Journal: Molecular Therapy

Authors: Romain Hardet, Shu-Hung Wang, Sandrine Delignat, Marine Blandin, Reinaldo Digigow, Cornelia Gottwick, Markus Heine, Lígia Margarida Marques Mesquita, Marco Fanzutti, Anna-Lisa Vocaturo, Disha Mungalpara,  Olivier Boyer, Sébastien Lacroix-Desmazes, Sabine Fleischer, Sahil Adriouch

Summary

Liver sinusoidal endothelial cells (LSECs) naturally cross-present antigens and induce T cell tolerance. Targeting LSECs with peptide-coupled nanoparticles offers an efficient strategy to induce antigen-specific immune tolerance. Previous preclinical and clinical studies have shown that peptide-coupled nanoparticles can effectively inhibit T cell responses to the selected cognate peptide epitopes. However, clinical situations such as viral-vector-mediated gene therapy would benefit from simultaneous tolerance induction to multiple epitopes/antigens, posing a significant challenge. In this study, we used mouse models of adeno-associated virus (AAV)-mediated gene transfer to assess the in vivo effects of peptide-loaded nanoparticles designed to tolerize immune responses to transgene- or/and capsid-derived epitopes. We report here for the first time that LSEC-targeting nanoparticles coupled to a single peptide epitope promoted extension of tolerance to multiple relevant epitopes/antigens and simultaneously tolerized both CD4+ and CD8+ T cell responses. This tolerance spreading, which we termed “Tspread,” remained specific to the transgene- and capsid-derived antigens conveyed by the administered AAV vector and did not impair immune responses to an unrelated vaccine antigen. These findings delineate a novel LSEC-mediated tolerance spreading with important clinical implications for viral-vector gene therapy, where tolerance to multiple epitopes/antigens is essential for long-term expression of therapeutic genes.

Journal: Journal of Hepatology

Authors: Antonella Carambia, Barbara Freund, Dorothee Schwinge, Oliver T Bruns, Sunhild C Salmen, Harald Ittrich, Rudolph Reimer, Markus Heine, Samuel Huber, Christian Waurisch, Alexander Eychmüller, David C Wraith, Thomas Korn, Peter Nielsen, Horst Weller, Christoph Schramm, Stefan Lüth, Ansgar W Lohse, Joerg Heeren, Johannes Herkel

Summary

It is well-known that the liver can induce immune tolerance, yet this knowledge could, thus far, not be translated into effective treatments for autoimmune diseases. We have previously shown that liver sinusoidal endothelial cells (LSECs) could substantially contribute to hepatic tolerance through their ability to induce CD4+ Foxp3+ regulatory T cells (Tregs). Here, we explored whether the Treg-inducing potential of LSECs could be harnessed for the treatment of autoimmune disease.

We engineered a polymeric nanoparticle (NP) carrier for the selective delivery of autoantigen peptides to LSECs in vivo. In the well-characterized autoimmune disease model of experimental autoimmune encephalomyelitis (EAE), we investigated whether administration of LSEC-targeting autoantigen peptide-loaded NPs could protect mice from autoimmune disease.

We demonstrate that NP-based autoantigen delivery to LSECs could completely and permanently prevent the onset of clinical EAE. More importantly, in a therapeutic approach, mice with already established EAE improved rapidly and substantially following administration of a single dose of autoantigen peptide-loaded NPs, whereas the control group deteriorated. Treatment efficacy seemed to depend on Tregs. The Treg frequencies in the spleens of mice treated with autoantigen peptide-loaded NPs were significantly higher than those in vehicle-treated mice. Moreover, NP-mediated disease control was abrogated after Treg depletion by repeated administration of Treg-depleting antibody.

Our findings provide proof of principle that the selective delivery of autoantigen peptides to LSECs by NPs can induce antigen-specific Tregs and enable effective treatment of autoimmune disease. These findings highlight the importance of Treg induction by LSECs for immune tolerance.

