SiSaf Ltd.

Positive topline results in a Phase II clinical trial of a licensee’s alopecia treatment using the ProSilic® variant of SiSaf’s Bio-Courier® delivery technology Formulation of the small molecule drug with ProSilic has demonstrated its ability to deliver novel formulations that address stability, efficacy and side effect issuesLicensee’s product could become the first approved therapy and standard of care for mild to moderate alopecia areata, which represents over half of the estimated 800,000 alopecia areata (AA) patients in the USResults demonstrate the wider partnering opportunities for topical Bio-Courier delivered products in dermatology and other indications such as ophthalmology GUILDFORD, United Kingdom, June 10, 2024 (GLOBE NEWSWIRE) -- SiSaf Ltd, a biopharmaceutical company that has developed a range of proprietary Bio-Courier® drug delivery technologies, today announced that a licensee of the ProSilic® variant of its technology has reported positive topline results from a randomised, placebo-controlled, multi-dose Phase II trial evaluating its topical treatment for mild to moderate (patchy) alopecia areata (AA), commonly known as spot baldness. This demonstrates the ability of SiSaf’s technology to deliver innovative new formulations that address stability, efficacy and side effect issues. The API in the licensee’s drug product is a small molecule with a well-established safety profile in dermatology, which works through modulating the inflammatory response and the proliferation of T-cells by disruption of the signalling pathways. However, until now the instability of the molecule and its side effects have limited its efficacy and therapeutic application. Formulation with Bio-Courier technology has helped overcome these limitations and has transformed the molecule into a highly effective drug. Dr Suzanne Saffie-Siebert, PhD, founder and Chief Executive Officer of SiSaf said: “We formulated the molecule with ProSilic, one of the variants of our Bio-Courier delivery platform. This has stabilized the drug and has enabled controlled drug release, which reduces the molecule’s oxidative reactivity and boosts its anti-inflammatory potential. ProSilic also improves permeation into the skin epidermis and the hair follicle bulb target.” “Among the range of Bio-Courier technologies, ProSilic is particularly well suited for dermal applications, such as seen here in treating spot baldness. By addressing the key drawbacks of the API, ProSilic creates a highly effective treatment option for Alopecia Areata – as indicated by the Phase II data.“ The Phase II study results announced by SiSaf’s licensee saw 158 participants with mild or moderate AA receive one of four doses - ranging from 0.25% to 2% — or placebo applied over 24 weeks. Around 76% of the 1% dose cohort met the study’s primary endpoint of a more than 30% improvement in severity of alopecia. 18% and 27% of the 1% and 2% dose cohorts, respectively, saw total hair regrowth, compared to just 3% of the placebo group. The Bio-Courier/ProSilic® formulated product was well tolerated with no major adverse events. AA is understood to be an autoimmune disease under which cells in the immune system surround and attack hair follicles leading to patchy hair loss. Over half of AA patients suffer from the mild to moderate form of the disease, which is associated with a significant disease burden, including depression and anxiety. The impact on quality of life for mild to moderate patients is equivalent to those with severe AA and yet no approved therapies exist for these patients. Based on the Phase II data, the licensee is moving into late-stage clinical development and, if successful, it could become the first approved therapy and standard of care for mild to moderate AA, which represents over half of the estimated 800,000 AA patients in the US. Under the terms of its licensing agreement, the terms of which are undisclosed, SiSaf is entitled to milestone payments as well as royalties on product sales. Dr Suzanne Saffie-Siebert, added, “We have a wealth of preclinical data demonstrating the safety and efficacy of our Bio-Courier delivery platform for a wide range of APIs and targets. We are pleased that one of our formulations has now demonstrated positive results in a Phase II clinical trial. These positive and highly encouraging data demonstrate the significant input of SiSaf’s delivery technology for dermal indications and open up wider partnering opportunities for Bio-Courier® formulated products for other topical applications, in both dermatology and ophthalmology. SiSaf has already generated promising data in relation to the treatment of psoriasis or hypertrophic and keloid scars.” In addition to the SiSaf SIS-302-AA partnered program for Autoimmune Alopecia, SiSaf has