Cabaletta Bio, Inc. · NASDAQ:CABA
Cabaletta Bio — Investor Presentation (April 2021)
30 slides from Cabaletta Bio's investor presentation, Apr 6, 2021
Slide 1: Corporate Presentation April 2021
Corporate Presentation April 2021 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 Developing highly specific CAAR T products to treat B cell-mediated autoimmune diseases Where there is a biologic opportunity for deep and durable, perhaps curative, responses Leveraging a clinically validated CAR T product design and manufacturing process through Penn alliance Pr
Slide 5: 2020 progress and anticipated 2021 milestones
2020 progress and anticipated 2021 milestones Validate MuSK-CAART manufacturing process with CMO partner DSG3-CAART Multiple U.S. sites open for enrollment Dosing initiated in DesCAARTes™ clinical trial Acute safety data from first cohort 1H211 In vivo target engagement data presented at AAN MuSK-CA
Slide 6: Our scientific platform leverages clinically validated CAR T technology
Our scientific platform leverages clinically validated CAR T technology CAR T Therapy Chimeric Antigen Receptor T cell Kymriah CAAR T product candidates are designed for selective and specific elimination of the pathogenic B cells CAAR T Therapy Chimeric AutoAntibody Receptor T cell CABA CAAR T AUTO
Slide 7: CABA platform (Cabaletta Approach for Selective B cell Ablation)
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 Scientifi
Slide 8: Pipeline includes multiple disease targets where cure is possible
Therapeutic Area Indication Program Discovery2 Preclinical Phase 1 Phase 2/3 Dermatology Mucosal Pemphigus Vulgaris DSG3-CAART Mucocutaneous Pemphigus Vulgaris DSG3/1-CAART Neurology MuSK Myasthenia Gravis MuSK-CAART Hematology Hemophilia A w/ FVIII Alloantibodies FVIII-CAART Pipeline1 includes mult
Slide 9: DSG3-CAART for patients with mucosal pemphigus vulgaris
DSG3-CAART for patients with mucosal pemphigus vulgaris
Slide 10: DSG3 antibodies are considered necessary and sufficient to cause PV
DSG3 antibodies are widely considered to be necessary and sufficient to cause PV1 PV is an optimal lead indication for CAAR T therapy Spindler, Volker, et al. "Mechanisms causing loss of keratinocyte cohesion in pemphigus." Journal of Investigative Dermatology 138.1 (2018): 32-37. Schmidt, Enno, et
Slide 11: Current treatments require broad immunosuppression with safety risks and transient efficacy
Current treatments require broad immunosuppression associated with safety risks and transient efficacy Overview of Pemphigus Vulgaris Image credit: D@nderm. Rituximab label, 08/2020 revision. Joly, Pascal, et al. "First-line rituximab combined with short-term prednisone versus prednisone alone for t
Slide 12: 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 13: No evidence of toxicity with selective and specific target engagement
Tolerability Target Engagement No evidence of toxicity at clinically relevant doses with selective and specific target engagement DSG3-CAART preclinical data1,2 INDICATOR RESULTS In vitro off-target toxicity No specific cytotoxicity at clinically relevant cell numbers vs FcgR-expressing cells No con
Slide 14: DesCAARTes: Phase 1 clinical trial in mucosal-dominant PV
Study Endpoint & Objectives Primary Endpoint: Adverse Events, including Dose Limiting Toxicity (DLT) DLTs include any grade 3 or 4 CRS or neurotoxicity, or any grade 2 CRS or neurotoxicity that failed to improve to ≤ Grade 1 or baseline within 7 days Secondary Objectives: DSG3 ELISA titer changes, r
Slide 15: Safety assessed acutely (Day 8) and at months
Safety assessed acutely (Day 8) 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
Slide 16: DSG3-CAART target engagement in the presence of soluble antibodies
Preclinical studies demonstrated DSG3-CAART target engagement in the presence of soluble antibodies 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." Sci
Slide 17: Target engagement in presence of physiologic DSG3 antibody titer
DSG3-CAART demonstrated target engagement in presence of physiologic DSG3 antibody titer Active Immune Model: Target engagement despite soluble antibody1 Lee, Jinmin, et al. "Antigen-specific B-cell depletion for precision therapy of mucosal pemphigus vulgaris." The Journal of Clinical Investigation
Slide 18: Data suggest preconditioning may not be necessary
Data suggest preconditioning may not be necessary beyond leukemia / lymphoma Similar efficacy at 10x cell dose increase without lymphodepletion in multiple myeloma1 Over a decade of persistence of CAR T cells in patients with HIV2 Potential activating effect of soluble antibody is a key consideratio
Slide 19: DSG3/1 CAARs designed 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 20: MuSK-CAART for patients with MuSK myasthenia gravis
MuSK-CAART for patients with MuSK myasthenia gravis
Slide 21: High unmet need in MuSK myasthenia gravis
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 22: No confirmed off-target toxicity observed with MuSK-CAART to date
Additional in vitro studies demonstrated no confirmed off-target toxicity observed with MuSK-CAART to date MuSK-CAART showed in vitro selective & specific target engagement1 https://cslide-us.ctimeetingtech.com/aan2020/attendee/eposter/poster/2402?q=payne. MuSK-CAART Ig1 Ig2 Ig3 Fz MuSK1A 3-28 4A3 C
Slide 23: 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 were 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
Slide 24: Manufacturing
Manufacturing Cabaletta Bio’
Slide 25: Three-stage manufacturing approach allows efficient allocation of capital
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 26: Clinically validated CART19 cell manufacturing process mitigates risks
Utilizing a clinically validated CART19 cell manufacturing process mitigates risks Cross referenced Penn CART19 IND including CMC process1 Penn process, not Novartis process, avoiding Kymriah release challenges2 Engineering runs have demonstrated efficient manufacture of DSG3-CAART cells from PV pat
Slide 27: Corporate Summary
Corporate Summary Cabaletta Bio’
Slide 28: 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 29: Anticipated 2021 milestones
Anticipated 2021 milestones DSG3-CAART: DesCAARTesTM Clincal Trial 1H21: Acute safety data from 1st cohort1 2H21: Additional topline data on completed dose cohort(s)1 MuSK-CAART Validate manufacturing process with CMO partner 2H21: MuSK-CAART IND filing 1. Assumes no future impact due to COVID-19.
Slide 30: Corporate Presentation April 2021
Corporate Presentation April 2021