respiratory tract; infection, chronic

当前，各地感染者暴增，叠加冬春季流感高发，咳嗽咳痰等症状普遍存在。同时，止咳药市场集中度相对较低，药店该如何选品？患者又该如何选药？PART01冬春季流感高发，止咳用药市场旷阔12月14日，据国家卫健委官网消息，即日起不再公布无症状感染者数据，愈来愈多民众对“当好自身健康的第一责任人”有了更深感触。从北京市卫健委公布的北京市定点医院救治的本土新冠肺炎病例临床表现来看，咽干、咳嗽、咳痰是病例普遍存在症状。通常而言，即使非新冠感染，普通感冒、流行感冒、急慢性呼吸道感染、急慢性肺部感染、肺结核、哮喘等也会引起咳嗽，咳嗽作为呼吸道疾病中最为常见的症状之一，发病率非常高。轻微的咳嗽一般可自我痊愈， 但咳嗽往往连绵不断， 严重影响人的作息、 生活和工作，更重要的是，咳嗽长期不愈会对气管、支气管及肺部造成伤害，严重的可诱发哮喘，后果严重。此前几年，止咳品类发展增速较稳，2019年达到顶峰，后受疫情影响，整体销售额以及增长率均有所降低，但随着“四类药”，即退烧、止咳、抗病毒、抗生素类药品逐渐恢复正常销售，整个止咳用药市场发展也将进入较稳的增长阶段。尤其目前已进入冬春季节，气候变化下往往容易患呼吸道类疾病，因此，止咳用药销售情况也会更加乐观。PART02止咳中成药更受欢迎据米内网此前数据，止咳用药在零售药店约占5％的份额，是常用药物之一。在重点城市实体药店终端，止咳用药中成药与化学药的比例约为9：1，中成药占绝对优势。单从中成药市场来看，米内网预计2022年中国城市实体药店终端销售额超过1亿元的OTC药品有240个，合计销售额超过890亿元，其中化学药（含生物药）占94个，中成药占146个。146个销售额过亿的OTC中成药分布在13个大类，其中呼吸系统疾病用药上榜数量最多，共42个，而在呼吸系统疾病用药的子类中，共有16个止咳祛痰平喘用药上榜，超过感冒用药、清热解毒用药，是呼吸系统疾病用药中占比最大的子类。可见，中成药在止咳祛痰平喘领域备受消费者认可。PART03下一匹止咳药“黑马”会是谁？米内网数据显示，2019年中国城市实体药店终端呼吸系统中成药的销售规模在300亿元以上，同期公立医疗机构终端呼吸系统疾病中成药销售额超过400亿元。疫情爆发后，受客流量减少及防控政策等影响，该大类的销售规模在2020年开始逐步下滑，但随着2022年政策调整，预计呼吸系统疾病中成药在药店的市场份额会保持在20%以上，仍是实体药店终端最畅销的中成药品类。有零售药店药师反馈，在民众认知度方面，不同于感冒药中认知度一骑绝尘的连花清瘟、感冒灵，“止咳药没有特别火的”，整体市场集中度相对较低。智旗战略咨询预计，整个止咳祛痰平喘用药市场有望在2026年达到500亿，谁会是这一领域的下一匹“黑马”？日前，国家中医药管理局发布《新冠病毒感染者居家中医药干预指引》，针对五类成人常见症状发布治疗方案，其中连花清咳片被两次提及。连花清咳片是继连花清瘟之后，以岭药业于2020年5月获批上市的呼吸系统又一独家专利中药，宣肺泄热、化痰止咳，被市场视作连花清瘟的“姊妹药”。尽管“年龄不大”，但连花清咳已被多份国家级、省级诊疗方案推荐。不止是《新冠病毒感染者居家中医药干预指引》，此前，福建、北京、山东、湖北、河北、四川、重庆、黑龙江、山西等13个省（市）的新型冠状病毒肺炎中医药诊疗方案、流感中医药诊疗案中都有连花清咳的身影。PART04更对症的止咳中成药除新冠肺炎这一特殊情况外，连花清咳对于改善急性、慢性支气管炎等常见病引发的咳嗽咳痰症状同样有效。据悉，连花清咳片组方融汇自东汉张仲景《伤寒论》中麻杏石甘汤以及明代叶文龄《医学统旨》中清金化痰汤，合以清半夏、前胡清泄肺热，化痰止咳，山银花、连翘、牛蒡子清热解毒，透热达表，大黄通腑泄肺。从中医视角来看，该药组方依据“宣肺泄热，化痰止咳”为治法，顺应肺之生理特性，从而使邪气去，痰火消，咳嗽咳痰症状自然好转。一项《连花清咳片治疗急性气管-支气管炎的随机双盲、安慰剂对照、多中心临床研究》显示：连花清咳片组较对照组，患者的咳嗽消失率提高40.6%（49%:8.4%）；可有效缓解患者咯痰、咽干口渴、心胸烦闷等症状；临床用药安全，未出现与该药相关的不良反应。急性支气管炎的系列基础研究显示，连花清咳片止咳化痰起效迅速，能明显缩短单位时间内的咳嗽、咳痰次数，减轻气道炎症引起的气道高反应性，缓解气道痉挛，具有显著的镇咳作用。同时通过减少痰液分泌，稀释痰液黏度、促进痰液排出，来通畅呼吸道。在慢性支气管炎的基础研究中，连花清咳片同样表现出可降低慢性支气管炎的气道弹性阻力，提高肺顺应性，减少支气管及肺组织中中性粒细胞、炎性介质和细胞因子浸润，对减少气管损伤，控制气道炎症有良好疗效。咳嗽咳痰作为呼吸系统疾病最常见的症状，其用药市场规模在后疫情时代依然可观。连花清咳片入选国谈品种，医保目录，并连续登上由家庭医生在线、新生代市场监测机构联合发布的“中国家庭常备药上榜品牌”榜单，既能看出其疗效已获得众多医患认可，也体现了其在化痰止咳用药领域拥有较好的市场前景，具备成为“黑马”的潜力。

LAU-7b first inflammation-controlling drug to demonstrate clinical benefit in adults with CF, complementary to administration of CFTR modulators Study achieves clinically meaningful reduction in lung function loss at 6 months, measured as absolute change in ppFEV1, reaching statistical significance in the Per Protocol population MONTREAL--(BUSINESS WIRE)-- Laurent Pharmaceuticals Inc. (the “Company”), a clinical-stage biopharmaceutical company developing LAU-7b (oral fenretinide) as a first-in-class inflammation-controlling drug candidate for Cystic Fibrosis (CF), announces the presentation of results from its placebo-controlled Phase 2 APPLAUD 24-week clinical study in adults with CF at the North American Cystic Fibrosis Conference (NACFC) currently held in Philadelphia, United States. Study results