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MabPlex Opens New Phase III and Commercial Manufacturing Facility

MabPlex International, a fully integrated Contract Development and Manufacturing Organization (CDMO) with sites in China and the United States, has inaugurated their new manufacturing facility in Yantai, Shandong, China.

The grand opening and ribbon-cutting ceremony for their new facility took place on September 6, 2018.

Photo 1.0: Jianmin Fang, Ph.D, Chairman and CEO of MabPlex International, Ltd. speaking during the opening ceremony of the company’s new manufacturing facility in Yantai, Shandong (China).

The company, one of the few providers of large-scale ADC production worldwide, was founded in 2013 and specializes in providing complete biologics development and manufacturing solutions. The unique technical expertise helps the company to provide effective solutions for the development and manufacturing of monoclonal antibody and antibody-drug conjugate (ADC) therapeutics, from cell line development and process characterization, to conjugation optimization and cGMP manufacturing.

MabPlex was the first company to manufacture an antibody-drug conjugate in clinical trials in China.


The new manufacturing facility in Yantai, Shandong (China), along with the process development sites in San Diego, CA (USA) and Shanghai (China), will strengthen the company’s ability to meet the needs of new and current clients as they progress to the commercialization phase of their products…


Milestone
This milestone will enhance MabPlex’s ability to deliver Phase III and commercial development and manufacturing solutions to clients in multiple global markets and expand the company’s manufacturing operations to a total of approximately 750,000 ft²; with 400,000 ft² devoted specifically to cGMP execution.

The completed facility includes six independent cell culture suites, four independent purification suites, and a cGMP warehouse. Each of the six cell culture suites will support up to two single-use bioreactors at volumes of up to 2,000L (with a maximum capacity of 24,000L).

“With a growing number of novel and increasingly complex drug constructs in early development pipelines and new targeted therapies, such as ADCs, in late stage development and moving to commercialization, there is a growing global demand for specialized CDMOs,” noted  Jianmin Fang, Ph.D, Chairman and CEO of MabPlex International, Ltd.

The new facility was built in response to the growing, global, demand for biomanufacturing capacity and complies with all international manufacturing regulations.

“This new facility, along with the opening of our San Diego and Shanghai process development sites, will increase our capacity to meet the needs of our new and current clients as they progress to commercialization,” Fang added.

Earlier this year, MabPlex USA, a subsidiary of MabPlex International, Ltd., opened the company’s new state of the art Process Development Center of Excellence located in La Jolla, CA (USA) near San Diego, CA (USA) with scale up capacity to 200L, offering world class expertise supporting cell line development, upstream and downstream process development, antibody-drug conjugate (ADC) development, analytical development and formulation development.


Editorial Review: December 13, 2018

Featured Image: MabPlex New Facility in Yantai, China Courtesy: © 2010 – 2018 MabPlex. Used with permission.

Copyright © 2018 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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Benefitting from the Worldwide Supply Chain in the development of Antibody-drug Conjugates

Timing is everything.

Just over a decade ago, the pharmaceutical industry and R&D in China was dominated by generics and plagued with insufficient technical capacity and fewer investments at the initial stage of novel drug development.

Although China’s entry in the global pharmaceutical R&D industry started relatively late, substantial government support and a thriving economy, has changed the industry. In recent years, the country, as a whole, has achieved colossal success in building a modern industry.

China’s success is, in large part, the result of the countries Thousand Talent program, a 2008 government initiative targeting Chinese-born academics and workers who trained overseas – in the United States and Europe – and encouraging them to ‘come home’ with promises of grants and tax breaks.

In addition, the Chinese government has increased funding focused on graduating large numbers of university-trained Chinese scientists, which, in turn, helped the growth of venture capital and private equity funds that can directly invest in Chinese biopharmaceutical industries.

And the results of these targeted ‘investments’ have been impressive.

Combined with a burgeoning middle-class and rapidly-aging society, China presents vast opportunities for R&D, making the country an important innovator of pharmaceutical products. Managing a worldwide supply chain, in 2017, China invested approximately US $13.2 billion in medical and pharmaceutical R&D. This accounts for 8.9% of the total global medical and pharmaceutical R&D investment in the same period.

