SphingoGene, Inc. Delaware C-Corporation James S Norris PhD Board President and Interim CEO norrisjs@musc.edu

1. Small Molecule Platform Improving Radiation Treatment SphingoGene, Inc.Delaware C-Corporation James S Norris PhD Board President and Interim CEO norrisjs@musc.edu

2. Objective To obtain funding or partnerships in order to complete preclinical development of SPG105 for IND filing

3. Sphingolipids/Ceramides • A family of lipids involved in cell signaling • Cell differentiation • Proliferation • Programmed cell death – apoptosis

4. Dysregulation of ceramide accumulation is a common mechanism of resistance to therapies Sphingolipids are mediators of cell death in response to cancer therapies

5. Sphingolipids as Therapeutics Alleviate resistance to Chemotherapy Radiation Therapy Synergistic killing with targeted therapies (combination therapy) TKIs – imatinib, dasatinib, nilotinib, sorafenib, sunitinib HDAC inhibitors – vorinostat mAbs– Rituximab, milatuzumab

6. Current SphigolipidDrugs – Still Early Fingolimod (Gilenya, Novartis) First oral drug for Multiple Sclerosis $1.2B sales in 2012, up 147% from 2011 iSONEP (Lpath) Phase 2 clinical development for wet AMD (macular degeneration) $500M partnerships with Pfizer Others - in preclinical development

7. SPG105 is a small molecular drug that inhibits acid ceramidase

8. Rational for Our Drugs Mechanism of Action: Cancer Cell Death Ceramide Acid Ceramidase Radiation Therapy Prevents ceramide accumulation Allows escape from cell death

9. How our drugs work: Cancer Cell Death Ceramide Acid Ceramidase SPG105 Inhibits Acid Ceramidase And Potentiates Radiation Induced Cancer Killing Radiation Therapy Prevents ceramide accumulation Allows escape from cell death

10. Background on SphingoGene • Founded in 2006 by scientist-entrepreneurs at the Medical University of South Carolina (MUSC) • Obtained exclusive worldwide rights to the intellectual property from MUSC

11. Why Start with Prostate Cancer? • “My granddad died of prostate cancer. I have dedicated my thesis work which has led to our lead clinical compoundto him.” Joseph Cheng MUSC MD/PhD candidate SphingoGene Researcher • “Hurry up! The Baby Boom generation is getting prostate cancer!” Ken Burger Author of “Baptized in Sweet Tea” Prostate Cancer Patient, Charleston, S.C.

12. U.S. Cancer Stats – Prostate Cancer Most Prevalent Source: Cancer Facts and Figures 2012 http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-031941.pdf

13. Prostate Cancer • Forms in male prostate gland • Most common cancer in men • Risk increases withage • In 2012: • 241,740 men will be diagnosed • 25,170 will die from the disease

14. How Our Platform Works • Ceramide levels increase during radiation therapy; leads to cancer cell death • Acid ceramidase (AC) and Sphingosine Kinase (SK) activity increase during radiation therapy in cancer cells • AC reduces ceramide levels, SK forms S1P, both permitting cancer cell survival • Our compounds inhibit AC or SK or mimic ceramide making radiation or other therapies more effective at inducing cancer cell death

15. Progress and Leads • Clinical efficacy established in animal models of cancer at nM concentrations • Dose Escalation: No toxicity observed at effective doses and 20 X higher doses Lead Small Molecule Candidates (of 40):

16. In Vivo Efficacy SG105 (clinical lead) Significantly Reduces Tumor Size; in vivo mouse Xenograft Prostate Tumor Model Control (n=6) Radiation (Rad) Only (n=10) Vehicle Only (n=8) Vehicle + Rad (n=10) SPG105 Only (n=10) SPG105 + Rad (n=10) Log 2 Tumor Size (% of initial volume)

17. In Vivo Efficacy SPG105 Significantly Reduces Mortality; in vivo mouse Xenograft Prostate Tumor Model Percent Survival

18. Xenograph toxicity studies I don’t have the figures. Would you please insert?

19. PK/PD studies

20. There is No Significant Toxicity Observed in Blood Chemical Test in Animal after Multiple Injections (150mg/kg ip every other day x5) Toxicity Study

21. Toxicity Study

22. Our Value Proposition • Enhances Radiotherapy leading to more effective cancer treatment • Fewer side effects • Achieve same clinical benefit with reduced radiation • Better quality of life • Greater preservation of sexual function • Reduce incidence of relapse = Reduced overall treatment costs and reduced death rate • Small Molecules = Easy manufacturing and delivery

23. More effective radiotherapy of prostate cancer means: Same clinical benefit with reduced radiation Fewer side effects Greater preservation of sexual function and continence issues Reduced incidence of relapse Targets mechanism of radioresistance Reduced death rates

24. Market opportunity • United States: 241,740 cases/year • Worldwide: 903,500 cases/year • @50% of patients will receive IR therapy. 21-44% of these patients will relapse. In a couple of studies 50% of patients relapsed and 51% of them had local disease (not metastatic) making local control relevant to survival. Our preclinical indication is that SPG105/IR therapy will reduce relapse and improve survival.

