Xina Pharma Advances Innovative Systemic Inhaled Antiemetic into IND Stage with Orphan Drug Designation from FDA

With the rise of innovation awareness in China’s pharmaceutical industry, many companies choose to develop entirely new drugs by starting with the discovery of novel structures and targets. However, the high rewards of innovative drugs are counterbalanced by significant risks, such as the “80/20 rule” and the “double ten” cost structure (ten years and $1 billion), which is why many small biotech startups fail to survive until the end.

For small pharmaceutical startups, innovative formulations represent a favorable entry point. Reformulated products can deliver tangible clinical benefits while enjoying patent protection with a term of 20 years. Furthermore, during the regulatory approval process, reformulated products do not require duplication of studies already conducted for the original innovator drug; only supplementary studies addressing the specific modifications are needed, which can significantly shorten the approval timeline.

Therefore, reformulated drug products represent a sound choice, both in terms of the clinical benefits they offer to patients and the control that startups can exert over their investments in capital, time, and risk.

However, reformulated products also face their own pain points, namely, competing with the originator drugs in the market. While reformulated products offer superior efficacy compared to originator drugs, their pricing space is also influenced by the originator drugs. Therefore, reformulated products must not only match the efficacy of originator drugs but also strictly control costs and development time.

Let's take a look.Zhejiang Xina Pharmaceutical Co., Ltd. (hereinafter referred to as "Xina Pharmaceutical")How Can a Startup Break Through? Building an Innovative Platform Technology for Systemic Inhalation Formulations and the Methods and Theories Worth Learning for Pharmaceutical Startups.

Xina Pharmaceuticals was established in 2019 and co-founded by Dr. Lu Biao and Dr. Li Xiaodong. The company independently owns a mature technological platform for innovative systemic inhalation formulations, providing more convenient and effective inhalation drug delivery solutions for the comprehensive optimization of original drugs.

When askedDr. Li Xiaodong, Chairman and Chief Executive Officer of Xina PharmaceuticalsWhen asked why he chose to delve deeply into the industry rather than continue with scientific research, he said, “This is related to my past experiences and a shift in mindset. After completing my Ph.D. at the University of Rochester, I joined the National Institutes of Health (NIH) in the United States to continue my postdoctoral work. At that time, I was indeed fully committed to pursuing a career in scientific research, but I observed a phenomenon in the field of healthcare.”

“Most countries around the world invest heavily in basic scientific research to enable more scientists to invent and discover cutting-edge technologies. Meanwhile, there is also substantial demand from both patients and healthcare providers in the pharmaceutical sector.”Among these, many unresolved medical pain points are not due to the inaccessibility of cutting-edge technologies, but rather the lack of a critical link in successfully translating advanced scientific research achievements into commercial products."This intermediate stage of industrialization not only accelerates the translation of scientific research outcomes but also creates a substantial number of job opportunities. After recognizing this, I left the research institution to join the industry, and it has been 15 years since then."

In 2008, Dr. Li Xiaodong joined HANA and met Dr. Lu Biao.

Dr. Lu Biao earned his Ph.D. in Biostatistics from the University of California, Berkeley (UC Berkeley). Biostatistics plays a critical role in the design and implementation of clinical trials, data collection, data analysis, and subsequent regulatory submissions and approvals. The primary challenge in clinical trials is the limited sample size available prior to drug approval; therefore, statistical analyses are required to demonstrate efficacy and other relevant parameters.

Dr. Lu Biao entered the industry from this perspective and has since accumulated over 25 years of experience in the research and development, clinical trials, and management of anticancer and inhaled drugs.He has overseen the approval of multiple drug candidates and has previously held executive positions at several Fortune 500 companies (Gilead, Abbott, Allergan) as well as successful startups (MAP, NeurogesX, HANA, etc.).

After knowing each other for 13 years, Dr. Lu Biao and Dr. Li Xiaodong have progressed from working together to co-founding a startup. When asked why they chose innovative inhaled antiemetics as their entry point for entrepreneurship, Dr. Li Xiaodong stated, “Systemic inhaled formulations address unmet medical needs with a substantial potential market. Moreover, developing reformulated products entails lower difficulty and risk compared to the development of entirely new drugs.”

Dr. Li Xiaodong continued, “Developing inhaled antiemetics is highly challenging; otherwise, other companies or institutions would have already secured the relevant patents. What Xina Pharmaceuticals needs to do is rise to the challenge and overcome the hurdles associated with innovating dosage forms, while ensuring clinical advantages.”

Including Dr. Lu Biao and Dr. Li Xiaodong, Xina Pharma’s core team has an average of over 20 years of experience in drug R&D. Its expert advisory team covers the entire pharmaceutical development lifecycle, including research and development, formulation, production quality control, toxicology testing, clinical trials, data analysis, and regulatory submission and approval.

Under the leadership of its core team, Sina Pharma is dedicated to building an innovative technology platform for systemic inhaled formulations.

When it comes to inhaled formulations, their delivery target has been the lungs for many years, and currently more than 90% of inhaled formulations are used to treat pulmonary diseases such as asthma and chronic obstructive pulmonary disease (COPD). By designing drugs that rapidly enter the bloodstream through the alveoli while minimizing their residual presence in the lungs, systemic inhaled medications can be developed.

