The Pharmaceutical Industry at a Glance Survey of preclinical stage alliances and acquisitions - Comparison between Japan and other countries

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Daisuke Kanai, Senior Researcher, Pharmaceutical Industry Policy Institute
Kiyoshi Morimoto, Senior Researcher, Pharmaceutical Industry Policy Institute
Chie Yoshiura, Senior Researcher, Pharmaceutical Industry Policy Institute

SUMMARY

1. Introduction

In the October 2023 issue of the National Institute of Biomedical Innovation Policy Research Paper Series No. 81, "The Actual Situation and Prospects for Co-Creation Drug Discovery Centered on Academia, Drug Discovery Ventures, and Pharmaceutical Companies" (Takasago), it was pointed out that Emerging Biopharma (hereinafter referred to as EBP) as well as academia play an important role in drug discovery toward practical application. In the U.S., where EBPs play an important role in drug discovery for commercialization, the development of EBP-derived candidate substances is active, and many partnerships and acquisitions, such as licensing and asset acquisition, are being conducted for preclinical-stage candidate substances created through these ^activities1).

Many companies recognize the importance of securing preclinical candidates for innovative ^{drugs2, 3).} Many candidate substances are not only developed in-house, but are also acquired from other companies through alliances and ^{acquisitions4)}.

This survey focuses on transactions, alliances, and acquisitions of preclinical candidate substances conducted by companies and organizations in various countries between January 2010 and March 2025 (hereinafter referred to as "preclinical alliances and acquisitions"), and analyzes trends in Japan through several items. We also compare the preclinical alliances and acquisitions conducted by Japan with those conducted by other countries, and clarify the characteristics of Japan and other countries.

At the Drug Discovery Ecosystem Summit in 2024, the goal was set to "make Japan a land of drug discovery that can contribute to the world " ⁵⁾ and various measures are being taken by the public and private sectors to achieve the ^{goal6, 7)}. In this report, we discuss the policies for academic ^{research8) and} biopharmaceutical ^{development9) in} light of the actual situation of preclinical partnerships and acquisitions.

Survey Methodology

The survey covered 1,202 preclinical partnerships and acquisitions made by companies and organizations around the world between January 2010 and March 2025, as reported by Evaluate ^{PharmaⓇ (} as of March 2025), of which the top eight countries (in descending order of number: the United States, the United Kingdom, Japan, Switzerland, China, France, Germany, and South Korea) made the most preclinical partnerships and acquisitions. The top eight countries (in descending order of number of deals: U.S., U.K., Japan, Switzerland, China, France, Germany, and South Korea) made up the 1,013 deals. Preclinical collaborations and acquisitions are defined by Evaluate ^PharmaⓇ as "in-licensing," "acquisitions," "joint ventures," "product in-licensing," and "co-development of in-house candidates with external parties or combinations of in-house and third-party licensed products.

The 1,013 cases were preclinical collaborations/acquisitions for New Molecular Entity (NME) candidates, which were conducted during the survey period and for which the marketing rights held by the company or organization conducting the collaboration/acquisition were in the U.S. or worldwide, including the U.S. The preclinical collaboration/acquisition is for a candidate substance. On the other hand, we excluded candidate substances for which no preclinical collaboration/acquisition had taken place, such as those developed entirely in-house, because such information was not available. The 1,013 cases included preclinical alliances and acquisitions conducted not only by listed companies but also by non-listed companies. However, as information on preclinical alliances and acquisitions is published in Evaluate ^{PharmaⓇ (} as of March 2025) only if it is publicly available as of March 2025, preclinical alliances and acquisitions that are not publicly available and cannot be published are excluded from the scope of this survey. This is a limitation of this study.

The survey excludes the cases of discontinuation of development, suspension, transfer, etc. after the preclinical collaboration/acquisition, since multiple pieces of information are missing, and preclinical collaboration/acquisition for candidate substances for which development is in progress or has already been filed, approved, or launched as of March 2025 is adopted.

Information as of March 2025 was used for the development stage after the preclinical collaboration/acquisition. In addition, in cases where multiple alliances/acquisitions were conducted for a single candidate substance for the purpose of obtaining multiple indications, etc., only the alliance/acquisition with the most advanced development stage in the world as of March 2025 was taken and counted as one alliance/acquisition per candidate substance.

