CABA Cabaletta Bio Inc

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Exhibit 99.1

 

Cabaletta Bio Reports First Quarter 2024 Financial Results and Provides Business Update

– No CRS or ICANS of any grade observed during the 28-day DLT observation window for either of the first patients dosed with CABA-201 in the RESET-Myositis^™ and RESET-SLE^™ trials –

– Initial clinical data from each of the first patients in the RESET-Myositis and RESET-SLE trials to be presented at a satellite symposium at the EULAR 2024 Congress in June –

– Evaluating CABA-201 without preconditioning by initiation of the RESET-PV^™ sub-study within the ongoing DesCAARTes^™ trial in pemphigus vulgaris –

PHILADELPHIA, May 15, 2024 – Cabaletta Bio, Inc. (Nasdaq: CABA), a clinical-stage biotechnology company focused on developing and launching the first curative targeted cell therapies designed specifically for patients with autoimmune diseases, today reported financial results for the first quarter ended March 31, 2024, and provided a business update.

“With no CRS or ICANS of any grade observed in either of the first patients from the RESET-Myositis and RESET-SLE trials, we look forward to presenting initial translational and clinical data from both patients during a satellite symposium at the EULAR 2024 Congress on June 14^th,” said Steven Nichtberger, M.D., Chief Executive Officer and Co-founder of Cabaletta. “In addition to implementing our development path for CABA-201, we have made substantial progress on two innovations designed to optimize the patient and physician experience. First, we are evaluating CABA-201 without preconditioning through the incorporation of the RESET-PV sub-study within the ongoing DesCAARTes trial in patients with pemphigus vulgaris, expanding CABA-201 development into dermatology. Second, we demonstrated the potential to eliminate the need for apheresis by using a blood draw to obtain the starting material for the CABA-201 manufacturing process as presented at the ASGCT meeting. We are evaluating the opportunity to incorporate an apheresis-free process into our ongoing CABA-201 clinical program. By executing on our CABA-201 development strategy and integrating these types of innovations, we believe that we are well positioned to deliver on the full potential of the targeted cell therapies that we are developing to provide durable, drug-free remissions for patients with a broad range of autoimmune diseases.”

Recent Operational Highlights and Upcoming Anticipated Milestones

Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) Strategy

CABA-201: Autologous, engineered T cells designed with a chimeric antigen receptor containing a fully human CD19 binder and a 4-1BB co-stimulatory domain as a potential treatment for a broad range of autoimmune diseases across multiple therapeutic portfolios where B cells contribute to the initiation and/or maintenance of disease.

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Rheumatology Portfolio

 

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Myositis (idiopathic inflammatory myopathies)

 

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In March 2024, Cabaletta announced the first patient had been dosed in the Phase 1/2 RESET-Myositis trial. No evidence of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade was observed during the 28-day dose-limiting toxicity (DLT) observation window following administration. Patient enrollment in the Phase 1/2 RESET-Myositis trial is ongoing and initial clinical data from the first patient is anticipated to be presented in a satellite symposium at the EULAR 2024 Congress in June.

 

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During the first quarter of 2024, Cabaletta announced that the U.S. Food and Drug Administration (FDA) granted regulatory designations to CABA-201 in myositis, including Fast Track Designation for the treatment of patients with dermatomyositis, Orphan Drug Designation for the treatment of idiopathic inflammatory myopathies (IIM, or myositis) and Rare Pediatric Disease Designation for the treatment of juvenile dermatomyositis.

 

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Systemic lupus erythematosus (SLE)

 

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The first patient has been dosed in the Phase 1/2 RESET-SLE trial. No evidence of CRS or ICANS of any grade was observed during the 28-day DLT observation window following administration. Patient enrollment in the Phase 1/2 RESET-SLE trial is ongoing and initial clinical data from the first patient is anticipated to be presented in a satellite symposium at the EULAR 2024 Congress in June.

 

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In March 2024, Health Canada issued a No Objection Letter in response to a Clinical Trial Application for the RESET-SLE trial submitted by Cabaletta, enabling the Company to begin the process to activate clinical trial sites and pursue patient enrollment for the RESET-SLE trial in Canada.

 

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Systemic sclerosis (SSc)

 

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During the first quarter of 2024, Cabaletta announced that the FDA granted regulatory designations to CABA-201 in SSc, including Fast Track Designation for the treatment of patients with SSc and Orphan Drug Designation for the treatment of SSc.

