Jefferies 2014 Global Healthcare Conference

Transcription

1 Jefferies 2014 Global Healthcare Conference Edward Lanphier President & CEO Sangamo BioSciences, Inc. June 5, 2014

2 Forward Looking Statements This presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of various factors and uncertainties in our strategy, sufficiency of our cash resources, product development and commercialization of our products, clinical trials, revenues from existing and new collaborations, our research and development and other expenses, our operational and legal risks and any other statements that are not historical fact. Sangamo BioSciences, Inc. Annual Report on Form 10-K, recent and forthcoming Quarterly Reports on Form 10-Q, recent Current Reports on Forms 8- K and 8-K/A, and other SEC filings discuss some of the important risk factors that may affect our business, results of operations and financial condition. We undertake no obligation to revise or update publicly any forward-looking statements for any reason. 2

3 Sangamo BioSciences Focused on the development of a new class of human therapeutics that function at the DNA level with the goal of Engineering s Driven by multiple robust technology platforms Zinc finger proteins (ZFPs) can be designed to bind to any DNA sequence with singular specificity Targeted genome editing and gene regulation Broad AAV delivery capabilities, manufacturing and IP Broad commercial applications in research reagents, transgenic animals, agriculture, manufacturing and human therapeutics Significant partnerships and strong balance sheet Dominant intellectual property position 3

4 Toolbox for Engineering s TM Zinc Finger Protein Gene Regulation Domain ZFP Transcription Factor (ZFP TF) ZFP Nuclease (ZFN) Gene Editing Domain Repress Knockout Activate Correct/Add 4

5 Sangamo has successfully monetized its ZFP technology platform Partners Applications Proprietary ZFP Therapeutics Programs Hemoglobinopathies Sickle Cell Disease b-thalassemia Hemophilia A & B Huntington s Disease Two Remaining Targets 5 Plant Agriculture Research Tools Transgenic Animals Protein Manufacturing

6 Current Sangamo ZFP Therapeutic Development Programs In Vivo Strategy 1 Systemic (Liver) Hemophilia Factors 7, 8, 9, 10 Shire Lysosomal Storage Disorders Gaucher, Fabry, Pompe, MPSI/Hurler, MPSII/Hunter, MPS VI Alpha-1 Antitrypsin Deficiency Other ZFP Therapeutics Strategies (AAV) 2 3 Direct Tissue Brain Huntington s disease Shire, Alzheimer s disease (NGF) * Heart Congestive Heart Failure, monogenic diseases Lung Cystic Fibrosis, monogenic diseases Eye Monogenic diseases Muscle Monogenic diseases Non-Stem Cells T-cells HIV T-cells Oncology Ex Vivo Strategy (mrna) Blue = Partnered programs Green = Active proprietary Sangamo programs * Phase 2 AD and PD programs acquired from Ceregene 4 6 Stem Cells CD34+ Hemoglobinopathies (SCD, β-thalassemia) - BIIB AIDS Lymphoma Rare Diseases (Several) Universal Donor Cells Several

7 Sangamo ZFP Therapeutics Pipeline SB-728-T for HIV/AIDS Program Lead Indication ZFP Approach Product Strategy Goal SB-728 HIV / AIDS Ex Vivo T-cells Hemophilia In Vivo Systemic (Liver) SB-LSD Lysosomal Storage Disorders In Vivo Systemic (Liver) Multiple Huntington s Disease In Vivo Direct Tissue SB-SCD Hemoglobinopathies (e.g., Sickle Cell Disease) Ex Vivo Stem Cells Multiple Other ZFP Therapeutics Various Various 7

8 SB-728-T: ZFN-mediated CCR5 Knockout in CD4+ T-cells CD4 T-cell + HIV CCR5 5 T A C CCAACGCGAATT A T G G C G G C G T G C G C T T A A C G C A T G GGT 3 A T G GGTTGCGC T T A A T A C C G C C G C A C G C G A A T T G C G T A C CCA ZFNs 3 5 SB-728-T (CCR5 K-O) Reservoir Reduction Acute effect on viral load (VL) Viral load Copies/ ml Hypothesis Days from Baseline Subject Treatment Interruption Absolute CD4 Count 10 7 Absolute CD8 Count Pentamer VIral Load 10 6 Set Point Maximizing biallelic CD4 CCR5 K-O may provide functional control of HIV Pentamer Duplication / L Cells / L SB Phase 2 - Cytoxan pre-treatment 8

