2025 年 12 月 14 日 生物医药Ⅱ 新药周观点 ： 国内多个企业布局 INHBE siRNA，减脂不减肌值得期待 本周新药行情回顾： 2025 年 12 月 8 日-2025 年 12 月 14 日，新药板块涨幅前 5：圣诺医 药（+30.88%）、东曜药业（+16.37%）、海创药业（+13.91%）、益方 生物（+11.29%）、加科思（+10.56%）；跌幅前 5：科济药业（- 14.19%）、荣昌生物（-10.09%）、乐普生物（-9.18%）、海思科（- 9.12%）、再鼎医药（-8.39%）。 本周建议关注标的： 考虑板块后续仍有多个催化值得期待，包括学术会议、数据读出、 多个 BD 兑现等，仍建议关注： 1）已获 MNC 认证未来海外放量确定性高的品种：三生制药、联邦制 药、科伦博泰等； 2）存在海外数据催化的品种：贝达药业、和黄医药、映恩生物等； 3）下一个可能海外授权 MNC 的重磅品种：复宏汉霖、石药集团、益 方生物等； 目前全球已有多家公司布局靶向 INHBE 的 siRNA 药物，其中 5 款药 物已进入临床开发阶段；此外国内企业也已积极布局这一领域，包 括大睿生物、圣因生物 ...

Core Viewpoint - BioNTech SE reported a significant earnings miss while exceeding revenue expectations, highlighting challenges in its financial performance and the impact of its partnerships on revenue generation [2][6]. Financial Performance - BioNTech reported an earnings per share (EPS) of -$0.14, missing the estimated EPS of $0.75, and showing a decline from the previous year's EPS of $0.81 [2][6]. - The company exceeded revenue expectations with $1.78 billion, compared to the estimated $1.09 billion, largely due to its partnership with Bristol-Myers Squibb [2][6]. - The financial metrics indicate challenges, with a negative price-to-earnings (P/E) ratio of -62.09 and an earnings yield of -1.61% [5]. Revenue Sources - Revenue gains were attributed to ongoing sales of the Comirnaty COVID vaccine and upfront payments from Bristol-Myers Squibb, although a decrease in COVID-19 vaccine sales volumes partially offset these gains [3][6]. Cost Structure - Research and development expenses increased to 564.8 million euros, while selling, general, and administrative expenses decreased to 148.5 million euros [4]. Financial Stability - BioNTech maintains a low debt-to-equity ratio of 0.015 and a strong current ratio of 8.61, indicating financial stability and a robust ability to cover short-term liabilities [5][6]. Pipeline Development - The oncology pipeline, led by pumitamig, is progressing but currently lacks best-in-class data or approvals, creating uncertainty regarding future revenue potential [4].

Financial Data and Key Metrics Changes - Total revenues for Q3 2025 were EUR 1,519 million, an increase from EUR 1,245 million in Q3 2024, primarily driven by a $700 million recognition from the BMS collaboration [34] - The net loss for Q3 2025 was EUR 29 million, compared to a net income of EUR 198 million in the same period last year, mainly due to settlement disputes [36] - Cash, cash equivalents, and security investments totaled EUR 16.7 billion at the end of Q3 2025, including a $1.5 billion upfront payment from BMS [36] Business Line Data and Key Metrics Changes - The company is focusing on two priority pan-tumor programs: pumitamig and mRNA cancer immunotherapies, with multiple ongoing phase II and III trials [39] - Significant progress was made in advancing pumitamig, with global registration trials in lung cancer and plans to initiate a TNDC phase III trial [8][9] Market Data and Key Metrics Changes - The company continues to see stable market share and pricing for its COVID-19 vaccine, COMIRNATY, with U.S. vaccination rates around 20% [81] - The updated revenue guidance for 2025 was increased to EUR 2.6 billion - EUR 2.8 billion, mainly due to the BMS collaboration [37] Company Strategy and Development Direction - The company aims to build a global immunotherapy powerhouse, focusing on a diversified clinical pipeline that includes mRNA immunotherapies and next-generation immunomodulators [5][6] - The strategy includes a three-wave plan for pumitamig, focusing on establishing foundational indications, expanding opportunities, and elevating clinical impact through novel combinations [14][15] Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of generating meaningful data across oncology programs to steer late-stage decisions and maintain financial discipline [39] - The company is committed to transforming scientific advances into late-stage progress in priority oncology programs while preparing for commercialization [11] Other Important Information - The company hosted its second AI day, showcasing AI-based approaches for personalized therapy development [10] - The company plans to present additional clinical data at the upcoming annual Innovation Series R&D Day event on November 11 [39] Q&A Session Summary Question: Market opportunity for MSS-CRC and first-line gastric cancer - Management highlighted that both indications are high medical need areas, and the combination of VEGF-A and PD-L1 blocking has potential for improved clinical benefit [44][45] Question: Delay in BLA filing for BNT323 - The delay is due to ongoing discussions with the FDA regarding additional data needs, with plans to submit in 2026 [52][71] Question: Strategy for pumitamig's establishment and elevation - The three-wave strategy is designed to focus on speed to market while generating data in combination studies [56][57] Question: Phase II details for BNT327 in triple-negative breast cancer - Management confirmed that efficacy, safety, and dose data will be presented at SABCS [62] Question: Collaboration with Bristol Myers Squibb - The collaboration involves a Joint Steering Committee for decision-making on clinical development, allowing flexibility for both partners [88][89]

