Infigratinib Phosphate

一、开场介绍会议时间：2025年第四季度主持人说明：介绍会议目的，回顾2025年第四季度业绩，讨论公司转型拐点（如encaleret、BBP-418、LGMD2I及infigratinib的III期阳性结果）及财务状况；提醒会议包含前瞻性陈述，存在风险与不确定性。管理层发言摘要：ChinmayShukla（战略财务高级副总裁）：介绍参会人员（首席执行官NeilKumar、首席商业官MatthewOutten、首席财务官ThomasTrimarchi等），说明会议议程包括Attruby商业表现、公司转型及财务回顾。NeilKumar（首席执行官）：强调公司正从现金消耗型向现金流型业务转型，2027年末预计开始产生现金，2028年利润将超6亿美元；重点提及infigratinib在软骨发育不全中的III期数据（主要终点身高速度改善2.1厘米/年，p<0.0001）及Attruby的商业增长。二、财务业绩分析核心财务数据第四季度总收入：1.542亿美元（同比增长显著），其中Attruby产品净收入1.46亿美元，特许权使用费收入530万美元，许可和服务收入290万美元；全年总收入：5.021亿美元（2024年为2.219亿美元），Attruby全年产品净收入3.624亿美元；运营成本与费用：第四季度2.937亿美元（同比增加6180万美元，主要因销售及管理费用增长），全年10亿美元（同比增加2.106亿美元）；资产负债表关键指标：年底现金、现金等价物及有价证券5.875亿美元；完成发行6.325亿美元2033年到期可转换票据。关键驱动因素收入增长主要由Attruby销售驱动，反映一线采用加速、新患者增加、处方者扩大及高持久性；运营成本增加主要因支持Attruby商业上市的销售及管理费用投入；研发费用减少因Attruby和BEYONTTRA获批后研发活动减少。三、业务运营情况分业务线表现Attruby（ATTR心肌病治疗）：第四季度新患者处方份额超25%，截至2月20日累计7,804名患者开始治疗，重复使用及患者持久性超预期；第四季度产品净收入1.46亿美元，全年3.624亿美元。市场拓展Attruby在一线患者中采用加速，处方者数量持续增长，医生对其“近乎完全稳定”“快速起效”（最早1个月）的差异化优势认可度提升；非美国市场：BEYONTTRA销售带来特许权使用费收入，欧洲市场因野生型ATTR心肌病孤儿药exclusivity持续至2030年，基本盘稳定。研发投入与成果后期管线：encaleret（ADH1）、BBP-418（LGMD2I）、infigratinib（软骨发育不全）均获III期阳性顶线结果；infigratinib：III期研究达到主要终点（身高速度较基线增加2.1厘米/年，p<0.0001），关键次要终点身体比例改善（8岁以下儿童p<0.05），安全性良好（无严重不良事件）；患者发现：encaleret已识别超1,700名独特患者，LGMD2I团队正加速诊断与患者识别。运营效率商业团队：Attruby销售团队扩张，成员经验丰富，推动处方增长；成本控制：研发费用因成熟项目减少而下降，现金消耗呈季度下降趋势。四、未来展望及规划短期目标（2026-2027年）推进encaleret、BBP-418、infigratinib的监管上市，预计2026年末或27年初获批；支持Attruby在全球市场的持续增长，扩大处方者覆盖及患者获取；维持现金消耗稳定，2026年底随Attruby收入增长开始下降。中长期战略（2028年及以后）成为现金流生成引擎，2028年利润预计超6亿美元，跻身生物制药行业前20-30名（按现金流/EBITDA）；研发聚焦遗传病领域，利用高效研发引擎（III期项目成本低于3亿美元，技术成功率高于行业平均）推动有机增长；探索管线扩展：如encaleret用于慢性甲状旁腺功能减退症，infigratinib用于其他身高障碍。五、问答环节要点Attruby增长驱动因素问：Attruby增长持续而竞争对手放缓的原因？答：核心驱动包括“近乎完全稳定”的临床数据、快速起效（1个月内）、经验丰富的商业团队，以及医生对疗效和安全性的认可；新患者处方呈“第二波加速”，反映市场对差异化优势的逐步认知。临床差异化与长期数据问：何时有增量现实世界数据支持Attruby的临床益处差异？答：2025年底将公布现实世界证据，重点包括早期心肾影响、房颤（AF）事件减少（70%reduction）及变异型患者疗效（风险比0.41）；血清TTR升高与死亡风险降低相关（每增加1mg/dL，风险降低5%）。上市准备与现金消耗问：三个后期项目的上市准备及未来12-18个月现金流规划？答：沿用Attruby上市的严谨策略，全球布局团队；现金消耗2026年保持稳定，年底随Attruby收入增长下降，运营支出因上市准备逐渐增加但受毛利驱动可控。竞争格局（infigratinib）问：infigratinib与CNP通路疗法及其他FGFR3抑制剂的竞争优势？答：infigratinib疗效（野生型生长速度6厘米/年）和安全性（无FGFR1/2毒性、低磷血症轻微）具差异化；其他FGFR3抑制剂存在VEGFR3相关风险（如伤口愈合受损），CNP类有血管舒张问题，infigratinib或成“最后一个同类药物”。TAF知识产权与仿制药影响问：tafamidis仿制药上市对Attruby的影响？答：美国知识产权地位较强（专利覆盖至2030年代），且Attruby临床优势（疗效、起效速度）驱动医生选择，仿制药难以替代；历史案例（如PAH、他汀类）显示差异化药物在仿制药时代仍能增长。PRV资格与非稀释性资本问：管线中哪些项目有资格获得优先审评券（PRV）及预期时间？答：BBP-418（LGMD2I）、infigratinib（软骨发育不全）、Canavan基因治疗获罕见儿科疾病指定，获批后可获PRV；GondolaBio合作项目也可能符合条件，PRV价格当前2-3亿美元。六、总结发言管理层强调公司已进入转型拐点，三个后期项目III期成功推动管线成熟，Attruby商业势头强劲；未来聚焦监管上市（encaleret、BBP-418、infigratinib）及生命周期扩展，2028年目标成为现金流引擎；坚持高效研发与有机增长，利用现有商业基础和现金储备（超10亿美元）捕捉内在价值，确保股东回报。查看业绩会议全文

BioMarin's decision to withdraw Roctavian from the market resulted in charges of about $240 million over the fourth quarter of 2025, including a $119 million inventory write-off. Just three months after further scaling back its support for the struggling hemophilia A gene therapy Roctavian, the company is walking away altogether by pulling the treatment from the market. The move follows a “comprehensive effort” to identify a potential buyer for the therapy, BioMarin explained Monday in its fourth-quarter earnings press release. Back in October, the company had decided to divest Roctavian, with CEO Alexander Hardy citing the approach as “consistent with BioMarin's portfolio strategy” and offering “the most promising opportunity for ensuring continued patient access to Roctavian,” he said at the time.  