股份發行人及根據《上市規則》第十九B章上市的香港預託證券發行人的證券變動月報表 致：香港交易及結算所有限公司 公司名稱: 來凱醫藥有限公司 呈交日期: 2025年9月4日 I. 法定/註冊股本變動 | | | | 1. 股份分類 | 普通股 | 股份類別 | 不適用 | | 於香港聯交所上市 (註1) | | 是 | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | 證券代號 (如上市) | 02105 | 說明 | | | | | | | | | | | 法定/註冊股份數目 | | | 面值 | | | 法定/註冊股本 | | | 上月底結存 | | | 5,000,000,000 | USD | | 0.00001 | USD | | 50,000 | | 增加 / 減少 (-) | | | 0 | | | | USD | | 0 | | 本月底結存 | | | 5,000,000,000 | USD | | 0.00001 | USD | | 50,000 | 本月底法定/註冊股本總額： USD 50,000 FF30 ...

Group 1 - Rongchang Biologics (09995.HK) increased by 7.44% [1] - Yongtai Biologics-B (06978.HK) rose by 5.69% [1] - Gilead Sciences-B (01672.HK) saw a gain of 4.41% [1] - Laika Pharmaceuticals-B (02105.HK) experienced a rise of 3.18% [1]

[Definitions](index=3&type=section&id=Definitions) [Company Information](index=8&type=section&id=Company%20Information) [Business Highlights](index=10&type=section&id=Business%20Highlights) [Advancing Clinical Trials](index=10&type=section&id=Advancing%20Clinical%20Trials) LAE102 (ActRIIA monoclonal antibody) Phase I SAD study for obesity completed in China, showing good tolerability and sustained pathway blockade, with Phase I MAD study initiated in China and a Phase I clinical trial started in the US in collaboration with Eli Lilly - LAE102 Phase I SAD study completed in China, showing good tolerability, no serious adverse events reported, and dose-dependent increase in Activin A levels, indicating sustained pathway blockade[14](index=14&type=chunk)[15](index=15&type=chunk) - LAE102 Phase I MAD study initiated recruitment in China by end of March 2025, aiming to assess safety, tolerability, pharmacokinetics, and pharmacodynamics[16](index=16&type=chunk) - Clinical collaboration agreement signed with Eli Lilly, with Lilly responsible for the US Phase I clinical trial, the Group retaining global rights, and the first subject dosed in the US Phase I clinical trial in May 2025[16](index=16&type=chunk) [ActRII Product Portfolio](index=10&type=section&id=ActRII%20Product%20Portfolio) Beyond LAE102, the company is developing LAE103 (ActRIIB selective antibody) and LAE123 (ActRIIA/IIB dual antagonist monoclonal antibody), both with IND-enabling studies initiated, LAE103 received FDA IND approval for Phase I, and LAE123 is planned for Phase I in 2026 - LAE103 (ActRIIB selective antibody) and LAE123 (ActRIIA/IIB dual antagonist monoclonal antibody) initiated IND-enabling studies in 2024[17](index=17&type=chunk) - LAE103's IND application submitted to US FDA by end of June 2025, received IND approval in July 2025, with Phase I clinical study planned for H2 2025[19](index=19&type=chunk) - Preclinical results for LAE102, LAE103, and LAE123 show them to be high-affinity functional antagonists, inhibiting ligands causing muscle atrophy and fat accumulation; LAE102 demonstrates excellent potential in weight management, and LAE123 can treat diseases requiring complete ActRIIA and ActRIIB inhibition[18](index=18&type=chunk) [LAE002 (afuresertib) + Fulvestrant for HR+/HER2– Breast Cancer, Phase III](index=11&type=section&id=LAE002%20%28afuresertib%29%20%2B%E6%B0%9F%E7%BB%B4%E5%8F%B8%E7%BE%A4%E6%B2%BB%E7%96%97HR%2B%2FHER2%E2%80%93%20Breast%20Cancer%2C%20Phase%20III) LAE002 (afuresertib) combined with fulvestrant for HR+/HER2– breast cancer Phase III clinical trial AFFIRM–205 has initiated recruitment in China, with subject enrollment planned for Q4 2025 and NDA submission in H1 2026 - LAE002 (afuresertib) combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer Phase III clinical trial AFFIRM–205 initiated recruitment in China in May 2024[20](index=20&type=chunk) - Subject enrollment is planned for completion in Q4 2025, with New Drug Application (NDA) submission to China CDE in H1 2026[20](index=20&type=chunk) [LAE002 (afuresertib) + LAE001/Prednisone for mCRPC, Phase II](index=11&type=section&id=LAE002%20%28afuresertib%29%20%2B%20LAE001%E2%81%84%E6%B3%BC%E5%B0%BC%E6%9D%BE%E6%B2%BB%E7%99%8CmCRPC%2C%20Phase%20II) LAE002 (afuresertib) combined with LAE001 for mCRPC Phase II international multi-center clinical trial completed, showing a median rPFS of **8.1 months**, good efficacy, and tolerability, with FDA approval for Phase III pivotal trial protocol - LAE002 (afuresertib) combined with LAE001 for mCRPC Phase II international multi-center clinical trial completed in 2024[21](index=21&type=chunk) - Median rPFS was **8.1 months**, a significant improvement compared to **2-4 months** for standard treatment, with the combination therapy generally well-tolerated[21](index=21&type=chunk) - The Group received FDA approval for the LAE201 Phase III pivotal trial protocol in mCRPC patients after SOC treatment[21](index=21&type=chunk) [Preclinical Candidate (PCC) Progress](index=12&type=section&id=Preclinical%20Candidate%20%28PCC%29%20Progress) In addition to ActRII series drugs, the company has multiple PCC advancements in oncology, including PI3Kα mutant selective inhibitor LAE118 entering IND-enabling studies, USP1 inhibitor LAE120's IND application submitted and approved by FDA, and WRN mutant selective inhibitor LAE122 completing PCC confirmation - PI3Kα mutant selective inhibitor LAE118 entered IND-enabling study phase in Q4 2024[22](index=22&type=chunk) - USP1 inhibitor LAE120's IND application submitted to FDA in January 2025, and a 'Study May Proceed' letter received in February 2025[22](index=22&type=chunk) - WRN mutant selective inhibitor LAE122 completed PCC confirmation in March 2025[22](index=22&type=chunk) [Expected Milestones in H2 2025](index=12&type=section&id=Expected%20Milestones%20in%20H2%202025) The company expects to complete subject recruitment for AFFIRM–205 China Phase III trial, initiate LAE103 Phase I clinical study, and announce key results from LAE102 China Phase I MAD study and US Phase I clinical trial in H2 2025 - Complete subject recruitment for AFFIRM–205 China Phase III trial[23](index=23&type=chunk) - Initiate LAE103 Phase I clinical study[24](index=24&type=chunk) - Announce key results from LAE102 China Phase I MAD study and US Phase I clinical trial[25](index=25&type=chunk) [Financial Summary](index=13&type=section&id=Financial%20Summary) Financial Summary for the Six Months Ended June 30, 2025 | Metric | 2025 (RMB thousands) | 2024 (RMB thousands) | Change (RMB thousands) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | R&D Expenses | 105,192 | 126,148 | (20,956) | -16.6% | | Administrative Expenses | 42,321 | 30,380 | 11,941 | 39.3% | | Loss for the Period | 129,637 | 143,706 | (14,069) | -9.8% | | Total Comprehensive Loss for the Period | 133,399 | 138,548 | (5,149) | -3.7% | - The decrease in R&D expenses was primarily due to a **RMB 17.8 million** milestone payment related to the AFFIRM-205 Phase III clinical trial incurred in H1 2024, with no such expense in the current reporting period[26](index=26&type=chunk) - The increase in administrative expenses was mainly due to higher equity-settled share-based payment expenses[26](index=26&type=chunk) [Management Discussion and Analysis](index=14&type=section&id=Management%20Discussion%20and%20Analysis) [Company Overview and Strategic Focus](index=14&type=section&id=Company%20Overview%20and%20Strategic%20Focus) The company is a clinical-stage biopharmaceutical company focused on metabolic diseases, cancer, and liver fibrosis, with seven clinical trials initiated, an experienced management and R&D team, a comprehensive ActRII and cancer pipeline, and plans to seek strategic collaborations for accelerated development and commercialization - The company is a science-driven, clinical-stage biopharmaceutical company focused on metabolic diseases, cancer, and liver fibrosis[27](index=27&type=chunk) - As of June 30, 2025, seven clinical trials have been initiated for LAE102, LAE002 (afuresertib), LAE001, and LAE005[27](index=27&type=chunk) - The company has an excellent R&D team of **60** employees, including **11** PhDs and **33** Masters[27](index=27&type=chunk) - A