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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of The Securities Exchange Act of 1934

October 2, 2023

Date of Report (Date of earliest event reported)

 

 

CABALETTA BIO, INC.

(Exact name of Registrant as Specified in its Charter)

 

 

 

Delaware   001-39103   82-1685768
(State or other jurisdiction
of incorporation)
  (Commission
File Number)
  (I.R.S. Employer
Identification No.)

 

2929 Arch Street, Suite 600,

Philadelphia, PA

    19104
(Address of principal executive offices)     (Zip Code)

(267) 759-3100

(Registrant’s telephone number, including area code)

Not Applicable

(Former name or former address, if changed since last report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of Each Class

 

Trading
Symbol(s)

 

Name of Each Exchange

on Which Registered

Common Stock, par value $0.00001 per share   CABA   The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. 

 

 

 


Item 7.01

Regulation FD Disclosure.

On October 2, 2023, Cabaletta Bio, Inc. (the “Company” or “Cabaletta”) posted to the “Investors & Media” section of the Company’s website at www.cabalettabio.com an updated corporate presentation (the “Corporate Presentation”). A copy of the Corporate Presentation is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K.

On October 2, 2023, the Company issued a Press Release announcing that the Company’s third Investigational New Drug (“IND”) application for CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, has been cleared by the U.S. Food and Drug Administration (the “FDA”) for a Phase 1/2 study in patients with systemic sclerosis (“SSc”) (the “Press Release”). A copy of the Press Release is attached hereto as Exhibit 99.2 to this Current Report on Form 8-K.

The information contained in Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1 and 99.2 attached hereto, is being furnished and shall not be deemed to be “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section and shall not be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.

 

Item 8.01

Other Events.

On October 2, 2023, the Company issued the Press Release announcing that the Company’s third IND application for CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, has been allowed to proceed by the FDA for a Phase 1/2 study in patients with SSc. The Company plans to initiate a Phase 1/2 clinical trial of CABA-201 across two parallel SSc cohorts – one cohort of six patients with severe skin manifestations and a separate cohort of six patients with severe organ involvement associated with systemic sclerosis. Consistent with the previously announced CABA-201 IND clearances for lupus and myositis, the starting dose for the trial, 1 x 106 cells/kg, was informed by the high degree of similarity between CABA-201 and the CD19-CAR T construct administered to a patient with severe, diffuse SSc in the recent Annals of Rheumatic Diseases publication.

SSc is a rare and potentially fatal chronic autoimmune disease characterized by progressive skin and internal organ fibrosis that can be life-threatening, including interstitial lung disease, pulmonary hypertension, and scleroderma renal crisis. Although the etiology of SSc is not well understood, the pathogenic role of autoantibodies and B cells in SSc provides a rationale for studying CAR T therapy in this population. SSc affects approximately 88,000 patients in the U.S., and typically affects middle-aged individuals, particularly women. Standard treatment options, which have modest effects, include generalized immunosuppressive agents or drugs targeted to specific symptomatic manifestations. Autologous hematopoietic stem cell transplant may provide some benefits in organ involvement, but carries significant risks, including mortality, infertility, and secondary autoimmune disease, limiting its potential to be applied broadly. Due to the lack of adequate treatments, the risk of mortality in systemic sclerosis remains high, with an average survival of approximately 12 years following diagnosis.

The Phase 1/2 clinical trial will be an open-label study of CABA-201 in subjects with SSc across two parallel cohorts. The severe skin cohort will include six patients with severe skin involvement, and the organ cohort will include six patients who meet the pulmonary, cardiac, or renal involvement criteria regardless of skin involvement. Subjects will receive a one-time infusion of CABA-201, using the same dose being used in the lupus and myositis clinical trials of CABA-201, 1 x 106 cells/kg, preceded by a standard preconditioning regimen of fludarabine and cyclophosphamide. Key inclusion criteria include patients between ages 18 and 70 (inclusive), evidence of significant skin, pulmonary, renal, or cardiac involvement, and significant organ involvement despite use of immunosuppressants. Key exclusion criteria include a primary diagnosis of another rheumatic autoimmune disease, treatment with a B cell depleting agent within six months or treatment with a biologic agent within three months. As the third trial within Cabaletta’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) strategy, this study is intended to evaluate the potential ability of CABA-201 to transiently, but completely, eliminate B cells throughout the body, potentially enabling an immune system reset associated with a slowing or halting of active inflammatory disease progression in patients with SSc.


Forward Looking Statements

The information under this Item 8.01 contains “forward-looking statements” of the Company within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including without limitation, express or implied statements regarding its expectations regarding: Cabaletta’s ability to grow its autoimmune-focused pipeline; the ability to capitalize on and potential benefits resulting from published, third-party academic clinical data and a recently released abstract by the same academic group at the upcoming American College of Rheumatology Convergence 2023 meeting; the anticipated market opportunities for CABA-201 in SSc patients; the Company’s business plans and objectives; Cabaletta Bio’s expectations around the potential success and therapeutic benefits of CABA-201; the Company’s plans to initiate separate Phase 1/2 clinical trials of CABA-201 in subjects with SSc, SLE and myositis, including its anticipated progress, clinical trial design, ability to leverage its experience in autoimmune cell therapy and autoimmune disease product development for each clinical trial; the Company’s planned initial clinical data read-out from the CABA-201 program in the first half of 2024; Cabaletta’s ability to enroll the requisite number of patients and dose each dosing cohort in the intended manner in its Phase 1/2 clinical trials of CABA-201; and the ability to accelerate Cabaletta’s pipeline and develop meaningful therapies for patients, including in collaboration with academic and industry partners and the ability to optimize such collaborations on its development programs.. Any forward-looking statements in this Item 8.01 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 DSG3-CAART, MuSK-CAART and CABA-201; the risk that the results observed with the similarly-designed construct employed in the recent Nature Medicine and Annals of Rheumatic Diseases 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 or enrollment rates that are lower than expected; 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 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; 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 and subsequent filings with the Securities and Exchange Commission. All information in this Item 8.01 is as of the date of this Current Report on Form 8-K, and the Company undertakes no duty to update this information unless required by law.

 

Item 9.01

Financial Statements and Exhibits.

