年度報告 2024 目錄 | 公司資料 | 2 | | --- | --- | | 主席報告 | 4 | | 管理層討論及分析 | 6 | | 董事會報告 | 21 | | 董事及高級管理層 | 48 | | 企業管治報告 | 55 | | 獨立核數師報告 | 71 | | 綜合損益表 | 76 | | 綜合全面收益表 | 77 | | 綜合財務狀況表 | 78 | | 綜合權益變動表 | 80 | | 綜合現金流量表 | 81 | | 綜合財務報表附註 | 83 | | 釋義 | 137 | | 四年財務概要 | 144 | 公司資料 執行董事 劉利平博士 （本公司董事會主席兼行政總裁） 於萌女士 非執行董事 提名委員會 劉利平博士 （主席） 李靖博士 孔德偉先生 聯席公司秘書 高麗萍女士 （於二零二四年十二月十九日獲委任） 朱璧敏女士 於莉女士 （自二零二四年十二月十九日起辭任） 朱迅博士 馬立雄先生 （董事會副主席） 江峰先生 李鋰先生 （自二零二四年二月二日起辭任） 獨立非執行董事 譚擘先生 李靖博士 孔德偉先生 審核委員會 譚擘先生 （主席） 李靖博士 孔德偉先生 薪酬委員會 李靖博士 （主席） 劉 ...

智通财经APP讯，君圣泰医药-B(02511)公布，公司自主研发的肠肝抗炎及代谢调节剂熊去氧胆小檗硷 (HTD1801)在中国2型糖尿病(T2DM)患者中开展的两项3期临床试验(SYMPHONY 1和SYMPHONY 2)达 成主要疗效终点及多个次要疗效终点。 在两项研究中，治疗24周后，HTD1801治疗组中达到HbA1c<7.0%的患者比例显着高于安慰剂组。与安 慰剂相比，HTD1801可同时显著降低餐后血糖及空腹血糖。此外，HTD1801展现出糖脂同降能力，可 显着降低低密度脂蛋白胆固醇 (LDL-C)、非高密度脂蛋白胆固醇(non-HDL-C)。另外，HTD1801治疗能 够降低与心血管事件及T2DM患者临床结局密切相关的炎症标记物γ-谷氨酰转移酶(GGT) 和超敏C反应 蛋白(hs-CRP)。 这两项3期临床试验结果充分证明了HTD1801一药多效、为T2DM患者提供综合获益的特性。基于此次 发布的积极的临床试验数据，君圣泰医药计划于今年内向国家药品监督管理局(NMPA)药品审评中心 (CDE)递交HTD1801治疗T2DM适应症的新药上市申请(NDA)。 两项研究中，HTD1801皆表现出良好的安 ...

香港交易及結算所有限公司及香港聯合交易所有限公司對本公告的內容概不負責，對其準確性 或完整性亦不發表任何聲明，並明確表示，概不對因本公告全部或任何部分內容而產生或因倚 賴該等內容而引致的任何損失承擔任何責任。 HighTide Therapeutics, Inc. （於開曼群島註冊成立的有限公司） (Stock Code: 2511) 截至二零二四十二月三十一日止年度的 全年業績公告 我們是一家新型生物製藥公司，專注於研究和開發代謝性疾病領域的突破性治療 方案，為全球患者帶來綜合獲益。 代謝性慢病治療領域存在重大的未滿足臨床需求，給患者和其家庭帶來了沉重負 擔。這些疾病往往具有共通的致病機製，從而導致多種代謝性共病的發生，這不 僅加劇了疾病管理的複雜性，還使得患者預後不佳。我們正在開發能解決疾病核 心問題並降低患者共病風險的突破性治療方案，旨在為患者帶來全面健康獲益。 我們的核心產品熊去氧膽小檗堿(HTD1801)是一種靶向腸-肝系統的口服抗炎及代 謝調節劑，作為熊去氧膽酸和小檗堿形成的離子鹽，是一種具有獨特雙機製的新 分子實體（NME），通過激活AMPK及抑制NLRP3炎症小體發揮其生物學活性。 激活AMP ...

