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Item 1. Business

2026-03-23 compared with 2025-03-31 · 265 added, 286 removed, 589 unchanged (48% of the section changed)

We are a clinical-stage biotechnology company focused on the discovery and development of innovative engineered T cell therapies that have the potential to provide deep and durable, perhaps curative, responses with one-time administration for patients with autoimmune diseases.

Our proprietary CABA ® , or Cabaletta Approach to B cell Ablation, platform encompasses two strategies.

Our CARTA, or Chimeric Antigen Receptor T cells for Autoimmunity, approach is designed to potentially reset the immune system.

Our legacy CAART, or Chimeric AutoAntibody Receptor T cells, approach is designed to engineer T cells to selectively engage and eliminate only disease-causing B cells.

We believe our CABA ® platform has the potential to safely enable complete and durable responses for a broad range of autoimmune diseases and that it has potential applicability across dozens of autoimmune diseases that we have identified, evaluated and prioritized.

Resecabtagene autoleucel (rese-cel, formerly referred to as CABA-201) is a 4-1BB co-stimulatory domain-containing fully human CD19-CAR T construct designed to treat patients with a broad range of autoimmune diseases and our lead product candidate within the CARTA strategy.

Rese-cel is designed to achieve transient and deep depletion of all B cells following a single treatment by using T cells engineered to express an antibody fragment that recognizes a B cell receptor expressed on the surface of all B cells.

The construct is designed to allow for the deep elimination of all B cells, including all B cells that contribute to disease, with subsequent repopulation by healthy naïve B cells.

This approach has the potential to reset the immune system, providing meaningful durable and complete clinical responses to patients off immunosuppressive therapies.

In March 2023, the United States Food and Drug Administration, or the FDA, granted clearance of our rese-cel Investigational New Drug, or IND, application for treatment of SLE in patients with active lupus nephritis, or LN, or active SLE without renal involvement.

SLE is a chronic, potentially severe, autoimmune disease, most commonly impacting young women between the ages of 15 and 40 with higher frequency and more severity in people of color, where the immune system attacks healthy tissue throughout the body.

SLE affects an estimated up to 320,000 patients in the U.S., and 150,000 patients in Europe, with LN as the most common end-organ manifestation, affecting approximately 40% of SLE patients.

In May 2023, we announced the FDA granted Fast Track Designation for rese-cel, designed to deplete CD19-positive B cells and improve disease activity in patients with SLE and LN.

The RESET-SLE TM Phase 1/2 clinical trial of rese-cel is designed to treat six SLE patients with active LN, and in a separate parallel cohort, six patients with active SLE without renal involvement, with a single weight-based dose of 1.0 x 10 6 cells/kg.

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

In October 2024, the European Medicines Agency allowed a CTA submitted by Cabaletta for the RESET-SLE TM trial to proceed, enabling us to begin the process of activating clinical trial sites and pursuing patient enrollment for the RESET-SLE TM trial.

The trial is open for enrollment across multiple sites in the United States and one site in the European Union.

In May 2023, the FDA granted clearance of our rese-cel IND application for treatment of idiopathic inflammatory myopathies, or IIM, or myositis.

Myositis refers to a group of autoimmune diseases characterized by inflammation and muscle weakness.

The three myositis subtypes being evaluated in the RESET-Myositis TM Phase 1/2 clinical trial of rese-cel affect approximately 70,000 patients in the U.S.

and approximately 85,000 patients in Europe and typically affect middle-aged individuals, particularly women.

The RESET-Myositis TM clinical trial, which is actively enrolling patients, is designed to treat six patients with dermatomyositis, six patients with anti-synthetase syndrome, and six patients with immune-mediated necrotizing myopathy, all in separate parallel cohorts.

We announced the FDA granted Fast Track Designation for rese-cel for the treatment of patients with dermatomyositis to improve disease activity and Orphan Drug Designation for rese-cel for the treatment of myositis in January and February 2024, respectively.

We are a late clinical-stage biotechnology company focused on the discovery and development of innovative engineered T cell therapies that have the potential to provide deep and durable, perhaps curative, responses with one-time administration for patients with autoimmune diseases.

Our proprietary CABA ® , or Cabaletta Approach to B cell Ablation platform, focuses on the CARTA approach.

CARTA refers to Chimeric Antigen Receptor T cells for Autoimmunity and is designed to potentially reset the immune system.

Based on clinical data reported to date, we believe our CABA ® platform has the potential to safely enable complete and durable responses for a broad range of autoimmune diseases and that it has potential applicability across dozens of autoimmune diseases that we have identified, evaluated and prioritized.

Resecabtagene autoleucel, or rese-cel (formerly referred to as CABA-201), is a 4-1BB co-stimulatory domain-containing fully human CD19-CAR T construct designed to treat patients with a broad range of autoimmune diseases and our lead product candidate within the CARTA strategy.

Rese-cel is designed to achieve transient and deep depletion of all B cells following a single, weight-based infusion of T cells that are engineered to express an antibody fragment that recognizes a B cell receptor expressed on the surface of all B cells.

The construct is designed to allow for the deep elimination of all B cells, including all B cells that contribute to disease, with subsequent repopulation by healthy transitional, naïve B cells.

This approach has demonstrated the potential to reset the immune system and result in meaningful clinical responses without chronic therapy requirements in patients.

The efficacy and safety of rese-cel was recently reviewed along with all other commercial and academic constructs in development in a February 2026 Nature Biotechnology publication.

In December 2025, we initiated a registrational trial with rese-cel for patients with dermatomyositis or anti-synthetase syndrome.

In addition, we have ongoing Phase 1/2 trials evaluating rese-cel with a standard preconditioning regimen, fludarabine and cyclophosphamide, in systemic lupus erythematosus, or SLE, in patients with active lupus nephritis, or LN, or active SLE without renal involvement, systemic sclerosis, or SSc, and generalized myasthenia gravis, or gMG.

In addition to our core development program across multiple indications using standard preconditioning regimens and standard manufacturing processes with partnered Contract and Development Manufacturing Organizations, or CDMOs, based on early data from a phase 1/2 trial evaluating rese-cel without preconditioning in pemphigus vulgaris patients, we are evaluating rese-cel without preconditioning in non-renal SLE and LN patients.

In addition, in January 2026 we announced INDa clearance for rese-cel to be manufactured using an automated manufacturing platform – the Cell Shuttle TM from Cellares - offering the potential for scalability to produce rese-cel for thousands of patients per year with minimal capital investment by the Company.

The first clinical experience from these patients is expected to be presented in the first half of 2026.

Durability data from the no preconditioning SLE, LN and PV patients as well as the patients treated with rese-cel manufactured by the Cellares Cell Shuttle TM is expected to be presented in the second half of 2026.

RESET-Myositis ®

The three adult myositis subtypes, dermatomyositis, or DM, anti-synthetase syndrome, or ASyS, and immune-mediated necrotizing myopathy, or IMNM, being evaluated in the RESET-Myositis ® Phase 1/2 clinical trial of rese-cel affect approximately 80,000 patients in the U.S.

Myositis typically affects middle-aged individuals, particularly women, and disease is often refractory, despite existing therapies.

In the United States, we believe approximately 20% to 25% of the prevalent population, or 16,000 to 20,000 people, would be potentially eligible patients for rese-cel.

The RESET-Myositis ® Phase 1/2 clinical trial is designed to treat at least six patients with DM, or ASyS, at least six patients with IMNM, as well as at least six patients with juvenile idiopathic inflammatory myopathy, or JIIM, all in separate parallel cohorts, with a single weight-based dose of 1.0 x 10 6 cells/kg.

We announced the FDA granted Fast Track Designation for rese-cel for the treatment of patients with dermatomyositis and Orphan Drug Designation for rese-cel for the treatment of myositis in January and February 2024, respectively.

In March 2024, we announced the FDA granted Rare Pediatric Disease designation for rese-cel for juvenile dermatomyositis.

The trial is open for enrollment across multiple sites in the United States and one site in the United Kingdom.

In October 2023, we announced that the FDA granted clearance of our rese-cel IND application for treatment of systemic sclerosis, or SSc.

In May 2025, we

announced the FDA granted Regenerative Medicine Advanced Therapy, or RMAT, designation to rese-cel for the treatment of myositis.

Based on clinical data presented in October 2025 at the American College of Rheumatology, or the ACR, Convergence 2025, we have initiated a DM/ASyS registrational cohort within the RESET-Myositis ® trial.

There are approximately 60,000 patients with DM in the U.S.

who have IVIg as their only FDA-approved treatment option and approximately 15,000 patients with ASyS in the U.S.

who have no FDA-approved treatment options.

Our registrational trial design includes a 16-week primary endpoint of moderate or major TIS response while off immunomodulators and on no or low-dose steroids.

Based on the safety data from the phase 1/2 cohort, the protocol permits outpatient administration.

In addition, we are planning for a pediatric submission in juvenile idiopathic inflammatory myopathy, or JIIM, based on data available at the time of adult submission from the ongoing Ph 1/2 cohort to support a pediatric label claim.

The planned size of 17 patients for the registrational cohort is based on the assumed treatment effect of rese-cel in DM/ASyS patients and an estimated background rate.

The estimated background rate will be determined from a retrospective analysis of an external myositis patient registry and will include patients with similar inclusion criteria as those in the registrational DM/ASyS cohort.

Based on comprehensive literature review to estimate the background rate, we estimate the likelihood of an active, refractory myositis patient achieving moderate or major TIS response within 16 weeks and concurrently discontinuing all immunomodulators to be less than 10%.

Changes in the assumed background rate would result in a change in the number of rese-cel treated patients who would need to achieve the primary endpoint in the 17-patient registrational cohort.

The registrational cohorts will evaluate the same single, weight-based infusion of rese-cel at 1 x 10 6 cells/kg as used in the Phase 1/2 myositis cohorts with similar enrollment criteria.

As presented at ACR Convergence 2025, all myositis patients in the Phase 1/2 DM/ASyS cohort with sufficient follow-up who met key registrational inclusion criteria exceeded the registrational primary endpoint, demonstrating major TIS responses with no immunomodulators.

Based on discussions with the FDA, we plan to use pooled rese-cel safety data from across the entire RESET TM clinical trial program to supplement myositis specific safety data for the Biologics License Application, or BLA, submission in myositis, and the required safety database is expected to be approximately 100 autoimmune disease patients treated with the same single weight-based dose.

We initiated enrollment in the registrational DM/ASyS cohort in December 2025 and anticipate BLA submission in 2027.

