Sitryx Reports Positive Phase 1b Results for First-in-Class Oral PKM2 Modulator SYX-5219 in Patients with Moderate to Severe Atopic Dermatitis
Proof of concept demonstrated for first-in-class oral therapy, addressing multiple aspects of atopic dermatitis
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- Proof of concept demonstrated for first-in-class oral therapy, addressing multiple aspects of atopic dermatitis pathology and with the potential to deliver lasting benefit to patients
- SYX-5219 was safe and well-tolerated over the six-week treatment period
- Clinically meaningful and statistically significant improvements over placebo demonstrated across key measures of atopic dermatitis disease activity including EASI score, PP-NRS (itch score) and vIGA at day 43
- Significant correlation of change in several atopic dermatitis biomarkers with improvement in disease activity
- Data support advancement into Phase 2 trials in atopic dermatitis and other indications, expected in 1H 2027
Oxford, UK and Boston, MA – 13 October 2026 – Sitryx Therapeutics (“the Company”), a clinical-stage biopharmaceutical company developing novel oral therapies to restore immune balance in autoimmune and inflammatory disease, today announced positive topline results from its Phase 1b clinical trial evaluating lead clinical program SYX-5219, a first-in-class oral pyruvate kinase M2 (PKM2) modulator, in adults with moderate to severe atopic dermatitis (AD).
The results for this pioneering approach provide the first clinical evidence that modulating immune cell metabolism through targeting PKM2 can translate into meaningful clinical benefit for patients with atopic dermatitis.
Iain Kilty, Chief Executive Officer of Sitryx, said: “These positive results are an exciting milestone for Sitryx and a testament to the excellent execution by our team and clinical partners. We have provided the first human validation for a differentiated oral therapy, demonstrating activity across multiple clinical endpoints and biomarkers in patients with atopic dermatitis. We have high confidence in PKM2 modulation as a differentiated therapeutic approach. The concordant data provide a strong foundation for advancing SYX-5219 into Phase 2 in atopic dermatitis and exploring its broader potential across inflammatory diseases.”
The randomized, double-blind, placebo-controlled Phase 1b trial evaluated the safety, tolerability and initial efficacy of SYX-5219 in 35 adults with moderate to severe AD across sites in the United States and Europe. Patients were randomized 2:1 to receive SYX-5219 or placebo for 6 weeks, with safety and efficacy assessments conducted through the treatment period and a 14-day off-treatment follow-up.
SYX-5219 was safe and well tolerated over the six-week treatment period. Pharmacokinetic (PK) and target engagement findings were consistent with those observed in the earlier healthy volunteer studies.
Differences from placebo were observed across all clinical endpoints from Day 8, with separation increasing throughout the dosing period. SYX-5219 achieved the Company’s exploratory efficacy targets for both skin disease severity, measured by the Eczema Area and Severity Index (EASI), and itch, measured by the Peak Pruritus Numerical Rating Scale (PP-NRS). Clinically meaningful placebo-adjusted improvements in these measures, together with positive validated Investigator Global Assessment (vIGA) scores and supportive biomarker findings, provide early clinical evidence of SYX-5219 activity in patients with AD and support further development of this differentiated oral treatment approach. At 6 weeks, the placebo-adjusted change in total EASI score was approximately 28% and the difference in PP-NRS itch score versus placebo was approximately 48%. An increasing number of patients showed at least a one-point improvement in the vIGA over time.
Reduction in several AD-related biomarkers, including CCL-17/TARC and CCL-11/eotaxin, significantly correlated with an improvement in disease activity. Other exploratory biomarker analyses included decreases in validated and clinically relevant biomarkers for atopic disease including serum interleukin-13 (IL-13) and immunoglobulin E (IgE), with larger decreases observed in patients with comorbid asthma. Additional biomarker findings from this study support investigation of PKM2 modulation in asthma and other inflammatory diseases.
The concordance of PK/target engagement, clinician-rated skin improvement, patient-reported itch relief, and treatment-associated biomarker changes provides early clinical validation of PKM2 modulation in inflammatory disease.
Alan Irvine, MD, DSc, Professor of Dermatology at Trinity College Dublin, President of the International Eczema Council and Principal Investigator for the trial, said: “Despite advances in treatment, many people with atopic dermatitis still need alternative options to achieve better control of their disease. There is a particular need for effective, safe oral therapies and treatments that act through new biological pathways, broadening the choices available to patients and clinicians. SYX-5219’s novel PKM2 approach and these encouraging early results make it an important candidate for further investigation.”
Ravi Rao, Head of R&D and Chief Medical Officer of Sitryx, commented: “We are delighted with these data. The improvements in skin disease severity and itch address two of the most important burdens for people living with atopic dermatitis. Positive vIGA findings and supportive biomarker changes add to our excitement in the clinical results. Together with the favorable safety profile observed, these findings highlight SYX-5219’s potential to deliver meaningful benefit to patients. Our thanks to all those who supported and participated in this trial, particularly those people living with atopic dermatitis. We look forward to building on these results in larger and longer studies across a range of indications.”
Sitryx will present the full Phase 1b dataset at a forthcoming scientific congress and intends to submit the results for peer-reviewed publication. The Company is finalizing the design of its Phase 2 trial of SYX-5219 in adults with moderate to severe atopic dermatitis, expected to begin in 1H 2027. Evaluation of additional autoimmune and inflammatory indications for SYX-5219 is ongoing.
SYX-5219 and Atopic Dermatitis
SYX-5219 offers first-in-class potential as an oral, disease-modifying anti-inflammatory therapy, targeting PKM2, a critical enzyme that regulates cell metabolism. Modulation of PKM2 alters the function of T lymphocytes and other inflammatory cells, representing a differentiated, broad, immunomodulatory, anti-itch and pro-barrier repair profile that could drive sustained disease remission in atopic dermatitis. By modulating immune cell metabolism rather than targeting a single inflammatory signal, SYX-5219 has the potential to deliver broad immunomodulatory effects while supporting restoration of immune balance.
Atopic dermatitis is the most common chronic inflammatory skin disease, affecting more than 200 million people worldwide, with over five million people in the United States and Europe living with moderate to severe disease. Despite the availability of injectable biologics and oral targeted therapies, many patients remain inadequately controlled, and demand for effective oral treatments with a favorable long-term tolerability profile remains high.
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For more information about Sitryx please contact:
ICR Healthcare
Mary-Jane Elliott, David Daley, Evi Useh
+44 (0)20 3709 5700
Sitryx@icrhealthcare.com
About Sitryx
Sitryx is a clinical-stage biopharmaceutical company developing novel oral therapies to restore immune balance in autoimmune and inflammatory disease. The Company has a broad pipeline of novel small molecule candidates targeting major autoimmune indications with high unmet need. Its lead candidate, SYX-5219, is a potentially first-in-class PKM2 modulator in development for atopic dermatitis as a once-daily oral therapy with future development potential across multiple autoimmune diseases.
Established with seed funding from SV Health Investors, Sitryx has an international syndicate of specialist investors including SV Health Investors, Sofinnova Partners, Oxford Science Enterprises, Longwood Fund, Eli Lilly and Company, and GSK.
Sitryx is headquartered in Oxford, UK with additional presence in Boston, MA. For more information, please visit www.sitryx.com.
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