Cabaletta Bio, Inc.

Cabaletta Bio, Inc. is a late clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies for autoimmune diseases, leveraging its proprietary CABA® platform, which utilizes the Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) approach ¹. The company's lead product candidate, resecabtagene autoleucel (rese-cel), formerly CABA-201, is a fully human CD19-CAR T construct designed to achieve transient and deep depletion of all B cells following a single, weight-based infusion of T cells ². This approach aims to reset the immune system, allowing for repopulation by healthy transitional, naïve B cells, and has demonstrated potential for meaningful clinical responses without chronic therapy requirements ³.

The company's core business model revolves around the research, development, and eventual commercialization of these engineered T cell therapies. Revenue generation is currently not from product sales, as the company is clinical-stage, but rather through financing activities such as private placements, public offerings of common stock, and "at-the-market" offerings ⁴. Primary customer segments, once products are commercialized, are expected to be patients with autoimmune diseases where B cells play a role in initiating or maintaining the disease, with a focus on conditions like dermatomyositis, anti-synthetase syndrome, systemic lupus erythematosus, systemic sclerosis, and generalized myasthenia gravis ⁵. The company aims to become a fully integrated cellular therapy company, initially focusing on the United States, with future expansion into the European Union and Asia-Pacific geographies, potentially with strategic partners ⁶.

Cabaletta Bio's pipeline is centered on rese-cel for multiple autoimmune indications. The RESET-Myositis® Phase 1/2 clinical trial evaluates rese-cel in dermatomyositis (DM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), and juvenile idiopathic inflammatory myopathy (JIIM), affecting approximately 80,000 patients in the U.S. ⁷. A registrational trial for DM/ASyS was initiated in December 2025, targeting approximately 60,000 DM patients and 15,000 ASyS patients in the U.S. ⁸. The RESET-SLE™ Phase 1/2 clinical trial is for systemic lupus erythematosus (SLE), affecting up to 320,000 patients in the U.S., including those with lupus nephritis (LN) ⁹. The RESET-SSc™ Phase 1/2 clinical trial addresses systemic sclerosis (SSc), impacting approximately 90,000 patients in the U.S. ¹⁰. The RESET-MG™ Phase 1/2 clinical trial targets generalized myasthenia gravis (gMG), affecting about 100,000 patients in the U.S. ¹¹. Lastly, the RESET-PV® trial evaluates rese-cel as monotherapy without preconditioning in pemphigus vulgaris (PV), which affects approximately 15,000 patients in the U.S. and 20,000 in Europe ¹².

For the fiscal year ended December 31, 2025, Cabaletta Bio reported net losses of $167.9 million ¹³. This compares to a net loss of $115.9 million for the year ended December 31, 2024 ¹⁴. As of December 31, 2025, the company had an accumulated deficit of $517.0 million ¹⁵. Cash, cash equivalents, and investments totaled $133.6 million as of December 31, 2025 ¹⁶. The company has no revenue from product sales to report for these periods.

Comparing year-over-year, the net loss increased from $115.9 million in 2024 to $167.9 million in 2025, indicating a significant increase in expenses, primarily related to research and development activities as the company advances its clinical programs ¹⁷. The company has not generated any revenue from product candidates, so there are no revenue growth by segment or margin changes to report.

Significant operational developments during the period include the initiation of a registrational trial with rese-cel for patients with dermatomyositis or anti-synthetase syndrome in December 2025 ¹⁸. In January 2026, the company announced IND clearance for rese-cel manufactured using Cellares' automated manufacturing platform, the Cell Shuttle™, with initial clinical experience expected in the first half of 2026 and durability data in the second half of 2026 ¹⁹. Fast Track Designation for rese-cel was granted by the FDA for dermatomyositis and SSc in January 2024, and for SLE and LN in May 2023 ²⁰. Orphan Drug Designation for rese-cel was granted for myositis in February 2024 and for SSc in March 2024 ²¹. Rare Pediatric Disease designation for rese-cel for juvenile dermatomyositis was granted in March 2024 ²². In May 2025, RMAT designation was granted to rese-cel for myositis, and in November 2025, for SLE and LN ²³. In January 2026, RMAT designation was granted for SSc ²⁴. The company also announced registrational cohort designs in RESET-SLE™ in January 2026 ²⁵. In October 2025, initial clinical and translational data from the RESET-PV® trial evaluating rese-cel without preconditioning were announced, showing substantial B cell depletion and rapid reduction in autoantibodies ²⁶. The company expanded its partnership with Cellares in June 2025 and January 2026 to support the RESET™ clinical program ²⁷. In February 2026, Cabaletta notified Minaris of its intent to permit the term of their manufacturing agreement to expire in August 2026 ²⁸.

