ASGR1

-Phase 1a trial demonstrated acceptable safety and tolerability with no reported serious adverse events-Phase 1a data demonstrated target engagement, a pharmacodynamic effect and effects on liver function-Initiating Phase 1b proof-of-concept trial in severe alcohol-associated hepatitis- Expect to Present Safety, PD and PK Data for SZN-043 at Upcoming Medical Meeting in 2024 SOUTH SAN FRANCISCO, Calif., April 01, 2024 (GLOBE NEWSWIRE) -- Surrozen, Inc. (“Surrozen” or the “Company”) (Nasdaq: SRZN), a company pioneering targeted therapeutics that selectively activate the Wnt Pathway for tissue repair and regeneration, today provided an update on the Phase 1a clinical trial of SZN-043 in healthy volunteers and patients with cirrhosis. The Phase 1a study was completed in February 2024. SZN-043 demonstrated acceptable safety and tolerability in all subjects, with evidence of target engagement, Wnt signal activation and effects on liver function. The observed safety and pharmacodynamic activity were the basis for the Company’s previous announcement that it planned to initiate enrollment in the Phase 1b study in alcohol-associated hepatitis. The randomized, placebo-controlled Phase 1a trial enrolled a total of 48 subjects, including 40 healthy volunteers and 8 patients with cirrhosis and a history of liver disease. Single or multiple IV doses were administered in doses ranging from 0.5mg/kg to 3 mg/kg. There were no serious adverse events nor infusion reactions observed. In the planned Phase 1b trial dose range (0.5mg/kg to 1.5 mg/kg), adverse events assessed to be drug related were mild to moderate and all resolved during the study. In healthy volunteers a few asymptomatic and transient transaminase elevations (ranging from mild to moderate) were observed which resolved without intervention, and with no clinical sequelae. There were no drug related adverse events reported in patients with cirrhosis at any dose. The pharmacokinetics of SZN-043 were consistent with our expectations and supportive of the planned doses, schedule and route of administration for alcohol-associated hepatitis. In cirrhotic patients with a history of liver disease, the Phase 1a study also demonstrated dose dependent pharmacodynamic (PD) activity through activation of Wnt signaling as assessed by the methacetin breath test. This test measures activation of the Wnt pathway via the metabolism of a Wnt target gene (CYP1A2) substrate. Target engagement was confirmed via transient increases in alkaline phosphatase (ALP). Increases in ALP are indicative of SZN-043 binding to its targeting receptor ASGR1 and reduction in its capacity to clear ALP, consistent with observations in other ASGR1 binding agents. Cirrhotic patients also showed evidence of liver function effects after treatment with SZN-043 as measured by HepQuant which is a test that measures cholate clearance, a liver specific function that quantifies liver function. ”We are excited to have observed activation of Wnt signaling, target engagement and improvement in markers of liver function during the Phase 1a studies and are pleased to advance SZN-043 into the Phase 1b clinical trial in severe alcohol-associated hepatitis. We look forward to presenting the encouraging Phase 1a data at an upcoming medical conference - the first clinical data for this innovative antibody-based approach to modulating the Wnt pathway,” said Craig Parker, President and Chief Executive Office of Surrozen. “Progress with our platform technologies supports our belief that modulation of the Wnt pathway has the potential to provide important new therapeutic options through targeted tissue regeneration.“ The Company is in the process of initiating the multi-center Phase 1b clinical trial in multiple countries and expects that proof-of-concept data from this trial may be available in the first half of 2025. The study will enroll patients with severe alcohol-associated hepatitis in an open-label trial. The Company plans to evaluate safety, pharmacokinetics, immunogenicity and a number of efficacy endpoints including MELD score, Lille score and survival. The MELD and Lille scores have been shown to correlate with clinical improvement and 90-day survival. About SZN-043 for Severe Alcohol-Associated HepatitisSZN-043 is the first development candidate using Surrozen’s SWEETS™ technology. Surrozen is developing SZN-043 for severe liver diseases, initially focusing on alcohol-associated hepatitis. The Company has completed a Phase 1a clinical trial in patients with chronic liver disease and healthy volunteers. SZN-043 demonstrated acceptable safety and tolerability in all subjects, with evidence of target engagement, Wnt signal activation and effects on liver function. The Company is initiating the Phase 1b clinical trial in patients with severe alcohol-associated hepatitis and expects that proof-of-concept data from this trial may be available in the first half of 2025. About SZN-413 for Retinal DiseasesSZN-413 is a bi-specific antibody targeting Fzd4-mediated Wnt signaling designed using Surrozen’s SWAP™ technology. It is currently being developed for the treatment of retinal vascular-associated diseases. Data generated by Surrozen with SZN-413 in preclinical models of retinopathy demonstrated that SZN-413 could potently stimulate Wnt signaling in the eye, induce normal retinal vessel regrowth, suppress pathological vessel growth and reduce vascular leakage. This novel approach could thus potentially allow for regeneration of healthy eye tissue, not only halting retinopathy, but possibly allowing for a full reversal of the patient’s disease. In the fourth quarter