- Preclinical data highlight MTHFD2 as a promising metabolic target in autoimmune disease, providing strong validation for the advancement of SIT-047, Sitryx’s MTHFD2 inhibitor program, into clinical development
- SIT-047, with first-in-class potential as a disease-modifying treatment for psoriatic arthritis, expected to enter the clinic in 2026
Oxford, UK and Boston, MA – 28 October 2025 – Sitryx Therapeutics (“the Company”), a clinical-stage biopharmaceutical company developing novel oral therapies to restore immune balance in autoimmune and inflammatory disease, has presented new preclinical data demonstrating that inhibition of MTHFD2 (methylenetetrahydrofolate dehydrogenase 2), a key enzyme in one-carbon metabolism, modulates pathways central to autoimmune disease and serves as a promising metabolic target in pathogenic immune responses.
The data, presented at the American College of Rheumatology (ACR) Convergence 2025 in Chicago, underpin the Company’s SIT-047 program, a novel, oral MTHFD2 inhibitor.
They demonstrate that inhibition of MTHFD2, a mitochondrial enzyme upregulated in inflammatory tissue, resulted in reduced proliferation of B and CD4⁺ T cells while preserving overall cell viability, underscoring dual action on both T and B cell arms of adaptive immunity. The studies further showed that MTHFD2 inhibition reduced antigen-specific immune responses and supressed pathogenic cytokine production, reducing severity of autoimmune inflammation in preclinical models.
Ravi Rao, Chief Medical Officer of Sitryx, commented: “MTHFD2 represents a compelling new metabolic target with the potential to selectively reprogram disease-driving immune cells. These findings demonstrate that such metabolic intervention can achieve targeted immune modulation, furthering our confidence in SIT-047 as a next-generation autoimmune therapy with the potential to drive sustained disease remission and transform patient care.”
SIT-047, Sitryx’s novel, oral candidate, has demonstrated strong efficacy in preclinical models and holds first-in-class therapeutic potential across a range of autoimmune conditions where MTHFD2 is strongly upregulated, including psoriatic arthritis, rheumatoid arthritis, lupus, Crohn’s disease, ulcerative colitis, and atopic dermatitis. Sitryx announced the nomination of SIT-047 for clinical development in psoriatic arthritis in May 2025, with entry into the clinic expected in 2026.
POSTER DETAILS
Poster title: MTHFD2 is a Novel Metabolic Target in Autoimmune Disease
Session: T Cell Biology & Targets in Autoimmune & Inflammatory Disease
Abstract number: 0991
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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 in 2018 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.
