Authors: Tian Sun, Chinese Antibody Society
Authors: Minhua Chu, PharmaDJ
Authors: Danni Yin, PharmaDJ
Editor: Justin Fischer
We are excited to announce that PharmaDJ, a leading trade media publishing house and consulting firm, and the Chinese Antibody Society (CAS) will collaborate to provide comprehensive analysis and reports about therapeutic antibody licensing deals between Chinese biopharma and overseas companies. This is our first business report for the first half of the 2021.
Nineteen antibody deals were closed at a total value of ~ $7.8 billion in H1 2021. Thirteen of them were licensing-in deals; 6 were out-licensing deals (Figure 1). Among all the assets involved, ten assets were in the pre-clinical stage, six programs were in clinical development, and four programs were approved products.
Figure 1 Overview of antibody licensing deals closed in H1 2021 (data source: PharmaDJ)
Sixty-three percent of the assets licensed are naked monoclonal antibodies (mAbs) (Figure 2). While most of these mAbs focus on oncology targets, two of them target neurodegenerative diseases. With the FDA’s controversial approval of Biogen’s aducanumab for the treatment of Alzheimer’s disease (1), pharmaceutical companies are ramping up the development of treatments for difficult neurological diseases. In China, SciNeuro Pharmaceuticals (赛神医药), backed by a $100 million Series A round co-led by Lilly Asia Ventures and Arch Venture Partners, licensed Eli Lilly’s alpha-synuclein mAb to treat Parkinson’s disease. Simcere Pharmaceutical (先声药业), following its $460 million IPO in Hong Kong in 2020, licensed Vivoryon Therapeutics’ anti N3pE amyloid Ab to treat Alzheimer’s disease.
Figure 2 Breakdown of antibody licensing deals by types of antibody modalities (data source: PharmaDJ)
Three bispecific antibodies (BsAb) (Roche’s emicizumab, Amgen’s blinatumomab, and Jassen’s amivantamab) have been approved by the US FDA since 2014. Global BsAb market is valued at $490 million in 2020 and expected to reach $810 million by 2027 (2). With the advances in BsAb technologies and the regulatory support from the FDA (the FDA recently published a BsAb development guidance (3)), nearly 160 bispecific and multispecific antibodies are in the clinical development (4). In China, we've seen 4 BsAb license-in deals in H1 2021- Two are in clinical stages and two are in pre-clinical stages. Below are brief introductions of the two clinical stage assets.
●TR009 BsAb: Elpiscience (科望生物) licensed TRIGR Therapeutics’ TR009, an anti- VEGF x DLL4 BsAb to treat advanced cancers. In a Phase 1a study, TR009 monotherapy demonstrated Clinical Benefit Rate (CR+PR+SD) of 67% in heavily pre-treated patients that had failed multiple previous therapies (5). In contrast to DLL4 and other Notch-targeted therapies, TR009 has not shown pulmonary hypertension or other cardiac toxicities. TR009 is the second clinical stage BsAb Elpiscience licensed from overseas companie after licensing anti- PD-1 x 4-1BB BsAb (INBRX-105) from Inhibrx,
●PRV-3279 BsAb: Hangzhou-based Huadong Medicine (华东医药) licensed Provention Bio’s PRV-3279, an anti- CD32B x CD79B BsAb to treat systemic lupus erythematosus (SLE). In its Phase 1b study, PRV-3279 was well tolerated in healthy volunteers with no serious adverse events. PRV-3279 demonstrated sustained binding to B cell and reduction of IgM without B cell depletion. PRV-3279 represents the addition to Huadong's growing autoimmunology portfolio (6).
Like BsAb, antibody-drug conjugate (ADC) is another hot modality in recent business deals. The ADC sales are expected to reach $16.4 billion in 2026 (7). Although the number of ADC deals is low in our covered period (only 1 out of 19), domestic ADC development is making significant progress. RemeGen (荣昌生物) won its first HER2-ADC approval in China in June 2021 (8), kicking off the beginning of China’s domestic ADC era. Top-tier Chinese ADC companies, such as Miracogen (美雅珂), ProfoundBio (普方生物), and DAC Biotech (多禧生物), led by ADC veterans, who have worked for reputable ADC companies like Seagen and ImmunoGen. We expect to see increasing ADC transactions, collaborations, and clinical announcements in China.
