96. Brewing Medicines with Synthetic Biology: Antheia's Christina Smolke on Ending Drug Shortages

[00:00:06] Karl: Dr. Christine Smolke. we are so pleased to have you on the Grow Everything podcast today. I suspect you're joining us from somewhere in the Bay Area. You've got the beautiful Anthea background. How are you doing today?

[00:00:20] Christina: I'm doing very well. Thank you. And looking forward to our conversation.

[00:00:24] Karl: Yeah, you and I have met and had conversations a number of times over the years at SynBioBeta at JP Morgan. And, I'm going to just start in media rest, it feels like a long time ago. It probably wasn't that long ago. Your lab at Stanford made headlines because you guys engineered yeast to produce opioids that got a attention.

[00:00:44] Karl: And I feel like that was, you can tell me it feels like that was the Genesis of Anthea. you transitioned using that technology, but tell us about. Engineering yeast to produce opioids. What was your motivation for doing that? What were some of the challenges you face and how did that turn into Anthea?

[00:01:02] Karl: If that's the way it happened.

[00:01:04] Christina: Yeah, no, great question. So, the genesis that work really came back to being able to push the frontiers of what is possible with biotechnology, especially biotechnology as a manufacturing platform for critical molecules. and, maybe even taking a step back. If we think about the science, I am trained as a chemical engineer.

[00:01:27] Christina: My labs at, Stanford and prior to that, even Caltech, I was training students and postdocs in really the cutting edge of chemical engineering. And what we arrived at, in terms of really strong need, in the technology space was, we as a scientific, area have built out chemical synthesis to be this really powerful technology, where we use it, we rely on it to basically do bottom up synthesis of molecules that are important for us.

[00:01:52] Christina: and it's, transformed the world that we live in, but there are limitations. It ultimately relies on non renewable, feedstock, essentially and uses relatively unsustainable process steps. and we can see that impacting, basically the world globally. So it was taking a step back and saying, as engineers, we see what biology is capable of, in terms of its ability to perform synthesis.

[00:02:14] Christina: The challenge has always been it's not harnessable. For us, as humans were reliant on, taking what we get, but we really don't have a complimentary way to program biology in a bottom up synthesis route. That was really the genesis of what we were doing in my labs from an academic perspective. Now, how did we arrive at opiates as test case for that?

[00:02:34] Christina: It was really about number one, how do we pick a problem? that can push the science, but that also has impact so that if we are successful, it can really lead to something, that will have significant impact on industry, but also on, , human health, And planetary health. so that then led us to think about, Again, okay, what is important for human health and planetary health?

[00:02:54] Christina: Actually, pharmaceutical ingredients, how we make our medicines, how we make them, but also how we make them accessible to people, was one of the key, factors there. And also because it advanced the science. So again, when you think about a lot of the critical medicines that we rely on, their synthesis is actually very complicated, they are very complex molecules. They can take anywhere of 30 to 50 synthesis steps. That is something that chemical synthesis, actually cannot do. Cannot deliver on right now, which is why when you look at, for example, medicinal opiates, medicinal painkillers, um, or even addiction treatment medicines.

[00:03:30] Christina: We don't make them by chemical synthesis, we are extracting these compounds, from plants in the same way that we have done for hundreds of years. Because. Chemical synthesis can't make them in efficient ways at scale. we wanted to basically, pick problem cases where biology could really shine, And it's, not trying to basically compete with really efficient chemical synthesis processes right now, but let's look at where chemical synthesis falters. Let's look at where there's a really big need in terms of human health and in particular accessibility to really critical medicines. and then let's really push the science and say, why can't we do better?

[00:04:04] Christina: Than extracting from an animal or plant, what has to happen from the scientific and technology perspective so that we can do better. And let's use that as the problem that we actually then, work to build a technology solution around. That was what really motivated, that work at Stanford, prior to Caltech.

[00:04:21] Christina: And so, what was the technology challenge? It was, basically how do you take a microorganism like yeast something that can grow really inexpensively and really quickly on a feedstock like sugar and convert that to well, we're used to using it to convert it to ethanol and beer and wine but also organic acids, but how can we basically reprogram the yeast? So that it will go through that same process, but convert sugar to this, really important critical medicine, and do so in a way, that leads to greater efficiency, better cost savings, better control. the technical challenge then.

[00:04:57] Christina: Was okay. Now to get used to basically make this compound, you have to program it and bring in, 30 or more different enzymatic process steps, Because it's very different from what you would ordinarily make. That was. a transformative challenge in the space, Because up to that point, basically the state of the art was, we can maybe bring three to five enzymes into, a bacteria or a yeast strain, to make this molecule that looks very similar to what yeast would already make, and that was the state of the art of Metabolic engineering and synthetic biology.

