GNT-0003

Strong revenue generation in Q4 2023 including SEK 43m in Idefirix® product sales supported by growth in new markets such as U.K., Germany, and Spain Encouraging results from first-in-human trial of HNSA-5487 Initiation of phase 1b trial of imlifidase as pre-treatment to Sarepta's SRP-9001 in DMD LUND, Sweden, Feb. 2, 2024 /PRNewswire/ -- Hansa Biopharma, the pioneer in immunomodulatory enzyme technology for rare IgG mediated diseases, today announced its business update and year-end report for January to December 2023 . Highlights for the fourth quarter of 2023 Strong commercial performance. Total Q4 revenue of SEK 50m including SEK 43m in product sales and SEK 7m under our agreement mainly with Sarepta. Idefirix® sales were driven by growth in new markets such as U.K., Germany, and Spain. Medical guidelines and recommendations including use of Idefirix® implemented on a national level in Italy and Germany. NICE-01 phase 1 (HNSA-5487): Following positive results from the first-in-human trial of HNSA-5487, the lead candidate from the NiceR program for repeat dosing, an analysis of additional exploratory endpoints on IgG recovery and immunogenicity is being conducted for completion in 2024. AMR (antibody-mediated transplant rejection) phase 2: Full data published in December 2023. Imlifidase met the primary endpoint; explorative secondary outcome measures were not designed nor sufficiently powered to show statistical significance versus the control arm. GBS (Guillain-Barré Syndrome) phase 2: Positive high-level data announced in December 2023 as imlifidase demonstrated positive safety, tolerability, and early efficacy outcomes. Further analysis will contextualize the efficacy data. SRP-9001-104 phase 1b trial (Duchenne Muscular Dystrophy, DMD): The first clinical study with imlifidase as a pre-treatment to Sarepta's SRP-9001 gene therapy in DMD was initiated mid-December 2023. First patient is expected to be dosed in early 2024. On October 17, 2023, Hansa announced 5-year data from the long-term follow-up study of imlifidase, demonstrating 90% patient survival and 82% graft survival in extended pooled analysis with data from the 17-HMedIdeS-14 study. On December 5, 2023, Hansa announced plans to restructure the organization to better align and focus on key clinical development and commercial priorities. The planned restructuring should result in an approximately 20-25% reduction in the current workforce and will provide approximately SEK 75-85 million in annual savings, when fully implemented. Clinical pipeline update US ConfIdeS phase 3 trial (kidney transplantation): 104 patients have been enrolled with 40 of 64 targeted patients randomized in this pivotal U.S. open label, randomized, controlled trial of imlifidase in kidney transplantation. GOOD-IDES-02 phase 3 (anti-GBM disease): 18 of 50 targeted patients enrolled in this global pivotal phase 3 trial in