BioNTech's Vision and Strategy - BioNTech aims to build a global immunotherapy powerhouse translating science into survival[13] - BioNTech has distributed 5 billion doses of COVID-19 vaccine globally[12] - BioNTech is leveraging AI to pioneer personalized immunotherapies[62] InstaDeep's AI Capabilities and Technologies - InstaDeep's AI supercomputer, Kyber, has ~500 PetaFLOPS of Nvidia H100 GPUs and 86,000 CPU Cores[105] - InstaDeep's AI training platform, AIChor, has seen +15,000 experiments per month in 2025 with +75% GPU usage[109] - Nucleotide Transformer (NTv3) pre-trained on genomes from >150,000 species and post-trained on >17,000 functional tracks across 16 species[154] AI-Driven Innovation in Genomics and Proteomics - InstaNovo V2 achieves up to 2x the number of identifications in peptide sequencing[263] - AI-assisted tissue annotation tool increased pathologist efficiency fivefold (5x)[265] - AI pipeline achieves an average 50,000-fold TCR binding enhancement increase over WT[345]

Core Insights - Bristol Myers Squibb (BMY) announced positive data from the late-stage study on iberdomide for patients with relapsed or refractory multiple myeloma (RRMM) [1][8] - The phase III EXCALIBER-RRMM study demonstrated statistically significant improvement in minimal residual disease (MRD) negativity rates compared to the control arm [2][8] - The study is designed to assess dual-primary endpoints of MRD negativity and progression-free survival (PFS), with additional secondary endpoints including overall survival (OS) and health-related quality of life [3] Study Details - The EXCALIBER-RRMM study is a multicenter, two-stage, randomized, open-label trial evaluating iberdomide in combination with Darzalex and dexamethasone versus Darzalex, bortezomib, and dexamethasone [1][3] - The safety profile of iberdomide in combination with daratumumab and dexamethasone is consistent with previous studies, and the trial will continue to evaluate PFS and OS [4] - BMY plans to discuss the results with health authorities as iberdomide represents a novel class of medicines called CELMoDs, which may change the treatment landscape for multiple myeloma [5] Portfolio Expansion - BMY's Growth Portfolio includes drugs such as Opdivo, Orencia, and Yervoy, as the company seeks to expand its pipeline due to the adverse impact of generics on its legacy portfolio [6] - BMY's shares have decreased by 17.8% year-to-date, while the industry has grown by 5.2% [6] Collaboration and New Developments - BMY is collaborating with BioNTech on the development of pumitamig, a bispecific antibody for extensive-stage small cell lung cancer, which has shown a 76.3% confirmed objective response rate in interim data [9][10] - The approval of Cobenfy for schizophrenia broadens BMY's portfolio and validates its acquisition of Karuna Therapeutics, representing a new pharmacological approach to treating schizophrenia [11][12]

