Guggenheim 3rd Annual Healthcare Innovation Conference - ADAGENE INC

Explicit Guidance:

• Clinical Data Timing: Expect first clinical update from the Phase 2 Project Optimus trial (late-line MSS-CRC) in the first half of 2027; Phase 2 data from the Investigator Sponsored Trial (IST) in the neoadjuvant colorectal setting in 2027.
• Cash Runway: Extended cash runway through the second half of 2028, following a $70 million raise earlier in the year.
• Regulatory Milestones: Expect FDA discussions regarding Phase 3 design for late-line MSS-CRC in the first half of 2027, with potential Phase 3 initiation planned for the later half of 2027.
• Global Expansion: Plan to enroll patients for asset ADG138 (double-mask T-cell engager) in China first, with potential global scope expansion to follow; potential for early clinical data in 2027.

Business-Segment Outlook:

• Lead Asset (ADG126/Muza):
  • Late-line MSS-CRC (without liver mets): Anticipating Phase 3 randomized trial design with Overall Survival (OS) as primary endpoint. Potential co-primary endpoint of Objective Response Rate (ORR) for accelerated approval, subject to FDA discussion.
  • Control Arm Flexibility: Control arm to be determined based on line of therapy (e.g., Lonsdorf-Bev for pure 3rd-line; FOLFIRI/Regorafenib for 4th-line+; or physician choice for mixed populations).
  • Label Strategy: Seeking a label restricted to patients without liver metastases, aiming to be a first-in-class indication in colorectal cancer.
• Collaboration (Insight Biotechnology):
  • Combo: Investigating ADG126 + PD-1/TGF-beta bispecific. Aims to improve response rates in patients with and without liver metastases (current Insight data shows 23% and 12% ORR respectively).
  • Timeline: Insight controls trial timelines and data readouts; enrollment recently started.
• Neoadjuvant Colorectal (IST):
  • Strategy: Testing high-dose loading schedule (20 mg/kg followed by 10 mg/kg Q3W) to induce deep responses and potential event-free survival (EFS) benefit in a chemo-free regimen setting.
  • Potential Path: Initiation of a formal Phase 2 study possible in 2027 or post-IST data readout if results are supportive.
• Hepatocellular Carcinoma (HCC):
  • Indication: First-line HCC in combination with Atezolizumab/Bevacizumab.
  • Target Benchmark: Aiming for >40% ORR and doubled PFS compared to standard of care (AtezoBev) to justify advancement into larger studies.

Market and Competitive Outlook:

• Competitive Landscape: Positioning ADG126 as differentiated against first-generation CTLA-4 inhibitors (e.g., Ipilimumab, Tremelimumab) via 10x higher ADCC and best-in-class masking efficiency, allowing high dosing (up to 20 mg/kg) with <10% discontinuation due to adverse events.
• Therapeutic Window: Anticipated expansion of the therapeutic index for CTLA-4 inhibition via protease-sensitive masking requiring high target (CTLA-4) expression and high protease concentration in the tumor microenvironment.
• Unmet Need: Addressing the lack of FDA-approved neoadjuvant therapies for colorectal cancer; targeting durable responses and OS "tail" effects in late-line settings where standard care remains poor.
• Platform Validation: Expansion of the SafeBody platform to T-cell engagers via collaboration with Third Arc Bio; potential for further licensing or partnership activities.

Macro / Industry Outlook:

• Regulatory Pathway: Confidence in FDA alignment for patient sub-segmentation (no liver mets) based on prior end-of-Phase 1 interactions and precedents (e.g., Agenis's Batman trial).
• Pricing/Dosing Strategy: Utilizing non-standard, high-dose schedules (up to 20 mg/kg) compared to standard CTLA-4 dosing (1–3 mg/kg) to maximize efficacy while managing safety.
• Geographic Strategy: Phased global development with China serving as the initial launch market for the CD3/ER2 T-cell engager (ADG138).

Strategic Initiatives:

• Partnering & BD: Continued active business development for the SafeBody platform; existing expansion of collaboration with Sanofi (equity holder) and Third Arc Bio (T-cell engager focus); no specific timing for new deals but intent to remain active.
• Asset Pipeline Advancement:
  • Advancement of ADG138 (double-mask T-cell engager targeting CD3/ER2) from clearance to clinical enrollment in China.
  • Potential Phase 3 initiation for ADG126 in late-line MSS-CRC by H2 2027.
  • Transition from IST data to potential Phase 2 design in neoadjuvant colorectal cancer in 2027.

Risks and Headwinds to Outlook:

• Regulatory Uncertainty: FDA approval for ORR as a co-primary endpoint for accelerated approval is described as an "upside scenario" and requires confirmation. Control arm composition remains "to be determined" post-interaction.
• Clinical Dependency: Future pathway for neoadjuvant CRC and Phase 3 initiation in late-line CRC is contingent on the quality and maturity of Phase 2 data expected in H1 2027.
• Timeline Sensitivity: Data readouts for the Insight collaboration and ADG138 are dependent on sponsor (Insight) timelines and enrollment rates in China.
• Safety Profile: While current data shows low discontinuation rates, the unmasked nature of other CTLA-4s limits therapeutic index; efficacy must be proven in neoadjuvant settings to justify chemo-free approaches.

Management Tone on the Future:

• Confidence: High confidence in the differentiated mechanism (10x ADCC, high masking efficiency) and safety profile at high doses.
• Optimism: Expressed strong excitement regarding the Insight collaboration and the potential to improve outcomes in the neoadjuvant and HCC settings.
• Strategic Clarity: Clear, defined timelines for catalysts (H1/H2 2027) and a structured approach to regulatory discussions (FDA meetings planned post-Phase 2 readout).

Miscellaneous:

• Dosing Differentiation: Highlighting the contrast between ADG126's high-dose capability (10–20 mg/kg) versus traditional CTLA-4 agents (1–3 mg/kg).
• Data Precedents: Citing Agenis's (Botulinum/Barcinumab) BATTLE trial and BMS's NIVO-EP data as precedents supporting the neoadjuvant and late-line value propositions.
• Financial Context: $70 million capital raise previously secured to fund ongoing trials and collaboration expansion.