In collaboration with industry giants, Enko Chem is revolutionizing the agricultural industry by accelerating the development of safer and more effective herbicides, disease protection, insect control, and yield enhancement solutions. This quest for better crop protection chemistries brings innovations from pharmaceuticals and machine learning to create acceleration.

Tom Meade, Chief Science Officer at Enko Chem joins host Victoria Meyer on The Chemical Show to share insights on their target-based discovery platform, the importance of data in their research, and the challenges and advantages of integrating DNA and chemistry.

 

Killer Quote: “In order to revolutionize crop protection chemistries, we need to embrace the power of data, technology, and collaboration. By combining these elements, we can accelerate the development of safe and effective solutions that address the challenges facing our agriculture industry.– Tom Meade

Join us to learn more about the following this week:

  • Chemistry’s key role in global agricultural industry, food security, and crop protection
  • Target based discovery in agricultural , leveraging techniques built in pharma
  • Utilizing data and AI in the agricultural industry 
  • The role of regulators including EPA and USDA in AgChem
  • Prioritizing safety in agricultural innovation

In this episode, Victoria and Tom delve into Enko’s mission to shorten the development timeline for crop protection chemistries while exploring the challenges and advantages of their target-based discovery platform, which aims to identify specific targets for herbicides and pesticides. Tom also shares the importance of data in Enko’s research and development process, as well as their use of automated systems and machine learning models. 

 

This episode is sponsored by Clariant. Are you grappling with the lightning pace of regulatory and compliance changes in the printing inks industry? Do you want to know more about PFAS, supply chain transparency and extended producer responsibility? Check out Episode 137 of The Chemical Show to learn about PTFE-free solutions with Clariant and NAPIM. 

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Listen to the Interview with Tom Meade of Enko Chem Here:

Revolutionizing Crop Protection Chemistries with Tom Meade of Enko Chem

Welcome back to The Chemical Show. This is Victoria Meyer. Today, I am speaking with Tom Meade, who is the chief science officer for Enko Chem. Tom has over 30 years of experience in the agriculture sector, focusing on the discovery of novel crop protection chemistries. He began his career at Micogen discovering insect resistant traits, which he then broadened into leadership responsibilities, small molecule discovery and other cool things. When that company was acquired by Dow, Tom went to Enko in 2017 as part of the startup team, and we’re going to be learning more about that today. Tom, welcome to The Chemical Show.

Thank you, Victoria. It’s nice to be here.

Glad to have you here. What’s your origin story? What got you interested in agriculture, chemistry, and ultimately led you to Enko?

No background in agriculture. I grew up in suburban Southern California, just outside Los Angeles and was a math/science geek and got exposure, when I was my mid-teens, to agriculture via a friend’s brother who managed one of the big farms in the Central Valley of California. That was exciting and different enough for me to decide that was the path I wanted to take. So I did. I went to UC Davis for undergraduate and then UC Riverside, so two big agriculture schools in California. What’s maybe a little interesting for some folks, I studied entomology, insect science. What I was really interested in was the chemical basis by which plants protect themselves from insects.

Plants can’t move. And so they’ve got to protect themselves and they do it by chemistry. So I did a lot of chemistry. Then how that affects the insects and their susceptibility to disease. So then I took a little disease and biotechnology, all of which on my career arc led me to Mycogen and then ultimately to Dow Agro.

That’s cool. Now you’re at Enko, so can you tell us a little about Enko?

Enko was founded by our CEO, Jacqueline Heard, and a venture fund called Antara Capital seeded the company in 2017. The thesis was that there were drug discovery technologies that were applicable to discovering drugs to protect people where we want to drugs to protect plants. That’s what we talked about, these crop health chemistries. There was a foundational technology that was being widely applied in drug discovery called DNA encoded chemical libraries or DELs. That was the start of the company, we had an active collaboration with a company called X Chem who are leaders in the DEL field. So we worked with them and we started off by validating that we could use the technology to discover chemistries for crop health herbicides specifically, so controlling weeds.

We were successful in that. And that led to then continued rounds of funding and expansion. So not only moving molecules down the pipeline for its commercialization, but expanding into completely new novel targets where there’s no chemistry in the marketplace, and into other areas for protecting plants from disease, insects and parasitic worms. We also have a small program directed at helping plants increase their yield. That’s our scope and that’s our arc.