Product Development and Clinical Trials - HighTide Therapeutics has developed a pipeline of 5 candidate products targeting 8 indications related to metabolic and digestive diseases, with 2 candidates currently in clinical stages[7]. - The candidate HTD1801 (Ursodeoxycholic Acid) is in Phase II trials for severe hypertriglyceridemia and primary sclerosing cholangitis, with fast track and orphan drug designations in the US and Canada[8]. - The company has completed Phase IIa and IIb studies for metabolic-associated fatty liver disease in the US, Hong Kong, and mainland China[8]. - HTD4010, a peptide drug, has completed Phase I trials for alcoholic hepatitis in Australia[8]. - HighTide Therapeutics aims to provide effective and safe treatment options for complex metabolic and digestive diseases, addressing unmet clinical needs[7]. - HighTide Therapeutics is focused on developing multi-functional and multi-target therapies to improve overall clinical benefits for patients[7]. - The pipeline includes candidates HTD1804, HTD1805, and HTD2802, which are in various stages of development for obesity, metabolic diseases, and inflammatory bowel disease, respectively[8]. - HTD1801 is a new molecular entity targeting intestinal and hepatic inflammation and metabolic regulation, crucial for treating metabolic and digestive system diseases[9]. - The IIa study of HTD1801 in patients with metabolic-associated fatty liver disease (MAFLD) and type 2 diabetes showed statistically significant improvement in liver fat content compared to placebo[10]. - The ongoing IIb study of HTD1801 for MAFLD with type 2 diabetes has completed patient enrollment as of March 2024, with data readout expected in the first half of 2025[11]. - HTD1801 has demonstrated significant therapeutic effects on glucose metabolism, including statistically significant reductions in HbA1c and fasting blood glucose levels in clinical trials conducted in China[12]. - The company initiated a Phase III registration trial for HTD1801 in treating type 2 diabetes in November 2023, with patient enrollment for two Phase III trials completed by June 2024[13]. - HTD1801 treatment has shown to improve key metabolic markers and liver injury indicators in type 2 diabetes patients, particularly in those with more severe disease[12]. - HTD1801's unique mechanism of action may provide significant metabolic benefits for patients with MAFLD and type 2 diabetes, addressing the complex relationship between these conditions[11]. - The company anticipates completing clinical trials for HTD1801 and data readout by 2025, positioning it as a promising treatment option for metabolic complications[13]. - HTD1801 has shown statistically significant reduction in serum alkaline phosphatase levels, a key biomarker for cholestatic liver disease, compared to the placebo group in the Phase II clinical trial[14]. - The Phase II clinical trial for HTD1801 in primary sclerosing cholangitis was completed in August 2020 in the US and Canada, demonstrating good safety profiles including liver-related safety[14]. - Clinical pre-trial studies indicate that HTD1801 may improve lipid levels in models of metabolic-associated fatty liver disease[15]. - The company plans to initiate Phase II clinical trials for HTD1801 in severe hypertriglyceridemia based on clinical progress and resource allocation[16]. - HTD4010 is in early clinical development for the treatment of alcoholic hepatitis, a severe condition characterized by acute liver inflammation[17]. - HTD1804 is being evaluated for its effects on obesity, which is increasingly linked to various health risks including cardiovascular diseases and type 2 diabetes[18]. - HTD1805 is a multifunctional small molecule drug in preclinical stages aimed at treating metabolic diseases, showing potential similar to HTD1801[19]. Financial Performance - The company recorded a loss of RMB 210.9 million for the six months ended June 30, 2024, compared to a loss of RMB 549.7 million for the same period in 2023[32]. - Other income and gains increased by 68.7% to RMB 38.3 million for the six months ended June 30, 2024, compared to RMB 22.7 million for the same period in 2023, primarily due to an increase in government grants of approximately RMB 15.1 million[27]. - Research and development costs rose by 68.2% to RMB 202.0 million for the six months ended June 30, 2024, from RMB 120.1 million for the same period in 2023, mainly due to an increase in third-party contract expenses of approximately