LabOps Leadership_Behzad Mahdavi: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.
Kerri Anderson:
By building a platform to share challenges, thoughts from leaders, and network together, the LabOps Leadership Podcast is elevating LabOps professionals as well as the industry as a whole.
Samantha Black:
With the intent of unlocking the power of LabOps, we deliver unique insights to execute the mission at hand, to standardize LabOps, and empower LabOps leaders.
Kerri Anderson:
I’m Kerri Anderson.
Samantha Black:
And I’m Samantha Black. Welcome to the LabOps Leadership Podcast.
Samantha Black:
Great, Behzad, thanks for joining us today. We’re so excited to have you here today.
Behzad Mahdavi:
Good morning, Samantha, and thank you very much for having me on your platform.
Samantha Black:
Great, well, I’m excited for this conversation and I know it’s going to be really interesting and you have a great wealth of experience. So let’s jump right in, and can you just start off by telling us a little bit about your background and how you got to where you are today?
Behzad Mahdavi:
With pleasure. My background is very simple. The best way to describe it is thinking about a triangle with three equal sides. On one side you have the innovative disruptive technologies, on the second side, you have market …, and on the last side that you have a finance. My expertise which happen to be also my passion is the operating inside of this triangle and consists on the creating, implementing, and operating impactful technology-based growth strategies to open new segment of the market for companies. The fourth dimension that I have added to this triangle during my career, whenever it was possible and applicable was being patient-centric, meaning during your daily work with having patient in mind as a final user and this patient can be yourself or your children or one of your family member. I have operated in this four-dimensionalal space for more than 20 years in a various position as executive, CEO, chairman of the board, member, investor, but also as entrepreneur, and founder. I have worked both for a large organization like the … CRIBIQ, Lonza, Catalent, as well as the smaller one, including the startups like Exosomics, Electron Technologies in various life sciences field ranging from early cancer detection to biopharma with high focus on the cell and gene therapy and manufacturing of new modalities. I joined Ginkgo as a SVP of the BioPharma Manufacturing and Life Science Tools last August, leading Ginkgo commercial effort in the growing areas of bioreagents, cell and gene therapy, and new biopharmaceutical. On the educational side, I have studied in France, where I completed my chemical engineering school and master’s degrees and then completed my PhD in electrochemistry in Canada along with the MBA to will cover different sides of the triangle that we just talked about. So that’s a is a simplified version of me in a nutshell.
Samantha Black:
I love that, I’m going to have to steal that model for describing my life, I love that. So can we just take a step back and talk about the patient-centric approach? So in like the clinical sciences and more of the downstream medicine, we hear this term a lot, but I think it’s kind of unique in the bio tools space for somebody to have that as a main focus of theirs. Can you talk a little bit more about how specifically you’re patient-centric in designing tools, biological tools, when maybe you’re further away from the patient than, say, somebody in medicine or somebody in clinical science?
Behzad Mahdavi:
No, this is a very good question, actually. So the importance of patient-centric is bringing a …, a degree of care and precision in what you are doing every day because a patient is involved at the end, but also unbelievable motivation and satisfaction on a daily basis, especially when you see the result of your work. Maybe the best example I can give you here, I remember that I felt very strongly, actually, this satisfaction and this connection, when, first, the four patients were treated successfully at the Sheba Medical Center with a CD19 CAR T-cell therapy manufactured using the laws of fully automated cocoon manufacturing platform that had initiated and built your strategy passionately when I was at Lonza. So even it was a true luxury, so you are not asleep during the clinical studies, but you are getting basically what you are developing at one point in contact with the patient, and that’s basically the implication of that is. So you have always have in mind basically what you are doing at one point when you touch the patient, what would be the impact of that? And that’s, as I said, bring you another dimension to what you are doing, which is very valuable.
Samantha Black:
Yeah, I think that’s incredible, and I think with the technologies that exist today, we’re seeing that cycle shorten, and you can actually, in some parties’ lifetime or several times throughout somebody’s career, we can have these moments of connection to the patient, and I think that is truly incredible, and like you said, it’s a huge motivation so I just love that perspective, and I think it’s something that’s also really important to keep in mind, so that’s awesome. Let’s focus in on what you’re doing today, though. So can you talk a little bit about what Ginkgo’s doing and what problem they’re trying to solve in the pharmaceutical industry, and maybe some of like the big approaches that they’re taking to solve those problems?
