Azeliragon

摘要：“产品中的管线”（pipeline-in-a-product）策略正成为生物科技领域的新焦点：通过一款药物靶向基础生物过程，覆盖多种疾病适应症，既能拓展商业价值，又能提升研发效率。本文聚焦五家新兴生物科技公司的实践，解析这一策略的核心逻辑、潜在优势，以及小公司在资源分配、并行开发中面临的独特挑战。一、“一药多治”：从明星药物到新兴策略 Humira 曾以 212 亿美元年销售额登顶 “全球药王”，Keytruda 如今以超 290 亿美元年收入接棒 —— 这两款 “印钞机” 级药物的共同特质，被行业定义为 “产品中的管线”：一款分子能通过靶向基础生物过程，覆盖多种慢性疾病。 Pharma analytics firm Evaluate 指出，这类药物需满足核心条件：靶向免疫级联、细胞检查点、代谢通路等 “跨疾病基础生物过程”，且有明确生物学机制证明其与多种疾病的关联。此外，还需具备 “显著的临床差异化” 和 “良好的安全性”，才能支持在不同人群中探索适应症。 这一策略的吸引力显而易见：既能解锁组合疗法潜力，又能延长 revenue 周期，甚至增强与支付方谈判的筹码。但对小公司而言，并行推进多个适应症的临床开发，意味着巨大的预算压力和运营挑战 ——“既要应对拥挤的竞争格局，又要避免不同适应症上市时的内部资源冲突。”Cooley LLP 生命科学合作与许可负责人 Ken Krisko 坦言。 二、五家公司的差异化实践1. Cantex：靶向 RAGE，横跨癌症与呼吸疾病 佛罗里达生物科技公司 Cantex 押注小分子药物 azeliragon，其靶点 RAGE 受体被证实与多种癌症、肺部疾病的发生发展密切相关。目前，该药物正推进胰腺癌、乳腺癌、胶质母细胞瘤及乳腺癌脑转移（获 FDA 孤儿药资格）的研发，同时布局重症哮喘、慢阻肺等呼吸疾病。 其最成熟的项目是针对重症肺炎的 III 期试验（最初针对新冠，后扩展至所有住院肺炎患者），旨在验证 azeliragon 能否预防急性肾损伤这一致命并发症，预计 2026 年 4 月完成主要终点。“小公司的风险在于精力分散，可能导致各适应症疗效证据不足。”CEO Stephen Marcus 强调，“必须基于疗效可能性、试验成本和医疗需求精准选择目标疾病。”2. Cognition：聚焦神经退行性疾病，靶向 sigma-2 受体 与 Cantex 的跨领域布局不同，纽约和宾夕法尼亚州的 Cognition Therapeutics 专注神经领域，其口服药物 zervimesine 通过靶向 sigma-2 受体，清除神经元间的毒性淀粉样蛋白斑块，延缓认知衰退。 2025 年阿尔茨海默病协会国际会议（AAIC）上，II 期数据显示：该药物能改善路易体痴呆患者的神经精神、认知和运动功能，且能阻止轻中度阿尔茨海默病患者的认知恶化（已完成与 FDA 的 II 期结束会议）；针对年龄相关性黄斑变性继发的地图样萎缩，II 期试验也观察到病灶生长放缓。“目前尚无其他药物在这三类疾病中均获阳性 II 期结果。”CEO Lisa Ricciardi 表示，这种 “一药多治” 模式能优化资源，同时拓宽市场。3. Airway：模拟肺表面活性蛋白，深耕肺部疾病 俄亥俄州的 Airway Therapeutics 认为，理想的 “产品中的管线” 需同时满足 “靶向多疾病机制” 和 “具备多重特性”—— 其重组蛋白 zelpultide alpha 正是如此：模拟内源性肺表面活性蛋白 SP-D，既能清除肺部病原体，又能抑制炎症。 该药物的优先适应症是婴儿支气管肺发育不良（BPD），2024 年 12 月启动全球 III 期试验（计划入组 300 余名缺乏 SP-D 的早产儿），此前 Ib 期数据显示，其能降低 BPD 发生率及机械通气需求。此外，公司还计划探索社区获得性肺炎、哮喘、慢阻肺等适应症，与 Regeneron 和赛诺菲的 Dupixent 形成部分适应症重叠。“小公司无法同时推进所有适应症，必须优先选择数据强度高、医疗需求大且竞争格局清晰的领域。”CEO Marc Salzberg 解释。4. Diakonos： dendritic 细胞疫苗，追逐 Keytruda 的广谱抗癌路 受 Keytruda 启发，休斯顿的 Diakonos Oncology 开发树突状细胞疫苗 dubodencel，利用患者自身肿瘤抗原激活免疫系统。I 期数据显示，其能显著扩增 CD4 + 和 CD8 + 记忆 T 细胞，12 个月总生存率优于标准治疗，且副作用轻微；目前 II 期试验已启动，首名胶质母细胞瘤患者于上月入组。 “这类药物前期复杂度和成本更高。”CEO Jay Hartenbach 坦言，尽管公司 2024 年 5 月融资 2000 万美元，仍需 “有序推进试验”，“可以通过组合研究等战略合作聚焦特定适应症，而非同时铺开。”5. Immunophotonics：可注射聚合物，激活实体瘤免疫 密苏里州的 Immunophotonics 则以 IP-001 切入 —— 这款聚糖聚合物既能作为抗原库留住抗原，又能招募并激活抗原呈递细胞，增强免疫应答。“其优势在于可与光热疗法、肿瘤消融等局部治疗结合，将这些操作转化为免疫激活事件。”Ken Krisko 评价，“一个平台，多条治疗路径。” 公司的 INJECTABL 临床项目正探索结直肠癌、软组织肉瘤、非小细胞肺癌等实体瘤：INJECTABL-1（Ib/IIa 期）已完成 41 名晚期患者给药；INJECTABL-3（II/III 期）将联合消融治疗，针对以消融为标准疗法的适应症。“需提前规划扩展和替代用途，同时借助外部合作推进管线扩张。”CEO Lu Alleruzzo 表示，公司正与欧洲心血管和介入放射学会合作设计试验。 三、前景：潜力与执行能力的博弈 “产品中的管线” 策略为小公司提供了 “以小博大” 的可能，但成功的关键在于平衡 —— 既要利用药物的广谱潜力，又要避免资源过度分散。正如 BioPharmCatalyst 高级总监 John Gagliano 所言：“这些资产蕴藏巨大机遇，但需要持续的战略投入和精准的多适应症上市执行。” 对这五家公司而言，接下来的临床试验结果、资源分配效率和合作策略，将决定它们能否复制 Humira 与 Keytruda 的传奇。 参考来源：https://www.biospace.com/business/5-biotechs-taking-the-pipeline-in-a-product-approach-to-drug-development 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不本站。

iStock, Andrii Yalanskyi The platform strategy of using one molecule to target an underlying biological pathway to address many different diseases can be a goldmine for smaller companies. But it also has a unique set of challenges, not least of which is the budgetary and operational strain that come with clinical development across many indications. From 2012 to 2020, AbbVie’s I&I blockbuster Humira reigned as the most valuable drug in the world . Sales peaked in 2022, when the biologic brought in $21.2 billion and became the highest-grossing drug of all time . Now, after losing patent protection and market share to biosimilars, Humira has ceded the throne to Merck’s PD-1 inhibitor Keytruda, which last year hit upwards of $29 billion in revenue , comfortably beating all its competitors. The market dominance of these two drugs was driven by several factors, but there is one crucial similarity between them: Both are what pharma analytics firm Evaluate calls pipelines-in-products. That is, drugs from which “several chronic disease indications can be squeezed out.” In order for a molecule to be a good pipeline-in-a-product candidate it must target “fundamental