Forte Biosciences (FBRX) Study Update summary

Study background, rationale, and mechanism

• FB102 is an anti-CD122 antibody targeting IL-2 and IL-15 pathways, blocking signaling to inhibit autoreactive T and NK cell activation in celiac disease and other autoimmune conditions.

• The mechanism aims to suppress pathogenic immune responses while sparing regulatory T cells, potentially reducing autoimmune activity without compromising immune regulation.

• Celiac disease lacks approved therapies, with a significant unmet need for patients unresponsive to a gluten-free diet.

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

• FB102's dual blockade may offer advantages over single-target drugs in development for celiac disease.

Phase 1B study design and execution

• Randomized, double-blind, placebo-controlled phase 1B trial enrolled 32 subjects (24 FB102, 8 placebo) at nine sites in Australia and New Zealand.

• Subjects received four weekly doses of FB102 (10 mg/kg) or placebo, followed by a 16-day gluten challenge with escalating gluten doses.

• Baseline demographics were balanced, with mean age ~40 years and similar villus height:crypt depth ratios and IEL counts.

• Endoscopy biopsies and symptom tracking were performed at baseline and after the gluten challenge.

• 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 improvement in composite histology (VCIEL) score versus placebo (p=0.0099), with a mean change from baseline of 0.079 for FB102 vs. -1.849 for placebo.

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

• Villus height:crypt depth ratio improved by 73% for FB102 compared to placebo.

• FB102 provided a 42% reduction in gluten-induced symptoms, including nausea, diarrhea, vomiting, abdominal pain, and bloating (4.0 vs. 6.9 events per subject).

• Safety profile was favorable, with most adverse events mild or moderate and balanced across groups; only one severe adverse event (grade 3) occurred in the placebo group.