Behzad Mahdavi:
Yeah, it’ll be a pleasure. So Ginkgo is a fascinating company and addressing two of most critical industrial problems in drug discovery and manufacturing. But let’s talk about the, this issue and how we address them at the Ginkgo. First, we see the industrial trend is changing somewhat in regards of new therapeutic modalities. If we travel back in time, we notice the addition of new therapeutic modalities in pharma is accelerating tremendously. We were adding an average about three new modalities every 20 years, but what, we are now about to add the triple of this amount in the next five years. So let’s think about that. If you go back 50 years ago, we had the small molecules, a vaccine and natural medicines, 30 years later, we added the peptides, the monoclonal antibodies and other recombinant protein. In the last 20 years, we added the CAR-T, viral vector, gene therapy, and mRNA. And now suddenly the next five years we will add microbiome, allergenic cell therapy, multispecific IPSC, …. drug conjugate, in-vivo expression, gene editing, and the exosome as the latest newcomer. So one in each of these … varies in term of the maturity and the growth potential, in all the cases, they are built on advanced complex biological system, and in most of the cases, artisanal manufacturing processes are involved far from industrialization and more closer to art. So therefore what we see basically in the industry, in this new cycle of the modality trend, with the faster growth, more biologically complex, a shorter period of development time before getting to the market, and therefore, limited time to understand and optimize the biologic component of the drug, causing the high cost of the manufacturing and difficulty to manufacture at the scale. Immediately … more, you know, what I mean by this biologic optimization is that in the massive design space you have a number of the combination design that can give you either a better therapeutic efficacy and therefore you need less to manufacture as you need lower dose or it gives you the same efficacy, but the easier manufacturability or sometimes both actually. But we know that the biology and biological optimization is an extremely complex process requiring designing, building, testing, analyzing, and learning sometimes millions of the robust and the complex experiment in a relatively short period of time. So as a result, the pharma industry, due to the absence of a proper platform, has largely neglected this opportunity. And in focusing on the speed to market by splitting biologically on optimized therapies but yet efficient compared to a standard of care to the market. So these therapies then are being put in the hands of the CDMOs who are asked to produce a greater quantities and lower cost but be limited the traditional tool at their goals. And that is where basically we end up with the cost of manufacturing for these therapies in the cell and gene therapy ranging from a few hundred thousand of dollars to millions of dollars per dose. I remember actually, Peter Mark said, the director of the FDA’s Center for Biologics Evaluation and Research, recently characterized the very likely reimbursement as the 800-pounds gorilla in the room to show the importance of cost management for the future of the cell and gene therapy. Now, let’s come back actually, and see basically how Gingko will address, basically, this problem that I have just described. So what we have done, we have invested and built hundreds of thousands of square feet of integrated robotic lab space at Seaport in Boston, where we can run for our partners’ workflows consisting of highly automated, high throughput, highly personalized biological experiment supported by the most advanced and innovative technologies so we can run millions of intelligent, iterative design, build test, learn cycles, enabling the rapid prototyping optimization and development of advanced therapies in real manufacturing settings. This infrastructure and installation, combined with pragmatic and machine learning, fed with the real experimental data over the last decades, allowing to have a better understanding of the biological design space and the pretty fast to get to an optimized therapy to deliver optimal desired function. So that’s the first problem we try to solve. I can maybe go to the next problem, actually, in the industry, but maybe pause here to see if there is any question on the first one.
Samantha Black:
Yeah, no, I think that’s a very relevant problem that you are trying to solve, and a very difficult one. I think the economics of these new therapies is not solved yet, so I think that as many people working on this problem as possible is worthwhile. And I think, I could put on my scientist hat or I could put on my patient hat, and I think for our listeners, we talk about personalized therapies or these advanced therapies that are targeted to one patient or a limited number of patients, so the first thing that comes to my mind is safety. So you’re working on hundreds of different things instead of aspirin. And so how, in this process, when you’re developing so many different tools, are you keeping maybe safety in mind when you’re developing these tools? Because you’re verifying, you’re confident in them, but you know, from the patient side, how can somebody be sure about that these tools that are being developed at such a rapid pace are really safe?