anti-glomerular basement membrane (anti-GBM) disease. Completion of enrollment is expected in 2025. Investigator-initiated phase 2 trial (ANCA-associated vasculitis): 3 of 10 targeted patients enrolled. Events after closing period On January 6, 2024, Hansa and NewBridge Pharmaceuticals announced their partnership to enable supply of Idefirix® to kidney transplant patients in the Middle East and North Africa (MENA). On February 1, 2024, Hansa Biopharma and Medison Pharma announced positive reimbursement decision in Slovenia for Idefirix® in highly sensitized kidney transplant patients. With this, commercial access to Idefirix® has now been obtained in 14 European countries. First patient treated in the new Eurotransplant Desensitization Program, under the Acceptable Mismatch Program, which is intended to transform desensitization across eight European member countries including Germany, the Benelux and select Eastern European countries. Financial summary Søren Tulstrup, President and CEO of Hansa Biopharma, comments "Hansa enters 2024 in a strong position to successfully execute on our key priorities. I am encouraged by the performance of Idefirix® against key launch metrics and the continued progress we have achieved across our pipeline development activities. I am particularly excited about the encouraging first results from the first-in-human trial of HNSA-5487, Hansa's lead candidate in the NiceR program. It is our aim with this new enzyme to enable repeated infusions and thereby target diseases and conditions where either a prolonged IgG-free window or intermittent therapy is desirable. If successful, this new approach could enable innovative treatment approaches in a broad range of indications, including chronic auto-immune diseases. In kidney transplantation, we continue to see good commercial progress in Europe, including the implementation of treatment guidelines in both Italy and Germany and continued growth in the number of hospitals with desensitization protocols in place, while sales were supported by growth in key new markets such as U.K., Germany, and Spain. During the fourth quarter, we also saw increased patient identification through organ allocation systems such as Eurotransplant where both a first and second wave patient assessment took place with the new Desensitization Program. This new pilot program, under the Acceptable Mismatch Program, is intended to transform desensitization across eight European member countries including Germany, the Benelux and select Eastern European countries. In the U.S., we continue enrollment in the phase 3 ConfIdeS trial in kidney transplantation to accelerate randomization of patients. As previously guided, completion of randomization is expected by mid-2024, with a BLA submission expected in 2025 following a 12-month follow-up on kidney function, measured through the mean estimated glomerular filtration rate (eGFR). Beyond our