeloid leukemia (AML) AML is a hematologic cancer characterized by dysregulated maturation of myeloid cells and failure of the bone marrow to properly function. AML is themost common type of acute leukemia in adults. Approximately 19,000 new AML cases occur annually in the United States, and approximately 27,000 newcases occur annually in Europe. The average age of an AML patient is 67 years. The National Cancer Institute estimated that the one-year survival rate foradult patients with AML was approximately 34%. The one-year survival rate for AML after first relapse is approximately 20%. Current first-line treatments forAML include chemotherapy drugs such as cytarabine in combination with an anthracycline such as daunorubicin. In certain circumstances, allogeneic stemcell transplantation is also used. In second-line AML, while there are currently no approved treatments, typical therapies include additional chemotherapy,often cytarabine again at various dosages and regimens. Despite a moderate to high proportion of patients obtaining a CR with first- and second-linechemotherapy, many of these responding patients still unfortunately have a high relapse rate and poor OS and thus are in need for additional measures forlonger term benefit. Myeloproliferative Neoplasms A number of other rare hematologic diseases, each qualifying as an unmet medical need, express IL-3R including certain myeloproliferative syndromes, orMPNs, such as mastocytosis, clonal eosinophilic disorders, myelofibrosis, and chronic myelomonocytic leukemia. For a majority of patients with theseconditions, there is no effective, disease modifying therapy. Mastocytosis. Systemic mastocytosis is a proliferative disorder characterized by an overabundance of mast cells in various organs and tissues. Mastocytosiscan be systemic or localized to one or a few organs. The WHO classifies mastocytosis into the following categories: cutaneous, indolent, systemic (withassociated hematologic non-mast cell lineage disease), aggressive systemic, mast cell leukemia, mast cell sarcoma, and extracutaneous astrocytoma. There areapproximately 3,000 cases of mastocytosis diagnosed annually in the United States. Patients with indolent disease typically have a favorable prognosis,whereas aggressive cases of mastocytosis carry an overall survival of under 3.5 years. There are no currently approved drugs and no cure for mastocytosis.Treatment for aggressive variants includes various chemotherapy agents, imatinib (Gleevec), corticosteroids, and antihistamines. Eosinophilic disorders. Primary (clonal) eosinophilic disorders include chronic eosinophilic leukemia, or CEL, idiopathic hypereosinophilic syndrome, orHES, lymphocyte-variant HES, and primary eosinophilia associated with an 8p11 chromosomal translocation. These rare disorders are characterized by apersistently elevated eosinophil count that may result in various symptoms depending on which organs are involved. Damage to the heart, lungs, peripheralnervous system, and other organs can occur. An acquired (non-familial) form of HES is particularly aggressive and debilitating. Acquired forms of HES aresubclassified as secondary (reactive), idiopathic, and clonal HES, the latter often transitioning into CEL, which can result in myocardial fibrosis andcongestive heart failure. Eosinophils are known to ubiquitously express the IL-3R. Current treatments for CEL include corticosteroids, mepolizumab,alemtuzumab (Campath), and imatinib (Gleevec), the latter of which is approved by the FDA for approximately 10% of HES patients who express theFIP1L1-PDGFRA fusion protein. However, some of these agents can cause severe toxicity and may not induce durable responses. Therefore, newer and moreeffective therapies are needed for certain patients, including those with symptomatic disease and/or extra-cutaneous organ involvement. Myelofibrosis. Primary myelofibrosis, or PMF, is characterized by the proliferation of an abnormal clone of hematopoietic progenitor cells in the bonemarrow and other sites, which results in fibrosis, or the replacement of the bone marrow with collagenous connective tissue fibers that, in turn, causesdecreased blood cell counts. The yearly calculated incidence of PMF in the U.S. ranges from approximately 1,260 to 4,410 individuals per year. Median ageat diagnosis is 65 years. About 20% of affected patients are less than 55 years of age. Manifestations include decreased blood cell counts, splenomegaly thatis commonly painful, and increased immature white blood cells and basophils in the peripheral blood. The one known treatment of potential long-termbenefit is high-dose chemotherapy followed by allogeneic stem cell transplantation. Other treatment options are largely supportive, and do not alter thecourse of the disorder. These options may include administration of folic acid, allopurinol, and/or blood cell transfusions. Corticosteroids, alpha-interferonand/or hydroxyurea are also used. Splenectomy is sometimes considered as a treatment option for patients with PMF in whom massive splenomegaly iscontributing to anemia because of hypersplenism, particularly if there is a heavy requirement for blood transfusions. Ruxolitinib (Jakafi), which hasrecently received regulatory approval in the United States and elsewhere for the treatment for PMFs, has been associated with symptomatic improvement andincreased overall survival, but its overall benefits can be short lived. Lenalidomide (Revlimid) and thalidomide (Thalomid) may also be used in itstreatment, though peripheral neuropathy can be a troublesome side effect. Chronic myelomonocytic leukemia. Chronic myelomonocytic leukemia, or CMML, is characterized by increased numbers of monocytes and immature bloodcells (blasts) in the peripheral blood and bone marrow, as well as abnormal appearing cells (dysplasia) in at least one type of blood cell. CMML featurescharacteristics of both a myelodysplastic syndrome, or MDS, as well as a myeloproliferative disorder, or MPD. In the United States, the incidence of CMMLis approximately 3,150 individuals per year and the disease affects approximately 9,450 individuals per year. One of the most common symptoms of CMMLis splenomegaly, found 9®®®®®®Table of Contents in approximately half of cases. Other less frequent symptoms consist of anemia, fever, weight loss, night sweats, infection, bleeding, synovitis,lymphadenopathy, skin rashes, pleural effusion, pericardial effusion and peritoneal effusion. CMML can transform into acute myeloid leukemia, or AML, inabout 20%-30% of cases. Most cases are dealt with as supportive rather than curative because most therapies do not effectively increase survival. Supportivemeasures include blood transfusions and growth factors such as erythropoietic and granulocyte-stimulating factor. Reasons for more definitive treatmentinclude the presence of fevers, chills, weight loss, symptomatic organ involvement, increasing blood counts, leukostasis, blood clotting, and/or progressivedecreasing blood cell counts. The demethylating agents azacitidine (Vidaza) and decitabine (Dacogen) have been used to treat CMML. High dosechemotherapy followed by bone marrow transplantation is also employed to treat CMML, and may provide long term benefit. Multiple myeloma (MM) MM is a hematologic malignancy that is characterized by the dysfunction of plasma cells, which are white blood cells that produce antibodies. During MM,malignant plasma cells overproduce abnormal monoclonal antibodies and can interfere with normal blood cell function in the bone marrow leading toimmunodeficiency. Other common clinical manifestations of advanced MM include osteolytic bone lesions and renal disease. The bone marrow, or BM,microenvironment confers growth, survival, and drug resistance of MM cells, and it has recently been shown that plasmacytoid dendritic cells, or pDCs,which express high levels of IL-3R, are significantly increased in the BM of patients with MM and promote MM proliferation. Approximately 22,000 newcases of MM are reported annually in the United States and approximately 33,000 new MM cases are reported annually in Europe. The median age atdiagnosis is approximately 62 years for men and 61 years for women. The median overall survival after conventional treatments is 3-4 years, but high-dosetreatment followed by autologous stem cell transplantation can extend the median survival to 5-7 years. Despite FDA approved therapies for MM, includingthalidomide (Thalomid), lenalidomide (Revlimid), bortezomib (Velcade), dexamethasone (Decadron), carfilzomib (Krypolis), and pomalidomide(Pomalyst), most patients invariably relapse from the disease. Hairy cell leukemia Hairy cell leukemia. Hairy cell leukemia, or HCL, is an uncommon hematological malignancy characterized by a clonal accumulation of abnormal Blymphocytes. Approximately 2,000 new cases of HCL occur annually in the United States. The median age at diagnosis is approximately 62 years with malepredominance. Although the 6-year overall survival rate has been estimated to be approximately 80% and there are FDA approved therapies for HCL,including cladribine, pentostatin, and interferon, there is no permanent cure for the disease. Myelodysplastic syndrome (MDS) MDS is a group of hematologic malignancies characterized by dysfunction of the blood and bone marrow, resulting in decreased peripheral blood countsand, at times, evolution into AML. Approximately 16,000 new cases of MDS are reported annually in the United States and approximately 15,000 to 25,000new MDS cases are reported annually in Europe. MDS occurs most commonly in males 70 years or older. Five-year survival rates for MDS patients varysignificantly depending on disease severity and prognosis and range from approximately 55% for low-risk patients, to 7% to 35% for intermediate-riskpatients. Virtually all high-risk MDS patients die within five years. Treatment paradigms for MDS patients vary depending on disease classification and riskcategory. Current first-line treatments include azacitidine (Vidaza®), decitabine (Dacogen®), lenalidomide (Thalomid®), growth factors such aserythropoietic and granulocyte-stimulating factor, chemotherapy, and stem cell transplantation in certain cases. We believe that a large number of patientseither do not respond or relapse following first-line treatment, and there are no approved therapies and limited effective treatment options in this high-risksetting. Chronic Myeloid Leukemia (CML) Chronic myeloid leukemia, or CML, is a hematopoietic stem cell disease resulting in impaired bone marrow function. Annually, approximately 5,000 newcases are reported in the United States each year and approximately 4,000 to 9,000 new cases are reported each year in Europe. The five-year OS rate for CMLpatients is 57%. When CML advances to an accelerated or blastic phase, the median OS is less than one year. In patients who have failed or are intolerant totyrosine kinase inhibitors, or TKIs, a relapsed or refractory setting, the median OS is four to 11 months. Current first-line treatments for CML include threeTKIs: imatinib (Gleevec), nilotinib (Tasigna) and dasatinib (Sprycel). In cases of relapse, second and third-line treatments include a TKI not previouslyused in that patient. In certain circumstances, interferon or bone marrow transplantation is also used. 10®®®®®®®®®®®Table of Contents Hodgkin’s lymphoma (HL) Hodgkin’s lymphoma, or HL, is a cancer of the lymphatic system that commonly affects lymph nodes in the neck or the area between the lungs and behindthe breastbone. Approximately 9,000 new HL cases occur annually in the United States and approximately 12,000-17,000 cases occur annually in Europe.The disease has four subtypes, including nodular sclerosis, lymphocyte-rich, mixed cellularity, and lymphocyte-depleted HL, all of which produce increasednumbers of a unique cell type called “Reed-Sternberg” cells. These cells are considered to be the clonal tumor cells of HL and are known to express the IL-3R. Although combination chemotherapy and/or radiation therapy are affective at combating this disease, 20-30% of patients relapse after initial treatment orhave primary refractory disease. Of these patients, those who do not obtain a complete remission, or CR, prior to transplantation, or who relapse after secondline therapy, have few effective therapeutic options. Recently, brentuximab vedotin (Adcentris) received regulatory approval in the United States andelsewhere for the treatment of recurrent or refractory HL. SL-701 Overview SL-701 is an immunotherapy designed to direct the immune system to attack targets present on brain cancer. SL-701 is comprised of several short syntheticpeptides that correspond to epitopes of targets including IL-13Rα2, EphA2, and survivin, present on brain cancer. The synthetic peptides that correspond toIL-13Rα2 and survivin are novel artificially constructed mutants designed to be immunogenic to potentially amplify the clinical anti-tumor immuneresponse. High-grade gliomas, or HGGs, are the most aggressive brain cancers and have a poor prognosis. Treatment options are limited, particularly for adult patientswith recurrent or refractory HGG, including glioblastoma multiforme, or GBM, and pediatric patients with HGG, including brainstem glioma, or BSG, andnon-brainstem glioma, indications. In two completed investigator sponsored Phase 1/2 clinical trials, an earlier version of this therapy, delivered with animmunostimulant, poly-ICLC, demonstrated single agent anti-tumor activity, including multiple tumor shrinkages, disease stabilizations, and an overallsurvival signal, in adult and pediatric patients with HGG. There were major objective tumor responses (i.e., tumor regressions) reported in these studies,consisting of two CRs in GBM and six PRs. An additional patient achieved tumor shrinkage, in the form of a minor response, or MR, and another achievedprolonged disease free survival following complete surgical resection (i.e. a clinical complete response, or CRc) in these studies. We have since advanced SL-701 into a corporate sponsored Phase 2 trial in adult patients with second-line GBM. In the initial stage of this trial, SL-701 wasadministered with different immunostimulants, GM-CSF and Imiquimod, relative to the previous investigation sponsored Phase 1/2 trials which used poly-ICLC as immunostimulant. Objective responses have yet to be reported and patients continue to be followed for progression free survival, or PFS, overallsurvival, or OS, and late response. During the current stage of this trial, we are using the poly-ICLC immunostimulant, a toll-like receptor 3 (TLR3) agonistshown to activate NK cells and CD8+ T cells, in order to more closely simulate the regimen of the previous trial that was associated with multiple majorobjective responses. In addition, we have added bevacizumab (Avastin®) to the regimen as we believe there are emerging data that anti-angiogenic therapiesmay enhance certain immunotherapy approaches such as SL-701. This trial is currently enrolling patients. In January 2015, SL-701 was awarded Orphan Drug designation from the FDA for the treatment of glioma. Potential SL-701 Indications High-grade glioma (including adult glioblastoma and pediatric non-brainstem and brainstem glioma) Gliomas are histologically heterogeneous tumors that are derived from glial cells in the brain. Gliomas are graded from 1 to 4, based on WHO classifications,with grade 4 glioma (i.e., glioblastoma, or GBM) and grade 3 glioma (i.e., anaplastic glioma, or AG) as the most aggressive gliomas and referred to as high-grade gliomas, or HGGs. GBM makes up the majority of HGG cases, with an annual incidence in adults of approximately 10,000 in the United States and15,000 to 18,000 in Europe. The standard of care for newly diagnosed adult GBM is resection, if operable, followed by a combination of radiation and temozolomide (i.e., the Stuppregimen). Although this combination treatment has improved patient outcomes, 85% to 90% of patients ultimately relapse, with a median OS from diagnosisof 15 months. Bevacizumab (Avastin Roche AG) received accelerated, but not full, approval for adults with recurrent or refractory adult GBM based, in part,on a response-rate endpoint. However, most recurrent patients receiving bevacizumab (Avastin) do not have durable clinical benefit, and the median OS forthese second-line patients is approximately eight to nine months. Currently, no therapies have been approved for GBM patients who fail bevacizumab, whichcarries a median OS of three to four months. 11®®®Table of Contents Pediatric HGG, which includes non-brainstem HGG and brainstem glioma, or BSG, is a highly malignant disease with very poor outcomes. The annualincidence of pediatric HGG is approximately 1,600 to 2,000 in the United States and approximately 3,400 in Europe. No therapy has been shown to have afavorable outcome in this population and almost all patients relapse after receiving first-line treatment. Pediatric patients with newly diagnosed HGG aretypically treated with surgery, chemotherapy and/or radiation and have an expected median OS from diagnosis of less than one year. SL-801 SL-801 is a structurally novel, oral, small molecule that reversibly inhibits XPO1 (Exportin-1), also known as CRM-1 (Chromosome Region Maintenance-1),a nuclear transport protein. XPO1 has been shown to regulate nuclear export of many of the major tumor suppressor proteins and oncogenic cell growthregulators. Overexpression of XPO1 has been reported in many cancer types and is associated with aggressive tumor behavior and poor patient prognosis.Inhibition of XPO1 has been shown to restore tumor suppressor function and proper cell cycle regulation, leading to apoptosis of cancer cells. XPO1 has alsobeen shown to be a clinically validated target in both solid and hematological cancers. SL-801 has demonstrated broad and potent preclinical activity in a wide array of solid and hematologic tumors in both in vitro and in vivo xenograftexperiments. In a screen against 240 cancer cell lines, SL-801 possessed strong anti-tumor activity, with 50% growth inhibitory (GI) values less than 10 nMin 21.3% of cell lines and less than 100 nM in 95.8% of cell lines. As a single agent, SL-801 also significantly prolonged overall survival and inhibitedtumor growth in several murine xenograft models of human multiple myeloma, as well as in xenograft models of acute lymphoblastic leukemia, non-smallcell lung cancer and prostate carcinoma, in well-tolerated single-dose or multi-dose regimens. In contrast to the prototypical XPO1 inhibitor leptomycin B,which may bind irreversibly to XPO1 and caused significant toxicities in Phase 1 trials, data indicate that SL-801 binding to XPO1 is more reversible thanleptomycin. SL-801’s ability to more reversibly bind XPO1 offers the potential to develop flexible dosing schedules that could enable recovery in normaltissues, mitigate side effects, broaden the therapeutic index, and enhance efficacy. We recently opened an IND for SL-801 and are advancing SL-801 into corporate sponsored Phase 1 disease-directed, proof-of-concept trials initially inadvanced solid cancers and potentially, in the future, hematologic cancers. Patents and Proprietary Rights Our intellectual property portfolio consists of 36 issued patents and over 45 pending applications in the U.S. and worldwide of both in-licensed andStemline-originated inventions. Patents and Proprietary Rights Covering Stemline’s Drug Candidates We have an exclusive worldwide license to SL-401. These patent rights include issued U.S. Patents 8,470,307, 7,763,242 and 9,181,317 covering methods oftreating AML, BPDCN and MDS that expire in 2027, as well as two issued and two allowed foreign patents. There are additional pending U.S. applicationsdirected to methods of using SL-401 to treat other diseases that, if issued, would also expire in 2027. In addition, we have filed foreign patent applications forthe method of using SL- 401 to treat various diseases, although there can be no assurances that such patents will be issued. In addition to patent protection,we also have the exclusivity afforded by the FDA’s orphan designation of SL-401 for the treatment of both AML and BPDCN and by the provisions of theBiologics Price Competition and Innovation Act of 2009. See “Government Regulation — Orphan Drug Designation” and “— U.S. Patent Term Restorationand Marketing Exclusivity—Biologics Price Competition and Innovation Act of 2009.” We have an exclusive worldwide license to SL-701 component, IL-13Rα2 mutant, a non-exclusive worldwide license to SL-701 component, EphA2, andhave filed U.S. and foreign patent applications to SL-701 component, survivin mutant. This intellectual property consists of an issued U.S. composition ofmatter patent (U.S. Patent 7,612,162) directed to an immunogenic mutant IL-13Rα2 peptide expiring in 2026, issued U.S. method of use patents (U.S. Patents7,297,337 and 8,114,407) directed to the use of EphA2 peptide expiring in 2025 and 2026, issued U.S. method of use patent (U.S. Patent 8,859,488) directedto the combined use of IL-13Rα2 mutant and EphA2 peptides expiring in 2026, and pending U.S. and foreign patent applications directed to the use of animmunogenic mutant survivin peptide which, to the extent it issues, would be expected to expire in 2033. We also have additional pending patentapplications directed to methods of using SL-701 components to treat certain diseases which if issued, for which there can be no guarantee, would provideadditional protection in the United States and certain non-U.S. territories and would expire in 2025, 2031, or 2033. In addition to patent protection, we alsohave the exclusivity afforded by the FDA’s orphan designation of SL-701 for the treatment of glioma and by the provisions of the Biologics PriceCompetition and Innovation Act of 2009. See “Government Regulation — Orphan Drug Designation” and “— U.S. Patent Term Restoration and MarketingExclusivity—Biologics Price Competition and Innovation Act of 2009”. We have an exclusive worldwide license (with the exception of Japan, Korea, Taiwan, and China) to SL-801. These patent rights include issued U.S. Patents8,084,454 and U.S. Patent 8,415,357 covering composition of matter and uses of SL-801 that expire in 1250Table of Contents 2030 and 2028, respectively, as well as six issued and three allowed foreign patents that expire in 2028. We also have additional pending patent applicationsdirected to SL-801 which if issued, for which there can be no guarantee, would provide additional protection in certain non-U.S. territories and would expirein 2028. We also in-licensed or own certain patent rights, which includes issued patents and pending patent applications in the U.S. and abroad, to our preclinicalassets. Patents and Proprietary Rights Covering Cancer Stem Cell, or CSC, Focused Intellectual Property We have exclusive worldwide rights to early and broad patents and patent applications in the CSC field covering CSC therapeutics, diagnostics, includingcompanion diagnostics, and drug discovery: · A therapeutic patent (U.S. Patent 8,038,998) that covers a method to treat cancer through use of monoclonal antibodies and other antibody-basedcompounds that target CSCs, and related pending applications that cover methods to treat cancer through use of small molecule or oligonucleotide-based compounds that target CSCs. Patent protection for these patent families extends from 2017 or 2019, as applicable; · A diagnostic patent (U.S. Patent 6,004,528), and related pending applications, that covers the diagnosis of cancer through detection of CSCs. Patentprotection extends from 2017 or 2019, as applicable; · Seven issued patents that cover methods to treat cancer through use of monoclonal antibodies and other antibody-based compounds directed to ninespecific key targets: Frizzled, Glypican-3, Tie-1, CD133, Smoothened, Patched, CD44, ESA, and 67LR. These U.S. Patents are: 7,361,336; 7,427,400;7,504,103; 7,608,259; 8,715,945; 8,846,325; and 8,784,772. Patent protection extends from 2017, 2019, or 2032, as applicable; · Two pending U.S. patent applications filed in 2006 directed to CSC-directed therapies and regimens, including CSC-directed therapies and regimens foruse in combination with companion diagnostics. Patent protection, to the extent it issues, would be expected to extend to 2027; · A pending patent application that covers oligonucleotide-based oncology therapies, including CSC-targeted therapeutics, which target microRNA.Patent protection, to the extent it issues, would be expected to extend to 2022; · A family of intellectual property covering methods to treat cancer through use of antibody-based compounds directed to IL-3Rα as well as compositionof matter covering IL-3Rα-targeted antibody conjugates, including U.S. Patent 7,651,678; U.S. Patent 6,733,743; U.S. Patent 8,163,279; U.S. Patent8,852,551; U.S. Patent 8,992,910; and other pending applications. Patent protection, to the extent it has or may issue, would be expected to extend to2021 or 2028, as applicable; and · Pending patent applications covering CSC-focused drug discovery, including a novel high throughput screen to discover compounds that target CSCs.Patent protection, to the extent it issues, would be expected to extend to 2025. Intellectual Property Strategy We continually assess our intellectual property strategy in order to fortify our position in our market space. To that end, we are prepared to file additionalpatent applications in any of the above families should our intellectual property strategy require such filings and/or where we seek to adapt to competition orseize business opportunities. Further, we are prepared to file patent applications relating to the other products in our pipeline soon after the experimental datanecessary for a strong application become available and our cost-benefit analyses justify filing such applications. In addition to filing and prosecuting patent applications in the United States, we typically file counterpart patent applications in Europe, Canada, Japan,Australia, and additional countries where we think such foreign filing is likely to be beneficial. We do not know if patents will be issued for all of the patent applications in our portfolio. Furthermore, for patent claims now issued and for claims to beissued in the future, we do not know if such claims will provide significant proprietary protection to our drug candidates and proprietary technologies or ifthey will be challenged, circumvented, or invalidated. Our success will in part depend on our ability to obtain and maintain patents protecting our drugcandidates, technologies and inventions, to operate without infringing the proprietary rights of third-parties, and to enforce and defend our patents andensure others do not infringe on our proprietary rights. The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained. In most countries in which we file, thepatent term is 20 years from the earliest date of filing a non-provisional patent application. In the United States, a patent’s term may be shortened if a patent isterminally disclaimed over another patent or as a result of delays in patent prosecution by 13Table of Contents the patentee, and a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S. Patentand Trademark Office in granting a patent. The term of a patent that covers an FDA-approved drug or biologic may also be eligible for patent term extension, which permits patent term restoration ascompensation for the patent term lost during the FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act of 1984, or theHatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration of the patent. The length of the patent term extension is relatedto the length of time the drug or biologic is under regulatory review. Patent extension cannot extend the remaining term of a patent beyond a total of 14 yearsfrom the date of product approval and only one patent applicable to an approved drug or biologic may be extended. Similar provisions are available inEurope and other foreign jurisdictions to extend the term of a patent that covers an approved drug or biologic. In the future, if and when our pharmaceuticalproducts receive FDA approval, we expect to apply for patent term extensions on patents covering those products. We anticipate that some of our issuedpatents may be eligible for patent term extensions. For more information regarding U.S. patent laws, see “Business — Government Regulation.” In addition to the patent term extension rights described above, any of our product candidates that receive FDA approval may also be eligible for marketexclusivity protection under the Federal Food, Drug and Cosmetic Act or the Biologics Price Competition and Innovation Act of 2009. For more informationregarding market exclusivity laws, see “Business — Government Regulation.” Many pharmaceutical companies, biotechnology companies and academic institutions are competing with us in the field of oncology and filing patentapplications potentially relevant to our business. In order to contend with the inevitable possibility of third-party intellectual property conflicts, from time totime, we review and assess the third-party intellectual property landscape for competitive and other developments that may inform or impact our intellectualproperty development and commercialization strategies. From time to time, we may find it necessary or prudent to obtain licenses from third-party intellectual property holders. Where licenses are readily available atreasonable cost, such licenses are considered a normal cost of doing business. In other instances, however, where a third-party holds relevant intellectualproperty and is a direct competitor, a license might not be available on commercially reasonable terms or available at all. Accordingly, we attempt to managethe risk that such third-party intellectual property may pose by conducting, among other measures, freedom-to-operate studies to guide our early-stageresearch away from areas where we are likely to encounter obstacles in the form of third-party intellectual property. As our programs advance, we continue tomonitor the intellectual property landscape in an effort to assess the advisability of licensing third-party intellectual property or taking other appropriatesteps to address such freedom-to-operate or development issues in the manner we deem in the best interests of the Company. With respect to third-party intellectual property, it is impossible to establish with certainty that our product candidates or discovery platform will be free ofclaims by third-party intellectual property holders or whether we will require licenses from such third-parties. Even with modern databases and on-line searchengines, literature searches are imperfect and may fail to identify relevant patents and published applications. Even when a third-party patent is identified, wemay conclude upon a thorough analysis, that we do not infringe the patent or that the patent is invalid. If the third-party patent owner disagrees with ourconclusion and we continue with the business activity in question, we might face patent litigation by the third-party. Alternatively, we might decide toinitiate litigation in an attempt to have a court declare the third-party patent invalid or not infringed by our activity. In either scenario, patent litigationtypically is costly and time-consuming, and the outcome is uncertain. The outcome of patent litigation is subject to uncertainties that cannot be quantified inadvance, for example, the credibility of expert witnesses who may disagree on technical interpretation of scientific data. Ultimately, in the case of an adverseoutcome in litigation, we could be prevented from commercializing a product or using certain aspects of our discovery platform as a result of patentinfringement claims asserted against us and/or face a significant monetary damages award. This could have a material adverse effect on our business. To protect our competitive position, it may be necessary to enforce our patent rights through litigation against infringing third-parties. Litigation to enforceour own patent rights is subject to the same uncertainties discussed above. In addition, however, litigation involving our patents carries the risk that one ormore of our patents will be held invalid (in whole or in part, on a claim-by-claim basis) or held unenforceable. Such an adverse court ruling could allow third-parties to commercialize our products or our platform technology, and then compete directly with us, without payment to us. 14Table of Contents License and Research Agreements Scott and White Memorial Hospital Research and License Agreement (SL-401) In June 2006, we entered into a research and license agreement with Scott and White Memorial Hospital (Temple, Texas) for SL-401, our biologic targetedtherapy directed to the IL-3R. Under the agreement, Scott and White has granted us an exclusive, royalty-bearing, worldwide license under certain patentrights, know-how and materials to research, develop, make, have made, formulate, use, sell, offer to sell and import SL-401, and any products containing orcomprising such compound in finished dosage pharmaceutical form, for the diagnosis, prophylaxis and/or treatment of any disease or condition in humans oranimals. The patent rights exclusively licensed to us under the agreement are described in more detail above under “Business — Patents and ProprietaryRights.” We must pay Scott and White royalties based on adjusted gross sales, by us or our sublicensees, of products containing the licensed compound for a period often years following the first commercial sale of each product in each country. The royalty rates for each product range from the low- to mid-single digits andare tiered based on our annual sales. We have sublicensing rights under the agreement, subject to our paying to Scott and White a percentage of the up-frontpayments we receive from a sublicensee. We must exercise commercially reasonable efforts to develop and commercialize a licensed product and to achieve certain regulatory milestones withincertain periods, subject to extensions based on unforeseen technical, scientific, intellectual property or regulatory issues. If we fail to comply with ourdiligence obligations with respect to at least one licensed product, then Scott and White may convert our exclusive license to a non-exclusive license. The agreement survives until the later of the expiration of the last to expire licensed patent or the date on which we owe no further payments to Scott andWhite, after which our license becomes fully paid, irrevocable, perpetual, non-exclusive and royalty-free. We may terminate the license in whole or on acountry-by-country and product-by-product basis upon prior written notice to Scott and White. If either we or Scott and White breach a material obligationunder the agreement, and such obligation is not cured within a specified period of time following written notice from the other party, then the non-breachingparty may terminate the agreement upon an additional written notice. In addition, the agreement provides for Scott and White to conduct a research program with SL-401. In March 2010, the agreement was amended to furtherthe regulatory advancement of SL-401. We have made certain payments to Scott and White for such research services pursuant to the agreement, which todate total approximately $1.0 million in the aggregate. Additionally, we have been granted the exclusive right of reference to its IND for our own regulatoryfilings. We may assign the agreement to an affiliate of ours, a purchaser of all or substantially all of our assets or in connection with a merger, change incontrol or similar transaction by us. University of Pittsburgh Exclusive License Agreement to IL-13Rα2 peptide (SL-701 component) In September 2009, we entered into an exclusive license agreement with the University of Pittsburgh, or the University, for the composition of matter, and usewith other components, of a proprietary immunogenic mutant analog peptide of IL-13Rα2, an active ingredient of SL-701, our brain cancer immunotherapycandidate. Under the agreement, the University grants us an exclusive worldwide license under certain patent rights to make, have made, use, sell and importbrain cancer peptide antigen immunotherapies (including SL-701, which has been developed by the University under a separate immunotherapy namedesignated by the University). The patent rights exclusively licensed to us under the agreement are described in more detail above under “Business —Patents and Proprietary Rights.” The University retains the right to practice the licensed patent rights for non-commercial education and research purposes.The license is also subject to certain retained rights of the United States government. Our right to grant sublicenses to third parties is subject to the priorwritten approval of the University, which the University may not unreasonably withhold or delay. We paid the University an initial license fee and will pay the University annual license maintenance fees until the first commercial sale of a licensed product.To date, we have paid an aggregate of approximately $0.6 million in fees to the University under the agreement. We must also pay the University a low-single digit royalty as a percentage of net sales of licensed products by us or our sublicensees, with standard provisions for royalty offsets to the extent weneed to obtain any rights from third-parties to commercialize the licensed products. We must also pay a minimum annual royalty following the firstcommercial sale of a licensed product, but only to the extent the minimum annual royalty amount is greater than the annual royalty otherwise due. We alsomust pay the University a percentage of non-royalty revenue we receive from our sublicensees, which decreases if we enter into the applicable sublicenseagreement after a certain clinical milestone has been met. We also must make certain payments to the University of up to approximately $4.2 million uponthe achievement of specific regulatory and commercial milestone events. 15Table of Contents We must use our commercially reasonable best efforts to develop or commercialize a licensed product as soon as practicable, and to continue active, diligentmarketing efforts throughout the term of the agreement. We also must adhere to certain specific regulatory milestones with respect to initiating clinical trialsand submitting an application for regulatory approval of a licensed product. If we fail to meet any such milestone through no fault of our own, we maynegotiate with the University a one-time extension of the applicable dates, subject to paying the University a fee. If we do not meet the extended milestonedates, then the University may terminate the agreement. The agreement survives until the expiration of the last to expire licensed patent. The University may terminate the agreement if we default in the performanceof any of our obligations and do not cure the default within a specified period of time after receiving notice from the University, or if we challenge thevalidity, enforceability or ownership of the license patent rights anywhere in the world. The University may also terminate the agreement if we cease to carryout our business or become bankrupt or insolvent. We may terminate the agreement for any reason upon prior written notice to the University and payment ofall amounts due to the University through the date of termination. Any sublicense agreement entered into prior to termination will survive, subject to certaincustomary conditions. We may assign the agreement to an affiliate of ours, a purchaser of all or substantially all of our assets or in connection with a merger,change in control or similar transaction by us. Non-Exclusive License Agreement to EphA2 peptide (SL-701 component) In March 2012, we entered into a non-exclusive license agreement with the University for the use of EphA2 epitopes, another active ingredient of SL-701.Under the agreement, the University grants us a non-exclusive worldwide license under certain patent rights to use the EphA2 peptide in or packaged withthe IL-13Rα2 peptide, as well as other immunotherapies we may develop and own or exclusively control, for the diagnosis, treatment or prevention ofdiseases and tumors of the brain in human patients. The patent rights licensed to us under the agreement are described in more detail above under“Business — Patents and Proprietary Rights.” The University retains the right to practice the licensed patent rights for non-commercial education andresearch purposes. The license grant is also subject to certain retained rights of the United States government. We may only grant sublicenses to third partieswho are permitted sublicensees under the exclusive IL-13Rα2 peptide license agreement with the University. We must pay the University an initial license fee, and will pay the University annual license maintenance fees until the net sales of a licensed product exceeda specified amount. To date, we have paid an aggregate of approximately $50,000 in fees to the University under the agreement. We must also pay theUniversity a customary low-single digit royalty for the license as a percentage of net sales of licensed products by us or our sublicensees, with standardprovisions for royalty offsets to the extent we need to obtain any rights from third-parties to commercialize the licensed products. We must also pay aminimum annual royalty following the first commercial sale of a licensed product, but only to the extent the minimum annual royalty amount is greater thanthe annual royalty otherwise due. We must use our commercially reasonable best efforts to develop or commercialize a licensed product as soon as practicable, and to continue active, diligentmarketing efforts throughout the term of the agreement. We also must adhere to certain specific regulatory milestones with respect to initiating clinical trialsand submitting an application for regulatory approval of a licensed product. If we fail to meet any such milestone by certain specified dates, then theUniversity may terminate the agreement. The agreement survives until the expiration of the last to expire licensed patent. The University may terminate the agreement if we default in the performanceof any of our obligations and do not cure the default within a specified time period of receiving notice from the University. The University may alsoterminate the agreement if we cease to carry out our business or become bankrupt or insolvent. We may terminate the agreement for any reason upon priorwritten notice to the University and payment of all amounts due to the University through the date of termination. Any sublicense agreement entered intoprior to termination will survive, subject to certain customary conditions. We may assign the agreement to an affiliate of ours, a purchaser of all orsubstantially all of our assets or in connection with a merger, change in control or similar transaction by us. Non-Exclusive License Agreement to use and reference certain data, information and regulatory filings (SL-701) In March 2012, we entered into a non-exclusive license agreement with the University. Pursuant to the agreement, we acquired a non-exclusive, worldwidelicense to use and reference certain know-how, information and data that is contained in the INDs covering the clinical trials of SL-701 that were conductedby the University for the development, manufacture, regulatory approval and commercialization of pharmaceutical products. We may grant sublicenses inconjunction with a sublicense to a permitted sublicensee under the exclusive IL-13Rα2 peptide license agreement with the University. We paid the University an initial license fee, as well as payments following a regulatory milestone. To date, we have paid an aggregate of approximately$27,500 in fees to the University under the agreement. We also must pay the University a percentage of non-royalty revenue we receive from oursublicensees. We must use our commercially reasonable best efforts to develop or commercialize a product derived from the use of the licensed data orinformation as soon as practicable. We also must adhere to a 16Table of Contents specific regulatory milestone with respect to submitting an application for regulatory approval that incorporates the licensed data or information, and if wefail to meet the milestone, the University may terminate the agreement unless we have pre-paid the milestone payment listed above. The term of the license agreement is 20 years, and the University may terminate the agreement earlier (i) if we default in the performance of any of ourobligations and do not cure the default within a specified time period, (ii) upon the termination of the exclusive IL-13Rα2 peptide license agreement with theUniversity, or (iii) if we cease to carry out our business or become bankrupt or insolvent. We may terminate the agreement at any time prior to incorporatingor referencing the data or University INDs, after a specified number of days following written notice. We may assign the agreement to an affiliate of ours, apurchaser of all or substantially all of our assets or in connection with a merger, change in control or similar transaction by us. Cambridge University Technical Services Limited Exclusive Patent and Non-Exclusive Know-How License Agreement (Platform Technology) In September 2004, we entered into a license agreement with Cambridge University Technical Services Limited, or CUTS, relating to ourStemScreen platform technology. Under the agreement, we acquired an exclusive, royalty-bearing, worldwide license under patent rights owned by CUTS todevelop, manufacture, have manufactured, use, sell, offer to sell, market, have marketed, import, have imported, export and have exported products coveredby the patent rights, including a platform technology to discover and screen for compounds that target CSCs. The patent rights exclusively licensed to usunder the agreement are described in more detail above under “Business — Patents and Proprietary Rights.” The license is subject to certain rights retainedby CUTS for academic research and teaching. We also acquired a non-exclusive, worldwide license to know-how related to the licensed patent rights. Theagreement provides us with full sublicensing rights. Under the agreement, we paid an upfront license fee and are obligated to make milestone payments of upto an aggregate of $1.7 million upon specified regulatory events, as well as pay royalties of less than 1% on sales of licensed products. CUTS may terminatethe agreement, including our rights to the platform technology, for specified cause or upon certain events involving our bankruptcy or insolvency. CanBas, Ltd License for SL-801 On December 26, 2014, we entered into a license agreement with CanBas, Ltd. for SL-801. SL-801 is a small molecule, reversible inhibitor of XPO1. Underthe terms of the agreement, CanBas has granted us an exclusive, royalty-bearing, worldwide (excluding Japan, Korea, China and Taiwan) license, undercertain patent rights, know-how and materials to research, develop, make, have made, formulate, use, sell, offer to sell and import SL-801, and any productscontaining or comprising such compound in finished dosage pharmaceutical form, for the treatment of any disease or condition in humans. The patent rightsexclusively licensed to us under the agreement are described in more detail above under “Patents and Proprietary Rights Covering Stemline’s DrugCandidates.” We are responsible to pay annual technical advisory fees over the next three years totaling 330 million Japanese Yen (JPY), if the clinical developmentcontinues over this time period. Additionally, we must pay CanBas tiered royalties based on aggregate net sales, by us or our sublicensees, of productscontaining the licensed compound until the latest date of a period of ten years following the first commercial sale of each product in each country; the dateupon which there are no more valid claims or the expiration or termination of the last regulatory exclusivity period. The royalty rates start in the low singledigits and are tiered up based on annual net sales. In the future, we may also be responsible, based on the achievement of specific clinical-development,regulatory and sales-based commercial milestones, for certain payments to CanBas of up to $86 million. We have sublicensing rights under the agreement,subject to our paying to CanBas a standard royalty percentage of the payments we receive from a sublicensee. We must exercise commercially reasonable efforts to develop and commercialize a licensed product and to achieve certain regulatory milestones withincertain periods, subject to extensions based on unforeseen technical, scientific, intellectual property or regulatory issues. The agreement survives until the later of ten years following the first commercial sale of each product in each country; the date upon which there are no morevalid claims; or the expiration or termination of the last regulatory exclusivity period, after which our license becomes fully paid, irrevocable, perpetual, non-exclusive and royalty-free. We may terminate the license for any or no reason upon 60 days advance written notice to CanBas. If either we or CanBas breach amaterial obligation under the agreement, and such obligation is not cured within a specified period of time following written notice from the other party, thenthe non-breaching party may terminate the agreement upon an additional written notice. 