Speakers: “Manufacturing with precision fermentation technology” Rasmus Rune Hansen, 21st.BIO “Biomanufacturing …
I’m I’m rosmus Hansen as Matt said I’m uh the director of uh of client development and and project management here at the 21st bio um the part about project managements I think stems from the when we started the company and and each of us had like 10 different hats we were wearing at the same time so project management seems like a seemed like a a nice bucket of of other things uh these days I’m using more and more my time at um attracting new clients and also running uh projects with clients um I’m originally a microbiologist and a and a European patent attorney uh spent 19 years at at Novo science before switching to 21st bio so I want to talk about manufacturing uh with the Precision fermentation let’s see this slides are not changing there we go so if you look uh in the bottom left corner you see the source here is McKenzie and Company bio revolution in in 2020 they made this report where um where they calculated that uh that actually 60% of the physical input uh in in today’s world uh can be produced with Biology uh of course a lot a lot of the stuff that we we use is uh B based on Rock concrete steel stuff like that uh but also a lot of the energy and materials based on fossil fuels can actually be supplemented uh or or even substituted um with things that are made out of biology um we talked about some years ago in noval Sims that sugar was the new oil uh you can say back then a lot of the Technologies were not mature enough to really make this transition uh I think today we have a much better shot at it uh you can say both there’s there’s more urgency there’s uh there’s more Supply chains that are under pressure also in in Foods um and of course the production technology on the biological side have uh have evolved a lot since then um so not changing so what we do at 21st bio is uh we’re providing technology for production of proteins with Precision fermentation so it’s not our ambition to be a production company uh we want to uh to develop uh and optimize Technologies for our clients and then they need to go out and and either establish production facilities or produce with contract manufacturers um and uh take a product to Market uh a lot of those products will be B2B uh some of them will also be b2c but but we see ourselves as uh you can say not necessarily the very first part of of the supply chain uh because if you look on the left here the molecules can either be be something you take from nature we have later on milk protein as an example uh something you take from a cow or potentially a human as well um the molecules can also be invented uh or screened in large screening programs to find the molecule that has the best uh capabilities for for for some certain application so then once you find your you found your molecule we can help you actually make the production technology that enables you to produce the molecule economically feasible in in large scale um and I think the core competencies here is the strain development where the strains are are cloned with with the genes encoding your molecule and optimized and then the processes uh for fermentation and downstream development are are being um developed and and and optimized and then then lastly I think we see a very important point in helping our clients transition to larger scale um as you’ll see in a few slides we’ve we’ve invested in Pilot facilities here in uh in subo Copenhagen where we are based um to enable customers to get to the the first 1200 lers uh and from there we help them move on typically to a CMO with with larger volumes uh for some of them also into their their own facilities um but we’ve seen really that the ging step going from from the lab uh and into the larger fermentors both there’s been a a lack of capacity but there’s certainly also a lack of Competency to uh to do that step and it’s something we see that it’s quite often being underestimated how difficult it is um I think coming from the the industrial world we we all know examples where even established companies they I mean sometimes they even use uh two years to to do a successful Tech transfer um of their own strain from one facility to maybe to a new one so I think a lot of a lot of startups really really underestimate how difficult it can be often times it it’s related to you know the process conditions you run in your lab or maybe even in your pilot you you cannot you cannot copy those conditions one to one when going into another facility if you’re if you’re going into a CMO for example that CMO is used for a lot of other things um at the same time uh so obviously the conditions that the equipment need to be able to run over has quite broad ranges um but maybe it cannot accommodate you know the specific ranges that you need for your process then you need to do a lot of optimization to find okay then what’s the what’s the best alternative uh and and that’s not necessarily easy right sometimes you need to even invest in specific equipment uh at the CMO to really uh be able to get uh good enough performance um yeah so I would say our core competence actually spans quite broadly here uh inhouse we do the strain development we do the process uh development and optimization in in a scale up to 1200 liters um and then we have uh the fermentation and DSP Consultants that helps the client go into the CMO do the trick tick transfer and then succeed with the with the first runs in uh in larger scale course that’s where you start to commit a lot of money right when you when you run the larger fermentors um it’s a you know cut per run increases a lot so you want to do that uh right as quickly as possible so just briefly on uh on the