Enabling Local Production of Protein Therapeutics - Dr. Kerry Love, Sunflower Therapeutics

Hi everybody, and welcome to this week's Talking Biotech podcast brought to you by Collabora. Now, during the COVID epidemic, or at least the beginning of the pandemic, we had a lot of discussion about how we were going to generate new therapeutics to treat a problem. And we saw some pretty amazing things happen with respect to moving an idea from a concept to an actual therapeutic. And all of this was enabled by a really efficient chain of events, along with plenty of infusion of government money to make this kind of thing happen very quickly. It was a great example of what can be done to move a therapeutic to application relatively fast when there's ability to do it, when there's capital there, and when there's capacity to amplify it, to build it. And so all of this is a great example that we could go to solve a real problem in healthcare in just— what was it— 11 months. But that's not true for everybody. There are places in the world where concepts thrive, but the capacity to implement them does not. And if there was a company that could assist with that, that, both in the raising of capital to do it as well as to actually getting it into a pipeline that may be of great benefit to helping with healthcare solutions worldwide. So today we're speaking with Dr. Carrie Love. She's the CEO and President of Sunflower Therapeutics. Welcome to the podcast, Dr. Love. Thank you.

Thank you, Kevin.

Yeah, this is really, really exciting to talk to you because it's a little departure from where we normally are with the podcast. So Could you tell me a little bit more about the general idea behind Sunflower Therapeutics and what's the problem that you want to solve?

Yeah, no, I really appreciate the opportunity. So at Sunflower, we consider ourselves solution providers, Kevin, to the broader industry of people trying to bring protein-based products to diverse market segments, to consumers. So that might be protein-based drugs, therapeutics, vaccines, maybe alternative food products. Cosmetics, right? So there's a ton of different products that now in this new biotech age use protein. And so we're kind of helping to support that. You ask about kind of what are our core technologies that enable us to provide solutions? We are experts in small footprint manufacturing. So that's a way to be very efficient in deploying bioprocess really anywhere in the world using a small footprint equipment approach. And we're experts in using microbes to do that, right? So those are things like bacteria or yeast, right, to make protein really efficiently and quickly for diverse market segments.

So let's talk about small footprint technologies. I mean, it sounds a little bit jargony. And so when we're talking about small footprint, is it something that you have equipment that you can deploy internationally that can be of interest and of use to, say, a small startup somewhere in Africa or in Asia?

Yeah, exactly. So small footprint manufacturing is a means of deploying bioprocess, typically using integrated and continuous techniques, right? So interestingly, drugs and therapeutics are actually the only consumer good that we don't collectively make in a continuous and integrated fashion. And so that's really what small footprint manufacturing is doing for bioprocess. It's minimizing those unit operations, right? Making them smaller, usually fully automated and integrated. So that they can be deployed as a piece of hardware really wherever those processes are needed.

Well, what's the need? I guess it seems like if you're a company that has a plan to develop XYZ, you would already have that in place. So why is there even a necessity for this?

Yeah, it's a great question. And I think fundamentally, Kevin, it's that good ideas can really come from anywhere, right? We saw this kind of boom with additive manufacturing, right? Using things like 3D printing about 10 to 20 years ago. where we saw diverse solutions coming from all different parts of the world. We're now seeing that same thing happening in biotech, right? So you're right, if you're a big company and you already have capacity, maybe this isn't as relevant to you unless you wanna break into a new market. But bioeconomies don't exist everywhere all over the globe. In spite of the fact that we have huge populations in diverse locations, there is no, for example, commercial product manufacturing On the African continent, right? Africa imports 95% of all of their healthcare-related goods and services, including personal protective equipment. So they're actually not producing product for their own needs and use. They're importing it, which causes a major, major healthcare-related trade deficit.

Is there a utility of having local manufacturing in terms of speed of deployment of something like PPE in the event of like a breakout of Ebola or something like that?

