Episode #111| Bench to Bedside: Bioprinting Innovation Virtual Event Recording

Everyone talks about printing organs, but the closest thing to real impact often starts with something less flashy and far more practical: the materials. We bring together founders and operators working across bioprinted implants, structural bone substitutes, cryopreserved tissue models, and natural biopolymer manufacturing to answer one question that matters: what actually makes advanced biofabrication translate from bench to bedside?

We dig into bone regeneration and why scaffolds fail when they can’t balance strength, vascular support, and predictable resorption. You’ll hear how absorbable polyurethane platforms aim to avoid acidic degradation while letting teams program mechanics and timelines, plus how 3D printed beta-tricalcium phosphate ceramics can deliver structural consistency and then remodel into native bone. The conversation stays grounded in the realities that decide adoption: predicates and evidence expectations for FDA 510(k), the heavier burden of EU MDR, and the uncomfortable truth that clearance doesn’t guarantee reimbursement.

Then we shift to new approach methodologies for drug development, where cryobioprinting tackles the biggest blocker in bioprinted tissues: logistics. If tissues can be frozen, inventoried, shipped, and used on demand, bioprinting becomes a consumable workflow instead of an artisanal one-off. We close with a candid translation playbook for natural biopolymers and a high-volume pediatric use case: dissolvable chitosan ear tubes designed to reduce repeat surgeries, plus the pricing and coverage strategy needed to make that upgrade viable.

Subscribe, share this with a builder in medtech or biotech, and leave a review with your biggest takeaway: which bottleneck matters most right now, materials, regulation, reimbursement, or scale-up?

Event link: https://3dheals.com/bench-to-bedside-bioprinting-innovations/

YouTube highlights: Stay tuned

Transcript

Welcome And Why Materials Matter

SPEAKER_06 0:00

Welcome to our uh event today. We are focusing on bioprinting, bench to bedside. My name is Chenny Chen. I'm the founder and CEO of 3D Heels. We have founded this company uh 10 years ago with the intention to number one is to educate the public about what 3D printing can and cannot do. And number two is to connect networks of people so that they can innovate and help one another. Uh so this is sort of number one and number two. And we have a number three mission, which is now increasingly becoming more important, is to help early stage startup with fundraising. And early stage is defined as even precede, although usually you know precede is very early, to uh Series A. So that's the kind of company we can help at no cost to the company or the investors, and we connect these uh companies to institutional investors and not just uh single individual Android investor. So if you're uh thinking about something in the garage uh or even already kind of later in stage uh and interesting in the program, please let me know. Just email me directly. Uh the program is called Pitch 2ED if you haven't heard of it already. Okay, so without further ado, I'd like to uh introduce this topic, which has been very interesting for me and for the public for quite a few, I wasn't more than decades, several decades since the inception of organovo. And the immediate reaction from the public is always we want to print an organ, which is still a very noble um goal, and I think some companies might might actually get there within five years. Uh but I think a more closer goal is implants, is bioprinted implants using polymers. But one important thing about bioprinted implants is material science. Without the proper material, as you all know, we're not gonna we're gonna achieve, not gonna be able to achieve more with a new uh manufacturing process. So our first speaker is um from Bizwara Biomedical and uh is Dr. Niti Surivastava. Uh I'm trying my best to say your name, sorry if I butchered it. Um so and and also um Dr. Rob Bizwara is um also here to answer any questions after the presentation. So here we go. And the other speakers can off-screen uh so that we can give Nini the space.

The Real Goal Beyond Organs

SPEAKER_00 2:40

Okay. Can you see the presentation?

SPEAKER_06 2:43

Yes.

SPEAKER_07 2:44

Okay, okay.