RMB 70.8 million[29]. - The group reported a net loss of RMB 210.945 million for the six months ended June 30, 2024, compared to a net loss of RMB 549.744 million for the same period in 2023[44]. - Adjusted net loss for the six months ended June 30, 2024, was RMB 156.909 million, compared to RMB 105.349 million for the same period in 2023[44]. - The company reported a total comprehensive loss of RMB 208,148,000 for the period, a significant reduction from RMB 586,343,000 in the same period last year[96]. - The company reported a significant increase in equity-settled share-based payment arrangements, totaling RMB 54,036,000 for the six months ended June 30, 2024, compared to RMB 28,445,000 for the same period in 2023[99]. - The company recorded a cash outflow from operating activities of RMB 183,507,000 for the six months ended June 30, 2024, compared to RMB 143,908,000 for the same period in 2023[99]. - The company incurred financing costs of RMB 481,000 for the six months ended June 30, 2024, compared to RMB 201,000 for the same period in 2023[99]. - The company’s total liabilities decreased to RMB 1,907,256,000 as of June 30, 2024, from RMB 1,696,311,000 as of December 31, 2023[98]. - The company’s equity attributable to owners was RMB 548,662,000, down from RMB 702,774,000, reflecting a decrease of 22%[97]. - The company reported a basic loss per share of RMB (0.47) for the six months ended June 30, 2024, compared to RMB (2.16) for the same period in 2023, with a weighted average of 452,074,904 shares outstanding[119]. - The total income tax expense for the six months ended June 30, 2024, was RMB 538,000, compared to RMB 26,000 for the same period in 2023, reflecting an increase due to the company's operations in various jurisdictions[117]. Shareholder Information - As of June 30, 2024, Dr. Liu Liping holds 81,000,000 shares, representing approximately 15.74% of the issued shares[60]. - Dr. Liu also has voting rights over 16,351,927 shares, accounting for 3.18% of the issued shares[60]. - Mr. Ma Lixiong controls 30,194,154 shares, which is 5.87% of the total issued shares[60]. - Major shareholder Li Li holds 77,804,710 shares, which is 15.11% of the total issued shares[64]. - Hepalink Biotechnology II Limited has a beneficial ownership of 64,289,500 shares, accounting for 12.49% of the issued shares[64]. - Founder BVI has a beneficial ownership of 81,000,000 shares, representing 15.74% of the total issued shares[64]. - The company has established a consistent action agreement among major shareholders to align on operational and development matters since September 1, 2019[62]. - The total number of issued shares as of June 30, 2024, is 514,770,668[65]. - The company has a total of 41,225,472 shares held under the 2020 Employee Stock Ownership Plan, representing 8.01% of the issued shares[64]. Corporate Governance and Compliance - The company has complied with the corporate governance code, except for the separation of the roles of Chairman and CEO, which are held by the same individual[49]. - The audit committee, consisting of three independent non-executive directors, reviewed the interim results and found them to comply with relevant accounting standards[55]. - The company did not engage in any significant litigation that could adversely affect its financial position or operational performance during the reporting period[52]. - The board does not recommend the distribution of an interim dividend for the six months ending June 30, 2024[57]. - As of June 30, 2024, the company has no other disclosures regarding the interests or short positions of directors or senior executives[63]. Market and Strategic Outlook - The company is investing 50 million USD in R&D for new technologies aimed at treating metabolic-related diseases[132]. - Market expansion plans include entering two new international markets by Q3 2024, projected to increase market share by 5%[134]. - The company has completed a strategic acquisition of a biotech firm for 300 million USD, enhancing its product pipeline[133]. - The company provided guidance for the next quarter, expecting revenue to be between 1.3 billion USD and 1.5 billion USD, indicating a potential growth of 10% to 25%[133]. - New product launches are anticipated to contribute an additional 200 million USD in revenue over the next year[134]. - The company is focusing on addressing severe hypertriglyceridemia, a condition linked to serious health issues, which aligns with its therapeutic goals[135].

