This is our discussion with Tetsu Yung which was recorded for the Solutions OP Clinical Trials podcast. You can listen to the original recording here. Please note that the interview below is adapted and not a transcript. This was done to improve readability.
Interviewer: Welcome to today’s episode of the podcast. The topic of this episode is clinical research in Japan, and with my guest, we will cover what is required to set up a clinical trial in Japan, as well as initiatives the Japanese government has to support small companies and start-ups interested in conducting clinical research in Japan.
My special guest today is Tetsu Jung, who has a very broad range of experience and expertise. He holds a PhD in cellular and molecular biology and also has an MBA in finance and international business. He has previously worked at major pharmaceutical companies such as EISAI, as well as at CROs such as Fortrea, LabCorp, and Covance. And I’m really impressed that he knows 5 languages.
Thank you, Tetsu, for joining me today. I’ll start by asking him the first question: to tell me a bit more about yourself and your experience in clinical research in Japan.
Tetsu: Thank you very much for inviting me. It’s a tremendous honour to talk to you about not just clinical research, but also the life science industry and how it’s going in general in Japan.
I would really love to discuss many aspects, as Japan is actively pushing to improve its output in the life sciences, and as you briefly mentioned, there is a significant government effort to support startups and small companies. So I will touch upon some of these points today, starting with who I am, why I do this, particularly with Japan, or why I speak the languages you mentioned.
I am half Taiwanese, half Japanese, so I grew up in Taiwan. My childhood years and memories are all from Taiwan, with a Taiwanese father and a Japanese mother. I spent the school year in Taiwan and, for a few weeks to a few months of the summer holiday, in Japan, until the end of my primary education. Afterwards, I moved to where I am now, Quebec, Canada, to complete my high school, then university, and later graduate studies. What was initially just for students on student visas eventually became a full immigration process, and the whole family ended up moving over. I began with my aunt, as a student, but then we enjoyed the experience so much that the whole family came over. We’re all Canadians now.
Throughout university, I studied biology and then specialised in molecular biology for my PhD. After completing my PhD, I moved to Japan as a postdoctoral researcher, securing a grant from the Japan Society for the Promotion of Science. This is a JSPS grant for postdocs, and that’s how my career in Japan began, first as a Postdoc at the Tokyo Institute of Technology, then I transitioned to the pharmaceutical industry which is EISAI, very well known for their Alzheimer’s drugs, starting with Aricept, and now progressing to Lecanemab.
Then I moved over to clinical operations, managing the Japan segment of global clinical studies, which makes up about half of my career in Japan. That, in a nutshell, is my career outline, from my postdoc and then EISAI to clinical operations at Covance, which became LabCorp, now spun out as Fortrea. Two years ago, I started my own small consultancy called Tetsunagi Consulting.
Tetsunagi is simply an exotic word that includes my first name. Tetsunagi means handshake or hand holding, symbolising the collaborative spirit and how I guide my clients by holding their hands. During my postdoc years at Tokyo Institute of Technology, a classmate or schoolmate of mine suggested this name, and it was an immediate hit from the start.
Interviewer: You really have international experience working especially with Japanese companies, helping them bridge people between Western countries and Japan.
Tetsu: I feel like the strength I tried to build it from a very small area up to a wider one. I had a mentor at McGill University, where I did my bachelor’s and MBA. That professor told me, if you don’t know what you’re going to do in life, go as small as possible. He meant, for example, to specialise in microbiology or nanotech, or go as miniature as possible and then expand.
Later in life, I did undertake a postdoctoral position for about five years at the Tokyo Institute of Technology, focusing on very basic research in cellular processes such as DNA repair, transcription, and oncology-related topics that I was really concentrating on at the time. I believe this experience has helped me build a very solid scientific foundation.
Then I went over to EISAI, where I combined my MBA knowledge with my scientific background, assisting the CSO at the time, Dr Yoshimasu. He took me under his wing for a few years and really gave me exposure to every aspect of the drug development chain, from very early-stage work in the labs, such as high-throughput screening and medicinal chemistry, to some regulatory work and extensive clinical development. Along the way, I also gained some experience in business development and related areas.