Yeah, absolutely. I think there's advantages to speed and to preserving that whole chain of deployment for both drugs and related products and services, right? Certainly we saw this in the pandemic, right? Being able to deploy quickly enables both mass vaccination, it's also more cost effective. So when we think about Africa not having this, this was a huge, huge barrier and part of why they didn't reach 60% population vaccination until actually pretty late in 2023. So, I mean, that's significant.

What are the bottlenecks that exist with, say, deployment to new threats? So something new arises. I mentioned COVID-19, coming up with new therapeutics for SARS-CoV-2. But how useful is it to have these things more localized in terms of logistics and storage and all that stuff?

Yeah, great question. I mean, I think it really depends on what it is that we're combating against, right? So if we think about, for example, an infectious disease, right, a new potential pandemic threat, being able to deploy quickly and very close to the site of kind of massive infection is actually really helpful for containment, right? Being able to do that quickly and thoroughly. You also often get better buy-in when you're talking about making a product locally using local or regional labor, right? There's a lot of vaccine hesitancy in diverse parts of the world when we think about product that gets pushed in as opposed to product that's homegrown, right? That's true across many market segments for consumer goods.

Oh, that's really true because so much trust, especially in places like Africa that has a colonial history, that there is a certain inherent mistrust in someone coming from the outside and saying, hey, have we got something for you?

And I— Rightfully so, Kevin, right? I mean, I think this is the challenge, right? I mean, I think historically the Global North has used populations in the Global South as a means for clinical trial execution, but not necessarily for the benefit of those therapeutics that are actually being deployed in clinical trials in region. So it's really challenging, right? And so I think distributed manufacturing, which is really powered by small footprint approaches, helps to overcome some of that loss of trust.

I see distributed manufacturing. I think that's a really cool concept. So that's— so the principal idea is distributed manufacturing, but how many different things can you support to manufacture like that?

Yeah, it depends on the technology, Kevin. So Sunflower's technology is incredibly diverse, right? It's really applicable to lots of different kinds of protein-based products. So, you know, our technology for producing bulk drug substance could make a vaccine antigen one week, and then you could turn around and deploy the same hardware to make a monoclonal antibody the week after. Or a hormone or an insulin product, right? So really thinking thoughtfully about the way that the equipment is constructed and deploys a bioprocess is, is part of that.

I see. So most of these are protein-based therapeutics, or are you also dabbling in mRNA and other goodies like that these days?

Yeah, so mRNA is a totally different technique, Kevin, right? So it's not a protein-based product and it's not made using a living host. Interestingly, you have to have a lot of protein to make an mRNA product. So actually, there's significant advantage if you want to make mRNA to having systems like ours from Sunflower in your region to make all those raw materials. But what we're talking about is making protein-based products. So again, maybe it's a subunit for a subunit vaccine, maybe it's a hormone, right? Something like an insulin product or human growth hormone, right? These are essential medicines.

Yeah, or gene. This is all done in creating proteins, and this is done in microorganisms. So what kind of microorganisms is typically used in production of proteins?

Yeah, it depends on the protein product and the process that's been invented for that product. We tend to use yeast, Kevin. We think that that's a great balance between the, the kind of speed that you get from a microorganism, right, because yeast double very quickly, every 2 to 3 hours. But yeast also are eukaryotes, right, which, as you know as a microbiologist, means they have membranes, they have organized organelles inside of each cell that actually create the right transit of proteins between their inception and the surface, right? Most of the products we make in yeast are secreted. So, so we're using that cell as a little factory to help us with the quality control during the production.

Oh, very good. It's, it, we'll talk with Dr. Carrie Love, who's the founder and CEO and president of Sunflower Therapeutics. We'll talk to her a little bit more about Some of the success stories on the other side of the break. This is the Talking Biotech Podcast by Collabra, and we'll be back in just a moment. And now we're back on the Talking Biotech Podcast. We're speaking with Dr. Carrie Love. She's the founder, CEO, and president of Sunflower Therapeutics. And in the first part, we talked a lot about the need and what was being done to help meet that need of small footprint manufacturing that can happen throughout the world with a deployable module. So pretty cool stuff. And this is all Protein, as we discussed so far, protein-based therapeutics that are being generated in yeast. But when you're talking about yeast, you're talking about a couple different critters here. Are you using baker's yeast or are you using Pichia pastoris?