of 2022, Surrozen entered into a strategic partnership with Boehringer Ingelheim for the research and development of SZN-413 for the treatment of retinal diseases. Under the terms of the agreement, Boehringer Ingelheim received an exclusive, worldwide license to develop SZN-413 and other Fzd4-specific Wnt-modulating molecules for all purposes, including as a treatment for retinal diseases, in exchange for an upfront payment to Surrozen of $12.5 million. Surrozen will also be eligible to receive up to $587.0 million in success-based development, regulatory, and commercial milestone payments, in addition to mid-single digit to low-double digit royalties on sales. After an initial period of joint research, Boehringer Ingelheim will assume all development and commercial responsibilities. About Wnt SignalingWnt signaling plays key roles in the control of development, homeostasis, and regeneration of many essential organs and tissues, including liver, intestine, lung, kidney, retina, central nervous system, cochlea, bone, and others. Modulation of Wnt signaling pathways has potential for treatment of degenerative diseases and tissue injuries. Surrozen’s platform and proprietary technologies have the potential to overcome the limitations in pursuing the Wnt pathway as a therapeutic strategy. About SurrozenSurrozen is a clinical stage biotechnology company discovering and developing drug candidates to selectively modulate the Wnt pathway. Surrozen is developing tissue-specific antibodies designed to engage the body’s existing biological repair mechanisms with a current focus on severe liver and eye diseases. For more information, please visit www.surrozen.com. Forward Looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. Forward-looking statements generally are accompanied by words such as “will,” “plan,” “intend,” “potential,” “expect,” “could,” or the negative of these words and similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These forward-looking statements include, but are not limited to, statements regarding Surrozen’s discovery, research and development activities, in particular its development plans for its product candidates SZN-043, and SZN-413 (including anticipated clinical development plans and timelines, and the availability of data, the potential for such product candidates to be used to treat human disease, as well as the potential benefits of such product candidates), and the Company’s partnership with Boehringer Ingelheim, including the potential for future success-based development, regulatory, and commercial milestone payments, in addition to mid-single digit to low-double digit royalties on sales . These statements are based on various assumptions, whether or not identified in this press release, and on the current expectations of the management of Surrozen and are not predictions of actual performance. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on as a guarantee, an assurance, a prediction, or a definitive statement of fact or probability. Actual events and circumstances are difficult or impossible to predict and will differ from assumptions. Many actual events and circumstances are beyond the control of Surrozen. These forward-looking statements are subject to a number of risks and uncertainties, including the initiation, cost, timing, progress and results of research and development activities, preclinical or and clinical trials with respect to SZN-043, SZN-413 and potential future drug candidates; the Company’s ability to fund its preclinical and clinical trials and development efforts, whether with existing funds or through additional fundraising; Surrozen’s ability to identify, develop and commercialize drug candidates; Surrozen’s ability to successfully complete preclinical and clinical studies for SZN-043, SZN-413, or other future product candidates; the effects that arise from volatility in global economic, political, regulatory and market conditions; and all other factors discussed in Surrozen’s Annual Report on Form 10-K for the year ended December 31, 2022 and Surrozen’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 under the heading “Risk Factors,” and other documents Surrozen has filed, or will file, with the Securities and Exchange Commission. If any of these risks materialize or our assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that Surrozen presently does not know, or that Surrozen currently believes are immaterial, that could also cause actual results to differ from those contained in the forward-looking statements. In addition, forward-looking statements reflect Surrozen’s expectations, plans, or forecasts of future events and views as of the date of this press release. Surrozen anticipates that subsequent events and developments will cause its assessments to change. However, while Surrozen may elect to update these forward-looking statements at some point in the future, Surrozen specifically disclaims any obligation to do so, except as required by law. These forward-looking statements should not be relied upon as representing Surrozen’s assessments of any date after the date of this press release. Accordingly, undue reliance should not be placed upon the forward-looking statements. Investor and Media Contact:Investorinfo@surrozen.com

