Dicerna Pharmaceuticals, Inc.

LONDON, Oct. 31, 2024 (GLOBE NEWSWIRE) -- e-therapeutics plc, a company integrating computational power and biological data to discover life-transforming RNAi medicines, today announced business updates, including its unaudited interim results for the six months to 31st July 2024. Ali Mortazavi, CEO, said: “We continue to make strong and rapid progress towards becoming a clinical-stage biotech company, as we advance our pipeline of novel GalOmic therapies, aiming to file our first IND submission in 2025. I am also excited about the ongoing evolution of HepNet. Our investment in AWS infrastructure demonstrates our commitment to integrating cutting-edge technologies across our platform. To further these efforts, we are thrilled to welcome Dr Lee Clewley as our Vice President of Applied AI and to announce the promotion of Dr Natalie Pursell to Vice President of Early-stage Development. With a powerful AI-driven platform and a growing GalOmic pipeline, we continue to be well-equipped to transform the landscape of RNAi therapeutics as we advance towards clinical trials.” GalOmic Pipeline Progress ETX-312 for the treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH): ETX-312 continues to progress through IND-enabling studies with an IND submission anticipated during 2025.ETX-148 for the treatment of Bleeding Disorders: ETX-148 IND-enabling studies initiated, with an IND submission anticipated during 2026.ETX-407 for the treatment of Dry Age-Related Macular Degeneration: ETX-407 continues to progress through the initial phase of IND-enabling studies, following a stage-gated approach to ensure the efficient use of capital.ETX-258 for the treatment of Heart Failure: This program has completed preclinical proof-of-concept studies, with selected data due to be presented at the upcoming American Heart Association Conference.ETX-394 for the treatment of MASH: Our second MASH program continues to advance through preclinical proof-of-concept studies. ETX-394 targets different disease biology to ETX-312, silencing another novel and differentiated target gene. HepNet Platform Updates Infrastructure Development: We are working with Amazon Web Services (AWS) to accelerate advancement of our Generative AI capabilities, leveraging AWS’ global leadership in AI and cloud infrastructure to enhance the design and scalability of our systems with cutting-edge large-language model (LLM) technologies via AWS Bedrock.Application of Latest Artificial Intelligence: We continue to leverage the latest developments in AI to enhance existing processes, including our target-indication assessment workflow that enables us to nominate new programs with confidence in biology, developability, and commercial viability. Additional Corporate Updates Expanding our Leadership Team Dr Natalie Pursell was promoted to VP, Early-stage Development. Natalie has served as Head of Preclinical Development at ETX since April 2023, using her extensive knowledge of preclinical research and oligonucleotide therapeutics to drive the progress of our GalOmic pipeline. Prior to this, she held leadership positions at RNA biotech companies such as Dicerna Pharmaceuticals and Moment Biosciences.Addition of Dr Lee Clewley to ETX as VP, Head of Applied AI and Informatics. Lee specialises in integrating AI into medicine discovery and delivery processes. Most recently, Lee was Head of Applied AI at GSK, where he led the development of a number of innovative projects designed to accelerate biopharma pipelines. Strengthening the Board: Jeremy Punnett was appointed to the Board of Directors in July 2024. Jeremy is a fund manager at M&G Investment Management Ltd and has been involved in numerous private and public investment transactions, including M&G’s most recent investment in ETX. Financial Highlights Cash Position: Cash and cash equivalents were £41.0 million as of 31 July 2024, including a fundraise of £28.9 million gross in June 2024 (31 January 2024: £20.7 million).Operating Loss: Operating loss was £7.5 million as of 31 July 2024 (H1 2023/24 loss: £7.0 million).Research and Development Expenses: R&D expenditure increased to £5.6 million for H1 2024/25 (H1 2023/24: £5.3 million), reflecting investment in industry-leading talent and continued advancement of our pipeline.General and Administrative Expenses: General and administrative costs rose to £2.0 million (H1 2023/24: £1.8 million) due to increased spend on human resources to continue the growth of our expert team, alongside further consultancy costs to support operations and progression of our pipeline towards the