Cabaletta Bio : Corporate Presentation

Corporate Presentation

MAY 2024

© 2024 Cabaletta Bio. All rights reserved.

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-PVsub-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.

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

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Realizing the vision to transform autoimmune disease treatment

Engineered CABA-201 specifically for use in autoimmune patients

• Leveraging data from an academic 4-1BB CD19- CAR T construct with favorable safety data & durable, drug free remissions1

Designed & implemented novel Phase 1/2 clinical program to accelerate path to approval

• No requirement for dose escalation
• Independent, parallel 6-patient cohorts
• Broad portfolio of trials in autoimmunity

1H24:

No reported CRS or ICANS in first myositis or SLE patients2

Clinical update on each patient anticipated at

EULAR symposium

2H24: Additional data from myositis & SLE trials

Initial clinical data in SSc & gMG trials

		Evaluating CABA-201 without preconditioning in PV study
		Advancing program to potentially eliminate apheresis
Initiated CABA-201 dosing in	Cash runway	Securing scalable commercial manufacturing
two company-sponsored studies	into 1H26

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.

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2. Within the 28-day dose limiting toxicity observation window for each patient.

Pipeline targeting autoimmune diseases with high unmet need

Innovative and scalable clinical strategy with potential for accelerated development path

Program		Trial	Preclinical		Phase 1/2	Pivotal
				Dermatomyositis
		RESET-Myositis	Anti-synthetase syndrome			Rheumatology
				Neurology
				IMNM			Dermatology
		RESET-SLE	Lupus Nephritis			Contains cohort(s) without preconditioning
		Non-Renal SLE
CABA-201	FTD
4-1BBCD19-CAR T	RESET-SSc	Skin + Organ Cohort	IND
		Skin Cohort	cleared
		RESET-MG	AChR-Ab pos. gMG	IND
		AChR-Ab neg. gMG	cleared
		RESET-PV	Sub-study1	Mucocutaneous & mucosal pemphigus vulgaris

CAART FTD

Chimeric AutoAntibody

Receptor T cells

DesCAARTes	Mucosal pemphigus vulgaris2
MusCAARTes	MuSK-Ab positive MG2

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.

Chimeric Antigen Receptor T Cells for Autoimmunity

CABA-201

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Academic data: Immune system reset in autoimmune patients

Promising clinical responses in 15 patients across several autoimmune diseases with 4-1BBCD19-CAR T1,2

100%

Objective clinical

response rate in SLE,

myositis, SSc

T cell expansion & B cell depletion within 1st month enabled robust clinical improvement by 3 months

<7%

Rate of CRS more severe than fever (1/15)

11/15 patients reported by Erlangen group with CRS, 10/11 with fever*

Single grade 1 ICANS event reported (transient dizziness)

*One grade 2 CRS (increased

oxygen requirement in patient with

pre-existing lung disease3)

2+

Years of SLE

durable drug-free

remission

Up to 29 months of follow-up in the 15 patients reported by Erlangen group

3-7

Months to naïve B cell repopulation

In patients with ≥5 months

of follow-up, complete B cell elimination followed by return of healthy naïve B cells within median of

~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.

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

Cabaletta's CD19 binder with similar in vitro & in vivo activity to FMC631,2 (binder used in academic report3)

No CRS or ICANS reported in either of

the first myositis or SLE patients

Fully human anti-CD19 binder

Similar binding affinity & biologic activity to FMC63, with binding to the same epitope1,2

4-1BB costimulatory domain

Same co-stim. domain as used in academic studies

CD3-zeta signaling domain

CABA-2015

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

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.

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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

Neuro

Undiscl.

U.S.

Prevalence

Myositis

Typical onset middle age

Only FDA-approved therapy is IVIg in DM

High mortality due to lung

& cardiac involvement

~66k

SLE

Affects young women &

people of color

~40% with lupus nephritis, which carries ~25% risk of death or ESRD within 10y

~160-320k

SSc

Middle age onset common

Progressive skin & organ fibrosis with lung, cardiac, renal damage

Average survival of 12y

~88k

gMG

Bimodal age of onset

Profound weakness that

can be disabling

Risk for myasthenic crises,

with respiratory failure

~55k

2024

Autoimmune diseases in which B cells play a key role

Over 1 million

CABA-201 also to be evaluated in the absence of preconditioning in pemphigus vulgaris sub-study

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

ASyS
Cohort		CABA-201
	Single
	infusion1

Lupus
Nephritis		CABA-201
Cohort
	Single
	infusion1

Skin + Organ

Involvement

Cohort

CABA-201

Single

infusion1

AChR+
gMG		CABA-201
Cohort
	Single
	infusion1

DM
Cohort		CABA-201
	Single
	infusion1
IMNM
Cohort		CABA-201
	Single
	infusion1

Non-renal
SLE		CABA-201
Cohort
	Single
	infusion1

Severe Skin

Involvement

Cohort

CABA-201

Single

infusion1

AChR-
gMG		CABA-201
Cohort

Single

infusion1

CD19-CAR T clinical data reported in academic literature2

No CD19-CAR T clinical data

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.

2. The data reported in the academic literature does not employ CABA-201.

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