 

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Cabaletta expects to report initial clinical data from the Phase 1/2 RESET-SSc™ trial in the second half of 2024.

Dermatology Portfolio

 

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Pemphigus vulgaris (PV)

 

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Cabaletta is working with active clinical sites to incorporate the RESET-PV sub-study within the Phase 1 DesCAARTes trial following the submission of a protocol amendment. The RESET-PV sub-study will evaluate CABA-201 as a monotherapy without preconditioning in patients with mucosal PV (mPV) and mucocutaneous PV (mcPV).

Neurology Portfolio

 

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Generalized myasthenia gravis (gMG)

 

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Cabaletta expects to report initial clinical data from the Phase 1/2 RESET-MG™ trial in the second half of 2024.

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Past and Upcoming External Scientific Presentations

 

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In May 2024, Cabaletta presented new preclinical data at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting demonstrating the ability to manufacture autologous CD19-CAR T cells from a blood draw as a potential alternative to apheresis. Whole blood collections from 80mL to 200mL were successfully used in lieu of apheresis material to produce CAR T cells that demonstrated similar growth, viability, memory phenotype and cytotoxicity across 3 healthy donors. In addition, CD19-CAR T cells were manufactured successfully from whole blood sourced from 2 lupus patients and showed expected T cell memory subtype and cytotoxic functionality.

 

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In June 2024, Cabaletta plans to present initial clinical data from each of the first patients treated with CABA-201 in the RESET-Myositis and RESET-SLE trials in a EULAR European Congress of Rheumatology 2024 Industry Symposia session titled “Immune Reset: The Potential of CAR T Cell Therapy to Transform the Treatment of Patients with Autoimmune Disease” at 8:15 a.m. CEST on Friday, June 14, 2024, in Vienna, Austria.

Chimeric AutoAntibody Receptor T (CAART) cells Strategy

 

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DSG3-CAART: Cabaletta is evaluating desmoglein 3 chimeric autoantibody receptor T (DSG3-CAART) cells as a potential treatment for patients with mPV. The DesCAARTes trial is not currently dosing patients with DSG3-CAART as we evaluate clinical and translational data from the combination cohort, where patients were pre-treated with IVIg, cyclophosphamide and fludarabine prior to DSG3-CAART infusion, with the aim of improving persistence and activation of DSG3-CAART compared to findings from the no preconditioning cohorts previously reported.

 

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MuSK-CAART: Cabaletta is evaluating muscle-specific kinase (MuSK) chimeric autoantibody receptor T (MuSK-CAART) cells as a potential treatment for patients with MuSK-associated myasthenia gravis (MuSK MG). The MusCAARTes™ trial is not currently dosing patients as we evaluate clinical and translational data from the A1 and A2 cohorts, where patients were treated with MuSK-CAART without preconditioning.

Upcoming Investor Events

Cabaletta plans to participate in the following upcoming investor conferences:

 

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H.C. Wainwright 2nd Annual BioConnect Investor Conference at NASDAQ, which is being held on May 20, 2024 in New York, NY.

 

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Jefferies Global Healthcare Conference, which is being held from June 5-6, 2024 in New York, NY.

 

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Goldman Sachs 45th Annual Global Healthcare Conference, which is being held from June 10-13, 2024 in Miami, FL.

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First Quarter 2024 Financial Results

 

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Research and development expenses were $22.0 million for the three months ended March 31, 2024, compared to $12.4 million for the same period in 2023.

 

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General and administrative expenses were $6.1 million for the three months ended March 31, 2024, compared to $4.5 million for same period in 2023.

 

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As of March 31, 2024, Cabaletta had cash, cash equivalents and short-term investments of $223.8 million, compared to $241.2 million as of December 31, 2023.

The Company expects that its cash, cash equivalents and short-term investments as of March 31, 2024, will enable it to fund its operating plan into the first half of 2026.

