Dual IL-4Rα/IL-31 Blockade Advances Into Patient Trials

Bambusa Therapeutics, a clinical-stage biotechnology company developing next-generation bispecific antibodies for immunology and inflammation, recently announced 2 key milestones for its lead program, BBT001. The company presented first-in-human data from its ongoing phase I trial at the 2025 European Academy of Dermatology and Venereology (EADV) congress and subsequently initiated dosing in patients with moderate to severe atopic dermatitis (AD).¹

Phase I Healthy Volunteer Data

The single-ascending-dose (SAD) portion of the phase I study evaluated BBT001 in healthy adult volunteers. Reported findings included:

• Safety and tolerability: BBT001 demonstrated a favorable safety profile across all tested dose levels, with no dose-limiting adverse events.
• Pharmacokinetics: The antibody showed an extended half-life of approximately 33 days, suggesting the potential for infrequent dosing regimens.
• Target engagement: Rapid and sustained IL-4Rα binding with downstream pSTAT6 inhibition was observed through at least 8 weeks post-dose.
• Biomarker response: Dose-dependent, rapid, and sustained reductions in thymus and activation-regulated chemokine (TARC/CCL17) levels were noted, maintained beyond week 8.

The degree of TARC reduction in healthy volunteers was described as “unprecedented” relative to baseline levels, raising the possibility of synergistic activity from dual blockade of IL-4Rα and IL-31. TARC is recognized as a pharmacodynamic biomarker correlating with disease activity and treatment response in AD.

Transition to Patient Dosing

Following the healthy volunteer study, Bambusa Therapeutics has initiated dosing in adults with moderate to severe AD within the same trial. This marks the company’s first patient enrollment only 16 months after its inception. The trial, designated BBT001-001, is a randomized, placebo-controlled study evaluating single and multiple ascending doses in both healthy subjects and patients. Study endpoints include safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and preliminary clinical activity. Additional clinical data are anticipated in 2026.

Mechanism of Action and Potential Clinical Implications

BBT001 is a first-in-class, half-life-extended bispecific antibody that simultaneously targets IL-4Rα and IL-31 signaling pathways. IL-4Rα blockade underlies the mechanism of established therapies such as dupilumab, addressing type 2 inflammation through inhibition of IL-4 and IL-13 signaling. IL-31, on the other hand, plays a critical role in pruritus and cutaneous neuroimmune interactions. By combining inhibition of both IL-4Rα and IL-31, BBT001 may theoretically provide broader disease control, with the potential for faster onset of action and greater relief of itch symptoms compared with current monotherapies.²

The observed extended half-life further supports less frequent dosing schedules, which may improve patient adherence and treatment convenience if efficacy and safety are confirmed in later-stage trials.

Next Steps in Clinical Development

While the phase I results in healthy volunteers are encouraging, the relevance to clinical outcomes in atopic dermatitis remains to be established. Key questions for clinicians include:

• Will dual blockade translate into superior improvements in EASI, IGA, and pruritus scores compared with existing biologics?
• How will safety and immunogenicity compare with established IL-4Rα inhibitors?
• Could extended dosing intervals provide meaningful quality-of-life advantages for patients?

The ongoing BBT001-001 trial will be critical in addressing these questions and establishing proof-of-concept efficacy in patients with moderate to severe AD.

Broader Pipeline

Beyond BBT001, Bambusa Therapeutics is advancing additional bispecific antibody programs, including:

• BBT002: targets IL-4Rα and IL-5, in Phase I development for asthma, COPD, and chronic rhinosinusitis with nasal polyps.
• BBT003/BBT004: preclinical candidates in gastroenterology and rheumatology indications.

Conclusion

Early phase I data suggest that BBT001 is well tolerated, exhibits extended pharmacokinetics, and achieves deep reductions in a validated biomarker of type 2 inflammation. The initiation of patient dosing represents an important milestone, but definitive conclusions regarding clinical benefit in AD await results from ongoing and future studies. For clinicians, BBT001 represents a novel approach to targeting both inflammatory and pruritic pathways, with the potential to broaden the therapeutic landscape if forthcoming data confirm clinical efficacy and safety.

References

1. Bambusa Therapeutics announces highly positive healthy volunteer results and first atopic dermatitis patient dosed in phase I trial of BBT001. News release. Bambusa Therapeutics. Published September 25, 2025. Accessed September 26, 2025. https://www.prnewswire.com/news-releases/bambusa-therapeutics-announces-highly-positive-healthy-volunteer-results-and-first-atopic-dermatitis-patient-dosed-in-phase-i-trial-of-bbt001-302567230.html
2. Bambusa Therapeutics announces first subject dosed in phase 1 clinical Trial of BBT001, a novel multi-targeting, half-life extended bispecific antibody for the treatment of atopic dermatitis and other inflammatory skin diseases. News release. Bambusa Therapeutics. Published February 28, 2025. Accessed September 26, 2025. https://www.prnewswire.com/news-releases/bambusa-therapeutics-announces-first-subject-dosed-in-phase-1-clinical-trial-of-bbt001-a-novel-multi-targeting-half-life-extended-bispecific-antibody-for-the-treatment-of-atopic-dermatitis-and-other-inflammatory-skin-diseases-302388661.html