biological processes . . . that underlie multiple disease states,” BioPharmCatalyst senior director John Gagliano told BioSpace in an email. Immune cascades, cellular checkpoints and metabolic pathways are good examples of these processes. There should also be a “clear biological rationale” that links the biological pathway the asset is targeting to the diseases it seeks to address, he added. But broad mechanistic applicability is just the beginning. A good pipeline-in-a-product should also have “compelling clinical differentiation” as well as a “strong safety profile,” which in turn will allow its investigation across different populations, Gagliano explained. If a molecule ticks all these boxes and clears all regulatory hurdles, it could be a big commercial boon. “In today’s therapeutic landscape, these products typically unlock the power of combination therapies,” Ken Krisko, partner and head of Life Sciences Corporate Partnering and Licensing at Cooley LLP, told BioSpace in an email. The platform strategy also comes with “the potential for extended revenue over time,” Krisko continued, allowing companies to “place larger bets on the development and manufacturing infrastructure” for these molecules. If approved, he added, pipeline-in-a-product assets “offer unparalleled ability to combine commercialization strategy and improve leverage in payer negotiations.” Of course, these are all only true if the company can execute in the market. And on that front, this platform approach comes with a unique set of barriers and challenges, especially for smaller companies, including the operational strain that comes with running drug development and commercialization in parallel. Less-established players will need to “navigate a crowded competitive landscape, supporting each new indication while allocating resources strategically to avoid internal competition between launches,” according to Krisko. “The key is recognizing that while these assets offer tremendous opportunity, they require sustained strategic commitment and excellent execution across multiple launches,” Gagliano told BioSpace . In this piece, BioSpace reviews up-and-coming pipeline-in-product molecules, going beyond the Keytrudas and the Humiras—even past the GLP-1s—to focus on assets from smaller players that are taking on big risk for a huge potential reward. Cantex Harnasses RAGE for Cancer, Respiratory Cantex Pharmaceuticals is leveraging the pipeline strategy to address diseases across more than one therapeutic area. The Florida biotech is building its business on the small-molecule drug azeliragon, which according to CEO Stephen Marcus is “relevant to a broad range of illnesses.” Azeliragon targets a central receptor called RAGE, which “has been strongly implicated in the initiation and progression” of many different common cancers and lung conditions, Marcus explained to BioSpace in an email. In line with this activity, Cantex is advancing the drug for pancreatic cancer, breast cancer and glioblastoma, as well as for brain metastasis from different primary malignancies . The FDA in December 2024 granted azeliragon orphan drug designation for brain metastasis from breast cancer. Cantex is also working on respiratory indications, including severe asthma and advanced chronic obstructive pulmonary disease. Of these, the most mature program for azeliragon is in severe pneumonia. A Phase III study —which was originally in COVID-19 but later expanded to include all hospitalized pneumonia patients—will test whether azeliragon’s RAGE action can prevent acute kidney injury, a common complication that can lead to death in these patients. The study is ongoing and has a primary completion date in April next year . But while azeliragon’s mechanism gives Cantex “multiple options for clinical development,” Marcus said that small companies like his still face the “risk that a lack of focus will produce insufficient evidence of effectiveness across” all of its potential indications. “Careful selection of the