Forte Biosciences (FBRX) Study Update summary

Study background and mechanism

• FB102 is an antibody targeting CD122, a subunit of the IL-2 and IL-15 receptor, aiming to inhibit proliferation and activation of autoreactive NK and T cells implicated in celiac disease and other autoimmune conditions.

• The mechanism selectively blocks IL-2 and IL-15 signaling in pathogenic cells while sparing regulatory T cells, preserving immune regulation.

• IL-2 and IL-15 are genetically and mechanistically linked to celiac disease pathogenesis, driving T cell-mediated intestinal damage.

• FB102 blocks both IL-2 and IL-15, potentially offering advantages over single-target drugs in development for celiac disease.

• Celiac disease affects approximately 2.5 million people, with significant unmet need due to lack of effective treatments beyond gluten avoidance.

Study design and execution

• The phase 1B trial enrolled 32 subjects at nine sites in Australia and New Zealand, randomized 3:1 to FB102 (24) or placebo (8), with a 16-day gluten challenge and four doses of FB102 at 10 mg/kg.

• Subjects received three weekly doses of FB102 or placebo, followed by a gluten challenge and a fourth dose.

• Endoscopy biopsies were performed at baseline and after the gluten challenge to assess gut morphology and inflammation.

• Baseline demographics and histological parameters were well balanced between treatment arms, with mean age ~40 years.

• No dropouts occurred; treatment emergent adverse events were primarily mild, with no grade 3 or higher serious adverse events in the FB102 arm.

Efficacy and safety results

• FB102 showed statistically significant benefit on the composite histological VCIEL endpoint versus placebo (p=0.0099).

• Mean IEL density decreased by 1.5 in FB102 group versus an increase of 13.3 in placebo (p=0.0035).

• Mean change in villus height:crypt depth ratio from baseline was -0.046 for FB102 vs. -0.173 for placebo, a 73% improvement.

• FB102 reduced gluten challenge-induced GI symptoms by 42% compared to placebo (4.0 vs. 6.9 events per subject).

• Safety profile was favorable, with most adverse events mild or moderate and similar rates between groups; only one severe event occurred, in the placebo group.