[00:05:29] Christina: So to be able to take it from, five enzymes to 30 or 40, that was really a step change. , that was really what drove the work. and again, it was around. If we can make that step change, then we can really. Enable a bottom up synthesis approach that's complimentary synthetic chemistry, but one that leverages the power of biology, And really, ultimately, from that perspective, when you look at it, it's, getting away from nonrenewable, feedstock, Nonrenewable resources, and giving us a much more sustainable. Way of producing these compounds, not relying on really harsh solvents, And creating a lot of pollution and waste as a byproduct, but giving us that sustainable way that nature basically performs its chemistry.

[00:06:08] Christina: So that was really the motivation of that work. Why did we, choose opiates? It was because of their really critical role in the health care system, one, they are essential medicines, palliative care and pain management is actually really important. for, humane, care.

[00:06:24] Christina: And it's one where if you look globally, organizations like the World Health Organization have highlighted that the vast majority of the population actually does not have sufficient access to these types of medicines. Of course, it's a reverse problem in the US, but it's one if you think globally where access is really actually important and having a way to produce it.

[00:06:42] Christina: in a more controlled way, in a more transparent way could actually, give solutions to both problems. but was really, then, melding the two of impact on human health, critical role in the healthcare system, driving transformative advances in the science.

[00:06:57] Erum: Christina, thank you so much for that. I mean, I've been so excited to speak with you because there are just so many wins with your process and your approach to pharmaceutical manufacturing. And, I'm here at Messaginglab Yes, we do communications, but we also look at the business strategies. I have a lot of business related questions for you.

[00:07:13] Erum: But for now, You mentioned the limitations or the inaccessibility in different parts of the world to support some of these drugs, right? There's been global drug shortages. It's been common. and what I want to know more from your perspective is there are plenty of challenges that current, Pharmaceutical manufacturers face, there's limitations in their infrastructure, but can you talk about some of those current hurdles with building us as pharmaceutical manufacturing capacity to meet some of these global drug shortages?

[00:07:44] Christina: Yeah, absolutely. you started with, the global drug shortages, so how did we get here? Why is this happening? essentially we went through a period of time where,the pharmaceutical supply chain basically evolved globally and it evolved globally in the way that many of our supply chains have evolved, but essentially to optimize on costs.

[00:08:04] Christina: To optimize on volumes and capacity, All those things go together. And so what you ultimately saw is the way that it evolved is that, you have very strong geographical concentration of where manufacturing of our pharmaceutical ingredients takes place, And most of it is not occurring in countries like the U. S. So over 80 percent of our pharmaceutical ingredients are not produced in the U. S. And then we primarily rely on two different countries, basically India and China for a lot of the production. at some point, That seemed okay, Again, it was the poor optimizing cost and volumes, but now, we're running into challenges with the way that it's evolved.

[00:08:38] Christina: What it means ultimately is that there is a lot of, single source failures, basically in our supply chains because with the conventional technology and having to optimize for volumes, you might have maybe one or two producers that really have built up scale to make. one or two products, but if that facility goes down for whatever reason, whether it's, Basically related to a regulatory issue right at a quality issue which can happen if it's related to weather or even a pandemic when you have these Places go down that means that a sole supplier has gone out for making this drug and you don't have Capacity that can bring it up very quickly.

[00:09:13] Christina: So that's one of the big challenges. The other challenge, of course, especially with the ingredients that we focus on is that you are reliant on, agricultural sourcing, which has very high latency, very strong unpredictability from season to season. And it's only getting worse as we see weather patterns change, and other kinds of events disrupt these types of, supply chains.

[00:09:33] Christina: So with these two things, coming together again, what we see is that. We are experiencing an increased frequency and duration of drug shortages, And it's a really critical medicines people are surprised that we have shortages on whether it's, cold medicines, which we experienced the last winter to ADHD medicines, to chemotherapeutics.

[00:09:52] Christina: It's just it's affecting, uh, broad swath of this. that's how we got here now. the question is how do we provide solutions, we're really strongly on the camp of We need to be able to leverage advanced manufacturing technology to be able to provide resiliency and basically better ways of manufacturing for these critical ingredients.

[00:10:11] Christina: So basically not trying to, basically move conventional approaches back to the U. S. Right. or Back to particular regions and saying, we're just going to build more factories that leverage conventional technology because there are limitations there. And that's certainly why it moved offshore to begin with.

