Better media, better outcomes

Introduction:

This webinar will focus on understanding the time and cost of custom media and proprietary off-the-shelf media. We will cover such things as:

  • The upfront and long-term cost of custom and proprietary off-the-shelf media
  • Why custom media is worth the investment and reduces long-term costs
  • Two case studies for custom media

Full Webinar Recording:

To watch a recording, simply click here.

Video Clip On Lead Times:

To watch a clip on lead times, simply click here.

Video Clip On Cost:

To watch a recording on cost, simply click here.

Webinar Audio Recording:

Listen to the audio:

 

Webinar Transcript:

Rachel Gauvin:             My name is Rachel Gauvin. I’m Head of Program Management at Nucleus Biologics. We’re all happy to have you here for the webinar today. We have this poll, which I will share the — can you all see the results of the poll? “Which is more expensive, Custom Media or Proprietary Off-The-Shelf?” We have 57% say Custom, 14% say Proprietary, and 29% say, “I don’t know.” And, “For the development of your media, which takes longer?” Custom comes in at 71%, and I don’t know at 29%. So there’s those results. Super fun.

We’re happy to have you here for the webinar. I just want to encourage you all to use the Q&A function throughout the webinar today to type in any thoughts or questions you may have. We’ll have plenty of time at the end to address those, so just use that function throughout, and that will be great for discussion at the end of the webinar.

To get us started, we will kick off. For those of you that may have found us before, we did have a previous webinar to this called “Better Media, Better Outcomes.” This is on our website to view. If you’ve not seen it or if you want a refresher, that’s on our website to take a look at. Today is “Faster Media, Faster Outcomes” webinar. You are here, so that’s great. We have the future, upcoming webinar, “Intelligent Media Formulation Using Machine Learning,” which we’re really excited about. You all should get notified when that is available for registration, but we have this fun-filled free, old webinars that we’ll be moving forward with.

We have great panelists today, and I’d love for each of them to introduce themselves. Dave, do you want to start?

David Sheehan:             Hi, I’m David Sheehan. I’m the Founder and CEO of Nucleus Biologics and excited for today’s presentation.

Roddy O’Connor PhD:   Hi, I’m Roddy O’Connor. I’m a Research Assistant Professor at UPenn, and it’s great to be back for webinar number two.

Alex Klarer:                  Hi, my name is Alex Klarer. I’m the Head of Cell Therapy Development at CDMO BioCentriq.

David Smith PhD:         Hi, my name is David Smith. I’m the VP of Technical Operations at Ori Biotech. Looking forward to a debunking of all those theories around media.

Rachel Gauvin:             We’re looking forward to it, and thank you all for being here. Alright, Dave, do you want to give us a little recap of September?

David Sheehan:             Yeah, sure. So, if you missed the prior webinar, I encourage you to go back. It was really a — it turned out to be a very good discussion and a lot of great Q&A afterwards. Really, what came out of it was the concept that media can be a competitive advantage in your therapy development. Whereas a lot of people just think of media as an afterthought as they’re going through their process, what we actually came to the conclusion in that webinar was it can be something that really improves the potency of your therapy.

There were a couple of key points, and I took screenshots of the individual slides. One, there’s a perception out there that even standard basal media is all the same, and the reality is it’s not. This upper left panel is actually the amino acids and soluble vitamins from five different vendors’ DMEM, and if you can see the colors, those colors should all be lining up in columns because each column is a different amino acid or soluble vitamin. And the reality is it doesn’t. There were no two vendors that were the same, which means there’s a lot of variability in even straight-up basal media.

The second panel in the upper right is around how just changing the protein source in your media that you’re expanding your cells in will change the potency of a CAR-T cell, and the cells were grown in either Physiologix plus OpTmizer, which is a common off-the-shelf basal media, or human serum plus OpTmizer. And, what you saw there, the key was in the challenge dose, which was one quarter a therapeutic dose. There was a full log difference in tumor suppression in cells that were grown in Physiologix versus human serum. So just changing the protein source can affect potency.

Then, the last panel there at the bottom, it’s basically around what — there’s a perceived impediment to going custom, and one of the concerns is “What’s the development time?” But, if you look at the development cycle, you probably have a year or a year and a half before you go into actually the pre-IND stage and during that period, there’s ample time to develop a custom media. So some of the perceived impediments are around cost; it’s around development time and, maybe, expertise, and I think what we want to talk about is let’s drill down on these items today. Let’s really understand how each one of them — in the origin of somebody’s perceived impediments.

