Episode #102| Can Bioprinting Reshape The Future of Immunology?

We explore how to move IVIG from donor scarcity to on‑demand manufacturing with tissue‑engineered bioreactors, and why that shift could lower costs, expand access, and improve consistency. We dig into polyclonal advantages, regulatory guardrails, scaling plans, and what success would mean for complex biologics beyond antibodies.

• Defining a bioreactor that recreates human tissue niches
• Why polyclonal IVIG remains essential across 100+ conditions
• Limits of donor‑dependent plasma supply and regional variability
• Complex therapeutics as a new manufacturing category
• Cost targets of 10–100x reduction and CapEx shrink
• Coffee‑cup reactors and near‑term validation milestones
• Quality metrics including pathogen panels and glycosylation
• Donor variability, blending strategies, and future immortalization
• Clinical impact of moving from rationing to earlier use
• Funding update and industry partnerships

Please listen to the disclaimer at the end of this podcast.

Show notes: https://3dheals.com/episode-102-can-bioprinting-bioreactor-reshape-the-future-of-immunology/

About our guests:

Dr. Melanie Matheu is an immunologist, inventor, and biotechnologist recognized for pioneering work in high-resolution tissue engineering and human immunology. She received her PhD in Physiology and Biophysics with a focus on Immunology from UC Irvine and completed postdoctoral training at VIB (Ghent University, Belgium) and UC San Francisco, where she specialized in 2-photon imaging and cellular immune responses. As founder of Prellis Biologics, Dr. Matheu brought forward laser-based tissue bioprinting to solve complex challenges in organ transplantation and therapeutic antibody discovery. She later co-founded Lyric Bio, where she serves as Chief Scientific Officer, advancing scalable biomanufacturing platforms and rapid human immune system modeling. Dr. Matheu has authored numerous peer-reviewed publications, holds multiple patents, and is a passionate advocate for innovation at the intersection of immunology and bioengineering.

Kevin Shannon (Kayj) holds a degree in Molecular Biology from Princeton University and a MBA from Stanford Graduate School of Business. Kayj has held positions spanning the biotech ecosystem including start-ups, big pharma, venture capital, and consulting. As part of Corporate Strategy at Amgen, he worked with Amgen’s C-Suite to shape long-term strategy, built partnerships in novel therapeutic modalities, and led investments in emerging categories including cell & gene therapy, antibody engineering, single cell analysis, and quantum computing. Kayj has also consulted for multiple VC funds where he developed investment theses and performed

Chapters

• 0:00 A Bold Question: Tissue On Demand
• 1:06 Meet The Founders And The Mission
• 1:22 How Lyric Recreates Human Tissue
• 3:28 Why IVIG Matters And Where It Fails
• 7:33 Donor-Dependent Supply And Diversity
• 10:44 Complex Therapeutics Defined
• 13:13 Manufacturing Approach And Cost Targets
• 16:33 Bioreactor Design And Scaling Plans
• 19:54 Regulation, Quality, And Safety Metrics
• 22:05 Risks, Variability, And What Keeps Them Up
• 23:24 Who They Want To Meet
• 24:32 Event Invite And Disclaimer

Transcript

SPEAKER_02: 0:02

Hi there! Welcome to the Lattice episode number 102. What if we could recreate human tissue outside of the body? Not in a giant stainless steel tank, but in a bioreactor the size of your hand. What if life-saving therapeutics like IVIG, currently limited by global plasma supply, could be manufactured at 100 times lower cost and with 10,000 fewer donors? Our guests, Melanie Matthew, immunologist, bioprinting pioneer and founder of Paris Bio, and K Shannon, biotech operator with deep roots in pharma and venture, a building exactly that at Lyric Bio. If you ever wondered whether the future of complex therapeutics could shift from donor-dependent scarcity to on-demand tissue-engineered abundance, buckle up. This conversation will change how you think about medicine. Enjoy. Please listen to the disclaimer at the end of this podcast. Hello, hello. Welcome to the pod. Today we have Melanie Matthew and Kate Shannon, co-founders of Lyric Bio, to join us. And I'm really excited to hear more about what this startup does. Melanie and Kate, why don't you tell us what your startup does?