SLE affects an estimated up to 320,000 patients in the U.S., with LN as the most common end-organ manifestation, affecting approximately 30-40% of SLE patients.

The RESET-SLE TM Phase 1/2 clinical trial is designed to treat six SLE patients with active LN, and in a separate parallel cohort, six patients with active SLE without renal involvement, with a single weight-based dose of 1.0 x 10 6 cells/kg.

In May 2023, we announced the FDA granted Fast Track Designation for rese-cel in patients with SLE and LN.

In November 2025, we announced the FDA granted RMAT designation to rese-cel for treatment of SLE and LN.

In January 2026, Cabaletta announced registrational cohort designs in RESET-SLE TM to evaluate the current rese-cel weight-based dose of 1 million cells/kg in a single infusion with preconditioning, including two independent, single-arm cohorts, one consisting of patients with non-renal SLE and one consisting of patients with LN each evaluating approximately 25 patients with unique endpoints in each cohort.

Complete Phase 1/2 data from both cohorts is anticipated in the first half of 2026.

Cabaletta will provide an update on next steps for these cohorts in 2026, subject to dose-ranging data evaluating rese-cel without preconditioning in lupus patients.

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.

SSc affects approximately 90,000 patients in the U.S.

and approximately 60,000 patients in Europe, typically middle-aged individuals, particularly women.

The RESET-SSc TM Phase 1/2 clinical trial of rese-cel is designed to treat six patients with severe skin manifestations and six patients with severe organ involvement associated with SSc.

We announced the FDA granted Fast Track Designation for rese-cel for the treatment of patients with SSc to improve associated organ dysfunction and Orphan Drug Designation

for rese-cel for the treatment of systemic sclerosis in January and March 2024, respectively.

The trial is open for enrollment across multiple sites in the United States.

In November 2023, the FDA granted clearance of our rese-cel IND application for treatment of generalized myasthenia gravis, or gMG, a subset of patients with myasthenia gravis, or MG.

MG is a rare autoimmune disease characterized by autoantibodies that interfere with signaling at the neuromuscular junction, or NMJ, leading to potentially life-threatening muscle weakness.

SSc affects approximately 90,000 patients in the U.S., typically middle-aged individuals, particularly women.

The RESET-SSc TM Phase 1/2 clinical trial of rese-cel is designed to treat six patients with severe skin manifestations and six patients with severe organ involvement associated with SSc, each in separate parallel cohorts, with a single weight-based dose of 1.0 x 10 6 cells/kg.

We announced the FDA granted Fast Track Designation for

rese-cel for the treatment of patients with SSc to improve associated organ dysfunction and Orphan Drug Designation for rese-cel for the treatment of SSc in January and March 2024, respectively.

In January 2026, Cabaletta announced the FDA granted RMAT designation to rese-cel for treatment of SSc.

Complete Phase 1/2 data from both cohorts is anticipated in the first half of 2026, and we anticipate announcing the registrational cohort design for SSc in the first half of 2026.

MG is a rare autoimmune disease characterized by autoantibodies that interfere with signaling at the neuromuscular junction, leading to potentially life-threatening muscle weakness.

The majority of patients with MG have autoantibodies known to be pathogenic based on their interference with proteins in the NMJ, of which the majority target AChR.

gMG affects approximately 100,000 patients in the U.S.

and approximately 100,000 patients in Europe.

Symptoms of gMG include profound muscle weakness throughout the body, disabling fatigue, and potential shortness of breath due to respiratory muscle weakness, with risk for episodes of respiratory failure.

Standard of care therapies include cholinesterase inhibitors, steroids, immunomodulators, and biologics, which typically require chronic administration, increasing the risk of serious long-term side effects.

The RESET-MG TM Phase 1/2 clinical trial of rese-cel is designed to treat six patients with AChR-positive gMG and six patients with AChR-negative gMG, each in separate parallel cohorts.

The trial is open for enrollment across multiple sites in the United States.

In May 2024, we announced that we are working with active clinical sites to incorporate the RESET-PV TM trial as a sub-study within the Phase 1 DesCAARTes TM trial following the submission of a protocol amendment.

The RESET-PV TM trial will evaluate rese-cel as a monotherapy without preconditioning in patients with mucosal pemphigus vulgaris, or mPV, and mucocutaneous pemphigus vulgaris, or mcPV.

Approximately 15,000 patients in the U.S.

and approximately 20,000 patients in Europe are affected by PV.

The trial is open for enrollment across multiple sites in the United States.

In June 2024, we announced the initial clinical data from each of the first two patients dosed with rese-cel in the RESET-SLE TM and RESET-Myositis TM trials.

In both of these patients, no cytokine release syndrome, or CRS, immune effector cell-associated neurotoxicity syndrome, or ICANS, infections or serious adverse events were observed through data cut-off of May 28, 2024.

Rese-cel exhibited the anticipated profile of CAR T cell expansion and contraction with complete B cell depletion observed in both patients by day 15 post-infusion.

Improvements in both patients’ specific disease measures were observed, consistent with academic experience of a similar 4-1BB CD19-CAR T.

In late June 2024, a lupus nephritis patient with very active, refractory disease was dosed with rese-cel and experienced Grade 1 CRS and a protocol-defined dose-limiting toxicity of Grade 4 ICANS.

The ICANS resolved rapidly following standard management.

The study’s Independent Data Monitoring Committee reviewed data from the patient, and recommended that the study proceed as designed, without delay, at the current dose.

We recommended protocol modifications designed to improve patient safety, including enhanced monitoring for fever and neurologic symptoms along with seizure prophylaxis for all patients, in line with the practice at many academic sites including at Erlangen University, the site of the CD19-CAR T studies led by Dr.

Georg Schett.

In July 2024, we provided standard notice to the FDA and communicated details of the event and proposed protocol changes to all active clinical sites within the RESET TM clinical trial program, including the requirement that the investigator promptly discuss the appropriateness and timing of infusion with the trial’s Medical Monitor.

In November 2024, we announced updated clinical data at the American College of Rheumatology Convergence 2024 conference in the first 8 patients dosed across the lupus, myositis and systemic sclerosis clinical trials.

Clinical data from these patients in the RESET-SLE TM , RESET-Myositis TM trial and RESET-SSC TM trial were presented in oral and poster presentations where compelling clinical responses were observed in lupus and myositis patients with up to six months of follow-up, and the first SSc patient demonstrated an emerging, drug-free clinical response.

In January 2025, we announced the FDA granted clearance of our rese-cel IND application for treatment of multiple sclerosis, or MS.

In addition, we announced the FDA granted Fast Track Designation for rese-cel for the treatment of relapsing and progressive forms of MS.

The RESET-MS TM trial is a Phase 1/2 open-label, dose escalation study of rese-cel in subjects with relapsing and progressive forms of MS, evaluated in separate cohorts.

The RESET-MG TM Phase 1/2 clinical trial of rese-cel is designed to treat six patients with AChR-positive gMG and six patients with AChR-negative gMG, each in separate parallel cohorts, with a single weight-based dose of 1.0 x 10 6 cells/kg.

In October 2025, we announced that rese-cel was generally well tolerated across two AChR-positive and two AChR-negative patients (both seronegative;

no anti-MuSK or anti-LRP4 antibodies).

No CRS (cytokine release syndrome) occurred in three of four patients, and grade 2 CRS occurred in AChR-pos-2 that resolved with no sequelae.

As of the September 11, 2025 data cut-off, two evaluable patients (AChR-neg-1 and AChR-neg-2) remained off immunomodulatory medication and achieved significant improvements in MG-ADL (with AChR-neg-1 achieving Minimal Symptom Expression).

AChR-pos-1 is not evaluable due to use of a prohibited cytotoxic medication that may have inhibited CAR T activity and AChR-pos-2 has insufficient follow-up.

Both cohorts have been fully enrolled.

Complete Phase 1/2 data from both cohorts is anticipated in the first half of 2026, and we anticipate announcing the registrational cohort design for studies in MG in mid-2026.

Pemphigus vulgaris, or PV, is an autoimmune disease that occurs when the immune system produces antibodies that attack a protein called desmoglein, or DSG.

DSG normally enables skin cells and the cells lining the inside of your mouth, nose, throat, eyelids, etc.

to bind tightly together.

Disruption by the antibodies directed to DSG causes the painful blisters and erosions characteristic of PV.

Approximately 15,000 patients in the U.S.

and approximately 550,000 patients in Europe are affected by MS.

In February 2025, we announced updated clinical and translational data from the first 10 patients in the RESET TM clinical trial program, with a data cut off of January 8, 2025.

Overall, clinical responses continued to deepen over three SLE patients in DORIS remission, the first LN patient achieving complete renal response, and the first dermatomyositis patient maintaining a major total improvement score, or TIS improvement.

Each of these patients discontinued all immunosuppressants and were off or tapering steroids as of January 8, 2025.

The safety profile continued to suggest a favorable risk-benefit in the first 10 patients dosed with 90% of patients having experienced either no CRS or Grade 1 CRS and 90% of patients having experienced no ICANS.

In March 2025, we learned of an important protocol deviation in the RESET-SSc TM trial.

In this case, the patient reported a fever three days prior to infusion.

The Cabaletta Medical Monitor was not notified by the investigator prior to the site infusing the patient.

Nine days following rese-cel infusion, the patient experienced a dose-limiting toxicity of grade 3 immune effector

cell-associated neurotoxicity syndrome (ICANS) based on a transient period of confusion.

There was no cerebral edema, seizures or motor dysfunction associated with the ICANS event, and the patient was arousable throughout.

The ICANS resolved rapidly following treatment with dexamethasone, and the patient was discharged without further symptoms.

After data review, the Independent Data Monitoring Committee recommended that the trial proceed at the current dose without delay and endorsed our proposal to require investigators to affirmatively confirm in writing to the company the absence of fevers or evidence of infection.

As of March 14, 2025, 56 clinical sites across the U.S.

and Europe were actively recruiting with 33 patients enrolled across the RESET TM clinical trial program.

Our manufacturing strategy is comprised of two stages.

The initial stage is designed to leverage the extensive early-stage manufacturing expertise of our academic partners and contract development and manufacturing organizations, or CDMOs, for rapid early development and clinical supply, and in parallel partner with commercially compliant CDMOs capable of supporting late-stage clinical studies and commercial production.

Our aim is to achieve full manufacturing readiness through expanded CDMO relationships, establishment of our own manufacturing facilities, and/or through strategic partnership(s).

We are leveraging the expertise in cell and vector manufacturing of our partners at the Children’s Hospital of Philadelphia, or CHOP, and the University of Pennsylvania, or Penn.