[00:10:26] Christina: But if we look at biotechnology, There's a lot of advantages that biotechnology can provide. why we should be making those types of investments. First and foremost, we talked a bit about, how it really transforms, robustness, and, allows for a more on demand and agile process, So think about what we're replacing. We're replacing a process of growing, plant material or animals and extracting from that, has a manufacturing cycle time of two years. Our process produces the same quantity of material, in two weeks, The fermentation process itself takes four days, and we've done it.

[00:10:58] Christina: We're operating it and take sizes that are, hundreds of thousands of liters, robustly. so that's hugely transformative. But the other, I think, critical thing about biotechnology in terms of offering solutions Is that it's a much more agile and repurposable, technology when it comes to infrastructure.

[00:11:15] Christina: So again, I think part of the challenge with conventional technology is that you have things that are very purpose built. So you have a facility that's making a chemotherapeutic. You can't actually just switch that facility to make a cold medicine, or to make, an addiction treatment medicine.

[00:11:30] Christina: They're very purpose built in terms of the unit operation. you can make one or two things there and that's that. Fermentation is completely different because the fermentation vessel is very repurposable. And what changes is the microorganism that you put in there. So you can imagine, having just a whole cell bank of different strains of yeast that are engineered to produce different medicines.

[00:11:51] Christina: Could be a chemotherapeutic, could be a pain medicine, could be an addiction treatment medicine, and you can go from making one to the other in that same facility in basically one day. All you have to do is just go through, clean out the fermenter and you put the new yeast strain in, that repurpose ability is huge in terms of how we think about infrastructure investment and solving this problem in the U S because we don't have to make particular bets and say, all right, we're going to, invest a hundred million dollars in a facility that's purpose built for this chemotherapeutic.

[00:12:18] Christina: but there's only so much finite amount of capital we can really invest in building a state of the art, biomanufacturing facility. Okay. We now have, capability internally, and the U. S. is really a leader in this, too, in terms of developing. The assets, the different microbial drug factories that are producing different drug ingredients, and you can have a facility that can make, tens to hundreds of different products on the flip of a dime, basically, or, within a period of one day.

[00:12:42] Christina: again, I just think that's, it's really important to understand that because it's a much smarter way for us to think about. How we invest and reinvigorate the infrastructure in the U. S. just solve a few different things. One, of course, is, you grow the bio economy.

[00:12:53] Christina: You grow the U. S. Is leadership in biotechnology. But you also then solve this issue of how do we bring back resiliency in our critical supply chains? Pharmaceutical ingredients being one of this. How do we, continue to, bring that resiliency, transparency and control.

[00:13:08] Christina: and it can do all of that in a much more efficient way.

[00:13:11] Karl: I think, what you said about drug shortages is something most people don't know about. I think the list that's out there's at any given time, 200 drugs that are in shortage.

[00:13:21] Karl: And they can be anything from lidocaine to the things that are used to knock you out in, surgery. And, This became something that was being critically looked at during the last administration, I've been working on drug shortages, maybe 10 years ago, but it really became acute because the supply chain, as you said, really became dependent on India and China, and a lot of times what would happen is that you'd have this.

[00:13:44] Karl: supply chain issues around quality. So that's part of the reason why it's really important to be addressing this. Now, when I think about Anthea and you're going to talk about your pipeline, I always thought what I was always fascinated by was the research you had done at Stanford when it came to opioids.

[00:13:59] Karl: And just thinking about, and correct me if I'm wrong, I'm under the impression that the opiod Supply chain really depends on one place in the world, poppies are grown, not in Afghanistan, where they're grown for illicit purposes, but I think in Tasmania, correct me if I'm wrong. And so when I think about what you guys do and what you just said is you basically could build a facility, you can containerize it, which Moderna did during the pandemic.

[00:14:22] Karl: To be able to produce vaccines in places that didn't have vaccine factories. I think before the pandemic you only had vaccines produced in china in north america and europe the southern hemisphere didn't have any places But moderna turned out on the head so talk to us about the pipeline.

[00:14:38] Karl: What are you guys producing and is what I just said right or am I totally wrong? Generally,

[00:14:45] Christina: so what you said is generally correct. I generally, I mean, I'll make one, correction, Which is to say, you were right. That Tasmania is one of the primary, sources of, medicinal opiates, With this poppy farming.

[00:14:57] Christina: but there is probably about. For other regions of the world, which do supply this material, as well, Hungary, Turkey, Spain and France basically are, some of the regions, especially when we look at global supply of medicinal. Opiates, but comes back to the point that it is geographically concentrated and actually different regions will focus on different products because it's not just one product, that this plant is producing.