(d) Exbibits

 

99.1    Cabaletta Bio, Inc. Corporate Presentation, dated October 2023, furnished herewith.
99.2    Press Release issued by the registrant on October 2, 2023, furnished herewith.
104    Cover Page Interactive Data File (embedded within the Inline XBRL Document).


SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned, hereunto duly authorized.

 

    CABALETTA BIO, INC.
Date: October 2, 2023     By:  

/s/ Steven Nichtberger

      Steven Nichtberger, M.D.
      President and Chief Executive Officer

Exhibit 99.1 Corporate Presentation OCTOBER 2023 © 2023 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 and CABA™ platform; our ability to grow our autoimmune-focused pipeline; the ability to capitalize on and potential benefits resulting from (i) the translational research partnership with Professor Georg Schett; (ii) the exclusive license agreement with IASO Bio; and (iii) the published systemic sclerosis (SSc) case report in a CD19-CAR T treated patient with SSc; the anticipated market opportunities for CABA-201 in SSc patients; 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” and provide deep and durable responses for patients with autoimmune diseases; our plans for Phase 1/2 clinical trials of CABA-201 in patients with systemic lupus erythematosus (SLE), myositis and SSc, including our anticipated progress, clinical trial design, and ability to leverage our experience in autoimmune cell therapy; our planned initial clinical data read-out in the first half of 2024 for patients treated with CABA-201; our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and advance the trial as planned in our Phase 1/2 clinical trials of CABA-201; the ability to retain and recognize the intended incentives conferred by any Fast Track Designations for CABA-201; the timing any planned regulatory filings for our development programs; the progress and results of our DesCAARTes™ Phase 1 trial, including the significance and impact around reported safety and clinical and translational data of cohorts from our DesCAARTes™ trial, and our ability to advance dose escalation and initiate combination cohorts and to optimize our targeted cell therapy; our ability to implement a pre-treatment regimen, the outcomes of such pre-treatment regimen and the potential ability to enhance in vivo DSG3-CAART exposure; the therapeutic potential and clinical benefits of our product candidates; the expectation that Cabaletta may improve outcomes for patients suffering from SLE, SSc, myositis, mucosal pemphigus vulgaris, myasthenia gravis, or other autoimmune diseases; our ability to escalate dosing as high as 15 billion cells in cohort A6m, initiate dosing in a combination cohort or otherwise; our ability to evaluate, and the potential significance of, the relationship between DSG3-CAART persistence and potential clinical responses in patients with mPV; our ability to safely retreat additional patients and whether we will continue to observe a lack of immune-mediated clearance of DSG3- CAART cells after retreatment and repeat dosing of patients; our ability to successfully complete our preclinical and clinical studies for our product candidates, including our ability to enroll the requisite number of patients, dose each dosing cohort in the intended manner, and progress the trial; the ability of MuSK-CAART to target B cells that differentiate into antibody secreting cells, which produce autoantibodies against muscle-specific kinase; our ability to obtain and maintain regulatory approval of our product candidates, including our expectations regarding the intended incentives conferred by and ability to retain Orphan Drug Designation and Fast Track Designation for our product candidates, as applicable; the further expansion and development of our modular CABA™ platform across a range of autoimmune diseases; our ability to 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, implement an enhanced manufacturing process and further develop our internal manufacturing strategy, capabilities and facilities; our potential commercial opportunities, including value and addressable market, for our product candidates; our expectations regarding our use of capital and other financial results; and our ability to fund operations into the fourth quarter of 2025. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “should” and “could,” and similar expressions or words, identify forward-looking statements. Various risks, uncertainties and assumptions could cause actual results to differ materially from those anticipated or implied in our forward-looking statements. Such risks and uncertainties include, but are not limited to, risks related to the success, cost, and timing of our product candidate development activities and preclinical studies and clinical trials, risks related to our ability to demonstrate sufficient evidence of safety, efficacy and tolerability in our preclinical studies and clinical trials of CABA-201, DSG3-CAART and MuSK-CAART, the risk that the results observed with the similarly-designed construct, including, but not limited to, due to dosing regimen, are not indicative of the results we seek to achieve with CABA-201, our plans to evaluate additional cohorts in the DesCAARTes™ trial, including a cohort implementing a pre-treatment regimen, the risk that signs of biologic activity or persistence may not inform long-term results, the risk that persistence observed with effective CART-19 oncology studies in combination with lymphodepletion is not indicative of, or applicable to, clinical responses in patients with mPV, risks related to clinical trial site activation or enrollment rates that are lower than expected, our ability to protect and maintain our intellectual property position, risks related to our 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


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


® Cabaletta : Pursuing cures for a broad range of autoimmune diseases Leveraging years of experience with cellular therapy in autoimmunity to initiate CABA-201 clinical trials CARTA Strategy | CABA-201 (4-1BB CD19-CAR T) to be evaluated in parallel myositis, SLE & SSc Phase 1/2 studies Advancing myositis, SLE & systemic sclerosis trials with efficient designs, including starting dose & parallel cohorts 6 1-3 • 1.0 x 10 cells/kg initial dose of CABA-201 is identical to dose in academic myositis, SLE & SSc studies • Independent, parallel cohorts with 6 patients each – 3 in myositis (DM, ASyS & IMNM); 2 in SLE (LN & non-renal); 2 in SSc (skin & organ) CABA-201 has been specifically engineered for patients with autoimmune diseases • Fully human CD19 binder with data in ~20 oncology patients – clinical safety profile supporting further evaluation in autoimmunity 4 1-3 • Same 4-1BB costimulatory domain and similar CD19 binder affinity as used in the academic myositis, SLE & SSc studies Potential to cure a broad range of autoimmune diseases where B cells have a role initiating and driving disease • Clinical data from multiple academic institutions reinforcing potential of CD19-CAR T in autoimmunity with early industry studies underway • Opportunity to address unmet need in autoimmune diseases across rheumatology, neurology, nephrology and dermatology, among others CAART Strategy | DSG3-CAART & MuSK-CAART clinical studies evaluating combination regimens DesCAARTes™ trial of DSG3-CAART in mucosal pemphigus vulgaris – Flu / Cy plus IVIg cohort enrolling MusCAARTes™ trial in MuSK myasthenia gravis – leveraging insights from experience with DSG3-CAART 5 Initial CABA-201 3-month clinical efficacy & tolerability data expected by 1H24 | $176M cash with runway into 4Q25 CARTA – Chimeric Antigen Receptor T cells for Autoimmunity; CAART – Chimeric AutoAntibody Receptor T cells; IND – Investigational New Drug; SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; DM – Dermatomyositis; ASyS – Anti-synthetase syndrome; IMNM – Immune-mediated necrotizing myopathy; Flu – Fludarabine; Cy – Cyclophosphamide 1. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 2. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023). 3. Bergmann, Christina, et al. AB0816 Treatment of a Patient with Severe Diffuse Systemic Sclerosis (Ssc) Using CD19-targeting CAR-T-cells. (2023): 1621-1621. 4. Dai, Zhenyu, et al. Development and functional characterization of novel fully human anti‐CD19 CARs for T‐cell therapy. Journal of Cellular Physiology 236.8 (2021): 5832-5847. 4 5. Reported as of 2Q 2023 10-Q.


