8-K

 

 

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

Date of Report (Date of earliest event reported): June 2, 2020

 

 

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 5.07

Submission of Matters to a Vote of Security Holders.

Cabaletta Bio, Inc., a Delaware corporation (the “Company”) held its Annual Meeting of Stockholders (the “Annual Meeting”) on June 2, 2020. As of April 15, 2020, the record date for the Annual Meeting, there were 17,624,503 outstanding shares of the Company’s common stock. The Company’s stockholders voted on the following matters, which are described in detail in the Company’s Definitive Proxy Statement filed with the U.S. Securities and Exchange Commission on April 23, 2020: (i) to elect one director, Brian Daniels, M.D., as a Class I director of the Company to serve for a three-year term expiring at the Company’s 2023 annual meeting of stockholders and until his successor has been duly elected and qualified, subject to his earlier death, resignation or removal (“Proposal 1”) and (ii) to ratify the appointment of Ernst & Young as the Company’s independent registered public accounting firm for the fiscal year ending December 31, 2020 (“Proposal 2”).

The Company’s stockholders approved the Class I director nominee, Brian Daniels, M.D., recommended for election in Proposal 1 at the Annual Meeting. The votes cast at the Annual Meeting were as follows:

 

For

  

Withheld

  

Broker Non-Votes

9,666,638

   1,147,329    823,061

The Company’s stockholders ratified the appointment of Ernst & Young as the Company’s independent registered public accounting firm for the fiscal year ending December 31, 2020, recommended for ratification in Proposal 2 at the Annual Meeting. The votes cast at the Annual Meeting were as follows:

 

For

  

Against

  

Abstain

  

Broker Non-Votes

11,529,472

   107,556    0    0

No other matters were submitted to or voted on by the Company’s stockholders at the Annual Meeting.

 

Item 7.01

Regulation FD Disclosure.

On June 3, 2020, the Company posted to the “Investors & Media” section of the Company’s website at www.cabalettabio.com an updated corporate presentation providing a corporate overview and updated development plan (the “Corporate Presentation”). A copy of the Corporate Presentation is attached hereto as Exhibit 99.1 and is incorporated by reference into this Item 7.01 of this Current Report on Form 8-K.

The information contained in Item 7.01 of this Current Report on Form 8-K 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 9.01

Financial Statements and Exhibits.

(d) Exhibits

 

99.1

Cabaletta Bio, Inc. Corporate Presentation, dated June 3, 2020.


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: June 3, 2020     By:  

/s/ Steven Nichtberger

      Steven Nichtberger, M.D.
      President and Chief Executive Officer
EX-99.1

Slide 1

Corporate Presentation JUNE 2020 Exhibit 99.1


Slide 2

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 and does not constitute an offer to sell or a solicitation of an offer to buy securities, nor shall there be any sale of any securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. 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 neither this Presentation, nor any sale of securities, shall 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” relating to our business, operations, and financial conditions, including, but not limited to, current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development plans, our preclinical and clinical results and other future conditions. 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. Factors which could cause actual results to differ materially from those in the forward-looking statements include, among others, the success, cost, and timing of our product candidate development activities and preclinical studies and clinical trials, our ability to obtain and maintain regulatory approval for our product candidates, our ability to commercialize our product candidates, future agreements with third parties in connection with the development or commercialization of our product candidates, the size and growth potential of the market for our product candidates, our ability to contract with third-party suppliers and manufacturers and our ability to develop internal manufacturing capabilities and facilities, the accuracy of our estimates regarding expenses, future revenue, capital requirements, and needs for additional financing, and our ability to obtain and maintain intellectual property protection for our product candidates. 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, uncertainties caused by adverse economic conditions, including, without limitation, as a result of extraordinary events or circumstances such as the COVID-19 pandemic, and any business interruptions to our operations or to those of our clinical sites, manufacturers, suppliers, or other vendors resulting from the COVID-19 pandemic or similar public health crisis. 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. 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.