value chain here we think it’s quite important that that um to kind of include the farmers here uh of course as I just said we developed uh processes and strains and so forth uh but but really fermentation is based on agricultural output uh typically it’s it’s purified sugar uh that’s what these processes have been developed for um because so far in history even though companies like Novis have produced large quantities it’s still quite small volumes and quantities compared to what we are potentially looking at in the future so going into lower value compounds like milk protein Silk protein for example we’re talking about potential volumes that are much much larger than what you know all the enzymes no enzymes has produced over the years um and there of course the carbon source is uh is super important uh because these molecules are going to be competing uh at low cost so you need cheap sugar sources which means they need to be fairly close to where you operate um they need to be purified only to the the the level that’s necessary um and and so forth so uh so the farmers play a a very important role and I think the one of the reasons we also want to highlight that is that when we move into milk proteins for example um we want to emphasize that there’s really no conflict with the farmers we’re talking about substituting molecules not replacing them uh because there such a a big demand for protein over the the many coming years that we need still all the available Production Technologies running at full speed so so the biological input both from us from the farmers as well um then there’s a fermentation and purification side of it which of course the CMOS play a large role here because they have established capacity um you know all the St startups that are operating in this field none of them have production capacity all of them more or less need to start with a CMO um which is difficult because a CMO is never optimized to your specific process so you’ll never have the best production economy with a CMO but it’s what enables you to get into the market start selling your your your product uh but eventually at least that’s if you have a product of any significant volume eventually you need to to build your own facility because that’s where you can start optimizing um and and and saving on your cost every year it’s it’s definitely one of the most important parts of of Nova’s success over the years that they’ve been able to uh improve strains and processes year year after year with about 5% um and you don’t get those uh Optimum izations and savings if you continue operating with a a CMO you can say in a nutshell you don’t really have the same you don’t have the same objective as the CMO right because every time you you do an optimization you actually need less of their capacity um so so they they don’t really have a big interest in in helping with that then lastly on on the product side um a lot of the outputs are going to be powdered proteins uh because that’s a very nice and stable form it’s easy to transport uh it needs to be probably resolubilized uh when formulated into products it can be food products for example uh drinks and and and and Foods where protein and protein functionality is tested or is is needed um and then we have the picture here of of the roles of of silk thread which is a nice example which is not food but a material that is is is not really uh available from any other sources uh because this this particular one is spider silk and uh and spiders cannot be grown industrially they they eat each other so so so the silk that you you know from your clothing is made by Silk worm it’s it’s it’s used to make a cocoon uh not a not a spider web so the properties are completely different of course the the products are produced by by b2c or B2B companies um and then uh purchased by fcmg companies making food products for example or uh or materials so here we sit in the very early end of the of the supply chain and the value chain we operate in in quite a broad variety of of fields uh Foods in terms of uh volumes um and and probably also potential right now I think the most important ones the milk proteins are are very important a lot of startups operating in this field because it’s so it’s it’s so obvious it’s h these proteins are good they’re nutritious but they also come from animals that that don’t have a very nice uh sustainability footprint that’s especially true for the milk proteins to a less extent for the egg proteins cell-based Meats it’s not something we do but there’s a lot of ingredients necessary for for the media uh for for self-based Meats um a lot of the ingredients are very very expensive growth factors for example that are known from s cultures in Pharma uh and there’s a big need to to produce those in uh in cheaper ways that are maybe not farma GMP but still have the right functionalities materials silks for example for textiles can also be uh something like collagens gelatines for for personal care compounds that today are extracted from from animals um use both in in in biofarma in in creams uh other personal care products um then agriculture where of course insecticides and fungicides typically are based on on chemistry uh chemistry which is uh not easily being degraded in the environment afterwards and and and oftentimes also have uh much broader uh activities than are needed now we we’re starting to see protein and peptides that are much more closely directed to specific pests uh which can be either insects or fungi potentially also bacteria um Rec compant and then lastly a fairly new field which is which is very very very interesting in in mining we see that a lot of the minerals that are used for uh for electrification uh I think more than 90% of those