Business Of Biotech
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Business Of Biotech
BoB@JPM: Ran Zheng, Landmark Bio
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Ran Zhang was hire number one at Landmark Bio back in 2021. Today, she's CEO of the 70+ employee cell and gene therapy manufacturer. We caught up with her and Life Science Leader chief editor Ben Comer at the JP Morgan Healthcare Conference in San Francisco for a discussion on Landmark's role in addressing the ATMP patient access and cost reduction challenges. Along the way, we cover innovations in distributed manufacturing, non-viral gene delivery, and the importance of collaboration with academia to make these transformative therapies widely available.
The 2025 BoB@JPM series is supported by Alston & Bird, whose national health care and life sciences practice has more than 100 attorneys actively involved and integrated across the full spectrum of legal disciplines including regulatory, compliance, public policy, transactional, corporate governance, securities, FDA, biotechnology, intellectual property, government investigations, and litigation practice areas. Learn more at www.alston.com.
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Ran Zheng had already built a storied career at Amgen when she took the biotech dive with Orchard Therapeutics, where she served as CTO for a few years before being tapped on the shoulder as hire number one at Landmark Bio in 2021. I'm Matt Pillar and I'm Ben Comer, and this is the Business of Biotech. Jp Morgan edition.
Ben Comer:We're here in San Francisco with Ran for a talk on how she's applying a diverse history of biologic therapeutic development experience to her role at Landmark building and deploying next-generation cell and gene therapy manufacturing technology. Ran, thanks for joining us. And it's Deploying Next Generation Cell and Gene.
Ran Zheng:Therapy Manufacturing Technology, ran. Thanks for joining us and it's great to see you. Thank you very much, pleasure to be here.
Matt Pillar:It's a pleasure to have you here. I know it's a very busy week for you, so I appreciate you coming along to spend some time with us, and I want to get the show off the ground here by talking a little bit about you specifically. As I noted, you were Landmark's first hire, which is pretty cool. I'm sure there's a pretty interesting story there because the company's grown substantially in subsequent years. But what were you doing prior and why did you kind of take that leap to Landmark?
Ran Zheng:Yeah, great question. I have been very fortunate to work with a great group of people at a great company. I spent six years at Amogen, worked in different products in different functions. The last few years, while I was with Amogen, I had opportunity to touch on some unique modalities neoantigen oncolytic virus, srna. I was awestruck by this new class of medicine and the transformative potential those medicines can bring to patients. I worked on a lot of biologic products. Most of them are treatment, not cure. Some of the cell and gene therapy products have a curative potential and they're once and done and allow patients to live normal life. It's just amazing and I want to see more of those products on the market. And I also observed some gaps in the development and the commercialization of cell and gene therapies in the development and the commercialization of cell and gene therapies and I thought a lot of what we have learned in biologics, development and commercialization can be applied to this field and help accelerate the development.
Matt Pillar:Yeah, many of those gaps, ramin. I want to pause there for a minute and talk about some of those gaps. Many of those gaps remain gaps around manufacturability for one, but then beyond manufacturability when we get past that hurdle distribution administration did you feel like Landmark might give you an opportunity to play a role in kind of addressing those challenges too?
Ran Zheng:Yeah, you know, maybe I will also pause a moment and to maybe kind of recap and regroup my thoughts here yeah, regroup my thought here. So I wouldn't call it a landmark bio. Give me the unique opportunities. Maybe what I could just anchor on what a landmark bio was set up to do is to remove some of the bottlenecks in the early days of cell and gene therapy development. In the early days of cell and gene therapy development, and the opportunity we have there is not just from the technology perspective but also really partner with other companies to help address some of the challenges we have seen in this space.
Matt Pillar:So maybe what I can you know, if you can just let me know what some of your questions are. Oh, I know I pulled that one out of left field.
Ran Zheng:No, no, no, I have not seen the briefing because I know Kathy decided that you have some briefing but I didn't get a chance to. Oh, that's all right, that's okay, yeah.
Matt Pillar:Let me ask you this so you left Amgen for Landmark, Landmark being a startup, Was there any trepidation or concern around making the jump from such an established company to? I mean, I understand the intent.
Ran Zheng:Right, right, yeah, no. Well, lamar Bell is not my first startup company. Okay, so you would yeah yeah, so it was actually the third startup company, but the second after Amogen Experience. Vulture Therapeutics was also a young company. When I joined, I wouldn't call it a startup. It has about 150-ish people maybe when I joined so, but it's much smaller company.