Behzad Mahdavi:
No, the safety is really, is the main concern, and of course, is through the clinical trials, and that’s remained the number one, basically, focus for the pharma. And today I think this is not the three at all neglected. So everyone did, looking at drug actually is really looking at the safety aspect and the quality aspect. But I think at the same time what has been neglected in some extent is the other two components. One is the question of the quality, but in order to get to this industrialization of the medicine, you need to be sure also, you are able to produce them at the quantity that is needed for the patient, but also at the cost, which is affordable by the payer but at the same time provide a return on investment for the therapy developer who has taken the risk of the development of this drug. So there is a equilibrium and this industry realization in some extent happen only if you have these three elements of quality, quantity, and cost all at the same time. So that’s the challenge today that says that the safety is number one and we are focusing on that. But at the same time, you can actually keep your drug as safe but optimize that in a way that you can have either a better efficacy, as we said, or a better manufacturability of the drug. And that’s basically drive the two other elements that we discussed in term of the cost and the quantity and manufacturability that you can control. So that’s the short answer to your question.
Samantha Black:
No, I love that because it’s so complex and it is, the amount of things that you’re taking into consideration all while trying to get something to market. It’s an enormous amount of factors and I think it brings me confidence knowing that people are thinking this through so much and have all these processes in place. It should really build confidence that these therapies are going to be effective, safe, and hopefully, one day very cost-effective for us moving forward.
Behzad Mahdavi:
No, absolutely. So question of the safety is always comes after this, is that once you have your candidates, all of them go through the safety elements, it’s just to be sure that you have the right candidates actually, and then go to the safety and then clinical trial. So just to have a higher probability of this success during your trial goal, but also, once you know, you are successful at, you know, your drug is safe and is efficient, to be sure actually you are able to manufacture that and you don’t have any extra surprises after, basically, this process.
Samantha Black:
Right, and that’s the importance of doing all this upfront work, right? I think so many times people just see the outcome of the clinical trial, and they don’t appreciate the hundreds of candidates that were in process to get to that one. So I think this podcast is really about shedding a light on research and development of the tools and technologies, and so I think that this just sheds a huge light on the complexity and the care that goes into producing a final product.
Behzad Mahdavi:
Absolutely.
Samantha Black:
Yeah, so let’s move on to your second challenge.
Behzad Mahdavi:
Yeah, so the second challenge, the other industry issue, as you may know, is the therapy development has two basic parts: discovery and manufacturing. So … is afford a largely siloed and sequential. So what happened in that case is the bottlenecks and challenges in manufacturing steps are worked out long after the central component of the shipment are locked down. From a biologic point of view, as we said, the true trials and … So when a drug reaches the manufacturing stage, it’s too late to engage with the biologic component of the drug. In that case, we are limiting our toolkits to traditional process manufacturing and operational optimization, which enable at best only incremental improvement. So at Ginkgo we dramatically change how we approach development of these groundbreaking treatments by integrating biological optimization with manufacturing optimization of the therapy. So we applied the same concept of the high throughput optimization on the manufacturing side to assure that the optimal … is manufacturable and we can fight easily the optimal manufacturing condition from a very early on in the same way. So in summary, the Ginkgo platform integrates drug discovery and manufacturability, and delivers to its partners both advanced optimized product from a biological point of view to deliver optimal functions and optimal manufacturability along with optimal manufacturing conditions. And this package is spread of the peace of mind for any therapy or by reagent developer to go to next steps. So that’s basically the second problem that we try to solve with our platform.
Samantha Black:
So that’s a shift in the traditional way of developing drugs, right? Like it’s always been very sequential, finish one step, move on to the next step. So you’re kind of doing things in tandem in order to assure that when you get to the clinical stage or to the patient stage, that you’re going to have a product that can be easily manufactured for all of the reasons that you just mentioned in the previous question.
Behzad Mahdavi:
Absolutely, absolutely, and this is really the opportunity coming back to Peter Mark’s comments. I believe if the cost is 800-pound gorilla in the room, then this opportunity of advanced biological optimization and integrating, basically, biological optimization with manufacturing optimization is 8,000-pound of elephant hidden inside of the bioreactor.
