Full Press Release Details
Corporate Presentation DECEMBER 2022
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financial conditions, and include, but are not limited to, express or implied statements regarding our current beliefs, expectations and assumptions regarding: our business, future plans and strategies for our CAAR T and CARTA technologies and
CABA platform; Cabaletta's ability to grow its autoimmune-focused pipeline; the ability to capitalize on and potential benefits resulting from the translational research partnership with Professor Georg Schett and the exclusive license
agreement with IASO Bio; the timing of our planned submission of an Investigational New Drug application (IND) for CABA-201 to the U.S. Food and Drug Administration; statements regarding regulatory filings regarding its development programs; the
progress and results of our DesCAARTes Phase 1 trial, including the significance and impact around reported safety and clinical and translational data of cohorts from our DesCAARTes trial; the therapeutic potential and clinical
benefits of our product candidates; the expectation that Cabaletta Bio may improve outcomes for patients suffering from mucosal pemphigus vulgaris, myasthenia gravis, or other autoimmune diseases; our ability to escalate dosing as high as 10 to 15
billion cells in cohort A6m, initiate dosing in a combination cohort or otherwise; Cabaletta's plans to implement a pre-treatment regimen and the potential ability to enhance in vivo DSG3-CAART exposure; our ability to advance dose escalation
in the DesCAARTes Phase 1 trial at the current dose ranges for the current cohorts and any projected potential dose ranges for future cohorts, and to optimize our targeted cell therapy; our ability to evaluate, and the potential significance
of, the relationship between DSG3-CAART persistence and potential clinical responses in patients with mPV; our ability to safely retreat additional patients and whether we will continue to observe a lack of immune-mediated clearance of DSG3-CAART
cells after retreatment and repeat dosing of patients; our ability to successfully complete our preclinical and clinical studies for our product candidates, including CABA-201, our ongoing Phase 1 DesCAARTes trial, and our ongoing Phase 1
MusCAARTes trial of MuSK-CAART, including our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and progress the trial; the ability of MuSK-CAART to target B cells that differentiate into
antibody secreting cells, which produce autoantibodies against muscle-specific kinase; our ability to obtain and maintain regulatory approval of our product candidates, including our expectations regarding the intended incentives conferred by and
ability to retain Orphan Drug Designation and Fast Track Designation for DSG3-CAART for the treatment of pemphigus vulgaris and Orphan Drug Designation and Fast Track Designation for MuSK-CAART to improve activities of daily living and muscle
strength in patients with MuSK antibody-positive myasthenia gravis; the further expansion and development of our modular CABA platform across a range of autoimmune diseases; our ability to contract with third-party suppliers and
manufacturers, implement an enhanced manufacturing process and further develop our internal manufacturing strategy, capabilities and facilities; our potential commercial opportunities, including value and addressable market, for our product
candidates; our expectations regarding our use of capital and other financial results; and our ability to fund operations into the first quarter of 2025. Words such as, but not limited to, "look forward to," "believe,"
"expect," "anticipate," "estimate," "intend," "plan," "would," "should" and "could," and similar expressions or words, identify forward-looking
statements. Various risks, uncertainties and assumptions could cause actual results to differ materially from those anticipated or implied in our forward-looking statements. Such risks and uncertainties include, but are not limited to, risks related
to the success, cost, and timing of our product candidate development activities and preclinical studies and clinical trials, risks related to our ability to demonstrate sufficient evidence of safety, efficacy and tolerability in our preclinical
studies and clinical trials of CABA-201, DSG3-CAART and MuSK-CAART, the risk that the results observed with the similarly-designed construct employed in the recent Nature Medicine publication are not indicative of the results we seek to achieve with
CABA-201, our plans to evaluate additional cohorts in the DesCAARTes trial, including a cohort implementing a pre-treatment regimen, the risk that signs of biologic activity or persistence may not inform long-term results, the risk that
persistence observed with effective CART-19 oncology studies in combination with lymphodepletion is not indicative of, or applicable to, clinical responses in patients with mPV, risks related to clinical trial site activation or enrollment rates
that are lower than expected, our ability to protect and maintain our intellectual property position, risks related to our relationship with third parties, uncertainties related to regulatory agencies' evaluation of regulatory filings and