About CABA-201

CABA-201 is designed to deeply and transiently deplete CD19-positive B cells following a one-time infusion, which may enable an “immune system reset” with the potential for durable remission without chronic therapy in patients with autoimmune diseases. Cabaletta is evaluating CABA-201 in multiple autoimmune conditions including systemic lupus erythematosus (SLE), myositis, systemic sclerosis (SSc), generalized myasthenia gravis (gMG) and pemphigus vulgaris (PV). Cabaletta is conducting four Phase 1/2 RESET^™ clinical trials evaluating CABA-201 with a total of nine cohorts that can advance simultaneously, employing a similar parallel cohort design and starting dose of 1 x 10⁶ cells/kg without a dose escalation requirement. CABA-201 is also being evaluated in the absence of preconditioning in a separate sub-study within the DesCAARTes^™ trial for patients with PV.

About Cabaletta Bio

Cabaletta Bio (Nasdaq: CABA) is a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies that have the potential to provide a deep and durable, perhaps curative, treatment for patients with autoimmune diseases. The CABA^™ platform encompasses two strategies: the CARTA (chimeric antigen receptor T cells for autoimmunity) strategy, with CABA-201, a 4-1BB-containing fully human CD19-CAR T, as the lead product candidate being evaluated in the RESET^™ (REstoring SElf-Tolerance) clinical trials in systemic lupus erythematosus, myositis, systemic sclerosis and generalized myasthenia gravis and in the RESET-PV^™ sub-study within the DesCAARTes^™ clinical trial in pemphigus vulgaris, along with the CAART (chimeric autoantibody receptor T cells) strategy, with multiple clinical-stage candidates, including DSG3-CAART for mucosal pemphigus vulgaris and MuSK-CAART for MuSK-associated myasthenia gravis. The expanding CABA^™ platform is designed to develop potentially curative therapies that offer deep and durable responses for patients with a broad range of autoimmune diseases. Cabaletta Bio’s headquarters and labs are located in Philadelphia, PA.

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Forward-Looking Statements

This press release contains “forward-looking statements” of Cabaletta Bio within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including without limitation, express or implied statements regarding: Cabaletta’s ability to grow its autoimmune pipeline; Cabaletta’s future plans and strategies for its CAAR T and CARTA technologies and the company’s business plans and objectives as a whole; statements regarding regulatory filings for its development programs, including the planned timing of such regulatory filings and potential review by regulatory authorities; Cabaletta’s ability to retain and recognize and its expectations around the intended incentives conferred by Fast Track Designation and/or Orphan Drug Designation for CABA-201 for the treatment of multiple autoimmune diseases; Cabaletta’s ability to retain and recognize and its expectations around the potential benefits and incentives provided by FDA’s rare pediatric disease designation for CABA-201; Cabaletta’s expectations around the potential success and therapeutic benefits of CABA-201, including its belief that CABA-201 may enable an “immune system reset” with the potential for durable remission without chronic therapy in patients with autoimmune diseases; the Company’s advancement of separate Phase 1/2 clinical trials of CABA-201 in patients with SLE, myositis, SSc and gMG and advancement of a RESET-PV sub-study within the ongoing DesCAARTes trial in PV, including updates related to status, safety data, or otherwise and the expected timing of the related data read-outs; Cabaletta’s plans to eliminate the need for apheresis by using a simpler collection process to obtain the starting material for the CABA-201 manufacturing process; Cabaletta’s ability to accelerate its pipeline, develop meaningful therapies for patients and leverage its research and translational insights; the Company’s expectations for the efficiency of the trial design for its Phase 1/2 clinical trials of CABA-201 and for its RESET-PV sub-study within the ongoing DesCAARTes trial in PV; Cabaletta’s planned initial clinical data read-out at the EULAR 2024 Congress in June 2024 for patients with myositis and SLE treated with CABA-201; Cabaletta’s additional planned initial clinical data read-outs for patients with SSc and gMG treated with CABA-201 or otherwise; Cabaletta’s advancement of the process to activate clinical trial sites and pursue patient enrollment for the RESET-SLE trial in Canada; Cabaletta’s planned assessment of its DesCAARTes^™ and MusCAARTes^™ trials; use of capital, expense and other financial results in the future; ability to fund operations into the first half of 2026 and the anticipated contribution of the members of Cabaletta’s executives to the company’s operations and progress.

Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to regulatory filings and potential clearance; the risk that signs of biologic activity or persistence may not inform long-term results; Cabaletta’s ability to demonstrate sufficient evidence of safety, efficacy and tolerability in its preclinical studies and clinical trials of CABA-201; the risk that the results observed with the similarly-designed construct employed in academic publications, including due to the dosing regimen, are not indicative of the results we seek to achieve with CABA-201; risks related to clinical trial site activation, delays in enrollment generally or enrollment rates that are lower than expected; delays related to assessment of clinical trial results; risks related to unexpected safety or efficacy data observed during clinical studies; risks related to volatile market and economic conditions and public health crises; Cabaletta’s ability to retain and recognize the intended incentives conferred by Orphan Drug Designation and Fast Track Designation or other designations for its product candidates, as applicable; risks related to Cabaletta’s ability to protect and maintain its intellectual property position; risks related to fostering and maintaining successful relationships with Cabaletta’s collaboration and manufacturing partners, including in light of recent legislation; uncertainties related to the initiation and conduct of studies and other development requirements for its product candidates; the risk that any one or more of Cabaletta’s product candidates will not be successfully developed and/or commercialized; and the risk that the initial or interim results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Cabaletta’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Cabaletta’s most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Cabaletta’s other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Cabaletta undertakes no duty to update this information unless required by law.

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CABALETTA BIO, INC.

SELECTED FINANCIAL DATA

(unaudited; in thousands, except share and per share data)

Statements of Operations

 

		Three Months Ended March 31,
		2024				2023
		Unaudited
Operating expenses:
Research and development		$	21,954			$	12,435
General and administrative			6,077				4,521
Total operating expenses			28,031				16,956
Loss from operations			(28,031	)			(16,956	)
Other income:
Interest income			2,984				1,102
Net loss			(25,047	)			(15,854	)
Net loss per share of voting and non-voting common stock, basic and diluted		$	(0.51	)		$	(0.45	)

Selected Balance Sheet Data

 

		March 31, 2024				December 31, 2023
		(unaudited)
Cash, cash equivalents and investments		$	223,845			$	241,249
Total assets			240,457				253,650
Total liabilities			18,737				17,452
Total stockholders’ equity			221,720				236,198

Contacts:

Anup Marda

Chief Financial Officer

investors@cabalettabio.com

William Gramig

Stern Investor Relations, Inc.

william.gramig@sternir.com

Exhibit 99.2 Corporate Presentation MAY 2024 © 2024 Cabaletta Bio. All rights reserved.

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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 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 benefits of CABA-201, including our belief that CABA-201 may enable an “immune system reset”; Cabaletta's belief of the potential for CAR T to enable a paradigm shift in autoimmunity, including its potential achieve durable remissions without chronic therapy;; 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, clinical trial design, 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 planned initial clinical data read-out in the first half of 2024 at the EULAR 2024 symposium for patients with myositis and SLE treated with CABA-201; our planned initial clinical data read-out in the second half of 2024 for patients with SSc and gMG 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, including IND applications; 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™ and MusCAARTes™ Phase 1 trials; 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 therapeutic potential and clinical benefits of our product candidates; 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; 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 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 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, 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, 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 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 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 rights thereto. 2

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Develop and launch the first curative targeted cellular therapies for patients with autoimmune diseases 3 3

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Realizing the vision to transform autoimmune disease treatment 2H24: Additional data 1H24: from myositis & No reported SLE trials CRS or ICANS in first myositis Initial clinical 2 or SLE patients data in SSc & gMG trials Designed & implemented novel Phase 1/2 clinical program to Clinical update accelerate path to approval on each patient Engineered CABA-201 anticipated at • No requirement for dose escalation specifically for use in EULAR • Independent, parallel 6-patient cohorts autoimmune patients symposium • Broad portfolio of trials in autoimmunity • Leveraging data from an academic 4-1BB CD19- CAR T construct with favorable safety data & durable, drug free 1 remissions Evaluating CABA-201 without preconditioning in PV study Advancing program to potentially eliminate apheresis Cash runway Initiated CABA-201 dosing in Securing scalable commercial manufacturing into 1H26 two company-sponsored studies SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis 1. Müller, 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. 4 2. Within the 28-day dose limiting toxicity observation window for each patient.

