Over the past five years China has emerged as a major force in the research and development of innovative therapies for the treatment of cancer and hematological malignancies. According to the Swiss Investment bank UBS Group, China currently holds the largest share of the global ADC pipeline at over 42% with ADC drug-candidates developed by Chinese companies recognized by global companies accounting for more than 40% of global ADC out-license deals in 2023 alone.[1]

Against this backdrop, Chinese companies like RemeGenJiangsu-Hengrui Medicine, and Zhejiang Medicine/NovoCodex have ventured into the ADC-space through active research and development as well as significant partnerships with global pharmaceutical companies developing novel treatment options in oncology.

For example, Jiangsu-Hengrui Medicineis is developing SHR-A1904, a novel ADC with an optimized drug-antibody ratio (DAR), consisting of an anti-Claudin 18.2 antibody attached to a lipophilicity-enhanced topoisomerase I inhibitor payload via a cleavable linker. The novel ADC’s molecular design enhances plasma stability and bystander effect with balanced safety. In preclinical studies the investigational drug demonstrated a favorable efficacy, safety, and PK profile.

Claudins are tetraspan transmembrane tight-junction proteins that regulate epithelial barriers.[2]  Claudin 18.2 has a restricted expression profile in normal tissues. It physiologically expresses in the tight junction supramolecular complex of gastric mucosa. [3] However, prior studies demonstrate that frequent ectopic activation of Claudin 18.2 can be found in a diversity of malignant entities such as gastric, pancreatic, esophageal, ovarian, and lung tumors, which makes Claudin 18.2 a pan-cancer target. [4]

Advertisement #3 
Axplora
 

Strategic Alliances
According to data published in GlobalData‘s Pharmaceutical Intelligence Center Deals Database, between 2019 and 2023 a total of 537 strategic alliances were signed between global pharmaceutical companies and Chinese drug developers. Among these were 218 exclusive deals in oncology, or 41% of the overall deals.

Approximately 73% of these transactions included monoclonal antibodies and small molecules. In addition, a total of 10% of transactions included antibody-drug conjugates.

“The percentage of deals in China in oncology therapy area has increased gradually from 41% in 2019 to 56% in 2023,” noted Nelluri Geetha, Pharma Analyst at GlobalData.

One of the largest strategic agreements included a transaction between Seagen (now Pfizer) and RemeGen for disitamab vedotin (RC48; Aidexi®), a newly developed ADC targeting HER2 that is comprised of hertuzumab coupling monomethyl auristatin E (MMAE) via a cleavable linker.  In 2021, the year the deal; was signed, the agreement was valued at US $ 2.6 billion.

In 2023 GSK signed an exclusive licensing deal for US $85 million cash for Hansoh Pharma’s gynecologic cancer asset HS-20089, a B7-H4 targeted ADC currently assesses in a Phase 1a/1b clinical trial in China. After preclinical data demonstrated that HS-20089 inhibited tumor cell growth expressing B7-H4 in vitro and in vivo, Hansoh began studying the investigational drug in patients with advanced solid tumors.

In 2023 Bristol Myers Squibb (BMS) paid $800 million upfront for a phase 2 bispecific candidate targeting EGFRxHER3. On the other end of the deal is SystImmune, a Washington-based subsidiary of China’s Sichuan Biokin Pharmaceutical. The deal’s total value could reach up to US $ 8.4 billion if all milestones are met.

LegoChem and Janssen
In December 2023 Korea-based LegoChem Biosciences entered into a license agreement with Janssen Biotech, a Johnson & Johnson company, to develop and commercialize LCB84, a Trop2 directed ADC using LegoChem Biosciences’ next-generation ADC platform technology and Trop2 antibody licensed from Mediterranea Theranostic. Preclinical data demonstrated a differentiated safety and efficacy profile compared across multiple cancers, showing LCB84’s promise as a Trop2-targeting ADC.

Under the terms this agreement, LegoChem Biosciences granted Janssen an exclusive, worldwide license for the development and commercialization of LCB84 in which the company is eligible for up to US $ 1.7 billion in total consideration including an upfront payment of US $ 100 million, an option exercise payment of US $ 200 million as well as potential development, regulatory, and commercial milestone payments, plus tiered royalties on net sales.

Merck/EMD Serono and Jiangsu Hengrui Pharmaceuticals
In October 2023 German based Merck paid US $169.35 million upfront for the exclusive license rights to develop, manufacture and commercialize Jiangsu Hengrui Pharmaceuticals Co’s HRS-1167 – a potent and selective PARP1 (poly (ADP-ribose) polymerase 1) trapping inhibitor. The deal also included the option of an exclusive license that will give Merck the same rights for SHR-A1904.

