Cartesian Therapeutics, Inc. · NASDAQ:RNAC
Cartesian Therapeutics — Selecta Biosciences — Investor Presentation (June 2017)
38 slides from Cartesian Therapeutics's investor presentation, Jun 21, 2017
Slide 1: Corporate Overview
June 21, 2017 Corporate Overview
Slide 2: Safe Harbor / Disclaimer
Safe Harbor / Disclaimer 2 Any statements in this presentation about the future expectations, plans and prospects of Selecta Biosciences, Inc. (“the company”), including without limitation, the progress of the Phase 1/2 clinical program of SEL-212, the potential of SEL-212 to treat severe gout patie
Slide 3: Immunogenicity is Now Recognized as a Serious Challenge for Biologic Therapies
Immunogenicity is Now Recognized as a Serious Challenge for Biologic Therapies COMPROMISED EFFICACY Anti-drug antibodies (ADAs) neutralize therapeutic benefit 3 UNPREDICTABLE RESPONSE Changed PK/PD through drug-ADA interaction SAFETY RISK Hypersensitivity reactions can impact patients I M M U N O G
Slide 4: Imagine If We Could…
IMAGINE IF WE COULD… 1. Effectively treat many more patients with existing biologics 2. Enable a new generation of novel non-immunogenic biologics for rare and serious diseases 4
Slide 5: The Key: Mitigate Anti-Drug Antibodies by Inducing Regulatory T Cells
The Key: Mitigate Anti-Drug Antibodies by Inducing Regulatory T Cells Naïve T cell Lymph Node B cell Helper T cell Dendritic cell SVP-Rapamycin Biologic drug Preventing ADAs Inducing a tolerogenic response to a biologic drug (antigen) Regulatory T cell Implementing the message Sending precise inst
Slide 6: Leveraging Nanoparticles to Deliver Instructions to the Immune System
Leveraging Nanoparticles to Deliver Instructions to the Immune System I.V. Injection (6hr post-injection) Spleen Spleen harvested 24 hr after I.V. Injection of fluorescent NPs SVP Antigen SVP Macrophages Dendritic cells B cells 6
Slide 7: Example of Immune System Education
7 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-Rapam
Slide 8: Plan for SVP Immune Tolerance Platform Expansion
Proprietary program(s) Potential program(s) 8 SEL-212 for Chronic Severe Gout Commercially attractive Rare disease Rapid ADA onset Clear endpoint Adult patients Single Treatment Chronic Treatment Adult Patients Cancer Patients Pediatric Patients Oncology (LMB-100) Enzyme Replacement Therap
Slide 9: SEL-212 for Chronic Severe Gout
SEL-212 for Chronic Severe Gout
Slide 10: Selecta's Lead Product Candidate: SEL-212
Selecta’s Lead Product Candidate: SEL-212 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 inhibitory antibodies in ~60% of patients and car
Slide 11: Substantial Unmet Need for Chronic Severe Gout Patients
Substantial Unmet Need for Chronic Severe Gout Patients 11 Tophi Significantly Increase Mortality Risk3 No/not diagnosed tophi 8.3 3.1 5.2 4.7 0.5 Patients Rx treated Primary care, endo, nephro, other Rheumatologists U.S. Gout Patients (million)1 530,000 370,000 Estimated SEL-212 Target Patient Popu
Slide 12: What is Chronic Severe Gout?