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Pipeline targeting autoimmune diseases with high unmet need Innovative and scalable clinical strategy with potential for accelerated development path Phase 1/2 Pivotal Program Trial Preclinical Dermatomyositis Rheumatology Anti-synthetase syndrome RESET-Myositis™ Neurology IMNM Dermatology Contains cohort(s) without preconditioning Lupus Nephritis RESET-SLE™ FTD Non-Renal SLE CABA-201 4-1BB CD19-CAR T Skin + Organ Cohort IND RESET-SSc™ cleared Skin Cohort AChR-Ab pos. gMG IND RESET-MG™ cleared AChR-Ab neg. gMG 1 RESET-PV™ Sub-study Mucocutaneous & mucosal pemphigus vulgaris FTD 2 Mucosal pemphigus vulgaris CAART DesCAARTes™ Chimeric AutoAntibody 2 MuSK-Ab positive MG Receptor T cells MusCAARTes™ RESET™ – REstoring SElf-Tolerance; IMNM – Immune-mediated necrotizing myopathy; SLE – Systemic lupus erythematosus; Ab – Antibody; AChR – Acetylcholine receptor; gMG – Generalized myasthenia gravis 1. Sub-study incorporated into DesCAARTes™ study. 2. Currently being evaluated in a Phase 1 trial and not currently dosing patients with DSG3-CAART or MuSK-CAART. 5 2. FDA Fast Track Designation received in dermatomyositis, SLE and lupus nephritis, systemic sclerosis, mucosal pemphigus vulgaris, and MuSK-Ab positive MG.

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Chimeric Antigen Receptor T Cells for Autoimmunity CABA-201 6

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Academic data: Immune system reset in autoimmune patients 1,2 Promising clinical responses in 15 patients across several autoimmune diseases with 4-1BB CD19-CAR T <7% 3-7 Rate of CRS more Months to naïve B severe than fever cell repopulation (1/15) 100% 2+ Years of SLE Objective clinical durable drug-free response rate in SLE, 11/15 patients reported by myositis, SSc remission Erlangen group with CRS, In patients with ≥5 months 10/11 with fever* of follow-up, complete B cell elimination followed by Single grade 1 ICANS event return of healthy naïve B T cell expansion & B cell reported (transient dizziness) Up to 29 months of follow-up st cells within median of depletion within 1 month *One grade 2 CRS (increased in the 15 patients reported by ~3 months enabled robust clinical oxygen requirement in patient with Erlangen group 3 pre-existing lung disease ) improvement by 3 months One IIM subject reported to have recurrence of muscle disease ~12 months after CD19-CAR T administration; BCMA-CAR T therapy planned CRS – Cytokine release syndrome; ICANS – Immune effector cell-associated neurotoxicity syndrome 1. Müller, 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. 2. The construct utilized in these studies has a similar design to CABA-201, sharing the 4-1BB costimulatory domain, but is a different construct. 7 3. Taubmann J, et al. Efficacy and Safety of CAR-T-Cell Treatment in Refractory Antisynthetase Syndrome – Data of the First Three Patients [ACR abstract; Nov 14, 2023].

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CABA-201 CABA-201: CD19-CAR T specifically designed for autoimmunity 1,2 3 Cabaletta’s CD19 binder with similar in vitro & in vivo activity to FMC63 (binder used in academic report ) No CRS or ICANS reported in either of the first myositis or SLE patients Clinical data reported by IASO using 4 licensed CD19 binder in oncology Fully human anti-CD19 binder Similar binding affinity & biologic activity to FMC63, Fully human binder 1,2 with binding to the same epitope Evaluated as dual-CAR combined with CD22 binder with standard Flu/Cy preconditioning 4-1BB costimulatory domain Data reported in ~20 patients to date Same co-stim. domain as used in academic studies B cell leukemia and lymphoma in IIT in China CD3-zeta signaling domain Safety data supports autoimmune development 5 CABA-201 IIT – Investigator-initiated trial; Flu/Cy – Fludarabine/Cyclophosphamide 1. 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. 2. 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. 3. Müller, 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. 4. Evaluated as part of CT120, a dual-CD19xCD22 CAR T product candidate under development by Nanjing IASO Biotherapeutics, Co., Ltd. (IASO Bio). 5. Transmembrane domain in CABA-201 is CD8α 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-γ production in preclinical studies. The CD8α transmembrane domain is employed in tisagenlecleucel. 8