core markets, we continue to expand access to imlifidase for highly sensitized kidney transplant patients through a new commercial partnership with NewBridge Pharmaceuticals in the MENA region. The new collaboration is rooted in the existing European conditional marketing authorization for Idefirix® and pending applications for marketing authorization in the respective MENA markets. Further, I am also pleased to see positive data from our long-term follow-up study further supporting the clinical benefit of imlifidase in kidney transplantation out to year five. The five-year data demonstrate graft survival in line with outcomes seen at 3-years post-transplant. Beyond kidney transplantation, we shared data read-outs from two phase 2 programs in AMR and GBS. In the AMR phase 2 trial (16-HMedIdes-12), imlifidase met the primary endpoint demonstrating statistically significant reduction in donor-specific antibodies (DSAs) observed among imlifidase patients within five days of treatment as compared to plasma exchange which is a common part of a standard of care treatment. While we are encouraged to have met the primary endpoint, it is important to note that the secondary endpoints were not met as the trial was not designed nor sufficiently powered to show a statistically significant difference between the two arms given the heterogeneity of patients, involving many patients with an additional cellular component of the immune rejection, and the small number of patients enrolled. Patients with an acute AMR may be best placed to benefit from a rapid and significant reduction in DSA levels. In the GBS phase 2 study (15-HMedIdeS-09), high level data was announced in December 2024 demonstrating that imlifidase was safe and well tolerated when administered prior to standard of care, including rapid improvement in disease-related efficacy measures. Further analysis of efficacy data will be conducted this year. In our pivotal phase 3 program in anti-glomerular basement membrane (anti-GBM) disease (GOOD-IDES-02), we continue to see good progress, with 18 of 50 targeted patients enrolled as of February 2, 2024. Completion of enrollment is expected in 2025. Further, I am happy to report that the first clinical study with imlifidase in gene therapy was recently commenced by our partners from Sarepta Therapeutics. In the phase 1b study, imlifidase is being investigated as a pre-treatment to Sarepta's FDA approved SRP-9001 (Elevidys) gene therapy in Duchenne Muscular Dystrophy (DMD). First patient is expected to be dosed in due course. Lastly, we recently announced plans to restructure the organisation to better align and focus on key clinical development and commercial priorities. This is expected to result in an approximate 20-25% reduction in the current workforce and will yield approximately 75-85 million SEK in annual savings when fully implemented. While we firmly believe this initiative is