other information related to our product candidates, our ability to retain and recognize the intended incentives conferred by any Orphan Drug Designation and Fast Track Designations, the risk that any one or more of our product candidates will not
be successfully developed and commercialized, the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies, the impact of COVID-19 on the timing, progress,
interpretability of data, and results of ongoing or planned clinical trials and risks relating to as a result of extraordinary events or circumstances such as the COVID-19 pandemic, and any business interruptions to our operations or to those of our
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Develop and launch the first curative
targeted cellular therapies for patients with autoimmune diseases
Leveraging years of clinical experience
with cell therapy for autoimmune diseases to evaluate two strategies Cabaletta : Pursuing cures for a broad range of autoimmune diseases CAART - Chimeric AutoAntibody Receptor T cells; CARTA - Chimeric Antigen Receptor T cells for
Autoimmunity; IND - Investigational New Drug; SLE - Systemic lupus erythematosus; RA - Rheumatoid arthritis; mPV - Mucosal pemphigus vulgaris Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic
lupus erythematosus." Nature Medicine (2022): 1-9. Dai, Zhenyu, et al. "Development and functional characterization of novel fully human anti CD19 CARs for T cell therapy." Journal of Cellular Physiology 236.8 (2021): 5832-5847. Mullin,
Emily. "How a Living Drug' Could Treat Autoimmune Disease." WIRED, 16 Sept 2022. Assumes no dose-limiting toxicities are observed in the cohort, uninterrupted enrollment and no delays due to COVID-19 resurgence occur in the
trial. Subject to clearance of CABA-201 IND by the FDA. CAART: Advancing clinical studies to increase CAART activity & explore additional indications DesCAARTes trial in mPV ongoing: Enrolling combination sub-study (pre-treatment with
IVIg & cyclophosphamide) 1 month safety and persistence data anticipated in 1Q234 MusCAARTes trial in MuSK myasthenia gravis: Initiated in 4Q22; received FDA Fast Track Designation Higher starting cell dose and early implementation of
combination strategy as early as the fifth subject treated in the trial Cash runway into 1Q25, inclusive of recently announced financing Initial CABA-201 clinical data5 as well as 6-month combination data from DesCAARTes &
MusCAARTes trials expected by 1H244 CARTA: CABA-201 (4-1BB CD19-CAR T) on track for 1H23 IND submission Builds on recent academic clinical data1 demonstrating that CD19-CAR T may potentially reset the immune system in patients with SLE
Exclusive translational research partnership with lead investigator on the academic study1 is informing CABA-201 clinical development Exclusive global license for clinically-evaluated, fully human CD19 binder with favorable clinical tolerability
profile in ~20 oncology patients Similar construct design to CD19-CAR T used in the academic SLE study, including 4-1BB costimulatory domain1,2 Potential to cure many common autoimmune diseases such as SLE, RA, myositis and systemic sclerosis3
One CABA platform, two
strategies to address autoimmune diseases Complementary strategies to optimize clinical outcomes using cellular therapies in autoimmune diseases Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus."
Nature Medicine (2022): 1-9. Ellebrecht, Christoph T., et al. "Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease." Science 353.6295 (2016): 179-184. Fully Human Anti-CD19 Targeting Domain CARTA
Chimeric Antigen Receptor T cells for Autoimmunity CAART Chimeric AutoAntibody Receptor T cells CABA-201 4-1BB Costimulatory Domain & CD3-Zeta Signaling Domain DSG3-CAART Potential to reset the immune system' in patients with
autoimmune diseases driven by B cells, through generalized transient B cell depletion and repopulation of healthy B cells1 In autoimmune diseases with a limited number of well-defined pathogenic autoantibodies, permanent antigen-specific B cell
depletion may provide an elegant biologic solution to disease2 Autoantigen Targeting Domain 4-1BB Costimulatory Domain & CD3-Zeta Signaling Domain
Biologic opportunity for cure or
treatment may be possible in dozens of B-cell mediated autoimmune diseases* CABA platform may apply across a range of autoimmune diseases Pemphigus Vulgaris1,2,3 Pemphigus Foliaceus1,2,3 Epidermolysis Bullosa Acquisita3 Bullous
Pemphigoid1,2,3 Lupus Nephritis3,4 Membranous Nephropathy1,2,3 Goodpasture's Syndrome1,2,3,4 Myasthenia Gravis1,2,3,5 Multiple Sclerosis6 Neuromyelitis Optica3 Chronic Inflammatory Demyelinating Polyneuropathy1.2 Anti-NMDAR Encephalitis3,6
Lambert-Eaton Syndrome5 Systemic Lupus Erythematosus3,4,5,6 Rheumatoid Arthritis2,3,4 Myositis5 Systemic sclerosis6 ANCA-Associated Vasculitis3,4,5 Immune Thrombocytopenic Purpura3 Thrombotic Thrombocytopenic Purpura1,2,3 Antiphospholipid
Syndrome4,5 Autoimmune Hemolytic Anemia3 Type 1 Diabetes3,6 Graves' Disease3,5 Hashimoto's Disease5 Illustrative list of diseases where biologic opportunity for cure or treatment with CAART or CARTA approach may be possible. Diseases in
bold represent where clinical studies are underway or plan to be initiated by Cabaletta or by Professor Schett Koneczny, Inga. "Update on IgG4-mediated autoimmune diseases: new insights and new family members." Autoimmunity Reviews (2020): 102646.