[00:15:20] Christina: so there's some specialization there as well. but you're absolutely correct. When you think about them going to fermentation, it completely opens up in terms of where you produce, because now you don't have to think about soil quality. You don't have to think about weather, all these different things, which is currently now what restricts.

[00:15:35] Christina: where these crops get grown. you can much more think about, where does it make sense to supply, a particular region? And that comes back again to the point that I made in the beginning around, organizations like the World Health Organization, Putting out, regular reports where it talks about accessibility, to, pain medicines, right?

[00:15:52] Christina: Because it is something where there's such a disparate, accessibility issue across the world. and it's considered a very high importance that, the entire world has some form of access to palliative care because it is so critical when you look at things like.

[00:16:04] Christina: Cancer treatment and different types of humane treatment for different types of whether it's surgery, whether it's, chemotherapeutics, et cetera.

[00:16:11] Christina: And now you switch to talk a little bit about Antheia's pipeline, because one of the key points, I think For me was one of the primary goals of developing this as a platform technology is that The problem is much bigger than one particular class of medications, As you said health, shortages and drugs hitting every area And it is a very actually a very significant and the other thing that people don't realize, beyond just drug shortages is that it's a very significant fraction of our medicines today that we rely on That do rely on agricultural sourcing, these 2 things combined mean, as they have builds out its pipeline, our intent, and what we're executing on is really to apply this to, many of our most essential and critical medications, and especially ones, for which, again, there is, variability, in the supply chains, and that this is continuing to get worse as we look at how, global dynamics, are continuing to evolve. so, for our pipeline, we span a variety of different areas, this includes areas, of, pain management, addiction treatment, rescue medications, it also includes, sedatives.

[00:17:13] Christina: and then going into areas of oncology, anti infectives, as well, so there's seven broad categories of medications, that we are focused on right now and it really does span a very diverse swath but again, the primary sort of thing that we look at when we develop our pipeline is first and foremost what are medications that play a really critical role in public health, and global health And for that, we will look at, okay, what medications are on the world to health organization essential medicine list, what medications are on the FDA essential medicine list, we, try to triangulate across different, essential medicine lists that different organizations have produced. and then we'll look at, what are the challenges in the existing supply chain, Are these drugs under shortage?

[00:17:53] Christina: How long have they been under shortage? How much is the supply chain and the way that is being produced? and again, what is Antheia's technology going to bring in terms of advantages for sourcing?

[00:18:02] Erum: Can you talk to us a little bit more about how Anthea fits into the pharmaceutical industry? Are your customers big pharma and they're looking for. New ways to, supplement their drug supply. can you share a little bit more about how it fits into the farm industry?

[00:18:16] Christina: Absolutely. fit in different ways, but let's focus on, the start with what we've talked about today, which is, when we apply Our technology platform to develop a disruptive manufacturing process for a drug ingredient, this pipeline that I talked about, these are already approved drugs, So , they're not innovative drugs, , where they still have to go through clinical trials, And grow the market. These are drugs, that have existed on the market for long periods of time. Ultimately, the molecules themselves are generics. And so there are multiple pharma companies that basically use these molecules to formulate drug products, We are a drug ingredient supplier. In this case, which means, we basically develop the technology in many cases. And with our first products, we are basically manufacturing the ingredient. and then we are selling the ingredient to the, to our customers, which are pharma companies, right? But pharma companies will basically take that ingredient.

[00:19:06] Christina: it will ultimately get formulated into a drug product and then make its way to the patients. In this way that the industry is organized, they're already and currently purchasing ingredient from different vendors which they use to produce their products and we become basically an alternative vendor for them for sourcing this ingredient and again, why would they make the switch?

[00:19:26] Christina: It's really around surety of supply they understand that they have experienced, the challenges basically with, sourcing from agricultural suppliers and vendors. and having to worry about, disruption in a crop or failure of a crop from year to year. the surety of supply is a big thing for them.

[00:19:42] Christina: They understand, the technology and the advances, The advantages that this brings in terms of surety of supply, time, and then, cost as well as sustainability, that final thing is something that you see more and more. Of course, it's been more prevalent outside of pharma, but now even within pharma, sustainability and being able to Get to more sustainable metrics with their manufacturing processes Is something that is becoming increasingly important depending on the region.

[00:20:07] Karl: Now, earlier you had said that you guys have scaled to be able to produce, you said hundreds. I don't know if you said tens of thousands or hundreds of thousands of liters, but really a significant amount. And we know that other companies have struggled in synthetic biology to produce to scale up production.

[00:20:24] Karl: What is it that you guys are doing differently to, be able to go to those quantities?

