Corporate Presentation. March 2018

Transcription

1 Corporate Presentation March 2018

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 1995, as amended. These forward-looking statements include, but are not limited to, the design of clinical trials and expected timing for release of data; the anticipated clinical development milestones and other potential value drivers in the future; the expected benefits of the collaboration with Pfizer and Kite, the expanded capability of Sangamo s technologies; the research and development of novel gene-based therapies and the application Sangamo s ZFP technology platform to specific human diseases; corporate partnerships; and the potential of Sangamo s genome editing technology to treat genetic diseases. 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. Factors that could cause actual results to differ include, but are not limited to, the dependence on the success of clinical trials of lead programs, the lengthy and uncertain regulatory approval process, uncertainties related to the timing of initiation and completion of clinical trials, whether clinical trial results will validate and support the safety and efficacy of Sangamo s therapeutics, uncertainties related to the initiation and completion of clinical trials, whether clinical trial results will validate and support the safety and efficacy of Sangamo s therapeutics, the reliance on partners and other third-parties to meet their obligations, and the ability to establish strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that Sangamo and its partners will be able to develop commercially viable genebased therapeutics. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo s operations and business environments. These risks and uncertainties are described more fully in Sangamo s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q as filed with the Securities and Exchange Commission. Forward-looking statements contained in this presentation are made as of the date hereof, and Sangamo undertakes no obligation to update such information except as required under applicable law. 2

3 We are committed to translating ground-breaking science into genomic therapies that transform patients lives 3

4 Sangamo is investing across four technology platforms for genomic medicines Gene Therapy Genome Editing Cell Therapy Gene Regulation 4

5 2017 was a foundational year for Sangamo Optimized ZFP platform and invested in novel AAV vectors and non-viral delivery First ever patient treated with in vivo genome editing Achievements 2 global collaborations with Pfizer Strengthened balance sheet Invested in new HQ, manufacturing facility and secured cgmp vector supply chain 5 active clinical programs 5

6 2018 is promising to be transformative Establish additional collaborations Strengthen leadership team and expand footprint to Europe Goals Present preliminary data from lead clinical programs File IND for ST-920 Fabry disease; support Bioverativ BIVV-003 sickle cell disease IND filing Operationalize ZFP platform improvements; continue to set gene editing standards for precision, efficiency and specificity Establish new headquarters and construct cgmp manufacturing facility in Brisbane, California 6

7 Clearly defined scope of the Kite-Gilead deal Strategic Collaboration in Oncology T cells and NK cells Ex Vivo genome editing (ZFNs and AAV) Cell Therapy Oncology CARs, TCRs, and NKRs directed to tumor antigens Autologous and allogeneic products Solid and liquid tumor types 7

8 Kite-Gilead deal economics $150M $3.01B Upfront payment $300M in potential per product milestone payments, up to 10 times Cell Therapy Oncology Tiered royalties on net sales 8

9 Our vision to develop and commercialize our own products, built on Sangamo s foundational research engine Sangamo Research Engine Forward Integration Discovery Pre-clinical Phase I/II Clinical Phase III / Commercial Inherited Metabolic Diseases Rare Patient Population In-Licensing Central Nervous System Small/Large Patient Population Novel Delivery Immunology Large Patient Population 9

10 Sangamo is rapidly advancing product candidates across its internal therapeutic areas Therapeutic Area Research Preclinical Phase 1/2 Phase 3 Inherited Metabolic Diseases MPS I (SB-318) MPS II (SB-913) Fabry Disease (ST-920) Undisclosed Targets CNS Diseases Tauopathies Undisclosed Targets Gene Therapy Genome Editing Cell Therapy Gene Regulation Immunology Undisclosed Autoimmune Disease Targets Other Targets Inherited Metabolic Diseases Central Nervous System Immunology o In Vivo delivery of ZFNs with AAV (MPS I, MPS II) o Progress in solving delivery o Emerging translational scientific and technical advances suggest synergistic, large opportunity o Internal gene therapy program o Advancing Tau internally (Fabry disease) o Anticipated validation from NHP o Establishing cell therapy platform o Evaluating new targets for rare data and CNS partnership in immunological disorders patient populations 10

