Huaxian Pharma: Expanding from Small Molecules to Oligonucleotides – Building an Integrated CRDMO Platform

Over the past decade, China’s biopharmaceutical industry has undergone a transformation from generic drugs and traditional Chinese medicine (TCM) preparations to innovative drugs. Emerging pharmaceutical companies have flourished, while established firms have upgraded their strategic layouts, with the entire sector actively embracing the new vitality brought by innovation.

Beneath the Vitality Lie Greater Challenges. Both emerging and established pharmaceutical companies face similar issues, including limited R&D teams, incomplete organizational structures, and weak process expertise. Meanwhile, constrained R&D budgets remain a critical consideration for these enterprises. What they need are CXO partners that combine strong technical capabilities with flexible cost solutions.

As a CRDMO enterprise, HwaGen Pharmaceutical is committed to providing customers with solutions that balance cost, innovation, and speed, offering one-stop services spanning R&D, manufacturing, and regulatory filings from preclinical studies through to commercialization. HwaGen Pharmaceutical focuses on the development of high-difficulty, specialized active pharmaceutical ingredients (APIs) and intermediates in the fields of anti-tumor, antiviral, and anti-respiratory disease therapies, having served over 200 global innovative drug clients to date.

In 2023, HwaGen Pharmaceutical embarked on a new journey by establishing capabilities in the research, development, and manufacturing of small nucleic acid drugs, while also expanding its presence from South China to East China, a hub for innovative pharmaceutical companies.

Dr. Ye Weiping, Founder of HwaGen Pharmaceutical

Ye Weiping, founder of HwaGen Pharmaceutical, holds a Bachelor of Science in Chemistry and a minor in Economics from the China Center for Economic Research at Peking University, as well as a Ph.D. in Chemistry from the National University of Singapore. He is a Professor-level Senior Engineer. He has been honored with titles such as Expert of the National Major Talent Program and Recipient of the State Council’s Special Allowance.

During his tenure as Chief Chemist at GlaxoSmithKline, Ye Weiping oversaw process development for two global innovative drugs and led green innovation initiatives for eight original patented drugs. He received the “Outstanding Contribution Award” three times, accumulating extensive experience in the process development of innovative pharmaceuticals. After leaving GlaxoSmithKline, Ye joined Pfizer, where he became the youngest Asia-Pacific Manager in its Global Outsourced Supply Department. Within six months, he secured a new supplier for azithromycin and launched regulatory registration projects in over 180 countries worldwide.

In 2011, Ye Weiping, who was in Singapore, observed that China’s pharmaceutical innovation industry was poised for takeoff, boasting abundant talent reserves and vast potential. On the other hand, through years of experimental work, Ye Weiping recognized thatCompared with traditional synthetic technologies, biocatalysis and organocatalysis offer advantages such as high selectivity, high efficiency, low pollution, and low cost, making them green manufacturing processes that pharmaceutical companies worldwide are actively adopting.However, at that time, the domestic technological foundation was still very weak.

That year, Ye Weiping resolutely returned to China and founded Raffles Pharmaceuticals. Leveraging several patented technological inventions, Raffles integrated asymmetric synthesis technology, continuous-flow microchannel reaction technology, and enzymatic catalysis technology to establish an innovative process platform characterized by low cost, safety, high efficiency, and environmental sustainability.

In December 2015, HwaGen Pharmaceutical was established.

“If we compare R, D, and M to three stages, HwaGen Pharmaceutical likely started with D (Development), providing services such as laboratory process development and regulatory filing research for clients, then progressed to M (Manufacture) for GMP-scale production, and finally advanced into the R (Research) stage of drug discovery,” introduced Ye Weiping.

GMP Factory in Dayawan, Huizhou, Guangdong

With the commissioning of its green chemistry GMP R&D and production base, built with an investment of 400 million yuan, HwaGen Pharmaceutical has established end-to-end capabilities for small-molecule drugs from Development (“D”) to Manufacturing (“M”). Located in Daya Bay, Huizhou, this GMP-compliant facility covers an area of 28,000 square meters.², with seven API production lines and a total reactor volume of 200,000 liters, capable of meeting hundred-ton-scale production demands. It has successfully passed the GMP audit conducted by the EU Qualified Person (QP) and can support dual regulatory submissions in China and the United States.