a necessary action to help us deliver on our important mission, it was obviously a difficult decision to take as it impacts our most valuable asset – our people. We are grateful for the commitment and relentless efforts of our colleagues who have worked tirelessly to advance potentially lifesaving medicines for people suffering from serious immunological diseases and conditions and we remain committed to supporting those colleagues impacted by the restructure. I look forward to keeping you updated on our continued progress, with several upcoming important milestones to be achieved across our platform and franchises in 2024." Upcoming milestones and news flow 2024 First high level data read-out from phase 1b study in DMD with Sarepta (NEW) 2024 GBS Phase 2: Outcome of the comparative efficacy analysis 2024 Genethon Crigler-Najjar Phase 1/2: Initiate clinical study with imlifidase prior to GNT-0003 2024 HNSA-5487: Further analysis around endpoints in FIH trial 2024 U.S. ConfIdeS (Kidney tx) Phase 3: Complete randomization 2025 U.S. ConfIdeS (Kidney tx) Phase 3: BLA submission 2025 Anti-GBM disease Phase 3: Completion of enrollment (NEW) Updated financial calendar 2024 Mar 20, 2024 Annual Report 2023 Apr 18, 2024 Interim Report for January - March 2024 June 27, 2024 2024 Annual General Meeting in Lund, Sweden July 18, 2024 Half-year Report January - June 2024 Oct 24, 2024 Interim Report for January - September 2024 Conference call details Hansa Biopharma will host a telephone conference Friday February 2, 2024, 14:00 CET / 8:00am EST. The event will be hosted by Hansa Biopharma's CEO, Søren Tulstrup, CCO, U.S. President, Matthew Shaulis, CSO Hitto Kaufmann and CFO, Donato Spota. The presentation will be held in English. Slides used in the presentation will be live on the company website during the call under "Events & Presentations" and will also be made available online after the call. To participate in the telephone conference, please use the dial-in details provided below: Sweden: +46 8 12 41 0952 UK: +44 203 769 68 19 USA: +1 646 787 0157 Participant access code: 765135 The webcast will be available on The year-end report and latest investor presentation can be downloaded from our web: Interim report January to December 2023 Investor road show presentation Q4, 2023 This is information that Hansa Biopharma AB is obliged to make public pursuant to the Securities Markets Act. For more information: Klaus Sindahl, VP Head of Investor Relations M: +46 (0) 709 298 269 E: [email protected] Stephanie Kenney, VP Global Corporate Affairs M: +1 (484) 319 2802 E: [email protected] About Hansa Biopharma Hansa Biopharma is a pioneering commercial-stage biopharmaceutical company on a mission to develop and commercialize innovative, lifesaving and life altering treatments for patients with rare immunological conditions. Hansa has developed a first-in-class immunoglobulin G (IgG) antibody