SYX-5219, an experimental once-daily pill from Sitryx Therapeutics, a company co-founded by Trinity College Dublin's Professor Luke O'Neill, reduced eczema severity and itch compared with placebo in a small Phase 1b trial of 35 adults, according to company results released on 13 October 2026. The full data have not yet been peer reviewed.
Sitryx, which is based in Oxford in the UK and Boston in the US, announced the topline results in a press release. Trinity College Dublin followed on 15 October with its own announcement, because the drug grew out of research in Professor O'Neill's laboratory and part of the trial ran at St James's Hospital in Dublin.
- Drug: SYX-5219, a first-in-class oral pyruvate kinase M2 (PKM2) modulator, developed as a once-daily pill.
- Trial: randomised, double-blind, placebo-controlled Phase 1b in 35 adults with moderate to severe atopic dermatitis, six weeks of treatment.
- Results (company-reported): about 28% placebo-adjusted change in EASI severity score and about 48% difference in itch score at six weeks.
- Safety: the company says SYX-5219 was safe and well tolerated over six weeks. Adverse event details were not released.
- Irish link: research by Dr Eva Palsson McDermott and Prof Luke O'Neill at Trinity; trial led by Trinity's Prof Alan Irvine, with a site at St James's Hospital.
- Next step: a Phase 2 trial in moderate to severe atopic dermatitis expected to start in the first half of 2027.
What the Phase 1b trial found
The trial tested safety, tolerability and early signs of efficacy in 35 adults with moderate to severe atopic dermatitis, the most common form of eczema, at sites in the United States and Europe. Patients were randomised two to one to SYX-5219 or placebo for six weeks, followed by 14 days off treatment.
| Measure | Result at six weeks |
|---|---|
| EASI (skin severity score) | Placebo-adjusted change of approximately 28% |
| PP-NRS (peak itch score) | Difference versus placebo of approximately 48% |
| vIGA (investigator assessment) | An increasing number of patients improved by at least one point over time |
| Onset | Differences from placebo seen across clinical endpoints from Day 8 |
| Biomarkers | Reductions in CCL-17/TARC and CCL-11/eotaxin that correlated with improvement; lower serum IL-13 and IgE |
The company describes the improvements in EASI, itch and vIGA at day 43 as clinically meaningful and statistically significant. It also reported that drug levels and target engagement matched those seen earlier in healthy volunteers.
The Trinity College Dublin connection
Sitryx was founded by six researchers, one of whom is Professor Luke O'Neill of Trinity College Dublin. According to Trinity, SYX-5219 "was developed by Sitryx from ground-breaking research carried out by Dr Eva Palsson McDermott and Prof. Luke O'Neill in Trinity", and Sitryx has supported research in Professor O'Neill's laboratory at the Trinity Biomedical Sciences Institute.
"Our work implicating PKM2 in inflammation led to Sitryx developing a PKM2-targeted drug called SYX-5219 that is now showing substantial promise as a new treatment for atopic dermatitis and possibly other inflammatory diseases," Professor O'Neill said in the Trinity release.
The trial was led by Professor Alan Irvine, Professor of Dermatology at Trinity and President of the International Eczema Council, in centres in the US and Europe, including the clinical research facility at St James's Hospital. "Many patients need an orally active medicine to control their disease and these encouraging results give us hope that further trials will confirm the benefits we've seen with SYX-5219," he said. "I'm especially pleased that this early stage clinical trial was conducted in part in the Wellcome Trust HRB-supported Clinical Research Facility in St James's Hospital."
Why an oral eczema drug matters
Many advanced treatments for moderate to severe eczema are injectables. In the company release, Professor Irvine said that "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." Sitryx says atopic dermatitis affects more than 200 million people worldwide, including over five million with moderate to severe disease in the US and Europe.
SYX-5219 works on PKM2, an enzyme involved in cell metabolism. The company's thesis is that modulating it can dampen inflammation through a new route. "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," said Iain Kilty, Chief Executive of Sitryx.
What is not yet known
These are early, company-reported topline results from a small trial, and several details have not been released:
- The dose or doses tested, and the number of patients in each arm.
- P-values, confidence intervals and responder rates such as EASI-75.
- The number and type of adverse events.
- When and where the full data will be presented. The company says it will present them at a forthcoming scientific congress and submit them for peer-reviewed publication.
There is also an unexplained difference in patient numbers. When enrolment completed in June 2026, the company described the study as evaluating SYX-5219 in 50 adult patients. The results release reports 35 adults with moderate to severe atopic dermatitis. The trial is part of a multi-part study that also included healthy volunteers, which may account for the gap.
What comes next
Sitryx expects a Phase 2 trial in adults with moderate to severe atopic dermatitis to begin in the first half of 2027, and it is evaluating other indications, including asthma. "We look forward to building on these results in larger and longer studies across a range of indications," said Ravi Rao, Head of R&D and Chief Medical Officer. Trinity's release refers to further clinical trials over the next one to two years. No timeline for approval or availability to patients has been given.
Frequently Asked Questions (FAQ)
Q: What is SYX-5219?
A: An experimental once-daily oral drug from Sitryx Therapeutics that modulates the enzyme PKM2 to reduce inflammation. It is being tested for moderate to severe atopic dermatitis.
Q: Is Sitryx an Irish company?
A: Sitryx is headquartered in Oxford, UK, with a presence in Boston. It is Irish co-founded: Trinity College Dublin's Professor Luke O'Neill is one of its six founders, and the drug came from research in his lab.
Q: How many patients were in the trial?
A: 35 adults with moderate to severe atopic dermatitis, randomised two to one to SYX-5219 or placebo for six weeks.
Q: Can patients get SYX-5219 now?
A: No. It is still in clinical development, with a Phase 2 trial expected to start in the first half of 2027.
Q: Have the results been peer reviewed?
A: Not yet. They are topline company results; Sitryx plans to present the full data at a scientific congress and submit them for publication.
Conclusion and Outlook
SYX-5219 has cleared an important early hurdle, with company-reported reductions in eczema severity and itch over six weeks and no safety concerns flagged so far. The trial was small and the full data are still to come, so the Phase 2 study planned for the first half of 2027 will be the real test. For Ireland it is a clear example of Trinity research moving into the clinic, with a Dublin hospital helping to run the trial.
This article reports research news and is not medical advice. Cover image: AI-generated illustration. It does not show any real person, patient or product.
Sources
- Sitryx Therapeutics, Sitryx Reports Positive Phase 1b Results for First-in-Class Oral PKM2 Modulator SYX-5219 in Patients with Moderate to Severe Atopic Dermatitis, 13 October 2026 (also on GlobeNewswire)
- Trinity College Dublin, Trinity researchers develop pioneering new medicine for atopic dermatitis, 15 October 2026
- Sitryx, About Sitryx
- Sofinnova Partners, Sitryx completes enrollment in Phase 1b trial of SYX-5219, June 2026