That was a great experience. I still love that company. I did leave, not because I hated it. I’d still be there if I had the choice, but due to very family-related reasons. I got married to a girl from Nagasaki, and for those who don’t know, Nagasaki is about a two-hour flight from Tokyo. Back in the day, companies didn’t allow working from home, whereas Covance, the company I eventually moved to, did allow it, even in Japan. It was quite avant-garde at the time. I had to make a choice between family life and professional life, and I chose family without any hesitation.
It was tough to leave, but I would do it in a heartbeat if you asked me again. So I got married and then went to Nagasaki, working for this company in Tokyo. It’s an American company.
Interviewer: Based on your experience in Japan, what are the main requirements to get a clinical trial approved there, and how long does it typically take from your perspective working in Japan?
Tetsu: Overall, I would say the process is similar to that in the US, with the parallels, like a pre-IND meeting and IND submission. On a conceptual level, it is the same.
The main differences are in the operations. For example, even in the pre-IND meeting, there is usually only one pre-IND in principle in the US. However, in Japan, there is a similar process. They don’t call it an IND; they refer to it as a CTN for clinical trial notification. So, there are those pre-meetings too, but they typically involve one formal meeting and several smaller, informal discussions.
I don’t know what the direct translation is, but essentially it’s a series of short, informal meetings to discuss a specific topic. It’s about discussions, but there’s a small thing you need to tweak for the main event. In Japan, many things happen that way. You have an ongoing discussion that you can gradually adjust until it reaches the main event, which effectively becomes the ceremony because of all the adjustments made beforehand. That’s how it works for regulatory meetings in Japan.
The clinical trial notification also involves a 30-day wait, similar to the IND, but you need to submit a clinical trial notification for each study you conduct. In the US, the IND is submitted once per drug or programme, right? So, in that sense, you need to submit a clinical trial notification for every study, although the second one has a shorter wait of about 15 days.
Interviewer: Out of curiosity, what level of translation do you require for documents? I believe that’s often the most daunting aspect for companies, wondering whether they need to translate everything, or what your experience is with all the documents, including the protocol.
Tetsu: Obviously, yes. All the key ingredients need to be translated into Japanese. I was working at Covance or now for Fortrea, and usually what we do is we say the official version is the English one, but for operational purposes, the Principal Investigator (PI) can use the Japanese translation. So that’s how we sort of frame it, in case there’s a difference in interpretation between the two languages, it has to be translated into Japanese for use.
It’s very straightforward and aligns more with how the US handles submissions, because in Europe it’s a bit more complicated. I don’t have a lot of experience with Europe, but for the few I have had, it’s always been a bit more complicated. But overall, if we go back to the timeline from clinical trial notification to first patient in, it’s usually about 3 months for feasibility.
You go to a site, talk to the investigator, and give them a questionnaire. They’ll look at what’s possible and what’s not. If it’s good, you move on to what is called pre-study visits, or PSV. A few companies have different names for that, but essentially, you’re qualifying sites for the study. From that point on, we’re talking 3 to 6 months. It can be as quick as 3 months, but it’s usually 5 or 6 months before you get your first patient in, depending on the indication, clinical trial material operations, and whatnot. So 3 to 6 months, but it’s quite predictable in that sense. All the documentation is standard and used in Japan.
For many of these procedures, what’s complicated is that, from a foreign lens, it seems complicated, but in Japan it’s very normal for every site to have its own contract template and budget table. It’s like a point sheet, so in Japan, due to the system’s rigidity, you basically don’t negotiate much. There’s not much room for negotiation. The only thing is maybe the study duration, depending on how you see it, but usually there’s not much room for negotiation. Whatever the site says, you just have to accept it, for the most part.
But that makes the contracting process quite fast, whereas in the states, I hear horror stories where you just can’t get the PI to sign, and then it’s like take 3, 4, 5 months down the road just for that contract signature, right? I hear that quite a lot, and that doesn’t happen in Japan. It’s essentially 3 to 6 months, with 3 on the very fast end and 6 months at the slow end, but you can predict it quite well.
Interviewer: It’s quite similar in Europe, by the way. It also takes us 5 to 6 months to get the site open. So, basically, the contracting is different. In the UK, we have a contract template used across all hospitals. They use the same template, and the budget is also standardised to some extent, so there isn’t much negotiation, similar to Japan. So that one in the UK is streamlined.