achieved a statistically significant treatment difference in favour of LAU-7b in the absolute change in the percent predicted forced expiratory volume in one second (ppFEV1), the primary variable, through 24 weeks (1.23 percentage points; p=0.0486) in people that completed at least five months of treatment (Per Protocol population, N=122), and a clinically meaningful reduction of 49% in the loss of lung function at 24 weeks, relative to placebo. Statistically significant clinical benefit was also observed in the relative change in ppFEV1 through 24 weeks (2.34 percentage points; p=0.0351), as well as in the plasma levels of C-reactive protein (p=0.029), an important marker of systemic inflammation. Pre-specified subgroup analysis suggests a higher benefit in subjects with ppFEV1 greater than 70% at baseline, and the effect appears to be maintained in the subgroup of subjects already receiving CFTR modulators, including TRIKAFTA®. The results also passed robustness analyses, despite heterogeneous study population and pandemic interference. The study confirmed that LAU-7b has a predictable and acceptable safety profile, with no unexpected serious adverse events reported. “The potential clinical benefits of reducing the loss of lung function demonstrated with LAU-7b in the APPLAUD study, especially when administrated on top of CFTR modulators, are very promising and represent a first with a drug candidate addressing inflammation in adults with CF,” said Michael Konstan, MD, Vice Dean for Translational Research at Case Western Reserve University School of Medicine in Cleveland, and Co-Lead Investigator for the study. “It is really exciting to see this significant progress toward bringing medicines targeting loss of lung function in people with CF, an important and rather neglected aspect of this disease,” added Larry Lands, MD, PhD, Director, Pediatric Respiratory Medicine at McGill University Health Centre in Montreal, and Co-Lead Investigator for the study. “These results showed that the proposed LAU-7b treatment approach is complementary to CFTR modulation, confirming earlier preclinical research by McGill researchers demonstrating LAU-7b’s potential to rescue and preserve CFTR modulator’s effect during cellular stress.” “These results underscore the important clinical benefit potential of LAU-7b and Laurent’s commitment to delivering the next scientific breakthrough in this disease,” said Radu Pislariu, MD, President and CEO of Laurent Pharmaceuticals. “We want to thank all study participants and their families who put their trust in us, the staff at the clinical sites, the Cystic Fibrosis Foundation, and all our collaborators for their support and partnership throughout this study, conducted in unprecedented pandemic conditions.” The key outcomes from the study are presented in NACFC Poster #168, and were selected for oral presentation as part of the Session W21 (Evidence Based Medicine - Update on Clinical