One CABA™ platform, two strategies to address autoimmune diseases Complementary strategies to optimize clinical outcomes using cellular therapies in autoimmune diseases CARTA CAART Chimeric Antigen Receptor T cells for Autoimmunity Chimeric AutoAntibody Receptor T cells Potential to ‘reset the immune system’ in patients with autoimmune In autoimmune diseases with a limited number of well-defined diseases driven by B cells, through generalized transient B cell pathogenic autoantibodies, permanent antigen-specific B cell 1,2 3 depletion and repopulation of healthy B cells depletion may provide an elegant biologic solution to disease Fully Human Autoantigen Targeting Domain Anti-CD19 Targeting Domain 4-1BB Costimulatory Domain & 4-1BB Costimulatory Domain & CD3-Zeta Signaling Domain CD3-Zeta Signaling Domain CABA-201 DSG3-CAART 1. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 2. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023). 5 3. Ellebrecht, Christoph T., et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science 353.6295 (2016): 179-184.


CABA™ platform may apply across a range of autoimmune diseases Biologic opportunity for cure or treatment may be possible in dozens of autoimmune diseases* 1,2,3,5 • Myasthenia Gravis Neurology 6 • Multiple Sclerosis 3,4,5,6 • Systemic Lupus Erythematosus 3 • Neuromyelitis Optica • Idiopathic inflammatory myopathy • CIDP (Chronic Inflammatory 5 (IIM, myositis) 1.2 Demyelinating Polyneuropathy) Rheumatology 6 3,6 • Systemic sclerosis • Anti-NMDAR Encephalitis 2,3,4 • Rheumatoid Arthritis 5 • Lambert-Eaton Syndrome 3,4,5 • ANCA-Associated Vasculitis 1,2,3 • Pemphigus Vulgaris 3 • Immune Thrombocytopenic Purpura 1,2,3 1,2,3 • Pemphigus Foliaceus Dermatology Hematology • Thrombotic Thrombocytopenic Purpura • Epidermolysis Bullosa 4,5 • Antiphospholipid Syndrome 3 3 Acquisita • Autoimmune Hemolytic Anemia 1,2,3 • Bullous Pemphigoid 3,6 3,4 • Type 1 Diabetes • Lupus Nephritis Endocrinology 3,5 1,2,3 • Graves’ Disease Nephrology • Membranous Nephropathy 5 1,2,3,4 • Hashimoto’s Disease • Goodpasture’s Syndrome • Illustrative list of autoimmune diseases where B cells may play a role in initiating or maintaining disease, and where biologic opportunity for cure or treatment with CAART or CARTA approach may be possible. • Diseases in bold represent where clinical studies are underway or plan to be initiated by Cabaletta 1. Koneczny, Inga. Update on IgG4-mediated autoimmune diseases: new insights and new family members. Autoimmunity Reviews (2020): 102646. 2. Huijbers, Maartje G., et al. IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders. Annals of the New York Academy of Sciences 1413.1 (2018): 92. 3. Ludwig, Ralf J., et al. Mechanisms of autoantibody-induced pathology. Frontiers in immunology 8 (2017): 603. 4. Suurmond, Jolien, and Betty Diamond. Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity. The Journal of clinical investigation 125.6 (2015): 2194-2202. 5. Xiao, Ze Xiu, Joseph S. Miller, and Song Guo Zheng. An updated advance of autoantibodies in autoimmune diseases. Autoimmunity Reviews (2020): 102743. 6 6. Hampe, Christiane S. B cells in autoimmune diseases. Scientifica 2012 (2012).


Pipeline targeting autoimmune diseases where cure is possible Discovery Phase 1/2 Phase 2/3 CABA™ Platform Indication Program Preclinical Dermatomyositis Myositis (IIM, Idiopathic Anti-Synthetase IND cleared Inflammatory Syndrome 1 Myopathy) Immune-Mediated Necrotizing Myopathy CARTA Lupus Nephritis Systemic Lupus CABA-201 Chimeric Antigen Erythematous IND cleared 4-1BB CD19-CAR T 1 Non-Renal Receptor T cells (SLE) SLE for Autoimmunity Severe Skin Involvement Systemic IND cleared 1 Sclerosis (SSc) Organ Involvement Multiple Undisclosed Indications 2 Mucosal CAART 3 DSG3-CAART Pemphigus Vulgaris Chimeric MuSK AutoAntibody 3 MuSK-CAART Myasthenia Gravis Receptor T cells 1. CABA-201 is being evaluated in separate clinical trials for myositis, SLE & SSc. 2. Additional CAART pipeline candidates include PLA2R-CAART in preclinical stage for PLA2R membranous nephropathy, DSG3/1-CAART in discovery stage for mucocutaneous pemphigus vulgaris & 2 undisclosed targets in discovery stage. 7 3. Currently being evaluated in a Phase 1 trial.