Tests being performed in Enko lab to advance crop protection chemistries

That’s pretty cool. I think most people, certainly those of us in the Western world, take our food supply chains for granted. I actually grew up part of the time on a small family farm. So I was around a lot of crops and crop protection, although I didn’t necessarily understand it as being part of the broader chemical industry, or even really what the agricultural companies were in Agchemistry. But I think about it as an industry that’s really transformed a lot through the years. We hear about a lot of different new, novel and growing technologies. That chemistry really plays a key role in agriculture and food security.

Can you just talk a little bit about the importance of that and the importance of crop protection as it relates to the global agricultural industry?

Yeah great question. You ask most people where their food comes from, and you know what the answer is, the grocery store. I think everyone realizes that’s the proximate, but ultimately it comes from a farm. There is a growing awareness of where our food comes from and the impact of growing food on the environment. It’s important to realize that, if we don’t protect our crops from pests or even today using solutions that are beginning to fade in terms of their effectiveness, it’s easy to lose 20 to 40 percent of the yield that a farmer is growing to these pests. It’s really essential to being able to put food on the tables of people around the world. The companies that do this are very focused on producing, safe and effective products, but innovation is lagged. The industry standard from the time that a molecule becomes commercialized, from the time it is first synthesized and tested, to the time it’s commercialized is about 15-16 years. It’s a long time.

Is that driven by just the corporate and the development timeline to testing, or is this driven by FDA? I’m guessing a lot of this is either FDA or some other acronym driving it. But what drives that timeline?

It’s both and in the United States, the agency that’s the lead for registering these crop protection chemistries is the EPA, the Environmental Protection Agency. There’s consultation with the USDA and with the FDA and with the Fish and Wildlife Service. But, there is a process that big companies have, and they’re looking at both safety and cost effectiveness. So a lot of that drives the timing, but in that 13 to 16 year time frame, they don’t publish numbers on the time it takes to actually discover and synthesize that molecule that becomes commercial. That can be, we estimate from our experience and what we see in the literature, 5 to 8 years of work to get to that point.

So it’s a big investment. It takes a long, long time, which kind of leads to this slow innovation.

So what makes Enko’s approach to this different? Because I think you guys are trying to really shorten some of that development life cycle or timeframe.

Yes, we are. The biggest impact is on the earlier end, but we are seeing and anticipate follow on benefits as we get into the more guideline driven types of work and success there.

What do you mean when you say guideline driven?

So for registration, there are specific guideline studies conducted under good laboratory practice or GLP that the regulatory agencies require. When you get to that point your ability to save a lot of time or money is really restricted by the requirements.

The process is still the process as it relates to the government and the data and the information they need to ensure efficacy and safety and all of that.

Yes. So the opportunity space and the one we’re very focused on is getting to that point. Doing that as quickly and as cost effectively, but then also with a real focus on safety. So what we’ve done is we have built a platform that is exclusively target based discovery, and that is a big difference from what the big major companies do.

What does that mean? Target based discovery?

So we actually look for chemistries that act at a specific molecular target.

That allows us to focus on advocacy. So we use a systems approach to identify targets that we are confident if we find a chemistry that interacts at that target, it will produce the desired effect. It will eliminate the weed, it will eliminate the disease or the insect but not the non target like animals, other insects and crops. That’s the difference. The way that it’s done and why it takes so long and costs a lot of money for the big companies is they take what we would call a screening or phenotypic based approach. If they’re looking for a new herbicide, they synthesize a lot of chemistry and they spray it on weeds. When something works, then they start to optimize that and typically, they would then try and figure out what the target is. But that, most often is well after you’ve got a chemistry and you’re optimizing it and you’re working it forward. That’s a big difference.

We start with the target, and we only work on things that act at specific targets.

Makes sense. And it seems like it would be much more efficient. If you’re going for a very specific end use or a specific target, you can eliminate a lot of extra work by focusing in.

Yeah, absolutely right. You can. The other piece, the key, so we say target based discovery, it’s not like that’s necessarily new. But what is new is that we are using these back to these DNA encoded chemical libraries or DELS, which are produced combinatorial chemistry libraries. So using the power of multiplication, they can be very large and diverse.

The breakthrough realized in the mid 2000s with next generation sequencing technologies, every molecule that we screen has a DNA barcode attached to it. So we conduct very large screen in terms of the number of molecules very quickly, very efficiently. We screen in every experiment tens of billions of molecules. As opposed to in the standard industry approach, in a good year you might screen 50,000 molecules. So the diversity we start with is huge.