Product Development and Clinical Trials - The company has developed a pipeline of 5 candidate products targeting 8 indications, with 5 indications currently in clinical stages[3] - HTD1801, a core product, is in key development stages and targets multiple metabolic and digestive system diseases, including severe hypertriglyceridemia and primary sclerosing cholangitis[4] - The company has completed Phase IIa trials for metabolic-associated fatty liver disease in the US and Phase II trials for type 2 diabetes in mainland China[3] - The company aims to provide effective and safe treatment options for complex metabolic and digestive system diseases, addressing unmet clinical needs[2] - HTD1801 is recognized as a multi-functional and multi-target candidate drug, focusing on the regulation of critical pathways related to metabolic and digestive diseases[4] - The company has received fast track designation and orphan drug designation for certain indications, enhancing the development process[3] - The company is committed to developing innovative therapies for complex metabolic and digestive diseases, leveraging extensive experience in building and developing a diverse pipeline[2] - The company has completed Phase I trials for HTD4010 in Australia, indicating progress in its product development pipeline[3] - The ongoing Phase IIb study of HTD1801 for MAFLD patients with type 2 diabetes has been initiated in the US, Hong Kong, and mainland China, with patient enrollment completed in March 2024[6] - HTD1801 demonstrated significant improvements in glucose metabolism, including statistically significant reductions in HbA1c and fasting blood glucose levels in Phase I and II studies conducted in China[8] - The Phase II study results presented at the European Association for the Study of Diabetes in October 2023 indicated that HTD1801 significantly reduced HbA1c, supporting its potential as a new oral medication for type 2 diabetes[8] - HTD1801 showed greater improvements in multiple cardiovascular metabolic endpoints compared to GLP-1 receptor agonists in patients with MAFLD and type 2 diabetes[6] - The ongoing analysis of HTD1801 treatment indicated improved gastrointestinal tolerance over time, supporting its long-term use for chronic diseases like MAFLD[6] - The data from the 2024 American Diabetes Association Scientific Sessions highlighted HTD1801's effectiveness in improving key metabolic and liver injury markers in type 2 diabetes patients[8] - HTD1801 is positioned as a unique treatment option for patients with type 2 diabetes and associated conditions, emphasizing the importance of controlling these symptoms for overall disease management[8] - The company has initiated Phase III clinical trials for HTD1801 in China for the treatment of type 2 diabetes, expected to complete by 2025[9] - Two Phase III trials (SYMPHONY-1 and SYMPHONY-2) for HTD1801 are set to complete patient enrollment by June 2024[9] - HTD1801 has shown statistically significant reduction in serum alkaline phosphatase levels in Phase II trials for primary sclerosing cholangitis compared to the placebo group[11] - HTD1801 has received Fast Track and Orphan Drug designations from the FDA for the treatment of primary sclerosing cholangitis, expediting the regulatory review process[11] - Clinical pre-study indicates HTD1801's potential to improve triglyceride levels in severe hypertriglyceridemia patients with baseline triglycerides over 200 mg/dL[12] - The company is advancing HTD4010 for alcoholic hepatitis, currently in Phase I clinical development[13] - HTD1804 is being evaluated for its effects on obesity, which is increasingly linked to various health risks globally[14] - HTD1805 is a multifunctional small molecule drug in preclinical stages aimed at treating metabolic diseases, showing potential similar to HTD1801[15] - HTD2802 is a multifunctional drug in preclinical stages aimed at treating inflammatory bowel disease, showing positive effects on stool formation and reducing inflammatory cytokine levels[16] Financial Performance and Expenses - Other income and gains increased by 68.7% from RMB 22.7 million to RMB 38.3 million for the six months ending June 30, 2024, primarily due to government subsidies[22] - R&D costs rose by 68.2% from RMB 120.1 million to RMB 202.0 million for the six months ending June 30, 2024, driven by increased third-party contract expenses[24] - The company recorded a loss of RMB 210.9 million for the six months ended June 30, 2024, compared to a loss of RMB 549.7 million for the same period in 2023[26] - The adjusted net loss for the six months ended June 30, 2024, was RMB 156.9 million, compared to RMB 105.3 million for the same period in 2023, indicating an increase in losses[38] - The total employee benefit expenses for the six months ended June 30, 2024, amounted to RMB 62.6 million, up from RMB 45.3 million for the same period in 2023, reflecting a significant increase due to stock incentive plans[41] - The company had a total of 68 employees as of June 30, 2024, unchanged from the previous year, with 42 in discovery and clinical development[39] - The company reported a total comprehensive loss of RMB 