The agreement also included an option to an exclusive license worldwide (ex-China) to develop, manufacture and commercialize Jiangsu Hengrui Pharmaceuticals Co’s SHR-A1904. In addition, Merck KGaA, Darmstadt, Germany, has the option to co-promote the drug in China.

“This partnership with Jiangsu Hengrui Pharmaceuticals Co fully aligns with both our external innovation ambition and our oncology research and development strategy by diversifying our robust internal pipeline in our focus areas of DNA damage response inhibition and antibody-drug conjugates,” noted Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business of Merck KGaA, Darmstadt, Germany.

“The synergies with our portfolio offer broad potential for development and the opportunity to advance more therapeutic options for patients with difficult-to-treat cancers,” Bar-Zohar added.

According to GlobalData, SHR-A1904 complements Merck’s internal preclinical and clinical ADC portfolio applying different linker payload technologies. The first ADC developed using Merck/EMD Serono’s own technology, M9140, a CEACAM5-targeting ADC, is being evaluated in an ongoing Phase Ia/b study in patients with metastatic colorectal cancer (NCT05464030)

Roche and MediLink
In January 2024 Roche signed worldwide collaboration and license agreement with China-based MediLink Therapeutics.  The agreement which grants Roche exclusive global rights for the development, manufacturing, and commercialization of MediLink’s YL211, a novel, investigational  ADC targeting mesenchymal epidermal transforming factor (c-MET) for treating solid tumors, has a potential value of US $ 1 billion

The agreement with Roche follows MediLink’s agreement with BioNTech for the development of a next-generation ADC candidate against the Human Epidermal Growth Factor Receptor 3 (HER3) with an estimated value of US 1 billion.

Clinical trials
According to GlobalData, the top five countries for the ongoing Phase 1, Phase 2, and Phase 3 clinical trials of innovator oncology drugs in the Asia-Pacific (APAC) region include China, Japan, Australia, South Korea, and India, with China alone responsible for 59% of all clinical studies, followed by Japan with 14% and Australia 12%.

“China is the most populous country in the APAC region, it also has an expanding pharma market and robust pipeline, thereby meeting the healthcare needs of the increasing population. The immense growth of the pharma industry in China, facilitated growth in the entire APAC region,” Geetha explained.

“China’s innovative therapies and strategic partnerships are about to reform the oncology landscape. The increased number of partnerships for the oncology therapy area and broad focus on small molecules, monoclonal antibodies, and conjugated monoclonal antibodies is expected to bring further change in the oncology landscape in China with a greater number of monoclonal antibodies and small molecules expected to get into the market in near future,” Geetha concluded.

Note: Strategic alliance deals for multiple therapy areas including oncology also happened. However, for analysis, only exclusive oncology deals were considered.

Clinical trials
Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors – ClinicalTrials.gov ID NCT05464030.

Reference
[1] APAC Focus: China ADC drugs – a rising force in cancer treatment. UBS Investment Bank. Online. Last accessed on April 20, 2024
[2] Schlingmann B, Overgaard CE, Molina SA, Lynn KS, Mitchell LA, Dorsainvil White S, Mattheyses AL, Guidot DM, Capaldo CT, Koval M. Regulation of claudin/zonula occludens-1 complexes by hetero-claudin interactions. Nat Commun. 2016 Jul 25;7:12276. doi: 10.1038/ncomms12276. PMID: 27452368; PMCID: PMC4962485.
[3] Xu B, Liu F, Liu Q, Shi T, Wang Z, Wu N, Xu X, Li L, Fan X, Yu L, Liu B, Wei J. Highly expressed Claudin18.2 as a potential therapeutic target in advanced gastric signet-ring cell carcinoma (SRCC). J Gastrointest Oncol. 2020 Dec;11(6):1431-1439. doi: 10.21037/jgo-20-344. PMID: 33457012; PMCID: PMC7807267.
[4] Singh P, Toom S, Huang Y. Anti-claudin 18.2 antibody as new targeted therapy for advanced gastric cancer. J Hematol Oncol. 2017 May 12;10(1):105. doi: 10.1186/s13045-017-0473-4. PMID: 28494772; PMCID: PMC5427576.

Featured Image: Funding Contract. Courtesy: © 2010 – 2024 Fotolia/Adobe. Used with permission.

Advertisement #4