comprehensive ActRII product portfolio (LAE102, LAE103, LAE123) and oncology pipeline (LAE002 (afuresertib), LAE001, and seven other preclinical candidates) has been established[28](index=28&type=chunk)[29](index=29&type=chunk) - Plans to seek strategic partners to accelerate the development and commercialization of candidate drugs[30](index=30&type=chunk) [Market Opportunity Analysis](index=15&type=section&id=Market%20Opportunity%20Analysis) Global obesity patients are projected to exceed **1.2 billion** by 2030, driving urgent treatment demand for associated diseases, while significant unmet medical needs persist in cancer treatment, particularly for HR+/HER2- metastatic breast cancer, mCRPC, PROC, and TNBC, where existing therapies are limited and suboptimal - The global obese population is

Summary of the Conference Call for LaiKai Pharmaceuticals Company Overview - LaiKai Pharmaceuticals is focused on developing innovative therapies, particularly in the fields of obesity and cancer treatment, with several core products in various stages of clinical development [2][4][5]. Financial Performance - Cash reserves decreased from 700 million RMB in the same period last year to approximately 633 million RMB in the first half of this year, with net cash around 630 million RMB [2][4]. - The net loss slightly reduced from 173 million RMB to 129 million RMB year-over-year [4]. Core Products and Clinical Development - **LQA102**: Currently in Phase I clinical trials, expected to complete MAD (Multiple Ascending Dose) studies by the end of September [2][5]. - **LQA103**: Recently received FDA IND approval, with plans to initiate human trials in the second half of the year [2][5]. - **LAE123**: In the IND enabling stage, with human trials planned for next year [2][5]. - **LAE002**: An AKT inhibitor in Phase III trials for breast cancer in China, with patient enrollment expected to complete in Q4 this year and data readout in the first half of next year [2][5]. Key Clinical Data and Insights - **Bimagrumab**: Data from Eli Lilly indicates a weight loss of over 10% with bimagrumab alone, and over 22% when combined with semaglutide, validating the efficacy of receptor antibodies for obesity treatment [2][8]. - **L2Q a (LQA102)**: Demonstrated significant advantages in weight loss and muscle preservation, with over 41% fat reduction in three weeks during preclinical studies [3][10]. - **AKT Pipeline**: The AKT pipeline is positioned for breast and prostate cancer, with expectations for NDA submission in Q2 next year [12][29]. Market Interest and Strategic Positioning - International market interest is high, as evidenced by Eli Lilly's acquisition of bimagrumab for $1.925 billion and Merck's acquisition of Acero Farm for $11.5 billion, indicating the potential of LaiKai's product portfolio [2][9]. - Multiple multinational corporations (MNCs) are exploring opportunities in the weight loss sector post-ADA conference [9]. Future Directions and Collaborations - LaiKai is actively pursuing partnerships and collaborations, particularly for the 102 and 103 projects, which are expected to enhance business development (BD) opportunities and transaction sizes [18][34]. - The company is also focusing on the development of combination therapies with GLP-1 drugs to address muscle loss associated with obesity treatments [21][27]. Safety and Efficacy Considerations - The MAD study for LQA102 is designed to assess safety and efficacy, with no new safety signals observed thus far [13][14]. - Long-term safety of bimagrumab has shown positive metabolic outcomes, including significant reductions in waist circumference and inflammatory markers [32][33]. Conclusion - LaiKai Pharmaceuticals is positioned at the forefront of innovative drug development in obesity and cancer treatment, with a strong pipeline and significant market interest. The company is focused on advancing its clinical trials and exploring strategic partnerships to maximize shareholder value [35].