are controlled by China um and for example the Department of Defense in the US sees this as a major Supply crisis actually they they don’t like being very dependent on China for for these types of minerals including the rare earth that are very very important for for the electrification and Battery Technology um so the doe is actually or the dod Department of Defense is investing quite extensively in technology to extract minerals from spent mines um and some of these Technologies includes peptides and proteins which for some reason can bind to these Min minerals I think it’s it’s probably based on microbes that are trying to defend themselves against these uh toxic minerals and then they have they produce peptides uh that can bind them um probably to make them less harmful yes moving on so um this may be quite well known to you but but I I want to mention it anyway so um there’s a lot of challenges of scaling protein production and whereas you can say the very uh the very first part of the of the chain here the capabilities of making molecules designing new molecules uh that has been uh democratized so to say right you can do a lot with in silico screening uh you can do computer modeling come up with with new proteins and other compounds that that that has some specific applications that are improved compared to uh what was known before uh screening robots are being uh more accessible and can do can do high througho screening of lots and lots of lots of of protein variants um so that part is is quite easy um but the challenge is that you can make a lot which works in in the lab right but the the difficult part comes when you want to upscale it to to like the real life um and one thing is the microbial strain platforms uh so a lot of the work done in in small scale is based on University strains or public strains which are not really optimized for producing at large scale um um at the same time you have you have access to molecular tools that are are public uh they can be pretty good but but again um not really made for upscaling um lastly the competences for actually taking Technologies into large scale typically they’ve been sitting in the big companies um and and they’ve not been available broadly for smaller companies um I think that’s that’s beginning to change I think we see more more senior people from the big companies are are spreading out into uh into the startups but but I think for for some years you know after maybe 2020 and a couple of years from there uh this part of the journey was really really vastly uh underestimated how difficult it is and how how different these competences are compared to what you know if you’ve only worked in a lab and I think that was kind of what actually was the basis of of uh what our Founders saw when they when they kind of decided there’s a need and and we can help uh meet that need um so what they wanted to do was basically yeah accelerate the world’s quest for for these sustainable foods and materials you know over the years been a lot of good Innovation uh that really appap and the upscaling um and one important part of that was you can make a nice uh nice nice strain to produce your protein for example but if you if you’re not able to reach productivity levels or tighter levels that are going to be economically feasible I mean then you’re going to fail um and they saw that that this The Strain library that they have at noesis the former over SS um that that this library was capable of making production strains that could deliver uh productivity in in kind of an order of magnitude better than than what you saw a lot of other places so the idea really was to bring this technology to to be available for uh for other companies outside the the the core areas of of noesis which of course are the enzymes today I think we are approaching around 60 employees in uh in Copenhagen Denmark and uh in Davis California and and we are accelerating uh this in with with two different models I would say so one of them is strain development for uh for specific uh proprietary compounds so for example if uh if you’re a company and you’ve done your your protein screening and you’ve selected a variant of some molecule which is now more thermostable or it has changed functionality or something you can file a patent on your compound then we can make a strain specifically for your compound it’s exclusive to you because you own the compound it allows you to to go into the market uh and sell your compound exclusively with with good production economy you need to be able to control uh the application testing application development formulation uh everything that’s Downstream from from producing the molecule um but we can enable you to produce it at uh at at commercially relevant um production economy in the other model there are some proteins where we’ve said these proteins have so large potential uh that uh we want to make them available to a lot of companies in parallel uh and the first one we selected was uh becto globine the the biggest uh protein in in Whey from cow’s milk um so we developed a production strain for blg b electr globine um and we develop it to a certain point uh and then we offered it out in the market uh to customers that needs to to do the scaling uh do the application development and also do the downstream process development um we many companies actually want to to do their own DSP to give the molecule specific properties that are different from from from others have they want to patent around that uh to kind of Mark out their their space um other companies are focusing on on application development to make make products out of the out of the protein um but I think the main uh the main reason for offering this this program as we call it is that um the potential volumes of of the milk proteins are are so large that it’s going to take a lot of uh a lot of companies to to cover the field in combination uh and likely some of them are going to fail as well so so there’s definitely enough space for everybody um we are we’re working on a new program uh with the casins so casin being the the the major proteins in milk that are particularly used for cheese um and we are starting to to offer that into the market as well and the last Point here fast to Market um the important point being that the trins we have from noesis have been approved both in the US and in in Europe for production of food enzymes meaning that they are well known to the regulatory authorities um been uh adapted over many many years so that potential toxins and problematic side activities have been removed which means that uh it’s much easier to uh to have them approved for uh by the regulatory authorities um it’s quite easy to get the grass notification in the US uh it’s certainly not the same in Europe uh regardless whether your strain are known to them or not um I think that’s a that’s a whole separate discussion but that’s one of the uh that’s one of the points in this industry where Europe is really really lacking behind so an example uh um substituting milk protein milk consists of about 3% protein I think there are around 200 different proteins in milk um the the major ones being the quines which constitute around 80% of these uh about 3% um the way being uh I think the fourth the biggest protein in in the way is blg but obviously you can see that that of the whole content of the milk the protein is just a a fairly small part but these proteins are very very nice they have nice amino acid Constitution they they are very good nutritious proteins um and therefore it makes a lot of sense to try to uh to replicate them with uh another production technology yeah with uh with an Outlook to 10 billion people uh to be fed uh it’s quite clear that um with the with the current Production Technologies we are not going to be able to supply um enough protein especially uh protein produced by animals take up a lot of space and of course if you talk about cows they emit a lot of greenhouse gases especially methane which is uh which is not good if you look at um at uh the LCA of producing milk proteins by a Precision fermentation it’s quite clear that you can uh you can actually on more or less all parameters um reduce the input very very significantly if we look at the water use uh the the reduction is uh more than 95% um of course because cows live a long life drink a lot of water uh a lot of water goes into also uh you know processing the milk um so here you just do that much much more efficiently when you talk about the land use I think it’s a 70 60 or 70% of all agriculture is used to produce feed to to an so obviously if you have much much more efficient conversion of of your biomass to protein which a microb can do you can save a lot of land um and that land can either be used to to uh you can say capture CO2 in in trees for example um or it could be produ used to produce uh other crops that that humans can eat greenhouse gas emission is is very very large especially because cows burb a lot of of methane um so potential huge savings there and then also a very very nice uh savings on on energy lastly we we wanted to brag a little bit about this um again the self-affirmation Gras so the grasp process you uh you submit to the FDA in the US your uh your doia in the doia you describe your production process uh for the way you you make your compound and you argue that it’s safe for for a lot of different reasons in our case we argue that it’s safe because the strain has been used for a lot of other approved food products it’s a strain which is actually found in in food products in Japan for example it’s a fungus called aspila oray so even the strain itself can be used for food and then the protein we’re producing is more or less identical to to what cows are producing and of course then we know that humans have been exposed to these uh compounds for many many years so now the we’ve got the What’s called the self-affirmed grass status in the US which allows our customers to to actually go on the US market and sell the Protein that’s not happening yet because none of them have have scaled uh to a size where they are actually entering the market um but we expect them to do that during 25 so that was my last slide Matt you said a short round of questions now and then uh a longer round of discussion later sure yeah I I think for the sake of time we might move on to Kelly but thank you so for thisa it’s fantastic I I know I person have a of questions and I’m really excited about the work that you’re doing so thank you so much all right I’ll stop sharing okay uh I’m gonna share my screen here great okay there we go are you seeing the slideshow yes we are okay great um so I just have a few slides they’re not nearly as professional as the ones that Rasmus just showed us so but uh um I’m going to give a little bit of background on myself a little bit on some things that I learned about uh scaling up uh working with Industrial Products at AG biome and then some general needs that I perceive in the industry and a little bit about um what stable fermentation can offer which uh I’m working with them as a consultant right now so um so let’s see how we do this effici there we go okay so short little bio for me um I have degrees in chemical engineering and environmental engineering I had started a company called Pastoria bioscience which was a biopesticide company um sold that to senta I did work at AGG biome for about six years which was a local biotech company here that um produced