Cartesian Therapeutics, Inc. · NASDAQ:RNAC

Cartesian Therapeutics — Selecta Biosciences — Investor Presentation (January 2017)

54 slides from Cartesian Therapeutics's investor presentation, Jan 9, 2017

  1. Slide 1: January 2017 Corporate Presentation

    January 2017 Corporate Presentation

  2. Slide 2: Safe Harbor / Disclaimer

    Safe Harbor / Disclaimer Any statements in this presentation about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the company”), including without limitation, statements regarding the development of its pipeline, the company's expectations about receiving payments from S

  3. Slide 3: Pioneering Precision Immune System Communication for Rare and Serious Diseases

    Pioneering Precision Immune System Communication for Rare and Serious Diseases Clinical-Stage Company focused on addressing the immunogenicity caused by biologic treatments Lead Program in Phase 2 with initial data expected in the first half of 2017 Upside Potential with immune stimulating programs

  4. Slide 4: Immunogenicity is a Serious Challenge to Biologic Therapy Development

    The Experts Agree Immunogenicity is a Serious Challenge to Biologic Therapy Development COMPROMISED EFFICACY Anti-drug antibody (ADA) formation neutralizes therapeutic benefits 4 UNPREDICTABLE RESPONSE Changed PK/PD through drug-ADA interaction SAFETY RISK Hypersensitivity reactions can impact patie

  5. Slide 5: Our Mission: Unlocking the Full Potential of Biologics

    R&D Failures Clinical Trial Failures Limited Market Uptake 5 Current patient population Potential patient population for biological drugs Enable new technologies Enhance existing drugs Rescue failed drugs Expand patient use Enable new classes of drugs Our Mission: Unlocking the Full Potential of Bio

  6. Slide 6: Imagine If We Could…

    IMAGINE IF WE COULD… 1. Effectively treat many more patients with existing biologics 2. Enable a host of new disease treatments for patients with rare and serious conditions 6

  7. Slide 7: The Key: Precise Communication with the Immune System

    The Key: Precise Communication with the Immune System Targeting immune cells Sending precise instructions Implementing the message Eliciting an amplified response Taken up by dendritic cells, which initiate and regulate immune responses Deliver a message of immune tolerance or activation by controll

  8. Slide 8: Mitigating Anti-Drug Antibodies by Inducing Regulatory T Cells

    Mitigating the Formation of Anti-Drug Antibodies by Inducing Regulatory T Cells 8 Potential to enable new therapies and improve efficacy/safety of existing biologics Regulatory T cell Naïve T cell Lymph Node B cell Helper T cell Targeting immune cells Dendritic cellSending precise instructions Impl

  9. Slide 9: Platform Designed to be Utilized Broadly

    Platform Designed to be Utilized Broadly 9 IMMUNE TOLERANCE SVP Encapsulated Rapamycin Encapsulating Nanoparticle PLA+PLA-PEG Targeted Immunotoxins AntibodiesViral VectorsEnzymes SVP-Rapamycin’s preclinical, clinical and manufacturing data can be applied across a broad range of product candidates

  10. Slide 10: Example of Immune System Education

    10 Example of Immune System Education Advate-Specific ADAs Day 0 7 14 21 28 57 81 123 143 187 Advate Advate Advate Advate Advate T im e (D a y s ) A n ti -F V II I a n ti b o d y ( µ g /m l) 0 5 0 1 0 0 1 5 0 2 0 0 0 2 0 4 0 6 0 8 0 ******* Teach + Treat Treat Empty Nanoparticle + Advate or SVP-Rapa

  11. Slide 11: Significant Platform Building Opportunity

    SEL-212 Refractory and chronic tophaceous gout Methylmalonic Acidemia (MMA) - Anc80 Vector Ornithine Transcarbamylase (OTC) Deficiency – AAV Vector Significant Platform Building Opportunity Therapeutic Enzymes Gene Therapy Oncology • Myozyme (Pompe) • IgA Protease • Other ERT • Additional Anc80 prog

  12. Slide 12: Product Candidate Selection Framework

    Product Candidate Selection Framework Immunogenicity Barrier for target drug/candidate that has underlying potential for efficacy Rare and Serious Disease with a high unmet need Clear Clinical and Regulatory Path based upon the strength of pre-clinical data and established clinical endpoints Ownersh