But with the enhancement of R&D, the strengthening of the regulatory framework and the perfection of clinical trial data of audits and inspections, R&D spending is expected to continue to increase.

A report published by Chisult Insight showed that China’s pharmaceutical R&D spending is expected grow to US $29.2 billion in 2021, representing 18.3% of the total amount of the global pharmaceutical R&D in that year.

CDMO
Over the last decade there has been a growing number of Chinese contract development and manufacturing organizations (CDMO), such as MabPlex International (Yantai 264006, Shandong, China), that offer integrated, end-to-end services and open-innovation platforms to support pharmaceutical R&D and manufacturing for both small and large molecules.

From Generics to Innovative drugs
Leading Chinese pharmaceutical companies, historically focusing on the manufacturing of generics, are now investing in, and building, capabilities designed to develop and manufacture new and innovative drugs.

Their intent is to draw on the specific needs of Chinese patient’s needs, while, at the same time, capitalizing on knowledge from other markets, including Europe and the United States.


“Although China’ is the world’s second largest pharmaceutical market after the United States, some of the most effective modern medicines are not yet available.”


This approach is further supported by a group of innovative biotech companies founded over the past five years that focus on addressing global unmet medical needs.

According to health-care information company IQVIA, in 2017 China was the world’s second-largest national pharmaceutical market worth $122.6 billion. China is also the biggest emerging market for pharmaceuticals with growth expected to reach $145 billion to $175 billion by 2022.

Turning point
As a result, today, the biotechnology industry in China is at a turning point, with many key elements in place for innovation: an educational system churning out doctorates and strong basic research, substantial financial backing from both private investors and public sectors, regulations that are becoming globally harmonized, a changed legal environment designed to effectively secure Intellectual Property (IP) rights – which are among the most valuable resources for pharmaceutical and biotech companies – and a vibrant group of entrepreneurial leaders with ambitions for China and abroad.

Unmet medical needs
Western pharmaceutical and biotechnology companies, both in the United States and Europe, interested in working with Chinese biotechnology and life science industries, find a country facing significant unmet medical needs — particularly in cancer, neurology and diabetes — and a rapidly aging, often medically naïve (untreated) population. This, in turn, makes China unique for clinical trials.

Availability
Although China is the world’s second largest pharmaceutical market after the United States, some of the most effective modern medicines are not yet available.

Of 42 anti-cancer drugs approved globally in the past five years, for example, only four are currently available in China. With reforms on the way, this is expected to change rapidly.

Recent regulatory changes bring imported drugs to China more quickly, and local biotechnology and pharmaceutical are racing to develop novel, advanced, therapeutics for both the domestic and global markets.

Attractive for R&D
A generally low-cost base, a large pool of highly qualified research subjects, increased scientific capabilities, local industry’s knowledge, a general lack of regulatory and cultural impediments often found in other countries and insight into the country’s growing drug markets have made China an attractive country for R&D.

And following the implementation of comprehensive government reforms in the regulation of drug development and clinical trials, the country has become even more attractive.

In 2015 the Chinese government reformed the China Food and Drug Administration’s (CFDA) review and approval system for drugs and medical devices. These reforms have had a profound impact on the entire healthcare industry in China, affecting both Chinese and foreign companies pursuing development and registration of pharmaceutical drugs and medical devices in China. The CFDA reforms initiated less than 3 years ago and the regulatory changes these reforms have brought are expected to catalyze the pharmaceutical industry in China.

Since the reform began, the CFDA has issued hundreds of new policies, guidelines, and draft opinions to optimize the regulatory landscape. The results – progress – in reforming the system has been significant.

For example:

  • The backlog of 22,000 drug applications reported in August 2015 have been to about 8,000 by the end of 2016;
  • A total of seventeen batches of 227 applications, including both Clinical Trial Applications (CTAs) and New Drug Applications, were granted priority review status by June 2017.
  • Since the beginning of the reform, 10 provinces are now running Drug Marketing Authorization Holder pilots.
  • The number of reviewers at the Center for Drug Evaluation has increased from about 150 in 2015 to 600 by the end of 2016. It is expected that this number of reviewers will further grow in the years ahead.
  • An expert-committee system that taps into external expertise to support review and approval of innovative drugs is being established.

