Overseas Business Expansion - Overseas business grew rapidly in 2022, with over 2,800 models developed and more than 2,000 pre-clinical pharmacology and efficacy evaluation services provided to over 400 global clients[4][5] - The company established an innovation center in Germany in 2022 and is expanding its facility in Boston, USA, to accelerate globalization[8] - The company expanded its overseas sales team and established a German subsidiary in 2022, leading to significant sales growth in preclinical pharmacological efficacy evaluation and CRO services[57] - Overseas business revenue and its proportion of total revenue continue to increase, with a new subsidiary established in Heidelberg, Germany in 2022 and expansion of the Boston experimental facility[93] - The company will expand its overseas drug R&D service market to promote rapid growth in overseas sales revenue[155] RenMice Platform Development - The RenMice platform expanded with the addition of RenNano mice, enabling development in fully human monoclonal antibodies and nanobodies[6] - The company out-licensed its RenMice platform to well-known pharmaceutical companies such as Merck KGaA, Beigene, and Janssen under Johnson & Johnson, highlighting its innovation strength[7] - The company’s antibody development business utilizes the RenMice platform to form a library of 400,000 to 500,000 antibody sequences for over 1,000 targets, enabling the identification of potential therapeutic antibody molecules[12] - The RenMice platform consists of three chromosome-engineered mice (RenMab, RenLite, RenNano) and has enabled the development of a new TCRm technology platform for intracellular target antibody drug development[52] - RenMab platform enables the generation of fully human monoclonal antibodies with subnanomolar affinity and specificity, utilizing RenMab mice with full human heavy and kappa light chain variable region replacement[53] - RenLite platform produces high-affinity bi-specific antibodies and ADCs, with YH012 and YH013 currently at CMC stage, targeting two tumor-associated antigens to overcome non-tumor cytotoxicity[53] - RenNano platform produces fully human single-chain antibody fragments without in vitro humanization, saving time and cost, and enabling high-throughput development of heavy chain antibodies with nM-level affinity[55] - TCRm platform generates fully human antibodies targeting intracellular MAP epitopes, with higher affinity and specificity than TCR, enabling effective targeting of intracellular antigens[55] Project Integrum Progress - Project Integrum is progressing smoothly, with the company expected to complete most of the project by Q3 2023, generating 400,000-500,000 fully human antibody sequences for over 1,000 innovative targets[6] - The company aims to complete Project Integrum to access high-quality antibody molecules with abundant epitope recognition, leveraging its innovative drug R&D platforms[9] - By Q3 2023, Project Integrum is expected to complete most of its work, generating a library of 400,000 to 500,000 fully human antibody sequences covering more than 1,000 innovative targets[52] - Project Integrum (千鼠萬抗) has knocked out more than 680 target genes in target KO RenMab and over 260 target genes in target KO RenLite as of December 31, 2022[52] - The company's annual sales revenue from Project Integrum is currently driven by upfront fees, with milestone fees and royalties expected to grow significantly as more antibody molecules/sequences are transferred[51] Drug Pipeline and Development - The company achieved a major breakthrough in 2022 with diversified business models, including pre-clinical products and services, which sustained steady growth, and antibody development business, which offers high potential for revenue and long-term growth[7] - In 2022, the company adjusted its drug pipeline development priorities, establishing 11 selected antibody drug product pipelines, including fully human monoclonal antibodies, bispecific antibodies, and bispecific antibody ADC[7] - Four out of six clinical-stage drug candidates have reached out-licensing or transfer deals with partners like Tracon and Syncromune, with positive R&D progress[7] - YH005 ADC (RC118), out-licensed to RemeGen, received two orphan drug designations from the U.S. FDA and is progressing smoothly in clinical research[7] - YH008, a fully human dual antibody, has been