208,148,000 for the period, compared to RMB 586,343,000 in the previous year, marking a 64.5% decrease in total comprehensive losses[54] - Basic and diluted loss per share for the period was RMB 0.47, compared to RMB 2.16 in the previous year, indicating a significant reduction in loss per share[53] - Research and development costs increased to RMB 201,974,000 from RMB 120,088,000, reflecting a 68.3% rise in investment in R&D[53] - Total assets decreased to RMB 1,121,772,000 from RMB 1,494,000,000, a decline of 25% year-over-year[55] - Cash and bank balances decreased to RMB 171,046,000 from RMB 392,395,000, a reduction of 56.4%[55] - Current liabilities decreased to RMB 54,621,000 from RMB 79,811,000, a reduction of 31.6%[55] - The company has not generated any revenue from major customers during the reporting period[62] - The company continues to focus on biopharmaceutical research and development as its sole reportable segment[60] - Government subsidies related to expenditure increased to RMB 23,938 thousand in 2024 from RMB 8,875 thousand in 2023, reflecting a growth of 169.5%[63] - Bank interest income rose to RMB 2,465 thousand in 2024, compared to RMB 696 thousand in 2023, marking an increase of 253.6%[63] - The total income tax expense for the six months ended June 30, 2024, was RMB 538 thousand, up from RMB 26 thousand in 2023, indicating a substantial increase of 1,973%[71] Corporate Governance and Compliance - The company emphasizes the importance of good corporate governance to enhance management and protect shareholder interests, adhering to applicable corporate governance codes[42] - The board consists of two executive directors, three non-executive directors, and three independent non-executive directors, ensuring a strong independent element[43] - The audit committee, comprising three independent non-executive directors, has reviewed the interim results and found them to comply with relevant accounting standards[49] - The board does not recommend the distribution of an interim dividend for the six months ending June 30, 2024[51] - The company has confirmed compliance with the standards for securities trading by directors during the reporting period[44] - There were no significant lawsuits or arbitrations that could adversely affect the financial position or operational performance of the company during the reporting period[46] - The report was issued by the executive director and CEO, Dr. Liu Liping, indicating leadership accountability[74] - The financial data presented is unaudited for the period ending June 30, 2024, highlighting the preliminary nature of the figures[74] - The company is committed to timely financial reporting and transparency in its operations[74] Investments and Financial Position - The company made significant investments of USD 12.5 million in two structured entities, Apollo Multi-Asset Growth Fund and Chaince Capital Fund LP, prior to the listing date[32] - The investments in the funds generated approximately RMB 1.0 million in investment income for the six months ended June 30, 2024[32] - The fair value loss of convertible redeemable preferred shares decreased from RMB 399.6 million to zero following the conversion to ordinary shares after the company's listing[23] - The fair value change of convertible redeemable preferred shares was RMB 399.6 million for the six months ended June 30, 2023, which was not applicable for the current period[38] - Approximately 80.0% of the unutilized proceeds will be allocated to fund ongoing clinical research and development activities for HTD1801, with an expected timeline for use by December 2025[48] - About 5.0% of the unutilized proceeds will be used for the continued development of HTD1804 for obesity, also expected to be utilized by December 2025[48] Operational Insights - The company is actively seeking domestic partners with strong commercialization networks in the field of type 2 diabetes[16] - The R&D team consists of over 30 experienced scientists and physicians, focusing on clinical development strategies and trial design[20] - The R&D team is responsible for coordinating all clinical development activities and ensuring compliance with regulatory requirements[18] - The company provides ongoing education and training programs to maintain employee quality, knowledge, and skill levels[41] - The increase in trade payables may indicate growth in operational activities or expansion efforts[74] - The company is focused on maintaining strong relationships with suppliers to ensure smooth operations[74] - The financial summary reflects the company's ongoing strategies in managing its liabilities[74]