clinic.Headcount: Headcount (excluding Non-Executive Directors) was 39 as of 31 July 2024 (31 January 2024: 38). About e-therapeutics plc e-therapeutics plc ("ETX") uniquely combines computation and RNAi to discover and develop life-transforming medicines. ETX's proprietary RNAi chemistry platform, GalOmic™, enables generation of specific, potent, and durable siRNA therapeutics for effective silencing of novel gene targets in hepatocytes. The cutting-edge HepNet™ computational platform allows ETX to discover better medicines faster through generation of novel insights and increased automation across all stages of drug development. HepNet™ encompasses an extensive hepatocyte-specific knowledgebase and a suite of advanced AI-driven approaches which enable identification of novel gene targets, rapid target-indication assessment, and predictive in silico siRNA design. The Company has specialist expertise and a robust position in applying computation to biology. Its computational approaches have been extensively validated through generation of data from pipeline programs and successful drug discovery collaborations with biopharma companies, such as Novo Nordisk, Galapagos NV, and iTeos Therapeutics. Leveraging the combined capabilities of HepNet™ and GalOmic™, ETX is progressing a therapeutic pipeline of highly differentiated RNAi candidates across a variety of therapeutic areas with high unmet need. The Company has generated positive proof-of-concept data on preclinical assets in metabolic dysfunction-associated steatohepatitis (MASH), dry age-related macular degeneration (dry AMD), haemophilia, heart failure, and cardiometabolic disease, further validating its computationally enhanced approach to research and development. ETX is currently progressing its GalOmic™ therapies towards the clinic with its most developed assets, ETX-312 for MASH, ETX-148 for bleeding disorders, and ETX-407 for dry AMD, at the IND-enabling stage. Press Contactpress@etherapeutics.co.uk Investor Relations Contactinvestorrelations@etherapeutics.co.uk Unaudited Interim Results for the Six Months to 31st July 2024 INCOME STATEMENT FOR THE PERIOD ENDED 31 JULY 2024 6 months ended31 July 20246 monthsended 31 July 2023Year ended 31 January 2024 (unaudited)(unaudited)(audited) £’000£’000£’000Revenue-160318Cost of sales---Gross profit-160318Research and development expenditure(5,554)(5,324)(10,247)Administrative expenses(1,966)(1,806)(3,865)Operating loss(7,520)(6,970)(13,794)Interest income277343740Interest expense(28)(4)(27)Loss before tax(7,271)(6,631)(13,081)Taxation1,0091,0371,915Loss for the period/year attributable to equity holders of the Company(6,262)(5,594)(11,166)Loss per share: basic and diluted(0.89)p(0.97)p(1.91)p STATEMENT OF COMPREHENSIVE INCOME FOR THE SIX MONTHS ENDED 31 JULY 2024 6 months ended31 July 20246 months ended31 July 2023Year ended31 January 2024 (unaudited)(unaudited)(audited) £’000£’000£’000Loss for the period(6,262)(5,594)(11,166)Other comprehensive income---Total comprehensive income for the period/year attributable to equityholders of the Company(6,262)(5,594)(11,166) STATEMENT OF CHANGES IN EQUITY FOR THE PERIOD ENDED 31 JULY 2024 SharecapitalSharepremiumRetainedearningsTotal £’000£’000£’000£’000As at 31 January 2023582112,613(80,151)33,044Total comprehensive income for the period Loss for the period--(5,594)(5,594)Total comprehensive income for the period--(5,594)(5,594)Transactions with owners, recorded directly in equity Issue of ordinary shares121-22Equity-settled share-based payment transactions--5959Total contributions by and distribution to owners1215981As at 31 July 2023583112,634(85,686)27,531Total comprehensive income for the period Loss for the period--(5,572)(5,572)Total comprehensive income for the period--(5,572)(5,572)Transactions with owners, recorded directly in equity Issue of ordinary shares114-15Equity-settled share-based payment transactions--1919Total contributions by and distribution to owners1141934As at 31 January 2024584112,648(91,239)21,993Total comprehensive income for the period Loss for the period--(6,262)(6,262)Total comprehensive income for the period--(6,262)(6,262)Transactions with owners, recorded directly in equity Issue of ordinary shares19328,714-28,907Equity-settled share-based paymenttransactions--2525Total contributions by and distribution to owners19328,7142528,932As at 31 July 2024777141,362(97,476)44,663 STATEMENT OF FINANCIAL POSITION AS AT 31 JULY 2024 31 July 202431 July 202331 January2024 Note (unaudited)(unaudited)(audited) £’000£’000£’000Non-current assets Intangible assets 658301407Property, plant