Ben Comer:What did bring you to Landmark Bio? Did you know Alan Garber before joining? How did you land there?
Ran Zheng:I don't know Alan Garber.
Ben Comer:You don't.
Ran Zheng:No, I don't, so it was probably a cold call from a recruiter, but I have read the initiative so I learned a little bit about what they try to do. I thought they have a very unique value proposition and it's great purpose and they're trying to do something to close the gaps and I'm willing to help.
Ben Comer:Yeah.
Ran Zheng:Yeah.
Ben Comer:You also, I think, worked to improve the manufacturing function while you were at Amgen. Correct me if I'm wrong. Were there learnings while you were at Amgen? Correct me if I'm wrong. Were there learnings that you brought from Amgen to your positions after that, including Landmark?
Ran Zheng:Yeah, I started at Amgen as a process development scientist and I worked in different functions in PD, manufacturing, quality and supply chain. There are a lot of learnings in biologic development, particularly in the CMC space, and many of those learnings are applicable, including understanding of applicable, including understanding of products and understanding the quality attributes. Understanding how the processes affect those quality attributes and ultimately potentially impact the outcome of the products is very important. There are a lot of fundamental learnings that we have gained over the past two decades are applicable to this new field. So that's why, when I joined Landmark Bio even though the company is very much oriented towards bio manufacturing to provide services and to partner others, I have built a team with people who come from the pharmaceutical industry, have done years of work in development and commercialization of biologics and commercialization of biologics.
Ran Zheng:Because not just the experience in development, but also understanding how the development should be done.
Matt Pillar:Yeah, is it the fundamentals that best translate? I'm curious because I hear this frequently. Like you know, we can't. As we improve the cell and gene manufacturing paradigm, we should lean into things that we've learned along the way in more traditional biologics. Is that sort of a you know, stick to the fundamentals conversation, or are there specific, I guess, process or manufacturing steps or lessons that translate from things like antibodies and vaccines to the cell and gene manufacturing?
Ran Zheng:Yeah, you know we're getting deep in that space, right? So there is a fundamental kind of principles on how to develop a manufacturable process. We're talking about the manufacturability of the process, the scalability of the process and the transferability of the process. Those fundamentals are the same. The principles are the same, it's just a very different modality. You have to apply the principles and maybe understand your modality and go from there yeah from there?
Matt Pillar:Yeah, what would you say if you looking back on the past four years at Landmark? How would you sort of characterize or quantify the progress that Landmark has contributed to addressing some of these challenges?
Ran Zheng:Yeah, so two of the unique major challenges in cell energy and therapy space are first, one is the logistical challenges, what we call logistical challenges for patients. You know, eight out of ten patients who are eligible for CAR T therapies are not able to get to the CAR T therapies because they just don't have the access. The second challenge is probably more on the company side, on the business side, the financial challenges. It takes a lot of capital to develop, manufacture, deliver the products, but with the high cost of manufacturing, cost of goods that translates to a lower margin and lower return on investment. So I think that challenge is needed to overcome so that the therapies can benefit more patients. So what Landmark Bell has done in the past few years since its launch is you know, this is public knowledge we partner with Galapagos, a European cell therapy companies, and work with them to establish distributed manufacturing Network. We are their first bio manufacturing partner in United States and the goal For distributed manufacturing is to make the CAR T products close to where patients are Many US patients even today if they want to get access to CAR T products. Close to where patients are. Many US patients even today if they want to get access to CAR T products and they have to travel to where the treatment centers are established, usually in major cities like Boston, san Francisco, new York City. But if you live in some other places it's difficult for a patient to get the treatment Distributed. Manufacturing make the products closer to where a patient lives so patient can receive treatment close to where they live. So I think that's one thing that we have been working with them for a couple of years a little bit over a year now.
Ran Zheng:The second challenge we're talking about is how you could reduce cost of goods, cell and gene therapy.
Ran Zheng:Today most of them are exovagal cell therapies.
Ran Zheng:They take materials from patients or donors, their cells and doing gene modification and give back to patients, and that process is very complex.