Core Viewpoint - The company reported a loss of 130 million yuan in the first half of 2025, a slight improvement from a loss of 144 million yuan in the same period last year, highlighting its ongoing challenges in achieving profitability and revenue generation [1] Pipeline and Product Development - The company's pipeline focuses on two main areas: ActRII target drugs in the metabolic field aimed at weight loss and muscle gain, and various targets in the oncology field including AKT and CYP17A1 [3][5] - The ActRII target drug LAE102 has become the core of the company's valuation, with ongoing clinical research aimed at developing it as a new therapy for muscle-related and other diseases [5][6] - LAE102 is positioned uniquely as it aims to achieve both fat loss and muscle gain, a shift from its initial focus on cancer treatment [6][7] - The company has initiated clinical trials for LAE102, with plans to complete the primary phase of the U.S. trial by the fourth quarter of 2025 [7][8] Clinical Trials and Collaborations - The company has partnered with Eli Lilly to conduct Phase I clinical trials for LAE102 in the U.S., retaining global rights for the drug [7] - LAE103 and LAE123, additional ActRII antibody drugs, are also in development, with LAE103 having received FDA approval for clinical trials [8] - The company is actively seeking strategic partnerships to accelerate the development and commercialization of its products, particularly LAE002 and LAE001 in the oncology space [9][10] Market Position and Challenges - The company faces significant challenges in the oncology sector, particularly with the AKT target, where many competitors have struggled to achieve successful drug approvals [10] - Despite the innovative potential of LAE102, its clinical value remains to be fully validated, and the company's future valuation hinges on the success of its clinical trials [7][9]

Core Viewpoint - The company, LaiKai Pharmaceuticals, focuses on high-quality fat reduction and muscle gain in weight loss, addressing unmet needs in the oncology field, and possesses globally competitive pipelines [1][2]. Group 1: Investment Highlights - LaiKai Pharmaceuticals is a science-driven, clinical-stage biopharmaceutical company expected to enter a revenue-generating phase, with projected revenues of 0, 0, and 280 million yuan for 2025, 2026, and 2027 respectively, and net profits of -300 million, -313 million, and -190 million yuan for the same years [1]. - The company is assigned a target price of 29.19 HKD using DCF absolute valuation method and is rated as a buy [1]. Group 2: Research and Development Focus - The focus on fat reduction and muscle gain is a key research area in the future weight loss drug sector, with a need for differentiated innovation in "fat reduction + muscle gain" to address high muscle loss during weight loss and rebound weight gain [1]. - LaiKai Pharmaceuticals has established a comprehensive pipeline targeting the ActRII signaling pathway, including LAE102, LAE103, and LAE123 [1]. Group 3: Oncology Pipeline - The core pipeline LAE002 (afuresertib) is one of only two late-stage clinical AKT inhibitors globally targeting breast and prostate cancer, offering higher efficacy, better drug action, and improved safety [2]. - LAE002 addresses unmet medical needs in oncology, covering indications such as breast cancer, prostate cancer, ovarian cancer, and PD-1/PD-L1 resistant solid tumors [2]. Group 4: Management Team - The management team of LaiKai Pharmaceuticals has extensive experience and a deep understanding of relevant target pathways, with the chairman, Dr. Lü Xiangyang, being a co-inventor of Bimagrumab and having over 20 years of experience in the ActRII pathway [2]. - Key members of the board, including Dr. Ge Xiangju and Director Xie Ling, have backgrounds in international pharmaceutical companies like Novartis, specializing in new drug discovery, clinical development, and registration [2].

