Dr. Zhao Xiaobin of Haichang Biopharma: Overcoming Nucleic Acid Drug Delivery Challenges and Accelerating Commercialization

Recently, "going global" has become a highly discussed topic in the biopharmaceuticals industry. This trend is not only about BD collaborations between Biotech firms and multinational corporations (MNCs), but also involves how Chinese Biotechs can navigate approvals from overseas regulatory bodies such as the FDA and EMA to truly bring their products onto the international stage, benefiting a broader patient population.

At the International Innovative Drug Regulatory Forum of the 8th China Pharmaceutical Innovation and Investment Conference,Haichang Biotech Founder and President Dr. Xiaobin Zhao Delivered a Speech on "Based on QTsome^TMTheme Speech on "The Development and Clinical Translation of Nucleic Acid Drugs"He discussed the experience of utilizing regulatory knowledge and technological innovation to bring new drugs to international markets by sharing the case of Haichang Biotech advancing its products into international clinical trials.

Haichang Biotech, established in 2013 and headquartered in Hangzhou Medicine Port, is a national high-tech enterprise with independent innovation capabilities and global intellectual property rights, focusing on the development of innovative biopharmaceutical technologies. The company centers on the development and industrialization of drug delivery systems, specializing in the development of nucleic acid innovative drugs and high-end complex injectables. Haichang Biotech is low-key and pragmatic, steadily advancing its product pipeline, having already pushed multiple drugs into clinical trials, with commercial projects imminent.

The following are the key points of Dr. Zhao Xiaobin's speech:

QTsome™ is a quadrivalent-trivalent lipid nanoparticle gene delivery platform independently developed by Haichang Biotech. With this platform, Haichang Biotech is making advancements in the fields of nucleic acid innovative drugs and high-end complex injectables, covering multiple areas such as infectious disease prevention, tumor immunotherapy, anti-tumor treatments, and pain management.

Using QTsome™, Haichang Biotech is committed to addressing three pressing issues within the industry:

The first is how to achieve good tissue distribution during the drug delivery process.For example, when developing vaccines, it is necessary to distribute the drug into muscle tissue rather than internal organs such as the liver or spleen; if it is a tumor drug, it needs to be delivered to specific tumor tissues.

Secondly, there is the issue of intracellular drug delivery,It is not only about delivering drugs to specific tissues and cells, but also achieving the delivery and release of specific intracellular components.

The third is the issue of delivery carrier stability.Many delivery technologies, including lipid nanoparticles (LNPs), are thermodynamically unstable. Therefore, it is necessary to maintain the stability of the delivery carrier through formulation or optimized processes.

Compared with traditional lipid nanoparticle delivery technology, QTsome™ uses two unique cationic lipids that can ionize under specific conditions. Leveraging their high sensitivity to environmental pH, QTsome™ optimizes drug tissue distribution and administration while significantly improving stability. Additionally, QTsome™ exhibits high biosafety and low toxicity.

Based on the QTsome™ platform, Haichang Biotech has initially focused its nucleic acid drug research and development on primary liver cancer. Primary liver cancer is the fourth leading cause of cancer-related deaths globally and currently lacks effective treatment options. Traditional therapeutic drugs include Sorafenib and PD-1, but they struggle to meet the treatment needs of patients with drug resistance. Notably, Asia and Africa are high-incidence areas for liver cancer, with 72% of affected populations residing in these two regions. In light of the scarcity of medical resources, Haichang Biotech aims to address unmet clinical needs that cannot be resolved by traditional small-molecule drugs or antibody drugs like PD-1 through targeted delivery technology.

Haichang Biotech's HC0301 is an antisense nucleic acid drug targeting AKT-1, focusing on primary liver cancer.

PI3K/AKT is a conventional signaling pathway that rapidly activates corresponding downstream targets through PI3K phosphorylation. Currently, there are already drugs targeting the upstream and downstream of this pathway, but AKT has not yet been successfully targeted. Many companies are actively seeking molecules with targeting properties from the perspective of small-molecule drugs, mostly based on the combination of tyrosine mutation site screening and the characteristics of the mutation sites to develop small-molecule compounds.

Haichang Biotech has found another way to develop the new drug HC0301 targeting AKT-1. In QTsome^TMWith the support of nucleic acid delivery technology, the key issues of low intracellular uptake efficiency and insufficient targeting of nucleic acids have been addressed. Meanwhile, HC0301 has been ensured to possess highly selective specificity and low likelihood of drug resistance, which will well meet the needs for liver cancer treatment.

Currently,HC0301's Phase I clinical trial in the United States is nearing completion and has demonstrated very good safety and efficacy. Phase II clinical trials are expected to be conducted in Hong Kong and the United States next year, with exploration of other solid tumor indications.In addition, HC0301 has recently successfully obtained FDA Orphan Drug Designation.

Now, HC0301 has been well validated in clinical practice, and Haichang Biotech has begun preparations for subsequent industrial production and entry into Phase II and Phase III clinical trials.

In fact, the industrial chain of nucleic acid drugs itself is not sound. In this track, there are significant challenges in the supply of clinical samples and GMP compliance. With the rapid development of the biopharmaceutical industry over the past three years, especially as nucleic acid drugs have shown greater therapeutic potential, nucleic acid drug companies have gradually increased their options in terms of CDMOs (Contract Development and Manufacturing Organizations) and CMOs (Contract Manufacturing Organizations).

In order to ensure the smooth industrialization of the drug, Haichang Biotech has established a continuous production process team in Hangzhou to meet the needs of product commercialization and clinical trials.This team has accumulated rich experience in projects such as nucleotide drugs and liposomes, while also involving aspects like patent protection and technical secret protection.In addition, Haichang Biotech has established a production base with eight GMP workshops spanning over 60,000 square meters, preparing in advance for the commercial production of the company's products.

On the production side, Haichang Biotech advances the research and development as well as the production of its products according to international standards. Based on high-standard preliminary drug design, safety verification, and the cultivation of professional team members, the company aims to achieve global promotion of its products through an integrated production base.