Sitryx Therapeutics has initiated its first-in-human Phase 1a clinical trial evaluating SYX-5219, a potential disease-modifying treatment for atopic dermatitis. The UK-based clinical-stage biopharmaceutical company received Clinical Trial Authorisation from the UK's Medicines and Healthcare products Regulatory Agency (MHRA) to begin the study, marking a significant milestone in the development of this novel oral therapy.
SYX-5219 represents the second program from Sitryx's portfolio to enter clinical development, following the commencement of a Phase 1 trial for SYX-1042 (an itaconate mimetic) by partner Eli Lilly in 2024.
Novel Mechanism Targets Immune Cell Metabolism
SYX-5219 is a first-in-class oral therapy that modulates pyruvate kinase M2 (PKM2), a critical enzyme regulating cell metabolism. By targeting PKM2, the drug alters B and T lymphocyte function, potentially rebalancing the immune system and normalizing immune cell function.
"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," said Iain Kilty, Chief Executive Officer of Sitryx.
Preclinical data have demonstrated that SYX-5219 reduces inflammatory markers and enhances skin barrier repair, supporting its potential as a disease-modifying therapy rather than just a symptomatic treatment.
Two-Part Clinical Development Plan
The Phase 1a trial initiated in the UK is an interventional placebo-controlled study designed to assess the safety, tolerability, and pharmacokinetics of SYX-5219 in healthy volunteers. This represents the first part of a broader development program, with a Phase 1b trial in adults with moderate to severe atopic dermatitis expected to commence later in 2025 across the UK, Europe, and the US.
Ravi Rao, Chief Medical Officer of Sitryx, highlighted the significance of this approach: "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."
Addressing a Significant Unmet Need
Atopic dermatitis represents a substantial global health burden, affecting over 200 million individuals worldwide. More than five million people in the US and Europe suffer from moderate to severe forms of the disease, experiencing persistent inflammation and severe itching that significantly impacts quality of life.
Current treatment options for atopic dermatitis, particularly oral therapies, remain limited. 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.
Unlike existing biologic and JAK inhibitor therapies, SYX-5219 aims to offer long-term disease control with an improved safety profile. The oral administration route could provide a significant advantage over injectable biologics for patient convenience and adherence.
Broader Implications for Inflammatory Diseases
The novel mechanism of action of SYX-5219 suggests potential applications beyond atopic dermatitis. By modulating PKM2 and rebalancing immune function, the therapy could potentially address a broad range of inflammatory and autoimmune conditions.
Sitryx's approach focuses on restoring immune balance through targeted metabolic interventions, representing an emerging frontier in immunology research. This strategy aligns with growing interest in the field of immunometabolism, which explores the relationship between cellular metabolism and immune function.
Company Background and Funding
Established in 2018 with seed funding from SV Health Investors, Sitryx has raised $85 million to date from an international syndicate of specialist investors including SV Health Investors, Sofinnova Partners, Oxford Science Enterprises, Longwood Fund, Lilly, and GSK.
In 2020, Sitryx formed an exclusive global licensing and research collaboration with Eli Lilly and Company. The first program from this collaboration, SYX-1042 (an itaconate mimetic), is now in clinical development at Lilly, with a Phase 1 trial initiated in January 2024.
Headquartered in Oxford, UK, Sitryx continues to develop its pipeline of novel small molecule candidates targeting major autoimmune indications with high unmet need, with SYX-5219 representing its lead candidate.
