Original Baiqi rice net
Highlights
With the continuous improvement of R&D innovation and commercialization capabilities, Chinese local pharmaceutical companies are becoming important targets for all-round cooperation between multinational pharmaceutical companies (MNCs). On April 8, Sino Biopharma and Boehringer Ingelheim announced a strategic cooperation to jointly develop and commercialize Boehringer Ingelheim's oncology drug pipeline in Chinese mainland based on their respective advantages and resources. Different from the past, this "innovation alliance" cooperation method greatly goes beyond simple market investment or pipeline licensing, but the two sides jointly develop and commercialize together, which can be said to be the first real strong alliance between Chinese and foreign pharmaceutical companies.
Chengrun Xie, CEO of Sino Biopharma, and Mohammed Tawil, President and CEO of Boehringer Ingelheim Greater China, shook hands at the signing ceremony
The ability to innovate and commercialize has been recognized, and the local BIG PHARMA may become the first choice for MNC cooperation
In recent years, MNC has accelerated the adjustment of its business in China and has increasingly cooperated with local enterprises. In the secondary market, Eli Lilly Asia and AstraZeneca have invested in the establishment of foundations to provide financing for a number of domestic pharmaceutical companies, while in the secondary market, Amgen has purchased a 20.5% stake in BeiGene, Pfizer has purchased a 9.9% stake in CStone, Sanofi has a stake in Innovent Biologics, and MNC's direct acquisition of biotech and direct licensing of pipelines are more common. According to incomplete statistics, in the first quarter of 2024, more than 10 licensing transactions have been authorized by multinational pharmaceutical companies to domestic pharmaceutical companies.
Among them, the cooperation between Sino Biopharma and Boehringer Ingelheim (BI) is very unique and worthy of in-depth analysis. On the one hand, BI has chosen Sinopharma as its most important oncology pipeline partner in the highly competitive and capable Chinese market, which is a high recognition of Sinobio's innovation ability and commercialization. According to Endpoints News, although Boehringer Ingelheim has been active in China, with more than 4,000 employees, it does not have an oncology drug sales team. Detlev Mennerich, head of BI Global BD, said in the report that he attaches great importance to the commercial team of Sinobio Pharmaceutical, and expects the cooperation between the two parties to achieve the effect of 1+1 greater than 2 or even greater than 3. One source, speaking on condition of anonymity, revealed, "Three years ago, BI sought the evaluation opinion of a consulting firm to find a local partner, and Sinobio was the only company recommended at that time. ”
According to public information, Sino Biopharma is currently one of the top five pharmaceutical companies in China's oncology field, with more than 40 innovative oncology pipelines and projects, and a professional oncology sales team of nearly 3,000 people, with a total sales volume of 8.8 billion yuan in 2023.
On the other hand, from the perspective of the "gene" attribute of the enterprise, the two parties are both "old money" family pharmaceutical companies with a history of 100 years, and there are many similarities in terms of innovation and inheritance, stable management structure, and abundant cash flow, which may be another important incentive for this cooperation.
Finally, at a time when the domestic pharmaceutical industry and market environment are undergoing profound changes, multinational pharmaceutical companies need to make decisive strategic adjustments if they want to embrace the new opportunities in the Chinese market as always. A senior pharmaceutical industry investor said that the development of MNC in China is facing various challenges such as patents, compliance, and marketing, and the cooperative relationship between Sino Biopharma and BI can ensure that the interests of both parties are maximized, and also lay a solid foundation for further cooperation in the future. It is foreseeable that more in-depth and comprehensive cooperation between MNC and Chinese local pharmaceutical companies will become a trend.
"International cooperation is an inevitable trend in the development of the pharmaceutical industry. Liu Yu, founding partner/general manager of BGI, said that China Big Pharma has the advantage of local resources in participating in the benefit distribution of the back-end commercialization value of international innovative drugs, and similar cooperation is beneficial to strengthening the R&D strength, professional academic promotion ability of local enterprises, and accelerating the process of internationalization. For MNC, in the face of the great changes in China's medical system and the urgent need for a new market model to achieve a balance between front-end innovation + back-end commercialization efficiency, by leveraging the resources and network of Big Pharma in China, it can help reduce the cost of market development, achieve commercialization quickly and efficiently, and enjoy the huge market in China.