SPEAKER_00: 1:21

Yeah, absolutely. So at the core, what Lyric invented and what we're able to do is we can recreate human tissue in a bioreactor. And that's a kind of big advantage over existing technologies where cells are kind of fluttering around in suspension, and it gives us two kind of major advantages. The first is cell density. So we're about a hundred times greater cell density than any existing technology, which translates to efficiency of manufacturing. So we can produce just about any protein for a fraction of the cost of existing biographic technologies. The second advantage that we get, and the one that we're kind of leveraging most with our initial products, is we can recreate specific tissue niches. And so that expands the types of cells that we're able to culture at least densities and allows us to produce a lot of therapeutics that right now the only way to get them is from human donors. And so that's what we're focusing on initially, specifically with a product called IVIG that is collected solely from human plasma. We've developed a process that allows it to manufacture it in a bioreactor. So we're, you know, slashing the number of donors needed to produce a therapeutic and producing it for a fraction of the cost of the existing process, you know, kind of with the goal of expanding access to this lifesaving drug.

SPEAKER_02: 2:40

Yeah. So when I was preparing for this podcast and I was looking at your bios, this is like a match made in heaven between you guys. Cage, you have a very extensive VC background, commercial background with MGN and a bunch of other uh pharma companies. And then Melanie, you have extensive technology background. You were the founder, you still are on the board, I believe, for Preless Bio, which is a phenomenal legendary bioprinting startup focusing on two photon laser bioprinting technology, which I believe you're one of the inventors of, or maybe the inventor. I'm not really sure.

SPEAKER_01: 3:16

That's right. Yeah, the first pattern um was ideated out of my graduate school lab. I was thinking a lot about two photon printing, but in my graduate school work, I was working on two photon imaging. And so, you know, looking at these tissues for day in, day out for almost 15 years and analyzing how immune cells move within tissues and how lymph nodes are structured really inspired me to think about how we can recreate this tissue and retain all the fundamental ingredients that make a lymph node work and drive a proper immune response in vivo. And can we do that with something, you know, that allows for high-resolution, high fidelity structures to be built that really create these cell niches so that you get true replicative biology in a dish. And so that's that's really what prelates can do. It's fantastic. And, you know, taking that technology into another um area, biomanufacturing is is really exciting for me. It was really exciting for me. I pitched the board a few years ago on it, got them really excited about it, and uh they decided to let me go off and do it.

SPEAKER_02: 4:31

I'm very excited about it. I mean, we we all started learning about bioprinting because everybody wants to print a kidney, you know. Right. But then we're allowed to holy grail.

SPEAKER_01: 4:40

Yeah.

SPEAKER_02: 4:42

I, you know, I think, you know, why didn't we think about this earlier? You're an immunologist. And producing these mass scalable products that are really needed, really solved it on that need as opposed to print one kidney for one person. Could be incredibly so I I can see the potential in this for sure. But let's rewind a little bit of the market and just why the clinical aspect. Why do we need so many immunoglobulins?

SPEAKER_00: 5:12

Yeah, so it's a you know drug that's used across a hundred different diseases right now. It's an incredibly powerful therapeutic. And it's used, you know, not just multiple diseases, but kind of you know multiple categories of disease, everything from organ transplants to autoimmune disease to you know treating the effects of oncology drugs. And so it's an extremely powerful drug that's used very wise for and is life-saving in many indications.

SPEAKER_02: 5:42

Yeah, I'm surprised to hear that IVIG or subcutaneous IG, and now it's a neuro uh deliverer method, can treat both immunodeficiency and also auto-umine disease. That kind of like it's kind of conflicting.

SPEAKER_00: 5:57

It is an interesting contradiction, isn't it?

SPEAKER_02: 5:59

Do you mind if just unpacked that? Um, I mean, whoever is here wants to chime in.

SPEAKER_00: 6:04

I I think that's a question for Melanie.

SPEAKER_01: 6:07

Yeah. So um for a long time, people didn't even understand how IVIG worked. You know, it was kind of first brought about in the 1950s and 60s, and it's one of the oldest kind of biotherapeutic products out there, truly. And, you know, it's collected from human plasma. We all make antibodies. Antibodies are transferable between people, you know, the mother to child immunity through breast milk is delivered through antibodies. And so they're this really powerful kind of therapeutic that not only reacts to pathogens and forms kind of like this pathogenic memory of all your vaccines and everything you've been exposed to, but also can be used to kind of flush out pathogenic antibodies in the case of autoimmune disease. Because we kind of have set, we have an internal set point for how much antibody we have. And so when you give a bolus of non-pathogenic antibodies, helpful antibodies, um, it can kind of flush out the pathogenic antibodies and um reduce that immune response as well. So those are kind of two of the major mechanisms by which they work. It helps to protect people from pathogens, and it can help reduce pathogenic antibodies and inflammation. Now, there are some inflammatory responses that it IVIG extra IVIG does seem to shut down, and we're not exactly sure how that works still, even in biology. We just know it does, and it's been used for decades in these indications like Kawasaki's disease, for example.

