CSF-1R

Gilde Healthcare Leads Series B Extension, Joining Premier Syndicate of Leading Life Science Investors Funding Supports Registrational Phase 3 TANGENT Trial of Emactuzumab, a Best-in-Class CSF-1 Receptor Targeted Antibody, for the Treatment of Tenosynovial Giant Cell Tumour TANGENT Study Underway with First Patients Dosed DUBLIN, Ireland and OXFORD, United Kingdom, Oct. 30, 2024 (GLOBE NEWSWIRE) -- SynOx Therapeutics Limited (“SynOx”), a late clinical-stage biopharmaceutical company developing a novel treatment for CSF-1 related and macrophage-driven disorders, today announced that it has raised additional funding in a final close of its Series B financing. The Series B extension was led by new investor Gilde Healthcare and brings the total capital raised by SynOx in the round to $92 million including earlier investments from Forbion, HealthCap and Bioqube Ventures. Proceeds from the financing are supporting a registrational Phase 3 clinical trial of emactuzumab, a potentially best-in-class CSF-1 receptor (CSF-1R) inhibiting monoclonal antibody for the treatment of Tenosynovial Giant Cell Tumour (TGCT). In conjunction with the closing of the Series B extension, SynOx today announced that the first patients have been dosed in its Phase 3 registrational study of emactuzumab. The study, named TANGENT, is a global, multi-centre, randomized, double-blind, placebo-controlled Phase 3 trial designed to evaluate the efficacy and safety of emactuzumab in patients with TGCT. The study’s primary outcome measure is overall response rate (ORR). Investigators will also assess several secondary outcomes including functional and quality of life measurements, impact on tumour volume, and duration of response. Investigators expect to enrol approximately 130 patients in the trial. Additional study details can be found on ClinicalTrials.gov (Identifier: NCT05417789). TGCT is a rare, non-malignant but aggressively growing tumour of the synovium, primarily located in knee, hip, and ankle joints and caused by excessive production of CSF-1. It is a chronically debilitating disease for patients causing loss of function of the affected joints, pain, stiffness and limited range of motion. Emactuzumab specifically inhibits CSF-1R and earlier clinical work in TGCT1 showed it to be a highly effective, next-generation therapy with a short treatment cycle, rapid onset of action and long duration of response. “We are pleased to add Gilde Healthcare to our impressive investor syndicate and are appreciative for their support of our team and our vision for the potential of emactuzumab to address the unmet needs, and improve the quality of life, of TGCT patients around the world,” said Ray Barlow, Ph.D., Chief Executive Officer of SynOx. “The dosing of patients in the TANGENT trial marks an important milestone for SynOx and is a testament to the dedication and hard work of our team. We look forward to efficiently conducting this study and continuing to pursue our goal of advancing emactuzumab toward market for TGCT patients in desperate need of new treatment options.” As part of the Series B extension, Arthur Franken, general partner at Gilde Healthcare, will join the SynOx Board of Directors. Mr. Franken brings more than two decades of venture and growth capital investment expertise, including several public listings and trade sales. “We are pleased to join SynOx as an investor and help support the late-stage development of emactuzumab, which we believe has a best-in-class profile as a CSF-1R targeted antibody. Importantly, we also believe that the SynOx team is well positioned to successfully complete clinical development of emactuzumab and deliver this important treatment option to TGCT patients,” said Mr. Franken. About Tenosynovial Giant Cell Tumour (TGCT)Tenosynovial Giant Cell Tumour (TGCT), previously termed pigmented villonodular synovitis (PVNS), is a type of tumour that affects the soft tissue lining of joints and tendons. TGCTs are locally destructive and can be aggressive tumours. TGCT is a chronically debilitating disease which often impacts patients throughout their lives. It causes loss of function of the affected joints, pain, stiffness, limited range of motion and a significant impact on the quality of life as a result. Most patients receive surgical intervention, with three-year post-surgery recurrence rates in more than 50% of patients2. Symptoms typically progress slowly but can be aggressive and destructive. If left untreated complications include moderate to severe joint deformity, degenerative articular changes, and osteoarthritis, which if severe enough, can lead to cortical bone destruction and occasionally the need for arthrodesis or amputation. About CSF-1 and EmactuzumabCSF-1 (or macrophage colony-stimulating factor) is a cytokine that binds to the CSF-1 receptor(CSF-1R) expressed on macrophages and certain other cells, with effects on production, differentiation, and function of these cells. Emactuzumab is a humanised IgG1 CSF-1R targeted antibody that inhibits and depletes macrophages in the tumour tissue. Importantly, emactuzumab has the potential to offer a short course of treatment. The compound was originally discovered and developed by Roche and has been tested in several Phase 1/1b studies as a monotherapy and in combination with other agents, including chemotherapeutics and immunotherapies. In clinical studies as a monotherapy in 63 patients with TGCT, emactuzumab has shown a substantial effect on tumour response (ORR ~71%) while being well tolerated1. Phase I/II studies indicated good tolerability and a manageable safety profile and substantial preliminary efficacy in TGCT patients with rapid, robust tumour reduction, clinical benefit and durable response. Emactuzumab may also have utility in other macrophage-driven diseases, including graft-versus-host disease, and the company is actively considering potential options in these areas. About SynOx TherapeuticsSynOx Therapeutics Limited is a Dublin and Oxford-based, late clinical-stage biopharmaceutical company developing emactuzumab, a best-in-class monoclonal antibody against CSF-1R, for the treatment of Tenosynovial Giant Cell Tumour (TGCT) and other CSF-1 related and macrophage driven disorders. SynOx is led by an experienced team of industry professionals with a successful track record of developing and commercializing novel therapeutics. The company is backed by a strong syndicate of premier life science investors including Forbion, HealthCap, Bioqube Ventures, Gilde Healthcare and Medicxi. 1 Cassier et al., “Long-term clinical activity, safety and patient-reported quality of life for emactuzumab-treated patients with diffuse-type tenosynovial giant-cell tumour,” European Journal of Cancer 141:162-170, 2020.2 Lin F, et al. JHEOR, 2022.

