The Pharmaceutical Industry at a Glance Survey on New Drug Discovery Companies (Originators) from the Perspective of Drug Development Pipeline by Drug Discovery Modality

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Hideyuki Kagii, Senior Researcher, Pharmaceutical Industry Policy Institute

1 Introduction

In recent years, drugs utilizing new drug discovery modalities, such as nucleic acid drugs, gene therapy, and gene-cell therapy, have emerged and are having a significant impact on the treatment of cancer and genetic diseases that have been difficult to treat in the past.

The practical application of these new modalities is closely related to the advancement of science and technology, and it is difficult for pharmaceutical companies to invest in highly uncertain technologies, so academia and start-up companies play an important role in their creation.

In addition to small molecule and antibody drugs, which are the mainstream in the current pharmaceutical market, this survey focuses on nucleic acid drugs, gene therapy, gene cell therapy, and cell therapy as relatively new modalities that have been put to practical use in recent years, and examines the characteristics (company classification, nationality, etc.) of the companies that discovered them (originators). The characteristics of the originators (e.g., company classification, nationality, etc.) were investigated.

2 Survey Methodology

The data were collected from the EvaluatePharma database (New Molecular Entity ( ^NME1 )), which contains new active ingredients, and the originators were categorized by nationality and company classification. Data as of September 2020 were used for this analysis, supplemented by publicly available information for some data not yet included in EvaluatePharma.

(1) NME Counting Method

In this study, the most advanced development phase per NME was counted as one case, and NMEs that were already on the market and being developed for other indications were not counted as a development phase. In addition, the cases from Phase I (hereafter referred to as "P1") to submission were treated as developmental products and included in the analysis in this survey.

(2) Originator counting method

In Evaluate, the definition of an originator is "a company that first discovered / invented the active ingredient of a given compound or product. The originator was identified based on public information such as company websites and press ^releases2). Once an originator has been identified for an individual NME, it remains unchanged even if the originator is acquired by a company (e.g., Genentech was acquired by Roche, but the Genentech record as the originator remains unchanged even after the acquisition by Roche). Genentech was acquired by Roche.) In cases where there were multiple originators, such as in co-development, the number of discoveries per company was counted by dividing the number of discoveries by the number of originating companies (e.g., in the case of co-discovery by two companies, the number of discoveries per company was counted as 0.5).

(iii) Modality classification

The modality classification in this survey corresponds to the Evaluate classification as ^follows3).

(iv) Company classification

Evaluate's classification of firms was based on the following three types of firms: Global Major (major global pharmaceutical firms, abbreviated as "Global" in this report), Regional Major (firms that develop and market new drugs in specific regions, and that conduct their own research and development while also conducting research and development for other firms. They conduct R&D in-house and also license in compounds and products from other companies and research institutes. Companies that target multiple disease areas. In this paper, we will refer to them as "Regional"), Biotechnology (developing new active ingredient-containing drugs and biopharmaceuticals, often small companies oriented toward novel technologies, but also including companies such as Gilead Sciences, Celgene, Biogen, etc.), and Specialty (companies that develop their own drugs and sell them in their own regions. ), Specialty (companies that conduct original research but do not focus on novel drugs or focus on only one disease area), and others. Depending on the characteristics of a company, multiple company classifications may be assigned to a single company, but the larger company classification is used (e.g., a company classified in both Global Major and Biotechnology is classified as Global). For example, companies classified as both Global Major and Biotechnology were classified as Global. Among Japanese major pharmaceutical companies, Takeda Pharmaceutical Company Limited was classified as Global, while others were classified as Regional.

3 Results

Total number of NMEs covered by this analysis

Table 1 shows the number of NMEs by development stage. In this study, NMEs in the P1 to application stages for each modality were included in the analysis. The lower part of Table 1 shows the percentage of co-created products to the number of NMEs in the P1 to application stages (development products). In each modality, the number of NMEs co-created by multiple companies accounted for only a few percent of the total.

3.1 Originator analysis of developed products

Nationality of Originator

Figure 1 shows the nationality of the originator of the developed products (those corresponding to the P1 to application stages in Table 1). In all modalities, U.S.-based companies lead the world in drug discovery, accounting for about 40% of all small molecule drugs and about 60% of all nucleic acid drugs.

Japanese companies accounted for about 10% of all small molecule and nucleic acid drugs, but 1 to 4% of antibody and other biopharmaceuticals, which is lower than that of small molecule and nucleic acid drugs. In addition, the percentage of gene-cell therapy products created in China and cell therapy products created in South Korea was higher than for other modalities (these are analyzed in Section 3.2).

For reference, Figure 2 shows the nationality of the originators of small molecule drugs launched between 2000 and 2019. The percentage of U.S.-based companies is 35% of the total, which is lower than that of R&D products, while the percentage of Japanese companies is 17%, which is higher than that of R&D products.

2) Originator's company classification

Figure 3 shows the percentage of originators by company category (Global, Regional, Specialty, Biotechnology, etc.). The percentage of companies classified as Biotechnology is the largest for all modalities, but is particularly large for gene cell therapy and cell therapy. Global's share is only a few percent for new modalities such as nucleic acid drugs and cell therapy. In gene therapy, gene-cell therapy, and cell therapy, the contribution of universities is larger than that of other modalities.

(3) Year of Originator's establishment

As mentioned above, large companies such as Gilead Sciences, Celgene, and Biogen are also included in Biotechnology in the Evaluate classification. Therefore, we classified the originators (excluding academia and public research institutions) by the year of establishment (Figure 4).