cleaving enzyme therapy, which has been shown to enable kidney transplantation in highly sensitized patients. Hansa has a rich and expanding research and development program, based on the Company's proprietary IgG-cleaving enzyme technology platform, to address serious unmet medical needs in transplantation, autoimmune diseases, gene therapy and cancer. Hansa Biopharma is based in Lund, Sweden and has operations in Europe and the U.S. The Company is listed on Nasdaq Stockholm under the ticker HNSA. Find out more at hansabiopharma.com. The following files are available for download: SOURCE Hansa Biopharma AB

嘉宾阵容以及授课话题已曝光，点击图片查询，合作热线：王晨 180 1628 8769基因疗法通过修饰、操作或删除基因从而改变基因组的变化，有望解决传统小分子、抗体药成药性差或无法根治疾病的问题。在过去的十年间，基因疗法在癌症、遗传性疾病以及传染性疾病等多个领域的临床治疗中取得了突破性的进展。目前，针对传统方法无法治疗、预防或治愈的疾病，基因疗法让广大患者看到了“治愈”的希望。《医学新视点》为您盘点今年以来在《柳叶刀》（THE LANCET）、《新英格兰医学杂志》（NEJM）等医学顶刊发表的与基因疗法相关的研究，以飨读者。▲基因疗法整体上可以分为基因增补疗法（A）和基因编辑疗法（B）两类（图片来源：参考文献[4]）“首款”血友病B基因疗法数据公布，患者有望一针“治愈”！以往，中度至重度血友病B患者需要通过终生、持续的凝血因子IX替代治疗来预防出血事件的发生。Etranacogene dezaparvovec是全球“首个”血友病B基因疗法，可通过AAV5载体将凝血因子IX的Padua基因变异体（FIX-Padua）递送到肝内的靶细胞，产生比正常活性高5~8倍的凝血因子IX蛋白。一项发表于NEJM的开放标签、3期研究（HOPE-B研究）纳入了54例患有中重或重度血友病B的男性成年患者，并给予这些患者etranacogene dezaparvovec单次输注治疗。分析结果显示，患者在治疗后的几周内即可产生足够的凝血因子IX，且活性保持在较高水平。在研究导入期到治疗后的第7~18个月，患者的年出血率从4.19降到了1.51；凝血因子IX的活性在治疗后18个月随访时较基线上升了34.3%；94%的患者在接受治疗后两年内停止了所有预防性替代治疗，且患者健康相关生活质量显著改善。研究中未发现患者出现与治疗相关的严重不良反应。值得一提的是，etranacogene dezaparvovec还有望为患者提供持久保护。另外一项发表在Blood期刊上的临床研究数据表明，单剂量基因治疗能够为中度至重度血友病患者提供超过8年的充分保护。基因疗法面临的重要挑战之一：剂量选择CRISPR基因编辑技术的出现和应用，为遗传性疾病的治疗带来了前所未有的希望。杜氏肌营养不良症是一种X染色体隐性遗传疾病，由X染色体上编码抗肌萎缩蛋白的Dystrophin基因突变所致。全球大约每3500名新生男婴中就有1人罹患此病，患者通常在3~5岁时开始发病（最早表现出进行性腿部肌无力），并大多在20~30岁因呼吸和心脏衰竭而死亡。发表于NEJM的一篇论文显示，一位名叫Terry Horgan的杜氏肌营养不良症患者在接受重组腺相关病毒9型（rAAV9）载体递送的CRISPR基因编辑治疗（即CRD-TMH-001疗法）后不幸去世。该例患者在接受治疗后第6天出现急性失代偿性心衰并持续心脏骤停，并在2天后死亡。CRD-TMH-001疗法是“首款”个体化CRISPR基因编辑疗法，也是“首款”获批临床的治疗杜氏肌营养不良症的CRISPR基因编辑疗法。研究中患者接受的静脉注射剂量为1×1014 vg/kg。尸检结果显示，患者出现了严重的急性呼吸窘迫综合征伴弥漫性肺泡损伤，肝脏中转基因的表达极少，器官中也没有腺相关病毒9型（AAV9）抗体或效应T细胞反应方面的证据。这些发现提示，患者因为对高剂量的重组腺相关病毒（rAAV）产生的先天免疫反应而死亡。在定制腺相关病毒（AAV）基因疗法时，剂量的选择仍将是一个重要挑战。抗肌萎缩蛋白可能引起潜在免疫作用在另外一项NEJM发表的研究中，6例杜氏肌营养不良症患者接受了重组腺相关病毒2型（rAAV2）载体递送的功能性、微型、抗肌萎缩蛋白基因疗法。分析结果发现，治疗后患者体内可检测到抗肌萎缩蛋白特异性T细胞，提供了相关基因存在表达的证据（虽然研究人员并未在患者骨骼肌中观察到功能性蛋白）。不过，在输注载体治疗前，研究人员在2例患者中意外检测到循环抗肌萎缩蛋白特异性T细胞的存在。值得一提的是，分析还发现，回复突变体抗肌萎缩蛋白纤维（可通过缺失的内源性基因表达功能性、截短的抗肌萎缩蛋白）含有自身反应性T细胞靶向的表位。因此，未来我们在设计和监测杜氏肌营养不良症的实验性疗法时，还应当考虑T细胞对自身和非自身抗肌萎缩蛋白表位的潜在免疫作用。《柳叶刀》重磅综述：精准基因治疗的新时代《柳叶刀》发表的一篇综述详细总结了基因编辑技术的最新进展及其疾病治疗潜力（包括扩大治疗选择、使部分类型疾病的治疗成为可能）。该综述指出，基因疗法整体上可以分为基因增补疗法和基因编辑疗法两类。其中，基因增补疗法主要用于治疗由单一基因缺陷引起的遗传性疾病（如囊性纤维化、血友病和某些遗传性视网膜病变），该疗法通过向患者体内输送正常副本的基因，以补充缺失或不正常的基因，从而恢复其正常功能。此外，基因编辑疗法通过编辑技术（如CRISPR/Cas9）直接在患者的DNA层面上修改或修复缺陷基因，这种方法不是添加新基因，而是更改现有的基因序列。目前，基因编辑疗法还存在很多亟待解决的问题，但该疗法在不同医疗场景中具备着广泛的应用前景。肝脏代谢疾病中“首次”通过临床试验证明基因疗法的疗效今年，NEJM同样公布了在研基因疗法治疗克里格勒-纳贾尔（Crigler-Najjar）综合征的1/2期临床试验结果。Crigler-Najjar综合征是一种罕见的遗传性代谢疾病，由UDP-糖基转移酶1多肽A1（UGT1A1，一种特异性肝酶）缺乏引起，导致游离胆红素在血清和身体所有组织中潜在致死性蓄积，可在大脑中产生毒性。