INSIDE INFORMATION
Combination of ATO with copper salts will allow BioSenic to work towards reducing the dosage of ATO in future trials overall and maintain efficacy
Mont-Saint-Guibert, Belgium, March 30, 2023, 7am CET – BIOSENIC (Euronext Brussels and Paris: BIOS), the clinical stage company specializing in severe autoimmune/inflammatory diseases and cellular repair, today announces that data providing additional details about the mechanism of action of its lead API arsenic trioxide (ATO) to prevent autoimmune diseases has now been published in a peer-reviewed paper. The article entitled “Optimal combination of arsenic trioxide and copper ions to prevent autoimmunity in a murine HOCl-induced model of systemic sclerosis” also details an original ATO formula to maximize efficacy in fighting autoimmunity and reducing side effects. The peer-reviewed paper is published in Frontiers in Immunology. This new formulation data has been completed following pre-clinical activities and does not constitute data validated through clinical trial. BioSenic has already demonstrated safety and efficacy of arsenic trioxide in clinical programs targeting Chronic Graft-versus-Host Disease (cGvHD), with a successful Phase 2 trial and a Phase 2a trial on systemic lupus erythematosus (SLE). BioSenic considers that the clinical data it has generated during the last two decades will be adequate for its trial submissions of new indications in the field of autoimmunity and inflammatory diseases. “BioSenic is making further significant progress in elucidating the fundamental mechanism of action of arsenic trioxide. Our company is in the process of further understanding the efficacy of arsenic trioxide in the treatment of various autoimmune diseases, where the pleiotropic effects of arsenic trioxide may contribute to significantly controlling and restoring a normal functioning immune system. This involves using ATO to manage the effects on the oxidative stress status of activated immune cells, on their ability to regulate the release of several pro-inflammatory cytokines or chemokines, or even on modulating the intensity of induction of inflammatory pathways, by directly interfering with regulatory proteins. This is done in order to get a better understanding on the way to positively interact with the pathophysiological, harmful mechanisms leading to chronic pathology in various autoimmune conditions. BioSenic has a number of forthcoming milestones across its clinical pipeline. This includes the launch of a Phase 3 trial in Chronic Graft-versus-Host Disease this year and a Phase 2b trial being prepared for systemic lupus erythematosus later on” said Francois Rieger, PhD, BioSenic's Chairman and CEO. “The publication of this new peer-reviewed paper details the mechanism of action of ATO combined with copper salts as well as an ideal formulation to maintain efficacy while reducing ATO side effects. This will be critical for further ATO clinical development, including a Phase 2b trial in systemic sclerosis, which is a rare chronic autoimmune disease with no significant therapeutic option. We look forward to a fast delivery of new clinical results on all these conditions for the market, our investors, and chronically ill patients.” The new peer-reviewed article also demonstrates that the efficacy of ATO is partly related to the generation of Reactive Oxygen Species (ROS), with a marked activation of oxidative cell phenomena and the ensuing selective deletion of activated -pathogenic- immune cells and fibroblasts. They improved the basic API’s efficacy by combining ATO with copper (Cu2+), a divalent cation, which has Fenton-like properties, explaining its capacity to increase oxidative cell stress. BioSenic combines ATO with copper chloride since they both cooperate to trigger the production of ROS. As a result, 50 percent less ATO is needed in combination with copper to observe the same efficacy as ATO alone to treat experimental SSc in a pre-clinical model. BioSenic’s CSO, Dr Carole Nicco, has had a decisive input in the understanding of the mechanism of action of arsenic trioxide, making a significant contribution to this paper and another published in Frontiers in Immunology in 2022 “A Fenton-like cation can improve arsenic trioxide treatment of sclerodermatous chronic Graft-versus-Host Disease in mice”. Biosenic ‘s work in this part of its pipeline is now oriented towards gaining further evidence for using the combination of ATO with copper salts to treat auto-immune diseases and other conditions. She also contributed to the first two papers along these lines, on cGvHD and SSc, as previously described by Kavian et al. (J Immunol 2012 May; Arthritis Rheum 2012 Oct). About BioSenic BioSenic is a biotech company focused on (i) the development of innovative products to address high unmet needs in orthopedics and (ii) exploiting the possibilities offered by the therapeutic use of arsenic salts (mainly arsenic trioxide (ATO) for patients with autoimmune diseases. Key target indications for the platforms include Graft versus Host Disease (GvHD), Systemic lupus erythematosus (SLE), Systemic Sclerosis (SSc) and high-risk tibial fractures and other orthopedics indications, such as osteoarthritis, by combining new and tested, IP protected, techniques.Following the merger in October 2022, BioSenic combines the strategic positionings and strengths of Medsenic and Bone Therapeutics. The merger also enables Biosenic to add to its innovative cell therapy platform and strong IP for tissue repair or protection with an entirely new arsenal of various anti-inflammatory and anti-autoimmune formulations using the immunomodulatory properties of 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 BioSenic technology