So I’m guessing this is where AI and machine learning starts to fit in. Is that right? Is that how you guys are getting to that place?

Yeah. We started this company from a white sheet of paper. And when we did that, Jacqueline and I both having come from big established companies and having seen the difficulties in, trying to assemble legacy data systems to talk to each other and get data all in one place. We said, no, we’re not doing that. We’re going to be a data company. So we built our data systems from the ground up with the intent that they are all going to connect. They’re all going to talk to each other.

We’re going to put data in the hands of scientists and that includes the data from our DNA encoded library screens. So in a DNA encoded library screen, there’s an experimental design we generate from every experiment. We generate over a billion data points. So we’ve got tens of billions of molecules.

That is a lot of data.

We’d still be going through experiment number 1, and we probably wouldn’t get to a fraction of a percentage if you were doing it manually. So it’s big and highly structured. I’m not a machine learning expert, but any machine learning expert will tell you, that’s what it takes to make great machine learning models. We use automated systems to process data to get data quickly in the hands of scientists. We also get, not just our scientists or chemists who are looking at molecules and what came out of the DNA encoded library screen, but then also to our data scientists who are building these machine learning models and making predictions. So at the end of the day, we access this huge chemical space. We have a very effective filter to get down to a small number of really interesting things. But there are a small number of really diverse and really actionable chemistries.

We choose from among those what we work on. That’s the basis of our strategy.

Scientist in Enko lab working on crop protection chemistries

That’s really interesting. In fact, we just wrapped up The Chemical Summit, which is a 2 day event held here in The Woodlands and one of the topics we talked a lot about was AI and digitization. The opportunity for it to really transform the chemical industry and in a variety of places, including in product development. One of the challenges that everybody collectively identifies is the data structure and the organization. So you talk about your ability to start with a blank sheet of paper and do the mapping, because the mapping of all this data that already exists is really hard. You’ve got to figure out what makes sense. Is it in the right format? How do you bring it together? So it sounds like you’ve really started with Enko, because you’ve had the ability to start from a blank sheet of paper. Starting at the ground level, getting the structures right, getting the data in the format that you need so that you can actually utilize it and accelerate it effectively.

Yep, absolutely. It sounds trivial, but it is not trivial. It is really complicated. So that’s a big investment space for us and then scraping other data is important, too. So we can talk about that.

Yeah, so what I was going to say is, 2 things that you talk about that to me are really different than, what I think the typical chemical company would talk about is number one data scientists. So the whole idea of having data scientists in house and as a core part of the development and discovery process is transforming. I think this is where we’re going in the industry, but we’re not there yet. So that’s one piece. Then the second piece is, you’re talking a lot about DNA and that’s not something I typically think of when I think about chemistry, whether it AgChem or other forms of chemistry. I’m used to carbon molecules and putting all the pieces together. I think this is different. Where does the chemistry fit in? How do the chemistry and the DNA fit together?

Yep. That represents some challenges, too. We’ve got illustrations where we illustrate the size of a typical small molecule in the chemistry that we’re working with compared to the DNA. So you can visualize this very tiny molecule with a flexible linker and in this massive piece of DNA, the barcode associated with it. The screening we do is an affinity screen. We have a very high quality functional target. We incubate the protein target with chemistry.

We wash away the things that don’t bind. Then we identify what binds by just sequencing the barcodes. That’s the DNA piece. When it comes to testing the molecule, we’re not testing the molecule with the DNA. We’re actually synthesizing the things we’re interested in without the DNA to see if it’s functional. It’s a way of getting to chemistry. It is not integrated into the product. There is no DNA barcode attached to what we’re ultimately producing.

But it’s a very effective way. Again, we go from 140 billion or 25 billion, depending on the library molecules in the screen, to we test 50. So that is a hugely effective filter and speaks to way we can access this chemical diversity, there’s no way you can test a billion molecules and get to some number that you can work with.

Yeah. Are you guys using third party data? Is there public data sets that you’re leveraging or are you having to create the data sets yourself? How does that work?

Yeah, we use some third party data. So we branded our platform. It’s called Enkompass. In Enkompass, we’ve got these DNA encoded libraries, we got all our target knowledge and biology. But we also use structural biology. So we do a lot. We solve proprietary structure.

So proprietary chemistry with the target of interest. We use some public structures and build homology models. This is another differentiation for us in that, we start off programs because we know the target and we know how the molecule binds at the target. We use structure-based design for optimization straight away. That is really the exception in the industry. More common in drug discovery, but not for agricultural chemistry.