9 Recent updates on HIV Program SB-728-T Trials : ASGCT Meeting Update on Effects on Viral Load SB Cohort 5 subject: Continuing functional control of viral load for 45 weeks while off antiretroviral medication (ART) SB subject (1 g/m 2 Cytoxan): Greater than two-log decrease in viral load from peak during TI, sustained for 24 weeks SB-728-mR-HSPC $5.6 million Strategic Partnership Award from California Institute for Regenerative Medicine (CIRM) provides matching funds for Phase 1 clinical trial at City of Hope IND to be filed mid-2014 Study will enroll HIV-infected Immune Non-Responders (INR) Approximately 20 % of HIV-population who control virus on ART but whose CD4 cell counts fail to recover, complementary to population targeted by SB-728-T At significant risk from progressive AIDS-related syndromes Pre IND studies funded by an earlier CIRM $14.5 million Disease Team Research Award 9

10 SB-728-T HIV/AIDS Program Summary and Next Steps Completed SB Cohort 5 (CCR5 Δ-32 heterozygotes) and all dose cohorts of SB Cytoxan pre-treatment Sustained functional control of HIV in the absence of ART Cytoxan dose escalation achieved threshold of engraftment associated with HIV viral functional control Expansion of SB at optimal cytoxan dose 1 g/m 2 12 subjects to establish functional control POC Process development mrna permits improved modification efficiencies and repeat dosing if necessary Ongoing evaluation of viral DNA reservoir depletion and expansion/ persistence of CCR5 modified and CD4 stem cell & T CM populations 10

11 Sangamo ZFP Therapeutics Pipeline Hemoglobinopathies Program Lead Indication ZFP Approach Product Strategy Goal SB-728 HIV / AIDS Ex Vivo T-cells Hemophilia In Vivo Systemic (Liver) SB-LSD Lysosomal Storage Disorders In Vivo Systemic (Liver) Multiple Huntington s Disease In Vivo Direct Tissue Hemoglobinopathies (e.g., Sickle Cell Disease) Ex Vivo Stem Cells Multiple Other ZFP Therapeutics Various Various 11

12 Hemoglobinopathies are genetic disorders of hemoglobin How can ZFPs be used to cure Hemoglobinopathies? Ex vivo ZFN-modification of the Bcl11a gene in CD34+ stem cells enables a curative autologous bone marrow transplant in both β-thalassemia and sickle cell disease Building upon emerging science related to fetal hemoglobin regulation, we intend to develop Sangamo s novel gene editing technology to create a single approach that has the potential to functionally cure both sickle cell disease and beta-thalassemia. Douglas E. Williams, Ph.D., EVP R&D, Biogen Idec 12

13 Targeted genome editing in human repopulating haematopoietic stem cells - Nature Publication Efficient zinc finger nuclease (ZFN)-mediated, targeted gene insertion in hematopoietic stem cells (HSCs) ZFN-mediated functional reconstitution of the IL2RG gene in the progeny of HSCs from the bone marrow of a symptomatic fourmonth-old SCID-X1 patient Data support the clinical translation of this approach for SCID-X1, and other immunodeficiencies and monogenic diseases Provides safer alternative to randomly integrating viral vectors The ability to accomplish targeted integration of a therapeutic gene in HSCs represents a major step forward in the quest for more precise and safe gene therapies. Luigi Naldini, MD, PhD, Director, San Raffaele Telethon Institute for Gene Therapy Published as an Advance Online Publication in Nature (05/29/14) 13

14 Sangamo ZFP Therapeutics Pipeline In Vivo Protein Replacement Platform (IVPRP) Program Lead Indication ZFP Approach Product Strategy Goal SB-728 HIV / AIDS Ex Vivo T-cells Hemophilia In Vivo Systemic (Liver) SB-LSD Lysosomal Storage Disorders In Vivo Systemic (Liver) Multiple Huntington s Disease In Vivo Direct Tissue SB-SCD Hemoglobinopathies (e.g., Sickle Cell Disease) Ex Vivo Stem Cells Multiple Other ZFP Therapeutics Various Various 14

15 Sangamo s In Vivo Protein Replacement Platform Broadly Leverageable Albumin Gene: Very strong promoter ZFN ZFN Requires < 1% for normal levels Donor: Homology Gene of Interest Homology Hemophilia A Hemophilia B Gaucher Fabry MPS II (Hunter) Other $6B $1B $1B $600M $500M $Billions 15