and equipment 1,103175988 1,7614761,395Current assets Tax receivable 2,9442,5371,935Trade and other receivables 512302470Prepayments 419647504Cash and cash equivalents 41,04324,84520,665 44,91828,33123,574Total assets 46,67928,80724,969Current liabilities Trade and other payables 1,4951,1862,266Lease Liability 42490393Contract liabilities --- 1,9191,2762,659Non-current liabilities Lease Liability 97-317Total liabilities 2,0161,2762,976 Net assets 44,66327,53121,993Equity Share capital2777583584Share premium 141,362112,634112,648Retained earnings (97,476)(85,686)(91,239)Total equity attributable to equityholders of the Company 44,66327,53121,993 CASH FLOW STATEMENT FOR THE PERIOD ENDED 31 JULY 20246 months ended31 July 20246 months ended31 July 2023Year ended31 January2024 (unaudited)(unaudited)(audited) £’000£’000£’000Loss for the period/year(6,262)(5,594)(11,166)Adjustments for: Depreciation, amortisation and impairment266271535Loss on disposal of fixed assets--1Interest income(277)(343)(740)Interest expense28427Equity-settled share-based payment expenses255978Taxation(1,009)(1,037)(1,935)Operating cash flows before movements in working capital(7,229)(6,640)(13,200)(Increase)/Decrease in trade and other receivables43(137)(162)Increase/(Decrease) in trade and other payables(771)(110)965Tax received--1,500Net cash from operating activities(7,957)(6,887)(10,897)Interest received277343740Interest paid(28)(4)(27)Acquisition of property, plant and equipment(374)(5)(247)Acquisition of other intangible assets(259)(103)(234)Movement in short term investments---Net cash from investing activities(384)231232Net proceeds from issue of share capital28,9072237Repayment of lease liability(188)(210)(396)Net cash from financing activities28,719(188)(359)Net decrease in cash and cash equivalents20,378(6,844)(11,024)Cash and cash equivalents at the beginning of the period/year20,66531,68931,689Cash and cash equivalents at the end of the period/year41,04324,84520,665 Notes 1. Basis of Preparation These unaudited interim financial statements do not comprise statutory accounts as defined within section 434 of the Companies Act 2006. The Company is a public unquoted limited company; and is incorporated and domiciled in the United Kingdom. The address of its registered office is 4 Kingdom Street, Paddington, London, W2 6BD, UK. Statutory accounts for the year ended 31 January 2024 were approved by the Board of Directors on 5 June 2024 and delivered to the Registrar of Companies. The report of the Auditor on the accounts was unqualified, did not contain an emphasis of matter paragraph and did not contain any statement under section 498 of the Companies Act 2006. While this interim statement, which is neither audited nor reviewed, has been prepared in accordance with the recognition and measurement criteria of international accounting standards in conformity with the requirements of the Companies Act 2006 this announcement does not in itself contain sufficient information to comply with IFRS. It does not include all the information required for the full annual financial statements and should be read in conjunction with the financial statements as at, and for the year ended, 31 January 2024. It does not comply with International Accounting Standard ("IAS") 34 'Interim Financial Reporting'. The accounting policies applied in preparing these interim financial statements are the same as those applied in the preparation of the annual financial statements for the year ended 31 January 2024 (as defined therein) other than standards, amendments and interpretations which became effective after 1 February 2024. New standards, amendments and interpretations not adopted in the current financial year have not been disclosed as they are not expected to have a material impact on the Company’s financial statements. 2. Share Capital 31 July 2024 31 July 202331 January 2024 (unaudited)(unaudited)(audited)In issue - fully paid Ordinary shares of £0.001 each (number) 777,074,147582,694,162584,335,487Allotted, called up and fully paid Ordinary shares of £0.001 each (£'000)777583584 During the six-month period to 31 July 2024, 192,666,667 new ordinary shares of 0.1p each were issued following an equity fundraise of £28.9 million by way of two direct subscription of funds, managed by M&G Investment Management Limited and Ora Ventures Limited; £19.65 million and £9.25 million raised respectively. In addition, 71,993 new ordinary shares of 0.1p each were issued at a price of 9.95p each in lieu of fees payable to a non-executive director in accordance with his service agreement.

