As of June 30, 2021, the company had 1,735 employees, including 891 R&D personnel, accounting for 51.35% of the total employees;

(Report Producer/Author: Everbright Securities, Lin Xiaowei, Wang Mingrui)

, Rongchang Biological: Three major technology platforms assist development, and an international management team implements the implementation

1.1, Committed to the research and development of innovative biopharmaceuticals with autoimmune, tumor and ophthalmic characteristics

Rongchang Biotechnology is an enterprise with a global vision dedicated to the research and development of innovative drugs in the fields of autoimmunity, tumors, ophthalmology and other major diseases. Founded in 2008, Rongchang Biologics is committed to discovering, developing, producing and commercializing first-in-class and best-in-class biological drugs, and creating a number of new biological drugs with significant clinical value for autoimmunity, tumors, ophthalmology and other major disease areas. The company has built a comprehensive, end-to-end innovative biopharmaceutical R&D and industrialization system, covering all key aspects including drug discovery, preclinical pharmacology, process and quality development, clinical development, and large-scale production in compliance with GMP standards. of drug research and development and industrialization. The company has an industry-leading production system that complies with global GMP standards, including production workshops and supporting facilities for cell culture, purification, preparation and canning, including 21×2000L disposable bag bioreactor . It plans to put the company into operation by the end of 2025. The total production capacity of raw liquid is expanded to 86000L.

company maintains a stable shareholding structure through a concerted action agreement. Ten natural persons, including Wang Weidong, Fang Jianmin, Lin Jian, Wang Liqiang, Wang Xudong, Deng Yong, Xiong Xiaobin, Wen Qingkai, Yang Minhua, and Wei Jianliang, are the company's joint actual controllers. The 10 joint actual controllers and relevant entities signed an agreement in April 2020 Action Agreement, committing to take concerted actions on the company's decision-making on major matters for at least 36 months from the date of signing of the concerted action agreement to the date of the company's A-share listing, using the voting rights of the company that each directly or indirectly holds. Voting, and the opinion with the largest proportion of voting rights shall be the unanimous opinion to ensure the stability of the company's control. Yantai Rongda is the actual controller's shareholding platform, and Yantai Rongqian, Yantai Rongyi, and Yantai Rongjian are the company's employee shareholding platforms. The executive partners of these platforms and Yantai Rongshi are Wang Weidong; Wang Weidong is the sole partner of RongChang Holding Director; Fang Jianmin holds 100% of I-NOVA's equity, and I-NOVA is Fang Jianmin's shareholding platform.

1.2, Three major technology platforms help develop

Rongchang Biotech has three major technology platforms, including antibody and protein fusion platform, antibody-drug conjugate (ADC) platform and bifunctional antibody (HiBody) platform. The company develops drugs in multiple biotherapeutic fields based on three major platforms. It can discover, screen and develop new molecules, develop proprietary technologies, and efficiently optimize production processes, thereby ensuring end-to-end integration of drugs in the R&D pipeline from R&D to commercialization. .

has a wide range of products under development, and a number of drug candidates have entered clinical and commercial stages. As of July 2, 2022, the company has entered the commercialization stage of 2 products, namely tetacept and vedicitomab , and has multiple products in the clinical and preclinical stages.

company has a R&D team with high academic level, strong academic theory and professional background, and strong R&D strength. As of June 30, 2021, the company has 1,735 employees, including 891 R&D personnel, accounting for 51.35% of the total employees; the company's R&D personnel include 33 Ph.D.s and 324 masters. Those with master's degrees and above account for the total R&D personnel 40.07%.

1.3. The international management team implements

. The company's main management has rich experience in the pharmaceutical industry at home and abroad. The company's co-founder, CEO and chief scientific officer, Dr. Fang Jianmin, has more than 20 years of experience in biopharmaceutical research and development and more than 40 drug invention patents. He is also the company's core product (including Tatacept, Vidicitumab) the inventor of. The company's co-founder and chairman Wang Weidong has 25 years of enterprise, operation and management experience in the pharmaceutical field. Chief Medical Officer Dr. He Ruyi has worked in the US FDA and China Food and Drug Administration for nearly 20 years, including more than 17 years in FDA. He has held multiple strategic leadership positions and is China's most authoritative in the field of clinical development of drugs and global regulatory systems. one of the experts.President Dr. Fu Daotian was the vice president and executive director of Livzon Pharmaceutical Group . He has 28 years of experience in US biopharmaceuticals and has experience in successfully submitting NDA and leading clinical development projects. Management has the capabilities to lead the company into global commercialization. The company has a management team with rich R&D and operation experience in the pharmaceutical industry at home and abroad, such as Dr. Fang Jianmin and Dr. He Ruyi, who are able to lead ongoing research projects to submit to both China and the United States, and some products have received FDA breakthrough therapy, fast track, etc. Qualification certification and strong global competitiveness. The entire management team has rich experience in drug development, clinical design, and drug launch R&D and application, which is conducive to building global competitiveness. The

Scientific Advisory Board communicates regularly to grasp the latest needs of the industry. The company has established a scientific advisory board composed of well-known authorities to provide regular consulting services, including: advice on business strategies and goals, academic updates and technical briefings related to R&D plans, advice on innovative drug targets, mechanisms and models, Implications for new drug development programs and market data and intelligence on biopharmaceuticals. Regular communication ensures that the company grasps the hot trends in the innovative drug industry and adjusts R&D strategies in real time.