approved by the FDA and NMPA for clinical trials, with an exclusive out-licensing agreement for Greater China with Chipscreen NewWay[7] - The company has strategically built a pipeline of 11 drug candidates, including 6 clinical-stage and 5 pre-clinical stage candidates as of December 31, 2022[13][15] - Four of the drug candidates have out-licensing arrangements with different collaborators, all discovered through the company's proprietary antibody discovery platform[16] - Core products include YH003, a humanized IgG2 agonistic monoclonal antibody targeting CD40, and YH001, a humanized anti-CTLA-4 IgG1 monoclonal antibody[14][17] - The company's R&D strategy focuses on self-directing early clinical development, then co-developing/transferring development to biotech and biopharmaceutical companies for Phase II/III clinical development and commercialization[16] - YH001 is being co-developed with Tracon for selected indications, with the company receiving double-digit tiered net sales royalties in North America and retaining rights outside North America[20][21] - YH002 intratumoral combination therapy has been licensed to Syncromune, with the company entitled to upfront payments, milestone payments, and tiered net sales royalties[20][21] - YH005 antibody has been licensed to RemeGen, with the company receiving upfront and milestone payments, and entitled to additional licensing fees for YH005-ADC development[21] - The company is collaborating with ISU ABXIS to develop a tri-specific antibody based on the YH003 sequence[21] - YH008 bispecific antibody has been exclusively licensed to Chipscreen NewWay for clinical development and commercialization in Greater China, while the company retains global rights outside Greater China[21] - The company currently has no plans to invest its own resources to lead Phase III clinical development and commercialization in the near future[16] Clinical Trial Progress - YH003 Phase I clinical trial in Australia enrolled 26 patients, with 20 in dose escalation and 6 in dose expansion stages[23][25] - YH003 Phase I trial determined RP2D at 0.3mg/kg, with 65.0% of subjects in Part I and 16.7% in Part II reporting Grade 3 or above adverse events[23][25] - YH003 Phase II MRCT for PDAC enrolled 47 subjects in first-line treatment 2C cohort and 45 subjects in second-line treatment 2B cohort as of December 31, 2022[26][28] - YH003 Phase II clinical trial for mucosal melanoma in China showed good clinical benefit in 9 evaluable subjects with no new safety signals as of December 31, 2022[26][29] - YH003 combined with PD-1 and YH001 Phase I trial enrolled 12 subjects for advanced solid tumors as of December 31, 2022[26][29] - YH003 Phase I trial in Australia reported 2 subjects with partial response (PR), including one with ocular melanoma achieving complete response (CR) after nearly 2 years[26][27] - YH003 Phase I trial in Australia reported 3 subjects with stable disease (SD), including one with NSCLC maintaining SD until database lock[26][27] - YH003 received IND approvals for Phase II MRCT from U.S. FDA, TGA, MedSafe, NMPA, and Taiwan FDA between June and November 2021[26][28] - YH003 Phase I trial in Australia reported 10 subjects (50.0%) in Part I and 1 subject (16.7%) in Part II experienced serious treatment-emergent adverse events (TEAEs)[23][25] - YH003 Phase I trial in Australia completed database lock on August 22, 2022, with no treatment-related serious TEAEs reported in both Part I and Part II[23][25] - YH004 Phase I clinical trial in Australia completed first patient dosing in December 2021, with 8 subjects enrolled as of December 31, 2022, receiving doses ranging from 0.01 mg/kg to 0.3 mg/kg[32] - YH001 Phase I clinical trial in Australia showed favorable safety and efficacy, with 5 out of 26 evaluable patients achieving partial response and 11 achieving stable disease as of December 31, 2022[38][39] - YH001/KN035SAR101 Phase I/II clinical trial in the US, sponsored by Tracon Pharmaceuticals, began patient recruitment in November 2022, targeting 176 patients with advanced or metastatic sarcoma[39] - YH001 received IND approval from the US FDA in October 2021 and NMPA approval in January 2022 for Phase I clinical trials in China[32] - YH001 combined with toripalimab showed good tolerability up to 4.0 mg/kg dose levels in Australia, with 26 out of 29 enrolled patients being evaluable[38][39] - YH001 