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SphingoGene, Inc. Delaware C-Corporation James S Norris PhD Board President and Interim CEO Small Molecule Platform Improving Radiation.

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Presentation on theme: "SphingoGene, Inc. Delaware C-Corporation James S Norris PhD Board President and Interim CEO Small Molecule Platform Improving Radiation."— Presentation transcript:

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

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

3 3 A family of lipids involved in cell signaling Cell differentiation Proliferation Programmed cell death – apoptosis

4 4 Dysregulation of ceramide accumulation is a common mechanism of resistance to therapies

5 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 5

6 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 6

7 7

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

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

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 10

11 “My granddad died of prostate cancer. I have dedicated my thesis work which has led to our lead clinical compound to 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. Why Start with Prostate Cancer? 11

12 12 Source: Cancer Facts and Figures 2012

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

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 14

15 DrugTargetStage of Development SPG 105AC Inhibitor Clinical lead; efficacy established in rodent tumor xenograft models and cell culture models of prostate and breast cancers SPG 103 Ceramide-like Drug Efficacy established in rodent tumor xenograft pancreatic cancer models and cell lines SPG 104SK1 InhibitorClinical Efficacy in vitro and in vivo pending Clinical efficacy established in animal models of cancer at nM concentrations Dose Escalation: No toxicity observed at effective doses and 20 X higher doses Progress and Leads Lead Small Molecule Candidates (of 40): 15

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

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

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

19 19

20 20 Un-treatedCremophoreLCL521 Un-treatedCremophoreLCL521 ModeMeansSDMeansSDMeansSDModeMeansSDMeansSDMeansSD ALB(g/DL) WBC(10/L) ALP(U/L) LYM (10/L) ALT(U/L) MON (10/L) AMY(U/L) GRA (10/L) TBIL(mg/DL) LY % BUN(mg/DL) MO % CA++(mg/DL) GR % PHOS(mg/DL) RBC (12/L) CRE (mg/DL) HGB (g/DL) GLU (mg/DL) HCT % NA+ (MMO/L MCV ( fl ) K+ (MMO/L) MCH (pg) TP (g/DL) MCHC (g/DL) GLOB (g/DL) RDWc % n=4PLT (10/L) PCT % MPV ( fl ) PDWc % n=4 There is No Significant Toxicity Observed in Blood Chemical Test in Animal after Multiple Injections (150mg/kg ip every other day x5)

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 22

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 23

24 Market opportunity 24 United States: 241,740 cases/year Worldwide: 903,500 of patients will receive IR therapy % 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 25

26 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 Other Markets Estimated worldwide market projected in billions 26

27 3.5M new cases/yr; 2.5M death/yr 27 Source: The National Cancer Registry under the Ministry of Health

28 Radiation Therapy for Other Cancers – Candidates for SPG105 Lung Gy in fractions Breast Gy in fractions Pancreas Gy in fractions Melanoma Gy in 6-30 fractions (big variability) Head and Neck Gy in 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. 28

29 Competing Radiosensitizer Drugs 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. 29

30 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. 30

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

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/ A1  Issued patent for SPG103; US8,093,393 B2  Patent pending for SPG104; US 2012/ A1 32

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: 33

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 34

35 35 GMP synthesis Formulation Toxicity testing (rats, non- human privates

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

37 Anticipated Financial Needs Projected cost for each milestone GMP Synthesis (SBIR)$149,400 Formulation$79,100 Toxicity Testing (rats, non human primates)$1,618,649 Phase I Trial (Hollings Cancer Center)$1,100,000 Phase II Trial (Hollings Cancer Center)$3,640,000 37

38 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 Management Team & Advisors 38

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 39

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 40

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 41

42 1165/seeking-a-cure-musc-biotech-spinoff-wages-its-own-small-war- on-cancer 1010/improved-prognosis-tech-transfer-at-musc 42

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