However, regulatory changes are ongoing in China. And while the impact of new reorganizations, such as the establishment in March 2018 of the new State Market Regulatory Administration (SMRA) and State Drug Administration (SDA), which will replace the CFDSA, are still unknown, the results will be far-reaching.

Global Clinical trials
The current regulatory approval for pharmaceutical agents in China is, in many cases, based on clinical trials that have been carried out in the country. But in order to be designated Investigational New Drug a Chinese legal entity must submit the drug registration application. And since clinical trial applications are also considered to be drug registration applications, overseas drug manufacturers in the United States or Europe interested in conducting clinical trials in China without legal representation in the country, must apply for product registration through an agent with professional knowledge and familiarity with Chinese laws and regulations.

In contrast to many other countries, the CFDA is also responsible for authorizing the import of Intellectual Properties (IPs). Prior to the import or manufacture of medicinal products protected by IPs, the CFDA needs to issue an import drug license for each individual IP.
This has a direct impact on the development of clinical trials. For example, for multi-center trials, documentation demonstrating that the clinical trial’s imported drugs have been prepared according to good manufacturing practices (GMPs) should be included in the application dossier.

The CFDA will, however, prioritize the review and approval of foreign innovative drugs, such as novel, investigational antibody-drug conjugates (ADCs) that are either manufactured in China, manufactured at a facility in the United States or European Union and are simultaneously under review for marketing authorization by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA).

In addition, the drug testing institute must conduct sample testing and specifications verification of the IP in order to issue a Certificate of Analysis as part of the CFDA’s approval requirements for all registered drugs.
Finally, as part of the approval to conduct clinical trials, China has a decentralized process for the ethical review of clinical trial applications. As part of this process, approvals are required from institutional level ethics committees for each trial site. This process is implemented through a three-tiered framework consisting of national ethics committees, provincial ethics committees, and institutional level ethics committees.
In contrast, United States (US) has a decentralized process for the ethics review of clinical trials in which the sponsor is required to obtain approval from an institutional level ethics committee, referred to as institutional review boards (IRBs), for each study.

Growing Interest
Many of the new regulations and requirements as well as new requirements yet to be implemented, have also contributed to the global pharmaceutical industry’s interest in conducting clinical trials in China. This has directly led an increased interest by US and European companies to work with a Chinese contract research organization (CRO) and contract (development) and manufacturing organizations (C(D)MO) such as MabPlex International.

The regulatory environment has, no doubt, boosted China’s ambitions plans to be a primary market for CROs and CDMOs. Most of the top 20 multinational pharmaceutical companies have been expanding their footprint in China by setting up R&D facilities through various legal structures. And global biopharmaceutical companies including Bristol-Myers Squibb (BMS), Pfizer, Roche, GlaxoSmithKline (GSK), Johnson & Johnson and Novo Nordisk are developing partnerships with Chinese companies.

While this approach mitigates traditional development risks, it also leverages local efficiencies, allowing global biopharmaceutical companies to add operational value due to familiarity with the market and regulatory requirements. In turn, this leads to shortened approval times and reduced development costs.

Made in China 2025
Growth in the Chinese biopharmaceutical industry is also expected as a result of a recent designation of biotech, in addition to other industries like robotics, aircraft, and electric cars, as one of the targeted industries in which the country wants to achieve an independent major position in by 2025.

Currently, China has ambitions for exporting generic medication around the globe. This ambition is evidenced by the growing number of generic drugs approved by regulatory agents in the United States and Europe.

This growth has been quite impressive. In 2017, Chinese pharmaceuticals obtained U.S. Food and Drug Administration approvals for 38 generic drugs, up from 22 such approvals in 2016.

Innovative drugs
However, in addition to becoming a manufacturing hub for generic drugs, China has also ambitions to develop and manufacture novel, innovative, pharmaceutical agents, as is evidenced by the development of antibody-drug conjugates (ADCs).

Today, antibody-drug conjugates are among the most complex drugs available. By combining an antibody with a cytotoxic payload, these drugs are directly targeting cancer cells, while, at the same time, leaving healthy cells alone.

