Eva Pharma for Pharmaceuticals & Medical Appliances SAE

创新药领域的“点石成金”正在照进现实。 Paragon Therapeutics神似美国药版的“微创”，当然这指的是其衍生出多家上市公司强大操作，但其衍生出的Biotech上市后却个个都给投资者带来丰厚的回报。而不同的是，Paragon Therapeutics并未上市，使得其不存在损害中小投资者利益的问题。 目前，Paragon Therapeutics已经衍生出了5家上市公司，其中包括4家专注于自免的Biotech，分别为Apogee Therapeutics、Spyre Therapeutics、Oruka Therapeutics和Jade Biosciences，肿瘤领域的Biotech则是有Crescent Biopharma。 Paragon Therapeutics由来自宾夕法尼亚州的风投机构Fairmount于2021年创立，其开发策略简单粗暴，从已衍生Biotech的管线看，其主要直接针对相对成熟的靶点开发下一代长效抗体药物，技术上也多采用专利过期的YTE改造策略。 01 不一样的资本操作思路 细心地投资者会发现，Paragon Therapeutics衍生的5家公司中只有Apogee Therapeutics是通过常规的IPO通道实现上市，其余四家均通过诸如反向合并这类“借壳”的方式实现上市。 以专注炎性肠病的Spyre Therapeutics为例，Spyre Therapeutics“借壳”对象是Aeglea，Aeglea为开发罕见代谢疾病药物的Biotech，由于在2023年其核心产品I/II期试验中期结果低于市场预期陷入绝境，最终Aeglea以换股交易的方式收购Spyre Therapeucs，Aeglea原股东获得合并公司的约5.5%股份。 而在近期完成“借壳”的Jade Biosciences，其借壳对象为Aerovate Therapeutics，Aerovate公司是一家核心管线伊马替尼改剂型为干粉版本配合吸入器吸入治疗肺动脉高压的Biotech，合并前净现金接近1亿美元，Aerovate在与Jade合并前向原股东分配6500万美元现金，同时原股东将获得合并公司后的约1.5%股份。 从Paragon衍生公司过往案例来看，其目标对象均为小市值低于2亿美元甚至低于5000万美元的“烟蒂Biotech”，在合并之前往往会带资入组配套一笔融资以支撑合并公司支撑发展2-3年或获得核心管线概念性验证数据。另外，原有壳公司的股东股权比例将压缩在很低的比例，保证了合并公司的股权结构健康和未来上市公司盘面潜在的抛压。 Paragon系列公司为什么热衷于反向并购实现借壳上市？ 反向收购实现上市很早在美国已经成为潮流，主要好处在于：1）相比IPO，反向收购相对花费时间更短，更有利于Biotech实现快速上市；2）反向收购的成本主要包括买壳费用、律师费、会计师费和财务顾问费等，通常远低于IPO的费用；3）对于这类已经“攒好局”的Biotech而言，上市的确定性和运作的灵活性反而是更重要的因素，传统的IPO往往有不少不确定因素。 02 已验证的Paragon衍生公司数据 简单粗暴的策略下，Paragon已经成功孵化出了3个具备一定市值体量的上市公司，Apogee、Spyre、Oruka目前市值分别为35.75亿美元、20.35亿美元和9.34亿美元（截至笔者撰文时），而这三家公司上市的时间分别为2023年7月、2023年11月和2023年9月，上市交易后涨幅巨大。 这三家公司的分别有各自深耕的细分赛道，Apogee、Spyre、Oruka核心管线分别对应特异性皮炎、炎性肠病、银屑病三个大适应症领域，并且有各自对标的成熟商业化药物。 Apogee核心管线是IL-13单抗APG777，其对标的是礼来Lebrikizumab（2024年9月获得FDA批准上市），IL-13作为和IL-4功能相似的调节因子，在特异性皮炎适应症（AD）开发潜力巨大，Evaluate Pharma曾经将Lebrikizumab列为2026年AD领域的第三大销售单品，预估销售额为9.9亿美元。而APG777由于对IgG1骨架进行改造（携带了YTE突变和LALA突变），拥有超长的半衰期，二期临床推行3或6个月一针维持剂量（Lebrikizumab为2或4周一针维持剂量）。 在已有的APG777一期临床数据显示：其不仅在不同剂量拥有长达75天的半衰期，同时在可以持续深度抑制pSTAT6和TARC（IL-13靶点和AD疾病相关生物标记物）长达三个月，这样的初步数据展现出了“同类最佳药物”的潜质。 Spyre Therapeutics的核心管线是α4β7单抗SPY001，其对标武田Vedolizumab（2023年销售额超过50亿美元）。整合素α4β7是淋巴细胞表面表达的归巢受体，其可以通过与粘膜地址蛋白细胞粘附分子-1（MAdCAM-1） 的相互作用，使淋巴细胞不受控地迁移到炎症部位，产生自身免疫疾病等病症。Vedolizumab作为α4β7整合素拮抗剂的成功在于，其通过选择性阻断α4β7整合素与其天然配体 MAdCAM-1间的相互作用，抑制T淋巴细胞进入肠道固有层和肠道相关淋巴组织（GALT），减轻肠道炎症，而不损害全身免疫反应。 还是熟悉的味道，SPY001是一种经过工程化改造、延长半衰期的抗α4β7单抗。在临床前小鼠和NHP模型上，SPY001相比于Vedolizumab延长3倍以上的半衰期。另外，SPY001相比vedolizumab具有更好的药物维持，一年仅需注射4-6针。 SPY001一期临床中期数据显示，其300mg、600mg皮下注射组的半衰期分别超过90天、100天，远长于Vedoliz约55-76.5天。另外，SPY001在单次递增剂量（SAD）试验中剂量高达1000mg，在多次递增剂量（MAD）试验中剂量高达600mg时仅出现1级不良事件，这意味着SPY001有望通过300mg或600mg的皮下注射分别实现每3个月（Q3M）或每6个月（Q6M）的给药频率，显然亦具备“同类最佳药物”的潜质。 