The current development of the Chinese bispecific antibody market

The current development of the Chinese bispecific antibody market

Monoclonal antibody drugs, known as the “biological missile”, is emerging at a rapid speed in the recent years. It has sparkled a worldwide interest, and a range of important treatments were born from it, including Rituxan, the first chimeric antibody for treating tumors, Adalimumab, the famous rheumatoid arthritis monoclonal antibody, Avastin, the 2014 global sales Champaign, and Opdivo and Keytruda, the hottest immune checkpoint therapies in the market right now.

Other than the medications above, the bispecific antibody is another rising star in the red-hot monoclonal antibody field.

Bispecific antibodies consist of two specific antigen binding sites that interact with target cells and functional cells at the same time. Compared to the traditional monoclonal antibodies, this structure is able to enhance bispecific antibodies’ tumor killing effects to 100 or even 1000 times stronger and reduce the doses to just 1/2000.

The worlds’ first approved bispecific antibody is Fresenius’s Removab, which is used in the treatment of malignant ascites. However, it has not been greenlighted by FDA so far and is only marketed in Europe. Currently, the only FDA-backed bispecific antibody is Amgen’s Blinatumomab, which is recommended for the treatment of Philadelphia chromosome-negative(Ph-) recurrent/refractory precursor B-cell acute lymphoblastic leukemia.

In 2014, Roche has bagged Dutalys, an Austrian biotechnology company, with $487 million and obtained access to its bispecific platform DutaMab. And Roche is not the only one. A slew of pharma giants also sees the potential of bispecific antibodies and is stepping up their efforts to devote resources and apply capitals into the field, including Johnson & Johnson, Sanofi, etc.

According to a 2016 report from ChinaTech Securities, the combined investment in this sector from all major pharma companies has reached close to a total of $4 billion.

Technical difficulties

Technology is the key. At present, there are more than 30 bispecific platforms worldwide. Among them, MacroGenics’s DART system is the most popular one, applied by a range of companies, including Johnson & Johnson, Pfizer, Takeda, etc.

Across the globe, China currently has four bispecific technology platforms, including iTAB from Generon Biomed, DPL from Adagene, Ybody from YZY Bio, and FIT-Ig from EpimAb Biotherapeutics, also used by Innovent Bio.

Clinic progress

As of September 2017, a total of 68 bispecific antibody clinical trials are ongoing in the world, of which 31 studies are carrying out in the United States. Among them, most are recruiting or just completed its recruitment for Phase 1 or Phase 2 trials. Currently, 25 projects are finished, but only 10 of them have published their data.

So far, Amgen has the highest number of ongoing projects, up to seven; Roche and MacroGenics follow right after — each has three projects; Johnson & Johnson and Merck each has two; Pfizer and Eli Lilly each has one.

Undoubtedly, Amgen is the biggest player in the field. Currently, its most advanced bispecific candidate Blinatumomab is in phase 3 clinical trial to compare with traditional chemotherapies, with the goal to understand its efficacy and safety in leukemia and acute lymphocytic disease. It is expected to be completed by 2022.

Neovii also has a candidate in the late-stage clinical trial. Its Catumaxomab has started a combined phase 2 and phase 3 study in 2004. In the trial, its therapeutic effect on EpCam-positive tumors, such as gastric cancer, colon cancer, breast cancer, etc., was tested. This project was completed in 2009, but no experimental results have been announced so far.

Roche is another strong competitor in this bispecific antibody race. Although it does not have the largest number of projects in the pipeline, its ACE-910 was once the most promising candidate in the eyes of industry experts and watchers.

This is just part of the equation. Big pharmas are not the only ones who have their hands in this sector. Biotech companies are also making impressive processes. MacroGenics is one good example.

In December 2014, Johnson & Johnson has penned a $700 million license agreement with MacroGenics to receive the global authorization of its bispecific antibodies. It came just weeks before Takeda’s $500 million deal with MacroGenics to acquire its preclinical drug MGD011.