17®Table of Contents Competition The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis onproprietary products. While we believe that our scientific knowledge, technology, and development experience provide us with competitive advantages, weface potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academicinstitutions, governmental agencies and public and private research institutions. Any product candidates that we successfully develop and commercializewill compete with existing therapies and new therapies that may become available in the future. There are several biopharmaceutical companies whose primary focus appears to be developing therapies against CSCs, including Verastem, Inc., OncoMedPharmaceuticals, Inc., Sumitomo Dainippon Pharma Co. Ltd., Bionomics Limited and Stemcentrx, Inc. There are also several biopharmaceutical companiesthat do not appear to be primarily focused on CSCs, but may be developing at least one CSC-directed compound. These companies include Astellas PharmaUS, Inc., Boehringer Ingelheim GmbH, Geron Corp., GlaxoSmithKline plc, Ignyta, Inc., Macrogenics Inc., Micromet, Inc. (an Amgen, Inc. company),Pfizer Inc., Roche Holding AG, Sanofi U.S. LLC, and others. Additionally, there are a number of companies working to develop new treatments forhematologic cancers, which may compete with SL-401 and SL-801, including AbbVie, Inc., Ambit Biosciences Corporation (now a Daiichi Sankyocompany), Amgen, Inc., Astex Pharmaceuticals (now an Otsuka Pharmaceutical company), Celator Pharmaceuticals, Inc., Celgene Corporation, Cellectis,Cyclacel Pharmaceuticals, Inc., Eisai Co. Ltd., Genzyme Corporation (now a Sanofi company), Immunogen, Inc., Janssen Pharmaceutical Companies ofJohnson and Johnson, Karyopharm Therapeutics, Inc., Novartis AG, Seattle Genetics, Inc., and Sunesis Pharmaceuticals, Inc., among others. There are also anumber of drugs used for the treatment of brain cancer that may compete with SL-701, including, Avastin (Roche Holding AG), Gliadel (Eisai Co. Ltd.),and Temodar (Merck & Co., Inc.). There are a number of companies working to develop brain cancer therapeutics with programs in clinical testing,including Agenus Inc., Bristol-Myers Squibb, Inc., Cortice Biosciences, Inc., Celldex Therapeutics, Inc., CytRx Corporation, GenSpera, Inc.,GlaxoSmithKline plc., ImmunoCellular Therapeutics, Ltd., Northwest Biotherapeutics, Inc., Novartis AG, Roche Holding AG and others. Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing,conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical,biotechnology and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. Thesecompetitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patientregistration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Small or early-stage companies may alsoprove to be significant competitors, particularly through collaborative arrangements with large and established companies. The key competitive factors affecting the success of all of our product candidates, if approved, are likely to be their efficacy, safety, convenience, price, thelevel of generic competition and the availability of reimbursement from government and other third-party payors. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have feweror less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA or otherregulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong marketposition before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or other third-party payorsseeking to encourage the use of generic products. If our therapeutic product candidates are approved, we expect that they will be priced at a significantpremium over any competitive generic products. The most common methods of treating patients with cancer are surgery, radiation and drug therapy, including chemotherapy, hormone therapy and targeteddrug therapy. These therapies are numerous and varied in their design, therapeutic application and mechanism of action. As a result, they may providesignificant competition for any of our product candidates for which we obtain market approval. In addition to currently marketed oncology therapies, thereare also a number of products in late stage clinical development to treat cancer. These products in development may provide efficacy, safety, convenienceand other benefits that are not provided by currently marketed therapies. As a result, they may provide significant competition for any of our productcandidates for which we obtain market approval. Competition for SL-401 There are a number of companies working to develop new treatments for AML and other hematologic cancers, including Agios, Inc., Ambit BiosciencesCorporation (now a Daiichi Sankyo company), Astex Pharmaceuticals (now an Otsuka Pharmaceutical company), Boehringer Ingelheim, CelatorPharmaceuticals, Inc., Celgene Corporation, Cellectis, Cyclacel Pharmaceuticals, Inc., Eisai Co. Ltd., 18®®®Table of Contents Epizyme, Inc., Genzyme Corporation (now a Sanofi company), Immunogen, Inc., Janssen Pharmaceutical Companies of Johnson and Johnson, SeattleGenetics, Inc., and Sunesis Pharmaceuticals, Inc., among others. Competition for SL-701 There are a limited number of drugs used for the treatment of brain cancer, including Temodar (Merck & Co., Inc.), nitrosoureas includingGliadel (Eisai Co., Inc.), and Avastin (Roche Holding AG). There are a number of companies working to develop brain cancer therapeutics with programsin clinical testing including Agenus Inc., Bristol-Myers Squibb, Inc., Cortice Biosciences, Inc., Celldex Therapeutics, Inc., CytRx Corporation,GenSpera, Inc., GlaxoSmithKline plc., ImmunoCellular Therapeutics, Ltd., Northwest Biotherapeutics, Inc., Novartis AG, Roche Holding AG and others. Competition for SL-801 Karyopharm Therapeutics is the only company, to our knowledge, that currently has an XPO1 inhibitor in clinical development. Karyopharm’s selinexor isbeing evaluated in a number of clinical trials in both solid and hematologic cancers, with the most advanced clinical programs in AML, multiple myelomaand diffuse Large B-Cell lymphoma, or DLBCL. Government Regulation Government authorities in the United States, at the federal, state and local level, and in other countries extensively regulate, among other things, the research,development, approval, manufacture, testing, quality control, packaging, labeling, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of products such as those we are developing. Any pharmaceutical candidate that wedevelop must be approved by the FDA before it may be legally marketed in the United States or by the appropriate foreign regulatory agency before it may belegally marketed in foreign countries. United States Drug Development Process In the United States, the FDA regulates drugs under the Federal Food, Drug and Cosmetic Act, or FDCA, and implementing regulations. Drugs are also subjectto other federal, state and local statutes and regulations. Biologics are subject to regulation by the FDA under the FDCA, the Public Health Service Act, or thePHSA, and related regulations, and other federal, state and local statutes and regulations. Biological products include, among other things, viruses,therapeutic serums, vaccines and most protein products. The process of obtaining regulatory approvals and the subsequent compliance with appropriatefederal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. Failure to comply with theapplicable United States requirements at any time during the product development process, approval process or after approval, may subject an applicant toadministrative or judicial sanctions. FDA sanctions could include a clinical hold, refusal to approve pending applications, warning or untitled letters, productrecalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution,disgorgement of profits, civil or criminal penalties, or withdrawal of an approval. Any administrative action or judicial enforcement action could have amaterial adverse effect on us. The process required by the FDA before a drug or biological product may be marketed in the United States generally involves the following: · Completion of preclinical laboratory tests, animal studies and formulation studies according to Good Laboratory Practices or other applicableregulations; · Submission to the FDA of an Investigational New Drug Application, or an IND, which FDA must clear before human clinical trials may begin; · Performance of adequate and well-controlled human clinical trials according to the FDA’s current Good Clinical Practices, or GCPs, and inaccordance with human subject protection regulations, to establish the safety and efficacy of the proposed drug or biologic for its intended use; · Submission to the FDA of a New Drug Application, or an NDA, for a new drug product, or a Biologics License Application, or a BLA, for a newbiological product; · Satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug or biologic is to beproduced to assess compliance with the FDA’s current good manufacturing practice regulations, or cGMPs, to assure that the facilities, methodsand controls are adequate to preserve the drug’s or biologic’s identity, strength, quality and purity; · Potential FDA inspection of the nonclinical and clinical trial sites that generated the data in support of the NDA or BLA; and 19®®®Table of Contents · FDA review and approval of the NDA or BLA and successful resolution of any questions that arise in the review process. The lengthy process of seeking required approvals and the continuing need for compliance with applicable statutes and regulations post-approval require theexpenditure of substantial resources. There can be no certainty that approvals will be granted. Before testing any compounds with potential therapeutic value in humans, the drug or biological candidate enters the preclinical testing stage. Preclinicaltests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of thedrug or biological candidate. The conduct of the preclinical tests must comply with federal regulations and requirements including good laboratorypractices. The sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data orliterature and a proposed clinical protocol, to the FDA as part of the IND. The IND automatically becomes effective 30 days after receipt by the FDA, unlessthe FDA places the clinical trial on a clinical hold within that 30-day time period. In such a case, the IND sponsor and the FDA must resolve any outstandingconcerns before the clinical trial can begin. The FDA may also impose clinical holds on a drug or biological candidate at any time before or during clinicaltrials due to safety concerns or non-compliance. Accordingly, we cannot assure that submission of an IND will result in the FDA allowing clinical trials tobegin, or that, once begun, issues will not arise that suspend or terminate such trial. Clinical trials involve the administration of the drug or biological candidate to healthy volunteers or patients having the disease being studied under thesupervision of qualified investigators; often these are physicians not employed by or under the trial sponsor’s control. Clinical trials are conducted underprotocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters tobe used to monitor subject safety. Each protocol must be submitted to the FDA as part of the IND. Clinical trials must be conducted in accordance with theFDA’s good clinical practices requirements, regulations for the protection of human subjects and with applicable cGMP requirements. Further, each clinicaltrial must be reviewed and approved by an independent institutional review board, or IRB, at or servicing each institution at which the clinical trial will beconducted. An IRB is charged with protecting the welfare and rights of trial participants and considers such items as whether the risks to individualsparticipating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves trial recruitment materials andthe informed consent form that must be used as part of the informed consent process with each clinical trial subject or his or her legal representative and mustmonitor the clinical trial until it is completed. Human clinical trials prior to approval are typically conducted in three sequential Phases that may overlap or be combined: · Phase 1. The drug or biologic is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption,metabolism, distribution and excretion. In the case of some products for severe or life-threatening diseases, especially when the product may betoo inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients having the specificdisease. · Phase 2. The drug or biologic is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarilyevaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule forpatients having the specific disease. · Phase 3. Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population atgeographically dispersed clinical trial sites. These clinical trials, which usually involve more subjects than earlier trials, are intended toestablish the overall risk/benefit ratio of the product and provide an adequate basis for product labeling. Generally, at least two adequate andwell-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA or BLA. Post-approval studies, or Phase 4 clinical trials, may be conducted after initial marketing approval. These studies are used to gain additional experience fromthe treatment of patients in the intended therapeutic indication and may be required by the FDA as part of the approval process. Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and written IND safety reports must be submitted tothe FDA by the investigators for serious and unexpected adverse events or any finding from tests in laboratory animals that suggests a significant risk forhuman subjects. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all. The FDA or the sponsoror its data safety monitoring board may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients arebeing exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is notbeing conducted in accordance with the IRB’s requirements or if the drug or biologic has been associated with unexpected serious harm to patients. 20Table of Contents Concurrent with clinical trials, companies usually complete additional animal studies and develop additional information about the chemistry and physicalcharacteristics of the drug or biologic as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMPrequirements. The manufacturing process must be capable of consistently producing quality batches of the drug or biological candidate. In addition,companies must develop and validate analytical methods for testing the identity, strength, quality and purity of raw materials, in-process material and thefinal drug or biologic. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the drugor biological candidate does not undergo unacceptable deterioration over its shelf life. U.S. Review and Approval Processes The results of product development, preclinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted onthe drug or biologic, proposed packaging and labeling and other relevant information are submitted to the FDA as part of an NDA or BLA requestingapproval to market the product. The submission of an NDA or BLA is subject to the payment of substantial user fees; a waiver of such fees may be obtainedunder certain limited circumstances. We believe that we will be required to submit BLAs for SL-401 and SL-701, and to submit an NDA for SL-801. In addition, under the Pediatric Research Equity Act, or PREA, an NDA or a BLA, or supplement to an NDA or a BLA, that covers a new active ingredient,new indication, new dosage form, new dosing regimen, or new route of administration must contain data to assess the safety and effectiveness of the drug orbiologic for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation forwhich the product is safe and effective. The FDA may grant deferrals for submission of pediatric data or full or partial waivers. PREA does not apply to anydrug or biologic for an indication for which orphan designation has been granted unless FDA were to issue a regulation to require pediatric assessments. The FDA reviews all NDAs and BLAs submitted before it accepts them for filing and may request additional information rather than accepting an NDA orBLA for filing. Once the submission is accepted for filing, the FDA begins an in-depth review of the NDA or BLA. Under the goals and policies agreed to bythe FDA under the Prescription Drug User Fee Act, or PDUFA, the FDA has established a performance goal of ten months in which to complete its initialreview of a standard NDA or BLA and respond to the applicant, and a performance goal of six months for a priority NDA or BLA. The FDA does not alwaysmeet its PDUFA goal dates for standard and priority NDAs and BLAs. After the NDA or BLA submission is accepted for filing, the FDA reviews the NDA to determine, among other things, whether the proposed product is safeand effective for its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity,strength, quality and purity. The FDA reviews a BLA to determine, among other things, whether the product is safe, pure and potent and the facility in whichit is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, purity and potency. In addition to its ownreview, the FDA may refer applications for novel drug or biological products or drug or biological products which present difficult questions of safety orefficacy to an advisory committee, typically a panel that includes clinicians and other experts in the disease area, for review, evaluation and arecommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisorycommittee, but it considers such recommendations carefully when making decisions. On September 27, 2007, the Food and Drug AdministrationAmendments Act of 2007 was enacted, giving the FDA enhanced post-market authority, including the authority to require post-marketing studies and post-marketing clinical trials related to serious risks, labeling changes based on new safety information, and compliance with risk evaluation and mitigationstrategies, or REMS, approved by the FDA. The FDA’s exercise of this authority can result in delays or increased costs during the period of productdevelopment, clinical trials and regulatory review and approval, which may also increase costs related to complying with new post-approval regulatoryrequirements, and increase potential FDA restrictions on the sale or distribution of approved products. During the approval process, the FDA will determinewhether a REMS is necessary to assure the safe use of the drug or biologic post-approval. If the FDA concludes that a REMS is needed, the sponsor of theNDA or BLA must submit a proposed REMS; the FDA will not approve the NDA or BLA without a REMS, if required. Before approving an NDA or BLA, the FDA will inspect the facilities at which the product is to be manufactured. The FDA will not approve the productunless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent productionof the product within required specifications. Also, in this inspection, FDA seeks to determine whether the manufacturing conforms with applicationcommitments, the authenticity and accuracy of data, and the adequacy of the company’s analytical methodology. Additionally, before approving an NDA orBLA, the FDA will typically inspect one or more clinical sites to assure compliance with current good clinical practices, or cGCPs. If the FDA determines theapplication, data, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies in the submission and often willrequest additional testing or information. 21Table of Contents The NDA or BLA review and approval process is lengthy and difficult and the FDA may refuse to approve an NDA or BLA if the applicable regulatory criteriaare not satisfied or the agency requires additional clinical data or other data and information. Even if such data and information is submitted, the FDA mayultimately decide that the NDA or BLA does not satisfy the criteria for approval. Data obtained from clinical trials are not always conclusive and may besusceptible to varying interpretations, which could delay, limit or prevent regulatory approval. In addition, protocol deviations or data discrepancies coulddelay, limit or prevent regulatory approval. The FDA will issue a “complete response” letter if the agency decides not to approve the NDA or BLA. Thecomplete response letter usually describes all of the specific deficiencies in the NDA or BLA identified by the FDA. The deficiencies identified may be minor,for example, requiring labeling changes, or major, for example, requiring additional clinical trials. Additionally, the complete response letter may include recommended actions that the applicant might take to place the application in a condition forapproval. If a complete response letter is issued, the applicant may either resubmit the NDA or BLA, addressing all of the deficiencies identified in the letter,or withdraw the application. If a product receives regulatory approval, the approval may be limited to specific diseases and dosages or the indications for use may otherwise be limited,which could restrict the commercial value of the product. Further, the FDA may require that certain contraindications, warnings or precautions be included inthe product labeling. In addition, the FDA may require Phase 4 testing which involves clinical trials designed to further assess a product’s safety andeffectiveness and may require testing and surveillance programs to monitor the safety of approved products that have been commercialized. Orphan Drug Designation Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which isgenerally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States andfor which there is no reasonable expectation that the cost of developing and making a drug or biological product available in the United States for this typeof disease or condition will be recovered from sales of the product. Orphan product designation must be requested before submitting an NDA or BLA. Afterthe FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphanproduct designation does not convey any advantage in or shorten the duration of the regulatory review and approval process. If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, theproduct is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug or biologicalproduct for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphanexclusivity. Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtainapproval for the same product but for a different indication for which the orphan product has exclusivity. Orphan product exclusivity also could block theapproval of one of our products for seven years if a competitor obtains approval of the same drug or biological product for the same indication as defined bythe FDA or if our drug or biological candidate is determined to be contained within the competitor’s product for the same indication or disease. If a drug orbiological product designated as an orphan product receives marketing approval for an indication broader than what is designated, it may not be entitled toorphan product exclusivity. Orphan drug status in the European Union has similar but not identical benefits in the European Union. In June 2013, SL-401 was awarded Orphan Drug Designation from the FDA for the treatment of BPDCN. Previously, in February 2011, we received OrphanDrug Designation for SL-401 for the treatment of AML. In September 2015, SL-401 received Orphan Drug designation from the European Medicines Agency(EMA) for the treatment of AML. In November 2015, SL-401 was granted Orphan Drug designation by the EMA for the treatment of BPDCN. In addition, wereceived Orphan Drug Designation for SL-701 for the treatment of glioma in January 2015. Expedited Development and Review Programs The FDA has a Fast Track program that is intended to expedite or facilitate the process for reviewing new drug and biological products that meet certaincriteria. Specifically, new drug and biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threateningcondition and demonstrate the potential to address unmet medical needs for the condition. Fast Track designation applies to the drug product alone or incombination with one or more other drugs for the specific indication for which it is being studied. Unique to a Fast Track product, the FDA may considerreviewing sections of the NDA or BLA on a rolling basis before the complete application is submitted. In addition, the sponsor and FDA would agree on aschedule for the submission of the sections of the NDA or BLA. If the FDA agrees to a rolling review of a NDA or BLA, and determines that the schedule isacceptable, the sponsor pays any required user fees upon submission of the first section of the NDA or BLA. Any product submitted to the FDA for marketing approval, including those submitted to a Fast Track program, may also be eligible for other types of FDAprograms intended to expedite development and review, such as priority review and accelerated approval. Any 22Table of Contents product is eligible for priority review if it has the potential to provide safe and effective therapy where no satisfactory alternative therapy exists or asignificant improvement in the treatment, diagnosis or prevention of a disease compared with marketed products. The FDA will attempt to direct additionalresources to the evaluation of an application for a new drug or biological product designated for priority review in an effort to facilitate the review with thegoal of taking Agency action on a marketing application within 6 months. Additionally, a product may be eligible for accelerated approval. Drug or biological products studied for their safety and effectiveness in treating serious orlife-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may receive accelerated approval, which means that theymay be approved on the basis of adequate and well-controlled clinical studies establishing that the product has an effect on a surrogate endpoint that isreasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity. As a conditionof approval, the FDA generally requires that a sponsor of a drug or biological product receiving accelerated approval perform adequate and well-controlledpost-marketing clinical studies to establish safety and efficacy for the approved indication. Failure to conduct such studies, or conducting such studies thatdo not establish the required safety and efficacy may result in revocation of the original approval. In addition, the FDA currently requires as a condition foraccelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch or subsequent marketing ofthe product. Fast Track designation, priority review and accelerated approval may expedite the development or approval process. Post-Approval Requirements Any drug or biological products for which we receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, cGMPcompliance, record-keeping requirements, reporting of nonconforming distributed products which would require field alert reports (FARs) for NDAs andbiological product deviation reports (BPDRs) for BLAs, reporting of adverse events, providing the FDA with updated safety and efficacy information on anannual basis or as required more frequently for specific events, product sampling and distribution requirements, complying with certain electronic recordsand signature requirements and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumeradvertising, prohibitions against promoting drugs and biologics for uses or in patient populations that are not described in the drug’s or biologic’s approvedlabeling (known as “off-label promotion”), rules for conducting industry-sponsored scientific and educational activities, limitations on comparative orsuperiority claims and promotional activities involving data presentations. Failure to comply with FDA requirements can have negative consequences,including for cause inspections; warning or untitled letters from the FDA, including demands for correction or removal of noncomplying product; adversepublicity; mandated corrective advertising or communications with doctors; and civil or criminal penalties. Although physicians may prescribe legallyavailable drugs and biologics for off-label uses, manufacturers may not market or promote such off-label uses. We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our product candidates. Manufacturers ofour product candidates are required to comply with applicable FDA manufacturing requirements contained in the FDA’s cGMP regulations. cGMPregulations require among other things, quality control and quality assurance as well as the corresponding maintenance of comprehensive records anddocumentation. We are required by law to establish adequate oversight and control over raw materials, components and finished products furnished by ourthird-party manufacturers, which we establish by contract, supplier qualification and periodic audits, but unforeseen circumstances could affect our third-party manufacturers’ compliance with applicable regulations and standards. Drug and biologic manufacturers and other entities involved in the manufactureand distribution of approved drugs and biologics are also required to register their establishments and list any products made there with the FDA and complywith related requirements in certain states, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance withcGMP and other laws. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintaincGMP compliance. Discovery of problems with a product after approval may result in serious and extensive restrictions on a product, manufacturer, or holderof an approved NDA or BLA, including suspension of a product until the FDA is assured that quality standards can be met, continuing oversight ofmanufacturing by the FDA under a “consent decree,” which frequently includes the imposition of penalties for failure to comply with the terms of the consentdecree, audits conducted by outside experts, extensive reporting requirements, and possible withdrawal of the product from the market. Historically, theminimum term of an FDA consent decree has been five years, and violation of consent decree terms results in the extension of the consent decree term. Major changes to the manufacturing process and other types of major changes, such as adding new indications, require prior FDA approval before beingimplemented. Moderate and minor changes require FDA notification but not prior approval. The FDA also may require post-marketing testing, known as Phase 4 testing, risk minimization action plans and surveillance to monitor the effects of anapproved product or place conditions on an approval that could otherwise restrict the distribution or use of the product. 23Table of Contents On July 9, 2012, the Food and Drug Administration Safety and Innovation Act, among other things, renewed the drug user fee program, expanded the FDA’sinspection records access and required manufacturers to establish appropriate oversight and controls over their suppliers and the supply chain, including rawmaterial suppliers and contract manufacturers, as a part of cGMP compliance. On November 27, 2013, the Drug Quality and Security Act, which included theDrug Supply Chain Security Act, was enacted to, among other things, build an electronic, interoperable system to identify and trace certain prescription drugsas they are distributed in the United States. Requirements for the tracing of products through the pharmaceutical distribution supply chain took effect onJanuary 1, 2015 for manufacturers and building internal systems to ensure compliance with this law will require dedication of resources. In addition, this lawrequires engaging in transactions only with authorized trading partners and can limit the pool of available trading partners. U.S. Patent Term Restoration and Marketing Exclusivity Drug Price Competition and Patent Term Restoration Act of 1984 Depending upon the timing, duration and specifics of the FDA approval of the use of our drug and biologics candidates, some of our United States patentsmay be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as theHatch-Waxman Amendments. The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lostduring federal regulatory review preceding the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patentbeyond a total of 14 years from the product’s approval date. The patent term restoration period is generally one-half the time between the effective date of anIND and the submission date of an NDA or a BLA plus the time between the submission date of an NDA or a BLA and the approval of that application. Onlyone patent applicable to an approved drug or biologic is eligible for the extension and the application for the extension must be submitted within 60 days ofapproval and prior to the expiration of the patent. The United States Patent and Trademark Office, in consultation with the FDA, reviews and approves theapplication for any patent term extension or restoration. In the future, we may apply for restoration of patent term for one of our currently owned or licensedpatents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing ofthe relevant NDA. Federal Food, Drug and Cosmetic Act Market exclusivity provisions under the FDCA, which are independent of patent status and any patent related extensions, can also delay the submission orthe approval of certain applications of companies seeking to reference another company’s NDA. If the new drug is a new chemical entity subject to an NDA,the FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain approval of an NDA for anew chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which isthe molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not accept for review an abbreviated newdrug application, or ANDA, or a 505(b)(2) NDA submitted by another company for another version of such drug where the applicant does not own or have alegal right of reference to all the data required for approval. However, such an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patentslisted with the FDA by the innovator NDA holder. The FDCA also provides three years of marketing exclusivity for an NDA, or supplement to an existingNDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to beessential to the approval of the application, for example new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only theconditions associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original activeagent. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would berequired to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstratesafety and effectiveness. Pediatric exclusivity is another type of regulatory market exclusivity in the United States. Pediatric exclusivity, if granted by the FDA, adds six months toexisting exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may begranted based on the completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial. Biologic products that are subject tothe PHSA are not eligible for pediatric exclusivity under the FDCA. Biologics Price Competition and Innovation Act of 2009 The Biologics Price Competition and Innovation Act of 2009, or BPCIA, amended the PHSA to create a new licensure framework for biosimilar products,which could ultimately subject our biological product candidates to competition. Under the BPCIA, a 24Table of Contents manufacturer may submit an application for licensure of a biological product that is “biosimilar to” or “interchangeable with” a referenced, branded biologicproduct. Previously, there had been no licensure pathway for such biosimilar or interchangeable products. For purposes of the BPCIA, a reference product isdefined as the single biological product licensed under a full BLA against which a biological product is evaluated in an application submitted under afollow-on BLA. The BPCIA also created a 12-year period of reference product exclusivity, which can be extended to 12.5 years with pediatric exclusivity. The 12-yearexclusivity period begins on the date of first licensure of the reference product under the PHSA and during which the licensure of a follow-on application fora biosimilar or interchangeable product cannot be made effective. During the first four years (or four and one-half years with pediatric exclusivity) of the 12-year period, an application for a biosimilar or interchangeable version of the reference product cannot be submitted to the FDA. Under the FY2014 budgetproposal President Obama submitted to Congress in 2013, the Administration requested that reference product exclusivity would decrease from 12 to sevenyears beginning in 2013. Congress has not yet enacted such a change in the BPCIA, but could move to enact such a decrease in the reference productexclusivity period. The BPCIA includes limits on obtaining 12-year reference product exclusivity for certain changes or modifications to the reference product. A separate 12-year reference product exclusivity period does not apply to: · a BLA supplement for the product that is the reference product; · a subsequent BLA filed by the same reference product sponsor or manufacturer (or a licensor, predecessor in interest, or other related entity) for achange (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosingschedule, dosage form, delivery system, delivery device or strength; or · a modification to the structure of the biological product that does not result in a change in safety, purity or potency. In February 2012, the FDA issued three draft guidance documents on biosimilar product development. The FDA is soliciting comments on the draft guidancedocuments which are described by the FDA as follows: (1) Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, which isintended to assist companies in demonstrating that a proposed therapeutic protein product is biosimilar to a reference product for the purpose of submittingan application, called a “351(k)” application, to the FDA. This draft guidance describes a risk-based “totality-of-the-evidence” approach that the FDA intendsto use to evaluate the data and information submitted in support of a determination of biosimilarity of the proposed product to the reference product;(2) Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product, which provides an overview of analytical factors to consider whenassessing biosimilarity between a proposed therapeutic protein product and a reference product for the purpose of submitting a 351(k) application; and(3) Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009, which provides answersto common questions from people interested in developing biosimilar products. We cannot predict when or whether these draft guidance documents will befinalized or what changes the agency may make in its approach to implementation of the BPCIA. In addition to creating a 12-year period of reference product exclusivity, the BPCIA clarifies the interaction of that exclusivity with orphan drug exclusivity,such that, if a reference product has been designated for a rare disease or condition the licensure of a biosimilar or interchangeable version of a referenceproduct for such disease or condition may only occur after the later of the expiration of any applicable seven-year orphan drug exclusivity or the 12-yearreference product exclusivity (or seven and one-half years and 12.5 years with pediatric exclusivity). Like pediatric exclusivity applicable to drug products approved under the FDCA, pediatric exclusivity applicable to biological reference products is subjectto an exception. Pediatric exclusivity will not apply to either the 12-year reference product or the seven-year orphan drug exclusivity periods if the FDA hasnot determined that the study reports a BLA sponsor submitted in response to a written request for pediatric studies met the terms of that request before ninemonths prior to the expiration of such period . Our biological product candidates, if approved, could be considered reference products entitled to 12-year exclusivity. Even if our products are considered tobe reference products eligible for exclusivity, another company could market a competing version of any of our biological products if the FDA approves afull BLA for such product containing the sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety,purity and potency of their product. The BPCIA also sets forth a complex mechanism for resolving patent disputes that involves a step-wise exchange of information prior to the initiation of apatent infringement lawsuit against a biosimilar or interchangeable product sponsor. Unlike the Hatch-Waxman Act, the BPCIA provides no automatic stayon approval of a biosimilar product application, except an interchangeable product receives the lesser of one year of exclusivity after the date of firstcommercial marketing or 18 months of exclusivity after a final court 25Table of Contents decision or dismissal of a patent challenge or, if the applicant has not been sued, after approval. The BPCIA does not prevent a competitor from conductingits own clinical trials and submitting a full BLA on the same or similar product. There is also currently substantial uncertainty as to how certain terms of the BPCIA will be interpreted by the Courts, which may affect the timing of the entryof a biosimilar or interchangeable product to market, and the required notice that the owner of the reference product exclusivity must be given by the ownerof the application of a biosimilar or interchangeable product. Should the courts resolve the interpretation issues in favor of the biosimilar or interchangeableproduct applicants, the BPCIA may offer more limited exclusivity to the reference product than currently believed. Other U.S. Healthcare Laws and Compliance Requirements In the United States, our activities are potentially subject to regulation by various federal, state and local authorities in addition to the FDA, including theCenters for Medicare and Medicaid Services, or CMS (formerly the Health Care Financing Administration), other divisions of the United States Department ofHealth and Human Services (e.g., the Office of Inspector General and the Office of Civil Rights), the United States Department of Justice and individualUnited States Attorney offices within the Department of Justice, state attorney generals and state and local governments. For example, sales, marketing andscientific/educational grant programs must comply with the federal Antikickback Statute, the federal False Claims Act, the privacy and security provisions ofthe Health Insurance Portability and Accountability Act, or HIPAA, and similar state laws, each as amended. Pricing and rebate programs must comply withthe Medicaid rebate requirements of the Omnibus Budget Reconciliation Act of 1990, the Veterans Health Care Act of 1992, and the federal AntikickbackStatute, each as amended. If products are made available to authorized users of the Federal Supply Schedule (FSS) of the General Services Administration,additional laws and requirements apply. Under the Veterans Health Care Act, or VHCA, drug companies are required to offer certain pharmaceutical productsat a reduced price to four federal agencies including the United States Department of Veterans Affairs, the United States Department of Defense, the CoastGuard, the Public Health Service and certain private Public Health Service designated entities (including the Indian Health Service) in order forreimbursement to be available for our product under Medicare and Medicaid. FSS pricing to these four agencies must be equal to or less than the federalceiling price (“FCP”), which is, at a minimum, 24% off the Non-Federal Average Manufacturer Price for the prior fiscal year. Participation under the VHCArequires submission of pricing data and calculation of discounts and rebates pursuant to complex statutory formulas, as well as the entry into governmentprocurement contracts governed by the Federal Acquisition Regulations. In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors ofpharmaceutical products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers ordistributors have no place of business within the state. Some states also impose requirements on manufacturers and distributors to establish the pedigree ofproduct in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracingproduct as it moves through the distribution chain. Several states have enacted legislation requiring pharmaceutical companies to establish marketingcompliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities,and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data topharmaceutical companies for use in sales and marketing, and to prohibit certain other sales and marketing practices. All of our activities are potentiallysubject to federal and state consumer protection and unfair competition laws. In addition, in August 2013, the federal Physician Payment Sunshine Act tookeffect and requires annual reporting by prescription drug manufacturers with at least 1 approved product of certain payments and transfers of value made tophysicians and teaching hospitals. Post-approval of any of our product candidates, we will need to ensure compliance with annual tracking and reporting ofthese payments and transfers of value to CMS. Europe and Worldwide Government Regulation In addition to regulations in the United States, we will be subject to a variety of regulations in other jurisdictions governing, among other things, clinicaltrials and any commercial sales and distribution of our products. Whether or not we obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to thecommencement of clinical trials or marketing of the product in those countries. Certain countries outside of the United States have a similar process thatrequires the submission of a clinical trial application much like the IND prior to the commencement of human clinical trials. In the European Union, forexample, a clinical trial application, or CTA, must be submitted to each country’s national health authority and an independent ethics committee, much likethe FDA and IRB, respectively. Once the CTA is approved in accordance with a country’s requirements, clinical trials may proceed. The requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. In allcases, the clinical trials are conducted in accordance with International Conference on Harmonisation (ICH) / WHO 26Table of Contents Good Clinical Practice standards and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki. To obtain regulatory approval of an investigational drug or biological product under European Union regulatory systems, we must submit a marketingauthorization application to the European Medicines Agency, or the EMA. The application used to file an NDA or a BLA in the United States is similar tothat required in the European Union, with the exception of, among other things, country-specific document requirements. For example, the EMA has alreadyestablished a number of guidelines for approval of various biosimilars. For other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct ofclinical trials, product licensing, pricing and reimbursement vary from country to country. In all cases, again, the clinical trials are conducted in accordancewith GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki. If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatoryapprovals, product recalls, seizure of products, operating restrictions and criminal prosecution. Pharmaceutical Coverage, Pricing and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any drug or biological candidates for which we obtain regulatory approval. Inthe United States and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part onthe availability of reimbursement from third-party payors. Third-party payors include government health administrative authorities, managed care providers,private health insurers and other organizations. The process for determining whether a payor will provide coverage for a drug or biological product may beseparate from the process for setting the price or reimbursement rate that the payor will pay for the drug or biological product. Third-party payors may limitcoverage to specific drug or biological products on an approved list, or formulary, which might not include all of the FDA-approved drug or biologicalproducts for a particular indication. Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness ofmedical products and services, in addition to their safety and efficacy. We may need to conduct expensive pharmacoeconomic studies in order to demonstratethe medical necessity and cost-effectiveness of our products, in addition to the costs required to obtain the FDA approvals. Our drug or biological candidatesmay not be considered medically necessary or cost-effective. A payor’s decision to provide coverage for a drug or biological product does not imply that anadequate reimbursement rate will be approved. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient torealize an appropriate return on our investment in product development. In 2003, the United States government enacted legislation providing a partial prescription drug benefit for Medicare recipients, which became effective at thebeginning of 2006. Government payment for some of the costs of prescription drugs and biologics may increase demand for any products for which wereceive marketing approval. However, to obtain payments under this program, we would be required to sell products to Medicare recipients throughprescription drug plans operating pursuant to this legislation. These plans will likely negotiate discounted prices for our products. Federal, state and localgovernments in the United States continue to consider legislation to limit the growth of healthcare costs, including the cost of prescription drugs andbiologics. Future legislation could limit payments for pharmaceuticals such as the drug or biological candidates that we are developing. Different pricing and reimbursement schemes exist in other countries. In the European Community, governments influence the price of pharmaceuticalproducts through their pricing and reimbursement rules and control of national healthcare systems that fund a large part of the cost of those products toconsumers. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has beenagreed. To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost-effectivenessof a particular drug or biological candidate to currently available therapies. Other member states allow companies to fix their own prices for medicines, butmonitor and control company profits. The downward pressure on healthcare costs in general, particularly prescription drugs and biologics, has become veryintense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country. The marketability of any drug or biological candidates for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement. In addition, emphasis on managed care in the United States has increased and we expectwill continue to increase the pressure on pharmaceutical pricing. Coverage policies and third-party reimbursement rates may change at any time. Even iffavorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policiesand reimbursement rates may be implemented in the future. 27Table of Contents Manufacturing We do not currently own or operate any manufacturing facilities for the clinical or commercial production of our drug candidates. For past investigatorsponsored studies, all drug substance and drug product for SL-401 and SL-701 was manufactured at academic and contract manufacturing organizations, orCMO, facilities, as directed by our academic collaborators. We have now developed manufacturing processes that are suitable for full-scale cGMPmanufacturing. Additionally, we have qualified FDA-audited third-party CMOs to produce sufficient quantities of SL-401, SL-701, and SL-801 drugsubstance and drug product of suitable quality for our active and contemplated corporate sponsored clinical trials and potential commercialization. Ourmanufacturing programs are being managed with oversight by our manufacturing team, which is comprised of full-time employees and consultants withexperience in manufacturing pharmaceutical drug substance and drug products. SL-401 Manufacturing and Supply SL-401 is a recombinant protein generated from an antibiotic-resistance driven DNA-based plasmid vector and manufactured by bacterial fermentation in E.Coli. For past investigator sponsored studies, SL-401 was manufactured at Wake Forest University. We have optimized the protein expression, generatedcGMP master and working cell banks, and developed the fermentation and purification steps of our manufacturing process to be suitable for scale-up instandard manufacturing equipment. This technology has been transferred to a third-party CMO with expertise in bacterial fermentation, which has furtheroptimized and scaled-up the process in their cGMP production suite. The SL-401 drug substance has now met standard industry quality specifications and isadequate to support our ongoing and planned corporate sponsored clinical trials. The drug product formulation and manufacturing process has beentransferred to a third-party CMO with expertise in sterile product manufacture for clinical and commercial supply, and they have successfully produced drugproduct meeting cGMP requirements for use in clinical studies. SL-701 Manufacturing and Supply SL-701 is an immunotherapy that is comprised of several short synthetic peptides. Each of the component peptides of SL-701 is manufactured individuallyby solid-phase synthesis and all have been prepared to acceptable quality specifications in cGMP manufacturing equipment by our third-party CMO. Themanufacturing scale and product quality is adequate to supply our active and planned corporate sponsored clinical studies. We have also developed a stableformulation that combines the individual peptides in a single sterile solution to generate SL-701 drug product. This manufacturing process was transferred toa third-party CMO with expertise in sterile product manufacture. This CMO has produced multiple cGMP drug product batches of sufficient quality andquantity to supply our corporate sponsored clinical trials. SL-801 Manufacturing and Supply SL-801 is a small molecule that is prepared via synthetic organic chemistry. We have completed process development and cGMP manufacturing at anadequate scale to supply our ongoing and planned corporate sponsored clinical studies. We have also developed a stable solid-oral tablet formulation thathas been produced using cGMP manufacturing equipment at our third-party CMO. We believe that the manufacturing scale and product quality is adequateto supply our active and planned corporate sponsored clinical studies. Sales and Marketing We believe the infrastructure required to commercialize oncology products is relatively limited, which may make it cost-effective for us to internally developa marketing and sales force. If SL-401, SL-701 and/or SL-801 are approved by the FDA and other regulatory authorities, we plan to potentially build theinfrastructure to commercialize these products in North America and Europe ourselves. However, we will remain opportunistic in seeking strategicpartnerships in these and other markets when advantageous. The commercial infrastructure of specialty oncology products typically consists of a targeted, specialty sales force that calls on a limited and focused groupof physicians supported by sales management, internal sales support, an internal marketing group, and distribution support. Additional capabilities importantto the oncology marketplace include the management of key accounts, such as managed care organizations, group-purchasing organizations, specialtypharmacies, oncology group networks, and government accounts. As SL-401 and SL-701 are being developed for orphan indications with a relatively smallnumber of treating physicians, we anticipate that a reduced infrastructure, including a small, targeted sales force, will be sufficient to support our sales andmarketing objectives. In order to implement this infrastructure, we will have to allocate management resources and make significant financial investmentsincluding some prior to product approval to prepare for the commercial launch of an approved product, including preparation of marketing and sales trainingmaterials in compliance with legal and regulatory requirements. 28Table of Contents We may elect in the future to utilize strategic partners, distributors, or contract sales forces to assist in the commercialization of our products. Research and Development Company sponsored research and development expenses totaled $29.5 million in 2015, $21.2 million in 2014 and $16.2 million in 2013. “Research anddevelopment expenses” consist of costs associated with the development of our product candidates and our platform technology, which include: clinical trialcosts, CMC-related costs, nonclinical costs, employee related expenses, external research and development expenses, license fees and milestone paymentsrelated to in-licensed products and technology, and facilities, depreciation and other allocated expenses. See “Item 7. Management’s Discussion andAnalysis of Financial Condition and Results of Operations—Overview.” Employees As of March 14, 2016, we had 24 full-time employees, 5 of whom hold Ph.D. or M.D. degrees. None of our employees is subject to a collective bargainingagreement or represented by a trade or labor union. We believe that we have a good relationship with our employees. Item 1A. Risk Factors You should carefully consider the following risks and uncertainties. If any of the following occurs, our business, financial condition and/or operating resultscould be materially harmed. These factors could cause the trading price of our common stock to decline, and you could lose all or a substantial part of yourinvestment. Risks Related to Development, Clinical Testing and Regulatory Approval of Our Product Candidates We are heavily dependent on the success of our clinical product candidates, SL-401, SL-701, and SL-801, and we cannot provide any assurance that any ofour product candidates will be approved or commercialized. To date, we have invested a significant portion of our efforts and financial resources in the acquisition and development of our product candidates, SL-401and SL-701, which we are advancing through clinical development. Additionally, we are advancing SL-801 toward clinical trials. Our future successdepends heavily on our ability to successfully manufacture, develop, obtain regulatory approval, and commercialize these product candidates, which maynever occur. We currently generate no revenues from our product candidates, and we may never be able to develop or commercialize a marketable drug. Before we generate any revenues from product sales, we must complete preclinical and clinical development of one or more of our product candidates,conduct human subject research, submit clinical and manufacturing data to the FDA, qualify a third-party contract manufacturing organization, or CMO,receive regulatory approval in one or more jurisdictions, satisfy the FDA that our CMO is capable of manufacturing the product in compliance with cGMP,build a commercial organization, make substantial investments and undertake significant marketing efforts ourselves or in partnership with others. We are notpermitted to market or promote any of our product candidates before we receive regulatory approval from the FDA or comparable foreign regulatoryauthorities, and we may never receive such regulatory approval for any of our product candidates. We have not submitted a biologics license application, or BLA, or a new drug application, or NDA, to the FDA, or similar market approval applications tocomparable foreign authorities, for any of our product candidates. We cannot be certain that any of our product candidates will be successful in clinical trialsor receive regulatory approval for trial initiation or marketing. Further, the FDA may not agree with our interpretation of the clinical safety and efficacy of ourproduct candidates and our product candidates may not receive regulatory approval even if they are successful in clinical trials. If we do not receiveregulatory approvals for our product candidates, we may not be able to continue our operations. Even if we successfully obtain regulatory approvals tomarket one or more of our product candidates, our revenues will be dependent, in part, upon the size of the markets in the territories for which we gainregulatory approval and have commercial rights. In addition, our revenues will be dependent, in part, upon the market acceptance of our products onceapproved. If the markets for patient subsets that we are targeting are not as significant as we estimate, we may not generate significant revenues from sales ofsuch products, if approved. We may not have the resources to conduct and oversee our product development programs without assistance from third parties. In the execution of ourproduct development programs, we may have to rely on collaborations with clinical partners as well as clinical research organizations, CMOs, vendors andservice providers. Failure of these entities to satisfactorily conduct clinical research or to provide the services requested by the company may negativelyimpact on our product development programs, including but not limited to program delays or preventing approval of our product candidates. We plan to seek regulatory approval to commercialize our product candidates in the United States, and potentially in the European Union and additionalforeign countries. While the scope of regulatory review and approval is similar in other countries, to obtain separate regulatory review and approval in manyother countries we must comply with numerous and varying regulatory requirements of such countries regarding safety and efficacy, clinical trials andcommercial sales, pricing and distribution of our product candidates, and we cannot predict success in these jurisdictions. 29Table of Contents Clinical drug development involves a lengthy and expensive process with an uncertain outcome. Clinical testing is expensive and can take a substantial amount of time to complete. Its outcome is inherently uncertain. In addition, failure can occur at anytime during clinical development, including after significant resources have been invested. We cannot predict whether we will encounter challenges with anyof our clinical trials that will cause us, or regulatory authorities, to delay, suspend or terminate those trials. Clinical trials can be delayed or halted for many reasons, including: · delays or failure reaching agreement on acceptable terms with prospective contract manufacturing organizations, or CMOs, contract researchorganizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly dependingon the circumstances; · failure of our third-party contractors, including CROs and CMOs, or our investigators, to comply with regulatory requirements or otherwisemeet contractual obligations in a timely manner; · delays or failure in obtaining the necessary approvals from regulators, institutional review boards, or IRBs, or scientific review committees, orSRCs, in order to commence or continue a clinical trial or to market our product candidates; · our inability to manufacture, or obtain from third-parties, adequate supply of drug substance, drug product or adjuvant therapies sufficient tocomplete our preclinical studies and clinical trials; · risk of loss of drug product, adjuvants and/or other components of the product, due to third-party storage and distribution of such supplies; · the FDA requiring alterations to any of our study designs, overall strategy or manufacturing plans; · delays in patient enrollment, variability in the number and types of patients available for clinical trials, poor accrual, or high drop-out rates ofpatients in our clinical trials; · clinical trial sites deviating from trial protocol or dropping out of a trial and our inability to add new clinical trial sites; · difficulty in maintaining contact with patients after treatment, resulting in incomplete data; · poor effectiveness of our product candidates during clinical trials; · safety issues, including serious adverse events associated with our product candidates and patients’ exposure to unacceptable health risks; · receipt by a competitor of marketing approval for a product targeting an indication that one of our product candidates targets, such that we arenot “first to market” with our product candidate; · governmental or regulatory delays and changes in regulatory requirements, policy and guidelines; or · differing interpretations of data by the FDA or similar foreign regulatory agencies. We could also encounter delays if a clinical trial is suspended or terminated by us, by the institutional review boards, or IRBs, where such trial is beingconducted, by the Data Safety Monitoring Board, or DSMB, if one is utilized for any such trial, or by the FDA or other regulatory authorities. Such authoritiesmay suspend or terminate a clinical trial due to a number of factors, including, among other things, failure to conduct the clinical trial in accordance withregulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities resulting inthe imposition of a clinical hold, safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulationsor administrative actions or lack of adequate funding to continue the clinical trial. We plan to advance SL-801 through clinical trials. There are unknown risks with respect to dosing, administration, pharmacokinetics, bioavailability, safetyand efficacy that we expect we will learn about during clinical development. We have not yet completed a corporate-sponsored clinical trial. Consequently, we may not have the necessary expertise or capabilities, including adequatestaffing, to successfully manage the execution and completion of any of our clinical trials, and ultimately obtain marketing approval for our productcandidates in a timely manner, or at all. 30Table of Contents If we are able to conduct a pivotal clinical trial of a product candidate, the results of such trial may not be adequate to support marketing approval. Becauseour product candidates are intended for use in life-threatening diseases, in most cases we ultimately intend to seek marketing approval for each productcandidate based on the results of a single pivotal clinical trial. As a result, these trials may receive enhanced scrutiny from the FDA. For any such pivotal trial,if the FDA disagrees with our choice of primary endpoint or the results for the primary endpoint are not robust or significant relative to control, are subject toconfounding factors, or are not adequately supported by other study endpoints, including possibly overall survival, or OS, or overall response rate, or ORR,the FDA may refuse to approve a BLA or NDA based on such intended pivotal trial. The FDA may require the completion of additional clinical trials as acondition for approving our product candidates. If we experience delays in the completion of, or termination of, any clinical trial of our product candidates, the commercial prospects of our productcandidates will be harmed, which will have a negative impact on our ability to commence product sales and generate product revenues from any of ourproduct candidates. In addition, any delays in completing our clinical trials will increase our costs and slow down our product candidate development andapproval process and may negatively impact our ability to raise additional capital to support these increased costs. Delays in completing our clinical trialscould also allow our competitors to obtain marketing approval before we do or shorten the patent protection period during which we may have the exclusiveright to commercialize our product candidates. Any of these occurrences may harm our business, financial condition and prospects significantly. In addition,many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatoryapproval of our product candidates. Results of earlier clinical trials may not be predictive of the results of later-stage clinical trials. The results of preclinical studies and early stage, including investigator sponsored, clinical trials of product candidates may not be predictive of the results ofsubsequent later stage, including corporate sponsored, clinical trials. Product candidates in later stage clinical trials may fail to show the safety and efficacyresults demonstrated in earlier studies despite having progressed through preclinical studies and earlier clinical trials. Many companies in thebiopharmaceutical industry have suffered significant setbacks in later stage clinical trials due to adverse safety profiles or lack of efficacy, notwithstandingpromising results in earlier studies. Similarly, our clinical trial results may not be successful for these or other reasons. This drug development risk is heightened by any changes in ongoing and future clinical trials compared to completed clinical trials. As product candidatesare advanced through preclinical studies to early and later stage clinical trials and towards approval and commercialization, it is customary that variousaspects of the development program, such as manufacturing and methods of administration and dosing, are altered along the way in an effort to optimizeprocesses and results. While these types of changes are common and are intended to optimize the product candidates for late stage clinical trials, approvaland commercialization, such changes do carry the risk that they will not achieve these intended objectives. For example, the results of our ongoing and futureclinical trials may be adversely affected by the following changes: · As we optimize and scale-up production of SL-401, SL-701, and SL-801 there have been manufacturing, formulation, fill-finish and otherprocess and analytical changes that are part of the optimization and scale-up necessary for producing drug substance and drug product of aquality, quantity and stability sufficient for later stage clinical development and commercialization. Delays, including failures, in any of thesesteps may delay initiation and completion of clinical trials. We may also need to demonstrate comparability between newly manufactured drugsubstance and/or drug product relative to previously manufactured drug substance and/or drug product. Demonstrating comparability maycause us to incur additional costs or delay initiation or completion of our clinical trials including the need or choice to initiate a dose escalationstudy and, if unsuccessful, could require us to complete additional preclinical or clinical studies of our product candidates. · We have changed the treatment regimen of SL-401 to a multi-cycle regimen, in which patients will receive more than one treatment cycle, ratherthan a single-cycle treatment as used in the completed clinical trial. Although we anticipate that patients receiving multiple cycles of SL-401may derive greater clinical benefit than from a single cycle, there is a risk of toxicity or a lack of efficacy arising from multiple cycles. · We plan to treat patients with certain diseases or conditions that have not yet been treated with SL-401. These may include certainmyeloproliferative diseases such as mastocytosis, hypereosinophilic syndrome, myelofibrosis, chronic myelomonocytic leukemia, as well asother malignancies including hairy cell leukemia, multiple myeloma, or MM, and early stages of acute myeloid leukemia, or AML. In theseinstances, we may choose to treat patients at several different doses and multi-cycle dosing regimens to determine the optimal doses andschedules for both near-term and long-term safety and disease control in each indication. 31Table of Contents · We may determine, based on safety and efficacy, that certain doses and regimens of SL-401 for particular indications are optimal for initial near-term therapy whereas the same, or other, doses and regimens are optimal for longer-term maintenance therapy. · We plan to develop SL-701 as an injection administered under the skin, or subcutaneously, in our trials. The 701-Ped-G Study and 701-Adult-LGG Study used this method of delivery. The 701-Adult-RHGG Study used a different method of delivery, in which dendritic cells, which are atype of immune cell, were removed from the patient, exposed to immunogenic peptides, and then re-injected into or near a lymph node of thepatient (intra/peri-nodally). Thus, our plan continues the subcutaneous injection method used in two of the previous studies and represents achange from one of the previous studies. · We are manufacturing and formulating SL-701 as a mixture of IL-13Ra2 mutant peptide, EphA2 peptide, a new survivin mutant peptide, and atetanus toxoid peptide. An earlier version of this immunotherapy, which included IL-13Ra2 mutant and EphA2 peptides, was mixed withadditional peptides in previous studies, including a different survivin peptide. · In the initial stage of our SL-701 corporate-sponsored trial we used granulocyte-macrophage-colony-stimulating factor, or GM-CSF, andimiquimod as the immunostimulants. In the current stage of our SL-701 trial, we are using poly-ICLC as the immunostimulant, which was theimmunostimulant used, along with an earlier version of SL-701, in the previous investigator-sponsored study. · In some of our current or future trials, we may combine SL-401 or SL-701 with other therapies such as chemotherapy, radiation, targetedtherapy, or anti-angiogenic therapy. We have not yet clinically tested these combinations. While there do not appear to be overlappingtoxicities with these combinations, there is always the risk of unforeseen toxicities. We plan to combine SL-401 with pomalidomide in myelomaand SL-701 with bevacizumab and immunostimulants in brain cancer. Any of the aforementioned, or other, changes could make the timing, including initiation, patient accrual, or results of our clinical trials or other futureclinical trials, less predictable and could cause our product candidates to perform differently, including causing toxicities, which could delay or suspendcompletion of our clinical trials, delay or prevent approval of our product candidates, and/or jeopardize our ability to commence product sales and generaterevenues. If we experience delays in the enrollment of patients in our clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented. We may not be able to continue clinical trials for our product candidates if we are unable to locate and enroll a sufficient number of eligible patients toparticipate in these trials as required by the FDA or other regulatory authorities. Patient enrollment, a significant factor in the timing of clinical trials, isaffected by many factors including the size and nature of the patient population, the proximity of patients to clinical sites, the eligibility criteria for the trial,the design of the clinical trial, competing clinical trials and clinicians’ and patients’ perceptions as to the potential advantages of the drug being studied inrelation to other available therapies, including any new drugs that may be approved for the indications we are investigating. SL-401 and SL-701 are beingdeveloped in hematologic and brain cancers, respectively, both of which are orphan indications (i.e., rare diseases). SL-401 is being developed initially inBPDCN and other rare diseases, including certain myeloproliferative disorders, as well as AML, and SL-701 is being developed in adult and pediatric braincancer. Some of these represent orphan indications for which there are very limited independently reported data on annual incidences. If the incidences ofthese diseases are very low, including lower than our estimates or estimates of our third-party contractors, this could significantly delay patient enrollment inany one or more of our ongoing or future clinical trials. SL-801 is being developed in a number of advanced solid tumors, some of which may be orphanindications. If we fail to enroll and maintain the number of patients for which the clinical trial was designed, the statistical power of that clinical trial may be reduced,which would make it harder to demonstrate that the product candidate being tested in such clinical trial is safe and effective. Additionally, enrollment delaysin our clinical trials may result in increased development costs for our product candidates, which would cause the value of our common stock to decline andlimit our ability to obtain additional financing. Our inability to enroll a sufficient number of patients for any of our current or future clinical trials wouldresult in significant delays or may require us to abandon one or more clinical trials altogether. 32Table of Contents The regulatory review and approval processes of the FDA and comparable foreign authorities are lengthy, time-consuming and inherently unpredictable,and if we are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed. The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable and depends upon numerous factors, including thesubstantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of preclinical and clinical datanecessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions. We may berequired to undertake and complete certain additional preclinical or clinical studies to generate data related to toxicity and other data required to support thesubmission of an IND or a BLA or an NDA to the FDA or comparable foreign authorities. We have not obtained regulatory approval for any product candidateand it is possible that none of our existing product candidates or any product candidates we may seek to develop in the future will ever obtain regulatoryapproval. Furthermore, approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by oneforeign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA. Our product candidates alone or in combination with any adjuvant, immunostimulant including poly-ICLC, or other agents with which we may combine ourdrug candidates, could fail to receive regulatory approval for many reasons, including the following: · the FDA or comparable foreign regulatory authorities may disagree with the design, conduct or findings of our clinical trials; · the FDA may identify protocol deviations or data quality or integrity concerns with our preclinical or clinical trials; · we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a product candidate is safe andeffective for its proposed indication; · the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities forapproval; · we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; · the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; · the data collected from clinical trials of our product candidates or the adequacy of our right of reference to it may not be sufficient to support thesubmission of a BLA or an NDA or other submission or to obtain regulatory approval in the United States or elsewhere; · the FDA or comparable foreign regulatory authorities may fail to approve the manufacturing processes or facilities of third-party manufacturers withwhich we contract for clinical and commercial supplies; · the FDA or comparable foreign regulatory authorities may fail to approve any companion diagnostics we develop; and · the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering ourclinical data insufficient for approval. This lengthy and costly review process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval tomarket SL-401, SL-701, SL-801, or any of our other product candidates that we may advance into and through clinical trials, which would significantly harmour business. In addition, even if we were to obtain approval, regulatory authorities may approve any of our product candidates for fewer or more limited indications thanwe request, may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve a product candidate with a label thatdoes not include the labeling claims necessary or desirable for the successful commercialization of that product candidate, including based on productcontraindications, warnings or precautions. In addition, we may not be able to ultimately achieve the price we intend to charge for our product candidates.Moreover, in many foreign countries, a product candidate must be approved for reimbursement before it can be approved for sale in that country. Any of theforegoing scenarios could materially harm the commercial prospects for our product candidates. Our approach to the discovery and development of product candidates that target CSCs is unproven, and we do not know whether we will be able todevelop any products of commercial value. Research on CSCs is an emerging field and, consequently, there is ongoing debate regarding the importance of CSCs as an underlying cause of tumorinitiation, propagation, recurrence, resistance, and metastasis. In addition, there is some debate in the scientific community regarding the definingcharacteristics of these cells. 33Table of Contents Although there is general consensus that some cancer cells have tumor-initiating capacity, there also is some debate in the scientific community regardingthe defining characteristics and the origin of these cells. Some believe that normal adult stem cells transform into CSCs. Others believe that non-CSC cancercells can transform into CSCs and, therefore, a definitive CSC cannot be readily isolated or targeted. In addition, some believe that targeting CSCs should besufficient for a positive clinical outcome, while others believe that, at times or always, targeting CSCs should be coupled with targeting tumor bulk for apositive clinical outcome. We believe that SL-401 and SL-701 target both tumor bulk and CSCs. However, it is conceivable that SL-401, SL-701 and any other product candidates thatwe develop may not effectively target tumor bulk or CSCs or, even if they do, they may not have a beneficial clinical outcome. In addition, it is conceivablethat our platform technology may ultimately fail to identify any commercially viable drugs to treat human patients with cancer or any other disease orcondition. If we are not successful in discovering, developing and commercializing additional product candidates, our ability to expand our business and achieve ourstrategic objectives may be impaired. Although we expect to focus a substantial amount of our efforts on the continued clinical testing and potential approval of SL-401, SL-701, and SL-801,another key element of our strategy is to identify and test additional compounds A portion of the research that we are conducting involves new and unprovendrug discovery methods, including our proprietary StemScreen platform technology, as well as the testing of new compounds and potential new uses ofexisting compounds. The drug discovery that we are conducting using our StemScreen platform technology may not be successful in identifyingcompounds that are useful in treating humans with cancer. Research programs designed to identify product candidates require substantial technical, financialand human resources, whether or not any product candidates are ultimately identified. Our research programs may initially show promise in identifyingpotential product candidates, yet fail to yield product candidates for clinical development or commercialization for many reasons, including the following: · the research methodology used may not be successful in identifying potential product candidates; · competitors may develop alternatives that render our product candidates obsolete; · a product candidate may, on further study, be shown to have harmful side effects or other characteristics that indicate it is unlikely to be effective orotherwise does not meet applicable regulatory criteria; · a product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or at all; and · a product candidate may not be accepted as safe and effective by regulatory authorities, patients, the medical community or third-party payors. If we are unable to identify suitable compounds for preclinical and clinical development, we may not be able to obtain sufficient product revenues in futureperiods, which could result in significant harm to our financial position and adversely impact our stock price. Even if we receive regulatory approval for any of our product candidates, we will be subject to ongoing FDA regulatory requirements, which requiresignificant resources. Additionally, our product candidates, if approved, could be subject to labeling and other restrictions and market withdrawal and wemay be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products. Any regulatory approvals that we or our potential strategic partners receive for our product candidates may also be subject to limitations on the approvedindicated uses for which the product may be marketed or to the conditions of approval, may contain product contraindications, warnings, or precautions thatlimit use of our product candidates or may contain requirements for potentially costly post-marketing testing, including Phase 4 clinical trials, andsurveillance to monitor the safety and efficacy of our product candidates. In addition, if the FDA approves any of our product candidates, the manufacturingprocesses, testing, packaging, labeling, storage, distribution, field alert or biological product deviation reporting, adverse event reporting, advertising,promotion and recordkeeping for the product will be subject to extensive and ongoing regulatory compliance requirements. These requirements includesubmissions of safety and other post-marketing information and reports, as well as continued compliance with cGMP for commercial manufacturing andcompliance with cGMP and good clinical practices, or GCP, for any clinical trials that we conduct post-approval. In addition, any regulatory approvals willtrigger compliance with the Federal Physician Payment Sunshine Act reporting requirements or related state marketing disclosure laws. Later discovery ofpreviously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with our third-party manufacturers ormanufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: · restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory product recalls; 34®®Table of Contents · warning letters or holds on clinical trials; · refusal by the FDA to approve pending applications or supplements to approved applications filed by us or our strategic partners, or suspension orrevocation of product license approvals; · product seizure or detention, or refusal to permit the import or export of products; and · injunctions, fines or the imposition of other civil penalties or criminal penalties. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in theUnited States or abroad. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are notable to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability,which would adversely affect our business. Risks Related to Our Financial Position and Capital Requirements We have incurred net operating losses since our inception and anticipate that we will continue to incur substantial operating losses for the foreseeablefuture. We may never achieve or sustain profitability, which would depress the market price of our common stock, and could cause you to lose all or a partof your investment. We have incurred net losses from operations from our inception through December 31, 2015 of approximately $109.6 million. We do not know whether orwhen we will become profitable. To date, we have not commercialized any products or generated any revenues from product sales. Our losses have resultedprincipally from costs incurred in development and discovery activities. We anticipate that our operating losses will substantially increase over the nextseveral years as we execute our plan to expand our discovery, research, development and potential commercialization activities. We believe that our existingcash, cash equivalents, short-term investments and long-term investments including the cash proceeds received from our Additional Offering during the firstquarter of 2015, will be sufficient to fund our operations and our capital expenditures for at least the next two years. If our cash is insufficient to meet futureoperating requirements, we will have to raise additional funds. If we are unable to obtain additional funds on terms favorable to us or at all, we may berequired to cease or reduce our operating activities or sell or license to third-parties some or all of our intellectual property. If we raise additional funds byselling additional shares of our capital stock, the ownership interests of our stockholders will be diluted. If we need to raise additional funds through the saleor license of our intellectual property, we may be unable to do so on terms favorable to us, if at all. In addition, if we do not continue to meet our diligenceobligations under our license agreements for our product candidates that we have in-licensed, including SL-401, SL-701, and SL-801, we will lose our rightsto develop and commercialize those product candidates. If we do not successfully develop and obtain regulatory approval for our existing and future product candidates and effectively manufacture, market and sellany product candidates that are approved, we may never generate product sales, and even if we do generate product sales, we may never achieve or sustainprofitability on a quarterly or annual basis. Our failure to become and remain profitable would depress the market price of our common stock and couldimpair our ability to raise capital, expand our business, diversify our product offerings or continue our operations. A decline in the market price of ourcommon stock also could cause you to lose all or a part of your investment. We will require additional financing to achieve our goals, and a failure to obtain this capital when needed could force us to delay, limit, reduce orterminate our product development or commercialization efforts. Since our inception, most of our resources have been dedicated to the discovery, acquisition and preclinical and clinical development of our productcandidates. We have expended and believe that we may continue to expend substantial resources for the development of SL-401, SL-701, and SL-801, aswell as other product candidates and drug discovery and acquisition efforts. These expenditures will include costs associated with general administration,facilities, research and development, acquiring new technologies, manufacturing product candidates, conducting preclinical experiments and clinical trials,obtaining regulatory approvals, commercializing any products approved for sale, and costs associated with operating as a public company. We have no significant current source of revenue to sustain our present activities, and we do not expect to generate revenue until, and unless, we obtainapproval from the FDA or other regulatory authorities, and we successfully commercialize one or more of our compounds. As the outcome of our ongoing andfuture clinical trials is highly uncertain, our estimates of clinical trial costs necessary to successfully complete the development and commercialization of ourproduct candidates may differ significantly from our actual costs. In addition, other unanticipated costs may arise. As a result of these and other factorscurrently unknown to us, we may need to seek additional funds sooner than planned, through public or private equity, debt financings or other sources, suchas strategic partnerships and alliances and licensing arrangements. In addition, we may seek additional capital due to favorable market conditions or strategicconsiderations even if we believe we have sufficient funds for our current or future operating plans. 