SPEAKER_00: 7:34

Physicians often refer to it as the kitchen sink.

SPEAKER_01: 7:37

Yeah.

SPEAKER_00: 7:38

And yeah, it's it's what they throw when nothing else is working. And yeah, sometimes it just seems to work, and even the physicians don't understand what it's like.

SPEAKER_02: 7:47

Well, that that's when I hear that COVID, uh, during COVID time, people start to throw out IVIG.

SPEAKER_01: 7:54

So yeah, so for SARS-CoV-2, it didn't work very well. And there are a couple of reasons. Very acute viral infections where you don't have IVIG from people who've been previously exposed to that virus doesn't seem to work so well. You know, I think people during that time, people were reaching for anything they thought might help, right? So maybe it would tamp down the inflammation. But in terms of targeting COVID as a pathogen, the IVIG off the shelf from six months prior to major exposures happening in the US and elsewhere wasn't really a great option for treating the virus, right? Because you didn't have that pathogen memory in that pool of antibodies.

SPEAKER_02: 8:41

So when a doctor is telling me IVIG, that's a bad warning sign that he really doesn't know what is going on. Um so tell me, what is the current status of how we manufacture or collect these immunoglobulins?

SPEAKER_00: 8:59

Yeah, so right now it comes, you know, 100% of it comes from human plasma donations. And so, you know, the current process is the major companies, they have plasma collection centers, you know, set up across the United States. People go in and in the United States and I think four other countries are actually allowed to be paid for their plasma. So in the US, they go in, they're paid to um donate their plasma. Uh that plasma, you know, millions of liters of it, is then shipped to centralized fractionation facilities where they extract the antibody, kind of the therapeutic part of the plasma, out, and you know, package that as a therapeutic, and then that they ship out to hospitals and to patients.

SPEAKER_03: 9:44

So this is like a mixture of everybody's IVIG kind of thing.

SPEAKER_00: 9:50

Intentionally so, yes. So actually that is a feature, not a bug, of the product, but you want to have a high diversity of antibodies. You want to make sure that you have antibodies against, you know, all the pastors or as many pathogens as you possibly can. And so that's part of the reason why we pull, you know, one is you know it takes 10 donations to get a single dose of IVIG. So the only commercially feasible way to get enough is to pull it. But also there is an advantage from an efficacy standpoint of getting that antibody diversity.

SPEAKER_02: 10:26

But does that mean that North America collection would be different from Asian collection?

SPEAKER_04: 10:32

It does.

SPEAKER_00: 10:33

Um is looking to a lot.

SPEAKER_01: 10:36

Yeah, so there almost seems to be like a terroir for antibodies, if you will. So in certain populations and certain groups of people, um, you can actually see almost different pathogen response patterns and even potentially different therapeutic indications. So one thing I think is really interesting is IPIG has been attempted to be used for slowing Alzheimer's progression, right? And there is an antibody, a monoclonal antibody in the market right now that does seem to slow Alzheimer's progression. It does have a lot of side effects and it is a monoclonal. Polyclonal is often better because that's how our immune system will natively respond to something. But some scientists were wondering why in some clinical trials IBIG seemed to work well for Alzheimer's, slowing Alzheimer's progression. In other clinical trials, it absolutely failed. And it turns out that there are regions or groups of people, maybe, or just whatever plasma donation happened to have occurred that time that have higher amounts of anti-Tau antibody in them relative to others. And so this may be the reason why some of these clinical trials haven't worked for Alzheimer's, whereas others have. And so we find that, you know, as a team, Cage and I find that very interesting because when you establish a manufacturing process for something that is really just kind of pulled from the population at large, you might be able to capture some of that therapeutic efficacy, which which we think is interesting.