[00:20:28] Christina: Yeah. No, it's a great question. So first and foremost we have scaled, our processes basically at 120 000 liters with our manufacturing partner and demonstrated, that the process is robust and it's consistent and no attrition and performance from, how it behaves at one liters, basically in the lab.

[00:20:46] Christina: certainly I think most people who understand the synthetic biology industry, would agree that's a really, wonderful milestone to show that, and many companies have stumbled, on that scale up process.

[00:20:55] Christina: So coming back to your question, then how is Nthea, different? I would say one thing about Nthea, think probably comes back to just, how we started and then the founders, think it's focused. and being really laser focused on delivering what we say we're going to deliver, and ensuring that we allow our team to be focused on that particular problem.

[00:21:15] Christina: and I say this in the context of, what I've seen with the industry, Is that there's so much potential of the technology, and there's so much that it can be used for. I think a lot of times what we've seen is that, we've even experienced it internally, Is, people want to pull you in different directions of, okay, this is great.

[00:21:30] Christina: But, you could be doing this and why aren't you doing this? And, we have this really great idea for a partnership, and you should be doing that. But all of that takes bandwidth, and basically, Diverts attention away from what your primary goal would be. And so again, I think what I would say in terms of what I attribute our success to is, Antheia's ability to remain laser focused on the goals that we set out for and making sure that we don't dilute our efforts too early on because there is so many exciting things that we can do with this technology.

[00:21:58] Christina: We get confronted with it every day and it's like, okay, yes, all these things are really exciting, but we need to make sure we deliver, on this piece of it, and we need to make sure that we're allowing our team to stay focused on it and not pulling them off in too many different directions.

[00:22:11] Christina: So I think that's. a key piece that I would say. And then the only second thing I would just say is, really having a team that has the experience and has seen, where things stumble, , and really, setting their objectives to say, let's be really realistic about what we think is possible.

[00:22:26] Christina: Let's understand where things have stumbled and failed in the past. And let's make sure that we're anticipating that, and really trying to catch things before we just, go off to scale, but let's really try to bring in all of the learnings, That we have collected together as an industry, to bring that in and really try to anticipate it and catch it before it gets too far.

[00:22:44] Erum: Yeah, that clearly is a winning strategy. The focus is, really important. But so no skunk works happening on the side. No 80 20 dip, like 20 percent going into something unique.

[00:22:55] Christina: And, you know, I think that, there's always, I would say that there's always some level of, I'm not going to say that there's no skunk quirks and there's no kind of, how do we think about Anthea in five or 10 years. Absolutely. We have those conversations, we have, certain people on the team who are thinking about that.

[00:23:11] Christina: Think the industry has to be careful, but also as a company, what I can say for myself as a company and someone who's trying to steer this company, basically, deliver on what we say we're going to deliver and also, be, judicious with how we use our funds.

[00:23:24] Christina: It's just as a startup. We have a limited right there. You have a limited time frame to basically hit certain value points and demonstrate that you can deliver. , and you have a limited set of money that for your investors money, , to do that. And what I've gotten some advice from advisors and mentors, generally around company building You need to make sure you define exactly what you're going to be held accountable for, and it should not be a huge are the critical things to deliver on, and then you need to make sure that you've organized your team around being able to deliver on that. Everything else, nice to have, but don't make those nice to have cannot and in danger, the need to have.

[00:23:59] Christina: And if that means that you're going to tell people, no, we don't have the money to start this, Or no, we're not going to accept this partnership because it's going to pull too many resources in a way that does not make sense for us to do this, then you have to do that. And you may not be popular

[00:24:13] Erum: Yeah.

[00:24:13] Christina: some people.

[00:24:14] Christina: , but, I think you have And, certainly what we're seeing today, it goes in waves, Sometimes, there's a certain mentality of, yes, we want to fund companies that are saying they can do everything.

[00:24:24] Christina: we've seen that, doesn't necessarily lead to success. what we've tried to, stay the course on an NTA is that it's really important to get these first critical proof points out and show and really validate the technology.

[00:24:36] Christina: validate that for your first couple To show that you can check those boxes and answer that question. Because I think that's where we get. Distracted a lot, The science is wonderful in the science. We can do a lot of things with, but we need to make sure that these other layers are there.

[00:24:49] Christina: We need to make sure that we've delivered. We've set that up. Then once you have that core, you can begin to diversify that more, but you don't want to do that necessarily. I don't think you want to do that too early because you really have a certain set of time and trajectory to really demonstrate the de risk game, not just of the science.