Ran Zheng:They also deal with live cells and the product is also very complex. There are a lot of constraints in the supply chain that all lead to higher cost of goods and a lower net margin, which is challenging. And if you can only imagine that there's a way to turn the complex ex vivo cell products into something more like biologics and you can give patients just like biologic injectables or IV products, and how many more patients would be able to benefit, how much lower the cost of products that could be. So one of the technological innovation area that we have been focusing on is non-viral gene delivery to be able to achieve this kind of in-vivo CAR-T, to be able to achieve this kind of to leverage a human body to make the products inside of the human, to lower the cost of goods this may be a very naive question but theoretically when I think about distributed manufacturing it occurs to me that that would actually exacerbate in some ways that cost of goods and cost of distribution supply chain issues.
Matt Pillar:It seems like it would exacerbate that problem like make it worse, because now we're taking a few manufacturing nodes and multiplying them across the country. How do you rationalize that?
Ran Zheng:Yeah, that's a great question. If you don't have the technologies to support that kind of distributed manufacturing network, that could increase cost of goods. That could increase cost of goods. So the manufacturing technology platform and the supply chain platform Galapagos has deployed allow manufacturing process to be very efficient and it's very easy to tech transfer. It's a closed process, seven-day win-to-win electronic batch record so you manage information data flow electronically. Everything is standardized. So I definitely see that it's not your yesterday's distributed manufacturing where everything is, you know, manual and less standardized, because it's highly platformed and it's standardized. It will reduce the errors through the transfer. It will help reduce the human errors, improve the consistency. Of course this is something that's very new and we will have to see in the next few years how that will work out, but we're very optimistic for that.
Ben Comer:Yeah, when distributed manufacturing, is that satellite manufacturing, centers that are more spread out? Is it actually on site, like at a health care delivery center, where that happens?
Ran Zheng:Yeah, no, it's not at the bedside yet. It's in a GMT manufacturing facility that's close to medical center.
Ben Comer:And those are rapidly expanding in number at this point, or is that the goal eventually? Well, the goal eventually is to establish many manufacturing capabilities near the medical centers where you can make the products. And if you can standardize that process and make it really efficient to your point, then that's how you get around raising the cost of goods, yeah, okay.
Matt Pillar:When you addressed that you talked about the process development, often a gap in early stage processes coming out of academia needing to be sort of redeveloped when they make clinical progress, much less commercialization progress. A little bit about that like how does, how has landmark contributed to the, the academic exercise of, you know, moving from academia to a commercial, commercially viable business, and is that driven by industry or is academia driving that as well? Sort of what's the lay of the land there?
Ran Zheng:Yeah, you know what we have seen in this field in the past 20 years, particularly in cell energy and therapies. The innovations almost exclusively always started in academic centers, where small biotech companies were the science drive, how the products have been developed and made, but not a lot of considerations If you have to make the products not only for one patient, two patients, but hundreds, thousands, millions of patients. So what we have seen a lot of early cell and gene therapy products are based on laboratory protocols that could work, you know, for a fewer number of patients, but it does not drive consistency and word robustness and that will lead to some repeated work later on. So what we have seen is that some early phase clinical trials conducted at an academic setting academic setting, the proof of concept, the clinical results is outstanding, but the process is not robust enough and is not suitable for larger clinical trials or commercialization. What they end up to be is that you repeat those clinical trials and that is a lot of waste, A lot of money, A lot of money and a lot of time right.
Ran Zheng:So what we do is that we work with the principal investigators from academia or the startup companies. We help them to understand what is the ultimate goal for the development is to bring this drug to market and in order to do that we need to make sure that the processes of manufacturing the products is robust and can deliver reliable, consistent product quality. So, with that in mind, to design the manufacturing processes, the materials, and to source the materials, the starting materials for the manufacturing processes, starting materials for the manufacturing processes in the early days, so that you get some kind of standardization to make the process more suitable for commercial use, less changes that you have to make later on. That will reduce some of the kind of wasted work.
Matt Pillar:Our friends at Alston and Byrd set us up with some amazing space to record during JPM week. The firm's national healthcare and life sciences practice has more than 100 attorneys actively involved in the healthcare industry across the full spectrum of legal disciplines. The signature strength of this practice is its ability to master complex representations that draw on the coordinated expertise of its regulatory compliance, public policy, transactional corporate governance, securities, fda, biotech, ip, government investigations and litigation practice areas. Alston Byrd represents life sciences companies and their partners in corporate stages ranging from private to newly public to well-established, and in a variety of stages of product development, from preclinical to post-approval commercial launch. Learn more at alstoncom and tell them you learned about them. On the business of biotech themcom and tell them you learned about them?
