Topas Therapeutics GmbH

Topas Therapeutics, a small German biotech company attempting to quell overactive immune systems, has revealed the first data from a study of its “tolerance induction” therapy for celiac disease. The results, to be presented at the Digestive Disease Week conference on Monday, come more than six months after Topas first declared success in the study via a press release , without divulging any data. The company discussed the therapy and shared the data with Endpoints News in an exclusive interview ahead of the conference, though many questions remain about the results. The 38-person trial focused on the safety of the company’s experimental nanoparticle treatment over seven weeks, its ability to steer immune cells toward a less inflammatory state, and patient-reported changes in gastrointestinal symptoms. Topas executives told Endpoints that the therapy was successful against those goals, even though granular data on safety and patient outcomes was missing from the presentation. They conceded that bigger and longer studies are still needed, but added that any relief from celiac disease would be a breakthrough. “There is both very much a medical need and big commercial opportunity in celiac,” Topas CEO Hugo Fry told Endpoints. Celiac disease is caused by an unwanted immune reaction to gluten, which is abundant in food. There’s no treatment or cure for the condition that, by some estimates, may affect as many as 1 in 100 people. Despite that, there are relatively few drug developers working on treatments. Topas is one of three companies, along with Anokion and Takeda, developing a potential immune tolerizing therapy in a Phase 2 study. Rather than merely tamping down on inflammation, the efforts aim to retrain the immune system to ignore triggers like gluten. “Tolerization is at that disease-modifying, almost curative end of the spectrum,” Fry said. It aims to do so by presenting nanoparticles decorated with tidbits of peptides that resemble the problematic parts of proteins that set off the immune system, known as antigens. For the celiac therapy, dubbed TPM502, the company uses three nanoparticles, each with a different antigenic peptide from the gluten protein. In many ways, the goal is opposite to that of a vaccine, which presents antigens to build the body’s reaction and create an immune response. Instead, Topas’ infused nanoparticles target specific cells in the liver that serve as a calming zone for T cells, where they learn to live peacefully alongside antigens that don’t warrant being attacked. “That’s the body’s natural hub of induced tolerization,” Fry said. “And it pushes them through that natural route.” Celiac was a good place to start looking for signals that the tolerization approach was working because doctors can easily provoke the immune system to flare up by having participants consume gluten, said Topas chief medical officer Cristina de Min. The company tested four doses of its nanoparticle therapy, ranging from 0.72 micromolar to 7.2 micromolar, in 26 patients. The other 12 patients got a placebo. Participants got the drug or placebo on day 1 and day 15 of the study and then consumed gluten a week later. De Min said that “the drug was remarkably safe,” largely resulting in side effects that resemble gluten consumption in celiac disease, including headache, pain, nausea and vomiting in 27 patients. But the company didn’t break this safety data down by side effect, or between participants who got the drug versus placebo. The company also said that there were three “grade 3” adverse events, the second highest severity, but didn’t say what they were. To get an idea of whether the treatment was working, Topas measured the release of the inflammatory immune protein IL-2 in response to being “challenged” with gluten. Only the highest dose of the therapy resulted in a significant decrease in IL-2 release. But when studying the gene expression of T cells before and after the therapy, the company found that all dose levels helped turn on genes that tamped down on inflammation and reduced genes that promoted inflammation. Topas also asked patients to rate their gastrointestinal symptoms before and after the treatment. The company said that people who got higher doses of the therapy had reduced symptoms, but the presentation was light on specific details. Topas emphasized that the study was not designed to test for efficacy. Another major caveat was the study’s strict inclusion criteria. Topas screened 391 people and recruited only one-tenth of them. Many prospective participants were excluded because they didn’t produce high enough levels of IL-2 in response to gluten consumption. “We wanted to make sure that only patients with measurable response would be involved,” de Min said. Even more patients were excluded because they didn’t have the certain immune system genotype that Topas focused on in this study. Topas is planning a Phase 2b study that will include a broader range of immune genotypes, accounting for 85% to 90% of people with celiac disease. Topas also wants to develop a tolerization therapy for type 1 diabetes, Fry said. But doing so will require more funding, and Fry is setting out to raise a €70 million Series D round. The company is currently funded through 2026 and isn’t planning to start a new study before then, he said.