Journal: Frontiers of Immunology

Authors: Shu-Hung Wang, Isabelle Serr, Reinaldo Digigow, Barbara Metzler, Alexey Surnov, Cornelia Gottwick, Muhammad Alsamman, Daria Krzikalla, Markus Heine, Miriam Zahlten, Agata Widera, Disha Mungalpara, Muharrem Şeleci, Marco Fanzutti, Lígia Margarida Marques Mesquita, Anna-Lisa Vocaturo, Johannes Herkel, Antonella Carambia, Christian Schröter, Dikran Sarko, Johannes Pohlner, Carolin Daniel, Cristina de Min, Sabine Fleischer

Summary

Journal: Immunology

Authors: Antonella Carambia, Cornelia Gottwick, Dorothee Schwinge, Stephanie Stein, Reinaldo Digigow, Muharrem Şeleci, Disha Mungalpara, Markus Heine, Fenja A Schuran, Carlotta Corban, Ansgar W Lohse, Christoph Schramm, Joerg Heeren, Johannes Herkel

Summary

Autoimmune diseases are caused by adaptive immune responses to self‐antigens. The development of antigen‐specific therapies that suppress disease‐related, but not unrelated immune responses in general, is an important goal of biomedical research. We have previously shown that delivery of myelin peptides to liver sinusoidal endothelial cells (LSECs) using LSEC‐targeting nanoparticles provides effective protection from CD4 T‐cell‐driven autoimmune encephalomyelitis. Here, we investigated whether this methodology might also serve antigen‐specific treatment of a CD8 T‐cell‐driven autoimmune disease. As a model for CD8 T‐cell‐mediated autoimmunity, we used OT‐1 T‐cell‐driven cholangitis in K14‐OVAp mice expressing the cognate MHC I‐restricted SIINFEKL peptide in cholangiocytes. To study whether peptide delivery to LSECs could modulate cholangitis, SIINFEKL peptide‐conjugated nanoparticles were administered intravenously one day before transfer of OT‐1 T cells; five days after cell transfer, liver pathology and hepatic infiltrates were analysed. SIINFEKL peptide‐conjugated nanoparticles were rapidly taken up by LSECs in vivo, which effectively cross‐presented the delivered peptide on MHC I molecules. Intriguingly, K14‐OVAp mice receiving SIINFEKL‐loaded nanoparticles manifested significantly reduced liver damage compared with vehicle‐treated K14‐OVAp mice. Mechanistically, treatment with LSEC‐targeting SIINFEKL‐loaded nanoparticles significantly reduced the number of liver‐infiltrating OT‐1 T cells, which up‐regulated expression of the co‐inhibitory receptor PD‐1 and down‐regulated cytotoxic effector function and inflammatory cytokine production. These findings show that tolerogenic LSECs can effectively internalize circulating nanoparticles and cross‐present nanoparticle‐bound peptides on MHC I molecules. Therefore, nanoparticle‐mediated autoantigen peptide delivery to LSECs might serve the antigen‐specific treatment of CD8 T‐cell‐driven autoimmune disease.

Journal: British Journal of Dermatology

Hamburg, Germany, May 6, 2025 – Topas Therapeutics presented positive clinical proof-of-concept data demonstrating gluten-specific tolerance induction in celiac disease (CeD) patients. Data from a Phase 2a clinical trial evaluating TPM502, 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, TPM502-treated patients reported a beneficial impact on symptoms post a gluten challenge. Developed using Topas’ proprietary platform, TPM502 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 TPM502 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, TPM502 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 2a study evaluated TPM502 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.[1] 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 TPM502 (from 0.72 μmol to 7.2 μmol total peptide dose) on day 1 and day 15. A total of 26 patients received TPM502 and 12 received placebo. The gluten challenge was repeated 7 days after the second administration of TPM502 or placebo. As reported in the DDW presentation, TPM502 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 TPM502 treatment at the highest dose, which was maintained throughout the study period of 1 month following the last TPM502 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 TPM502 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 TPM502-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.”

The abstract was selected for presentation in two sessions at DDW. Further details are listed below and available for registered attendees on the DDW conference website.

Session Title: American Gastroenterological Association (AGA) Clinical Science Plenary
Session Date & Time: Monday, May 5^th, 08:00 – 9:30 am PDT
Abstract Title: 621: Safety, Tolerability and Pharmacodynamic Effects of TPM502, a Mixture of Tolerizing Nanoparticles for Treatment of Celiac Disease (CeD)
Presenter: Knut 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

Session Title: AGA Presidential Plenary: AGA at its Best and the Best of AGA
Session Date & Time: Monday, May 5^th, 10:00 – 11:30 am PDT
Abstract Title: Sp832: Safety, Tolerability and Pharmacodynamic Effects of TPM502, a Mixture of Tolerizing Nanoparticles for Treatment of Celiac Disease (CeD)
Presenter: Knut 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

Hamburg, Germany, March 17, 2025 – 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.