来源：药渡 撰文：睿睿李     编辑：维他命 心血管疾病是全球居民死亡的主要原因，有着巨大的未满足需求。开发和商业化可以单独或联合使用的新疗法，对于有效解决已知风险因素并推进患者护理尤为重要，这也是药企研发战略的关键组成部分。 2024年10月7日，阿斯利康宣布与石药集团签订独家许可协议，推进早期新型小分子脂蛋白（a）干扰剂（简称Lp(a)干扰剂）YS2302018的开发。该干扰剂有潜力为血脂异常患者提供更多的获益。根据协议，石药集团将获得阿斯利康的1亿美元首付款，此外还有最高3.7亿美元的潜在开发里程碑付款和最高15.5亿美元的潜在销售里程碑付款，以及根据该产品的年度销售净额计算的分层销售提成。 01 明星靶点孕育潜力疗法 血脂异常的特征是血液中脂质和脂蛋白水平升高，特别是低密度脂蛋白（LDL）胆固醇（也称为“坏胆固醇”）的升高。脂蛋白（a）是低密度脂蛋白（LDL）的一种形式，在血流中对胆固醇的运输起着关键作用。 脂蛋白（a）水平升高以及LDL胆固醇升高是心血管疾病的已知危险因素，包括冠状动脉疾病和中风。据估计，每年在全球范围内血脂异常导致了260万人死亡。 虽然目前已经有心血管疾病相关的治疗方法，但全球血脂异常的疾病负担仍在增加。超过70%的动脉粥样硬化性心血管病（ASCVD）患者仍不能达到LDL胆固醇的控制目标，因此高危患者急需更多样化且更有效的治疗选择。 脂蛋白（a）是血脂异常的一个非常重要的靶点，与多种心脏代谢疾病有关。降低异常的血脂已被证明对心血管疾病的预后有改善作用，并且还可以降低严重心血管事件的风险。 因此，脂蛋白（a）同时也是各大跨国药企竞相布局的靶点。从市场来看，这一靶点的竞争多以小干扰RNA（siRNA）或反义寡核苷酸（ASO）为主。例如： 安进与Arrowhead合作开发的Olpasiran（siRNA）进入了3期临床阶段； 礼来与Dicerna的Lepodisiran（siRNA）在今年启动了3期临床； 诺华与Ionis合作开发的Pelacarsen（ASO）处于3期临床阶段。 而由石药集团发现的YS2302018则是一种小分子候选药物，相比之下可谓另辟蹊径。目前，已有研究证明它能有效防止脂蛋白（a）的形成，展现出极好的临床应用前景。 02 阿斯利康勇闯降脂药赛道 近几个月，阿斯利康已将其AZD0780（一种正在研究的口服小分子PCSK9抑制剂，用于治疗血脂异常）确定为2030年可能推出的一系列关键候选药物之一。该分子可以使90%的胆固醇升高患者达到目标控制水平。基于各种证据，其销售预测非常可观。 图1. 阿斯利康在心血管、肾脏和代谢领域的管线，来源：阿斯利康官网 最近，阿斯利康又买入石药集团的临床前候选小分子YS2302018，目的是将其开发为一种新型降脂疗法，可用于单独或联合治疗一系列心血管疾病适应症，包括与口服小分子PCSK9抑制剂AZD0780联合使用。 这些产品线布局在一定程度上会使阿斯利康与礼来形成竞争。在1期试验中，礼来公司的脂蛋白（a）形成小分子抑制剂将脂蛋白水平降低了65%。礼来公司于今年早些时候完成了muvalaplin（也称为LY3473329）的2期试验，并继续将该分子列入中期研发计划。 这波领先优势暂时被礼来占据。不过，YS2302018可以有效防止脂蛋白（a）形成的临床前证据仍然说服了阿斯利康开展这次与石药集团的合作，侧面反映了阿斯利康对这一新分子的信心和决心。 阿斯利康表示，这款分子的目标人群是近70%的心血管疾病患者。这部分患者虽然服用了高强度他汀类药物，但仍不能达到指南指导的低密度脂蛋白胆固醇目标限度。这是由于依从性差和单药治疗往往不够有效等问题造成的。 阿斯利康在1期试验中将合用口服PCSK9抑制剂与单用标准护理他汀类药物进行了比较，结果发现合用疗法可以把LDL胆固醇水平降低52%。阿斯利康设想，与YS2302018结合使用可以同时降低脂蛋白（a），因此可能会产生进一步的临床益处。 03 阿斯利康与石药强强联合 大药企收购小药企产品来丰富自己管线的操作并不少见，不过像这次阿斯利康与石药集团这样量级的合作，确实是强强联合。 阿斯利康正在投资一系列药物来降低心血管疾病风险因素并减缓慢性心血管疾病的进展，包括AZD0780。对于阿斯利康来说，购入YS2302018进一步强化了公司的心血管产品组合，可以帮助患者更有效地管理他们的血脂异常和相关的心血管代谢疾病。 这次合作石药集团将从阿斯利康获得1亿美元的预付款，还有权获得高达19.2亿美元的进一步开发和商业化里程碑付款，以及分层销售提成。 在其他治疗领域，石药集团和阿斯利康已经取得了丰硕的成果。例如在肺癌治疗领域，石药集团人源化EGFR单克隆抗体联合阿斯利康奥希替尼，在治疗EGFR 20号外显子插入突变（EGFR ex20ins）的非小细胞肺癌方面的出色成果得到了国际学术界的广泛认可。 这样的合作为推动创新药上市注入了强大的动力，一方面它让更多患者能够早日受益于先进的治疗药物，另一方面它让药企能够借助经济获益进一步推动自己的发展。 小 结 根据《中国血脂管理指南（2023年）》，降脂药物联合应用已经成为中国降脂治疗的基本趋势和重要策略。血脂异常可能导致动脉粥样斑块形成，从而引发心脑血管疾病，因此早期干预非常重要。基于这一重要的靶点，阿斯利康通过自研和收购等策略，布局了强劲的产品组合。 降脂药物的发展前景充满挑战与机遇，技术进步、个性化医疗和精准医疗的发展将不断塑造药物市场格局。大大小小的药企合作将不断为新药的研发和商业化推广添砖加瓦。 参考资料： 1. 阿斯利康官网 2. AstraZeneca pays CSPC $100M for preclinical heart disease drug, teeing up combos and Lilly rivalry Oct 7, 2024 6:12am www.fiercebiotech.com *声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！ 礼来能否反超诺和诺德？后来者将居上乎？ 药企裁员风波持续 | 九月汇总 礼来多奈单抗日本获批，浅谈：阿尔茨海默病从病理机制到创新药物的探索之路

