Periodic Reporting for period 1 - DIAMANTE (Revolutionizing Autoimmune Therapy: Antigen Specific Immunotherapy for Rheumatoid Arthritis with Virus Nanoparticles)
Berichtszeitraum: 2025-01-01 bis 2025-12-31
In autoimmune diseases, the body’s immune system mistakenly targets its own healthy cells, tissues and organs, causing inflammation and damage. There is currently no cure for autoimmune diseases that are increasing in incidence globally. DIAMANTE Srl. develops plant-based peptide drugs. With our proprietary Plant Molecular Farming Platform, we aim to develop cutting-edge treatments for autoimmune diseases through virus nanoparticles (VNP). Our patented protected VNPs’ mode of action is based on Antigen Specific Immunotehrapy. This means that our VNPs are able to re-educate the immune system to immune tolerate the specific body’s own cell (autoantigen) causing the disease. Our Proof-of-concept studies in Rheumatoid Arthritis (RA - our first indication) animal models have shown complete remission of arthritic symptoms. Currently, there is no cure or preventive measure for this chronic condition; first-line treatments revolve around immunosuppression, causing several side effects. Our drug will be the first treatment based on the restoration of self-tolerance, while maintaining the immune system’s ability to defend itself against foreign threats; hence reducing potential harmful side effects. With the EIC-funded DIAMANTE project, the company aims to pursue clinical testing of its patented virus nanoparticles for antigen-specific immunotherapy
In RP1, significant progress was made in optimizing the upstream and downstream production processes to be easily scalable, meet regulatory requirements and support planned (pre-) clinical activities.
We completed the optimization of the downstream production process, increasing the original yield fivefold, higher purity of TBSV.pLip. better physo-chemical characteristic of the final product, faster operational timelines, and a scalable production workflow suitable for GMP manufacturing. A batch intended for toxicology studies in a GMP-like environment has been produced, ensuring compliance with the standards required for preclinical testing. In parallel, the facility layout and procedures were redesigned to align with GMP regulations and to further improve process performance. Key actions completed include: recruitment of a Qualified Person and a QA Manager; execution of a gap assessment for full Quality Management System (QMS) implementation, including main QMS procedures, with 12 SOPs already implemented.
On technical side, progress continued in the execution and refinement of the toxicology program, including an in vitro phase and an in vivo one. The in vitro phase has been fully completed, while the animal phase is on goind. We are applying for Scientific Advice with AEMPS (Spain), proposing to conduct the toxicology program in a single animal species.
The toxicology study design includes a Part A, an initial in vitro phase aimed at evaluating the effects of the particles on PBMCs from healthy donors and THP 1 cells, focusing on cell viability and on the induction of pro inflammatory cytokines. The results demonstrated the absence of toxic and inflammatory effects, confirming the actual safety profile of the product. Part B involves the in vivo toxicology study., which has been submitted for scientific advice, for approval to perfom the study in a single animal species, in accordance with the 3Rs principle and regulatory expectations.
During this period, we defined a clear regulatory strategy for the clinical development of our product, and the Phase 1 clinical trial design has been completed. All preparatory activities for study initiation have been finalized, including the definition of the study protocol, identification of key stakeholders, scientific advice with AEMPS, and an audit of the selected clinical site.
We completed the optimization of the downstream production process, increasing the original yield fivefold, higher purity of TBSV.pLip. better physo-chemical characteristic of the final product, faster operational timelines, and a scalable production workflow suitable for GMP manufacturing. A batch intended for toxicology studies in a GMP-like environment has been produced, ensuring compliance with the standards required for preclinical testing. In parallel, the facility layout and procedures were redesigned to align with GMP regulations and to further improve process performance. Key actions completed include: recruitment of a Qualified Person and a QA Manager; execution of a gap assessment for full Quality Management System (QMS) implementation, including main QMS procedures, with 12 SOPs already implemented.
On technical side, progress continued in the execution and refinement of the toxicology program, including an in vitro phase and an in vivo one. The in vitro phase has been fully completed, while the animal phase is on goind. We are applying for Scientific Advice with AEMPS (Spain), proposing to conduct the toxicology program in a single animal species.
The toxicology study design includes a Part A, an initial in vitro phase aimed at evaluating the effects of the particles on PBMCs from healthy donors and THP 1 cells, focusing on cell viability and on the induction of pro inflammatory cytokines. The results demonstrated the absence of toxic and inflammatory effects, confirming the actual safety profile of the product. Part B involves the in vivo toxicology study., which has been submitted for scientific advice, for approval to perfom the study in a single animal species, in accordance with the 3Rs principle and regulatory expectations.
During this period, we defined a clear regulatory strategy for the clinical development of our product, and the Phase 1 clinical trial design has been completed. All preparatory activities for study initiation have been finalized, including the definition of the study protocol, identification of key stakeholders, scientific advice with AEMPS, and an audit of the selected clinical site.
Autoimmune diseases represents a substantial healthcare challenge worldwide. Among these, Rheumatoid Arthritis (RA) stands as one of the most prevalent, affecting 86 M individuals globally. It is characterized by chronic pain, debilitating fatigue, and joint destruction, leading to significant limitations in daily life. Actual treatment options have advanced but they primarily focus on symptom management and immune suppression, lacking a cure. These therapies often result in side effects, elevating the economic burden of RA, with global costs estimated at €80 billion. RA's profound impact on patients, healthcare systems, and despite ongoing research efforts, there is still an urgency for innovative solutions to enhance patient well-being, reduce societal costs, and address the complexities of this autoimmune disease. Diamante offers a groundbreaking therapeutic approach called "Antigen-Specific Immunotherapy" (ASI). Unlike current non-specific treatments that lead to generalized immune suppression, ASI selectively targets self-reactive immune cells while preserving overall immune function. ASI boasts key features, including precise antigen targeting, immune tolerance induction, potential disease modification, reduced side effects, and the possibility of long-lasting effects. Our innovation lies in the use of "Virus Nanoparticles” (VNPs) derived from plant viruses displaying immunodominant peptides to enhance stability, solubility, and immunogenicity. These VNPs are produced through our proprietary "Plant Molecular Farming” (PMF) platform, a cost-effective, scalable, and versatile method with regulatory alignment. Our pre-clinical studies have identified a lead candidate for treating RA. By leveraging ASI and VNPs, Diamante revolutionizes RA therapy, providing a precise and transformative treatment that enhances patients' QoL while minimizing side effects. With our project we will go through the Phase I clinical trials and the establishment of the essential GMP facilities to produce our VNPs and launch our solution into the market by 2030