  13. Slide 13: Immune Tolerance Pipeline

    Immune Tolerance Pipeline Indication Description Preclinical Phase 1 Phase 2 Proprietary ADA Mitigation Programs Refractory Gout SVP-Rapamycin co-administered with pegsiticase (SEL-212) Methylmalonic Acidemia (MMA) SVP-Rapamycin co-administered with Anc80 vector Ornithine Transcarbamylase Deficiency

  14. Slide 14: 2p) ® = > N c Ww (6) = >) {b) Qa (40) —

    2p) ® = > N c Ww (6) = >) {b) Qa (40) — ®O ie =

  15. Slide 15: Enzyme Therapy's Immunogenicity Challenges

    Potential to treat many rare and serious diseases with enzyme replacement and microbial enzyme therapies High immunogenicity seen in response to virtually all enzyme replacements for lysosomal storage diseases Most are foreign to the patient’s immune system and can provoke immune responses No altern

  16. Slide 16: Developing SEL-212: The First Non-Immunogenic Uricase Enzyme Product Candidate

    Developing SEL-212: The First Non-Immunogenic Uricase Enzyme Product Candidate Immunogenicity Barrier ▪ Uricase is highly effective in breaking down uric acid deposits, but is foreign to the human immune system, causing immunogenicity ▪ Two approved products (Krystexxa and Elitek) cause neutralizing

  17. Slide 17: Severe Gout is a Rare and Serious Disease with Substantial Unmet Needs

    No/not diagnosed tophi Severe Gout is a Rare and Serious Disease with Substantial Unmet Needs 8.3 3.1 5.2 4.7 0.5 US Gout Patients Rx Treated Primary Care, Endo, Nephro, Other Rheum* Gout Patient Stocks (million)1 530,000 370,000 Estimated SEL-212 Target Patient Population1 US Gout treated at Rheum

  18. Slide 18: SEL-212 Phase 1/2 Clinical Program Status

    SEL-212 Phase 1/2 Clinical Program Status Phase 1b Phase 1a Phase 2 Patient visits complete Data presented in December 2016 Trial complete Both goals achieved Patient dosing started in October 2016 Objective Demonstrate that SEL 212: Mitigates ADAs Enables prolonged control of uric acid Define ef

  19. Slide 19: Phase 1b Multicenter U.S. Clinical Trial

    Phase 1b Multicenter U.S. Clinical Trial 19 Clinicaltrials.gov NCT02648269 *Excludes exploratory group of 5 patients at 0.03 mg/kg SEL-212 0.5 mg/kg SVP-Rapamycin 0.3 mg/kg SVP-Rapamycin 0.1 mg/kg SVP-Rapamycin 0.03 mg/kg SVP-Rapamycin 0.3 mg/kg SEL-212 0.03 mg/kg SEL-212 Pegsiticase alone 0.15 mg/k

  20. Slide 20: Clinical Activity of SVP-Rapamycin + Pegsiticase

    20 0 2 4 6 8 1 0 0 2 4 6 8 1 0 0 2 4 6 8 1 0 S e ru m U ric A cid ( m g /d L ) 0 2 4 6 8 1 0 0 2 4 6 8 1 0 Day 0 7 14 21 30 Loss of control over serum uric acid levels by day 14 No effect on serum uric acid levels Dose-dependent reduction in serum uric acid levels 0.03 mg/kg SVP-Rapamycin 0.4 mg/kg

  21. Slide 21: Clinical Activity of SVP-Rapamycin + Pegsiticase

    21 0 2 4 6 8 1 0 0 2 4 6 8 1 0 S e ru m U ric A cid ( m g /d L ) 0 2 4 6 8 1 0 0 2 4 6 8 1 0 0.03 mg/kg SVP-Rapamycin 0.4 mg/kg Pegsiticase 0.10 mg/kg SVP-Rapamycin 0.4 mg/kg Pegsiticase 0.4 mg/ kg Pegsiticase only 0.03, 0.1, 0.3 mg/kg SVP-Rapamycin only 0.30 mg/kg SVP-Rapamycin 0.4 mg/kg Pegsiticas