Is Enko actually producing these crop protection chemistries then and putting them into the market or are you partnering with other companies to help them get new products to market faster?

The answer is both. We’re not given that long timeframe. As I talked about earlier, we believe that we can get there a lot faster. Now, will we ultimately be able to speed up the registration, the regulatory process? Maybe someday, but not today. But we’re on the way. Our most advanced products are herbicide chemistries, and we’re just approaching the point where you’d say we would do those guideline driven studies. So the studies would actually be submitted for registration.

So this is a really long bet for you guys. This is a long journey, and I’ve spoken with a number of executives and leaders of, let’s just call it green technology companies, new technology companies and new chemistry companies. The one common theme is there is no such thing as an overnight success. It takes years. Jennifer Holmgren from Lanzatec, I had the opportunity to interview her about a year or so ago and, it was 19 years before they really got to critical commercial success. It takes a lot of fortitude and investment and trust to get there.

Yes, so not only are we on that path, but, to that point, we’ve got collaborations with buyer crop science, with Syngenta and New Farm. The Bill and Melinda Gates Foundation led our Series B investment. Really, as we think about where the world population is growing and getting high tech, modern technologies into the hands of growers who need them. That was their interest in investing in us.

Crop sample in Enko lab, a key component of identifying new crop protection chemistries

So one of the things when I think about AgChem broadly is there has been innovations along the way. There’s been products that have been introduced that we thought were awesome. And then there’s backlash. So I think Roundup would be maybe the most notable one which seemed like a tremendously great solution. Now there’s discoveries or concerns about side effects and other effects that have taken place. And obviously, a lot of lawsuits that we don’t need to discuss. But I think this whole aspect of safety, environmental safety and human safety is really critical. There’s also this real big backlash against GMOs, right? Genetically modified, whatever the O is.

A lot of concern about GMOs in our food supply and non GMOs. Where does Enko fit into this mix of what’s out there what’s been developing and where it’s going? How do you guys look at that?

The approach we take with targets, we can select targets and we select targets based on safety and that can be that the target is present in a plant, but it’s not present in an animal. So there’s some inherent safety there. But we’re also, I will say sophisticated scientists, because we look at structures and we look at how we can design safety. We’ve been very successful where there are the same class of biochemical target in a weed and in an animal. We have been able to discover and design chemistry based on structural differences that we can say this is why it works on a weed and it doesn’t work on an animal. And, we can build that level of safety in the Ag ecosystem. Roundup ready crops is a great, great example.

They were commercialized in the mid nineties, a huge success. Really revolutionized weed control. Weed control just became, a no brainer. You had a Roundup ready crop, and you sprayed glyphosate, and you controlled all your weeds. With that reliance on a single technology, we know what happens. These biological systems are complex. Your living systems, they respond. How did they respond? Weeds started to develop resistance to glyphosate.

We see that in insecticides and we see that in fungicides. So the industry and growers globally, they understand this, that there is no silver bullet. We need to be looking at a combination of technologies and approaches and we are very focused on that. We’re not saying we are not the silver bullet. We are going to fit into these and we’re going to fit into the digitization of agriculture new application technologies. We embrace all that. That’s us, and that’s our difference.

I think to me what it sounds like, it’s just a more diverse set of solutions that can and will be applied in the future. To a certain degree, if you think about the ability to accelerate this development cycle. You have the opportunity to develop more and to have that diversity of systems and diversity of products, because you’ve got the ability and the resources to be able to target not just one molecule, but many.

We’re certainly engaged with regulatory agencies that look at our approach and say, okay, that’s a different way of doing things. And does that bring some benefits that we should, give you credit for? The credit being that, we can get the solutions in the hands of growers faster. The other piece is, and this is important, this goes back to the Gates investment and thinking about, where the population is growing and where the needs are globally. If you’ve got this really expensive process, it takes a long time, then you have to have a market opportunity that will pay back. Investors are investors. I invest in my 401k to make a return. But if we shorten that, we decrease that investment and increase the success rate, which are all things in our remit, then we look forward to addressing some important but smaller opportunities. So we decrease that financial hurdle.

So on a personal level, you’ve gone from leadership at a giant company to leadership at a startup company. What are the similarities and differences that stand out for you?