. The commercialization of Tatarcept and Vidicitomab has started, and the innovative product echelon continues to enrich

2.1. Tatarcept (RC18): starting from lupus to expand the broad space for self-immunization

Core product Tatarcept Pu (RC18) is a new dual-target fusion protein independently developed by the company for the treatment of autoimmune disease . Currently, RC18 is mainly developed for 7 autoimmune diseases, including systemic lupus erythematosus , neuromyelitis optica spectrum disease, rheumatoid arthritis , IgA nephropathy , Sjogren's syndrome, multiple sclerosis and Myasthenia gravis , etc. As of 2022.7.2, the development status of various indications is:

Tatacept is a TACI-Fc fusion protein that targets BLyS and APRIL (two important related to B cell -mediated autoimmune diseases. Cell signaling molecule ) to treat a variety of B cell-mediated autoimmune diseases including systemic lupus erythematosus (Systemic Lupus ErythematOSus, SLE).

2.1.1. The advantages of treating systemic lupus erythematosus are obvious

SLE is a chronic, multi-system specific autoimmune disease, and many factors will affect the occurrence and development of SLE. The cause of SLE is still unclear. Research shows that genetics, endocrine, infection, immune abnormalities and environmental factors are all related to the onset of SLE. SLE is inherited in a polygenic manner in most patients, and genetic superposition of environmental factors may trigger immune dysregulation of B cells, T cells, and cytokines . SLE has obvious racial and gender characteristics. In terms of race, it is more common in black and Asian people, and in terms of gender, it is more common in women. The male-to-female ratio is 1:7-9, and the most common age of onset is 20-40 years old. The clinical diagnosis of SLE is complex and existing standards have limitations. The diagnosis of SLE mainly relies on clinical manifestations, laboratory examinations, histopathology and imaging examinations. Currently, SLE is mainly diagnosed in clinical practice according to the American College of Rheumatology (ACR) classification criteria, which have a sensitivity of 96% and a specificity of 93%. However, the ACR criteria still have limitations. They do not include all symptoms of SLE and are more suitable for identifying advanced patients.

SLE lacks effective treatments with few side effects, and there is great clinical demand. According to the "2020 Chinese Guidelines for the Diagnosis and Treatment of Systemic Lupus Erythematosus" (jointly formulated and promulgated by the Rheumatology Society of the Chinese Medical Association, the National Clinical Research Center for Skin and Immune Diseases, etc.), the SLE medication principles are based on hydroxychloroquine , glucocorticoids , immunosuppressants , biological agents and other measures are used sequentially. Although glucocorticoids and immunosuppressants such as will play a certain role in severe SLE, they are likely to cause serious side effects.At present, there is no particularly effective treatment for SLE in the world. Existing treatments cannot achieve both efficacy and side effects. There are still a large number of patients waiting for more effective treatments with fewer side effects.

SLE has a huge therapeutic potential, and patients often require lifelong treatment. Due to the nature of SLE, patients are usually young and require lifelong treatment to control the disease state. According to the Frost & Sullivan Report, the number of SLE patients worldwide increased from 7.467 million in 2016 to 7.7955 million in 2020, of which the United States increased from approximately 273,000 to 282,400, and China increased from approximately 1,002,100. 1,034,900 people. It is estimated that by 2025, the number of SLE patients worldwide will reach 8.1856 million; by 2030, the number of SLE patients worldwide is expected to reach 8.5512 million. Regarding the SLE patient population suitable for RC18, Frost & Sullivan predicts that the applicable population in the United States will increase from approximately 74,000 in 2020 to 78,000 in 2025, and that in China will increase from approximately 280,300 in 2020 to 280,300 in 2025. About 403,500 people.

The SLE drug market is expected to grow, and the CAGR of the SLE biopharmaceutical market in China and the United States is expected to exceed 20% from 2025 to 2030. According to the Frost & Sullivan Report, the global SLE treatment drug market is expected to grow from US$1.6 billion in 2020 to US$6.5 billion in 2025, with a compound annual growth rate of 32.8% from 2020 to 2025, and is expected to grow at 21.0% The compound annual growth rate will increase to US$16.9 billion in 2030; The market size of the US SLE treatment drug market is expected to grow from US$1 billion in 2020 to US$3.8 billion in 2025, with a compound annual growth rate from 2020 to 2025 is 32.0%, and is expected to grow at a compound annual growth rate of 20.4% to US$9.7 billion in 2030; among which, the growth rate of the U.S. SLE biopharmaceutical market is higher than the overall growth rate, and the penetration rate of biopharmaceuticals and continues to increase. In 2020, China's systemic lupus erythematosus treatment drug market will reach US$300 million, with biological drugs accounting for a small proportion. In the future, with the continuous launch of my country's systemic lupus erythematosus biological drug products and the increasing clinical penetration rate of biological drugs, China's systemic lupus erythematosus treatment drug market will continue to increase. The market size of lupus erythematosus biologic drugs is expected to rapidly increase to US$3.2 billion in 2030.

