Gusen Pharma Accelerates Global Development of Anti-COVID Drug GS-00202, a 3CL Protease Inhibitor, with IND Filed and International Strategy Underway

In the third year of the COVID-19 pandemic, the dominant viral strain driving the global epidemic has evolved from Delta to Omicron, and further to the BA.4/BA.5 subvariants, which exhibit greater immune escape capabilities and a higher propensity for reinfection, with transmissibility increasing several-fold. As of July 30, 2022, the cumulative number of confirmed COVID-19 cases worldwide had exceeded 575 million.

Currently, the mainstream global antiviral drugs for COVID-19 treatment are primarily categorized into two classes: small-molecule drugs and neutralizing antibodies. As neutralizing antibody therapies have shown diminishing efficacy against SARS-CoV-2 variants and are receiving declining attention, greater hope is being placed on the continuous iteration of small-molecule anti-COVID-19 drugs to realize the vision of managing COVID-19 as a common influenza-like illness.

Since 2020, Anovent has actively strategized and developed innovative anti-COVID-19 drugs in response to the outbreak of the novel coronavirus pneumonia. Among these, GS-00202 targets the SARS-CoV-2 3CL protease (3CL^pro) as the target, an IND application has already been submitted, and it is about to enter the clinical stage.

3CL^proIt is an enzyme essential for coronavirus replication, primarily acting during the initial replication stage after the virus enters host cells, and inhibits 3CL^proProtease activity effectively blocks viral replication at its source.

Secondly, 3CL^proThe cleavage site is “highly conserved” within the genus Coronavirus, making naturally occurring mutations that are not drug-induced unlikely; in other words, this protease is similar across different coronaviruses. Therefore, the same 3CL protease inhibitor is generally applicable to various strains of SARS-CoV-2, demonstrating broad-spectrum activity.

Meanwhile, due to 3CL^proNo human homologs have been reported, 3CL^proThe inhibitor is theoretically expected to exhibit weaker inhibitory effects on human proteases, thereby reducing the risk of adverse effects and enhancing safety.

3CL^proWith its high efficacy against SARS-CoV-2 and optimal selectivity, this inhibitor has emerged as the most promising target for novel small-molecule drugs among numerous anti-COVID-19 drug targets. Pfizer’s Nirmatrelvir (Paxlovid), the first marketed drug targeting this mechanism, remains the most successful COVID-19 therapeutic to date, achieving sales of $8.1 billion in the second quarter of 2022.

As early as 2021, Anovent screened multiple potential targets and compounds, ultimately selecting 3CL^protarget, and after the design, synthesis, and screening of new compounds, the anti-COVID-19 candidate drug GS-00202 was developed.

GS-00202 is a deuterated derivative of nirmatrelvir that achieves improved pharmacokinetic properties while maintaining comparable efficacy.

Pharmacodynamic studies have shown that, against the Omicron variant, the in vitro (cellular) antiviral activity EC of GS-00202₅₀of 0.11 μM, with in vivo pharmacodynamics and survival rates in mice comparable to those of Nirmatrelvir. Pharmacokinetic studies showed that, compared with Nirmatrelvir, GS-00202 exhibited systemic exposure (AUC_0-∞) increased to 2-fold; after a single intragastric administration in dogs, the systemic exposure (AUC_0-∞) increased to 1.4-fold. The tissue distribution of the two compounds was largely similar, and their metabolic pathways, metabolites, and excretion profiles were basically comparable. Toxicology studies in rat and dog models showed no significant toxic responses after single and repeated administrations at high, medium, and low doses, nor any evidence of genotoxicity or reproductive toxicity. Comprehensive non-clinical studies demonstrated that GS-00202 and Nirmatrelvir are equivalent in efficacy and safety, but GS-00202 exhibits superior pharmacokinetic properties.