In 2021, the CRO R&D headquarters located in Pingshan, Shenzhen, commenced operations, covering an area of 6,500 m².². Coupled with the launch of the drug discovery and evaluation service platform in Nanshan, Shenzhen,HwaGen Pharmaceutical has established a one-stop custom R&D and manufacturing capability spanning from preclinical stages to commercial production, upgrading its business model to “CRDMO.”Since then, ShenZhen HwaGen Pharmaceutical Co., Ltd. has been able to not only provide customers with custom R&D and manufacturing of APIs, but also offer services such as new molecule synthesis, screening, and evaluation.

Furthermore, HwaGen Pharmaceutical is actively positioning itself at the forefront of innovative drug development, offering services such as novel molecular building blocks, XDC payloads, DMPK studies, pharmacological and efficacy evaluations, early toxicology assessments, and bioanalysis.

Shenzhen Pingshan R&D Center

“Each project presents its own unique challenges; HwaGen must possess robust technical capabilities and a diverse portfolio of platforms to address a broad spectrum of customer needs,” said Ye Weiping. Following this path, ShenZhen HwaGen Pharmaceutical Co., Ltd. has been continuously building and refining its technological platforms.

Leveraging its profound understanding of process scale-up and Chemistry, Manufacturing, and Controls (CMC), HwaGen Pharmaceutical has established a comprehensive platform for route selection, process design, and R&D management, covering the entire lifecycle of small-molecule drug development. By integrating the full spectrum from preclinical stages to commercialization, the CMC technology platform achieves greater consistency. Furthermore, adopting an end-to-beginning process design philosophy helps reduce costs for clinical supply and commercial production, while aligning with Quality by Design (QbD) principles for active pharmaceutical ingredients (APIs) to ensure seamless subsequent CMC development.

HwaGen Pharmaceutical’s adoption of metal-organic catalysis, small organic molecule catalysis, and enzymatic biocatalysis technologies significantly reduces the generation of waste water, waste gas, and solid waste, delivering substantial environmental benefits. In line with practical business needs, the HwaGen team leverages three asymmetric catalysis pathways to help select the most suitable chiral catalysts, chiral starting materials, and chiral auxiliaries for industrial-scale production, thereby effectively lowering production costs and enhancing reaction efficiency.

This platform offers three technical pathways for continuous flow channel processes, designed to handle specialized operations such as nitration and hydrogenation, as well as high-risk, rapid reactions sensitive to mass and heat transfer. It addresses safety and environmental concerns during industrial scale-up. For early-stage projects, it enables safe and rapid scaling; for commercial projects, it strives to enhance safety and environmental compliance while reducing costs.

The HwaGen team proposes the strategy of “digital empowerment, automation-driven efficiency, and intelligent innovation,” leveraging high-quality business data for machine learning training to build an intelligent management platform featuring data analytics, process parameter recommendations, high-throughput synthesis, and automated experimentation. Meanwhile, by optimizing semi-automated parallel processes with AI assistance, the team has significantly improved the efficiency of synthetic route design within molecular development.

In March this year, HwaGen Pharmaceutical signed a project cooperation agreement with Baidu Intelligent Cloud. Leveraging its “Cloud-AI Integration” architecture, Baidu Intelligent Cloud will provide HwaGen Pharmaceutical with services including digital infrastructure development and support for intelligent model development.

With breakthroughs in chemical modification technologies and delivery vectors, the safety and efficacy concerns of small nucleic acid drugs have been fully addressed. Since 2018, small nucleic acid drugs have entered their third period of robust growth.