RC18 The current competitive landscape is better. Among the biological agents used for SLE, only belimumab and anifrolumab have been approved for marketing in the United States, and only belimumab and tatacept have been approved for marketing in China. There are only 3 biologics in Phase III clinical stages worldwide. Compared with belimumab, whose patent is expected to expire in 2025, RC18's patent expiration is in 2027, giving it a relatively sufficient time for sales and promotion. The remaining early-stage products under development have a higher risk of R&D failure and do not currently compete directly with RC18.

Judging from the SRI-4 response rate data, Rongchang Biotech's Tatasercept has shown excellent therapeutic effectiveness for this type of patients, with a significant improvement compared to placebo, and has the potential to become a Me-better drug in the future. potential.

2.1.2. Broad spectrum of indications.

Since Tatacept targets BLyS and APRIL, two important cell signaling molecules related to B cell-mediated autoimmune diseases, it is effective against a variety of B cell-mediated autoimmune diseases. All diseases have therapeutic potential. At present, in addition to SLE indications, Tatacept has been approved for marketing, and clinical trials are being advanced for multiple indications, such as neuromyelitis optica spectrum disorder (NMOSD), rheumatoid arthritis (RA), Sjögren's syndrome syndrome (SS), immunoglobulin (IgA) nephropathy, multiple sclerosis (MS), myasthenia gravis (MG), etc. The current clinical treatment methods for many of these indications are relatively blank, with strong demand and ideal competitive landscape, and are expected to Maintain the strong comprehensive competitiveness of products over a longer period of time.

2.2, Vedicitomab (RC48): the forerunner of domestic ADCs

Vedicitomab (RC48) is a new antibody-drug conjugate (ADC) independently developed by the company for HER2 expression (including low expression) ) of solid tumors , two major indications are currently on the market.HER2 is a member of the epidermal growth factor receptor (EGFR) family and is expressed in a variety of tissues. Its main function is to promote cell proliferation and inhibit cell apoptosis . Overexpression of HER2 may lead to tumorigenesis. Currently, RC48 shows promising efficacy in multiple cancer types and has the potential to be developed for multiple indications.

The main mechanism of action of vedicitomab is to selectively deliver the anti-cancer agent MMAE to HER2-expressing tumor cells, thereby killing tumors. The main process includes: 1) Specific binding to tumor cells and mediating endocytosis: The HER2 antibody part of vedicitomab binds to the HER2 extracellular domain on the surface of tumor cells with high affinity, and then the vedicitomab molecule is endocytosed by the cells and transported to lysosome ; 2) enzyme cleavage and releases toxins: In the acidic environment of lysosomes, the activated lysosomal enzyme specifically cleaves the linker of vedicitomab and releases the cytotoxic pentapeptide covalently linked to it. Small molecule - tubulin depolymerizing agent MMAE; 3) Toxin-mediated tumor cell apoptosis: MMAE released within the cell binds to microtubules or tubulin, destroys the intracellular microtubule network, and causes mitotic cell cycle arrest. and cell apoptosis.

RC48 has a unique molecular structure, which mainly includes a new type of high HER2 affinity humanized antibody with independent intellectual property rights, efficient endocytosis effect and intracellular enzymatic linker. The optimized antibody has higher target affinity. Although RC18 and Roche/Genentech's HER2 ADC drug "Trastuzumab Antibody Maytansine (T-DM1)" also target the HER2 target, they specifically target HER2 The epitopes on the receptors are different. The cleavable linker of RC18 improves the toxic effect on tumor cells and the serum stability and safety of ADC drugs through the "by-side killing effect". At the same time, the company has mastered all key technologies for a complete set of ADC drugs from research and development to commercialization, forming high technical barriers. Judging from preclinical data, RC48 has higher HER2 affinity, selectivity and stronger "by-side killing effect" than competing product T-DM1. According to in vitro test results, the half-maximal effect concentrations (EC50) of RC48 and trastuzumab antibodies were 6.4 pM and 20.1 pM respectively, demonstrating the higher HER2 affinity of RC48. When RC48 is cultured alone with HER2-negative cells, it has no or limited effect on the cells; when HER2-expressing cells are co-cultured with HER2-negative cells, it also has a killing effect on HER2-negative cells, reflecting the "bypass killing effect" of RC48. . Experiments in Balb/c nude mice showed that RC48 at a dose of 3.3 mg/kg had a stronger “by-side killing effect” than trastuzumab antibody at 10 mg/kg.

2.2.1. Filling the clinical gap of HER2 gastric cancer

Gastric cancer (GC) is highly prevalent in my country, and there is still a lack of effective treatments for HER2 low expression and advanced metastatic gastric cancer. According to the Chinese Gastric Cancer Diagnosis and Treatment Standards (2018 Edition), the incidence rate of gastric cancer in my country ranks second, second only to lung cancer, and the mortality rate ranks third. There are many studies on targeted drugs for gastric cancer, but the only drugs that have been commercialized are first-line treatment of anti-HER2 and second/third-line treatment of anti-angiogenic pathways. There are currently no other effective molecular targeted drugs for patients with advanced gastric cancer. Currently, patients with gastric cancer with high HER2 expression already have trastuzumab combined with chemotherapy regimens, but gastric cancer with low HER2 expression still lacks effective targeted treatment options, and patients also lack HER2 therapeutic drugs after entering the second and third lines of treatment. .