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CABA-201 REstoring SElf-Tolerance (RESET™) Phase 1/2 trials advancing SLE & myositis trials currently enrolling, with a broadening portfolio to realize the potential of CABA-201 Phase 1/2 Trials Preclinical Rheum Myositis SLE SSc gMG 2024 Neuro Undiscl. > > > > Typical onset middle age Affects young women & Middle age onset common Bimodal age of onset people of color Autoimmune diseases Only FDA-approved Progressive skin & organ Profound weakness that in which B cells play a therapy is IVIg in DM ~40% with lupus nephritis, fibrosis with lung, cardiac, can be disabling key role which carries ~25% risk of renal damage High mortality due to lung Risk for myasthenic crises, death or ESRD within 10y & cardiac involvement Average survival of 12y with respiratory failure U.S. ~66k ~160-320k ~88k ~55k Over 1 million Prevalence CABA-201 also to be evaluated in the absence of preconditioning in pemphigus vulgaris sub-study 9 SLE – Systemic lupus erythematosus; DM – Dermatomyositis; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis; ESRD – End-stage renal disease

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CABA-201 Clinical strategy to reduce risk, maximize reach & accelerate timelines Broad investigation of CABA-201 in well-defined patient populations with the same dose & similar design RESET-Myositis™ RESET-SLE™ RESET-SSc™ RESET-MG™ Lupus ASyS Skin + Organ AChR+ Nephritis Cohort Involvement gMG CABA-201 CABA-201 CABA-201 CABA-201 Cohort Cohort Cohort Single Single Single Single 1 1 1 1 infusion infusion infusion infusion Non-renal Severe Skin AChR- DM SLE Involvement gMG Cohort CABA-201 CABA-201 CABA-201 CABA-201 Cohort Cohort Cohort Single Single Single Single 1 1 1 1 infusion infusion infusion infusion IMNM CD19-CAR T clinical data 2 CABA-201 Cohort reported in academic literature No CD19-CAR T clinical data Single 1 infusion Each cohort to include 6 patients treated with an identical dose – without dose escalation requirement – and designed to inform discussions with FDA on registrational path for each indication SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis; ASyS – Anti-synthetase syndrome; DM – Dermatomyositis; IMNM – Immune-mediated necrotizing myopathy 1. 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. 10 2. The data reported in the academic literature does not employ CABA-201.

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CABA-201 RESET-Myositis™: Phase 1/2 study design for CABA-201 Patient dosing commenced; enrolling patients with active myositis with DM, ASyS or IMNM subtypes Screening Phase 1/2 Study Design Study Objectives Open-label trial with parallel 6-subject cohorts Adults 18-65y Primary objective Safety & tolerability within CABA-201 Clinical IIM diagnosis DM 28 days of infusion 6 1 Single dose of 1x10 cells/kg Subtype based on serology Disease activity despite CABA-201 Categories of key standard of care ASyS secondary objectives 6 1 Single dose of 1x10 cells/kg Recommended vaccines • Pharmacokinetics / pharmacodynamics CABA-201 Cancer associated myositis IMNM • Myositis serology 6 1 Single dose of 1x10 cells/kg Significant lung or cardiac • Myositis clinical activity – impairment Total Improvement Score Equivalent to dose of 4-1BB CD19-CAR T used in Treatment with anti-B cell 1,2 • Functional & radiographic academic report along with standard preconditioning agent within prior ~6 months evidence of disease Treatment with biologic agent within prior ~3 months IIM – Idiopathic inflammatory myopathy; DM – Dermatomyositis; ASyS – Anti-synthetase syndrome; IMNM – Immune-mediated necrotizing myopathy 1. 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. 11 2. Müller, 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. Key exclusion criteria Key inclusion criteria

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CABA-201 RESET-SLE™: Phase 1/2 study design for CABA-201 Patient dosing commenced; enrolling patients with active SLE with or without renal involvement Screening Phase 1/2 Study Design Study Objectives Open-label trial with parallel 6-subject cohorts Adults 18-65y Primary objective Safety & tolerability within Clinical SLE diagnosis CABA-201 SLE with lupus 28 days of infusion Confirmatory serology nephritis 6 1 Single dose of 1x10 cells/kg Disease activity despite Categories of key standard of care secondary objectives CABA-201 SLE without Recommended vaccines • Pharmacokinetics / 6 1 renal disease Single dose of 1x10 cells/kg pharmacodynamics Treatment with anti-B cell • SLE serology agent within prior ~6 months Equivalent to dose of 4-1BB CD19-CAR T used in • SLE clinical activity 1,2 academic report along with standard preconditioning Treatment with biologic agent within prior ~3 months Similarly designed Phase 1/2 trials – RESET-SSc™ & RESET-MG™ – advancing in SSc & gMG SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis 1. 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. 12 2. Müller, 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. Key exclusion criteria Key inclusion criteria