The complexity is evidenced by the fact that since 2000, when the first ADC was approved in the United States, only 3 other antibody-drug conjugates have been approved, while more than 150 investigational agents have been or are currently in a clinical development program.

In an article published in the July 2018 edition of the International Immunopharmacology, researchers and scientists from RemeGen (Yantai 264006, Shandong, China) and MabPlex International, RemeGen’s development and manufacturing partner, confirmed the development of novel treatment options for B-cell lymphoma, one of the most refractory tumors.
Jointly established by Rongchang and Professor Fang Jianmin, RemeGen has developed a novel antibody-drug conjugate called RC48. In September 2015 this investigational agent became the first ADC in China to be approved by CFDA for inclusion in clinical trials.
RC48 is mainly used for the treatment of HER2 over-expression in gastric cancer, lung cancer, breast cancer, ovarian cancer, and bladder cancer.

MabPlex
Among the growing CDMOs in China is MabPlex International. Based in Yantai, a port city in Shandong province, China, and founded in 2013, the company specializes in the development and GMP manufacturing of recombinant proteins, antibody therapeutics and antibody-drug conjugates for its global customers.

From its inception, the company was designed to aide Western pharmaceutical companies, especially companies focusing on the development of innovative drugs, especially complex agents like antibody-drug conjugates or ADC. To accomplish the goal of attracting foreign clients, the company is establishing a track record by working with Chinese biotechnology companies to ‘win over’ these Western companies. And while some of MabPlex’ Chinese clients are looking to develop and manufacture drugs for the Chinese market, other companies are intently focusing on the development of complex, novel drugs to supply Western markets.

Multinational collaboration
Partnerships between Western pharmaceutical companies and Chinese CDMOs – to develop novel, innovative, drugs, has been rapidly growing.

These partnerships may take various forms, each with their own challenges, risks and benefits. One option includes a licensing agreement. Other options may include co-development or a joint venture.

With the tremendous advantages made by China’s industrial advances and progress made over the last decade, US and European companies can greatly benefit from developing these partnerships with Chinese companies

This is especially so in the development of novel, innovative, pharmaceutical agents.

Webinar
To take advantage of the options, we will address the unique position of China in the global biopharmaceutical industry and the benefits working with Chinese R&D may bring to Western pharmaceutical companies, like MabPlex International in a two-part webinar.

This webinar series “Drug Development in China: What you Need to Know,” will include a discussion of important steps in bio manufacturing, research & development and drug development in China and a discussion of challenges and treats, trends in biopharmaceutical manufacturing, clinical trials and regulatory issues. A discussion of the regulatory reforms, which includes the transition of the CFDA to a new State Market Regulatory Administration (SMRA) and a new State Drug Administration (SDA) will also be included.


¹In March 2018, China established the State Market Regulatory Administration (SMRA), which will take on the responsibilities of the China Food and Drug Administration (CFDA) and several other government entities. The SMRA’s State Drug Administration will replace the CFDA. However, regulating the life sciences and healthcare space in particular, the restructuring also establishes a new State Drug Administration (SDA) which will be supervised by the SAMR. The reorganization acknowledges that the regulation of drugs, medical devices and cosmetics products still requires a highly specialized and dedicated government agency. The new SDA will maintain its own branches at the provincial level and leave the post-approval enforcement duties at the lower municipal and county levels to the consolidated SAMR branches. The new agency is expected to become one of the most   powerful market regulators to address the ever-mounting concerns about drug and food safety, protection of intellectual property and product quality issues in general.

²This webinar will also include the latest (available) updates regarding the ongoing regulatory reforms in China, which includes the transition of the CFDA to a new State Market Regulatory Administration (SMRA). Although information about SAMR’s restructuring and appointments, as well as any new policy goals and initiatives are expected to be released in due time, it is yet unknown whether the SAMR and the new State Drug Administration (SDA) which will be supervised by the SAMR, will change direction from the course set by the CFDA or continue to implement the previous CFDA reform initiatives. The reorganization may might delay actual implementation of previously announced initiatives.