Okay, next slide. We’ll start with some basic definitions. When we talk about custom media, we’re talking about a formulation that’s built based on ingredients that are specified by you; you know every single component that’s in your media. The common approaches are you can either start with a basal media formulation, or you can build it de novo and make it completely custom, but it’s got to be optimized to the CQAs that you’re trying to achieve within your therapy’s ecosystem. Every ecosystem that you’re growing your cells in is unique; therefore, you’re going to have unique metabolic requirements.

Whereas, POTs, which is proprietary off-the-shelf media, has a very specific definition in our mind. It means cell-specific media that’s developed by a media manufacturer. They spent time and developed it, but it’s secret in both composition and concentration. Most companies are not willing to disclose the ingredients of their formulation; therefore, as the user, you can only really modify the performance of that media by adding reagents at point of use. There’s limitations on how much customization you can do.

So we’ve established, and this was a slide that we presented in September, that media is a critical part of your therapy ecosystem. We pretty much showed that small changes in your media can have a material impact in your potency — not only the protein example that I used earlier, but also we showed one with arginine and with glucose restriction and the impact on potency.

So, if you look at this dilemma — and to us and probably to a lot of scientists, it has been a dilemma — proprietary off-the-shelf, it’s unknown ingredients, it’s not your IP, and you’re locked into a sole source relationship with that supplier. The upsides are supposedly faster regulatory, and it should be in stock. Whereas, custom, historically, had really long lead times, was very challenging to iterate, but you own the media, you know every ingredient, it can become part of your IP portfolio. So the question really is then: “Okay, well, what’s the development cycle and cost for each of these processes?” And I’m going to cover the development cycle portion, and then David will cover the cost.

So, if you look at traditional custom, the weakness is the manufacturing process and the configuration and quoting. That is really the Achilles heel of traditional custom media manufacturing. If you look at it, you’ve got to research components, you’ve got to figure out what your configuration is, fill out online forms and, or download forms, fill them out, work with a manufacturer, get queued up, and the whole cycle can take, if you’re going to go through two iterations, almost a year to develop custom media. Clearly, that’s not a viable alternative, and you buying all of the individual components is also probably problematic. Whereas going with propriety off-the-shelf, you can research suppliers, you can get a whole bunch of different suppliers in-house and then start media testing and development, and then you can add supplemental reagents.

So, obviously, custom, there’s a lot of benefits to it, but if the lead time is a year, it’s a non-starter for most people. And, really, the issue with proprietary off-the-shelf is that it’s a lot of trial and error. If you look at — here’s a list of potential companies that you could try their T-cell media formulations and then reagents if you’re doing T-cell work. If you have seven reagents, that’s 125 unique combinations, and that doesn’t count if you’re modifying concentrations. That’s just putting it in there as a individual component. If you multiply that by the number of basal media tested and then add in some concentration ranges, you’re looking at thousands of test conditions. This is only with just these reagents listed here, so the issue is that you have to use trial and error because you don’t know what’s in the media. This is not ideal either, so it’s truly a dilemma. You have two less than ideal solutions that you have to choose from if you’re the scientist.

So what we created was a new model for custom. The idea was that you could go online on NB-Lux and research components, configure, and quote, and we’ll show you how long that takes. It’s usually less than two weeks, and actually the fastest part of that is going online and doing the ordering. We do small lot manufacturing, down to two liters, that takes around four weeks. It gives you six weeks to do your testing and iteration on multiple versions. Basically, compared to proprietary off-the-shelf, what we’ve been able to do is compress the lead time for custom media development down to 22 weeks.

So it takes the same amount of time to develop custom as it does to create a proprietary off-the-shelf formulation, and at the end, what you’re left with is a formula that you own, that is resident on NB-Lux so that you can at any time go in, you can change the quantity, you can change the packaging, configuration, you can change the testing. It’s basically like a Lego set that allows you to build off of it. With proprietary off-the-shelf, you’re left with media that is going to require additional reagents that you’re going to have to add at point of use.

I’m going to turn it over to David. But, basically, what we have gone through and proven is that development time is equal. But what about cost? That’s really the next question. There’s a perception and from the survey, clearly, the perception is that cost of custom is higher.

