Q4 and Full Year 2017 Conference Call. February 22, 2018

Transcription

1 Q4 and Full Year 2017 Conference Call February 22, 2018

2 Agenda Welcome McDavid Stilwell VP, Corporate Communications and Investor Relations Q and Full Year Review and Recent Highlights Dr. Sandy Macrae Chief Executive Officer Business and Strategic Update Curt Herberts Chief Business Officer Q4 and Full Year 2017 Financial Review Kathy Yi Chief Financial Officer Clinical Development Dr. Ed Conner Chief Medical Officer Research and Discovery Dr. Michael Holmes VP, Research

3 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. 3

4 Corporate Overview and Recent Highlights Dr. Sandy Macrae Chief Executive Officer

5 We are committed to translating ground-breaking science into genomic therapies that transform patients lives 5

6 Sangamo is investing across four technology platforms for genomic medicines Gene Therapy Genome Editing Cell Therapy Gene Regulation 6

7 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 7

8 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 8

9 Business and Strategic Update Curt Herberts Chief Business Officer Kite / Gilead Collaboration Therapeutic Area Strategy

10 Kite / Gilead deal scope 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 10

11 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 11

12 Investment across key therapeutic areas with a balanced approach to product development Hematology Inherited Metabolic Diseases Central Nervous System Oncology Immunology Hemophilia A (SB-525) Hemophilia B (SB-FIX) Beta-thalassemia (ST-400) Sickle cell disease (BIVV-003) MPS I (SB-318) MPS II (SB-913) Fabry disease (ST-920) Tauopathies ALS/FTLD (C9ORF72) Huntington s disease CAR / TCR / NKR Cell Therapies Genome edited cell therapies for autoimmune disorders Internal investments around Inherited Metabolic Diseases and Immunology 12

13 Product portfolio diversified across therapeutic area and technology Therapeutic Area Research Preclinical Phase 1/2 Phase 3 Collaborator Hematology Hemophilia A (SB-525) Hemophilia B (SB-FIX) Beta-thalassemia (ST-400) Sickle Cell Disease (BIVV-003) Inherited Metabolic Diseases MPS I (SB-318) MPS II (SB-913) Fabry Disease (ST-920) 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 13

14 Financial Review Kathy Yi Chief Financial Officer Q4 and Full Year 2017 Financial Results

15 Q4 and full year 2017 financial results Revenues Operating Expenses Q Q FY 2017 FY 2016 $in MM, except per share data Year End 2017 Cash: $245M R&D G&A Total Operating Expenses Operating Loss (13.8) (9.8) (56.4) (72.6) Net Loss (13.1) (9.6) (54.6) (71.7) Revenues: $37M Net Loss per Share ($0.15) ($0.14) ($0.70) ($1.02) Cash Net Provided by (Used in) Operations (20.3) 7.7 Ending Cash Balance $245M $143M Opex: $93M 15

16 Sangamo Clinical Development Dr. Ed Conner Chief Medical Officer SB-525: Hemophilia A SB-FIX: Hemophilia B SB-318: MPS I SB-913: MPS II ST-400: Beta-thalassemia

17 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 17

18 SB-913: MPS II clinical program summary Phase I/II Open Label Study Patients Cohorts Data Up to 9 adult (18+) males with attenuated MPS II 3 dose cohorts Preliminary data expected by mid-2018 Clinical Trial Status IND open Study initiated 5 sites active 2 subjects treated US Regulatory Designations Orphan Drug designation Fast Track designation Rare Pediatric Disease designation 18

19 SB-318: MPS I clinical program summary Phase I/II Open Label Study Patients Cohorts Data Up to 9 adults (18+) with attenuated MPS I 3 dose cohorts Preliminary data expected in 2018 Clinical Trial Status IND open Study initiated 5 sites active Multiple patients screening US Regulatory Designations Orphan Drug designation Fast Track designation Rare Pediatric Disease designation 19

20 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 Filed Study initiated 4 sites active Study initiation US Orphan Drug designation Fast Track designation 20

21 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 21

22 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 3 patients treated US EMA Regulatory Designations Orphan Drug designation Fast Track designation Orphan Medicinal Product designation 22

23 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 23

24 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 24

25 Sangamo Research Dr. Michael Holmes VP, Research ST-920: Fabry disease Oncology C9ORF72-linked ALS/FTLD

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

27 Manufacturing allogeneic T-cell therapies with ZFNs cgmp Manufacturing Facility HLA knock-out TCR knock-out Targeted insertion of CAR gene Healthy Donor Apheresis Isolate T-cells from a healthy donor s blood T-cell Manufacturing Transient, non-viral delivery of ZFN mrna to manufacture universal CAR-T cells via singlestep, multiplexed gene editing Harvest & Storage Universal CAR-T cells are harvested, cryo-preserved and stored in a secure cell bank Infusion (Patients) Universal, off-the-shelf CAR-T cells are infused into new patients, on-demand 27

28 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% 28

29 Simultaneous multiplex editing efficiencies: 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) 29

30 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 30

31 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 31

32 Closing Remarks Dr. Sandy Macrae Chief Executive Officer

33 Thank you.