Last Editorial Review: October 9, 2018

Featured Image: Photo by Hanny Naibaho on Unsplash

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New Reports Suggests Antibody-drug Conjugates Market to Set Phenomenal Growth in Key Regions by 2023

A new market research report published in late June by HTF market Intelligence Consulting, suggests that the Antibody-drug conjugates (ADC) Market in China is expected to grow exponentially.

The study forecast growth to 2022 and presents an in-depth strategic assessment of the antibody-drug conjugates, highlighting a number of influencing factors impacting or reinforcing market environment, including government policy, technological changes along with market drivers.

Growing footprint
One of the key markets covered by the authors of the report is China and highlights the growth in China, the increased, and growing, manufacturing base and geographic footprint. Finally, the report strategically profiles key players in the market and comprehensively analyze their growth strategies.

With a population of 1.4 billion [*] and a rapidly expanding economy, China has become a manufacturing powerhouse. In addition, China is pursuing a goal of becoming a major hub for international bio-pharmaceutical product research, development and manufacturing. In realizing the first steps in this ambitious goal, China has, over the past decade, become a major destination for the global pharmaceutical industry to conduct R&D activities.[1]

The study, which entirely focuses on antibody-drug conjugates, considers key data such as (current) revenue, market size, expected growth, and price from all major biotechnology and pharmaceutical companies operating in China.


[*] 2017

Last Editorial Review: July 4, 2018

Featured Image: Life scientists Business.  Courtesy: © 2010 – 2018. © Fotolia. Used with permission.

Copyright © 2018 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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Andrew Huang: “ADC’s Are Among the most Powerful Options to Increase Drugability of a mAb”

With a population of 1.4 billion [*] and a rapidly expanding economy, China has become a manufacturing powerhouse. In addition, China is pursuing a goal of becoming a major hub for international bio-pharmaceutical product research, development and manufacturing. In realizing the first steps in this ambitious goal, China has, over the past decade, become a major destination for the global pharmaceutical industry to conduct R&D activities. This growth has drastically changed the pharmaceutical landscape, challenging Chinese companies in raising the quality of their products, while, at the same time, challenging them in expanding their development and manufacturing capacity to serve both global and national markets. [1]

Partly the results of China’s population growth and increasing domestic medical needs, the country has, according to a recent report published by UBM’s CPhI China, become the world’s biggest producer and exporter of active pharmaceutical ingredients or APIs.  Today, the country is responsible for nearly 40% of global API production. But the Chinese pharmaceutical market has still huge opportunities for growth. 

With government’s increasing investment in healthcare and R&D, China offers unique opportunities for innovative products and technologies, and collaboration between global and domestic pharmaceutical companies.

According to the China Food and Drug Administration (CFDA), the government’s significant investment in healthcare led to an increased – and more innovative – R&D pipeline and a growing importance of China as center of bio-pharmaceutical development and manufacturing.  The government’s investment has also cultivated companies with capabilities that are comparable – and competitive – with North American and European R&D, putting high-cost, global-centric R&D models at a real disadvantage.

Eliminating Concern
The growth of China’s bio-pharmaceutical industry is also the result of effectively securing Intellectual Property (IP) rights.  IP rights are among the most valuable resources for pharmaceutical and biotech companies, and their  protection often dictates the future success of the companies involved. While poor IP protection and enforcement have often been cited as limiting factors in the growth of pharmaceutical companies’ drive to carry out R&D in China, recently revised patent laws have increased overall global trust and are expected to effectively deter copycat drug makers.  And while, according to the US-China Business Council, some concern remains, China’s IP laws and regulations increasingly reflect international standards, allowing Chinese authorities to better protect and enforce IP rights.[2]

According to a study about the business of life sciences, pharmaceuticals and healthcare sector in China, published by Deloitte China Life Sciences and Health Care in Shanghai, the increased IP protection and enforcement has resulted in a growing number of global pharmaceutical companies being increasingly attracted to the idea of having a R&D center in China or, alternatively, partnering with Chinese partners.[3]

Furthermore, a general low cost base, a large pool of highly qualified research subjects, increasing scientific capabilities, the local industry’s knowledge, a general lack of regulatory and cultural impediments often found in other countries and insight into the country’s growing drug markets have made China an attractive country for R&D.