SPEAKER_02: 12:08

Yeah, I mean, while preparing for those podcasts, I found this entire field extremely interesting. I mean, in fact, a lot of larger pharma companies right now are working in the space working on various kinds of treatment for especially autoimmune inflammatory processes. Now, since we're on the topic of the technology, I think a little bit more unpacking here is gonna be interesting because you know we just talk about how valuable polyclonal IVIG is than monoclonal. So this is not just totally replica. So you you want to tell us how you manufacture your version of IVIG and how is it different from what we have right now, better or worse, pros and cons trade-offs?

SPEAKER_01: 12:59

So we're really in the RD development stage right now. And so our plan is to be producing this from several donors and blending it still. We're not ready to step away and say, okay, only these 10 donors will be sufficient to produce a good IBIG. And we're not quite ready to take the step towards immortalization yet because we want to make sure we understand what a very good donor set looks like before we we take a step in that direction. Um but for now, you know, Cage and I are planning to build out a process that allows us to expand the number of doses of IBIG from a single donor. So instead of um multiple plasma donations, about a thousand or so to create, you know, one dose of you know, IBIG. Well, sorry, it's seven to ten actually for one dose, but instead of a thousand or so plasma donations, we think one donation of white blood cells can produce about a thousand doses of IBIG. That said, we're going to need lots of donors of those immune cells, so 100, a couple thousand or so to create a blended product that will be similar to what we see on the market today.

SPEAKER_00: 14:10

Yeah, so we're we're targeting a 10,000-fold reduction in the number of donors that we need to supply kind of the global IG market. And then, you know, really for our initial product, we're focused on solving the costs and supply issues. You know, there's a very effective therapeutic on the market. We're trying to make sure that what we initially produced looks exactly like that. But then I think beyond that, kind of a second and maybe third generation products, there are a lot of really interesting things that you can start to do. You can start to tune the therapeutic because it's no longer coming out of a person. You know, we have it in a you know controlled bioreactor where we can start you know making it more efficacious, trying to make it safer, you know, fiddling with it a little bit to improve its properties.

SPEAKER_02: 14:58

Right. If you provide, if you produce a line of IVIG that's similar to what we have right now, I would say that's a good enough product, right? And and and if you found like super donors, which reminds me of this TV show, The Last of Us, maybe you found this like just amazing individual that has the best profile and then can save the world. What are the metrics you're you guys are looking at to see, you know, this is a good enough product ready for market versus this is an amazing product that's like changing the world?

SPEAKER_00: 15:32

Well, I think you know, just being able to mimic what's already on the market, you know, getting this same therapeutic and safety profile as you know, human IG or IVIG plastic and human donors, I think that's a product that's gonna change the world. Um because you know it is a supply-constrained market. Um, there is not enough IVIG being produced for physicians to prescribe it the way they want. This is actually something we found out during this process that was really interesting. When we first sought out, at least when I first set out, I thought we were solving a cost problem where our major selling point was, you know, we're gonna be able to produce this for 10 to 100 times cheaper than the current process. But when we started talking to physicians, what we started to learn is even at major hospitals, you know, major hospital systems, the way they prescribe IVIG is regulated. And they're not able to prescribe it the way that they want. You know, one great example is in um uh oncology patients, you know, chemotherapy depletes your immune system, so IVIG is used to help patients help overcome infections. The way they prescribe it right now is they put a patient on chemotherapy, they wait for them to get an infection. Once they have an infection, they treat them with IVIG, help them get over the infection, and then they pull them off IVIG. Um, and wait for them to get another infection and repeat the process. And that's done because it is a supply-constrained drug. But when you talk to these physicians, they want to start them on IVIG as soon as they start them on chemotherapy. Why are we waiting for these patients to get an infection? We know it's very likely that it's gonna happen. Why don't we just start them on IVIG right away? And so that's kind of when we talk to physicians, what they get really excited about, they're like, you know, we're solving a supply problem, not necessarily just a cost problem.

SPEAKER_02: 17:24

Yeah, I'm I'm really excited to hear this because you know, the reason why antibiotics is overprescribed is because they're freaking cheap. So if IVIG can be really cheap, I bet, and also not producing the superbug phenomenon. Exactly. I bet they're gonna prescribe it first. I mean, money definitely is a constraint. The reason why we're now having an exponential increase, not just on tematics prescription, but also CTs, since I'm a radiologist, is because they are more economically affordable.