Ben Comer:on the business of biotech, is that something you would characterize, I guess, as kind of landmark bios um sweet spot, being able to take a process in academia or a process in a small startup and help to standardize it and make it into something that could be scaled commercially. Do you see that as your kind of primary aim?
Ran Zheng:It's definitely one of the unique features for Landmark Bio and the competitive advantage for us as well. I probably mentioned a little bit earlier we we're in this space provide CMC services to a lot of our partners. The people that we build are most of them are from drug development companies, so this is an organization built by drug developers for drug developers, so we understand what it's really going to take to develop the processes, develop the product and get to the market. It definitely help our clients and our partners to minimize some of the I would say the pitfalls and the unfortunate errors that you know many others made in the early days.
Ben Comer:Yeah. Do the challenges faced by a cell or gene startup vary a lot, or are there some key challenges that you mentioned? You know, for example, non-viral vector delivery as something that I think you're working toward and it also represents a hurdle for the sector? Are there other areas that continue to be challenges that you know that developers and Landmark Bio are working to overcome?
Ran Zheng:There are a lot of challenges. First of all, cell and gene therapies are such a broad category we tend to lump them together, but cell and gene therapies, you know, including cell therapies, including gene-modified cell therapies, viral vectors. So there are some unique aspects of the challenges that different depends on the different specific modalities you know. For example, when we talked about the viral vector in the AAV space, the titer, the purity, you know, definitely is one of the challenges from the CMC perspective, but from efficacy perspective, the capsid and the design of the capsid.
Ran Zheng:There are a lot of unique challenges. We're certainly not doing everything to address all the challenges over there and we want to focus on the things that we believe that can move the needle. For example, we think cell therapy is going to stay. There are already blockbuster pathologist cell therapies are there. If we can make those therapies better and if we can manufacture them faster and cheaper, that will allow patients or provide better access to patients, just at least from manufacturing perspective. That's really our approach. We're very optimistic in the non-myogen delivery space because we truly believe if we can turn the complex product into a relatively simpler product, easier to manufacture, easier to deliver, that will really change the field.
Matt Pillar:Yeah, you're in an interesting space because in many ways you have a firsthand look at not just innovation but business volume right, and I've had a couple of conversations today with cell and gene therapy leaders who talk about sort of the ebb and flow of the economic interest, the finance community's interest in gene therapy. I guess, more specifically, what's your take on that from your perspective, given that you see, you know, you see the innovation firsthand, you see the volume of of interest in manufacturing services firsthand, do you have a good feeling, heading into 25, that business will be robust on the innovation and funding scale, or is there any cause for concern?
Ran Zheng:I am a firm believer of cell and gene therapies and the transformative potentials this class of therapies can bring to patients. And you know it's already beyond the proof of concept. Beyond the proof of concept, the challenges we're facing is from, from business perspective, is that, yes, we have seen the benefit on patients, but we want to see more patients being benefited by this new class of medicine. Look, the innovation has no value if it does not reach to patients. Yeah, um, I think that's that's really the fundamental challenges over there. Uh, right now, we want, we want this class of therapies to be able to reach broader patient population. Um, and in order to that, there are some technological hurdles and we have to overcome. But I I think the science is proven and it's validated in human. We know it works and we know it has curative, transformative potential and it's it's on us to make this work yeah, it's uh, it's interesting to me too.
Matt Pillar:Like you said, the cell and gene therapies is a sort of a basket term for a whole bunch of different approaches. How does a company like Landmark ensure that you have the expertise not just the capacity, but the expertise to stay on top of all this stuff?
Ran Zheng:yeah, yeah, um, we, we set up our business to have quite a broad capabilities, so we're not just focusing on cell therapies or gene therapies, so we have a capability using cell gene and messenger RNA, for a couple of reasons. One reason is we think this field is still early and the winners are yet to emerge. And we have seen the field moving from ex-vivo to in-vivo, because we think that's where the field is going. But we need to start in ex-v and we want to capture the current opportunities, but still with eye towards the future. And that's how we set up.
Ran Zheng:And there are a lot of spaces, a lot of areas we can innovate, and we definitely not try to do everything. And, as I mentioned, some places that we try to do everything, and as I mentioned that you know some places that we try to innovate, as a non, for example, non-viral gene delivery. We think that's the area that we should focus on because it address the underlying issues for cell and the gene therapy. You've got to be able to deliver the genetic material to the right cells and that's what we need to focus on.