disease targets based on likelihood of efficacy, the cost of clinical trials, and the need for such a therapy are crucial,” he added. Cognition Focuses on Neuro With Zervimesine Whereas Cantex is looking to apply its platform strategy across a diverse set of therapeutic areas, New York– and Pennsylvania-based Cognition Therapeutics is leaning into the neurodegenerative space. Zervimesine is an orally available drug that works by targeting the sigma-2 receptor. This mechanism, according to CEO Lisa Ricciardi, is “functionally distinct from other approaches for neurodegenerative diseases” and allows zervimesine to “displace” toxic amyloid-beta plaques from the spaces between neurons, in turn preventing damage and potentially slowing cognitive decline. Cognition is proposing the drug for Alzheimer’s disease, dementia with Lewy bodies and geographic atrophy secondary to age-related macular degeneration, with recent data underlining the therapeutic potential of zervimesine for all three conditions. At the 2025 Alzheimer’s Association International Conference in June, results from the Phase II SHIMMER trial showed that in patients with dementia with Lewy bodies, zervimesine improved neuropsychiatric, cognitive, motor and functional performance. Also at AAIC 2025, the Phase II SHINE trial found that zervimesine could arrest further cognitive deterioration in patients with mild or moderate Alzheimer’s disease. Cognition has completed a “ productive ” end-of–Phase II meeting with the FDA for zervimesine in this indication. Similarly, the mid-stage MAGNIFY trial documented slower lesion growth in patients with geographic atrophy. “To our knowledge, there is no other agent which has shown positive Phase II results across these disease entities,” Ricciardi told BioSpace in an email. For smaller players like Cognition, Ricciardi said that pipelines-in-products such as zervimesine offer a “strategic advantage” by allowing for “resource optimization” while also giving the companies access to a “broadened market potential.” Airway Focuses on the Lungs With Zelpultide Alpha For Marc Salzberg, CEO and chief medical officer of Airway Therapeutics, a good pipeline-in-a-product must possess at least one of two key characteristics. It should either address underlying mechanisms for multiple conditions or have multiple properties. “In the case of zelpultide alpha, both apply,” Salzberg told BioSpace in an email. Zelpultide alpha is a recombinant human protein that works by mimicking the endogenous protein SP-D, a lung surfactant that under healthy conditions helps clear pathogens from the lungs while also minimizing inflammation. This mechanism of action allows zelpultide alpha to modulate pulmonary inflammatory and immune responses, while also reducing bacterial, fungal and viral infections, according to Airway’s website . The Ohio biotech is primarily testing zelpultide alpha for bronchopulmonary dysplasia (BPD) in infants, for which it launched a global Phase III study in December 2024. The trial aims to enroll more than 300 preterm infants who lack SP-D in their lungs. Phase Ib data, presented May 2024 , showed that zelpultide alpha lowered BPD incidence in preterm neonates versus air sham, while also reducing the need for mechanical ventilation. “It is essential to design a development program which is prioritized,” Salzberg explained to BioSpace , adding that small companies like Airway “cannot afford to develop a platform therapy across multiple indications in parallel.” In choosing BPD as its priority indication, Airway looked at the strength of the data backing zelpultide alpha, the level of medical need and the competitive landscape, he added. Still, Airway plans to capitalize on zelpultide alpha’s broad potential for respiratory indications. The biotech is also testing the molecule for community-acquired pneumonia, for which it is in early-stage development. In addition, the company sees zelpultide alpha’s therapeutic potential for asthma, chronic obstructive pulmonary