SPEAKER_01: 17:56

Exactly. And it's funny that you mentioned superbug, because when you look at something like IBIG, you are tapping into a polyclonal immune response, right? So much less likely to allow for a superbug to escape, even versus a monoclonal antibody, right? So if you have a monoclonal antibody against a virus like we saw back in COVID, regenerons, antibody, lilies, antibody, it was very easy for the virus to mutate around the specificity of a single antibody or even a dual antibody product. But when you look at something like IVIG, you will have multiple antibodies that recognize different parts of a virus product, even if it's from an immunization, not the complete virus. And so that really will shut down a viral pathogen. It will shut down a bacterial pathogen much better than um antibiotics, small molecules, et cetera. So if we can bring that cost down and a safety profile up, I think you know we may be on to something really helpful there.

SPEAKER_02: 19:01

Absolutely. Now, ultimately, Laura Bio has a preparatory bioreactor, is which you guys uh are working on to manufacture these large some large amount of antibodies or immunoglobulings. What is exact design, if you don't mind, of just share with us a little bit. If hopefully it's not top secret, but you know, a general idea what is behind it.

SPEAKER_01: 19:27

Yeah. So again, we we're in the RD and development stage here, but in general, we are tapping into the core technology developed of Prelis, which is the ultra high resolution, ultra fast bioprinting, where we can produce an internal component of this bioreactor, the internal components being where the cells live, their niches that will supply oxygen and nutrients the same way you would inside the body. It ensures good oxygen and nutrient distribution, and we can produce. Set really fast. So right now, our current estimate is a couple of hours to print our MVP bioreactors internal substrate. And we believe that we'll support a near tissue density set of B cells. So it's almost like we're recreating a human spleen in vitro.

SPEAKER_02: 20:19

I see. Now, also the other new concept I have learned during my research process is this concept of complex therapeutics. Can you define that for us and what's included and how is it relevant to larric bio beyond just immunoglobulin?

SPEAKER_00: 20:39

Yeah, absolutely. So, you know, Ellen and I came up with complex therapeutics because we couldn't there wasn't a great word to describe the type of therapeutics that we're going after. And so, you know, what we mean by complex therapeutics are therapies that you know are too complex to be manufactured in you know with existing bioreactive technologies. And so you know how this applies to IVID is IVIDs are polychlonal antibodies, millions of different antibodies. And so if we were trying to try and produce this therapeutic using existing technologies, you know, the way we make monoclonal antibodies right now is we genetically modify a Cho cell, a manufacturing cell line, to produce one antibody. Um, and that's not always a cheap process. Now, imagine multiplying that by a million. So you have to go and individually modify a million different Cho cell lines to produce a million different antibodies. That just very quickly becomes cost inefficient. And so, you know, probably could produce this therapeutic using existing technologies, it'd just be way more expensive than even getting it from human donors. Then there's you know a lot of therapeutics that are like that, where the science exists to produce them at small scale outside of the human body. So IVIG is one of them, stem cells, red blood. We kind of have an idea of how we could get cells to start producing these therapeutics. We just can't do it at scale and cost-sufficiently enough to actually make it a viable process for producing therapeutics. And so that's why we call them complex, because they're just too complex to be manufactured efficiently with the existing technologies. And that's what we're targeting for cellularic.

SPEAKER_01: 22:37

Yeah. So other examples of a complex therapeutic would be something like a stem cell, right? We don't have a great process other than growing stem cells up in culture for expanding those populations. And it's wildly inefficient, and that's because we're not providing those stem cells with the niches that they are used to living in, right? And the proper three-dimensional kind of signaling they get. Stem cells are highly sensitive to their environment. Even if you have them cultured on like a hard versus soft surface, they will start to differentiate like immediately just from like detecting the surface that they're on. And so, you know, unlocking kind of that bioproduction in three dimensions, I think is applicable beyond IVIG in the future. And um, Cage and I, yeah, Cage and I came up with that because we were kind of casting around for how do we describe this as a process because it is so distinct from current manufacturing processes.

SPEAKER_02: 23:38

Yeah, I'm actually surprised to hear that how you quote unquote expand a stem cell is actually culture them. I really thought it was a giant tank that has like tons of cells in it. Because you remember this company.

SPEAKER_01: 23:54

Okay.

SPEAKER_02: 23:55

Because I remember Rooster Bio has a preparatory technology to expand the cells, but never really dug deep into how they do it.

SPEAKER_01: 24:03

They are doing, I believe Rooster Bio is doing um still static culture, but like a big tank. So I think they have holo fiber bioreactors of some sort or some. Yeah. So the stem cells aren't just floating around in in the ether kind of.