David Smith PhD:         Thanks, David. So we’re going to start with POTS here. We’re just looking at a couple of brands there, adding a bit of protein in and some of those reagents — just very ballpark figures. Obviously, four examples here taken from the T-cell world, looking at sort of a smidge on the $300 for a liter there, and I think that’s sort of a number to keep in your head and should be one that you’re all pretty familiar with. In the grand scheme of things, that’s a pretty low price. It’s where the market stands today, and we’re pretty happy with that.

I think, on the next slide, we’ve sort of taken a dive into “What does it really mean in terms of what you have to do in upstream and downstream of that,” as David mentioned, “as we can get now get the development time to very similar?” It’s now the cost that we start looking at. I guess, firstly, you just draw your eyes on the measure. Most of yours, it’s to that bottom right corner, which I think is probably where the data, based on the question that was asked upfront of the webinar, $470 per liter and sort of the two-liter scale… That’s really been the large problem with going custom is if you want a small batch of manufacturing, generally it takes a long time, and it costs a lot.

There’s a lot of things to unpick in that. I think, as you scale up — and it’s obviously the aim of everyone here, to get to that commercial finish line. Even sort of phase two, phase three, the volume of liter, you get the 200-liter batches pretty quickly. We’re looking at eight, ten liters per patient for autologous now. It’s not many patients that you need 200 liters for. So, now, you’re actually saying, “Okay, custom is probably cheaper, the 189 versus that 300.”

There’s a lot of other things to unpick in there. David obviously mentioned some of the how you order it, owning the IP, those sorts of things, but take a look on the left — you’re ordering from three, four, five, six different suppliers? That’s three, four, five, six different supply agreements, contracts, that you have to put in place, prices that can vary that change that bottom line figure. You’re then going into the clean room and having all of those together, so now you’ve got clean room time on top of that, you’ve got the facility that you need to do on top of that, all of these things that if you go custom, you don’t have to think about. It will have absolutely everything you need in that one pot and send it to you.

And, in that blue box there, QC, that’s something actually that I didn’t even thought about until I started putting some of these slides together. You’re getting a QC on your base media, you’re getting the QC on your reagents and your protein, what you’re not getting and understanding actually what’s in that big pot at the bottom when someone’s gone in the lab and made that. Yep, there’s batch records, they’ve signed off, it’s validated, but I can assure you there’s variability in that pot, probably far less variability in the custom pot, which you’re doing over on the right, of which you’ve now got a COA of exactly what is in that pot. That pot has been tested for you. I think that’s a really important feature to pull out of that.

As we dive into the next slide, onto more sort of the development costs — and I think, again, this idea, when you’re at the development scale and you need small batches, you’re right; it’s more expensive to do the custom. You’re looking at sort of the 26k — and it’s just an average development process that we’re running through here — on media versus 18 for the POTS. We’ve shown as the development times, that blue block, it’s actually the same. So, in total, you’re looking at 115-ish, down to sort of 105. So there is a bit of a difference there, but it’s not too much and, actually, the important thing is actually the time. The actual cost of the material is not driving this model at all. It’s the time. The big blue bar is what’s driving what you actually have.

So, then, you start to wonder if you know what’s in your media pot, if you can change things, can you actually develop things faster? And do you need to go through as many iterations, as they mentioned, the 125 combinations if you got seven reagents without looking at concentrations? Can you actually do development faster? which is one thing.

And the next thing is, that’s just in development. As you move forward into the next slide and you start looking at your life cycle costs, the important thing here is that development bar doesn’t even show on here. We just said  that there’s a 100-somethingk on there? Doesn’t even show when you’re looking at your phase one, your phase two, your phase three. Just looking at the media costs, the numbers rapidly go up as your numbers of patients go up.

So, if you’re worried about saving sort of your $10,000 in development — and I understand that. Every penny, every dime, every dollar, you’ve got to account, when actually, you making a decision at that development is going to have an astronomical effect when you get later. And this is Commercial High: 5000 patients. You’re spending sort of the 8 to 12 million just on the media alone. And look at the difference. There’s $4 million every year for every 5000 patients in this model that we’ve put together. I think that box in the middle really strikes a chord with that rate. When you look at how you trade from a biotech standpoint, which is 30 times your earnings, if you take that 4 million times about 30, you’re 120  million of company value. You can write off 120 million of your company value by potentially choosing POTS over custom just in this model.

