Cabaletta Bio, Inc. · NASDAQ:CABA
Cabaletta Bio — Investor Presentation (January 2020)
42 slides from Cabaletta Bio's investor presentation, Jan 10, 2020
Slide 1: Selective B cell ablation for autoimmune disease
Selective B cell ablation for autoimmune disease January 2020 EXHIBIT 99.1
Slide 2: Disclaimer and forward-looking statements
The following presentation, including any printed or electronic copy of these slides, the talks given by the presenters, the information communicated during any delivery of the presentation and any question and answer session and any document or material distributed at or in connection with the pres
Slide 3: Our vision: first curative targeted cellular therapies for autoimmune diseases
Develop and launch the first curative targeted cellular therapies for patients with autoimmune diseases Our vision
Slide 4: Developing CAAR T products with a biologic opportunity for cure
Developing CAAR T products (Chimeric AutoAntibody Receptor T) where there is a biologic opportunity for cure (over two dozen potential targets identified) by designing CAARs to selectively eliminate ONLY pathogenic B cells displaying targeted antibody while leveraging CART19 design and manufacturing
Slide 5: Leadership, Scientific Advisory Board and Board of Directors
Diversified with long-standing history of professional collaborations among team and with co-founders Leadership Steven Nichtberger, MD President, CEO & Chairman Scientific Advisory Board Board of Directors Michael Milone, MD PhD Co-chair, Co-founder Aimee Payne, MD PhD Co-chair, Co-founder Jay Sieg
Slide 6: Scientific platform and strategy
Scientific platform and strategy CAR T CELL CD19 CANCER CELL Chimeric Antigen Receptor T cell Kymriah Targeting Domain ANTI-CD19 ANTIBODY FRAGMENTS HEALTHY B CELL CD137 Costimulatory Domain CD3-Zeta Signaling Domain CAR T Therapy No Antibody-Mediated Immunity CAAR T Therapy Normal Immune System CAAR
Slide 7: Our CABA Platform
Our CABA (Cabaletta Approach for Selective B cell Ablation) Platform Proven ability to identify multiple product candidates Epitope mapping to determine regions targeted by autoantibodies Optimizing CAAR construct / design with the goal of selectively ablating reactive B cells Preclinical in vitro a
Slide 8: Cabaletta Pipeline
Cabaletta Pipeline * In our discovery stage, we perform epitope mapping and optimize CAAR construct and design. ** May not be required if Phase 2 is a registrational clinical trial. Multiple disease targets with preclinical evidence of selective and specific target engagement DSG3-CAART Mucosal Pemp
Slide 9: CAR T approved for B cell cancers; Cabaletta filling adjacent white space
CAR T therapy products are approved for B cell cancers Cabaletta product candidates are filling an adjacent white space Clinical Pivotal Marketed Oncology B Cell-Mediated Allo/Autoimmune Diseases DSG3-CAART (mPV) MuSK-CAART (MG) FVIII-CAART (HemA inhibitor) DSG3/1-CAART (mcPV) Preclinical / Discover
Slide 10: CAAR T white space and patent portfolio
CAR T therapy products are approved for B cell cancers Cabaletta product candidates are filling an adjacent white space Clinical Pivotal Marketed CAR T (Oncology) / CAAR T (Allo/Autoimmune) T-reg, NK, TCR, RBC, macroph1… Oncology B Cell-Mediated Allo/Autoimmune Diseases Preclinical / Discovery Paten
Slide 11: Patent rights pursued on a target by target basis
Patent rights pursued on a target by target basis Pursuing multiple levels of protection for CAAR constructs protein, nucleic acid, and engineered cells; and their use Expiration Dates: 2035-2039 (without patent term extensions) First issued US patent for CAAR therapy in pemphigus Exemplary Composit
Slide 12: DSG3-CAART for mucosal pemphigus vulgaris patients
DSG3-CAART for mucosal pemphigus vulgaris patients
Slide 13: Pemphigus Vulgaris CAAR T Preclinical Development (video)
Pemphigus Vulgaris CAAR T Preclinical Development (video) Ellebrecht…Milone, Payne, Science 2016 Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease Christoph T. Ellebrecht,1 Vijay G. Bhoj,2 Arben Nace,1 Eun Jung Choi,1 Xuming Mao,1 Michael Jeffrey Cho,1 Giovan
Slide 14: Pemphigus Vulgaris