Slide 3

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


Slide 4

Cabaletta overview Engineering and developing CAAR T products to treat B cell-mediated autoimmune diseases Leveraging commercially approved CART19 technology though Penn partnership Pursuing targets where there is a biologic opportunity for cure with the CABA platform First mover advantage developing highly specific targeted cell therapy for autoimmune diseases Preclinical pipeline led by MuSK-CAART for myasthenia gravis with IND filing anticipated in 2H211 IND-enabling studies ongoing with in vivo preclinical data presented at 2020 American Academy of Neurology Manufacturing validation on track with CMO partner to initiate in 2H20 Issued U.S. patent on lead clinical program with emerging robust IP portfolio Issued CAAR T product patent covers all or any part of the relevant human antigens (DSG3 and DSG1) Lead clinical program, DSG3-CAART, in mucosal pemphigus vulgaris (mPV) patients DesCAARTes™ trial ready to launch with clinical acute tolerability (8 day) data from initial cohort by 1H211 Multiple clinical sites engaged across the U.S. supported by validated manufacturing partnership with Penn Fast Track and Orphan Drug Designations granted in 1H20 Cash runway into at least 3Q22 with $131 million in cash at March 31, 2020 1 Assumes lifting of current COVID-19-related restrictions and no future restrictions due to subsequent COVID-19 resurgence


Slide 5

CAR T Therapy CAAR T Therapy Our scientific platform leverages CAR T technology Chimeric AutoAntibody Receptor T cell CABA CAAR T Chimeric Antigen Receptor T cell Kymriah


Slide 6

CABA (Cabaletta Approach for Selective B cell Ablation) platform Epitope mapping to determine regions targeted by autoantibodies Optimize CAAR construct / design with the goal of selectively ablating reactive B cells Preclinical in vitro and in vivo testing to evaluate efficacy and safety Scientific, clinical and commercial assessment to inform product candidate development Vector & Clinical Cell manufacturing Clinical trials DSG3-CAART MuSK-CAART


Slide 7

Indication Program Discovery1 Preclinical Phase 1 Phase 2 Phase 32 Mucosal Pemphigus Vulgaris DSG3-CAART Mucocutaneous Pemphigus Vulgaris DSG3/1-CAART MuSK Myasthenia Gravis MuSK-CAART Hemophilia A w/ FVIII Alloantibodies FVIII-CAART Pipeline addressing multiple disease targets 1 In our discovery stage, we perform epitope mapping and optimize CAAR construct and design. 2 May not be required if Phase 2 is a registrational clinical trial.


Slide 8

DSG3-CAART for patients with mucosal pemphigus vulgaris


Slide 9

Working to meet an unmet need for patients Overview of Pemphigus Vulgaris Image credit: D@nderm 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. Kushner, Carolyn J., et al. "Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus." JAMA dermatology (2019). Jancin, Bruce. “Rituximab bests mycophenolate in pemphigus vulgaris,” Dermatology News, Nov 2019, Vol. 50:11, p. 2.; Press Release, Roche, 14 Oct 2019. Mucosal PV1 25% of U.S. pemphigus vulgaris Mucocutaneous PV1 75% of U.S. pemphigus vulgaris http://www.danderm-pdv.is.kkh.dk/atlas/3-157.html http://www.dermis.net/bilder/CD008/550px/img0042.jpg Associated Antibody Anti-DSG3 Anti-DSG3 + Anti-DSG1 Clinical Signs Painful blisters of the mucous membranes (mouth, nose, larynx, esophagus, eyes, genitalia, rectum) Blisters on orifices and skin Disease Incidence 350 US / 600 EU 1,050 US / 1,800 EU Disease Prevalence 4,250 US / 6,250 EU 12,750 US / 18,750 EU Current Treatment Landscape Broad immunosuppression Modestly effective Poorly tolerated B cell depletion with rituximab2,3,4 Offers transient remission Majority of responders relapse Chronic B cell depletion with rituximab 5.4% annual risk of severe infection Up to 1.9% lifetime risk of fatal infection