[00:25:06] Christina: But of the scale up of the operations but also of the commercial right and that really does require a lot of focus

[00:25:12] Erum: Yeah,

[00:25:13] Karl: absolutely. We talked about, drug shortages being a national security issue. And earlier this year, you had Secretary of State Anthony Blinken visit you guys for a panel discussion about the importance of biotech innovation in the United States. That's something we talk a lot about with Our audience at the same time, you guys were awarded a government grant to that supported the onshoring of pharmaceutical ingredient production.

[00:25:41] Karl: Can you maybe discuss what those government initiatives signal for you? And also for the broader biotech biopharma, send bio industries.

[00:25:50] Christina: Yeah, absolutely. I mean, think signals is that the government, Is aware the government is listening. The government, is looking at ways to support this critical technology. we've seen this in stages. you even talked a little bit about, conversations and discussions.

[00:26:04] Christina: You're having the prior administration, we see this, this administration, most notably, we had the executive order on the bioeconomy, we've had executive orders on critical supply chains, , pharmaceutical ingredients being one of those.

[00:26:15] Christina: I think all of these come. Together to a narrative, which is really, to say, first and foremost, biotechnology, synthetic biology, bioengineering, whatever you want to refer to it, it is critical in terms of, rebuilding and, first of all, addressing, challenges we face, with our critical supply chains, but even much more so, In terms of bio surveillance, all these things, the U. S. needs to be a leader. specific to Anthea, the focus discussion is really on critical supply chains. And so when you see these different things come together, when you look at the Consortium the contract agreement was awarded through that.

[00:26:50] Christina: I think that's really a recognition. There's a lot of work and education that went into that, right? But ultimately, that's a recognition by the government that, this is a technology that is actually, that is through, as for I B. M. S. C. so this is a technology that we believe is actually ready now to provide solutions at scale, For the U. S. population we are now, making strategic investments to ensure that be successful, really address challenges. We're seeing and pharmaceutical ingredients, supply chains and leveraging biomanufacturing as a solution. So I think that's a critical step.

[00:27:20] Christina: when you look at Secretary of State. think it's really around a narrative and a discussion about what does the U. S. need to do to ensure that it continues to lead in this space? And I think specifically there the conversation is also around not just what the U. S. does internally, but But how it coordinates with its partners to ensure because again, it is really important what the U.

[00:27:40] Christina: S. does internally. but we have to also, recognize that this is a global network of nations, And we have to look at how we coordinate not just within the U. S. But with, friend nations and partner nations to really ensure again that biotechnology.

[00:27:54] Christina: can be used to ensure a flourishing society and that the technology itself is used and made available in a way that's going to basically benefit the entire global population. So when we talk about things that are relevant directly to human health. in things where we're seeing very clear breakdowns and just a disparity in terms of access.

[00:28:13] Christina: I think those conversations really are very important, How do we set up the appropriate partnerships and collaborate on a global scale, to ensure that we can leverage this technology to provide solutions that are going to impact. Everybody in a positive way, and the US should be a leader in that.

[00:28:29] Christina: to me, that's those two things represent and, I also feel that they build upon each other in a broader narrative that we are seeing, build out, , in Washington, DC this may be one area where there is very strong bipartisan support on, the us first of all needs to do more to bring this resiliency to critical supply chains, pharmaceutical ingredients being one of those, and the U. S. government should have a role in ensuring, in incentivizing that, in various ways, , but ultimately ensure that the innovation and the leadership that's being shown on the technology and science side is something, that goes to create meaningful solutions, and allow for the U.

[00:29:04] Christina: S. to continue its leadership.

[00:29:05] Erum: that's incredible. talking about Nthea, there's so many wins, as I mentioned, Sustainable manufacturing, it's faster, it's more secure. and that's really exciting. but when are we leapfrogging this method forward? this method of pharmaceutical manufacturing and how is NTF promoting this as a pharmaceutical industry?

[00:29:25] Erum: when are we going to just completely transform? Cause it sounds like a plant extraction. That's not the most sustainable method in force takes a long time. when are we going to do the flip? And I know it's something you think about all the time, but please share.

[00:29:38] Christina: Yeah, no, it's a great question. . of the aspects of leapfrogging the way that,we view it or we discuss it internally, , part of that is really, coordinating, partnering. With the infrastructure investments that need to happen to allow this to scale and in particular areas.

[00:29:54] Christina: 1 of the things you alluded to, questions was infrastructure and infrastructure to support by a manufacturing. This is something that the US actually is behind on. so, for example, in this case, where we are manufacturing now is actually in Europe.

[00:30:08] Christina: We're not manufacturing in the U. S. Because we could not find, , the infrastructure available for us to do this with a manufacturing partner in the U. S. , there's just more available facilities for us to partner with, , in Europe, That's a limitation, ?and we're hoping to address that over time with the partnerships that we have through the biomap consortium and some of the other partnerships that we're building But in terms of leapfrogging that's actually one of the key barriers that I see right now You know when I think about this because at enthea, our processes are ready to scale We have scaled them.