16 Albumin is Very Highly Expressed Baxter Pfizer Genzyme Biomarin Disease Hemophilia A Hemophilia B Gaucher Fabry Pompe MPSI/Hurler MPS VI Product Advate BeneFIX Cerezyme Fabrazyme Myozyme Aldurazyme Naglazyme Brand Image Dose (mg/week for 75kg patient) Half Life (minutes) % of Albumin Production Rate *1.125 ^ ± ± ± ± (median) % 0.056% 0.063% 0.047% 0.938% 0.054% 0.094% *Assumes prophylaxis regimen of 30 IU/kg delivered every other day, and a specific activity of 7000 IU / mg. ^ Required dose depends on disease severity, target factor level, factor level responsiveness to treatment (recovery), and factor half life mg/wk assumes severe disease (no endogenous factor), a target level of 40% of normal, a recovery of (0.78% - kg) / IU (average stated on the insert), a specific activity of 200 IU / mg, a half life of 22.4 hours (mean observed in clinical trials), and treatment every third day. We only need a very small fraction of natural albumin expression to drive therapeutic levels of the new protein. 6/5/

17 Sangamo s In Vivo Protein Replacement Platform can be applied to Hemophilia Factor VIII & Factor IX Albumin Gene: Very strong promoter ZFN ZFN Donor: Homology Gene of Interest Homology Hemophilia A Hemophilia B Gaucher Fabry MPS II (Hunter) Other $6B $1B $1B $600M $500M $Billions 17

18 In Vivo Protein Replacement Platform Broadly Leverageable In Vivo Protein Replacement Platform is leverageable to numerous Lysosomal Storage Disorders: Hemophilia A Hemophilia B Gaucher Fabry MPS II (Hunter) Other $6B $1B $1B $600M $500M $Billions 18

19 Sangamo s In Vivo Protein Replacement Platform is Highly Disruptive Hemophilia Factor 7, 8, 9, 10, 11, 13 & Von Willebrand, Protein C ($7B) Lysosomal Storage Diseases ($3B) Gaucher ($1B) Fabry ($600M) Pompe ($500M) MPS I Hurler Syndrome ($200M) MPS II Hunter Syndrome ($500M) MPS IV Morquio Syndrome MPV VI Maroteux-Lamy Syndrome ($200M) Niemann-Pick Disease Cystinosis α-1 Antitrypsin Deficiency ($500M) Hereditary Angioedema ($300M) Other Metabolic Diseases Wilson Disease Tyrosinemia Citrullinemia Phenylketonuria OTC Deficiency Familial Hypercholesterolemia Familial Lipoprotein Lipase Deficiency (LPLD) Total Current Market >$11 Billion Per Year Blue = Shire funded gene targets 19

20 Sangamo ZFP Therapeutics Pipeline Huntington s Disease Program Lead Indication ZFP Approach Product Strategy Goal SB-728 HIV / AIDS Ex Vivo T-cells Hemophilia In Vivo Systemic (Liver) SB-LSD Lysosomal Storage Disorders In Vivo Systemic (Liver) Multiple Huntington s Disease In Vivo Direct Tissue SB-SCD Hemoglobinopathies (e.g., Sickle Cell Disease) Ex Vivo Stem Cells Multiple Other ZFP Therapeutics Various Various 20

21 Huntington s disease is a fatal neurodegenerative monogenic disease What causes Huntington s disease? Huntington s disease is caused by a mutation in the Huntingtin gene (multiple CAG repeats), causing production of a toxic protein % of alleles normal alleles disease alleles HD occurs when the Huntingtin gene has >35 CAG repeats CAG count How can ZFPs be used to treat Huntington s disease? ZFP Transcription Factors selectively repress ( ) the mutant Huntingtin gene reduces mutant Huntingtin protein 21

22 Allele-specific repression in Huntington s disease patient cell lines Normalized Scaled Expression Cell Line: Mutant: Wild Type: Patient #1 Patient #2 Patient #3 Patient #4 Patient # Difference: same WT WT WT Mut WT Mut WT Mut WT Mut Control Patient Cell Line 2 Patient Cell Line 3 Patient Cell Line 4 Patient Cell Line 5 22

23 Huntington s disease Program: Preclinical Data Update ZFP TF selectively represses expression of mutant, disease-causing form of huntingtin gene while expression of normal gene unchanged in mouse models and HD patient-derived cell lines Positive effects on symptoms in animal models of HD Reduction of aggregates of mutant huntingtin protein in ZFP TFtreated regions of the brain aggregates associated with severity of the disease in humans Increased levels of protection of medium spiny neurons - nerve cells that are progressively lost in the brains of HD patients Statistically significant reduction in clasping behavior in ZFP TF treated compared to control HD mouse model In vivo delivery using AAV 23