Since stepping down as CEO of Alnylam Pharmaceuticals three years ago, John Maraganore has lent his talents widely, joining the boards of up-and-coming biotechnology companies, advising them on strategy and allying with some of the venture firms that back those young drugmakers.His latest role returns him to his Alnylam roots. On Tuesday, City Therapeutics launched with a plan to build the next generation of the RNA interference medicines Alnylam pioneered. Maraganore, who co-founded City with a group of venture capitalists, scientists and other Alnylam veterans, will serve as the biotechs executive chair.At Alnylam, we launched the birth of RNAi therapeutics as a new class of medicines, Maraganore said in a statement announcing Citys debut. We see the potential for RNAi to emerge as the next major category of high-impact medicines, rivaling if not exceeding the success of monoclonal antibodies.New innovation is needed to realize this future, and we believe City Therapeutics can lead this next chapter, he added.City plans to innovate in several ways, including by tweaking the components of the biological process by which RNA interference, or RNAi, works. Typically, RNAi is described as a technique to silence genes. It does so via small, interfering strands of RNA that trigger cleavage of the messenger RNA instructions cells use to produce proteins.City aims to design new kinds of RNAi triggers that similarly spark mRNA cutting, but are smaller and more potent. One example is what City terms cleavage-inducing tiny RNAs, the acronym for which led to the biotechs name.The startup also aims to design targeting molecules, or ligands, that enable the delivery of these engineered RNA strands to more types of cells and tissues. (The approved RNAi medicines that Alnylam and rival Dicerna Pharmaceuticals have to date developed are all aimed at the liver.)To get started, City has $135 million in funding from a large syndicate of investors that includes Arch Venture Partners, an early investor in Alnylam. Also backing City are Fidelity Management & Research, Invus and Regeneron Ventures, along with several other firms.The time to re-enter the RNAi revolution is now, and our investment in City Therapeutics is based on our conviction that RNAi therapeutics will expand as a major category of breakthrough medicines, said Robert Nelsen, a managing director and co-founder of Arch, in a statement.City didnt disclose which diseases it will target, but expects to begin clinical testing for its first program at or around the end of next year. The company hopes to advance one or two new drugs into the clinic each year after that.Its not the only biotech startup setting out to improve on RNAi medicines. On Monday, Judo Bio launched with plans to bring RNAi drugs to the kidney by using what it calls ligand-siRNA conjugates. Maraganore is also on Judos advisory board. '