The number of gastric cancer patients worldwide and in my country is growing continuously, with my country accounting for 40% of the cases. According to the Frost & Sullivan Report, the number of new patients worldwide increased from 980,000 to 1.089 million from 2016 to 2020, with a CAGR of 2.7%, of which approximately 470,000 were in China; it is expected that by 2025, the number of new patients worldwide will reach 125.6 million cases, with a CAGR of 2.9% from 2020 to 2025, of which approximately 546,000 are in China; it is expected that by 2030, the number of new patients worldwide will reach 1.435 million, with a CAGR of 2.7% from 2025 to 2030, of which approximately 622,000 are in China.

my country's gastric cancer drug market continues to grow, and is expected to maintain a growth rate of 10% from 2020 to 2030. The continued growth in the number of gastric cancer patients globally and in my country has driven the continuous expansion of the gastric cancer drug market.According to the Frost & Sullivan Report, the global gastric cancer drug market is expected to grow from US$14.4 billion in 2020 to US$24.2 billion in 2025, with a CAGR of 11.0% from 2020 to 2025E, and will grow to US$36.4 billion in 2030. my country's gastric cancer drug market is expected to grow from US$4.3 billion in 2020 to US$7.9 billion in 2025, with a CAGR of 12.8%, and to US$12.8 billion in 2030.

As of July 2021, the company has basically completed the Phase II registration clinical trial of vedicitumab for HER2 overexpression (IHC2+ or IHC3+) advanced or metastatic gastric cancer in China. The trial recruited 127 patients who had previously Patients with HER2-overexpressing gastric cancer or gastroesophageal junction adenocarcinoma who had received at least two chemotherapy treatments, 60 of whom had received at least three treatments. In terms of efficacy, as of June 22, 2020, phased clinical data analysis, among all 127 patients, the confirmed ORR assessed by the independent review committee was 24.4% (95%CI: 17.2%, 32.8%), and the median PFS 4.1 months (95%CI: 3.5, 4.8), and the median OS was 7.6 months (95%CI: 6.6, 9.0). In terms of safety, the most commonly reported TRAEs were decreased white blood cell count (53.5%), alopecia (52.8%), decreased neutrophil count (49.6%), and fatigue (45.7%). Taken together, vedicitomab showed clinically significant remission effects and survival rates in patients with HER2-overexpressing gastric cancer or gastroesophageal junction adenocarcinoma, and showed a good benefit/risk ratio. The company

launched a phase III confirmatory clinical trial of vedicitomab for the treatment of gastric cancer in September 2020. The main efficacy endpoint is overall survival. It plans to recruit a total of 351 patients and plans to complete the last trial in Q4 2023. Patients will be enrolled and a complete study summary report will be submitted before 2026. In July 2018, the company obtained the US FDA's orphan drug designation for vedicitomab for the treatment of gastric cancer, and can enjoy the seven-year market exclusivity period of vedicitomab for gastric cancer after marketing approval in the United States. . According to the company's pre-IND discussions with the U.S. FDA in June 2020, the company submitted an IND for Phase II trials for the treatment of gastric cancer to the U.S. FDA in September 2020, and received fast track designation from the U.S. FDA in November 2020. , the company will choose an opportunity to launch the experiment. In addition, the company will choose the opportunity to submit a clinical trial application for vedicitomab in the treatment of gastric cancer to the European EMA in the future. (Report source: Future Think Tank)

2.2.2. Filling the clinical gap of urothelial cancer

The recurrence rate of urothelial cancer is high, and the current single-drug treatment regimen faces the problems of low efficiency and limited efficacy. Urothelial carcinoma is a malignant tumor originating from the urothelium of the bladder and is prone to recurrence and metastasis. The current treatment methods for urothelial cancer include chemotherapy, immunotherapy , antibody conjugate drug , fibroblast growth factor receptor (FGFR) inhibitors, etc. A variety of treatment combinations. Currently, the treatment options for patients with advanced urothelial cancer in China are relatively limited. Currently, there are only two immunotherapy drugs: tislelizumab from BeiGene and Junshi Biotech ’s toripalimab. According to the company's prospectus , about 48% of urothelial cancer patients have a certain level of HER2 expression, of which about 20% have low HER2 expression. RC48 has the basis to treat such patients. The number of patients with urothelial cancer is growing steadily globally and in China. According to the Frost & Sullivan Report, the number of new urothelial cancer patients worldwide increased from approximately 468,000 cases in 2016 to approximately 516,000 cases in 2020, and is expected to reach 586,000 cases by 2025, and 662,000 cases by 2030. 10,000 cases, the CAGR from 2020 to 2030 is approximately 2.5%. The number of new patients with urothelial cancer in China increased from approximately 69,000 cases in 2016 to approximately 77,000 cases in 2020, and is expected to reach approximately 91,000 cases by 2025, and approximately 106,000 cases by 2030. In 2020- The CAGR in 2030 is approximately 3%. The global and Chinese urothelial cancer drug market is expected to grow rapidly from 2020 to 2030. According to the Frost & Sullivan Report, the global urothelial cancer treatment drug market will grow from US$2.7 billion in 2020 to US$6.9 billion in 2025, with a CAGR of 21.2% from 2020 to 2025E.Since China has fewer approved drugs, China's urothelial cancer treatment drug market is expected to grow faster than the global market, growing from US$170 million in 2020 to US$900 million in 2025, with a CAGR of 39.7% from 2020 to 2025E. , the CAGR from 2025 to 2030E is 14.8%.

