STIFEL 2026 HEALTHCARE CONFERENCE - AN2 THERAPEUTICS INC

Explicit Guidance:

• Financial Runway: Current cash position of $80 million is sufficient to execute current programs through 2029.
• Phase 2 Data Disclosures:
  • Polycythemia Vera (PV): Topline data anticipated mid-year to third quarter of 2027 (following initiation in Q1 of current year); interim data for first 10 sentinel patients expected Q1.
  • Mycobacterium abscessus: Topline data expected in 2027.
  • Chagas Disease: Topline Phase 2 data expected second half of 2027.
• Phase 3 Initiatives: Potential initiation of a registrational development program for PV in 2028, contingent on Phase 2 success.

Business-Segment Outlook:

• Polycythemia Vera (PV):
  • Pipeline Status: Moving into global Phase 2 trial (US, Australia, India) with sentinel dosing commencing this year.
  • Clinical Benchmark: Aiming to demonstrate hematocrit maintenance below 45% and reduction in phlebotomy frequency compared to placebo.
  • Competitive Positioning: Differentiation expected via oral administration (vs. injectables), unique mechanism of action (globin-focused vs. iron starvation/hepcidin), and red-cell specificity (no impact on platelets/WBCs).
  • Market Potential: Opportunity to partner with a single entity to advance both PV and M. abscessus indications; pricing expected to be similar to existing orphan drugs (e.g., Araccas, Ruxolitinib).
• Mycobacterium abscessus:
  • Target Population: ~15,000 patients in the US; high unmet need in treatment-refractory patients with cavitary disease.
  • Efficacy Strategy: Aiming for culture conversion and patient-reported outcomes (PROs) improvement; seeking a 4-month follow-up duration to validate curative potential.
  • Differentiation: Drug is 250x more potent against abscesses than MAC; strong preclinical data suggests activity in intracellular and extracellular settings.
• Chagas Disease:
  • Target Population: ~10 million global patients, including >300,000 in the US; potential market size of ~$30 billion if fully treated in the US (comparable to Hepatitis C).
  • Clinical Strategy: "Test and treat" implementation model; 4-month follow-up considered predictive of long-term efficacy (analogous to SVR12 in Hep C).
  • Strategic Outlook: Likely candidate for partnership/licensing with a larger biopharma company due to the need for significant diagnostic and awareness infrastructure.
• Preclinical Pipeline:
  • ENPP1: Advancing candidate for Hypophosphatasia (HPP) with focus on oral formulation; best-in-class profile selected for pediatric safety and long-term use.
  • Oncology (ENPP1): Monitoring competitor data (Riva Sciences in colorectal cancer) to time asset activation; awaiting validation of target utility in humans.
  • PI3K/PI4K: Leveraging acquired assets and Novartis/Synovative precedent to pursue "pan mutant" inhibitors targeting helicase, aiming for better progression-free survival in breast cancer patients with PI3K mutations.

Market and Competitive Outlook:

• PV Landscape: Highly active; Ruxolitinib approval and M&A activity indicate validation of the space. Management views the oral route as the primary differentiator for patients seeking non-injectable options.
• Anti-infective Landscape: M. abscessus faces significant competition in the general market but has zero FDA-approved alternatives, creating a white-space opportunity.
• Oncology Landscape: Acknowledges crowded space (Loxo, Scorpion, Relay, Novartis/Synovative acquisition) but identifies a specific white space for true pan-mutant inhibitors with high wild-type selectivity to minimize toxicity.

Macro / Industry Outlook:

• Regulatory: Management anticipates FDA acceptance of PROs and culture conversion endpoints for M. abscessus registration; expects similar pricing precedents for orphan indications (PV and abscesses).
• Diagnostic Infrastructure: HCV parallel suggests a "heavy lift" in diagnostic screening and awareness is required for Chagas market transformation, necessitating a partner with broad commercial bandwidth.

Strategic Initiatives:

• M&A / In-Licensing: No explicit M&A plans for new assets; focus remains on advancing internal preclinical pipeline (ENPP1, PI3K).
• Partnerships: Explicitly seeking a partner for the "dual market" of PV and M. abscessus; strategic interest from Merck, ISI, J&J, and GSK noted for the Chagas program.
• Asset Advancement: Accelerating HPP candidate; waiting for clinical validation of ENPP1 in oncology before committing to Phase 1.
• Capital Allocation: Maintaining capital efficiency; $80M cash runway supports three Phase 2 readouts and preclinical advancement without immediate capital raises.

Risks and Headwinds to Outlook:

• Clinical Failure: Risk that Phase 2 data for PV, M. abscessus, or Chagas may not meet efficacy or statistical thresholds required for registration.
• Target Validation: ENPP1 in oncology remains an "unvalidated human target"; success depends on confirming clinical activity observed in preclinical and early competitor data.
• Implementation Challenges: Chagas market growth is contingent on establishing routine screening (neonate/blood bank) which has not been historically adopted.
• Competitive Pressure: In oncology and PI3K, competitor moves (e.g., Novartis/Synovative) or toxicity issues with existing agents could shift the therapeutic standard.

Management Tone on the Future:

• Confidence Level: Highly optimistic and confident ("very excited," "super excited," "never been stronger").
• Strategic Shift: Management emphasizes a transition from a single-focus entity to a "robust pipeline" company with diversified indications (Hematology, Anti-infectives, Rare Disease, Oncology) providing risk mitigation.
• Growth Narrative: Describes 2027 as a "big year" with multiple inflection points (data readouts) and a "good problem" regarding multiple orphan indications for the same drug platform.
• Hedging: Explicitly notes waiting on oncology data before advancing, demonstrating a disciplined approach to capital allocation despite excitement.

Miscellaneous:

• Chemistry Platform: Highlighted the versatility of boron chemistry, evidenced by recent approvals in African sleeping sickness (Cofazibor) and potential for novel targets (CPSF3).
• Trial Design Details: PV trial includes a sentinel arm (10 patients) for safety, followed by dose-finding (250mg–750mg), randomized Part 2, and an extension Part 3 for durability.
• Patient Population: M. abscessus trial targets severely treatment-refractory patients with 3x more years of disease and multidrug resistance compared to prior MAC studies.