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Prana reports prolonged Type 2 biomarker suppression with IL-4Rα/TSLP bispecific

Prana reports prolonged Type 2 biomarker suppression with IL-4Rα/TSLP bispecific

Phase I data from a placebo-controlled study in healthy adults suggest that PRA-216, a bispecific antibody that simultaneously blocks IL-4Rα and TSLP, can suppress multiple Type 2 inflammatory biomarkers for at least 12 weeks from a single subcutaneous dose — a pharmacodynamic profile that, if replicated in patients, would place it above the dosing frequency of most approved biologics in asthma, chronic obstructive pulmonary disease (COPD), and atopic dermatitis.

San Diego-based Prana Therapies presented the results at the European Respiratory Society (ERS) International Congress 2026 in Barcelona. The Phase I/II trial enrolled 57 healthy adults across seven single- and multiple-ascending-dose (SAD and MAD) cohorts. In the 600 mg MAD cohort — dosed every two weeks for three doses — PRA-216 produced 100% inhibition of pSTAT6, 100% reduction in blood eosinophils, 50% reduction in serum TARC, and 25% reduction in IgE, sustained for at least 12 weeks. The drug achieved 85% subcutaneous bioavailability and was well-tolerated, with no serious adverse events, no Grade ≥3 treatment-emergent adverse events, no injection site reactions, and no reports of conjunctivitis.

PRA-216 targets both IL-4Rα, blocking the shared receptor subunit for IL-4 and IL-13 signaling, and TSLP, an upstream epithelial cytokine that initiates Type 2 inflammatory cascades. Combining these two mechanisms in a single molecule distinguishes it from the two most commercially relevant comparators: Sanofi/Regeneron's Dupixent (dupilumab), which targets IL-4Rα alone, and AstraZeneca's Tezspire (tezepelumab), which targets TSLP alone. No approved biologic currently blocks both nodes simultaneously.

Dupilumab requires every-two-week or every-four-week injections across its approved indications; tezepelumab is dosed monthly. GSK's Exdensur (depemokimab), an anti-IL-5 antibody approved in December 2025 for severe eosinophilic asthma, set a new convenience benchmark at twice-yearly dosing, but is restricted to a single indication and a single pathway. Prana's Phase I data support a potential every-12-week interval for PRA-216 across three indications simultaneously — a combination that no approved agent currently offers.

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These are pharmacodynamic data from healthy volunteers, not efficacy data from patients. The biomarker readouts are consistent with dual pathway inhibition, but whether they translate into clinical benefit in asthma, COPD, or atopic dermatitis remains to be established in Phase II. Prana has initiated three Phase II trials; the COPD study is listed as not yet recruiting at time of writing. Patient data from all three programs are expected in 2027.

The results also serve as clinical validation of Prana's INSPIRE platform, which the company describes as a fully IgG-based multispecific antibody architecture designed to address half-life, manufacturability, and subcutaneous delivery limitations that have historically constrained multispecific formats. PRA-216 is the platform's lead program; Prana said it is advancing additional bispecific and trispecific candidates from the same technology.


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