two partnered programs in ophthalmology, SIS-201-CD and SIS-202-CDC for the treatment of corneal dystrophy. The company’s in house pipeline is focused on RNA treatments for musculoskeletal disorders and cancer. Image: Hair follicle localization with Bio-Courier® ABOUT SISAF SiSaf is an RNA therapeutics company with a proprietary delivery platform. Its lead programs are a siRNA treatment for Osteopetrosis ADO2 and a partnered siRNA treatment for Corneal Dystrophy. The company is in the process of expanding its pipeline to other fields, including oncology. SiSaf’s proprietary Bio-Courier® delivery platform combines organic materials with inorganic silicon to improve the stability, solubility, safety, and targeting of a wide range of molecules, including biologicals such as nucleic acids. Led by founder and leading biomaterials specialist Dr. Suzanne Saffie-Siebert, SiSaf is a venture capital-backed private company. Headquartered in Guildford, UK, it has fully integrated research labs and bio-analytical facilities, a scalable technology to fast-track development, and a growing patent estate with extensive freedom to operate. To learn more, please visit sisaf.com and follow SiSaf on LinkedIn and X. MEDIA ENQUIRIES Scius communications (for SiSaf) Sue Charles – sue@sciuscommunications.com +44 7968726585 Daniel Gooch – daniel@sciuscommunications.com +44 7747875479

An undisclosed licensee of SiSaf’s Bio-Courier technology has completed patient enrolment for its clinical trial of an alopecia treatment using SiSaf’s hybrid silicon lipid nanoparticle delivery technology The Phase II clinical trial is testing the safety and efficacy for the treatment of mild-to-moderate alopecia areata, an autoimmune condition leading to patchy hair loss Guildford, UK, 12 December 2023 – SiSaf Ltd, a biopharmaceutical company developing RNA therapeutics for rare diseases, today announced that an undisclosed licensee of its Bio-Courier delivery technology has completed target patient enrolment for the Phase II clinical trial of a treatment for mild-to-moderate (patchy) alopecia areata. The trial’s drug product uses one of the variants of SiSaf’s Bio-Courier delivery platform to enable control of drug release, in order to reduce the drug’s oxidative reactivity and improve its anti-inflammatory potential whilst allowing permeation into the skin epidermis and the hair follicle bulb target. The topical formulation works through modulating the inflammatory response and the proliferation of T-cells by disruption of the signalling pathways. Alopecia areata is understood to be an autoimmune disease under which cells in the immune system surround and attack hair follicles leading to patchy hair loss. Over half of Alopecia areata patients suffer from the mild to moderate form of the disease. The study is a randomized, placebo-controlled trial in 158 patients and will evaluate the safety and efficacy of the drug formulation as a topical treatment compared to placebo in adult subjects with mild to moderate alopecia areata (SALT score <50). Dr Suzanne Saffie-Siebert, PhD, founder and Chief Executive Officer of SiSaf said, “We have a wealth of preclinical data demonstrating the safety and efficacy of our Bio-Courier delivery platform for a wide range of APIs and targets. We are pleased that one of our formulations has now entered human Phase II trials and we look forward to the results in Q2 next year. This treatment demonstrates the potential of SiSaf’s delivery technology for dermal indications.” -Ends- ABOUT SISAF SiSaf is an RNA therapeutics company with a proprietary delivery platform. Its lead programs are a siRNA treatment for Osteopetrosis ADO2 and a partnered siRNA treatment for Corneal Dystrophy. The company is in the process of expanding its pipeline to other fields, including oncology. SiSaf’s proprietary Bio-Courier delivery platform uses silicon stabilized hybrid lipid nanoparticles (sshLNP) to improve the stability, safety, and transfection efficiency of RNA. sshLNP remove the need for an ultra-cold chain and unlike conventional lipid nanoparticles, they can be manufactured empty and the RNA can be introduced in a separate step. Led by founder and leading biomaterials specialist Dr. Suzanne Saffie-Siebert, SiSaf is a venture capital-backed private company. Headquartered in Guildford, UK, it has fully integrated research labs and bio-analytical facilities, a scalable technology to fast-track development, and a growing patent estate with extensive freedom to operate. To learn more, please visit Follow us on LinkedIn and X MEDIA ENQUIRIES Scius communications (for SiSaf) Sue Charles – sue@sciuscommunications.com +44 7968726585 Katja Stout – katja@sciuscommunications.com +44 7789435990 Issued for and on behalf of SiSaf by Charles Consultants (Life Sciences) Ltd.

