GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - CABALETTA BIO INC

Financial Performance:

• The company holds approximately $300 million in cash reserves, providing a runway extending into the first quarter of 2028, which aligns with the anticipated Biologics License Application (BLA) submission timeline.
• The firm highlights significant manufacturing efficiency advantages over oncology CAR-T peers, citing high T-cell viability and lower out-of-spec rates due to the healthy donor profile of autoimmune patients.
• Management notes a rapid trajectory for outpatient administration in clinical trials, faster than industry benchmarks for prior CAR-T products, suggesting lower hospitalization costs.

Guidance and Future Outlook:

• Blaise submission for the myositis indication (Rezacel) has been advanced to the first quarter of 2028, following a temporary enrollment slowdown that has since reversed.
• Data updates regarding the Pre-conditioning (PC)-free regimen across Lupus, Pemphigus, and Myasthenia Gravis are expected to be disclosed in the first half of 2026.
• The company plans to include Juvenile Myositis data in the Myositis BLA application, potentially qualifying for a Priority Review Voucher (PRV) to fund future operations.
• Long-term commercial strategy aims to scale site certifications immediately to accommodate potential future launches for Systemic Sclerosis (SSc).

Business Segments and Product Lines:

• Rezacel (CD19 CAR-T): The lead program demonstrates robust efficacy and safety across a portfolio of autoimmune diseases, including Dermatomyositis, Lupus Nephritis, Systemic Sclerosis, and Juvenile Myositis.
• Dermatomyositis (Myositis): Phase 1/2 data shows durability with patients achieving major/moderate TIS responses at one year while off immunomodulators and steroids; this indication is the focus of the upcoming pivotal trial.
• Systemic Sclerosis (SSc): The registrational program has initiated, targeting patients with Interstitial Lung Disease (ILD); Phase 1/2 data reported a 9% improvement in Forced Vital Capacity (FVC) at one year, contrasting with standard care which typically stabilizes or declines lung function.
• Lupus Nephritis: Phase 1/2 data indicates 100% of patients achieving DORIS remission via repeat kidney biopsy at follow-ups ranging from six months to two years, suggesting potential deep healing of kidney tissue.
• PC-Free Development: Evaluating pre-conditioning-free regimens in Lupus, Pemphigus, and Myasthenia Gravis to improve accessibility and safety.

Market and Competitive Landscape:

• The company positions itself as a differentiated leader in the autoimmune CAR-T space, contrasting its safety profile with recent adverse events experienced by competitors like Bristol Myers Squibb and Novartis.
• Rezacel is characterized by a well-characterized routine manufacturing process, weight-based dosing, a fully human CAR construct, and a 4-1BB co-stimulatory domain to optimize the benefit-risk profile.
• Management identifies a market transition where the rheumatology community is moving from viewing CAR-T as novel to accepting it as a viable treatment class for meaningful autoimmune diseases.
• Commercialization strategy focuses on three distinct patient cohorts (Adult Dermatomyositis, Juvenile Myositis, and Systemic Sclerosis) with strategic site selection based on patient mobility and commutable radius.

Risks and Challenges:

• Recent adverse safety events in the broader cell therapy sector caused a temporary slowdown in pivotal study enrollment, though management reports this has been mitigated through proactive communication with investigators.
• Regulatory scrutiny remains high regarding the definition of clinical responses and the necessity of pre-conditioning; the company is gathering substantive data to determine a go-forward direction for PC-free regimens.
• The need to balance rapid adoption for outpatient dosing with safety protocols to avoid detractors from the emerging safety data.

Management Commentary and Tone:

• Executive tone is highly confident, citing that the safety and efficacy vision defined 4-5 years ago has been validated by the recent ACR conference data.
• Management emphasizes the "deepening" of responses over time, noting that patients off immunomodulators continue to improve up to the one-year mark.
• The CMO highlighted the company's agile response to market concerns, having proactively educated investigators on the specific safety profile of Rezacel to resume enrollment momentum.
• The CCO expressed excitement regarding the commercial value of the juvenile population, particularly the long-term payer value proposition for treating children.

Analyst Questions and Answers:

• Enrollment & Guidance: Analyst asked about enrollment; CFO confirmed significant uptick in screening after addressing investigator concerns, enabling the acceleration of the BLA timeline to Q1 2028.
• Pivotal Design: Analyst queried the connection between Phase 1/2 and registrational design; Management confirmed the studies are similar in design, dose, and patient criteria, increasing confidence in translatability.
• Safety Profile: Analyst asked about differentiation from competitors; Management reiterated that 94% of patients experienced no CRS or Grade 1 CRS, and 96% experienced no ICANS, with zero cases of IECHS observed.
• Outpatient Dosing: Analyst inquired about the feasibility of outpatient dosing; Management confirmed high success in trials due to the low toxicity profile, projecting rapid adoption in outpatient clinics.
• Manufacturing: Analyst asked about manufacturing success rates; Management noted superior success rates compared to oncology due to healthy donor T-cell viability.
• PC-Free Regimen: Analyst asked for an update on pre-conditioning free plans; Management stated they are waiting for substantive data from Lupus, Pemphigus, and Myasthenia Gravis before making a strategic decision in H1 2026.

Other Key Points:

• The company is leveraging the potential inclusion of Juvenile Myositis in the BLA to potentially secure a Priority Review Voucher, a strategic financial asset.
• Recent FDA interaction confirmed plans to submit Phase 1/2 data for durability in the BLA package, potentially utilizing 2-3 years of follow-up data.
• The SSc program targets the most severe subset of autoimmune rheumatic disease (ILD), where standard of care is limited to stabilizing function, highlighting Rezacel's potential to improve FVC.
• The company is actively engaging with payers and insurers, who are showing increased interest in the durability and potential one-time cure aspects of the therapy.