The writing had long been on the wall for BioMarin to part with Roctavian, which was first approved in 2023 as the first one-time gene therapy for hemophilia A. Since mid-2024, the company has left its gene therapy manufacturing plant in an “idle state” as it dwindled its Roctavian operations to solely the U.S., Germany and Italy, three markets where the drug has secured reimbursement policies. At the time, the goal was to cut Roctavian’s direct annual expenses to $60 million starting in 2025 and make the product profitable by the end of 2026.Now, after BioMarin was unsuccessful in finding a “qualified buyer” to take on the product, the company will officially withdraw the med from the market, it said. This decision resulted in charges of about $240 million over the fourth quarter of 2025, including a $119 million inventory write-off and $118 million in asset value impairments.Roctavian sales came out to $36 million in 2025, up from 2024’s $26 million. The drug was still seeing some commercial use in its end of days, with a man in Michigan becoming the state’s first patient to use the therapy outside of clinical trials upon being infused in January, the Detroit Free Press reported earlier this month.Still, broad uptake has long been an uphill battle for the gene therapy as it competes with a variety of treatments including, Roche’s blockbuster Hemlibra, Sanofi’s newer sales driver Altuviiio and Novo Nordisk’s Alhemo. Common gene therapy hurdles, such as eligibility limitations and reimbursement struggles, also pulled Roctavian back. Upon taking the helm in 2023, Hardy had outlined three potential paths for the drug. While the focus at the time was on “establishing the opportunity” for Roctavian, a divestment was listed as Hardy’s third option. BioMarin's post-Roctavian future As BioMarin leaves Roctavian behind, the company is looking to a new chapter after inking its largest-ever transaction late last year with a $4.8 billion acquisition of Amicus Therapeutics. The deal gives BioMarin two potential blockbusters in Fabry disease drug Galafold and Pompe disease combination treatment Pombiliti-Opfolda. The addition of Amicus’ portfolio would “accelerate BioMarin’s revenue growth immediately upon close,” Hardy said at the time. The deal is expected to wrap up in the second quarter of this year. Any contribution from the Amicus products is excluded from BioMarin’s 2026 guidance, which forecasts between $3.3 billion to $3.4 billion in full-year sales. In 2025, the company collected revenue of $3.2 billion, up 13% from 2024. BioMarin attributed much of its yearly growth to market gains for its collection of enzyme therapies, as well as achondroplasia treatment Voxzogo. With $927 million in 2025 sales, Voxzogo is the company’s biggest revenue driver. But William Blair analysts argued in a Tuesday note that BioMarin will ultimately require “additional business development” to fully offset the anticipated Voxzogo erosion to come from new market entrants over the next two years. That competition could come from BridgeBio and its oral candidate infigratinib, which recently showed a statistically significant improvement in annualized height velocity from baseline in a phase 3 trial of children with achondroplasia. Mizuho analysts predicted that BridgeBio’s option could “very well end up being the agent of choice for this indication,” pointing to the wide age group trialed and the convenience of an oral offering. Voxzogo, meanwhile, is administered as a daily subcutaneous injection. However, BioMarin has another achondroplasia option up its sleeve in its early-stage BMN 333, which could be a “potentially superior version of Voxzogo,” an Evercore ISI analyst pointed out after the company revealed positive phase 1 results in August.