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The future of health care - Part 1: Biotech innovation

Thomas Mucha, Geopolitical Strategist
Wen Shi, PhD, CFA, Global Industry Analyst
2022-06-30T12:00:00-04:00  | S1:E8  | 35:20

The views expressed are those of the speaker(s) and are subject to change. Other teams may hold different views and make different investment decisions. For professional/institutional investors only. Your capital may be at risk.

Episode notes

Health care investor Wen Shi joins host Thomas Mucha to discuss the future of biotech innovation. They explore the potential of gene editing, targeted protein degradation, artificial intelligence, and much more, highlighting their impact on everything from patient outcomes to geopolitics.

Transcript

THOMAS MUCHA: Biotechnology is one of the most important and perhaps least understood global industries. It’s critical to the success of the broader healthcare system, of course, and to the quality of life of billions of people around the planet. But it’s also a key part of the geopolitical backdrop, with biowarfare and bioterrorism getting a higher profile in today’s more competitive great power backdrop. In fact, the Pentagon’s acting principal director for biotechnology, Stephanie Rogers, recently declared, “The nation that leads the world in biotech will accrue enduring economic, societal, and defense gains.” So clearly, the industry is on the minds of policymakers, especially in a world of global pandemics and global competition. To help sort it out, and to focus on what’s driving this very important industry, we’re joined today by Wen Shi, a global industry analyst on Wellington’s healthcare team who conducts fundamental research on the global biotech industry. Wen, welcome to WellSaid. 

WEN SHI: Thank you Thomas, it’s great to be here. 

THOMAS MUCHA: So, let’s start at the very top. And what, in your view, is the current state of the biotech industry? 

WEN SHI: Everyone in this world has a shared experience over the past two and a half years, namely living through a pandemic. That started in the early part of 2020, and the biotech industry has been at the forefront of creating solutions, both in terms of vaccines, and in terms of therapeutics. Because of that focus on the pandemic, there has been a broader interest from investors, from policymakers, and from the general public in the sector, as well. And also, because of some of the macroeconomic factors, such as the Fed lowering interest rates. So that really has created a tailwind for money flow coming to the biotech sector, that primarily happened in the second half of 2020, just coming out of the initial shock of COVID, and into the early part of 2021. However, fast forward a little bit, since the beginning of ’21 until today, the sector has been in a bit of a hangover.

THOMAS MUCHA: So, did the market get ahead of itself? 

WEN SHI: Yeah, I guess you could say that, right? That tailwind lasted only less than a year, and what happened is that there are a number of headwinds facing the sector, specifically there are some uncertainties regarding how the drugs are approved, how the drugs are paid for, whether there was just too much excitement in the sector, and since the beginning of 2021, the sector actually has corrected by more than 50 percent, which would make it almost worse than any other sector in the S&P. 

THOMAS MUCHA: All right, so that’s an interesting overview of where the sector has been. It was obviously a key feature for investors, and now it’s come down. So, in this environment where do you see opportunities over the short-term, but more importantly, over the long-term?

WEN SHI: Yeah. So, biotech, as you know, is a sector known for utilizing the best technologies, the best scientific understanding to develop therapeutics and treat diseases. I think over the longer term, we are very excited about some of the novel technologies or tools that are being developed in the space. 

THOMAS MUCHA: What are some of those? 

WEN SHI: Right, so a good example is gene editing. So, gene editing is the subject of a Nobel Prize just one or two years ago. The analogy I like to use for gene editing is that it is a pair of molecular scissors that can precisely make cuts or edits in the genome, or in the DNA, which determine who we are. So, this technology was only invented in 2013, however, just in less than 10 years, has really taken off, so now there are multiple clinical programs for the potential cure of sickle cell disease, for some neurological and cardiac conditions. They’re all in the clinical testing. So, the one in sickle cell disease might actually go in front of the FDA by the end of this year. So, there is a lot of excitement in that front. I would say we are excited about these kind of technologies. Another example of a technology is called targeted protein degradation, or TPD, to be short. So, this is a small molecule chemical drug that can potentially go into different parts of the body, and it can go against targets that are maybe involved in cancer or other diseases. So, the advantage of this TPD approach is that these molecules can be taken by mouth, they are oral, so you can avoid injections, you can avoid infusions, and then you can also potentially go after targets that are not addressable by traditional means. So, these are some examples of the technologies that we’re excited, maybe in a 5-year timeframe, or a 10-year timeframe.