Currently, there are only a small number of targeted drugs for HER2-positive urothelial cancer, and only vedesitomab and Daiichi Sankyo’s Enhertu have disclosed clinical data. Vedicitomab has shown the potential to improve the survival of tumor patients in patients with ≥2 lines of urothelial cancer. The ORRs in the two clinical trials were 51.2% and 50.0% respectively, and the median OS were 13.9 months and 14.2 respectively. months, and has a good safety profile, and is expected to become a new treatment option for patients with HER2-positive urothelial cancer in the future.

combined with PD-1 has excellent data for urothelial cancer

Preclinical studies have shown that ADC and PD-1 may have a synergistic anti-tumor effect. Rongchang Biotech further explored the treatment of vedicitumab combined with toripalimab Efficacy and safety in metastatic urothelial carcinoma. As of April 22, 2022, the RP2D of this study is vedicitumab 2 mg/kg + toripalimab 3 mg/kg, with 6 patients enrolled in the dose escalation phase and 35 patients enrolled in the dose expansion phase. The number of previous treatment lines was 0 in 25 patients (60.98%), and ≥1 in 16 patients (39.02%). The HER2 expression status was 5 cases IHC 3+ (12.20%), 19 cases IHC 2+ (46.34%), 14 cases IHC 1+ (34.15%), and 3 cases IHC 0 (7.32%); the PD-L1 expression status was 28 There were 13 cases with CPS 10 (68.29%) and 13 cases with CPS ≥ 10 (31.71%). Efficacy data showed that as of April 22, 2022, among 39 patients with at least two tumor assessments, the cORR was 71.8% (95% CI: 55.1, 85), including 3 CR (7.7%), 25 PR (64.1%); DCR was 92.3% (95%CI: 79.1, 98.4). First-line cORR was 73.9%, six subgroups HER2 IHC (2 + /3 +) PD-L1 (+), HER2 IHC (2 + /3 +) PD-L1 (-), HER2 IHC (1+) PD- The cORR of L1 (+), HER2 IHC (1+) PD-L1 (-), HER2 IHC (0) PD-L1 (+), HER2 IHC (0) PD-L1 (-) is 85.7% and 86.7% respectively. ,50%,60%,0% and 50%. mPFS was 9.2 months and mOS was not reached.

Vedicitumab combined with toripalimab has shown good efficacy in patients with urothelial carcinoma. The company launched a Phase 3 clinical study (NCT05302284) of vedicitumab combined with toripalumab versus platinum-containing standard chemotherapy for first-line mUC patients on April 28, 2022.

shows efficacy in HER2-negative urothelial carcinoma

In previous clinical studies, it was found that vidicitumab can still benefit from treatment for some IHC 2+/FISH- patients. This study further explores vidicin Efficacy of cetuzumab in patients with HER2-negative (HER2 IHC 1+/0) advanced urothelial carcinoma. This study was an open-label, single-center, single-arm phase II clinical trial. Main inclusion criteria included: Histology confirmed advanced urothelial carcinoma, HER2 negative (IHC 0 or 1+), ECOG PS 0-1, and at least 1 prior systemic therapy. Vedicitumab was administered every 2 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. A total of 19 patients have been enrolled as of February 2022. The median age was 64 years. Six patients had HER2 IHC 0 and 13 patients had HER2 IHC 1+. Most patients (13/19) had visceral metastases. Fifteen patients (79%) received at least 2 lines of systemic therapy.

Among 19 evaluable patients, the objective response rate was 26.3% (95% CI: 9.1%, 51.2%) and the disease control rate was 94.7% (18/19). The median progression-free survival was 5.5 months (95% CI: 3.9, 6.8), and the median overall survival was 16.4 months (95% CI: 7.1, 21.7). The best efficacy of the 6 HER2 IHC 0 patients was stable disease (SD). The objective response rate was 38% (5/13) in patients with HER2 IHC 1+, 31% (4/13) in patients with visceral metastases, 17% (1/6) in patients with liver metastases, and ≥2 lines of systemic therapy. is 27% (4/15).

Common treatment-related adverse events include leukopenia (52.6%), hypoesthesia (47.4%), alopecia (47.4%), AST elevation (42.1%), ALT elevation (42.1%), neutral Granulocytopenia (42.1%), fatigue (42.1%), nausea (26.3%), and vomiting (15.8%).Most of these adverse events were grade 1 or 2. The grade 3 adverse event was neutropenia (10.5%). There was only one serious adverse event related to RC48-ADC, which was an increase in serum creatine phosphokinase. Overall, this phase II trial confirmed the efficacy of vedicitomab in patients with HER2-negative urothelial carcinoma, with a median overall survival of 16.4 months and most treatment-related adverse events of grade 1-2. Similar to previous monotherapy studies of vedicitomab, adverse reactions were generally controllable.

