Triveni Bio has initiated dosing in its first-in-human Phase 1 clinical trial of TRIV-509, a novel antibody treatment targeting kallikreins 5 and 7 (KLK5/7) for moderate-to-severe atopic dermatitis (AD). This milestone marks the company's transition to clinical-stage development and represents the first of three clinical trials Triveni plans to begin in 2025.
The Phase 1 trial will assess the safety and tolerability of TRIV-509 in healthy volunteers before advancing to patient studies later this year. TRIV-509 is being positioned as a differentiated treatment option for AD and other barrier-related diseases through its unique mechanism of action.
"Triveni's transition into the clinic with TRIV-509 marks a significant milestone in our strategy to advance orthogonal mechanisms that deliver enhanced efficacy and convenience," stated Bhaskar Srivastava, M.D., Ph.D., Chief Medical Officer of Triveni Bio.
Novel Mechanism Targeting Skin Barrier Dysfunction
TRIV-509 represents a new therapeutic approach by targeting the kallikrein pathway, which plays a critical role in AD pathogenesis. Kallikreins 5 and 7 are epidermal serine proteases that, when pathologically overactive in AD, degrade structural proteins like desmoglein-1 (DSG1), compromising skin barrier integrity and promoting inflammation.
Unlike existing therapies that primarily target inflammatory pathways, TRIV-509 addresses three fundamental aspects of AD pathology: barrier dysfunction, inflammation, and itch. By inhibiting KLK5/7, the treatment aims to directly intervene at the level of protease-mediated skin damage.
Jennifer Dovey, Ph.D., Chief Scientific Officer of Triveni Bio, emphasized the significance of their approach: "We are pleased to share human ex vivo data which, alongside existing in vivo data, demonstrate TRIV-509's impact on key markers of barrier integrity and epidermal differentiation, further underscoring the critical role of KLK5 and KLK7 in AD pathogenesis."
Compelling Preclinical Evidence
Recent presentations at the Society for Investigative Dermatology (SID) 2025 Annual Meeting showcased TRIV-509's promising effects in AD patient explants. The data revealed several key findings:
- Significant reduction in epidermal thickness (14-28%) in patient samples
- Marked decrease (80%) in Ki-67 positive basal keratinocytes, indicating downregulation of epidermal turnover
- Reduction in parakeratosis by 31%, suggesting improved epidermal maturation
- Up to 313% increase in desmoglein-1–positive cells, indicating restoration of proper cell-cell adhesion and barrier architecture
These results align with previous in vivo models where TRIV-509 demonstrated superior efficacy compared to IL-4 receptor inhibition, which is the mechanism of action for dupilumab, a current standard of care for moderate-to-severe AD.
Expanding Pipeline with Bispecific Approach
Building on the KLK5/7 inhibition platform, Triveni is also advancing TRIV-573, a next-generation bispecific antibody that combines KLK5/7 inhibition with IL-13 blockade. This dual-targeting approach aims to simultaneously repair the skin barrier while reducing Th2-driven inflammation.
At the Protein Engineering & Cell Therapy Summit (PEGS), Triveni presented data highlighting TRIV-573's favorable characteristics, including high affinity and extended half-life. The bispecific antibody is currently in IND-enabling studies.
"We are highly encouraged by the progress of our first and potentially best-in-class pipeline and we look forward to initiating patient studies later this year," added Dr. Srivastava.
Clinical Development Strategy
Triveni Bio's clinical development plan includes three studies set to begin in 2025:
- The current Phase 1 trial in healthy volunteers to establish safety and tolerability
- Two additional patient studies in moderate-to-severe atopic dermatitis planned for the second half of 2025
This aggressive development timeline reflects the company's confidence in their novel mechanism and the significant unmet need in atopic dermatitis treatment, particularly for approaches that can address multiple aspects of the disease pathology.
Potential Clinical Impact
If successful, TRIV-509 could represent a significant advancement in AD treatment by offering a mechanism that directly addresses skin barrier dysfunction—a fundamental aspect of the disease that is not directly targeted by current biologics.
The half-life extended formulation of TRIV-509 also suggests potential for convenient dosing, which could improve treatment adherence and patient quality of life compared to existing options.
As Triveni Bio progresses its clinical program, the dermatology community will be watching closely to see if this novel kallikrein-targeting approach can deliver on its promise of enhanced efficacy and convenience for patients with moderate-to-severe atopic dermatitis.
