Phase 1 Trial of PKM2 Modulator SYX-5219 for Atopic Dermatitis Underway

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Sitryx Therapeutics announced today the initiation of a phase 1a clinical trial evaluating its drug SYX-5219, an oral pyruvate kinase M2 (PKM2) modulator, in atopic dermatitis (AD).¹

The first-in-human clinical trial initiation follows clinical trial authorization from the UK’s Medicines and Healthcare products Regulatory Agency.²

A Novel Approach to AD Treatment

SYX-5219 represents a first-in-class oral therapy with disease-modifying potential. It is designed to target PKM2, a key enzyme in cellular metabolism that plays a crucial role in immune cell function. By modulating PKM2, SYX-5219 aims to alter B and T lymphocyte activity, rebalance immune responses, and ultimately drive sustained disease remission.

Phase 1a Clinical Trial Design

The phase 1a trial, now underway in the UK, is a randomized, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics of SYX-5219 in healthy volunteers. This initial study is part of a broader 2-phase investigation, with a phase 1b trial planned for 2025 to assess the drug’s effects in adults with moderate to severe AD. The phase 1b segment is expected to expand into multiple regions, including the UK, Europe, and the US.

Preclinical data for SYX-5219 have demonstrated its ability to reduce inflammatory markers and promote skin barrier repair,² further supporting its potential as a treatment for AD and other inflammatory diseases.

Perspectives on SYX-5219’s Potential

Iain Kilty, PhD, chief executive officer of Sitryx, described the initiation of the phase 1 trial as a major milestone.

“By targeting PKM2, SYX-5219 has the potential to redefine the treatment paradigm for atopic dermatitis and other autoimmune diseases, marking a new phase in precision immunology,” Kilty said in a news release.¹ “We are excited to advance SYX-5219 into the clinic and work towards delivering meaningful, lasting benefits to patients.”

Echoing this sentiment, Ravi Rao, MD, PhD, chief medical officer of Sitryx, highlighted the need for more effective oral treatment options for AD.

“Atopic dermatitis remains a challenging condition with few effective oral therapies,” Rao said.¹ “SYX-5219 is designed to provide a convenient once-daily oral treatment with a unique mechanism of action that directly targets metabolic imbalances driving immune dysfunction. This trial will initially provide crucial data on the safety and pharmacokinetics of SYX-5219 before investigating the clinical and biological effect on patients with atopic dermatitis, laying the groundwork for future studies aimed at developing treatments that not only manage symptoms but also aim for sustained disease remission.”

Sitryx’s Expanding Clinical Pipeline

SYX-5219 is the second Sitryx program to enter clinical development, following the advancement of SYX-1042, an itaconate mimetic licensed to Eli Lilly and currently in phase 1 trials.

Sitryx’s broader pipeline includes multiple small-molecule candidates targeting immune-mediated diseases with significant unmet medical needs.

References

1. Sitryx initiates phase 1 clinical trial of potential disease-modifying treatment for atopic dermatitis SYX-5219. News release. Globe Newswire. March 20, 2025. Accessed March 20, 2025. https://www.globenewswire.com/news-release/2025/03/20/3046078/0/en/Sitryx-initiates-Phase-1-clinical-trial-of-potential-disease-modifying-treatment-for-atopic-dermatitis-SYX-5219.html
2. Sitryx nominates SYX-5219 a novel, oral and targeted PKM2 activator for clinical development in atopic dermatitis. News release. Globe Newswire. April 10, 2024. Accessed March 20, 2025. https://www.globenewswire.com/news-release/2024/04/10/2860630/0/en/Sitryx-nominates-SYX-5219-a-novel-oral-and-targeted-PKM2-activator-for-clinical-development-in-atopic-dermatitis.html