Hamburg, Germany, October 15^th, 2024 – 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.

Hamburg, Germany, May 7th, 2024 – Topas Therapeutics, a clinical-stage biotech company developing novel antigen-specific immune tolerance therapies to treat autoimmune disorders, announced today the appointment of Hugo Fry as its new Chief Executive Officer. Bringing three decades of experience including senior management and executive roles at both large pharmaceutical and innovative biotechnology companies, Hugo has a significant track record in leading companies from early research and development through product commercialization.

“Hugo joins Topas at the right time to provide his broad expertise and strategic direction as we advance our mission of developing novel, disease-modifying treatment options for a range of autoimmune and inflammatory diseases,” commented Erich F. Greiner, Executive Chairman of Topas Therapeutics. “With data from a Phase 2a trial of lead candidate TPM502 in celiac disease expected later this year, we believe Hugo’s leadership will drive value for the company and fully leverage the potential of its innovative approach.”

“Topas is at the forefront of tolerance induction therapy with a cutting-edge nanoparticle technology platform designed to elicit immune tolerization in T-cell-mediated diseases,” said Hugo Fry, CEO of Topas Therapeutics. “As I take the helm, I am excited to advance the work of this talented team and look forward to leading Topas’ strategic efforts to progress our corporate and clinical development.”

Hugo Fry has an extensive and diverse career spanning three decades within the pharmaceutical and biotechnology sectors, characterized by strategic and leadership roles, including Chief Commercial Officer at Imbria Pharmaceuticals and Chief Business Officer and Managing Director at 20Med Therapeutics as well as CEO of RQ Biotechnology. With a focus on guiding companies toward success, Hugo has previously led R&D, Industrial Affairs as well as Commercial teams and is experienced in licensing, fundraising and forging strategic partnerships. He has also held several executive positions spanning multiple countries, including Managing Director of Sanofi UK and Ireland, and Vice President and Chief Marketing Officer for the Sanofi Pasteur MSD joint venture, along with being the Vice-President of the Association of the British Pharmaceutical Industry. Hugo holds a B.Sc. in Chemistry from the University of Salford and has completed further studies in Finance at London Business School and Leadership at Duke University.

• Building on positive clinical data from Topas’ Phase 1 study of TPM203 in pemphigus vulgaris patients, the Phase 2a study in celiac disease patients initiates clinical development for TPM502 and aims to achieve clinical proof of concept
• Recent leadership team expansion reflected by the additions of Christian Schröter as COO and Mireia Gómez-Angelats as CBO

Topas Therapeutics, a clinical stage biotech company developing novel antigen-specific immune tolerance therapies to treat autoimmune disorders, announced today the launch of a Phase 2a clinical study (NCT05660109) evaluating the safety, tolerability and pharmacodynamics of TPM502 in patients with celiac disease. Engineered leveraging the company’s Topas Particle Conjugates (TPCs) nanotechnology, TPM502 is a mixture of nanoparticles carrying gluten specific antigenic peptides comprising the major gluten epitopes for HLA-DQ2.5 present in the majority of celiac disease patients. The company has received approval to initiate TPM502’s clinical development in a Phase 2a study based on TPM502 preclinical data and clinical results from the Phase 1 study assessing Topas’ TPC TPM203 in patients with pemphigus vulgaris. Celiac disease is an autoimmune disorder affecting multiple millions of patients worldwide who suffer from symptoms ranging from mild digestive discomfort to severe long-lasting complications.

“The Phase 2a study will determine the capacity of TPM502 to promote immune tolerization in celiac disease patients and will confirm the safety profile of TPCs. It will also further establish the potential of the Topas platform to generate novel therapeutics for the treatment of T-cell-mediated diseases,” commented Cristina de Min, MD, Chief Medical Officer of Topas Therapeutics. “The development of TPM502 is a significant step forward in the advancement of our immune tolerance-based clinical pipeline and illustrates our mission to bring novel disease-modifying treatments to patients with limited pharmacological options.”