BioSenic’s technology is based on two main platforms: 1) The allogeneic cell and gene therapy platform, developed by BioSenic with differentiated bone marrow sourced Mesenchymal Stromal Cells (MSCs) that can be stored at the point of use in hospitals. Its current investigational medicinal product, ALLOB, represents a unique, proprietary approach to organ repair and specifically to bone regeneration, by turning undifferentiated stromal cells from healthy donors into bone-forming cells on the site of injury after a single local injection. These cells are produced via a BioSenic's scalable manufacturing process. Following the CTA approval by regulatory authorities in Europe, BioSenic has initiated patient recruitment for the Phase IIb clinical trial with ALLOB in patients with difficult tibial fractures, using its optimized production process. ALLOB is currently being evaluated in a randomized, double-blind, placebo-controlled Phase IIb study in patients with high-risk tibial fractures, using its optimized production process, after a successful first safety and efficacy study (Phase 1/2a) on fractured long bones, with late delayed union. The patient recruitment has been halted late February 2023 with 57 patients and the new rules permitted for statistical analysis should allow BioSenic to get the main results of this trial much earlier than anticipated in the original protocol, since they are expected by mid-2023. 2) The Arsenic TriOxide (ATO) platform developed by Medsenic. The immunomodulatory properties of ATO have demonstrated a double basic effect on cells of the immune system. The first effect is the increase of the cell oxidative stress in activated B, T or other cells of the innate/adaptative immune system to the point they will enter a cell death program (apoptosis) and be eliminated. The second effect is potent immunomodulatory properties on several pro-inflammatory cytokines involved in inflammatory or autoimmune cell pathways. One direct application is its use in onco-immunology to treat GvHD (Graft-versus-Host Disease) in its chronic, established stage. GvHD is one of the most common and clinically significant complications affecting long-term survival of allogeneic hematopoietic stem cell transplantation (allo-SCT). GvHD is primarily mediated by the transplanted immune system that can lead to severe multiorgan damage. Medsenic had been successful in a Phase II trial with its intravenous formulation, allowing arsenic trioxide to be granted an orphan drug designation status by FDA and EMA and is heading towards an international Phase III confirmatory study, with a new, IP protected, oral (OATO) formulation. Moderate to Severe forms of Systemic Lupus erythematosus (SLE) is another selected target, using the same oral formulation. ATO has shown good safety and significant clinical efficacy on several affected organs (skin, mucosae and the gastro-intestinal tract) in a Phase IIa study. Systemic Sclerosis is, in addition, part of the clinical pipeline of BioSenic. Preclinical studies on pertinent animal models are positive. This gives good grounds to launch a Phase II clinical protocol for this serious disease that badly affects skin, lungs or vascularization, and with no actual current effective treatment. In addition, BioSenic is developing an off-the-shelf next-generation improved viscosupplement, JTA-004, consisting of a unique combination of plasma proteins, hyaluronic acid - a natural component of knee synovial fluid, and a fast-acting analgesic. JTA-004 intends to provide added lubrication and protection to the cartilage of the arthritic joint and to alleviate osteoarthritic pain (OA) and inflammation. In March 2023, after the identification of new OA subtypes, BioSenic delivered a new post-hoc analysis of its Phase III JTA-004 trial on knee OA with positive action on the most severely affected patient population. This new post-hoc analysis changes the therapeutic profile of the molecule and potentially allows for the possibility of stratifying patients for a new, optimized Phase III clinical study. BioSenic, which does not intend to allocate R&D resources to support the clinical development of JTA-004 and will continue to focus its R&D activities on the development of its autoimmune (ATO) and cell therapy (ALLOB) platforms, is now seeking to collaborate with existing and potential partners to explore options for the future development of JTA-004 based on this new post-hoc analysis. For further information, please contact: BioSenic SAPr. François Rieger, PhD, Chief Executive OfficerTel: +33 (0)671 73 31 59investorrelations@biosenic.com For Belgian Media and Investor Enquiries:BepublicBert BouserieTel: +32 (0)488 40 44 77bert.bouserie@bepublicgroup.be For International Media Enquiries:IB CommunicationsNeil Hunter / Michelle BoxallTel: +44 (0)20 8943 4685neil.hunter@ibcomms.agency / michelle@ibcomms.agency For French Media Enquiries:NewCap MediaAnnie-Florence LoyerTel: +33 (0)1 44 71 00 12afloyer@newcap.fr For French Investor Enquiries:Seitosei ActifinGhislaine GasparettoTel: +33 (0)1 56 88 11 22ggasparetto@actifin.fr 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.
