Cabaletta Bio, Inc. (CABA)·Q3 2024 Earnings Summary

Executive Summary

• Q3 2024 advanced CABA-201 across autoimmune indications with 16 patients enrolled, 10 dosed, and 40 U.S. clinical sites actively recruiting; cash and investments were $183.0M with runway into H1 2026 .
• Clinical signals were encouraging: consistent, complete B‑cell depletion by day ~22, emerging drug‑free responses in non‑renal SLE, myositis and initial SSc; safety largely favorable with low‑grade CRS in 3/8 evaluable patients and one previously reported Grade 4 ICANS outlier linked to suspected occult infection and protocol now recommends delaying infusion ≥2 weeks post-fever and seizure prophylaxis .
• Management expects to meet FDA in 2025 to discuss registrational designs and began European expansion with EMA CTA for RESET‑SLE; manufacturing scale-up continued (Lonza, Cellares) to support late-stage and commercial readiness .
• Wall Street consensus (S&P Global) for EPS and revenue was unavailable due to request limits, so we cannot assess beat/miss this quarter; CABA remains pre-revenue, with increasing R&D to drive clinical execution [GetEstimates error].

What Went Well and What Went Wrong

What Went Well

• CABA-201 showed consistent PK/PD with peak CAR T expansion day 8–15 and complete B-cell depletion by ~day 22; early naïve B‑cell repopulation at ~8 weeks in first evaluable patients supports an “immune reset” mechanism .
• Clinical responses off immunosuppressants: all three non‑renal SLE patients had no clinical symptoms on SLEDAI‑2K at latest follow‑up; one LN patient improved SLEDAI from 22→8 with >90% proteinuria reduction; first adult DM patient improved CDASI‑A (25→9) and muscle strength by day 29; first IMNM patient continued response at 6 months; first SSc patient showed early skin score improvement .
• Operational traction: 16 patients enrolled, 10 dosed across RESET; 40 U.S. sites; EMA CTA authorized for RESET‑SLE; runway into H1’26; plan to meet FDA in 2025 on registrational pathways .

What Went Wrong

• One LN patient (outlier) experienced Grade 4 ICANS and late cytopenias; analyses suggested abnormal pro‑inflammatory cytokines and possible occult infection; protocol amended to delay infusion ≥2 weeks post-fever and add seizure prophylaxis recommendations .
• R&D and G&A escalated YoY/QoQ reflecting clinical scale-up and manufacturing readiness, expanding operating losses as expected for clinical-stage programs (R&D Q3: $26.3M vs $13.8M YoY; Net loss Q3: $(30.6)M vs $(16.4)M YoY) .
• S&P Global estimate data was not retrievable due to API limit; cannot benchmark EPS vs consensus this quarter [GetEstimates error].

Financial Results

Notes:

• Pre-revenue clinical-stage company; margin metrics not applicable.
• Cash runway into H1 2026 reiterated .

KPIs and operational progress

Guidance Changes

No revenue, margin, OpEx or tax rate forward guidance was provided (typical for clinical-stage biotech). Citations as noted above.

Earnings Call Themes & Trends

Management Commentary

• “Focused clinical execution has resulted in 40 U.S. clinical sites actively recruiting… we are encouraged by the accelerating pace of enrollment and, data permitting, anticipate meeting with the FDA next year regarding registrational program designs for CABA‑201.” — CEO Steven Nichtberger .
• “The clinical data… support the potential of the current dose of CABA‑201 to provide immunosuppressant‑free, compelling clinical responses… [LN] data suggested an occult infection… subjects with fever prior to infusion will wait a minimum of two weeks before CABA‑201.” — CMO David Chang .
• “CABA‑201 provided consistent and complete B cell depletion… naïve B‑cell repopulation as early as eight weeks… supporting immune system reset.” — CMO David Chang .
• “Our efficient clinical trial design… and anticipated expansion into Europe in 2025 provide a differentiated opportunity to accelerate development of CABA‑201.” — CMO David Chang .

Q&A Highlights

• Analysts probed residual SLEDAI lab activity; management emphasized clinical resolution and noted dsDNA persistence can occur without clinical disease, consistent with partner academic data; proteinuria in Class V LN often slow to normalize .
• LN outlier safety: secondary cytokine peak distinct from initial CAR T expansion; evidence pointed to infectious response; protocol changes included ≥2‑week delay post-fever and recommended seizure prophylaxis (e.g., Keppra) .
• Enrollment/registrational path: discussions with FDA as early as 2025; may extend existing trials rather than start de novo Phase 3; durability expectations of ≥12–18 months drug‑free remission resonated with physicians .
• No‑preconditioning strategy: PV sub‑study to assess feasibility and durability before broad expansion; launch strategy likely to retain LD regimen initially given proven durability, with parallel development of LD‑free arms .
• Biopsies and translational endpoints: kidney biopsies permitted; longitudinal B‑cell receptor sequencing prioritized to confirm durable immune reset .

Estimates Context

• S&P Global consensus estimates for EPS and revenue were unavailable due to exceeded request limits, preventing a formal beat/miss assessment for Q3 2024. Values would normally be retrieved from S&P Global; in this instance the data was not accessible [GetEstimates error].
• Company remains pre‑revenue; EPS tracked at $(0.62) vs $(0.56) in Q2 and $(0.51) in Q1 as clinical investments scaled .

Key Takeaways for Investors

• Clinical momentum and breadth: consistent PK/PD, complete B‑cell depletion, and emerging drug‑free efficacy across SLE, myositis, and SSc underpin a differentiated autoimmune CAR‑T profile; reset biology supported by early naïve B‑cell repopulation .
• Safety management refined: protocol updates (delay post‑fever, seizure prophylaxis) address the LN outlier; overall safety picture shows mostly low/no CRS and no new ICANS events since August report .
• Regulatory trajectory: EMA CTA authorization in Europe and planned FDA registrational discussions in 2025 indicate rising confidence in path to pivotal programs; watch for cohort completions and durability readouts .
• Manufacturing scalability: Lonza tech transfer, expanded Cellares automation, and extended WuXi dedicated suite position CABA‑201 for late‑stage and commercial readiness, including potential apheresis‑free workflows .
• Cash runway adequate into H1’26; expect continued operating loss as R&D scales; dilution risk manageable but present given clinical ambitions .
• Near-term trading catalysts: incremental RESET data readouts, FDA/EMA interactions, site activation pace, and PV sub‑study LD‑free results; durability signals (≥12–18 months drug‑free) will be critical for valuation re‑rating .
• Medium-term thesis: if drug‑free remission and safety hold across multiple autoimmune cohorts, CABA‑201 could redefine treatment in high‑need indications; execution on registrational strategy and manufacturing scale will be the key enablers .

References:

• Q3 2024 8‑K press release and selected financials .
• Q3 2024 10‑Q (financial statements, MD&A, liquidity) .
• Q2 2024 8‑K press release (prior quarter trend) .
• Q1 2024 8‑K press release (prior quarter trend) .
• Press releases: ACR presentation details (Sept 25) ; ACR data update (Nov 18) .
• Investor call transcript (Nov 18) –.