THOMAS MUCHA: So, what about short-term opportunities in the sector? 

WEN SHI: Yeah, so in the short-term, we have to be mindful of the broader macro backdrop. So, in the context of financial tightening, in the context of Fed raising interest rates, the biotechs with exciting science, but drugs that are five years away from potentially generating revenue, those tend to be out of favor. So, we have to balance our excitement about a science with the macroeconomic environment. So, in nearer term, we are on the margins more interested in companies that already have important products on the market. So, an example of a company like that has a suite of drugs for the treatment of cystic fibrosis, right? So, cystic fibrosis affects more than 70,000 individuals in this world. It’s a devastating genetic disease, and we know the exact cause of that disease. So, with this company, they can have drugs that can specifically address the underlying cause of the cystic fibrosis disease, and to make the patients feel better, to make their lungs function better, and potentially improve their life expectancy as well. So, this is the kind of companies that we are focusing on in recent in the recent past. 

THOMAS MUCHA: I want to go a little bit deeper into this gene editing concept that you mentioned. Is that CRISPR, is that what that’s about? 

WEN SHI: CRISPR is the best-known example of gene editing, but gene editing as a technology has been around for decades, right? So, there are older tools available. So, for example, there are different kind of scissors, but those scissors may not be precise or they’re just very hard to engineer. So, what is revolutionary about the CRISPR technology is that it works really well, you can target almost anywhere in the genome, and then it’s very precise you have relatively low level of off-target cuts, right, which are bad. And most importantly, they are really easy to program. So, anybody with a PhD, and even a graduate student in the lab, they can just go on the internet, they can type in which gene they want to edit, and then a pair of scissors, so to speak, just pop out. And so that really revolutionized the gene editing technology and made it accessible by academic people and by companies alike. 

THOMAS MUCHA: So, on these better scissors what’s the practical implication here? Is it that it shortens the research and development process? That it is able to target more diseases? I mean what’s the wow factor?

WEN SHI: Yeah, all of the above. I think there are hundreds or even thousands of genetic diseases. These are diseases that could be as rare as only a couple hundred patients in the US, or it could be as common as 100,000 or more. And then for a lot of these, because of the sequencing of the human genome 20-plus years ago, there is an increasing understanding as to what genetic mutations cause these diseases. If we know that there is this so-called gain of function or having a function that’s not supposed to be there, you could use the scissors to cut it out. On the other hand, if there’s a loss of function, or if a function is missing, then it’s a little bit more complicated, right? So, not only do you need to cut it, but you also need to replace with something else. So, those type of technologies, the latter kind, are a little bit further out but the ultimate dream is to be able to address any monogenic disease, which means that a genetic disease caused by mutations in a single gene. 

THOMAS MUCHA: So, you cut out the bad stuff. 

WEN SHI: You cut out the bad stuff, and then you potentially also, in some situations, you also need to replace with the good stuff, right? Replacing with the good stuff is harder to do than just cutting. 

THOMAS MUCHA: Awesome. So, this is a 5 to 10-year window, you think? 

WEN SHI: Yeah, I think there are different diseases that are going to be addressable in different timeframes. The lowest hanging fruit will be to cutting something in something like a blood cell. So, the blood cell, you can extract from the human body, you can do your cutting in a petri dish, so to speak, right? And then you can infuse it back into the patient. So, those are straightforward. And right next to that, you have doing cuts in the human liver, which is the organ that’s easiest to get to. The longer term you have things like replacement with the functional copies, you have things like going to the brain, and going into other parts of the body, which are, yeah, probably closer to 10 years away.

THOMAS MUCHA: Got you, okay. So, thanks for that. That’s a good explanation of something that has been confusing to me for a long time. 

WEN SHI: Yeah, absolutely. 

THOMAS MUCHA: Another big area of innovation for the biotechnology industry is, of course, the treatment of cancer. What is the current state of cancer treatments? 

WEN SHI: This is an area that I focused on for a very long period for personal interest, for academic interest, and there are two main approaches for treating cancer in the last couple decades. So, one is so-called precision oncology, or delivering of drugs that addresses specific drivers or causes of different type of cancers. So, these are mutations in the cells that cause these cells to grow and expand without any control. Right? So, that’s one approach, or precision oncology. And the second approach that it really took off in the last 10 years or so is the so-called immuno-oncology. So, what this approach involves is that it revs up the body’s own immune system to target and kill those cancer cells. So, you and I, we walk around, we don’t typically have cancer. And the main reason for that is that the body’s own immune system plays as a sentry role to identify and eliminate any cancer cells. So, but for whatever reason, this process is not working properly in the cancer context, but there are specific therapeutics, either drugs or even some immune cell therapy that could be used to reactivate or replace the missing immune system and target the cancer. 