Chimeric Antigen Receptor T Cells for Autoimmunity CABA-201 8


Academic data: Immune system reset in autoimmune patients Promising clinical responses observed across several autoimmune diseases in academic CD19-CAR T trials Emerging clinical data with 2 5 8 SLE (N=5) Myositis (N=1) Systemic sclerosis (N=1) Robust improvement 1 4-1BB CD19-CAR T in… in clinical disease activity Systemic lupus within 3 months of 2-4 erythematosus patients CD19-CAR T 8 treatment Myositis patients (anti- + Rapid and deep CD19 B cell depletion 4-7 synthetase subtype) 4 Return of healthy naïve B cells within 7 months Favorable safety data with CD19-CAR T regimen 4,8 Systemic sclerosis patients 4 100% of patients with objective clinical disease response 3 Published data as of Oct 2, 2023 Complete SLE responses up to 2 years with no relapses SLE – Systemic lupus erythematosus; SLEDAI-2K – Systemic Lupus Erythematosus Disease Activity Index 2000; EUSAR – European Scleroderma Trials and Research 1. The construct utilized in these studies has a similar design to CABA-201, sharing the 4-1BB costimulatory domain, but is a different construct. 2. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 3. Taubmann, J., et al. OP0141 Long Term Safety and Efficacy Of CAR-T Cell Treatment in Refractory Systemic Lupus Erythematosus-Data from the First Seven Patients. (2023): 93-94. 4. Taubmann J, Müller F, Aigner M, Minopoulou I, Knitza J, Werner D, Bergmann C, Kroenke G, Mackensen A, Schett G. Tolerability of CAR T Cell Therapy in Autoimmune Disease [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). 5. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023). 6. Taubmann, Jule, et al. Rescue therapy of antisynthetase syndrome with CD19-targeted CAR-T-cells after failure of several B cell depleting antibodies. Rheumatology (Oxford, England) (2023): kead330. 7. Pecher, Ann-Christin, et al. CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome. JAMA 329.24 (2023): 2154-2162. 9 8. Bergmann, Christina, et al. AB0816 Treatment of a Patient with Severe Diffuse Systemic Sclerosis (Ssc) Using CD19-targeting CAR-T-cells. (2023): 1621-1621. SLEDAI-2K Total improvement score EUSTAR activity index


CABA-201 CABA-201: CD19-targeting CAR T therapy for autoimmune diseases 1,2 3,4 Cabaletta’s CD19 binder with similar in vitro & in vivo activity to FMC63 (binder used in academic studies ) CABA-201 Clinical data reported by IASO using 1 Similar in vitro & in vivo biologic activity to FMC63 5 licensed CD19 binder in oncology In vitro CABA-201 Fully human Fully human binder anti-CD19 CD19 binder used in Evaluated as dual-CAR combined with CD22 3,4 academic studies binder binder with standard Flu/Cy preconditioning In vivo Data reported in ~20 patients to date 4-1BB B cell leukemia and lymphoma in IIT in China costimulatory domain Safety data supports autoimmune CD3-Zeta development signaling domain CD19-CAR Construct Same co-stimulatory domain as used in academic studies SLE – Systemic lupus erythematosus; IIT – Investigator-initiated trial; Flu/Cy – Fludarabine/Cyclophosphamide; CRS – Cytokine release syndrome; ICANS – Immune effector cell-associated neurotoxicity syndrome 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. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 4. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023). 5. Evaluated as part of CT120, a dual-CD19xCD22 CAR T product candidate under development by Nanjing IASO Biotherapeutics, Co., Ltd. (IASO Bio). 10


CABA-201 Myositis: Strong scientific rationale & significant disease burden ~66K U.S. patients with IIM subtypes with B cell involvement; frequently severe, with limited treatment options Potential manifestations & subtype prevalence Autoimmune disease with B cell involvement 1 Key myositis subtypes based on underlying immune • Idiopathic inflammatory myopathies (IIMs, or myositis) 1 mechanisms & clinical characteristics are a group of autoimmune diseases characterized by inflammation and muscle weakness 1 High burden on function & quality of life 2 • Typical onset middle age; more common in females • Symptoms may include weakness, fatigue, pain, shortness of breath and difficulty swallowing • Mainstay of therapy is glucocorticoids with a steroid-sparing 2 agent (i.e. methotrexate, azathioprine, mycophenolate, rituximab) ~43K U.S. pts Dermatomyositis (DM) • Only FDA-approved therapy is IVIg (intravenous immunoglobulin) in dermatomyositis subtype 3,4 ~17K U.S. pts • Many patients have disease that remains refractory Anti-synthetase syndrome (ASyS) • Therapies carry potential long-term side effects 5 ~6K U.S. pts Immune-mediated • High mortality rate due to interstitial lung disease (ILD), necrotizing myopathy (IMNM) cardiovascular disease and/or malignancy 1. Lundberg, Ingrid E., et al. Idiopathic inflammatory myopathies. Nature Reviews Disease Primers 7.1 (2021): 86. 2. Kronzer, Vanessa L., et al. Incidence, Prevalence, and Mortality of Dermatomyositis: A Population‐Based Cohort Study. Arthritis Care & Research 75.2 (2023): 348-355. 3. Badshah, Aliena, et al. Antisynthetase syndrome presenting as interstitial lung disease: a case report. Journal of Medical Case Reports 13.1 (2019): 1-6. 4. Coffey, Caitryn, et al. “Incidence of Antisynthetase Syndrome and Risk of Malignancy in a Population-based Cohort (1998-2019)” [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). 11 5. Shelly, Shahar, et al. Incidence and prevalence of immune‐mediated necrotizing myopathy in adults in Olmsted County, Minnesota. Muscle & Nerve 65.5 (2022): 541-546.


CABA-201 Phase 1/2 study design for CABA-201 in patients with myositis CABA-201 to be evaluated in patients with active myositis, including DM, ASyS & IMNM Study Endpoint & Objectives Phase 1/2 Study of CABA-201 Primary objective: Evaluate safety & tolerability of CABA-201 in subjects with Open label trial to evaluate CABA-201 in subjects with active myositis within 28 days of infusion active idiopathic inflammatory myopathy (IIM, or myositis) Key secondary objectives include CABA-201 effects on: Parallel Cohorts • Myositis clinical disease activity; • Functional & radiographic evidence of disease; DM • Myositis serology; and SCREENING CABA-201 MONITORING • Pharmacokinetics / pharmacodynamics (N = 6) Key Inclusion Criteria ASyS SCREENING CABA-201 MONITORING • Age ≥ 18 to ≤ 65 years (N = 6) • Clinical IIM diagnosis per the 2017 EULAR/ACR classification criteria • Disease activity despite prior or current treatment with standard of care treatments IMNM SCREENING CABA-201 MONITORING Key Exclusion Criteria (N = 6) • Cancer-associated myositis 6 1 Dose of 1x10 cells/kg • Significant lung or cardiac impairment Equivalent to dose of 4-1BB-containing CD19-CAR T • Treatment with B cell depleting agent within ~6 months 2,3 used in recent academic studies • Treatment with biologic agent within ~3 months Consistent track record of execution by team across multiple clinical studies evaluating novel cell therapy candidates for patients with autoimmune diseases 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. 2. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 12 3. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023).