Samantha Black:
Right, yeah, that’s, yeah. No, I think it’s very important work. So I think, and it’s very innovative. I think if all medicines could be developed this way would, it’s almost breaking the system, I hate to say that, but in a good way, so that we can make things more affordable and really make innovative, life-saving medicines faster, cheaper, and get them to the people who need them faster.
Behzad Mahdavi:
Yes, absolutely. You’re absolutely right. And again, we have these two component that we can be within the biology itself and the optimization of the manufacturing condition. But this is powerful, maybe I can give you one example of this platform. So we have worked with the other one on the vaccine decapping enzyme during the COVID, and we have used actually both of these platforms, so on the cell engineering as well as on the manufacturing optimization, and we have been able to increase the output of the plant, basically, of the bioreactors by a factor of ten. So ten times more, getting basically out of the same system. We have done the same thing with the Moderna, we have increased the output by a factor of four. So this is very important because when we talk about the ten times more, it means that also from the cost perspective, from the manufacturing perspective, now you have a ten times the less of CapEx, if you want to build a new plant, or out of the same facility, you can get ten times more of the same drugs. So that is improve your cost of your goods sold. This is kind of the impossible target to achieve through conventional manufacturing improvements by the operational improvements or by the design of the bioreactors. So these are the leapfrog improvement that we can bring by just touching basically the biology of the products.
Samantha Black:
Yeah, and that is a case for investing early in these technologies and investing in the upfront cost of doing this research and doing the work that you guys are doing instead of downstream spending your money on figuring out manufacturing after you have the best candidate ever and gets too far down the line. So I think, again, I think it’s transforming the way that drugs are made, and I think that’s really incredible. So just a quick question on that example, though. Would this be the case that somebody comes to you with a product candidate already and they ask you to work on this candidate, or is Ginkgo actually generating new candidate, drug candidates for itself?
Behzad Mahdavi:
No, actually, so this is very clear. So what we have developed here is a, really, platform available to pharma industry, to any company at any size is a welcome to this platform, use this platform for its own benefit and development. So we are not drug development companies, we are not CDMO either, so really, if you are still, also a very high technology platform and we are serving, basically, our customers to bring it better and cheaper, basically, product to the market. So for example, when you come to our platform, it can be both actually. So some people come and have already existing product and that they want just to be sure that the manufacturing condition are more optimized or sometimes just that, be able actually to do some measuring over the current product they have to create a better version of that. So these are the possibilities. Sometimes people come in, they really have no idea, the best example of that is an enzyme. If you think about the enzyme and the biocatalyst side of that, there are some chemical reaction happen and ideally you want to replace that we are, with an enzyme enzymatic reaction, and this is sometimes you need to find new enzymes and this is actually one of our strength is because we have access to metagenomics, the massive metagenomic libraries, and we can actually look in the nature to find sometimes a beta version or a proper basically product that doing work. And then that would be the starting point, and then we can engineer that further really to optimize the biological component and later on the manufacturing. So it doesn’t matter where you are, either you are at very early stage or you are in the middle. As soon as you want to optimize, basically, your platform in one way or another, Ginkgo platform can be used actually, for these companies.
Samantha Black:
Awesome, so it sounds like it’s a very flexible platform that you guys are building, and allows you to serve all different types of partners across your business, and across the pharmaceutical industry as a whole.
Behzad Mahdavi:
Absolutely, sbsolutely, and we’re very flexible business model as well.
Samantha Black:
Awesome, so would you just mind telling us a little bit about the critical activities that are needed to keep the platform up to date and stay even maybe ahead of the curve?
