GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - ADICET BIO INC

Financial Performance:

• No specific revenue, earnings, or cash flow metrics were disclosed as the company remains in clinical development with no commercial products on the market.
• Manufacturing costs are estimated to be well below 20% of autologous CAR-T therapies, approaching the cost profile of monoclonal antibodies due to off-the-shelf allogeneic production.
• Current capital allocation is focused on clinical trial execution (LN, SLE, Systemic Sclerosis, Prostate Cancer) rather than revenue generation.

Guidance and Future Outlook:

• Management expects to provide an update on the in vivo CAR-T pipeline in the "very near future," with IND-enabling studies ongoing but not yet filed.
• Systemic Sclerosis (SSc) data update, including 10 patients with at least 12 months of follow-up, is targeted for the second quarter of next year.
• Prostate cancer program (ADI-212) is scheduled to begin patient dosing in Q1 of the upcoming year, with data expected within the next 12 months.
• A comprehensive data readout for the pivotal lupus nephritis (LN) study, covering all 22 patients at the 12-month mark, is anticipated in Q1 of next year.

Business Segments and Product Lines:

• ProloCel (Allogeneic Gamma-Delta-1 T cells): The core asset showing immunosuppressant-free remission in Lupus Nephritis (LN) and Systemic Lupus Erythematosus (SLE). Current data shows 50% complete renal response (CRR) in LN and 54% DORIS remission in the entire lupus population, sustained for up to 21 months.
• In Vivo CAR-T Pipeline: A differentiated platform utilizing "bolt-on" technologies to enhance potency and selectivity, expected to be updated imminently.
• ADI-212 (Prostate Cancer): An allogeneic gamma-delta-1 T cell targeting PSMA, engineered with membrane-bound IL-12 (to modify tumor microenvironment) and MET-12 knockout (to enhance serial killing).
• Other Programs: Ongoing study in Systemic Sclerosis (SSc) and Rheumatoid Arthritis (RA) to evaluate lymphodepletion requirements.

Market and Competitive Landscape:

• Target Population: Estimated addressable market of ~35,000 patients in the US for LN and ~35,000 for non-renal SLE (total ~70,000 severe cases), exceeding the population for some existing NHL cell therapies.
• Competitive Advantage: Unlike alpha-beta T-cells (which are autologous and toxic) or B-cell specific therapies (which require chronic dosing and do not achieve remission), ProloCel offers off-the-shelf availability, superior safety (low CRS/ICANS), and the potential for a single-dose, immunosuppressant-free cure.
• Market Sentiment: Management notes the market has recently punished oncology cell therapy stocks but believes gamma-delta-1 T cells offer uncorrelated value in the autoimmune space due to distinct mechanisms of action (immune reset) compared to alpha-beta T cells or mRNA approaches.

Risks and Challenges:

• Pivotal Study Design: Finalizing the number of patients and endpoints with the FDA, particularly regarding the inclusion of non-renal SLE in the pivotal LN study.
• Manufacturing Scalability: While costs are lower, ensuring consistent quality and supply for an off-the-shelf allogeneic product remains a critical operational hurdle.
• Lymphodepletion Dependency: Preclinical and field data suggest CyFlu (cyclophosphamide/fludarabine) may be necessary for efficacy, though a small RA study is underway to confirm; this adds procedural complexity compared to lymphodepletion-free attempts by competitors.
• Regulatory Uncertainty: No current FDA-approved therapy offers immunosuppressant-free remission, making the "bar for success" for the pivotal study subjective and difficult to benchmark.

Management Commentary and Tone:

• Tone: Highly confident and data-driven, emphasizing the uniqueness of the gamma-delta-1 mechanism and the quality of the clinical data (immune reset, durable remission).
• Strategic Focus: Management has deliberately paused patient enrollment (stopping at 22 patients) to avoid redundancy before the pivotal study, stating 22 patients is a robust dataset comparable to major players like Novartis and BMS prior to their pivotal trials.
• Differentiation: Strong emphasis on the safety profile and off-the-shelf nature of the therapy as key differentiators from autologous alpha-beta CAR-Ts and chronic B-cell therapies.

Analyst Questions and Answers:

• Data Context: Confirmed the 12-month data covers 13 of the 22 enrolled patients (LN/SLE), with the remaining patients expected to reach 12-month follow-up by year-end; 100% of patients (except one with minor proteinuria increase) remain immunosuppressant-free.
• Durability: Evidence of "immune reset" observed via CD19 depletion and the generation of new naive B-cell clones; no loss of efficacy anticipated as patient numbers grow, as the cohort size is sufficient for the pivotal study.
• FDA Interaction: Initial meeting confirmed 12-month CRR as the primary endpoint for LN; a second meeting this quarter aims to align on including SLE in the same pivotal trial.
• Safety: FDA generally requires ~100 patient exposures for this modality; the company currently has ~45 exposures and anticipates meeting this threshold easily in the pivotal study (likely 50+ patients).
• Commercialization: Manufacturing is done via single-donor runs producing multiple doses, significantly reducing cost and complexity compared to patient-specific autologous manufacturing.

Other Key Points:

• Mechanism of Action: Gamma-delta-1 T cells homing to tissues (rather than blood) makes them ideal for autoimmune diseases and solid tumors where tissue antigen presentation occurs.
• Safety Profile: Significantly lower incidence of Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) compared to alpha-beta CAR-Ts.
• Fertility: Data indicates no fertility concerns with the current low-dose CyFlu lymphodepletion regimen, with disease-free pregnancies observed.
• Pipeline Expansion: The in vivo CAR-T program utilizes specific targets and SCFEs (scaffold-cell fusion elements) to achieve potent, low-dose T-cell engagement, distinct from current bispecific or lentiviral approaches.