Core Insights - The pharmaceutical MNC supply chain has extremely high entry barriers, requiring years for supplier certification through cross-departmental audits in technology, quality, EHS, and compliance. Once included in the qualified supplier list, a strong lock-in effect is formed, making it difficult for new entrants to disrupt the existing supply structure even if they meet technical standards, thus demonstrating a strong first-mover advantage [4][7]. - MNCs demand far more than conventional quality compliance, emphasizing full-process controllability and risk management capabilities. Compliance with guidelines such as EU GMP and ICHQ is required, along with the establishment of traceability systems and safety stock. Any process changes or relocation of production sites must undergo strict and time-consuming certification [4][7]. - In procurement decisions, MNCs are relatively insensitive to price factors, prioritizing the integrity of the supply chain over cost. For MNCs, API costs represent only a small portion of their terminal formulation sales, leading them to pay a premium for stable, traceable, and zero major quality incident supply capabilities, viewing supply chain resilience as a core competitive advantage rather than a cost item. Thus, entering the MNC supply chain often means effectively avoiding "price internalization" [4][7]. - Investment recommendations include innovative drug and device companies such as Furuya Co., Aonlikang, Shutaishen, Weichuang Bio, and others. From the perspective of CXO and raw materials, companies like WuXi AppTec, Jiuzhou Pharmaceutical, Chengda Pharmaceutical, and others are suggested for attention [4][7]. Market Performance Overview - As of November 21, 2025, the TTM-PE of the pharmaceutical and biotechnology industry is 48.84 times, which is 100% higher than the historical lowest PE valuation of 24.38 times on January 3, 2019. The premium rate relative to the CSI 300 is 252%, exceeding the historical lowest valuation premium of 124% on February 6, 2018, by 128 percentage points, and is 11 percentage points higher than the average valuation premium rate of 241% over the past decade [8][12]. - From November 17 to November 21, 2025, the pharmaceutical and biotechnology sector experienced a decline of 6.88%, ranking 22nd among 27 sub-industries. The chemical raw materials sector saw the largest decline at -8.60% [12][15]. Industry Dynamics - Pfizer's Class 1 new drug, Matacizumab, was approved for marketing on November 21, 2025, for the routine prevention and treatment of bleeding in patients with severe hemophilia A or B [20]. - Boehringer Ingelheim's Class 1 new drug, BI764198, was proposed for inclusion as a breakthrough therapy on November 18, 2025, targeting primary focal segmental glomerulosclerosis [21]. - The PD-1 inhibitor H drug, Surulutumab, developed by Fuhong Hanlin, was officially included as a breakthrough therapy on November 20, 2025, for gastric cancer treatment [22]. - On November 17, 2025, FDA approved the biosimilar of Tysabri, developed by Sandoz, for multiple sclerosis and Crohn's disease [23].

证券研究报告 创新药周报20251123： 首个APOC3 siRNA疗法获批上市用于治疗FCS 2025-11-23 证券分析师 刘浩 执业编号：S0360520120002 邮箱：liuhao@hcyjs.com 联系人 段江瑶 邮箱：duanjiangyao@hcyjs.com 联系人 吴昱爽 邮箱：wuyushuang@hcyjs.com 本报告由华创证券有限责任公司编制 卖的出价或询价。本报告所载信息均为个人观点，并不构成对所涉及证券的个人投资建议。 请仔细阅读PPT后部分的分析师声明及免责声明。 @2021 华创版权所有 第一部分 本周创新药重点关注 国内创新药回顾 02 全球新药速递 03 01 代谢疾病与核酸靶向疗法 证券研究报告 资料来源：Umidakhon Makhmudova, et al.，Advances in nucleic acid-targeted therapies for cardiovascular disease prevention，Eliot A. Brinton, et al.，Familial chylomicronemia syndrome and treat ...