biopesticides and also uh traits for crop plants um out of a very large library of Novel microbes and I went from there to a company called join bio which is up in Boston and they were producing biofertilizers which were engineered microbes for that um I was the VP of R&D at oh that there’s no name on that one all right that’s DMC biotechnologies which is a a local company here uh they have a lab here in morseville North Carolina near RTP and another one in Boulder Colorado um and then the last one there which also the name didn’t come through uh anyway slide translation not always working that is the logo logo for Sable fermentation which is a a new local cdmo for fermentation and downstream processing here so I have a lot of background in producing biological products uh doing the process development doing the scale up the registration and the um actual commercialization of products for agriculture and for industrial production and so some of the things that I’ve learned from what goes on with these small companies uh and this applies not only to AGG biome but to all of those other companies I work for um and rasma already alluded to a lot of this finding tollers to produce even relatively small pilot batches up to 100 liters can be very challenging um there aren’t a lot of facilities that will that will do that especially for nonfarm non phological products non um human Pharma uh and so people need to build in more time for that this is a thing that I think trips up a lot of small companies is not leaving enough time to uh deal with some of these issues and the next one then of course is getting the permits right um uh the regulatory regime of course is different everywhere you go um in the US it even varies state by state and so you have to get uh permits at a national level and a state level and sometimes even a local level even to just move your microbes around um much less to produce them at larger scale and then to release them into the environment if that’s what the product is for um so people need to build in more time for that um you need to build in time to get the operators at a contract facility or a to are familiar with working with new novel microbes um this is going to be the case with a lot of these novel industrial processes too even if your host strain is ecoli um the engineered strain that you’re bringing to them um from a a process like something that that uh 21st bio would do for you is not going to be familiar to that Toller and so they need extra time to understand how to handle that microb what its specific quirks are in their process and as rasma saluted every facility is slightly different so it’s not going to be optimal for your micro even coming out of a professional uh optimization process like 21st bio is going to offer so you got to build in time for that um your Tech transfer pricing is going to be very important as for a small company you have to understand you know a Toller is going to charge for their time to start off with and so you want that to be that you want that to be a separate body of work from the actual manufacturing and moving to an outcome based pricing that’s what’s important for a small company and as was previously discussed you know you as the as the producer your incentives are not the same as the Toller the Toller wants to charge you for as many runs as possible you as the producer want to produce in as few runs as possible so as to optimize your your production cost um so that’s that’s a negotiation that people don’t often uh plan ahead for or think it’s going to take as long as it does or be as contentious as it can um and it’s it’s just one of these are just a few things that you know I have I’ve learned in in doing a lot of this that is it’s just going to be very impactful all of these things as we move into a more biobased um manufacturing economy and then um some of the other things that uh Jen suggested that I should discuss with all of you today are General issues that have come up in the field of biomanufacturing and so again some of this we’ve already alluded to in Rasmus talk but there there really aren’t that many options um at the pilot scale so 500 liters up to about 25,000 lers it’s very difficult to find a facility that will produce at those levels and um the the facilities that are available are you know in high demand right so it can it can be challenging and and that’s the scale you know up to about 25,000 liters that a small biotech company especially for agriculture is trying to produce at kind of right at that level to do their initial field trials their registration trials their sort of regulatory process they don’t they don’t need a 100,000 lers of material um but it’s often difficult to find this intermediate scale fermentation um and we already heard that uh every process needs different Downstream processing so a Toller may or may not have the right equipment it may not be similar to what you’ve worked within the lab it may not translate immediately depending on how your microb behaves um and so you might actually have to go to another facility for that and I experienced that numerous times at different companies where we could find a fermentation Toller but then the downstream processing either they didn’t have the right equipment or they didn’t have it on the same site um having to then you know contract with a yet a third company to go actually do the downstream processing especially drying a lot of fermentation facilities don’t have extensive capabilities for drying um and so that can also complicate your your bio Manu manufacturing process so as we’re thinking about you know developing all of these um bioeconomy type infrastructure um it’s important to think about DSP in ter in addition to fermentation right how are how are we going to enable that um and then I didn’t even get into formulation which is a a whole other can of worms that you can get into after you’ve done you’ve done all of that um and then the other thing that happens when you’re scaling up is of course that your supply chain is not optimal right your your raw materials can be hard to find in those exact intermediate quantities it’s easy to buy um you know one kilo or five kilos from Sigma but you don’t want that unit pricing when you get up to trying to produce even at 25,000 liters and yet some of the raw material producers are not used to selling anything at less than tank car uh volumes and and so you know getting getting your supply chain to match up with what you need to produce can be challenging um and high unit course unit costs of course drive up the cost of the final product and that’s not what you’re after so um all of those are issues that that uh have have come up for me um and then this slide is really just about the digging in a little bit more into the lack of some of those resources um I a lot of the products that we’re talking about these Industrial Products the things that that the McKenzie uh study showed can be produced by biology um often can be difficult to find a place to do it because the most of the facilities if they’re if they’re geared for pharmaceutical production or certain other kinds of products if your product is non Pharma and non food they don’t want to handle it uh the the two regulatory regimes you know especially in the US between the FDA and the USDA and the EPA uhuh they will they will not try to make those match and so it is not cost effective for a facility that’s doing cgmp that is making Pharmaceuticals that is making you know food ingredients to handle a product that doesn’t fit into that regime you could do it but then of course it drives your cost up and especially for products that are Commodities or for agriculture uh the cost uh just doesn’t make sense for what you need to be able to sell that product for so that’s that’s an issue um another uh problem comes up when you’ve got a non-canonical host right if your if your host is anything other than eoli or sacy or basilis um the facilities are going to say wow how do we how do we make sure that everything in our facility is clean if it’s a spor forer especially if it’s a spor forer and it’s not you know something they’re used to handling they’re like oh my God how are we going to make sure that you know everything is clean for that for the next customer or our own production that’s coming in after that um if you have a a non canonical microbe and maybe you haven’t engineered it but it’s you know a wild type host strain that came directly from the environment you probably don’t want to use antibiotics in that fermentation because it’s probably not engineer it’s not resistant to standard antibiotics right and so um we ran into this at a biome where we had a pilot scale facility that was otherwise very accommodating happy to work with us everything was going fine and then they found out they couldn’t use antibiotics to control the the cleanliness in their facility and they were completely at a loss like well we don’t we don’t know what to do now so that was a problem um and then if you if you’ve gone even further where you have canonical host and you’ve engineered that microb and then you want to produce it at scale and then you want to ship it and you want to release it and everything else you’re going to have a whole different regulatory regime your contract facility is going to want to see you know copies of all of your permits they want to know you know how can they be sure that this microbe isn’t hazardous to themselves to their workers to release you know they don’t they of course don’t want to get in trouble if they have an accidental spill of the stuff so they you know there’s going to be a lot of additional regulatory documentation and just kind of getting everybody comfortable with that and then there’s going to be a new growth protocol there’s going to be new down Downstream processing so like I said earlier you got to build in extra time for the tech transfer around things like that so um all all of this stuff I think kind of doesn’t really doesn’t really surface in people’s attention when they’re talking about biomanufacturing until they’re pretty far down the road um so I’m hoping that you know this kind of a forum we can you know have some discussion about how to make that situation better so um as a consultant for Sable fermentation I can uh discuss a little bit about what Sable offers um Sable is a new company cdmo uh starting up here in the Research Triangle Park area it’s actually going to be in Wake Forest North Carolina and um Sable is offering Consulting and technoeconomic Analysis services so I didn’t even I didn’t even touch on tea but that’s another another area where um you know make making sure that a biom manufactured product is actually capable of making money it you know can be produced economically in such a way that the manufacturer will actually survive um this is this is a service there’s other companies that are offering this but we have a lot of expertise on the team so we’re we’re offering that and then uh a process development optimization scale up uh spray drying and analytical all of that is covered by the the equipment and the expertise we currently have on the team to dig into that a little more so Sable has fermentation up to 200 liters currently that’s uh being installed I think next week in the facility and then the plan is to go up to 25,000 liters with additional capacity uh on the same site and then uh all of this other equipment is already also available and is getting