Huijbers, Maartje G., et al. "IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders." Annals of the New York Academy of Sciences 1413.1 (2018): 92. Ludwig, Ralf J., et al. "Mechanisms of autoantibody-induced pathology." Frontiers
in immunology 8 (2017): 603. Suurmond, Jolien, and Betty Diamond. "Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity." The Journal of clinical investigation 125.6 (2015): 2194-2202. Xiao, Ze Xiu, Joseph S. Miller, and
Song Guo Zheng. "An updated advance of autoantibodies in autoimmune diseases." Autoimmunity Reviews (2020): 102743. Hampe, Christiane S. "B cells in autoimmune diseases." Scientifica 2012 (2012). Dermatology Nephrology Neurology Rheumatology
Hematology Endocrinology
Foundational CAR T technology
clinically validated in treating B cell-mediated cancers and SLE1 Cabaletta: Advancing targeted cell therapy to autoimmunity Marketed Pivotal Clinical Preclinical / Discovery Oncology B Cell-Mediated Allo/Autoimmune Diseases CAR-T / CAAR-T T-reg,
NK, TCR, RBC, macrophage, TIL Note: Landscape for illustrative purposes only. Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9.
Pipeline targeting autoimmune diseases
where cure is possible Additional disease targets in discovery stage in our CAART pipeline portfolio include hemophilia and two undisclosed indications. CABA Platform Indication Program Discovery Preclinical Phase 1 Phase 2/3 CARTA Chimeric
Antigen Receptor T cells for Autoimmunity Multiple Undisclosed Indications CABA-201 4-1BB CD19-CAR T CAART1 Chimeric AutoAntibody Receptor T cells Mucosal Pemphigus Vulgaris DSG3-CAART MuSK Myasthenia Gravis MuSK-CAART PLA2R Membranous Nephropathy
PLA2R-CAART Mucocutaneous Pemphigus Vulgaris DSG3/1-CAART
Chimeric Antigen Receptor T Cells for
Autoimmunity CABA-201
SLE - Systemic lupus
erythematosus; scFv - Single chain variable fragment; SLEDAI-2K - Systemic Lupus Erythematosus Disease Activity Index 2000; CRS - Cytokine release syndrome; ICANS - Immune effector cell-associated neurotoxicity syndrome
Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9. The construct utilized in this study has a similar design to CABA-201, sharing the 4-1BB costimulatory domain, but is
a different construct. Fludarabine (Flu) 25 mg/m2/d intravenously day -5 to day -3; Cyclophosphamide (Cy) 1,000 mg/m2/d intravenously on day -3 Exclusive translational research partnership with lead investigator informing our CD19 clinical strategy
Academic clinical data: Immune system reset in 5/5 SLE patients1 SLE disease activity 5/5 refractory SLE patients treated with 4-1BB CD19-CAR T2 resulting in rapid, deep and transient depletion of CD19+ B cells1 All 5 patients with moderate to
severe disease Preconditioning with standard Flu/Cy regimen2 Dose of 1x106 CD19-CAR T cells/kg CD19 binder: 4-1BB costimulatory domain & FMC63 scFv Clinical & serologic responses by 3 mo. after 4-1BB CD19-CAR T therapy with promising safety
profile1 Anti-dsDNA antibodies undetectable in 5/5 All SLE-associated antibodies reduced Complement levels normalized No - or only mild - CRS observed Grade 1 fever in 3/5 patients No neurotoxicity / ICANS Repopulation of healthy B
cells1 New B cells reappeared in 5/5 patients between 2-5 months Limited decline in vaccination titers Durable clinical responses1 5-17 months of follow up Responses maintained with no need for SLE-associated medications CAR T cells CD19+ B cells
White blood count Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Days Days Days Cells/microliter N/microliter
Cabaletta's CD19 binder with
similar in vitro & in vivo activity to FMC631 (binder used in academic SLE study2) CABA-201: CD19-targeting CAR T therapy for autoimmune diseases SLE - Systemic lupus erythematosus; IIT - Investigator-initiated trial; Flu/Cy -
Fludarabine/Cyclophosphamide; CRS - Cytokine release syndrome; ICANS - Immune effector cell-associated neurotoxicity syndrome Dai, Zhenyu, et al. "Development and functional characterization of novel fully human anti CD19 chimeric
antigen receptors for T cell therapy." Journal of Cellular Physiology 236.8 (2021): 5832-5847. Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9. Evaluated as
part of CT120, a dual-CD19xCD22 CAR T product candidate under development by Nanjing IASO Biotherapeutics, Co., Ltd. (IASO Bio). CD19 binder for CABA-201 CD19 binder used in academic SLE study2 In vitro (Nalm 6) In vivo Fully human anti-CD19 binder
4-1BB costimulatory domain CD3-Zeta signaling domain CABA-201 Similar in vitro & in vivo biologic activity to FMC631 Same co-stimulatory domain as used in academic SLE study2 CD19-CAR Construct Clinical Data for Licensed CD19 Binder3 Fully human
binder Evaluated within dual-CAR combined with CD22 binder with standard Flu/Cy preconditioning Evaluated in ~20 patients to date3 Under evaluation in patients with B cell leukemia and lymphoma in IIT in China Promising tolerability data to date3
Used in oncology patients with high target cell burden CABA-201
Differentiated asset, exclusive
translational insights & track record of timely CAART clinical implementation Accelerating development of CABA-201 for autoimmune diseases SLE - Systemic lupus erythematosus Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for
refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9. IND submission for CABA-201 anticipated in first half of 2023 1 Cabaletta is uniquely positioned to efficiently advance CABA-201 in autoimmune diseases Expertise in conducting