In the case of small molecule drugs, antibody drugs, and nucleic acid drugs, the majority were created by companies established before 1990, but approximately 40-50% were established in 2000 or later, indicating that even small molecule drugs with a long history as drugs are created by relatively young companies established within 20 years. On the other hand, gene-cell therapy and cell therapy have been developed in the past. On the other hand, in the case of gene-cell therapy and cell therapy, companies established after 2000 accounted for 60-70% of the total, and the percentage of products created by companies established more than 30 years ago was small compared to other modalities.

(4) Top originators in terms of number of discoveries by modality

Table 2 shows the top originators of nucleic acid drugs, gene therapy, gene-cell therapy, and cell therapy, which are treated as new modalities in this survey. In nucleic acid drugs, Ionis of the United States (developed and marketed by Biogen of the United States), the originator of the nucleic acid drug spinraza, which is included in the top 100 drugs in terms of sales in 2019, stands out. In gene therapy, European companies have a strong presence, but the top three companies (including NPOs) were all established in the 1990s. Cellular Biomedicine Group, the top company in gene cell therapy, is a U.S. company developing CAR-T for blood cancers targeting anti-BCMA, anti-CD19, and anti-CD20, but has its R&D base in China and conducts clinical trials there. Therapeutics is a biotech company that was at the forefront of research in the CAR-T space, but was acquired by Celgene in 2018 for about $9 billion. In cell therapy, the majority of companies were founded in the 2000s or later, but in terms of nationality, companies from Asia, such as China, Taiwan, and South Korea, are also prominent.

On the other hand, large global or regional pharmaceutical companies and Japanese companies were not among the top performers in these modalities.

3.2 Originator Survey by Nationality (CJK)

Focusing on new modality drugs created in Asia, we surveyed gene cell therapy by Chinese firms, cell therapy by Korean firms, and new modality development trends in Japan.

(1) Gene cell therapy products discovered by Chinese companies

There are 39 gene-cell therapy products developed by Chinese originators, including 17 originators (including one from Peking University) (see Table 3). Among these products, those in development not only in China but also in Japan, the U.S., and Europe are Anti-B-cell maturation antigen (BCMA) CAR-T cell therapy created by Genscript Biotech (P3 stage in China, Japan, the U.S., and Europe), CD19 CAR-T cell therapy created by Peking University, and CD20 CAR-T cell therapy created by Peking University (P3 stage in China, Japan, the U.S., and Europe). CD19 CAR T cells (PKNGUT) created by Beijing University (P2 in China and Europe), and CT053 created by CARsgen Therapeutics (P2 in China and P1 in the US). In terms of Mechanism of Action, CAR-T therapies targeting CD19 accounted for the largest number of 15 products, but CAR-T therapies including other targets are the mainstay of the market. (Table 3, bottom).

(2) Cell therapy products discovered by Korean companies

The number of cell therapy products developed and marketed by Korean originators totaled 21, including 8 originators (Table 4, top). Of these, one product, Cellgram-LC (autologous bone marrow-derived mesenchymal stem cells for P2 and liver disorders in Korea and the U.S.), created by Pharmicell (established in 2002), is in development in either Japan, the U.S., or Europe. CHA Bio & Diostech (established in 2002) has mass cell culture and cryopreservation technologies and currently markets three products in Korea, including autologous fibroblast-derived skin sheets and autologous adipocyte-derived mesenchymal stem cells for burn therapy, as well as three products in the United States and two products in overseas markets, including Astellas (formerly OCATA Therapeutics) and Pluristem Therapeutics (Israel) and other overseas partners.

The Mechanism of Action of cell therapy products created by Korean originators are mainly mesenchymal stem cells (Table 4, bottom).

(3) NMEs created by domestic originators

Table 5 shows the classification of originators and the number of NMEs created by domestic originators. Small molecule and antibody drugs are mainly created by pharmaceutical companies (Global, Regional, and Specialty are collectively referred to as "Pharma"), while the involvement of universities, mainly Biotechnology companies, in the creation of new modalities is significant. In this respect, the situation was generally similar to the global situation.

4 Summary and Discussion

In this survey, we investigated the originators of the development pipeline, focusing on new modalities. In terms of the number of discoveries, U.S.-based companies lead in all modalities, but Chinese and Korean companies are also making their presence felt in the creation of gene-cell therapy and cell therapy. However, the products created by Chinese and Korean companies are mainly developed domestically, and only a few are developed in Japan, the U.S., and Europe. Shibuguchi has analyzed the clinical development trends of new drugs in Chinese pharmaceutical companies in ^detail6).

6) Looking at the global development of new drugs by the category of the company that created them, the majority of new drugs were created by Biotechnology in all modalities, but the percentage was higher for new modalities. On the other hand, it is interesting to note that Biotechnology or companies established within 20 years contributed to the creation of a certain percentage (30-40%) of small molecule drugs, which have a long history as pharmaceutical products. From the perspective of pharmaceutical companies with strengths in clinical development and sales, partnering with such biotech and start-up companies is an important option to reduce the risk of conducting R&D on their own and to enhance their pipelines.

In the area of gene therapy, however, so-called megapharmaceutical companies classified as "global" have been making large acquisitions of startup companies in recent years. In the gene therapy field, however, megapharmaceutical companies classified as "Global" have been making large-scale acquisitions of startup companies in recent years.

Although this is a new modality, many of the companies driving the creation of each modality were established in the late 1980s and 2000s. It takes 10 or 20 years from the development of a new technology to its delivery to patients as a drug, and start-up companies need to raise funds in parallel with technology development in order to survive.

In order for Japanese companies to make their presence felt in this new modality, it is important for academia, industry, and government to work together to develop and commercialize technologies that are 20 to 30 years in the future. In this regard, I would like to conclude with a few words.

Conclusion

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