[00:30:36] Christina: and we're actually now, making product for customers, for commercial, but , if we don't have the infrastructure, ? That limits where we can scale. And so that comes into conversations, at least in the U. S. that we can directly have, which is okay.

[00:30:48] Christina: How do we address this problem? Is it investing in facilities that are going to set up conventional manufacturing approaches for these drug ingredients? And we talked about the limitations there in terms of, not agile, a lot of investment, for one or two drugs. How do you make that? how do you make those kind of bets?

[00:31:03] Christina: Versus saying, no, we're actually going to take a strategy here of leveraging advanced manufacturing, setting up state of the art facilities, , and really leveraging kind of the innovation that's being driven, through our scientists, and leaders, and using that to rebuild these supply chains.

[00:31:16] Christina: So, 1, I think leapfrogging is enabled by those types of strategic infrastructure investments. Two, I think the other thing of that is then, how does the industry come along? because typically pharma is conservative industry, and I would agree with that.

[00:31:29] Christina: but I think what you're seeing is that, actually, Pharma is where a lot of innovation has been welcomed, And the regulation within pharma, while some people view that as a hurdle, I think it actually can be a feature because it sets up very clearly what the requirements are. And because it's standardized, It means that everybody in the industry follows it an example that is, within this process. we have to go through different regulatory approvals, right? But there are very streamlined ways to do that. And the standards, That we have to meet to basically be comparable to the existing product are very well defined because there's regulations.

[00:32:06] Christina: Everybody in the industry has the same standard. So it's not like if I supplied a customer a, because there's no regulations, they have a different spec than customer B. So for every different customer, I have different specs that I have to, you try to basically fulfill to get them to buy my material.

[00:32:21] Christina: That's not how it is, There's a consistent spec that everybody uses. If we can meet that, single product can be purchased, by companies all over the world. So that's what I mean to say that a lot of times we think that, pharma is, slow moving and the regulatory presents hurdles.

[00:32:35] Christina: I actually think it's a feature, that we can use because it means that there's one standard that's held and we can fulfill everybody's standards if we can meet that. the second thing I would just say is that, well, think when you work within that framework, it provides the guidelines by how you do these types of changes.

[00:32:50] Christina: And we have seen pharma basically welcome innovation. Again, all you have to do is go back to the example of biosynthetic insulin, , where, you used to basically extract insulin from pigs and cows. That was, how it was done now, Recombinant DNA technology allowed us to make a synthetic version of insulin that could be fermented in a microorganism.

[00:33:11] Christina: It wasn't a long time for the industry to basically make that transition, right? Because it was offering clear benefits to the supply chain, where again, it wasn't a cost was certainly one thing, but it was also just predictability. , resilience, and having a much more consistent process, one that can scale easily, it's all of that rolled into the industry making a pretty quick pivot, , once that new technology was enabled.

[00:33:33] Christina: I think we have to keep all of this in mind. within that context, I would say, you have to keep in mind. The framework of regulatory when you're bringing this type of innovation, to the industry of pharma. But the argument that we see is that can actually be a benefit in terms of providing the guidelines of what you need to meet.

[00:33:49] Christina: And then you're working with an industry, and partners and customers that understand the technology have seen these types of transitions before. And if there's clear value at. That's being added in the supply chain. they have shown that they can welcome it.

[00:34:02] Karl: Yeah, mean, being mindful of time because I know we're going to hit the time very quick, but, it's interesting to me to hear you talk about biomanufacturing. From the Anthea point of view and the fact that you guys had to go to Europe for your first products because there it does seem like there is a lot of new manufacturing capacity coming on board and big pharma has been buying up capacity and yet on the other hand, we hear this, push pull from the symbiotic side that there's not enough capacity.

[00:34:30] Karl: Yes, there is. There's just not enough products. When will you guys have product that is being produced here in the United States and how do you think the pharma supply chain will change over the next decade based on a technology like what you guys are developing

[00:34:45] Christina: It's a great question. So, absolutely right. There's a lot of push pull. There's also a lot of evolution and that because, the government is starting to make some targeted investments and expanding capacity. one thing I would just highlight, within the broader synthetic biology conversation is Not all capacity is for any purpose, So for us, we need relatively large tanks, So, 100, 000 liter plus, tank sizes, but we need to be able to operate in a relatively controlled environment, So there needs to be certain controls in place so that you can make it, c g m p or follow c g m p guidelines, which is different than if you're making a commodity chemical that doesn't go through those same regulations.