In Europe, it’s slightly different because they tend to have different budgets for each country and then negotiate based on that, but it’s quite straightforward in the UK, similar to what you’re saying about Japan. There’s not much negotiation; you just need to accept the country template and go on with it.
Tetsu: Some of these things can get very scary for global sponsors. For example, I had a study for a cardiovascular indication, these are huge studies with thousands of patients, even tens of thousands, depending on the specific indication. We had to recruit 400 patients in Japan across 36 sites, and one of the sites is still very traditional Japanese, they made you pay all the costs upfront at signature, and not on a patient-by-patient basis. I doubt they can do that today. There’s always a small upfront fee for overheads and whatnot, maybe 20-30% of the entire budget, but that specific site required a 100% upfront payment, which really scared them.
The sponsors back in the day, and I had a call from the COO of the company saying, ‘Are you sure we’re going to sign this contract for $1.225 million US dollars?’ That’s how it works, but Japan works on an honour basis, right? And if they said they’re going to do it, they’re going to do it. In fact, the PI recruited very quickly, fulfilled his contract very quickly, and then went on to do an extension.
Interviewer: That’s fascinating. You see, probably that’s why people are scared. If they do that in Europe and someone promises they’ll recruit, it doesn’t mean they’ll do it. It’s just a promise, that’s all. You can see the cultural differences here.
Tetsu: Yes, Japanese deliver on time and on quality. You just got to trust the system, but it’s hard when you come from a system that’s more based on scrutiny and neat, proof-first. And this is reflected in interpersonal relationships as well. I’ve had people I’ve worked with, and I’ve really decided I cannot work with this person for the Japanese market because he’s going to be suspicious of every interaction that comes our way, and that’s just not going to fly in Japan.
You have to trust first, and if things go wrong, you find a way to amend. 99.9% of the time, people have come with good faith. Japan is one of the few countries in the world where you could lose your wallet and find it again 99 times out of 100. I know because my wife has lost it, and I don’t know how many times. It’s always found near the nearest Hoban, which is like the police station near you. It’s hard to believe, but it is like that.
Interviewer: That’s really very interesting, and the cultural differences are fascinating. From your point of view, what do you think companies need to know when they prepare to set up clinical trials in Japan? What are your recommendations, and how should they approach the matter?
Tetsu: Like I’ve been trying to say, it is a very good, tremendously efficient and high-value market. I guess I don’t really need to expand too much on that in a top-notch premier science country with all the Nobel Prizes in the world, right? But it’s complex in its operation and complex in the psychology. As I’ve been telling you, if you start by saying that you need to prove your value to me, it already puts a crack in the interpersonal relationship from the get-go.
It’s hard. It’s even though it’s the first time you’re meeting somebody, with the Japanese, you need to come with good faith and sort of trust that the person will deliver on whatever he or she said. If he’s going to deliver something by Monday, the chances are very good that he will deliver on Monday. That’s the sort of thing that you’ve got to know how to work the system in Japan. And be able to rely on and trust people, because you’re not going to do it alone.
It’s just so many intricacies you have to know in Japan to get things working, and from that perspective, when somebody doesn’t respond to an email, what does he or she mean? Did you write something wrong, or sometimes it’s because they don’t like to say no? As I just mentioned, if they say something or promise it, they feel very obligated to deliver it, but if they don’t say it and keep it grey until the next trigger, maybe a meeting at the next conference or whatever, they can sort of let it go by.
These are all different cultural cues and nuances that one needs to know. It’s very complex. You need to learn quite a bit. It’s like if you want to climb the mountain of Japan, like you climb Mount Everest, you can give it a try and take the time you need to do it, or you can hire a Sherpa, somebody who knows how the system works.
There are a lot of people and companies now who are specialising in this type of work, providing Japan access services. Many consultants and many big companies are doing this. Obviously, it is also because Japan needs foreign business, so it is a win-win in that sense. I mentioned at the top of the interview that Japan is making a huge push. From a resource’s perspective, from the money perspective, using tax money, they’re really trying to do many types of initiatives for that.
Interviewer: That’s very interesting what you’re saying, because in Western countries, we tend to overpromise and everyone is pushing to get everything done by yesterday. It’s really interesting to see the cultural difference, where people won’t promise something, they know they won’t deliver.