So that 50% higher cost as you go to commercial, that’s what is going to start driving the success, the cost of goods of your product. It’s not going to be a cost of goods in development phase one, phase two — which people aren’t worried about it, most people don’t think about it. I really want to stress how important it is to think about it early, to make that choice because it is going to make a big difference later. We know that if you’re in phase three Commercial Low and you go, “I wish I could have gone custom.” That comparability cost now, you’re going to take that yellow line, you’re going to add x million dollars on top of your comparability in order to get to that blue line. And, potentially, you’ve just lost all of the benefit of the blue line. I think vital.

So just a quick summary to go through. Hopefully, what Dave and David have shown you right there now — so the development costs for the media are actually dominated by labor hours. It’s probably not a big surprise to you, but it does mean that maybe we shouldn’t turn away expensive media at first glance. Maybe it’s a longer-term solution. The development time, as Dave showed for NB-Lux, now is the same as POTS. You can get this media at the same time. The actual scale production cost is a lot less, 33% less, going custom that POTS in our models.

It’s the crucial thing, right? If you take cost out of the picture, even if they were the same cost, you own the formula, it’s your IP, you can move it to any manufacturer, you’re not locked in, you’re not locked into the wedding photographer price. This idea that once you go commercial, there’s an extra zero on the end of your media price. You say, “Who owns it?” You want to go from bottles to bags? You can do that. If you want to go from one-liter to five-liter bags, you can do that. You can take your IP knowledge, your formula, and you can have a second source supplier. You’re not relying on that one person that manufactures in one site that sometimes gets a hurricane rattle through, right? You can set up that second source.

And, another one, this cost of failed lot. If something goes wrong, how do you investigate if your media is the problem? Anyone tried to understand if you turn to your current POTS supplier and ask if there’s any issues? Of course, they’re going to say no. But you actually own everything that’s in there. You can really do root cause analysis and find out. It’s on your bottom line there: scaled production. You’re looking at millions of dollars of cost just for the media itself, let alone the IP, the manufacturing cost, failed lots, and things. I think it’s a really important thing.

With that, I’m going to hand over to Roddy to take you through a case study and example.

Roddy O’Connor PhD: Thank you, David. So we thought it’d be quite interesting to actually go through a case on one of the challenges we had here at Penn. We were reaching out to Dave Sheehan and saying, “Get the platform up. We need this. We really need it.” We’re often asked what fuels CAR-T cell killing and very interested in metabolism here and the metabolic activity of CAR-T. We quickly realized in these studies that there’s inherent limitations in the proprietary media. You really can’t discern kind of the impact on individual components very easily because you’re just given a bottle of media and everything’s already in it.

So the goal really was to use this platform with ease, the NB-Lux, and design a media lacking — we’re specifically interested now in looking at the role of individual amino acids and how they fuel CAR-T cell metabolism and growth. So we wanted to jump on the platform, design a media lacking a given amino acid, and see how that influences things like potency, killing, growth, mitochondrial function. That’s exactly what we did, and the platform was very easy to use. We got our media as was noted earlier very quickly, and we’re excited to share some of the data with you.

We can go to — just going to show an introductory slide and kind of the idea of CAR-T cell therapies in case people aren’t aware. We often give an analogy of soldiers, that if you isolate T cells from a patient — think of the cells as patients, and you want to increase their numbers. This is where they kind of rewire their metabolism to support their growth. And we give them this weapon, this CAR, to redirect their specificity against distinct cancer antigens. So these cells are grown over time ex vivo, and then they’re kind of reinfused back into the patient like a task force back to the battlefield.

We can go to the next slide. Thanks, Rachel. From our earlier work, and this is published, we’ve looked at kind of using a very simple media. This is easy to obtain, a media lacking glutamine, where we add isotopically-labeled tracers, such as a glutamine tracer, so it’s uniformly labeled, and we do some kind of hardcore biochem where we follow or trace its contribution through the TCA cycle and look at mitochondrial function specifically.