35Table of Contents Our future capital requirements depend on many factors, including: · the number and characteristics of the product candidates we pursue; · the scope, progress, results and costs of researching and developing our product candidates, and conducting preclinical and clinical trials; · the ability of our product candidates to progress through clinical development successfully; · the timing of, and the costs involved in, obtaining regulatory approvals for our product candidates; · the cost of commercialization activities if any of our product candidates are approved for sale, including marketing, sales and distribution costs; · the cost associated with securing and establishing commercialization and manufacturing capabilities for our product candidates and any productswe successfully commercialize; · our ability to establish and maintain strategic partnerships, licensing or other arrangements and the economic and other terms of such agreements; · the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing patent claims, including litigation costs and the outcomeof such litigation; · the timing, receipt and amount of sales of, or royalties on, our future products, if any; · our need and ability to hire additional management and scientific and medical personnel; · the effect of competing technological and market developments; and · our need to implement additional internal systems and infrastructure, including financial and reporting systems. Additional funds may not be available when we need them, on terms that are acceptable to us, or at all. If adequate funds are not available to us on a timelybasis, we may be required to: · delay, limit, reduce or terminate preclinical studies, clinical trials (including patient accrual) or other research and development activities for one ormore of our product candidates; · delay, limit, reduce or terminate manufacturing of our product candidates; or · delay, limit, reduce or terminate our establishment of sales and marketing capabilities or other activities that may be necessary to commercialize ourproduct candidates. We will need to raise additional funds to complete our clinical trials and achieve positive cash flow. Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies orproduct candidates. We will likely seek to raise additional capital through a combination of private and public equity offerings, debt financings, strategic partnerships andalliances and licensing arrangements. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownershipinterests of existing stockholders will be diluted, and the terms may include liquidation or other preferences that adversely affect stockholder rights. Debtfinancing, if available, may involve agreements that include covenants limiting or restricting our ability to take certain actions, such as incurring debt,making capital expenditures or declaring dividends. If we raise additional funds through strategic partnerships and alliances and licensing arrangements withthird-parties, we may have to relinquish valuable rights to our technologies or product candidates, or grant licenses on terms that are not favorable to us. If weare unable to raise additional funds through equity or debt financing when needed, we may be required to delay, limit, reduce or terminate our productdevelopment or commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and marketourselves. 36Table of Contents Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price. There can be no assurance that deterioration in credit and financial markets and confidence in economic conditions will not occur. Our general businessstrategy may be adversely affected by an economic downturn, a volatile business environment or an unpredictable and unstable market. If equity and creditmarkets deteriorate, it may make any necessary equity, debt, or other financing more difficult to secure, more costly, more dilutive, and less favorable toexisting shareholders. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our growthstrategy, financial performance and stock price and could require us to delay or abandon our business and clinical development plans. In addition, there is arisk that one or more of our current service providers, manufacturers and other partners may not survive these difficult economic times, which could directlyaffect our ability to attain our operating goals on schedule and on budget. There is a possibility that our stock price may decline, due in part to the volatilityof the stock market and the general economic downturn. Risks Related to Our Business and Industry We are a clinical stage company with no approved products, which makes it difficult to assess our future viability. We are a clinical stage biopharmaceutical company with a limited operating history. We have not yet demonstrated an ability to successfully overcome manyof the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biopharmaceutical area. Forexample, to execute our business plan, we will need to successfully: · execute product candidate development activities; · obtain required regulatory approvals for the development and commercialization of our product candidates; · maintain, defend, leverage and expand our intellectual property portfolio; · build and maintain sales, distribution and marketing capabilities, either on our own or in collaboration with strategic partners should ourproducts obtain market approval; · gain market acceptance for our products should they obtain market approval; · develop and maintain GMP compliant manufacturing and distribution capabilities sufficient to support the intended scope of our pre-clinicaland clinical development plans and the potential commercial demand for our product(s); · develop and maintain any strategic relationships we elect to enter into; · satisfy our obligations under our license and other agreements; and · manage our spending as costs and expenses increase due to drug discovery, preclinical development, clinical trials, regulatory approvals,manufacturing and commercialization. If we are unsuccessful in accomplishing these objectives, we may not be able to develop product candidates, raise capital, expand our business or continueour operations. We face substantial competition, which may result in others discovering, developing or commercializing products before, or more successfully, than we do. Our future success depends on our ability to demonstrate and maintain a competitive advantage with respect to the design, development andcommercialization of product candidates. Our competitors may succeed in developing competing products before we do for the same indications we arepursuing, obtaining regulatory approval for products or gaining acceptance for the same markets that we are targeting. If we are not “first to market” with oneof our product candidates, our competitive position could be compromised because it may be more difficult for us to obtain marketing approval for thatproduct candidate and successfully market that product candidate as a second competitor. We expect any product candidate that we commercialize will compete with products from other companies in the biotechnology and pharmaceuticalindustries. For example, there are a number of biopharmaceutical companies focused on developing therapeutics that target CSCs, including Verastem, Inc.,OncoMed Pharmaceuticals, Inc., Sumitomo Dainippon Pharma Co. Ltd., Bionomics Limited and Stemcentrx, Inc. There are also several biopharmaceuticalcompanies that do not appear to be primarily focused on CSCs, but 37Table of Contents may be developing at least one CSC-directed compound. These companies include Astellas Pharma US, Inc., Boehringer Ingelheim GmbH, Geron Corp.,GlaxoSmithKline plc, Macrogenics Inc., Micromet, Inc. (an Amgen, Inc. company), Pfizer Inc., Roche Holding AG, Sanofi U.S. LLC, and others. Additionally, there are a number of companies working to develop new treatments for hematologic cancers, which may compete with SL-401 and SL-801,including AbbView, Agios, Inc., Ambit Biosciences Corporation (now a Daiichi Sankyo company), Amgen, Astex Pharmaceuticals (now an OtsukaPharmaceutical company), Celator Pharmaceuticals, Inc., Celgene Corporation, Cellectis, Cyclacel Pharmaceuticals, Inc., Eisai Co. Ltd., GenzymeCorporation (now a Sanofi company), Janssen Pharmaceutical Companies of Johnson and Johnson, Karyopharm Therapeutics, Inc., Novartis AG, SeattleGenetics, Inc., and Sunesis Pharmaceuticals, Inc., among others. There are also a number of drugs used for the treatment of brain cancer that may compete withSL-701, including, Avastin (Roche Holding AG), Gliadel (Eisai Co. Ltd.), and Temodar (Merck & Co., Inc.). There are also a number of drugs used for thetreatment of brain cancer that may compete with SL-701, including, Avastin® (Roche Holding AG), Gliadel® (Eisai Co. Ltd.), andTemodar® (Merck & Co., Inc.). There are a number of companies working to develop brain cancer therapeutics with programs in clinical testing, includingAgenus Inc., Bristol-Myers Squibb, Inc., Cortice Biosciences, Inc., Celldex Therapeutics, Inc., CytRx Corporation, GenSpera, Inc., GlaxoSmithKlineplc., ImmunoCellular Therapeutics, Ltd., Northwest Biotherapeutics, Inc., Novartis AG, Roche Holding AG and others. Many of our competitors have substantially greater commercial infrastructures and financial, technical and personnel resources than we have. In addition,many are farther along in their clinical development programs. We may not be able to compete unless we successfully: · design and develop products that are superior to other products in the market; · conduct successful preclinical and clinical trials; · attract qualified scientific, medical, sales and marketing and commercial personnel; · obtain patent and/or other proprietary protection for our processes and product candidates; · obtain required regulatory approvals; and · collaborate with others in the design, development and commercialization of new products. Established competitors may invest heavily to quickly discover and develop novel compounds that could make our product candidates obsolete. In addition,any new product that competes with an approved product must demonstrate compelling advantages in efficacy, convenience, tolerability and safety in orderto overcome price competition and to be commercially successful. If we are not able to compete effectively against our current and future competitors, ourbusiness will not grow and our financial condition and operations will suffer. If we fail to attract and keep senior management and key scientific personnel, we may be unable to successfully develop our product candidates, conductour clinical trials and commercialize our product candidates. Our success depends in part on our continued ability to attract, retain and motivate highly qualified management, clinical and scientific personnel. We arehighly dependent upon our senior management as well as other employees, consultants and scientific and medical collaborators. As of March 14, 2016, wehad 24 full-time employees, which may make us more reliant on our individual employees than companies with a greater number of employees. Althoughnone of these individuals has informed us to date that he or she intends to retire or resign in the near future, the loss of services of any of these individuals orone or more of our other members of senior management could delay or prevent the successful development of our product pipeline, completion of ourongoing and future clinical trials or the commercialization of our product candidates. Although we have not historically experienced unique difficulties attracting and retaining qualified employees, we could experience such problems in thefuture. For example, competition for qualified personnel in the biotechnology and pharmaceuticals field is intense. We will need to hire additional personnelas we expand our clinical development and commercial activities. We may not be able to attract and retain quality personnel on acceptable terms. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development andcommercialization strategy. Our consultants and advisors may be employed by employers other than us and may have commitments under consulting oradvisory contracts with other entities that may limit their availability to us. 38®®®Table of Contents If our employees commit fraud or other misconduct, including noncompliance with regulatory standards and requirements, our business may experienceserious adverse consequences. We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees could include intentional failures to comply with FDAregulations, to provide accurate information to the FDA, to comply with manufacturing standards we have established, to comply with federal and statehealthcare fraud and abuse laws and regulations, to report financial information or data accurately or to disclose unauthorized activities to us. In particular,sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, salescommission, customer incentive programs and other business arrangements. Employee misconduct could also involve the improper use of informationobtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation. We have adopted a Code of BusinessConduct and Ethics, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activitymay not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuitsstemming from a failure to be in compliance with such laws or regulations. If any such actions are instituted against us, and we are not successful in defendingourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or othersanctions. We may encounter difficulties in managing our growth and expanding our operations successfully. As we seek to advance our product candidates through clinical trials, we will need to expand our development, regulatory, manufacturing, marketing andsales capabilities or contract with third-parties to provide these capabilities for us. As our operations expand, we expect that we will need to identify,commence and manage additional relationships with various strategic partners, qualified suppliers, manufacturers and other third-parties. Future growth willimpose significant added responsibilities on members of management. Our future financial performance and our ability to commercialize our productcandidates and to compete effectively will depend, in part, on our ability to manage any future growth effectively. To that end, we must be able to manageour development efforts and clinical trials effectively and hire, train and integrate additional management, administrative and sales and marketing personnel.The hiring, training and integration of new employees may be more difficult, costly and/or time-consuming for us because we have fewer resources than alarger organization. We may not be able to accomplish these tasks, and our failure to accomplish any of them could prevent us from successfully growing ourcompany. If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of our productcandidates. We face an inherent risk of product liability as a result of the clinical testing of our product candidates and will face an even greater risk if we commercializeany products. For example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during product testing,clinical study, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, afailure to warn of dangers inherent in the product, negligence, strict liability and a breach of warranties. Claims could also be asserted under state consumerprotection acts. If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to limitcommercialization of our product candidates. Even successful defense would require significant financial and management resources. Regardless of themerits or eventual outcome, liability claims may result in: · decreased demand for our product candidates or products that we may develop; · injury to our reputation; · withdrawal of clinical trial participants and inability to enroll future clinical trial participants; · costs to defend the related litigation; · a diversion of management’s time and our resources; · substantial monetary awards to trial participants or patients; · product recalls, withdrawals or labeling, marketing or promotional restrictions; · loss of revenue; 39Table of Contents · the inability to commercialize our product candidates; and · a decline in our stock price. Our inability to obtain and retain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims couldprevent or inhibit the commercialization of products we develop. Although we maintain liability insurance, any claim that may be brought against us couldresult in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurancecoverage. Our insurance policies also have various exclusions, and we may be subject to a product liability claim for which we have no coverage. We willhave to pay any amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, andwe may not have, or be able to obtain, sufficient capital to pay such amounts. Our relationships with customers and third-party payors in the United States and elsewhere will be subject to applicable anti-kickback, fraud and abuseand other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm anddiminished profits and future earnings. Healthcare providers, physicians and third-party payors in the United States and elsewhere play a primary role in the recommendation and prescription of anyproduct candidates for which we obtain marketing approval. Our future arrangements with third-party payors and customers may expose us to broadlyapplicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships throughwhich we market, sell and distribute our products for which we obtain marketing approval. Restrictions under applicable federal, state and foreign healthcarelaws and regulations include the following: · the federal healthcare anti-kickback statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receivingor providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase,order or recommendation of, any good or service for which payment may be made under federal and state healthcare programs such as Medicareand Medicaid; · the federal False Claims Act imposes criminal and civil penalties, against individuals or entities for knowingly presenting, or causing to bepresented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal anobligation to pay money to the federal government and also includes provisions allowing for private, civil whistleblower or “qui tam” actions; · the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended by the Health Information Technology forEconomic and Clinical Health Act (“HITECH”), imposes criminal and civil liability for executing a scheme to defraud any healthcare benefitprogram. HIPAA and HITECH also regulate the use and disclosure of identifiable health information by healthcare providers, health plans andhealthcare clearinghouses, and impose obligations, including mandatory contractual terms, with respect to safeguarding the privacy, securityand transmission of identifiable health information as well as requiring notification of regulatory breaches. HIPAA and HITECH violations mayprompt civil and criminal enforcement actions as well as enforcement by state attorneys general; · the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making anymaterially false statement in connection with the delivery of or payment for healthcare benefits, items or services; · the federal transparency requirements under the Health Care Reform Law requires manufacturers of drugs, devices, biologics and medicalsupplies to report to the Department of Health and Human Services information related to physician payments and other transfers of value andphysician ownership and investment interests; · analogous state laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements andclaims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, and some statelaws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevantcompliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related topayments to physicians and other healthcare providers or marketing expenditures; and · analogous anti-kickback, fraud and abuse and healthcare laws and regulations in foreign countries. Efforts to ensure that our business arrangements with third-parties will comply with applicable healthcare laws and regulations will involve substantial costs.It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case lawinvolving applicable fraud and abuse or other healthcare laws and regulations. If our 40Table of Contents operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significantcivil, criminal and administrative penalties, damages, fines, exclusion from government funded healthcare programs, such as Medicare and Medicaid, and thecurtailment or restructuring of our operations. If any of the physicians or other providers or entities with whom we expect to do business are found to be not incompliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcareprograms. If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that couldhave a material adverse effect on the success of our business. We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use,storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous and flammable materials, including chemicalsand biological materials. Our operations also produce hazardous waste products. We generally contract with third-parties for the disposal of these materialsand wastes. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use ofhazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costsassociated with civil or criminal fines and penalties. Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from theuse of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmentalliability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials. In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current orfuture laws and regulations may impair our research, development or production efforts. Failure to comply with these laws and regulations also may result insubstantial fines, penalties or other sanctions. Risks Related to Commercialization of Our Product Candidates If we are unable to establish or implement our own sales, marketing and distribution capabilities in a timely matter or enter into licensing or collaborationagreements for these purposes, we may not be successful in commercializing our product candidates. We currently have a relatively small number of employees and do not have a sales or marketing infrastructure, and we, including our executive officers, donot have any significant sales, marketing or distribution experience. We will be opportunistic in seeking to either build our own commercial infrastructure tocommercialize SL-401, SL-701, SL-801, and any future product candidates if and when they are approved, or enter into licensing or collaboration agreementsto assist in the future development and commercialization of such product candidates. To develop internal sales, distribution and marketing capabilities, we will have to invest significant amounts of financial and management resources, some ofwhich will be committed prior to any confirmation that SL-401, SL-701, and/or SL-801 will be approved. For product candidates for which we decide toperform sales, marketing and distribution functions ourselves, we could face a number of additional risks, including: · our inability to recruit and retain adequate numbers of effective sales and marketing personnel; · the inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians to prescribe any future products; · the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companieswith more extensive product lines; · unforeseen costs and expenses associated with creating an independent sales and marketing organization; and · our inability to build our own commercial infrastructure to manufacture, market and sell our product candidates; and · our inability to build and staff, or enter a partnership to support, a commercial distribution capability. Where and when appropriate, we may elect to utilize contract sales forces or strategic partners to assist in the commercialization of our product candidates. Ifwe enter into arrangements with third-parties to perform sales, marketing and distribution services for our products, the resulting revenues or the profitabilityfrom these revenues to us are likely to be lower than if we had sold, marketed and 41Table of Contents distributed our products ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell, market and distribute ourproduct candidates or may be unable to do so on terms that are favorable to us. We likely will have little control over such third parties, and any of these thirdparties may fail to devote the necessary resources and attention to sell, market and distribute our products effectively and may engage in conduct thatsubjects us to significant regulatory enforcement action. If we do not establish sales, marketing and distribution capabilities successfully and in compliance with legal and regulatory requirements, either on our ownor in collaboration with third-parties, we will not be successful in commercializing our product candidates. Our commercial success depends upon attaining significant market acceptance of our product candidates, if approved, including SL-401, SL-701, and SL-801, among physicians and other healthcare providers, patients, third-party payors and, in the cancer market, acceptance by the operators of major cancerclinics. Even if SL-401, SL-701, SL-801, or any other product candidate that we may develop or acquire in the future obtains regulatory approval, the product maynot gain market acceptance among physicians, third-party payors, patients and the medical community. For example, current cancer treatments such aschemotherapy and radiation therapy are well established in the medical community, and doctors may continue to rely on these treatments. The degree ofmarket acceptance of any products for which we receive approval for commercial sale depends on a number of factors, including: · the efficacy and safety of our products, as demonstrated in clinical trials, and the degree to which our products represent a clinically meaningfulimprovement in care as compared with other available therapies; · the clinical indications for which our products are approved; · acceptance by physicians, operators of major cancer clinics and patients of our products as a safe and effective treatment; · the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; · the potential and perceived advantages of our products over alternative treatments; · the cost of treatment in relation to alternative treatments; · the availability of adequate reimbursement and pricing by third-parties and government authorities; · the continued projected growth of oncology drug markets; · relative convenience and ease of administration; · the prevalence and severity of adverse side effects; and · the effectiveness of our sales and marketing efforts. If our approved drugs fail to achieve market acceptance, we would not be able to generate significant revenue. Even if we are able to commercialize any product candidates, the products may become subject to unfavorable pricing regulations, third-partyreimbursement practices or healthcare reform initiatives, which would harm our business. The regulations that govern marketing approvals, pricing and reimbursement for new drug products vary widely from country to country. In the United States,recently passed legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtainingapprovals. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins aftermarketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmentalcontrol even after initial approval is granted. As a result, we might obtain marketing approval for a product in a particular country, but then be subject toprice regulations that delay our commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able togenerate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more productcandidates, even if our product candidates obtain marketing approval. Our ability to commercialize any products successfully also will depend in part on the extent to which reimbursement for these products and relatedtreatments will be available from government health administration authorities, private health insurers and other 42Table of Contents organizations. Government authorities and third-party payors, such as private health insurers and health maintenance organizations, decide whichmedications they will cover and how much they will pay for them. A primary trend in the U.S. healthcare industry and elsewhere is cost containment.Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particularmedications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and arechallenging the prices charged for medical products. We cannot be sure that reimbursement will be available for any product that we commercialize and, ifreimbursement is available, the level of reimbursement. Reimbursement may impact the demand for, or the price of, any product candidate for which weobtain marketing approval. Obtaining reimbursement for our products may be particularly difficult because of the higher prices often associated with drugsadministered under the supervision of a physician. If reimbursement is not available or is available only to limited levels, we may not be able to successfullycommercialize any product candidate for which we obtain marketing approval. There may be significant delays in obtaining reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which thedrug is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for reimbursement does not imply that any drugwill be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim reimbursementlevels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according tothe use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporatedinto existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcareprograms or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower pricesthan in the United States. Third-party payors often follow Medicare coverage policy and payment limitations in setting their own reimbursement policies.Our inability to promptly obtain coverage and profitable payment rates from both government-funded and private payors for any approved products that wedevelop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financialcondition. Healthcare policy changes may have a material adverse effect on us. Our business may be affected by the efforts of government and third-party payors to contain or reduce the cost of healthcare through various means. Forexample, the Patient Protection and Affordable Care Act and the Health Care and Education Affordability Reconciliation Act of 2010 (collectively, theAffordable Care Act or ACA), enacted in March 2010, substantially changed the way healthcare is financed by both governmental and private insurers, andsignificantly impacted the pharmaceutical industry. With regard to pharmaceutical products, among other things, the ACA is expected to expand andincrease industry rebates for drugs covered under Medicaid programs and make changes to the coverage requirements under the Medicare Part D program.The Supreme Court upheld the ACA in the main challenge to the constitutionality of the statute in 2012. The Supreme Court also upheld federal subsidies forpurchasers of insurance through federally facilitated exchanges in a decision released in June 2015. While other challenges remain to portions of the ACA,these two cases were generally viewed as the only existential threats to the statute that have been raised so far. Proposals such as expanding the Medicaiddrug rebate program to the Medicare Part D program, providing authority for the government to negotiate drug prices under the Medicare Part D program andlowering reimbursement for drugs covered under the Medicare Part B program have been presented to Congress in 2016, including by the currentAdministration, but implementation likely will be challenging in light of strong opposition to these proposals as well as the current political climate. TheAdministration can rely on its existing statutory authority to make policy changes that could have an impact on the drug industry. For example, theMedicare program has proposed to test alternative payment methodologies for drugs covered under the Part B program. In general, we cannot predict theimpact that the ACA or any other legislative or regulatory proposals will have on our business. Regardless of whether or not the ACA is changed or modifiedby Congress or the Supreme Court, we expect both government and private health plans to continue to require healthcare providers, including healthcareproviders that may one day purchase our products, to contain costs and demonstrate the value of the therapies they provide. Our therapeutic product candidates for which we intend to seek approval as biological products may face competition sooner than expected. With the enactment of the Biologics Price Competition and Innovation Act of 2009, or BPCIA, as part of the Health Care Reform Law, an abbreviatedpathway for the approval of biosimilar and interchangeable biological products was created. The new abbreviated regulatory pathway establishes legalauthority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as “interchangeable.” The FDA definesan interchangeable biosimilar as a product that, in terms of safety or diminished efficacy, presents no greater risk when switching between the biosimilar andits reference product than the risk of using the reference product alone. Under the BPCIA, an application for a biosimilar product cannot be submitted to theFDA until four years, or approved by the FDA until 12 years, after the original brand product identified as the reference product was approved under a BLA.The new law is complex and is only beginning to be interpreted by the FDA. As a result, its ultimate impact, implementation and meaning are subject touncertainty. While it is uncertain when any such processes may be fully adopted by the FDA, any such processes could have a material adverse effect on thefuture commercial prospects for our biological products. We believe that if any of our product candidates, such as SL-401,SL-701 or SL-801, were to receive marketing approval by the FDA as a biological productunder a BLA, such an approved product(s) should qualify for the 12-year period of exclusivity. However, there 43Table of Contents is a risk that the U.S. Congress could amend the BPCIA to significantly shorten this exclusivity period potentially creating the opportunity for genericcompetition sooner than anticipated. Moreover, the extent to which a biosimilar, once approved, will be substituted for any one of our reference products in away that is similar to traditional generic substitution for non-biological products is not yet clear, and will depend on a number of marketplace and regulatoryfactors that are still developing. In addition, a competitor could decide to forego the biosimilar route and submit a full BLA after completing its ownpreclinical studies and clinical trials. In such cases, any exclusivity to which we may be eligible under the BPCIA would not prevent the competitor frommarketing its product as soon as it is approved. Risks Related to Our Dependence on Third Parties Third parties have conducted initial clinical trials of our product candidates in the past, and our ability to influence the design and conduct of such trialswas limited. Our current and future corporate-sponsored trials will also require us to rely on various third parties. Any failure by a third party to meet itsobligations with respect to the clinical and regulatory development of our product candidates may delay or impair our ability to obtain regulatoryapproval for our products. We are currently advancing our clinical stage product candidates through multiple corporate-sponsored clinical trials under corporate-sponsoredinvestigational new drugs, or INDs. Previously, we had not sponsored any INDs or any clinical trials relating to SL-401 or SL-701. Instead, faculty members atacademic institutions conducted and sponsored all INDs and clinical trials relating to our drug candidates. Because the completed trials relating to our drugcandidates were investigator-sponsored, we did not control the design or conduct of the previous trials, and it is possible that the FDA will not view theseprevious trials as providing adequate support for future clinical trials or regulatory filings, whether controlled by us or third parties, for any one or morereasons, including elements of the design or execution of the previous trials or safety concerns or other trial results. In addition, we have relied on contractual arrangements with academic institutions and investigators that provide us certain information rights with respect tothe completed investigator-sponsored trials, including access to and the ability to use and reference the data, including for our own regulatory filings,resulting from the completed trials. If these obligations are breached by the investigators or institutions, or if the data prove to be inadequate then our abilityto conduct our planned corporate-sponsored clinical trials may be adversely affected. Additionally, the FDA may disagree with the adequacy of ourinterpretation of preclinical, manufacturing, or clinical data from these clinical trials. If so, the FDA may require us to obtain and submit additionalpreclinical, manufacturing, or clinical data relating to our planned trials and/or may not accept such additional data as adequate for our regulatory filings. We rely on, and expect to continue to rely on, third parties to monitor, support, conduct and/or oversee clinical trials of our product candidates and, insome cases, to maintain regulatory files for our product candidates. If we are not able to maintain or secure agreements with such third parties onacceptable terms to monitor, support, conduct and/or oversee these clinical trials, if these third parties do not perform their services as required, or if thesethird parties fail to timely transfer any regulatory information held by them to us, we may not be able to obtain regulatory approval for, or commercialize,our product candidates. We rely on academic institutions, CROs, hospitals, clinics and other third-party collaborators who are outside our control to monitor, support, conduct and/oroversee preclinical and clinical studies of our product candidates. As a result, we have less control over the timing and cost of these studies and the ability torecruit trial subjects than if we had conducted these trials wholly by ourselves. In our corporate sponsored trials of SL-401 and SL-701, we have continued toengage various third parties and intend to do so with our SL-801 program as well. If we are unable to maintain or enter into agreements with these third-parties on acceptable terms, or if any such engagement is terminated, we may be unable to enroll patients on a timely basis or otherwise conduct our trials inthe manner we anticipate. In addition, there is no guarantee that these third-parties will devote adequate time and resources to our studies or perform asrequired by contract or in accordance with regulatory requirements. If these third-parties fail to meet expected deadlines, fail to adhere to protocols or fail toact in accordance with regulatory requirements or our agreements with them, or if they otherwise perform in a substandard manner or in a way thatcompromises the quality or accuracy of their activities or the data they obtain, then clinical trials of our product candidates may be extended, delayed orterminated, and as a result we may not be able to commercialize our product candidates. We may not be successful in establishing and maintaining strategic partnerships, which could adversely affect our ability to develop and commercializeproducts. We may seek to enter into strategic partnerships in the future, including alliances with other biotechnology or pharmaceutical companies, to enhance andaccelerate the development and commercialization of our products in territories outside the United States. We face significant competition in seekingappropriate strategic partners and the negotiation process is time-consuming and complex. Moreover, we may not be successful in our efforts to establish astrategic partnership or other alternative arrangements for any future product candidates and programs because our research and development pipeline may beinsufficient, our product candidates and programs may be deemed to be at too early of a stage of development for collaborative effort and/or third-parties maynot view our 44Table of Contents product candidates and programs as having the requisite potential to demonstrate safety and efficacy. Even if we are successful in our efforts to establishstrategic partnerships, the terms that we agree upon may not be favorable to us and we may not be able to maintain such strategic partnerships if, for example,development or approval of a product candidate is delayed or sales of an approved product are disappointing. If we ultimately determine that entering into strategic partnerships is in our best interest but either fail to enter into, are delayed in entering into or fail tomaintain such strategic partnerships: · the development of certain of our current or future product candidates may be terminated or delayed; · our cash expenditures related to development of certain of our current or future product candidates would increase significantly and we mayneed to seek additional financing; · we may be required to hire additional employees or otherwise develop expertise, such as sales and marketing expertise, for which we have notbudgeted; · we will bear all of the risk related to the development of any such product candidates; · the competitiveness of any product candidate that is commercialized could be reduced; and · with respect to our platform technology, StemScreen, we may not realize its potential as a means of identifying and validating new cancertherapies. We rely on third-party manufacturers to produce and supply our clinical and preclinical product candidates and we intend to rely on third-partymanufacturers to produce commercial supplies of any approved products. Any failure by a third-party manufacturer to produce supplies for us may delayor impair our ability to initiate or complete our clinical trials, commercialize our products or continue to sell any products we commercialize. We do not currently own or operate any manufacturing facilities, and we lack sufficient internal staff and infrastructure to produce clinical and preclinicalproduct candidate supplies ourselves. As a result, we work with third-party contract manufacturing organizations, or CMOs, to produce SL-401, SL-701, andSL-801 in acceptable quality and quantity for our ongoing and future clinical trials. If we are unable to maintain such third-party manufacturing sources, orfail to do so on commercially reasonable terms or on a timely basis, we may not be able to successfully produce, develop, and market SL-401, SL-701, and/orSL-801, or may be delayed in doing so. We purchase and plan to purchase immunostimulants used with SL-701 from third-parties. Whereas GM-CSF andImiquimod are commercially available products, poly-ICLC (Hiltonol®) is a development stage candidate and not commercially available. We do not have aright to manufacture poly-ICLC directly or through third-party CMO’s and are dependent on the distributor of poly-ICLC for clinical supply. We also expect to rely upon third-parties to produce drug product required for the clinical trials and commercialization of our other product candidates,including SL-501. If we are unable to arrange for third-party manufacturing