Trials in CF). About the Phase 2 APPLAUD clinical study APPLAUD was a double-blind, placebo-controlled study in adults with CF, randomized (1:1) to LAU-7b or placebo for 6 months. The goal of the study was to evaluate the safety of LAU-7b and its effect on preservation of lung function by reducing inflammation. Eligible subjects had ppFEV1 between 40% and 100% at screening and had had at least one pulmonary exacerbation (PEx) in the prior year. The study drug was administered orally once daily, in addition to standard of care, including all commercially available CFTR modulators. The primary efficacy endpoint was the absolute change from baseline in ppFEV1 at 24 weeks. Secondary endpoints included parameters related to PEx, systemic inflammatory and lipidomic biomarkers, and quality of life. Study randomized 166 adults with CF at 40 sites in the US, Canada and Australia, of which 122 completed a minimum five months of study medication (Per Protocol population). Both arms were very comparable in terms of age, BMI, gender distribution and lung function at baseline. The safety and efficacy pro this study supports the use of ppFEV1 as the primary efficacy variable for confirmatory studies, with longer treatment duration. About Cystic Fibrosis Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 people worldwide. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene and is characterized by viscous secretions in different exocrine tissues, and an aberrant inflammatory response leading to chronic pulmonary infection and loss in lung function over time. Severe pulmonary dysfunction is the primary cause of death in CF. About LAU-7b LAU-7b (oral fenretinide) is a novel drug candidate that acts on cell membrane lipids to modulate inflammation signaling and protein trafficking. Membrane lipid imbalance is believed to play a role in aberrant pulmonary inflammation in individuals with CF, leading to irreversible lung damage over time. Fenretinide was shown to correct the levels of certain membrane phospholipids and sphingolipids in multiple in vitro and in vivo models of CF, improving resolution of inflammation and the stabilization of CFTR in the epithelial apical membrane during inflammatory stress, a self-protective mechanism complementary to CFTR modulators. About Laurent Pharmaceuticals Laurent Pharmaceuticals is a clinical stage biotech company focusing on the modulation of cell membrane lipids for addressing life-threatening diseases. The company’s lead drug candidate, LAU-7b, is a proprietary oral formulation of fenretinide, an atypical retinoid with a well-documented safety pro in more than 3,000 patients. Existing data suggest that low-dose fenretinide has the potential to modulate certain membrane lipids and exerts antiviral, inflammatory-controlling, and antifibrotic properties. LAU-7b is currently being evaluated as a potential therapeutic for COVID-19 and Cystic Fibrosis. For more information, please visit .

