# Targeting the CCR6-CCL20 pathway for treatment of psoriatic joint and entheseal inflammation

> **NIH NIH R44** · XLOCK BIOSCIENCES, LLC · 2024 · $966,201

## Abstract

Project Summary/Abstract
The goal of this project is to develop and validate a novel therapeutic lead compound for the treatment of
psoriatic arthritis (PsA). Chemokines orchestrate the migration of inflammatory cells during normal immune
responses and are required for immune tissue development and homeostasis. When aberrant chemokine
function occurs, improper recruitment of immune cells can lead to a variety of inflammatory pathologies with
devastating effects on a patient’s quality of life. The chemokine CCL20 and its G protein-coupled receptor
CCR6 drive the development of psoriatic disease through the initiation and continuous recruitment of
inflammatory Th17-expressing cells into skin and connective tissue. Our published biochemical, cell-based and
in vivo studies prove that an engineered recombinant protein that mimics the dimeric version of the natural
CCL20 molecule completely reverses its normal pro-inflammatory functional profile. In a Phase I SBIR project,
the lead compound (CCL20LD) reduced the signs of established psoriatic dermatitis (PsD) in a preclinical
mouse model that faithfully recapitulates human psoriasis. Unexpectedly, CCL20LD treatment also alleviated
joint and tendon inflammation, demonstrating efficacy in a clinically relevant model of human psoriatic
arthritis. The same project also yielded a favorable preliminary safety profile with no indication of liver or
kidney toxicity and a validated manufacturing and quality control protocol. There is a significant need for new
treatments for psoriatic arthritis because current options carry the risk of immunosuppression and loss of
efficacy over time. This Direct-to-Phase II proposal builds on the completed Phase I milestones to complete
preclinical testing and optimization of CCL20LD and assemble the necessary efficacy, safety, and
manufacturing data for an IND application and clinical trials for psoriatic arthritis. XLock Biosciences, LLC (XL)
will manufacture the CCL20LD protein and direct the studies proposed in three specific aims. In Aim 1, XLock
will improve the in vivo stability of the first generation CCL20LD molecule with modifications known to extend
the circulating half-life of biologic drugs. In Aim 2 XL and its academic collaborators at UC Davis will establish
the therapeutic dose and schedule which produces the strongest anti-psoriatic effect in joint tissues in the
shortest time period. Lastly, in Aim 3, XL’s collaborators at the Medical College of Wisconsin will measure
CCL20LD’s immunomodulatory activity and its effect on rodent susceptibility to commensal fungal infection.
Altering CCR6 signaling through the engineering of its native ligand is an innovative paradigm shift in clinical
approaches for treating auto-inflammatory diseases. Development of engineered CCL20 variants as biological
therapeutics will have significant positive impact for psoriatic arthritis patients by reducing side effects and
providing a drug with extended therapeutic lifetimes. Moreov...

## Key facts

- **NIH application ID:** 10902026
- **Project number:** 5R44AR081754-02
- **Recipient organization:** XLOCK BIOSCIENCES, LLC
- **Principal Investigator:** William R Clarke
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $966,201
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10902026

## Citation

> US National Institutes of Health, RePORTER application 10902026, Targeting the CCR6-CCL20 pathway for treatment of psoriatic joint and entheseal inflammation (5R44AR081754-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10902026. Licensed CC0.

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