sources, or to do so on commercially reasonable terms or on a timely basis, wemay not be able to complete development of such other product candidates or market them. Reliance on third-party manufacturers entails risks to which we would not be subject if we manufactured product candidates ourselves, including reliance onthe third-party for regulatory compliance and quality assurance, the possibility of breach of the manufacturing agreement by the third-party because of factorsbeyond our control (including a failure to synthesize and manufacture our product candidates in accordance with our product specifications) and thepossibility of termination or nonrenewal of the agreement by the third-party, based on its own business priorities, at a time that is costly or damaging to us.We will be dependent on the ability of these third-party manufacturers to produce adequate supplies of drug product to support our clinical developmentprograms and future commercialization of our product candidates. In addition, the FDA and other regulatory authorities require that our product candidatesbe manufactured according to cGMP and similar foreign standards. Any failure by our third-party manufacturers to comply with cGMP or failure to scale upmanufacturing processes, including any failure to deliver sufficient quantities of product candidates of acceptable quality in a timely manner, could lead to adelay in, or failure to obtain, regulatory approval for trial initiation or marketing of any of our product candidates. In addition, such failure could be the basisfor action by the FDA to withdraw approvals for product candidates previously granted to us and for other regulatory action, including recall or seizure, fines,imposition of operating restrictions, total or partial suspension of production or injunctions. We rely on our third-party manufacturers to purchase from third-party suppliers the materials necessary to produce our product candidates for our clinicalstudies. There are a small number of suppliers for certain capital equipment and materials that we use to manufacture our drugs. Such suppliers may not sellthese materials to our manufacturers at the times we need them or on commercially reasonable terms. We do not have control over the process or timing of theacquisition of these materials by our manufacturers. Moreover, we currently do not have any agreements for the commercial production of these materials.Although we 45®Table of Contents generally do not begin a clinical trial unless we believe we have a sufficient supply of a product candidate to complete the clinical trial, any significant delayin the supply of a product candidate or the material components thereof for a clinical trial, including an ongoing clinical trial, due to the need to replace athird-party manufacturer could considerably delay completion of our clinical studies, product testing and potential regulatory approval of our productcandidates. If our manufacturers or we are unable to purchase these materials after regulatory approval has been obtained for our product candidates, thecommercial launch of our product candidates would be delayed or there would be a shortage in supply, which would impair our ability to generate revenuesfrom the sale of our product candidates. We are working with our contract manufacturers to optimize the manufacturing processes for drug substance and drug product of our product candidates sothat these product candidates may be routinely produced in adequate quantities of adequate quality, and at an acceptable cost, to support our clinical trialsand ultimate commercialization. Our manufacturers may not be able to control batch to batch variability below an acceptable threshold, increasing the risk ofbatch failures, which could cause significant delays and increased costs to our programs. Our manufacturers may not be able to manufacture our productcandidates at a cost or in quantities or in a timely manner necessary to develop and commercialize them. If we successfully commercialize any of our drugs,we may be required to establish or access large-scale commercial manufacturing capabilities. In addition, assuming that our drug development pipelineincreases and matures, we will have a greater need for clinical trial and commercial manufacturing capacity. To meet our projected needs for commercialmanufacturing, third-parties with whom we currently work may need to increase their scale of production and/or we will need to secure additional suppliers. We rely on a single third-party to manufacture and supply our drug substance and a single third-party to manufacture and supply our drug product foreach of our product candidates. Any problems experienced by our third-party manufacturers or their vendors could result in a delay or interruption in thesupply of our product candidate to us until the third-party manufacturer or its vendor cures the problem or until we locate and qualify an alternativesource of manufacturing and supply. The manufacturers of our product candidates require specialized equipment and utilize complicated production processes that would be difficult, timeconsuming and costly to duplicate. For each of our product candidates we currently rely on third-party manufacturers to purchase from their third-partyvendors the materials necessary to manufacture our product candidates for our clinical studies. Any prolonged disruption in our third-party manufacturersvendor’s ability to supply materials for our manufacturing could have a significant negative impact on our ability to manufacture products on our own andwould cause us to seek additional third-party manufacturing contracts, thereby increasing our development costs and timelines and any commercializationcosts. In addition, our third-party manufacturers may experience problems not related to their vendors that could also have a significant negative impact onour ability to manufacture products on our own and would cause us to seek additional third-party manufacturing contracts, thereby increasing ourdevelopment costs and timelines and any commercialization costs. We may face losses related to the supply of drug substances, drug product, adjuvants andother components of the product due to third-party distribution and storage of such product. We may suffer losses due to third-party manufacturer shortagesor supply shortages of their vendors. We may suffer losses as a result of business interruptions that exceed coverage under our manufacturer’s insurancepolicies. Events beyond our control, such as natural disasters, fire, sabotage or business accidents could have a significant negative impact on our operationsby disrupting our product candidate development and commercialization efforts until our third-party manufacturer can repair its facility or we can put inplace alternate third-party contract manufacturers to assume this manufacturing role, which we may not be able to do on reasonable terms, if at all. Inaddition, if we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities andprocedures that comply with quality standards and with all applicable regulations and guidelines and that they can successfully transfer our manufacturingprocesses to produce product of equivalent quality and quantity. FDA approval of the new manufacturer may also be required. The delays associated with theverification of a new manufacturer or the reverification of an existing manufacturer could negatively affect our ability to develop product candidates orproduce approved products in a timely manner. Any delay or interruption in our clinical studies or in the development, validation and commercialization ofour product candidates could negatively affect our business. To the extent we elect to enter into licensing or collaboration agreements to partner our product candidates, our dependence on such relationships mayadversely affect our business. Our global commercialization strategy for certain of our product candidates may depend on our ability to enter into agreements with collaborators to obtainassistance and funding for the development and potential commercialization of these product candidates. Supporting diligence activities conducted bypotential collaborators and negotiating the financial and other terms of a collaboration agreement are long and complex processes with uncertain results.Even if we are successful in entering into one or more collaboration agreements, collaborations may involve greater uncertainty for us, as we have less controlover certain aspects of our collaborative programs than we do over our proprietary development and commercialization programs. We may determine thatcontinuing to collaborate under the terms provided is not in our best interest, and we may terminate such collaboration. Our collaborators could delay orterminate their agreements, and our products subject to collaborative arrangements may never be successfully commercialized. 46Table of Contents Further, our future collaborators may develop alternative products or pursue alternative technologies either on their own or in collaboration with others,including our competitors, and the priorities or focus of our collaborators may shift such that our programs receive less attention or resources than we wouldlike, or they may be terminated altogether. Any such actions by our collaborators may adversely affect our business prospects and ability to earn revenues. Inaddition, we could have disputes with our future collaborators, such as the interpretation of terms in our agreements. Any such disagreements could lead todelays in the development or commercialization of any potential products or could result in time-consuming and expensive litigation or arbitration, whichmay not be resolved in our favor. Even with respect to certain other programs that we intend to commercialize ourselves, we may enter into agreements with collaborators to share in theburden of conducting clinical trials, manufacturing and marketing our product candidates or products. In addition, our ability to apply our proprietarytechnologies to develop proprietary compounds will depend on our ability to establish and maintain licensing arrangements or other collaborativearrangements with the holders of proprietary rights to such compounds. We may not be able to establish such arrangements on favorable terms or at all, andour future collaborative arrangements may not be successful. Risks Related to Our Intellectual Property Rights We could be unsuccessful in obtaining adequate patent protection for one or more of our product candidates. We cannot be certain that patents will be issued, or that issued or allowed patents will not later be found to be invalid and/or unenforceable. The patentposition of biotechnology and pharmaceutical companies is generally uncertain because it involves complex legal and factual considerations. The standardsapplied by the U.S. Patent and Trademark Office and foreign patent offices in granting patents are not always applied uniformly or predictably. For example,there is no uniform worldwide policy regarding patentable subject matter or the scope of claims allowable in biotechnology and pharmaceutical patents.Consequently, patents may not issue from our pending patent applications. As such, we do not know the degree of future protection that we will have on ourproprietary product candidates and technology. Our patents and patent applications may not be sufficient to protect our products and product candidates from commercial competition. For example, wecannot obtain a composition of matter patent for SL-401 due to earlier published prior art. We have however obtained U.S. and foreign patents for certainmethods of using SL-401 to treat AML, BPDCN and MDS. In addition, we have filed additional U.S. and foreign patent applications for the method of usingSL-401 to treat AML, MDS, BPDCN, and other diseases although there can be no assurances that such patents will issue. Failure to obtain patents directed toall approved uses of SL-401 would enable a competitor to market SL-401 for such unpatented indication(s), which could lead to price erosion for sales of SL-401 for our patented indications through off-label use. With respect to SL-701, although we have licensed an issued U.S. patent directed to the compositionof matter for the mutant immunogenic IL-13Rα2 peptide, we do not have any foreign composition of matter patent protection. We do not expect that we willbe able to obtain such protection outside the U.S. in the future although we do have foreign pending patent applications, including an issued patent inAustralia, that seek to cover certain uses of this peptide. While we have a non-exclusive license to issued U.S. patents directed to methods of use for theEphA2 peptide, we do not have any composition of matter patent protection although we do have rights to foreign pending patent applications that seek tocover certain uses of this peptide. While we have filed U.S. and foreign patent applications directed to methods of use of a new survivin mutant peptide foruse in SL-701, we do not have any composition of matter patent protection. With respect to SL-801, we licensed issued patent in the U.S. and abroad directedto composition of matter for the SL-801 compound. While we have patent applications pending in the United States and Canada directed to ourStemScreen technology, we currently have no issued patents covering StemScreen. Although we have various patent applications pending in the United States and abroad that we anticipate may result in additional protection for SL-401, SL-701, SL-801 and StemScreen, there can be no assurance that any of these applications will result in an issued patent, or that if they issue, they will provideadditional meaningful protection for these assets. Our inability to obtain adequate patent protection for our product candidates or platform technology couldadversely affect our business. Issued patents covering one or more of our product candidates could be found invalid or unenforceable if challenged in court. If we were to initiate legal proceedings against a third-party to enforce a patent covering one of our product candidates, the defendant could counterclaimthat our patent is invalid and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceabilityare commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, for example, lack of patentablesubject matter, novelty, obviousness, written description or non-enablement. Grounds for an unenforceability assertion could be an allegation that someoneconnected with prosecution of the patent withheld relevant information from the U.S. Patent and Trademark Office, or made a misleading statement, duringprosecution. The outcome following legal assertions of invalidity and unenforceability during patent litigation is unpredictable. With respect to the validityquestion, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were 47®®®Table of Contents unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhapsall, of the patent protection on one or more of our product candidates or certain aspects of our platform technology, StemScreen. Such a loss of patentprotection could have a material adverse impact on our business. Claims that our product candidates or StemScreen, or the sale or use of our products or technology infringe the patent rights of third-parties could resultin costly litigation or could require substantial time and money to resolve, even if litigation is avoided. We cannot guarantee that our product candidates, the use of our product candidates, or our platform technology, StemScreen, do not infringe third-partypatents. Third-parties might allege that we are infringing their patent rights or that we have misappropriated their trade secrets. Such third-parties might resortto litigation against us. The basis of such litigation could be existing patents or patents that issue in the future. Our failure to successfully defend against anyclaims that our product candidates or platform technology infringe the rights of third-parties could also adversely affect our business. For example, we areaware of a third-party European patent directed to one of the peptides used in SL-701. We may need to seek a license with respect to one or more of thesethird-party patents in order to commercialize our products. No assurance can be given that any such licenses will be available, or that they will be availableon commercially acceptable terms. Failure to obtain any required licenses could restrict our ability to commercialize our products in certain territories orsubject us to patent infringement litigation, which could result in us having to cease commercialization of our products and subject us to money damages insuch territories. It is also possible that we failed to identify relevant patents or applications. Patent applications covering our products or platform technology could havebeen filed by others without our knowledge. Additionally, pending patent applications which have been published can, subject to certain limitations, be lateramended in a manner that could cover our platform technologies, our products or the use of our products. In order to avoid or settle potential claims with respect to any patent rights of third-parties, we may choose or be required to seek a license from a third-partyand be required to pay license fees or royalties or both. These licenses may not be available on acceptable terms, or at all. Even if we or any future strategicpartners were able to obtain a license, the rights may be nonexclusive, which could result in our competitors gaining access to the same intellectual property.Ultimately, we could be prevented from commercializing one or more of our product candidates, or be forced to cease some aspect of our business operations,if, as a result of actual or threatened patent infringement claims, we are unable to enter into licenses on acceptable terms. Patent litigation could also exposeus to significant monetary damages. This could harm our business significantly. Defending against claims of patent infringement or misappropriation of trade secrets could be costly and time consuming, regardless of the outcome. Thus,even if we were to ultimately prevail, or to settle at an early-stage, such litigation could burden us with substantial unanticipated costs. In addition, litigationor threatened litigation could result in significant demands on the time and attention of our management team, distracting them from the pursuit of othercompany business. Unfavorable outcomes in intellectual property litigation could limit our research and development activities and/or our ability to commercialize certainproducts. If third-parties successfully assert intellectual property rights against us, we might be barred from using certain aspects of our platform technology, or barredfrom developing and commercializing certain products. Prohibitions against using certain technologies, or prohibitions against commercializing certainproducts, could be imposed by a court or by a settlement agreement between us and a plaintiff. In addition, if we are unsuccessful in defending againstallegations of patent infringement or misappropriation of trade secrets, we may be forced to pay substantial damage awards to the plaintiff. There is inevitableuncertainty in any litigation, including intellectual property litigation. There can be no assurance that we would prevail in any intellectual propertylitigation, even if the case against us is weak or flawed. If litigation leads to an outcome unfavorable to us, we may be required to obtain a license from thepatent owner, in order to continue our research and development programs or to market our product(s). It is possible that the necessary license will not beavailable to us on commercially acceptable terms, or at all. This could limit our research and development activities, our ability to commercialize certainproducts, or both. Most of our competitors are larger than we are and have substantially greater resources. They are, therefore, likely to be able to sustain the costs of complexpatent litigation longer than we could. In addition, the uncertainties associated with litigation could have a material adverse effect on our ability to raise thefunds necessary to continue our clinical trials, continue our internal research programs, in-license needed technology, or enter into strategic partnerships thatwould help us bring our product candidates to market. In addition, any future patent litigation, interference or other administrative proceedings will result in additional expense and distraction of our personnel.An adverse outcome in such litigation or proceedings may expose us or any future strategic partners to loss of our proprietary position, expose us tosignificant liabilities, or require us to seek licenses that may not be available on commercially acceptable terms, if at all. 48®®®Table of Contents Intellectual property litigation may lead to unfavorable publicity that harms our reputation and causes the market price of our common stock to decline. During the course of any patent litigation, there could be public announcements of the results of hearings, rulings on motions, and other interim proceedingsin the litigation. If securities analysts or investors regard these announcements as negative, the perceived value of our product candidates, platformtechnology, programs, or intellectual property could be diminished. Accordingly, the market price of our common stock may decline. SL-401, SL-701, SL-801, some of our other product candidates, and our platform technologies are protected by intellectual property licensed from third-parties including academic institutions. If the licensors terminate the licenses or fail to prosecute patent applications or maintain or enforce theunderlying patents, our competitive position, market share, and business prospects will be harmed. We are a party to several license agreements relating to certain patents and patent applications owned by third-parties, upon which certain aspects of ourbusiness depend. In particular, we hold an exclusive license from Scott and White Memorial Hospital, or Scott and White, for SL-401 and SL-501 and threelicenses, including an exclusive license and two non-exclusive licenses, from the University of Pittsburgh relating to SL-701. Our license agreement withScott and White survives, unless earlier terminated, until the later of the expiration of the last to expire licensed patent or the date on which we owe no furtherpayments to Scott and White. Our exclusive and our non-exclusive patent license agreements with the University of Pittsburgh survive, unless earlierterminated, until the expiration of the last to expire licensed patent, and our non-exclusive license with the University of Pittsburgh to use and referencecertain clinical trial data and information survives for a term of twenty years unless earlier terminated. We hold an exclusive license from CanBas, Ltd. for SL-801 in all worldwide territories other than Japan, Korea, Taiwan, and China. The agreement with Canbas, Ltd. survives until the later of ten years followingthe first commercial sale of each product in each country; the date upon which there are no more valid claims; or the expiration or termination of the lastregulatory exclusivity period, after which our license becomes fully paid, irrevocable, perpetual, non-exclusive and royalty-free. We also hold licenses fromacademic institutions relating to intellectual property underlying other product candidates and our StemScreen platform technology. We expect to enterinto additional license agreements as part of the development of our business. Our current or future licensors may not successfully prosecute certain patentapplications under which we are licensed and on which our business depends. Even if patents issue from these applications, our licensors may fail to maintainthese patents, may decide not to pursue litigation against third-party infringers, may fail to prove infringement, or may fail to defend against counterclaims ofpatent invalidity or unenforceability. In addition, in spite of our best efforts, our licensors might conclude that we have materially breached our licenseagreements and might therefore seek to terminate the license agreements, thereby removing our ability to obtain regulatory approval and to market productscovered by these license agreements. Our licensors may also seek to terminate the license agreements if we fail to satisfy our diligence obligations and/ormeet specified milestones or upon insolvency. From time to time, we have had to request extensions of our development obligations contained in some of ourlicense agreements, and we may need to seek further extensions in the future. Although we have obtained such extensions in the past, there can be noassurance that our licensors will continue to extend the development timelines or other milestones contained in our license agreements. If these in licensesare terminated, or if the underlying patents fail to provide the intended market exclusivity, we could lose our rights to develop and commercialize theproduct candidates governed by the licenses and competitors would have the freedom to seek regulatory approval of, and to market, products identical toours. This could have a material adverse effect on our competitive business position and our business prospects. We could be unsuccessful in obtaining patent protection on one or more components of our platform technology. We believe that an important factor in our competitive position relative to other companies in the field of targeted oncology therapeutics is our proprietaryinnovative platform technology, StemScreen. We believe that this platform is useful for identifying new potential product candidates. We have pendingU.S. and Canadian patent applications for StemScreen, however, there is no guarantee that any of such pending patent applications will result in issuedpatents, and, even if patents eventually issue, there is no certainty that the issued claims will have adequate scope to preserve our competitive position. Inaddition, by practicing our technology in jurisdictions where we do not have patent protection, third-parties could substantially weaken our competitiveposition in oncology research and development. Confidentiality agreements with employees and third-parties may not prevent unauthorized disclosure of trade secrets and other proprietary information. In addition to patents, we rely on trade secrets, technical know-how, and proprietary information concerning our business strategy in order to protect ourcompetitive position in the field of oncology. In the course of our research and development activities and our business activities, we often rely onconfidentiality agreements to protect our proprietary information. Such confidentiality agreements are used, for example, when we talk to vendors oflaboratory or clinical development services or potential strategic partners. In 49®®®Table of Contents addition, each of our employees is required to sign a confidentiality agreement upon joining our company. We take steps to protect our proprietaryinformation, and our confidentiality agreements are carefully drafted to protect our proprietary interests. Nevertheless, there can be no guarantee that anemployee or an outside party will not make an unauthorized disclosure of our proprietary confidential information. This might happen intentionally orinadvertently. It is possible that a competitor will make use of such information, and that our competitive position will be compromised, in spite of any legalaction we might take against persons making such unauthorized disclosures. Trade secrets are difficult to protect. Although we use reasonable efforts to protect our trade secrets, our employees, consultants, contractors, or outsidescientific collaborators might intentionally or inadvertently disclose our trade secret information to competitors. Enforcing a claim that a third-party illegally obtained and is using any of our trade secrets is expensive and time consuming, and the outcome isunpredictable. In addition, courts outside the United States sometimes are less willing than U.S. courts to protect trade secrets. Moreover, our competitors mayindependently develop equivalent knowledge, methods and know-how. Our research and development strategic partners may have rights to publish data and other information to which we have rights. In addition, we sometimesengage individuals or entities to conduct research relevant to our business. The ability of these individuals or entities to publish or otherwise publiclydisclose data and other information generated during the course of their research is subject to certain contractual limitations. These contractual provisionsmay be insufficient or inadequate to protect our confidential information. If we do not apply for patent protection prior to such publication, or if we cannototherwise maintain the confidentiality of our proprietary technology and other confidential information, then our ability to obtain patent protection or toprotect our trade secret information may be jeopardized. Intellectual property rights do not necessarily address all potential threats to our competitive advantage. The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may notadequately protect our business, or permit us to maintain our competitive advantage. The following examples are illustrative: · Others may be able to make compounds that are the same as or similar to our product candidates but that are not covered by the claims of thepatents that we own or have exclusively licensed. · We or our licensors or any future strategic partners might not have been the first to make the inventions covered by the issued patent or pendingpatent application that we own or have exclusively licensed. · We or our licensors or any future strategic partners might not have been the first to file patent applications covering certain of our inventions. · Others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectualproperty rights. · It is possible that our pending patent applications will not lead to issued patents. · Issued patents that we own or have exclusively licensed may not provide us with any competitive advantages, or may be held invalid orunenforceable, as a result of legal challenges by our competitors. · Our competitors might conduct research and development activities in countries where we do not have patent rights, or where the applicablelaws provide a safe harbor exemption from infringement liability for certain research purposes, and then use the information learned from suchactivities to develop competitive products for sale in our major commercial markets. · We may not develop additional proprietary technologies that are patentable. · The patents of others may have an adverse effect on our business. 50Table of Contents Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates. As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining andenforcing patents in the biopharma industry involve both technological complexity and legal complexity. Therefore, obtaining and enforcing biopharmapatents is costly, time-consuming and inherently uncertain. In addition, Congress has passed patent reform legislation which provides new limitations onattaining, maintaining and enforcing intellectual property. Further, the Supreme Court has ruled on several patent cases in recent years, either narrowing thescope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations. In addition to increasinguncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents,once obtained. Depending on decisions by the U.S. Congress, the federal courts, and the U.S. Patent and Trademark Office, the laws and regulationsgoverning patents could change in unpredictable ways that would weaken our ability to obtain new patents or to enforce our existing patents and patents thatwe might obtain in the future. Risks Related to Our Common Stock The market price of our common stock may be highly volatile and our stockholders could incur substantial losses. The market price of our common stock may be highly volatile, and could be subject to wide fluctuations in response to various factors, some of which arebeyond our control. Since our initial public offering which occurred in January 2013, the price of our common stock has ranged from $3.88 per share to$47.25 per share. The stock market in general and the market for biopharmaceutical companies in particular have experienced extreme volatility that hasoften been unrelated to the operating performance of particular companies. The market price for our common stock may be influenced by many factors,including: · results from or delays of clinical trials of our product candidates, as well as results of regulatory reviews relating to the approval of our productcandidates; · our decision to initiate a clinical trial, not to initiate a clinical trial or to terminate an existing clinical trial; · our dependence on third-parties, including clinical research organizations and contract manufacturing organizations, trial sites, clinical trialsponsors and clinical investigators; · our ability to commercialize our product candidates, if approved; · the results of our efforts to discover, develop, acquire or in-license additional product candidates or products; · new products, product candidates or new uses for existing products or technologies introduced or announced by our competitors and the timingof these introductions or announcements; · regulatory or legal developments in the United States and other countries; · our ability to maintain the license agreements for our product candidates; · developments or disputes concerning patent applications, issued patents or other proprietary rights; · the recruitment or departure of key scientific or management personnel; · the level of expenses related to any of our product candidates or clinical development programs; · actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; · variations in our financial results or those of companies that are perceived to be similar to us; · sales of common stock by us or our stockholders in the future, as well as the overall trading volume of our common stock; · changes in the structure of healthcare payment systems; 51Table of Contents · market conditions in the pharmaceutical and biotechnology sectors; · general economic, industry and market conditions and other factors that may be unrelated to our operating performance or the operatingperformance of our competitors, including changes in market valuations of similar companies; and · the other factors described in this “Risk Factors” section. We are an “emerging growth company” and the reduced disclosure requirements applicable to emerging growth companies could make our commonstock less attractive to investors. We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and we have and intend to continueto take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not “emerging growthcompanies” including not being required to comply with the auditor attestation requirements of Section 404(b) of the Sarbanes-Oxley Act, and exemptionsfrom the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments notpreviously approved. We cannot predict if investors will find our common stock less attractive because we have and may continue to rely on theseexemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stockprice may be more volatile. We may take advantage of these reporting exemptions until we are no longer an “emerging growth company.” We will remain an“emerging growth company” until the earliest of (i) the last day of the fiscal year in which we have total annual gross revenues of $1 billion or more;(ii) December 31, 2018; (iii) the date on which we have issued more than $1 billion in nonconvertible debt during the previous three years; or (iv) the date onwhich we are deemed to be a large accelerated filer under the rules of the SEC. Our executive officers, directors and principal stockholders maintain the ability to exert substantial influence over all matters submitted to stockholdersfor approval. Our executive officers, directors and principal stockholders beneficially own shares representing approximately 40.5% of our outstanding capital stock. As aresult, if these stockholders were to choose to act together, they would be able to exert substantial influence over all matters submitted to our stockholders forapproval, as well as our management and affairs. For example, these persons, if they choose to act together, would exert substantial influence over theelection of directors and approval of any merger, consolidation or sale of all or substantially all of our assets. This concentration of voting power could delayor prevent an acquisition of our company on terms that other stockholders may desire. Provisions in our corporate charter documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders,more difficult and may prevent attempts by our stockholders to replace or remove our current management. Provisions in our corporate charter and our bylaws may discourage, delay or prevent a merger, acquisition or other change in control of us that stockholdersmay consider favorable, including transactions in which they might otherwise receive a premium for their shares. These provisions could also limit the pricethat investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. Among otherthings, these provisions: · establish a classified board of directors such that not all members of the board are elected at one time; · allow the authorized number of our directors to be changed only by resolution of our board of directors; · limit the manner in which stockholders can remove directors from the board; · establish advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our board ofdirectors; · require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by writtenconsent; · limit who may call special stockholder meetings and the matters transacted at such meetings; · authorize our board of directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” thatwould work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by ourboard of directors; and 52Table of Contents · require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast to amend or repeal certainprovisions of our charter or bylaws. Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, whichprohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date ofthe transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribedmanner. Any provision in our corporate charter or our bylaws or Delaware law that has the effect of delaying or deterring a change in control could limit theopportunity for our stockholders to receive a premium for their shares of our common stock, and could also affect the price that some investors are willing topay for our common stock. We incur significant costs as a result of operating as a public company, and our management is required to devote substantial time to complianceinitiatives. As a public company, we incur and will continue to incur significant legal, accounting and other expenses. We are subject to the reporting and otherrequirements of the Securities Exchange Act of 1934, as amended, or the Exchange Act, the Sarbanes Oxley Act of 2002, or the Sarbanes Oxley Act, and theDodd Frank Wall Street Reform and Protection Act, as well as rules subsequently adopted by the SEC and the NASDAQ Stock Market, or NASDAQ. Theserules and regulations require, among other things, that we file annual, quarterly and current reports with respect to our business and financial condition andestablish and maintain effective disclosure and financial controls and corporate governance practices. Changes in these rules and regulations can createuncertainty for public companies, increasing legal and financial compliance costs and making some activities more time consuming. Our management andother personnel devote a substantial amount of time to these compliance initiatives. If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately report our financial results orprevent fraud. As a result, stockholders could lose confidence in our financial and other public reporting, which would harm our business and the tradingprice of our common stock. Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with adequate disclosure controlsand procedures, are designed to prevent fraud. Any failure to implement required new or improved controls, or difficulties encountered in theirimplementation could cause us to fail to meet our reporting obligations. In addition, any testing by us conducted in connection with Section 404 of theSarbanes-Oxley Act, or the subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls overfinancial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our financial statements or identifyother areas for further attention or improvement. Inferior internal controls could also cause investors to lose confidence in our reported financial information,which could have a negative effect on the trading price of our common stock. We are required to disclose changes made in our internal controls and procedures on a quarterly basis and our management is required to assess theeffectiveness of these controls annually. However, for as long as we are an “emerging growth company” under the JOBS Act, our independent registeredpublic accounting firm will not be required to attest to the effectiveness of our internal controls over financial reporting pursuant to Section 404. We could bean emerging growth company for up to five years. An independent assessment of the effectiveness of our internal controls could detect problems that ourmanagement’s assessment might not. Undetected material weaknesses in our internal controls could lead to financial statement restatements and require us toincur the expense of remediation. We do not anticipate paying any cash dividends on our capital stock in the foreseeable future. We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to finance the growth anddevelopment of our business, and we do not anticipate paying any cash dividends on our capital stock in the foreseeable future. In addition, the terms of anyfuture debt agreements may preclude us from paying dividends. As a result, capital appreciation, if any, of our common stock will be your sole source of gainfor the foreseeable future. Item 1B. Unresolved Staff Comments None. 53Table of Contents Item 2. Properties Our corporate and executive office is located in New York, New York. Our New York facility consists of subleased space at 750 Lexington Avenue, EleventhFloor, New York, New York 10022. Item 3. Legal Proceedings We are not a party to, and our property is not the subject of, any material pending legal proceedings. Item 4. Mine Safety Disclosures Not applicable. 54Table of Contents Part II Item 5. Market for the Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock is listed on the NASDAQ Capital Market and trades under the symbol “STML” and has been publicly traded since January 31, 2013. Priorto that time, there was no public market for our common stock. The following table sets forth the high and low closing sales prices for our common stock asreported on the NASDAQ Capital Market for the periods indicated. Fiscal Year Ended December 31, 2015High LowFirst Quarter$18.94$12.77Second Quarter17.0211.38Third Quarter13.248.31Fourth Quarter9.925.88 Holders The number of record holders of our common stock as of March 14, 2016, was 117. This number does not include beneficial owners whose shares are held bynominees in street name. Dividends We have never declared or paid any cash dividends on our common stock and do not anticipate paying any cash dividends in the foreseeable future. Anyfuture determination to pay dividends will be at the discretion of our board of directors. Securities Authorized for Issuance under Equity Compensation Plans The following table contains information about our equity compensation plans as of December 31, 2015. Equity Compensation Plan InformationPlan CategoryNumber ofsecurities to beissued uponexercise ofoutstanding optionsand restricted stock Weighted-averageexercise price ofoutstandingoptions Number ofsecuritiesremainingavailable forfuture issuanceunder equitycompensationplans (excludingsecurities reflectedin column (a))(a) (b) (c)Equity compensation plans approved by security holdersOptions2,121,726$10.74527,353Restricted stock553,045N/A—Equity compensation plans not approved by security holders———Total2,674,771—527,353 Common Stock Performance Graph The following graph compares the cumulative total stockholder return on our common stock for the period from January 28, 2013 through December 31,2015, with the cumulative total return over such period on (i) the U.S. Index of The NASDAQ Stock Market and (ii) the Biotechnology Index of TheNASDAQ Stock Market. The graph assumes an investment of $100 on January 28, 2013, in our common stock (at the closing market price) and in each of theindices listed above, and assumes the reinvestment of dividends. 