Aiming at the 130 billion domestic market, 3 cutting-edge new anti-tumor drugs are eye-catching
According to data released by the World Health Organization's International Agency for Research on Cancer (IARC), China has become a veritable "cancer country", with the highest number of new cases and deaths in the world. According to data from Minenet, in recent years, with more and more innovative drugs approved for marketing, superimposed clinical rigid demand attributes, the sales of anti-tumor drugs (chemical drugs + biological drugs) in China's three major terminal and six major markets have reached 100 billion yuan, exceeding 130 billion yuan in 2022 and 70 billion yuan in the first half of 2023, and the annual sales are expected to reach a new high.
Sales of antineoplastic drugs (chemical drugs + biological drugs) in China's three major terminals and six major markets in recent years (unit: 100 million yuan)
Source: Minenet Grid Bureau Database
In this cooperation between Sino Biopharma and BI, 3 cutting-edge anti-tumor drugs in the late clinical stage have attracted much attention!
Brigimadlin: Facing the dilemma of biliary tract cancer treatment and developing new treatment strategies
Brigimadlin (BI907828) is a highly potent, orally active murine bimicrosome homologous gene 2-oncoprotein p53 (MDM2-p53) antagonist that inhibits the interaction between TP53 and its negative regulator MDM2, resulting in cell cycle arrest or apoptosis in tumor cells with TP53 wild-type status.
At present, no MDM2-p53 antagonist has been approved worldwide. Among the new drugs under development, Boehringer Ingelheim's Brigimadlin, Roche's Idasanutlin, and Rigel Pharmaceuticals' DS-3032 are all in phase III clinical trials. Among the many new drugs under development with the same target, Brigimadlin has advantages in the mechanism of action: on the one hand, it can directly target tumor cells, block the interaction of MDM2-p53, lead to tumor cell cycle arrest or apoptosis, thereby inhibiting the growth and spread of tumor cells, and on the other hand, it also has immunomodulatory functions, which can increase CD8+ T cell populations and induce anti-tumor immune memory, thereby enhancing the anti-tumor effect. In terms of pharmacokinetic properties, Brigimadlin has high bioavailability and a half-life of 30 to 60 hours, which can meet a variety of different clinical dosing regimens.
At present, biliary malignant tumors are the second largest hepatobiliary malignant tumors after hepatocellular carcinoma, and although a variety of treatment methods have been applied to the systemic treatment of advanced patients, most of them have poor efficacy. Brigimadlin has entered a pivotal Phase III clinical trial for the indication of dedifferentiated liposarcoma (DDLPS), which has been granted Fast Track Designation by the FDA, and orphan drug designation for the indication of biliary tract cancer (BTC). Early clinical data suggests that Brigimadlin is also expected to bring additional benefits to patients with other solid tumors such as biliary tract cancer, soft tissue sarcoma, and bladder urothelial carcinoma.
Brigimadlin's global R&D landscape
Source: Minenet Global New Drug R&D Database
Lung cancer HER2 TKI Zongertinib: Promising for better tolerability and efficacy
Zongertinib (BI1810631) is a highly selective human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor (TKI) that covalently binds to the tyrosine kinase domain (TKD) of wild-type and mutant HER2 receptors, including those with exon 20 mutations.
Compared with the first- and second-generation TKIs, the third-generation drugs with high selectivity have shown better clinical efficacy, and can overcome the drug resistance caused by the T790M mutation, and are well tolerated, and have become mainstream drugs. A number of third-generation HER2 TKIs have been approved in China, among which the total sales of osimertinib, ametinib, and furmetinib in China's three major terminals and six major markets in 2022 will be close to 8 billion yuan.
Zongertinib has been granted Fast Track Designation by the FDA for the treatment of patients with NSCLC harboring HER2 mutations who have progressed on or after platinum-based therapy. Zongertinib is currently in a global Phase III clinical trial for the first-line treatment of patients with unresectable locally advanced or metastatic non-squamous NSCLC harboring HER2 gene mutations.
Zongertinib全球III期临床情况
Source: Minenet Global New Drug R&D Database
DLL3/CD3 bispecific antibody BI764532: 1+1>2 is expected
BI764532 is a delta-like canonical Notch ligand 3/cluster 3 (DLL3/CD3) bispecific T cell engager that selectively activates cytotoxic T cells and causes them to act on DLL3-expressing tumors.
At present, more than 10 bispecific antibody drugs have been approved for marketing around the world, and the global sales scale will exceed US$8 billion in 2023. CD3 is a membrane antigen widely distributed on the surface of mature T cells and has become a gold target for the development of bispecific antibody drugs in the world, while DLL3 is highly expressed in small cell lung cancer and low expression in normal tissues, which is expected to achieve precision treatment, and the physical connection of the two cells forms a cell pair, which is expected to play the role of "1+1>2".