CABA-201 SLE & Lupus Nephritis: High unmet clinical need ~320,000 SLE patients in the U.S., ~40% with LN, who face increased risk of kidney failure & death Potential SLE Manifestations SLE is a chronic autoimmune Skin & Lupus nephritis (LN) is a 1 mucosa disease that affects ~160-320K serious complication of SLE, patients in the U.S. & over 3 Kidneys affecting ~40% of SLE patients 2 3 million people worldwide Lungs • Potential for life-threatening complications • Within 10 years of LN diagnosis: Heart 3 • End-stage renal disease: 17% 5 • Disproportionately affects • Mortality: 12% Neurological • young women Joints, muscles 3,4 • people of color & bones • Current therapies include steroids, 3 Blood & immunosuppressive agents and biologics vascular • Significant unmet need remains despite • Many patients progress and/or relapse Immune system current therapies, which require chronic • Significant risk of adverse effects abnormalities administration and carry significant • Require long-term administration treatment-related risks 1. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, Liang MH, Kremers HM, Mayes MD, Merkel PA, Pillemer SR, Reveille JD, Stone JH; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008 Jan;58(1):15-25. 2. Tian, J., Zhang, D., Yao, X., Huang, Y., & Lu, Q. (2023). Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Annals of the Rheumatic Diseases, 82(3), 351-356. 3. Hoover PJ, Costenbader KH. Insights into the epidemiology and management of lupus nephritis from the US rheumatologist's perspective. Kidney Int. 2016 Sep;90(3):487-92. 4. Lewis, M. J., & Jawad, A. S. (2017). The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus. Rheumatology, 56(suppl_1), i67-i77. 5. Hahn, B. H., Mcmahon, M. A., Wilkinson, A., Wallace, W. D., Daikh, D. I., Fitzgerald, J. D., ... & Grossman, J. M. (2012). American College of Rheumatology guidelines for screening, treatment, and 13 management of lupus nephritis. Arthritis care & research, 64(6), 797-808.


CABA-201 Fast Track Phase 1/2 study design for CABA-201 in patients with SLE Designation CABA-201 to be evaluated in patients with active SLE with or without renal involvement Study Endpoint & Objectives Phase 1/2 Study of CABA-201 Primary objective: Evaluate safety & tolerability of CABA-201 in subjects with Open label trial to evaluate CABA-201 in subjects with SLE with active LN or SLE without renal involvement within 28 days of infusion active SLE Parallel Cohorts Key secondary objectives include CABA-201 effects on: • SLE clinical disease activity, and • SLE serology, as well as SLE with • Pharmacokinetics / pharmacodynamics lupus SCREENING CABA-201 MONITORING nephritis (N = 6) Key Inclusion Criteria • Age ≥ 18 to ≤ 65 years SLE without • Clinical SLE per the 2019 EULAR/ACR classification criteria renal • Positive ANA titer or anti-dsDNA antibody SCREENING CABA-201 MONITORING involvement • Disease activity despite prior or current treatment with standard of care (N = 6) 6 1 Key Exclusion Criteria Dose of 1x10 cells/kg Equivalent to dose of 4-1BB-containing CD19-CAR T • Treatment with B cell depleting agent within 6 months 2,3 used in recent academic studies • Treatment with biologic agent within 3 months Consistent track record of execution by team across multiple clinical studies evaluating novel cell therapy candidates for patients with autoimmune diseases SLE – Systemic lupus erythematosus; EULAR – European League Against Rheumatism; ACR – American College of Rheumatology 1. Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide prior to a single dose CABA-201. 2. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 14 3. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023).


CABA-201 Systemic Sclerosis (SSc): Profound unmet need & limited options 1,2 ~88K SSc patients in the U.S., with intractable progression leading to chronic morbidity & high mortality 2 1 Rare, potentially fatal, chronic disease Potential manifestations & classification • Typically, middle age onset & more common in females Progressive fibrosis and scarring of the skin and • Characterized by progressive skin & internal organ fibrosis, often internal organs in SSc may lead to severe & sometimes irreversible 2 life-threatening complications • Potential systemic manifestations that may be life-threatening, such as interstitial lung disease, cardiac dysfunction, pulmonary Skin fibrosis hypertension & scleroderma renal crisis Raynaud (>90%) phenomenon 4 (90%) • Average survival of ~12 years following diagnosis Interstitial lung disease (40%) Lack of adequate treatment options Pulmonary Arterial 2 Hypertension (15%) • Current treatments include generalized immunosuppression or Cardiac involvement drugs targeted to specific symptomatic manifestations Telangiectasia 3 (15%) Calcinosis (75%) Ulcers (25%) • Autologous hematopoietic stem cell transplant may provide some (40%) Musculoskeletal problems (65%) benefits in organ involvement, but is associated with significant 2 toxicities Renal crisis (5-10%) Gastrointestinal The pathogenic role of autoantibodies & B cells in SSc complications (90%) provides rationale to evaluate CAR T therapy to potentially slow or halt disease progression 1. Bergamasco A, Hartmann N, Wallace L, Verpillat P. Epidemiology of systemic sclerosis and systemic sclerosis-associated interstitial lung disease. Clin Epidemiol. 2019;11:257-273. 2. Allanore Y, Simms R, Distler O, Trojanowska M, Pope J, Denton CP, Varga J. Systemic sclerosis. Nat Rev Dis Primers. 2015 Apr 23;1:15002. doi: 10.1038/nrdp.2015.2. PMID: 27189141. 3. Steen, Virginia D., and Thomas A. Medsger Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis & Rheumatism. 43.11 (2000): 2437-2444. 15 4. Mayes MD. Scleroderma epidemiology. Rheum Dis Clin North Am. 2003;29(2):239-254.