The multi-center, double-blind, randomized, placebo-controlled Phase 2a trial will include 42 adult patients diagnosed with celiac disease and will evaluate the safety, tolerability and pharmacodynamic effects of 2 administrations of TPM502 in dose escalating cohorts. Immune tolerance and symptom severity will be assessed following exposure to gluten. For more information on the Ph2a, please visit clinicaltrials.gov.

The company also announced two appointments to its executive management team. Mireia Gómez-Angelats, PhD, has joined as Chief Business Officer and Christian Schröter, PhD, as Chief Operating Officer, adding significant international pharmaceutical experience to Topas’ leadership as the company moves to mid-stage clinical development. Topas most recently welcomed Cristina de Min, MD, who joined the company as Chief Medical Officer at the end of 2021.

Erich F. Greiner, Executive Chairman at Topas Therapeutics commented: “Topas is moving at a fast pace with the initiation of its second clinical study. We look forward to adding Christian and Mireia´s expertise to the executive team. They each bring two decades of experience in the pharmaceutical industry, which will be invaluable as Topas advances its platform into clinical development.”

Prior to joining Topas Therapeutics, Dr. Christian Schröter worked at Merck Group for more than 20 years, in multiple countries and at increasing levels of responsibility. He was notably Head of Strategy, Global Healthcare Operations, and Senior Director, Pharma Business Integration. He obtained his PhD in immunology at the University of Tübingen.

Dr. Gómez-Angelats brings a track record of pharmaceutical experience from the US and Europe, in roles with increasing responsibilities in business development and R&D at Novartis, Bristol Myers Squibb, Johnson & Johnson and Almirall. Mireia holds a PhD in biochemistry and molecular biology from the University of Barcelona.

Biographies of Mireia Gómez-Angelats and Christian Schröter are available here.

About Celiac Disease

Celiac disease is an autoimmune disorder characterized by an aberrant immune reaction to ingested gluten that results in damage to the small intestine. It affects 1% of the population and manifests through a wide range of digestive as well as non-digestive symptoms. Diagnosed patients are limited to a gluten-free diet, nevertheless, in a third of cases, severe symptoms persist despite gluten avoidance. There is currently no available medical treatment for celiac disease.

About Topas Particle Conjugates

Topas Particle Conjugates are polymer-coated iron oxide nanoparticles comprising a proprietary biocompatible polymer and conjugated disease-relevant antigens. They are designed to deliver antigens to liver sinusoidal endothelial cells, which have potent immune-tolerogenic capabilities including triggering antigen presentation to T cells and tolerance induction. In clinical and preclinical studies, TPCs have elicited an outstanding safety profile and rapid clearance. The TPC platform has generated two clinical-staged drug candidates, TPM502 and TPM203, and has the potential to address multiple indications across the spectrum of autoimmune and inflammatory diseases.

Topas Therapeutics GmbH (Topas), a private biotechnology company developing immune tolerance-inducing drugs to treat and potentially cure a variety of autoimmune diseases, today announced the appointment of Cristina de Min, M.D., as Chief Medical Officer. In this position, she will be responsible for Topas’ clinical development programs based on its proprietary Topas Particle Conjugates technology platform, with a focus on lead product candidate, TPM203, currently in clinical development for the treatment of pemphigus vulgaris, and TPM502 for the treatment of celiac disease, which is expected to enter the clinic in the coming months.

Klaus Martin, Ph.D., Chief Executive Officer, said: “I am thrilled to welcome Cristina to Topas. She is a great addition to our team as she brings a wealth of experience from the translational stage of drug development through regulatory approval. Her strategic acumen combined with her hands-on approach will be invaluable as we move our programs through development and the regulatory process.”

Dr. de Min spent eleven years at Roche in various executive positions, including Life Cycle Leader for the development of the IL-6 receptor antagonist tocilizumab (Actemra) for rheumatic diseases. She also served as Medical Director of Roche’s affiliate in Italy, where she set up the medical department. This included creating a new structure based on therapeutic areas and defining and implementing new processes. Following her years at Roche, she joined Novimmune, serving for nine years as Chief Medical Officer before the company was acquired by Swedish Orphan Biovitrum (SOBI). At Novimmune, she set up the clinical development department and was responsible for the global development strategy for drug candidates from translational activities across all phases of clinical development and registration, as well as prioritizing the portfolio.

