Celldex Therapeutics (CLDX) investor relations material

Study background and rationale

• Phase II study evaluated barzolvolimab in prurigo nodularis (PN), a chronic, itch-driven skin disease with significant comorbidities and unmet need.

• Prior phase I-B study with IV barzolvolimab showed promising results in PN, prompting further investigation.

• Mast cell depletion was hypothesized to provide clinical relief due to their role in chronic itch and increased presence in PN lesions.

Study design and patient population

• Randomized, double-blind, placebo-controlled Phase 2 trial in adults with moderate-to-severe PN across six countries and 48 sites, enrolling 140 patients.

• Patients received placebo or barzolvolimab (150 mg or 300 mg subQ every four weeks after a 450 mg loading dose) for 24 weeks, followed by 16 weeks of observation.

• Participants had ≥20 PN nodules, WI-NRS ≥7, and IGA-CNPG-S ≥3 at baseline; mean age was 57–60 years with disease duration of 6–8 years.

• Study included an open-label extension for patients with persistent symptoms post-treatment.

Efficacy results

• Study did not meet primary or secondary endpoints; no significant improvement in itch or skin lesions compared to placebo at either dose or timepoint.

• Profound systemic mast cell depletion was achieved, as shown by reduced serum tryptase, but no clinical benefit was observed.

• No differentiation from placebo in key secondary endpoints, including Investigator's Global Assessment and combined itch/IGA response.

• Discrepancy noted between positive phase I-B (IV) and negative phase II (subQ) results; possible impact of administration route.

• Data suggest mast cells may not be the key pathogenic driver in PN.