HER2-overexpressing urothelial carcinoma continues to prolong survival

In previous clinical trials of RC48-C005 and RC48-C009, vedicitomab was effective in HER2-overexpressing (IHC 2+/3+) locally advanced or metastatic urothelial carcinoma. It has shown good efficacy and controllable safety in patients with epithelial cancer, and has been approved for marketing in China. This meeting summarized the data from the two studies for analysis, including recently updated efficacy, safety and overall survival data. Both trials were single-arm, multicenter phase II clinical trials. Eligible patients were those aged 18 to 80 years with unresectable mUC whose histological HER2 overexpression (IHC2+ or 3+) was confirmed by a central laboratory. Patients had received at least one systemic chemotherapy (64.5% of patients had received ≥ 2 lines of systemic chemotherapy, and 90.7% had visceral metastases). From November 2017 to September 2020, RC48-C005 and RC48-C009 enrolled a total of 107 HER2-overexpressing (IHC2+ or 3+) LA/mUC patients, including 80 men with a median age of 63 years [40 -79]. The study results showed that the cORR was 50.5%, PR was 53 cases, SD was 34 cases, and DCR was 82.2%. Similar efficacy responses were observed in prespecified subgroups. The cORR in patients with liver metastases was 52.1% (25/48), while the cORR in patients with prior PD-1/L1 therapy was 55.6% (15/27). The cORR of patients with HER2 IHC2+ and FISH+ or IHC3+ was 62.2% (28/45), the cORR of patients with HER2 IHC2+ and FISH unknown was 55.6% (5/9), and the cORR of patients with HER2 IHC2+ and FISH- was 39.6% (21/53) ).

107 subjects had a mean OS follow-up of 19.1 months. In both clinical trials, median OS was more than 1 year, and in the current pooled analysis, mOS was 14.2 months, which continues to be prolonged. mPFS was 5.9 months (95%CI: 4.1,7.2).

The most common treatment-related adverse events (TRAE) were hypoesthesia (50.5%), leukopenia (49.5%), increased aspartate aminotransferase (42.1%), and neutropenia symptoms (42.1%), hair loss (40.2%), fatigue (39.3%), increased alanine aminotransferase (35.5%), and decreased appetite (31.8%). Grade ≥3 TRAEs occurred in 58 (54.2%) subjects, but ≥5% only included hypoesthesia (15.0%), neutropenia (12.1%), and r-GT elevation (5.6%). Overall, vedicitomab can significantly improve the response rate and achieve long-term survival benefit in patients with HER2-overexpressing metastatic urothelial cancer who have received at least one systemic chemotherapy in the past. Similar effects were observed in different subgroups of patients. Efficacy response, such as patients who have previously received PD-1/L1, patients with visceral metastasis, etc., and drug safety is controllable.

2.2.3. Comprehensive layout for patients with high and low expression of HER2 in breast cancer

The company is conducting a series of clinical studies on Vidicitumab for breast cancer patients. In the Phase I and Phase Ib clinical trials, the company has initially explored Vidicitumab. Safety and effectiveness of toxumab. In May 2021, the company disclosed the latest clinical data of vedicitumab in breast cancer at ASCO. The results disclosed this time are a pooled analysis of previous studies, including the following studies: C001 CANCER (NCT02881138): dose escalation Phase I study (0.5, 1.0, 1.5, 2.0 and 2.5mg/kg), HER2-positive patients adopted a 3+3 design; C003 CANCER (NCT03052634): Phase Ib study, HER2-positive subgroup doses were 1.5, 2.0 and 2.5mg/kg kg, the dose for the IHC 2+/FISH- and IHC 1+ HER2 low expression subgroups was 2.0 mg/kg. Research is currently being advanced for patients with IHC 1+; as of 2020.12.31, 118 female breast cancer patients have been enrolled, of which 70 (59.3%) are HER2 positive and 48 (40.7%) have HER2 low expression.At baseline, 77 (65.3%) had liver metastases, 50 (42.4%) were ECOG PS1, and 47 (39.8%) had received ≥3 prior chemotherapy regimens.

2.3, RC28: A Better Solution for Angiogenic Eye Diseases

Some eye diseases (such as wet age-related macular degeneration, diabetic macular edema, and diabetic retinopathy) are caused by blood vessels growing into the macula, causing fluid to flow out of the macula. Blood vessels leak into the eye, leading to progressive vision loss and even blindness, so drugs that slow the growth of new blood vessels could potentially slow the progression of the disease. At present, a number of antibody drugs targeting this type of disease have been approved for marketing around the world, such as aflibercept, ranibizumab, etc., and have achieved great success in commercialization, proving the potential space contained in this treatment field.

Most of the current mainstream antibody drugs for fundus diseases such as aflibercept and ranibizumab are VEGF single-target antibody drugs. However, the current challenge faced by this type of therapy is that when inhibiting the VEGF pathway, other pro-angiogenic factors (such as FGF-2) expression may be upregulated. The company's RC28 is a genetically recombinant fusion protein of VEGF receptor, FGF receptor and the Fc segment of human immunoglobulin. Through a dual-targeting mechanism, it simultaneously blocks angiogenic factors of the VEGF and FGF families, thereby more effectively Inhibit abnormal growth of blood vessels.