The countries surveyed were the United States, the United Kingdom, Japan, Switzerland, China, France, Germany, and South Korea (1,013 in total), in descending order of the number of preclinical alliances and acquisitions. When comparing Japan with other countries, the U.S., which has the largest number of alliances and acquisitions, was considered independently and divided into three groups: Japan, the U.S., and six other countries.

For originators, which are the targets of alliances and acquisitions, we used the classification published in Evaluate ^PharmaⓇ by Evaluate (as of March 2025). For originators, medical institutions, research institutions, and public institutions were summarized as Academia, and Biotechnology and Specialty were summarized as EBP.

The modality monoclonal antibody defined by Evaluate's Evaluate ^{PharmaⓇ (} as of March 2025) includes multiple antibody (msAb) and antibody drug conjugate (ADC).

In this report, various indicators and classifications used in Evaluate ^{PharmaⓇ (} as of March 2025) are used in English.

Results

3-1 Number of preclinical alliances and acquisitions by country and percentage by country

Evaluate's Evaluate ^{PharmaⓇ (} as of March 2025) shows 1,202 preclinical collaborations and acquisitions worldwide between January 2010 and March 2025, with Japan having the third highest number of preclinical collaborations and acquisitions with 77, or 6% of the global total. The U.S. ranked first with 619 deals, accounting for 52% of the total (Figure 1).

The types of preclinical alliances and acquisitions included "in-licensing," "acquisitions," "joint ventures," "product in-licensing," and "co-development of in-house candidates with external parties or combination of in-house and third-party licensed products," with licensing accounting for about 70% of all cases (Table 1).

3-2 Preclinical Collaboration/Acquisition Targets in Each Country from Originator's Perspective

By originator, 75% of all preclinical alliances/acquisitions in Japan were for EBPs (Fig. 2). EBPs were the most common targets of preclinical alliances and acquisitions in Japan, the U.S., and the other six countries, a common trend. Looking at the nationalities of the EBPs that were the target of preclinical alliances or acquisitions by the top eight countries, the United States accounted for 49% (349/708 cases), followed by China, the United Kingdom, South Korea, and France. Japanese nationals accounted for 29/4% of the EBPs, tied with Switzerland for sixth place (Figure 3).

In Japan, 10% of the total were preclinical partnerships or acquisitions for academia, ranking second only to EBPs. This percentage is similar to that of the other six countries, but the U.S., at 24%, is about 2.5 times higher than Japan, which is one of the characteristics of the U.S. (Figure 2). Looking at the nationalities of the academia targeted by the top eight countries for preclinical alliances and acquisitions, the U.S. accounted for the majority at 73% (138/189), followed by the U.K., France, and Japan. Regarding preclinical alliances and acquisitions of academia, the U.S. was the most common country for both the nationality of the implementing organization and the nationality of the target of the alliance or acquisition (Figure 4).

3-3 Preclinical Collaborations and Acquisitions by Modality

Looking at the modalities of preclinical alliances and acquisitions, small molecule chemistry and monoclonal antibody (including msAb and ADC) were the most common in Japan, the U.S., and the other six countries, in that order, with these two modalities accounting for more than 60% of all preclinical alliances and acquisitions, These two modalities accounted for more than 60% of all preclinical alliances and acquisitions, a trend common to all countries (Figure 5). As with all preclinical alliances and acquisitions (3rd place, 8% = 77/1,013), Japan ranked 2nd (8% = 33/420) out of 8 countries for preclinical alliances and acquisitions related to small molecules chemistry, indicating that as in other countries, small molecules chemistry As in other countries, small molecules chemistry is a modality that Japanese companies and organizations are focusing on in their preclinical alliances and acquisitions (Figure 6).

Gene therapy and cell therapy accounted for 9% and 8% of the total in Japan, respectively, compared to 6% and 3% in the U.S. and 1% and 2% in the other six countries (Fig. 5).

As for the characteristics of the other countries, Vaccine showed a high percentage of 7% in the U.S. and 6% in the other six countries, compared to 2% in Japan.