Oruka Therapeutics的首发核心管线为ORKA-001，这是一款IL-23 p19的抑制剂，对标艾伯维的Skyrizi（2023年全球销售额为77.63亿美元）。IL-23是治疗 银屑病及其他自免疾病的热门靶点之一，Skyrizi凭借着较低的注射频次（在2次初始剂量后，每年接受4次维持剂量治疗）和强力的治疗效果保持高速的增长和市场领导地位。 ORKA-001工程化改造更绝，使用了YTE突变，公司预计人体半衰期约为74天，未来给药可能一年一次或一年两次，较Skyrizi延长2-4倍。2024年12月底，Oruka Therapeutics启动了的I期健康志愿者试验，计划在24名健康志愿者中评估三个剂量水平，一方面主要评估其人体半衰期是否能达到50天和75天，分别支持未来ORKA-001每6个月、年度的给药方案；另一方面，还需要评估ORKA-001是否媲美已获批的IL23抗体相当的安全性特征。 纵览上述3家Paragon衍生公司的策略和已有临床数据，可以发现Paragon主打在各个自免的大适应症上对标重磅炸弹的长效抗体获得初步性的成功，各个衍生公司取得“市值膨胀”的佳绩，这条路径已经被验证可以量产纳斯达克上市Biotech。 03 留有遐想的新Biotech 接下来，Paragon瞄准了新的风口：IgA肾病和近来热门的PD-1/VEGF双抗。 专注于IgA肾病的Jade Biosciences核心管线为JADE-001，其作为一款长效抗APRIL药物，对标药物大概率是大冢制药的Sibeprenlimab。Sibeprenlimab目前尚未商业化，其采取每月1次皮下注射的给药方式，临床三期数据显示：接受Sibeprenlimab治疗1年后，高剂量组患者平均尿蛋白降幅高达62%，具备当前“同类最佳药物”的潜力。 Jade Biosciences的策略在于，一方面通过拿手的YTE修饰延长半衰期，公司预计的人体半衰期超过50天；另一方面筛选出与APRIL结合能力更强的抗体（结合亲和力强，比Sibeprenlimab高超过5倍、比Zigakibart高超过14倍），以实现对APRIL更深度的阻断。 另外Jade Biosciences的信心源自于，公司观察到Sibeprenlimab在三期研究中可能存在剂量不足的情况，这也为JADE-001提供了差异化的机会。不过JADE-001需要在2025年下半年才能进入临床阶段，市场大概率需要在2026年上半年才能看到JADE-001的临床数据。 市场或许更好奇的是Crescent Biopharma，无论是IL-4Rα抗体，还是IL-23抗体和α4β7抗体都好，它们都已经经历了不同的公司对该靶点多样化策略的数据验证，进而能够Paragon高层做出更优的对标选择。 PD-1/VEGF双抗可能则完全不同，目前只有康方生物/Summit的AK-112经历过大样本关键临床的数据验证，积累数据是完全不足的。另一点市场好奇的在于，过去在自免领域，过去Paragon的策略可以通过半衰期改造、抗体亲和力等熟悉的技术手段来进行“Me better”改造，具备很高成功率；而放在双抗或者肿瘤领域，可能并不是简单改长效及提高依从性就能让投资者买单的，并且双抗的改造会比单抗更为复杂，这也是Crescent Biopharma未来的看点。同样其核心管线CR-001的临床数据，也要等到2026年之后了。 结语：国内投资者如果看Paragon Therapeutics这种孵化模式，其实很容易想到过去辉煌一时的“微创模式”，微创模式抛开公司的内部治理问题，其实崩灭的本质是国内器械市场各个赛道内卷背后引来的政策紧箍致使市场空间萎缩。而Paragon不同在于，自免药物各个细分赛道数量足够多、海外市场足够大而政策风险较小（至少目前来看是这样的），这样最终才能孵化出一个个上市公司，短期内互不侵扰。 当然了，海外创新药公司和资本的孵化模式、资本运作模式，国内Biotech们可以借鉴学习的，还有很多。 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！ 请注明：姓名+研究方向！ 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。

Welcome to Endpoints News’ manufacturing briefs, where we bring you essential news on new builds, collaborations, recalls and more. Lonza is expanding its manufacturing sites in Rewari, India, and Suzhou, China, for hard gelatin capsules, the CDMO said Thursday, despite the company flagging last week that it is looking to exit the capsule and health ingredients market. The new manufacturing lines will be online in the third quarter of 2025. BioCentriq is building a new 60,000-square-foot headquarters in Princeton, NJ, which will have cell therapy manufacturing, the CDMO said Tuesday. The factory also has potential for future clinical and commercial manufacturing expansions up to 30,000 square feet. The site will be fully operational in the second quarter of next year. Thermo Fisher Scientific is divesting its commercial samples business to Knipper Health for an