THOMAS MUCHA: So, what about these emerging technologies that you hear so much about in biotech? Artificial intelligence, data analytics, synthetic biology, these are the issues that the geopolitical strategists get concerned about as well. So, how does that impact the future of the industry, in your view? 

WEN SHI: Yeah, so there are a couple things there. Artificial intelligence, the use of machine learning and other aspects as it pertains to drug discovery is a newer subject for us as biotech analysts, right? So, we didn’t study machine learning during our graduate programs. But what we are really learning is from Wellington’s internet and software analysts, so for example, there is this really well-known program that can help companies figure out what do the proteins, or what do the disease targets in the body look like, based on the sequence of those proteins. So, we were just meeting with one of the biotech companies, and they recently obtained a license to the software that can make an almost impossible task possible, over a period of days to weeks, right? So that really has the potential of accelerating the drug discovery process. There are a couple key inputs into that process. So first, the algorithms are improving. And second, the data sources that input into the process are also improving. So, as you probably know, for anything that’s data analytics, it’s like garbage in, garbage out, right? So, the data source is also improving, and finally computing power, has been sort of really exploding astronomically, right? So, these are the factors that will likely make it more tractable to incorporate machine learning and AI into the drug development process, right? So, that’s one part of your question. And the other part, as it relates to the bioterror, or geopolitical stuff, that again is a new area for us. We didn’t quite study the geopolitical tensions, or the great power competition in our graduate programs, as you might imagine. And this is something that we’ve learned a lot from people like yourself, and trying to be more aware as well as what the Department of Defense or some of the other national security folks are paying attention to, right? So, that frankly has not been a main topic of conversation, but I could envision that. It’s sort of these two different groups of people who are maybe coming at this from different angles and they’re not necessarily talking to each other. 

THOMAS MUCHA: Yeah, I would agree with that. I think the biotech piece of this in great power competition is in its early stages.

WEN SHI: Mm-hmm.

THOMAS MUCHA: But there is a recognition from the national security standpoint that it’s a very important industry, it does have these weaponized aspects to it, of course, but it also has much broader socioeconomic implications that are wound up with great power competition. And so it’s one of those industries that policy makers are seeing in a more strategic light. And I’m wondering, which of these geopolitical issues to you, you know, as a researcher, strikes you as being the most relevant? 

WEN SHI: I think from a biotechnology perspective, the US is by far the dominant player in the world. Right, not even Europe, right, not China. Because I think for the companies I follow, the most cutting-edge sciences anywhere in the world, I would say 80, 85 percent, if not 90 percent, are localized in the US between Boston, Cambridge, and the West Coast, right? So those are really the two hub for our sector. Regarding the role of China, so as you probably know, during the most recent five-year plan, the life sciences, the biotechnology sector has been emphasized by the Chinese government as a focus area together with other areas of leading technology. I think in the 2015 timeframe, and since then, there were a number of policy improvements that favor the biotechnology industries. As for example, how easy is it to get the drug approved by the Chinese equivalent of the Food and Drug Administration. Right? How much are these novel drugs paid for? As well as the funding and other kind of scientific support, and etc., right? So, there was a huge flow of both capital and talent into the biotech sector between 2015 and 2020. However, I think some of those policies have reversed, which is also analogous to the reversal of the policies in other sectors, such as the internet, education, right? So, you will see that there has been some tightening of how these drugs are paid for, for example. So, I think the Chinese biotech sector, which I followed for seven years had a pretty good run, but at best, they are at a stage that they could compete, or they could do a me too, or me better, of some of the latest technologies in the US. But I have seen very few example of something directly originating from China that’s best in the world. Right? So, they’re not there yet. That’s probably going to take 10 years because the biotech innovation is a long cycle business. And it’s harder to copy than even semiconductors, I always say.

THOMAS MUCHA: So, one of the issues in the US/China great power competition, in these advanced industries like biotech, like semiconductors, like advanced communications, like space technologies, is this idea of mutual dependence, right? Supply chains that are integrated and researchers that go from one country to the other. What are the connections between the US and the Chinese biotech sectors? 