Cristina de Min, M.D., Chief Medical Officer, said: “I am excited to join the Topas team. I have been very impressed with the data generated to date with the Topas Particle Conjugates technology platform, which show the potential of the platform and the opportunity to bring more effective, potentially curative therapies to patients who today have limited treatment options. I look forward to working with the team to advance the product candidates in pemphigus vulgaris and celiac disease, as well as other programs in earlier stages of development, such as in rheumatoid arthritis and Type I diabetes.”

Topas Therapeutics GmbH (Topas), a private biotechnology company developing immune tolerance-inducing drugs to treat and potentially cure a variety of autoimmune diseases, today announced that the Company has successfully extended its Series B round with an additional €18 million (~$22 million) raised, bringing the total for this financing to €40 million. All of Topas’ existing investors participated in the extension.

The funding will be used to obtain clinical proof of concept in two programs and to accelerate the Company’s proprietary pipeline based on the Topas Particle Conjugates technology platform. In addition to lead program, TPM203, which is continuing in clinical development for the treatment of pemphigus vulgaris, a second product candidate, TPM502, is now slated to enter the clinic for the treatment of celiac disease by the end of this year.

Topas will also be advancing several of its pre-clinical-stage programs, including one for the treatment of rheumatoid arthritis and one for Type I diabetes. Topas’ novel technology induces antigen-specific immune tolerance by harnessing the liver’s natural tolerization capabilities. The Company is utilizing this platform to develop products for autoimmune diseases where better treatment options and cures are urgently needed.

Klaus Martin, Ph.D., Chief Executive Officer of Topas, said: “We are excited by the trust our investors are showing by participating in this extended financing round, recognizing our progress and underpinning their great belief in the potential of Topas’ innovative technology and programs. This strong support is enabling us to accelerate our product development work and to advance several programs in parallel. We look forward to seeing the first clinical results from our platform, expected later this year.”

Topas has raised a total of €58 million since its inception. The recent Series B extension is enabling the Company to accelerate the development of various autoimmune disease programs.

Erich F. Greiner, M.D., Chairman of the Supervisory Board, said: “I am very pleased and grateful that all of Topas’ investors decided to further strengthen the Company and its programs. We are delighted by the progress we have made to date with the Topas nanoparticle conjugate technology platform and eagerly await the first clinical results. Once clinical proof of concept is established, we see multiple opportunities for this unique and versatile platform to rapidly generate additional exciting programs in a variety of disease areas. The Topas technology has the potential to bring truly breakthrough products to patients with diseases of high unmet medical need for which there are currently no effective or curative treatment options.”

Topas Therapeutics GmbH (Topas), a Hamburg, Germany-based private platform company leveraging the natural immune tolerance induction capabilities of the liver, today announced the successful closing of a €22 million (~$26 million) Series B financing round. New investors Vesalius BioCapital III and BioMedPartners co-led this transaction, which included participation from all of Topas’ existing investors. The funding will be used to advance the Company’s proprietary pipeline based on the Topas Particle Conjugates technology platform. This includes progressing lead program TPM203, currently in clinical development for the treatment of pemphigus vulgaris, and bringing TPM501, Topas’ candidate for the treatment of celiac disease, into the clinic.

Klaus Martin, Ph.D., Chief Executive Officer of Topas, said: “I am particularly gratified to begin my tenure at Topas with the completion of a successful financing round. We are grateful for the ongoing support of our existing investors and are proud to have had such high calibre new investors participate. They share our belief about the strong potential of Topas’ innovative technology platform, and I am very happy to welcome them as new members of the Supervisory Board.”

Marc Lohrmann, Managing Partner of Vesalius Biocapital III, said: “We are delighted to join Topas Therapeutics in its Series B round and look forward to contributing to the future success of the Company. We are excited about the opportunities of the unique and versatile Topas tolerization platform and are highly committed to supporting the new CEO, Klaus, and the whole management team, to accelerate the development of the Company’s promising clinical programs.”

Michael Wacker, Ph.D., Partner of BioMedPartners, said: “The immune tolerance space is an area of untapped potential. We are impressed by the Topas Particle Conjugates technology and its potential to ameliorate and in some cases even cure a variety of immune-mediated diseases. Together with our fellow investors, we look forward to seeing the Company advance its lead program, TPM203, in the debilitating autoimmune disease, pemphigus vulgaris, as well as bring other programs forward into the clinic.”