Slide 10

DSG3-CAART encompasses all known pathogenic epitopes Ohyama, Bungo, et al. "Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2–based swapped molecules." Journal of investigative dermatology 132.4 (2012): 1158-1168. Antibodies that target the specific extracellular domain are shown below each extracellular domain. EC5 directed antibodies are not known to be pathogenic DSG3-CAART Costimulatory Domains anti-EC4 P2C1, P5D4, P5B6, P3A6, P5E4 2 anti-EC3 AK18 2 anti-EC2 PVB28, AK19 2 anti-EC1 AK23, Px43, Px44, 62G2C11, F779 2 EC1 EC2 EC3 EC4 Transmembrane Domain Cytoplasmic tail % of PV sera targeting each domain1 91% 71% 51% 19% 12% EC5 EC1 EC2 EC3 EC4 CD137 CD3z DSG3 Protein


Slide 11

Tolerability Target Engagement No evidence of toxicity at clinically relevant doses with selective and specific target engagement DSG3-CAART preclinical data INDICATOR RESULTS In vitro off-target toxicity No specific cytotoxicity at clinically relevant cell numbers vs FcgR-expressing cells No interactions confirmed with human membrane proteins In vivo off-target toxicity No off-target effects detected at clinically relevant doses Anti-DSG3 autoantibody titer Serologic ‘remission’ - dose-dependent elimination of anti-DSG3 B cells and antibodies CAAR T cell engraftment Dose-dependent increase in CAAR-positive cells observed via flow cytometry Tissue blistering Histologic ‘remission’ - no blistering of oral mucosa Anti-DSG3 hybridoma outgrowth Significantly delayed outgrowth despite soluble anti-DSG antibodies


Slide 12

Study Endpoint & Objectives Primary Endpoint: Adverse Events, including Dose Limiting Toxicity Secondary Objectives: DSG3 ELISA titer changes, rate of/time to/duration of remission, manufacturing success rate, CAAR T expansion/persistence DesCAARTes™: Phase 1 clinical trial in mucosal-dominant PV (mPV) patients FDA has requested, and the Company has agreed, that we will share data from cohort A to inform a discussion on the optimal design of cohort C. According to FDA guidance, the submission of cohort A data is not gating to planned enrollment in cohort B. Open-label study to determine the maximum tolerated dose & fractionation of DSG3-CAART Part Cohort # Subjects A – Dose Escalation Fractionated infusion at increasing dose levels A1-A4 3 (+3) per cohort B – Dose Consolidation Consolidating selected dose fractions into a single infusion B1-B2 3 (+3) per cohort C – Expansion1 Expanded subject enrollment at final selected dose C ~12 Total ~30 (+18) Age: ≥18 Inadequately managed by standard immunosuppressive therapies Confirmed diagnosis Active disease Anti-DSG3 antibody positive Rituximab in last 6 months Prednisone > 0.25mg/kg/day Other autoimmune disorder requiring immunosuppressive therapies Recent investigational treatment ALC < 1,000 at screening Major Inclusion Criteria Major Exclusion Criteria SCREENING PERIOD FOLLOWED (2-4 WEEKS) TREATMENT PERIOD (1-3 WEEKS) Next Patient