Ad hoc announcement pursuant to Art. 53 LR Study start-up activities nearly complete for COPILOT, the first part of the Phase 3 ColiFin® program, including regulatory and ethics committee approvals of trial sites Enrollment of Phase 1 trial of inhaled murepavadin in healthy volunteers continues with top-line results expected by year-end 2022 Analysis of balixafortide PK/safety clinical trial in renally impaired subjects completed; results expected to be announced this fall Good progress in earlier-stage pipeline derived from macrocycle platform Variety of partnering and funding options continue to be vigorously explored Cash and cash equivalents of CHF 7.0 million as of June 30, 2022 expected to finance operations through January 2023 Renewal of the IRIS equity-linked financing facility for up to CHF 15m completed, which may extend cash runway as needed to achieve additional corporate partnering and financing milestones Conference call scheduled for today, Tuesday, September 6, 2022, at 8 AM EDT / 2 PM CET ALLSCHWIL, Switzerland, Sept. 06, 2022 (GLOBE NEWSWIRE) -- Spexis AG (SIX: SPEX), a clinical-stage biopharmaceutical company focused on rare diseases and oncology, today announced its financial results for the first half of 2022 and provided a strategic business update. “Despite the ongoing very challenging financial markets, we continue to make steady progress with Spexis,” said Jeff Wager, M.D., Chairman & CEO of Spexis. “Our two cystic fibrosis programs are proceeding as smoothly and as quickly as possible given market conditions, with inhaled murepavadin expected to generate top-line results by the end of 2022 and ColiFin® to begin Phase 3 testing in the first half of 2023, assuming sufficient funding.” He continued: “In addition, we continue to vigorously pursue a variety of financing, corporate partnering and strategic transaction possibilities to advance our portfolio and our macrocycle platform as a leader in this space.” 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®: The Company continues to focus its resources on its lead program ColiFin®, which is being developed for the treatment of chronic lung infections in cystic fibrosis (CF) patients. While the introduction of CFTR modulators in recent years has improved and extended the lives of CF patients, progressive lung function decline due to chronic lung infections remains a major problem and is projected to rise as patients live longer, further increasing the need for safe and effective therapies. ColiFin® is believed to also have strong therapeutic potential in non-CF bronchiectasis (nCFBE) and chronic obstructive pulmonary disease (COPD). A significant number of these patients suffer from chronic Pseudomonas aeruginosa (PA) lung infections, representing far larger markets than that of CF. Spexis has worldwide rights to ColiFin® ex-Europe and is focused on developing the product first for the U.S. market. Spexis is preparing a Phase 3 program in adult and adolescent CF patients with moderate to severe lung function impairment and chronic PA lung infection. The Phase 3 program includes the COPILOT safety and tolerability pilot clinical trial. Its objective is to evaluate and confirm the use of once or twice daily dosing for COPA, the planned single efficacy and safety Phase 3 trial. PA infection accounts for two-thirds of CF chronic lung infections and is the leading cause of lung function decline and mortality in CF patients. Prior to starting the COPILOT pilot trial or COPA Phase 3 trial with ColiFin®, Spexis needs to secure additional funding but is continuing to advance clinical trial readiness through a variety of internal and externally contracted clinical operations activities. In addition, as reported in July, the Company had originally planned to engage clinical trial sites in Ukraine and Russia. In view of the ongoing Ukraine war, the trial was expanded to sites in other countries. The process of site initiation is proceeding well, and the COPILOT trial is now planned to start in H1 of 2023, and aims to provide dosing data for COPA, which is now expected to initiate in H2 2023. Balixafortide, discovered from Spexis’ macrocycle platform, is a potent, specific and highly selective inhibitor of CXCR4, which plays a role in a number of tumor types as well as non-oncology indications. As reported in the Company’s July 28, 2022 update, Spexis is analyzing existing clinical and preclinical data with balixafortide to help determine the appropriate path forward for this program, including potential new indications, and recently published data demonstrating synergistic efficacy in combination with docetaxel in metastatic prostate cancer. These data and others in development will inform future decisions on the program. In addition, this fall, the Company expects to report the results of its recently completed safety/PK study of balixafortide in human subjects with renal impairment. This clinical trial was initiated pursuant to interactions with the FDA as a condition to potentially include such patients in any future labeling claim. The Company also expects to share additional data and more details on its development plan for balixafortide later in 2022. Inhaled murepavadin (iMPV), a novel inhaled therapeutic specifically targeting PA and discovered from Spexis’ macrocycle platform, is currently in a Phase 1 study in healthy volunteers to