FOSL2

As a malignant disease of the liver cells, hepatocellular carcinoma (HCC) is one of the main causes of cancer-related deaths. While the treatment options for this aggressive type of cancer remain limited, the incidence is increasing. A research team has now described a molecular signalling pathway that plays a key role in the development of liver cancer, thereby identifying a potential new starting point for the development of therapeutic treatments. As a malignant disease of the liver cells, hepatocellular carcinoma (HCC) is one of the main causes of cancer-related deaths. While the treatment options for this aggressive type of cancer remain limited, the incidence is increasing. A research team led by Latifa Bakiri and Erwin Wagner from MedUni Vienna’s Clinical Institute for Laboratory Medicine has now described a molecular signalling pathway that plays a key role in the development of liver cancer, thereby identifying a potential new starting point for the development of therapeutic treatments. The results of the study have just been published in the journal Proceedings of the National Academy of Sciences (PNAS). In their research, the international team led by MedUni Vienna, built on earlier study results that had suggested the involvement of certain transcription factors (c-Fos and c-Jun) in the development of hepatocellular carcinomas. Transcription factors are proteins involved in numerous cellular processes, including the control of genes associated with the development of HCC. To advance these findings, the scientists developed a new mouse model. The experiments carried out with these proteins showed that the combination with previously unexplored (Fra) proteins in this context triggers the cascade of tumour formation. Specifically, this involves the interaction between c-Jun and Fra-2, which the studies showed to be essential in the development of liver cancer. "It is remarkable that we were able to reverse tumour growth by switching off the protein combination of c-Jun and Fra-2," reports the head of the study Erwin Wagner. The study also showed that tumour growth can be stopped by blocking a specific gene (c-Myc). "Accordingly, our research results suggest that the molecular signalling pathway we have identified represents a promising starting point for further research into HCC and the development of new therapeutic measures," concludes first author Latifa Bakiri. Hepatocellular carcinoma is an aggressive tumour with rapid progression and limited therapeutic options. Even though the incidence has increased significantly in Western countries in recent decades, this type of cancer is still comparatively rare. However, due to its poor prognosis, HCC is one of the most common causes of cancer-related deaths. HCC occurs in particular in the context of advanced liver disease (cirrhosis, chronic hepatitis B) and is often only diagnosed at a late stage.

PRESS RELEASE Preclinical data in a transgenic mouse model shows beneficial effects on various clinical symptoms analogous to those observed in human systemic sclerosis.Findings may further support future clinical program. Mont-Saint-Guibert, Belgium, 20 March 2024, 7.00am CET – BioSenic (Euronext Brussels and Paris: BIOS), the clinical-stage company specializing in serious autoimmune and inflammatory diseases and cell therapy, presented the latest data on arsenic trioxide (ATO) for systemic sclerosis (SSc) at the 8th Systemic Sclerosis World Congress 2024. The data, obtained with the laboratory of Yannick Allanore, MD, Ph.D. from the Hospital Cochin, builds additional evidence for the use of ATO in multiple autoimmune conditions, as observed in various animal models and in recent pilot human clinical trials. The scientific communication presented by Anne Cauvet and Pr. Allanore demonstrated the efficacy of ATO in Fra2 transgenic mice, which is used as a disease model of symptomatic SSc, a chronic autoimmune disease marked by multi-organ fibrosis. BioSenic has previously showed that ATO, a first-in-class specific immunomodulatory drug, has significant therapeutic action in humans, and the company is progressing several formulations for autoimmune diseases in clinical trials. The researchers further reported that ATO resulted in significant lung histological changes, a trend towards a decrease in various fibrotic makers and a strong reduction in vascular remodeling in the SSc mouse model. The mechanism of action of ATO appears to involve a marked counteraction of the immune activation characteristic of SSc, particularly Tcell involvement. These positive findings have encouraged BioSenic to continue studying ATO for potential use in SSc. François Rieger, PhD, President of the Board and CEO of the BioSenic Group, said: “Our past data, including several animal models of autoimmune diseases and recent Phase 2 trials in systemic lupus erythematosus and chronic graft-versus-host-disease, have shown the remarkable therapeutic benefits of BioSenic’s liquid ATO solution for various autoimmune conditions with critical unmet medical needs. The more recent data for another serious autoimmune disease, systemic sclerosis, has given convincing preclinical evidence to support a Phase 2 trial for patients affected by this disease, which has no cure. The well-known safety of ATO’s pharmacologically active ingredient mean derived products, including an oral formulation (OATO), may follow FDA’s rapid 505(b)(2) regulatory path.” Understanding the mechanisms of action of arsenic on target cells is essential to determine the best conditions of use and possibly optimal combinations with other drugs. The work of several research teams worldwide has highlighted the autoimmunity-regulating, anti-fibrotic and vascular remodeling properties of arsenic, with potential to treat the lethal lesions in SSc and other autoimmune pathologies. Dr. Carole Nicco, BioSenic’s CSO and COO, said: "We are pleased to highlight these results, which complement previous findings in another preclinical model of non-genetic but induced-SSc. All our preclinical data, taken together, provide a coherent picture of the significant therapeutic effect we can expect in human patients suffering from severe