  22. Slide 22: Anti-Uricase Antibody and Serum Uric Acid Levels

    Uric acid (mg/dL) ADA (Titer) 108-0010 7 1080 103-0015 6 9720 104-0032 1.9 1080 109-0012 6.3 1080 104-0036 8.8 9720 Day 30 Subject number Day 30 Anti-Uricase Antibody and Serum Uric Acid Levels Uric acid (mg/dL) ADA (Titer) 107-0027 <0.1 Neg 107-0028 <0.1 Neg 104-0050 <0.1 Neg 104-0060 <0.1 120 103-

  23. Slide 23: Phase 1a and Phase 1b Safety Overview

    Phase 1a and Phase 1b Safety Overview Current unaudited data • Pegsiticase only - Generally well tolerated at all dose levels • SVP-Rapamycin alone - 17x dose range tested to determine maximum tolerated dose (MTD) - At 0.5 mg/kg, two SAEs (stomatitis) - Known side effect of rapamycin - Resolved with

  24. Slide 24: "3 + 2" Dosing Phase 2 Trial Ongoing with Initial Data Expected in 1H17

    “3 + 2” Dosing Phase 2 Trial Ongoing with Initial Data Expected in 1H17 1 29 57 85 113Days Cohort 1 Cohort 2 Cohort 3 Cohort 4 0.2 mg/kg Pegsiticase 0.2 mg/kg Pegsiticase 0.4 mg/kg Pegsiticase 0.4 mg/kg Pegsiticase 0.05 mg/kg SVP-Rapamycin + 0.2 mg/kg Pegsiticase 0.2 mg/kg Pegsiticase 0.05 mg/kg SVP

  25. Slide 25: Gene Therapy

    Gene Therapy

  26. Slide 26: Gene Therapy's Immunogenicity Challenges

    AAV-based gene therapy is maturing but restricted by several types of immunogenicity, limiting application breadth 2. Cellular immune responses associated with loss of transgene expression observed in recently reported hemophilia B trials, limiting maximum tolerated dose 1. Pre-existing antibodies t

  27. Slide 27: Mitigating AAV Immunogenicity and Enabling Repeat Dosing in Mice

    Mitigating AAV Immunogenicity and Enabling Repeat Dosing in Mice… Serum Factor IX Expression 0 2 0 4 0 6 0 0 5 0 0 0 1 0 0 0 0 1 5 0 0 0 2 0 0 0 0 2 5 0 0 0 D a y s A n ti - A A V 8 A n ti b o d y T it e r Anti-AAV8 Antibody Titer 0 20000 40000 60000 80000 100000 120000 140000 160000 180000 200000 3

  28. Slide 28: …and Non-Human Primates

    …and Non-Human Primates 1) Control NP 2) SVP-Rapamycin 3) SVP-Rapamycin AAV8-GAA AAV8-human Factor IX Day 0 Day 30 Day 45 Screen d-12 d3 d15 d45N eu trali z ing An tibod y T it e r AAV8-Specific ADAs Control NP SVP-Rapamycin SVP-Rapamycin Day 45 Serum Human Factor IX Hu m a n F a ct o r IX (n g /m l

  29. Slide 29: Depletion of Regulatory T Cells Restores Anti-AAV8 Antibody Response

    N o d e p le t i o n C D 2 5 d e p le t i o n 0 5 0 0 0 1 0 0 0 0 1 5 0 0 0 2 0 0 0 0 * * a n t i- A A V 8 I g G ( n g / m L ) Depletion of Regulatory T Cells with Anti-CD25 Antibody Restores Anti-AAV8 Antibody Response N o D e p le t i o n C D 2 5 D e p le t i o n 0 11 0 0 4 21 0 0 4 31 0 0 4 4

  30. Slide 30: Developing a Repeat Dose Gene Therapy for OTC Deficiency

    Developing a Repeat Dose Gene Therapy for Ornithine Transcarbamylase (OTC) Deficiency Immunogenicity Barrier ▪ Infants require treatment prior to metabolic crisis to avoid CNS effects; retreatment likely needed as patients grow ▪ Repeat gene therapy dosing impossible due to neutralizing antibodies t

  31. Slide 31: Developing the Only Known Gene Therapy Candidate for MMA

    Developing the Only Known Gene Therapy Candidate for Methylmalonic Acidemia (MMA) Immunogenicity Barrier ▪ Infants require treatment prior to metabolic crisis to avoid CNS effects; retreatment likely needed as patients grow ▪ Repeat gene therapy dosing impossible due to neutralizing antibodies to vi