Yeah, we use Pichia pastoris for a couple of reasons. One is really fundamental from a microbiology perspective, Kevin. Again, I think you'll appreciate this. Baker's yeast actually isn't as well organized inside of the cell. They're organized like a mammalian cell, which means you can make really complicated proteins that usually you'd have to use a CHO cell or a more expensive organism. But they don't have some of the pitfalls of bacteria, right? Like endotoxins, right? Which are some kind of toxic byproducts that come along with those cells when you cultivate them to make protein. So great balance there, but we're somewhat agnostic, right? Many of our customers are interested in using our equipment with other microbes.

Right.

That's fine. It's built to do the job for whatever people are interested in doing, right? And we're actually presently starting to work on show-ready systems as well.

Okay, I see that. Now that can work because it depends on what your— I guess you say your partner in the production is looking to grow and in the process, right? So yeah, Pinky is really cool because it's such a— I haven't used it in 22 years, but it was a really efficient Microbe in terms, I guess if it was livestock, we'd say feed conversion. You put in a little bit of stuff and get a lot out, which is really pretty cool.

Yeah, totally. And we see the same. So we're able to grow really high-density cultures in our continuous fermentation systems. You know, some other benefits of Pichia is there, it's well recognized by regulators worldwide. Most of the global insulin supply is made in Pichia. We've got monoclonals that are approved by the FDA that are made in Pichia, lots of other products. So there's a, there's a good comfort with that as an organism, right? But again, it's really capable. That's what you have to have.

So the concept of having a small footprint bioreactor type situation that you can amplify some sort of a therapeutic product, or I shouldn't even say that, a protein product. There's an increasing need, even in places like, you know, my lab, where we need a specific peptide or protein generated. And to have that done can be either expensive or require some extra expertise. Are there maybe university-level models of this that could be deployed that Would allow us to custom generate different proteins?

Yeah, absolutely. I mean, that's really what we're made to do, Kevin, is to support innovators like you all the way through the whole value chain, even beginning in academia. Our smallest system, the Daisy Petal system, right, which is a benchtop fermentation system deploying continuous fermentation, perfect for a university lab. I mean, it has the output capacity to make product really in quantities even enough to support, you know, first-in-human clinical work. But it's a great size for an academic lab. We actually deployed a couple of early access systems in academic labs here in North America in 2022 just to get some great customer feedback, which we did.

Oh, very nice. So where is the most interest right now? When you say you're internationally exposed to help bring these, the, I can't remember the term now, the deployable manufacturing. Yeah, distributed manufacturing.

Distributed manufacturing, okay.

So you have distributed manufacturing, Where is it being distributed to?

Yeah, great question. And we're getting a lot of traction in diverse locations in the Global South. So we're excited that our first systems that are going to be commercially deployed later this year are actually going to go to India. So that's super exciting. They're going to go to a vaccine developer. We also have a lot of engagement in Africa, specifically in South Africa. We work with a group There's a group there based in Pretoria, the Council for Scientific and Industrial Research. They're super interested in this as a way to help them take innovation into the clinic and ultimately into the marketplace. So the benefits are really being seen by diverse innovators in the Global South, and we're getting that traction.

Does it seem like COVID or the development of the COVID vaccine, either the RNA but also the protein types of the COVID vaccine, did that really increase the interest in this kind of deployable manufacturing strategy because of the ability to quickly adapt to a new pathogen threat? Do you think that those things are maybe a little bit related?

Yeah, I mean, I would say kind of the timing was all right, Kevin. You know, I've been at this from an innovative standpoint since 2013, so it's been, you know, more than 10 years that I've been working kind of on this technology in its precursor form. And we had a lot of interest even early on kind of in the work that we did before we became Sunflower when we were at MIT. I think what COVID did was really amplified the interest just in biotechnology product development in general, but it also put a magnifying glass over the fact that capacity is not evenly distributed in the world. I think that was really what came out of the pandemic. And, you know, that's a big problem. And now we're seeing a very large response to it.