What is Chronic Severe Gout? (1) IMS, Desk Research (2) Selecta rheumatologist interviews, Crystal patient registry (3) Choi HK et al, Tophaceous Gout and the Risk of Mortality: A General Population-Based Study, ACR, Sept. 2016 (4) Zhu Y, et al, Comorbidities of gout and hyperuricemia in the US gene
Slide 13: Resolving Tophi and Uric Acid Deposits with Monthly Uricase Treatments
Resolving Tophi and Uric Acid Deposits with Monthly Uricase Treatments 13 6.8 6.0 Seru m U ri c A c id ( m g /d L ) Time Transition from uricase to oral therapies Before1 After1 Uric acid deposits Calcium deposits Very low sUA levels enable rapid tophi resolution 12-24 week treatment cycle (1) Arujo
Slide 14: Phase 1b Demonstrates SEL-212's Clinical Activity for ≥30 Days
14 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
Slide 15: Phase 1b Trial Shows Correlation Between ADA Titers, Pegsiticase Activity and sUA
Phase 1b Trial Shows Correlation Between ADA Titers, Pegsiticase Activity and sUA 15 0 5 1 0 1 5 2 0 2 5 3 0 0 3 6 9 1 2 0 5 1 0 1 5 2 0 2 5 3 0 0 3 6 9 1 2 0 5 1 0 1 5 2 0 2 5 3 0 0 3 6 9 1 2 0 5 1 0 1 5 2 0 2 5 3 0 0 3 6 9 1 2 S e ru m u ri c a cid ( m g /d L ) 0 5 1 0 1 5 2 0 2 5 3 0 1 0 - 1 1 0
Slide 16: Clinical Objectives of SEL-212 Program
Clinical Objectives of SEL-212 Program Phase 1b Phase 1a Phase 2 Demonstrate that SEL 212: Mitigates ADAs Enables prolonged control of uric acid for >30 days Define effective monthly dose of pegsiticase Demonstrate rapid formation and kinetics of ADAs Demonstrate SEL-212’s safety, tolerability a
Slide 17: Phase 2 Trial Overview
Trial Completion Phase 2 Trial Overview 17 • Patients with symptomatic gout and serum uric acid levels >6 mg/dL • Safety, tolerability and pharmacokinetics of multiple doses of SEL-212 and pegsiticase alone • Reduction of serum uric acid levels • Reduction of ADA levels • Multiple ascending dose coh
Slide 18: Status of Phase 2 Trial Cohorts
18 Status of Phase 2 Trial Cohorts Cohort Treatment Weeks 0, 4, 8 Treatment Weeks 12 + 16 Status Pegsiticase SVP-Rapamycin Pegsiticase 1 0.2 mg/kg None 0.2 mg/kg Enrollment terminated 2 0.4 mg/kg None 0.4 mg/kg Enrollment terminated 3 0.2 mg/kg 0.05 mg/kg 0.2 mg/kg Dosing completed 4 0.4 mg/kg 0.05
Slide 19: Minimal Effective Dose of SEL-212 Now Defined
19 Minimal Effective Dose of SEL-212 Now Defined 0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0 0 3 6 9 1 2 SU A (m g/d L) 0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0 0 3 6 9 1 2 SU A (m g/d L) 0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 1 5 1 6 1 7 1 8 1 9 2 0 0 3 6
Slide 20: Cohort 6: Minimal Effective Dose of SEL-212
20 Cohort 6: Minimal Effective Dose of SEL-212 • Sustained reduction of sUA after two injections of pegsiticase alone suggests induction of immune tolerance • Cohort being expanded to 10 evaluable patients # Stopping rules met (sUA level >1 mg/dL at 21 days after dosing) Unaudited data as of June 12
Slide 21: Cohort 7: 0.2 mg/kg of Pegsiticase + 0.1 mg/kg of SVP-Rapamycin
21 Cohort 7: 0.2 mg/kg of Pegsiticase + 0.1 mg/kg of SVP-Rapamycin • sUA remains controlled in a majority of patients following repeat doses • One patient withdrew consent after experiencing cholecystitis (not related to study drug) • One patient experienced an infusion reaction and fully recovered
Slide 22: Cohort 8: 0.4 mg/kg of Pegsiticase + 0.1 mg/kg of SVP-Rapamycin
22 Cohort 8: 0.4 mg/kg of Pegsiticase + 0.1 mg/kg of SVP-Rapamycin • sUA remains controlled in a majority of patients following repeat doses • Two patients met stopping rules • One of these patients was inadvertently re- dosed; experienced an infusion reaction and fully recovered 0.4 mg/kg Pegsitica
Slide 23: Results to Date Suggest Reduction in Flare Frequency During SEL-212 Therapy
23 • Urate lowering therapies typically increase the incidence of flares at the beginning of therapy • Data indicate SEL-212 lowers flares compared to pegsiticase alone 0 . 0 5 0 . 0 8 0 . 1 0 2 0 4 0 6 0 % P a t i e n t s w i t h f l a r e i n m o n t h s 1 - 3 % P a t ie n t s w it h f la r e s S