chronic autoimmune diseases with unmet medical needs." The results were presented at the 8th Systemic Sclerosis World Congress last week in Prague, Czech Republic. About BioSenic BioSenic is a leading biotech company specializing in the development of clinical assets issued from its Medsenic’s arsenic trioxide (ATO) platform. Key target indications for the autoimmune platform include graft-versus-host-disease (GvHD), systemic lupus erythematosus (SLE), and now systemic sclerosis (SSc).Following the merger in October 2022, BioSenic combined the strategic positionings and strengths of Medsenic and Bone Therapeutics. The merger specifically enables Medsenic/Biosenic to develop an entirely new arsenal of various anti-inflammatory and anti-autoimmune formulations using the immunomodulatory properties of ATO/oral ATO (OATO).BioSenic is based in the Louvain-la-Neuve Science Park in Mont-Saint-Guibert, Belgium. Further information is available at http://www.biosenic.com. About the main Medsenic/BioSenic technology platform The ATO platform provides derived active products with immunomodulatory properties and fundamental effects on the activated cells of the immune system. One direct application is its use in onco-immunology to treat GvHD (Graft-versus-Host Disease) in its chronic, established stage. cGvHD is one of the most common and clinically significant complications affecting long-term survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Medsenic has been successful in a phase 2 trial with its intravenous formulation, Arscimed®, which has orphan drug designation status by FDA and EMA. The company is heading towards an international phase 3 confirmatory study, with its new, IP-protected, OATO formulation. Another selected target is moderate-to-severe forms of systemic lupus erythematosus (SLE), using the same oral formulation. ATO has shown good safety and significant clinical efficacy on several affected organs (skin, mucosae, and the gastrointestinal tract). Systemic sclerosis is now full part of the clinical pipeline of Medsenic/BioSenic. This serious chronic disease badly affects skin, lungs, or vascularization, and has no current effective treatment. Preclinical studies on pertinent animal models are positive, giving good grounds to launch a phase 2 clinical protocol, using new immunomodulatory formulations of APIs recognized to be active on the immune system. The company is currently focusing its present R&D and clinical activities on a selective, accelerated development of its autoimmune platform. Note: The allogeneic cell therapy platform-originating from the previous listed company Bone Therapeutics company, may be of renewed interest by using isolated and purified differentiated bone marrow Mesenchymal Stromal Cells (MSCs) as a starting material for further isolation of passive or active biological subcellular elements. Indeed, these cells may provide new subcellular vesicles potentially able to deliver a unique and proprietary approach to organ repair. BioSenic is now involved in determining new patentable approaches in this complex area of cell therapy. For further information, please contact: BioSenic SAFrançois Rieger, PhD, Chief Executive OfficerTel: +33 (0)671 73 31 59investorrelations@biosenic.com International Media Enquiries:IB CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency For French Investor Enquiries:Seitosei ● ActifinGhislaine GasparettoTel: +33 (0)1 56 88 11 22 ghislaine.gasparetto@seitosei-actifin.com Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the company or, as appropriate, the company directors’ current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the company nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.

Data demonstrated soquelitinib was active in six inflammatory/immune disease models and provides rationale for development in a range of additional Th2- and Th17-mediated diseases Soquelitinib’s unique mechanism of action inhibited the production of Th2 and Th17 cells, providing upstream attenuation of several validated cytokine targets such as IL-4, IL-5, IL-13, IL-17 BURLINGAME, Calif., Nov. 01, 2023 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today announced the publication of preclinical data that demonstrated the potential of ITK inhibition as a novel approach to treat T cell-mediated inflammatory and immune diseases. Corvus’ ITK inhibitors include soquelitinib (formerly known as CPI-818), which was used in the preclinical studies and is currently in clinical trials for oncology indications, and several next-generation molecules that are being optimized for use in a variety of inflammatory and immune disease indications. “Our research on soquelitinib and selective ITK inhibition is uncovering valuable new information about immune function and the role of ITK in different diseases,” said James Rosenbaum, M.D., senior vice president of research at Corvus. “The activity of soquelitinib in various inflammatory and immune disease models highlights the essential role of ITK in multiple T cell functions. Our publication demonstrates that soquelitinib can impact disease-associated cytokines by targeting the cellular sources, specifically Th2 and Th17 cells, which produce cytokines like IL-4, IL-5, IL-13 and IL-17. We believe that blocking the source of cytokine production upstream offers advantages over existing therapies that individually target specific cytokines.” Professor Yannick Allanore, M.D., Ph.D., Professor of Rheumatology, Université Paris Cité, Institut Cochin, Paris, France, and a co-author of the publication, said, “Pulmonary fibrosis and systemic sclerosis are often fatal diseases for which current therapy is inadequate. Soquelitinib utilizes a novel mechanism and was effective in our model related to systemic sclerosis which is based on Fra2 gene overexpression, a model designed to represent human lung disease manifestations. Based on these data, we are eager to evaluate soquelitinib in a clinical trial for fibrotic diseases.” The publication, entitled “Soquelitinib, A Selective Inhibitor of Interleukin- 2- Inducible T Cell Kinase (ITK), is Active in Several Murine Models of T Cell-Mediated Inflammatory Disease,” highlights data