WEN SHI: Yeah, so I think there are a couple different components. So, for the US biotech industry there was a tremendous excitement in the last couple years and there are hundreds of companies being formed, a lot of which is in virtual formats. So, they have a couple people, and then they draw up some plans, and then they send it to China. And then those companies will send those drugs back and then they will send to some other companies maybe in China or elsewhere to test those in the animals before these drugs are taken into human testing.

THOMAS MUCHA: So, they’re in the supply chain, in the R&D supply chain.

WEN SHI: So, they are in the R&D supply chain. So, late last year, when one of these Wuxi companies was put on the US government unverified list there was a lot of nervousness, or concern, by the biotech companies in the US as to what does that mean exactly? We have to go to the internet, we have to talk to you to figure out what’s an unverified list, what are the implications, and then we are concerned that if the geopolitical tensions worsen in the coming years, then does that mean similar companies are going to be cut off from the US biotech supply chain? And then another example is that we have this other biotech company that’s making a rare disease drug for Pompe disease and this drug is in front of the FDA for a potential approval later this year. However, one of the problems is that this particular product is being made in Wuxi, China. And because of the COVID lockdowns, and because of other issues, it’s been next to impossible for the FDA to send somebody to the plant in Wuxi, and to inspect it, and make sure they’re doing a proper job. As a result, I think the approval of this particular product by a US biotech company is getting delayed and then we don’t even know if they’re going to be approved this year or not. There are other examples, other companies, that are trying to license products that are already developed or approved in the US and try to develop and commercialize that in China. I think in the last few years, it would have been a win/win situation because the US biotechs are never going to set up shop in China because they don’t have the money and capabilities, and then these other companies the in-licensers, they will come in and they know the people on the ground, they have good relationships with the agencies in China, and they can commercialize it. And then because of the geopolitical tensions, there are concerns whether this business model is going to continue to exist five years from now. So, I think these kind of companies are also suffering. And then in the third bucket, we have multinational companies. So, these are some of the pharmaceutical companies, as well as large biotechs that have operations in China, and because of some of the not so favorable reimbursement policies in the last year or so, these companies are sort of curtailing their investment in China as well. So, for example, big companies that used to get a lot of their growth from China, but now China is falling down the list in terms of their contributors. 

THOMAS MUCHA: So, it’s an example where geopolitics is making the sector more complex, more research inputs for you, for me, for other people around the firm. I do want to ask you about your research process and philosophy. I mean, how do you approach such a complex subject, and how do you apply those insights that you have in the investment context? I mean you mentioned you talked to lots of people around the firm. 

WEN SHI: Sure.

THOMAS MUCHA: But what’s, what’s your sort of secret sauce? 

WEN SHI: So, I think as biotech analysts our North Star is that the companies need to develop drugs that work and that will address significant diseases and alleviate human suffering. It sounds very simple. I think having drugs that work and are meaningful, that’s the most important, that’s our checklist one, two, and three. Because the drug needs to work, it needs to be paid for, and then there needs to be large enough market in which it’s going to garner sales despite any current or future competition, right? So, the way we look at this is that we will be digesting the scientific literature, we will understand how the disease are treated, we understand where the unmet needs are. And then how does the new technologies and how does the clinical programs of these biotechs, how do they address those unmet needs in important disease areas. So, whether it’s cancer, or diabetes, or Alzheimer’s, etc. And basically, we make a judgment as to whether we think this drug is going to work or not and whether they’re going to make an impact. And then there are certainly other factors in terms of the track record of the management team, in terms of the balance sheet, etc., right? But again, like I said, the North Star is drugs that work.

THOMAS MUCHA: So, it starts with the science, marry it with the market opportunity -- 

WEN SHI: Yes.

THOMAS MUCHA: -- and then layer over the business aspects of it? 

WEN SHI: That’s exactly right.

THOMAS MUCHA: Okay. Good, well how does working at Wellington then impact that philosophy? 