11 Current internal and external product portfolios diversified across therapeutic area and technology Therapeutic Area Research Preclinical Phase 1/2 Phase 3 Collaborator Inherited Metabolic Diseases MPS I (SB-318) MPS II (SB-913) Fabry Disease (ST-920) Hematology Hemophilia A (SB-525) Hemophilia B (SB-FIX) Beta-thalassemia (ST-400) Sickle Cell Disease (BIVV-003) CNS Diseases Tauopathies ALS/FTLD - C9ORF72 Huntington s Disease Oncology Autologous and Allogeneic CAR/TCR/NKR Immunology Undisclosed Autoimmune Disease Targets Investigator Sponsored Clinical Research HIV (T cell and Stem Cell) Gene Therapy Genome Editing Cell Therapy Gene Regulation 11

12 Sangamo Clinical Development SB-525: Hemophilia A SB-FIX: Hemophilia B SB-318: MPS I SB-913: MPS II ST-400: Beta-thalassemia

13 Sangamo s AAV cdna gene therapy platform: potential for potent therapeutic solutions for adults with rare monogenic diseases Packaging into AAV vectors Delivery In the liver transgene liver cell DNA nucleus therapeutic gene AAV vectors liver cell 13

14 SB-525: Hemophilia A clinical program summary Phase I/II Open Label Study Patients Cohorts Data Up to 20 adult (18+) males with severe hemophilia A 6 potential dose cohorts Preliminary data expected by mid-2018 Clinical Trial Status IND open Study initiated 8 sites active 4 subjects treated US EMA Regulatory Designations Orphan Drug designation Fast Track designation Orphan Medicinal Product designation 14

15 In vivo genome editing of albumin: harnessing the liver s most highly expressed locus Packaging into AAV vectors Delivery In the liver zinc finger nucleases transgene + albumin gene AAV vectors Strong albumin promoter H TG H transgene 15

16 SB-FIX: Hemophilia B clinical program summary Phase I/II Open Label Study Patients Cohorts Data Up to 12 adult (18+) males with severe hemophilia B 3 dose cohorts Timing dependent on enrollment U.S. Clinical Trial Status U.K. Clinical Trial Status Regulatory Designations IND open CTA granted Study initiated 4 sites active Study initiation US Orphan Drug designation Fast Track designation 16

17 SB-318 / SB-913: MPS I / MPS II clinical program summaries Phase I/II Open Label Study Patients Cohorts Data Up to 9 adults (18+) with attenuated MPS I / MPS II 3 dose cohorts Preliminary data beginning in mid-2018 Clinical Trial Status INDs open Studies initiated 10 sites active 2 subjects treated US Regulatory Designations Orphan Drug designation Fast Track designation Rare Pediatric Disease designation 17

18 Autologous, gene-edited cell therapies for beta-thalassemia and sickle cell disease Apheresis Isolate CD34+ Hematopoietic stem cells from patient s blood 1 Patient 4 Infusion ST-400 stem cells are infused back to the patient (with myloablative preconditioning to promote engraftment) Functional RBCs with fetal hemoglobin produced from ST-400 stem cells BCL11A Enhancer Sequence 2 3 cgmp Manufacturing Facility Gene editing Manufacture ST-400 stem cells via transient, non-viral delivery of ZFN mrna Deletion BCL11A Enhancer Knocked Out Harvest ST-400 stem cells are cryo-preserved and shipped to treatment center 18

19 ST-400: Beta-thalassemia clinical program overview Phase I/II Open Label Study Patients 6 adults (18+) with transfusion-dependent beta-thalassemia Clinical Trial Status Cell Therapy Autologous, ex vivo therapy of HSCs Increase production of fetal hemoglobin Reduce or eliminate blood transfusions Strategic Advantages Goals IND open First site initiation in Q First subject enrolled mid-2018 Leverages naturally-occurring, protective mechanism to increase fetal-hemoglobin Highly efficient, precise gene editing; low risk of insertional mutagenesis Non-viral delivery of ZFNs Potentially superior long-term safety profile 19