55Table of Contents COMPARISON OF 5 YEARS CUMULATIVE TOTAL RETURN*Among Stemline Therapeutics, Inc., the NASDAQ Composite Indexand the NASDAQ Biotechnology Index * $100 invested on January 28, 2013 in stock or index, including reinvestment of dividends.Fiscal year ending December 31. Item 6. Selected Financial Data You should read the following selected financial data together with our financial statements and the related notes appearing at the end of this Form 10-K andthe “Management’s Discussion and Analysis of Financial Condition and Results of Operations” section of this Form 10-K. We have derived the financialinformation from our audited financial statements. Our historical results for any prior period are not necessarily indicative of results to be expected in anyfuture period. Year Ended December 31,201520142013 2012 2011 Statement of operations data:Grant Revenue$654,160$335,287$71,000$—$—Operating expenses:Research and development$29,458,676$21,240,599$16,178,744$3,376,962$1,629,026General and administrative8,828,8438,084,5807,871,7193,090,6111,088,028Total operating expenses38,287,51929,325,17924,050,4636,467,5732,717,054Loss from operations(37,633,359)(28,989,892)(23,979,463)(6,467,573)(2,717,054)Other income:1,6093,607280,687301,68446,673Other expense———(35)(9,670)Interest expense——(516,871)(118,765)(98,643)Interest income387,889156,31019,1369,90724,068Net loss$(37,243,861)$(28,829,975)$(24,196,511)$(6,274,782)$(2,754,626)Net (loss) / income attributable tocommon stockholders percommon share:Basic and Diluted$(2.15)$(2.23)$(2.35)$(1.82)$(0.80)Weighted average number ofcommon shares:Basic and Diluted17,289,02112,936,74110,317,3513,441,9953,441,995 56Table of Contents As of December 31, 2015 2014 2013 2012 2011 Balance sheet data:Cash and cash equivalents$13,376,196$25,007,217$44,200,420$2,025,338$5,829,886Total assets$98,215,623$60,494,992$85,281,196$5,029,611$6,453,096Long-term liabilities$648,190$607,999$643,000$2,037,296$1,665,346(Deficit)$(97,439,602)$(60,195,741)$(31,365,766)$(7,169,255)$(894,473)Total stockholders’equity/(deficit)$88,111,956$55,413,151$79,624,388$(2,508,420)$3,205,340 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations Unless the context requires otherwise, references in this report to “Stemline,” “Company,” “we,” “us” and “our” refer to Stemline Therapeutics, Inc. The following discussion and analysis contains forward-looking statements about our plans and expectations of what may happen in the future. Forward-looking statements are based on a number of assumptions and estimates that are inherently subject to significant risks and uncertainties, and our resultscould differ materially from the results anticipated by our forward-looking statements as a result of many known or unknown factors, including, but notlimited to, those factors discussed in “Item 1A. Risk Factors.” See also the “Special Cautionary Notice Regarding Forward-Looking Statements” set forth atthe beginning of this report. You should read the following discussion and analysis in conjunction with “Item 6. Selected financial Data,” “Item 8. Financial Statements andSupplementary Data,” and our financial statements beginning on page F-1 of this report. Overview We are a clinical stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing proprietary oncology therapeutics.We are currently developing three clinical stage product candidates: SL-401, SL-701, and SL-801. SL-401 is a targeted therapy directed to the interleukin-3 receptor, or IL-3R (CD123), present on a wide range of hematologic cancers. SL-401 is beingadvanced through a Phase 2 registration-directed clinical trial in patients with blastic plasmacytoid dendritic cell neoplasm, or BPDCN. Data from the initialstage of this ongoing trial demonstrated a high overall response rate, or ORR, with multiple complete responses, or CRs. Patients continue to be followed foroverall response, response duration, progression free survival, or PFS, and overall survival, or OS, and new patients are enrolling into the study. Results fromthis trial could potentially support registration in the U.S. Clinical studies with SL-401 are also open in additional malignancies including acute myeloidleukemia, or AML, in CR with minimal residual disease, or MRD, and high-risk myeloproliferative neoplasms, or MPNs. SL-701 is an immunotherapy designed to activate the immune system to attack tumors. SL-701 is comprised of three synthetic tumor-specific peptides, two ofwhich are mutant and selected for potentially enhanced immune effects, that are designed to direct the immune system to their corresponding cell surfacetargets overexpressed on tumors including glioblastoma multiforme, or GBM. SL-701 in combination with bevacizumab and an immunostimulant iscurrently being advanced through a Phase 2 trial in adult patients with second-line GBM. SL-801 is a novel, oral, small molecule, reversible inhibitor of Exportin-1, or XPO1, a key nuclear transport protein. SL-801 has demonstrated potentpreclinical in vitro and in vivo antitumor activity against a wide array of solid and hematologic cancers. We recently opened an investigational new drug, orIND, for SL-801 and are advancing SL-801 into a Phase 1 clinical trial in patients with advanced cancers. We have devoted substantially all of our resources to develop our product candidates, manufacture our product candidates, build our intellectual propertyportfolio, business plan, raising capital, and provide general and administrative support for these 57Table of Contents operations. We have generated minimal revenues to date, have not generated any revenue from product sales, and have funded our operations primarilythrough public and private sales of common stock and private sales of convertible preferred stock to our investors. From inception through December 31,2015, we have received net proceeds of $165.7 million from the sale of common stock, $12.5 million from the sale of convertible preferred stock and$0.9 million from the issuance of convertible debt. The convertible preferred stock was retired in March 2010 and the convertible debt was converted intocommon stock in April 2013. During the first quarter of 2015, we received additional net cash proceeds of $64.1 million from the underwritten publicsecondary offering and sale of 4,353,877 shares of our common stock. We have never been profitable and our net loss from operations was $37.2 million for the year ended December 31, 2015, $28.8 million for the year endedDecember 31, 2014 and $24.2 million for the year ended December 31, 2013. We expect to incur significant expenses and increasing operating losses for theforeseeable future. We expect our expenses to increase in connection with our ongoing activities, particularly as we advance our product candidates throughpreclinical activities and clinical trials to seek regulatory approval and, if approved, commercialize such product candidates. Furthermore, we expect to incuradditional costs associated with operating as a public company. Accordingly, we will need additional financing to support our continuing operations. Wewill seek to fund our operations through public or private equity or debt financings or other sources. Adequate additional financing may not be available tous on acceptable terms, or at all. Our failure to raise capital as and when needed would have a negative impact on our financial condition and our ability topursue our business strategy. We will need to generate significant revenues to achieve profitability, and we may never do so. Financial Operations Overview Revenue We have not generated any revenue from product sales and we have generated minimal revenues to date, all relating to a $2.5 million research fundingreceived to date from the Leukemia and Lymphoma Society, or LLS, where we recognized revenue of $0.7 million during 2015, $0.3 million during 2014and $0.1 million during 2013. In the future, we may generate revenue from product sales. In addition, to the extent we enter into licensing or collaborationarrangements, we may have additional sources of revenue. If we fail to complete the development of our product candidates in a timely manner or obtain regulatory approval for them, our ability to generate futurerevenue, and our results of operations and financial position, would be materially adversely affected. Research and Development Expenses The following table shows our research and development expenses for the years ended December 31, 2015, 2014 and 2013: Year Ended December 31,20152014 2013SL-401$13,750,593$9,171,431$4,880,863SL-7013,156,1163,940,8401,296,720SL-8012,611,51494,791—Personnel expenses8,923,1187,286,3397,497,951Other expenses1,017,335747,1982,503,210 Total research and development expenses$29,458,676$21,240,599$16,178,744 Research and development expenses consist of costs associated with the development of our product candidates and our platform technology, which include: · clinical trial costs; · CMC-related costs; · nonclinical costs; · employee-related expenses, including salaries, benefits, travel and stock-based compensation expense, and consultant costs; · external research and development expenses incurred under arrangements with third-parties, such as contract research organizations, or CROs,contract manufacturing organizations, or CMOs, academic institutions, and consultants; 58Table of Contents · license fees and milestone payments related to in-licensed products and technology; and · facilities, depreciation and other allocated expenses, which include direct and allocated expenses for rent and maintenance of facilities,depreciation of leasehold improvements, equipment and supplies. We expense research and development costs to operations as incurred. We account for nonrefundable advance payments for goods and services that will beused in future research and development activities as expenses when the services have been performed or when the goods have been received, rather thanwhen the payments are made. We use our employee and infrastructure resources across multiple research and development projects. We do not allocate employee-related expenses ordepreciation to any particular project. The components of our research and development costs are described in more detail in “Results of Operations.” We anticipate that our research and development expenses will increase significantly in future periods as we seek to complete development of our mostadvanced product candidates, SL-401, SL-701, and SL-801, and continue to develop our other product candidates and our platform technology. Weanticipate the majority of our research and development expense will be devoted to the development of SL-401, SL-701, and SL-801. The successful development of our product candidates is highly uncertain. As of this time, other than as discussed above, we cannot reasonably estimate orknow the nature, timing and estimated costs of the efforts that will be necessary to complete development of our product candidates or the period, if any, inwhich material net cash inflows from our product candidates may commence. This is due to the numerous risks and uncertainties associated with developingdrugs, including the uncertainty of: · the scope, rate of progress and costs of our planned, as well as any additional, clinical trials and other research and development activities; · future clinical trial results; · the potential benefits of our product candidates over other therapies; · our ability to market and commercialize, either on our own or with strategic partners, and achieve market acceptance for any of our productcandidates that we are developing or may develop in the future; · the costs, timing and outcome of regulatory approvals; and · the costs of preparing, filing, prosecuting, defending and enforcing patent claims and other intellectual property rights. A change in the outcome of any of these or similar variables with respect to the development of a product candidate could mean a significant change in thecosts and timing associated with the development of that product candidate. For example, if the FDA or other regulatory authority were to require us toconduct clinical trials beyond those which we currently anticipate will be required for the completion of clinical development of a product candidate or if weexperience significant delays in enrollment in any clinical trials, we could be required to expend significant additional financial resources and time on thecompletion of clinical development. General and Administrative Expenses General and administrative expenses consist primarily of salaries and related costs for personnel, including stock-based compensation expense. The primaryfunctions included in our general and administrative expenses are legal, finance, human resources, investor relations, and business development departments.Other general and administrative expenses include facility costs, insurance expenses and professional fees for legal, business development, consulting andaccounting services. We anticipate that our general and administrative expenses will be higher in future periods to support increases in our research and development activities,which will result in increased payroll, expanded infrastructure, increased legal, business development, compliance, accounting and investor and publicrelations expenses associated with being a public company, among other factors. 59Table of Contents Interest Income Interest income consists of interest earned on our cash, cash equivalents, short-term investments and long-term investments. Given the current interest rateenvironment and that our primary investment is in 100% U.S. Treasury and Agency securities and related money market funds coupled with FDIC-insuredbank certificates of deposits, we expect interest income to be minimal in future quarters. Interest Expense Interest expense consists primarily of cash and non-cash interest costs related to our previously outstanding debt. In addition, we capitalize costs incurred inconnection with the issuance of debt. We amortize these costs over the life of our debt agreements as interest expense in our statement of operations. Critical Accounting Policies and Estimates To understand our financial statements, it is important to understand our critical accounting policies and estimates. We prepare our financial statements inaccordance with generally accepted accounting principles, or GAAP. The preparation of financial statements also requires us to make estimates andassumptions that affect the reported amounts of assets, liabilities, costs and expenses and related disclosures. We base our estimates on historical experienceand on various other assumptions that we believe to be reasonable under the circumstances. Actual results could differ significantly from the estimates madeby our management. To the extent that there are differences between our estimates and actual results, our future financial statement presentation, financialcondition, results of operations and cash flows will be affected. We believe that the accounting policies discussed below are critical to understanding ourhistorical and future performance, as these policies relate to the more significant areas involving management’s judgments and estimates. Our significant accounting policies are described in more detail in the notes to our financial statements appearing at the end of this Form 10-K. However, webelieve that the following accounting policies are the most critical to aid you in fully understanding and evaluating our financial condition and results ofoperations. Accrued Research and Development Expenses As part of the process of preparing our financial statements, we are required to estimate our accrued expenses. This process involves reviewing quotations andcontracts, identifying services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for theservice when we have not yet been invoiced or otherwise notified of the actual cost. The majority of our service providers invoice us monthly in arrears forservices performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in our financialstatements based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with the service providers andmake adjustments if necessary. The significant estimates in our accrued research and development expenses include fees paid to CROs and CMOs,consultants and other third-party organizations in connection with research and development and administrative activities for which we have not yet beeninvoiced. We base our expenses related to CROs and CMOs on our estimates of the services received and efforts expended pursuant to quotes and contracts with CROsand CMOs that conduct research and development on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract tocontract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services providedand result in a prepayment of the research and development expense. In accruing service fees, we estimate the time period over which services will beperformed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from ourestimate, we may adjust the accrual or prepaid accordingly. Although we do not expect our estimates to be materially different from amounts actuallyincurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may vary and couldresult in us reporting amounts that are too high or too low in any particular period. Income Taxes We use the liability method of accounting for income taxes as set forth in the authoritative guidance for income taxes. Under this method, we recognizedeferred tax liabilities and assets for the expected future tax consequences of temporary differences between the respective carrying amounts and tax bases ofour assets and liabilities. 60Table of Contents We continue to assess the realizability of our deferred tax assets, which primarily consist of net operating losses, or NOL, carry-forwards. In assessing therealizability of these deferred tax assets, management considers whether it is more likely than not that some portion or all of the deferred tax assets will berealized. We establish valuation allowances when necessary to reduce deferred tax assets to the amounts expected to be realized. The factors used to assessthe likelihood of realization include our latest forecast of future taxable income and available tax planning strategies that could be implemented to realizethe net deferred tax assets. As of December 31, 2015, 2014 and 2013, our deferred tax assets had full valuation allowances on them as we did not havesufficient positive evidence to recognize such deferred tax assets. The Internal Revenue Code of 1986, as amended (the “Code”), provides for a limitation of the annual use of net operating losses and other tax attributes(such as research and development tax credit carryforwards) following certain ownership changes (as defined by the Code) that could limit our ability toutilize these carryforwards. At this time, we have not completed a study to assess whether an ownership change under section 382 of the Code has occurred, orwhether there have been multiple ownership changes since our formation, due to the costs and complexities associated with such a study. We may haveexperienced various ownership changes, as defined by the Code, as a result of past financing transactions. Accordingly, our ability to utilize theaforementioned carryforwards may be limited. Additionally, U.S. tax laws limit the time during which these carryforwards may be applied against futuretaxes. Therefore, we may not be able to take full advantage of these carryforwards for federal or state income tax purposes. If any of our products are approved for commercial sale and we start to realize profitability, we may determine that there is sufficient positive evidence tosupport a reversal of, or decrease in, the valuation allowance on our deferred tax assets. If we were to reverse all or some part of our valuation allowance, ourfinancial statements in the period of reversal would likely reflect an increase in assets on our balance sheet and a corresponding tax benefit to our statementof operations in the amount of the reversal. As of December 31, 2015, we had net operating losses of $58.6 million for both federal and state purposes, (of which $15 million will result in a benefit toadditional paid in capital upon realization as they relate to excess benefits from stock option exercises) and research and development credits of $14.9million which expire in 2024 through 2035. We have applied Accounting Standards Codification (ASC) 740-10, Accounting for Uncertainty in Income Taxes — an Interpretation of FASB StatementNo. 109, on January 1, 2007. We analyzed our tax position in all jurisdictions where we are required to file an income tax return and concluded that we donot have any material unrecognized tax benefits. We file U.S. income tax returns as well as tax returns for any state jurisdiction in which we are authorized toconduct business. Our policy is to recognize interest and penalties accrued on any unrecognized tax benefit within the provision for income taxes on thestatement of operations. We have no interest or penalties accrued for any unrecognized tax benefits for any periods presented. Our annual provision for income taxes and the determination of the resulting deferred tax assets and liabilities involve a significant amount of managementjudgment. Management’s judgments, assumptions and estimates relative to the current provision for income taxes take into account current tax laws, ourinterpretation of current tax laws and possible outcomes of current and future audits conducted by foreign and domestic tax authorities. We operate withinfederal, state and international taxing jurisdictions and are subject to audit in these jurisdictions. These audits can involve complex issues that may requirean extended period of time to resolve. Stock-Based Compensation We account for stock-based compensation in accordance with the provisions of ASC 718, Compensation—Stock Compensation. Accordingly, compensationcosts related to equity instruments granted are recognized over the requisite service periods of the awards on a straight-line basis at the grant-date fair valuecalculated by either using a Black-Scholes option pricing model for stock option valuations or the closing stock price on date of grant for restricted stock.Additionally, under the provisions of ASC 718, we are required to include an estimate of the number of awards that will be forfeited in calculatingcompensation costs. Any changes to the estimated forfeiture rates are accounted for prospectively. For stock options granted as consideration for services rendered by non-employees, we recognize expense in accordance with the requirements of ASC Topic505-50, Equity Based Payments to Non-Employees. Non-employee option grants that do not vest immediately upon grant are recorded as an expense over thevesting period of the underlying stock options. At the end of each financial reporting period prior to vesting, the value of these options, as calculated usingthe Black-Scholes option-pricing model, is re-measured using the fair value of our common stock and the non-cash expense recognized during the period isadjusted accordingly. Since the fair market value of options granted to non-employees is subject to change in the future, the amount of the future expensewill include fair value re-measurements until the stock options are fully vested. 61Table of Contents Revenue Recognition We have not yet generated any revenue from product sales. Our sole source of revenue is grant revenue related to $2.5 million of research grants received todate from the Leukemia and Lymphoma Society. Grant payments received prior to our performance of work required by the terms of the research grant arerecorded as deferred revenue and recognized as grant revenue once work is performed and qualifying costs are incurred. Results of Operations Comparison of Years Ended December 31, 2015 and 2014 Research and development expense. Research and development expense was $29.5 million for the year ended December 31, 2015, compared with $21.2million for the year ended December 31, 2014, which represents an increase of $8.3 million. The higher costs were primarily attributable to the ramp up inclinical and manufacturing development activities for our SL-401 and SL-801 clinical programs, partially offset by a decrease in SL-701 manufacturingrelated expenses. The increase in research and development costs associated with SL-401 is primarily driven by higher expenses related to administration ofour clinical trials. Partially offsetting this increase in costs for SL-401 were lower manufacturing development expenses of $1.2 million. Additionally, weincurred higher research and development expenses of $2.5 million related to our SL-801 clinical program. The increase in SL-801 expenses is primarilyrelated to $1.2 million in manufacturing development activities including CMC-related expenses for the manufacture of drug substance and drug product,coupled with $0.7 million of licensing costs. The decrease in costs for SL-701 is primarily driven by lower manufacturing development expenses of $0.7million. As we continue to ramp up our clinical trial activities for SL-401 and SL-801 during 2016, we expect that our research and development expenseswill increase compared to prior periods. We expect this increase in costs will continue for the foreseeable future. General and administrative expense. General and administrative expenses were $8.8 million for the year ended December 31, 2015, compared with $8.1million for the year ended December 31, 2014, which represents an increase of $0.7 million. The higher costs were primarily attributable to an increase innon-cash stock based compensation expense relating to administrative employees of $1.0 million coupled with an increase in compensation expenses of $0.4million. Partially offsetting the higher expenses were lower consulting costs of $0.3 million. Interest income. Interest income was $0.4 million for the year ended December 31, 2015, compared with $0.2 for the year ended December 31, 2014. Theincrease in income of $0.2 million is due to the increase in cash, cash equivalents, short-term investments and long-term investments on our balance sheet asa result of the successful completion of our secondary equity offering during the first quarter of 2015. Comparison of Years Ended December 31, 2014 and 2013 Research and development expense. Research and development expense was $21.2 million for the year ended December 31, 2014, compared with $16.2million for the year ended December 31, 2013, which represents an increase of $5.0 million. The higher costs were primarily attributable to the ramp up inclinical and manufacturing development activities for our SL-401 and SL-701 compounds. The increase in research and development costs associated withSL-401 and SL-701 is primarily driven by higher expenses of $4.0 million and $1.2 million, respectively, for administration of our clinical trials andadditional costs relating to the manufacturing of SL-401. As we continue to ramp up our clinical trial activities for SL-401 and SL-701 during 2015, weexpect that our research and development expenses will increase compared to prior periods. We expect this increase in costs will continue for the foreseeablefuture. General and administrative expense. General and administrative expenses were $8.1 million for the year ended December 31, 2014, compared with $7.9million for the year ended December 31, 2013, which represents an increase of $0.2 million. The higher expense was driven by an increase in rent, outsidelegal and audit fees totaling $0.7 million to support the increased governance responsibility of a public company, partially offset by a reduction in financialconsulting expenses of $0.6 million. Interest income. Interest income was $0.2 million for the year ended December 31, 2014, compared with $19,136 for the year ended December 31, 2013. Theincrease in income of $0.2 million is due to the interest earned from our investments in U.S. Treasury and Agency securities and related money market funds. Interest expense. Interest expense was $0 for the year ended December 31, 2014, compared with $0.5 million for the year ended December 31, 2013. Thedecrease in expense of $0.5 million is due to the conversion of our 2.45% convertible notes to common stock in April 2013. Other income. Other income was $3,607 for the year ended December 31, 2014 and $0.3 million for the year ended December 31, 2013. This income in 2013was primarily related to the research and development credit refund received from the City of New York. 62Table of Contents Liquidity and Capital Resources Sources of Liquidity We have financed our operations to date primarily through proceeds from sales of common stock and convertible preferred stock, and issuances ofconvertible debt. To date, we have not generated any revenue from the sale of products. We have incurred losses and generated negative cash flows fromoperations since inception. Since inception and through December 31, 2015, we received net proceeds of $165.7 million from the sale of common stock, $12.5 million from the sale ofconvertible preferred stock and $0.9 million from the issuance of convertible notes. In addition, on January 8, 2015, we completed a follow-on publicoffering (the “Additional Offering”), selling 3,800,000 shares at an offering price of $15.75 per share. On February 10, 2015, the underwriters exercised in fulltheir over-allotment option to purchase an additional 553,877 shares at an offering price of $15.75 per share. Aggregate gross proceeds from the AdditionalOffering, including the exercise of the over-allotment option, were $68.6 million, and net proceeds received after underwriting fees and offering expenseswere approximately $64.1 million. As of December 31, 2015, our cash, cash equivalents and short and long-term investments totaled $97.5 million. We primarily invest our cash, cashequivalents, short-term investments and long-term investments in 100% U.S. Treasury and Agency securities and related money market funds and FDIC-insured bank certificates of deposit, with the balance in commercial bank operating accounts. We believe that our existing cash, cash equivalents, short-terminvestments and long-term investments including the cash proceeds received from our Additional Offering in the first quarter of 2015, will be sufficient tofund our operations and our capital expenditures for at least the next two years. Cash Flows The following table sets forth the primary sources and uses of cash for each of the periods set forth below: Year Ended December 31,20152014 2013 Net cash used in operating activities$(25,589,442)$(25,713,445)$(16,118,487)Net cash provided by/ (used) in investing activities(50,922,458)6,384,968(40,708,687)Net cash provided by financing activities64,880,879135,27499,002,256Net increase (decrease) in cash and cash equivalents$(11,631,021)$(19,193,203)$42,175,082 Operating activities. The use of cash in all periods resulted primarily from our net losses adjusted for stock-based compensation expense, non-cashdepreciation expense and changes in the components of working capital. The net cash used in operating activities in 2015 and 2014 primarily resulted fromresearch and development expenses as we continued our clinical trial activities relating to SL-401, SL-701, and SL-801. The increase of net cash used inoperating activities in 2014 and 2013 was primarily the result of higher research and development expenses as we ramped up our clinical trial preparationsfor SL-401 and SL-701. The additional research and development costs also included CMC-related expenses for the manufacture of drug substance and drugproduct of our product candidates in development. Investing activities. The net cash used in investing activities for 2015 reflects purchases and redemptions of short-term and long-term investments within ourU.S. Treasury-related investment and bank certificate of deposit portfolios, net of maturities. The net cash provided by investing activities for 2014 reflectssales and maturities of long-term investments within our U.S. Treasury-related investment portfolio net of re-investments. The net cash used in investingactivities during 2013 resulted primarily from the purchase of long-term U.S. Treasury Agency securities. Financing activities. The net cash provided by financing activities for 2015 resulted primarily from our Additional Offering and sale of 4,353,877 shares ofour common stock which generated gross cash proceeds of $68.6 million ($64.1 million cash proceeds, net of expenses). The net cash provided by financingactivities for 2014 resulted from the exercise of stock options. The net cash provided by financing activities for 2013 resulted from the net cash proceedsreceived from our initial public offering in January 2013 and secondary public offering in May 2013. Funding Requirements All of our product candidates are still in clinical or preclinical development. We expect to continue to incur significant expenses and increasing operatinglosses for the foreseeable future. We anticipate that our expenses will increase substantially if and as we: 63Table of Contents · continue the ongoing clinical trials, and initiate the planned clinical trials, of our product candidates, SL-401, SL-701 and SL-801; · continue the research and development of our other product candidates, including SL-501 and our platform technology; · seek to identify additional product candidates; · acquire or in-license other products and technologies; · seek marketing approvals for our product candidates that successfully complete clinical trials; · establish, either on our own or with strategic partners, a manufacturing, sales, marketing and distribution infrastructure to commercialize anyproducts for which we may obtain marketing approval; · maintain, leverage and expand our intellectual property portfolio; and · add operational, financial and management information systems and personnel, including personnel to support our product development andfuture commercialization efforts. Our existing cash and cash equivalents will enable us to fund our operating expenses and capital expenditure requirements for at least the next two years. Wehave based this estimate on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect.Because of the numerous risks and uncertainties associated with the development and commercialization of our product candidates, and the extent to whichwe may enter into collaborations with third-parties for development and commercialization of our product candidates, we are unable to estimate the amountsof increased capital outlays and operating expenses associated with completing the development of our current product candidates. Our future capitalrequirements will depend on many factors, including: · the progress and results of the clinical trials of our product candidates; · the scope, progress, results and costs of compound discovery, preclinical development, laboratory testing and clinical trials for our otherproduct candidates; · the extent to which we acquire or in-license other products and technologies; · the costs, timing and outcome of regulatory review of our product candidates; · the costs of future commercialization activities, including product sales, marketing, manufacturing and distribution, for any of our productcandidates for which we receive marketing approval; · revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive marketing approval; · our ability to obtain government funding and operational support for our planned clinical trial of SL-701 in our clinical programs; · the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defendingintellectual property-related claims; and · our ability to establish any future collaboration arrangements on favorable terms, if at all. Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debtfinancings, collaborations, strategic alliances and licensing arrangements. We do not have any committed external source of funds. To the extent that we raiseadditional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders will be diluted, and the terms of thesesecurities may include liquidation or other preferences that adversely affect the rights of a common stockholder. Debt financing, if available, may involveagreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expendituresor declaring dividends. If we raise additional funds through collaborations, strategic alliances or licensing arrangements with third-parties, we may 64Table of Contents have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that maynot be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our productdevelopment or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop andmarket ourselves. Expected Cash Requirements for Contractual Obligations The following table presents our expected cash requirements for contractual obligations for each of the following years subsequent to December 31, 2015: Less than1-3 3-5 More thanTotal1 yearyears years 5 yearsOperating lease obligations (1)$3,024,000$513,0001,674,000837,000—Clinical trial obligations (2)22,263,57612,162,01410,101,562——Manufacturing (3)2,242,7971,348,699894,098——License agreements (4)3,783,5851,029,0952,073,190261,300420,000Other commitments (5)1,200,9941,169,75331,241——Total$32,514,952$16,222,561$14,774,091$1,098,300$420,000 (1) Operating lease obligations reflects our lease agreement with respect to our corporate offices at 750 Lexington Avenue, New York, New York, for amonthly rent of $69,750. The term of this lease agreement is 42 months and it expires on December 31, 2019. (2) We have agreements in place with various contract research organizations (CROs) to facilitate research, clinical and data management services inconnection with our three clinical-stage product candidates: SL-401, SL-701, and SL-801. (3) Includes commitments to our third party drug substance and drug product manufacturers. Also includes contractual obligations for stability testingon drug substance and drug product inventory. (4) We have executed several license agreements. Other than the payments noted in the table above, milestone and royalty payments associated withlicensing have not been included as management cannot reasonably estimate if or when they will occur. These agreements include the following: · Under a research and license agreement with Scott and White Hospital for SL-401, we are required to pay royalties on annual sales of licensedproducts. · Under three separate license agreements with the University of Pittsburgh, we are required to make aggregate development and regulatorymilestone payments associated with SL-701 and pay royalties on net sales of licensed products. · Under an exclusive patent and non-exclusive know-how license agreement with the Cambridge University Technical Services Limited, relatedto our StemScreen platform technology, we are required to make milestone payments upon specified regulatory events and pay royalties onsales of licensed products. · On December 26, 2014, we entered into a license agreement with CanBas, Ltd for SL-801. SL-801 is a small molecule, reversible inhibitor ofXPO1. Under the terms of the agreement, CanBas has granted us an exclusive, royalty-bearing, worldwide (excluding Japan, Korea, China andTaiwan) license, under certain patent rights, know-how and materials to research, develop, make, have made, formulate, use, sell, offer to sell andimport SL-801, and any products containing or comprising such compound in finished dosage pharmaceutical form, for the treatment of anydisease or condition in humans. We are required to make milestone payments upon the achievement of various clinical development,regulatory and commercial milestones. Additionally, we are required to pay tiered royalties on net sales of licensed products. 65®Table of Contents (5) Other commitments include $1.0 million in severance obligations and certain sponsored research. Certain contractual payment obligations will extend beyond five years until certain specified milestones are achieved. For purposes of this calculation,we have assumed that these payment obligations have only been made in the eighth year. However, these payments would continue each subsequentyear until the specified milestones are achieved. Off-Balance Sheet Arrangements We did not have during the periods presented, and we do not currently have, any relationships with any organizations or financial partnerships, such asstructured finance or special purpose entities, that would have been established for the purpose of facilitating off-balance sheet arrangements or othercontractually narrow or limited purposes. Tax Loss Carryforwards As of December 31, 2015, we had net operating losses of $58.6 million for both federal and state purposes, which are available to reduce future taxableincome. We also had federal tax credits of approximately $14.9 million, which may be used to offset future tax liabilities. The net operating loss and taxcredit carryforwards will expire at various dates through 2035. Net operating loss and tax credit carryforwards are subject to review and possible adjustmentby the Internal Revenue Service and state tax authorities and may become subject to an annual utilization limitation pursuant to the change in ownershiprules of Internal Revenue Code Section 382 and 383. The amount of the annual limitation is determined based on the value of our company immediatelyprior to the ownership change. Subsequent ownership changes may further affect the limitation in future years. At December 31, 2015, we recorded a 100%valuation allowance against our net operating loss and tax credit carryforwards, as we believe it is more likely than not that the tax benefits will not be fullyrealized. Recently Adopted Accounting Standards See Note 2 to our financial statements for recently adopted accounting standards. Jumpstart Our Business Startups Act of 2012 The JOBS Act permits an “emerging growth company,” of which we are one, to take advantage of an extended transition period to comply with new orrevised accounting standards applicable to public companies. We have “opted out” of this provision and, as a result, we will comply with new or revisedaccounting standards as required when they are adopted. This decision to opt out of the extended transition period under the JOBS Act is irrevocable. Item 7A. Quantitative and Qualitative Disclosures about Market Risk We are exposed to market risk related to changes in interest rates. We had cash, cash equivalents, short-term investments and long-term investments of $97.5million as of December 31, 2015, $58.6 million as of December 31, 2014 and $84.4 million as of December 31, 2013, consisting of cash, U. S. Treasury andAgency securities and Treasury-related money market funds and FDIC-insured bank certificates of deposit. Our primary exposure to market risk is interestrate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because our investments are primarily in Treasury-relateddebt securities and bank certificates of deposit. Our available for sale securities are subject to interest rate risk and will fall in value if market interest ratesincrease. Due to the short-term duration of our investment portfolio and the low risk profile of our investments, an immediate 100 basis point change ininterest rates would not have a material effect on the fair market value of our portfolio. We contract with CROs and CMOs. We may be subject to fluctuations in foreign currency rates in connection with these agreements. Transactionsdenominated in currencies other than the functional currency are recorded based on exchange rates at the time such transactions arise. As of December 31,2015, 2014 and 2013, all of our liabilities were denominated in our functional currency. Item 8. Financial Statements and Supplementary Data Our financial statements and the notes thereto, included in Part IV, Item 15(a), part 1, are incorporated by reference into this Item 8. Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure None. 66Table of Contents Item 9A. Controls and Procedures Evaluation of Disclosure Controls and Procedures Our management, with the participation of our Chief Executive Officer (principal executive officer) and Chief Accounting Officer (principal financial officer),evaluated the effectiveness of our disclosure controls and procedures as of December 31, 2015. The term “disclosure controls and procedures”, as defined inRules 13a-15I and 15d-15(e) under the Securities Exchange Act of 1934, as amended, or the Exchange Act, means controls and other procedures of acompany that are designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act isrecorded, processed, summarized and reported, within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include,without limitation, controls and procedures designed to ensure that information required to be disclosed by a company in the reports that it files or submitsunder the Exchange Act is accumulated and communicated to the company’s management, including its principal executive and principal financial officers,as appropriate to allow timely decisions regarding required disclosure. Management recognizes that any controls and procedures, no matter how welldesigned and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluatingthe cost-benefit relationship of possible controls and procedures. Based on the evaluation of our disclosure controls and procedures as of December 31, 2015,our Chief Executive Officer and Chief Accounting Officer concluded that, as of such date, our disclosure controls and procedures were effective. Management’s Report on Internal Control over Financial Reporting Our management is responsible for establishing and maintaining adequate internal control over financial reporting for our company. Internal control overfinancial reporting is defined in Rule 13a-15(f) or 15d-15(f) promulgated under the Exchange Act as a process designed by, or under the supervision of, thecompany’s principal executive and principal financial officers and effected by the company’s board of directors, management and other personnel, to providereasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance withGAAP and includes those policies and procedures that: (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect thetransactions and dispositions of the assets of the company; (ii) provide reasonable assurance that transactions are recorded as necessary to permit preparationof financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of our company are being made onlyin accordance with authorizations of management and directors of the company; and (iii) provide reasonable assurance regarding prevention or timelydetection of unauthorized acquisition, use, or disposition of our company’s assets that could have a material effect on the financial statements. Internal control over financial reporting is designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation offinancial statements prepared for external purposes in accordance with generally accepted accounting principles. Because of its inherent limitations, internalcontrol over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of effectiveness to future periods are subject tothe risk that controls may become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures maydeteriorate. Our management, with the participation of our Chief Executive Officer (principal executive officer) and Chief Accounting Officer (principal financial officer),assessed the effectiveness of our internal control over financial reporting as of December 31, 2015. In making this assessment, our management used thecriteria set forth in the Internal Control—Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission.Based on its assessment, management concluded that our internal control over financial reporting was effective as of December 31, 2015 based on thosecriteria. Changes in Internal Control over Financial Reporting No change in our internal control over financial reporting occurred during the quarter ended December 31, 2015 that has materially affected, or is reasonablylikely to materially affect, our internal control over financial reporting. Item 9B. Other Information None. 67Table of Contents Part III Item 10. Directors, Executive Officers and Corporate Governance The information required by this Item is incorporated herein by reference from our Proxy Statement for our 2016 Annual Meeting of Stockholders. Item 11. Executive Compensation The information required by this Item is incorporated herein by reference from our Proxy Statement for our 2016 Annual Meeting of Stockholders. Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters The information required by this Item is incorporated herein by reference from our Proxy Statement for our 2016 Annual Meeting of Stockholders. Item 13. Certain Relationships and Related Transactions and Director Independence. The information required by this Item is incorporated herein by reference from our Proxy Statement for our 2016 Annual Meeting of Stockholders. Item 14. Principal Accounting Fees and Services. The information required by this Item is incorporated herein by reference from our Proxy Statement for our 2016 Annual Meeting of Stockholders. 68Table of Contents Part IV Item 15. Exhibits, Financial Statements Schedules. (a) 1. Financial Statements The following financial statements of Stemline Therapeutics, Inc. are filed as part of this report. ContentsPage Report of Independent Registered Public Accounting FirmF-2 Balance Sheets as of December 31, 2015 and 2014F-3 Statements of Operations for the Years ended December 31, 2015, 2014 and 2013F-4 Statements of Comprehensive Loss for the Years ended December 31, 2015, 2014 and 2013F-5 Statements of Stockholders’ Equity (Deficit) for the Years ended December 31, 2015, 2014 and 2013F-6 Statements of Cash Flows for the Years ended December 31, 2015, 2014 and 2013F-7 Notes to the Financial StatementsF-8 2. Financial Statement Schedules All schedules are omitted as the information required is inapplicable or the information is presented in the financial statements or the related notes. 3. Exhibits Exhibit No. Description 3.1Restated Certificate of Incorporation of Stemline Therapeutics, Inc., filed as Exhibit 3.1 to Form 8-K on February 6, 2013 (File No.001-35619) and incorporated herein by reference. 3.2Amended and Restated Bylaws of Stemline Therapeutics, Inc., filed as Exhibit 3.2 to Form 8-K on February 6, 2013 (File No. 001-35619)and incorporated herein by reference. 3.3Certificate of Amendment of Restated Certificate of Incorporation of Stemline Therapeutics, Inc., filed as Exhibit 3.3 to Form 10-Q onAugust 14, 2013 (File No. 001-35691) and incorporated herein by reference. 4.1Specimen certificate evidencing shares of common stock, filed as Exhibit 4.1 to Form S-1/A on June 20, 2012 (File No. 333-180515) andincorporated herein by reference. 4.2Form of Representative’s Warrant Agreement, filed as Exhibit 4.2 to Form S-1/A on November 14, 2012 (File No. 333-180515) andincorporated herein by reference. 10.1†Research and License Agreement by and among the Company, Scott and White Memorial Hospital, Scott, Sherwood and BrindleyFoundation and Arthur E. Frankel, M.D., dated June 15, 2006; as amended by that certain First Amendment to Research and LicenseAgreement dated December 9, 2008, that certain Second Amendment to Research and License Agreement dated March 17, 2010 and thatcertain Third Amendment to Research and License Agreement dated July 12, 2011, filed as Exhibit 10.1 to Form S-1/A on June 20, 2012(File No. 333-180515) and incorporated herein by reference. 10.2†Exclusive License Agreement between the Company and the University of Pittsburgh, dated September 30, 2009, filed as Exhibit 10.2 toForm S-1/A on June 20, 2012 (File No. 333-180515) and incorporated herein by reference. 69Table of Contents Exhibit No. Description 10.3†Exclusive Patent and Non-Exclusive Know-How License Agreement between the Company and Cambridge University TechnicalServices Limited, commenced September 16, 2004, filed as Exhibit 10.3 to Form S-1/Aon June 20, 2012 (File No. 333-180515) and incorporated herein by reference. 10.4†Non-Exclusive License Agreement between the Company and the University of Pittsburgh, dated March 30, 2012, filed as Exhibit 10.4to Form S-1/A on June 20, 2012 (File No. 333-180515) and incorporated herein by reference. 10.5†Non-Exclusive License Agreement between the Company and the University of Pittsburgh, dated March 21, 2012, filed as Exhibit 10.5to Form S-1 on April 2, 2012 (File No. 333-180515) and incorporated herein by reference. 10.6*Employment Agreement, dated November 6, 2011, between the Registrant and Eric K. Rowinsky, M.D., filed as Exhibit 10.6 to Form S-1on April 2, 2012 (File No. 333-180515) and incorporated herein by reference. 10.7*Employment Agreement, dated June 15, 2012, between the Registrant and Ivan Bergstein, M.D., filed as Exhibit 10.8 to Form S-1/A onJune 20, 2012 (File No. 333-180515) and incorporated herein by reference. 10.8*Form of Indemnification Agreement between the Registrant and each director, filed as Exhibit 10.9 to Form S-1/A on June 20, 2012 (FileNo. 333-180515) and incorporated herein by reference. 10.9*Amended and Restated 2004 Employee, Director and Consultant Stock Plan, filed as Exhibit 10.10 to Form S-1on April 2, 2012 (FileNo. 333-180515) and incorporated herein by reference. 10.10*Form of Incentive Stock Option Agreement under Amended and Restated 2004 Employee, Director and Consultant Stock Plan, filed asExhibit 10.11 to Form S-1 on April 2, 2012 (File No. 333-180515) and incorporated herein by reference. 10.11*Form of Non-qualified Stock Option Agreement under Amended and Restated 2004 Employee, Director and Consultant Stock Plan, filedas Exhibit 10.12 to Form S-1 on April 2, 2012 (File No. 333-180515) and incorporated herein by reference. 10.12*2012 Equity Incentive Plan, filed as Exhibit 10.13 to Form S-1/A on July 19, 2012 (File No. 333-180515) and incorporated herein byreference. 10.13*Form of Incentive Stock Option Agreement under 2012 Equity Incentive Plan, filed as Exhibit 10.14 to Form S-1/A on July 19, 2012(File No. 333-180515) and incorporated herein by reference. 10.14*Form of Nonstatutory Stock Option Agreement under 2012 Equity Incentive Plan, filed as Exhibit 10.15 to Form S-1/A on July 19, 2012(File No. 333-180515) and incorporated herein by reference. 10.15Exclusive License Agreement between the Company and Dr. Ivan Bergstein M.D., effective as of December 1, 2003, filed asExhibit 10.18 to Form S-1/A filed on June 20, 2012 (File No. 333-180515) and incorporated herein by reference. 70Table of Contents Exhibit No. Description 10.16Assignment Agreement between the Company and Ivan Bergstein, M.D., effective as of June 15, 2012, filed as Exhibit 10.20 to Form S-1/A on June 20, 2012 (File No. 333-180515) and incorporated herein by reference. 10.17*Offer Letter between the Company and Eric L. Dobmeier, dated April 25, 2012, filed as Exhibit 10.21 to Form S-1/A on June 20, 2012(File No. 333-180515) and incorporated herein by reference. 10.18*Offer Letter between the Company and J. Kevin Buchi, dated March 2, 2012, filed as Exhibit 10.22 to Form S-1/A on June 20, 2012 (FileNo. 333-180515) and incorporated herein by reference. 10.19*Offer Letter between the Company and Kenneth Zuerblis, dated March 8, 2012, filed as Exhibit 10.23 to Form S-1/A on June 20, 2012(File No. 333-180515) and incorporated herein by reference. 10.20Amendment No. 1 to Assignment Agreement between the Company and Ivan Bergstein, M.D., dated as of November 7, 2012, filed asExhibit 10.26 to Form S-1/A on November 14, 2012 (File No. 333-180515) and incorporated herein by reference. 10.21*Employment Agreement between the Company and David G. Gionco, dated January 16, 2014, filed as Exhibit 10.1 to Form 8-K onJanuary 23, 2014 (File No. 001-35619) and incorporated herein by reference. 10.22†License Agreement by and between Stemline Therapeutics, Inc. and the CanBas Co., Ltd, dated December 26, 2014, filed asExhibit 10.30 to Form 10-K on March 16, 2015 (File No. 001-35619) and incorporated herein by reference. 10.23*Amendment No.1 to the 2012 Equity Incentive Plan, adopted March 13, 2015, filed as Exhibit 10.31 to Form 10-K on March 16, 2015(File No. 001-35619) and incorporated herein by reference. 10.24*Amendment No.1 to the Amended and Restated 2004 Employee, Director and Consultant Stock Plan, adopted March 13, 2015, filed asExhibit 10.32 to Form 10-K on March 16, 2015 (File No. 001-35619) and incorporated herein by reference. 10.25*Separation Agreement, dated October 27, 2015, between the Company and Eric Rowinsky, M.D, filed as Exhibit 10.1 to Form 8-K onOctober 29, 2015 (File No. 001-35619) and incorporated herein by reference. 10.26*Employment Agreement between the Company and Kenneth Hoberman, dated January 7, 2016, filed as Exhibit 10.1 to Form 8-K onJanuary 13, 2016 (File No. 001-35619) and incorporated herein by reference. 21.1List of subsidiaries of Stemline Therapeutics, Inc. 23.1Consent of Ernst & Young, LLP. 24.1Power of Attorney (included on signature page). 31.1Certificate of principal executive officer pursuant to Rule 13a-14(a)/15d-14(a), as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. 31.2Certificate of principal financial officer pursuant to Rule 13a-14(a)/15d-14(a), as adopted pursuant to Section 302 of the Sarbanes-OxleyAct of 2002. 71Table of Contents Exhibit No. Description 32.1Certificate of principal executive officer pursuant to 18 U.S.C. § 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of2002. 32.2Certificate of principal financial officer pursuant to 18 U.S.C. § 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of2002. 101The following financial information from Stemline Therapeutics, Inc.’s Annual Report on Form 10-K for the year ended December 31,2015, formatted in XBRL (eXtensible Business Reporting Language): (i) Consolidated Balance Sheets, (ii) Consolidated Statements ofOperations, (iii) Consolidated Statements of Stockholders’ Equity, (iv) Consolidated Statements of Cash Flows, (v) the Notes toConsolidated Financial Statements. † Confidential treatment has been granted with respect to the omitted portions of this exhibit. Confidential materials omitted and filed separately with theSecurities and Exchange Commission.* Management contract or compensatory plan, contract or agreement. 72Table of Contents STEMLINE THERAPEUTICS, INC. Index to Financial Statements Contents Report of Independent Registered Public Accounting FirmF-2Balance Sheets as of December 31, 2015 and 2014F-3Statements of Operations for the Years Ended December 31, 2015, 2014 and 2013F-4Statements of Comprehensive loss for the Years Ended December 31, 2015, 2014 and 2013F-5Statements of Stockholders’ Equity (Deficit) for the Years Ended December 31, 2015, 2014 and 2013F-6Statements of Cash Flows for the Years Ended December 31, 2015, 2014 and 2013F-7Notes to Financial StatementsF-8 F-1Table of Contents Report of Independent Registered Public Accounting Firm The Board of Directors and StockholdersStemline Therapeutics, Inc. We have audited the accompanying balance sheets of Stemline Therapeutics, Inc. as of December 31, 2015 and 2014, and the related statements ofoperations, comprehensive loss, stockholders’ equity (deficit) and cash flows for each of the three years in the period ended December 31, 2015. Thesefinancial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on these financial statements based onour audits. We conducted our audits in accordance with the standards of the Public Company Accounting Oversight Board (United States). Those standards require thatwe plan and perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement. We were not engagedto perform an audit of the Company’s internal control over financial reporting. Our audits included consideration of internal control over financial reportingas a basis for designing audit procedures that are appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of theCompany’s internal control over financial reporting. Accordingly, we express no such opinion. An audit also includes examining, on a test basis, evidencesupporting the amounts and disclosures in the financial statements, assessing the accounting principles used and significant estimates made by management,and evaluating the overall financial statement presentation. We believe that our audits provide a reasonable basis for our opinion. In our opinion, the financial statements referred to above present fairly, in all material respects, the financial position of Stemline Therapeutics, Inc. atDecember 31, 2015 and 2014, and the results of its operations and its cash flows for each of the three years in the period ended December 31, 2015, inconformity with U.S. generally accepted accounting principles. /s/ Ernst & Young LLP MetroPark, New JerseyMarch 14, 2016 F-2Table of Contents STEMLINE THERAPEUTICS, INC.Balance Sheets December 31,2015 2014AssetsCurrent assets:Cash and cash equivalents$13,376,196$25,007,217Short-term investments32,663,24528,976,147Prepaid expenses and other current assets651,8891,636,808Total current assets46,691,33055,620,172Furniture and fixtures, net95,661230,000Long-term investments51,428,6324,644,820Total assets$98,215,623$60,494,992Liabilities and stockholders’ equityCurrent liabilities:Accounts payable and accrued expenses$9,455,477$4,473,842Total current liabilities9,455,4774,473,842Deferred grant revenue616,949607,999Other liabilities31,241—Total liabilities10,103,6675,081,841Stockholders’ equity:Preferred stock $0.0001 par value, 5,000,000 shares authorized, none issued and outstanding atDecember 31, 2015 and 2014——Common stock $0.0001 par value, 33,750,000 shares authorized at December 31, 2015 and 2014.18,235,020 shares issued and outstanding at December 31, 2015 and 13,285,232 shares issued andoutstanding at December 31, 20141,8251,329Additional paid-in capital185,703,423115,604,563Accumulated other comprehensive income (loss)(153,690)3,000Accumulated deficit(97,439,602)(60,195,741)Total stockholders’ equity88,111,95655,413,151Total liabilities and stockholders’ equity$98,215,623$60,494,992 See accompanying notes. F-3Table of Contents STEMLINE THERAPEUTICS, INC.Statements of Operations Year Ended December 31,20152014 2013 Revenues:Grant revenue$654,160$335,287$71,000Operating expenses:Research and development29,458,67621,240,59916,178,744General and administrative8,828,8438,084,5807,871,719Total operating expenses38,287,51929,325,17924,050,463Loss from operations(37,633,359)(28,989,892)(23,979,463)Other income1,6093,607280,687Interest expense——(516,871)Interest income387,889156,31019,136Net loss$(37,243,861)$(28,829,975)$(24,196,511)Net loss per common share:Basic and Diluted$(2.15)$(2.23)$(2.35)Weighted-average shares outstanding:Basic and Diluted17,289,02112,936,74110,317,351 See accompanying notes. F-4Table of Contents Stemline Therapeutics, Inc.Statements of Comprehensive Loss Year Ended December 3120152014 2013 Net loss$(37,243,861)$(28,829,975)$(24,196,511)Other comprehensive loss:Unrealized gain (loss) on investments(155,081)50,287(43,775)Reclassification adjustment for gain on investments included in net loss(1,609)(3,512)—Other comprehensive gain (loss)(156,690)46,775(43,775)Comprehensive loss$(37,400,551)$(28,783,200)$(24,240,286) F-5Table of Contents Stemline Therapeutics, Inc.Statements of Stockholders’ Equity (Deficit) Accumulated AdditionalOther TotalCommon StockPaid-inComprehensiveEarningsStockholders’SharesCapitalCapitalLoss(Deficit)Equity (Deficit)Balance, December 31, 20123,476,5013474,660,488—(7,169,255)(2,508,420)Issuance of common stock for cash in connectionwith initial and secondary public offerings, netof issuance costs8,573,91185797,707,649——97,708,506Restricted stock grants296,56530(30)———Forfeiture of restricted stock grants(43,982)(4)4———Stock-based compensation——4,847,086——4,847,086Issuance of common stock in connection with theexercise of stock options550,801561,293,694——1,293,750Issuance of common stock in connection with theconversion of convertible notes252,547242,101,080——2,101,104Beneficial conversion related to interest expense——422,648——422,648Net loss————(24,196,511)(24,196,511)Change in unrealized gain (loss) on available forsale securities———(43,775)—(43,775)Balance, December 31, 201313,106,343$1,310$111,032,619$(43,775)$(31,365,766)$79,624,388Restricted stock grants138,66316(16)———Forfeiture of restricted stock grants(777)(0)0———Stock-based compensation——4,436,689——4,436,689Issuance of common stock in connection with theexercise of stock options33,0403135,271——135,274Net loss————(28,829,975)(28,829,975)Change in unrealized gain (loss) on available forsale securities———46,775—46,775Balance, December 31, 201413,277,269$1,329$115,604,563$3,000$(60,195,741)$55,413,151Restricted stock grants399,74240(40)———Stock award — outside services12,1001147,377——147,378Forfeiture of restricted stock grants(13,976)(1)1———Stock-based compensation——5,015,584——5,015,584ESPP compensation expense——55,515——55,515Issuance of common stock in connection with theESPP7,070149,489——49,490Issuance of common stock in connection with theexercise of stock options198,93820724,997——725,017Issuance of common stock in connection with thesecondary public offering4,353,87743564,105,937——64,106,372Net loss————(37,243,861)(37,243,861)Change in unrealized gain (loss) on available forsale securities———(156,690)—(156,690)Balance, December 31, 201518,235,020$1,825$185,703,423$(153,690)$(97,439,602)$88,111,956 See accompanying notes. F-6Table of Contents STEMLINE THERAPEUTICS, INC.Statements of Cash Flows Year Ended December 31,20152014 2013Cash flows from operating activitiesNet loss$(37,243,861)$(28,829,975)$(24,196,511)Adjustments to reconcile net loss to net cash used in operating activities:Depreciation153,797153,33376,667Stock-based compensation expense5,218,4774,436,6894,847,086Amortization of premium paid on marketable securities277,009249,264—Net gain on sale of marketable securities(1,609)(3,512)—Non-cash interest expense——94,223Mark-to-market of put option liability——(30,415)Beneficial conversion of convertible interest——422,648Changes in operating assets and liabilities:Prepaid expenses and other current assets984,919(1,343,892)6,173Related party receivable—199,615(199,615)Accounts payable and accrued expenses4,981,635(539,966)2,218,257Deferred grant revenue8,950(35,001)643,000Other liabilities31,241——Net cash used in operating activities(25,589,442)(25,713,445)(16,118,487)Cash flows from investing activitiesPurchase of furniture and fixtures(19,458)—(460,000)Purchase of marketable securities(105,565,837)(16,246,878)(40,248,687)Sale and maturities of marketable securities54,662,83722,631,846—Net cash used in investing activities(50,922,458)6,384,968(40,708,687)Cash flows from financing activitiesProceeds from issuance of common stock, net64,155,862—97,708,506Proceeds from exercise of stock options725,017135,2741,293,750Proceeds from issuance of convertible notes———Net cash provided by financing activities64,880,879135,27499,002,256Net (decrease)/increase in cash and cash equivalents(11,631,021)(19,193,203)42,175,082Cash and cash equivalents at beginning of period25,007,21744,200,4202,025,338Cash and cash equivalents at end of period$13,376,196$25,007,217$44,200,420Supplementary InformationOther information:Income tax paid———Interest paid——— See accompanying notes. F-7Table of Contents STEMLINE THERAPEUTICS, INC.NOTES TO FINANCIAL STATEMENTSDecember 31, 2015 1. Organization and Basis of Presentation Organization Stemline Therapeutics, Inc. (the “Company”) is a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing andcommercializing proprietary oncology therapeutics. The Company’s activities to date have primarily consisted of advancing its clinical stage programs,expanding and strengthening its intellectual property portfolio, developing its proprietary drug discovery platform, identifying and acquiring additionalproduct and technology rights and raising capital. The Company was incorporated in Delaware on August 8, 2003 and has its principal office in New York,New York. Stemline Therapeutics, Inc. has incurred losses from operations since inception of $109.6 million. Since its inception, most of its resources have beendedicated to the discovery, acquisition and preclinical and clinical development of its product candidates. In particular, it has expended and will continue toexpend substantial resources for the foreseeable future developing its clinical candidates, SL-401, SL-701, and SL-801 as well as its preclinical productcandidates and drug discovery and acquisition efforts. These expenditures include costs associated with general and administrative costs, facilities costs,research and development, acquiring new technologies, manufacturing product candidates, conducting preclinical experiments and clinical trials andobtaining regulatory approvals, as well as commercializing any products approved for sale. The Company anticipates incurring additional losses until suchtime, if ever, that it can generate significant sales of its products currently in development. The Company expects its research and development expenses toincrease significantly in connection with its ongoing and planned clinical trials. As a result, the Company expects to continue to incur significant andincreasing operating losses for the foreseeable future. If adequate funds are not available to the Company on a timely basis, or at all, the Company may berequired to terminate or delay clinical trials or other development activities for SL-401, SL-701 or SL-801, or for one or more indications for which it isdeveloping SL-401, SL-701 or SL-801, or delay its establishment of sales and marketing capabilities or other activities that may be necessary tocommercialize SL-401, SL-701 or SL-801, if the Company obtains marketing approval. 2. Summary of Significant Accounting Policies Use of Estimates The preparation of financial statements in conformity with generally accepted accounting principles in the U.S. (U.S. GAAP) requires management to makeestimates and assumptions that affect the reported financial position at the date of the financial statements and the reported results of operations during thereporting period. Such estimates and assumptions affect the reported amounts of assets, liabilities, revenues and expenses and disclosure of contingent assetsand liabilities in the financial statements and accompanying notes. Actual results could differ from those estimates. Cash Equivalents Cash equivalents consist of highly liquid instruments purchased with an original maturity of three months or less. At December 31, 2015 and 2014, cashequivalents consisted of deposits in financial institutions. The Company maintains its cash deposits and cash equivalents with well-known and stablefinancial institutions. Concentration of Credit Risk Financial instruments that potentially subject the Company to significant concentrations of credit risk consist primarily of cash equivalents. The Companyinvests its excess cash in major U.S. banks and financial institutions, and its deposits, at times, exceed federally insured limits. The Company has notexperienced any losses from credit risks. Investments The Company’s investments are considered to be available-for-sale and are carried at fair value. Unrealized gains and losses, if any, are reported as a separatecomponent of stockholders’ equity (deficit) and are not reflected in the statements of operations until a sale transaction occurs or when declines in fair valueare deemed to be other-than-temporary (“OTT”). The cost of investments classified as available-for-sale are adjusted for the amortization of premiums andaccretion of discounts to maturity and recorded in other expense and other income, respectively. Realized gains and losses, if any, are determined using thespecific identification method and are included in other income and other expense, respectively. Investments with original maturities beyond 90 days at thedate of purchase and which mature at, or less than twelve months from, the balance sheet date are classified as current. Investments with a maturity beyondtwelve months from the balance sheet date are classified as long-term. F-8Table of Contents Fair Value of Financial Instruments The Company’s financial instruments consist principally of cash and cash equivalents, investments, other current assets, accounts payable and accruedliabilities. Cash and cash equivalents, and long-term investments are carried at fair value (see Note 7). Financial instruments including other current assets,accounts payable and accrued liabilities are carried at cost, which approximate fair value given their short-term nature. Other-Than-Temporary Impairment Losses on Investments The Company regularly monitors its available-for-sale portfolio to evaluate the necessity of recording impairment losses for OTT declines in the fair value ofinvestments. Management makes this determination through the consideration of various factors such as management’s intent and ability to retain aninvestment for a period of time sufficient to allow for any anticipated recovery in market value. OTT impairment losses result in a permanent reduction of thecost basis of an investment. For the years ended December 31, 2015 and 2014, the Company did not realize any investment losses due to OTT declines in fairvalue. Furniture and Fixtures Furniture and fixtures are stated at cost, less accumulated depreciation. Depreciation is provided over the estimated useful lives of the respective assets, whichare between three to seven years, using the straight-line method. Impairment of Long-Lived Assets The Company reviews long-lived assets, (the Company’s furniture and fixtures), for impairment whenever events or changes in business circumstancesindicate that the carrying amount of the assets may not be fully recoverable. An impairment loss would be recognized when estimated undiscounted futurecash flows expected to result from the use of the asset and its eventual disposition are less than its carrying amount. The impairment loss, if recognized, wouldbe based on the excess of the carrying value of the impaired asset over its respective fair value. The Company purchased fixed assets during 2015 and 2013.For the years ended December 31, 2015, 2014, and 2013, the Company did not realize any impairment losses. Grant Revenue Recognition The Company has not yet generated any revenue from product sales and it has generated minimal revenues to date, all relating to $2.5 million in researchgrants received from the Leukemia and Lymphoma Society, or LLS. This research grant was awarded to the Company to support funding some of the costsfor the upcoming SL-401 clinical trials. Grant payments received prior to the Company’s performance of work required by the terms of the research grant arerecorded as deferred revenue and recognized as grant revenue once work is performed and qualifying costs are incurred. The Company has recognizedapproximately $0.7 million, $0.3 million, and $0.1 million of revenue related to the Leukemia and Lymphoma Society grant for the years endedDecember 31, 2015, 2014, and 2013, respectively, which reflect twelve months of revenue recognized, respectively, on a straight line basis, based on theCompany’s best estimates of the timing of work to be performed and qualifying costs incurred. Accrued Clinical Development Costs Outside research costs are a component of research and development expense. These expenses include fees paid to contract research organizations, or CROs,and other service providers that conduct certain clinical and product development activities on behalf of the Company. Depending upon the timing ofpayments to the service providers, the Company recognizes prepaid expenses or accrued expenses related to these costs. These accrued or prepaid expensesare based on management’s estimates of the work performed under service agreements, milestones achieved and experience with similar contracts. TheCompany monitors each of these factors and adjusts estimates accordingly. Research and Development Costs Research and development costs are comprised primarily of costs for personnel, including salaries and benefits; clinical studies administered by third partiesand managed by Stemline personnel; materials and supplies to support the Company’s clinical programs; contracted research; manufacturing; relatedconsulting arrangements; costs related to upfront and milestone payments under license agreements; and other expenses incurred to sustain the Company’soverall research and development programs. Internal research and development costs are expensed as incurred. Third-party research and development costsare expensed as the contracted work is performed. In certain circumstances, the Company is required to make advance payments to vendors for goods orservices that will be received in the future for use in research and development activities. In such circumstances, the advance payments are deferred and areexpensed when activities have been performed or when the goods have been received. F-9Table of Contents Income Taxes Income taxes are accounted for under the asset and liability method. Deferred tax assets and liabilities are recognized for the future tax consequencesattributable to the differences between the financial statement carrying amounts of existing assets and liabilities and the respective tax bases and operatingloss and tax credit carryforwards. Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable income in the years inwhich those temporary differences are expected to be recovered or settled. The effect on deferred tax assets and liabilities of a change in tax rates isrecognized in income in the period that includes the enactment date. The asset and liability method requires that deferred tax assets and liabilities be recorded without consideration as to their realizability. The deferred tax assetprimarily includes net operating loss and tax credit carryforwards, accrued expenses not currently deductible and the cumulative temporary differencesrelated to certain research and patent costs, which have been charged to expense in the accompanying statements of operations but have been recorded asassets for income tax purposes. The portion of any deferred tax asset for which it is more likely than not that a tax benefit will not be realized must then beoffset by recording a valuation allowance. A valuation allowance has been established against all of the deferred tax assets (see Note 12), as it is more likelythan not that these assets will not be realized given the history of operating losses. The Company recognizes the tax benefit from an uncertain tax position only if it is more likely than not to be sustained upon examination based on thetechnical merits of the position. The amount of the accrual for which an exposure exists is measured as the largest amount of benefit determined on acumulative probability basis that the Company believes is more likely than not to be realized upon ultimate settlement of the position. Stock-Based Compensation The Company accounts for stock-based compensation in accordance with the provisions of ASC 718, Compensation—Stock Compensation. Accordingly,compensation costs related to equity instruments granted are recognized over the requisite service periods of the awards on a straight-line basis at the grant-date fair value calculated using a Black-Scholes option pricing model for stock options and the closing stock price on date of grant for restricted stock.Additionally, under the provisions of ASC 718, the Company is required to include an estimate of the number of awards that will be forfeited in calculatingcompensation costs. Any changes to the estimated forfeiture rates are accounted for prospectively. For stock options granted as consideration for services rendered by non-employees, the Company recognizes expense in accordance with the requirements ofASC Topic 505-50, Equity Based Payments to Non-Employees. Non-employee option grants that do not vest immediately upon grant are recorded as anexpense over the vesting period of the underlying stock options. At the end of each financial reporting period prior to vesting, the value of these options, ascalculated using the Black-Scholes option-pricing model, is re-measured using the fair value of the Company’s common stock and the non-cash expenserecognized during the period is adjusted accordingly. Since the fair market value of options granted to non-employees is subject to change in the future, theamount of the future expense will include fair value re-measurements until the stock options are fully vested. Segment Information The Company reports segment information in accordance with applicable guidance on segment disclosures. The Company has one reportable segment. Recent Accounting Pronouncements In August 2014, the FASB issued a new Accounting Standards Update ASU 2014-15, Disclosure of Uncertainties about an Entity’s Ability to Continue as aGoing Concern. ASU 2014-15 provides guidance on management’s responsibility to evaluate whether there is substantial doubt about an organization’sability to continue as a going concern and to provide related footnote disclosures. The guidance is effective for annual periods ending after December 15,2016 and interim periods within annual periods beginning after December 15, 2016. Early adoption is permitted. In November 2015, the FASB issued a new Accounting Standards Update, Balance Sheet Classification of Deferred Taxes (ASU 2015-17). ASU 2015-17requires all deferred tax assets and liabilities, and any related valuation allowance, to be classified as non-current on the balance sheet. The classificationchange for all deferred taxes as non-current simplifies entities’ processes as it eliminates the need to separately identify the net current and net non-currentdeferred tax asset or liability in each jurisdiction and allocate valuation allowances. The Company elected to retrospectively adopt this accounting standardin the beginning of the Company’s fourth quarter of fiscal 2015. The adoption of this standard did not have any impact on the Company’s financialstatements due to full valuation allowance recorded on the Company’s deferred taxes. F-10Table of Contents In January 2016, the FASB issued a new Accounting Standards Update, Recognition and Measurement of Financial Assets and Financial Liabilities (ASU2016-01). ASU 2016-01 amends the guidance in U.S. GAAP on the classification and measurement of financial instruments. Although the ASU retains manycurrent requirements, it significantly revises an entity’s accounting related to (1) the classification and measurement of investments in equity securities and(2) the presentation of certain fair value changes for financial liabilities measured at fair value. The ASU also amends certain disclosure requirementsassociated with the fair value of financial instruments. The new standard is effective for fiscal years and interim periods within those fiscal years beginningafter December 15, 2017, with early adoption permitted for certain changes. The Company is currently evaluating the potential effects the new standard willhave of the Company’s financial statements and related disclosures. In February 2016, the FASB issued a new Accounting Standards Update, Leases (ASU 2016-02), ASU 2016-02 is aimed at making leasing activities moretransparent and comparable and requires most leases be recognized by lessees on the balance sheets as a right-of-use asset and corresponding lease liability,regardless of whether they are classified as finance or operating leases. The new standard is effective for annual reporting periods beginning afterDecember 15, 2018, including interim periods within that reporting period, with early adoption permitted. The Company is currently evaluating the impactof the new pronouncement on the Company’s financial statements and related disclosures. 3. Net Loss per Common Share The Company accounts for and discloses net loss per share using the treasury stock method. Net loss per common share, or basic loss per share, is computedby dividing net loss by the weighted-average number of common shares outstanding. Since the Company is in a net loss for all periods presented, diluted netloss per share is not presented since the common stock equivalents would have an anti-dilutive effect on the per share calculation. The following table sets forth the computation of basic and diluted net loss per share for the periods indicated: Year Ended December 31,20152014 2013Basic and Diluted loss per common share calculation:Net loss attributable to common shareholders — basic and diluted$(37,243,861)$(28,829,975)$(24,196,511)Basic and diluted weighted-average common shares17,289,02112,936,74110,317,351Basic and diluted net loss per share$(2.15)$(2.23)$(2.35) The difference between basic and diluted weighted-average common shares generally results from the assumption that dilutive stock options outstandingwere exercised, dilutive restricted stock has vested and outstanding warrants are issued. For the years ended 2015, 2014, and 2013, the Company reported aloss from operations and therefore, all potentially dilutive stock options, restricted stock, and outstanding warrants as of such date were excluded from thecomputation of diluted net loss per share as their effect would have been anti-dilutive. The total shares of stock options, restricted stock, and outstandingwarrants that could potentially dilute earnings per share in the future, but which were not included in the calculation of diluted net loss per share becausetheir effect would have been anti-dilutive were as follows: Year Ended December 312015 2014 2013Unvested restricted stock553,045283,446229,250Options outstanding2,121,7261,643,5321,228,486Warrants99,52999,52999,529Total2,774,3002,026,5071,557,265 F-11Table of Contents 4. Marketable Investments The following table summarizes the Company’s cash equivalents and available for sale securities: December 31, 2015 Gross Gross EstimatedAmortizedUnrealized Unrealized FairCostGains Losses ValueCash equivalents:Money market funds$7,914,115$—$—$7,914,115 Short-term investments:Fixed-income treasury portfolio:Fannie Mae2,005,785—(2,942)2,002,843Federal farm credit bank1,076,445—(1,856)1,074,589Federal home loan bank12,445,53061(9,764)12,435,827Freddie Mac1,005,272—(2,660)1,002,612 Certificate of Deposits16,150,513295(3,434)16,147,374 Total Short-term investments32,683,545356(20,656)32,663,245Long-term investments:Fixed-income treasury portfolio:Fannie Mae4,366,424—(15,213)4,351,211Federal farm credit bank6,290,607—(27,957)6,262,650Federal home loan bank14,113,301—(44,803)14,068,498Freddie Mac12,576,749—(41,382)12,535,367 Certificate of Deposits14,214,941703(4,738)14,210,906 Total Long-term investments51,562,022703(134,093)51,428,632 Total$92,159,682$1,059$(154,749)$92,005,992 December 31, 2014 Gross Gross EstimatedAmortizedUnrealized Unrealized FairCostGains Losses ValueCash equivalents:Money market funds$23,012,140$—$—$23,012,140 Short-term investments:Fixed-income treasury portfolio:Fannie Mae4,863,3712,338—4,865,709Federal farm credit bank11,432,3403,575(73)11,435,842Federal home loan bank6,859,2942,381(567)6,861,108Freddie Mac5,811,4052,133(50)5,813,488Total Short-term investments28,966,41010,427(690)28,976,147Long-term investments:Fixed-income treasury portfolio:Federal farm credit bank1,000,455—(1,126)999,329Federal home loan bank2,250,965—(3,426)2,247,539Freddie Mac1,400,136—(2,184)1,397,952Total Long-term investments4,651,556—(6,736)4,644,820 Total$56,630,106$10,427$(7,426)$56,633,107 F-12Table of Contents At December 31, 2015 and December 31, 2014, the remaining contractual maturities of available-for-sale investments classified as current on the balancesheet were less than 12 months, and remaining contractual maturities of available-for-sale investments classified as long-term were less than two years. There were no available-for-sale securities in a continuous unrealized loss position for greater than twelve months at December 31, 2015 and December 31,2014. The Company has the ability to hold such securities with an unrealized loss until its forecasted recovery. The Company determined that there was nomaterial change in the credit risk of the above investments. As a result, the Company determined it did not hold any investments with an other-than-temporary impairment as of December 31, 2015. 5. Prepaid Expenses and Other Current Assets Prepaid expenses and other current assets consist of the following at December 31, 2015 and 2014: December 31, December 31,2015 2014Prepaid third party vendor costs$195,305$654,643Deposits106,243106,243Prepaid insurance51,62346,748Other Receivable298,718829,174Total$651,889$1,636,808 6. Furniture and Fixtures Furniture and fixtures consist of the following at December 31, 2015 and 2014: December 31, December 31,2015 2014Office furniture and fixtures$479,458$460,000Less accumulated depreciation(383,797)(230,000)Furniture and fixtures, net$95,661$230,000 Depreciation expense was $153,797, $153,333, and $76,667 for the years ended December 31, 2015, 2014, and 2013, respectively. 7. Fair Value Measurements Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or mostadvantageous market for the asset or liability in an orderly transaction between market participants at the measurement date. Assets and liabilities that aremeasured at fair value are reported using a three-level fair value hierarchy that prioritizes the inputs used to measure fair value. This hierarchy maximizes theuse of observable inputs and minimizes the use of unobservable inputs. The three levels of inputs used to measure fair value are as follows: Level 1 — Quoted prices in active markets for identical assets or liabilities that the Company has the ability to access at the measurement date. Level 2 — Inputs other than quoted prices in active markets that are observable for the asset or liability, either directly or indirectly. Level 3 — Inputs that are unobservable for the asset or liability. The following fair value hierarchy table presents information about each major category of the Company’s financial assets and liability measured at fair valueon a recurring basis as of December 31, 2015 and 2014: December 31, 2015 Quoted Prices in Active Significant Markets for Other Significant Balance Identical Observable Unobservable at Assets Inputs Inputs December 31, (Level 1) (Level 2) (Level 3) 2015Assets:Cash and cash equivalents$13,376,196$—$—$13,376,196Short-term investments16,515,87116,147,374—32,663,245Long-term investments37,217,72714,210,905—51,428,632Total assets at fair value$67,109,794$30,358,279$—$97,468,073 F-13Table of Contents December 31, 2014 Quoted Prices in Active Significant Markets for Other Significant Balance Identical Observable Unobservable at Assets Inputs Inputs December 31, (Level 1) (Level 2) (Level 3) 2014Assets:Cash and cash equivalents$25,007,217$—$—$25,007,217Short-term investments28,976,14728,976,147Long-term investments4,644,820——4,644,820Total assets at fair value$58,628,184$—$—$58,628,184 There were no transfers between levels in the fair value hierarchy during any of the periods presented herein. Level 3 Disclosures The changes in fair value of the Company’s Level 3 put option liability during the years ended December 31, 2015, 2014, and 2013 were as follows: Level 3 Balance at December 31, 2012$30,415Fair value adjustment to put option liability included in other income(30,415)Balance as of December 31, 2013—Fair value adjustment to put option liability included in other income—Balance as of December 31, 2014$—Fair value adjustment to put option liability included in other income—Balance as of December 31, 2015$— For the year ended December 31, 2013, the changes in the fair value of the put option liability resulted from the expiration of the put option in conjunctionwith the conversion of half of the principal of the 2.45% convertible note, along with accrued interest, into common stock as a result of the IPO. The balanceof the note was converted into common stock in April 2013. No other changes in valuation techniques or inputs occurred during the year endedDecember 31, 2013. The fair value of the put option liability was determined utilizing a probability weighted discounted financial model based on management’s assessment ofthe likelihood of achievement of certain outcomes based on significant inputs not observable in the market, which causes it to be classified as a Level 3measurement within the fair value hierarchy. The valuation of the put option liability uses assumptions and estimates the Company believes would be madeby a market participant in making the same valuation. 