Adial Pharmaceuticals (ADIL) investor relations material

Lead program and rationale

• AT177 is a fully synthetic, patented oral AhR agonist prodrug designed for colon-targeted delivery and minimal systemic exposure in ulcerative colitis (UC).

• AT177 converts to indirubin, the most potent AhR agonist in indigo naturalis; the design aims to reproduce its clinical benefit with controlled, colon-focused delivery.

• Indigo naturalis studies support AhR as a UC target; an open-label maintenance study reported 73% clinical remission at 1 year, while the botanical extract is uncontrolled and not FDA-approved.

Preclinical and exposure evidence

• In a DSS mouse colitis model, AT177 performed comparably to indirubin and produced ~8x more colon AhR signaling.

• In a TNBS colitis model, oral AT177 reduced disease activity; histology showed preserved crypt architecture, restored epithelial integrity and reduced inflammatory infiltrate.

• Mini-pig data showed indirubin levels above the AhR EC50 throughout the colon; colon levels were up to 1,000x plasma levels, with lower plasma Cmax than cited tapinarof and obefazimod data in cross-study comparisons.

• CMC readiness includes a scalable synthetic process, colon-targeted formulation, 18+ month room-temperature drug-substance stability, completed kilogram-scale feasibility batches and initiated US-based GMP manufacturing.

Clinical path and financing

• Phase 1 initiation is planned for 1H 2027, with single- and multiple-ascending-dose studies followed by a Phase 1b UC proof-of-concept study.

• The financing plan includes $32M and an additional milestone tranche of up to $32M, intended to fund IND-enabling work and advance toward clinical proof-of-concept in UC.

• Timelines are estimates and depend on study results, FDA acceptance of the IND, manufacturing and funding; the milestone tranche is at the investor’s option.