20 Sangamo Research ZFN Technology Ex Vivo cell therapy ST-920: Fabry disease C9ORF72-linked ALS/FTLD

21 ZFNs: The platform of choice for therapeutic genome editing ZFN ZFN 21

22 ZFNs: The platform of choice for therapeutic genome editing Precision ZFNs Efficiency Specificity 22

23 Recent innovations drive exceptional performance Innovation Result Efficiency Precision Specificity New linkers for configuring DNA-binding modules 300-fold increase in design options for targeting any given sequence Efficiency Precision Specificity New dimer architectures yield higher modification activity Increase DNA editing efficiency to as high as 99.5% Efficiency Precision Specificity Phosphate contact tuning via replacement of key residues Off-target cleavage undetectable (>1000 fold reduction) 23

24 Allogeneic cell therapy production: high efficiency is critical for single-step multiplexed genome editing 1 KO + 1 KO + 1 TI Compounded Efficiency Very High 99% x 99% x 99% = 97% High 90% x 90% x 90% = 73% Medium 70% x 70% x 70% = 34% Low 50% x 50% x 50% = 13% 24

25 Cell therapy platform: simultaneous multiplex editing efficiencies with 3x ZFN KO + 1x targeted integration % EDITING POTENTIAL APPLICATION: Universal T cells with checkpoint gene knock-out % 9 6 % 9 3 % 9 1 % SINGLE STEP EDITING ZFN Knock-out TCR (TRAC) HLA-class I (β2m) CISH (checkpoint gene) Targeted Insertion GFP (into TRAC) T C R - 2 M - C I S H - G F P + 76% of cells have all 4 edits KO: TCR, β2m and CISH; TI: GFP (TRAC) 25

26 ST-920: Fabry disease gene therapy program overview Recent data from WORLDSymposium 2018 congress ST-920 Therapeutic Program Status IND enabling studies ongoing IND filing expected mid

27 Sangamo s ZFP-TF platform: precise and specific gene regulation to treat CNS diseases Packaging into AAV vectors Potential Routes of Administration In Neurons Gene cassette for ZFP-TFs Intracranial Intravenous ZFP-TF does not integrate into the genome Intrathecal AAV Vectors ZFP-TF represses tau DNA 27

28 Allele specific repression of C9ORF72 with ZFP-TFs exemplifies Sangamo s differentiated therapeutic approach to CNS diseases Expansion of Six Base Pair Repeat Causes Neuronal Degeneration C9ORF72 Normal Allele: ~2 30x Cooperative Inhibition by ZFP-TFs Represses Mutant C9 Transcripts C9ORF72 Sense TSS Antisense TSS Disease Allele: >100x 28

29 2018 Priorities

30 Balanced manufacturing strategy ensures cgmp clinical supply for current and future pipeline programs Sangamo owned cgmp facility along with expanded agreement with Brammer Bio enables flexible supply to support expanding pipeline Sangamo cgmp facility initially focused on product development and Phase 1/2 clinical trial supply for new pipeline programs Brammer agreement provides dedicated capacity for clinical supply of Sangamo s lead development programs Capability to manufacture AAV and autologous / allogeneic cell therapies Balanced manufacturing approach to ensure clinical supply and control of quality, cost and timelines *Digital rendering of Sangamo cgmp facility 30

31 2018 steps toward long-term success of Sangamo 1 Clinical Demonstrate clinical progress on core assets with preliminary clinical data beginning 1H Pipeline Technology Partnerships Corporate Advance ST-400 BT program with FPI in mid-2018 and support Bioverativ IND filing for SCD. File IND for Fabry disease Continue to set gene editing standards for precision, efficiency and specificity and operationalize platform improvements Collaborate with the right partners to deliver best-in-class medicines to patients (e.g. oncology, CNS) Establish new headquarters and construct state-of-the-art cgmp manufacturing facility in Brisbane, California 31

32 Thank you.