Based on the completion of comprehensive pharmaceutical and non-clinical studies (pharmacology and toxicology), the company submitted its Investigational New Drug (IND) application on a rolling basis through the fast-track channel for anti-COVID-19 drugs. IND filings in global markets, including Europe, the United States, and with the World Health Organization (WHO), are also being accelerated. It is expected that within 2022, the company will advance and complete Phase I clinical trials, leveraging the advantages of deuterated drug development—such as lower risk, faster progress, higher certainty, and greater success rates—to directly proceed to international multi-center Phase II-III clinical trials.

Pharmaceutical development of GS-00202 has also achieved multiple breakthroughs. The innovative deuterium-substituted synthesis process for the active pharmaceutical ingredient (API) fully realizes advantages such as high deuterium enrichment, stable and controllable manufacturing processes, and reasonable cost. Scaled-up production (50 kg/batch) was achieved in the second half of 2022. Meanwhile, the scaled-up manufacturing process for the drug product is highly efficient and stable, with controllable quality, fully meeting the requirements for non-clinical studies, clinical trials, and commercialization.

The company is actively expanding into international markets and has established strategic partnerships with CDMO companies for active pharmaceutical ingredients (APIs) and finished dosage forms that comply with the cGMP production quality systems of Europe and the United States, thereby supporting the industrialization and global commercialization of GS-00202.

Anovent places paramount importance on the intellectual property protection and strategic portfolio of GS-00202, holding full independent intellectual property rights.

In terms of core patents, targeting the novel molecular structure of GS-00202, the Company filed an invention patent for the compound titled “Novel Deuterated Cyano Compounds, Preparation Methods Thereof, Compositions and Applications Thereof” (CN20211123470**) in October 2021. Subsequently, it completed the filing of a crystal form patent titled “Crystal Form I of Deuterated Nirmatrelvir and Preparation Method Thereof” (CN20221026574**). Meanwhile, the Company has also filed patents covering synthesis processes, formulations, and uses to establish comprehensive patent protection, including the synthesis process patent titled “Preparation Method of a Deuterated Pharmaceutical Intermediate” (CN20221005740**), the formulation patent titled “A Pharmaceutical Composition and Its Antiviral Use” (CN20221005908**), and the use patent titled “A Pharmaceutical Composition with Synergistic Enhancement and Its Antiviral Use” (CN20221013442**).

The highly contagious Omicron variants BA.4/BA.5 are spreading globally, and SARS-CoV-2 may coexist with humans for the long term, creating a substantial clinical demand for novel, highly effective anti-COVID-19 therapeutics.

GS-00202 at 3CL^proIn terms of inhibitor drug development progress, it is in the first tier. GS-00202 will undergo head-to-head and double-blind Phase III clinical trials, becoming a 3CL inhibitor with efficacy and safety comparable to Pfizer's Nirmatrelvir.^proNovel inhibitor drugs to avoid the genetic and reproductive toxicities associated with other COVID-19 medications.

Anovent is a biopharmaceutical innovation company focused on the research, development, and commercialization of drugs for respiratory diseases.

Since its establishment in 2017, Anovent has rapidly emerged as a leader within just over five years, leveraging its advanced formulation, drug delivery technologies, and soft mist inhaler platform. It is the only company in China to have been awarded the National “Major Special Project” for New Drugs under the 13th Five-Year Plan for inhalable soft mist formulations, securing its position among the top-tier enterprises in China’s inhalation therapy sector.

Anovent has established its drug delivery platform based on high-end inhalation formulations—specifically, soft mist inhalers. The company has developed a robust pipeline of blockbuster first-to-file generics and innovative drugs for the treatment of traditional respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. It has successfully submitted marketing authorization applications in the European Union for two first-to-file generic soft mist inhalers, as well as Investigational New Drug (IND) applications in China for two innovative soft mist inhaler products. Additionally, the U.S. FDA marketing application for its first-to-file generic product is currently under review.

In response to the highly transmissible and pathogenic nature of the Omicron variant, Anovent is accelerating the development of its GS-00202 inhalation spray by leveraging its advanced inhaled aerosol delivery platform for respiratory diseases. This initiative aims to meet the substantial clinical need to block or reduce viral transmission, holding significant strategic importance in the fight against the pandemic.