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CABA-201 Evaluating CABA-201 without preconditioning in pemphigus Elimination of preconditioning may expand CAR T Updated PV Study Design opportunity for autoimmune patients Open-label umbrella trial incorporating CABA-201 • Published data in multiple myeloma suggests into DSG3-CAART study 1 preconditioning may not be necessary CABA-201 Mucocutaneous • Experience with and without preconditioning in PV in & mucosal PV DesCAARTes™ study Initiating sub-study without preconditioning As a well-defined autoantibody-mediated disease, DSG3-CAART PV is a potentially ideal evaluation setting Mucosal PV Dose-ranging cohorts in absence of • Anti-DSG antibodies necessary & sufficient for disease preconditioning 2 • Anti-DSG antibodies 98-100% sensitive & specific Mucosal PV Combination with IVIg & CY • Anti-DSG antibodies correlate with disease activity Mucosal PV • Depletion of B cells or antibodies improve disease Combination with IVIg, CY & fludarabine • Clinical scoring based on mucosal & skin disease DSG – Desmoglein; PV – Pemphigus vulgaris 1. Cohen, Adam D., et al. B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma. The Journal of Clinical Investigation 129.6 (2019). 13 2. Schmidt, Enno, et al. Novel ELISA systems for antibodies to desmoglein 1 and 3. Experimental dermatology 19.5 (2010): 458-463. Enrollment completed New sub-study

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Metrics to assess outcomes of B cell depletion in autoimmunity st For CABA-201, translational measures in 1 month may inform clinical outcomes at 3 months CAR T & 1 B cell levels CD19-CAR T Following treatment with autologous CD19-CAR T, 5 pts Cells with 14+ mo. of drug-free remission, as reported by 2 Erlangen group Healthy B Naïve cells B cells Autoreactive B cells Infusion 1 mo. 3 mo. 6 mo. 12+ mo. Metrics of Within 1 month ~3 months 5-12+ months evaluation q Autoantibody changesq Time to B cell repopulation Translational q B cell depletion: Timing & depth q Vaccine titer changesq B cell phenotype q CAR T expansion: Magnitude & timing measures q Inflammatory marker changesq Autoantibody changes q Rate of CRS more severe than fever q Early efficacy signalsq Durability of clinical activity q Rate & grade of ICANS Clinical data q Rate & severity of infectionq Rate & severity of infection q Rate & severity of infection q Hospitalization requirements Patient q Chronic maintenance therapy / q Chronic maintenance / q Apheresis & preconditioning concomitant medications, if any concomitant medications, if any experience q Single vs. multiple infusions SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis 1. Illustrative graphic, adapted from Taubmann, J., et al. OP0141 Long Term Safety and Efficacy Of CAR-T Cell Treatment in Refractory SLE-Data from the First Seven Patients. (2023): 93-94. 14 2. Müller, 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.

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Manufacturing strategy Staged approach allows for efficient allocation of capital while leveraging experienced partners Early Phase: Late Phase & Commercial: Penn, CDMOs & CABA Process Scale-Up & Commercialization Data-gated, staged investment Ongoing • Penn has reliably provided timely product for years • Evaluating paths to commercial-ready manufacturing: • Expanded commercial CDMO partnerships for • Expansion of CDMO relationships vector and cell product supply • Opportunities for automated manufacturing • Process development work on track to implement • Cabaletta-operated facility commercial-ready process in pivotal studies • Strategic partnership(s) • Continuous focus on innovations to address scale • Internal program • Cellares technology assessment program ongoing 15