Ambitious Plans
In China, regulatory approval for pharmaceutical agents is based on clinical trials that have been carried out in the country. This requirement has also contributed to the global pharmaceutical industry’s interest in conducting clinical trials in China – and, as a result, work with a Chinese contract research organization (CRO) and contract (development) and manufacturing organizations (C(D)MO).

The regulatory environment has, no doubt, boosted China’s ambitions plans to be a primary market for CROs and CDMOs. Most of the top 20 multinational pharmaceutical companies have been expanding their footprint in China by setting up R&D facilities through various enterprise structures. Large companies including Bristol-Myers Squibb (BMS), Pfizer, Roche, GlaxoSmithKline (GSK), Johnson & Johnson and Novo Nordisk continue to develop partnerships with Chinese companies.

This approach mitigates traditional development risks but also leverageg local efficiencies, allowing companies to add operational value due to familiarity with the market and regulatory requirements, leading to shortened approval times and reduced development costs. In turn, Chinese CROs are recruiting expert Chinese nationals with research experienced nurtured at top Western pharmaceuticals companies to staff domestic CROs.

Moreover, global pharmaceutical companies are starting to conduct R&D activity specifically related to Asian markets. The specificity is linked to the environmental, cultural and genetic factors, liver disease, certain cancers, and some communicable diseases that are more common in Asian countries, such as China and Thailand than in other countries around the world.

Expanding facilities
Among the growing CRO/CDMOs in China is MabPlex International. Based in Yantai, a port city in Shandong province, China, and founded in 2013, the company specializes in the development and GMP manufacturing of recombinant proteins, antibody therapeutics and antibody-drug conjugates for its global customers. To accommodate growing demand, MabPlex, in October 2016,  broke ground on the expansion of its bio-manufacturing facilities.

The construction of company’s new 428,000 sq. ft. facility is expected to be completed by August of 2017, with utility and HVAC validation finished by December 2017.  The fill/finish facility will be completely validated by March of 2018.

Earlier this year we interviewed Andrew C. Huang, MabPlex’ Senior Vice President of R&D. Huang has developed a robust and proprietary technology platform for the manufacturing antibody-drug conjugates based on covalent thiol conjugation Technology. The resulting Hertuzumab Vedotin, the first ADC being developed in China, has entered Phase I and Phase II clinical trials.

Prior to joining MabPlex International, Huang served for more than 17 years as a biomedical researcher at the University of California, Los Angeles (UCLA), a public research university in the Westwood district of Los Angeles, engaging in molecular medicine, including brain aging, diabetes, stem cells and protein folding research. He has published near 100 research articles, journal reviews and book chapters. During our interview we asked him about his company, the role his company plays in global bio-pharmaceutical development and manufacturing, the current expansion, the potential for antibody-drug conjugates and the regulatory env

Question/Peter Hofland: What excites you the most about the potential of ADCs?

Answer/Andrew Huang: Antibody drug conjugates are one form of combinatorial therapy that uses tumor-targeting antibodies and high-potency chemical drugs. Most antibodies alone have limited efficacy against malignant cancers. The efficacy of an antibody often increases synergistically when conjugated to a high-potency chemical drug. In addition to the enhancement efficacy, the ADC platform can rescue some  cytotoxic drugs, which are too toxic or have poor bioavailability on their own.

PH: What are your company’s major accomplishments over the past 12 months?

AH: We have completed several ADC projects, including providing ADCs for phase II clinical trials and one successful IND with better than expected results.

PH: … and what are your expectations for the next 12 months?

AH: Our ADC projects from US-based clients gradually increased over the last 12 months. And we expect that this will continue in the foreseeable future. That’s why we are expanding our ADC manufacturing capacity to accommodate [the doubling of the number of ADC projects].

PH: As a CDMO, what are the top three things that sets your company’s next-generation ADC platform apart?

AH: I think that there are three things that set us apart. The first thing includes our cysteine conjugate platform and our product quality in terms of conjugation efficiency and fraction of DAR4. The second differentiator is our proprietary thiol covalent conjugation technology and finally, our faster speed and efficiency of completing client’s task as compared to (other) leaders in the field.