Ben Comer:What sort of delivery materials I guess are leading the charge in that area to get away from viral vectors?
Ran Zheng:So we are looking into nanoparticle technologies. Lipid nanoparticle is one aspect. We also have other non-lipid nanoparticles. Is that?
Matt Pillar:does the innovation there, in terms of delivery vehicles, tend to happen from within, or is it largely influenced by the developers that you're working with? Innovation coming from the sponsor community?
Ran Zheng:Well, we have seen both, but in that space I think we see the opportunities that the sponsors would rely on their partners to bring the technologies. What we have seen more and more is that sponsors focusing on what inside of the particle, what inside that encapsulation which is the know, the design of the, the rna, the design of the dna and what the capability is we bring in, is more of how we could take those dna or rna or oligos and package them in a way that they can guide to the right cells and the right tissues.
Matt Pillar:Yeah, Do you have you noticed any particular, I guess, energy being devoted to developing delivery technologies that you know seek targets that are in places that were difficult or impossible to get to before, like the blood-brain barrier, different organs? Is there sort of a movement afoot there?
Ran Zheng:Yeah, you know, people try to deliver the targeted genes to muscles, to different cell types, because the current technologies, if you give the current lipid nanoparticle technology, you know formulations, most of them go to the liver. Lung is another space where I see a lot of development.
Ben Comer:Do you have a sense of the broad, I guess, cell and gene sector and how much it collaborates? And I'm thinking of, you know, 25 years ago with monoclonal antibodies, I think there were some companies at a kind of pre-commercial basis that would share knowledge and work together to try to bring that functionality forward. Is there a similar effort in cell and gene that you're aware of? I mean, is Landmark Bio working as a convener of sorts between different companies and helping to fill those gaps?
Ran Zheng:Yeah, we're part of the Ningbo, which is a consortium. They have a lot of initiatives in cell and gene therapy space. You know a lot of work being done in a V space. It's a pretty competitive space where people can share knowledge and experience.
Matt Pillar:Okay yeah, yeah. What are you most excited about in terms of the cell and gene space? You talked about your excitement for the transformative. You know opportunity, right, the patient opportunity in cell and gene, leading you to Landmark. Now you've been there for four years, looking ahead, you know, another four years perhaps, or even a year. What are you most excited about?
Ran Zheng:The opportunities ahead of us. I'm very excited about the opportunities in front of us where we can really make a difference. It took about 10 years to have a blockbuster of monoclonal antibodies early days and we already have a few blockbusters of cell and gene therapy on the market and start benefiting patients, and that is very exciting for us. And also the amount of innovation in this space. What we have seen is unprecedented. That is something. Also, the amount of innovation in this space. What we have seen is unprecedented. That is something that we're very excited about. Yeah, yeah.
Ben Comer:What are your goals for JP Morgan, if you have any that are specific to this conference?
Ran Zheng:My goal for JPM week is really to connect with the industry, peers, the colleagues, potential partners and collaborators, exchange ideas, explore collaboration opportunities and really discuss the trend of where we're going as an industry, as a sector. It's a very exciting week.
Matt Pillar:Yeah, where did you come in from? Are you right? Are you in the San Francisco area?
Ran Zheng:No, I am based in Boston, but I also have a house in Southern California.
Matt Pillar:Okay.
Ran Zheng:Yeah, so I actually came from the LA area, okaya area.
Matt Pillar:Okay, yeah. Well, this episode will drop more than likely sometime in February, so a few weeks from now. But as we sit right now, things aren't looking that great in LA. I'm hoping that everything's okay in your neighborhood.
Ran Zheng:Yeah, everything's okay in my neighborhood.
Matt Pillar:We're fortunate, but it's very challenging time, I'm sure yeah yeah, well, safe travels and thank you for spending, like I said, some of your very busy week with the business of biotech. I I appreciate you coming on the show and it's uh, it's great to get insight, like I great to get insight from uh, a leader in the cell and gene manufacturing space, given all the questions and challenges that are ahead, so we appreciate it. Thank you very much for having me. So that's Landmark Bio CEO Ran Zhang, I'm Matt Piller and I'm Ben Comer, and you just listened to the Business of Biotech from JPM 2025.
Ben Comer:Biotech from JPM 2025. Listen and subscribe whenever or wherever you listen to podcasts or take in our video casts at Bioprocess Online and Life Science Leader. Thanks for listening and see you next week.