WEN SHI: In my opinion, the Wellington healthcare franchise is one of the strongest investment franchises in the world. It really started under a gentleman named Ed Owens, who worked at Wellington for more than 30 years, and he had this tremendous track record of investing in overall healthcare that even though his tenure predates mine, we all learn a lot from him. And then it gets carried over to his disciple, who’s Jean Hynes, right? So, Jean again has been with Wellington for 30-plus years and even though she’s now the CEO of Wellington, she still is heavily involved in terms of managing assets for clients. And then on the biotech side, I learned a lot from Dr. Bob Deresiewicz, who used to be a professor at Harvard Medical School, and he really sort of trained us all we know about the drug development process, and how to assess biotechs. I also think that we have very strong access to management teams of any healthcare company around the world, whether it’s for therapeutics or for devices or for service companies and payers, right? So, we have a holistic understanding of the entire healthcare landscape. And to layer on top, we get a benefit from macro strategies, we benefit from other generalist portfolio managers and technicians, and others within the Wellington ecosystem to help us understand the broader market landscape. So, for example this year, as you know, with the Fed tightening, so we understand that this is a sort of good macro environment for defensive sectors such as the pharmaceuticals, right? So, we have been able to communicate that and work with a range of stakeholders within Wellington to communicate our ideas. 

THOMAS MUCHA: Great. I want to dig in a little bit more to your research process and, you know, obviously it’s been an extraordinary two and a half, three years for all of us. And I’m wondering, you know, how has COVID, how has the way this pandemic has played out, how has that impacted your long-term views on biotech? 

WEN SHI: Yeah, so one silver lining from the tragedy of COVID is that we know the biotech industry is critical for society. Everyone knows about the messenger RNA, or mRNA vaccines nowadays, right? So, we have the Comirnaty, we have Spikevax. Both of which came out of biotech companies. So, we have been following these companies for close to 10 years since their inception. And we know that these mRNA technologies, they didn’t just come out of nowhere. These technologies are built on a decade-plus of insights and, and experiments, and painstaking work, a lot of false starts, a lot of detours and failures, such that they are able to come up with a way to create a vaccine that’s packaged in a ball of fat and can deliver that into a billion human beings around the world and to elicit just the right amount immune response that mimic the virus without causing too much side effects. If you imagine the way that these vaccines were developed, right, I think the process started in January of 2020, and then the vaccines were put into people’s arms by the end of the same year. 

THOMAS MUCHA: Tremendous.

WEN SHI: Right? So, that is almost a miracle. And the one thing we learned is just how important the sector is and how important having a vaccine capability is, and most of which actually resides in the biotech sector. 

THOMAS MUCHA: And how applicable do you think these learnings will be to future diseases? 

WEN SHI: Yeah, of course we hope that we’re not going to deal with another pandemic any time soon or hopefully not in my lifetime or any of our lifetimes. But having the capabilities and this mRNA technology, again, you can turn around something very quickly for any kind of new emerging virus, whether it’s the monkeypox virus, there is the potential of doing something very quickly, and to update that on an annual basis, should the virus mutate. 

THOMAS MUCHA: You mentioned monkeypox, that’s obviously in the news. How concerned are you about that? 

WEN SHI: Yeah, so we are paying close attention, and so far we are not terribly concerned. This is very different from the SARS-CoV-2, which causes COVID, and the monkeypox virus is much bigger, it doesn’t spread as easily, you require close, personal contact, sexual or not, for transmission, right? So, it doesn’t have too much of the aerosol spread, like COVID does. And then more importantly, there are existing therapeutics and vaccines that are mostly approved for smallpox, which is a closely related virus, and then these are in the stockpiles, so should there be a bigger outbreak there are already tools available that we don’t even need to start from scratch.

THOMAS MUCHA: So, it has a scary name, a scary connection to smallpox -- 

WEN SHI: Yeah. Exactly. 

THOMAS MUCHA: -- but we’re not that, too worried about it right now?

WEN SHI: So far we are not as alarmed as we were back in January and February of 2020. 

THOMAS MUCHA: I’m going to hold you to that, Wen. 

WEN SHI: Mm-hmm. Well, we’ll talk in a month and we’ll see.

THOMAS MUCHA: Okay. So, I’m going to start to wind up the conversation with a few more like, personal questions about your journey, about your position here as a researcher. So, you know, you mentioned a long, sort of pedigree that Wellington --

WEN SHI: Mm-hmm.

THOMAS MUCHA: -- has of healthcare investors. How did you end up as one of those people? What was your path? 