目前光疗（phototherapy）为标准疗法，但是患者可能需要每天接受长达12小时的光疗，对生活质量产生严重影响。而且随着年龄的增长，光疗效果下降，目前“唯一”的治愈方法为肝脏移植。GNT0003利用腺相关病毒8（AAV8）载体表达编码UGT1A1的转基因，旨在通过一次性治疗，让患者的肝脏细胞自己生成UGT1A1，降低胆红素的水平。在这项1/2期临床试验中，总计5名严重Crigler-Najjar综合征患者接受了不同剂量的GNT0003的治疗。她们在接受治疗前需要每天接受超过6小时的光疗来将血清胆红素水平控制在300 μmol/L以下。试验结果显示，接受最高剂量基因疗法治疗的3名患者的血清胆红素水平显著下降，即使在停止光疗之后，胆红素水平仍然维持在毒性水平之下，并且维持长达80周。论文指出，这是在肝脏代谢疾病中“首次”通过临床试验证明基因疗法的疗效。3期试验数据揭示血友病A基因疗法2年结局血友病A是由于凝血因子VIII缺乏而引起的一种罕见遗传性出血性疾病，以男性患者多见。血友病A患者通常自幼发病，有终生出血倾向，成年患者中残疾率高达80%。Valoctocogene roxaparvovec通过腺相关病毒2型（AAV5）载体，将编码凝血因子VIII基因的功能性拷贝递送到患者体内，从而帮助患者恢复自身凝血因子VIII生产能力。此前，开放标签、单组、多中心、3期研究GENEr8-1的1年分析结果显示，134例接受高剂量（6×1013 vg/kg）的valoctocogene roxaparvovec单次给药治疗的血友病A患者，平均年化出血率下降了了84%。最新发表在NEJM的2年期结果表明，相较于接受常规预防性治疗，经valoctocogene roxaparvovec转基因治疗的重度血友病A患者2年后的年化出血率显著下降（降低幅度为84.5%）。值得关注的是，17例已接受转基因治疗长达3年的患者，仍表现出稳固疗效。囊性纤维化患者治疗的新希望囊性纤维化是一种常染色体隐性遗传疾病，由囊性纤维化跨膜调节因子（CFTR）基因的致病突变引起，可影响全身每个器官系统。自30多年前发现CFTR基因缺陷以来，囊性纤维化治疗的格局正在不断发生变化。THE LANCET在“2023囊性纤维化专辑（Cystic Fibrosis 2023）”中发表的一篇文章指出，近10%的囊性纤维化患者不符合使用目前CFTR调节剂药物的条件，如何满足这些患者的治疗需求是一项巨大的挑战。目前临床科研人员正致力于通过基因替换和基因编辑策略，来满足目前不符合CFTR调节剂药物治疗条件、无法耐受现有CFTR调节剂药物的囊性纤维化患者的需求。这些治疗策略包括变异特异性核酸疗法（如针对剪接突变和无义突变的反义寡核苷酸）和变异不确定性核酸疗法（包括吸入CFTR mRNA和借助于病毒载体的CFTR基因递送疗法）。这种“无药可治”的疾病，或将迎来“治愈”的可能！镰状细胞病是一种常染色体隐性遗传病，由HBB基因（该基因编码成人血红蛋白[α2β2]的β球蛋白亚基）突变引起。镰状细胞病的症状通常在婴儿期出现，因为γ-球蛋白基因（HBG1和HBG2）转录转变为β-球蛋白（HBB），从而导致红细胞中胎儿血红蛋白（α2γ2）转变为成人血红蛋白。OTQ923是一种自体、离体CRISPR-Cas9编辑的CD34+造血干细胞产品，主要是通过CRISPR-Cas9系统对HBG1启动子、HBG2启动子或两者进行靶向破坏。发表于NEJM的一项研究表明，CRISPR-Cas9破坏HBG1和HBG2基因启动子是诱导胎儿血红蛋白表达的有效治疗策略。将自体OTQ923药物输注给三例患有严重镰状细胞病的受试者，可在随访6~18个月期间持续诱导胎儿红细胞血红蛋白，并从而改善疾病的临床症状。随访结束时，所有患者均已植入并稳定诱导胎儿血红蛋白表达（胎儿血红蛋白占总血红蛋白的百分比为19.0%~26.8%）。小 结总体而言，基因疗法在临床上具有广泛的应用前景，其在多种“无药可治”的疾病中都展现出了优异的治疗效果，有望改变未来疾病领域治疗格局，给患者带去“治愈”新希望。扫描下方二维码，将有机会获得由药明康德内容团队整理出品的《2023年度细胞基因疗法前沿进展白皮书》。参考资料（可上下滑动查看）[1] S.W. Pipe et al. Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B. NEJM. Doi: 10.1056/NEJMoa2211644[2] Angela Lek et al. Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne’s Muscular Dystrophy. NEJM. Doi: 10.1056/NEJMoa2307798[3] Jerry R. Mendell et al. Dystrophin Immunity in Duchenne's Muscular Dystrophy. NEJM. Doi: 10.1056/NEJMoa1000228[4] Axel Schambach et al. A new age of precision gene therapy. THE LANCET. Doi: 10.1016/S0140-6736(23)01952-9[5] D'Antiga L et al. Gene Therapy in Patients with the Crigler-Najjar Syndrome. NEJM. Doi: 10.1056/NEJMoa2214084[6] Johnny Mahlangu et al. Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A. NEJM. Doi: 10.1056/NEJMoa2211075[7] Simon Y Graeber et al. The future of cystic fibrosis treatment: from disease mechanisms to novel therapeutic approaches. THE LANCET. Doi: 10.1016/S0140-6736(23)01608-2[8] Akshay Sharma et al. CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease. NEJM. Doi: 10.1056/NEJMoa2215643免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文经药明康德内容团队「医学新视点」微信公众号（ID：HealthHorizon）授权转载。欢迎个人转发至朋友圈，未经授权不得二次转载。嘉宾阵容以及授课话题已曝光，点击图片查询，合作热线：王晨 180 1628 8769戳“阅读原文”立即领取限量免费参会名额!