Tetsu: If you get them to make that promise, you can rely on it fairly well. That’s the soft side of things. On the hard side, as I mentioned earlier, a regulatory meeting has a lot of pre-meetings, so there’s a lead time.
I would definitely recommend that global companies, when they look at Japan, not just say, OK, I got the US done. Now let’s think about the rest of the world, including Japan. That’s quite late. The fastest way to include Japan is to include it in your pivotal study. To do that, you need to talk to the Pharmaceuticals and Medical Devices Agency (PMDA) well ahead of your final protocol in your pivotal study.
They have made changes, but now, in principle, don’t need a pharmacokinetics (PK) studies. Previously, you had to run what is called a run-in study, get Japanese patients’ PK before actually enrolling them in the main part of the study. Now they’ve taken that off. They’re just trying to make it easier for foreign companies to come in, but you still need to think of the strategy first in order to include Japan in your phase 3. That’s the fastest way.
It’ll cost you a little bit more for your pivotal study, but you’ll get to submit at the same time as you submit to the FDA and the EMA. It’s the fastest way rather than actually doing another big study afterwards.
Interviewer: I agree with you, probably that’s the best way to do it. So, my next question is a bit more about small companies and startups. Are there any initiatives from the Japanese government to encourage companies to run clinical trials in Japan, because I think there are quite a lot of things going on internationally?
People are trying to attract more startups and smaller companies to invest. Is there anything specific about the Japanese government that you know of and can share?
Tetsu: There have been a lot of initiatives, and it’s ongoing. I hear a lot of chatter about government initiatives to make Japan more global and to enable companies to come in more easily by reducing the barriers. One is what I just mentioned earlier, about the PK thing for global companies to come in, and there is like the Orphan Drug Designation (ODD), which is parallel to the US one. There’s a Sakigake designation, which is like a fast-track or breakthrough therapy designation.
All these things have their parallels in the US, but one thing that does not have a parallel in the US is a programme administered by a funding agency called AMED. This is a government agency that is basically the equivalent of the US NIH, and AMED has a programme called the Strengthening Programme for Pharmaceutical Startup Ecosystem. It’s a very long name. It’s a mouthful, but it’s very descriptive. It’s approximately $2.7 billion US dollars, a fund that started in 2022 and runs through to 2032, so a 10-year programme.
The model is very cool. AMED has a series of venture capitals (VCs) that are registered with them, so AMED-registered VCs. And if you come in as a startup and you get money from any one of these registered VCs, let’s say $10 million, then AMED will put in another $20 million on top of that, so 2 to 1, not even imagine, it’s 2 times the amount that the VC puts in. This is non-diluted. They don’t need any equity. They don’t sit on a board. They don’t want any control.
It is an amazing programme, and as amazing as it sounds, it is still struggling to find enough assets to invest in. So, they really opened it up to global start-ups to come into Japan. The minimum requirement, technically speaking, is that you need a local entity in Japan, just like you need a local entity when you go for those tax incentives in Australia, right? So that part is sort of the easy part.
But it is tax money, so AMED needs to justify to the Japanese people how they’re using these funds. It’s a huge chunk of money, but they need to say that they’re investing in an American company’s affiliate, which is addressing a very strong unmet medical need in Japan. They’re using Japanese vendors. They’re collaborating with a Japanese company or a Japanese university, or the technology comes from a Japanese university. They hire a CEO and groom them to become a global asset. You need that kind of Japan story, that narrative around your asset, in order to justify the use of these funds. That’s the part that’s hard to satisfy immediately for many companies,
However, you can build that narrative as you move from the discovery phase into your pre-Investigational New Drug (IND) and IND phases. The target for this grant is startups. It’s for companies that are technically 2 years before candidate selection, so very early, although I’ve never seen any that early. I think the sweet spot is around IND-enabling studies, the long-term talks and things like that. I think that’s kind of the sweet spot to get this grant and maximise its value, up to and including phase 2.
Interviewer: So that’s the early development, basically. That’s brilliant. I think that’s a great initiative.
Tetsu: Yeah, and they finally have some companies, including global companies that have recently set up in Japan, that have received that grant. I’m very close with the team running the programme at AMED, and every time we go to Bio or JP Morgan, we run the Japan Access sessions, which are always very popular. People don’t know about this, though they are becoming more aware of it; I’m hearing people talk about it all the time.