Topas also today reported changes to the Company’s Supervisory Board, effective immediately:

In connection with the financing, Marc Lohrmann, Vesalius Biocapital III, and Michael Wacker, Ph.D., BioMedPartners both have joined the Supervisory Board.

Existing Board member, Erich F. Greiner, M.D., has become Chairman. Dr. Greiner is CEO and President of Cedrus Therapeutics Inc. and has served on the Topas Supervisory Board since June 2016.

Sebastian Kreuz, Ph.D. has replaced Detlev Mennerich, Ph.D. on the Board as representative of the Boehringer Ingelheim Venture Fund.

About BioMedPartners

Based in Basel, Switzerland, BioMedPartners is an independent European venture capital firm that acts as lead-or co-lead investor providing private equity to early-to mid-stage life sciences companies. Since 2002, BioMedPartners has invested in several highly innovative companies of which twenty-two have already either successfully been acquired by leading biopharma companies or have completed an IPO. With more than CHF 350 million in capital under management and a strong team of experienced industry experts as well as an extensive scientific and pharma network, BioMedPartners has established itself as one of the leading early-stage human healthcare investors in Europe. In February 2018, the company announced the closing of BioMedInvest III, their third equity venture capital fund of CHF 100 million. In this third fund BioMedPartners is focusing on the build-up of companies with highly innovative early stage assets and technology platforms. The first investment of BioMedInvest III was in the Swiss immuno-oncology company Amal SA (Geneva) which has been acquired by Boehringer Ingelheim in June 2019.

For more information, please visit www.biomedvc.com.

About Vesalius Biocapital III

Vesalius Biocapital (Vesalius), the specialist life sciences venture capital investor, has supported companies active in human health through venture capital funds since 2007. Since inception, Vesalius has raised over €260 million in three funds and contributed to the development of over 30 companies. The team consists of seasoned life science professionals with healthcare industry, corporate finance and strategy consulting experience, supporting companies through their growth cycle. The team is based in Europe and explores investment opportunities and valuation potential for the portfolio.

Vesalius Biocapital III, launched in April 2017, announced a final close with EUR 120 million in commitments in 2019. The fund targets later-stage European life science companies in drug development, medtech, diagnostics and digital health.

For more information, please visit www.vesaliusbiocapital-3.com.

“The initiation of the first clinical study with our lead product candidate is an exciting and at the same time value-generating step forward for Topas,” said Timm Jessen, PhD, Chief Executive Officer. “Pemphigus vulgaris is a well characterized disease with extensive knowledge on the most related autoimmune antigen and biomarkers available. It provides a very good setting to demonstrate the successful translation of our Topas Particle Conjugates platform into the clinic. While treatments do exist for this painful condition, there currently is no cure, and we look forward to advancing TPM203 with the goal of helping patients with this debilitating disease.”

The Phase 1 trial is an open-label study designed to evaluate the safety, tolerability, and pharmacokinetics of TPM203, as well as to explore early signs of effectiveness for TPM203 to induce antigen-specific immune tolerance in this patient population. The study has a single-ascending dose phase, followed by a multiple dose phase. The trial is planned to treat 24 patients and will be conducted at approximately seven sites in Germany; the coordinating investigator is Prof. Michael Hertl from the Dept. of Dermatology and Allergology at University Medical Center Marburg.

Topas Particle Conjugates technology platform harnesses the liver’s natural immunology capabilities
Topas’ technology platform harnesses the natural mechanisms of the liver to promote immune tolerance to blood borne antigens. Small peptide-loaded nanoparticles, Topas Particle Conjugates (TPCs), mimic such blood borne antigens and are taken up by liver sinusoidal endothelial cells (LSECs). LSECs present these antigens to T cells under anti-inflammatory conditions conducive to the induction of tolerogenic regulatory T cells (Tregs) and/or by other mechanisms. Tregs are pivotal for immune tolerance, and their in vivo generation serves to re-instate healthy immune balance (homeostasis) and provide a cure for diseases characterized by undesirable or dysregulated inflammatory immune reactions. The fast and active uptake of circulating TPCs by LSECs leads to rapid clearance of the particles from the bloodstream, allows an exact dosing of the antigen residing in the liver and avoids undesired immune reactions. TPCs provide major competitive advantages, including in vivo traceability, dose-ability, biodegradability and scalability along GMP requirements.