PRESS RELEASE AB SCIENCE PROVIDES AN UPDATE ON THE DEVELOPMENT OF MASITINIB IN PROGRESSIVE FORMS OF MULTIPLE SCLEROSIS POST ECTRIMS 2024 Paris, 23 September 2024, 5.45pm CET AB Science SA (Euronext - FR0010557264 - AB) today provides an update on the development of masitinib in progressive forms of multiple sclerosis (MS), following the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 conference. The development of masitinib in progressive forms of multiple sclerosis is based on the MAXIMS study (AB20009), a randomized, double-blind, phase 3 study of masitinib 4.5 mg/kg/day in patients with primary progressive multiple sclerosis (PPMS) and non-active secondary progressive multiple sclerosis (nSPMS). The study enrolls patients with Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0, progression of disease for the last 2 years and absence of T1 Gadolinium-enhancing brain lesions. The primary endpoint of the study is the effect of masitinib on time to confirmed disability progression. The recent results of tolebrutinib in non-active secondary progressive MS presented at the ECTRIMS 2024 conference, reinforce the scientific hypothesis that targeting microglia in nSPMS is a valid approach. Tolebrutinib belongs to a class of drugs that target microglia through an enzymatic target called BTK (Bruton Tyrosine Kinase). Masitinib also targets microglia but through a different enzymatic target called M-CSFR1 (Macrophage Colony Stimulating Factor Receptor-1) and generated positive results in phase 2B (AB07002) [1], which are consistent with tolebrutinib data. EDSS progression confirmed at 3 months was reduced by 37% with masitinib in study AB07002 and by 23% with tolebrutinib in the Hercules study (although the reduction in study AB07002 did not reach the conventional 5% p-value since the study was not powered to detect a significant effect in this secondary endpoint, having 300 patients in the masitinib 4.5 or placebo arms as compared with 1100 patients in the Hercules trial).EDSS progression confirmed at 6 months was reduced by 32% with masitinib and by 31% with tolebrutinib. Importantly, Masitinib significantly improved manual dexterity measured by 9-hole Peg test, in study AB07002 (-4,28 ; p=0,0388).Masitinib has shown the ability to decrease serum neurofilament light chain (NfL) concentration in an animal model of MS, and by extension therefore, possibly neuronal damage [2].Masitinib not only targets microglia but also mast cells, which play a crucial role in progressive MS and in the experimental autoimmune encephalomyelitis (EAE) model of MS, as shown by numerous publications [3-13]. Masitinib benefits from a large safety database with long-term exposure across various indications. In non-oncology indications, around 2,200 patients have received at least one dose of masitinib, more than 1,300 patients have received masitinib for more than six months and close to 1,000 patients have received masitinib for more than one year. BTK safety profiles shows increase in liver injury, hypertension and infections which seem to be a class effect, leaving room for alternative drugs. As a conclusion, masitinib represents a potential credible alternative to BTK inhibitors in the development of new drugs both in primary and non-active secondary progressive MS. Professor Patrick Vermersch, MD, principal investigator of the MAXIMS study, Director of the Doctoral School Biology-Health of the University of Lille, commented: “Tolebrutinib data are important and pave the way to a series of new drugs in progressive forms of MS. Along with BTK inhibitors, masitinib represents a serious potential alternative in the two forms of progressive MS, primary and non-active secondary progressive MS, which remain the two unmet medical needs. The role of mast cells is not to be neglected in MS”. This new development fits well the strategy currently implemented for masitinib, as it further strengthens the scientific rationale for the development of masitinib in progressive forms of MS as well as the plausibility of the results generated with phase 2B/3 study AB07002. About the results of the previous phase 2B/3 study AB07002Study AB07002 met its primary analysis endpoint, demonstrating a statistically