Researchers have translated a cutting-edge tactic for treating genetic disorders into a fresh approach for potentially stymying cancer. Cell division is the generative spark of nearly every lifeform on Earth. But if healthy growth goes unchecked, cell division can turn lethal, overwhelming the organism. Such is the case with so-called oncogenes. When altered by a mutation, these growth-moderating genes go haywire, producing a geyser of cancer cells as a result. Oncogenes are also insidiously adept at generating tumors that over time become genetically "independent" from their origin, so it has been exceedingly difficult for scientists to shut down their replication at the source. Now Rockefeller University researchers have discovered a new way to target the oncogene behind a rare and often deadly liver disease using small interfering RNAs (siRNAs), an innate mechanism for silencing gene expression. As described in Molecular Therapy, the researchers slipped siRNAs inside fibrolamellar hepatocellular carcinoma (FLC) cells through a surface receptor, where they blocked the oncogene from producing illness-inducing proteins that lead to tumor formation. It's the first time that siRNAs have been used to hobble the progression of FLC, says first author Christoph Neumayer, a Ph.D. student in Rockefeller's Laboratory of Cellular Biophysics, headed by Sanford M. Simon. But the findings have wider applications as well. "That's the really exciting part," says Neumayer. "This is proof of concept that siRNAs can be used for FLC, as well as adult liver cancers, which are much more common, and other tumor types elsewhere in the body." The fusion oncogene FLC is caused by the fusion of two genes located on chromosome 19: DNAJB1, which produces heat-shock proteins that encourage cell homeostasis, and PRKACA, which produces an enzyme called kinase A that's key to cellular metabolic function. The resulting fusion, known as DNAJB1::PRKACA, brings together the proteins and a catalytic subunit of the kinase. This dysfunctional union promotes FLC formation, but how, exactly, is still unknown. Researchers in Simon's lab discovered that this fusion caused FLC in 2014, several years after Simon's own teenage daughter, Elana, was diagnosed with liver disease. After having the resulting tumor removed -- the only treatment option available to people with FLC -- Elana went on to collaborate with her father to unearth its cause, publishing the results in Science. Since then, Simon and his group have continued to reveal the mechanisms behind the disease as well as develop therapeutics. The siRNA research is part of a three-part strategy which also includes repurposing drugs for treating FLC and using molecules known as PROTACs to selectively degrade the DNAJB1::PRKACA protein that drives FLC. The drug repurposing is in advanced preparation for a clinical trial, and some of the PROTAC work is part of an international collaboration that was just awarded a $25 million Cancer Grand Challenges grant to develop treatments for high-risk, oncogene-driven cancers in children. Recently, Simon's lab discovered that they could completely stop FLC tumor growth in mice using shRNAs, short sequences of RNA that can be engineered to disrupt mRNA. The approach also caused many tumors to shrink or disappear. Having shown that quelling the fused oncogene killed tumor cells, they decided to experiment with derailing kinase A activity, which research indicated was driving tumor growth. Unlocking the cell door The problem was, fused kinase A and its "wild type" form are nearly identical, so "any drug you developed that blocks fused kinase A activity would affect all kinase A, including in normal cells," Neumayer says. "In other words, you would incur a host of problematic side effects." They had to find a way to disable toxic kinase while containing the impact so that kinase in other cells weren't affected. To do that, they specifically designed siRNAs to aim at the fusion. But because siRNAs cannot cross cell membranes, the researchers needed to figure out a way to get the siRNA inside. Luckily, a door into the cell had already been identified: a receptor called ASGR1 that's only expressed in liver cells. Its key had been too: a binding molecule known as GalNAc. Together, the duo function as a waste disposal team. GalNAc conjugate therapies, which attach siRNA molecules to the ligand to deliver therapies inside cells, are already on the market for conditions such as hereditary transthyretin-mediated amyloidosis and atherosclerotic cardiovascular disease. The team wondered if they could use the same approach to thwart the kinase driving FLC tumors. Stabilization and shrinkage To test their theory, the researchers attached a custom siRNA to the receptor's ligand and studied the method in a variety of tumor models in mice and in human cell cultures. The conjugate therapy was not only successfully delivered into the cells in all contexts, but it also caused a reduction of mRNA in the oncogene, preventing the production of the protein and resulting in the tumors stagnating or shrinking, unable to grow. They also did not detect any liver toxicity in the mice, indicating the animals tolerated the siRNAs well. "What we saw was tumor inhibition, when we had hoped to outright kill the tumor," Neumayer notes. "Our future direction will be to try to figure out how to improve that." They also tested the specificity of the siRNA by injecting it into tumor cells of another type of liver cancer. It had no toxic impact on them -- exactly as the researchers hoped. "We wanted to show that our siRNA is so targeted to the FLC fusion oncogene that it has no side effects on other cells -- even on other cancer cells," he notes. Neumayer says the findings suggest that siRNAs may be effective beyond FLC, capable of treating tumors throughout the body with a high degree of specificity: "I think siRNA medicines as a class will have a big impact over time as a new kind of genetic therapy."