SPEAKER_02: 24:19

So Cage, you're the money person in this partnership. Tell me in dollar sense, like what am I looking at in terms of the cost differentials? And I have more other money-related questions for you too. But that one first is what I'm looking at here.

SPEAKER_00: 24:36

So, you know, we're still in the RD stage. So exactly the cost reduction, you know, we don't know yet, but you know, we're looking at 10 to 100 times cheaper. And if you kind of just look at the you know, math based on you know what biology dictates or kind of what the literature dictates should happen, you take the cell density that you know we know process is capable of achieving, and the rates of antibody secretion of B cells in 3D static culture, and you kind of just multiply those two numbers together, you get a ridiculous number. I think it's well over a hundred times reduction in cost.

SPEAKER_02: 25:15

So, how much does one treatment cost right now?

SPEAKER_00: 25:19

Uh right now, I mean, it varies from country to country. The cost to produce it um kind of in the$40 to$60 range. Uh, and then it is sold in the US, I believe, for per gram. Per gram. Sorry. Yeah. Units are helpful. Yeah, so forty to sixty dollars per gram. And then sold in the United States for believe a little over a hundred dollars per gram.

SPEAKER_02: 25:46

And how many grams do you need for one treatment?

SPEAKER_00: 25:50

Uh let's just say this is actually an interesting question. I can use myself an example. So um, it does vary pretty significantly from disease to disease.

SPEAKER_02: 25:59

But uh, but let's say the seven approved diseases that I just looked up this morning.

SPEAKER_00: 26:03

So, well, we can use or I know I know the numbers for organ transplants off the top of my head because my dad is a cardiologist. But the you know, dosing for an organ transplant is two grams per cake.

SPEAKER_04: 26:18

Okay.

SPEAKER_00: 26:18

Which is a lot. To give you some context on that, I'm I'm a bigger guy, I'm about a hundred kilograms. And to produce enough IVIG, you know, to keep me alive if I had uh an organ transplant, I think it would take about 30 donors on a monthly basis. So 30 plasma donations on a monthly basis to get me enough therapeutic. So it is a lot of it is used actually what is it to they measure the US supply in kilotons, which I don't I can't think of another drug product, you know legal drug product other than maybe aspirin, where they actually they measure usage in kilotons. So quite a lot of it is used.

SPEAKER_02: 27:08

So they actually use that much, not just they need that much. They actually that's the current usage today. Oh my god.

SPEAKER_01: 27:15

Yeah, and even more would be prescribed if it were more readily available and cost effective.

SPEAKER_02: 27:20

No, I understand you're it just in the RD phase, but do you foresee uh especially for Melanie and technological side, can you reduce the cost of producing these down the line?

SPEAKER_01: 27:31

Let's say you have some signs of success and now people are slightly open to use it to Yeah, so the cost of production um is what Cage just detailed, right? And we're really looking at a 10 to 100 fold reduction in production costs. Um now that is just one part of the pipeline chain. There's um the purification, the formulations, all of those things. But you know, I think that when you develop a new manufacturing process around something that can slot into an existing one, that does give you a little time then to see if there's other refinements you can identify uh down the line as we develop it. So yeah, I do think that's a possibility.

SPEAKER_02: 28:16

Cool. Yeah, I I guess the you know scalability kind of have exponential effect. Not like software network network effect, but being larger definitely helps with a lot of things.

SPEAKER_04: 28:28

Absolutely.

SPEAKER_02: 28:29

So, Cage, uh you have some good news on the funding side. I saw your press release recently. You want to tell us a little bit about that?

SPEAKER_00: 28:38

Yes, so uh we recently wrapped up our our C financing. So we raised a little over six and a half million dollars from a great set of investors, including, you know, one strategic Meiji Pharma, who's you know, one of the major IVID providers in Asia.

SPEAKER_02: 28:54

Which I did not know. I thought they just make milk. That's that's what I thought.

SPEAKER_01: 28:58

And chocolate. They brought us some. And chocolate, right.

SPEAKER_00: 29:01

They do make I I can confirm they do make some fantastic chocolate. They they brought us some when they came and visited us.

SPEAKER_02: 29:08

Well, that's that's silver lining.

SPEAKER_00: 29:11

Yes, absolutely. We're gonna we're gonna have to get get some more. But yeah, so we uh we wrapped up the fundraising. We raised enough money to for us to hit our Series A goals. It's just kind of validation of the buyer actor, demonstrate that you know we can produce high quality IVIG at the scale and for the cost that we uh we think we get.

