GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - ADICET BIO INC

Explicit Guidance:

• Data Updates: Expect a data update with 12-month follow-up for all 22 patients in the autoimmune program (Lupus Nephritis/SLE) within the next few months; full data cut expected by year-end.
• Pivotal Study Initiation: Pivotal study data release anticipated in Q1 of the following year.
• Pipeline Updates:
  • Systemic Sclerosis data update expected in Q2 of the following year, covering 10 patients with at least 12-month follow-up.
  • In vivo CAR-T pipeline update expected in the "very near future."
• Clinical Milestones: Prostate cancer program (ADI 212) dosing to commence in Q1; data generation expected over the subsequent year.
• Enrollment Strategy: Enrollment stopped immediately to transition patients directly into the pivotal study; no new patient enrollment planned prior to pivotal start.

Business-Segment Outlook:

• Autoimmune (Lupus Nephritis/SLE): Targeting immunosuppressant-free remissions with an expected Complete Renal Response (CRR) rate of at least 40% and DORIS remission rates significantly higher than current market standards (current data shows ~50–54% CRR/DORIS vs. 10–15% for current therapies).
• Market Size: Estimated addressable population of ~35,000 patients in the U.S. for Lupus Nephritis (failed 2+ prior therapies) and ~35,000 for severe non-renal SLE, totaling 70,000 potential candidates.
• Manufacturing: Off-the-shelf allogeneic model allows high-dose scalability from single manufacturing runs (14-day cycle); manufacturing costs estimated to be well below 20% of total drug cost, comparable to antibody pricing models rather than autologous cell therapy.
• Oncology (Prostate): Program ADI 212 (anti-PSMA gamma-delta-1 T cells) incorporates membrane-bound IL-12 and MET-12 knockout to enhance potency and serial killing; aims to translate promising preclinical activity into clinical results.
• Systemic Sclerosis: 10-patient cohort expected to provide 12-month durability data in Q2 next year.
• In Vivo CAR-T: Significant investment in differentiated targeting and low-dose potency; development status is pre-IND (enabling studies underway).

Market and Competitive Outlook:

• Differentiation: Gamma-delta-1 T cells positioned as superior to alpha-beta CAR-Ts regarding safety (lower CRS/ICANS) and to B-cell specific therapies regarding the ability to induce immunosuppressant-free remissions rather than chronic suppression.
• Competitive Landscape: B-cell specific agents (bispecifics/mRNA) currently viewed as requiring chronic dosing (effectively chronic immunosuppressants) with no data supporting immune reset; alpha-beta T-cell therapies face higher safety hurdles and manufacturing complexity.
• Pivotal Study Design: Single-arm study; FDA has agreed to a 12-month CRR endpoint for Lupus Nephritis; discussions ongoing to include SLE endpoints in the same study.
• Safety Bar: FDA requirement of 100 patient exposures anticipated; current database includes 45 autoimmune patients, with 100+ expected post-pivotal initiation.

Macro / Industry Outlook:

• Regulatory: Active engagement with FDA; second meeting scheduled for the current quarter to finalize SLE inclusion and endpoints in the pivotal study.
• Industry Sentiment: Acknowledges investor caution due to past oncology and autoimmune disappointments; advocates for re-evaluation of gamma-delta-1 T cells as a distinct, high-efficacy, low-toxicity modality uncorrelated with previous failures.

Strategic Initiatives:

• Pivotal Study Execution: Startup activities underway with high investigator interest (U.S., Europe, Canada) driven by safety/efficacy data; enrollment to leverage established patient pools.
• Lymphodepletion Strategy: Pursuing standard Cy-Flu (Cyclophosphamide-Fludarabine) regimen based on field data; running a small RA study to confirm necessity of Cy-Flu over Cy-only for optimal B-cell depletion in gamma-delta-1 T cells.
• Manufacturing Scale: Utilizing internal capacity plus two CDMOs; no "magic donor" reliance; consistent release criteria across multiple donors.
• Pipeline Expansion: Developing bolt-on technologies for in vivo CAR-T; advancing prostate cancer program with dual-engineering (IL-12 secretion + MET-12 knockout).

Risks and Headwinds to Outlook:

• Enrollment Timing: Pivotal study initiation and data release depend on successful FDA endpoint agreement during the upcoming quarter's meeting.
• Safety/Lymphodepletion: Potential need for lymphodepletion (Cy-Flu) could impact patient acceptance or logistical complexity, though current data suggests low-dose safety and no fertility concerns.
• Durability: While 9/10 patients remain in remission at up to 21 months, long-term durability remains to be proven as follow-up extends to 3–4 months for the next update.
• Regulatory Uncertainty: Final patient count for the pivotal study (estimated ~50 for LN, potentially higher for SLE) not yet finalized; bar for success relies on demonstrating superior efficacy to non-existent "immunosuppressant-free" comparators.
• Pipeline Progress: In vivo CAR-T remains in pre-IND phase; timeline to clinical dosing not specified.

Management Tone on the Future:

• Confidence Level: High confidence in the "immune reset" capability and durability of gamma-delta-1 T cells, citing consistent remission data.
• Hedges: Qualifies that lymphodepletion will likely be required, though fertility impact is not anticipated; notes that SLE inclusion in the pivotal study depends on FDA agreement.
• Comparison to Prior: Contrasts current trajectory with historical autologous CAR-T failures, emphasizing the "off-the-shelf" advantage and improved safety profile as a structural shift from previous cell therapy disappointments.

Miscellaneous:

• Safety Profile: Data indicates significantly lower incidence of CRS and ICANS compared to alpha-beta CAR-Ts; 21-month follow-up shows sustained remission in all but one patient (who remained immunosuppressant-free despite slight proteinuria increase).
• Investor Education: Management explicitly urges investors to differentiate gamma-delta-1 T cells from alpha-beta and NK cells, highlighting unique cytokine secretion profiles that drive efficacy without corresponding severe toxicity.