  32. Slide 32: License Agreement with Spark Therapeutics

    License Agreement with Spark Therapeutics 32 • Announced in December 2016 • Provides Spark Therapeutics with exclusive worldwide rights to Selecta's SVP platform technology for up to five gene therapy targets. • Initial focus on combination of SVP with SPK-8011, Spark’s clinical Hemophilia A gene th

  33. Slide 33: Oncology

    Oncology

  34. Slide 34: Oncology's Immunogenicity Challenges

    Biologic therapies required to target tumor cells and mount a strong attack ADA issues common upon initial treatment cycle Several intermittent treatment cycles usually required to halt or reverse tumor growth Clinical trial use of global immunosuppressants may not be sufficiently effective to preve

  35. Slide 35: Developing a Recombinant Pseudomonas Immunotoxin Targeting Mesothelin

    Developing a Highly Potent Recombinant Pseudomonas Immunotoxin Targeting Mesothelin Benefit from Immunogenicity Removal ▪ LMB-100 induces neutralizing antibodies upon first dose in almost all patients, limiting dosing to one administration cycle; insufficient to control tumor ▪ Global immunosuppress

  36. Slide 36: Preclinical Data Supports SVP-Rapamycin + LMB-100 Combination Therapy

    Preclinical Data Supports the Benefits of SVP-Rapamycin + LMB-100 Combination Therapy Prevents formation of anti-drug antibodies Restores LMB-100’s anti-tumor response SVP alone does not accelerate tumor growth SVP-Rapamycin LMB-100 T u m o r G r o w t h D a y s s i n c e t u m o r i n o c u l a t i

  37. Slide 37: Immune Tolerance Pipeline

    Immune Tolerance Pipeline Indication Description Preclinical Phase 1 Phase 2 Proprietary ADA Mitigation Programs Refractory Gout SVP-Rapamycin co-administered with pegsiticase (SEL-212) Methylmalonic Acidemia (MMA) SVP-Rapamycin co-administered with Anc80 vector Ornithine Transcarbamylase Deficiency

  38. Slide 38: Allergy, Autoimmune and Immune Activation Pipeline

    Upside Potential With Selecta’s Allergy, Autoimmune and Immune Activation Pipeline Indication Description Preclinical Phase 1 Phase 2 Allergies and Autoimmune Programs Peanut Allergy SVP-adjuvant and SVP-food allergen Celiac Disease SVP-Rapamycin and SVP-gluten Type 1 Diabetes SVP-Rapamycin and SVP-

  39. Slide 39: Q3 Financial Overview

    Q3 Financial Overview For the Quarter Ended (In thousands, except share and per share data) September 30, 2016 September 30, 2015 Grant & Collaboration Revenue $1,048 $1,607 Research & Development Expenses 6,021 5,483 General & Administrative Expenses 2,495 2,195 Net Loss Attributable to Common Stoc

  40. Slide 40: See: SELECTA

    See: SELECTA

  41. Slide 41: SVP Peanut Allergy Program

    January 2017 SVP Peanut Allergy Program

  42. Slide 42: Safe Harbor / Disclaimer

    Safe Harbor / Disclaimer Any statements in this presentation about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the company”), including without limitation, statements regarding the development of its pipeline, the company's expectations about receiving payments from S

  43. Slide 43: Rationale for Selecta's Peanut Allergy Program

    Rationale for Selecta’s Peanut Allergy Program Growing Unmet Need: Prevalence has increased ~4-fold over last 20 years, affecting 1.4% of children in US Potential Life-Threatening Anaphylactic Responses Expansion Opportunities: Potential to address other allergies by combining SVP-Rapamycin with SVP

  44. Slide 44: Treating Allergies with Synthetic Vaccine Particles by Inducing Immune Switching

    Crude Peanut Extract (CPE) R848 Treating Allergies with Synthetic Vaccine Particles (SVP) by Inducing Immune Switching SVP-Immune Switching Particles SVP-CPE & SVP-R848 SVP-R848 was generally well tolerated in a phase 1 clinical nicotine vaccine trial for smoking cessation SVP Allergy Program* • Imm

  45. Slide 45: SVP Encapsulation of Crude Peanut Extract Maintains Major Allergens

    45 Ara h6 Lane Sample 1 MW standards 2 CPE lot #1 4 CPE lot #2 6 SVP-CPE (lot #1) 8 SVP-CPE (lot #1) 10 SVP-CPE (lot #2) 12 SVP-CPE (lot #2) Ara h1 1 2 3 4 5 6 7 8 9 10 11 12 Ara h2 Ara h3 SVP Encapsulation of Crude Peanut Extract Reproducibly Maintains Representation of Major Allergens CPE #1 CPE #