evaluate safety and tolerability of single and multiple ascending doses (SAD/MAD). The study is ongoing and top-line data are expected by the end of this year. Potential indications that could be eventually targeted with iMPV include CF, nCFBE and COPD in patients with chronic PA infection. OMPTA is another class of products derived from application of its macrocycle platform. Spexis was previously awarded funding from CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), a global non-profit partnership accelerating antibacterial products to address drug-resistant bacteria. This funding is to support the development of thanatin derivatives belonging to Spexis’ novel Outer Membrane Protein Targeting Antibiotic (OMPTA) class of therapeutics to potentially treat life-threatening infections caused by difficult-to-treat Gram-negative bacteria. This work is almost entirely funded by CARB-X, continues to move forward as planned, and was recently presented at the Gordon Research Conference New Antibacterial Discovery and Development event. Macrocycle platform Macrocycles are a proven chemical class of pharmaceutical therapeutics occupying the chemical space between small molecules and biologics. With a unique conformational balance of flexibility and rigidity, macrocycles can act on both extracellular and intracellular targets that are not easily accessible by other chemical classes. Indeed, since 2014, some 19 distinct macrocycle compounds have been approved by various drug regulatory authorities worldwide, involving a wide range of diseases and indications. More recently, with the emergence of the field of molecular glues and protein-protein interactions/degraders, macrocycles are increasingly recognized as possessing significant potential to target unique molecular targets and be combined with complementary technologies. Spexis possesses two distinct, highly diverse and very well characterized macrocycle libraries, together with deep data on same: PEMfinder®, which is comprised of peptidomimetic macrocycles, and MACROfinder®, which are small molecule macrocycles. Each library has distinct applications depending on the targets in question. In addition, Spexis has several pre-clinical leads for various indications which have already been considerably characterized. Spexis is looking to partner either these pre-clinical leads or the entire platform itself, potentially in combination with complementary technologies. Financial results In the first half of 2022, total loss was CHF 10.0 million, primarily driven by R&D expenses related to preparation of the ColiFin® Phase 3 program and other operating expenses. Total cash position was CHF 7.0 million (cash and cash equivalents) as of June 30, 2022, which is expected to finance operations through January 2023. On July 28, 2022, Spexis announced that it had renewed an equity-linked financing arrangement with the French company IRIS. The remaining CHF 13.6 million of the original agreement was replaced with a new equity-linked financing agreement which may raise, as needed, a gross amount of up to CHF 15.0 million over the period of two years. Key figures1 CHF million Income Statement 30.06.2022 30.06.2021 Total revenue 0.0 0.0 Research and development expenses -6.8 -0.3 Other operating expenses -2.8 -0.7 Net loss for the period -10.0 -1.0 Balance Sheet 30.06.2022 31.12.20213 Cash and cash equivalents 7.0 14.4 Total assets 40.0 50.0 Total equity 26.6 30.2 Average net cash burn2 1.3 0.2 Number of FTEs 27 28 Equity ratio in % 67 61 1) based on the consolidated IFRS financial statements 2) represents the average monthly cash used in operating and investing activities 3) Restated as a result of measurement period adjustments, refer to note 2.4 Business combinations of the half year report 2022, and correction of the presentation of Additional paid-in capital and Accumulated deficit, please refer to note 2.3 of the half year report 2022 The half year report 2022 is available for download on our website: Spexis H1 2022 financial results and business update call on September 6, 2022 at 14:00 CET/8:00 AM EDT Management will provide a business and financial update, followed by a Q&A session. To access the earnings call, please use the following details: France: Germany: Italy: Switzerland United Kingdom United States +33 (0)1 70 730 3 39 +49 (0)69 22222 5197 +39 02 0063 8217 +41 (0)44 580 7279 +44 (0)330 165 4012 +1 646-828-8073 Event Title: Spexis H1 2022 Financial Results and Business Update Confirmation code: 7688870 The presentation will also be available via webcast: Link for participants of the conference call (only slides, no audio, no delay): no-audio After the call, the presentation will be available via the above link. For further information please contact: For Investors: Hernan Levett Chief Financial Officer Spexis AG. +41 61 567 16 00 IR@spexisbio.com For Media: Dr. Stephan Feldhaus Feldhaus & Partner +41 79 865 92 56 feldhaus@feldhaus-partner.ch Raimund Gabriel MC Services spexis@mc-services.eu Europe: +49 89 210 228 0 Dr. Brigitte Keller/Laurie Doyle MC Services spexis@mc-services.eu Europe: +49 89 210 228 0 U.S.: +1 339 832 0752 About Spexis Spexis (SIX: SPEX) is a clinical-stage biopharmaceutical company based in Allschwil, Switzerland, focused on rare diseases and oncology. For further information please visit: . 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.