I've worked in my lab with scientists who've come from every corner of the world, and what I really like about that is that each one brings a different perspective to the way you solve a problem, or maybe an idea that really does complement what we're already doing that I would have never thought of. And I don't know that it's necessarily just a different scientist. I think it's maybe partially cultural and where they come from and the way they think about things being different. And does that really enable places which have maybe been historically underserved to really have the capacity to be able to manufacture their ideas?

Yeah, I think we have to combine that innovative spirit, which you're absolutely right, comes from diverse cultural perspectives. We have to combine that with the actual access to the technologies that are right-sized for people in these regions to deploy to their own benefit, right? It's not enough to just be excellently trained, right? My colleagues in Africa are are excellently trained. Africa runs clinical research better than anywhere else in the world. And my colleagues are just incredibly smart, thoughtful, innovative scientists. They don't have the same access to capital, for example, to build a half billion or billion dollar plant to make their product. So we've got to figure out how to lower that barrier, both in terms of the upfront cost and then the ongoing sustainability of a technology to enable them to participate in bioproduct and bioeconomy.

And are your colleagues in Africa working on therapeutics which are specific for African issues or local issues? Africa is a very diverse place, I know, but maybe regional issues that are more threatening, like malaria perhaps or something like that?

Yeah, exactly. I think that's the other thing that happens, Kevin, is when you have capacity in region, you actually can really meaningfully address in-region problems as well, right? It actually pulls assets from R&D, right into the clinic and ultimately into the marketplace. So, you know, I'm really hopeful that we're going to see a whole lot more of that over the next 10, 20 years as bioeconomies really rise up and start to thrive in Africa. I'll add something else that you're mentioning, which is really important, right? When we enable in-region creation of product for region, we're helping to create, you know, co-create a better product with regional scientists, right? So, So Africans are the most diverse people group on Earth, right? That continent is much more genetically diverse. And with that and the fact that drugs aren't made for Africans, right? Most drugs that are made in the Global North and deployed to Africans make them sick, actually. I was stunned to learn that 15% of Africans who receive a biologic drug go to the hospital.

Wow.

So we've gotta create or support a way for Africans to create products For Africans, it seems really logical, but it doesn't exist if we don't have that pull with the manufacturing capacity.

That's a really good point I never really thought of. I mean, I knew Africa was diverse because I've been all over the place. And when you go from Egypt to Morocco to South Africa to everywhere in between, it's all completely different. And so that's a really, really good point. What are the major protein therapeutics that are being generated in these startups? Are they mostly vaccines or something else?

Yeah, a lot of different kinds of products. And I would say it's not mostly startups in Africa that are doing this. It's mostly government-supported entities. Usually it's, you know, different kinds of research institutions or academic labs on continent. I think we're just starting to see startup companies launching out of these institutes and kind of trying to become commercially viable. There's a lot of work around HIV, right? Understandably so. The HIV burden is significant there. Also things like malaria, Other unmet tropical diseases like dengue or chikungunya, right? So things that really are relevant to the region, that's the bulk of the work that I'm aware of.

You know, I guess the, maybe the devil's advocate question is, is that when we're doing something at massive scale, it's easy to have many levels of quality control and you can, you know, test the batch and then they're all going to be same for the millions of individual batches in that group. And so how does this work in a smaller scale with respect to things like quality control, where you'd have to have some sort of oversight to make sure that the smaller deployable units are still giving you something good?

Yeah, it's the same as in large scale, Kevin. In fact, in many ways it's easier in small scale than it is in large scale, because every time you touch something as an operator, you have to go and test it and make sure that you didn't do anything to it. So if you think about doing that in ultra-large scale, that's actually harder. When you talk about small footprint manufacturing, especially using like Sunflower's fully integrated technologies, we're basically taking all of the unit operations that it takes to make a bulk drug substance, and we're combining them under one fully automated system with quality control. So humans don't touch anything in between unit operations. So there's no opportunity to screw stuff up, right? We still want the batch to be tested at the end, right? The bulk has to be tested at the end of that process before it can be released. That's just good manufacturing practice. So in many ways, the controls are the same, but the combination of smaller scale plus automation makes that actually a lot easier.

