Targeting CD122 has strong biologic rationale

Why target CD122?

• Targeting only the IL-15 cytokine addresses inflammation, but may allow pathogenic cell survival through alternative escape mechanisms
• CD122 is the shared receptor subunit through which both IL-15 and IL-2 signal
• IL-15 and IL-2 are central cytokines in pathogenic inflammation across broad inflammatory diseases
• Overactive signaling drives proliferation and survival of cytotoxic CD8+ and CD4+ T cell subsets and NK cells
• Inflammatory Th1 and Th2 cytokine secretion during T cell activation

ANB033 blocks CD122 to inhibit pathogenic immune cells

CD122 is the beta subunit (IL-2Rβ) of the receptor for IL-15 and IL-2

• Expressed on subsets of CD8+ and CD4+ T cells and NK cells

CD122 antagonism reduces these immune cell subsets

• Dependent on IL-15 and/or IL-2 for maintenance, proliferation and survival

Overexpressed in select diseases, including CeD gut or EoE

• IELs, including cytotoxic CD8+ and NK cells
• EoE: ILC2s

ANB033 demonstrated favorable safety, tolerability and PK profile in Phase 1a

Phase 1a results to date

• Safe and well tolerated
• No unexpected findings
• PK and PD support SC dosing

Favorable safety and tolerability

• No safety concerns at any dose
• No SAEs, severe AEs, or discontinuations
• Any adverse events mild or moderate
• No unexpected lab abnormalities
• No signs of viral infections
• No clinical pharmacology findings of concern

Rapid and sustained PK profile

• Favorable 2 to 3-week half-life with IV and SQ dosing
• Full receptor occupancy (RO) within hours and maintained for >30 days
• Dose response observed
• Modeled to achieve >IC90 on CD8+ T cells subsets in GI tissue
• Overall, no impact on peripheral total Treg counts

ANB033 significantly reduces CeD relevant CD8+ T cells and NK cells after single dose
Effect of ANB033 is limited to CD122 expressing cells