Core Viewpoint - Olema Pharmaceuticals (OLMA) shares experienced a significant increase following Roche's positive clinical results for its breast cancer drug giredestrant, indicating a strong market potential for oral SERDs in hormone-driven breast cancer treatment [1][3]. Company Developments - Olema's stock price nearly tripled on November 18, closing up 136% after Roche's announcement, and continued to rise in subsequent trading [1]. - The company's lead candidate, palazestrant, is an oral SERD targeting breast cancer, similar to Roche's giredestrant, which has shown promising results [3][4]. Market Potential - The success of Roche's giredestrant validates the oral SERD class, enhancing confidence in Olema's pipeline and positioning palazestrant as a viable contender in a multibillion-dollar market [4][6]. - Oppenheimer's analyst Matthew Biegler increased the probability of palazestrant's success from 50% to 75% following Roche's data, reflecting a more optimistic outlook for Olema [6]. Analyst Ratings - Biegler maintained an "Outperform" rating on Olema and raised the price target to $45, suggesting a potential upside of 105% from current levels [6]. - The consensus rating for OLMA stock is currently "Strong Buy," with a mean target of approximately $24, indicating a potential upside of about 9% [9].

Core Viewpoint - The positive results from Roche's oral SERD drug giredestrant in the lidERA trial have significantly boosted the stock of Olema Pharmaceuticals, indicating a de-risking effect for the entire SERD sector and positioning Olema's core asset, Palazestrant, as a leading candidate in breast cancer treatment [1][2][21]. Summary by Sections Roche's Giredestrant Trial Results - Roche announced that its oral SERD drug giredestrant achieved positive results in the lidERA study, marking the second Phase III positive data following the evERA trial at ESMO 2025 [2]. - The lidERA study involved over 4,100 patients and demonstrated statistically significant and clinically meaningful improvements in invasive disease-free survival compared to standard endocrine therapy for early-stage ER+/HER2- breast cancer patients [2][3]. Palazestrant's Mechanism and Development - Palazestrant, Olema's leading candidate, is a novel oral complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD) designed to inhibit estrogen receptor signaling and promote cancer cell degradation [4][5]. - Palazestrant's dual mechanism targets the root of resistance in breast cancer, offering a more effective treatment option compared to traditional SERDs [11][12]. Clinical Data and Future Prospects - Clinical data from ESMO 2025 showed that Palazestrant, in combination with ribociclib, achieved a median progression-free survival (PFS) of 15.5 months across all patients, with specific subgroups showing promising results [14][15][16]. - Palazestrant is currently undergoing two critical Phase III trials, with initial results expected in late 2026, which could pave the way for FDA submission and commercialization [8][9]. Industry Implications - The advancements in oral SERD therapies, particularly with Roche and Olema's developments, signify a paradigm shift in breast cancer treatment, moving towards more convenient and effective options for patients [20]. - The market is recognizing the value of Palazestrant, with potential peak sales estimated between $2.5 billion to $5 billion, indicating a significant opportunity for Olema in the competitive landscape of breast cancer therapies [17][21].