作者｜小鱼 小核酸药物是指不超过30个碱基对的寡核苷酸序列，包括反义核酸（ASO）、小干扰RNA（small interfering RNA，siRNA）、微小RNA（micro RNA，miRNA）、核酸适配体（Aptamer）等核酸小分子。它通过RNA干扰（RNA interference，RNAi）从转录后水平特异性调控靶基因的表达，以治愈靶基因相关疾病。小核酸药物的候选靶点丰富，适应症广泛，其中肿瘤和罕见病是其应用最多的领域。虽然小核酸药物有治“本”带来的长效性，但寡核苷酸的递送障碍重重，同时还存在靶毒性以及脱靶毒性等风险。针对上述挑战，本专题系列将归纳总结国内外龙头企业的小核酸核心平台、管线、交易融资、商业布局等情况。本期我们介绍Dicerna：“诺和诺德创新药版图重要组成”。Dicerna制药公司（Dicerna Pharmaceuticals, Inc.）成立于2007年，总部设在美国马萨诸塞州。Dicerna利用其专有的GalXC™和GalXC-Plus™ RNAi平台，基于RNAi选择性沉默致病基因原理，开发各种罕见与常见疾病的RNAi治疗方案。2021年11月，诺和诺德以33亿美元收购Dicerna，把Dicerna的RNAi平台添加到其多元化的研究技术平台中。仅2年时间，FDA于2023年10月3日批准诺和诺德的首款RNAi疗法Rivfloza（Nedosiran）。  01  Dicerna的GalXC™和 GalXC-Plus™技术平台有效降低RNAi技术的风险Dicerna拥有能够实现肝脏靶向（GalXC™）和肝外靶向（GalXC-Plus™）的递送平台，这2款递送平台能极好地补充诺和诺德现有的治疗管线。①GalXC™递送平台肝脏靶向的GalXC™递送平台采用皮下给药的方式，和Alnylam（详见：Alnylam: 引领RNAi二十年，目标成为TOP5 Biotech）、Arrowhead（详见：Arrowhead小核酸技术平台：RNAi布局紧凑，如箭在弦），同样，利用GalNAc较高的肝脏选择性，构建结构特异的siRNA。Dicer酶是人体细胞内RNAi天然起始点，Dicerna将GalNAc直接连接到专有Dicer底物短干扰RNA（DsiRNA）分子的延长区域，从而达到多种共轭转递结构，能够灵活、高效地结合目标配体，同时稳定RNAi双链，实现精准靶向。 区别于Alnylam的三触GalNAc递送系统，GalXC™在过客链中引入了单价GalNAc偶联的独特四环（tetraloop）结构，可增强偶联物的稳定性，同时，还能准确定位多个GalNAc配体，将siRNA成功递送至肝细胞。 另外，GalXC RNAi技术出色的药理学特性极大降低了药物开发的风险。● 仅在递送组织中沉默靶基因的特异性序列● 作用持续时间长，从数周至数月，患者依从性更好● 未观察到脱靶和副作用● 能够开发以前“难以驾驭”的靶标种类②GalXC-Plus™递送平台GalXC-Plus建立在GalXC良好的临床前和临床特性的基础上，包括可选择的核酸结构、各种配体，由此使得RNAi药物能够输送到多种组织，包括中枢神经系统、肌肉、脂肪组织、肿瘤等，为药物化学优化和扩展到新的治疗领域提供了额外的灵活性。 Dicerna的Dicer-substrate RNA和四环偶联技术在理论上比Alnylam的对应技术具有一定优势，而完成3期临床成功批准上市的Nedosiran，表明GalXC™技术经过了临床的验证，在实践上也有优势。  02  Dicerna的Pipeline：管线药物表现优异Dicerna已经开发了用于多种疾病的药物，专注于开发消化系统和内分泌系统相关的疾病的治疗方法，积极参与心脏病和高血压等心血管疾病的开发，尝试进军神经系统疾病、先天性疾病和肿瘤领域。此外，Dicerna已经开发了针对各种分子靶点的药物，包括C3、HBsAg、PCSK9、A2bR、ASGR1+I-乳酸脱氢酶、脂蛋白（a）和A1AT。这些靶点与不同的疾病对应，是Dicerna在其药物开发工作中的聚焦点。 Dicerna已经超越了药物发现的早期阶段。