The growing comprehension of the pathogenesis of celiac disease has paved the way for the exploration of alternative treatment strategies. These novel approaches are aimed at addressing the condition at its root cause, targeting the underlying mechanisms that trigger the immune response in individuals with celiac disease. These innovative approaches hold the promise of transforming the landscape of celiac disease treatment in the near future. LAS VEGAS, Nov. 19, 2024 /PRNewswire/ -- DelveInsight's ' Celiac Disease Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline celiac disease therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the celiac disease pipeline domain. Key Takeaways from the Celiac Disease Pipeline Report DelveInsight's celiac disease pipeline report depicts a robust space with 25+ active players working to develop 30+ pipeline therapies for celiac disease treatment. Key celiac disease companies such as Takeda, Sanofi, Entero Therapeutics, Pfizer, Topas Therapeutics, Anokion SA, Protagonist Therapeutics, Equillium, Theriva Biologics, Chugai Pharmaceutical, Novartis, Immunic, Mozart Therapeutics, Nemysis Ltd, Barinthus Biotherapeutics, Parvus Therapeutics, Kallyope, AMYRA Biotech AG, Forte Biosciences, LAPIX Therapeutics, Ahead Therapeutics, Allero Therapeutics, STEMCELL Technologies, IM Therapeutics, Provid Pharmaceuticals, Sigmoid Pharma, Janssen Biotech, Inc., Lumen Bioscience, IGY Life Sciences, Ahead Therapeutics, ANTOLRX, Imcyse, and others are evaluating new celiac disease drugs to improve the treatment landscape. Promising Celiac Disease pipeline therapies such as TAK-101, TAK-062, PRV-015, Latiglutenase, TAK-227, Ritlecitinib, TPM-502, KAN 101, PTG-100, EQ 102, SYN-020, DONQ52, CALY-002, IMU-856, MTX-101, E 40-02, VTP-1000, PVT-301, Research Program: Celiac disease, AMY02, FB 102, LPX-TIGI, AT 1718, ALL-001, SQZ TACs, Research Program: small molecule therapeutics, Research Program: DQ2/8, Research Program: SmPillformulations, Research Program: autoimmune disease therapeutics, IgY-112, AT 1715, Research programme: Celiac disease, and others are under different phases of Celiac Disease clinical trials. In October 2024, Topas Therapeutics announced positive topline results from its Phase IIa trial of TPM502, in patients with celiac disease. The study data serves as the first clinical proof of concept for Topas' proprietary nanoparticle platform and its potential to induce targeted, antigen-specific tolerogenic effects. In September 2024, Barinthus Biotherapeutics plc, a clinical-stage biopharmaceutical company developing novel immunotherapeutic candidates that guide T cells to control disease, announced the initiation of its first-in-human Phase I trial of VTP-1000 in adults with coeliac disease. In May 2024, Entero Therapeutics, Inc. (formerly First Wave BioPharma, Inc.) unveiled its new corporate name and website. The rebranding follows the recent business combination with ImmunogenX and reflects the Company's focus on addressing unmet needs in GI health that include celiac disease, an indication for which there are no approved medicines today. In March 2024, First Wave BioPharma announced the acquisition of ImmunogenX in an all-stock transaction with the combined company focused on advancing a GI pipeline comprised of multiple, late-stage clinical assets, including latiglutenase, a potentially first-in-class, near Phase III-ready, targeted, oral biotherapeutic for celiac disease. In February 2024, with the approval of the SQZ transaction, STEMCELL acquired substantially all of SQZ's assets including its entire portfolio of over 400 patents and trademarks, other intellectual property such as copyrights and trade secrets, proprietary equipment, and its head license with the Massachusetts Institute of Technology. In January 2024, Calypso Biotech BV announced that it had entered into an agreement to be acquired by Novartis AG ('Novartis'). Calypso's shareholders received an upfront payment of $250 million upon closing and are eligible to receive development milestones of up to $175 million based on the achievement of certain predetermined milestones. The acquisition gives Novartis full rights to CALY-002. Novartis intends to further explore CALY-002 across a wide variety of autoimmune indications with high unmet medical needs. Request a sample and discover the recent advances in celiac disease treatment drugs @ Celiac Disease Pipeline Report The celiac disease pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage celiac disease drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the celiac disease clinical trial landscape. Celiac Disease Overview Celiac disease is a chronic autoimmune disorder triggered by the ingestion of gluten, a protein found in wheat, barley, and rye. In individuals with celiac disease, the immune system mistakenly attacks the small intestine upon gluten consumption, leading to inflammation and damage to the intestinal lining, specifically the villi, which are essential for nutrient absorption. The exact cause of celiac disease is not fully understood, but it is known to involve a combination of genetic predisposition (usually associated with HLA-DQ2 or HLA-DQ8 genes) and environmental factors. Common symptoms of celiac disease include digestive issues such as diarrhea, bloating, gas, constipation, and abdominal pain. However, some individuals experience non-digestive symptoms, like fatigue, anemia, joint pain, skin rashes, and even neurological issues such as headaches or depression. Because of this broad symptom range, celiac disease is often underdiagnosed or misdiagnosed as other conditions. Diagnosis typically involves blood tests to detect specific antibodies (like tissue transglutaminase antibodies) and, if positive, is followed by an intestinal biopsy to confirm damage to the villi. Genetic testing may also be conducted in some cases to identify predispositions. The primary treatment for celiac disease is a strict, lifelong gluten-free diet. By avoiding