Balixafortide

Ad hoc announcement pursuant to Art. 53 LR Balixafortide, a potent CXCR4 inhibitor, to be evaluated for the treatment of pancreatic ductal adenocarcinoma (PDAC)Spexis closed capital commitments totaling USD $7.5 million supporting Phase 3 ColiFin® program in cystic fibrosis (CF) infectionsCOPILOT study expected to initiate in fourth quarter 2023Appointed Gonçalo Bernardes, PhD, as acting Head of Chemical BiologyAnnounced strong safety and pharmacokinetics results from first-in-human study with inhaled murepavadin, a novel macrocycle compoundEngaged Maxim Group LLC as M&A advisor to evaluate strategic transactions of which Spexis would be the surviving companyBusiness update conference call to be held in October ALLSCHWIL, Switzerland, Sept. 28, 2023 (GLOBE NEWSWIRE) -- Spexis AG (SIX: SPEX), a clinical-stage biopharmaceutical company focused on macrocycle therapeutics for rare diseases and oncology, today announced its financial results for the first half of 2023 and provided a strategic business update. “Spexis remains on track to deliver on the potential of our robust pipeline with multiple clinical development milestones on the horizon,” said Jeff Wager, M.D., Chairman & CEO of Spexis. “We anticipate initiating our Phase 3 ColiFin® program beginning with the COPILOT study in the fourth quarter supported by our financial partner on this program, SPRIM Global Investments. In addition, we have completed our initial analysis of further indication development potential for balixafortide. Based on our analysis, we are excited to announce balixafortide’s new focus on the treatment of PDAC where patients have long faced bleak and limited treatment options. Balixafortide’s well-documented and encouraging selective antagonism of the CXCR4 chemokine receptor and the new preclinical research illustrating its potential in PDAC have encouraged the company to focus our resources on the clinical development of balixafortide in this indication. We look forward to providing additional updates as our novel macrocycle derived pipeline continues to advance.” Pipeline status and plans The plans outlined below regarding the further development of various programs are subject to Spexis raising additional funds and/or entering into partnering agreements. Lead Program, ColiFin®: Spexis is committed to progressing its lead program ColiFin®, which is currently being developed to treat chronic lung infections in cystic fibrosis patients, but which also has strong therapeutic potential in non-CF bronchiectasis (nCFBE) and chronic obstructive pulmonary disease (COPD), as these patients also suffer from chronic Pseudomonas aeruginosa (PA) lung infections. ColiFin® has been approved in the EU as an inhaled therapeutic and holds Orphan Drug and QIDP designations in the U.S. The company has worldwide rights to ColiFin® ex-Europe and is preparing a Phase 3 program in CF patients which includes the COPILOT safety and tolerability trial, and the COPA efficacy trial. COPILOT is expected to initiate prior to the end of 2023. Capital commitments from SPRIM Global Investments (SGI) and additional institutional investors totaling USD $7.5 million to-date will enable the near-term initiation of COPILOT. The company’s clinical trial partnership with SGI, which includes debt facilities, is expected to provide Spexis with up to half of the Phase 3 clinical development costs of ColiFin®. Future milestones are contingent on securing additional capital and/or partnering agreements. Balixafortide: Today Spexis announced plans to pursue the clinical development of