CABA-201 Fast Track Phase 1/2 study design for CABA-201 in patients with SSc Designation CABA-201 to be evaluated in patients with systemic sclerosis with severe skin or organ involvement Study Endpoint & Objectives Phase 1/2 Study of CABA-201 Open label trial to evaluate CABA-201 in subjects with Primary objective: Evaluate safety & tolerability of CABA-201 in subjects with SSc at risk for organ disease progression within 28 days of infusion systemic sclerosis Key secondary objectives include CABA-201 effects on: Parallel Cohorts • SSc clinical disease activity, and • SSc serology, as well as SSc with • Pharmacokinetics / pharmacodynamics severe skin SCREENING CABA-201 MONITORING involvement Key Inclusion Criteria (N = 6) • Age ≥ 18 to ≤ 70 years • Evidence of significant skin, pulmonary, renal, or cardiac involvement SSc with • Skin and/or organ involvement despite prior or current treatment with standard of care organ • Diagnosis of limited or diffuse systemic sclerosis per the 2013 EULAR/ACR criteria SCREENING CABA-201 MONITORING involvement (N = 6) Key Exclusion Criteria 6 1 Dose of 1x10 cells/kg • Primary diagnosis of another rheumatic autoimmune disease Equivalent to dose of 4-1BB-containing CD19-CAR T • Treatment with B cell depleting agent within 6 months 2,3,4 used in recent academic studies • Treatment with biologic agent within 3 months Consistent track record of execution by team across multiple clinical studies evaluating novel cell therapy candidates for patients with autoimmune diseases SSc – Systemic sclerosis; EULAR – European League Against Rheumatism; ACR – American College of Rheumatology 1. Subjects will be treated with a standard preconditioning regimen consisting of fludarabine and cyclophosphamide prior to a single dose CABA-201. 2. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 3. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023). 16 4. Bergmann C, Müller F, Distler JHW, et al. “Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells.” Annals of the Rheumatic Diseases (2023);82:1117-1120.


CABA-201 Accelerating development of CABA-201 for autoimmune diseases Our product candidate & uniquely experienced people inform our differentiated development path Efficient clinical trial designs for CABA-201 facilitate rapid & broad development program Candidate with 4-1BB co-stim domain & similar binding Product 1-4 activity to academic CD19-CAR T Accelerating development • CABA-201 fully human binder lowers risk of immunogenicity • Exclusive translational partnership provided • Clinical tolerability profile based on use in ~20 oncology patients early insights with impact to timelines 1,2 • 4-1BB co-stim domain identical to that used in academic CD19-CAR T study • Efficient clinical trial designs across multiple autoimmune diseases with potentially Singular focus on potentially curative cell therapies for People therapeutic starting dose in parallel cohorts autoimmune disease since 2018 • 5 IND filings for autoimmune cell therapies, each cleared in routine 30-day window • Deep understanding & experience with • Experience informing efficient clinical strategy for CABA-201 across multiple indications complex cell therapy programs for autoimmune patients • CMO led development of the only two SLE products approved by FDA in the past 65 years • Leadership team members with extensive experience building cell therapy supply SLE – Systemic lupus erythematosus 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. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 17 4. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023).


Chimeric AutoAntibody Receptor T Cells DSG3-CAART & MuSK-CAART 18


DSG3-CAART Fast Track Fast Track Orphan Drug Ongoing DesCAARTes™ study in patients with mucosal PV Designation Designation Designation Enrolling in Flu / Cy / IVIg cohort to evaluate ability to improve engraftment & clinical activity ™ 1 Antibody-mediated disease DesCAARTes study of DSG3-CAART • Mucosal pemphigus vulgaris (PV) associated with anti-DSG3 Cohorts Combination (Pre-Treatment) Dose* Ongoing open-label antibodies Phase 1 study to A1 – A4 -- 20M to 7.5B determine the • Painful blisters of the mucous A6m -- Up to 15B maximum tolerated membranes, with potential for dose & to evaluate significant morbidity & mortality P4 IVIg / Cyclophosphamide (Cy) 2.5B safety of DSG3- • U.S. prevalence 3,250-4,750 CAART P4F IVIg / Cy / Fludarabine (Flu) 2.5B High unmet clinical need 2 4 • Broad immunosuppression, DSG3-CAART Peak Persistence modestly effective & poorly 1-2 tolerated * • Rituximab plus steroids (~3,500 3 mg/yr) may offer transient remission, but risks severe / 1,3 * Range of persistence observed in CD19-CAR T studies in B cell malignancies potentially fatal infections 1. Joly, Pascal, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. The Lancet 389.10083 (2017): 2031-2040. 2. Kushner, Carolyn J., et al. Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus. JAMA dermatology (2019). 3. Werth, Victoria P., et al. Rituximab versus Mycophenolate Mofetil in Patients with Pemphigus Vulgaris. New England Journal of Medicine (2021). 4. Volkov J, et al. “Correlative findings following DSG3-CAART infusion with & without combination preconditioning therapy in patients with Pemphigus Vulgaris (DesCAARTes study).” Poster presented th at: American Society Gene and Cell Therapy 26 Annual Meeting; 2023 May 18; Los Angeles, CA. 19 * 20M, 2.5B, 7.5B to 15B refers to the number of DSG3-CAART cells infused for patients in dosing cohorts A1 to A6m (M – millions; B – billions).


