China Biopharmaceutical Leader Inks Strategic Oncology Collaboration with Boehringer Ingelheim, Highlights Pipeline in Recent Filing

On April 8, 2024, Sino Biopharmaceutical Co., Ltd. (hereinafter referred to as “Sino Biopharm”) announced on the Hong Kong Stock Exchange that it had entered into a collaboration with Boehringer Ingelheim to bring Boehringer Ingelheim’s innovative oncology therapies to the Chinese market. Under the terms of the agreement, both parties will jointly develop and commercialize Boehringer Ingelheim’s oncology pipeline in China, and product revenues will be included in the consolidated financial statements of Sino Biopharm and its subsidiaries.

Regarding the entities involved in this collaboration, Boehringer Ingelheim and Sino Biopharm are two companies with which everyone is surely familiar.

Since its founding in 1885, Boehringer Ingelheim has remained an independent family-owned enterprise. As the world’s largest non-listed private company, it is wholly owned by the Boehringer, Liebrecht, and von Baumbach families, all of which are descendants of the founders or their sons-in-law. Having weathered two World Wars and multiple industrial revolutions, Boehringer Ingelheim has thrived and expanded to its present scale, while numerous small pharmacies established in the same era have vanished. This article will not delve into the detailed history of the Boehringer Ingelheim family’s rise to prominence.

Sino Biopharm is the main subject to be discussed next. It is also a family-owned enterprise, listed on the Hong Kong Stock Exchange in 2000, and was included as a constituent of the MSCI Global Standard Indexes – China Index in 2013. Its major subsidiaries include the Chia Tai Tianqing Group, which comprises Nanjing Chia Tai Tianqing, Beijing Tide Pharmaceutical, Chia Tai Fenghai, and Chia Tai Qingjiang Pharmaceutical, among others.

Previously, the group’s core business was generic drugs, with a presence in therapeutic areas such as liver disease and oncology.According to data from Menet, the top three companies among the top five domestic generic drug approval holders in 2021 were Yangtze River Pharmaceutical Group, Qilu Pharmaceutical, and Sino Biopharm, with 31, 21, and 20 approved varieties, respectively. Kelun Pharmaceutical had 17 approved varieties, and CSPC Pharmaceutical Group had 16. Among the generic drugs approved for these five corporate groups, a total of 11 varieties were the first generic versions launched in China. Notably, Sino Biopharm led with four first-to-market generics, earning it the title of “King of First Generics.”

In recent years, the generic drug industry has seen its profit margins gradually tighten due to factors such as centralized volume-based procurement, forcing companies to pivot toward innovative business models.Therefore, in 2018, Sino Biopharm confirmed its comprehensive transformation toward innovation, with R&D expenditure increasing year by year. In 2023, the investment reached RMB 4.4 billion, accounting for 16.8% of its revenue.Among these, investment in innovative drugs accounted for 77% of total R&D expenses. The number of innovative products rapidly increased from 2 in 2015 to 11 by the end of 2023, while the proportion of revenue from innovation surged from 11% to 38%.

As a leading domestic generic drug manufacturer that initially built its business on liver disease treatments, Sino Biopharm has achieved considerable success in transforming toward innovative pharmaceuticals. The group currently operates multiple research centers in Beijing, Nanjing, Lianyungang, Qingdao, and Shanghai, with a total R&D facility area of 170,000 square meters. Its R&D staff has grown rapidly from 500 in 2013 to over 2,700, while R&D expenditure accounts for more than 16% of total revenue.

Sino Biopharm has entered a period of intensive harvest for its innovative products, thanks to its substantial investment in innovation and early strategic layout.In 2023, six innovative drugs and biosimilars, including Yilishu, limaprost, bevacizumab, and rituximab, were approved and rapidly gained market traction after launch. The revenue from its innovative products reached RMB 9.89 billion last year, setting a new historical high for the group. Furthermore, according to the Insight database, nearly 3,000 clinical-stage innovative drug projects worldwide advanced in development during 2023. With more than 30 new drug advancements, Sino Biopharm ranked fifth among global pharmaceutical companies.