Core Viewpoint - The Hong Kong stock market's innovative pharmaceutical sector has rebounded strongly since 2025, with a cumulative increase of nearly 100%, and over 30 pharmaceutical companies have seen their stock prices double, making it a focal point in the capital market. The core driver of this trend is the revaluation of value, indicating that the sector's valuation remains attractive [1]. Group 1: Company Performance - Lai Kai Pharmaceutical has shown remarkable performance, with its stock price increasing over 300% in the past year, and multiple investment banks have set target prices above HKD 27 [2]. - The company has made significant breakthroughs in its core areas of metabolism and cancer treatment, showcasing its innovative research capabilities through the advancement of specific pipelines [5]. Group 2: Metabolic and Cancer Treatment Innovations - In the metabolic field, Lai Kai has built a comprehensive product portfolio centered around the ActRII pathway, gradually advancing these candidate drugs into clinical research to explore their therapeutic potential in muscle-related and other diseases [5]. - The LAE102 (ActRIIA monoclonal antibody) has demonstrated clear therapeutic value, with data from Eli Lilly showing that weight loss was entirely from fat, while muscle mass increased by 2.5% [5]. - LAE102 has shown better safety and tolerability compared to Bimagrumab, with no serious adverse events reported, indicating its potential as a best-in-class drug [6]. Group 3: Clinical Collaborations and Market Potential - Eli Lilly's acquisition of Bimagrumab for USD 1.925 billion and subsequent clinical collaboration with Lai Kai for LAE102 underscores the clinical value of LAE102 and accelerates its global development process [7]. - The LAE002 (afuresertib) is positioned to become the first domestic AKT inhibitor, with ongoing Phase III trials expected to complete recruitment by Q4 2023, aiming for a new drug application submission in mid-2026 [8]. Group 4: Long-term Growth Drivers - Lai Kai's growth is supported by its internationalization strategy and robust R&D system, which together create a solid foundation for sustainable development [9]. - The collaboration with Eli Lilly is expected to attract more multinational pharmaceutical companies, enhancing Lai Kai's position in the global innovative drug industry [10]. - The global obesity drug market is projected to exceed USD 100 billion by 2030, and LAE102 is well-positioned to capture a significant share of this market [10]. Group 5: R&D Advancements - Lai Kai continues to enhance its R&D capabilities, with multiple drug candidates progressing through various stages of development, including LAE103 and LAE120, which have received IND approvals [11]. - The company's strong innovation capabilities are translating into tangible R&D results, with its pipeline entering a phase of readiness for future growth [11]. Group 6: Financial Position - Lai Kai Pharmaceutical has a cash and bank balance of RMB 742 million, providing a solid financial foundation for ongoing innovative research and development [12]. - As innovative products like LAE002 and LAE102 approach commercialization, the market's recognition of Lai Kai's intrinsic value is expected to transition from growth expectations to value realization [12].

Core Viewpoint - The Hong Kong stock market's innovative pharmaceutical sector has rebounded strongly since 2025, with a cumulative increase of nearly 100%, and over 30 pharmaceutical companies have seen their stock prices double, indicating a significant capital market focus on this sector [1] Group 1: Company Performance - Lakai Pharmaceuticals has shown remarkable performance, with its stock price increasing over 300% in the past year, and multiple investment banks have set target prices above HKD 27 [2] - The company has made significant breakthroughs in the fields of metabolism and cancer treatment, showcasing its innovative research capabilities through the advancement of specific drug pipelines [5] Group 2: Metabolic Drug Development - Lakai Pharmaceuticals has established a comprehensive product portfolio centered around the ActRII pathway, gradually advancing these candidate drugs into clinical research to explore their therapeutic potential in muscle-related and other diseases [5] - The monoclonal antibody LAE102, targeting ActRIIA, has demonstrated clear therapeutic value, with data from Eli Lilly's Bimagrumab showing significant weight loss primarily from fat while preserving muscle mass [5][6] - LAE102's clinical trial results indicate good tolerability compared to Bimagrumab, with no serious adverse events reported, highlighting its potential as a best-in-class drug [6] Group 3: Strategic Collaborations - Eli Lilly's acquisition of Bimagrumab for USD 1.925 billion and subsequent clinical collaboration with Lakai Pharmaceuticals for LAE102 underscores the clinical value of LAE102 and accelerates its global development process [7] - The FDA has approved the clinical application of another ActRIIB monoclonal antibody, LAE103, which is set to initiate Phase I clinical trials in the second half of the year, further establishing Lakai's competitive advantage