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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 an

Key Takeaway: Cabaletta Bio, Inc. presented a corporate update detailing its efforts in developing innovative therapies for autoimmune diseases, specifically its CABA platform and the candidate CABA-201. The company has outlined plans for upcoming clinical trials, including a Phase 1/2 study for systemic lupus erythematosus and myositis, with an initial data readout anticipated in the first half of 2024. However, the presentation also highlighted various risks and uncertainties that could impact the success and timing of its drug development initiatives, particularly regarding regulatory approvals and clinical trial enrollments.

Market Sentiment Analysis

POSITIVE FACTORS

  • Cabaletta Bio is focused on growing its autoimmune pipeline.
  • CABA-201 may offer therapeutic benefits for patients with autoimmune diseases.
  • Plans are in place to conduct Phase 1/2 clinical trials for CABA-201.

CONCERNS & RISKS

  • There are various risks associated with the success and timing of product candidate development.
  • Uncertainties related to regulatory approvals can impede progress.
  • Enrollment rates in clinical trials may be lower than expected.

Full Press Release Details

Corporate Presentation MAY 2023 Exhibit
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 with the presentation (collectively, the "Presentation") has been prepared by Cabaletta Bio, Inc. ("we," "us," "our," "Cabaletta" or the "Company") and is made for
informational purposes only. This Presentation does not purport to be a prospectus, to be complete or to contain all of the information you may desire. Statements contained herein are made as of the date of this Presentation unless stated otherwise,
and this Presentation shall not under any circumstances create an implication that the information contained herein is correct as of any time after such date or that information will be updated or revised to reflect information that subsequently
becomes available or changes occurring after the date hereof. This Presentation may contain "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and
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; our ability to grow our 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; our expectations around the potential success and therapeutic benefits of CABA-201, including our belief that CABA-201 may enable an "immune system reset" and provide deep and durable responses for patients with autoimmune
diseases; our plans to initiate (i) a Phase 1/2 clinical trial of CABA-201 in patients with SLE, including our anticipated progress, clinical trial design, ability to leverage our experience in autoimmune cell therapy and lupus product development
and (ii) a Phase 1/2 clinical trial of CABA-201 in patients with myositis, including its anticipated progress, clinical trial design and ability to leverage its experience in autoimmune cell therapy; our planned initial clinical data read-out in the
first half of 2024 for patients treated with CABA-201; our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and advance the trial as planned in our Phase 1/2 clinical trials of CABA-201; the timing
any planned regulatory filings for our 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, and our ability to advance dose escalation and initiate combination cohorts and to optimize our targeted cell therapy; our ability to implement a pre-treatment regimen, the outcomes of such pre-treatment regimen and the
potential ability to enhance in vivo DSG3-CAART exposure; the therapeutic potential and clinical benefits of our product candidates; the expectation that Cabaletta may improve outcomes for patients suffering from systemic lupus erythematosus,
myositis, 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; 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 our product candidates, as applicable; 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, including, but not limited to, due to dosing regimen, employed in recent
publications, including the Nature Medicine and Lancet Rheumatology publications, including due to the dosing regimen, 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 clinical sites, manufacturers, suppliers, or other vendors resulting
from the COVID-19 pandemic or similar public health crisis. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly
update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are
reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, you are cautioned not to place undue reliance on these forward-looking statements. No representations or warranties (expressed or implied) are made
about the accuracy of any such forward-looking statements. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ materially from those contained in the
forward-looking statements, see the section entitled "Risk Factors" in our most recent annual report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in our other and subsequent filings with the
Securities and Exchange Commission. Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and
research. While the Company believes these third-party sources to be reliable as of the date of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any
information obtained from third-party sources. The Company is the owner of various trademarks, trade names and service marks. Certain other trademarks, trade names and service marks appearing in this Presentation are the property of third parties.
Solely for convenience, the trademarks and trade names in this Presentation are referred to without the and TM symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest
extent under applicable law, their rights thereto.
Develop and launch the first curative
targeted cellular therapies for patients with autoimmune diseases
Leveraging years of experience with
cellular therapy in autoimmunity to initiate CABA-201 clinical trials 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; DM - Dermatomyositis; ASyS - Anti-synthetase syndrome; IMNM - Immune-mediated necrotizing myopathy Mackensen, Andreas, et al. "Anti-CD19
CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9. M ller, Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023). 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. Assumes no dose-limiting toxicities are observed in the cohort and uninterrupted enrollment