Pemphigus Vulgaris Mucosal PV: 25% of U.S. pemphigus vulgaris Mucocutaneous PV: 75% of U.S. pemphigus vulgaris http://www.danderm-pdv.is.kkh.dk/atlas/3-157.html http://www.dermis.net/bilder/CD008/550px/img0042.jpg Associated Antibody Anti-DSG3 Clinical Signs Painful blisters of the orifices (mouth,
Slide 15: PV is an optimal lead indication for CAAR T therapy
DSG3 antibodies are widely considered to be necessary and sufficient to cause PV1 PV is an optimal lead indication for CAAR T therapy Serum anti-DSG3 antibodies are 98 - 100% sensitive and specific The DSG3 CAAR has published animal model proof-of-concept validation Depletion of B cells by rituximab
Slide 16: DSG3 EC1-4 CAAR designed to target all known pathogenic B cells in mPV
DSG3 EC1-4 CAAR is designed to target all known pathogenic B cells in mPV DSG3-CAART encompasses all known pathogenic epitopes Ohyama, Bungo, et al. "Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2–based swapped molecules." Journal of inve
Slide 17: No evidence of toxicity at clinically relevant doses
No evidence of toxicity at clinically relevant doses with selective and specific target engagement DSG3-CAART preclinical program summary of results Indicator Final Preclinical Results In vitro off-target toxicity No specific cytotoxicity observed at clinically relevant cell numbers toward a panel o
Slide 18: Study Endpoint & Objectives
Study Endpoint & Objectives Primary Endpoint: Adverse Events, including Dose Limiting Toxicity Secondary Objectives: DSG3 ELISA titer changes, rate of/time to/duration of remission, manufacturing success rate, CAAR T expansion/persistence Open-label study of DSG3-CAART in mucosal-dominant PV patient
Slide 19: Clinical trial assessments and timeframes
8 Days: Acute safety Up to Week -18: Screening Day -7 to -3: Pre-infusion visit 3 Months: Primary safety endpoint 3 years: Efficacy 15 yrs: Long-term follow-up CAART infusion Week -6 to -1: Apheresis and manufacturing Clinical trial assessments and timeframes Spindler, Volker, et al. "Mechanisms cau
Slide 20: Enrollment and expected data updates
Enrollment Patients dosed over 1-3 weeks for initial cohorts, then followed for at least 2-4 weeks before next patient Timelines may be delayed due to non-material changes or challenges, including among others: identifying appropriate patients for 1st trial of cell therapy in autoimmune disease miti
Slide 21: Soluble antibodies may alter DSG3-CAART proliferation dynamics
They can partially activate or inhibit DSG3 CAAR T cells1 Soluble antibodies may alter the dynamics of DSG3-CAART proliferation Ellebrecht, Christoph T., et al. "Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease." Science 353.6295 (2016): 179-184. Non-transdu
Slide 22: DesCAARTes trial will begin without a preconditioning regimen
The DesCAARTes trial will begin without a preconditioning regimen, but with a data-driven approach to potential incorporation as warranted Lymphodepletion Mechanism Oncology Autoimmunity Reduction of T cell growth cytokine sinks3 + + Depletion of suppressor cells4 + - Preconditioning regimens in CAA
Slide 23: MuSK-CAART for myasthenia gravis patients
MuSK-CAART for myasthenia gravis patients
Slide 24: MuSK MG is a highly feasible and valuable CAAR target
MuSK MG is a highly feasible and valuable CAAR target Clinically high unmet need with limited treatment options Like pemphigus, autoantibody titers drop after rituximab1,2, indicating the clinical potential of B cell depletion strategies in MuSK MG MuSK has similar modular structure and size as Dsg3
Slide 25: MuSK CAAR T cells specifically kill anti-MuSK target cells in vitro
MuSK CAAR T cells specifically kill anti-MuSK target cells in vitro Luciferase-expressing target B cells MuSK CAAR T cells luciferin Cell death No ATP = No bioluminescence Luminometer Luciferase Assay Negative control Anti-Ig2 MuSK domain Antibody Anti-Frizzle MuSK Domain Antibody Increased efficacy
Slide 26: FVIII-CAART for Hemophilia A inhibitor patients
FVIII-CAART for Hemophilia A inhibitor patients
Slide 27: B cell-mediated inhibition of Factor VIII reduces efficacy of replacement therapy
B cell-mediated inhibition of Factor VIII reduces efficacy of replacement therapy Hemophilia A and neutralizing alloantibodies https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A. Peyvandi, Flora, et al. "A randomized trial of factor VIII and neutralizing antibodie