disease and acute respiratory distress syndrome, as per Airway’s website . The first two indications mirror another famed pipeline in a product, Regeneron and Sanofi’s blockbuster Dupixent . Diakonos Chases Keytruda With a Dendritic Cell Vaccine With Keytruda currently reigning as king of the biopharma industry, many smaller players are looking to follow in its footsteps and develop drugs that can be used across a wide variety of oncology indications. One of these is Houston-based Diakonos Oncology, which is working on a dendritic cell vaccine called dubodencel. Part of the immune system, dendritic cells work by processing antigens—parts of a virus, for example, or bits of a tumor—to other immune players, in turn triggering an anti-cancer response. Diakonos is taking advantage of this pathway with a vaccine that uses a patient’s own cancer antigens to trigger a “powerful and natural immune response” against the cancer, according to the biotech’s website . Diakonos is advancing dubodencel in a Phase II trial for glioblastoma, with the first patient dosed last month . Phase I data in June showed that vaccination led to significant expansion of CD4+ and CD8+ memory T cells, with side effects being mostly mild. At 12 months, the overall survival rate was higher than the standard of care. For smaller companies like Diakonos, pipeline assets such as dubodencel “inevitably involve higher upfront complexity and costs,” CEO Jay Hartenbach told BioSpace in an email. In May, the biotech raised $20 million to support the development of dubodencel in glioblastoma, but even with this added infusion, Diakonos is approaching the drug’s development with discipline. “Success goes hand in hand with disciplined sequencing of trials,” Hartenbach said, noting that by wisely planning trials, companies can “leverage strategic partnerships for specific indications,” such as through combo studies. “Being able to target multiple indications does not mean the company should pursue them all at once,” he said. Immunophotonics Targets Solid Tumors With Injectable Polymer Like Diakonos, Missouri-based Immunophotonics is also chasing after Keytruda with IP-001 , a glycan polymer that functions both as an antigen depot and an activator of the immune system. Owing to its structure, IP-001 helps retain antigens at the injection site and prolongs their exposure to immune cells. The molecule also attracts antigen-presenting cells, facilitating their activation, in turn triggering strong downstream immune responses. “The versatility of IP-001 lies in its ability to be paired with various local treatments,” which in turn converts these procedures—such as photothermal therapy and tumor ablation—“into an immunologically active event,” Cooley’s Krisko told BioSpace. “One platform, multiple therapeutic avenues.” Lu Alleruzzo, CEO and co-founder of Immunophotonics, told BioSpace in an email that platform assets like IP-001 need a development strategy that takes “expansion and alternate use into account.” The biotech is putting this into practice with its INJECTABL clinical program, which is testing IP-001 in various solid tumors, including colorectal cancer, soft tissue sarcoma and non-small cell lung cancer. Last month, the company announced that the final patient had been dosed in INJECTABL-1, a Phase Ib/IIa trial in 41 patients with advanced disease. INJECTABL-3 will test IP-001 plus ablation treatments in certain key indications for which ablation is the current therapeutic standard, as per a September 2024 news release . Small biotechs should also consider external partnerships, Alleruzzo added, for “effective execution of pipeline expansion.” Partners could also open up combination regimens. Immunophotonics is also running the Phase II/III INJECTABL-3 trial in collaboration with the Cardiovascular and Interventional Radiological Society of Europe, which will nominate a steering committee to help with the study design, as well as leverage its contract research organization Next Research.