Slide 13

Safety assessed acutely and at 3 months, with ability to measure CAAR T engagement by 6 months DesCAARTes™ clinical trial assessments and timeframes Spindler, Volker, et al. "Mechanisms causing loss of keratinocyte cohesion in pemphigus." Journal of Investigative Dermatology 138.1 (2018): 32-37. To be potentially incorporated in future protocol amendments or trials after discussion with FDA. Key Risks Context and Mitigating Strategies Options to Consider2 CRS / Neurotoxicity Product designed to kill <1% of B cells Low initial dose with fractionation No lymphodepletion Manage with standard protocols Soluble antibody Fractionated dosing designed to mitigate against potential toxicity Pretreat w/ plasmapheresis or IVIG Limit soluble anti-DSG3 antibody inclusion criteria Insufficient efficacy / CAAR T engraftment Wide cell dose range planned Consider increased dose and/or preconditioning / lymphodepletion Disease flare with medication taper Limit dose of corticosteroid use to enroll Local / oral steroids; plasmapheresis Skin toxicity from cross-reactivity No preclinical signals Local / oral steroids; plasmapheresis New autoimmune disorder or worsening Patients with active autoimmune disorders requiring immunosuppressants excluded Autoimmune therapies as needed Up to Wk -18 Wk -18 to -1 Day -7 to -3 Pre-infusion visit CAART INFUSION Day 8 Acute safety data 3 Months Primary safety endpoint 6 Months Evidence of target engagement 3 Years Efficacy 15 Years Long-term follow-up Declining anti-DSG3 titers1 Assuming selective B cell ablation in 2-4 weeks, serum IgG (half-life ~3 weeks) should fall within 6 months Key efficacy measures DSG3 antibody titer (ELISA)1 Disease activity (clinical) Steroid / immunosuppressive use 8-10 weeks from screening to infusion


Slide 14

Preclinical data suggests soluble antibodies can partially activate or inhibit DSG3 CAAR T cells1 Soluble antibodies may alter the dynamics of DSG3-CAART proliferation Ellebrecht, Christoph T., et al. "Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease." Science 353.6295 (2016): 179-184. Antibodies derived from a hybridoma model. Non-transduced T cell. CFSE (carboxyfluorescein diacetate succinimidyl ester) is a dye used in flow cytometric monitoring that reduces in intensity as it is distributed in actively dividing cells. Non-dividing cells will retain more CFSE dye. Soluble anti-DSG3 induces CAART cell proliferation Inhibitory antibodies reduce but do not prevent DSG3-CAART target engagement Increased target engagement Decreased target engagement EC1-4 vs. PV Ab #12 EC1-4 vs. PV Ab #22 NTD3 vs. PV Ab #12 NTD3 vs. PV Ab #22 Cell division Increased T cell division compared to response to normal human IgG 4 Observations


Slide 15

Data suggest preconditioning may not be necessary to drive responses beyond leukemia / lymphoma Recent MM patient data showed non-significant differences in ORR and rate of cytokine release syndrome in patients receiving CART-BCMA with and without lymphodepletion1 Studies from three clinical trials for patients with HIV showed CAR T cells were detected in 98% of samples tested for at least 11 years after infusion Potential activating effect of soluble antibody on engraftment and function is a key consideration in autoimmune patients Multiple infusions, higher dose, and cytokine support may offer more tolerable approach for autoimmune patients Past successes in HIV and multiple myeloma without preconditioning plus differences in patient populations are relevant1,2 Preconditioning regimens in CAAR T cell therapy may not be required Cohen, Adam D., et al. "B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma." The Journal of Clinical Investigation 129.6 (2019). Scholler, John, et al. "Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells." Science translational medicine 4.132 (2012): 132ra53-132ra53. Gattinoni et al. “Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells.” The Journal of Experimental Medicine 202(7):907-912 Wang, Shu and Plautz “Host lymphodepletion augments T cell adoptive immunotherapy through enhanced intratumoral proliferation of effector cells: Cancer Research 65(20): 9547-54. Lymphodepletion Mechanism Oncology Autoimmunity Reduction of T cell growth cytokine sinks3 + + Depletion of suppressor cells4 + – – Lymphodepletion mechanism unlikely to apply + Lymphodepletion mechanism likely to apply


Slide 16

Key clinical trial milestones and data readouts Evaluate safety by dosing cohort Acute safety data to be evaluated at 8 days post-infusion Primary endpoint data at 3 months Spindler V, Eming R, Schmidt E, et al. Mechanisms Causing Loss of Keratinocyte Cohesion in Pemphigus. J Invest Dermatol 2018;138:32-7. Target engagement during dose escalation to be evaluated DSG3 antibody is necessary and sufficient to cause mPV (per consensus document1) DSG3 antibody half-life ~3 weeks Potential evidence of reduction of anti-DSG3 levels may be observed within 6 months Clinical responses including mucosal lesion response and absence of recurrence may take longer


Slide 17

DSG3/1 CAARs designed for mcPV DSG3 and DSG1 autoantibodies Most severe and common form of PV (~75%) Mucosal blistering, plus skin erosion and blistering Managed with immune suppression, similar to mPV High risk of relapse Potential for hospitalizations and fatal infections Plan to potentially submit an IND after review of safety and target engagement data from DSG3-CAART DSG3/1 CAART for mucocutaneous PV (mcPV) Ohyama, Bungo, et al. "Epitope spreading is rarely found in pemphigus vulgaris by large-scale longitudinal study using desmoglein 2–based swapped molecules." Journal of investigative dermatology 132.4 (2012): 1158-1168. DSG1-CAART and DSG3-CAART both demonstrated specific cytotoxicity in vitro Together, DSG1-CAART and DSG3-CAART demonstrated cytotoxicity towards anti-DSG3 and anti-DSG1 B cells EC1 EC2 EC3 EC4 Transmembrane Domain Cytoplasmic tail % of PV sera targeting each domain1 98% 26% 9% 4% 7% EC5 EC1 EC2 EC3 EC4 CD137 CD3z DSG1 DSG1 CAAR


Slide 18

MuSK-CAART for myasthenia gravis patients


Slide 19

6.0 - 7.5% All known extracellular domains can be included in the CAAR design High unmet need in MuSK myasthenia gravis; a valuable CAAR target Hain, Berit, et al. "Successful treatment of MuSK antibody–positive myasthenia gravis with rituximab." Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine 33.4 (2006): 575-580. 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. AChR MG Early Onset Age <50 ; F>M AChR MG Late Onset Age >50 ; M>F MuSK MG Seronegative MG Low affinity AChR, LRP4 Prevalence: ~65,000 patients in the US Typically more severe Limited treatment options Early onset – 7:1 females MuSK has similar modular structure and size as DSG3 lg1 lg2 lg3 Fz Similar to pemphigus, autoantibody titers drop after rituximab1,2, supporting the clinical potential of CAART in MuSK myasthenia gravis


Slide 20

MuSK-CAART showed similar potency against target cells that bind to different epitopes MuSK-CAART in vitro selective & specific target engagement1 https://cslide-us.ctimeetingtech.com/aan2020/attendee/eposter/poster/2402?q=payne % Specific lysis MuSK1A 3-28 CART19 MuSK-CAART NTD % Specific lysis % Specific lysis 4A3 MuSK-CAART Ig1 Ig2 Ig3 Fz MuSK1A 3-28 4A3


Slide 21

MuSK-CAART eliminated anti-MuSK target cells2 in an animal model where CART19 cells are a positive control MuSK-CAART demonstrated specific in vivo target engagement1 https://cslide-us.ctimeetingtech.com/aan2020/attendee/eposter/poster/2402?q=payne Target cells represent a B cell tumor line (CD19 positive) that has been modified to express the anti-MuSK antibody. MuSK CAAR CART-19 DSG3 EC1-3 Day 1 Day 3 Day 5 Day 7 Day 13 5.0e4 2.0e6 (Radiance) 3.0e5 2.0e6 . . . NTD Positive control Negative control Negative control CART19 MuSK-CAART DSG3 EC1-3 NTD