Absorbable Polyurethane For Bone

Clinical Proof And Scaffold Performance

Audience Q&A On Degradation

SPEAKER_00 2:45

Okay, I just want to thank you, 3D Heels, and Jenny, for the opportunity to present today. Uh, my name is Neeti Shrivassava, and I am director of RD and quality at Diswara Biomedical. And today I'm going to uh share how we are redefining bone regeneration using our absorbal polyurethane technology platform. And we are going to discuss the clinical need, the limitation of current materials, our absorbal technology, and how this is enabling the next generation 3D biofabrication. So I'll begin with a brief overview of our company and infrastructure, then we'll discuss bone biofabrication fundamentals, the current competitive landscape, and limitation of existing scaffold materials. From there, I'll introduce our absorbal polyurethane chemistry platform, the clinical validation and process capabilities. So, our company is a biomaterials innovation company specializing in absorbal polymer technology. We make PLGAs which are used in medical device and biomedical applications. We also make beyond PLGA polymer and PEG-based products. We operate in ISO and GMP certified facilities. We have labs both in USA and India, which is supporting our RD and manufacturing. Also, we have multiple FTA-approved commercial products for bone applications, which is based on our absorbal polyurethane technology platform. In addition, we are also currently conducting the GLP studies. We are making next generation tissue adhesive, tissue bond, which is an internal surgical adhesive for GI and ostemosis, and the work is funded by National Science Foundation, NSR. So this picture you can see we have around 6,000 square foot ISO 13485 and 9001 certified facility in USA. Our facility is located close to Princeton. It's in Hillsboro, New Jersey. And in addition, we also have around 15,000 square foot GMP and ISO 13485 certified facility in our India Lab too. So now let's come to bone and bone biofabrication represents the convergence of biomaterials, additive manufacturing, and biology. So the goal is to replicate the structural strength and biological function of native bone. So a successful scaffold must provide immediate mechanical stability, it should support vascularization, it should allow cell attachment and extracellular matrix formation, and also it should gradually resorb as the new bone starts forming. So the challenge is that many current materials fail to balance these properties simultaneously, and this is where the material science becomes critical. So the workflow is straightforward. First, we create the resorbable bone scaffold. Second, the cells are seeded and extracellular metrics begin forming. Then the tissue matures and the scaffold gradually resorbs. The materials must maintain the strength during early healing. They should degrade in a predictive manner without any inflammatory byproduct. If the degradation is too fast, we lose mechanical support, and if it is too slow, it impedes remodeling. So this is where the unmet need is. So in bone fabrication, we use synthetic polymers like PCL, TLA, polylactides, combination of polylactide and glycolite copolymers, polymethyl methacrylates, as you can see here, peg copolymers are also used, and polyurethane is used for tunable degradation and mechanical strength. Biological polymers like collagen, gelatin, and silk fibroin also offers biocompatibility and natural cell addition. There are also hybrid composites combined: polymer with hydroxyapatide and bioactive glass components for enhanced osteoconductivity and to increase the mechanical integrity. They combine these two. While resorbable polymers provide temporarily bone support and eliminate the need for secondary surgery with customizable strength and flexibility, however, most current polymers have limitations such as their brittle behavior, they have limited mechanical tunability, they have poor toughness under load and acidic degradation, and they one of the most important things is these polymers lead to acidic degradation, which is not good for cell growth. So, this is where polyurethanes offer a fundamentally different architecture in overcoming these issues, especially no acid release, which prevents the cell death. So here we have a landscape of current orthopedic scaffolds which focus mainly on soft tissue repair and not true bone regeneration. So most systems, as you can see here, they are collagen-based metrics combined with polyester, example polylactides. So these platforms are clinically effective, but they have material limitations. Like collagen-related challenges is biological variability and they can cause potential immunogenic concerns. While you see polyester-related challenges are they have very fixed degradation timelines and we have a very limited control on resorption behavior. Also, we have design limitation which limits the ability to independently tune the mechanical strength and degradation rates here. So many products here are designed basically for load sharing, not for load-bearing bone applications. So the ongoing challenge, if you can see from here, is predictable degradation, mechanical robustness. We need some fabrication flexibility, and so there's a clear material gap for true structural