About Pemphigus Vulgaris
PV, an orphan disease, is an autoimmune condition involving a painful blistering on the skin and mucous membranes. If extensive, blistering can lead to life-threatening fluid loss, infection, and disfigurement. In this disease, patients have autoantibodies against desmogleins (proteins that play a role in connecting cells), which disrupt the connections between the squamous cells of the epidermis and cause blisters that can easily burst. Treatment consists of immunosuppressive agents; prognosis is variable, but many patients have a higher than normal mortality rate, and there is no cure.

Meet with Topas at following industry Events this spring

• 2^nd Antigen-Specific Immune Tolerance Drug Development Summit 2019. March 26-28, 2019, Boston, MA, USA
• TReg Directed Therapies Summit, May 20-22, 2019, Boston, MA USA
• 2019 German Biotech Days (Deutsche Biotechnologietage 2019), April 9-10, 2019, Würzburg, Germany
• 20^th Annual Bio€quity Europe, May 20-21, 2019, Barcelona, Spain

Topas Therapeutics GmbH (Topas), a Hamburg, Germany-based private platform company leveraging the natural tolerance induction capabilities of the liver, today announced that the Company will participate at several conferences this spring.

Learn more about the Topas Particle Conjugates (TPC) technology platform at these upcoming conferences:

2^nd Antigen-Specific Immune Tolerance Drug Development Summit 2019
March 26-28, 2019
Boston, MA, USA

Timm Jessen, PhD, Chief Executive Officer of Topas, will give a talk entitled, “Preparation of Liver-Targeting Nanoparticles for Clinical Trials,” on March 28^th at 10:30 AM EDT.

As the race to generate compelling clinical data to prove the concept of antigen-specific immunotherapies gains momentum, the conference seeks to help large pharma, biotech, and academic researchers overcome the complexity of auto-immune mediated disorders, expand opportunities through combination strategies and undertake a more precise and antigen-specific approach to novel drug development. Please click here for more details about the event.

TReg Directed Therapies Summit
May 20-22, 2019
Boston, MA USA

Sabine Fleischer, MD, Head of Translational Medicine of Topas, will give a presentation entitled, “Leveraging Tolerogenic Nanoparticles to Induce Antigen-Specific Immune Tolerance in vivo,” on May 22^nd at 2:15 PM EDT.

The conference is dedicated to the clinical translation of engineered and stimulated cell therapy and small molecule approaches to deliver cures for autoimmune and inflammatory indications. For more information, click here.

Meet with Topas management at these industry events:

2019 German Biotech Days (Deutsche Biotechnologietage 2019)
April 9-10, 2019
Würzburg, Germany

Topas will attend this event. To request a meeting, please contact Dr. Timm Jessen at jessen@topas-therapeutics.com.

The 2019 German Biotech Days event is co-organised by BIO Deutschland and the Council of German BioRegions and provides a forum for all stakeholders in Germany’s biotech scene to exchange views and experiences. The conference is a meeting place for more than 850 representatives from business, science and government, including partners from funding institutions and public administration. The conditions for innovation in biotechnology and the wide range of biotech applications will be discussed through a series of talks, panel discussions and breakfast sessions. For more information, please click here.

20^th Annual Bio€quity Europe
May 20-21, 2019
Barcelona, Spain

Topas will give a corporate presentation and host 1X1 meetings at this event. To request a meeting with Topas, please sign up through the event’s partneringONE meeting system or contact Dr. Timm Jessen at jessen@topas-therapeutics.com. Bio€quity Europe is the seminal industry event for financial dealmakers looking for investor-validated life science companies positioning themselves to attract capital and for pharmaceutical licensing professionals to assess top prospects. Bio€quity Europe has showcased more than 800 leading European companies to thousands of investment and pharma business development professionals. Delegates from 24 nations attended the 2018 event. More information on the event can be found here.

• Sachs 18 th Annual Biotech in Europe Forum
• BIO-Europe® 2018
• Meetings around JP Morgan 36 th Annual Global Healthcare Conference
• Immunology of Diabetes Society Congress 2018
• Antigen-Specific Immune Tolerance Europe Conference

Hamburg, 27^th September 2018 – Topas Therapeutics GmbH (Topas), a Hamburg, Germany-based private platform company leveraging the natural tolerance induction capabilities of the liver, today announced that the Company will participate at the following conferences this fall:

Meet with Topas at the following industry events: