CasClear, CRISPR, and AI in Soybean Genetics: New AgTech Frontiers - Interview with Matt Begemann Interview

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So if we could take our CasClear technology, design it very specifically

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for their cancer, deliver it to that individual, and basically

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deliver cell-specific chemotherapy where it only destroys

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the cancer cells and it leaves all the normal cells intact. And

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that's the conceptual idea that we've built with CasClear in the oncology space.

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So Matthew, thank you for joining us today. To kick off this

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conversation, can you present a little bit about you, your background,

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and how you got involved in Confluence? Yeah.

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So I'm Matt Begeman. You know, I've been involved in agriculture for quite

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a long time. My family actually farms soybeans in Missouri. And so,

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you know, we're end users of the product. You know, always been interested in applied

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sciences. So I did my undergrad at the University of Missouri

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working on biochemistry and microbiology. And then I went up to Wisconsin and got

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my PhD in microbiology and worked in a chemical engineering lab.

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really focused on, you know, how can we use the energy of the

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sun to create commodity chemicals? And that world honestly fell

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apart because of the fracking revolution and chemistry got really cheap. And

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so then I ended up jumping into the agriculture side and I worked at a

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company called Benson Hill for about 10 to 12 years. And there

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we worked on trait discovery to improve plants.

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We built out gene editing tools to do it and we built out AI tools

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to enable people to use AI for plant breeding to increase

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productivity of plants. And then we got really focused on soybeans. Soybeans

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at the end of the day are the most efficient source of protein in the

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world. It's really hard to beat soybeans. At the end of the day, the

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world doesn't seem to be short calories, but we are short protein. There's

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increasing demand for protein and it is just an excellent source of protein. But

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it's not perfect. There's a lot of improvement to be made in soybean. And at

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Confluence Genetics, which bought Benson Hill out of bankruptcy a couple or a year

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ago, We're focused on improving soybeans. Commodity soybeans are

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great. There's a system built around it. But if we can make soybeans a little

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bit better, or even a lot better, we can have a dramatic impact on the

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entire agriculture supply chain, which helps everybody from a sustainability

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perspective all the way through an end consumer of getting a better product for a

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better price. And so I've been in the technology space for a long

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time. I've been in the agriculture space, and my career is really focused on

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Can I take discoveries in the lab and work with a commercial partner on the

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end to get it all the way out of the lab, all the way out

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of research and into somebody's hand who gets to use that product at the end

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of the day? Interesting. And for those who are

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not aware, what sort of challenges are faced

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by soybean growers? You know,

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it's a commodity crop, and it's a global commodity crop. And so if you think

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about a soybean farmer in the United States, Their competitor

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is their neighbor down the street who's also growing soybeans. But there are other competitors

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in South America and around the world. And it's a global supply chain.

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And soybeans need to go to Europe, they need to go to Asia.

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And obviously, they get turned into soybean meal and oil in the United States and

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fed to animals. And those prices are constantly fluctuating. And then

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you've got, you know, external pressures, whether it's the weather or

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something else that has an impact on your crop. And so as a soybean

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grower, you're gambling with your net worth every single year, which

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is really stressful. And there's so many technologies out there which you could be

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using, and you've got to make a decision on which technology should you use

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and what's going to have the best impact for your operation. And so, you know,

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farming is a challenging job. And it continues to get harder as

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the global supply chain changes. But if you talk to growers, you

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talk to farmers, they're ready for the challenge. And they're looking for, you know,

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companies like Confluence Genetics, to provide them with new technologies

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so that they can get a better product so that they can make more money

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on their acres, which is what they need at the end of the day to

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keep their operations alive and growing. And we're seeing also a lot of,

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maybe not a lot of, but some growers also turning away from other

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crops that are resource intensive into soybean, turning

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away from corn into soybean, things like this. Is this something that

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you're seeing as well? You know, I would, I would say that the

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decision has gotten more challenging than it used to be. It used to be a

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more straightforward decision on a corn-soy rotation.

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And then do you, you know, you put some winter wheat in there, especially in

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the United States? I think with fluctuating commodity prices, it becomes

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a much more challenging decision. And there's, there's a lot more strategy

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in terms of what are you going to grow this year? How do you plan

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for next year? So we do see more people interested in soy, and we

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see more people interested in doing specialty soy products that give

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them a premium. So at the end of the day, we sell seed,

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and the growers that work with us end up, you know, in some sort of

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relationship with another entity, where they get a premium for the product that they

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generate. And so they get to make a little bit more money than commodity soybeans.

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And so really, you know, that's how we help the grower is we create a

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more valuable product. And they get to sell, you know, their soybeans

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at the end of the day for a higher price, because it's a more valuable

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product. Whether it's going into aquaculture, human food, it's going

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into dairy, or it's going into poultry, there's a premium market for them and we

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unlock that. Interesting.

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Interesting. And now to talk about your company,

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Confluence Genetics. Recently there's been some updates

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on your platform, CasClear. Before we jump

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on that news, can you explain as well what CasClear is?

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for those who are not aware? Yeah, so CasClear is

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a CRISPR platform. It's not a gene editing tool. And so I really want to

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differentiate that. So traditional gene editing, it's a CRISPR

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nuclease, cuts DNA normally, and it has a guide RNA that tells

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it where to go in the genome and it makes a cut. And you can

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do that to, like we've done, is we improve the quality of soybeans through gene

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editing, right? You can use gene editing in the human

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space for different human applications, human

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therapies, but we've discovered something a little bit different. And so what we found

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in our lab is we thought we had discovered another CRISPR gene editing tool,

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but rather than doing gene editing and just making a single cut, after

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it finds its target and it does make a cut, what it does is it

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changes the shape of that nuclease and then it indiscriminately chews up

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the DNA and the RNA of that cell and it destroys that cell. So

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when we first discovered this in the lab, it was a challenge at first because

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it was hard to work with. Because we were growing it in bacteria and our

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bacteria were dying. And we quickly pivoted and said, you know what, we can use

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this as an antimicrobial. So it maintains the target specificity

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of CRISPR systems, right down to single base pair specificity. And now

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you can kill a bacteria with it. And then we started to ask, well, you

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know, could we kill a higher level organism, like something like a yeast? And

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yes, it can do that. And now you start to think about all the broad

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applications of it. So Or in agriculture, could we use it to kill plant

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pests? And so that's something that we've been working on in our lab

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is, can we turn this into a defensive trait for agriculture?

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And we filed some patent applications and we've made good progress on there. Could you

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use it in antimicrobials? I think absolutely. And then the

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other area where you could potentially use this Cas-Clear technology

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would be oncology. So at the end of the day, cancer is

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a mutation that pops up in somebody's cells as they're growing. They're called

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oncogenic mutations. With modern precision medicine, we're actually

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very good at going to a patient and sequencing their cancer

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and understanding what's the exact mutation that's causing their cancer.

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So if we could take our CasClear technology, design it very specifically

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for their cancer, deliver it to that individual, and basically

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deliver cell-specific chemotherapy where it only destroys

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the the cancer cells and it leaves all the normal cells intact. And

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that's the conceptual idea that we've built with CasClear in the oncology space.

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You know, we've had success in our lab and we've recently seen multiple

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universities, the University of Utah and UC

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Berkeley and Jennifer Doudna's lab. They've also been able to get this work in many

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different types of cancer cells, whether it's lung cancer, liver cancer,

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or, you know, generic lab cells that they've been growing. And

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they've most recently been able to demonstrate that it works in a mouse model.

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Wow. Yeah, it comes to show that plants are not that different from

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humans. At the end of the day, it's the same, it's the same

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technology that can get applied to different things, right? So, you know, the original gene

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editing technology like Cas9 can be applied to many different things.

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CasClear is in the same boat. It's a fantastic technology. And

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our goal is actually to enable as many, you know, different companies to use this

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technology as we can because we can't, you know, I can't work

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on soybeans and antimicrobials and oncology all at the same time, right?

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And so we've really got to partner with other companies to make this successful.

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I was wondering, as a company, how would you target? Would

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you still focus solely on soy, or would you also

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expand into other crops or maybe other areas such as

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oncology and so on? What would you offload to other

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companies, or at least partner with them,

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etc.? The vast majority of the company, including

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myself, we're very much focused on leading the way for

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high-quality soybean genetics. And that's our core

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competency. And that's our core focus area. And that's where the vast majority of the

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people in the company are focused on. We've got a couple of people

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that are working on gene editing in soy. For quality traits to further

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improve soybean quality. And they're also working on this CasClear technology

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to get the underlying chemistry much more efficient

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and ready to go for different use cases and applications. And so how

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we envision, you know, working with other companies in that space is we're the

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technology provider at the end of the day, we can license the technology, we can

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do co-development deals where we can leverage our expertise on

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optimizing CRISPR chemistry, which we're very good at. And we can leverage their

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capabilities, which is going to be on the oncology side and the delivery

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side. At the end of the day, it takes a community to deliver a

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product, whether it's in agriculture or in oncology. And on the oncology

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space, there's usually, you know, some kind of cargo and a delivery mechanism, and we're

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going to have to partner with somebody on the delivery side. And so we're very

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open to understanding how we fit within the ecosystem and

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where the technology provider and the developer. kind of becoming like

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the AWS of— Yeah,

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yeah. At the end of the day, you know, it can be a, it can

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be a generic technology, and we are focused on really making it better. And

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we enable the end user to be really successful with the product as well.

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Okay, interesting. Now to come back on the axe side, since this is

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our area of focus, what plan

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defense applications of your platform

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would look like. Yeah, the question behind this is like, would

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that go through the same— I know it's very different and it's very

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also a hot topic and so I want to talk about, but is it the

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same GMO gene editing regulatory pathways?

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I think you can go through a GMO regulatory pathway to get this

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across the finish line. Conceptually, if you had CasClear embedded in

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a plant, And it had specific targets for a

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bacterial pathogen, such as a Pseudomonas, a leaf blight. If it

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had, you know, a specific target for a fungal pathogen, you could potentially

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have a target for something like a nematode, a higher-level organism that you

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could constantly be updating. And so yes, that would be through a traditional GMO

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process. As you know, that's kind of a longer road to get across the finish

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line. We got a lot of work to build out efficacy of the product, but

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that's kind of our focus from a plant defense perspective.

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Okay. Even if from a regulatory standpoint, there's been some updates, at

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least in some parts of the world. So I don't know whether you guys are

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only focused on the US or you're also involved in Europe, but

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at least like there's been the new genomic technique frameworks in Europe and so

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on. So I guess, yeah, to kind

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of go back to this, CasClear is a CRISPR technology. It's

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not a gene editing technology. So to use it for defensive traits, it would

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really be a full GMO pathway. On the other side, where we're just

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doing gene editing in soybeans for quality traits, we do see that market

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start to open up, especially some of the changes in Europe, kind of going back

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to soybeans are a global commodity. If you're working on

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gene-edited soy, you really got to get through a regulatory process

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around the world. And that's really speeding up and opening up, which I think is

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fantastic. And it's going to open up a lot of opportunities in the agriculture

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space. As, you know, as somebody who's embedded in the technology

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and also works on the commercial side, it's frustrating for me to see

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we've been sitting on gene editing technology for over a decade. And there's just not

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a lot of products out there, even though it's a great technology. You know, there's

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times when it's regulatory that's really holding that back. So if you look at

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our soybean portfolio today, we have a lot of quality traits, and they're not

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gene edited. They're from natural genetic variation that we

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pulled from, you know, genetics from all over the world. And, you know,

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we've combined them through breeding. And that's also a decade-long

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activity, which gives us a bit of a moat, right? Because, you know, pulling those

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soybean genetics together for different quality traits for animal feed and

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human food applications, but it takes a long time. And we're in

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a really good spot now where we have pulled those together. And we can leverage

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our AI breeding to make it even better. But when we think about new traits

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flowing in, it would be fantastic if gene editing was more available and opened up.

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Yeah, actually that was one of the questions I had as well, is obviously

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recently we've been talking about AI at every single

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sauce, kind of. How does that impact the development

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and the use of your platform?

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Yeah. So, you know, we've been using AI to do breeding for a while

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now. It's different than the new AI models that have come out, the

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large language models. We certainly use that in-house for some

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work, but our AI breeding models are built on a

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slightly different platform. And the idea is if you take

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a soybean and you sequence it, and you don't even need a high level of

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sequence depth, from that sequence, we can predict its

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yield to a certain degree. And we are very good at predicting its quality

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traits, especially protein and oil and carbohydrate profiles.

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And because we can do that, we can leverage

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sequencing through our breeding program. So we have a tool called

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CropOS. And CropOS can look at all of the different soybean

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varieties we have. And our breeder can go in with their

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specifications, just like you're developing software. I want a

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soybean variety that grows at this maturity group to grow in, you know,

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Central Iowa across to Illinois. I want it to be high

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protein. I need it to have low anti-nutrients for poultry.

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And here's some other properties that I want. And CropOS will go in and

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look at all of the different germplasm we have. And it'll run

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millions of simulations, predict the best soybean

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varieties to cross, and then also provide our breeders with a

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recipe, a series of instructions on not just how to make the crosses,

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but How many progeny downstream do you need to look at in sequence and at

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what depth? And then how do we make selections down the line? And our team

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can execute on that using sequencing along the way to run

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predictions on all of those progeny. So when we take our

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material out to the field, we have a really good idea of its performance,

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especially on the quality trait side. And we're really just looking for what

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are the best yielding varieties that are still going to hit our product specs. And

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that's how we're leveraging AI and still using field breeding at the end of

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the day to do kind of those final measurements of yield so

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that we can deliver a valuable product. And what is the impact

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in terms of amount of time that's

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taken to develop such a thing? Yeah, there, I mean, there's a really

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big speed game here. If you're doing traditional breeding and you're making

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crosses once a year, maybe twice a year, and, you know, in the

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field in North America, and then in South America, development of a new soybean variety

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can take 8 to 10 years. You know, we're looking at closer to 6 years

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with our technology. Other companies are also, you know, very aggressive

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on using an AI platform and using indoor breeding like we

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are. The difference is, is it's less so on the AI

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platform. It's very similar to a lot of these LLMs we're seeing with, you

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know, Anthropic and ChatGPT and all these others, right? Everybody's got great

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models. But a big differentiator is what is the strategic data

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that you're feeding that model to drive the decision? So everybody can build

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an AI model in this space, but who has access to

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strategic data? And in our case, it's, we've got the sequence data

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and we got the phenotype data. So the protein, oil, carbohydrate profiles

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yield on really diverse germplasm around these quality

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traits. And our germplasm looks very different than the other companies.

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And so we've got, you know, a decade worth of breeding data and all

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of this phenotype data, and that enables our models to be really good

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at predicting things like protein and oil and quality

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composition. Whereas other companies, they just haven't generated that data because they

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haven't valued the quality traits. Yeah. I mean, data is the number

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one, is the new gold, I guess. Yeah. You've got to have data and it's

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got to be high quality data and it's got to be connected. So if you

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have a bunch of sequence data, but You don't have any of the phenotype data,

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there's, there's not much you can do. If you have decades worth of phenotype data,

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but you've never sequenced your populations or understand your population

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structure, you're also kind of stuck. You've got to really pull both of these together

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to enable those AI tools to really drive your breeding organization forward

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and make better products at the end of the day. That's our real goal.

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Yeah, absolutely. In terms of

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Now talking more about like growers adoption and so on,

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how has been the feedback provided by growers

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on using these, these crops? The

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feedback from growers is they've been looking for alternatives

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to commodity crops for a while. If you talk to a lot of growers,

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they've got limited options in terms of types of crops that they can

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grow. They've got limited options where they can sell it. And then

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they've got limited options if they want to get a premium for that product. You

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know, an example is something like organic. Organic is quite hard to get into.

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There's kind of a 3-year period where you've got to go through that process before

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you can really capture value off of it. So when we talk to

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growers, you know, if we can give them something where

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they're going to get a premium off of that variety, yield-wise, it's very

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similar to other commodity options they can get. And we've got

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herbicide-tolerant varieties coming out in the next couple of years, which make

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it even easier for a grower to adopt our technology because they don't have to

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necessarily change their agriculture practices. They can grow these

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varieties, they can be in an identity preserve program

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and get a premium for that product. And so it starts to make a lot

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of sense for them if they don't have to change their operation too much. And

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they can capture some extra value on the back end.

Speaker: 00:19:35

Interesting, interesting, very interesting. Now, in terms of looking

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ahead 5 years out, do you believe that Confluence would

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still primarily be a soy genetics company, or do you

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think it will become a larger group with different divisions, each focusing

Speaker: 00:19:51

on all the potential applications that that platform has?

Speaker: 00:19:55

We've got a lot of work to do in the next 5 years in soybeans.

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Soybeans are a big crop. In the United States alone, there's 85

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million acres. A lot of that goes into animal feed. We

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feel like we're really well positioned to capture as much of the animal feed

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market as we can. And so we're going to be really focused on capturing

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as much of this animal feed market. We also work in oil quality

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with the Hyolaic oil product. We have a lot of growth opportunity on

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both the Hyolaic side for Human food, but also dairy

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cows, high oleic soybeans are really taking off. And then on the animal feed

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side, the poultry market is huge. And we provide a lot of value

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in the poultry market. And so we've got a lot of work to grow there.

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And so in able to do that, we've got a lot of work to do

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to get new varieties out, get the herbicide tolerance traits out there,

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and really grow our maturity zones so that we can get to more

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farmers in the US. And so if you look at that 5-year roadmap, We're going

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to be busy in the soybean space, which is fantastic. You know, on the technology

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side, we're going to continue to develop those CRISPR technologies. And our goal is

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to license those out. If you look at these latest papers, yes, you

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know, they've used CasClear in test tubes on cancer cells and it

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works really, really well. You put it into a mouse and it

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works, but we haven't fully cured cancer in a mouse yet. So

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that means we've got some work to do to make the underlying technology

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better and build a better vehicle to package it in. And I think there's

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a little bit of work there. And then hopefully we can solve those problems.

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And now we can hand off this asset to somebody else who can really go

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turn it into an oncology therapy, which would be great for us

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as the technology provider, because at the end of the day, we want our

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technology out there. You know, we get a, we get a license royalty on the

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back end, which is fantastic, but then we can help out another group of

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people. At the end of the day, not everybody knows a farmer. Everybody eats, but

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not everybody knows a farmer. Everybody's been impacted by

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cancer, whether it's a family member or a friend, and

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you've gone through the pain of dealing with that situation. So

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if we can have an even bigger impact on both the food side and the

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human health side, and even those are obviously linked together because what we eat is

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important too, I think we'll have an even bigger impact on the world. And if

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the plant defense applications pan out, does that ever

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loop back and strengthen the core soy trait business?

Speaker: 00:22:19

Absolutely. Yeah. So our plan there would be to really focus on it for

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soybean plant defense. When we think about other areas where plant defense is a

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big deal, obviously your major row crops, yes, corn and

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soy, there's a lot of money to be made on defensive traits because they're constantly

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being bombarded with plant pathogens. A lot of other crops

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deal with pathogens quite a bit. Potato is a great example where it gets

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sprayed with pesticides a lot. A lot of your produce gets sprayed with

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pesticides a lot, same with cotton. So on the plant defense side, I think

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there's, there's kind of growing opportunities where we could get into some other spaces as

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well. But we would really need to partner with other organizations that

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know their pathogens really well. And again, we can work with them on being a

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technology provider. And if we make our underlying technology even

Speaker: 00:23:04

better, they're going to be in a much better situation to onboard

Speaker: 00:23:08

that technology into their group and be successful.

Speaker: 00:23:12

Fantastic. Well, Matthew, thank you. Thank you for your time

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and for answering all the questions. If people want to connect with you or

Speaker: 00:23:20

learn more about Confluence Genetics, how can they do so? You know,

Speaker: 00:23:23

confluence.ag is a great place to start if they're interested in our agriculture

Speaker: 00:23:27

business and what we're doing in the soybean space. We've got a lot of content

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up there on our soybean varieties and our animal feeding studies showing increased value

Speaker: 00:23:35

in poultry, aquaculture, and dairy. If people are

Speaker: 00:23:39

interested in the CastClear, castclear.com is a great

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place to go. And at both of those websites, they can either find

Speaker: 00:23:47

my contact information or contact information for the company, and they

Speaker: 00:23:51

can reach out to us to learn more. Okay, perfect. Well,

Speaker: 00:23:55

Matthew, thank you again. Thank you for your time. I appreciate it.