25. Financial Assumptions and Forecast • Based on annual estimated US prostate cancer cases treated with radiation therapy • Market penetration expected similar to other cancer therapeutics • No increase in cases, no relapses • $8000 per treatment per patient (drug cost) • Estimated worldwide market projected in billions

26. Other Markets • Platform applicable to the majority of solid tumors and any cancer for which patients receive radiation therapy, including internal radiotherapy (brachytherapy). • Approximate Incidence of other cancer markets (cases/year): • Lung: 1,600,000 • Breast: 1,380,000 • Pancreatic: 220,000 • Oral cavity: 263,900 • Brain: 237,913 • Total: 3,701,813 cases/year Estimated worldwide market projected in billions

27. China’s Cancer Crisis – Lung Cancer Prevalent 3.5M new cases/yr; 2.5M death/yr Source: The National Cancer Registry under the Ministry of Health http://www.chinadaily.com.cn/china/2013-01/10/content_16100330.htm

28. Radiation Therapy for Other Cancers – Candidates for SPG105 • Lung 60-70 Gy in 30-35 fractions • Breast 50.4 - 60 Gy in 28-33 fractions • Pancreas 50.4-54 Gy in 28-30 fractions • Melanoma 36-60 Gy in 6-30 fractions (big variability) • Head and Neck 60-70 Gy in 30-35 fractions. Potential: If clinical trials successfully model the preclinical data then SPG105 has the potential to become a standard of care blockbuster drug in the radiation treatment industry.

29. Competing RadiosensitizerDrugs • The first annual workshop for preclinical and clinical development of radiosensitizers took place at the NCI in August 2012 (JNCI, pages 1-8, 2012 advanced access). • Summary: • There are ongoing trials many of which are focused on biomarker indicators to improve patient selection. • A partial use of drugs being studied include standard chemotherapeutic drugs such as Gemcitabine, 5-Fu, Cisplatin while others are kinase inhibitors such as; Erlotinib, Bevacizumab as examples. • Other categories of drugs include ER inhibitor Tamoxifen and Her-2 inhibitors like Trastuzumab. • Two potential drugs that inhibit aspects of the ceramide-S1P rheostat with an unknown value in the radiation therapy domain include Fingolimod and ASONEP. Both of these drugs act downstream of SPG105. • A recent preclinical publication demonstrated rapamycin might be useful as a radiosensitizer.

30. SPG105 Specificity – “Cleaner” Than Fingolimod SPG105 is clean, unlike Gilenya which has multiple effects (“dirty drug”): It inhibits Acid Ceramidase by specifically targeting acidic compartments (lysosomes) and functioning in lysosomes to inhibit lysosomal enzyme. Investigations have not found actions anywhere else.

31. Therapeutic Potentials Beyond Radiation Sensitizer SPG105 can be used in resistance of different therapies that involve ceramide pathway. Chemotherapy TKI targeted therapies HDACI therapies mAb therapies

32. Patent Position • SphingoGene has filed broad patents around targets and various classes of compounds which can affect their targets • Lead Compounds: • Worldwide Patent pending for SPG105 (clinical lead); US 2011/0251197 A1 • Issued patent for SPG103; US8,093,393 B2 • Patent pending for SPG104; US 2012/0035268 A1

33. Regulatory Path and Timelines • Investigational New Drug Application (IND) Filing in US: • Phase I: Prostate Cancer Patients undergoing primary radiotherapy • Primary Endpoint: Safety/Tolerability • Phase IIa: Prostate Cancer Patients undergoing primary radiotherapy • Primary Endpoint: Safety/Tolerability • Second Endpoint: Efficacy/biochemical relapse Overall Timeline to Exit:

34. Company Funding to Date • NIH/NCI (University) Program Project Grant: $1.6million • NIH Small Business Technology Transfer (STTR) Grant: $432,000 • ARRA stimulus package: $180,000 • South Carolina Research Authority (SCRA) start-up funds and SBIR match: $125,000 • Total: $2.34 Million of Non-dilutive funding

35. Need $2M to Complete the Following: • GMP synthesis • Formulation • Toxicity testing (rats, non-human privates

36. Anticipated Funding • Phase I/II Small Business Innovative Research (SBIR) Grant (CA174027-01): $2,115,479 • Phase I STTR (CA177006-01): $346,792 • Up to $200,000 (SCRA) • Total: $2.6 Million of Non-dilutive Funding

37. Anticipated Financial Needs

38. Management Team & Advisors • James Norris, PhD, Chairman of the board and Interim CEO • Professor, Department of Microbiology & Immunology • Medical University of South Carolina (MUSC) • David Haselwood, Board Member & Business Advisor • Experienced life science VC, entrepreneur & operator • Burrill & Co, Roche, Proventys, Pharmasset, Primera • Yusuf Hannun, MD, Director of the Stony Brook University Cancer Center • Joel Kenney Professor of Medicine, and the Vice Dean for Cancer Medicine • World famous expert in sphingolipid biochemistry

39. Advisors: • Allen Conger, MBA University of Chicago Experienced investment banker • Andrew Barkan, BBA in management /finance Georgia State University. Asset Management & Investment Banking background. Work in asset management with Wells Fargo, as vice president, Oppenheimer & Company as director, and Morgan Stanley as senior vice president

40. Scientific Advisors and Collaborators • Besim Ogretmen, Ph.D., Key expert on sphingolipid metabolism • Xiang Liu, MD, PhD, Key scientist and expert on acid ceramidase in cancer • Alicja Bielawska, Ph.D., Key chemist • Zdzislaw M. Szulc, PhD key chemist

41. Clinical Advisors • Thomas Keane, MD, Chairman of Urology, Medical University of SC • Michael Lilly, MD, Professor Department of Medicine, Hem-Onc, Medical University of SC • David Marshall, MD, Associate Professor, Radiation Oncology, Medical University of SC • Carolyn Britten, MD, Associate Professor, Department of Medicine, Hem-Onc, Medical University of SC

42. Press http://www.postandcourier.com/article/20130429/PC05/130429267/1165/seeking-a-cure-musc-biotech-spinoff-wages-its-own-small-war-on-cancer http://www.postandcourier.com/article/20130429/PC05/130429270/1010/improved-prognosis-tech-transfer-at-musc