balixafortide, the Company’s potent and selective macrocyclic CXCR4 inhibitor, in PDAC, an aggressive form of pancreatic cancer with a poor survival rate. Balixafortide has been well-studied in clinical trials and has demonstrated a promising safety profile both as a monotherapy as well as in combination with other therapies. PDAC has been traditionally resistant to immunotherapy due to a combination of tumor microenvironment features unique to PDAC, but recent preclinical studies have shown the successful modulation of these factors using anti-CXCR4 antibodies, anti-programmed cell death protein 1 antibodies (anti-PD-1) and focal adhesion kinase inhibitors (FAKi). The combination of anti-CXCR4 antibodies, anti-PD-1 antibodies and FAKi led to a significantly decreased metastatic rates in a well-validated PDAC murine liver metastasis model. These results were subsequently validated substituting anti-CXCR4 antibodies for balixafortide. The synergistic effects of targeting PDAC with this regimen represents a unique opportunity for balixafortide to address the significant unmet need that has persisted in the fight against pancreatic cancer. PDAC accounts for more than 90% of pancreatic cancer diagnoses, and its poor survival rate is due to limited treatment options and the absence of an early diagnosis in many patients. The average 5-year survival rate is less than 10%, and pancreatic cancer represents an increasing and worrying proportion of cancer deaths. In 2023, the American Cancer Society projects over 50,000 patients will die of pancreatic cancer in the United States, the third-leading cause of cancer deaths. Despite a growing patient population, treatment options have remained limited, increasing the demand for novel therapeutics and approaches. Inhaled murepavadin (iMPV): Earlier in 2023, Spexis announced safety and pharmacokinetics results from the company’s first-in-human study with inhaled murepavadin, its novel macrocycle compound. Results indicated that iMPV was well tolerated at all dose levels and no serious adverse events were reported in the Phase 1 double-blind, randomized, placebo-controlled trial. iMPV was derived from Spexis’ macrocycle platform, validating its potential to generate clinically relevant therapeutics capable of drugging specific targets across a variety of rare diseases. The study was supported by the European Innovative Medicines Initiative (IMI), with iMPV successfully targeting the outer membrane of Pseudomonas aeruginosa, showing activity against highly resistant strains of bacteria. Spexis remains committed to addressing antibiotic resistance and progressing iMPV through the clinic. Macrocycle platform: Macrocycles remain a key differentiator at Spexis as this burgeoning area of drug discovery yields additional promise. The company’s leadership in the space represents an opportunity to yield novel therapeutics and the potential to combine macrocycles with a wide variety of complementary technologies, including, but not limited to, molecular glues and degraders. Spexis possesses two distinct, highly diverse and very well characterized macrocycle libraries, together with deep data on each: PEMfinder®, which is comprised of peptidomimetic macrocycles, and MACROfinder®, which are small molecule macrocycles. Each library has distinct applications depending on the targets involved, with several pre-clinical characterized leads for various indications having already been identified and characterized. As one example of the power of Spexis’ macrocycle platform, in June of this year, Spexis announced the publication