Undoubtedly, MacroGenics, with its strong technology platform and early molecular candidates, is leading the race in the biotech sector. It has inked a slew of deals with almost all major bispecific antibody pharma companies. Other than Johnson & Johnson and Takeda, it also formed an alliance with Pfizer, Merck, and Schweizer. Worth noting is that in 2015, MacroGenics has stroke a deal with Merck for a dual treatment with Keytruda, the hottest PD-L1 inhibitor.

Chinese bispecific antibody developers

Compared to western peers, the development of bispecific antibody has lagged behind in China. Currently, there is only one ongoing clinical trial — a randomized and controlled study of CIK cell therapy and bispecific antibody treatment on advanced hepatocellular carcinoma. It is co-organized by BenHealth and 302 Hospital and is currently recruiting patients for its phase 2 clinical trial.

According to a report from Artery Network, a total of 15 Chinese pharma companies are developing bispecific antibodies, including Livon Pharma and Jiangsu Hengri Medicine. Below, I have discussed the most promising ones.

YZY Bio

YZY Bio, a biotech company specialized in independent research and development of biomedicine, is leading the bispecific antibody development in China, whether it is the number of products or the progress of researches.

It has the largest variety of bispecific antibodies in development, up to a total of eight. Among them, their HER2/CD3 candidate against breast cancer is the most advanced one. According to the latest news, it has approved for clinical trials by the Chinese FDA, marking the first China independently developed bispecific antibody entering the clinical trial stage.

In May 2016, YZY Bio has completed a round of Series A financing, led by Panlin Capital, and inked a cooperation agreement with Shenogen Pharma Group.

Adagene

Adagene, founded in 2012, is committed to the development of a new generation antibody technology. Its co-founder Dr. Peizhi Luo is a serial entrepreneur. Equipped with extensive expertise and experience in antibody development and engineering, he has successfully started Abmaxis, which was acquired by Merck in 2006. After the acquisition, he served as the director of biologics and the head of antibody engineering there. Prior to that, Dr. Lou was the chief scientist at Xencor.

Adagene has completed a series A with $8 million in December 2014 and subsequently a series B with $29 million in January 2016. Investors included Fidelity Asia and WuXi Apptec.

On a separate note, Ge Li, the chairman of Wuxi AppTec, is also one of the company’s directors.

Henlius

Henlius, the rising star in the field of biologics, is a joint venture co-founded by Shanghai Fosun and a team of U.S. scientists in December 2009. The company is focused on the development and commercialization of biosimilars, modified biologics, and innovative monoclonal antibody. Relying on its resources both in China and the US, Henlius progressed rapidly and has established itself in the forefront of the antibody discovery field.

Henlius has penned collaboration deals with Kolltan Pharmaceuticals and Kite Pharma. Currently, it has 14 monoclonal antibodies under development, including two bispecific antibody drugs (HLX31 and HLX32).

In 2016, Henlius completed a $19 million round financing, led by HG Capital. At present, its valuation is estimated at more than $3 billion.

EpimAb Biotherapeutics

EpimAb Biotherapeutics is one of the youngest companies in the field of biologics; however, its power is no less than the established ones.

Founded in 2016, EpimAb is dedicated to the development of bispecific antibodies against tumors. Its founder Dr. Chenbing Wu was graduated from the University of Georgia and has worked on antibody discovery at Abbott for more than 10 years. He is also the inventor of DVD-lg, Abbott’s bispecific antibody technology platform.

EpimAb’s core technology is its unique and efficient dual bispecific antibody development platform FIT-Ig. Based on this platform, it has entered a cooperation with Innovent Bio, where Innovent Bio obtained the Chinese market access of FIT-Ig from EpimAb with $120 million and associated sales proceeds after product listings. Additionally, it has also inked deals with Kymab and WuXi AppTec to codevelop bispecific antibodies.

In April 2017, EpimAb has received $25 million Series A backing from Oriza, Decheng Capital, and 3E Bioventures. Currently, the company is slated to push its existing candidates into clinical trials, and it is predicted that the first will enter in 2018.

Note:

If you are interested in learning about the Chinese immunotherapy market. Please check out my article: A look of the major listed cell immunotherapy companies in China.

 

A look of the major listed cell immunotherapy companies in China

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