Similarities are, we’re all trying to do the same thing. Everyone’s trying to deliver a product into the marketplace and, along the same lines, I’d say that the other similarity is there are really smart people who work in both big companies and small companies. They’re almost all really motivated by, the societal benefit that can be delivered. So yes, they are for profit organizations. There’s no question about that. Differences, decision making is much faster and much easier in a startup. It’s a little more complicated now. We’re not big by any stretch of the imaginations, but when it was two people, it was pretty easy. Now it’s a few more.

I’d say the other thing that’s different is, when you work for a big company there’s a way the big company does things and everyone’s very happy with the success in the big company. So change because of that momentum, that inertia change is difficult. That is not the case here at Enko or in the startup world. It’s all about change.

That’s part of your DNA. If we go back to the DNA, a DNA of a startup company is about change and fast learning and making adjustments where they need to be made.

Yep, absolutely.

So what advice do you offer people that are looking to make a similar switch? Because it seems that you’re at the later part of your career, but I talked to a lot of people that are relatively new. Early in their career, because a lot of this development seems to be coming from universities. So university offshoots and a lot of young individuals that really want to be in a more entrepreneurial, small company environment. But there’s also people all across their career trajectory. They’re like, maybe this big company is not it. Maybe the opportunity is to go in and jump in feet first with a smaller startup in a more innovative environment. What’s the advice that you give people? Cause I’m sure people come to you and say, Tom, should I do this? And how do you approach that?

I’ve had a few of those discussions. I think this is my last job, I am at that place in my career. To be perfectly honest with you, I wish I had made a move like this 10 years earlier. That’s what I tell people. The big company experience is great.

Big companies are great. You learn a lot. They’re successful for good reasons. So learning, taking the basis of those successes and then applying it as we apply it here at Enko. I think working for a big company, it’s easy to feel there’s a lot of security. There’s career advancement within the company. It’s a big company. There’s some buffering. And it’s risky going to a startup.

What if the startup folds, and a lot of startups fold. But I think what I’ve certainly found is that there are a lot of opportunities outside of the big companies. If you’re smart and flexible and have a drive, then you don’t have to worry that the next job may not be in the town you’re in right now, but you will find a great opportunity. So I encourage anyone who even thinks about it to just go do it.

Yeah. I think it’s great. I spent a majority of my career with Shell and it was awesome. The learnings I gained there and the experiences I’ve gained were tremendous working with a great group of people. But as they always talk about, the golden handcuffs and it’s hard to step away. Once you do an entirely new set of opportunities opens up and you realize, oh, wow, there is this whole big world out here that exists differently and effectively and successfully away from the big companies.

Absolutely. I’m 100% with you.

Presentation in the Enko labs.

Yeah. So Tom, what’s next for you and Enko? What should we be looking forward to?

We continue to grow our pipeline. So I’ve talked about herbicides, but we’ve got crop disease control well developed, and we expect to be taking molecules forward very soon and then controlling insects. It’s a very exciting program that really got off the ground in a big way this year. It’s accelerating fast. Then the technology platform, I mentioned at the beginning that we started with Xchem. But we have now integrated the screening into our own organization. So we have our own DNA encoded library screening platform.

We continue to push the envelopes in terms of using machine learning models and integrating more and more data. So that will be a part of the next frontier for us. I think again, we continue to work on the early stuff, but using models and using big data to continue to optimize chemistry is an exciting place for us.

That’s pretty cool. So out of curiosity, is there a plan or is there interest in licensing your platform or allowing others to utilize your platform? Or are you doing this really for Enkos benefit and through your partnerships? How does that work?

Yeah, we don’t have a contract research model. That’s not us. We’re working with partners for very strategic intentions. But, our ultimate goal is to get products into the marketplace. We’ll do that longer term directly via Enko. Or we will do it, through partnerships.

Makes sense. Tom, thank you for this. I’ve enjoyed talking with you, and learning more about you and Enko in this whole crop protection space, which is, buggy in its own way.

Thanks, Victoria. This was great. I enjoyed the conversation.

Absolutely. And thanks everyone for reading. Keep reading, keep following, keep sharing, and we will talk again soon.

About Tom Meade:

Tom has over 30 years’ experience working in the agriculture sector focused on the discovery of novel crop protection chemistries and traits.  His career began at Mycogen discovering insect resistance traits, after which he broadened his leadership responsibilities to  small molecule discovery when the company was acquired by Dow. WideStrike cotton, Herculex corn, and Conkesta soy are among his successes there. Tom was Global Leader for Traits Discovery at Dow AgroSciences before joining Enko in 2017.

Tom is an author on 14 peer reviewed papers and an inventor on 27 U.S. patents.