Triveni Bio Launches First-in-Human Trial for TRIV-509 in Atopic Dermatitis

Triveni Bio announced today it has officially begun dosing healthy volunteers in a phase 1 clinical trial for TRIV-509.¹ This first-in-human trial marks a step forward in the development of the drug for moderate to severe atopic dermatitis (AD), which functions by modulating kallikrein activity.

The trial launch follows recent preclinical data which support TRIV-509’s ability to restore skin barrier function and downregulate inflammatory processes seen in AD.² In addition to this clinical milestone, Triveni also shared new details about its next-generation candidate, TRIV-573, further expanding its kallikrein-based therapeutic strategy.

A New Class of Therapeutics: Targeting KLK5 and KLK7

At the core of Triveni Bio’s pipeline is a genetically informed, antibody-based strategy to block epidermal serine proteases kallikrein 5 (KLK5) and kallikrein 7 (KLK7). These enzymes, though normally involved in skin desquamation, are pathologically overactive in AD, leading to degradation of critical structural proteins such as desmoglein-1 (DSG1), disruption of skin barrier integrity, and promotion of inflammation.³

TRIV-509 is a half-life extended monoclonal antibody that dually inhibits KLK5 and KLK7. Through this mechanism, it addresses 3 pillars of AD pathology: skin barrier dysfunction, chronic inflammation, and pruritus. TRIV-509 directly intervenes at the level of protease-mediated skin damage.

"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," said Bhaskar Srivastava, MD, PhD, chief medical officer of Triveni Bio, in a news release.¹

Promising Preclinical Results Presented at SID 2025

Data presented at the recent Society for Investigative Dermatology Annual Meeting highlighted TRIV-509’s ability to reverse key pathological features of AD in human skin explants.² In the study, skin biopsies from 3 patients with moderate to severe AD (IGA >2) were treated ex vivo with TRIV-509 for 72 hours.

Key findings from the analysis include:

• Epidermal Thickness Reduction: TRIV-509 reduced epidermal hyperplasia by 14% to 28% in 2 of the 3 patient samples.
• Decreased Keratinocyte Proliferation: A marked 80% reduction in Ki-67 positive basal keratinocytes was observed, indicating significant downregulation of epidermal turnover.
• Improved Epidermal Differentiation: Parakeratosis, a hallmark of aberrant epidermal maturation, was reduced by 31% in 1 patient’s sample.
• Restoration of Barrier Protein DSG1: Treated samples showed up to a 313% increase in desmoglein-1–positive cells, re-establishing proper cell-cell adhesion and barrier architecture.

Read more from Dermatology Times.

These findings are consistent with previous in vivo preclinical models in which TRIV-509 demonstrated superior efficacy over IL-4 receptor inhibition.

Expanding the Platform: TRIV-573 and Bispecific Innovation

Beyond TRIV-509, Triveni Bio is preparing to advance TRIV-573, a next-generation bispecific antibody that targets both KLK5/7 and IL-13.

TRIV-573 aims to combine the barrier-repairing benefits of KLK inhibition with potent anti-inflammatory action via IL-13 blockade. Preclinical evaluations presented at the Protein Engineering & Cell Therapy Summit demonstrated that TRIV-573 possesses high affinity, extended half-life, and a design tailored to optimize therapeutic outcomes across multiple AD phenotypes.

TRIV-573 is currently undergoing IND-enabling studies, with Triveni anticipating clinical development in the near future.

References

1. Triveni Bio doses first healthy volunteers in clinical trial for TRIV-509, coinciding with preclinical data presentations further validating novel kallikrein 5/7 biology in atopic dermatitis. News release. PR Newswire. May 21, 2025. Accessed May 21, 2025. https://www.prnewswire.com/news-releases/triveni-bio-doses-first-healthy-volunteers-in-clinical-trial-for-triv-509-coinciding-with-preclinical-data-presentations-further-validating-novel-kallikrein-57-biology-in-atopic-dermatitis-302461150.html
2. Mateer E, Asp E, e Sousa MS, et al. TRIV-509, a dual inhibitor of KLK5 and KLK7, rapidly improves barrier integrity and markers of epidermal differentiation in atopic dermatitis skin explants. Poster presented at: Society for Investigative Dermatology Annual Meeting; May 7-10; San Diego, California.
3. Guo CJ, Mack MR, Oetjen LK, et al. Kallikrein 7 promotes atopic dermatitis-associated itch independently of skin inflammation. J Invest Dermatol. 2020;140(6):1244-1252.e4. doi:10.1016/j.jid.2019.10.022