8. Accounts Payable and Accrued Expenses Accounts payable and accrued expenses consist of the following: December 31,2015 2014Accrued research and development costs$5,303,990$1,762,997Accrued compensation2,727,9651,696,728Short-term portion of deferred revenue822,604485,714Accrued legal245,329164,389Other accrued liabilities355,589364,014Total accounts payable and accrued expenses$9,455,477$4,473,842 F-14Table of Contents 9. Capital Structure Initial Public Offering On January 31, 2013, the Company completed its initial public offering (the “IPO”), selling 3,317,644 shares at an offering price of $10.00 per share. OnJanuary 29, 2013, the underwriters exercised in full their over-allotment option to purchase an additional 497,647 shares at an offering price of $10.00 pershare. Aggregate gross proceeds from the IPO, including the exercise of the over-allotment option, were $38.2 million and net proceeds received afterunderwriting fees and offering expenses were approximately $32.3 million. Additionally, upon the closing of the IPO, certain transactions were triggeredbased on a successful completion of an IPO. Convertible debt of $1.4 million principal, plus accrued interest thereon, was converted into 166,769 shares ofcommon stock. The Company recorded approximately $1.5 million of compensation expense related to certain bonuses and salary increases payable uponcontinued employment and the occurrence of a specified financing, including the consummation of an initial public offering. Finally, the Company recordedone-time compensation expense of approximately $1.4 million for certain options and restricted stock that fully vested upon the closing of the IPO. Representative’s Warrants On October 1, 2012, the Company agreed to issue to the representative of the underwriters in the IPO warrants to purchase up to 99,529 shares of theCompany’s common stock in the event of a successful public offering. The warrants are exercisable for cash or on a cashless basis at a price per share equal to$15.00. The term of the warrants is four years and they expire on January 28, 2018. Based on a successful public offering in January of 2013, these warrantswere issued and accounted for as a cost of issuance. The Company has determined, based upon a Black-Scholes model, that the fair value of the warrants onthe date of IPO was $413,146. The Company has accounted for the fair value of the warrants as a cost of issuance of common stock from the IPO resulting in acharge directly to stockholder’s equity. Common Stock At the 2013 annual meeting of stockholders held on June 19, 2013, the stockholders voted in favor of an amendment to the Company’s Restated Certificateof Incorporation to increase the Company’s authorized share capital by 11,250,000 shares of common stock. As of December 31, 2015, the Company wasauthorized to issue 33,750,000 shares of common stock. Dividends on common stock will be paid when, and if, declared by the board of directors. Each holder of common stock is entitled to vote on all matters andis entitled to one vote for each share held. The Company will, at all times, reserve and keep available, out of its authorized but unissued shares of commonstock, sufficient shares to effect the conversion of the shares of the stock options. Secondary Public Offerings On May 16, 2013, the Company completed a follow-on public offering (the “Secondary Offering”), selling 4,137,931 shares at an offering price of $14.50 pershare. On May 22, 2013, the underwriters exercised in full their over-allotment option to purchase an additional 620,689 shares at an offering price of $14.50per share. Aggregate gross proceeds from the Secondary Offering, including the exercise of the over-allotment option, were $69.0 million, and net proceedsreceived after underwriting fees and offering expenses were approximately $64.5 million. In addition, on January 8, 2015, the Company completed another follow-on public offering (the “Additional Offering”), selling 3,800,000 shares at anoffering price of $15.75 per share. On February 10, 2015, the underwriters exercised in full their over-allotment option to purchase an additional 553,877shares at an offering price of $15.75 per share. Aggregate gross proceeds from the Additional Offering, including the exercise of the over-allotment option,were $68.6 million, and net proceeds received after underwriting fees and offering expenses were approximately $64.1 million. The Company may seek additional capital through a combination of private and public equity offerings, debt financings and collaborations and strategic andlicensing arrangements. 10. Grant Revenue In October 2013, the Company entered into an award contract (“the Agreement”) with The Leukemia and Lymphoma Society (LLS). LLS is a nationalvoluntary health agency which, among other activities encourages and sponsors research relating to Leukemia, lymphoma, Hodgkin’s disease and myelomato develop therapies to cure or mitigate these Disease’s. To further its mission, LLS provides research funding to entities that can demonstrate after LLS’sreview process that their proposed research projects have scientific promise to advance LLS’s effort to find treatments and cures for the above Diseases andtheir complications. Pursuant to the F-15Table of Contents Agreement LLS agreed to provide funding to the Company not to exceed $3.5 million to fund the Company’s development program related to theCompany’s pre-clinical and clinical product development activities. Through December 31, 2015, the Company has received $2.5 million based onmilestones achieved. The Company could receive the additional $1.0 million based on the completion of certain milestone events. The Company hasrecognized approximately $0.7, $0.3 million, and $0.1 million of revenue related to the Leukemia and Lymphoma Society grant for the years endedDecember 31, 2015, 2014, and 2013, which reflects twelve months, twelve months, and three months of revenue recognized, respectively, on a straight linebasis, based on the Company’s best estimates of work performed and qualifying costs incurred. The agreement terminates when there are no longer anypayment obligations. 11. Stock-Based Compensation The Company’s 2012 Stock Equity Incentive Plan (the “2012 Plan”), which was adopted by the board of directors and approved by the stockholders inJuly 2012, became effective immediately prior to the closing of the Company’s initial public offering. In addition, the Company’s 2004 Stock Option andGrant Plan (the “2004 Plan”) was terminated effective immediately prior to the closing of the Company’s initial public offering. The 1,819,839 options topurchase common stock and 34,506 restricted stock awards executed prior to the effective date of such termination remain in full force and effect pursuant totheir terms and the terms of the 2004 Plan. The 2012 Plan initially authorized the Company to grant up to 1,663,727 shares of common stock to eligibleemployees, directors, and non-employee consultants and advisors to the Company in the form of options to purchase common stock of the Company at aprice not less than the estimated fair value at the date of grant. Under the provisions of the 2012 Plan, no option will have a term in excess of 10 years. As of December 31, 2015, there were 527,353 shares of common stock available for future grants under the 2012 Plan. Total compensation cost that has been charged against operations related to the above plans was approximately $5.2 million, $4.4 million, and $4.8 millionfor the years ended December 31, 2015, 2014, and 2013, respectively. The exercise of stock options and the vesting of restricted stock during the year endedDecember 31, 2015 generated an income tax deduction of approximately $2.9 million. The Company does not recognize a tax benefit with respect to anexcess stock compensation deduction until the deduction actually reduces the Company’s income tax liability. At such time, the Company utilizes the netoperating losses generated by excess stock-based compensation to reduce its income tax payable and the tax benefit is recorded as an increase in additionalpaid-in-capital. No income tax benefit was recognized in the statements of operations for share-based compensation arrangements for the years endedDecember 31, 2015, 2014, and 2013. The following table summarizes stock-based compensation related to the above plans by expense category for the years ended December 31, 2015, 2014, and2013: Year Ended December 31,20152014 2013Research and development$2,703,861$2,907,820$3,301,996General and administrative2,459,1011,528,8691,545,090Total$5,162,962$4,436,689$4,847,086 During the fourth quarter of 2015, the Company agreed to separation agreements with two former employees. Under the terms of these agreements, theCompany agreed to modify the vesting of these employees’ equity awards over a specified period in which the former employees will continue to serve asconsultants. As a result of the modification to these equity awards, the Company recorded a reduction to stock based compensation expense of $0.6 millionduring the fourth quarter of 2015. Stock Options The Company grants stock options to employees, directors and non-employee consultants, with exercise prices equal to the closing price of the underlyingshares of the Company’s common stock on the date that the options are granted. Options granted have a term of 10 years from the grant date. Options grantedto employees generally vest over a four-year period and options granted to directors vest in equal yearly installments over a three-year period from the date ofgrant. Options to directors are granted on an annual basis and represent compensation for services performed on the Board of Directors. Compensation cost forstock options granted to employees and directors is charged against operations using the straight-line attribution method between the grant date for theoption and each vesting date. The Company estimates the fair value of stock options on the grant date by applying the Black-Scholes option pricingvaluation model. The application of this valuation model involves assumptions that are highly subjective, judgmental and sensitive in the determination ofcompensation cost. The weighted-average key assumptions used in determining the fair value of options granted for the years ended December 31, 2015, 2014 and 2013, are asfollows: Year Ended December 31, 2015 2014 2013 Risk-free interest rate1.86%1.97%2.10%Expected volatility77.92%88.86%78.23%Dividend yield———Expected life6.15 years6.20 years6.26 years F-16Table of Contents Due to the lack of trading history, the Company’s computation of stock-price volatility is based on the volatility rates of comparable publicly heldcompanies over a period equal to the estimated useful life of the options granted by the Company. The Company’s computation of expected life wasdetermined using the “simplified” method which is the midpoint between the vesting date and the end of the contractual term. The Company believes that itdoes not have sufficient reliable exercise data in order to justify the use of a method other than the “simplified” method of estimating the expected exerciseterm of employee stock option grants. The Company has paid no dividends to stockholders. The risk-free interest rate is based on the zero-coupon U.S.Treasury yield at the date of grant for a term equivalent to the expected term of the option. For the years ended December 31, 2015, 2014, and 2013 the Company issued 198,938, 33,040, and 550,801 shares of the Company’s common stock,respectively, upon the exercise of outstanding stock options and received proceeds of approximately $725,017, $135,274 and $1.3 million, respectively. Forthe years ended December 31, 2015, 2014, and 2013 the Company realized no tax benefit from the exercise of stock options. As of December 31, 2015, therewas approximately $6.6 million of unrecognized compensation cost, adjusted for estimated forfeitures, related to unamortized stock option compensationwhich is expected to be recognized over a remaining weighted-average period of approximately 2.52 years. Total unrecognized compensation cost will beadjusted for future changes in estimated forfeitures. The Company’s stock options outstanding at December 31, 2015, 2014 and 2013 and changes during the years ended December 31, 2015, 2014 and 2013 arepresented below: Options Weighted-AverageExercise Price Weighted-AverageRemainingContractual Life AggregateIntrinsicValue Outstanding at December 31, 20121,819,839$2.76Options granted159,50019.08Options exercised(550,801)2.37Options forfeited(102,052)2.71Outstanding at December 31, 20131,326,486$4.89Options granted378,83121.07Options exercised(33,040)4.09Options forfeited(28,745)4.86Outstanding at December 31, 20141,643,532$8.64Options granted702,09413.74Options exercised(198,938)3.64Options forfeited(24,962)13.22Outstanding at December 31, 20152,121,726$10.746.73$5,713,945Options exercisable at December 31, 20151,055,992$6.135.40$5,286,524 The aggregate intrinsic value in the previous table reflects the total pretax intrinsic value (the difference between the Company’s closing stock price on thelast trading day of the period and the exercise price of the options, multiplied by the number of in-the-money stock options) that would have been receivedby the option holders had all option holders exercised their options on December 31, 2015. The intrinsic value of the Company’s stock options changesbased on the closing price of the Company’s common stock. The total intrinsic value of options exercised (the difference in the market price of theCompany’s common stock on the exercise date and the price paid by the optionee to exercise the option) was approximately $1.4 million, $0.4 million, and$14.8 million for the years ended December 31, 2015, 2014, and 2013, respectively. Restricted Stock The Company grants restricted stock to its employees, directors, and non-employee consultants. Restricted stock is recorded as deferred compensation andcharged against income on a straight-line basis over the vesting period, which ranges from one to four years in duration. Restricted stock to directors isgranted on a yearly basis and represents compensation for services performed on the Company’s Board of Directors. Restricted stock awards to directors vestin equal installments over a three-year period from the grant date. Compensation cost for restricted stock is based on the award’s grant date fair value, whichis the closing market price of the Company’s common stock on the grant date, multiplied by the number of shares awarded. The Company’s non-vested restricted stock at December 31, 2015, 2014, and 2013, and changes during the years ended December 31, 2015, 2014 and 2013are presented below: F-17Table of Contents Number of Shares Weighted-Average GrantDate Fair ValuePer ShareOutstanding at December 31, 201234,506$5.97Shares granted304,52818.18Shares vested(65,802)11.53Shares forfeited(43,982)23.35Outstanding at December 31, 2013229,25017.34Shares granted138,66321.90Shares vested(83,690)17.99Shares forfeited(777)25.05Outstanding at December 31, 2014283,446$19.36Shares granted399,74211.66Shares vested(116,167)18.50Shares forfeited(13,976)22.00Outstanding at December 31, 2015553,045$13.91 For the year ended December 31, 2015, the Company granted 399,742 shares of restricted stock, at a weighted-average grant date fair value of $11.66 pershare amounting to approximately $4.7 million in total aggregate fair value. At December 31, 2015, approximately 553,045 shares remained unvested andthere was approximately $4.6 million of unrecognized compensation cost related to restricted stock which is expected to be recognized over a remainingweighted-average period of approximately 2.72 years. The total fair value of restricted stock vested during the year ended December 31, 2015 wasapproximately $2.1 million. Performance Share Awards Subsequent to the closing of the IPO, certain options and restricted stock began to vest to directors, consultants and key employees. The Company recordedapproximately $1.4 million of stock-based compensation expense associated with 573,424 options with a weighted average exercise price of $2.38 and 8,625shares of restricted stock that fully vested upon consummation of an IPO. In addition, 281,895 options commenced vesting based upon the consummation ofthe IPO and the Company will record $1.8 million on the vesting of these options over their expected lives. For awards with performance conditions, such as capital raises, an IPO, a change in control or a sale of the company, no expense is recognized, and nomeasurement date can occur, until the occurrence of the event is probable. Awards Granted to Non-Employees The Company grants stock options, restricted stock, and unrestricted stock to non-employee consultants. The Company periodically re-measures the fairvalue of stock-based awards issued to non-employees and records expense over the requisite service period. Total compensation cost that has been chargedagainst operations related to stock based awards granted to non-employee consultants was approximately $0.3 million, $0.1 million, and $0.8 million for theyears ended December 31, 2015, 2014, and 2013, respectively. Employee Stock Purchase Plan In September 2015, the Company adopted its 2015 Employee Stock Purchase Plan (the “2015 ESPP”). The 2015 ESPP is qualified as an employee stockpurchase plan under Section 423 of the Internal Revenue Code of 1986, as amended (the “IRC”). Under the 2015 ESPP, the Company will grant rights topurchase shares of common stock under the 2015 ESPP (“Rights”) at prices not less than 85% of the lesser of (i) the fair value of the shares on the date ofgrant of such Rights or (ii) the fair value of the shares on the date such Rights are exercised. Therefore, the 2015 ESPP is considered compensatory underFASB ASC 718 since, along with other factors, it includes a purchase discount of greater than 5%. For the twelve months ended December 31, 2015, theCompany recorded approximately $55,515 of compensation expense, related to participation in the 2015 ESPP. 12. Income Taxes The benefit for income taxes consists of the following for the years ended December 31: 20152014 2013Deferred:Federal$(17,654,150)$(14,047,679)$(8,861,971)State and local(3,735,379)(2,520,711)(2,813,740)(21,389,529)(16,568,390)(11,675,711)Increase in valuation allowance21,389,52916,568,39011,675,711Total tax expense$—$—$— F-18Table of Contents A reconciliation of the statutory U.S. federal rate to the Company’s effective tax rate is as follows: Year Ended December 31, 2015 2014 2013 Percent of pre-tax income:U.S. federal statutory income tax rate(34.0)%(34.0)%(34.0)%State taxes, net of federal benefit(10.0)(8.8)(11.6)Permanent items(13.4)(14.7)(2.6)Change in valuation allowance57.457.548.2Effective income tax rate—%—%—% The tax effects of temporary differences that gave rise to significant portions of the deferred tax assets were as follows: December 31,2015 2014Current deferred tax assets:Accrued expenses$1,931,498$1,450,412Valuation allowance(1,931,498)(1,450,412)Total current deferred tax assets$—$— Noncurrent deferred tax assets:Net operating loss carryforwards$19,904,809$18,342,986Research and Development32,815,48813,986,047Nonqualified stock compensation3,772,7203,255,54156,493,01735,584,574Valuation allowance(56,493,017)(35,584,574)Total noncurrent deferred tax assets$—$— In assessing the realizability of deferred tax assets, the Company considers whether it is more likely than not that some portion or all of the deferred tax assetswill not be realized. The ultimate realization of deferred tax assets is dependent upon the generation of future taxable income during the periods in which thetemporary differences representing net future deductible amounts become deductible. Due to the Company’s history of losses, the deferred tax assets are fullyoffset by a valuation allowance at December 31, 2015, 2014 and 2013. The following table summarizes carryforwards of net operating losses and tax credits as of December 31, 2015: Amount ExpirationFederal net operating losses$58,554,286(A)2023-2035State net operating losses$58,612,492(A)2023-2035Research and development credits$14,936,7682023-2035 (A) Of which $15,039,184 will be a benefit to additional paid in capital upon realization as they relate to excess benefits from stock option exercises. The Internal Revenue Code of 1986, as amended (the “Code”) provides for a limitation of the annual use of net operating losses and other tax attributes (suchas research and development tax credit carryforwards) following certain ownership changes (as defined by the Code) that could limit the Company’s abilityto utilize these carryforwards. At this time, the Company has not completed a study to assess whether an ownership change under section 382 of the Code hasoccurred, or whether there have been multiple ownership changes since the Company’s formation, due to the costs and complexities associated with such astudy. The Company may have experienced various ownership changes, as defined by the Code, as a result of past financing transactions. Accordingly, theCompany’s ability to utilize the aforementioned carryforwards may be limited. Additionally, U.S. tax laws limit the time during which these carryforwardsmay be applied against future taxes. Therefore, the Company may not be able to take full advantage of these carryforwards for federal or state income taxpurposes. F-19Table of Contents The Company did not have unrecognized tax benefits as of December 31, 2015 and does not expect this to change significantly over the next twelve months.As of December 31, 2015, the Company has not accrued interest or penalties related to uncertain tax positions. The Company’s tax returns for the years endedDecember 31, 2008 through December 31, 2015 are still subject to examination by major tax jurisdictions. The Company will recognize interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 2015, 2014 and 2013, theCompany had no accrued interest or penalties related to uncertain tax positions and no amounts have been recognized in the Company’s consolidatedstatements of operations and comprehensive loss. For all years through December 31, 2015, the Company generated research credits but has not conducted a study to document the qualified activities. Thisstudy may result in an adjustment to the Company’s research and development credit carryforwards; however, until a study is completed and any adjustmentis known, no amounts are being presented as an uncertain tax position for these two years. A full valuation allowance has been provided against theCompany’s research and development credits and, if an adjustment is required, this adjustment would be offset by an adjustment to the deferred tax assetestablished for the research and development credit carryforwards and the valuation allowance. 13. Commitments and Contingencies License Agreements The Company has entered into research and development agreements with third-parties for the development of oncology products. These agreements requirethe Company to fund the development of such products and potentially make milestone payments and royalties on net sales in the future based on theCompany’s successful development of the products. The timing and the amount of milestone payments in the future are not certain. Under the Company’s license agreements, the Company could be required to pay up to a total of $112.9 million upon achieving certain milestones, such asthe initiation of clinical trials or the granting of patents. From inception through December 31, 2015, the Company has paid or accrued $3.7 million inpayments resulting from the execution of certain agreements, patent approvals, the initiation of sponsor research agreements, and compound developmentagreements. Milestone payments will also be due upon the issuance of certain patents, the initiation of certain clinical trials, the submission of regulatoryapplications and certain regulatory approvals, in addition to sales milestones and single digit royalties payable on commercial sales if any occur. Scott and White Memorial Hospital In June 2006, the Company entered into a research and license agreement, as amended in December 2008, March 2010 and July 2011 (collectively the “S&WAgreement”), with Scott and White Memorial Hospital and Scott, Sherwood and Brindley Foundation, and its affiliate Scott and White Clinic (collectively“S&W”) for the rights to SL-401 and SL-501. SL-401 is a clinical stage targeted therapy directed to the interleukin-3 receptor, or IL-3R, and is beingdeveloped to treat patients with hematologic cancers. SL-501 is a next generation IL-3R-targeted therapy and is in preclinical development. The Company isrequired to pay single-digit royalties on sales of these products, if any, and a percentage of upfront payments the Company may receive from a sublicensee.The S&W Agreement will expire in its entirety upon the later of (i) the 10th anniversary of the first commercial sale of a product, or (ii) the expiration of thelast issued patent claiming or covering a product. The Company may terminate the S&W Agreement at its sole discretion at any time after a specified numberof days following written notice and either party may terminate for a material breach of the agreement that is not cured within a specified number of days. University of Pittsburgh In September 2009, the Company entered into an exclusive license agreement with the University of Pittsburgh (“UP”) that covers patent rights claimingcomposition of a shortened variant of the IL-13Rα2 peptide (the “UP Agreement”) utilized by Stemline in its SL-701 composition. The Company paid UP anupfront license fee that was expensed to research and development cost for the year ended December 31, 2009. In addition to the upfront payment, theCompany is required to pay annual fees, milestone payments (which are contingent upon achievement of pre-defined clinical, regulatory and commercialevents), and, upon regulatory approval, single-digit royalty payments on net sales, and a percentage of non-royalty revenue from sublicensees, whichdecreases if the applicable sublicense agreement is entered into after a certain clinical milestone has been met. The UP Agreement will expire in its entiretyupon the expiration of the last issued patent claiming or covering the product. The Company may terminate the UP Agreement at its sole discretion at anytime after a specified number of days following written notice and UP may terminate for a material breach of the agreement by the Company that is not curedwithin a specified number of days. F-20Table of Contents In March 2012, the Company entered into a non-exclusive license agreement with UP that covers patent rights claiming use of a shortened peptide of EphA2,which the Company may use for the diagnosis, treatment or prevention of diseases and tumors of the brain and which the Company is currently utilizing in itsSL-701 composition. The Company paid UP an initial license fee and is required to pay UP annual license maintenance fees until the first commercial sale ofa licensed product, a single-digit royalty on sales, and a minimum annual royalty following the first commercial sale of a licensed product. The UPAgreement will expire in its entirety upon the expiration of the last issued patent claiming or covering the product. The Company may terminate the UPAgreement at its sole discretion at any time after a specified number of days following written notice and UP may terminate for a material breach of theagreement by the Company that is not cured within a specified number of days. In March 2012, the Company entered into a non-exclusive license agreement with UP for the right to use certain information and data contained in theapplications for investigational new drugs, or INDs, relating to clinical trials with an earlier version of SL-701 that were conducted by UP. The Company mayuse the information and data for the development, manufacture, regulatory approval and commercialization of pharmaceutical products. The Company paidUP an initial license fee and will be required to make a payment following a specified regulatory milestone, and a percentage of non-royalty revenue it mayreceive from any sublicensees. The UP Agreement will expire in its entirety in March 2032 unless earlier terminated by a party. The Company may terminatethe UP Agreement at its sole discretion at any time prior to incorporating or referencing the data or UP INDs, after a specified number of days followingwritten notice, and UP may terminate for a material breach of the agreement by the Company that is not cured within a specified number of days or if the IL-13Rα2 license agreement is terminated. CanBas, Ltd On December 26, 2014, the Company entered into a license agreement with CanBas, Ltd. (“CanBas”) for SL-801. SL-801 is a small molecule inhibitor ofXPO1. Under the terms of the agreement, CanBas has granted the Company an exclusive, royalty-bearing, worldwide (excluding Japan, Korea, China andTaiwan) license, under certain patent rights, know-how and materials to research, develop, make, have made, formulate, use, sell, offer to sell and import SL-801, and any products containing or comprising such compound in finished dosage pharmaceutical form. The patent rights exclusively licensed to theCompany under the agreement, which include issued patents in the U.S. and abroad, cover both composition of matter and use of SL-801. The Company hasadditional pending patent applications directed to SL-801 which would provide additional protection, should they issue, in certain non-U.S. territories. The Company is responsible to pay annual technical advisory fees over the next three years totaling 330 million Japanese Yen (JPY), if the clinicaldevelopment continues over this time period. Additionally, the Company must pay CanBas tiered royalties based on aggregate net sales, by the Company orits sublicensees, of products containing the licensed compound until the latest date of a period of ten years following the first commercial sale of eachproduct in each country; the date upon which there are no more valid claims or the expiration or termination of the last regulatory exclusivity period. Theroyalty rates start in the low single digits and are tiered up based on annual net sales. In the future, the Company may also be responsible, based on theachievement of specific clinical-development, regulatory and sales-based commercial milestones, for certain payments to CanBas of up to $86 million. TheCompany has sublicensing rights under this agreement, in which the Company would pay CanBas a standard percentage of the payments received by theCompany from a sublicensee. The Company must exercise commercially reasonable efforts to develop and commercialize a licensed product and to achieve certain regulatory milestoneswithin certain periods, subject to extensions based on unforeseen technical, scientific, intellectual property or regulatory issues. The agreement survives until the later of ten years following the first commercial sale of each product in each country; the date upon which there are no morevalid claims; or the expiration or termination of the last regulatory exclusivity period, after which the Company’s license becomes fully paid, irrevocable,perpetual, non-exclusive and royalty-free. The Company may terminate the license for any or no reason upon 60 days advance written notice to CanBas. Ifeither party breaches a material obligation under the agreement and such obligation is not cured within a specified period of time following written noticefrom the other party, then the non-breaching party may terminate the agreement upon an additional written notice. Other The Company has also licensed rights to certain technologies or intellectual property in the field of oncology. The Company is generally required to makeupfront payments as well as other payments upon successful completion of preclinical, clinical, regulatory or sales milestones. In addition, these agreementsgenerally require the Company to pay royalties on sales of the products arising from these agreements. These agreements generally permit the Company toterminate the agreement with no significant continuing obligation. F-21Table of Contents As part of the agreements discussed above, the Company has committed to make potential future milestone payments to third-parties as part of its licensingagreements. Payments generally become due and payable only upon the achievement of certain developmental, regulatory and/or commercial milestones.Because the achievement of these milestones is neither probable nor reasonably estimable, the Company has not recorded a liability on its balance sheet forany such contingencies. Contractual Agreements In February 2013, the Company entered into a bioprocessing services agreement with a vendor for approximately $2.9 million if all services are performedunder the contract. As of December 31, 2014, the contract services were performed on the initial work order and had been paid by the Company. During 2014and 2015, the Company entered into new work order agreements with this vendor totaling approximately $4.5 million, with services to be rendered on theseagreements through 2016. The Company has received and paid for services relating to these agreements in the amount of $3.8 million. The Company has agreements in place with CROs in connection with its clinical programs. The Company’s total expenditures in the future would beapproximately $22.3 million assuming the successful advancement of its programs. Lease Agreement In July 2013, the Company entered into a leasing agreement with respect to its corporate offices at 750 Lexington Avenue, New York, New York, for amonthly rent of $50,625. The term of this lease agreement is 36 months. The Company’s future annual minimum lease payments for each of the following calendar years are as follows: 2016$303,750$303,750 Rent expense charged to operations was approximately $0.6 million for the years ended December 31, 2015 and 2014, respectively. Rent expense is includedin general and administrative expenses in the Company’s Statement of Operations. 14. Related Party Items Receivable from Related Party In November 2013, the Company recorded a $0.2 million receivable from an executive of the Company related to New York State tax withholdings resultingfrom an exercise of stock options. This item is reflected on the Company’s December 31, 2013 balance sheet as a related party receivable. On June 15, 2012, the Company entered into an assignment agreement with Dr. Bergstein, the Company’s Chairman, President and Chief Executive Officerand owner of certain proprietary patent rights and related technology. Pursuant to the assignment agreement, as amended on November 7, 2012, effectiveimmediately prior to the registration statement for the Company’s initial public offering being declared effective by the Securities and ExchangeCommission, Dr. Bergstein agrees to assign, sell, transfer and convey to the Company all of his right, title and interest in and to these patent rights and relatedtechnology in exchange for $2.0 million in cash or a combination of cash and shares of Company common stock, payable only if, within five years of thedate of transfer, the Company either (i) has a change in control, as defined in the assignment agreement, or (ii) achieves a market capitalization of at least$200 million for a prescribed period. Under the terms of the assignment agreement, as amended, 50% of such payment shall be paid in cash and the remaining50% may be paid in shares of Company common stock, or a combination of cash and common stock, as determined by the Company. If the Company electsto settle payment in shares, the Company will value the shares at the date of issuance. None of the assigned patent rights and related technology hasalternative future uses, nor have they reached a stage of technological feasibility. The Company accounted for this transaction as an asset acquisition as itachieved a market capitalization of $200 million for the prescribed period because it did not acquire any processes or activities in addition to the assignedrights and technology. The Company has recorded the entire purchase price to acquire in-process research and development expense for the year endedDecember 31, 2013. The assignment agreement does not contain any vesting or rescission/refund provisions. F-22Table of Contents 15. Other Income The components of other income for the years ended December 31, 2015, 2014 and 2013 are as follows: Other Income:20152014 2013 Mark-to-market valuation adjustment to Put Option$—$—$30,415New York City Biotechnology R&D tax credit——249,477Other1,6093,607795Total other income$1,609$3,607$280,687 Other income includes funds from the City of New York for the 2013 Biotechnology Tax Credit program. The income from these programs is a reimbursementof expenses directly related to specific qualifying research programs in accordance with the guidelines of the respective tax credit programs and there are noperformance or refund obligations. These expenses were incurred in prior periods and therefore the income was recorded when the funds were received. Otherincome also includes the mark-to-market of the put option liability associated with the issuance of convertible notes. See Note 7 for further discussion of thePut Option. 16. Subsequent Events During February 2016, the Company entered into a new leasing agreement with respect to its corporate offices at 750 Lexington Avenue, New York, NewYork, for a monthly rent of $69,750. The term of this lease agreement is 42 months and expected to commence on July 1, 2016 and expire on December 31,2019. The aggregate minimum lease commitment over the 42 month term of the lease is approximately $2.7 million. The Company has provided thelandlord with a security deposit equal to three months’ rent, totaling $209,250. 17. Selected Quarterly Financial Data (Unaudited) Quarters EndedMarch31June30 September30 December 312015Net loss attributable to common stockholders$(7,677,463)$(10,153,716)$(9,233,076)$(10,179,606)Basic and diluted net loss per common share$(0.46)$(0.58)$(0.53)$(0.58)2014Net loss attributable to common stockholders$(8,999,926)$(6,012,698)$(6,885,157)$(6,932,194)Basic and diluted net loss per common share$(0.70)$(0.47)$(0.53)$(0.53) F-23Table of Contents Index to Exhibits Exhibit No. Description21.1List of subsidiaries of Stemline Therapeutics, Inc. 23.1Consent of Ernst & Young LLP, independent registered public accounting firm. 24.1Power of Attorney (included on signature page). 31.1Certificate of principal executive officer pursuant to Rule 13a-14(a)/15d-14(a), as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. 31.2Certificate of principal financial officer pursuant to Rule 13a-14(a)/15d-14(a), as adopted pursuant to Section 302 of the Sarbanes-OxleyAct of 2002. 32.1Certificate of principal executive officer pursuant to 18 U.S.C. § 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of2002. 32.2Certificate of principal financial officer pursuant to 18 U.S.C. § 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of2002. 101The following financial information from Stemline Therapeutics, Inc.’s Annual Report on Form 10-K for the year ended December 31,2015, formatted in XBRL (eXtensible Business Reporting Language): (i) Consolidated Balance Sheets, (ii) Consolidated Statements ofOperations, (iii) Consolidated Statements of Stockholders’ Equity, (iv) Consolidated Statements of Cash Flows, and (v) the Notes toConsolidated Financial Statements. Table of Contents SIGNATURES Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to besigned on its behalf by the undersigned, thereunto duly authorized. Date: March 14, 2016STEMLINE THERAPEUTICS, INC. By:/s/ Ivan Bergstein, M.D.Ivan Bergstein, M.D.Chairman, President and Chief Executive Officer Table of Contents POWER OF ATTORNEY KNOW ALL MEN BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Ivan Bergstein, M.D. his true and lawfulattorney-in-fact and agent, with full power of substitution and resubstitution, for him and his name, place and stead, in any and all capacities, to sign any orall amendments to this annual report on Form 10-K, and to file the same, with all exhibits thereto and other documents in connection therewith, with the SEC,granting unto said attorney-in-fact and agent, full power and authority to do and perform each and every act and thing requisite and necessary to be done inand about the premises, as fully to all intents and purposes as he might or could do in person, hereby ratifying and confirming all that said attorney-in-factand agent or any of his substitutes, may lawfully do or cause to be done by virtue hereof. Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, this Form 10-K has been signed by the following persons on behalf of theRegistrant on March 14, 2016, and in the capacities indicated: Signatures Title /s/ Ivan Bergstein, M.D.Ivan Bergstein, M.D.Chairman, President and Chief Executive Officer (Principal ExecutiveOfficer) /s/ David G. GioncoDavid G. GioncoVice President of Finance and Chief Accounting Officer (Principal Financialand Accounting Officer) /s/ Ron BentsurRon BentsurDirector /s/ J. Kevin BuchiJ. Kevin BuchiDirector /s/ Eric L. DobmeierEric L. DobmeierDirector /s/ Kenneth ZuerblisKenneth ZuerblisDirector /s/ Alan FormanAlan FormanDirector Exhibit 21.1 Stemline Therapeutics, Inc.List of Subsidiaries Stemline Therapeutics, Inc. does not have any subsidiaries. Exhibit 23.1 Consent of Independent Registered Public Accounting Firm We consent to the incorporation by reference in the following Registration Statements: (1) Registration Statement (Form S-3 No. 333-193726) of Stemline Therapeutics, Inc., (2) Registration Statement (Form S-8 No. 333-188115) pertaining to Stemline Therapeutics, Inc. 2012 Equity Incentive Plan and StemlineTherapeutics, Inc. Amended and Restated 2004 Employee, Director and Consultant Stock Plan, and, (3) Registration Statement (Form S-8 No. 333-206303) pertaining to Stemline Therapeutics, Inc. 2015 Employee Stock Purchase Plan; of our report dated March 14, 2016, with respect to the financial statements of Stemline Therapeutics, Inc. included in this Annual Report (Form 10-K) ofStemline Therapeutics, Inc. for the year ended December 31, 2015. /s/ Ernst & Young LLP MetroPark, New JerseyMarch 14, 2016 Exhibit 31.1 CERTIFICATION OF PERIODIC REPORTPURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002 I, Ivan Bergstein, M.D., certify that: 1. I have reviewed this annual report on Form 10-K of Stemline Therapeutics, Inc.; 2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; 3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects thefinancial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report; 4. The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined inExchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f))for the registrant and have: a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensurethat material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities,particularly during the period in which this report is being prepared; b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for externalpurposes in accordance with generally accepted accounting principles; c) Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectivenessof the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscalquarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect,the registrant’s internal control over financial reporting; and 5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to theregistrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions): a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonablylikely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control overfinancial reporting. Date: March 14, 2016/s/ Ivan Bergstein, M.D.Ivan Bergstein, M.D.Chief Executive OfficerPrincipal Executive Officer Exhibit 31.2 CERTIFICATION OF PERIODIC REPORT PURSUANT TO SECTION 302 OF THESARBANES-OXLEY ACT OF 2002 I, David G. Gionco, certify that: 1. I have reviewed this annual report on Form 10-K of Stemline Therapeutics, Inc.; 2. Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; 3. Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects thefinancial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report; 4. The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined inExchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f))for the registrant and have: a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensurethat material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities,particularly during the period in which this report is being prepared; b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for externalpurposes in accordance with generally accepted accounting principles; c) Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectivenessof the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscalquarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect,the registrant’s internal control over financial reporting; and 5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to theregistrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions): a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonablylikely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control overfinancial reporting. Date: March 14, 2016/s/ David G. GioncoDavid G. GioncoChief Accounting OfficerPrincipal Financial and Accounting Officer Exhibit 32.1 STATEMENT OF CHIEF EXECUTIVE OFFICER OFSTEMLINE THERAPEUTICS, INC.PURSUANT TO 18 U.S.C. SECTION 1350,AS ADOPTED PURSUANT TOSECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 In connection with the annual report of Stemline Therapeutics, Inc. (the “Company”) on Form 10-K for the period ended December 31, 2015 as filedwith the Securities and Exchange Commission (the “Report”), I, Ivan Bergstein, M.D., Chief Executive Officer of the Company, certify, pursuant to 18 U.S.C.§1350, as adopted pursuant to §906 of the Sarbanes-Oxley Act of 2002, that, based on my knowledge: 1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and 2) The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. Date: March 14, 2016/s/ Ivan Bergstein, M.D.Ivan Bergstein, M.D.Chief Executive OfficerPrincipal Executive Officer Exhibit 32.2 STATEMENT OF CHIEF ACCOUNTING OFFICER OFSTEMLINE THERAPEUTICS, INC.PURSUANT TO 18 U.S.C. SECTION 1350,AS ADOPTED PURSUANT TOSECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 In connection with the annual report of Stemline Therapeutics, Inc. (the “Company”) on Form 10-K for the period ended December 31, 2015 as filedwith the Securities and Exchange Commission (the “Report”), I, David G. Gionco, Chief Accounting Officer of the Company, certify, pursuant to 18 U.S.C.§1350, as adopted pursuant to §906 of the Sarbanes-Oxley Act of 2002, that, based on my knowledge: 1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and 2) The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. Date: March 14, 2016/s/ David G. GioncoDavid G. GioncoChief Accounting OfficerPrincipal Financial and Accounting Officer 

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