Phase I clinical trial in China demonstrated good tolerability up to 6.0 mg/kg dose levels as a single agent for advanced solid tumors[38] - YH001/KN035SAR101 study aims to determine the recommended Phase II dose and objective response rate for various sarcoma types, with Phase I data expected by the end of 2023[39] - YH001 received U.S. FDA approval for Phase II clinical trial in June 2021, Taiwan FDA approval in October 2021, and NMPA approval in November 2021[40] - YH001 Phase I/II clinical trial in combination with envafolimab and doxorubicin for soft tissue sarcoma patients was approved by FDA in August 2022, with the first patient dosed in November 2022[40] - YH001/KN035SAR101 Phase I/II clinical trial, sponsored by Tracon Pharmaceuticals, is expected to enroll 176 patients in the U.S., with Phase I data expected by the end of 2023[41] - YH002 Phase I trial in Australia demonstrated a favorable safety profile, with IND approvals from NMPA and U.S. FDA for Phase I trials in China and the U.S.[42] - YH008, an anti-PD-1/CD40 bi-specific antibody, received U.S. FDA approval in December 2022 and NMPA approval in March 2023 for Phase I clinical trials in advanced solid malignant tumors[43][45] - YH005, an anti-Claudin 18.2 antibody, received Phase I clinical approval in Australia in August 2021 and in China in September 2021, with ongoing dose escalation studies showing good safety and tolerability[47] - YH005 received two orphan drug designations from the U.S. FDA for the treatment of gastric cancer, including gastroesophageal junction cancer, and pancreatic cancer[47] Financial Performance - Revenue increased by 50.6% from RMB354.6 million in 2021 to RMB533.9 million in 2022, driven by growth in pre-clinical pharmacology and efficacy evaluation, animal models selling, and antibody development[120][121] - Gross profit rose by 58.4% from RMB247.4 million in 2021 to RMB391.8 million in 2022, with gross profit margin increasing from 69.8% to 73.4%[123][125] - Cost of sales increased by 32.7% from RMB107.1 million in 2021 to RMB142.1 million in 2022, in line with revenue growth[121][122] - Other gains and losses, net, surged by 238.7% from RMB25.6 million in 2021 to RMB86.7 million in 2022, primarily due to gains from disposal of interest in an associate and changes in fair value of financial assets[124][126] - Net change in fair value of biological assets decreased by 60.2% from RMB9.8 million in 2021 to RMB3.9 million in 2022, primarily due to a lower increase in humanized mice stock (1,000 heads in 2022 vs. 7,600 heads in 2021)[127] - Selling and marketing expenses increased by 19.5% from RMB42.0 million in 2021 to RMB50.2 million in 2022, mainly due to salary increases[127] - General and administrative expenses increased by 40.0% from RMB188.1 million in 2021 to RMB263.4 million in 2022, driven by higher staff costs and listing expenses[127] - Research and development expenses increased by 25.2% from RMB558.5 million in 2021 to RMB699.2 million in 2022, primarily due to increased staff costs, direct material costs, and depreciation/amortization expenses[128][129] - Staff costs (excluding share-based payment) accounted for 31.9% of total R&D expenses in 2022, up from 30.9% in 2021[130] - Cash at bank and on hand increased from RMB466.4 million in 2021 to RMB626.6 million in 2022, mainly due to net proceeds from the Global Offering[131][132] - Net cash generated from financing activities was RMB587.2 million in 2022, compared to RMB219.4 million in 2021[134] - Financial costs increased by 42.4% from RMB39.4 million in 2021 to RMB56.1 million in 2022, primarily due to higher lease liability interest[135] - Income tax expense was RMB0.8 million in 2022, compared to zero in 2021[136] - The company reported a net loss of RMB602.2 million in 2022, compared to RMB545.6 million in 2021[136] - Finance costs increased by 42.4% to RMB56.1 million in 2022, primarily due to higher interest on lease liabilities[137] - Income tax was RMB0.8 million in 2022, compared to nil in 2021[138] - The company incurred losses of RMB602.2 million in 2022, up from RMB545.6 million in 2021[139] - Outstanding loans totaled RMB178.8 million as of December 31, 2022, with interest rates ranging from 3.65% to 6.0%[140][143] - Gearing ratio increased to 1.43 in 2022 from 0.84 in 2021[140][143] - Net current assets decreased to RMB313.3 million in 2022 from