SPEAKER_04: 29:32

And what is the timeline that we can hear more good news from you?

SPEAKER_00: 29:40

So we're we're looking to hit uh a couple different endpoints. So you know, obviously, we're starting this in you know smaller than commercial scale bioreactors, which for us is one centimeter cubed. And so hopefully sometime in the next year, we'll have some initial data in these one centimeter cubed bioreactors demonstrating that you know a slightly smaller scale, we're getting the quantity and quality of antibody that we expect. And then closer to a you know, kind of 14 to 16 months time frame, we're looking for kind of full-scale proof of concept, which this is something we actually haven't mentioned yet, but it is really exciting. For us, full scale is 150 milliliters, so a little bit smaller than a coffee cup. That's what our commercial bioreactor is going to be. And you know, that bioreactor is capable of producing, we think, over a thousand doses of IVIG. And every single rod.

SPEAKER_01: 30:54

Um, you know, that scale, every person we've talked to who works in biomanufacturing, that's usually their test size, right? And we're looking at that being our MVP going forward. And so that's pretty exciting for us because scaling, we think, is the only issue we have. And that is the size we are scaling to. And so um, in terms of scientific risk, uh we're pretty excited about the ability to scale, the ability to just go to that size. And that would be our release product size. And so as Keige said, I think about 12 months or so, we're planning to have some really great data we can report out of the system and um a lot more on the way in the pipeline.

SPEAKER_00: 31:40

And going back to the money part of things, because I am the money guy, you know, what that translates to in you know, terms of CapEx is you know, right now you have these multiple hundred thousand square foot facilities for plasma fractionation where you have several kiloliter sized bioreactors with two-story massive bioreactors, and that's you know what we need right now to process enough plasma to get enough IVIG to supply the global market. We're shrinking that down. You know, instead of having these massive Q-story bioreactors, we have a bioreact that you're quite literally just gonna fit in the palm of your hand. And you know, instead of processing 9 million liters of plasma, we're looking at processing you know a few hundred liters of media or worth of bioreactor runs, a little more media, but 150, 150 liters worth of bioreactor runs in a facility that's you know is gonna be about the size of a small office building. And so it's a massive reduction in kind of the equipment and capital expenditure that we need to supply you know the US and the global market.

SPEAKER_02: 32:52

Yeah, that sounds exciting. I mean, it sounds like you can I can min maybe one day have my own personal bioreactor, just for me.

SPEAKER_01: 33:00

That that would be a fantastic dream, right? The it's almost like uh what's that cartoon? I may be dating myself here, the Jetsons or something. We could have like a little I need this product to help me through my day and type it into your bioreactor.

SPEAKER_02: 33:16

We need to find that a cartoon, including the show notes. Now Mello, you mentioned you mentioned a little bit about manufacturing quality control and risks. You want to expand on that? Like what, you know, now that you're in RD, what are you uh preparing for down the line for a regulatory process?

SPEAKER_01: 33:37

Yeah, so the FDA, because it's a a widely used kind of grandfathered-in product since you know, before monoclonal antibodies were even used, right? The FDA has some very light restrictions on IVIG. They want it to be responsive to three major pathogens, poliomiesals and diphtheria. And beyond that, there aren't too many requirements around manufacturing because really there's only one source, it's plasma. You get what you get, and then you blend, you know, thousands to hundreds of thousands of donors together for a final product. And so we are kind of going above and beyond and testing what we get out of a handful of donors. So not only are we testing for those pathogens, we'll be looking at up to um 14 different pathogens eventually. Right now, we kind of have four or five that were we think are critical. And then beyond that, you know, we're looking at antibody content itself, right? So the amount of different subclasses of the IGs that are present, we'll be tracking that. We'll be tracking cylation patterns as the sugar molecules that are put on the immunoglobulins that can affect their activity physiologically. So we'll be tracking that to make sure it looks like we have a pattern that that at least matches what is found off of a typical dose of IVIG, if not an improvement in quality, that would be fantastic. So there is a list of things that we'll be looking at and that I think are really important.

SPEAKER_02: 35:16

Fantastic. I just want to do that. Those are kind of the top three. There's like my education right there. Now we're we're we're we're kind of going beyond the time frame that we have set for this uh short interview, quote unquote. I just two other questions. One is what keeps you awake at night right now? Cage, I'll start with you, the money guy.

