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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. has released a corporate presentation detailing its ongoing development of the CABA-201 product candidate and its autoimmune-focused pipeline. The presentation emphasizes the potential of CABA-201 to provide effective treatments for various autoimmune diseases through innovative manufacturing processes. However, it also acknowledges several risks, including reliance on future clinical trial outcomes and the uncertainties in regulatory approvals. The company aims to advance through robust clinical strategies and collaborations while navigating inherent industry challenges.

Market Sentiment Analysis

POSITIVE FACTORS

  • Cabaletta Bio is advancing its autoimmune-focused pipeline with CAAR T and CARTA technologies.
  • The company has innovative approaches such as a simpler collection process for CABA-201 manufacturing.
  • CABA-201 shows potential for providing drug-free, durable clinical responses.

CONCERNS & RISKS

  • There are significant risks and uncertainties that could cause actual results to differ materially from expected outcomes.
  • Enrollment rates for clinical trials may be lower than anticipated, which could delay progress.
  • There is no guarantee that the results from preclinical studies will predict future outcomes in clinical trials.

Full Press Release Details

Corporate Presentation OCTOBER 2024
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; our
ability to grow our autoimmune-focused pipeline; the ability to capitalize on and potential benefits resulting from our research and translational insights; including those related to any similarly-designed constructs or dosing regimens; the
anticipated market opportunities for CABA-201 in patients with autoimmune diseases; the Company's business plans and objectives; our expectations around the potential success and therapeutic and clinical benefits of CABA-201 and our other
product candidates, including our belief that CABA-201 may enable achieving drug-free, durable meaningful clinical responses, through an immune reset; Cabaletta's belief of the potential for CAR T to enable a paradigm shift in autoimmunity
treatment; our plans for Phase 1/2 clinical trials of CABA-201 in patients with systemic lupus erythematosus (SLE), myositis, SSc, and generalized myasthenia gravis (gMG), and for advancement of a RESET-PV sub-study within the ongoing DesCAARTes
trial in PV, including the timing thereof, including our anticipated progress, timing of enrollment, expectations for the efficiency of trial designs, updates related to status, safety data, or otherwise and the expected timing of the related data
read-outs, and ability to leverage our experience in autoimmune cell therapy; 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, including IND applications; the progress and results of our MusCAARTes Phase 1 trial, including the significance and impact around reported safety and
clinical and translational data of cohorts from our MusCAARTes Phase 1 trial; Cabaletta's potential to eliminate the need for apheresis by using a simpler collection process to obtain the starting material for the CABA-201 manufacturing
process; the expectation that Cabaletta may improve outcomes for patients suffering from SLE, SSc, myositis, gMG, mucosal pemphigus vulgaris, MuSK myasthenia gravis, or other autoimmune diseases; the ability of our clinical strategy to reduce risk,
maximize reach and accelerate timelines of our Phase 1/2 clinical trials of CABA-201; expectation that clinical results will support CABA-201's safety and activity profile; statements regarding the timing of regulatory filings and interactions with
regulatory authorities, including such authorities' review of safety information from our ongoing clinical trials; our ability to successfully complete our preclinical and clinical studies for our product candidates, including our ability to enroll
the requisite number of patients, dose each dosing cohort in the intended manner, and progress the trial; our ability to increase enrollment from our rapidly expanding clinical network in the RESET clinical trial program; 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 Designations for our product candidates, as applicable;