Among the DLL3/CD3 bispecific antibody drugs under development worldwide, Boehringer Ingelheim is in advanced BI764532, and Phase II clinical trials for small cell lung cancer and other neuroendocrine cancers are underway, and the FDA has been granted Fast Track Designation for the treatment of DLL3-expressing advanced or metastatic large cell neuroendocrine carcinoma of the lung, and orphan drug designation has also been granted for the indication of small cell lung cancer.
BI764532 global R&D
Source: Minenet Global New Drug R&D Database
Self-developed + BD two-wheel drive, the product pipeline is becoming more and more fruitful
In recent years, Sino Biopharma has enriched its product pipeline through self-development + BD, rapidly achieved innovation and transformation, and accelerated the process of internationalization. In terms of self-development, it has built a rich product pipeline around the four advantageous areas of anti-tumor, liver disease, respiratory and surgical/analgesia. According to the company's announcement, R&D expenditure increased from 2.85 billion yuan in 2020 to 4.7 billion yuan in 2023, accounting for 12% of total revenue to 18%. At present, the company has 11 innovative drugs (including biosimilars) approved for marketing, and more than 90 Class 1 new drugs are in the clinical application stage or above in China, of which 10 new anti-tumor drugs have been submitted for NDA or are in phase III clinical trials, and can be marketed.
R&D of biopharmaceuticals in China in recent years (unit: 100 million yuan)
Source: Company announcement, compiled by Minenet
In terms of BD, Sino Biopharma vigorously promotes business development and strategic cooperation, and strives to become the best partner of global pharmaceutical companies. Since 2022, the company has reached more than 10 BD transactions, on the one hand, supplementing the existing pipeline by introducing innovative products, and on the other hand, effectively urging the self-research team to achieve progress and optimal or differentiated layout in project approval.
In 2023, Sino Biopharma successfully acquired F-star, a British biotechnology company on NASDAQ, becoming the first Chinese pharmaceutical transaction approved by the Committee on Foreign Investment in the United States (CFIUS) in the past three years, making Sino Biopharma a leader in the industry and becoming the preferred Chinese partner of global MNC and Biotech.
2022-present: BD transactions in China Biopharma
Source: Company announcement, compiled by Minenet
A number of BD projects have progressed rapidly under the impetus of Chinese biopharmaceuticals, such as Yiyi Biopharma's third-generation white drug F-627 (ibergostim α), which has been successfully approved in the United States and China, and Lanifibranor tablets have become the first PPAR agonist for NASH indications to enter phase III clinical trials in China.
Recently, Citeline, an internationally renowned consulting organization, released the "2024 Annual Review of Pharmaceutical R&D" and selected the world's top 25 pharmaceutical companies with pipeline scale. Among them, the scale of China's biopharmaceutical pipeline increased by 72% over the previous year, ranking 15th in the world and second among Chinese pharmaceutical companies.
According to data from Minenet, there are currently more than 90 Class 1 new drugs in China that are in the clinical application stage and above (excluding marketed new drugs and new indications), and the R&D pipeline is in a leading position among domestic pharmaceutical companies.
From the perspective of therapeutic areas, anti-tumor drugs accounted for about 60% of China Biopharma. Among them, NDAs have been submitted for 5 new drugs, including TQ-B3525 (PI3Kα/δ inhibitor, no drug with the same target has been approved in China), TQ-B3139 (c-Met/ALK/ROS inhibitor), TQ-B3101 (ALK/MET/ROS1 inhibitor), TQB2450 (PD-L1 monoclonal antibody) and gesuprexib (KRAS). G12C inhibitors, no drugs with the same target have been approved in China), and 5 new drugs are in phase III clinical trials, including TQB3823 (PARP1/2 inhibitors), TQB3616 (CDK4/6 inhibitors), TQB3454 (IDH1 inhibitors), FHND9041 (third-generation EGFR inhibitors) and AL2846 (c-Met inhibitors).
Sino Biopharma expects to launch more than 10 innovative products in the next three years (2024-2026), and more than 30 innovative products under development have the opportunity to be launched in 2030 or before, consolidating the company's leading position in innovation.
Sources: Minenet database, company announcements, etc
Note: The statistical scope of "China's Three Terminals and Six Major Markets" is as follows: urban public hospitals and county-level public hospitals, urban community centers and township health centers, urban physical pharmacies and online pharmacies, excluding private hospitals, private clinics, village clinics, and county and rural pharmacies; The statistics are as of April 12, if there is any omission, please correct!