9月12日，由美国基因与细胞治疗学会（ASGCT）主办的Molecular Therapy Nucleic Acids学术期刊发表SiSaf公司明星产品SIS-101-ADO的临床前研究论文，证明了该药物在动物体内治疗染色体显性遗传石骨症2型（ADO2）的安全性和有效性。SIS-101-ADO是英国公司SiSaf开发的一款抑制ADO2特异性突变基因Clcn7表达的siRNA与其专有Bio-Courier硅稳定的杂化脂质纳米颗粒（sshLNP）结合的临床前阶段候选药物，用于治疗儿童常染色体显性遗传石骨症2型（ADO2）的严重或危及生命的表现，包括视神经压迫致盲，牙齿和颅面发育异常以及脊柱侧弯。ADO2是基因突变造成的骨密度增加，具有缺陷结构的骨积聚，于是骨变脆且容易骨折。大约70%的ADO2患者由Clcn7（电压门控氯离子通道7）基因杂合错义突变引起，该基因编码CLC-7蛋白，CLC-7蛋白存在于溶酶体和破骨细胞褶皱膜上，其突变对骨和脑的影响最大。在ADO2最严重的形式中，患者表现为广泛的骨硬化，尤其是颅底、骨盆和椎骨，并出现多处骨折、骨髓炎、血液衰竭和感觉症状，包括视力和听力受损。全球每10万人种就有5.5人受到ADO2影响，目前没有批准上市的ADO2的治疗方法，也没有正在临床试验中的其他药物。SiSaf的Bio-Courier技术将专有的可生物吸收硅基质与表面脂质和氨基酸相结合，来稳定脂质纳米颗粒（LNP），这种结构克服了LNP递送的局限性。5月15日，SIS-101-ADO被FDA授予孤儿药指定（ODD）和罕见儿科疾病指定（PRDD）。石骨症患者的骨骼▲ 图片来源：Molecular Therapy Nucleic Acids在携带杂合突变Clcn7基因（Clcn7G213R）的ADO2小鼠模型中通过单次腹膜内注射SIS-101-ADO后，SIS-101-ADO显著下调了Clcn7G213R48小时股骨中的相关mRNA水平。在治疗后2周和4周（3次腹膜内注射/周）观察到确认性结果和骨恢复的表型，安全性也得到证明。▲ 图片来源：Molecular Therapy Nucleic AcidssshLNP硅脂纳米颗粒技术RNA疗法成功的关键在于其递送系统，它需要稳定和保护RNA分子不被降解，并且需要确保足够数量的RNA输送到靶细胞的细胞质，以引起所需的细胞反应，而几乎没有或没有不良影响或积累。LNP，▲ 图片来源：Sisaf官网脂质纳米颗粒（LNPs）是RNA药物采用的目前主流载体，但比较脆弱，当LNP的静电电位发生不良变化时，RNA会分离，过早释放从而无法发挥作用，因此需要超冷储存和运输。此外，LNP使用的高比例阳离子脂质在氧化时会产生毒性，LNP制备过程中使用的聚乙二醇（PEG）会触发抗体（αPEG Abs）反应，机体会将PEG识别为外来物，发起免疫反应来清除。sshLNP，▲ 图片来源：Sisaf官网SiSaf的Bio-Courier 硅稳定的杂化脂质纳米颗粒（sshLNP）RNA递送技术使得RNA更加持久稳定，提高了转染效率，具备非免疫原性、高效转染、无积累的特点。与传统的脂质纳米颗粒不同，它们可以空载体的形式运输，并且可以在单独的步骤中引入RNA。具体来说，有以下优点：1.硅的正电荷和高ζ电位静电结合和凝聚RNA，防止RNA过早解离并减少对潜在有毒阳离子脂质的依赖，减少免疫原性；2.