undisclosed sum. Knipper will absorb Thermo Fisher’s Memphis, TN, facility as well as an undisclosed number of employees. The transaction will be completed by September 2025 and will expand Knipper’s cold chain footprint, according to a Wednesday press release. New York’s first cell and gene therapy manufacturing facility has opened at the Roswell Park Comprehensive Cancer Center in Buffalo, according to a Monday release. The factory cost $98 million to build, with $30 million from Empire State Development. Eli Lilly and EVA Pharma have won approval for their insulin glargine injection from the Egyptian Drug Authority, Lilly said Tuesday. The companies started their partnership in December 2022, with Lilly supplying APIs to EVA, who manufactures the insulin products locally. Bavarian Nordic is licensing its mpox vaccine to the Serum Institute of India under a new partnership, it announced Monday. Bavarian will allow SII to manufacture and distribute the MVA-BN vaccine in India. Valneva is also licensing its single-shot chikungunya vaccine to SII, who will manufacture and seek approval for the asset in India and other parts of Asia, according to a Thursday release. Samsung Biologics is investing , via its Life Science Fund, in the Flagship-founded company Generate:Biomedicines, according to a Wednesday release. Generate uses AI software to discover and design protein therapies. No financial details were disclosed. Celltrion has launched a new CDMO arm, dubbed Celltrion BioSolutions, the company said Tuesday. Theratechnologies has submitted a Prior Approval Supplement to the FDA outlining the changes it made to the manufacturing of its drug Egrifta, which is approved in the US to reduce belly fat in HIV and lipodystrophy patients. The FDA has four months to OK the manufacturing changes, the company said Wednesday. VaxSen has drawn support from the US International Development Finance Corporation, the African Development Bank, and the International Finance Corporation worth $45 million to improve local vaccine supply chains in Africa, according to a Tuesday release. Polyrizon has tapped the CDMO Eurofins, also called Amatsiaquitaine, to supply material for its PL-14 allergy blocker, which is entering a study next year, according to a Wednesday release. French pharma company Biocodex tapped the logistics firm Kinaxis to access its supply chain platform, according to a Monday release. BioVaxys has secured 48 kgs of lipids to start its antigen packaging platform, the company said Tuesday. The platform can package mRNA, proteins, peptides and small molecules. Moberg Pharma has secured a new manufacturer and supplier of an ingredient (terbinafine) for its nail fungus drug named MOB-015, according to a Wednesday release.