of promising results for a novel class of macrocyclic, peptidomimetic antibiotics in Science Advances demonstrating potent in vitro and in vivo antimicrobial activity against MDR and XDR Enterobacteriaceae, including carbapenem-resistant and colistin-resistant strains. The novel antibiotics were developed by Spexis in close collaboration with Professor Oliver Zerbe’s group at the University of Zurich with substantial funding by Innosuisse and CARB-X. Corporate updates Spexis announced the appointment of Gonçalo Bernardes, Ph.D., as acting Head of Chemical Biology. Dr. Bernardes is a Full Professor of Chemical Biology and a Fellow of Trinity Hall College, Cambridge. He has co-founded companies using technologies developed in his lab and has been awarded three European Research Council grants, as well as awards from the Royal Society of Chemistry, International Chemical Biology Society, European Federation of Medicinal Chemistry and The Blavatnik Family Foundation. Dr. Bernardes also serves as a Senior Fellow at Flagship Pioneering, the largest global venture incubator. He completed his Ph.D. at the University of Oxford, U.K., and his postdoctoral work at the Swiss Federal Institute of Technology (ETH) in Zürich. Multiple discoveries made in his lab have been translated into leading biopharmaceutical companies. At Spexis Dr. Bernardes will focus his efforts on the company’s leading and proprietary macrocycle platform to produce novel therapeutics for the treatment of cancer and rare diseases. The Company expects to announce specific programs already in development in collaboration with Prof. Bernardes in the coming weeks and months. Financial results In the first half of 2023, Spexis’ total loss was CHF 3.9 million, primarily driven by research and development (R&D) expenditures of CHF 2.7 million. The total cash position was CHF 0.9 million (cash and cash equivalents) as of June 30, 2023. In August, Spexis closed additional capital commitments from SPRIM Global Investments and institutional investors totaling USD $2.5 million supporting the Phase 3 ColiFin® program in cystic fibrosis (CF) infections. Key figures1 CHF million Income Statement 30.06.2023 30.06.2022Total revenue0.00.0Research and development expenses-2.7-6.8Other operating expenses2-1.6-2.8Net loss for the period-3.9-10.0 Balance Sheet30.06.202330.06.2022Cash and cash equivalents0.91.8Total assets29.730.0Total equity17.319.4Average net cash burn30.51.0Number of FTEs2028Equity ratio in %5865 1based on consolidated IFRS financial statements 2net of other income 3represents the average monthly cash used in operating and investing activities The half year report 2023 is available for download on our website: Reporting* – Spexis (spexisbio.com) Spexis business update call to take place in October Management will provide a business and financial update, followed by a Q&A session. The specific date and time of said update shall be announced shortly. About Spexis Spexis (SIX: SPEX) is a clinical-stage biopharmaceutical company based in Allschwil, Switzerland, focused on macrocycle therapeutics for rare diseases and oncology. For further information please visit: www.spexisbio.com. For further information please contact: For Investors: Hernan LevettChief Financial OfficerSpexis AG.