Cabaletta Bio, Inc. · NASDAQ:CABA
Cabaletta Bio — Investor Presentation (June 2020)
31 slides from Cabaletta Bio's investor presentation, Jun 3, 2020
Slide 1: Corporate Presentation June 2020
Corporate Presentation JUNE 2020 Exhibit 99.1
Slide 2: Disclaimer
Disclaimer 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 wi
Slide 3: Develop and launch the first curative targeted cellular therapies for autoimmune diseases
Develop and launch the first curative targeted cellular therapies for patients with autoimmune diseases
Slide 4: Cabaletta overview
Cabaletta overview Engineering and developing CAAR T products to treat B cell-mediated autoimmune diseases Leveraging commercially approved CART19 technology though Penn partnership Pursuing targets where there is a biologic opportunity for cure with the CABA platform First mover advantage developin
Slide 5: CAR T Therapy vs CAAR T Therapy
CAR T Therapy CAAR T Therapy Our scientific platform leverages CAR T technology Chimeric AutoAntibody Receptor T cell CABA CAAR T Chimeric Antigen Receptor T cell Kymriah
Slide 6: CABA platform
CABA (Cabaletta Approach for Selective B cell Ablation) platform Epitope mapping to determine regions targeted by autoantibodies Optimize CAAR construct / design with the goal of selectively ablating reactive B cells Preclinical in vitro and in vivo testing to evaluate efficacy and safety Scientific
Slide 7: Pipeline addressing multiple disease targets
Indication Program Discovery1 Preclinical Phase 1 Phase 2 Phase 32 Mucosal Pemphigus Vulgaris DSG3-CAART Mucocutaneous Pemphigus Vulgaris DSG3/1-CAART MuSK Myasthenia Gravis MuSK-CAART Hemophilia A w/ FVIII Alloantibodies FVIII-CAART Pipeline addressing multiple disease targets 1 In our discovery st
Slide 8: DSG3-CAART for patients with mucosal pemphigus vulgaris
DSG3-CAART for patients with mucosal pemphigus vulgaris
Slide 9: Working to meet an unmet need for patients
Working to meet an unmet need for patients Overview of Pemphigus Vulgaris Image credit: D@nderm Joly, Pascal, et al. "First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label rand
Slide 10: DSG3-CAART encompasses all known pathogenic epitopes
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 investigative dermatology 132.4 (2012): 1158-1168. Antibodies that target the
Slide 11: Tolerability and target engagement preclinical data
Tolerability Target Engagement No evidence of toxicity at clinically relevant doses with selective and specific target engagement DSG3-CAART preclinical data INDICATOR RESULTS In vitro off-target toxicity No specific cytotoxicity at clinically relevant cell numbers vs FcgR-expressing cells No intera
Slide 12: 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 DesCAARTes™: Phase 1 clinical trial in mucosal-dominant PV (m
Slide 13: DesCAARTes clinical trial assessments and key risks
Safety assessed acutely and at 3 months, with ability to measure CAAR T engagement by 6 months DesCAARTes™ clinical trial assessments and timeframes Spindler, Volker, et al. "Mechanisms causing loss of keratinocyte cohesion in pemphigus." Journal of Investigative Dermatology 138.1 (2018): 32-37. To
Slide 14: Soluble antibodies can partially activate or inhibit DSG3 CAAR T cells
Preclinical data suggests soluble antibodies 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." Scien
Slide 15: Preconditioning may not be necessary beyond leukemia / lymphoma
Data suggest preconditioning may not be necessary to drive responses beyond leukemia / lymphoma Recent MM patient data showed non-significant differences in ORR and rate of cytokine release syndrome in patients receiving CART-BCMA with and without lymphodepletion1 Studies from three clinical trials
Slide 16: Key clinical trial milestones and data readouts
Key clinical trial milestones and data readouts Evaluate safety by dosing cohort Acute safety data to be evaluated at 8 days post-infusion Primary endpoint data at 3 months Spindler V, Eming R, Schmidt E, et al. Mechanisms Causing Loss of Keratinocyte Cohesion in Pemphigus. J Invest Dermatol 2018;13
Slide 17: DSG3/1 CAART for mucocutaneous PV
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 Plan to potentially submi
Slide 18: MuSK-CAART for myasthenia gravis patients
MuSK-CAART for myasthenia gravis patients
Slide 19: All known extracellular domains can be included in the CAAR design
6.0 - 7.5% All known extracellular domains can be included in the CAAR design High unmet need in MuSK myasthenia gravis; a valuable CAAR target Hain, Berit, et al. "Successful treatment of MuSK antibody–positive myasthenia gravis with rituximab." Muscle & Nerve: Official Journal of the American Asso
Slide 20: MuSK-CAART potency against target cells binding different epitopes
MuSK-CAART showed similar potency against target cells that bind to different epitopes MuSK-CAART in vitro selective & specific target engagement1 https://cslide-us.ctimeetingtech.com/aan2020/attendee/eposter/poster/2402?q=payne % Specific lysis MuSK1A 3-28 CART19 MuSK-CAART NTD % Specific lysis % S
Slide 21: MuSK-CAART eliminated anti-MuSK target cells in an animal model
MuSK-CAART eliminated anti-MuSK target cells2 in an animal model where CART19 cells are a positive control MuSK-CAART demonstrated specific in vivo target engagement1 https://cslide-us.ctimeetingtech.com/aan2020/attendee/eposter/poster/2402?q=payne Target cells represent a B cell tumor line (CD19 po
Slide 22: FVIII-CAART for Hemophilia A inhibitor patients
FVIII-CAART for Hemophilia A inhibitor patients
Slide 23: 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 24: FVIII-CAART in vitro proof of concept data
Selective and specific target engagement FVIII-CAART in vitro proof of concept data Cabaletta is engineering optimized constructs FVIII Domain(s) Signaling Domain Co-stimulatory Domain Linker/ Transmembrane E:T ratio
Slide 25: Manufacturing
Manufacturing Cabaletta Bio
Slide 26: Three-stage manufacturing strategy
Three-stage approach allows for efficient allocation of capital while leveraging experienced partners Manufacturing strategy Penn-sponsored CD19 CAR IND CMC data has been cross-referenced in DSG3-CAART IND to provide additional data reflecting alignment. Stage 3: Cabaletta Facility Commercialization
Slide 27: Conserving the clinically validated CD19 CAR manufacturing process
Conserving the clinically validated CD19 CAR cell manufacturing process minimizes confounding risks Penn process, not Novartis process; avoids Kymriah release challenges2 Cross referenced the Penn IND to minimize operational risk Development work has demonstrated efficient manufacture of DSG3-CAART
Slide 28: Corporate Summary
Corporate Summary Cabaletta Bio
Slide 29: Leadership team and Scientific Advisory Board
SCIENTIFIC ADVISORY BOARD Leadership team Aimee Payne, M.D., Ph.D. Co-Founder and Co-Chair Michael C. Milone, M.D., Ph.D. Co-Founder and Co-Chair Jay Siegel, M.D. LEADERSHIP TEAM Steven Nichtberger, M.D. President, CEO & Chairman Anup Marda Chief Financial Officer Arun Das, M.D. Senior Director BD G
Slide 30: Recent highlights and anticipated upcoming milestones
Recent highlights and anticipated upcoming milestones 1 Assumes lifting of current COVID-19-related restrictions and no future restrictions due to subsequent COVID-19 resurgence.
Slide 31: Corporate Presentation JUNE 2020
Corporate Presentation JUNE 2020