- Publication supports Topas’ approach to generating immune tolerance through in vivo autoimmune disease model data in type 1 diabetes and multiple sclerosis
- Topas’ platform leverages the capability of liver sinusoidal endothelial cells to promote tolerance in autoantigen-driven diseases
HAMBURG, Germany--(BUSINESS WIRE)--Topas Therapeutics today announced the publication of data highlighting the ability of its proprietary antigen-coupled nanoparticles’ to achieve tolerance induction in relevant autoimmune disease models, under the title “Nanoparticle Platform Preferentially Targeting Liver Sinusoidal Endothelial Cells Induces Tolerance in CD4+ T Cell-Mediated Disease Models” in the journal Frontiers in Immunology. The Topas platform consists of Topas Particles (TPs), that serve as a highly flexible scaffold for coupling with disease-relevant antigens to generate Topas Particle Conjugates (TPCs) that preferentially harness liver sinusoidal endothelial cells (LSECs) to generate antigen-specific tolerance. The publication describes the ability of TPCs to specifically reach LSECs and to generate tolerance in well-established animal disease models of Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). In addition to the proof-of-concept data from the Phase 2a trial evaluating Topas’ lead candidate TPM502 in adults with celiac disease, the preclinical data reported in the publication underscores the broad potential of this innovative platform approach.
In vivo data included in the publication show that intravenous administration of TPCs resulted in predominant uptake by LSECs with negligible uptake by other non-parenchymal liver cells, confirming its cellular targeting specificity. LSECs are lining the liver sinusoids, a position that puts them in direct contact with antigens in the blood. This location, combined with their extraordinary clearance and tolerogenic function, facilitate LSECs’ rapid uptake of nanosized peptide carriers for antigen-specific tolerance induction in various CD4+ T cell-dependent disease models. In a translational mouse model of T1D, a Topas particle mixture comprising five different peptide-coupled TPCs, significantly reduced the frequency of hyperglycemia onsets compared to control, suggesting that even for complex diseases such as T1D, induction of immune tolerance is possible. In a mouse model of multiple sclerosis (MS), administration of TPCs both prior to disease induction and during disease onset, significantly attenuated disease severity and mitigated demyelination within spinal cords as compared to the control, highlighting the TPCs’ ability to induce tolerance prophylactically and therapeutically.
“These published results, coupled with the efficacy data we have established in celiac disease, further support our broad development strategy of advancing TPM502 into a Phase 2b study in celiac disease patients while expanding our pipeline with TPC candidates in highly prevalent autoimmune diseases,” said Cristina de Min, MD, CMO of Topas Therapeutics. “We look forward to presenting the full data analysis of our Phase 2a study during the Digestive Disease Week in San Diego in May, as a further clinical demonstration of what we believe can be transformative approach in promoting immune tolerance.”
“The publication in Frontiers in Immunology underscores the potential of the innovative Topas platform for reinstating antigen-specific tolerance in many autoimmune diseases, while avoiding the complications of broad immunosuppression,” said Hugo Fry, CEO of Topas Therapeutics. “The data pave the way for exploring our TPCs in indications like type 1 diabetes and serves as a foundation to realize the significant potential across autoimmune and immune-mediated diseases.”
The open access article is available via this link.
About Topas Therapeutics
Topas Therapeutics, a clinical-stage biotech company, is advancing a highly differentiated and versatile approach to establish immune tolerance in autoimmune and immune-mediated diseases. Our proprietary Topas Platform, comprising antigen-coupled nanoparticles, targets liver sinusoidal endothelial cells to drive T cells toward tolerance. The topline readout from our Phase 2a clinical trial in celiac disease validates the power of this new drug modality and its potential to address a broad range of immune-mediated indications, positioning us to deliver significant therapeutic benefits to patients.
For further information: https://topas-therapeutics.com/
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