In in vitro studies, the company evaluated the efficacy of RC28 in a mouse model of oxygen-induced retinopathy (OIR). High oxygen pressure can cause an increase in the number of neovascular cell nuclei in the mouse retina, while RC28, VEGF-Trap (aflibercept) and FGF-Trap can significantly reduce the number of neovascular cell nuclei in OIR mice, among which RC28 shows better results than The same dose of VEGF-Trap or FGF-Trap had significantly stronger inhibitory effects.

RC28 is currently advancing clinical trials for various indications in an orderly manner. The Phase II trial of diabetic macular edema (DME) (the control group is Conbercept) will enroll the first subject in March 2021. Diabetic retinopathy (DR) The first subject was enrolled in the Phase II trial in 2021.6, and the Phase I trial of wet age-related macular degeneration (wAMD) was completed in 2022.1. As subsequent clinical trials of the product are carried out, RC28 will obtain more efficacy and safety data. If it can achieve better results than single-target VEGF inhibitors such as Conbercept, RC28 is expected to be a promising drug for DME, DR, Provide better clinical treatment options for patients such as wAMD.

2.4. Other early products: multiple highly innovative and differentiated products are being promoted in an orderly manner

In addition to Tatacept, Vidicitomab, and RC28, the company also has several highly innovative and differentiated products. These products will provide a solid foundation for the company's long-term healthy development. Some projects that have been advanced to the clinical stage include:

RC88: a novel mesothelin (MSLN)-targeted ADC for the treatment of MSLN-positive patients. Solid tumors, currently in Phase I clinical trials;

RC98: a new PD-L1 monoclonal antibody for the treatment of solid tumors. Preclinical research data shows that RC98 has comparable or potentially better targets than other PD-L1 antibodies. point affinity and anti-tumor effect, and has the potential to be combined with the company's other drug candidates (such as RC48 and RC88) to improve efficacy. It is currently in Phase II clinical trials;

RC108: a c-MET targeting ADC for It is currently in phase I clinical trials for the treatment of c-MET-positive solid tumors;

RC118: a new type of antibody-conjugated drug targeting Claudin 18.2. Its side-killing effect makes it effective in patients with Claudin 18.2 overexpression and high heterogeneity. Tumors have a stronger killing effect. Currently, domestic clinical trials have advanced to phase II trials, and phase I clinical trials have been carried out in Australia.

. The company’s core competitiveness: far-sighted strategic vision and steady international layout

3.1. Forsighted strategic vision

For innovative drugs, how can they still enter hospitals and allow hospitals to control the total cost of drugs? Doctors' willingness to prescribe this product has become the core proposition for establishing innovative drug research and development projects and building pipelines in the next era.At present, the domestic innovative drug industry is focusing on popular targets and treatment areas, and the competition is fierce. Price war pressure is high, and it is difficult to obtain ideal profit margins. If we change our thinking and choose niche markets for innovative drug research and development, there will be relatively no treatment methods. In the field, the competitive pressure is relatively small. On the other hand, innovative drugs developed for clinical blank areas often receive strong support from regulatory agencies, such as review and approval qualifications such as breakthrough therapies; niche markets in terms of medical insurance access negotiations and commercial market competition after approval for marketing Since there are few direct competitors and it solves the clinical needs, it is relatively easy to achieve medical insurance access and clinical sales of the product. Rongchang Biological's clinical development ideas perfectly match our ideas for research and development of innovative drugs in niche markets in terms of selection of indications and clinical trial design, and have obtained a relatively ideal commercialization space.

3.1.1. Vedicitomab: Broaden the indication layout and achieve a wider range of clinical value realization.

As the first HER2-ADC approved for marketing, the company’s clinical development is unique and has not Blindly imitating approved imported products, but developing a variety of rarely explored indications to realize clinical value on a larger scale. (Report source: Future Think Tank)

(1) The space beyond HER2 positivity

According to the definition of HER2 positivity according to the "Breast Cancer HER2 Detection Guidelines (2019 Edition)": more than 10% of cells appear complete cells after immunohistochemistry detection. HER2 gene amplification is detected by strong membrane staining (3+) and/or in situ hybridization.

The HER2-targeted drugs currently on the market are mainly targeted at HER2-positive patients, that is, patients with IHC 3+. However, for the large number of patients who do not meet this standard, there is a lack of effective treatments. The company has launched a Phase III clinical trial for locally advanced or metastatic breast cancer with low HER2 expression. The inclusion criteria are: low HER2 expression (defined as: IHC 2+ and FISH without amplification). The proportion of patients with low HER2 expression in the entire breast cancer population is not low. According to a data analysis of 12,467 patients from 19 domestic clinical centers by researchers such as Ruohong Shui, HER2 IHC 0/1+, IHC2+ and IHC3+ cases accounted for The ratios reached 48.5% (n=6048), 30.4% (n=3789) and 21.1% (n=2630) respectively. The results of 3164 cases of patients with HER2 gene amplification using ISH (FISH or dual-color silver-enhanced ISH) showed that the proportion of patients with no amplification by FISH reached 77.2% in IHC2+. Combining the above two data, we estimate that the proportion of patients with IHC2+ and no amplification by FISH in breast cancer is 30.4% × 77.2% = 23.5%.