MuSK-CAART Fast Track Orphan Drug Ongoing MusCAARTes™ study in patients MuSK+ MG Designation Designation Additional opportunity to evaluate CAART platform in disease with differentiated biology ™ MusCAARTes study of MuSK-CAART 1 Compelling biologic rationale, similar to PV Ongoing open-label study to determine the maximum tolerated • IgG4-dominant disease dose & to evaluate safety of MuSK-CAART 1,2 • Autoantibody titers drop after rituximab Part Cohort Subjects • Pathogenic B cells incompletely eliminated by rituximab 7 3 A – Monotherapy Dose Escalation 2 (+4) and persist during relapse A1-A3 Dose increasing from 500M with 2 (+4) design per cohort • Circulating anti-MuSK antibody titers may be ~90% lower 4,5,6 7 than anti-DSG3 antibody in PV A – Adaptive Combination Cohorts 2 (+4) A4+ 8 per cohort Combination cohorts , starting at A2 dose Differentiated market opportunity 2 B – Expansion B ~12 Expanded subject enrollment at final selected dose • Total U.S. MG prevalence 50,000 to 80,000 patients • MuSK+ MG comprises 6-7.5% of total MG population Study Endpoint & Objectives • Compared to AChR+ MG, MuSK+ disease is typically Primary Endpoint: Adverse Events, including DLT more severe with limited treatment options Secondary & Tertiary Objectives: CAART expansion/persistence, • MuSK+ disease has early onset, 7:1 females effect on serum anti-MuSK antibody titer, use of concomitant systemic medications, effect on clinical symptoms, manufacturing success rate MG – Myasthenia gravis * 500M refers to the number of MuSK-CAART cells infused for patients in dosing cohort A1 (M – millions). 1. Hain, Berit, et al. Successful treatment of MuSK antibody–positive MG with rituximab. Muscle & Nerve. 33.4 (2006): 575-580. 2. Illa, Isabel, et al. Sustained response to Rituximab in anti-AChR and anti-MuSK positive Myasthenia Gravis patients. Journal of neuroimmunology 201 (2008): 90-94. 3. Jiang, Ruoyi, et al. Single-cell repertoire tracing identifies rituximab-resistant B cells during myasthenia gravis relapses. JCI insight 5.14 (2020). 4. Matthews, Ian, et al. Muscle-specific receptor tyrosine kinase autoantibodies—a new immunoprecipitation assay. Clinica chimica acta 348.1-2 (2004): 95-99. 5. McConville, John, et al. Detection and characterization of MuSK antibodies in seronegative myasthenia gravis. Annals of neurology 55.4 (2004): 580-584. 6. Marino, Mariapaola, et al. Long-lasting rituximab-induced reduction of specific—but not total—IgG4 in MuSK-positive myasthenia gravis. Frontiers in immunology 11 (2020): 613. 7. A total of 6 subjects will need to have received the final selected dose in Part A of the study. 20 8. Cohorts A3 and A4 will be enrolled concurrently after cohort A2 is well-tolerated with a preference for enrollment into A4.


Corporate Summary 21


Manufacturing strategy Three-stage approach allows for efficient allocation of capital while leveraging experienced partners Stage 1: Stage 2: Stage 3: Penn CDMOs & CABA Process Commercialization & Scale-Up Data-gated, staged investment 2019 – 2021 – • Cell processing capacity secured • CDMOs for vector and cell processing • Leasing followed by engineering and 1 through Penn partnership with commercial support capabilities build out or acquisition of Cabaletta- operated manufacturing facility, and/or • SOPs previously used to develop multiple clinical stage CAR T products • Establishment of a strategic partnership to rapidly & reliably scale • Clinical vector validated manufacturing, leveraging the partner’s manufacturing expertise 22


Cabaletta Bio leadership 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, M.B.A. 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, M.B.A. Brian Daniels, M.D. Georg Schett, M.D. Scott Brun, M.D. Shawn Tomasello, M.B.A. Carl June, M.D. Jay Siegel, M.D. Iain McInnes, Ph.D., FRCP, FRSE, FMedSci Drew Weissman, M.D., Ph.D. Track record of operational success evaluating novel cell therapy candidates in autoimmunity across preclinical, clinical, manufacturing & regulatory domains 23


® Cabaletta : Pursuing cures for a broad range of autoimmune diseases Leveraging years of experience with cellular therapy in autoimmunity to initiate CABA-201 clinical trials CARTA Strategy | CABA-201 (4-1BB CD19-CAR T) to be evaluated in parallel myositis, SLE & SSc Phase 1/2 studies Advancing myositis, SLE & systemic sclerosis trials with efficient designs, including starting dose & parallel cohorts 6 1-3 • 1.0 x 10 cells/kg initial dose of CABA-201 is identical to dose in academic myositis, SLE & SSc studies • Independent, parallel cohorts with 6 patients each – 3 in myositis (DM, ASyS & IMNM); 2 in SLE (LN & non-renal); 2 in SSc (skin & organ) CABA-201 has been specifically engineered for patients with autoimmune diseases • Fully human CD19 binder with data in ~20 oncology patients – clinical safety profile supporting further evaluation in autoimmunity 4 1-3 • Same 4-1BB costimulatory domain and similar CD19 binder affinity as used in the academic myositis, SLE & SSc studies Potential to cure a broad range of autoimmune diseases where B cells have a role initiating and driving disease • Clinical data from multiple academic institutions reinforcing potential of CD19-CAR T in autoimmunity with early industry studies underway • Opportunity to address unmet need in autoimmune diseases across rheumatology, neurology, nephrology and dermatology, among others CAART Strategy | DSG3-CAART & MuSK-CAART clinical studies evaluating combination regimens DesCAARTes™ trial of DSG3-CAART in mucosal pemphigus vulgaris – Flu / Cy plus IVIg cohort enrolling MusCAARTes™ trial in MuSK myasthenia gravis – leveraging insights from experience with DSG3-CAART 5 Initial CABA-201 3-month clinical efficacy & tolerability data expected by 1H24 | $176M cash with runway into 4Q25 CARTA – Chimeric Antigen Receptor T cells for Autoimmunity; CAART – Chimeric AutoAntibody Receptor T cells; IND – Investigational New Drug; SLE – Systemic lupus erythematosus; SSc – Systemic sclerosis; DM – Dermatomyositis; ASyS – Anti-synthetase syndrome; IMNM – Immune-mediated necrotizing myopathy; Flu – Fludarabine; Cy – Cyclophosphamide 1. Mackensen, Andreas, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine (2022): 1-9. 2. Müller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023). 3. Bergmann, Christina, et al. AB0816 Treatment of a Patient with Severe Diffuse Systemic Sclerosis (Ssc) Using CD19-targeting CAR-T-cells. (2023): 1621-1621. 4. Dai, Zhenyu, et al. Development and functional characterization of novel fully human anti‐CD19 CARs for T‐cell therapy. Journal of Cellular Physiology 236.8 (2021): 5832-5847. 24 5. Reported as of 2Q 2023 10-Q.


Corporate Presentation OCTOBER 2023 © 2023 Cabaletta Bio. All rights reserved.