RMB427.7 million in 2021[141][144] - Total capital expenditure for 2022 was RMB410.6 million, primarily for facility and office building investments and scientific equipment purchases[146] - The company's equity in Doma Biopharmaceutical was diluted from 100% to 18.26% after a RMB940 million capital increase by investors and a RMB200 million subscription by the company[146] R&D and Innovation - The company has developed over 2,800 unique gene-edited mouse/cell line projects for antibody discovery and disease modeling[74][76] - The company launched hundreds of new animal models annually, contributing to satisfactory sales growth in 2022[77] - The company is expanding its animal models into neurological, cardiovascular, and metabolic diseases, in addition to its focus on tumor and autoimmune diseases[79][81] - The company has developed humanized mouse models for immune checkpoints and other targets, enabling pre-clinical evaluation of human antibody drugs[80][82] - The company's B-NDG mice, with severe immunodeficiency, are ideal for human cell and tissue transplantation studies[85] - The company humanized key cytokines and cytokine receptors in mice to evaluate the efficacy of human cytokine or cytokine receptor antibody drugs[84][86] - The company leverages its animal facility in Nantong, Jiangsu Province, to scale production and serve more customers[77] - The company typically signs 1-5 year framework agreements with clients and requires full payment within one month of invoicing[85] - The company's pre-clinical CRO business continues to grow rapidly with a high gross profit margin, maintaining long-term cooperation with nine of the top ten overseas pharmaceutical companies[93] - The company's antibody discovery business has grown at a high rate since 2020, maintaining a very high gross profit margin, with customer base expanding from domestic biotech companies to global pharmaceutical companies[94] - The company has developed a series of second-generation products based on B-NDG mice, including B-NDG B2m KO plus, B-NDG hIL15, and B-NDG hTHPO mice, to address specific research needs[89][91] - As of December 31, 2022, the company's R&D team has discovered and/or developed 11 drug candidates in its current pipeline[96] - The company has approximately 550 R&D personnel across three service centers, with 100 responsible for gene editing and animal models, 150 for pre-clinical pharmacology, 230 for antibody development, and 50 for clinical development[96] - R&D expenses for the year ended December 31, 2022, were RMB 699.2 million, with RMB 105.0 million (15.0%) allocated to core product development[97] - The company has established a model animal production center with three animal bases covering approximately 55,000 square meters, providing significant cost advantages[98] - The company collaborates with CROs and CDMOs for the development and clinical trials of its pipeline products, with CROs providing pre-clinical toxicity and safety evaluation services[99] - R&D expenses for the year ended December 31, 2022 were RMB699.2 million, with RMB105.0 million allocated to Core Products, accounting for 15.0% of total R&D expenses[100] - The company's quality management department consisted of approximately 45 employees as of December 31, 2022, with team members experienced in successful drug filings to the U.S. FDA and NMPA[103] - The company operates three animal model production facilities totaling approximately 55,000 sq.m., enabling cost-effective production of genetically engineered mice and disease models[101] - As of December 31, 2022, the company had approximately 1,000 suppliers, with over 900 based in China[107] - Expenses for CROs and CDMOs related to Core Products R&D were RMB71.4 million for the year ended December 31, 2022[110] - The company holds 263 registered trademarks, 105 authorized patents, and 4 software copyrights as of December 31, 2022, with 300 patent applications filed across 5 countries/regions[111] - The company has been granted 5 patents related to Core Products and has submitted 30 patent applications for the same[111] Future Plans and Strategies - The company plans to establish 400,000-500,000 fully human antibody sequence libraries covering more than 1,000 innovative targets to deepen cooperation with domestic and international pharmaceutical companies[153][154] - The company aims
百奥赛图-B(02315) - 2022 - 年度财报