occur in the trials. Advancing SLE and myositis trials with efficient designs (including starting dose and parallel cohorts) 1.0 x 106 cells/kg initial dose of CABA-201 is identical to dose used in academic SLE1 and myositis2 studies Parallel
cohorts with 6 patients each - SLE study with 1) LN & 2) Non-renal SLE; myositis study with 1) DM, 2) ASyS & 3) IMNM CABA-201 has been specifically engineered for patients with autoimmune diseases Fully human CD19 binder with data in
~20 oncology patients with safety profile supporting further evaluation in autoimmunity Same 4-1BB costimulatory domain and similar CD19 binder affinity3 as used in the academic SLE1 & myositis studies2 Potential to cure a broad range of
autoimmune diseases where B cells have a role initiating or maintaining disease DesCAARTes trial in mucosal pemphigus vulgaris - 1 month safety & persistence data anticipated 1H234 Enrolling in combination sub-study using
pre-treatment with IVIg & cyclophosphamide (Cy); cohort with fludarabine, Cy and IVIg planned MusCAARTes trial in MuSK myasthenia gravis - leveraging insights from experience with DSG3-CAART Initiated in 4Q22; received FDA Fast
Track Designation & Orphan Drug Designation CARTA Strategy | CABA-201 (4-1BB CD19-CAR T) to be evaluated in SLE & myositis Phase 1/2 studies CAART Strategy | DSG3-CAART & MuSK-CAART clinical studies evaluating combination regimens
CABA-201 data on clinical efficacy and tolerability in initial CABA-201 treated patients expected by 1H244
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. M ller, Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023). 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 cells1,2 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 disease3 Autoantigen Targeting Domain 4-1BB Costimulatory Domain & CD3-Zeta
Biologic opportunity for cure or
treatment may be possible in dozens of 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 autoimmune diseases where B cells may play a role in initiating or maintaining disease, and 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
Pipeline targeting autoimmune diseases
where cure is possible CABA-201 is being evaluated in separate clinical trials for myositis and SLE. Additional CAART pipeline candidates include PLA2R-CAART in preclinical stage for PLA2R membranous nephropathy, DSG3/1-CAART in discovery stage for
mucocutaneous pemphigus vulgaris, and two undisclosed targets in discovery stage. Currently being evaluated in a Phase 1 trial. CABA Platform Indication Program Discovery Preclinical Phase 1/2 Phase 2/3 CARTA Chimeric Antigen Receptor T cells
for Autoimmunity Myositis (IIM, Idiopathic Inflammatory Myopathy)1 Dermatomyositis CABA-201 4-1BB CD19-CAR T Anti-Synthetase Syndrome Immune-Mediated Necrotizing Myopathy CARTA Chimeric Antigen Receptor T cells for Autoimmunity Systemic Lupus
Erythematous (SLE)1 Lupus Nephritis CABA-201 4-1BB CD19-CAR T Non-Renal SLE Multiple Undisclosed Indications CAART2 Chimeric AutoAntibody Receptor T cells Mucosal Pemphigus Vulgaris DSG3-CAART3 MuSK Myasthenia Gravis MuSK-CAART3 IND cleared IND
Chimeric Antigen Receptor T Cells for
Autoimmunity CABA-201
SLE - Systemic lupus
erythematosus; ASyS - Anti-synthetase syndrome; 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; Anti-dsDNA Abs - Anti-double-stranded deoxyribonucleic acid antibodies Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9.
M ller, Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023). The construct utilized in this study has a similar design to CABA-201, sharing the 4-1BB costimulatory domain, but is a different
construct. Exclusive translational research partnership with lead investigator informing our CD19 clinical strategy Academic data: Immune system reset in SLE & myositis patients1,2 5/5 SLE patients Anti-dsDNA Abs undetectable Complement levels
normalized Myositis patient (anti-synthetase syndrome): Creatinine kinase dropped to normal Durable clinical responses1,2 5-17 months of follow up Off other immunosuppressive 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 Promising safety data1,2 Grade 1 CRS (fever) in 4/6 patients No ICANS of any grade 4-1BB CD19-CAR T3 resulted in rapid, deep & transient CD19+ B cell depletion
1x106 cells/kg preceded by standard Flu/Cy regimen CD19 binder (FMC63 scFv) & 4-1BB costim domain3 Clinical & serologic responses within 3 mo. of CD19-CAR T therapy in refractory patients with SLE1 & patient with myositis2 Repopulation
of healthy B cells1,2 New, na ve B cells in 6/6 pts in 2-5 months Limited decline in vaccination titers Rapid & robust improvement in clinical disease activity Normalization of serum markers of disease SLE (N=5) SLEDAI-2K Myositis (N=1)
Total improvement score
Cabaletta's CD19 binder with
similar in vitro & in vivo activity to FMC631 (binder used in academic studies2,3) 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. M ller,
Fabian, et al. "CD19-targeted CAR T cells in refractory antisynthetase syndrome." The Lancet (2023). 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 studies2,3 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 & myositis studies2,3 CD19-CAR Construct Clinical data reported by IASO using licensed CD19 binder4 Fully human binder Evaluated within dual-CAR combined with CD22 binder with standard Flu/Cy
preconditioning Data reported in ~20 patients to date4 B cell leukemia and lymphoma in IIT in China Safety data supports autoimmune development4 CABA-201

Frequently Asked Questions

What is the purpose of the Cabaletta Bio presentation?

The presentation serves informational purposes and is not a prospectus.

When can we expect initial clinical data for CABA-201?

Initial clinical data for CABA-201 is anticipated in the first half of 2024.

What risks are associated with Cabaletta Bio's product development?

Risks include the success of trials, safety evidence, and regulatory evaluations.

What does the term 'forward-looking statements' mean?

It refers to statements about future beliefs, plans, and expectations of the company.

Will Cabaletta Bio update forward-looking statements often?

Cabaletta Bio does not plan to publicly update these statements unless required by law.

Last updated: May 9, 2023