就管道而言，Dicerna有许多处于不同开发阶段的药物，12款药物处于临床前阶段，在实验室和动物模型中评估其潜在的疗效和安全性；3款药物进入临床Ⅰ期，已经在一小群志愿者或患者中进入测试阶段，以评估他们的安全性和剂量；2款药物（RG6346、Belesiran）进入临床Ⅱ期，正在更大的患者群体中进行测试，以进一步评估其疗效和副作用；1种药物（Nedosiran）完成临床Ⅲ期试验，已经被FDA批准上市。下面简单介绍Nedosiran、RG6346、Belesiran这3款已上市或临近上市药物。①Nedosiran治疗1型原发性高草酸尿症（PH1）2023年10月3日，美国FDA批准其RNAi疗法Rivfloza（Nedosiran）注射液（80 mg、128 mg或160 mg），用于降低9岁及以上儿童和成人PH1患者的尿草酸（Uox）水平。此次批准，是基于PHYOXTM2关键2期临床试验的结果和正在进行中的3期PHYOXTM3扩展研究的中期数据，显示接受Rivfloza治疗的患者，从第90天至第180天的24小时Uox排泄量与基线相较显著减少，13例接受额外6个月Rivfloza治疗的PH1患者维持了24小时Uox排泄量的降低。②RG6346治疗慢性乙肝RG6346处于Ⅱ期临床，Ⅰ期临床试验结果表明，RG6346能够将已经接受抗病毒疗法的慢性乙肝患者血液中的乙肝表面抗原（HBsAg）水平进一步降低1.8个指数水平（1.8 log10），并且在有些患者身上显示出长久的疗效。③Belcesiran治疗α-1抗胰蛋白酶缺乏症导致的肝损伤（AATD-LD）Belcesiran正在进行Ⅱ期试验，评估药物在AATD-LD参与者中的安全性、耐受性、药代动力学和药效学。探索AATD广阔市场的还有武田和赛诺菲，武田与Arrowhead合作的siRNA药物Fazirsiran已经完成Ⅱ期SEQUOIA试验并取得积极结果，Ⅲ期试验已于2023年3月开始；今年1月底，赛诺菲宣布收购Inbibrx，此次交易的核心是人类重组药物INBRX-101，目前正在临床Ⅱ期，以进一步评估INBRX-101治疗AATD的潜力。  03  Dicerna的商业交易：收购后Dicerna的其他合作伙伴该何去何从？除内部核心发现和临床候选药物产品管线外，Dicerna还与一些世界领先的制药公司建立了合作关系，包括诺和诺德、罗氏、礼来、Alexion Pharmaceuticals, Inc.、勃林格殷格翰、Alnylam Pharmaceuticals, Inc.等。 Dicerna与合作伙伴目前正在开展超过20项活性药物发现以及临床前和临床研究项目，主要专注领域包括心血管代谢、病毒、慢性肝脏和补体介导疾病，以及神经退行性疾病和疼痛。①勃林格殷格翰&Dicerna-非酒精性脂肪性肝炎（NASH） 2018年，勃林格殷格翰与Dicerna签订了一项针对NASH的小核酸药物协议。根据协议，Dicerna将获得勃林格殷格翰 2.01 亿美元的预付款及里程碑付款，另外还有最终的销售提成。然而被诺和诺德收购后，迟迟没有NASH药物合作进展的消息，今年1月3日，勃林格殷格翰宣布与苏州瑞博及其瑞典子公司Ribocure达成合作协议，共同开发治疗非酒精性或代谢功能障碍相关脂肪性肝炎（NASH/MASH）的小核酸创新疗法。②礼来&Dicerna-10+靶点深入合作 2018年，礼来与Dicerna公司宣布达成全球许可和研发合作，合作目标超过10个靶点。首付款1亿美元，外加1亿元的股权投资，令人心酸的是，诺和诺德的收购让礼来措手不及，合作无法继续，礼来不得不紧急自研GalNAc专利。所幸礼来的速度很快，自研的GalNAc专利WO202227186，优先权日2021年6月，早于诺和诺德收购Dicerna的日子。③Alexion&Dicerna-补体介导的疾病 2018年，Alexion和Dicerna宣布合作发现和开发补体介导疾病的RNAi疗法。Dicerna将获得2200万美元的预付款和1500万美元的股权投资。该协议为Alexion提供了两种临床前GalXC RNAi分子的全球独家许可以及开发和商业权利，并可选择另外两个候选药物。