Summary of Olema Pharmaceuticals Conference Call Company Overview - **Company**: Olema Pharmaceuticals - **Focus**: Development of treatment options for breast cancer, specifically targeting estrogen receptor positive, HER2 negative breast cancer, which constitutes about 70% of breast cancer cases [3][4] Lead Asset - **Lead Molecule**: Palazestrant - **Mechanism**: Complete estrogen receptor antagonist, effectively shutting down growth signals [3] - **Clinical Trials**: - **OPERA-01**: Phase 3 trial for second/third-line treatment, readout expected in late 2026 [4] - **OPERA-02**: Phase 3 trial for first-line metastatic treatment in combination with ribociclib, readout expected in late 2028 [4][5] - **OP3136**: KAT6 inhibitor in Phase 1 trials for breast cancer, prostate cancer, and non-small cell lung cancer [5] Industry Context - **Market Size**: - Current global market for CDK4/6 inhibitors is approximately $15 billion, expected to grow to $15 billion-$20 billion by 2030 [20] - First-line breast cancer treatment market estimated at $10 billion-$15 billion, with second/third-line market at about $5 billion in the U.S. [34] Competitive Landscape - **Roche's LIDARA Trial**: Positive interim results reported, indicating improved disease-free survival with giredestrant [9][10] - **Comparison with Roche**: Olema's palazestrant shows better progression-free survival (PFS) in both ESR1 mutant and wild type populations compared to Roche's data [12][21] Key Findings from Recent Data - **ESMO Presentation**: Olema's phase 2 data showed approximately 10 months PFS in ESR1 wild type, compared to 5.5 months in Roche's control arm [12] - **Regulatory Considerations**: OPERA-01 and OPERA-02 trials are designed to separately analyze ESR1 mutant and wild type populations, enhancing regulatory clarity [24][26] Collaborations - **Novartis**: Collaboration for ribociclib supply in OPERA-02 trial [29] - **Pfizer**: Collaboration for atirmociclib, aiming to explore next-generation endocrine therapies [30][32] Future Expectations - **Upcoming Data**: Phase 1 data for OP3136 expected in the first half of 2026, focusing on safety and preliminary efficacy [41] - **Potential Indications**: Besides breast cancer, OP3136 is being explored for prostate cancer and non-small cell lung cancer, with preclinical activity observed [42][43] Conclusion - Olema Pharmaceuticals is positioned to capitalize on significant market opportunities in breast cancer treatment, with promising clinical data and strategic collaborations enhancing its competitive edge in the industry [20][34]

Key Takeaways Roche's giredestrant showed significant invasive disease-free survival benefit in the phase III lidERA study.This is the first SERD study in the adjuvant setting to deliver a meaningful advantage over standard therapy.Positive interim data follow an earlier phase III win and support giredestrant's breast cancer programRoche (RHHBY) announced positive data from the late-stage lidERA Breast Cancer study on pipeline candidate giredestrant.Giredestrant is an investigational, oral, potent next-gene ...

Core Viewpoint - Olema Pharmaceuticals' stock surged significantly following positive phase 3 results from Roche's giredestrant study for early-stage breast cancer, indicating strong market interest and potential in the SERD drug sector [1][3]. Stock Performance - Olema Pharmaceuticals shares increased by 136.8%, reaching $20.17 during midday trading on Tuesday [3]. - The stock's rise was in stark contrast to Martin Shkreli's short position declaration, which suggested skepticism about Olema's valuation [1][2]. Analyst Ratings and Price Targets - HC Wainwright & Co. analyst Emily Bodnar maintained a Buy rating and raised the price target from $28 to $36 [4]. - Oppenheimer analyst Matthew Biegler kept an Outperform rating and increased the price target from $22 to $45 [4]. - JPMorgan maintained an Overweight rating and raised the price target from $29 to $32 [4]. Market Context - Shkreli criticized the overcrowded SERD market, implying that Olema's high valuation was unwarranted, yet the stock's performance suggests a differing market sentiment [2][3].

Core Insights - The drugmaker's results for giredestrant indicate a potential new treatment option for early-stage cancer, which is significant as most patients are diagnosed at this stage [1] Company Summary - The introduction of giredestrant could enhance the treatment landscape for early-stage cancer patients, potentially leading to improved patient outcomes [1]

Core Insights - Roche's experimental oral drug giredestrant has demonstrated efficacy in reducing the risk of recurrence of a common form of breast cancer post-surgery, positively impacting the company's stock performance and reinforcing its established reputation in oncology [1] Company Summary - The successful results of giredestrant contribute to Roche's portfolio in oncology, highlighting the company's ongoing commitment to cancer treatment innovation [1] - The positive market reaction indicates investor confidence in Roche's ability to deliver effective cancer therapies, which may enhance its competitive position in the pharmaceutical industry [1]

Core Insights - Genentech, a member of the Roche Group, announced positive Phase III results from the lidERA Breast Cancer study for giredestrant as an adjuvant endocrine treatment for ER-positive, HER2-negative early-stage breast cancer [1] Group 1 - The study met its primary endpoint at a pre-planned interim analysis [1] - The results showed a statistically significant outcome [1]