Behzad Mahdavi:
No, absolutely. So one of the critical areas basically here, as we discussed, the new modalities evolving very fast, so it’s all about the prediction, or maybe the better word, with the anticipation of what is coming as an industrial problem and how we are going to solve it, so to develop the platform in order to address these challenges. And of course, that we are listening and we are interacting every day with all these partners, we have more than 100 actually partners on our platform. So all of that is also source of the information and indication about the problems in the market, and we tried to adapt basically our platform to get there. Maybe I can give you a concrete example. Think about the mRNA right now is working on the vaccine side, and we know that the next wave will be around the therapeutic application of the mRNA, but we know that the challenges are very different in the sense of delivering a very low amount of dosage within 3 to 100 micrograms per dose. We need to deliver maybe 10, 100, and sometimes a 1000 times more, those in a very targeted manner. And therefore all the issues in terms of the double stranded RNA, the nature, … becomes a more important factor that needs to be solved. So that’s what we tried to kind of to see how we can prevent that. So that’s where we are starting to work, even in some cases at basically at the RNA level, in our case, to, creating the polymerase enzyme that can reduce double stranded RNA. So that’s a way basically to address the issue, working on the circular RNA to better and having a longer expression, creating high throughput platform for tissue specific tickets, and how, basically, we select them. So this is really the main activities, that critical activities with the team, but it’s not just that my team, it’s really across the organization because that’s what touches basically every thing, piece of the equipment, piece of the, knowledge from the market. So there is a lot of basically interaction to get to the right.
Samantha Black:
Yeah, and for those who might not be familiar, what is the like the makeup of your team? Who are the folks who are doing all this work? What are they? Engineers? Are they scientists? Who are the people on your team?
Behzad Mahdavi:
Yes. So it’s a highly scientific, actually, the drive and competitive, because if you look at it right now, we are around the 1200 basically employees, just around the 250 of these employees are just software engineers. Because as we discussed that, we have the highly automated robotic labs, and there is a, goal is really to simplify the cell engineering. And this is, involve a lot of robotics, a lot of liquid handling, a lot of political analysis, all the omics. So all of that needs to be integrated through the same, so that’s one element of that. But as I said, it’s not just the robotic in the sense that we replace the what the human does with just a robot, is really there is a lot of underlying technologies as well. So we have the technologies that can able to …, like the single cell level and the dual median offer analyses the per day really to understand what happened at the single cell level. So there is a lot of technology involved into this platform. So we have, also, the commercial team who needs to understand perfectly the market trends and the customer needs so we can basically match the customer need with this, all this platform, and it’s a different component of that.
Samantha Black:
Right, and maybe underlying all of that are people who keep the lights on, the operations team, who connect, who maintain all that equipment, who are in the lab, making sure that those folks have the supplies they need to do the experiments to build the technologies. So it sounds like all three of those, as a synthetic biology company, all three of those pieces in harmony together are really what’s enabling you to serve your customers.
Behzad Mahdavi:
Absolutely, absolutely.
Samantha Black:
Okay, so one other thing I wanted to ask you about before we finish up, you have such a wealth of knowledge and you’ve had some great experiences and you’re running a very large organization right now. So for those listeners out there, what is one piece of advice in your career that you would share to maybe help them, or that somebody might resonate with out there in the great ride world?
Behzad Mahdavi:
Yeah, that’s a very good, good question. I would say follow what you are passionate about, that’s a really number one advice. And number two, remain flexible. This pharma world is changing extremely fast the pace, and we need to remain also having a flexible mind and being able to adapt to this changing, and as much as we could, predicting what is coming, I think that would be the key to be successful.
Samantha Black:
Yeah, no, absolutely, I think those are wise words. I’m sure people can take a lot from that. Awesome, so the last thing we just have is you’re doing some incredible things at Ginkgo, so if somebody wanted to find out more about what you’re working on specifically or bigger projects at the company, how might somebody find out more about you or connect with you or even about the company?
Behzad Mahdavi:
Yeah, so the best way would be, I think maybe through LinkedIn. That way we then we stay connected, so that would be one way. We have also the website and you’re going to update that also very soon. So it’s going to be much nicer to navigate. So also you can use my email address, so BMahdavi@GinkgoBioworks.com.
Samantha Black:
Awesome, and we will link all of those in the show notes for everybody. So if you want to reach out, feel free to just click the link in the show notes. And really I think that everybody should connect with you because I think it’s fascinating and you guys are doing amazing things. So thank you for all your work and thank you for coming on the show today.
Behzad Mahdavi:
Yeah, my pleasure.
Kerri Anderson:
Thank you for tuning in to this episode of the LabOps Leadership podcast. We hope you enjoyed today’s guest.
Samantha Black:
For show notes, resources, and more information about LabOps Unite, please visit us at LabOps.Community/Podcast. This show is powered by Elemental Machines.
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