SPEAKER_04: 35:39

Oh what keeps me awake, running out of money always weighs weighs on my mind.

SPEAKER_00: 35:46

But I think you know, making sure that we can, you know, really recreate those tissue niches effectively. We know that if we put B cells in the right environment, you know, they're gonna produce antibodies. That's that's their job. And so I think for me it's you know making sure we can recreate that environment that the B cells expect in those bioreactors. It's what keeps me up at night, but it's also kind of what gives me confidence in our process because that's more of an engineering problem than a true biology problem. And yeah, engineering problems are a little easier to solve with several iterations versus biology has a tendency to throw things at you out of the us field.

SPEAKER_02: 36:39

Yeah, I forgot to mention that you also have a biomedical background. You technically you are an engineer yourself, right?

SPEAKER_00: 36:47

Uh not an engineer, but I have a biology background. I just I got out of the lab as soon as I could. I I wasn't cut out for it.

SPEAKER_02: 36:56

Yeah, me neither, I try have to say. That's that's me. Melanie, what about you? What keeps you awake at night?

SPEAKER_01: 37:02

Um, yeah, it's not dissimilar from what Cage was saying. Um the engineering process is something we are going to iterate on and really drive into a functional process, but all of that is so critically important because there's high donor-to-donor variability with B cells, right? And, you know, I think we will have some interesting learnings that aren't reported in the literature around how different donor B cells will behave in different situations, right? So some people will probably be phenomenal producers of the type of IVIG we'd love to make into a therapeutic, whereas others, you know, really may not be. And I think that donor-to-donor variability is kind of smoothed over by the scale at which IVIG is produced today and how many donors are put into it. But we want to be able to learn as quickly as we can which set of donors we would like to source from to make this phenomenal product. And then, you know, from there, I think those learnings we can translate into producing a more um, how do I want to say this, a more um consistent product for the market. Um, even just recently, a couple batches of IVIG were pulled by the FTA. Um, so it's not a risk-free product, truly. And I think if we can identify um some genetic backgrounds that produce great IVIG, immortalizing those cells will be another cost-effective step for everyone and producing a better product overall. So that kind of thing keeps me up at night. The biological variability we're trying to get around with it in engineering projects.

SPEAKER_04: 38:45

Okay, final question. Who do you want to engage with right now?

SPEAKER_02: 38:51

And how can people reach you if they want to engage you? Well, first of all, you want to engage with people who you want to reach out for. It's a bilateral situation here. So in your best scenario, who do you want to engage with?

SPEAKER_00: 39:04

Yeah, I think experts in the IVIG space. So everyone from researchers or physicians who are studying or prescribing IVIG to kind of uh companies that are producing it at scale. You know, we are experts in, you know, our kind of tissue engineering, bioprinting side of things and for Melanie, obviously immunology. But you know, we're on the newer side to IVIG, and so the more help we can get and the more support we can get on that side of things would be great for us.

SPEAKER_01: 39:39

Yeah, I'll second what Kate is saying. Um, the more thinking we can get around these, you know, problems, you know, insights we have from other people, that's always incredibly helpful. I think Cage is being a little humble and not noting that he and I have been able to reach out and have a set of great people we are already talking to. So um know we are we are chatting with some phenomenal industry leaders and they've already been incredibly helpful they're very bullish on what we're doing and they're excited about the prospect of bringing the kind of grandfather process of plasma donation into kind of you know 21st century manufacturing where where it's just an opportunity to produce a better product for less for everyone who needs it. Yeah.

SPEAKER_00: 40:28

I think that really speaks to the impact of the problem that we're solving that well before we even raised money um when this was still very much just an idea that Melanie and I had you know we were getting incredible traction with with a wide range of people you know from large companies all the way to positions.

SPEAKER_02: 40:48

Okay well that really is a great conclusion for this podcast. I would say to the seven followers of our podcast if you want to meet Melanie and Cage in person there's an opportunity coming up on January 11th we're hosting a small in-person event in San Francisco right before JP Morgan. So so Melanie and Cage hopefully I can see you guys there. Yeah well I'll be there absolutely thank you so much for joining us today. Thanks Jenny This podcast is for educational and informational purposes only the views expressed do not constitute medical or financial advice. The technologies and procedures discussed may not be commercially available or suitable for every case. Always consult with a licensed professional