Cabaletta Bio currently expects its existing cash, cash equivalents, and investments to be sufficient to fund its operations into the fourth quarter of 2026 ²⁹. This includes plans to complete the Phase 1/2 RESET-SLE™, RESET-Myositis®, RESET-SSc™, and RESET-MG™ trials, and to generate clinical data from the RESET-PV® dose escalation trial and RESET-SLE™ without preconditioning ³⁰. However, the company explicitly states that it will require significant additional financing to complete these clinical trials and any future clinical trials of these and other product candidates ³¹. If marketing approval is received, significant additional cash will be required to launch and commercialize product candidates ³².

A major growth area for Cabaletta Bio is the advancement of rese-cel across a broad range of autoimmune diseases. The company initiated enrollment in the registrational DM/ASyS cohort in December 2025 and anticipates Biologics License Application (BLA) submission in 2027 ³³. The registrational trial design includes a 16-week primary endpoint of moderate or major Total Improvement Score (TIS) response while off immunomodulators and on no or low-dose steroids ³⁴. The planned size of 17 patients for the registrational cohort is based on an assumed treatment effect and an estimated background rate of less than 10% for active, refractory myositis patients achieving the primary endpoint ³⁵. For SLE, registrational cohort designs were announced in January 2026 to evaluate the current rese-cel dose in two independent, single-arm cohorts of approximately 25 patients each, with complete Phase 1/2 data anticipated in the first half of 2026 ³⁶. For SSc, complete Phase 1/2 data is anticipated in the first half of 2026, and the registrational cohort design is expected to be announced in the first half of 2026 ³⁷. For gMG, complete Phase 1/2 data from both cohorts is anticipated in the first half of 2026, with the registrational cohort design expected in mid-2026 ³⁸.

Another significant growth vector is the development of differentiated innovations for rese-cel, including administration without preconditioning, which could enable market expansion, improve patient and provider experience, and accelerate outpatient adoption ³⁹. Initial clinical and translational data from the RESET-PV® trial evaluating rese-cel without preconditioning, announced in October 2025, showed substantial B cell depletion and rapid reduction in autoantibodies ⁴⁰. Based on this safety and early efficacy data, multiple patients have been enrolled at a higher dose cohort within the RESET-PV® study, and the no preconditioning approach was expanded in the RESET-SLE™ trial ⁴¹. The first clinical experience from patients treated with rese-cel manufactured by the Cellares Cell Shuttle™ is expected in the first half of 2026, with full clinical and durability data in the second half of 2026 ⁴².

Operationally, the company is focused on leveraging its cellular therapy knowledge and manufacturing experience to achieve scalability for commercial demand with minimal capital investment ⁴³. The manufacturing strategy utilizes proven external suppliers and aims for redundant supply capability for cellular products ⁴⁴. Process B is intended for initial commercial launch and is undergoing process validation activities in 2026 and 2027 to support BLA submission ⁴⁵. Initial clinical manufacturing data using Process C, an automated version of Process B with Cellares, is expected in 2026 ⁴⁶. If supportive, Process C will be further refined and validated to support commercial application post-BLA approval ⁴⁷. The company plans to launch utilizing multiple suppliers to ensure supply capacity and redundancy, while eliminating capital expenditure associated with a manufacturing facility ⁴⁸.