Investment Rating - The report does not explicitly state an investment rating for the industry [1] Core Insights - The domestic biopharmaceutical innovation is expected to accelerate, driven by the approval of the "Regulations on the Management of Clinical Research and Clinical Translation Applications of Biomedical New Technologies (Draft)" by the State Council on September 12 [2][12] - The report highlights the importance of promoting biomedical technology innovation and the need for regulatory frameworks to ensure safety and quality in clinical applications [2][12] - The report expresses optimism towards companies focusing on new biomedical technologies, particularly in areas such as gene editing, cell therapy, and stem cell research [2] Weekly Market Review - The biopharmaceutical sector experienced a decline of 0.36% from September 8 to September 12, underperforming compared to the Wind All A index (2.12%) and the CSI 300 index (1.38%) [7] - Among sub-sectors, medical devices (3.02%), in vitro diagnostics (2.0%), and pharmaceutical distribution (1.44%) showed the highest gains, while chemical preparations (-2.83%), raw materials (-1.06%), and blood products (-0.72%) faced the largest declines [7][8] - Notable stock performances included Zhend Medical (41.3%), Haooubo (28.0%), and Jimin Health (25.9%) with significant gains, while Yuekang Pharmaceutical (-18.4%), Maiwei Biotech-U (-14.4%), and Yirui Biotech (-14.0%) saw substantial losses [10] Industry News and Key Company Announcements - The report mentions significant events such as the collaboration between Shiyao Group and Kangning Jiere to develop a new drug for HER2-positive gastric cancer, which has been accepted for review by the National Medical Products Administration [12] - The report also notes the approval of a new drug by Johnson & Johnson for treating non-muscle invasive bladder cancer, marking a significant advancement in bladder cancer treatment [14] - BioNTech and Bristol Myers Squibb reported promising mid-term data for their bispecific antibody in treating extensive-stage small cell lung cancer, showing an objective response rate of 76.3% [14]

Core Insights - Bristol Myers (BMY) and BioNTech (BNTX) presented interim data from a mid-stage study on pumitamig combined with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) [1][10] Company Developments - Pumitamig is a bispecific antibody that combines PD-L1 checkpoint inhibition and VEGF-A neutralization, aimed at enhancing T cell response against tumors [2][3] - The interim analysis involved 43 untreated ES-SCLC patients, showing a 76.3% confirmed objective response rate, a 100% disease control rate, and a median progression-free survival of 6.8 months [3][10] - The combination therapy exhibited a manageable safety profile with no new safety signals and a low discontinuation rate, supporting ongoing pivotal studies [4][10] - Pumitamig received FDA Orphan Drug designation for small cell lung cancer treatment in 2025 [4][10] Industry Context - The dual-target cancer therapy space is competitive, with major players like Merck and Pfizer developing bispecific antibodies targeting PD-1 and VEGF [6] - Merck secured a global license for LM-299, a PD-1/VEGF bispecific antibody, while Pfizer licensed SSGJ-707, another bispecific antibody targeting the same proteins [7][8] Financial Performance - BMY shares have declined by 13% year-to-date, contrasting with the industry growth of 5.5% [12] - BMY is trading at a price/earnings ratio of 7.66X forward earnings, below its historical mean of 8.47X and the large-cap pharma industry's average of 14.94X [13] - The bottom-line estimate for 2025 has decreased to $6.50 from $6.56, while the estimate for 2026 has increased to $6.07 from $6.03 [14]

Core Insights - Bristol-Myers Squibb Company (NYSE:BMY) is recognized as an attractive investment opportunity by hedge funds due to its low valuation [1] - Positive interim data from a Phase 2 trial of the bispecific antibody pumitamig (BNT327/BMS986545) in combination with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) was presented [1][2] - The trial demonstrated encouraging anti-tumor activity and a manageable safety profile, with a discontinuation rate of 14% [2] Company Overview - Bristol-Myers Squibb is involved in the discovery, development, licensing, manufacturing, marketing, distribution, and sale of biopharmaceutical products globally [4] - BioNTech focuses on developing and commercializing immunotherapies for cancer and infectious diseases, primarily in Germany [4] Trial Details - The Phase 2 trial included 43 patients with previously untreated ES-SCLC and showed results consistent with a prior trial conducted in China [2] - Pumitamig operates through dual mechanisms: PD-L1 checkpoint inhibition and neutralization of VEGF-A, aimed at enhancing the immune response against cancer and depriving tumors of blood supply [3] - The positive results support the ongoing global pivotal Phase 3 trial, ROSETTA LUNG-01, which compares pumitamig plus chemotherapy against standard-of-care treatment [3] - Pumitamig received Orphan Drug designation from the US FDA for small-cell lung cancer treatment in 2025 [3]