Slide 24: Phase 2 Safety Overview
Phase 2 Safety Overview 24 • SEL-212 has been generally well tolerated at clinically active doses following repeated administrations • Eight SAEs reported to date in the trial: - Seven infusion reactions, four of which were in cohorts receiving pegsiticase alone or pegsiticase in combination with th
Slide 25: Phase 2 Adverse Events
25 Phase 2 Adverse Events Cohort Entire Study 1 2 3 4 5 6 7 8 N(%) 62 3 3 9 10 6 10 11 10 ≥ 1TEAE 50(80.1) 3 2 8 7 5 8 8 9 ≥ SAE 8 1 1 2 0 0 1* 1#, 1 1* Death 0 0 0 0 0 0 0 0 0 Discontinuation due to TEAE 9 1 1 2 0 0 1*, 1 1#, 1 1* Specific TEAEs Infusion reaction 8(12.9) 1 1 2 0 0 1*, 1 1 1* Gout f
Slide 26: Oncology
Oncology
Slide 27: Developing a Highly Potent Recombinant Pseudomonas Immunotoxin Targeting Mesothelin
Developing a Highly Potent Recombinant Pseudomonas Immunotoxin Targeting Mesothelin Benefit of Immunogenicity Mitigation ▪ LMB-100 induces inhibitory antibodies upon first dose in almost all patients, limiting dosing to one administration cycle; insufficient to control tumor ▪ Global immunosuppressa
Slide 28: Immunotoxin LMB-100
Immunotoxin LMB-100 • LMB-100: Pseudomonas exotoxin A linked to antibody Fab targeting mesothelin • Currently in Phase 1 clinical trials • Efficacy is limited by immunogenicity after one or two cycles in most patients Ira Pastan, M.D. Head, Molecular Biology Section National Cancer InstituteLMB-100
Slide 29: Clinical Activity of LMB-100 Precursor in Mesothelioma
Clinical Activity of LMB-100 Precursor in Mesothelioma Day 12 3 months 15 months Before treatment 1.6 months 8 months Patient 5 • Widely metastatic peritoneal mesothelioma • Survived 32 months Patient 3 • Extensive pleural mesothelioma • Survival >64 months (still alive) S u m o f ta rg e t le s io
Slide 30: Preclinical Data Supports the Benefits of 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
Slide 31: Gene Therapy
Gene Therapy
Slide 32: Selecta's Proprietary Gene Therapy Programs
Selecta’s Proprietary Gene Therapy Programs 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 viral capsid ▪ Cellular immune responses
Slide 33: Benefits of ADA Avoidance in Gene Therapy
Benefits of ADA Avoidance in Gene Therapy Inhibiting Liver Inflammation from First Dose Allowing for Repeat Dosing Enabling Dose Titration S V P E m p ty N P -1 0 1 2 3 4 5 C D 8 m R N A ( C t) CD8 T cell Liver Infiltrates S V P E m p ty N P 0 5 1 0 1 5 2 0 ** A L T a ct iv ity ( m U /m L ) Seru
Slide 34: Anc80/synMUT Proof of Concept in Mouse Model of MMA
0 5 0 1 0 0 1 5 0 2 0 0 0 5 0 0 1 0 0 0 1 5 0 0 2 0 0 0 D a y s M M A ( M ) A n c 8 0 -h A A T -M u t4 5 e 1 2 V G A A V 8 -h A A T -M u t4 5 e 1 2 V G Anc80/synMUT Proof of Concept in Mouse Model of MMA at ASGCT 2017 Anc80 or AAV8 Retro Orbital injection Reducing MMA Levels With Anc80 and AAV8 In
Slide 35: Demonstration of the Role of Regulatory T Cells
Day 0 19 20 21 32 0 1 28 Demonstration of the Role of Regulatory T Cells Data generated in collaboration with Dr. Federico Mingozzi, Genethon Effect can be Transferred to a Recipient T Reg Depletion Negates Effect a n ti -A A V 8 I g G ( g /m L ) E m p ty N P S V P 0 5 1 0 1 5 2 0 * * * Anti-AAV8
Slide 36: Immune Tolerance Pipeline
Indication Description Preclinical Phase 1 Phase 2 Proprietary ADA Mitigation Programs Chronic Severe Gout SVP-Rapamycin co-administered with pegsiticase (SEL-212) Mesothelioma & Pancreatic Cancer* SVP-Rapamycin co-administered with LMB-100 Methylmalonic Acidemia (MMA) SVP-Rapamycin co-administered
Slide 37: Q1 Financial Overview
Q1 Financial Overview For the Quarter Ended (In thousands, except share and per share data) March 31, 2017 March 31, 2016 Grant & Collaboration Revenue $137 $2,088 Research & Development Expenses 11,044 6,648 General & Administrative Expenses 3,875 2,381 Net Loss Attributable to Common Stockholders
Slide 38: See: SELECTA
See: SELECTA
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