For supply of lentiviral vector for the late-stage clinical and commercial manufacturing of rese-cel, we are working with Oxford Biomedica (UK) Limited, or Oxford.

We have also collaborated with WuXi Advanced Therapies, Inc., or WuXi, to serve as an additional and commercially compliant cell manufacturing partner for our MusCAARTes TM and RESET TM clinical trials to meet planned capacity and international supply requirements.

In July 2024, we entered into a new technology transfer agreement with Lonza Houston Inc., or Lonza, another commercially compliant CDMO, to execute a technology transfer of our expected commercial manufacturing process for rese-cel.

In December 2024, we entered into a Development and Manufacturing Services Agreement, or the Lonza Agreement, with Lonza to serve as one of our manufacturing partners for the global clinical development of rese-cel in multiple indications, including potential late-stage clinical trials and preparations for commercial readiness.

This improved process is nearly fully closed, semi-automated, and more easily scaled than the current process.

Transfer of this updated process will be performed from Cabaletta to Lonza in anticipation of being able to supply rese-cel drug product for any of Cabaletta’s ongoing and planned RESET TM clinical trials.

We plan to secure commercial, scalable manufacturing capabilities through multiple potential strategies, including expanding existing or establishing new CDMO relationships, leasing, building, qualifying and operating our own manufacturing facility, and/or establishing a strategic partnership to rapidly and reliably scale manufacturing by leveraging the partner’s manufacturing expertise.

We believe this later stage will enable control of product development and commercial supply for products arising from our CABA platform, enabling us to achieve continuous improvement of our product candidates.

Multiple members of our team have previously built and led organizations that have constructed and commissioned cell therapy facilities, which we believe will enable us to build our own manufacturing organizations and facilities, if desirable.

As part of our innovative manufacturing strategy where we intend to increase scale, reduce cost of goods and improve patient experience, in November 2023, we partnered with Cellares Corp., or Cellares, to evaluate their automated manufacturing platform, the Cell Shuttle TM , through the Cellares Technology Adoption Program, or TAP.

As part of the collaboration, the companies have agreed on a proof-of-concept technology transfer process for the automated manufacture and release testing of rese-cel.

In August 2024, we expanded our partnership with Cellares to facilitate the potential to incorporate the Cellares manufacturing platform to support the RESET TM clinical program.

In March 2025, we and Cellares announced the successful conclusion of the Technology Adoption Program on Cellares’ automated cell therapy manufacturing Cell Shuttle, facilitating the potential integration of the Cell Shuttle TM into our clinical and commercial, if approved, manufacturing strategy for rese-cel.

We are also evaluating pathways to improve patient experience and scalability of collection through the removal of the requirement for apheresis.

Data were published at the American Society of Cell and Gene Therapy conference in May 2024 illustrating the feasibility of this approach.

are affected by PV.

The ongoing RESET-PV ® trial is designed to evaluate rese-cel as a monotherapy without preconditioning in patients with mucosal pemphigus vulgaris, or mPV, and mucocutaneous pemphigus vulgaris, or mcPV.

In October 2025, we announced that rese-cel exhibited similar CAR T cell expansion and contraction kinetics relative to translational data reported from other RESET TM trials with preconditioning.

All three patients experienced substantial depletion of B cells within the first month post-infusion, with patients 2 and 3 achieving complete peripheral B cell depletion.

In these two patients, rapid reduction in autoantibodies to desmoglein was observed and the increase in peak B cell activating factor, or BAFF, was at the low end of the range of patients dosed with rese-cel plus preconditioning from pre-infusion through the latest follow-up, suggestive of potential deep B cell depletion in the tissue.

Additional follow up will be required to determine if the initial clinical effects are durable and to determine if the findings can be replicated in other autoimmune diseases.

Rese-cel was generally well tolerated with no immune effector cell-associated neurotoxicity syndrome, or ICANS, reported as of the data cutoff.

After infusion, patient 1 experienced transient fever (grade 1 cytokine release syndrome).

Patient 2 required a course of steroids for a disease flare in the first two weeks following infusion after discontinuing immunomodulators.

PDAI activity scores have formed the basis for recent regulatory approvals in PV, and total PDAI scores in these patients were also reported to be consistent with the PDAI activity scores in the late breaking clinical trial session.

PDAI improvements were most significant in the two patients who seemed to experience complete peripheral B cell depletion.

Our History and Team

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Milone is a renowned scientist in CAR T therapy and was a co-inventor of and a key driver in the preclinical discovery and development efforts that yielded Kymriah®, the first FDA-approved CAR T therapy for the treatment of B cell cancers.

Their research attracted the attention of a colleague Steven Nichtberger, M.D., an adjunct professor at the Wharton School at the University of Pennsylvania, and in 2017, based on over a year of interaction and discussions regarding the optimal strategy to advance the scientific opportunity into a commercially developed product portfolio that could offer potentially curative treatment options to patients, Drs.

Their research attracted the attention of a colleague Steven Nichtberger, M.D., a professor of practice in the Vagelos LSM program and adjunct professor at the Wharton School at the University of Pennsylvania, and in 2017, based on over a year of interaction and discussions regarding the optimal strategy to advance the scientific opportunity into a commercially developed product portfolio that could offer potentially curative treatment options to patients, Drs.

Payne, Milone and Nichtberger decided to launch Cabaletta Bio.

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Chang completed his fellowship in Rheumatology and was a faculty member in the Division of Rheumatology at the Perelman School of Medicine at the University of Pennsylvania prior to his transition to the biopharmaceutical industry.

Our legacy CAART platform has yielded two clinical-stage cell therapy programs in mPV and MuSK MG, which have required collaborations between specialists – dermatologists and neurologists – and oncologists who are responsible for administering the cell therapy at each site.

Given our track record of timely clinical trial implementation with CAART cell therapy in autoimmune diseases over the past five years at over a dozen sites across the United States, we believe that our team’s successful management of the complicated planning and logistics involved with implementation of these clinical trials has the potential to be an operating advantage.

While advancing the CAART product candidates in our Phase 1 DesCAARTes TM and MusCAARTes TM trials and establishing our position in the field of autoimmunity, we were encouraged by results from an initial case report published in the New England Journal of Medicine in August 2021 and a follow-up academic clinical study published in Nature Medicine in September 2022, showing the potential for CD19-CAR T cell therapy to transform the course of SLE.

Our Chief Commercial Officer, Steve Gavel, joined Cabaletta in October 2025 and was previously Senior Vice President, Global Cell Therapy Commercial Development at Legend Biotech from 2018 to 2025, reporting to the CEO, where he created and scaled its commercial organization and implementation of all CAR T logistics and management of the leading CAR T centers in the U.S., in partnership with Johnson & Johnson, to successfully launch and grow Carvykti ® , a treatment for patients with multiple myeloma.

Gavel led U.S.

commercial strategy at Celgene.

Cabaletta was founded with the purpose of developing targeted, potential curative engineered cell therapies for patients with autoimmune disease.

After three years developing a legacy form of cell therapy, we were encouraged by results from an initial case report published in the New England Journal of Medicine in August 2021 and a follow-up academic clinical study published in Nature Medicine in September 2022, showing the potential for CD19-CAR T cell therapy to transform the course of SLE.

In five patients with SLE, one-time treatment with a 4-1BB-containing CD19-CAR T cell therapy induced deep and durable clinical responses in all five patients within three months after treatment, with favorable tolerability.

Healthy B cells repopulated in all patients within five months of treatment, and responses remained durable off SLE-associated medications for up to 2.5 years of follow-up, as of February 2024.

Healthy B cells repopulated in all patients within five months of treatment, and responses remained durable off SLE-associated medications for up to 4 years of follow-up, as of September 2025.

These findings demonstrate the potential for CD19-CAR T cell therapy to “reset the immune system,” eliminating the cause of autoimmune disease with restoration of the healthy immune system.

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Prompted by the initial case report in the New England Journal of Medicine , we conducted a global search to identify the optimally designed product candidate for patients with autoimmune diseases to be highly similar to the construct used by Dr.

Schett in the Nature Medicine paper.

We are employing a clinically-evaluated fully human CD19 binder that has high similarity, including identical epitopes and similar binding activity, to the construct employed in the academic reports.

Georg Schett in the Nature Medicine paper.

We are employing a clinically-evaluated fully human CD19 binder that has high

similarity, including identical epitopes and similar binding activity, to the construct employed in the academic reports.

Our exclusive translational research partnership with Dr.

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Methods and Clinical Development , highlighting studies performed on serum samples from the first six SLE patients treated with CD19-CAR T cell therapy by Dr.

Georg Schett’s team.

Schett’s team.

The publication reports that in the three months following infusion, cytokine markers of systemic inflammation resolved, autoantibody titers declined, and humoral immunity was maintained.

Since announcing rese-cel in October 2022, Cabaletta has had five IND applications cleared within the routine 30-day period for the RESET TM Phase 1/2 clinical trials in SLE, myositis, SSc, gMG and MS, in addition to the RESET-PV TM trial that is evaluating rese-cel without preconditioning.

Since announcing rese-cel in October 2022, Cabaletta has had five IND applications cleared within the routine 30-day period for the RESET TM Phase 1/2 clinical trials in SLE, myositis, SSc, gMG and MS, in addition to the RESET-PV ® trial that is evaluating rese-cel without preconditioning.

Accelerated by the emerging clinical data with rese-cel, our team’s deep expertise in cell therapy in autoimmunity, demonstrated track record of strong clinical execution, positive regulatory interaction since 2018, and our successful cell therapy manufacturing, we are uniquely positioned to advance CD19-targeting cell therapy candidates to further our mission to develop therapies that deliver deep, durable and potentially curative responses for patients in a broad range of autoimmune diseases.

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To achieve this goal, key elements of our strategy include:

• Achieving compelling clinical responses and a favorable safety profile for our lead product candidate, rese-cel, across multiple autoimmune diseases driven by B cells.

Academic clinical data published in Nature Medicine in September 2022 and in NEJM in February 2024, demonstrated that a CD19-CAR T cell therapy with a 4-1BB co-stimulatory domain following lymphodepletion with fludarabine and cyclophosphamide induced complete clinical responses in five out of five patients with moderate to severe, refractory SLE, with up to 2.5 years of follow up, as of February 2024.

Our exclusive translational partnership with Dr.

Schett, the lead investigator of the study, is focused on generation of additional translational data to gain a deeper understanding of the immunologic mechanisms of response and clinical insights from ongoing and continued clinical studies in multiple autoimmune disease indications.