our ability to accelerate our pipeline and to develop meaningful therapies for patients, including in collaboration with academic and industry partners and the ability to optimize such collaborations on our development programs; our ability to
contract with third-party suppliers and manufacturers and retain such manufacturers, whether due to legislative action or otherwise; to implement an enhanced manufacturing process and further develop our internal manufacturing strategy, capabilities
and facilities; our ability to execute our manufacturing strategy to enable expansion of clinical supply and efficiently scale commercial supply for CABA-201; our potential commercial opportunities, including value and addressable market, for our
product candidates; and our expectations regarding our use of capital and other financial results, including our ability to fund operations into the first half of 2026. 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 and MuSK-CAART, the risk that the results observed with the similarly-designed construct, including, but not limited to, due to dosing regimen, are not indicative of the results we seek to
achieve with CABA-201, the risk that signs of biologic activity or persistence may not inform long-term results, the risk that persistence observed with effective CD19-CAR T 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 demonstrate sufficient evidence of safety, efficacy and tolerability in its
preclinical studies and clinical trials of CABA-201; risks that modifications to trial design or approach may not have the intended benefits and that the trial design may need to be further modified; our ability to protect and maintain our
intellectual property position, risks related to our relationships 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 Designations and Fast Track Designations, risks related to regulatory filings and potential clearance, 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, and risks related to volatile market and economic conditions
and public health crises. 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
Develop and launch the first curative
targeted cellular therapies for patients with autoimmune diseases
Realizing the vision to transform
autoimmune disease treatment 1H24: Reported initial myositis & SLE clinical data Securing efficient & scalable commercial manufacturing Advancing whole blood program to replace apheresis Enrolling PV trial of CABA-201 without preconditioning
Cash runway into 1H26 Engineered CABA-201 specifically for use in autoimmune patients Leveraging insights from academic clinical data1 Executing IND specific clinical program to potentially accelerate path to regulatory approval No requirement for
dose escalation Independent, parallel 6-patient cohorts Increased enrollment observed at industry-leading 30+ US clinical sites 2H243: Additional clinical data in myositis & SLE at ACR 2024 Initial clinical data in SSc at ACR 2024 FDA fast track
designation granted for CABA-201 in multiple indications2 SLE - Systemic lupus erythematosus; SSc - Systemic sclerosis; PV - Pemphigus vulgaris; ACR 2024 - American College of Rheumatology 2024 annual meeting from November
14-19, 2024. M ller, Fabian, et al. "CD19 CAR T-Cell Therapy in Autoimmune Disease-A Case Series with Follow-up." New England Journal of Medicine 390.8 (2024): 687-700. The construct utilized in these studies has a similar design to
CABA-201, sharing the 4-1BB costimulatory domain, but is a different construct. FDA Fast Track Designation received in dermatomyositis, SLE, lupus nephritis and systemic sclerosis. Initial clinical data in myasthenia gravis anticipated in 1H25.
Innovations in development
Innovative and scalable clinical
strategy with potential for accelerated development path Pipeline targeting autoimmune diseases with high unmet need Program Trial Preclinical Phase 1/2 Pivotal CABA-201 4-1BB CD19-CAR T RESET-Myositis CARTA Chimeric Antigen Receptor T cells
for Autoimmunity RESET-SLE RESET-SSc RESET-MG RESET-PV Sub-study1 CAART Chimeric AutoAntibody Receptor T cells MusCAARTes Dermatomyositis Anti-synthetase syndrome IMNM Lupus Nephritis Non-Renal SLE Skin + Organ