Pharma/Industry Questions
PH: MabPlex International is based in China. How big is the role of Chinese CDMOs in the world?

AH: The Chinese are gradually increasing their role as a worldwide CDMO family. However, right now, Chinese CDMO companies are limited in capacity because most Chinese companies focus mainly on Chinese business and they are not familiar with rules and business outside China. But that’s changing. Currently, more and more Chinese companies are starting (representative) offices in the United States and Europe to explore opportunities.

PH: How is the approach of Chinese companies different (or similar) to the approach of CDMOs in North America and Europe?

AH: Most CDMO companies in China are led by US/Europe “returnees” so most approaches are likely to be the same or (very) similar. The significant difference will be to fit Chinese “culture” and how to bridge the Eastern culture to Western one.

Regulatory landscape
PH: The unique properties of ADCs create technical challenges that require careful CMC considerations. Based on your experience in the development of ADCs what are some of the current regulatory challenges (with special focus on CMC)?

AH: A few years ago, during the Cambridge Healthtech Institute’s inaugural CMC Strategies for Antibody-Drug Conjugates meeting in Boston, Massachusetts, someone answered the same question by saying that antibody-drug conjugates are conceptually, very simple, but in practice, extremely complicated.  And I must agree with that. In it’s ‘simple’ complexity ADCs combine a monoclonal antibody, a chemical linker and a cytotoxic drug. Simply stated, as a result of the complex nature of an ADC, we need triple the amount of control and characterization to achieve the right formulation, stability and consistency for effective scale up and manufacturing if we want to meet the regulatory requirements.

And with the increased number of ADCs coming down the pipeline, it becomes imperative for pharmaceutical and biotechnology companies to consider the manufacturability of the ADCs. This means that they have to incorporate process design and CMC strategies early on in the development stage of an ADC.

Looking at our experience, some of the technical challenges require careful CMC considerations include homogeneous drug distribution, the highest possible fraction of DAR4 and the lowest possible fraction of DAR6 or higher with cysteine conjugation.

PH: Overall…What do you see is the biggest challenge in the development of ADCs?

AH: That’s the degree of homogeneous drug distribution.

But manufacturing ADCs not only involves technical challenges but also challenges in the areas of externalization of manufacturing, supply chain management and new technology considerations. That’s why regulators, looking at the highly toxic nature of ADC payloads, as well as the monoclonal antibody and linker chemistry thta make up an ADC, are concerned about the safety, potency and stability of the product and the workers involved in manufacturing it.

Regulatory implications
PH: How is the regulatory landscape in China different than the European of North American regulatory landscape?

AH: A few years ago, regulations in China for CDMOs were significantly different when compared to Western regulations. At that time the drug license and MFG (Drug Manufacturing) license had to be the same. This greatly limited Chinese CDMO development. However, after November 2015, China adopted a new policy for Marketing Authorization Holders (MAH). This new policy is similar to policies in the United States and Europe: the licenses for marketing authorization and manufacturing are separate.

PH: How has the creation of the China Food and Drug Administration (CFDA) and a restructuring of its regulatory system benefited Chinese CDMOs and in particular, your company?

AH: As mentioned, starting in November 2015, China enforced a new policy for Marketing Authorization Holders similar to policies in the United States and Europe. Prior to 2015, all bio-pharmaceutical companies were required by the China Food and Drug Administration (SFDA) to complete the biologic drug CMC and formulation-fill-finish by themselves. Only a chemical drug could be outsourced or contracted out to CRO/CDMOs. Now, biologics, like any chemical drugs, can be outsourced to CRO-CDMO, like MabPlex.  This includes  R&D and CMC, formulation, fill-finish and even IND submissions.

PH: One often heard concern from companies in North America and Europe is that despite vast improvements, concerns still persist about enforcement of intellectual property (IP) and patent laws in China. How does that impact CDMO business in China?

AH: These concerns have a deep impact on CDMO’s in China. We believe the only thing we can do is to continuously improve our IP enforcement, which is already at Western standards. In addition to our secure enforcement of IP protection, MabPlex has a morning meeting each day to emphasize to all our employees three things: IP, GMP and Safety!

PH: … and how does this, specifically, impact your business?