Due to the purposeful design of rese-cel to have a high level of functional and structural similarity to the construct used in these academic studies and engineered specifically for the use in autoimmune patients, we believe rese-cel may have the potential to transform the treatment of a broad range of autoimmune diseases.

We have five IND applications cleared for the RESET TM Phase 1/2 clinical trials in systemic lupus erythematosus, myositis, systemic sclerosis, generalized myasthenia gravis and multiple sclerosis in addition to the RESET-PV TM trial, which is evaluating rese-cel without preconditioning.

All of these clinical trials are currently recruiting patients.

As the academic data published to date showed robust clinical improvement with multiple years of follow-up in autoimmune patients, and given the similarity of rese-cel to the academic construct, we expect our initial clinical and translational data to provide insights that may predict longer-term outcomes.

• Utilizing our expertise in autoimmune cell therapy to enable a novel clinical strategy and efficient study design.

The first four RESET TM Phase 1/2 clinical trials – RESET-SLE, RESET-Myositis, RESET-SSc and RESET-MG – are comprised of independent cohorts with well-defined disease sub-types, each comprised of 6 patients, which can enroll and dose patients in parallel.

These trials are initiating at a weight-based cell dose that is equivalent to the weight-based dose of the 4-1BB-containing CD19-CAR T cell therapy used as was done in the academic publications (1.0 x 10 6 cells/kg) with the same preconditioning regimen of fludarabine and cyclophosphamide.

Each 6-patient cohort treated with an identical dose – without dose escalation requirement – is designed to inform discussions with the FDA on a registrational path for each indication, following the completion of any cohort.

Our clinical strategy enables broad investigation of rese-cel across ten cohorts with well-defined patient populations in these four RESET TM Phase 1/2 clinical trials with the same dose and similar design.

In addition, the RESET-PV TM trial is evaluating weight-based dosing of rese-cel without preconditioning.

We have also received FDA Fast Track Designation for rese-cel in SLE, lupus nephritis, dermatomyositis, systemic sclerosis and multiple sclerosis.

• Leveraging our cellular therapy knowledge and experience in addition to development efficiencies gained through our longstanding Penn collaboration to rapidly build fully integrated internal infrastructure.

We have differentiated expertise that we believe is uniquely suited to the continued buildout of our CABA platform, focused on autoimmune diseases.

Our management team has expertise in conducting complex, interdisciplinary autoimmune-focused cell therapy clinical trials with a track record of positive regulatory interactions to support cell therapies in autoimmune diseases since 2018.

We have had seven INDs for autoimmune cell therapies, each cleared within the routine 30-day period with six Fast Track Designations granted to date.

In addition, we have a successful track record of manufacturing novel cell therapy product candidates with academic and industry partners.

Not only does our team possess significant experience in the manufacturing of cell therapy product candidates, but our partnership with Penn allows us to utilize their existing infrastructure, which has accelerated our early development activities.

In parallel, we continue to build out our internal capabilities while developing and continuing to implement a path to manufacturing independence, with established commercial CDMO partnerships to provide vector and cell processing capabilities at commercial grade and scale.

• Achieving compelling clinical responses and a favorable safety profile for our lead product candidate, rese-cel, and demonstrating its ability to be administered in the outpatient setting.

In October 2025, we announced that all 4 DM/ASyS patients who met the key inclusion criteria for the myositis registrational cohort with sufficient follow-up achieved immunomodulatory-free TIS responses of moderate or major improvement at week 16, which formed the foundation to initiate the registrational cohort in DM and ASyS.

In December 2025, we initiated enrollment in the DM/ASyS registrational trial and we announced that in the first 40 patients dosed with rese-cel with preconditioning across 4 RESET TM trials, 95% of patients had either no CRS or Grade 1 CRS (transient fever) and 95% of patients experienced no ICANS.

Outpatient administration of rese-cel is permitted within the myositis registrational trial, and, if ultimately approved, for outpatient administration.

If successful, we believe outpatient administration can reduce hospital resource utilization and improve the reimbursement framework for the 30% of autoimmune patients who are Medicare-insured.

• Leveraging our cellular therapy knowledge and manufacturing experience to manufacture rese-cel with the ability to achieve scalability to meet commercial demand with minimal capital investment.

Our team has a successful track record of manufacturing novel cell therapy product candidates with academic and industry partners.

We plan to launch utilizing multiple suppliers to ensure supply capacity and redundancy, while eliminating capital expenditure associated with a manufacturing facility.

In addition, since 2023, we have partnered with Cellares Corporation, or Cellares, to incorporate automated manufacturing for rese-cel, which can enable scalability to produce rese-cel for thousands of patients per year with minimal capital investment, provide scheduling flexibility for rese-cel after commercialization and permit rapid expansion to support global expansion.

Cellares is currently a manufacturer of rese-cel for the RESET TM clinical program and we anticipate initial clinical experience with Cellares in the first half of 2026 with full clinical and durability data in the second half of 2026.

• Develop differentiated innovations for rese-cel, including rese-cel without preconditioning, which could enable market expansion, improve patient and provider experience and accelerate outpatient adoption in the commercial setting.

In October 2025, we announced initial clinical and translational data from the initial dose cohort in the RESET-PV ® trial evaluating rese-cel without preconditioning.

All three patients experienced substantial depletion of B cells within the first month post-infusion, with patients 2 and 3 achieving complete peripheral B cell depletion.

Meaningful early clinical responses were observed in all three patients starting in the first month post-infusion based on Pemphigus Disease Area Index, or PDAI, score for skin, scalp and mucosal surfaces.

Based on the safety and early efficacy data, multiple patients have now been enrolled at a higher dose cohort within the RESET-PV ® study, and the no preconditioning approach was expanded in the RESET-SLE TM trial.

We believe this innovation can potentially provide a simpler and more patient-focused alternative for lupus patients, many of whom are women of child-bearing potential, who may desire rese-cel without preconditioning.

Based on evaluation of clinical durability data, the no-preconditioning strategy may be incorporated into each of our clinical trials.

• Advancing the RESET TM Phase 1/2 clinical trials to address significant unmet patient need while continuing to commit to optimize the patient experience.

We are focused on developing the first potentially curative targeted cellular therapies for patients with autoimmune diseases.

We plan to expand development of rese-cel to a broad range of autoimmune diseases where the biologic opportunity for cure or treatment may be possible, addressing significant unmet patient need across multiple indications for rese-cel, with the goal of realizing the potential of rese-cel.

While potentially serving a broad range of patients, we are committed to advancing to optimize the patient experience through minimizing the requirement for inpatient stay, optimizing the preconditioning regimen, reducing the burden of apheresis, and/or innovating to address scale in autoimmune disease.

We plan to continue development of rese-cel across a broad range of autoimmune diseases where the biologic opportunity for cure or treatment may be possible, addressing significant unmet patient need across multiple indications for rese-cel, with the goal of realizing the potential of rese-cel.

B Cells in Autoimmune Diseases:

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Our Pipeline and Product Candidates

We are 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.

Our CABA platform encompasses two approaches – CARTA and CAART.

autoimmune diseases.

Our CABA ® platform focuses on the CARTA approach.

Our current product candidate pipeline is illustrated below.

FTD – FDA Fast Track Designation received in dermatomyositis, SLE and lupus nephritis, systemic sclerosis, and multiple sclerosis.

Additional pipeline candidate includes MuSK-CAART for MuSK-Ab positive MG, currently being evaluated in a Phase 1 trial.

Myositis patients can also be treated by neurologists or dermatologists;

lupus nephritis patients can also be treated by nephrologists.

RESET TM – REstoring SElf-Tolerance;

Ab – Antibody;

AChR – Acetylcholine receptor;

gMG – Generalized myasthenia gravis;

PV – Pemphigus vulgaris;

SLE – Systemic lupus erythematosus;

SSc – Systemic sclerosis.

FDA Fast Track Designation received in dermatomyositis, SLE and lupus nephritis, systemic sclerosis, generalized myasthenia gravis and multiple sclerosis.

FDA RMAT received in myositis, SLE, LN and systemic sclerosis.

Rese-cel for multiple autoimmune indications

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This strategy may be able to reset the immune system, providing potentially meaningful clinical responses to patients off immunosuppressive therapies.

Cabaletta is advancing six RESET TM Phase 1/2 clinical trials in SLE, myositis, SSc, gMG, PV and MS, with potential application in a broad range of other autoimmune diseases.

Cabaletta is advancing five RESET TM Phase 1/2 clinical trials in SLE, myositis, SSc, gMG and PV, with potential application in a broad range of other autoimmune diseases.

Rese-cel is comprised of a fully human anti-CD19 binder, which is the extracellular targeting domain.

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Compared to FMC63-CART, rese-cel exhibits comparable biologic activity in vitro and in vivo (Peng, et al).

Given its structural and functional similarity to the CD19-CAR T construct employed in the academic clinical study published in Nature Medicine , including incorporation of a 4-1BB co-stimulatory domain, we believe rese-cel may have the potential to reset the immune system and transform treatment of a broad range of autoimmune diseases with high unmet need.

Based on the clinical and translational data that we have presented to date and given rese-cel’s structural and functional similarity to the CD19-CAR T construct employed in the academic clinical study published in Nature Medicine , including incorporation of a 4-1BB co-stimulatory domain, we believe rese-cel may have the potential to reset the immune system and transform treatment of a broad range of autoimmune diseases with high unmet need.

Disease Backgrounds

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It is results in a range of clinical manifestations, including end organ damage and an increased risk of death.

SLE affects an estimated up to 320,000 patients in the U.S., and 150,000 patients in Europe.

SLE affects an estimated up to 320,000 patients in the U.S.

Lupus nephritis is the most common end-organ manifestation of SLE, affecting approximately 30-40% of SLE patients.

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Myositis is classified into several subtypes based on the underlying immune mechanisms and clinical characteristics.

Although the pathogenesis of myositis is not well understood, there are several subtypes thought to be driven by B cells, including

dermatomyositis, or DM, anti-synthetase syndrome, or ASyS, and immune-mediated necrotizing myopathy, or IMNM.

Although the pathogenesis of myositis is not well understood, there are several subtypes thought to be driven by B cells, including DM, ASyS and IMNM.

All three subtypes can lead to severe functional impairment and may be life-threatening.

Including juvenile myositis, or JIIM, patients, approximately 80,000 patients are affected by these subtypes in the U.S.

and approximately 85,000 patients in Europe.

Current standard of care typically involves medications to suppress the immune system and/or chronic intensive therapies such as intravenous immunoglobulin, or IVIg.