The collaboration of Lilly and EVA Pharma began in 2022 to provide affordable insulin. Credit: © 2022 Eva Pharma All Rights Reserved. Eli Lilly and EVA Pharma have announced approval from the Egyptian Drug Authority for the human insulin glargine injection to treat type 1 and type 2 diabetic patients. EVA Pharma manufactures the injection in partnership with Lilly. The collaboration, which began in 2022, aims to provide quality, affordable insulin to a minimum of one million type 1 and type 2 diabetic individuals in low to middle-income countries (LMICs) annually, predominantly in Africa. In under two years, EVA Pharma then established a new biologics manufacturing facility, completed stability testing and finalised insulin formulations, along with gaining the regulatory approval secured for the insulin injection locally. Lilly has been instrumental in supplying its active pharmaceutical ingredient (API) for insulin at a low cost and offering technology transfer to EVA. This has enabled the local formulation, filling and finishing of insulin vials and cartridges. In parallel, EVA has submitted its insulin injection for local regulatory approval. The collaboration also includes efforts to achieve World Health Organization (WHO) pre-qualification for insulin injection, which would affirm the high-quality standards of EVA’s medicines as set by WHO. The initiative aligns with the Lilly 30×30 goal, which aspires to enhance access to quality healthcare for 30 million people in resource-limited settings every year by 2030. Lilly International president and executive vice-president Ilya Yuffa stated: “For more than a century, Lilly has been at the forefront of diabetes care, offering innovative solutions that make life better for people around the world. “Our collaboration with EVA Pharma furthers our commitment to providing sustainable and accessible medicines worldwide. “ In September 2024, Lilly also agreed to license baricitinib manufacturing know-how to EVA, enabling the supply of treatments for immunological diseases in 56 LMICs across Africa. In a separate development, the China National Medical Products Administration (NMPA) approved Lilly’s Kisunla (donanemab-azbt, 350 mg/20 mL every four weeks injection for IV infusion) for adults with early symptomatic Alzheimer’s disease, including those with mild cognitive impairment and mild dementia stage who have confirmed amyloid pathology. The NMPA application was supported by data from the Phase III TRAILBLAZER-ALZ 2 trial.