installed so the Imaging equipment the analytical capabilities which it’s pretty unusual for a company of this size to actually have all of that analytical including the hplc so I’m pretty excited about that that’s going to that’s going to allow a lot of um data collection of the output of the fermentations that a facility like this typically doesn’t have uh and then there’s some there’s quite a lot of Downstream capability um uh tangential flow for concentration or centrifugation the tubular Bowl centrifuge is kind of an unusual piece of equipment again for a company this size that that allows for a very concentrated cellular paste to come out and that can be very useful especially if you want to go then dry your product um and then the company owns a spray dryer um which is already up and running and can we can offer that service right now if you have things that that need to be spray dried um so that’s that’s very exciting uh this is really filling a niche here uh as we discussed a little bit earlier it’s difficult to find uh tollers that will do all of this and I think um the team that Sable has available is really unique in this area also um Tony herself the founder of the company Tony BCI she had a a long career at agbiome and before that at BASF she’s a very capable commercial executive um her uh first hire was a fermentation engineer who I personally hired at AGG biome so I was very pleased about that uh she serjan has a lot of experience uh she worked at Maron bio she was at AGG biome for almost 10 years so she’s done a lot of process development a lot of scale up lot of Downstream process development um they hired the uh operator of the equipment that they purchased so that person knows all of that equipment inside and out backwards and forwards so that’s that’s very exciting and we’ll have a a really capable staff actually on the ground in the lab uh and then myself I’m currently working with them as an adviser um with all of my experience in doing this kind of process development Tech transfer regulatory strategy all of that so very very excited about what we can offer as a team um and that’s my last slide so happy to take questions about that and have a have a good discussion fantastic thank you Kelly that’s really interesting and it’s it’s really great to see all the work that you’ve been doing and that Sable is doing right now um selfishly I would love to ask a first question to kick things off and then open the floor up um both of these presentations have me burning with uh a bunch of questions but I I’ll just ask one uh and for me it’s like from the perspective of an academic thinking about a spin out or from a startup company um there really are such different incentives in the near term to be highly standardized to fit into what limited capacity there is for a CMO or cdmo and then in the longer term to sort of own your own process that you know as you can tailor you then get that cost down or you get that product quality to where you need it to be um and so with these very different mismatches I feel like there could be a lot of sort of ort of um pitfalls where if we take a very simple one like uh mode of operation maybe in the beginning you’re you’re optimizing everything and you’re strain around batch mode uh fermentation and then longer term maybe you’re like okay a longer continuous campaign might make sense when I have my own equipment to do so but maybe you have don’t have the genetic stability that far out or you know all these other considerations um to either of you have have some advice or um some considerations for someone who’s thinking about that maybe being dragged in one way or really good for a CMO but then they never make commercial viability like how how to think about that Rasmus do you wanna you want to tackle that one yeah yeah yeah I mean at least I would say that um that if you are if you are betting on on the wrong strain uh I mean all the time you use on that strain is eventually lost I would say it’s it’s it’s a blind alley so you need to make the right choice as early as possible Right a lot of our companies are are people who started out as molecular biologist in the lab because they knew how to make uh strain construction but they never had access to Industrial strains right so it’s a very very difficult decision for them to to abandon their own strain program uh quite often it’s their own capabilities it’s uh potentially having to even fire people in the company because you may not need those competences anymore uh you’ve made promises to investors that you’re going to own your production technology and so forth and and we cannot offer that right we we’re based on licensing the noesis technology um so I I think um yeah I think it’s not a good advice to try to to get as far as you can uh with with your own if you know that it’s never going to be good enough um of course you you may need to take it far enough to make small samples to to do application testing and so forth but but really trying to start scaling a technology which is never going to be economically feasible that that’s a waste of money yeah I I would Echo that and I I think that’s that’s another area where the technoeconomic analysis is so important you can you can use those mathematical models to help you project into the future you know is is a particular host or a particular particular U production pathway metabolic pathway are are those eventually going to be scalable and be economical to to produce with or or not and you’re absolutely right people do kind of get a little bit um attached to their own their own strain their own technology and so I think you have to you have to go at it with a very clear eye towards you know what what does this really look like in the future