Sitryx Advances Novel Oral Therapy SYX-5219 for Atopic Dermatitis with FDA IND Clearance

Last week, Sitryx Therapeutics shared that the company has received clearance from the US Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for SYX-5219, to support the initiation of a Phase 1b trial in adults with moderate to severe atopic dermatitis (AD) in the US.¹

“The FDA’s clearance of our IND application represents a pivotal milestone in the clinical development of SYX-5219, bringing us closer to delivering a much-needed treatment option for patients living with atopic dermatitis and other autoimmune conditions,” Iain Kilty, PhD, chief executive officer of Sitryx, said in a statement. “We look forward to initiating this trial and generating data that will guide the next stage of development, providing life-changing benefits to patients.”¹

A phase 1a trial is currently underway in the UK, following a Clinical Trial Authorisation (CTA) by the Medicines and Healthcare products Regulatory Agency (MHRA). The randomized, placebo-controlled study is designed to evaluate the safety, tolerability, and pharmacokinetics of SYX-5219 in healthy volunteers. Preclinical data for SYX-5219 have also demonstrated its ability to reduce inflammatory markers and promote skin barrier repair.²

“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,” Ravi Rao, MD, PhD, chief medical officer of Sitryx, said.²

SYX-5219 represents a first-in-class oral anti-inflammatory 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 in AD and other conditions with a differentiated broad, anti-itch, and pro-barrier repair profile.

“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 added. “We are excited to advance SYX-5219 into the clinic and work towards delivering meaningful, lasting benefits to patients.”²

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. Sitryx expects to initiate the trial for SYX-5219 in the first quarter of 2026.

“Atopic dermatitis affects over 200 million people worldwide and the persistent inflammation and severe itching associated with the disease significantly impacts the quality of life of patients. SYX-5219 offers a novel oral approach with the potential to deliver durable disease remission, and the upcoming Phase 1b study will provide important insights into its clinical and biological effects in patients, laying a solid foundation for future studies in atopic dermatitis and other conditions,” Rao said in a press release.¹

References

1. Sitryx receives FDA clearance of IND application for SYX-5219 for the treatment of atopic dermatitis. News release. Globe Newswire. Published October 2, 2025. Accessed October 6, 2025. https://www.globenewswire.com/news-release/2025/10/02/3160233/0/en/Sitryx-receives-FDA-clearance-of-IND-application-for-SYX-5219-for-the-treatment-of-atopic-dermatitis.html

2. Sitryx initiates phase 1 clinical trial of potential disease-modifying treatment for atopic dermatitis SYX-5219. News release. Globe Newswire. Published March 20, 2025. Accessed October 6, 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