TPM-502 Shows Positive Results

Data from a Phase II a clinical trial evaluating TPM 502, the company’s lead candidate, demonstrated a positive safety and tolerability profile, a significant reduction of the inflammatory responses to gluten and long-lasting phenotypic changes to gliadin-specific T cells. In addition, TPM 502-treated patients reported a beneficial impact on symptoms post a gluten challenge. Developed using Topas’ proprietary platform, TPM 502 consists of nanoparticles coupled with CeD disease-relevant antigens. The study findings were presented at Digestive Disease Week® (DDW) 2025 on Monday, May 5, 2025, in an oral presentation and were selected for the American Gastroenterological Association Presidential Plenary

“The data presented at DDW represent a significant validation of TPM 502 as a potential treatment for celiac disease. The observed safety profile, combined with the clear, dose-dependent reduction of IL-2 and IFN-γ release by gluten-specific T cells as well as phenotypic changes in antigen-specific CD4+ T cells, reinforces TPM502’s ability to precisely and durably modulate the underlying autoimmune response to gluten,” stated Knut E. A. Lundin, MD, PhD, Principal Investigator of the Phase 2a study and Professor and Head of Clinical Education at the Institute of Clinical Medicine, University of Oslo.

“By directly addressing the pathogenic T-cell activation central to celiac disease, TPM 502 could redefine the treatment paradigm and provide a much-needed therapeutic option for patients who currently have no approved alternatives to a lifelong gluten-free diet. Indeed, the gluten-free diet does not meet the medical needs of many celiac disease patients,” added Cristina de Min, MD, CMO of Topas Therapeutics.  “Our Phase 2a trial data also support the application of our nanoparticle platform for a range of autoimmune disease indications for which tolerance induction could be a transformative therapeutic approach.”

The multi-center, double-blind, randomized, placebo-controlled Phase IIa study evaluated TPM 502 in HLA-DQ2.5 positive adults with confirmed CeD on a gluten-free diet (NCT05660109). HLA-DQ2.5 is a very common genetic variant among CeD patients, representing approximately 90% of the total disease population.  A total of 38 patients that achieved a predefined IL-2 response to bolus gluten challenge (6 g gluten) were randomized and assigned to placebo or 1 of 4 dose cohorts, receiving 2 intravenous infusions of TPM 502 (from 0.72 μmol to 7.2 μmol total peptide dose) on day 1 and day 15. A total of 26 patients received TPM 502 and 12 received placebo. The gluten challenge was repeated 7 days after the second administration of TPM 502 or placebo. As reported in the DDW presentation, TPM 502 demonstrated a favorable safety profile. Treatment-related adverse events (TAEs) were reported in 27 patients, including 8 on placebo, with the majority being Grade 1 or 2 events such as nausea, headache, and vomiting; only a single patient experienced four Grade 3 TAEs.

Importantly, a significant and dose-related reduction of IL-2 and IFN-γ release by gluten-specific T cells was observed after TPM 502 treatment at the highest dose, which was maintained throughout the study period of 1 month following the last TPM 502 administration. In addition, immunomodulation was demonstrated by post-treatment phenotypic changes in gluten-specific CD4+ T cells consistent with T cell anergy or exhaustion and a significant increase in gluten-specific regulatory CD4+ T cells at the highest TPM 502 dose, suggesting the induction of regulatory status in these T cells. Patient-reported outcomes using a Celiac Disease Patient‐Reported Outcome (CeD PRO®) tool, indicated a dose-dependent reduction in gastrointestinal symptoms in TPM 502-treated patients compared to placebo, following the post treatment gluten challenge.

“Topas Therapeutics is committed to advancing TPM502 as a much-needed treatment option for celiac disease patients, building on data that represent a breakthrough for this and potentially other immune-mediated diseases,” said Hugo Fry, CEO of Topas Therapeutics. “With this validation of our technology and its ability to modulate immune responses in a precise and durable manner, we look forward to the next clinical steps for TPM502 and our pipeline.”