I’ll show you an example. Here we go. We’ve obtained a glutamine-free media previously and added a tracer at varying levels, so you have different concentrations, and then traced its contribution to short-chain CoAs in the mitochondria, acetyl-CoA and succinyl-CoA. But what happens when we want to look at other amino acids? This is very challenging to get the right type of media for this. So we jumped on NB-Lux. We can go to the next slide. We designed a media lacking arginine, and we basically performed the same kind of experiment, where we’re increasing the availability of an arginine tracer — so it’s isotopically-labeled, 13C — and we can follow its contribution into who were showing not just a kind of a mitochondrial function; we’re looking at the recycle, so looking at the ability of arginase to convert the tracer molecule arginine into ornithine. And we show this here that arginine supports a large contribution of ornithine levels in T-cells and with a dose-dependent effect.

Now, this would have been very challenging to do this with a regular media containing already one millimolar arginine. It’s not easy to obtain. Instead, we’re able to jump on the platform, develop this media with ease, and it opens the door for us to look for — there’s 20 other amino acids — other amino acids and look at their individual contribution to things like CAR-T cell killing, which will be of very interest to us.

We can go to the next slide. Really just to pull it all together that we had this challenge — there were certain medias available lacking glucose, lacking glutamine, but if you look beyond that, you really need a custom media and you need a platform you can use with ease and to kind of get the media quickly because this is when you have the idea and graduate students lose interest very quickly. We were able to do this with the NB-Lux platform and test with the tracer the ability of arginine, evaluate its contribution to T-cell function and CAR T-cell function. We really found the platform very helpful for our studies in looking at the role of arginine in T-cell function. So we can go — and, with that, actually, I’m going to pass it over to Alex for another case study of interest.

Alex Klarer:                  Thanks, Roddy. So, in this case study, we’re going to look at changing from a standard animal product–supplemented media onto a xeno-free vaccine media. What this company was looking to do was generate a novel vaccine, but they were struggling to eliminate the animal origin partly because they couldn’t get an in-depth analysis of their media and partly because they had done a lot of their CQA definition already and were looking to maintain that level of quality. You’ll see this is kind of a common endeavor for a lot of early-stage companies that are coming in with potentially an FBS-supplemented media and wanting to move over to something either serum-free or with a human origin protein supplement.

So the Nucleus Biologics Formulation Team was able to use a high throughput screening method to crew-cut, select a number of components, and formulate this xeno-free media that they were then able to carry into their process development in a rapid two-cycle test method, two cycles of testing — which is pretty standard for what you would see if you were to go for the proprietary method as well, harboring back to the discussion of timing between the two media approaches that Dave gave in the beginning. It resulted in providing an animal origin–free media that was equivalent or potentially even better, depending on which metric you’re looking at, at a lower cost.

Jump to the next slide. This is the high-level look at the data that came out from this screening process. Again, it was a two-step process — one, to remove the animal origin from the media and to redefine it as a custom media, and then optimize those parameters once they were able to gain a handle on the different components that would comprise the final media.

You can see the first image there the shift from the original proliferation curve in red, down to what it was prior to optimization in blue, and then once the media was able to be optimized, it looks to be significantly improved from the prior formulation. So not only were they able to remove the animal origin, but they were able to improve on the media. And obviously take into account this is an early phase product, so increasing the quality was acceptable and with the understanding that in some cases, if you’re a little bit later phase, maintaining the quality is preferable to increasing based on your regulatory filing stage at that point.

Then, below those growth curves, you see three images going through this development process to — you have a product that looks morphologically consistent with what you originally started with. This is just providing credence to the level of development and care that goes into this iteration process.

When we go to the next slide, what we see with being able to take a custom media development approach, as compared to your standard media development with POTS, is you’re adding an extra dimension into your media analysis. It’s enabling you to utilize multi-factor analysis and take a continuous data approach to designing your media composition.

With your typical proprietary media development experiments, you’re restricted to discrete sections of data defined within a particular media formulation. Since you’re not able to dig into exactly what is in your proprietary media, you might be adjusting some of the supplements but unable to give a true understanding of where your increases or decreases in yield are coming from. You’re only able to do a relative comparison between each base case, with each base case, we’re lying on the media formulation you’ve chosen, which then you’re limited by the amount of funding you have for that development project and thus limited to the number of proprietary medias you’re able to test. Your result is then you’re only able to say that you’re choosing the better of the media formulations that you’ve tested as opposed to saying you’re choosing the best media for your product. Then, on the right, what you see is a contour graph of what it would look like actually being able to test a continuous array of data points without having to go and have a really expensive and costly development experiment.