24 Strategic Acquisition of Sangamo Strategic Acquisition August 2013 Ceregene AAV Expertise and cgmp Manufacturing Experience Over 120 issued, pending or in-licensed patents WW Clinical and Pre-Clinical Assets Largest AAV CNS pre-clinical and clinical experience in the world Ongoing Phase 2 in Alzheimer s disease (fully funded by NIH, 2015 read-out) Regulatory Filings and Clinical Experience Approximately 115 patients treated on 7 clinical protocols Leverage for Internal Sangamo Timelines Leverage manufacturing experience, regulatory filings, and brain administration database to de-risk internal process (e.g. Sangamo-Shire Huntington program) 24

25 Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) May 21-24, 2014 in Washington, DC Fourteen oral and poster presentations given by Sangamo scientists and their academic collaborators Data from Sangamo's ZFP Therapeutic and research programs including: HIV/AIDS Huntington s disease and other monogenic diseases Cancer immunotherapy Advancements in the technology including delivery 25

26 ASGCT - Exploring Potential New Delivery Options and Target Tissues ASGCT Abstract #248: In Vivo Genome Editing Using Nuclease-Encoding Chemically Modified mrna First report of therapeutic genome editing using ZFNs in the lung Preclinical study in a mouse model of surfactant protein-b (SP-B) deficiency ZFN-mediated correction of mutant SP-B resulted in production of correct protein and a significant improvement in survival The data raise the possibility of utilizing modified-mrna and mrna/aav combinations for the treatment of other severe inherited lung diseases 26

27 Sangamo Clinical and IND Timelines Multiple INDs and Two Phase 2 Read-outs by YE SB-728-T (HIV/AIDS) Data Cytoxan Phase 2 Data Phase 2 Read-out SB-728-HSC IND Phase 1 Hemophilia B (Shire) IND Phase 1 Hemophilia A (Shire) IND Phase 1 β-thalassemia (Biogen) IND Phase 1 Sickle Cell (Biogen) IND Phase 1 LSD 1 IND Phase 1 LSD 2 IND Phase 1 Huntington (Shire) IND Phase 1 CERE-110 (Alzheimer s) Data Phase 2 Read-out 27

28 Near Term Catalysts and 2014 Goals ZFP Therapeutic Programs Program updates and milestones in 2014 (ASGCT- May 21-24) Hemophilia / LSDs Hemoglobinopathies Huntington s Disease SB-728-T Data at major medical meetings in 2014 (ASGCT) Pre-clinical Programs (ASGCT) Progress and visibility on new ZFP Therapeutic programs Therapeutic Partnerships Biogen Idec / Hemoglobinopathies collaboration Shire / Hemophilia & HD collaborations Leverage platform and forward integration Financial Guidance Begin 2014 $131.8M / YE 2014 >$225M 6/5/

29 Financial Overview Directional Cash Flow $275 $250 $225 $200 $175 $150 $125 $100 $75 $50 $25 $0 ($25) ($50) ($75) $ M $ M $131.8M ~$94 ~$70 ~$65 ~$24 ~$40 ~($40) ~($62) ~($47) Cash Inflows/Revenues Financing Cash Outflows/Expenses Ending Cash Includes expected cash flows under partnerships with Shire and Biogen Idec, Inc. * Assumes Shire had not yet selected a 6 th or 7 th target 29

30 Summary Sangamo s ZFP technology is a robust platform for genome editing and gene regulation Focused on the development of a new class of human therapeutics that function at the DNA level with the goal of Engineering s ZFP Therapeutics Summary POC data from In Vivo Protein Replacement Platform in NHPs demonstrated circulating levels of therapeutic protein sufficient for correction of a range of monogenic disease Robust modification and engraftment of HSCs and high level expression of fetal hemoglobin in Sickle Cell Disease/ß-thalassemia Highly specific ZFP TF repressor approach for Huntington s disease Sustained undetectable viral load & unprecedented reservoir depletion results from SB-728-T 30

31 Summary (continued) All programs line up to potentially have multiple INDs and two Phase 2 read-outs by YE2015 Major partnerships and sufficient cash to move all programs through value inflection points and still end 2015 with $220 - $225M in cash Our strategy creates significant near term value and mitigates risk via diversification and leverage Business model partnerships and proprietary programs Diverse therapeutic product development strategies Variety of addressable and well validated targets Balance sheet strength 31

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