大量紧密缩合的RNA静电键合到硅基质上，保护它们免受水解，延长其全身存活时间；3.硅准金属的结构完整性可防止颗粒的物理塌陷，从而在保持RNA完整性的同时进行冻干，减少了对聚乙二醇化的需求，这是避免超冷供应链存储需求的关键步骤；4.定制的表面脂质与pH依赖性硅/RNA键溶解相结合，最大限度地提高了转染效率；5.粒径、表面电荷和表面配体的添加的多功能性可实现RNA药物被动或主动细胞靶向和多种给药途径。6.涂覆在硅核心上的表面脂质和氨基酸控制硅水解的速度，提供特定细胞和组织的受控释放和靶向性。SiSaf的创始人是领先的生物材料专家Suzanne Saffie-Siebert博士，风险投资者包括Vickers Venture Partners和UK Future Fund，总部位于英国吉尔福德。SiSaf正在开发针对常染色体显性遗传疾病的siRNA治疗方法，包括罕见的骨骼疾病，如石骨症和软骨发育不全。SiSaf最近将其RNA研发管线拓展到肿瘤和眼科适应症，公司与美国眼科遗传病诊断研究公司Avellino Labs合作，开发了用于II型角膜营养不良的滴眼液RNA干扰疗法SIS-201-CD和CRISPR Cas9基因编辑疗法SIS-201-CDC。SiSaf产品管线,▲ 图片来源：Sisaf官网参考资料1.https://sisaf.com2.https://doi.org/10.1016/j.omtn.2023.08.020抗体行业在过去几十年中经历了快速而显著的发展，成为生物医药领域中一个快速发展且备受关注的领域。自20世纪80年代第一种单克隆抗体药物（Muromonab-CD3）获得批准以来，许多抗体药物已经被批准用于各种疾病的治疗，包括肿瘤、免疫性疾病和感染性疾病等。市场上已经有数十种成功抗体药物，并且在临床开发和研究中有更多的候选药物，预计未来将有更多新药上市。如今，除了传统的单克隆抗体，越来越多的新型抗体技术被陆续开发出来，包括双特异性抗体、多克隆抗体、人源化抗体、重组抗体、抗体偶联药物等。这些新技术使得抗体药物具有更高的特异性、亲和力、稳定性和生产可行性，拓宽了抗体的应用范围。今年是COVID-19大流行趋于稳定后的第一年，人民生活逐渐走向正轨，经济也在缓慢但有力的复苏之中，而各抗体企业也依然在不断奋进、不断突破、不断超越，使抗体领域蓬勃发展，硕果累累。为促进抗体行业的交流与创新，2023年10月14-15日第六届金秋十月抗体产业发展大会如约而至。会议旨在为研究人员提供一个互动交流的平台，有助于推动抗体产业的进一步发展。会议内容时间：2023年10月14-15日地点：苏州（酒店定向通知）规模：600-800人主办单位：生物制品圈、抗体圈指导单位：康维讯生物、夏尔巴生物会议费用：免费FREE!（仅收取50元报名定金，含参会学习、茶歇、会议手册，定金概不退还），9月15日报名定金提高到100元，先到先得，报完即止，超过9月20日预登记将收取会议费！报名方式：扫描下方二维码或点击文章最底部“阅读原文”→ 填写表格 → 报名成功（报名志愿者，承担一定工作，请慎重考虑，免交定金）！组委会获得报名信息后，根据报名信息进行初筛，并进一步与报名者沟通确认，实现精准邀请。最终有机会进入大会微信群（严格审核通过）。日程安排更多嘉宾仍在邀请中。。。。。。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。