Cohort AChR-Ab neg. gMG AChR-Ab pos. gMG Skin Cohort Rheumatology Neurology Dermatology FTD Mucocutaneous & mucosal pemphigus vulgaris2 Contains cohort(s) without preconditioning Juvenile Myositis Pediatric Indication MuSK-Ab positive MG2 FTD
RESET - REstoring SElf-Tolerance; IMNM - Immune-mediated necrotizing myopathy; SLE - Systemic lupus erythematosus; Ab - Antibody; AChR - Acetylcholine receptor; gMG - Generalized myasthenia gravis Sub-study
incorporated into DesCAARTes study. 2. Currently being evaluated in a Phase 1 trial. FDA Fast Track Designation received in dermatomyositis, SLE and lupus nephritis, systemic sclerosis, mucosal pemphigus vulgaris, and MuSK-Ab positive MG.
Chimeric Antigen Receptor T Cells for
Autoimmunity CABA-201
Cabaletta's CD19 binder with
similar in vitro & in vivo activity to construct used in academic studies1,3 CABA-201: CD19-CAR T specifically designed for autoimmunity IIT - Investigator-initiated trial; Flu/Cy - Fludarabine/Cyclophosphamide Peng, Binghao J, et
al. "Preclinical specificity and activity of CABA-201, a fully human 4-1BB containing CD19 CAR T therapy for treatment-resistant autoimmune disease." Poster presented at: American Society Gene and Cell Therapy 26th Annual Meeting; 2023
May 19; Los Angeles, CA. 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. M ller,
Fabian, et al. "CD19 CAR T-Cell Therapy in Autoimmune Disease-A Case Series with Follow-up." New England Journal of Medicine 390.8 (2024): 687-700. Evaluated as part of CT120, a dual-CD19xCD22 CAR T product candidate under development by
Nanjing IASO Biotherapeutics, Co., Ltd. (IASO Bio). Transmembrane domain in CABA-201 is CD8 vs. TNFRSF19 (Troy) utilized in the academic construct. The two transmembrane domains have not been shown to have a significant difference in function
or IFN- production in preclinical studies. The CD8 transmembrane domain is employed in tisagenlecleucel. Clinical data reported by IASO using licensed CD19 binder in oncology4 Fully human binder Evaluated as dual-CAR combined with CD22
binder with standard Flu/Cy preconditioning Data reported in ~20 patients to date B cell leukemia and lymphoma in IIT in China Safety data supports autoimmune development Fully human anti-CD19 binder Similar binding affinity & biologic activity
to FMC63, with binding to the same epitopes1,2 4-1BB costimulatory domain Same co-stim. domain as used in academic studies CD3- signaling domain CABA-2015
Below RESET trials are currently
enrolling, with a broadening portfolio to realize the potential of CABA-201 REstoring SElf-Tolerance (RESET ) Clinical Program for CABA-201 SLE - Systemic lupus erythematosus; DM - Dermatomyositis; SSc - Systemic sclerosis;
gMG - Generalized myasthenia gravis; ESRD - End-stage renal disease; PV - pemphigus vulgaris Additional autoimmune indication(s) also being evaluated in preclinical development with ~1M U.S. prevalence SSc gMG PV ~88k ~55k ~13k
Middle age onset common Progressive skin & organ fibrosis with lung, cardiac, renal damage Average survival of 12y Bimodal age of onset Profound weakness that can be disabling Risk for myasthenic crises, with respiratory failure Phase 1/2 Trials
Rheum Neuro Derm U.S. Prevalence No Flu/Cy Pure autoantibody & B-cell mediated autoimmune disease Characterized by painful blisters & erosions SLE ~160-320k Affects young women & people of color ~40% with lupus nephritis, which carries
~25% risk of death or ESRD within 10y > > > Myositis ~68k Typical onset middle age Only FDA-approved therapy is IVIg in DM High mortality due to lung & cardiac involvement >
Industry-leading U.S. clinical site
footprint across RESET program1 Data per clinicaltrials.gov as of October 4, 2024, as compared to companies with actively recruiting U.S. clinical sites for autoimmune cell therapy trials under company-sponsored INDs. 30+ actively recruiting
clinical sites in the U.S. across the RESETTM studies (15 SLE, 9 Myositis, 3 SSc, 3 MG, & 1 PV) SLE sites Myositis sites SSc sites MG sites PV sites
Broad investigation of CABA-201 in
well-defined patient populations with the same dose & similar design Clinical strategy to reduce risk, maximize reach & accelerate timelines SLE - Systemic lupus erythematosus; SSc - Systemic sclerosis; gMG - Generalized