In recent years, oncology has remained a key innovation focus for Sino Biopharm.

Previously, the group had established a product portfolio centered on anlotinib, with PD-1 and PD-L1 inhibitors as adjuncts.All five approved indications for anlotinib have been included in the National Reimbursement Drug List. The sixth indication, involving combination therapy with PD-L1 inhibitors and chemotherapy as first-line treatment for small cell lung cancer, is expected to gain approval this year. The seventh indication, combining anlotinib with PD-L1 inhibitors for third-line treatment of endometrial cancer, has been granted priority review by the Center for Drug Evaluation (CDE) and is anticipated to be approved in 2025. The total peak sales of anlotinib’s innovative oncology product portfolio, including combinations with PD-1 and PD-L1 inhibitors, are projected to reach RMB 10 billion.

This collaboration with Boehringer Ingelheim, a powerhouse partner, has enabled Sino Biopharm to acquire several blockbuster oncology products.

According to the announcement, the key projects in this collaboration include three pipelines in clinical development: brigimadlin, zongertinib, and BI 764532. Previously, all three products were granted Fast Track designation by the FDA, with brigimadlin and BI 764532 also receiving Orphan Drug designation.

Among them, Brigimadlin (BI 907828) is a murine double minute 2 (MDM2)-p53 antagonist that binds to MDM2 and inhibits the interaction between MDM2 and p53 proteins. It prevents MDM2 from suppressing p53, thereby restoring p53 function. Stabilization of p53 leads to the induction of TP53 target genes, resulting in cell cycle arrest or apoptosis in TP53 wild-type tumor cells.

Currently, the pipeline’s research on dedifferentiated liposarcoma (DDLPS) has entered Phase II/III clinical trials. In addition, brigimadlin is being investigated for the treatment of other cancers, such as biliary tract cancer (BTC), non-small cell lung cancer (NSCLC), pancreatic cancer, and other tumors with MDM2 amplification.Previously, the FDA had granted brigimadlin Fast Track designation for the treatment of dedifferentiated liposarcoma (DDLPS) and Orphan Drug designation for the treatment of BTC.

The core product, zongertinib (BI 1810631), is a selective human epidermal growth factor receptor 2 (HER2) inhibitor that covalently binds to the tyrosine kinase domain (TKD) of both wild-type and mutant HER2 receptors, including those with exon 20 mutations. Highly selective HER2 tyrosine kinase inhibitors (TKIs) may offer improved tolerability and efficacy.

Currently, the trial of zongertinib monotherapy in patients with advanced or metastatic solid tumors is in Phase I.The FDA has granted Fast Track designation to zongertinib (an investigational oral therapeutic for the treatment of patients with HER2-mutated NSCLC whose disease has progressed during or after platinum-based therapy).

Another core product, BI 764532, is a DLL3/CD3 bispecific T-cell engager. Preclinical studies have demonstrated that DLL3/CD3 monotherapy can effectively inhibit the growth of DLL3-positive small cell lung cancer (SCLC) xenograft models in a dose- and time-dependent manner.

Clinical trials of BI 764532 for the treatment of small cell lung cancer (SCLC) and other neuroendocrine carcinomas (NECs) are currently in Phase I and Phase II.Previously, BI 764532 was granted Fast Track designation by the FDA for the treatment of advanced or metastatic large-cell lung neuroendocrine carcinoma expressing DLL3, extensive-stage SCLC, and extrapulmonary NEC, as well as Orphan Drug designation for the treatment of SCLC.

In addition to the three clinical-stage products mentioned above, this strategic collaboration also covers multiple early-stage clinical projects of Boehringer Ingelheim. Leveraging Sino Biopharm’s local strengths and Boehringer Ingelheim’s global resources, both companies look forward to bringing accessible therapies to more cancer patients in China as soon as possible.