and those models can help um what what constitutes a minimum viable product in a biolog iCal process is a matter of uh intense debate right is it um is it a small production sample is it a microbe that’s been scaled up to a certain scale is it is it you know actual customer verification about the the product um I think it kind of depends on the industry that you’re that you’re trying to get into somebody’s got a hand up theirs Paul hi everyone um first thank you to both of you for very nice presentations um I have maybe uh two questions if I’m allow or or one question and one is more a naive question but um all of that is great as an end user a company who um you know may buy some of these ingredients because we are not in in the business of producing these ingredients so we’re going to buy um let’s say we have um potential supplier of these ingredients I’m left with um maybe two herles that are very lightly addressed so far or at least I’ve seen for every conversations I’ve had um there is very little conversations around the targeting the right protein functionality and how can we be sure that the technology that you guys are presenting are really making the right functionality of the proteins and if you talk to a few professors around they are saying that’s the biggest hle today there is lots of dreams promised but how do you get that and then the second is the CO2 footprint analysis lots of nice dreams also 90 plus% CO2 reduction but when you talk to some engineering companies they say these guys are dreaming it’s never going to be like this and hearing that there is no production capabilities or everything is being scaled up how can we really be sure of the CO2 footprint uh so so for me these are the two hurdles for these ingredients to be Mass market and then the second one is maybe more um on Kelly but it’s not the first time that I see uh people like this they talk about fermentation capabilities in liters but as an end user I don’t care liters I want to know how many kilos of powders can I get after the fermentation so it would be great if somehow um this area stops talking about fermentation volume of their of their fermenters but talk about uh yield or kilograms of powders that I get after spray drying yeah I’m gonna let Rasmus tackle the first one and then I I’ll tackle the second one yeah yeah so to the first one to for for the the LCA calculations I think you don’t really know until you have a dedicated Factory which is made to produce a specific protein right because then then you have the cheapest possible uh factory set up and it’s optimized uh to be as efficient as possible then then you really know um and and the numbers we are throwing around um I think they may be off but they’re not they’re not totally wrong uh for sure but uh but it’s when we talk about milk protein at least with our strain it’s not been scaled above uh above 10,000 liters yet so um so we don’t we don’t really know um your other question uh it slipped my mind could you just repeat the first question on the protein functionality yes the functionality you know from from a 21st bio point of view that’s that’s specifically the responsibility of our customers uh we will help make the strain and the production technology they need to feedback information to us if the if the protein is not working correctly for example do you have truncation of the inter Terminus or that that changes functionality or do you have glycosilation or phosphor relations or something that are that are off um that needs to be tested and the information needs to be fed back back to us so we can make the the the the proper amendments um so we we’ve decided that we want to stay out of of the application testing uh because our Heritage from no signs tells us that that’s just a huge task and and when you’re operating across many different fields uh that’s a that’s a big and and lengthy investment um but I think all of our customers in the milk space I mean they that that’s really what they focus on uh making the proteins work uh in in different aspects of of uh formulating food products um okay so then on the question of the uh the actual kilos of output from a given volume of fermentation um I think you’re absolutely right one of the one of the reasons that we end up in this situation is because people with my gra background the fermentation Engineers if you ask them you know well how much you know what kilos of output can I get from a 200 liter fermentation what they’ll say is it depends so um I think the the the tea can help a lot with that right you can you can use that technoeconomic analysis to say okay with this metabolic pathway engineered into this microbe that grows up to this level then you can expect to get you know this range of kilos of output especially if you use our spray dryer or whatever right you can you can easily model that if you have a little bit more information about the process um but with that said I think it would behoove us as uh as an industry to start talking about kilos of output right say and in a in a typical ecoli production process that means you get x amount of protein out of it um you know with all of those caveats that every process is going to be slightly different yeah Matt I have a customer call so I I need to to hop off yes of course and I I wanted to say it feels like we’re just picking up steam but I understand we we have to end at this point so thank you very much to both of our guests here if open to it happy to make some connections so happy to facilitate and discuss on both sides to see what happens if you want keep going out of here but thank you so much everyone for your time really really appreciate it really anybody wants to talk thanks you’re welcome bye bye fantastic bye cool