bone regeneration, as we can see from this slide. So this is exactly where Bezvada biomedical absorbal polyurethane platform is different. So this is a little busy slide, but I will try my best to explain this. So as you can see on the left hand side, we have MDI-based isocyanids. So the traditional polyurethanees are permanent materials, which is MDI or TDI-based, they are non-hydrolyzables, very biostable polyurethane. So at Bezwara Biomedical, we are developing a fundamentally different uh chemistry platform. So it's on the right hand side. So our innovation lies in hydraulytically degradable heart segments. So as you can see here, if you um between the two aromatic rings, there's no hydrolyzable links in MDI, and you can see on the right side there's an R. So um so we change we have made hydrolyzable MDI, putting that R in there. So how we engineer it is we um incorporate bioabsorbable isocyanates, which are derived from glycolic acid, lactide, caprolactone, and polydiaxonone linkers here. So this allows us to control the degradation from week to over a year, and this is this is based on a very known suture chemistry used in medical device devices. Even more importantly, the hydrolysis products are very biocompatible and also they allow us to precisely control the mass retention, the mechanical strength, and the degradation kinetics. So by adjusting again the glycolic, lactic, caprolactone segment length, we can very easily program our material and make the polyurethane there from. So these are uh examples of our novel absorbal aromatic diisocyanates. As I was mentioning to you, uh the first one has no hydrolyzable links, as you can see in the slide, the first structure. The second one is uh the glycolite base, it is fast absorbable, um uh fast absorbable, and uh while the PDO-based is has intermediate absorption profile, and caprolactone and lactide-based uh isocyanate monomers can take years to resorb in the body. And the hydrolysis products again are safe and biocompatible, supporting the development of linear and branched polyurethane for hydrogels and crosslink materials. So these are some of the examples of multi-armed isocyanate monomers that we have prepared. We can make branched polyurethane from them, which can be used for making polyurethane-based hydrogels and crosslink polyurethanes for very strong strengths and mechanical profiles. So, uh here I just want to show you uh the accelerated in vitro hydrolysis data for several absorbal polyurethane systems that we have prepared incorporating different uh degradable heart segment chemistry. So, under accelerated conditions, we observed a clear structure and degradation relationship here. So the glycolic acid-base system degrades the fastest due to increased hydrophobicity. The PDO-based system show intermediate degradation profiles while the lactive-containing formulations degrade more slowly because of the greater hydrophobicity and steric hindrance. This result shows us that by modifying the heart segment composition, we can systematically tune the degradation kinetics to match the desired absorption timeline for the bone regeneration applications. So, this is not a new chemistry, the chemistry is already clinically validated, and this includes more than 15 FDA-approved products, which is commercialized by our partner. Uh, the company name is Eberx. So, the product name is Montage, they have Montage line of products for PUDDI for bone applications, they have Fast Set PUDDI. Uh, we have Montage Flowable that you can uh can be used as a bone void filler, then we have pharma touch putty and bone void fillers again. The clinical studies demonstrated no device related adverse event, improved recovery, sorry, accelerated functional performance, and this also significantly did risk our expansion into 3D printed construct based on all this data we have so far. So the product montage is used in orthopaedic cranial trauma, cardiothoracic, and spine surgeries. It is very cohesive, setable, resorbable, easy to use, adheres to bone surface, and it hardens within a minute, which is very important for surgeons. So uh the clinical studies have shown that montage Puddy enhances sternal closure also and accelerates the post-operative recovery with no uh device-related adverse events so far, and it also adds a substantial cost benefit for healthcare system. Also, our base water polyurethanes are protected by multiple patents covering absorbal polyurethanes, uh bioabsorbal surgical articles, multi-body adhesive, we have semen composition for tissue hemostasis repair and reconstruction applications. So, this is a list of patents we have. So, now again, why polyurethane for bone? So, um from all the chemistry background that I have just provided, so polyurethane allows something unique. It is segmented polyurethane architecture provides distinct soft and hard domains. So the soft segment contributes to elasticity and toughness, while hard segment provides strength and modulus. So this architecture allowed independent tuning of mechanical properties and degradation, something very difficult to achieve with polyester-only systems. So for load-bearing bone scaffolds, toughness and fatigue resistance are very essential, which our polyurethane can fill the gap here. And our materials are very compatible with multiple fabrication methods. 