  46. Slide 46: SVP Treatment Inhibits Systemic Anaphylaxis in Peanut Allergy Models

    Therapeutic SVP Treatment Inhibits Systemic Anaphylaxis in Peanut Allergy Models T i m e a f t e r c h a l l e n g e ( m i n ) T e m p e ra tu re (  C ) 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 3 0 3 1 3 2 3 3 3 4 3 5 3 6 3 7 3 8 3 9 CPE challenge of SVP-treated and untreated mice 0 7 40 47 61 8

  47. Slide 47: Activity of SVP in a Peanut-Specific Cutaneous Anaphylaxis Model

    Activity of SVP in a Peanut-Specific Cutaneous Anaphylaxis Model T im e a fte r c h a lle n g e (m in ) E a r th ic k n e s s ; c h a ll e n g e -m o c k ( m m ) 0 2 0 4 0 6 0 8 0 -0 .0 5 0 .0 0 0 .0 5 0 .1 0 0 .1 5 0 .2 0 0 .2 5 * * * * * * * * * * /* * * * * /* * 0 7 40 47 61 82 104 CPE + alum (i.

  48. Slide 48: SVP-CPE Does Not Induce Anaphylaxis at >50x Higher Dose

    SVP-CPE Does Not Induce Anaphylaxis Even at >50x Higher Dose than Required for Efficacy 0 15 30 50 70 90 28 30 32 34 36 38 40 T im e a f te r c h a l le n g e (m in ) T e m p e ra tu re (  C ) * * * * * * * * * * * * * * * * * * * * 0 15 3 5 70 90 32 34 36 38 40 T im e a fte r c h a lle n g e (m in

  49. Slide 49: A Non-Human Primate Model of Allergy: Background Information

    A Non-Human Primates (NHP) Model of Allergy: Background Information • Goal to translate findings in rodents to non-human primates (NHP) • No NHP peanut allergy available • However, NHPs that are naturally allergic to Ascaris suum, a parasite, are available. The Ascaris model was used to validate fin

  50. Slide 50: Study Design for NHP Model of Ascaris-Mediated Allergic Rhinitis

    Intranasal ascaris challenge followed by acoustic rhinometry. Measurements Days: -14, 63, 77, 98 & 119 Subcutaneous Treatment: (Days 0, 7, 14, & 42) with SVP-R848 or SVP-Ascaris & SVP-R848 D Day: -14 0 7 14 42 49 63 70 77 84 98 105 119 126 Weeks post treatment 1 3 4 5 6 8 9 11 12 Study Design for NH

  51. Slide 51: SVP-Treated NHPs Showed Improved Rhinometry Scores

    SVP-Treated NHPs Showed Improved Rhinometry Scores at 5 Weeks After Treatment M in im u m C r o s s -S e c tio n a l A re a % o f P re -a s c a ri s c h a ll e n g e A re a [R 8 4 8 6 0 u g ] [R 8 4 8 6 0 u g ] D a y 6 3 [R 8 4 8 6 0 u g ] D a y 7 7 [R 8 4 8 6 0 u g /a s c 6 u g ] [R 8 4 8 6 0 u g /

  52. Slide 52: After Cycles, SVP-Treated NHPs Remained Allergy Free for >8 Months

    After 3 Cycles, SVP-Treated NHPs Remained Allergy Free for >8 Months Ascaris extract R848 SVP-R848SVP-Ascaris • In previous studies, NHPs typically returned to baseline levels (~20-30% of pre-ascaris challenge) by 8-11 weeks after treatment • After Cycle 1, majority of NHPs returned to baseline leve

  53. Slide 53: Target Profile and Differentiation of SVP in Peanut Allergies

    Target Profile and Differentiation of SVP in Peanut Allergies Treatable population Safety • Mild to moderate cases • Treatment success rate decreases with age of patients • Children preferred target group De-sensitization • Anaphylaxis and patient drop out from some clinical trials observed Onset an

  54. Slide 54: See: SELECTA

    See: SELECTA

Selecta Biosciences — Investor Presentation (January 2017) on 6ix