gluten, individuals with celiac disease can heal intestinal damage and prevent symptoms and complications. However, adherence to this diet requires vigilance, as even small amounts of gluten can trigger symptoms and damage. Find out more about celiac disease treatment drugs @ Drugs for Celiac Disease Treatment A snapshot of the Celiac Disease Pipeline Drugs mentioned in the report: Learn more about the emerging celiac disease pipeline therapies @ Celiac Disease Clinical Trials Celiac Disease Therapeutics Assessment The celiac disease pipeline report proffers an integral view of the celiac disease emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Celiac Disease Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous, Parenteral, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Gliadin inhibitors, Gluten modulators, Transglutaminase 2 inhibitors, Emt protein-tyrosine kinase inhibitors, Janus kinase 3 inhibitors, Alpha4beta7 integrin antagonists, Interleukin 15 inhibitors, Interleukin 21 inhibitors, Alkaline phosphatase replacements, HLA-DQ antigen inhibitors Key Celiac Disease Companies: Takeda, Sanofi, Entero Therapeutics, Pfizer, Topas Therapeutics, Anokion SA, Protagonist Therapeutics, Equillium, Theriva Biologics, Chugai Pharmaceutical, Novartis, Immunic, Mozart Therapeutics, Nemysis Ltd, Barinthus Biotherapeutics, Parvus Therapeutics, Kallyope, AMYRA Biotech AG, Forte Biosciences, LAPIX Therapeutics, Ahead Therapeutics, Allero Therapeutics, STEMCELL Technologies, IM Therapeutics, Provid Pharmaceuticals, Sigmoid Pharma, Janssen Biotech, Inc., Lumen Bioscience, IGY Life Sciences, Ahead Therapeutics, ANTOLRX, Imcyse, and others. Key Celiac Disease Pipeline Therapies: TAK-101, TAK-062, PRV-015, Latiglutenase, TAK-227, Ritlecitinib, TPM-502, KAN 101, PTG-100, EQ 102, SYN-020, DONQ52, CALY-002, IMU-856, MTX-101, E 40-02, VTP-1000, PVT-301, Research Program: Celiac disease, AMY02, FB 102, LPX-TIGI, AT 1718, ALL-001, SQZ TACs, Research Program: small molecule therapeutics, Research Program: DQ2/8, Research Program: SmPillformulations, Research Program: autoimmune disease therapeutics, IgY-112, AT 1715, Research programme: Celiac disease, and others. Dive deep into rich insights for new drugs for celiac disease treatment, visit @ Celiac Disease Drugs Table of Contents For further information on the celiac disease pipeline therapeutics, reach out @ Celiac Disease Treatment Drugs Related Reports Celiac Disease Epidemiology Celiac Disease Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted celiac disease epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Celiac Disease Market Celiac Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key celiac disease companies including Entero Therapeutics, Amgen, Provention Bio, Takeda, among others. Sjogren's Syndrome Market Sjogren's Syndrome Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Sjogren's syndrome companies including Horizon Therapeutics (Amgen), Dompe Farmaceutici, Sylentis, MorphoSys, Resolve Therapeutics, OSE Immunotherapeutics, Servier, Novartis, Johnson & Johnson , among others. Sjogren's Syndrome Pipeline Sjogren's Syndrome Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Sjogren's syndrome companies, including Novartis, Horizon Therapeutics, Bristol-Myers Squibb, Rise Therapeutics, Resolve Therapeutics, Dompe Farmaceutici, among others. 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HAMBURG, Germany I October 15, 2024 I Topas Therapeutics today announced positive topline results from its Phase 2a trial evaluating lead candidate, TPM502, in patients with celiac disease. The study data serves as the first clinical proof of concept for Topas’ proprietary nanoparticle platform and its potential to induce targeted, antigen-specific tolerogenic effects. The international, multi-center, double-blind, randomized, placebo-controlled Phase 2a trial ( NCT05660109 ) was initiated in 2023 to investigate the safety, tolerability and pharmacodynamics of two infusions of TPM502 in adult patients with celiac disease. Pharmacodynamic parameters were assessed through a gluten challenge after patients received treatment with TPM502 or placebo. Initial analysis showed that antigen-specific markers of tolerance induction exhibited a clear dose-response that reached statistical significance. Further, these antigen-specific effects persisted throughout the study’s follow-up period. TPM502 was safe at all doses investigated. Topas intends to submit the full data and analysis for presentation at an upcoming scientific conference and for publication in a peer-reviewed journal. “This first look at the TPM502 Phase 2a data is an important milestone for the Topas team and our mission to demonstrate that our platform induces antigen-specific tolerogenic effects. The data generated in this study underscore the potential of this versatile, novel modality in a broad spectrum of autoimmune and immune-mediated diseases,” said Hugo Fry, CEO of Topas Therapeutics . “ We believe these results provide a valuable springboard to the next stage of development for Topas and position the company extremely well in the immune-tolerance space.” Topas’ lead candidate, TPM502, leverages the company’s proprietary platform, a nanotechnology-based modality designed to induce targeted, antigen-specific immune tolerance. TPM502 is comprised of a mixture of nanoparticles that carry the major gluten epitopes for HLA-DQ2.5, present in the majority of celiac disease patients. TPM502 has been developed to establish long-term immune tolerance that will offer significant therapeutic benefit to celiac patients, who currently have no treatment options. The initiation of the Phase 2a study for TPM502 builds on promising preclinical data and the excellent safety profile demonstrated in the Phase 1 study assessing Topas’ TPM203 in pemphigus vulgaris patients. The company’s next development steps for TPM502 will be based on the full data analysis. 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/ SOURCE: Topas Therapeutics