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Securing & expanding our leadership in autoimmune cell therapy Rapidly advancing to address patient need Broadening potential to serve patients Advancing the RESET™ clinical trials Biologic opportunity for potential cure or paradigm-shifting treatment with the goal of delivering on our commitment to patients may be possible in dozens of autoimmune diseases • Rheumatoid arthritis • ANCA-associated vasculitis Rheumatology • Sjögren’s syndrome Myositis • Multiple sclerosis Systemic lupus erythematosus • Neuromyelitis optica Neurology • CIDP Systemic sclerosis • Membranous nephropathy Generalized myasthenia gravis Nephrology • Goodpasture’s syndrome Pemphigus vulgaris • Pemphigus foliaceus • Epidermolysis bullosa acquisita Dermatology • Bullous pemphigoid • Immune thrombocytopenic purpura Minimizing the requirement for inpatient stay • Thrombotic thrombocytopenic purpura Hematology • Antiphospholipid syndrome Optimizing the preconditioning regimen • Autoimmune hemolytic anemia 1 Seeking to remove the burden of apheresis • Type 1 diabetes • Graves’ disease Endocrinology • Hashimoto’s disease Innovating to address scale in autoimmune disease 16 1. Abstract 1372: Autologous CD19 CART Manufacturing from Whole Blood Collection for the Treatment of Autoimmune Disease. ASGCT 2024.

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Corporate Summary 17

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Cabaletta Bio leadership Track record of operational success evaluating novel cell therapy candidates in autoimmunity LEADERSHIP TEAM Steven Nichtberger, M.D. Samik Basu, M.D. Gwendolyn Binder, Ph.D. David J. Chang, M.D., M.P.H., FACR Arun Das, M.D. President, CEO & Chairman Chief Scientific Officer President, Science & Technology Chief Medical Officer Chief Business Officer Michael Gerard Heather Harte-Hall Anup Marda Martha O’Connor General Counsel Chief Compliance Officer Chief Financial Officer Chief HR Officer BOARD OF DIRECTORS SCIENTIFIC ADVISORY BOARD Steven Nichtberger, M.D. Richard Henriques Aimee Payne, M.D., Ph.D. Michael C. Milone, M.D., Ph.D. Co-Founder and Co-Chair Co-Founder and Co-Chair Catherine Bollard, M.D. Mark Simon Brian Daniels, M.D. Georg Schett, M.D. Scott Brun, M.D. Shawn Tomasello Carl June, M.D. Jay Siegel, M.D. From Fortune. Iain McInnes, Ph.D., FRCP, FRSE, FMedSci Drew Weissman, M.D., Ph.D. ©2023 Fortune Media IP Limited. All rights reserved. Used under license. 18

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Realizing the vision to transform autoimmune disease treatment 2H24: Additional data 1H24: from myositis & No reported SLE trials CRS or ICANS in first myositis Initial clinical 2 or SLE patients data in SSc & gMG trials Designed & implemented novel Phase 1/2 clinical program to Clinical update accelerate path to approval on each patient Engineered CABA-201 anticipated at • No requirement for dose escalation specifically for use in EULAR • Independent, parallel 6-patient cohorts autoimmune patients symposium • Broad portfolio of trials in autoimmunity • Leveraging data from an academic 4-1BB CD19- CAR T construct with favorable safety data & durable, drug free 1 remissions Evaluating CABA-201 without preconditioning in PV study Advancing program to potentially eliminate apheresis Cash runway Initiated CABA-201 dosing in Securing scalable commercial manufacturing into 1H26 two company-sponsored studies SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; gMG – Generalized myasthenia gravis 1. Müller, 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. 19 2. Within the 28-day dose limiting toxicity observation window for each patient.

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Corporate Presentation MAY 2024 © 2024 Cabaletta Bio. All rights reserved.

v3.24.1.1.u2

Document and Entity Information	May 15, 2024
Cover [Abstract]
Amendment Flag	false
Entity Central Index Key	0001759138
Document Type	8-K
Document Period End Date	May 15, 2024
Entity Registrant Name	CABALETTA BIO, INC.
Entity Incorporation State Country Code	DE
Entity File Number	001-39103
Entity Tax Identification Number	82-1685768
Entity Address, Address Line One	2929 Arch Street
Entity Address, Address Line Two	Suite 600
Entity Address, City or Town	Philadelphia
Entity Address, State or Province	PA
Entity Address, Postal Zip Code	19104
City Area Code	(267)
Local Phone Number	759-3100
Written Communications	false
Soliciting Material	false
Pre Commencement Tender Offer	false
Pre Commencement Issuer Tender Offer	false
Security 12b Title	Common Stock, par value $0.00001 per share
Trading Symbol	CABA
Security Exchange Name	NASDAQ
Entity Emerging Growth Company	true
Entity Ex Transition Period	false

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