Slide 22

FVIII-CAART for Hemophilia A inhibitor patients


Slide 23

B cell-mediated inhibition of Factor VIII reduces efficacy of replacement therapy Hemophilia A and neutralizing alloantibodies https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A. Peyvandi, Flora, et al. "A randomized trial of factor VIII and neutralizing antibodies in hemophilia A." New England Journal of Medicine 374.21 (2016): 2054-2064. Arruda, Valder R., and Ben J. Samelson‐Jones. "Gene therapy for immune tolerance induction in hemophilia with inhibitors." Journal of Thrombosis and Haemostasis 14.6 (2016): 1121-1134. FVIII neutralizing alloantibodies can block protein or gene replacement therapy Increased incidence in severe disease where native FVIII is not present Inhibitors persist in 70% of patients despite tolerance induction therapy3 Managing Hemophilia A patients with inhibitors can cost up to $1M per year HEMOPHILIA A POPULATION (US ONLY) Mild Moderate Severe FVIII levels 5-40% 1-5% <1% % of cases 25%1 15%1 60% (~12,000 patients)1,2 Consequence Bleeding after trauma or surgery Hemarthrosis, synovitis muscle contracture cerebral stroke, death Debilitating hemarthrosis muscle necrosis strokes, death Risk of FVIII neutralizing alloantibodies Minimal Moderate (~10%)3 High (~25%)3 ~3,000 US patients US Hemophilia A Population Total US: 20,000 patients Mild Moderate Severe Severe – FVIII Antibody


Slide 24

Selective and specific target engagement FVIII-CAART in vitro proof of concept data Cabaletta is engineering optimized constructs FVIII Domain(s) Signaling Domain Co-stimulatory Domain Linker/ Transmembrane E:T ratio


Slide 25

Manufacturing


Slide 26

Three-stage approach allows for efficient allocation of capital while leveraging experienced partners Manufacturing strategy Penn-sponsored CD19 CAR IND CMC data has been cross-referenced in DSG3-CAART IND to provide additional data reflecting alignment. Stage 3: Cabaletta Facility Commercialization & Scale-Up Data-gated investment Stage 1: Penn DSG3-CAART Phase 11 Stage 2: CDMOs & CABA Process MuSK-CAART Phase 1 Ample cell processing capacity secured through Penn partnership SOPs previously used to develop an FDA approved product Clinical vector validated CDMOs for vector and cell processing with commercial support capabilities Build out Cabaletta-owned manufacturing facility 2021 – 2019 –


Slide 27

Conserving the clinically validated CD19 CAR cell manufacturing process minimizes confounding risks Penn process, not Novartis process; avoids Kymriah release challenges2 Cross referenced the Penn IND to minimize operational risk Development work has demonstrated efficient manufacture of DSG3-CAART cells from PV patients3 Multiple runs contractually secured each month at Penn currently on track Subject to future COVID-19 impact DSG3 vector supply secured for next 2-3 years Vector production and cell processing are key risks mitigated by strategy, partnership, process and people Parallel steps in manufacturing process1 for CAR T vs CAAR T Penn-sponsored CD19 CAR IND CMC data has been cross-referenced in DSG3-CAART IND to provide additional data reflecting alignment. Manufacturing challenges were due to release specifications: https://www.biopharmadive.com/news/novartis-hits-car-t-manufacturing-snag-as-kymriah-sales-disappoint/528202/. T cells isolated from patients with a range of treatment regimens of low to high intensity were tested; the highest intensity regimen and patients with ALC<1000 cells/uL expanded less well and will be excluded from the trial design. Vector Production T Cell Activation Transduction CAAR T Expansion Concentration, Washing and Formulation Apheresis Collection of T cells


Slide 28

Corporate Summary


Slide 29

SCIENTIFIC ADVISORY BOARD Leadership team Aimee Payne, M.D., Ph.D. Co-Founder and Co-Chair Michael C. Milone, M.D., Ph.D. Co-Founder and Co-Chair Jay Siegel, M.D. LEADERSHIP TEAM Steven Nichtberger, M.D. President, CEO & Chairman Anup Marda Chief Financial Officer Arun Das, M.D. Senior Director BD Gwendolyn Binder, Ph.D. EVP Science & Technology David J. Chang, M.D., M.P.H. Chief Medical Officer J. Brian Stalter, J.D. General Counsel Martha O’Connor Chief HR Officer Iain McInnes


Slide 30

Recent highlights and anticipated upcoming milestones 1 Assumes lifting of current COVID-19-related restrictions and no future restrictions due to subsequent COVID-19 resurgence.


Slide 31

Corporate Presentation JUNE 2020