I saw online in the news that Sunflower was partnering with the Department of Defense for some things. So what is their major interest?

Yeah, so Sunflower actually operationalized in 2019 with a significant contract from the U.S. Department of Defense through the Joint Program Executive Office. And that actually helps support the building of our larger end-to-end Dahlia system prototype. The U.S. government's really interested in just increasing the local manufacturing base, right? That's important for us just in terms of of kind of our own vaccine sovereignty, our ability to respond, as you mentioned before, quickly to potential pandemic needs. But, you know, that's a technology that we can use to the benefit of warfighters worldwide as well, right? Often it's really hard to get medicines in theater where they're needed, either for warfighters or civilian populations in the region.

And this is something that the government has been, you know, Well, one of the big criticisms of the way that drugs are manufactured globally is that very few of them are actually manufactured here in the US. And so is there a potential for this kind of a platform to even serve domestic need in some capacity?

Absolutely. I mean, to be honest, Kevin, we think more is more. There's no reason why we shouldn't be using a distributed manufacturing concept to inform manufacturing here in the US. Involve diverse populations here in the US to participate in value creation of biotech products for the US, right? When you think about deploying an equipment concept that is very simplified and uses automation, like, we want people to be using our system who've never deployed bioprocesses before. So we've worked on all those human factors to make sure that anyone can be successful. So that means you could be doing manufacturing anywhere. It doesn't have to be in a biotech area like where I'm based in Boston, right? It could be in, I mean, frankly, it could be anywhere. It could be in Wyoming, it could be in Arkansas, it could be in Florida, right? It doesn't really matter, right?

Oh, very good. Is there a particular success story that really surprised you where somebody was able to use your equipment to do something revolutionary?

Yeah, I mean, I think I'll follow on what we were just talking about in terms of the simplicity of the human factors. So one of our early access systems went, as I mentioned, to a US-based university. Sounds like a lab a lot like yours, Kevin, where the graduate students are really interested in making protein-based products, but they're not experts in bioprocess, right? So they actually had never run a fermenter before. So we deployed that equipment and trained the students in that lab, and within about a week to 10 days, They ran a bioprocess on their own. They had never done it before. So I think that's a success story 'cause it just is proof positive that really anyone can do this, right? With a little bit of training and a piece of equipment that's geared toward accessibility.

Yeah, it also seems like a small company or startup in the States, for instance, that wanted to make some sort of boutique enzyme or something that would be, have a high demand in industrial use or maybe therapeutic use, that they would be all over this because if it allows— if it's kind of a plug-and-play opportunity to be able to take the hard part, which is the manufacturing part out of it, to be able to just use your idea. You know, is there like a turnkey retail side of this that could be deployable just for small company support in the US?

Yeah, absolutely. We call it plug and produce, Kevin, because that's how simple it is, right? Yeah. So we're actually commercializing our first product right now. So the Daisy Petal, Perfusion bioreactor system. This is that benchtop unit that we deployed as early access with academics. It is now ready for sale, right? We're engaging in commercial builds for customers. As I mentioned, you know, we'll deploy outside of the US, but we're getting interest and traction here too. And you're right, for, from a small company perspective, it's exactly the right size, the right level of, you know, not complexity, right? It's very simple. And that's what it's for. It's really to help people figure out where they want to go in the market before they know exactly what the demand is going to be.

What I really neglected to ask you about was kind of a philosophical basis of the company itself, because I noticed on the website you speak about it being a public benefit company. So can you tell me more about that philosophy?