So, if we were to compare the two approaches, your time to develop the media is consistent. It’s going to be three months in the custom approach and roughly three months on the POTS approach as well, and you’re still accomplishing the same task with arguably better results. And, at the end of it, you have a formula that is ready to be used, is owned by you, and is automatically available through the Nucleus Biologics portal, NB-Lux.  You’d have a formula that is ready for you to get shipped in and is pre-formulated, does not require the additives that you would need to be ordering in if you were to use a proprietary off-the-shelf.

Nucleus provided a video of their NB-Lux platform, so I will let that run. What we’re seeing here is a run through of the ordering process and how simple it is to choose your various additives, packaging format. Here, we’re going through all the different nutrients, proteins, salts that you might want to add to your media based on the development study here we’re doing, adding in straight in human serum as opposed to having to add that on the end-user side.

And we’re ready. Once we have the formulation and the confirmation that we like, you can go ahead and place your order right away. The formulation shows up on that screen as well.

So, maybe to prime for the Q&A session, I’ll leave you all with one last question: If NB-Lux development doesn’t take longer, is less expensive, and is more optimized, what’s stopping you from ordering custom media?

Rachel Gauvin:             Thank you, Alex. Thanks to all the panelists. Appreciate the insight there. We are open for Question and Answer. If you have questions or thoughts that you’d like to share, please put those in the Q&A area and I will address those. While we’re letting those trickle in, I’ll just open it up to the panelists if there’s anything they’d like to elaborate on or post to the group.

David Smith PhD:         I think the crucial thing for me and maybe that video that we ended on, having just looking at Christmas presents, it’s going to be a weird analogy that you’re going to get here from me — but you look on all these different websites and compare prices, and I think that’s something that even if you want to get patient material and you look at all the different websites, you go through them, and you see which one is the low cost one — I’ve heard something that media doesn’t do. You’re going to go, and you’re just going to get what the price is sort of thing. You can’t change anything, you can’t add features, you can’t change features. This is what it is. This is the price. This is what you have to pay. And I think, for me, you can go on NB-Lux, you can make whatever formula you want, you can have that idea just to get a price, just a comparison, put it in there, compare it to what your standard price is from any of the big suppliers that you’re doing now just to get a feel for that and see. I think that, for me, great fun just going on the website and just putting it in and seeing what it’s like, seeing what sort of cost it is, and actually running the type of ROI analysis that you saw today.

I think, prior to doing this, I haven’t really thought about the impact that it may have long term. And we just covered media today. Obviously, doing that on every single thing is where we need to get to as an industry to really start saying, “Why is our custom goods half a million a dose?” “Where can we make savings?” “How do we do that?” We’ve tackled media, and amazingly Nucleus  provide a platform that A, allows you to reduce the cost of it but also to test some of those theories out on the website. I think it’s that sort of approach for me that this industry needs to take more and more in order to reduce the cost. And, inevitably, I’m sure everyone, the panelists here and everyone on the line as well, hopefully, is thinking, “How do we get it to every single patient that needs it?” That’s the thing that drives me in this industry, and right now, one of the main things stopping us is cost.

Rachel Gauvin:             So we have a question here. Dave Sheehan, you mentioned ownership of the custom formulations. Can you elaborate? How does that work?

David Sheehan:             Yeah, it’s a great question. I think the way we think about this portal and this process is ultimately we want to create media where anybody anywhere in the world can get access to a formulation, and it can be unique to their ecosystem. So, if we’re doing the formulation work, the IP is the therapy company’s formulation. It’s not ours; we don’t own it. Most companies don’t file IP or file a patent on their formulas. They keep them as trade secrets. And I think as a therapy company, you probably want to do the same thing because you’ve worked out all of the small details in your ecosystem that are going to be unique to what you’re doing, whether it’s your transfection methodology, how you do the expansion, what kind of bioreactor you use — all of those are unique and are going to change the metabolism. But the way we view it is our business model isn’t based on owning IP; it’s based on providing custom media. So the therapy company will ultimately own the formulation.

Rachel Gauvin:             Great, thank you. So we have a question here: “Well, firstly, thanks for a great presentation, but is there anything unique to consider with custom versus standard shelf lives?