Planned capital allocation includes continued substantial spending on preclinical and clinical development of product candidates, including the RESET™ trials, and research and development for future product candidates ⁴⁹. The company has generated approximately $384.0 million in aggregate net proceeds from public offerings of common stock and pre-funded warrants since its initial public offering through December 31, 2025 ⁵⁰. During the year ended December 31, 2025, the company sold 4,160,176 shares through its 2025 ATM Program for net proceeds of $10.2 million ⁵¹. Subsequent to December 31, 2025, an additional 8,055,260 shares were sold for net proceeds of $22.6 million ⁵². As of December 31, 2025, there were 53,090,190 common stock warrants and pre-funded warrants to purchase 6,000,000 shares outstanding ⁵³.

Management has explicitly flagged that the company has identified conditions that raise substantial doubt about its ability to continue as a going concern for at least twelve months following the filing of this Annual Report on Form 10-K ⁵⁴. If the company is unable to secure additional funding beyond its current cash position that enables operations into the fourth quarter of 2026, it may be forced to delay, reduce, or discontinue product development programs or other operations ⁵⁵. The company also faces risks related to the regulatory approval process, which is lengthy and time-consuming, with potential for significant delays ⁵⁶. The novel nature of its product candidates creates further challenges in obtaining regulatory approval, as regulatory requirements are not entirely clear for CAR T cells for autoimmune disease or CAAR T cells for pemphigus ⁵⁷. Geopolitical tensions with China, including the BIOSECURE Act, could restrict the company's ability to engage China-based suppliers or service providers, potentially requiring termination or restructuring of arrangements, transitioning manufacturing, or delaying development activities ⁵⁸.

Cabaletta Bio faces several material risks, including its status as a clinical-stage company with a limited operating history and a history of significant losses, with an accumulated deficit of $517.0 million as of December 31, 2025 ⁵⁹. The company has identified conditions that raise substantial doubt about its ability to continue as a going concern for at least twelve months following the filing of this Annual Report on Form 10-K ⁶⁰, and will need to secure additional funding beyond its current cash position to extend operations into the fourth quarter of 2026 ⁶¹. Operational risks include high dependence on third-party manufacturers like Minaris, Lonza, and Cellares for current and future manufacturing needs, with potential for supply disruptions, delays, or limitations, including due to legislative action such as the BIOSECURE Act ⁶². The company is reliant on intellectual property licensed from Nanjing IASO Biotherapeutics Co., Ltd. (IASO), and termination of this agreement would result in the loss of significant rights ⁶³. Clinical development faces risks such as difficulties enrolling patients in trials, potential for serious adverse events like ICANS and CRS, and the possibility that results of earlier studies may not be predictive of future trial outcomes ⁶⁴. The regulatory approval process is lengthy and uncertain, particularly for novel cell therapies in autoimmune diseases, and changes in regulatory requirements or interpretations could cause delays or increased costs ⁶⁵. The company's registrational trials may rely on a single-arm design with an external control, which could be deemed unsuitable by regulatory authorities, leading to delays or denial of approval ⁶⁶. Competition is intense, with many competitors possessing greater financial resources and expertise ⁶⁷. Data privacy and security regulations, such as GDPR and state-level laws like CCPA and CPRA, impose stringent requirements and potential for significant fines or penalties for non-compliance ⁶⁸.

Management's message to shareholders conveys a focus on advancing innovative engineered T cell therapies for autoimmune diseases, with an emphasis on achieving deep and durable, potentially curative, responses. They highlight the proprietary CABA® platform and the lead product candidate, rese-cel, as central to this mission. Management explicitly states that the company expects its existing cash, cash equivalents, and investments to be sufficient to fund operations into the fourth quarter of 2026 ⁶⁹, but also acknowledges the need for substantial additional financing to complete clinical trials and commercialization efforts ⁷⁰. The three strategic priorities emphasized are: achieving compelling clinical responses and a favorable safety profile for rese-cel, leveraging cellular therapy knowledge and manufacturing experience to achieve scalability, and developing differentiated innovations for rese-cel, including administration without preconditioning, to enable market expansion and improve patient experience ⁷¹. Management also notes the initiation of a registrational trial for dermatomyositis/anti-synthetase syndrome in December 2025 ⁷² and anticipates BLA submission in 2027 ⁷³.