[00:35:21] Christina: So it's just to say, there can be different. Layers in terms of the facility and capacity that is available and that's coming online We have been working very hard to basically get our u. s based supply chain, set up and we are on track Hopefully, our plans are to be able to have production in the U. S. by early 2026, in terms of material coming out of, our partners facilities,

[00:35:41] Karl: so again, really, our goal is to be able to leverage biomanufacturing to be broader solution to ensure that drug shortages decrease.

[00:35:50] Christina: So, as you said, the numbers are really startling when you look at the number of drugs that are on active drug shortage. And it's. Something like 25 percent of, the most, active prescription, but 200 plus molecules, that are in shortage. And it's really alarming.

[00:36:04] Christina: so number one, our mission and hope would be that as you bring this online and as you really start to switch over the supply chains to have this greater agility, transparency. And traceability. our hope would be that number should go down. Because part of it is just clunkiness and the single source failures that I talked about.

[00:36:22] Christina: The other part is just the lack of transparency, the lack of traceability, because of how oblique, some of these supply chains get, it's actually what the FDA and others saw when they looked at this is they didn't know where some of these ingredients came from, And it's very hard to trace. And so then it's very hard to even track or anticipate when you're going to have, a shortage, Anyway, so I think that's really critical, Being able to bring the capacity online where you traceability, where you have, control. and then, how will it affect the industry?

[00:36:49] Christina: I would hope that it moves it to be one that's more nimble, where again, because of the long timelines, because of the risks associated, what you see right now is, planning and contracting can oftentimes, be done several years, right ahead of when you're actually going to get the material in hand.

[00:37:04] Christina: If you have something that's much more agile, much more on demand, you're You can then be basically planning more directly based upon what the demand is that you're seeing, that's the other thing is that when we are trying to predict two years, prior to actually getting material, a lot of things can happen, Yeah, I mean, we had a pandemic that happened, You have spikes in demand, for particular drugs to treat patients in the hospitals, and you go into shortages. So it's again, if you can move to something that's more agile, Where you have this capacity that can be repurposed redirected. If you have emergencies, or if you have shortages that gives the ability of the industry to be more agile.

[00:37:38] Christina: I think with other things that we're seeing, they are really focuses, earlier in the supply chain on, that manufacturing to the drug product, formulator. There's work being done by others on the drug product formulator to customer to try to make those more efficient.

[00:37:51] Christina: And I think if we can do more to basically begin to marry those and bring those together, you can really begin to rebuild, the industry in a way that allows agility, especially where we need it.

[00:38:00] Erum: That's incredible. Yeah. does need to be rebuilt. I mean, the fact that we can't trace some of these drugs now, but Antheia we can. think that again, it just adds to the list of wins that Antheia is bringing to the table. So very, very exciting. and I think we could talk to you for another like hour or so, but we don't have that time, unfortunately, but I would like to wrap it up because you did give some advice, but maybe more.

[00:38:23] Erum: Just to round it out, can you share some advice that you would give other founders in the biotech and that's in bio space in particular?

[00:38:31] Christina: Yeah, would reiterate some of what I said before, but, first and foremost, I think it's important to give yourself the space and the support around yourself to be able to focus, to be able to say these are things we can't do right now.

[00:38:44] Christina: and really, really identify for yourself again. What are the top? I don't know, three things that you need to deliver on any given year right or any given cycle and make sure that those are the things that you prioritize, the most, there's always going to be so many things that pull and distract, and could be really wonderful and exciting opportunities, but, just be Being really realistic about people's bandwidths and what, you can deliver on and what the priorities are and making sure that everybody on the team and yourself are aligned with that, and working together to achieve them.

[00:39:15] Christina: I think the second thing I would just say on top of that is clarity around that and transparency in terms of, communication, both with your immediate team and then the broader team. I think all of that is really important because if people, don't understand what the priorities are.

[00:39:30] Christina: Don't understand, where they should be focused. What is mission critical for the company, et cetera. Then I think that's also where, things get distracted. So transparency and also just, frankness,or being true to what is possible?

[00:39:44] Christina: and why certain things might not be possible, within a time frame so those to me would be key things that I would say Just try to make sure you keep front of mind as you're, making decisions as you're building, your own team your own mission, and then delivering on it.

[00:40:00] Karl: Amazing. Well, Christine, thank you so much for taking the time to speak to us and the Grow Everything audience today. We really appreciate it. I think we need to have you come back and tell us about your progress in 12 to 18 months.

[00:40:13] Christina: Yeah, I would love to do that. Thank you

[00:40:16] Karl: Thank you.