demonstrating that soquelitinib was active in six different models of T cell-mediated inflammatory and immune disease, including acute and chronic asthma, pulmonary fibrosis, systemic sclerosis (scleroderma), psoriasis, and acute graft versus host disease. The data also describe soquelitinib’s unique mechanism of action, providing rationale for the development of ITK inhibition in a range of additional Th2 and Th17 mediated diseases, including asthma, psoriasis, atopic dermatitis, chronic obstructive pulmonary disease (COPD), systemic sclerosis, lupus and other diseases. The published research was a result of collaborations between scientists at Corvus and researchers at both Memorial Sloan Kettering Cancer Center in New York and The National Institute of Health and Medical Research (INSERM) in France. The publication is now available online as a preprint at bioRxiv.org and on the Publications and Presentations page of the Corvus website. “We are making significant progress with soquelitinib and believe that Corvus is firmly positioned as a leader in the scientific and clinical development of ITK inhibition as a platform opportunity across cancer, inflammation and immune disease,” said Richard A. Miller, M.D., co-founder, president, and CEO of Corvus. “Our primary focus is treating T cell lymphomas and cancer and we are actively preparing for a registrational Phase 3 trial of soquelitinib for peripheral T cell lymphoma. With this new publication, we further demonstrate the wide range of opportunities for ITK inhibition across specific indications with ongoing patient needs for new therapies. In addition, we have a robust pipeline of next generation ITK inhibitors and a portfolio of intellectual property that we believe provide attractive partnering opportunities for companies focused on various inflammatory and immune diseases.” Key results from the preclinical studies described in the publication demonstrated that soquelitinib had the following observed effects in models of inflammatory disease: Acute and chronic asthma models: Significant reductions in Th2 cytokines IL-4, IL-5 and IL-13 in both models, along with reductions in a validated disease activity scoreReduction in IL-6 signifying amelioration of inflammation Systemic sclerosis (Fra2 gene overexpression) model: Improvement in clinical score and preservation of body weightImprovement in lung histology, reduction of fibrosis and improvement in pulmonary vascular hypertensionReduction of GATA3-expressing T cells, indicative of effect on Th2 cellsReduction of ROR gammaT cells (RORγT), indicative of effects on Th17 cells Pulmonary fibrosis (bleomycin-induced) model: More consistent reduction of pulmonary fibrosis compared to an FDA-approved medication (nintedanib)Similar reduction in GATA3 as the systemic sclerosis model resultsReduction in MMP2 and TGF beta, two messenger RNAs associated with fibrosis Psoriasis (imiquimod (IMQ)-induced) model: Improvement in epidermal thickness, erosion and inflammationIn vitro studies demonstrated a reduction in the expression of RORγT protein, a master transcription factor that is responsible for developing Th17 cells, and a corresponding dose-dependent reduction in IL-17 cytokine production Graft versus host disease (GVHD) model: Improvement in survival rates and corresponding decrease in clinical GVHD scoreNo impact on engraftment or graft-versus-tumor effect About Corvus PharmaceuticalsCorvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Corvus plans to initiate a Phase 3 registrational clinical trial for soquelitinib in patients with relapsed peripheral T cell lymphoma. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com. About SoquelitinibSoquelitinib (CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. The immunologic effects of soquelitinib lead to what is known as Th1 skewing and is made possible by the high selectivity of soquelitinib for ITK. Research on soquelitinib’s mechanism of action suggests that it has the potential to control differentiation of normal T helper cells and enhance immune responses to tumors by augmenting the generation of cytotoxic killer T cells and the production of cytokines that inhibit cancer cell survival. Soquelitinib has also been shown to prevent T cell exhaustion, a major limitation of current immunotherapy and CAR-T therapies. Optimal doses of soquelitinib have been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company plans to initiate a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed peripheral T cell lymphoma (PTCL). Forward-Looking StatementsThis press release contains forward-looking statements, including statements related to the potential safety and efficacy of the Company’s product candidates including soquelitinib, ciforadenant and mupadolimab; the potential use of soquelitinib to treat a variety of solid tumors and hematological cancers; the Company’s ability and its partners’ ability, as well as the timing thereof, to develop and advance product candidates through and successfully complete preclinical studies and clinical trials; the timing of and the Company’s ability to launch clinical trials including the potential registrational Phase 3 clinical trial for soquelitinib; and whether the Company is able to secure any partnerships or advance soquelitinib in any other indications. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Quarterly Report on Form 10-Q for the three months ended June 30, 2023, filed with the Securities and Exchange Commission on August 8, 2023, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of soquelitinib and its other product candidates; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials and release data from such studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the Company’s ability to enroll a sufficient number of patients in its clinical trials; the unpredictability of the regulatory process; regulatory developments in the United States, and other foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. INVESTOR CONTACT:Leiv LeaChief Financial OfficerCorvus Pharmaceuticals, Inc.+1-650-900-4522llea@corvuspharma.com MEDIA CONTACT:Sheryl SeapyReal Chemistry+1-949-903-4750sseapy@realchemistry.com