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Approximately 90,000 patients in the U.S.

and 60,000 patients in Europe are affected by SSc, commonly middle-aged women.

are affected by SSc, commonly middle-aged women.

Current treatments, which have modest effects, include generalized immunosuppression or drugs targeted to specific symptomatic manifestations.

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Generalized MG affects approximately 100,000 patients in the U.S.

and 100,000 patients in Europe.

Symptoms of gMG include profound muscle weakness throughout the body, disabling fatigue, shortness of breath due to respiratory muscle weakness and risk for episodes of respiratory failure.

Standard of care therapies include cholinesterase inhibitors, steroids, immunomodulators, and biologics, which often require chronic administration, increasing the risk of serious long-term side effects.

Pemphigus vulgaris is an autoimmune disease that occurs when the immune system produces antibodies that attack a protein called desmoglein, or DSG.

Pemphigus vulgaris is an autoimmune disease that occurs when the immune system produces antibodies that attack a protein called DSG.

DSG normally enables skin cells and the cells lining the inside of your mouth, nose, throat, and eyelids to bind tightly together.

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The risk of mortality among patients with PV has been reported to be 2- to 3-fold higher than in the general population.

Multiple sclerosis is an autoimmune-mediated demyelinating disease of the central nervous system (CNS), affecting approximately 750,000 people in the U.S.

and approximately 550,000 patients in Europe.

The disease is more common in women than men, with onset of symptoms frequently between the ages of 20 and 40.

The immune system attack on nerves within the brain and spinal cord impairs nerve electrical conduction, resulting in a wide range of symptoms including muscle weakness, sensory loss, visual impairment, incoordination, memory loss, fatigue, and walking difficulty.

MS is classified into relapsing or progressive forms based on the pattern of clinical symptoms over time, with 85-90% experiencing a fluctuating (relapsing) course, and 10-15% steadily accumulating neurologic disability from disease onset (progressive).

The pathogenesis of MS is multifactorial, with autoreactive B cells increasingly being recognized as a major driver of disease.

Current standard of care therapies require chronic administration, which can be associated increased long-term risk of serious side effects.

Clinical Development Plan

Cabaletta is advancing RESET TM Phase 1/2 clinical trials in SLE, myositis, SSc, gMG, PV and MS, with potential application in a broad range of other autoimmune diseases.

Our rese-cel Phase 1/2 RESET-SLE TM , RESET-Myositis TM , RESET-SSc TM , RESET-MG TM and RESET-PV TM trials are currently enrolling patients.

Cabaletta is advancing RESET TM Phase 1/2 clinical trials in SLE, myositis, SSc, gMG and PV, with potential application in a broad range of other autoimmune diseases.

These five RESET TM Phase 1/2 clinical trials are comprised of independent cohorts with specific objectively defined disease sub-types, which can enroll and dose patients in parallel, and each cohort is expected to be comprised of 6 patients.

The trials are initiating at a weight-based dose, which is equivalent to the dose of the 4-1BB CD19-CAR T used in the academic publications (1.0 x 10 6 cells/kg) with the same preconditioning regimen of fludarabine and cyclophosphamide, with the exception of the RESET-PV TM trial, which is evaluating rese-cel without preconditioning.

The trials are initiating at a weight-based dose, which is equivalent to the dose of the 4-1BB CD19-CAR T used in the academic publications (1.0 x 10 6 cells/kg) with the same preconditioning regimen of fludarabine and cyclophosphamide, with the exception of the RESET-PV ® and RESET-SLE TM trials, which contain cohorts that are evaluating rese-cel without preconditioning.

Our clinical strategy enables broad investigation of rese-cel across cohorts with well-defined patient populations in our Phase 1/2 clinical trials with the same dose and similar design.

We have also received FDA Fast Track Designation for rese-cel in SLE, lupus nephritis, dermatomyositis, systemic sclerosis and multiple sclerosis.

DSG3-CAART for Mucosal PV

DSG3-CAART is a CAAR T cell therapy expressing DSG3 as the extracellular domain of a chimeric immunoreceptor and is designed to enable specific cytotoxicity toward B cells autoreactive to DSG3.

We believe this strategy has the potential to directly eliminate the disease-causing cells in mucosal pemphigus vulgaris, or mPV, an autoimmune disease that causes blisters on the skin and mucous membranes, which may lead to lasting clinical remission without damage to the healthy immune system.

PV has two major subtypes:

(1) mPV, which is caused by DSG3 autoantibodies and affects the mucous membranes;

and (2) mcPV, which is caused by DSG3 and DSG1 autoantibodies, affecting both the mucous membranes and the skin.

PV affects approximately 15,000 prevalent patients in the U.S., of which approximately 25% have mPV and 75% have mcPV.

Like most autoimmune diseases, the current standard of care for PV relies on general immune suppression, which is often transiently effective but can lead to severe infection, potentially resulting in hospitalization and death.

Clinical Development Plan

The DesCAARTes TM trial is an open-label trial to assess the safety and tolerability of various dosing regimens of DSG3-CAART in the treatment of subjects with active mPV.

The FDA granted DSG3-CAART Orphan Drug Designation for the treatment of PV in January 2020 and Fast Track Designation for improving healing of mucosal blisters in patients with mPV in May 2020.

The DesCAARTes TM trial is no longer dosing patients for treatment with DSG3-CAART after evaluation of clinical and translational data from the combination cohort, where patients were pre-treated with IVIg, cyclophosphamide and fludarabine prior to DSG3-CAART infusion.

In October 2024, we presented data in an oral presentation at the European Society of Gene and Cell Therapy, or ESGCT, 31st Annual Congress showing that the use of preconditioning with DSG3-CAART did not provide serologic or clinical improvement and did not deeply deplete B-cell levels in patients with mPV.

MuSK-CAART for MuSK Myasthenia Gravis

MuSK-CAART is an investigational cell therapy aimed at treating patients with anti-MuSK antibody positive myasthenia gravis, or MuSK MG, who have active disease.

We believe this strategy has the potential to directly eliminate the disease-causing cells in MuSK MG – induced by autoantibodies targeting the neuromuscular junction leading to potentially life-threatening muscle weakness to enable a complete and durable response for this disease.

The current standard of care for patients with MuSK MG is typically corticosteroids in addition to one or more steroid-sparing immunosuppressive agents.

Clinical Development Plan

The MusCAARTes TM trial is an open-label trial to assess the safety and tolerability of various dosing regimens of MuSK-CAART in the treatment of subjects with active MuSK MG.

In February 2022, MuSK-CAART received Fast Track Designation from the FDA to improve activities of daily living and muscle strength in patients with MuSK antibody-positive myasthenia gravis.

We are currently evaluating clinical and translational data from the A1 and A2 cohorts in the MusCAARTes TM trial, where patients were treated with MuSK-CAART without preconditioning .

Manufacturing

Manufacturing Strategy

We are implementing a two-stage plan that we believe will ultimately enable us to achieve manufacturing independence.

Part of our strategy relies on engaging non-profit and commercial suppliers early and in a staged manner.

We believe partnering with proven and reputable manufacturing partners will allow us to efficiently deploy financial and personnel resources.

The early phase of this plan is ongoing and utilizes the deep expertise in cell and vector manufacturing from our partners at Children’s Hospital of Philadelphia, or CHOP, and Penn, as well as commercial CDMO partnerships.

We believe these facilities and partnerships will allow us to move efficiently into clinical trials with expanded commercial grade vector and cell product supply.

We are aware that changes in any manufacturing process or facility introduces regulatory and scientific risk to a development program, if the changes result in a product that is not comparable.

We plan to mitigate these risks across the two stages as follows:

• By securing contract development and manufacturing organizations, or CDMOs, as partners during the early phase of our manufacturing strategy early on for both vector and cell manufacturing.

We plan to prioritize potential partners who are qualified to, and have an established track record of, the commercial production of vector and cell products.

We believe this allows us to make one change in our supply partners during an early period of clinical development to facilitate in vitro comparability testing and clinical validation, prior to controlled clinical studies.

• As part of this strategy, in January 2021 and as amended in August 2022, we entered into an agreement with WuXi to serve as an additional cell processing manufacturing partner for our MusCAARTes TM trial and have since completed enabling engineering and patient production runs.

In August 2023, as amended in August 2024, we entered into an agreement with WuXi to serve as one of our manufacturing partners for the global clinical development of rese-cel in multiple indications, including potential late-stage clinical trials and commercial readiness activities for rese-cel.

• In order to expand our clinical supply to address the increasing pace of enrollment in our clinical trials as well as to prepare for registrational trial(s) across the RESET clinical development program while expanding our manufacturing options for rese-cel, Cabaletta has expanded its CDMO agreements with Lonza to supply rese-cel clinical product under current Good Manufacturing Practices as soon as the second half of 2025.

• In December 2021, we entered into the LSA with Oxford to supply lentiviral vector for the clinical and commercial development of our DSG3-CAART candidate.

Manufacturing supply is comprised of three primary components:

plasmid (for lentiviral vector production), lentiviral vector (for gene transfer in the cellular product) and cellular product (the final drug product).

manufacturing strategy utilizes proven external suppliers, with a philosophy of maintaining redundant supply capability for cellular products while leveraging inventory build for plasmid and lentiviral vector, to mitigate potential supply interruption risk.

We established and implemented a phase-appropriate manufacturing supply strategy that optimized financial resources and speed for early clinical phase, or the Process A, and which was designed to enable a transition to a partially automated and commercially scalable process prior to the initiation of our first pivotal study in 2026, or the Process B.

In addition, we are pursuing an automated version of Process B, or the Process C, capable of providing flexible and cost efficient supply at a scale that is estimated to be greater than what is achievable with the same footprint with Process B at existing CDMOs.

To support this manufacturing lifecycle plan, we designed and implemented a comparability strategy, which in alignment with our discussions with the FDA, supports the use of clinical safety data across Process A, B and C.

Accordingly, Process A is undergoing a planned obsolescence in 2026.

Process B is intended for initial commercial launch and is undergoing process validation activities in 2026 and 2027 to support BLA submission.

Initial clinical manufacturing data using Process C is expected in 2026.

If supportive, the process will be further refined and then put through process validation activities to support commercial application post BLA approval, in time to meet expanded commercial demand.

Contract and Development Manufacturing Organizations (CDMOs)

In December 2021, we entered into the License and Supply agreement, or the LSA, with Oxford Biomedica (UK) Limited, or Oxford, to supply lentiviral vector for the clinical and commercial development of a legacy product candidate.

In May 2023, we amended the LSA with Oxford to expand the license to include our rese-cel program.

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In June 2024, we and Oxford entered into a fourth amendment to the LSA eliminating royalties on net sales of products that incorporate the Oxford technology if Oxford manufactures the vector.

We believe these efforts will provide us with sufficient clinical-grade vector to move forward with our anticipated clinical trials.

• In conjunction with our efforts to secure commercial supply for rese-cel, we plan to advance innovative manufacturing strategies in order to increase scale, reduce cost of goods and improve the patient experience.

To this end, in November 2023, Cabaletta partnered with Cellares to evaluate Cellares’ automated manufacturing platform, the Cell Shuttle, through Cellares’ Technology Adoption Program.

As part of the collaboration, the companies have agreed on a proof-of-concept technology transfer process for the manufacture of rese-cel.

In August 2024, we expanded our partnership with Cellares to facilitate the potential to incorporate the Cellares manufacturing platform to support the RESET TM clinical program.

Cell Manufacturing

We have entered into a collaboration with the Clinical Cell and Vaccine Production Facility, or CVPF, at Penn, to provide focused scientific, technical and regulatory support for CAAR T and CAR T cell manufacture.

CVPF is accredited by the Foundation for the Accreditation of Cellular Therapy and is capable of and experienced at supporting manufacture for early-phase clinical trials of novel cell therapy products in first-in-man clinical trials.

We rely upon CVPF as one of our manufacturing partners to provide initial Phase 1 clinical trial drug supply for rese-cel.

Penn’s manufacturing process for rese-cel is directly related to the process developed at Penn for early clinical trials of CD19-CAR T, which subsequently became known commercially as Kymriah.

The process was later transferred to Novartis Pharmaceuticals Corporation and further modified for the Kymriah program.

As we scale our manufacturing for our product candidates to meet our expected needs for further clinical trials, and while we continue to utilize Penn for Phase 1/2 studies in the US, we have brought on board commercial CDMOs capable of global and fully GMP compliant manufacturing, as well as other third parties for the manufacturing and processing of our clinical trial materials.

Any CDMO that we select will be subject to cGMP requirements.

We believe the use of contract manufacturing for our pipeline programs will be cost-effective and allow us to rapidly prepare for clinical trials in accordance with our development plans.

In preparation for this transition, we have engaged multiple third-party contractors to manufacture clinical grade viral vector used to deliver the applicable CAAR or CAR gene into the T cells.

We have also initiated development work with certain contractors for cGMP and commercial vector production.

We expect third-party manufacturers will be capable of providing and processing sufficient quantities of our product candidates to meet anticipated clinical trial demands and commercial need.

In January 2021 and as amended in August 2022, we entered into an agreement with WuXi to serve as an additional cell processing manufacturing partner for our MusCAARTes TM trial and have since completed enabling engineering and patient production runs.

In August 2023, as

amended in August 2024, we entered into an agreement with WuXi to serve as one of our manufacturing partners for the global clinical development of rese-cel in multiple indications, including potential late-stage clinical trials for rese-cel.

In order to expand our clinical supply to address the increasing pace of enrollment in our clinical trials as well as to prepare for registrational trial(s) across the RESET clinical development program while expanding our manufacturing options for rese-cel, Cabaletta has expanded its CDMO agreements with Lonza, a leading CDMO, to supply rese-cel clinical product under current Good Manufacturing Practices as soon as the second half of 2025.

Starting in December 2024, we and Oxford entered into work orders for certain process validation activities as part of commercial readiness activities.

For early phase cellular product supply, in January 2021 and as amended in August 2022, we entered into an agreement with Minaris to serve as a cell processing manufacturing partner for a legacy program and have since completed enabling engineering and patient production runs.

In August 2023, as amended in August 2024, we entered into an agreement with Minaris to serve as our manufacturing partner for the global clinical development of rese-cel in multiple indications using Process A.

Minaris serves as a second CMDO for Process A, in addition to the Cell and Vaccine Production Facility, or CVPF, at the University of Pennsylvania, which has been phased out of clinical production supply as of 2026.

In order to expand our clinical supply to address the increasing pace of enrollment in our clinical trials, as well as to implement Process B and prepare for registrational trial(s) across the RESET TM clinical development program, we entered into a clinical supply agreement with Lonza to serve as a clinical supplier of rese-cel using Process B.

This clinical supply agreement supports the global clinical development of rese-cel, including potential late-stage clinical trials and preparations for commercial readiness.

Our manufacturing process at Lonza will be used for registrational trial enrollment and plans are underway for commercial launch and supply.

In conjunction with our efforts to expand scalable commercial supply for rese-cel through full automation of production, in November 2023, we partnered with Cellares to evaluate Cellares’ automated manufacturing platform, the Cell Shuttle TM , through Cellares’ Technology Adoption Program.

As part of the collaboration, we and Cellares agreed on a proof-of-concept technology transfer process for the manufacture of rese-cel.

In March 2025, we and Cellares announced the successful conclusion of the Technology Adoption Program on Cellares’ automated cell therapy manufacturing Cell Shuttle TM .

In June 2025 and January 2026, we expanded our partnership with Cellares to introduce the Cellares manufacturing platform to support the RESET TM clinical program.

In January 2026, we and Cellares entered into a clinical supply agreement with Cellares to service as a clinical supplier of rese-cel using Process C.

This clinical supply agreement supports the clinical development of rese-cel.

Engineering runs in Cellares’ GMP facility were completed, and our IND amendment has been cleared.

Initial clinical runs are ongoing in 2026 providing additional manufacturing and drug product quality data.

Based on the outcome of clinical manufacturing performance and comparability data, the Cell Shuttle TM may be integrated into our future commercial manufacturing strategy for rese-cel.

Commercialization

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Rese-cel is under development for autoimmune diseases with serious unmet medical need.

Based on the differentiated expertise of Cabaletta’s team members and our years of experience in conducting cell therapy clinical trials in autoimmunity, we are focused on being the first company to launch a cell therapy product for patients with autoimmune diseases, while continuing to innovate on next-generation approaches and differentiation strategies to deliver an optimal product candidate profile.

We aim to achieve full manufacturing independence through expanding our CDMO relationships, establishment of our own manufacturing facilities, and/or through a strategic partnership.

Based on the differentiated expertise of Cabaletta’s team members and our years of experience in conducting cell therapy clinical trials in autoimmunity, we are focused on launching an autologous CAR T product for patients with autoimmune diseases, while continuing to innovate on next-generation approaches and differentiation strategies to deliver an optimal product candidate profile.

We aim to launch rese-cel through expanding our CDMO relationships, including advancing a fully automated approach, offering the potential for scalability to produce rese-cel for thousands of patients per year with minimal capital investment.

Our development and commercialization efforts will focus initially on the United States, with expansion to the European Union and Asia-Pacific geographies, potentially with the support of strategic partners.

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Within the CAR T field, we recognize that a subset of companies with an investment and expertise in CAR T cell development for oncology indications have announced they intend to leverage their technology in autoimmune disease-affected populations.

We are aware of other pharmaceutical and biotechnology companies that are exploring CART-19 as well as other methods of engineering T cells, natural killer, or NK, cells or bispecific antibodies for the treatment of autoimmune conditions.

We are aware of other pharmaceutical and biotechnology companies that are exploring CD19-CAR T as well as other methods of engineering T cells, natural killer, or NK, cells or bispecific antibodies for the treatment of autoimmune conditions.

Many of the companies against which we are competing or against which we may compete in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do.

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We strive to protect the proprietary technologies that we believe are important to our business, including pursuing and maintaining patent protection intended to cover our product candidates and their use, as well as other inventions that are important to our business.

In addition to patent protection, we also rely on know-how, confidentiality agreements, invention assignment agreements and trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for,

patent protection, to develop and maintain our proprietary position.

proprietary position.

The confidentiality agreements are designed to protect our proprietary information and the invention assignment agreements are designed to grant us ownership of technologies that are developed for us by our employees, consultants or certain other third parties.

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Any patents that we hold may be challenged, circumvented or invalidated by third parties.

As of March 1, 2025, our in-licensed patent estate included seven granted U.S.

patents, seven granted foreign patents, seven pending U.S.

As of March 1, 2026, our in-licensed patent estate included eight granted U.S.

patents, ten granted foreign patents, six pending U.S.

patent applications, and 28 pending foreign patent applications.

See “Our Material Agreements - IASO Agreement” and “Our Material Agreements - Amended and Restated License Agreement with the Trustees of the University of Pennsylvania and the Children’s Hospital of Philadelphia.” As of March 1, 2025, our Cabaletta-owned patent estate included three U.S.

provisional patent applications and two pending international patent applications.

patent application and counterpart patent applications pending in Australia, Canada, China, Europe, and Hong Kong.

These patent applications, if issued, would be expected to expire in 2040.

The family also contains granted patents in China and Japan, which are scheduled to expire in 2040.

See “Our Material Agreements - IASO Agreement” and “Our Material Agreements - Amended and Restated License Agreement with the Trustees of the University of Pennsylvania and the Children’s Hospital of Philadelphia.” As of March 1, 2026, our Cabaletta-owned patent estate included three pending international patent applications, two pending U.S.

patent applications, and nine pending foreign applications.

With regard to our rese-cel product candidate, under the IASO Agreement, we have in-licensed one patent family which is directed to a CD19-specific chimeric antigen receptor and a CD19-specific antibody and contains granted patents in the United States, China, Japan, and Canada, which are scheduled to expire in 2040, without taking patent term adjustment or patent term extension into account.

The family also contains one pending U.S.

patent application and counterpart patent applications pending in Australia, China, Europe, and Hong Kong, which, if issued, would be expected to expire in 2040.

This patent family is owned by IASO and is exclusively licensed to us in the field of the license.

We also own two international patent applications drawn to methods of treating autoimmune diseases with a chimeric antigen receptor, including a CD19-specific chimeric antigen receptor.

Any granted patents claiming priority to these applications would be expected to expire in 2044.

We also own one U.S.

provisional patent application drawn to methods of treating autoimmune diseases with a chimeric antigen receptor, including a CD19-specific chimeric antigen receptor;

provisional patent application drawn to CD19-binding antibodies and CD19-specific chimeric antigen receptors;

provisional patent application drawn to methods of manufacturing cell-therapy compositions.

We also own two patent families containing two pending U.S.

patent applications and nine pending foreign patent applications drawn to methods of treating autoimmune diseases with a chimeric antigen receptor, including a CD19-specific chimeric antigen receptor, including certain treatment methods that have different preconditioning regimens.

Any granted patents in these two families would be expected to expire in 2044.

We also own one international patent application drawn to other dosing regimens for treating autoimmune diseases with a chimeric antigen receptor, including a CD19-specific chimeric antigen receptor;

one international patent application drawn to CD19-binding antibodies and CD19-specific chimeric antigen receptors;

and one international patent application drawn to methods of manufacturing cell-therapy compositions.

Any granted patents claiming priority to these applications would be expected to expire in 2045.

With regard to our MuSK-CAAR T cell product candidate, under the Amended and Restated License Agreement with Penn, we have in-licensed one patent family containing one issued U.S.

patent with claims directed to a CAAR containing an extracellular domain containing a MuSK autoantigen and nucleic acids encoding the CAAR.

This patent is scheduled to expire in 2039, without taking potential patent term extensions into account.

This family also contains a counterpart patent granted in Japan which is scheduled to expire in 2039, and counterpart patent applications pending in the U.S., Australia, Canada, China, Europe, Hong Kong, Israel, Japan, Korea, Mexico and New Zealand, which if issued, would be expected to expire in 2039.

This patent family is owned by Penn and exclusively licensed to us in the field of the license.

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

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Oxford Biomedica

In December 2021, we entered into a Licence and Supply agreement, or LSA, with Oxford wherein the LSA grants us a non-exclusive license to Oxford’s LentiVector® platform for its application in our DSG3-CAART program and puts in place a multi-year vector supply agreement.

In December 2021, we entered into the LSA with Oxford wherein the LSA grants us a non-exclusive license to Oxford’s LentiVector® platform for its application in our DSG3-CAART program and puts in place a multi-year vector supply agreement.

Under the terms of the agreement, we were required to pay Oxford an upfront fee, as well as costs associated with initial vector manufacturing activities.

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In June 2024, we and Oxford entered into a fourth amendment to the LSA eliminating royalties on net sales of products that incorporate the Oxford technology if Oxford manufactures the vector.

In December 2024, the Company and Oxford entered into a work order for certain process characterization activities as part of commercial readiness activities.

The Company can terminate the LSA or any work order under the LSA at will upon advance written notice and subject to certain cancellation fees.

WuXi Manufacturing Agreement

In January 2021, we entered into a Development and Manufacturing Services Agreement, or the WuXi Agreement, with WuXi to serve as an additional cell processing manufacturing partner for the MuSK-CAART Phase 1 clinical trial, or MusCAARTes TM trial.

The WuXi Agreement is scheduled to expire upon completion of WuXi’s services related to MuSK-CAART and rese-cel.

Under the August 2023 work orders, WuXi converted our non-dedicated suite to a dedicated suite for GMP manufacturing for our rese-cel and MuSK-CAART programs, or the Dedicated Suite, for an initial term of 18 months with two 18 month extensions at our sole option on six months' notice prior to the end of the term.

In August 2024, we notified WuXi that we would extend the initial term by 18 months through August 2026.

Starting in December 2024, we and Oxford entered into work orders for certain process characterization and process performance qualification activities as part of commercial readiness activities.

We can terminate the LSA or any work order under the LSA at will upon advance written notice and subject to certain cancellation fees.

Minaris Manufacturing Agreement

In January 2021, we entered into a Development and Manufacturing Services Agreement, or the Minaris Agreement, with Minaris to serve as an additional cell processing manufacturing partner for the MuSK-CAART Phase 1 clinical trial, or MusCAARTes TM trial.

The Minaris Agreement is scheduled to expire upon completion of Minaris' services related to MuSK-CAART and rese-cel.

In August 2023, as amended in August 2024, we entered into an agreement with Minaris to serve as one of our manufacturing partners for the global clinical development of rese-cel in multiple indications, including potential late-stage clinical trials and commercial readiness activities for rese-cel.

Under the August 2023 work orders, Minaris converted our non-dedicated suite to a dedicated suite for GMP

manufacturing for our rese-cel and MuSK-CAART programs, or the Dedicated Suite, for an initial term of 18 months with two 18 month extensions at our sole option on six months' notice prior to the end of the term.

In August 2024, we notified Minaris that we would extend the initial term by 18 months through August 2026.

In addition, we agreed to certain monthly minimum runs.

In August 2024, the 2023 work order related to GMP manufacturing was amended to reduce the minimum monthly runs through the end of 2024.

In lieu of the original $1.5 million termination fee under the terms of the WuXi Agreement, we would

incur up to a $1.08 million termination fee if we terminate both the rese-cel and MuSK-CAART work orders for any reason.

We may terminate for convenience the WuXi Agreement or any work order with six months' prior written notice, however, we may not terminate the Dedicated Suite without terminating both the MuSK-CAART and rese-cel GMP run work orders.

WuXi may terminate the WuXi Agreement or any work order for convenience on 18 months' prior written notice, but such notice may not be effective prior to February 2028.

In lieu of the original $1.5 million termination fee under the terms of the Minaris Agreement, we would incur up to a $1.08 million termination fee if we terminate both the rese-cel and MuSK-CAART work orders for any reason.

We may terminate for convenience the Minaris Agreement or any work order with six months' prior written notice, however, we may not terminate the Dedicated Suite without terminating both the MuSK-CAART and rese-cel GMP run work orders.

Minaris may terminate the Minaris Agreement or any work order for convenience on 18 months' prior written notice, but such notice may not be effective prior to February 2028.

In February 2026, we notified Minaris that we intend to permit the term to expire in August 2026.

Lonza Manufacturing Agreement

The Lonza Agreement has a term of five years and can be extended for an additional three year term upon notice to Lonza at least 18 months prior to the expiration of the Lonza Agreement.

We can terminate the Lonza Agreement at will upon nine months advance written notice to Lonza subject to the terms of the Lonza Agreement.

Lonza can terminate the Lonza Agreement at will upon 24 months advance written notice to us subject to the terms of the Lonza Agreement.

Under the initial work order, Lonza will perform cell therapy manufacturing activities for our CAR-T cell therapy product, rese-cel, for an initial term of 12 months with the ability to extend the manufacturing period on a rolling basis subject to the terms of the Lonza Agreement.

Cellares Agreement

In January 2026, we entered into a Development and Clinical Manufacturing Services Agreement, or the Cellares Agreement, with Cellares to serve as one of our manufacturing partners for the clinical development of rese-cel in multiple indications, including potential late-stage clinical trials and preparations for commercial readiness.

The Cellares Agreement has a term of five years.

We can terminate the Cellares Agreement at will by providing a certain advance written notice to Cellares subject to the terms of the Cellares Agreement.

Cellares can terminate the Cellares Agreement at will by providing a certain advance written notice to us subject to the terms of the Cellares Agreement.

Under the initial work order, Cellares will perform clinical cell therapy manufacturing activities for our CAR-T cell therapy product, rese-cel.

Amended and Restated License Agreement with the Trustees of the University of Pennsylvania and the Children’s Hospital of Philadelphia

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In the event of an uncured, material breach, Penn may terminate the License Agreement upon 60 days' written notice.

Master Translational Research Services Agreement

In October 2018, we entered into a Master Translational Research Services Agreement with Penn, or the Services Agreement, pursuant to which Penn agreed to perform certain services related to the research and development of the technology licensed to us under the License Agreement, as well as certain clinical, regulatory and manufacturing services.

The Services Agreement will expire on the later of (i) October 19, 2021 or (ii) completion of the services for which we have engaged Penn under the Services Agreement.

Either party may terminate this agreement with or without cause upon a certain number of days’ prior written notice.

The services encompassed by the Services Agreement are performed by different organizations at Penn pursuant to certain addenda to the Services Agreement, including the Center for Advanced Retinal and Ocular Therapeutics, or CAROT, Addendum, as amended in May 2020, and the CVPF Addendum.

In February 2023, we entered into a second Master Translational Research Services Agreement with Penn, or the CARTA Services Agreement, pursuant to which Penn agreed to perform certain research, development and manufacturing activities.

The CARTA Services Agreement will expire on the later of (i) February 9, 2026 or (ii) completion of the services for which we have engaged Penn under the CARTA Services Agreement.

Either party may terminate this agreement with or without cause upon a certain number of days’ prior written notice.

The services encompassed by the CARTA Services Agreement are performed by different organizations at Penn pursuant to certain addenda to the CARTA Services Agreement.

Government Regulation

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Our products are considered more than minimally manipulated and will require evaluation in clinical trials and the submission and approval of a BLA before we can market them.

Government authorities in the United States (at the federal, state and local level) and in other countries extensively regulate, among other things, the research, development, testing, manufacturing, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of

biopharmaceutical products such as those we are developing.

Our product candidates must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in foreign countries.

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Any agency or judicial enforcement action could have a material adverse effect on us.

Our drug product candidates must be approved by the FDA through the Biologics License Application, or BLA, process before they may be legally marketed in the United States.

Our drug product candidates must be approved by the FDA through the BLA process before they may be legally marketed in the United States.

The process required by the FDA before a biologic may be marketed in the United States generally involves the following:

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The central focus of an IND submission is on the general investigational plan and the protocol(s) for human trials.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the

proposed clinical trials and places the IND on clinical hold within that 30-day time period.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the proposed clinical trials and places the IND on clinical hold within that 30-day time period.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

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The duration of treatment is often extended to mimic the actual use of a product during marketing.

Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of a BLA.

Generally, two adequate and well-controlled Phase 3 clinical trials have been required by the FDA for approval of a BLA, although there are known exceptions, particularly for rare diseases.

FDA leadership announced in February 2026 that the FDA will, going forward, adopt the default position that one adequate and well-controlled trial, combined with confirmatory evidence, can serve as the basis of approval for novel products.

In certain instances, FDA may condition approval of a BLA on the sponsor’s agreement to conduct additional clinical trials to further assess the biologic’s safety and effectiveness after BLA approval.

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Failure to exhibit due diligence with regard to conducting Phase 4 clinical trials could result in withdrawal of approval for products.

in vitro testing that suggest a significant risk for human subjects, and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and the investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the biologic, findings from animal or in vitro testing that suggest a significant risk for human subjects, and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all.

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We may also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug product candidate as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the

drug product candidate as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the drug product candidate and, among other things, must develop methods for testing the identity, strength, quality, potency and purity of the final product.

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Before approving a BLA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether the facilities comply with cGMPs.

The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of

the product within required specifications.

The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

In addition, before approving a BLA, the FDA may also audit data from clinical trials to ensure compliance with GCP requirements.

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The Complete Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical trial(s), and/or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing.

If a Complete Response Letter is issued, the applicant may either resubmit the BLA, addressing all of the deficiencies identified in the letter, withdraw the application or request a hearing.