Leveraging its years of deep expertise in platform-based synthetic R&D and its GMP-compliant manufacturing capacity for chemical active pharmaceutical ingredients (APIs), HwaGen Pharmaceutical has expanded its business scope from small molecules to small nucleic acids."Strong synergies and ample production capacity create substantial growth opportunities for the oligonucleotide business."

HwaGen Pharmaceutical’s team initially focused on a critical challenge in oligonucleotide therapeutics—delivery.How Exogenous Oligonucleotides Evade Immune Defenses, Renal Filtration, and Degradative Enzymes to Enter Cells and Exert Their Effects: The Need for a Protective and Precisely Targeted Delivery Vector

Currently, the HwaGen Pharmaceutical team has established a strategic presence in lipid nanoparticles (LNPs), the most prominent delivery vector at present. By integrating process development with AI-assisted algorithms, we have achieved rapid design and synthesis of lipid molecules. Leveraging high-efficiency purification equipment, comprehensive characterization and testing capabilities, and an inventory of over 200 intermediate fragments with varying carbon chain lengths, HwaGen Pharmaceutical offers customized lipid molecule synthesis services, supporting production scales from milligrams to kilograms.

Meanwhile, the team at ShenZhen HwaGen Pharmaceutical Co., Ltd. has also developed GalNAc conjugates with high hepatic selectivity. These GalNAc conjugates avoid the immunogenicity associated with lipid molecules and enable direct and precise targeted delivery through efficient liver-specific uptake. In terms of upstream raw materials, HwaGen also provides customization, process development, and optimization for phosphoramidite monomers and active pharmaceutical ingredients (APIs).

Furthermore, leveraging its accumulated expertise in high-throughput synthesis screening, purification and characterization, and solid-phase synthesis, the oligonucleotide therapeutics business unit has established end-to-end capabilities ranging from custom synthesis, purification, and ultrafiltration to CMC regulatory filing services. The unit has now initiated preparations for commercial GMP manufacturing of oligonucleotide drugs.

In February this year, HwaGen Pharmaceutical’s R&D center in Xiangcheng, Suzhou, officially commenced operations. “Establishing an R&D platform in East China allows us to better align with customer needs and provide more responsive services,” said Ye Weiping. “From a talent perspective, locating in East China has also enabled HwaGen to attract more high-quality professionals.”

In an area of 5,000 m²²At its Xiangcheng R&D Center, HwaGen Pharmaceutical will establish a large-scale R&D team of over 200 members, with more than 30% holding master’s or doctoral degrees, making it the most comprehensive R&D unit within its multi-center layout strategy.

Suzhou Xiangcheng R&D Center

Leveraging its large-scale infrastructure and diverse talent pool, the Suzhou Xiangcheng R&D Center offers a wide range of research and development services, including CRDMO services for small-molecule drugs and oligonucleotide therapeutics, as well as compound purification, impurity isolation, and spectroscopic analysis.

Just as innovation-driven transformation brings both vitality and challenges, the CXO industry has also reached a critical juncture of de-bubbling and restructuring.

Before the headwinds arrived, HwaGen Pharmaceutical had already established a business operations center in Zhangjiang, Shanghai, and a U.S. commercial subsidiary, proactively expanding its business coverage and extending its service chain. Ye Weiping introduced, “WhenAs headwinds truly set in, we proactively adjusted our business priorities by allocating resources to the European market, which offered greater opportunities. We also conducted proactive project evaluation and screening. This approach helped maintain steady growth in our performance.”

In Ye Weiping’s view, de-bubbling represents a cyclical screening process within the industry. A return to rationality and the search for underlying patterns essentially reflect the industry’s progression toward healthier development. “Refined management, cost control, risk mitigation, and efficiency enhancement are all measures that we CXO enterprises are adopting to adapt to changes and seek new opportunities.”

Stepping out of the comfort zone of small-molecule drugs and making a bold entry into the oligonucleotide therapeutics arena, while pioneering AI-driven drug discovery and engaging closely with biotech firms, HwaGen Pharmaceutical has consistently advanced on its path to seek new opportunities and seize emerging prospects.