AH: Companies, especially North American and European companies, are still a little hesitant in dealing with new companies like us. However, we see more and more companies from the United States starting ADC business with us. We are confident that we will prove to our US and European colleagues that we are a trustful and reliable partner.

PH: Your company is experienced in ADC development and manufacturing. Are you planning to expand with additional development and manufacturing facilities in North America and Europe?

AH: We already established a branch (MabPlex Inc. USA) in USA last year. But our US branch will not include manufacturing.


[*] 2017

Last Editorial Review: May 24, 2017

Photo 1.0: Andrew C. Huang, MabPlex International’s Senior Vice President of R&D. Courtesy: © 2017 MabPlex  Featured Image: MabPlex headquarters, Yantai, Shandong, China. Courtesy: © 2017 MabPlex. Used with permission.

Copyright © 2017 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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LegoChem BioSciences and Fosun Pharma Sign License Agreement for Antibody-drug Conjugate Program

LegoChem Biosciences and Fosun Pharma have have signed a license and commercialization agreement for one of LegoChem’s Next Generation Antibody-Drug Conjugate (ADC) products and related technology for the Greater China market. Two companies also signed a Memorandum of Understanding (MoU) for three other ADC targets.

Antibody-Drug Conjugate are so-called next-generation anti-cancer drugs.  They have gained  wide attention in recent years.  The antibody-drug conjugation approach involves highly toxic molecules attached to highly specific – and precisely targeted – antibodies thereby increasing their tumor cell-killing capability. The  novel drugs are designed deliver the cell-killing agent directly to the tumor site.  While the cancer cell is killed, healthy cells can be spared from the devastating effects of the agent. Generally, an ADC binds to the tumor-associated target, is internalized and subsequently releases the potent drug inside the tumor cell.

Proprietary ADC technology
LegoChem’s technology represent proprietary ADC technologies include highly potent cell-killing drugs and sophisticated linker technologies. The agreement involves LegoChem’s first and most advanced internally developed antibody-drug conjugate with an undisclosed antibody targeting at multiple indications in cancer. Fosun Pharma will further develop this novel ADC in the Greater China region.

Further collaboration
Prior to the signing ceremony held at Fosun Pharma’s Shanghai facility, Yong-Zu Kim, MD, Chief Executive Officer of LegoChem, Yifang Wu, President of Fosun Pharma Development and Senior Vice President of Fosun Pharma Group, discussed further collaboration between two companies.

“After evaluating multiple ADC technologies being developed in United States, Europe and China, we believe that LegoChem is one of the leading second generation ADC technology hubs, and we are pleased to announce that our first collaboration is now in place between Fosun Pharma and LegoChem,” Wu said.

“As a second step, we signed a Memorandum of Understanding. This agreement will guide us  in creating additional projects involving antibody-drug conjugates using one of several antibodies being developed by Henlius, one of our subsidiaries.  We believe that the agreement with LegoChem works because their pipeline programs fit our strategy especially in terms of innovation our desire to move forward in entering a global market together,” Wu further noted.

“We are excited to initiate this opportunity which proves that LegoChem’s ADC technology is now globally recognized.  The agreement further allows us to broaden and accelerate other ongoing discussion with partners from the US, Europe, and Japan,” Yong-Zu Kim, CEO of LegoChem explained.  “We look forward to partnering with Fosun Pharma, China’s leading pharmaceutical company with global competence, and strongly believe that they will successfully develop the this and  additional antibody-drug conjugates.”

Under the agreement, Fosun Pharma will receive commercial rights in Greater China area including mainland China, Hong Kong, Macau, and Taiwan. LegoChem, in turn, will receive milestones and royalties from this agreement, and retains commercial rights outside of Greater China area.

Platform Technology
LegoChem’s antibody-drug conjugate technology is a next-generation platform technology that has successfully overcome weaknesses of the first-generation ADC technology, especially the stability in blood. This platform technology can be applied to a wide range of different antibody targets.


Last Editorial Review: August 18, 2015

Feature Image: Panoramic skyline at night, Shanghai, China, East Asia. Feature image Courtesy: © Mstyslav Chernov. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license. CC BY-SA 3.0

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