If a Complete Response Letter

is issued, the applicant may either resubmit the BLA, addressing all of the deficiencies identified in the letter, withdraw the application or request a hearing.

Even if such data and information is submitted, the FDA may ultimately decide that the BLA does not satisfy the criteria for approval.

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Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan drug designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug or biologic for the same indication for seven years from the date of such approval, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity on the basis of greater effectiveness or safety or providing a major contribution to patient care or in instances of drug supply issues.

If a product that has orphan drug designation subsequently receives the first FDA approval for the use or indication for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug or biologic for the same indication for seven years from the date of such approval, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity on the basis of greater effectiveness or safety or providing a major contribution to patient care or in instances of drug supply issues.

Competitors, however, may receive approval of either a different product for the same indication or the same product for a different indication but that could be used off-label in the orphan indication.

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The FDA has a Fast Track program that is intended to expedite or facilitate the process for reviewing new drugs and biological products that meet certain criteria.

Specifically, new drugs and biological products are eligible for Fast Track Designation if they are

intended to treat a serious or life-threatening condition and nonclinical or clinical data demonstrate the potential to address unmet medical needs for the condition.

Specifically, new drugs and biological products are eligible for Fast Track Designation if they are intended to treat a serious or life-threatening condition and nonclinical or clinical data

demonstrate the potential to address unmet medical needs for the condition.

Fast Track Designation applies to the combination of the product and the specific indication for which it is being studied.

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Benefits of such designation also include early interactions with FDA to discuss any potential surrogate or intermediate endpoint to be used to support accelerated approval.

An RMAT that is granted accelerated approval and is subject to post approval requirements may fulfill such requirements through the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, such as electronic health records;

An RMAT that is granted accelerated approval and

is subject to post approval requirements may fulfill such requirements through the submission of clinical evidence, clinical studies, patient registries, or other sources of real world evidence, such as electronic health records;

the collection of larger confirmatory data sets;

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The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of a BLA plus the time between the submission date of a BLA and the approval of that application, except that the review period is reduced by any time during which the applicant failed to exercise due diligence.

Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent.

Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the

PTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

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Interchangeability requires that a biological product be biosimilar to the reference product and that the product can be expected to produce the same clinical results as the reference product in any given patient and, for products administered multiple times, that the product and the reference product may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biological product.

However, complexities associated with the larger, and often more complex,

structure of biological products as compared to small molecule drugs, as well as the processes by which such products are manufactured, pose significant hurdles to implementation that are still being worked out by the FDA.

However, complexities associated with the larger, and often more complex, structure of biological products as compared to small molecule drugs, as well as the processes by which such products are manufactured, pose significant hurdles to implementation that are still being worked out by the FDA.

A reference biological product is granted twelve years of exclusivity from the time of first licensure of the product, and the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after first licensure.

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A third-party payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved.

Third party reimbursement may not be sufficient to enable us to maintain price levels high enough to realize an appropriate return on our investment in product development.

Third party reimbursement may not be sufficient to enable us to maintain price levels high enough to realize an appropriate return on our investment in product

In the United States, the principal decisions about reimbursement for new drug products are typically made by CMS, an agency within HHS.

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The containment of healthcare costs has become a priority of federal and state governments, and the prices of drugs, including biologics, have been a focus in this effort.

government, state legislatures and foreign governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for

substitution of generic products.

In many countries, the prices of drug products are subject to varying price control mechanisms as part of national health systems.

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Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain.

Several states have enacted legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities, and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales

and marketing, and to prohibit certain other sales and marketing practices.

All of our activities are potentially subject to federal and state consumer protection and unfair competition laws.

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Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.

If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.

Under the One Big Beautiful Bill Act of 2025, or OBBBA, this restriction was eliminated;

and effective for the 2028 initial price applicability year, all orphan drugs, regardless of the number of orphan drug designations or indications, are exempt from the Medicare drug price negotiation program.

implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.

The effects of the IRA on our business and the healthcare industry in general is not yet known.

Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain drug access and marketing cost disclosure and transparency measures, and designed to encourage importation from other countries and bulk purchasing.

Legally mandated price controls on payment amounts by third-party payors or other

restrictions could harm our business, financial condition, results of operations and prospects.

Certain states are also pursuing cost containment efforts through Prescription Drug Affordability Boards, or PDABs, and similar entities.

While many PDABs have been granted authority to promote drug price transparency and reporting, some states have granted PDABs more expansive authority, including to set Upper Payment Limits, or UPLs, on select, high price drugs.

The adoption and implementation of UPLs may put downward pressure on drug prices and impact our company’s future revenues.

Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, financial condition, results of operations and prospects.

In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

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Whether or not we obtain FDA approval of a product, we would need to obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries.

Certain countries outside of the United States have a similar process that requires the submission of a clinical trial application much like the IND prior to the commencement of human clinical trials.

In the EU, for example, a clinical trial application must be submitted to each country’s national health authority and an independent ethics committee, much like the FDA and IRB, respectively.

Once the clinical trial application is approved in accordance with a country’s requirements, clinical trial development may proceed.

Because biologically sourced raw materials are subject to unique contamination risks, their use may be restricted in some countries.

Certain countries outside of the United States have a similar process that requires the submission of a clinical trial authorization application much like the IND prior to the commencement of human clinical trials.

In the EU, for example, a clinical trial application must be submitted through the centralized EU platform (CTIS) for coordinated assessment by the competent authorities of the concerned Member States together with review by an ethics committee in accordance with national law, much like the FDA and IRB, respectively.

Once the clinical trial authorization application is approved in accordance with the applicable Member State requirements under the EU Clinical Trials Regulation, the clinical trial may proceed in the relevant Member State(s).

The requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.

In all cases, the clinical trials must be conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

To obtain regulatory approval of an investigational drug or biological product under EU regulatory systems, we must submit an MAA.

To obtain regulatory approval of a medicinal product in the EU, we must submit a marketing authorization application, or MAA.

The application used to file the BLA in the United States is similar to that required in the EU, with the exception of, among other things, country-specific document requirements.

The criteria for designating an “orphan medicinal product” in the EU are similar in principle to those in the United States.

A medicinal product can be designated as an orphan if its sponsor can establish that:

(1) the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition, (2) either (i) such condition affects no more than five in ten thousand persons in the EU when the application is made, or (ii) without the benefits derived from orphan status, it is unlikely that the marketing of the product in the EU would generate sufficient return to justify the necessary investment in its development;

(3) there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the EU or, if such method exists, the product would be of significant benefit to those affected by that condition.

An orphan designation provides a number of benefits, including fee reductions, regulatory assistance and the possibility to apply for a centralized EU marketing authorization.

Upon grant of a marketing authorization, orphan medicinal products are entitled to a ten-year period of market exclusivity, which means that the EMA and the competent authorities of the EU member states cannot accept another MAA, or grant a marketing authorization, or accept an application to extend a marketing authorization for a similar medicinal product for the same indication for a period of ten years.

A “similar medicinal product” is defined as a medicinal product containing a similar active substance or substances as contained in an authorized orphan medicinal product, and which is intended for the same therapeutic indication.

The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed pediatric investigation plan.

No extension to any supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications.

Orphan designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

The orphan exclusivity period may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for which it received orphan destination, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold.

Additionally, a marketing authorization may be granted to a similar medicinal product for the same indication as an authorized orphan product at any time if (i) a second applicant can

establish that its product, although similar to the authorized orphan product, is safer, more effective or otherwise clinically superior;

(ii) the marketing authorization holder for the authorized orphan product consents to a second medicinal product application;

or (iii) the marketing authorization holder for the authorized product cannot supply enough orphan medicinal product.

The PRIority MEdicines (“PRIME”), scheme is intended to encourage product development in areas of unmet medical need.

Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicine will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.

Products from small- and medium-sized enterprises may qualify for earlier entry into the PRIME scheme than larger companies.

Many benefits accrue to sponsors of therapeutic candidates with PRIME designation, including but not limited to early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and potentially accelerated MAA assessment once a dossier has been submitted.

Importantly, a dedicated EMA contact and rapporteur from the Committee for Medicinal Products for Human Use are appointed early in the PRIME scheme facilitating increased understanding of the product at the EMA’s Committee level.

A kick-off meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies.

Where, during the course of development, a medicine no longer meets the eligibility criteria, support under the PRIME scheme may be withdrawn.

The EU pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020.

The European Commission introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the European Union for all medicines (including those for rare diseases and for children).

In April 2024, the European Parliament adopted its position on the legislative proposals and, in June 2025, the Council of the European Union adopted its position.

A common position on the text was agreed upon on December 11, 2025, in the context of subsequent inter-institutional trilogue negotiations.

The proposed revisions remain to be adopted into EU law, and are not expected to become applicable before 2028.

For other countries outside of the EU, such as countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.

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The GDPR and UK GDPR apply extraterritorially, and we may be subject to the GDPR and UK GDPR because of our data processing activities that involve the personal data of individuals located in the European Union or United Kingdom, such as in connection with our EU and UK clinical trials.

Failure to comply with the requirements of the GDPR or UK GDPR and the applicable national data protection laws of the EU member states and UK may result in fines of up to €20,000,000 (or £17.5 million for the UK) or up to 4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, and other administrative penalties.

Failure to comply with the requirements of the

GDPR or UK GDPR and the applicable national data protection laws of the EU member states and UK may result in fines of up to €20,000,000 (or £17.5 million for the UK) or up to 4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, and other administrative penalties.

GDPR and UK GDPR regulations may impose additional responsibility and liability in relation to the personal data that we process and we may be required to put in place additional mechanisms to ensure compliance with the new data protection rules.

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Of those, 139 were engaged in research and development activities.

Two full-time employees are located in Switzerland.

Two full-time employees are located in Switzerland and two full-time employees are located in Germany.

We do not have any employees that are represented by a labor union or covered under a collective bargaining agreement.

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Therefore, we encourage investors, the media, and others interested in our company to review the information we post on the social media channels listed on our investor relations website.

Information that is contained in and can be accessed through our website or our social media posts are not incorporated into, and does not form a part of, this Annual Report on Form 10-K.

Information that is

contained in and can be accessed through our website or our social media posts are not incorporated into, and does not form a part of, this Annual Report on Form 10-K.

A copy of our Corporate Governance Guidelines, Code of Conduct and Business Ethics and the charters of the Audit Committee, Compensation Committee and Nominating and Corporate Governance Committee are posted on our website, www.cabalettabio.com, under the heading “Investors & Media.”

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business