Although patients with low HER2 expression account for a large proportion of breast cancer, there is currently a lack of excellent targeted therapy drugs for this type of patients. The company's vedicitomab is the first HER2-ADC to enter the HER2 low-expression market. It is a pioneer product in Phase III clinical trials of breast cancer. The company has enrolled the first patient in September 2020. It is leading the country in progress and has an excellent competitive landscape. It is expected to provide new treatment options for patients with low HER2 expression and compete in the highly intense HER2-positive market. to open up new market space.

(2) Markets other than breast cancer

HER2 mutated tumors In addition to breast cancer, other tumor types may also provide broad market space for HER2ADC, such as gastric cancer, urothelial cancer, biliary tract cancer, melanoma, bladder cancer, etc. etc., and Vidicitomab’s indication layout in the non-breast cancer field has a leading advantage in the country, which will provide the company with differentiated competitiveness in the future.

For vedesitumab, the main competitors it faces in the near future include Roche’s trastuzumab deruxtecan and Daiichi Sankyo/AstraZeneca’s trastuzumab deruxtecan. From the indications of these three products From a layout perspective, the clinical development idea of ​​vedicitomab is unique, avoiding the highly competitive field of HER2-positive breast cancer, opening up a number of unmet clinical gaps, and will provide a better market competition environment in the future.

3.1.2, Tatasercept: Avoid the Red Sea Competition of Autoimmune Diseases in Advance

The pharmacological mechanism of Tatasercept determines that this molecule may be effective against a variety of B cell-mediated autoimmune diseases, and the company is When doing clinical development of this molecule, we did not blindly follow market hot spots to develop major indications such as rheumatoid arthritis. Instead, we took a different approach and used lupus erythematosus as the first indication, with a relatively small number of people but a serious lack of high-quality drugs. And it has laid out a variety of diseases with clinical gaps. Judging from the current indication layout of Tatacept, there are not only rheumatoid arthritis, which has a broad market, but also areas such as myasthenia gravis, Sjögren's syndrome, and IgA nephropathy that are relatively blank in clinical practice. It has a multi-level layout of differentiated indications. It will provide products with unique competitive advantages. We expect that this clinical development idea will be very effective in avoiding fierce competition in sales and extending the life cycle of products.

3.2. Steady international layout

In order to realize the commercial value of the product’s clinical value in as many markets as possible, the company unswervingly promotes the internationalization strategy and continues to achieve fruitful results.

3.2.1, Vedicitomab: Licensed to Seagen, overseas clinical trials are progressing smoothly

In August 2021, the company reached a global exclusive license agreement with Seagen, an internationally renowned biopharmaceutical company in the United States, to develop and commercialize the company's Vedicitomab. Toxomab. The two regions are divided into Rongchang Bioregion including other Asian regions except Japan and Singapore, and Seagen obtains global development and commercialization rights outside the Rongchang Region. Seagen bears all costs related to clinical trials, development and registration in the Seagen region; the company will retain the rights to clinical development and commercialization of vedicitomab in the Rongchang Bioregion, and will bear the costs of conducting clinical trials, development and registration in the Rongchang Bioregion. All costs related to clinical trials, development and registration and other related activities. In addition, Seagen needs to pay the company an upfront payment of US$200 million (the company has received the downpayment in October 2021) and milestone payments of up to US$2.4 billion. At the same time, the company will receive Vidicitomab in the Seagen region. Gradient sales commissions on net sales range from high single digits to more than ten percent. The U.S. clinical trial of vedicitomab has enrolled the first patient on May 3, 2022 (clinical registration number: NCT04879329).

3.2.2, Tatacept: Promote clinical trials in the United States and solidly enter the international market.

The company has established an international drug registration system and has obtained multiple international clinical trial licenses for Tatacept (RC18). In the future, it will Fully promote the global multi-center clinical trial of Tatacept: The company will actively promote the Phase III global multi-center registration clinical trial of Tatacept for the treatment of systemic lupus erythematosus, and strive to submit marketing authorization applications globally as soon as possible; The company has obtained approval for the Phase II global clinical trial of Tatacept for the treatment of IgA nephropathy and is currently conducting the trial; the company is preparing to submit an IND application for Tatacept for the treatment of Sjögren's syndrome to the US FDA. In the future, the company will make every effort to promote the global multi-center phase II/III clinical trials of Tatasercept for the treatment of various autoimmune diseases, and strive to obtain global drug marketing authorization as soon as possible to establish the global B cell-mediated autoimmune status of Tatasercept. Leadership in immune diseases.

The SLE multi-center Phase III clinical trial of Tatacept has announced the clinical trial plan in 2022.4. The US Phase II clinical trial of IgA nephropathy has enrolled the first patient in 2021.11. With the steady progress of overseas clinical trials and the acquisition of international data, Tatacept Pu will gradually open up the international market, realize the clinical value of molecules on a larger scale, and help the company's performance achieve long-term and healthy development.

(This article is for reference only and does not represent any investment advice on our part. If you need to use relevant information, please refer to the original text of the report.)

Selected report source: [Future Think Tank]. Future Think Tank - Official website