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Triveni Bio
Science

Our science is built on three core pillars:

Genetically informed targets, advanced antibody engineering and novel disease biology.
Click the links below to learn more about each.

Novel disease biology

Moving beyond inflammation to address core drivers of disease

Our science starts with a focus on the underlying disease biology. We seek to break efficacy ceilings by prioritizing and targeting primary drivers of disease. In the case of atopic dermatitis (AD), current approaches focus on reducing downstream inflammation to improve symptoms. Our approach not only addresses this inflammation, but also tackles the root cause of AD by normalizing the skin barrier and addressing persistent itch.

KLK5/7 (kallikreins 5 and 7) are secreted serine proteases which play a key role in the vicious cycle of atopic dermatitis.

Studies have shown that a majority of AD patients show increased activity or expression of KLK5/7.

Barrier dysfunction

Over expression of KLK5/7 degrades key junctional proteins, resulting in compromised skin barrier integrity.

AD skin is dry, cracked, and vulnerable to irritants

Inflammation

KLK5 can trigger protease-activated receptor-2 (PAR2), which initiates pro-inflammatory cytokine release and other immune cascades in the skin.

Lesional AD skin appears red, swollen, and inflamed

Itch

KLK7 directly activates sensory neurons in the skin.

AD patients experience intense itch, which impacts sleep and quality of life 

Prioritizing targets with human relevance and mechanistic evidence ensures our drug discovery is rooted in compelling biology.

Explore the clinical programs built on these pillars

Visit our pipeline

Genetically informed targets

Genetics validate causal nodes of disease

Triveni leverages human genetics to reveal molecular drivers of disease. Using integrated multi-omic datasets, we construct molecular “knowledge graphs” that map mechanistic networks across diseases and identify the critical nodes of dysfunction.

This genetics-informed approach identified kallikreins 5 and 7 (KLK5/7) as key drivers of atopic dermatitis (AD) pathology. Our analyses uncovered the full allelic series including both risk alleles and protective variants, linking KLK5/7 activity to many barrier disorders, including AD.

KLK5/7 play a central role in many epithelial barrier diseases​

Tissue kallikreins

Secreted serine proteases

Site of activity

Epidermis​, lungs, and esophagus

Regulation

Regulated by endogenous inhibitor SPINK5

Advanced antibody engineering

Overcoming “undruggable” targets with innovative biologics

We are deploying cutting-edge antibody engineering techniques to modulate targets long considered intractable by antibody therapeutics. In the case of KLK5/7, our innovative approach has allowed us to overcome these historic challenges and identify a single antibody that binds to both targets of interest.

Our team engineered a high-affinity monoclonal antibody that binds both KLK5 and KLK7 with equal potency. This antibody, designated TRIV-509, is optimized with several unique features: 

  1. Competitive active site binder that specifically inhibits the active form of the target proteases
  2. Dual specificity IgG1 that binds to a shared epitope on KLK5 and KLK7
  3. Half-life extension (HLE) modifications that enable more convenient dosing
Learn more about the ongoing clinical trials of TRIV-509 here
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