3D printing, we can 3D print our polyurethane polymers for patient-specific implants we can prepare. We can also do electrospinning for uh extracellular matrix mimetic nanofiber applications. We can do solvent casting for porous bulk materials, and we can also do composite mineralization with hydroxyapatite or TCP for enhanced stiffness and osteoconductivity based on the required application. And together these techniques support customized high performance biomedical solutions. So, one chemistry we have multiple fabrication modalities, we have scalable across indications, it is not just printable, it is programmable for various needs. So, also we have done all these initial studies proving that we can uh make our scaffolds. Uh, this is this study is being done with our partners at Rudgers University, so Rudgers College. So, these slides highlight the biofabrication versatility of our absorbable polyurethane platform. We can tailor the mechanical properties and degradation profiles. The material is electrospinable, enabling the formation of nanofibrous mats that mimic extracellular matrix structure architecture. You can see on the first three images here, we have made the nano-woven mats for that application. We have also made the nanofibrous scaffolds that can support cell attachment and proliferation and new tissue formation bone applications. It's the tubular scaffold that we have prepared, shown in the picture here. The same chemistry can also be processed into compression molded films, tubular scaffolds, and porous foams, as you can see here in these three pictures. So, this demonstrates that one synthetic platform can be engineered to multiple scaffold formats. So, in this slide, I want to show you the melt processability of our absorbal polyurethane. So the materials are designed for extrusion into high-quality fibers using control rheological characterization. The rheometry study shows a stable melt flow index and a range of shear rates indicating consistent processing behavior. So we can easily extrude them into fibers. So this stability enables production of smooth uniform fibers suitable for textile and non-woven scaffold formats. The extruded fibers can be assembled into mats, structural scaffolds that can function as temporary resorbable frameworks in bone biofabrication. And the fiber-based architecture supports cell attachment, proliferation, and new tissue formation, as I mentioned earlier. Most importantly, the melt extrusion expands the biofabrication options beyond the solvent-based processing, which improves the scalability and the flexibility with the manufacturing. This is also a very important slide. It highlights the mechanical performance of our absorbal polyurethane films. We have got tensor strength reaches as high as 7000 psi with elongation exceeding 500%, demonstrating both strength and flexibility at the same time. As you can see, the table 1 shows how soft segment content influences the strength and elongation here. And on the other side, you see in the table 2, we have it demonstrates that soft segment molecular weight allows tuning of modulus and tensor performance. The higher the molecular weight, it'll be more mechanical strength it has. So overall, the segmented polyurethane design enables us to make a highly elastic strong material for load-bearing applications. So this light compares our absorbable polyurethane scaffold platform with commercially available clinical systems. With these polymers, these materials often have fixed compositions, limited ability to independently tune the strength and degradation at the same time. The collagen-based systems may also introduce biological variability and immunogenic consideration, as I mentioned earlier. In contrast, our polyurethane scaffold is fully synthetic, which is important. No acid release, so there's no acid forming and keep the tissue safe, no cell that there, and it is hydraulytically degradable technology platform. So it goes away as it heals and new bone starts forming. So the tunable hard and soft segments allow independent control over mechanical strength, elasticity, porosity, and degradation rate. This enables fully resorbable behavior without the long-term residual fragments left behind. So the key advantage here is it's the programmable structure, property relationship rather than fixed material compositions here, which our polyurethane technology can achieve. So this is our final slide. So in summary, our polyurethane platform provides fully synthetic, pathogen free, and customizable materials for bone regeneration and tissue engineering. With FDA approved products and proven clinical success and our strong IP portfolio, we are driving innovation in orthopedic biomaterial. And we are focused on overcoming current material limitations and improve the patient outcomes, which is very important. And this is through our next generation biofabrication technologies. So we look forward to collaborating with partners who share our vision of transforming the bone repair through smarter, safer, and more adaptable biomaterial. And with this, I'll wrap up my presentation. And thanks a lot for your time. And I'll be very happy to answer if you have any questions on this. Thank you.