+41 61 567 16 00IR@spexisbio.com Or Stephen Jasper Managing DirectorGilmartin Groupstephen@gilmartinir.com For Media: Dr. Stephan FeldhausFeldhaus & Partner+41 79 865 92 56feldhaus@feldhaus-partner.ch Disclaimer This press release contains forward-looking statements which are based on current assumptions and forecasts of Spexis management. Known and unknown risks, uncertainties, and other factors could lead to material differences between the forward-looking statements made here and the actual development, in particular Spexis’ results, financial situation, and performance. Readers are cautioned not to put undue reliance on forward-looking statements, which speak only of the date of this communication. Spexis disclaims any intention or obligation to update and revise any forward-looking statements, whether as a result of new information, future events or otherwise.

关注并星标CPHI制药在线CXCR4（趋化因子受体4）是一种已被证实的治疗靶点，也称为融合素或分化簇184（CD184），属于G蛋白偶联受体（GPCR）家族的一员，CXCR4为7次跨膜蛋白，全长共有352个氨基酸。正常情况下，CXCR4可帮助激活免疫系统，并刺激细胞移动。但是，当激活受体的信号途径调控失常时，CXCR4可引起癌细胞生长及扩散。CXCR4对肿瘤的生长、侵袭、血管生成、转移和对治疗药物的耐受性起着重要作用。而且CXCR4的高表达还与许多癌症亚型的不良预后和化疗抵抗相关，部分是通过增强癌症和基质之间的相互作用。       CXCR4拮抗剂能够改变肿瘤与基质的相互作用，使癌细胞对细胞毒性药物敏感，减少肿瘤生长和转移负担。其作用机制主要为：通过调控免疫细胞迁移、减轻肿瘤浸润、激活免疫细胞以消除肿瘤细胞，以及减少肿瘤微环境中的免疫抑制细胞。因此，靶向CXCR4被认为是一种非常有吸引力的治疗策略。       CXCR4研究概况       目前，全球仅有一款CXCR4拮抗剂上市，即Mozobil（plerixafor，普乐沙福）。该药物由AnorMED公司开发，随后由赛诺菲收购。2008年12月，Mozobil获FDA批准上市，用于联合粒细胞集落刺激因子（G-CSF），动员非霍奇金淋巴瘤和多发性骨髓瘤病人的造血干细胞进入外周血，以供收集和进行之后的自体移植。2018年12月，Mozobil作为非霍奇金淋巴瘤患者的造血干细胞移植动员剂在中国获批上市。Mozobil通过阻断CXCR4和SDF-1（基质细胞衍生因子-1）的相互作用，将造血干细胞自骨髓释放至外周血循环。       Mozobil的上市为CXCR4拮抗剂的新药开发带来了信心，目前已有越来越多的药企加入CXCR4靶向疗法的研发中。       处于临床阶段的CXCR4靶向疗法（来源：Cortellis、公开资料）       Mavorixafor       Mavorixafor是一款口服CXCR4拮抗剂，由X4 Pharmaceuticals研发，用于治疗WHIM综合征。这是一种罕见的遗传性联合免疫缺陷病，由CXCR4/CXCL12通路的过度信号转导导致骨髓中白细胞的动员和运输减少所致。其特征是血液中的嗜中性粒细胞和淋巴细胞水平非常低，患者会经历反复感染以及易患某些类型的癌症。       Mavorixafor通过阻断CXCR4的过度激活信号来调节免疫细胞从骨髓释放到外周血中。在一项名为4WHIM3的全球性、随机、双盲临床试验中，评估了Mavorixafor在31例12岁及以上WHIM综合征患者中的疗效和安全性。       在经过52周的治疗后，结果显示，Mavorixafor在试验中耐受性良好，并达到了主要和次要终点。药物组患者体内中性粒细胞与淋巴细胞的绝 对数量维持在具临床意义阈值之上的时间，明显优于安慰剂组患者。试验完成后，约90%的安慰剂组患者选择在开放标签试验延期中接受治疗。       在国内，和誉医药已获得mavorixafor在大中华地区肿瘤及WHIM适应症的商业化权益，并将主导其大中华地区多个肿瘤适应症的临床与商业开发。       Balixafortide       Balixafortide是Polyphor公司利用其大环肽技术平台开发的一款在研CXCR4拮抗剂，拟开发治疗乳腺癌。Balixafortide已进入III期临床研究阶段。此前，Balixafortide联合甲磺酸艾立布林注射液的疗法已获得FDA授予的快速通道资格，该联合疗法在晚期HER2阴性乳腺癌患者中表现出了良好的疗效。       在国内，复星医药于2020年8月获得了Balixafortide在大中华区的独家权益，该合作首付款和里程碑付款总额高达1.82亿美元。       Motixafortide       Motixafortide是BioLineRx和Biokine Therapeutics共同开发的一种靶向CXCR4的短合成肽。Motixafortide通过抑制CXCR4的功能，能够影响免疫细胞运输、效应T细胞的肿瘤浸润，以及减少肿瘤微环境中的免疫抑制细胞，从而将"冷"肿瘤变"热"。在一项针对多发性骨髓瘤自体造血干细胞移植的III期GENESIS试验中，Motixafortide联合G-CSF疗法动员造血干细胞并达到所有主要及次要终点。目前，BioLineRx公司已与FDA完成pre-NDA会议沟通。若顺利获批，Motixafortide将成为全球第二款CXCR4靶向药。       此外，motixafortide还在针对晚期胰腺导管腺癌（PDAC）二线治疗的IIa期单臂试验中取得了积极结果。研究显示，motixafortide与抗PD-1抗体Keytruda和化疗联用表现出可喜的抗癌活性，能够为患者带来临床获益。在国内，劲方医药于2022年6月引进了motixafortide。       CGT-1881CGT-1881是盛世泰科自主研发的一款高效、高选择性的新一代CXCR4拮抗剂，它采用口服给药，具有更好的用药便利性和可及性。CGT-1881适用于非霍奇金淋巴瘤或多发性骨髓瘤患者动员造血干细胞进入外周血，以便完成造血干细胞的采集与自体移植。值得一提的是，CGT-1881在口服生物利用度和穿越血脑屏障等方面具有明显优势。6月2日，CGT-1881完成 I 期临床试验首例受试者给药。       目前，CXCR4拮抗剂作为干细胞动员剂已经在临床上得到广泛应用，随着越来越多靶向CXCR4的创新疗法在临床研究中取得突破，这类产品有望为肿瘤、罕见病等更多疾病领域带来更多治疗选择和获益。       参考来源：       1. Jacobson, O. and I.D. Weiss, CXCR4 chemokine receptor overview: biology, pathology and applications in imaging and therapy. Theranostics, 2013. 3(1): p. 1-2.       2. X4 Pharmaceuticals Announces Positive Top-Line Results from 4WHIM Global, Pivotal Phase 3 Trial of Once-Daily, Oral Mavorixafor in WHIM Syndrome. Retrieved November 30, 2022 from https://investors.x4pharma.com/news-releases/news-release-details/x4-pharmaceuticals-announces-positive-top-line-results-4whim.       3. 杨志峰,杨清玲,陈昌杰.趋化因子SDF-1与受体CXCR4的研究进展[J].分子诊断与治疗杂志,2011,3(01):58-61.       【企业推荐】智药研习社近期课程报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~