in the metabolic drug space [8] Group 4: Cancer Drug Development - In the oncology sector, LAE002 (afuresertib), an AKT inhibitor, is positioned to become the first domestic AKT inhibitor, with ongoing Phase III clinical trials for specific breast cancer patients [9] - The market potential for AKT inhibitors is significant, as evidenced by AstraZeneca's Capivasertib, which is projected to achieve global sales of USD 430 million in 2024 and potentially reach USD 1 billion in the future [9] Group 5: Long-term Growth Strategy - Lakai Pharmaceuticals' growth is driven by both international expansion and a robust self-research system, creating a solid foundation for sustainable development [10] - The collaboration with Eli Lilly not only validates the company's research capabilities but also opens up opportunities for further partnerships with multinational pharmaceutical companies [11] - The company is actively discussing strategic collaborations to accelerate the development and commercialization of the ActRII product portfolio, with expectations of significant market penetration [11] Group 6: Financial Position - Lakai Pharmaceuticals has a cash and bank balance of RMB 742 million, providing a stable financial foundation for ongoing innovative research and development [13] - The anticipated market recognition of the intrinsic value of Lakai Pharmaceuticals is expected to transition from growth expectations to value realization as innovative products reach the market [13]

Core Viewpoint - The company reported a significant increase in other income and a reduction in R&D expenses, while also showing a decrease in losses, indicating a positive trend in financial performance and ongoing development of promising drug candidates [1][2][3] Financial Performance - The company achieved other income of RMB 19.908 million for the six months ending June 30, 2025, representing a year-on-year increase of 40.7% [1] - R&D expenses amounted to RMB 105 million, a decrease of 16.61% year-on-year [1] - The net loss for the period was RMB 130 million, which is a 9.79% reduction compared to the previous year [1] - As of June 30, 2025, the company had current assets of RMB 762 million, including cash and cash equivalents of RMB 677 million, indicating strong financial reserves for future R&D projects [1] Drug Development - LAE102, a monoclonal antibody targeting ActRIIA, has shown potential for muscle regeneration and weight control, with successful completion of the single ascending dose part of Phase I clinical trials for obesity treatment in China by the end of 2024 [1] - The company initiated a Phase III clinical trial (AFFIRM-205) in May 2024 for LAE002 (afuresertib), an oral AKT inhibitor, in combination with Fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer patients [2] - The Phase III trial is a multi-center, randomized, double-blind, placebo-controlled study aimed at evaluating the anti-tumor efficacy and safety of the combination therapy, with plans to complete subject enrollment by Q4 2025 and submit a New Drug Application (NDA) in H1 2026 [2] - The company has submitted an IND application for LAE103 to the FDA as of June 30, 2025, with plans to initiate Phase I clinical trials in the second half of 2025 [3]

Core Viewpoint - The company reported a significant increase in other income due to government subsidies, while R&D expenses decreased, leading to a reduced loss compared to the previous year [1][2]. Financial Performance - Other income reached RMB 19.908 million, a year-on-year increase of 40.7% [1] - R&D expenses amounted to RMB 105 million, a decrease of 16.61% year-on-year [1] - The loss for the period was RMB 130 million, a reduction of 9.79% compared to the previous year [1] - As of June 30, 2025, current assets totaled RMB 762 million, with cash and cash equivalents at RMB 677 million, indicating strong financial reserves for future R&D projects [1] Clinical Development - LAE102, a monoclonal antibody targeting ActRIIA, has shown potential for muscle preservation and weight control, with successful completion of the single ascending dose part of Phase I clinical trials for obesity treatment in China by December 2024 [1] - The company initiated a Phase III clinical trial (AFFIRM-205) in May 2024 for LAE002 (afuresertib) in combination with Fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer patients [2] - The Phase III trial is a multi-center, randomized, double-blind, placebo-controlled study aimed at evaluating the efficacy and safety of the combination therapy, with plans to complete subject enrollment by Q4 2025 and submit a New Drug Application (NDA) in H1 2026 [2] - The company is in discussions with potential partners to accelerate the regulatory approval and commercialization of LAE002 and LAE001 [2] Future Plans - The IND application for LAE103 was submitted to the FDA by the end of June 2025, with plans to initiate Phase I clinical trials in the second half of 2025 [3] - The company aims to evaluate the efficacy and safety of monoclonal antibodies targeting ActRIIA and ActRIIB through the Phase I clinical study of LAE103 [3] - Plans are also in place to advance LAE123 to Phase I clinical trials in 2026 [3]