WEN SHI: I have been interested in healthcare and treatment of diseases, and particularly cancer, since I was a teenager. And because of family reasons, family members affected by cancer. So that made me want to pursue an undergraduate major in biology at Johns Hopkins and that subsequently led to a post-graduate degree at Oxford University funded by a Rhodes Scholarship. My main goal was and has been to help develop therapeutics for serious diseases such as cancer. However, I quickly realized at Oxford that maybe the lab route was going to take forever, and I wasn’t making as much impact as I wanted. I made some pivots, so I was doing consulting for biopharmaceutical companies for a period of five years, and then I transitioned briefly to sell side research in biotech, and then I’ve been at Wellington since 2015.

THOMAS MUCHA: So, you feel like you can make an impact more quickly as an investor in these? 

WEN SHI: Yeah, so we really have a very privileged position overlooking the entire biopharmaceutical industry and then we have been involved in all sorts of biotech companies I talked about, and versus some of the smaller ones really, companies are raising private rounds, and they are just getting created, so we have a hand in terms of pushing forward some of these therapeutics into human testing, and into clinical development eventually of approval by the regulators and helping patients. 

THOMAS MUCHA: So Wen, another thing we like to do on this podcast is to highlight books that have had a big influence on our investors. I’m wondering if you have any book recommendations for our audience? 

WEN SHI: So, as an investor, one of the things I’ve been paying more attention to is the psychological aspects of decision making. In that context, I recently read two books by the Princeton psychologist Daniel Kahneman, and one is called Thinking Fast and Slow, and the other is called Noise. And these two books are instrumental in terms of helping me, maybe just be more aware of some of the cognitive biases, to be aware how the decisions are made, how inconsistent the process could be, right, which is what the second book, the more recent book Noise is about. And then how we can arrive at a better outcome, be consistent in our decision making for our clients. 

THOMAS MUCHA: Excellent. You know, Kahneman, I’m a big fan of his, as well. So last question, Wen. If you weren’t a healthcare investor at Wellington, obviously you’re a very talented person with a very rich and deep background, what would you be doing?

WEN SHI: That’s funny enough, so I’ve had this 30-year hobby of following international events, current events, and which in the more recent period will be geopolitics. So -- 

THOMAS MUCHA: So, basically you’re coming after my job.

WEN SHI: -- I think in an alternative timeline, I could be the geopolitical analyst at Wellington. 

THOMAS MUCHA: Yeah, I can attest that Wen writes very intelligent notes about geopolitics, which I read quite frequently. So, I appreciate that. 

WEN SHI: Thank you. 

THOMAS MUCHA: So, Wen, thank you so much for being a part of this. Thank you for what you do for Wellington. And it’s been great having you on the podcast. 

WEN SHI: Yeah, thank you so much, and I hope this was helpful. 

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Views expressed are those of the speaker(s) and are subject to change. Other teams may hold different views and make different investment decisions. For  professional/institutional investors only. Your capital may be at risk. Podcast produced June 2022.

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In Singapore, this material is provided for your use only by Wellington Management Singapore Pte Ltd (WM Singapore)  (Registration Number 201415544E). WM Singapore is regulated by the Monetary Authority of Singapore under a Capital Markets  Services Licence to conduct fund management activities and is an exempt financial adviser. By accepting this material you  represent that you are a non-retail investor and that you will not copy, distribute or otherwise make this material available to any  person.   In Australia, Wellington Management Australia Pty Ltd (WM Australia) (ABN 19 167 091 090) has authorized the issue of this  material for use solely by wholesale clients (as defined in the Corporations Act 2001). By accepting this material, you acknowledge  and agree that this material is provided for your use only and that you will not distribute or otherwise make this material available  to any person. Wellington Management Company LLP is exempt from the requirement to hold an Australian financial services  licence (AFSL) under the Corporations Act 2001 in respect of financial services provided to wholesale clients in Australia, subject to  certain conditions. Financial services provided by Wellington Management Company LLP are regulated by the SEC under the laws  and regulatory requirements of the United States, which are different from the laws applying in Australia.  In Japan, Wellington Management Japan Pte Ltd (WM Japan) (Registration Number 199504987R) has been registered as a  Financial Instruments Firm with registered number: Director General of Kanto Local Finance Bureau (Kin-Sho) Number 428. WM  Japan is a member of the Japan Investment Advisers Association (JIAA), the Investment Trusts Association, Japan (ITA) and the  Type II Financial Instruments Firms Association (T2FIFA).  WMIL, WM Hong Kong, WM Japan, and WM Singapore are also registered as investment advisers with the SEC; however, they will  comply with the substantive provisions of the US Investment Advisers Act only with respect to their US clients.  ©2022 Wellington Management Company LLP. All rights reserved.