3-4. preclinical alliance/acquisition targets in each country by therapeutic category

In terms of the drug class of preclinical alliances and acquisitions, the most common preclinical alliance/acquisition in the U.S. and the other six countries was for Oncology. The ratio was 40% in the U.S. and 45% in the other six countries, about twice as high as the 21% in Japan.

The most common preclinical alliance/acquisition in Japan was CNS, at 22%, a higher percentage than in the other countries (12-16%). The higher proportion of CNS and the lower proportion of Oncology in Japan were considered to be characteristic of Japan compared to other countries.

In addition, the proportion of immunomodulators in Japan (12%) was higher than in other countries (6%). On the other hand, 6% of systemicanti-infectives in Japan had a lower percentage than in other countries (10-12%) (Figure 7).

3-5. status of development stage after preclinical collaboration/acquisition by modality

The following modality was characterized by the survey of partnerships and acquisitions that had moved to the clinical stage of development as of March 2025 ("clinical transition") and those that continued in the preclinical stage ("preclinical continuation") after the preclinical partnership/acquisition. The ratio of clinical progression after preclinical collaboration/acquisition in chemistry was 0.83 in Japan, 0.73 in the U.S., and 0.71 in 6 other countries, assuming that the ratio of preclinical continuation was 1, The clinical transfer rate for monoclonal antibodies (including msAb and ADC) was 0.36 in Japan, 1.05 in the U.S., and 0.91 in the other six countries, showing a trend toward lower rates in Japan. Although these figures do not directly indicate the superiority of preclinical alliances and acquisitions conducted, there was a divergence between Japan and the other countries (Figure 8).

3-6. targets of preclinical alliances and acquisitions from the originator's viewpoint

Looking at the number of preclinical alliances and acquisitions conducted by companies and organizations in each country and their trends over time, the number of preclinical alliances and acquisitions peaked in 2021-2022 for all but Japan among the top eight countries. Japan, on the other hand, showed a gradual upward trend throughout the survey period, although in some years the number was lower than in others. However, no preclinical alliances or acquisitions were conducted in 2012 and in the period from January to March 2025 (Figures 9, 10, and 11).

Looking at originator trends over time for preclinical alliances and acquisitions from January 2010 to March 2025, all countries increased their preclinical alliances and acquisitions to EBPs from around 2018, with EBPs still having the largest number. In Japan, most of these acquisitions have been made to EBPs since 2018. On the other hand, preclinical alliances and acquisitions to academia showed a marked downward trend in recent years in both Japan, the United States, and the other six countries (Figure 9).

3-7. targets of preclinical alliances and acquisitions from the modality perspective and their transition over time

Looking at the trends of modalities over time, preclinical partnerships and acquisitions for small molecules chemistry and monoclonal antibodies (including msAb and ADC) in the U.S. and the other six countries have been numerous every year from around 2017 to the present, together accounting for 60-71% of the total. The ratio was also high, accounting for 71% (297/498 in the U.S. and 181/254 in 6 other countries since 2017) of the total. On the other hand, in Japan, although small molecules chemistry and monoclonal antibody (including msAb and ADC) accounted for more than half of the cases in some years, other modalities accounted for more than half of the cases in other years, and preclinical collaborations and acquisitions were conducted for many modalities. The trend differs from that of the U.S. and the other six countries (Fig. 10).

3-8. targets of preclinical alliances and acquisitions by drug class and their trends over time

Looking at the trends over time, preclinical alliances and acquisitions related to Oncology increased rapidly in the U.S. and the other six countries from around 2018, and since 2018, the ratio has remained high compared to other drug classes, at 41% (187/458) in the U.S. and 52% (126/241) in the other six countries (Figure 11). Japan, on the other hand, has been maintaining high rates of various types of medicinal products. On the other hand, Japan was characterized by the fact that preclinical alliances/acquisitions were implemented in various types of drug classes, and there were no shades of gray in the targets of preclinical alliances/acquisitions (Figure 11).

Conclusion and Discussion

It was mentioned earlier that the number of preclinical alliances and acquisitions in Japan ranked third in the world for the period from January 2010 to March 2025, and that the trend of preclinical alliances and acquisitions in Japan shows an increasing trend. In addition, there were some discrepancies between Japan and other countries in terms of the development stage status after preclinical alliances and acquisitions. We would like to look into the future course of the characteristics of preclinical alliances and acquisitions in Japan that differ from those in other countries as identified in this survey.