Financial Performance - For the fiscal year ending December 31, 2023, the company reported a pre-tax loss of RMB 939,230,000, representing a 393.8% increase compared to the pre-tax loss of RMB 190,205,000 in 2022[4]. - The net loss for the year was RMB 939,306,000, which is a 393.8% increase from the net loss of RMB 190,237,000 in the previous year[5]. - The adjusted net loss amounted to RMB 288,443,000, reflecting a 56.9% increase from the adjusted net loss of RMB 183,807,000 in 2022[4]. - The basic and diluted loss per share for the year was RMB 3.62, compared to RMB 0.75 in the previous year[5]. - The total comprehensive loss for the year was RMB 952,748,000, compared to RMB 223,888,000 in 2022[7]. - The company experienced a foreign exchange loss of RMB 2,031,000 from the translation of subsidiary financial statements[7]. - The financial results indicate a need for strategic adjustments to improve profitability and operational efficiency moving forward[4]. - The company did not declare or pay any dividends during the year, consistent with 2022[31]. - The loss recorded for the year ended December 31, 2023, was RMB 939.3 million, compared to a loss of RMB 190.2 million for the year ended December 31, 2022[76]. - The adjusted net loss for 2023 was RMB 288.4 million, compared to RMB 183.8 million in 2022, reflecting an increase in employee long-term incentive plan expenses and listing expenses[97]. Research and Development - Research and development costs rose to RMB 311,567,000, compared to RMB 182,651,000 in the prior year, indicating a significant investment in innovation[5]. - The company is focused on biopharmaceutical research and development, which is considered its sole reportable segment[16]. - The company has developed a pipeline of 5 candidate products targeting 9 indications, with 5 of these indications currently in clinical stages[39]. - HTD1801, the core product, is a new molecular entity aimed at treating various metabolic and digestive system disorders, currently in critical development stages[42]. - The company has completed Phase Ib/IIa trials for HTD1801 in Australia for hypercholesterolemia and Phase IIa trials in the US for metabolic dysfunction-associated fatty liver disease[44]. - The ongoing Phase IIb study of HTD1801 for MAFLD with type 2 diabetes has been initiated in the US, Hong Kong, and mainland China, with patient enrollment expected to complete by March 31, 2024[46]. - The Phase III registration clinical trial for HTD1801 in treating type 2 diabetes has been launched in China, with patient enrollment expected to complete in 2024 and data readout planned for the first half of 2025[48]. - The company is advancing HTD4010, a peptide drug in Phase I clinical development, targeting alcoholic hepatitis, a severe liver condition caused by excessive alcohol consumption[55]. - The company is also developing HTD1805, a multifunctional small molecule drug aimed at treating metabolic diseases, which is currently in preclinical stages[57]. - The company plans to evaluate the initiation of Phase II clinical trials for HTD1801 in treating severe hypertriglyceridemia based on its clinical progress and resource allocation[55]. Financial Position - Total non-current assets increased to RMB 16,283,000 from RMB 4,806,000, representing a growth of 238% year-over-year[9]. - Current assets decreased to RMB 778,753,000 from RMB 851,018,000, a decline of 8.5% compared to the previous year[9]. - Cash and bank balances rose to RMB 608,212,000 from RMB 412,340,000, marking a significant increase of 47.5%[9]. - Total current liabilities decreased to RMB 79,811,000 from RMB 1,319,720,000, a reduction of 93.9% year-over-year[9]. - The net asset value improved to RMB 702,774,000 from a negative RMB 470,528,000, indicating a turnaround in financial health[9]. - The debt-to-equity ratio as of December 31, 2023, was 0.5%, compared to 2% as of December 31, 2022[83]. - The company made significant investments of USD 12.5 million in two structured entities, with related assets valued at RMB 127.5 million as of December 31, 2023[85]. - The company reported a net loss of RMB 939.3 million for the year 2023, compared to a net loss of RMB 190.2 million in 2022[97]. Corporate Governance - The company has adopted a share incentive plan on January 22, 2020, and May 24, 2023[101]. - The company has confirmed compliance with the corporate governance code since the listing date, except for a deviation regarding the separation of roles between the Chairman and CEO[102][103]. - The board will continue to review the effectiveness of the corporate governance structure to assess the necessity of separating the roles of Chairman and CEO[105]. - The audit committee consists of three members, all of whom are independent non-executive directors, ensuring compliance with listing rules[113]. - The audit committee reviewed the financial performance for the year ending December 31, 2023, and confirmed that the financial results comply with relevant accounting standards and regulations[114]. Market Expansion and Future Plans - The company was listed on the Hong Kong Stock Exchange on December 22, 2023, marking a significant milestone in its growth strategy[10]. - The company plans to expand its business operations to Hebei Province, China, aiming to attract top talent in the northern region[116]. - Approximately 80.0% of the proceeds will be allocated to fund ongoing clinical development activities for HTD1801, amounting to HKD 155.2 million, expected to be utilized by December 2025[111]. - The company plans to submit a new drug application for HTD1801 for the treatment of type 2 diabetes to the National Medical Products Administration by 2025[58].