This is an amazing programme, not just for the start-up. You go out and hustle for $10 million, and suddenly you have $30 million in your bank account. That is easy to understand, but it’s also amazing for the VCs too. Imagine you put in $10 million into your asset, and somebody just comes along and gives you another $20 million to make it happen, right? You suddenly de-risk your asset by threefold, and the person doesn’t even want to take control, because they could easily take more control than you, given that they put in 200% of what you put in. But your equity is not diluted. Your power and your control are not diluted. So, this is an amazing program for the VCs and the investors as well.
Now, lots of global VCs are registering with AMED, including Blackstone, EQT, and QE. These are the latest additions to OTPG, and some of these bigger guys have been there forever since the inception. But many people are taking notice, and I’m hearing about this everywhere I go.
Interviewer: That’s really fascinating, and it’s a really great initiative. I think that’s a very clever way to attract investment into Japan.
And then I’m coming to my very last question: why should pharma companies consider the Japanese market as part of their drug development programme? I think you touch on this in many cases, but just as a final point, what would you like to say?
Tetsu: I’ll give you an easy one to remember that I use everywhere I go when I give presentations, and that really distils all the reasons to consider Japan as a market for you. And it’s in one acronym – JPRIME.
J stands for Japan. Japan is still a huge market, so that’s a no-brainer. P of the prime is premier science and innovation. I need to convince you with the number of Nobel Prizes we’ve had on a per capita basis. It’s by far a very strong scientific country.
And then R is for reliability and integrity. We touched on this earlier, talking about the honesty of the people and their reliability, and that they will deliver whatever they say they will, at the time they said they would. So that’s kind of a thing that’s not written out in CVs and whatnot, but it’s something that’s a kind of hidden cost elsewhere in the world, whereas in Japan, this business friction is just barely there, right?
I for infrastructure, infrastructure in Japan for drug development is very lean and efficient. All the legitimate travel logistics, the couriers, and all these delivery logistics are very efficient. Many of these things with the temperature-control system are just amazing, and that’s fully functional, as long as you know how to drive this Formula One car, right?
M is for market access and stability. It’s a country with a very low crime rate. It is very stable, easy to access from many major hubs around the world, with direct flights from all the major hubs in the world.
E is for economic advantage of the weak yen. And also the funding that I mentioned earlier. The yen is really weak right now. It used to be almost at parity with the US dollar before the pandemic, like $1 was about 100 to 105 yen. That’s 160 yen now. So, every dollar you spend in Japan right now goes 50 to 60 miles further. From an investment perspective, it’s huge, right?
And then, as I just mentioned, the funding is a no-brainer. The government is handing out money to you to come to Japan to make things work, and the programme I mentioned earlier is called the Strengthening Programme for Pharmaceutical Startup Ecosystem. So, it’s pharma, it’s therapeutics, but they are talking about MedTech. There are lots of brands at AMED that are available to small companies in Japan right now.
And again, they’re pushing and pushing and pushing to put Japan back on the map. I say back on the map, the global map, because Japan used to be a world leader in pharma in the 80s and 90s. For every three new chemical entities that came out, one came from the US, one from Japan, and the rest of the world shared the rest. So, those were the golden years, and today it’s like 2 out of 3 come from the US, and the rest of the world shares the remaining. Japan was like 7% or something.
Japan is really noticing this decline in productivity, and they want to push Japan back onto the map because we know we can. For whatever reason, it’s just been a slow decline over the past few decades, and it’s coming back fast. I am seeing activity everywhere, with a focus on Japan’s return.
Interviewer: Thank you so much for your time and for having this discussion. In addition, from a purely regulatory point of view, having access to Asia is essential for obtaining approval for your drug in Japan. So, it’s always considered a gateway if you want to get your drug to the Asian market.
Tetsu: Thank you for mentioning that. It is still one of the top 3 regulatory agencies in the world with the EMA, FDA, and PMDA. So, you get one in Japan, and then right away you can go to Korea and all the Asia-Pacific countries relatively easily.
Interviewer: Yeah, you have a fast track. It just looks better when you have approval from the Japanese authorities. So, Japan is a very promising place for your clinical trials. Definitely something to consider and to discuss with local experts if you want to go on a trip and set up your clinical trials in Japan. Thank you so much again, Tetsu, for joining me today.