随后，2020年12月15日阿斯利康以390亿美元收购了美国Alexion制药，一年后Dicerna也被收购，此合作无后续消息。④罗氏&Dicerna-慢性乙肝 2019年，罗氏（Roche）与Dicerna就治疗慢性乙肝的在研RNAi疗法RG6346达成合作开发协议，协议金额达到14.7亿美元，罗氏RG6346通过Ⅰ期临床试验概念验证结果，2022年1月17日在国内申报临床，进行II期临床研究探索。Dicerna被收购至今，期间伴随着罗氏自主研发治疗慢性乙肝ASO类药物RO-7062931的折戟，上海创新中心筛选发现一种可以降低HBV cccDNA水平的小分子cccDNA抑制剂。⑤Alnylam&Dicerna-α-1抗胰蛋白酶缺乏症相关肝病（AATD）、原发性高草酸尿症（PH） Alnylam与Dicerna合作不深。我们前面介绍过Alnylam可是RNAi治疗领域的领跑企业，同为小核酸知名药企，两者其实是竞争关系，不太可能深入合作。2020年4月，Alnylam和Dicerna就AATD达成RNAi治疗合作，并完成PH项目的交叉许可协议。收购前，Dicerna将领导自研DCR-A1AT（Belcesiran）和Alnylam（Fazirsiran）的ALN-AAT02在AATD疗法领域的全球临床开发和美国商业化；收购后，DCR-A1AT和ALN-AAT02药物研发速度竞赛白热化，目前Alnylam处于临床Ⅲ期，领先于Dicerna的临床Ⅱ期。  04  小结Dicerna拥有先进的RNAi药物引擎和细胞内递送技术，被收购后，依托诺和诺德在药物全球研发和商业化能力以及慢性疾病治疗领域内的行业领军地位，能够显著加快和扩展GalXC RNAi疗法的使命，为糖尿病患者、肥胖症、心血管疾病和NASH等慢性病患者，以及内分泌和出血性疾病等罕见病患者，研制出改变生命的精准治疗药物。互利共赢的局面下，也有不少牺牲，被收购后的Dicerna与之前企业的合作管线纷纷沉寂。此种情形下，礼来、勃林格殷格翰等药企只能另谋出路，寻找其他同领域合作者，或是自主研发等，都有效减缓了他们的管线进展和商业布局。因此，小编认为药企的危机不仅来源于内部药物研发临床的失败，外部行业大环境的萧条，也来源于竞争对手的经济行为干扰合作或是直接破坏合作，相当于药物管线的间接失败。参考资料：https://www.novonordisk-us.com/https://investors.alnylam.com/press-release?id=24701https://media.alexion.com/news-releases/news-release-details/alexion-and-dicerna-announce-collaboration-discover-and-develophttps://www.biospace.com/article/dicerna-and-roche-ink-hepatitis-b-deal-worth-up-to-1-67-billionhttps://investor.lilly.com/news-releases/news-release-details/lilly-and-dicerna-announce-rnai-licensing-and-researchhttps://www.medsci.cn/article/show_article.do?id=a86d120150ef  2024活动预告  6月13-14日，十年一药，日出东方！BiG十周年  关键词：  源头创新与转化、创新技术平台（PROTAC/分子胶；双抗ADC；小核酸药物；AI+大分子）、临床研究&国际化开发策略（肿瘤/CNS/自免/代谢疾病领域）▼关于BiGBiomedical Innovation Group2014年2月，一个专业机构：BiG生物医药创新社（Biomedical Innovation Group）在充满药味的上海张江应运而生，伴随着中国新药的黄金十载，BiG以“开放、民主、平等“的精神为宗旨，旨在为中国生物医药行业的发展创造一个滋养原创的生态环境。共建Biomedical创新生态圈！如何加入BiG会员？