There were also four immune checkpoint blockade (ICB) deals (Table 1) valued at more than $2.85 billion total and accounting for 40% of the disclosed total payments of all 19 deals. This data suggest increasing competition in the immunotherapy space. Given that almost every top-tier pharmaceutical company has a footprint in the PD-1 space and Novartis failed a pivot Phase III trial with its own anti-PD-1 mAb spartalizumab, it is not surprising that Novartis struck a $2.2 billion deal with BeiGene(百济神州) to license its tislelizumab to fill the gap (9).
Table 1 Summary of immune checkpoint blockade deals in H1 2021
Below are brief insights of the top two ICB deals:
●Tislelizumab: a humanized anti-PD-1 IgG4 designed to minimize binding to FcγR on macrophages. Tislelizumab is approved by the China National Medical Products Administration (NMPA) for the 1L treatment of patients with advanced non-small cell lung cancer and conditional approval for the treatment of patients with hepatocellular carcinoma, classical Hodgkin’s lymphoma and metastatic urothelial carcinoma. Recently in a Phase III pivot trial, tislelizumab demonstrated significant improved OS compared to chemo in patients with metastatic esophageal squamous cell carcinoma (10). The $2.2 billion licensing deal between Novartis and BeiGene will strengthen Novartis’ I/O portfolio and also help BeiGene gain a global footprint.
●Toripalimab (JS001): a recombinant humanized anti-PD-1 IgG4 with a high affinity to PD-1 and strong internalization capacity upon PD-1 binding. The US FDA has granted toripalimab one Breakthrough Therapy, one Fast Track, and three Orphan Drug Designations for the treatment of patients with nasopharyngeal carcinoma, mucosal melanoma, and soft tissue sarcoma. Although toripalimab is the first domestic anti-PD-1 mAb approved in China in 2018, it is relative slow to get a broad reimbursement coverage in China’s National Reimbursement Drug List compared to its domestic competitors (Hengrui/恒瑞医药’s camrelizumab, Innovent/信达生物’s sintilimab and BeiGene/百济神州’s tislelizumab). Through this licensing deal, Junshi (君实生物) will benefit from AstraZeneca’s marketing and sales’ strength to promote toripalimab’s update in China (11), whereas the $565 million deal with Coherus will help Junshi bring toripalimab to patients in the US and Canada.
Antibody therapeutics are experiencing unprecedented growth. The US FDA approved its 100th therapeutic antibody product in 2021 (4). Both globally and domestically, we see a concentrated effect to develop antibodies targeting the clinically validated targets such as PD-1/PD-L1, CD3 and HER2. To prevent over competition and promote true innovation, the NMPA recently published a draft guideline on cancer therapy development (12). While we applaud the booming antibody deals in China, we hope this guideline can provide some directions for upcoming licensing deals.
We thank Dr. Shouye (Shawn) Wang at CAS and Dr. Weimin Tang at I-MAB Biopharma for reviewing this article.
Table 2 List of all 19 deals closed in 2021 H1
(1) FDA’s Decision to Approve New Treatment for Alzheimer’s Disease
(2) Bispecific Antibody Market Size | Global Industry Research on Growth, Trends and Opportunity 2021-2027
(3) Bispecific Antibody Development Programs Guidance for Industry https://www.fda.gov/media/123313/download
(4) Asher Mullard, FDA approves 100th monoclonal antibody product, Nature Reviews Drug Discovery 20, 491-495 (2021)
(5) TRIGR Therapeutics Announces Publication of TR009/ABL001, Dual Angiogenic Bispecific Antibody Targeting VEGF/DLL4, in the International Journal of Molecular Sciences
(6) Provention Bio and Huadong Announce Strategic Collaboration to Develop and Commercialize PRV-3279 in Greater China
(7) Carolina do Pazo, Khurram Nawaz and Rachel M. Webster, The oncology market for antibody–drug conjugates, Nature Reviews Drug Discovery, 2021 https://www.nature.com/articles/d41573-021-00054-2
(8) China clears first homemade ADC, a HER2 med by RemeGen
(9) Novartis lays out $650M-plus for BeiGene's tislelizumab as its own PD-1 fails to impress
(10) Novartis investigational checkpoint inhibitor tislelizumab met primary endpoint of overall survival in pivotal Phase III trial of esophageal cancer after systemic therapy https://www.novartis.com/news/media-releases/novartis-investigational-checkpoint-inhibitor-tislelizumab-met-primary-endpoint-overall-survival-pivotal-phase-iii-trial-esophageal-cancer-after-systemic
(11) Junshi Biosciences and AstraZeneca Announce Strategic Collaboration to Commercialize Toripalimab in China
(12) Is China's drug regulator suddenly raising the bar on cancer med R&D? Not exactly, say experts