Among originators in Japan, preclinical alliances and acquisitions of EBPs were the most common. And looking at the trends over time in recent years, most of them were EBPs. On the other hand, preclinical alliances/acquisitions to academia were only 1 out of 44 in the last 6 years. During the study period, the ratio of preclinical alliances/acquisitions to academia in the U.S. was 2.5 times higher than in Japan, but even in the U.S., the ratio of academia has decreased significantly over the past few years. The detailed reasons for this are the subject of future research, and will be discussed in this paper in conjunction with the findings of a survey conducted by the Pharmaceutical and Industrial Policy Research Institute, "Survey on EBP-derived drugs in the U.S.: Comparison of biotech and small molecule products," Position Paper No. 8 (July 2025).

In this position paper, we reported the results of a survey of U.S. EBP-derived drugs approved in Japan, the U.S., and Europe in two or more ^regions10). The number of patents filed by academia alone or jointly is 2/33 for biopharmaceuticals derived from EBPs in the US, 18/78 for non-EBP-derived products in the US, 1/62 for small molecule drugs derived from EBPs in the US, and 8/8 for non-EBP-derived products in the US. The number of patents for non-EBP-derived products was as low as 8/63, and the majority of patents for U.S. EBP-derived drugs approved in Japan, the U.S., and Europe in two or more regions were filed either by U.S. EBPs alone or by pharmaceutical companies. Of the 15 biopharmaceuticals and 7 small molecule drugs that were "filed solely by academia," 11 and 4 were licensed out to U.S. EBPs, respectively. The position paper also mentioned the background of the founders of U.S. EBPs: 63% of U.S. EBPs that created biopharmaceuticals and 42% of U.S. EBPs that created small molecule drugs were founded by university graduates. These reports indicate that research and ideas in academia are refined and commercialized by EBPs and pharmaceutical companies. We will investigate whether this is also applicable to the results of this survey, and will also explore the causes of the decline.

With regard to modalities, it is also worth noting that not only in Japan, but also in the U.S. and six other countries, there are active preclinical partnerships and acquisitions for small molecule chemistry. This trend indicates that companies and organizations around the world still consider the development of small molecule drugs to be important and continue to pursue preclinical partnerships and acquisitions at a high rate. In particular, Japan was the world's second largest implementer during the period covered by this survey. There is a strong policy emphasis on promoting investment in biopharmaceuticals. On the other hand, policies to promote small molecule development seem to be less important than those for ^{biopharmaceuticals9)}. It is important to note that preclinical alliances and acquisitions of small molecules have been conducted in Japan as much as in other countries, and that the U.S. and other countries continue to focus on small molecules.

In addition, we noted that gene therapy and cell therapy accounted for a high percentage of preclinical alliances and acquisitions. However, looking at the number of preclinical alliances and acquisitions, Japan had 7 in Gene therapy and 6 in Cell therapy, which is not ahead of other countries in number compared to 36 and 20 in the U.S. and 4 and 5 in the other 6 countries.

In terms of drug classification, Japan had the highest percentage of preclinical alliances/acquisitions for CNS and the lowest percentage for Oncology, which was a characteristic trend in Japan. High and low numbers do not indicate superiority or inferiority. However, looking at trends over time in Japan, Japanese companies and organizations had preclinical alliances and acquisitions in various types of drug classes, while other countries concentrated on Oncology.

This study illustrates some of the trends in preclinical alliances and acquisitions in Japan and other countries. In order to further explore the results of this survey, it is necessary to clarify the reasons why the trends observed here are occurring. In addition, the practical application of the findings will be discussed in the following sections. In addition, it is desirable not only to effectively and efficiently implement preclinical alliances and acquisitions for practical use, but also to optimize alliances and acquisitions for candidate substances already in the clinical development ^stage11). We would like to discuss those investigations in the future.

Finally, we strongly hope that the Japanese pharmaceutical industry will lead the world, and that innovative drugs developed as the industry develops will contribute to many patients and the many people involved.

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