myasthenia gravis; ASyS - Anti-synthetase syndrome; DM - Dermatomyositis; IMNM - Immune-mediated necrotizing myopathy Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide
prior to a single dose CABA-201, followed by short inpatient stay. Ten disease-specific cohorts of 6 patients at the same dose - designed to inform discussions with FDA on registrational path for each indication ASyS Cohort Single infusion1
CABA-201 IMNM Cohort Single infusion1 DM Cohort Skin + Organ Involvement Cohort CABA-201 AChR+ gMG Cohort CABA-201 Lupus Nephritis Cohort CABA-201 Non-renal SLE Cohort Severe Skin Involvement Cohort AChR- gMG Cohort Single infusion1 Single infusion1
Single infusion1 Single infusion1 Single infusion1 Single infusion1 Single infusion1 CABA-201 Juvenile myositis cohort recently incorporated into trial CABA-201 CABA-201 CABA-201 CABA-201 Rheumatology Neurology
Clinical data to be presented at
ACR 2024; enrolling patients with active myositis with DM, ASyS and IMNM RESET-Myositis : Phase 1/2 study design for CABA-201 IIM - Idiopathic inflammatory myopathy; DM - Dermatomyositis; ASyS - Anti-synthetase syndrome; IMNM
- Immune-mediated necrotizing myopathy; CK - creatine kinase Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide prior to a single dose CABA-201, followed by short inpatient
stay. M ller, Fabian, et al. "CD19 CAR T-Cell Therapy in Autoimmune Disease-A Case Series with Follow-up." New England Journal of Medicine 390.8 (2024): 687-700. ASyS B cell-depleting agent within prior ~6 months Primary objective Safety
& tolerability within 28 days of infusion Categories of key secondary objectives Myositis clinical activity CK / muscle enzymes Myositis-specific autoantibody levels Adverse events PK / PD analysis Open-label trial with parallel 6-subject
cohorts Equivalent to dose of 4-1BB CD19-CAR T used in academic report along with standard preconditioning1,2 Screening Study Objectives Phase 1/2 Study Design Evidence of active disease despite standard of care Key inclusion criteria Cancer
associated myositis Key exclusion criteria Significant lung or cardiac impairment Adults 18-75y with a clinical IIM diagnosis Single dose of 1x106 cells/kg1 CABA-201 Single dose of 1x106 cells/kg1 CABA-201 Single dose of 1x106 cells/kg1 CABA-201 DM
IMNM Previous CAR T cell therapy and/or HSCT Subtype based on serology Our goal is to achieve compelling, drug-free, and durable clinical responses through an immune reset Juvenile myositis cohort recently incorporated into trial
Clinical data to be presented at
ACR 2024; enrolling patients with active SLE with or without renal disease RESET-SLE : Phase 1/2 study design for CABA-201 SLE - Systemic lupus erythematosus; SSc - Systemic sclerosis; gMG - Generalized myasthenia gravis
Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide prior to a single dose CABA-201, followed by short inpatient stay. M ller, Fabian, et al. "CD19 CAR T-Cell Therapy in Autoimmune
Disease-A Case Series with Follow-up." New England Journal of Medicine 390.8 (2024): 687-700. SLE with lupus nephritis SLE without renal disease Open-label trial with parallel 6-subject cohorts Equivalent to dose of 4-1BB CD19-CAR T used in
academic report along with standard preconditioning1,2 Screening Study Objectives Phase 1/2 Study Design Confirmatory serology B cell-depleting agent within prior ~6 months SLE: active, moderate to severe SLE, SLEDAI 2K 8 despite standard
therapy Key inclusion criteria Presence of kidney disease other than LN Key exclusion criteria Single dose of 1x106 cells/kg1 CABA-201 Single dose of 1x106 cells/kg1 CABA-201 Adults 18-65y with an SLE diagnosis Primary objective Safety &

Frequently Asked Questions

What is the purpose of the Cabaletta Bio presentation?

The presentation by Cabaletta Bio is for informational purposes only.

What technologies are discussed in the presentation?

The presentation covers CAAR T and CARTA technologies.

What is CABA-201 intended to treat?

CABA-201 is aimed at autoimmune diseases such as systemic lupus and myositis.

Does the presentation include future projections?

Yes, it contains forward-looking statements regarding business and clinical strategies.

What are potential risks mentioned in the presentation?

Risks include development uncertainties and challenges in clinical trial outcomes.

Last updated: Oct 4, 2024