David Sheehan:             No, what we’ve learned is that I think there’s maybe also just a perception that off-the-shelf media is — there’s a lot of novelty in it. And the reality is, it’s probably not that novel. It’s not like we created new amino acids. It’s the same combination, just different concentrations, so the shelf life is going to be pretty equivalent, unless you’re mixing the proteins in.

One of the things that we also do is stability studies. That’s a service that can help to make sure you know how shelf-stable your product is. But whether it’s proprietary off-the-shelf or custom, it’s going to be the same components that are going to drive your shelf life. It’s usually your protein sources.

Rachel Gauvin:             Thanks, Dave. Are there any other questions from the attendees here? Feel free to type those in.

Okay. Any other closing thoughts from our panelists? Sorry. I’m going to cut you off. We have a question here. Does NB-Lux do development work on customer cell lines?

David Sheehan:             Yes. The answer is yes. We do. We have a formulation service on the top level. You can click it and request it. Right now, in our labs, we probably have around 18 different cell types that we’re doing formulation work for at this time. It is an ongoing effort that we use a combination of high throughput screening and also machine learning, and you’ll learn more about that next month for the next webinar. I’m putting a plug in for the next webinar [laughs].

Rachel Gauvin:             Great. Thank you. I think that may do it for questions from the attendees, so I will leave space for any panelist who wants to give the closing remark. But we want to encourage you all to connect with us and stay in the loop on all that we’re up to, so that we can now charge as one.

David Sheehan:             Any comments from the panelists?

David Smith PhD:         I’ll come up with another analogy. Don’t worry. I think, for me, it’s just small steps to change this industry. I think this is exactly what we need. I’ll jump ship from the manufacturer onto the technology side and dive into that one to say it’s time this industry sort of tightens laces up and got going now. There’s a lot of great researchers out there. A lot of people will say manufacturing is the bottleneck, and the manufacturers will push it elsewhere and say, “I’ve seen both sides, seen all sides.” I think we’re in exactly the right time, right place now to really change how these are manufactured and how we get them to patients. So I’m personally looking forward to the next webinar as well because I think AI is going to be so important. I know we hear every single presentation everything going on about big data, data omics, how we can collect all this data. But we can’t really use it yet. And I think AI is going to be pretty important, not only in this industry but in all industries moving forward.

Alex Klarer:                  Yeah. And, just to add on to that, I think we’re all fairly aware of that variability that your donors add into your process, and in the last webinar, we were able to touch on that’s not the only source of undefinable variability and to kind of hand wave that impact on your process. Even your ability to troubleshoot failed batches and provide the quality the regulatory bodies are going to require of you is hugely important. As we increase our understanding of these therapies and the impacts on quality attributes that the inputs each have, we’ll have a stronger understanding of lower cost of goods, higher reliability for the patients, and, hopefully, better outcomes.

David Sheehan:             Roddy, any comment?

Roddy O’Connor PhD: I’m very thankful for the platform, and I think it’s helped us a lot. We’d have reps coming into Penn, well not so much in the pandemic but before, and they could promise this, that, and the other, but once you email them back, it’s untenable. You have to get so many litters produced, it’s so costly, and you have to wait so long. We all just lose interest in it. So, to be able to go on, design it ourselves, and get it so quickly and test it, generate data, it’s very helpful to us. And it will help the therapies too.

David Sheehan:             Yeah, great point. I think it’s really why we’re here, right? We’re here because we’re trying to create therapies to treat patients. And what we’re basically laying out is a roadway that is going to give you a better therapy and also make sure that you have comfort that there’s nothing to fear with going custom. It’s actually going to give you a better end product and more control over your therapy and if we do a good job of the formulation work, a better therapy. I think it checks all the boxes. It is a mindset change for the industry, but it’s a necessary one. I think it’s the direction that we all need to go in because it will get us into the clinic faster with these life-saving therapies.

Rachel Gauvin:             Absolutely. Well, thank you, everyone, attendees and panelists alike, for your time today. This is great information, a lot to take home and think about.

Like I said, there’s a third webinar upcoming, so we will be sure to make sure you guys get that information. So, thank you.

David Sheehan:             Thanks everybody.

Rachel Gauvin:             I hope you all have a great day.

David Sheehan:             Bye now.