GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - ADAGENE INC

Financial Performance:

• Raised $70 million earlier this year, extending cash runway into the second half of 2028.
• Sanofi holds a significant equity position as the second-largest shareholder following an investment and expanded collaboration.
• No specific revenue, profit margins, or earnings figures were disclosed as the company remains in clinical development stages.

Guidance and Future Outlook:

• Project Optimus (Phase 2): Enrollment complete for late-line mCRC patients without liver metastases; primary endpoint data (response rate) expected in H1 2027 to guide potential Phase 3 initiation later in 2027.
• Neoadjuvant Setting: Investigator-Sponsored Trial (IST) in Singapore aims for data readout in 2027 using a higher dosing regimen; potential to initiate Phase 2 post-readout if data is supportive.
• ADG138: Secured Chinese FDA clearance for the double-masked T-cell engager (CD3/ER2); patient enrollment in China anticipated first, with potential global expansion and early clinical data expected in the coming year.
• Phase 3 Strategy: Plans to discuss Phase 3 designs with the FDA in H1 2027, potentially targeting Overall Survival (OS) as the primary endpoint with ORR as a co-primary for accelerated approval scenarios.

Business Segments and Product Lines:

• Lead Asset (ADG126/Musa): A masked anti-CTLA-4 antibody featuring proprietary SafeBody technology that is protease-sensitive and requires high CTLA-4 expression for activation, widening the therapeutic window.
• Clinical Data (Late-line mCRC without liver mets):
  • Safety: Discontinuation rate due to adverse events <10% (comparable to Keytruda single-agent); tolerable at doses up to 20 mg/kg.
  • Efficacy: Confirmed Response Rate (ORR) of 15–36%; Median PFS of 4–5 months; Median Overall Survival (OS) near 20 months with a survival plateau.
• Partnerships:
  • InSight: Collaboration evaluating ADG126 combined with their PD-1/TGF-beta bispecific in mCRC; enrollment active with InSight controlling timelines.
  • Sanofi: Expanded early-stage discovery and development collaboration with significant equity backing.
  • Third Arc Bio: Collaboration expanding SafeBody platform application to T-cell engagers, with a deal expansion announced in 2025.
• Other Indications:
  • Hepatocellular Carcinoma (HCC): Data presented at AACR showed ADG126 added to standard of care (atezolizumab/bevacizumab) improved response rates (50% vs 20% control) and PFS trends in a small Phase 1b2 basket study.
  • Neoadjuvant: Investigating chemo-free regimen for potential to improve Event-Free Survival (EFS) via deep responses prior to surgery.

Market and Competitive Landscape:

• Differentiation: ADG126 binds a unique epitope compared to first-gen CTLA-4 inhibitors (ipilimumab, tremelimumab), demonstrating 10x higher ADCC activity.
• Unmet Need: Significant gap exists for approved neoadjuvant therapies in colorectal cancer; current standard of care offers poor outcomes in late-line settings without liver metastases.
• Competition: Peers like Agenus (Botalumab) and BMS (Nivo-EP) are exploring similar CTLA-4/PD-1 combinations; Adagene aims to differentiate via superior safety profile allowing higher doses and improved therapeutic index.

Risks and Challenges:

• Immune-Related Toxicity: While managed, expanding the therapeutic window remains critical to avoid immune-toxicity issues that historically limited CTLA-4 agents.
• Regulatory Path: FDA alignment on restricting the label to patients without liver metastasis requires confirmation, though management cites confidence based on prior interactions and precedents (e.g., Agenus's Batman trial).
• Clinical Execution: Success depends on validating efficacy in larger Phase 2 and 3 trials; survival data in neoadjuvant settings is a key metric that requires long follow-up.
• Competitive Pressure: Rapidly evolving landscape with new mechanisms (e.g., ADCs) and existing PD-1/CTLA-4 combos may impact market access.

Management Commentary and Tone:

• Confidence: Management expressed high confidence in the differentiation of the SafeBody platform, citing best-in-class masking efficiency and strong preclinical data replication.
• Strategic Focus: Emphasis on de-risking the regulatory path through early FDA interactions (e.g., End-of-Phase 1 meetings) and leveraging partnerships (InSight, Sanofi).
• Safety Narrative: Repeated emphasis on the ability to dose at high levels (up to 20 mg/kg) without compromising safety, contrasting sharply with first-generation agents limited to low doses.

Analyst Questions and Answers:

• Q: When to trigger Phase 3? A: Early Phase 2 readout (H1 2027) is expected to be sufficient for FDA discussions to design a Phase 3 trial targeting the non-liver mets population.
• Q: Phase 3 Design? A: Likely randomized with OS as primary; control arm to be determined (likely Lonsdorf-Bev for 3rd line, or Regorafenib/Fruquintinib for later lines); potential for ORR co-primary endpoint for accelerated approval.
• Q: Labeling Strategy? A: Aiming for a unique restriction to patients without liver metastases, positioning as a first-in-class label for this specific subpopulation.
• Q: InSight Collaboration Update? A: InSight sponsors the trial; they control data and timing. Rationale: ADG126 enables safer combination with PD-1/TGF-beta by masking CTLA-4 activity until activated.
• Q: HCC Opportunity? A: Strong interest in adding ADG126 to Atezolizumab/Bevacizumab standard of care; early data suggests potential to improve upon the ~36% response rate of Nivo-EP.
• Q: Neoadjuvant Timeline? A: Data expected in 2027 from the IST; higher dosing (loading dose + maintenance) is being tested to drive deeper responses compared to competitors giving only one cycle.

Other Key Points:

• ADG126 is a "masked" antibody that requires two conditions for activation: high concentration of specific proteases and high expression of the target (CTLA-4) in the tumor microenvironment.
• The neoadjuvant strategy prioritizes a "chemo-free" regimen to avoid derailing surgery, relying on the safety profile of ADG126 to induce deep pathological responses.
• Management highlighted the ability to combine ADG126 with various modalities (PD-1, bispecifics, T-cell engagers) due to the platform's safety margin.