Furthermore, Xina Pharmaceuticals has identified an opportunity: if its systemic inhalation formulation technology platform can be leveraged to develop a series of products, it holds the promise of becoming a comprehensive alternative to intravenous injection in non-hospital settings in the future.This vision is not merely a baseless aspiration for the future; based on the current results of animal pharmacokinetic studies conducted by Xina Pharmaceuticals:

Xinna Pharma’s systemic inhaled antiemetic formulation achieves a time to peak plasma concentration (Tmax) of less than 5 minutes, which is significantly shorter than that of oral administration (approximately 100 minutes). Its pharmacokinetic linearity is similar to intravenous injection, and the area under the curve (AUC) is comparable to that of intravenous administration. This indicates that nearly all of the active ingredient enters the bloodstream, with bioequivalence exceeding 95%. These findings demonstrate that the product can rapidly enter the circulation via the alveoli, achieving highly efficient delivery and systemic therapeutic effects with negligible pulmonary residual drug.

Overall, systemic inhaled antiemetic agents offer rapid onset, high administration efficiency, and enhanced safety, making them more suitable than existing routes of administration for the emergency treatment of nausea and vomiting in outpatients.

"In theory, reformulated products are less challenging to develop than originator drugs and offer more convenient and broader application scenarios. Does this mean there are no industry barriers? Dr. Li Xiaodong explained, 'In theory, systemic inhalation formulation platforms have strong technical transferability and a wide range of applications.'"However, "strong transferability" is predicated on the principle that "it is easy for those who know how."Inhaled drug administration is categorized into three types: nebulization, pressurized metered-dose inhalers (pMDIs), and dry powder inhalers (DPIs). Among these, dry powder inhalers are most suitable for establishing a systemic inhaled drug delivery technology platform.

"The development challenges of dry powder inhalers lie in the fact that when any substance reaches the micron level, surface electrostatic imbalance occurs due to van der Waals forces, causing these fine particles to adhere tightly together. The limited airflow, lung capacity, and negative pressure generated by humans during administration are insufficient to counteract electrostatic and van der Waals forces, preventing deagglomeration of the fine particles. This results in a larger aerodynamic particle size for the inhalation formulation, making it unable to penetrate deeply into the lungs and potentially remaining only in the oral cavity."

“The ease with which micronized particles can be deagglomerated is a key issue that pharmaceutical formulation science must address. This involves the synergistic interplay of multiple factors, including the micronization method, the addition of excipients post-micronization, and the particle size distribution of the excipients. Indeed, there are significant challenges in this area.”

Leveraging its innovative systemic inhalation formulation technology platform, Xina Pharma has currently developed a pipeline of more than ten projects. Its product portfolio includes oral inhaled formulations of ondansetron, granisetron, and palonosetron; an oral inhaled therapy for chronic obstructive pulmonary disease (COPD); an oral inhaled treatment for migraine; and novel targeted anticancer agents.

The successful development of the core project, ondansetron oral inhalation powder, marks Xina Pharma as the only company in the world to have successfully developed a dry powder inhaler for antiemetic therapy.

Currently, the flagship product, ondansetron dry powder inhaler, has been granted relevant U.S. patents, completed the U.S. FDA Pre-IND meeting, and received orphan drug designation from the FDA. The GMP production and quality control data for the ondansetron oral inhaler are excellent, no toxic side effects were observed in GLP animal toxicology studies, and the IND application is currently underway.

Ondansetron sees 18 million annual prescriptions and over $1 billion in annual sales in the United States. In the Chinese market, the compound annual growth rate (CAGR) of setron-class drugs has remained above 4% in recent years. According to data from Menet, the sales of antiemetics at public hospitals in key provinces and cities across China reached RMB 2.389 billion in 2018, a year-on-year increase of 1.61%, while the overall domestic market has surpassed RMB 8 billion.

Moreover, the 505(b)(2) approval pathway is expedited,It is expected that the Phase I clinical trial of ondansetron oral inhalation will be completed in the first half of next year, and the Phase III clinical trial can begin in the second half of next year. By 2024, ondansetron oral inhalation is expected to enter the commercial stage, generating tens of millions in sales revenue for Xina Pharmaceuticals.

In terms of funding, Sina Pharma secured RMB 20 million in Series A financing shortly after its establishment, with investors including Huafang Capital and Fupu Investment. As the project advances, Sina Pharma is currently undertaking a new round of financing to accelerate progress. In terms of collaborations, Sina Pharma has partnered with leading industry players such as Lonza and Catalent.

Looking to the future, Dr. Li Xiaodong stated, “Currently, Xina Pharma’s production is primarily carried out through collaborations with large international enterprises. After obtaining regulatory approvals and achieving profitability, we will establish our own manufacturing facilities in China. This approach will not only facilitate the repatriation of technology but also reduce production costs. Furthermore, once our proprietary facility is established, it will serve not only as a production site but also as an R&D center, and even potentially as a teaching base through collaborations with universities, thereby integrating industry, academia, and research.”

“In my view, pharmaceutical companies are not merely entities driven by survival and profit; they also bear the responsibility of giving back to society and improving the quality of life for patients. Looking ahead, we look forward to collaborating with the government and more like-minded partners to leverage Xina Pharmaceuticals’ innovative platform for systemic inhaled formulations, thereby developing more products that deliver social value.”