significant reduction in cumulative change on EDSS with masitinib 4.5 mg/kg/day (p=0.0256) [1]. This treatment-effect was consistent for PPMS and nSPMS. In addition, masitinib significantly reduced the risk of first disability progression by 42% and the risk of confirmed (3 months) disability progression by 37%. Masitinib also significantly reduced the risk of reaching an EDSS score of 7.0, corresponding to disability severe enough that the patient is restricted to a wheelchair (p=0.0093). The product's safety was consistent with the known risk profile of masitinib, with no elevated risk of infection. [References] [1] Vermersch P, Brieva-Ruiz L, Fox RJ, et al. Efficacy and Safety of Masitinib in Progressive Forms of Multiple Sclerosis: A Randomized, Phase 3, Clinical Trial. Neurol Neuroimmunol Neuroinflamm. 2022 Feb 21;9(3):e1148. [2] Hermine O, Vermersch P, et al. Masitinib limits neuronal damage, as measured by serum neurofilament light chain concentration, in a model of neuroimmune-driven neurodegenerative disease. Preprint. bioRxiv 2024.03.07.583695; doi: https://doi.org/10.1101/2024.03.07.583695 [3] Sandhu JK, Kulka M. Decoding Mast Cell-Microglia Communication in Neurodegenerative Diseases. Int J Mol Sci. 2021 Jan 22;22(3):1093. [4] Pinke KH, et al. Should mast cells be considered therapeutic targets in multiple sclerosis? Neural Regen Res. 2020 Nov;15(11):1995-2007. [5] Pinke KH, et al. Calming Down Mast Cells with Ketotifen: A Potential Strategy for Multiple Sclerosis Therapy? Neurotherapeutics. 2020 Jan;17(1):218-234. [6] Brown MA, Weinberg RB. Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease. Front Immunol. 2018;9:514. [7] Skaper SD, Facci L, Zusso M, Giusti P. An Inflammation-Centric View of Neurological Disease: Beyond the Neuron Front Cell Neurosci. 2018;12:72. [8] Hendriksen E, et al. Mast cells in neuroinflammation and brain disorders Neurosci Biobehav Rev. 2017;79:119-133. [9] Elieh-Ali-Komi D, Cao Y. Role of Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis. Clin Rev Allergy Immunol. 2017;52(3):436-445. [10] Conti P, Kempuraj D. Important role of mast cells in multiple sclerosis. Mult Scler Relat Disord. 2016;5:77-80. [11] Skaper SD, Facci L, Giusti P. Mast cells, glia and neuroinflammation: partners in crime?. Immunology. 2014;141(3):314-327. [12] Skaper SD, et al. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J. 2012;26(8):3103-3117. [13] Zappulla JP, Arock M, Mars LT, Liblau RS. Mast cells: new targets for multiple sclerosis therapy?. J Neuroimmunol. 2002;131(1-2):5-20. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment CP UPDATE ECTRIMS 2024. VEng VF

MONDAY, Sept. 23, 2024 -- For patients with recurrent or refractory graft-versus-host disease (GVHD), the colony-stimulating factor 1 receptor (CSF1R)-blocking antibody axatilimab results in a high incidence of overall response, according to a study published in the Sept. 19 issue of the New England Journal of Medicine . Daniel Wolff, M.D., from University Hospital Regensburg in Germany, and colleagues examined three different doses of axatilimab in a phase 2 study involving patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg, 1 mg, or 3 mg per kilogram of body weight every two weeks, every two weeks, and every four weeks, respectively (80, 81, and 80 patients in the 0.3-mg, 0.1-mg, and 3-mg dose groups, respectively). The primary end point was overall response in the first six cycles (complete or partial response). The researchers found that the primary end point was met in all dose groups; an overall response was seen in 74, 67, and 50 percent of patients in the 0.3-mg, 1-mg, and 3-mg dose groups, respectively. In the three dose groups, there was a reduction of more than 5 points on the modified Lee Symptom Scale in 60, 69, and 41 percent of patients, respectively. Dose-dependent transient laboratory abnormalities related to CSF1R blockade were the most common adverse events. "The study met its primary end point and showed the efficacy of axatilimab in patients across all three dose groups, with an overall response occurring in 50 to 74 percent of the patients," the authors write. The study was funded by Incyte and Syndax Pharmaceuticals, which manufacture and license axatilimab.