Full Press Release Details
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. M ller, 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. M ller, 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 na ve 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, M ller 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. M ller, 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. M ller, Fabian, et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. The Lancet (2023). 5. Evaluated as