Exhibit 99.2

 

LOGO

Cabaletta Bio Receives FDA Clearance of IND Application for Treatment of Systemic Sclerosis with CABA-201

– Third IND application clearance for CABA-201 within the past 6 months across a broad range of autoimmune diseases –

– Phase 1/2 clinical trial evaluating CABA-201 in systemic sclerosis features parallel cohort design and the same starting dose as the CABA-201 INDs for lupus and myositis –

– Three-month clinical data in initial patients treated with CABA-201 from Phase 1/2 trials in lupus and/or myositis remain on track to be reported by the first half of 2024 –

PHILADELPHIA, Oct. 2, 2023 – Cabaletta Bio, Inc. (Nasdaq: CABA), a clinical-stage biotechnology company focused on developing and launching the first curative targeted cell therapies for patients with autoimmune diseases, today announced that the Company’s third Investigational New Drug (IND) application for CABA-201, a 4-1BB-containing fully human CD19-CAR T cell investigational therapy, has been allowed to proceed by the U.S. Food and Drug Administration (FDA) for a Phase 1/2 study in patients with systemic sclerosis (SSc). The Company plans to initiate a Phase 1/2 clinical trial of CABA-201 across two parallel SSc cohorts – one cohort of six patients with severe skin manifestations and a separate cohort of six patients with severe organ involvement associated with systemic sclerosis. Consistent with the previously announced CABA-201 IND clearances for lupus and myositis, the starting dose for the trial, 1 x 106 cells/kg, was informed by the high degree of similarity between CABA-201 and the CD19-CAR T construct administered to a patient with severe, diffuse SSc in the recent Annals of Rheumatic Diseases publication.

“As we remain on track to deliver three-month clinical data from the initial patients treated with CABA-201 by the first half of 2024, the clearance of our third IND application for CABA-201 within the past 6 months demonstrates our relentless focus on developing CABA-201 for a broad portfolio of potential indications in patients with autoimmune diseases,” said Steven Nichtberger, M.D., Chief Executive Officer and Co-founder of Cabaletta. “Based on published, third-party academic clinical data and a recently released abstract by the same academic group at the upcoming American College of Rheumatology Convergence 2023 meeting reporting administration of CD19-CAR T cells to treat additional patients with systemic sclerosis, we believe CABA-201 has the potential to slow or halt the progression of this autoimmune disease, thereby providing an important treatment option for these patients who currently have very few available treatments.”

SSc is a rare and potentially fatal chronic autoimmune disease characterized by progressive skin and internal organ fibrosis that can be life-threatening, including interstitial lung disease, pulmonary hypertension, and scleroderma renal crisis. Although the etiology of SSc is not well understood, the pathogenic role of autoantibodies and B cells in SSc provides a rationale for studying CAR T therapy in this population. SSc affects approximately 88,000 patients in the U.S., and typically affects middle-aged individuals, particularly women. Standard treatment options, which have modest effects, include generalized immunosuppressive agents or drugs targeted to specific symptomatic manifestations. Autologous hematopoietic stem cell transplant may provide some benefits in organ involvement, but carries significant risks, including


mortality, infertility, and secondary autoimmune disease, limiting its potential to be applied broadly. Due to the lack of adequate treatments, the risk of mortality in systemic sclerosis remains high, with an average survival of approximately 12 years following diagnosis.

About the Phase 1/2 Clinical Trial of CABA-201 in SSc

The Phase 1/2 clinical trial will be an open-label study of CABA-201 in subjects with SSc across two parallel cohorts. The severe skin cohort will include six patients with severe skin involvement, and the organ cohort will include six patients who meet the pulmonary, cardiac, or renal involvement criteria regardless of skin involvement. Subjects will receive a one-time infusion of CABA-201, using the same dose being used in the lupus and myositis clinical trials of CABA-201, 1 x 106 cells/kg, preceded by a standard preconditioning regimen of fludarabine and cyclophosphamide. Key inclusion criteria include patients between ages 18 and 70 (inclusive), evidence of significant skin, pulmonary, renal, or cardiac involvement, and significant organ involvement despite use of immunosuppressants. Key exclusion criteria include a primary diagnosis of another rheumatic autoimmune disease, treatment with a B cell depleting agent within six months or treatment with a biologic agent within three months. As the third trial within Cabaletta’s CARTA (Chimeric Antigen Receptor T cells for Autoimmunity) strategy, this study is intended to evaluate the potential ability of CABA-201 to transiently, but completely, eliminate B cells throughout the body, potentially enabling an immune system reset associated with a slowing or halting of active inflammatory disease progression in patients with SSc.

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 systemic lupus erythematosus, myositis, and systemic sclerosis, and 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 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.

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 its expectations regarding: Cabaletta’s ability to grow its autoimmune-focused pipeline; the ability to capitalize on and potential benefits resulting from published, third-party academic clinical data and a recently released abstract by the same academic group at the upcoming American College of Rheumatology Convergence 2023 meeting; the anticipated market opportunities for CABA-201 in SSc patients; the Company’s business plans and objectives; Cabaletta Bio’s expectations around the potential success and therapeutic benefits of CABA-201; the Company’s plans to initiate separate Phase 1/2 clinical trials of CABA-201 in subjects with SSc, SLE and myositis, including its anticipated progress, clinical trial design, ability to leverage its experience in autoimmune cell therapy and autoimmune disease product development for each clinical trial; the Company’s planned initial


clinical data read-out from the CABA-201 program in the first half of 2024; Cabaletta’s ability to enroll the requisite number of patients and dose each dosing cohort in the intended manner in its Phase 1/2 clinical trials of CABA-201; and the ability to accelerate Cabaletta’s pipeline and develop meaningful therapies for patients, including in collaboration with academic and industry partners and the ability to optimize such collaborations on its development programs.

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 DSG3-CAART, MuSK-CAART and CABA-201; the risk that the results observed with the similarly-designed construct employed in the recent Nature Medicine and Annals of Rheumatic Diseases 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 or enrollment rates that are lower than expected; 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 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; 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 and subsequent 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.

Contacts:

Anup Marda

Chief Financial Officer

investors@cabalettabio.com

William Gramig

Stern Investor Relations, Inc.

william.gramig@sternir.com

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Document and Entity Information
Oct. 02, 2023
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Entity Central Index Key 0001759138
Document Type 8-K
Document Period End Date Oct. 02, 2023
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
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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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