Yeah, absolutely, Kevin. A public benefit company or a PBC, this is a for-profit C-Corp, right? So it's still a for-profit company. It's not a nonprofit, but it's a company that believes in doing well by doing good, right? And so what that means is that we have to serve both our fiduciary responsibilities to our shareholders alongside of our public benefit purpose, right? And for Sunflower, our public benefit purpose is improving the accessibility of health and wellness products for humans and animals worldwide. provide through our products and services or any other way that we can do that, right? So certainly that means that we're going to engage very intentionally in trying to be capacity builders in the Global South. But it also means that, for example, we donate 10% of our net profits every year to things that we think are really passionate, that we're passionate about, that are improving the lives and health of humans and animals, right? It's just a way where we can kind of walk our talk around being thoughtful and, you know, caregiving to the rest of the world in terms of accessibility for healthcare solutions.

That's wonderful. And I hope more people follow that kind of a model. And I know that this is sometimes really attractive to students who are currently in college. A very big difference between how they were 20 years ago and now. And so if students were interested in working for a company like Sunflower, like let's just say for Sunflower, who was building this kind of capacity and maybe not just in science, but like what do you look for in somebody who would fit the company well?

Yeah, I love that. I think, you know, obviously we have, you know, a number of company values that are embodied in different ways, but I think 3 characteristics that are really important to The first is intensity, right? We have to be intense about pursuing this thing that we want to do that's big and challenging. Initiative, right? I want people who are going to pick things up and start going whether we ask them to or not. And ultimately passion, right? So those are the kind of 3 core values I think that ultimately kind of are, I see as critical elements to success here in this business.

Well, that's interesting because those are things that you don't necessarily teach in the classroom. And so it's, which is really cool. And, but are there certain skills that you look for as well to complement those kinds of more value-based or values-based qualities?

Yeah, absolutely. I mean, we're looking for students or, you know, professionals with a diverse background in science. Maybe it's fermentation science, maybe it's, you know, molecular biology or strain engineering or just engineering in general, right? We've got chemical engineers, we've got process engineers, industrial engineers. But honestly, Kevin, more important than any of those kind of rear-wheel skills, right, are those front-wheel skills that we just talked about because we're really at the cutting edge of continuous bioprocess in our business. So, we kind of almost have to retrain anyone who joins us. Yeah, no, I get It's more important for people to have that passion and actually be coachable and really want to kind of pull with the rest of their colleagues, their teammates, than to have a specific skill set that we may or may not be able to really, you know, drive from.

Yeah, it's almost better, isn't it, to have somebody—

A lot of times it is, right? Because sometimes you're actually having to, like, reteach against, like, prior teaching, right? that's super cutting edge and innovative, right? Sometimes having a particular style of thought is a barrier, you know?

Yeah, I do a lot of deprogramming because I like to kind of, especially in shortcuts and things like that that people have adopted that really do end up in a compromise of final quality, they kind of go, okay, here's how we're going to do it the right way. And then that's what's so much fun. I see people using kits and shortcuts and not getting the products they want. And then so having to retrain folks, but I can teach them how to use a pipettor. I can't teach them to care. And I think that I love that part of the philosophy as we were speaking about it. This has been really eye-opening and really gives me a much better sense of the way the company works. And I really do appreciate the approach and the idea of building capacity. If people want to learn more about Sunflower Therapeutics, where would they look?

Yeah, they can look at our website, Kevin. So our website at www.sunflowertx.com. We also have a channel on LinkedIn and a YouTube channel actually, where we put videos out that are great explainers to try to help people understand our approach. So those would all be great places to look.

Very good. So Dr. Carrie Love, thank you very much for joining me today. And hopefully next time you have a big thing to talk about, let me know and we'll rejoin you again and hear about some more success stories.

Awesome. Sounds good, Kevin. Thanks for this opportunity.

And to the listeners, thank you very much for listening to the Talking Biotech Podcast. My voice cracked there. Thank you very much for listening again. I get excited about not just new products, but new ways to enable their capacity to build them so that they can serve the people they were meant to serve. It's really exciting to know that these kinds of technologies coming from the ability to generate capacity and do it from a public benefit corporation is a really good model that I hope catches on. This is the Talking Biotech podcast by Collabora, and we'll talk to you again next week.