Slide 28: Current management of FVIII neutralizing alloantibodies
Product Hemlibra FEIBA NovoSeven Mechanism Bispecific antibody binding FIX / FX Bypass inhibitor Bypass inhibitor Product Advate / Adynovate Eloctate Mechanism rFVIII therapy rFVIII therapy 3-fold increased risk of hemophilia related death; overall 40% higher mortality Current management of FVIII ne
Slide 29: FVIII-CAART Bridging Therapy
FVIII-CAART Bridging Therapy Potentially complementary to gene therapy products in development FVIII-CAART value proposition is unique Today Future Potential Inhibitors Immune Tolerance Induction (ITI) / Hemlibra Bypassing Therapy ITI Hemlibra Gene Therapy / rFVIII Poorly Managed No Inhibitors Cure
Slide 30: FVIII-CAART for hemophilia A patients with inhibitors
anti-A2 ~52% FVIII-CAART for hemophilia A patients with inhibitors Kahle, Joerg, et al. "Frequency and epitope specificity of anti–factor VIII C1 domain antibodies in acquired and congenital hemophilia A." Blood 130.6 (2017): 808-816. anti-A1 anti-C1 ~57% anti-C2 ~81% Epitopes on several domains of
Slide 31: Selective and specific target engagement: FVIII-CAART in vitro data
Selective and specific target engagement FVIII-CAART in vitro proof of concept data Cytotoxicity Cabaletta is developing optimized constructs designed to maximize the number of pathogenic domains and patients covered by the potential product candidate FVIII-CAAR Linker / Transmembrane Neg Control CA
Slide 32: DSG3/1-CAART for mucocutaneous PV patients
DSG3/1-CAART for mucocutaneous PV patients
Slide 33: DSG3/1 CAARs designed for mcPV
DSG3/1 CAARs designed for mcPV DSG3 and DSG1 autoantibodies most severe and common form of PV (~75%) mucosal blistering, plus skin erosion and blistering managed with immune suppression, similar to mPV high risk of relapse potential for hospitalizations and fatal infections Designed to cover all kno
Slide 34: No detected in vivo skin toxicity induced by DSG3/1-CAART
DSG1 CAAR T cells and DSG1 + DSG3 CAAR T No detected in vivo skin toxicity induced by DSG3/1-CAART DSG1 CAAR DSG3+DSG1 CAAR Anti-DSG CAR (Positive control) CART19 (Negative Control) CD3 H&E Designing optimal construct with both antigens in a single CAAR Lee, Jinmin, et al., "Preclinical development
Slide 35: Manufacturing
Cabaletta Bio Manufacturing
Slide 36: Manufacturing strategy: three stages
Manufacturing strategy: three stages Risk mitigating, capital efficient, milestone gated progression proceeding as planned Stage 1: Penn DSG3-CAART Phase 11 Stage 2: CMOs & CABA Process MuSK-CAART Phase 1 Stage 3: Cabaletta Facility Commercialization & Scale-Up Data permitting Partnership establishe
Slide 37: CAR T vs CAAR T manufacturing process
CAR T vs CAAR T manufacturing process1 Penn-sponsored CD19 CAR IND CMC data has been cross-referenced in DSG3-CAART IND to provide additional data reflecting alignment. Manufacturing challenges were due to release specifications: https://www.biopharmadive.com/news/novartis-hits-car-t-manufacturing-s
Slide 38: The Penn-Cabaletta Alliance and IND timeline
An experienced team has accelerated IND filing but faces expected ‘academic CMO’ challenges ahead The Penn-Cabaletta1 Alliance In addition to the cofounders, Steven Nichtberger, MD is a professor at Penn, and Gwendolyn Binder PhD is a former employee at Penn. Porter, David L., et al. "Chimeric antig
Slide 39: Financial Update
Cabaletta Bio Financial Update
Slide 40: Key financial highlights and funding history
Key financial highlights and funding history Financial Highlights 9 months ended 09/30/2019 Proforma 09/30/2019 Cash and Cash Equivalents $71.0mn $142.1mn1 Operating Expenses $12.8mn $12.8mn Cash Runway - At least through 1Q 2022 Funding History Round Date Amount ($mn) New Investors Convertible Note
Slide 41: Recent and anticipated catalysts
2019 Recruited uniquely qualified leadership team with longstanding connections Established broad alliance with Penn to accelerate DSG3-CAART clinical development Secured first issued US product patent and expanded portfolio Expanded Penn license to include filed patents for one additional target Ma
Slide 42: Selective B cell ablation for autoimmune disease
Selective B cell ablation for autoimmune disease January 2020