SPEAKER_06 22:32

Thank you, Nidhi. That's an excellent presentation. It looks like it looks like your portfolio has significantly grown since the last time we chatted. We do have one question from the audience, and I encourage everybody to submit their questions now into the QA box. One is from Esther. She said very interesting ability to tailor the degradation rates up to one year. However, the data on the slide only showed up to two days. Do you have any other data for the longer time duration?

SPEAKER_00 23:00

Yeah. So we are conducting that study, like in vivo studies for the degradation profile, it's ongoing and we'll get the data soon. But the table that I provided is for the accelerated studies we have performed, which corresponds to the longer degradation profile. And this is not a new, you know, the linker chemistry is switcher-based. So there's a lot of work has been done already on that, and they have proven that lactide-based polymer system, the absorption profiles is uh the one that I mentioned years, one to two years for lactide-based uh polymer.

SPEAKER_06 23:33

So there are previous studies that has similar compounds.

SPEAKER_00 23:36

Yeah, not for this particular polyurethane, but any system that has lactide in their absorption is longer. Yeah. But we the study is ongoing. And I like to have Dr. Rao, if you would like to add to this.

SPEAKER_07 23:48

Yeah.

SPEAKER_03 23:51

We yes, we have formulations where you can go from three months to two years. Um lot of data we have. Yeah.

SPEAKER_06 24:01

Okay, so I have some questions. Um, because you know, I know our audience, actually, I I I look at the list of the audience today. There are quite a few very technically savvy people, including Esther, who just asked the questions, but I am not, and I know there are some people who are unfamiliar with this. One is um, you know, it's just hard to imagine how you can monitor these um absorbable polymers uh in a person's body. Um, how do you usually monitor these degradation processes in in vivo?

SPEAKER_03 24:32

The the absorbable polymer chemistry is old. It is almost 50, 60 years. Um they have done sutures, stables, clips, and all absorbed polymers. Applications were developed there. So there's a plot of data showing the difference between glycolic acid versus lactic acid, paradiaxon is well established. Okay. So if if you look in the literature, you find it's so much information. Okay, great.

SPEAKER_06 25:03

That's that's that's a good start. Thank you, Raw. Um all right. Um so also there's a slide that like has a lot of information, but you mentioned it's very important, is about the mechanical properties of these materials. And you mentioned the uh, I guess the the tensor the tensor, the tensor strength. And but how do you can you compare that to some biological system? To you know, what does the uh 7000 mean? You know, what what does that what can that be compared to? Is that human bone or something else?

SPEAKER_03 25:36

No, you can't you can you cannot compare the human bone with that stuff. I think we are comparing with the commercial biostable polyurethane polymers, and we were as good or better than the biostable polyurethane, which are commercially uh applied for medical applications.

SPEAKER_06 25:54

But it compared biostable. Okay, uh so how far are we from the natural system? I'm just kind of curious. How far? Yeah, like you said we can't compare to the human bone. How but how far are we?

SPEAKER_03 26:11

Oh, the the films we pro we we were showing is we cannot compare to the human bone. But with the already using now um Ebnex is making uh formulations compared to the bone. They devise the uh formulations such a way that as the bone growth occurs, uh uh lactide polymer degrades slowly in a matter of two years. And while it's degrading, the bone human bone is going in there. That's why that's why it is so successful uh for the montage family. Uh the criminal growth growth is happening while lactide polymer is degrading.

SPEAKER_06 26:54

Yeah, that's awesome. That's actually the first time I know about the bone putty.

SPEAKER_08 26:58

Right.

SPEAKER_06 26:59

Um, all right, we have another question. Let's see, do you see a trade-off between this is from Rob, do you see a trade-off between target degradation rate and mechanical strength elongation? What is your approach to optimize the mechanical properties for each indication? Okay.

SPEAKER_03 27:18

So the mechanical properties it is controlled for polyurgence, especially there's a hard segment and a soft segment. So mechanical properties are controlled especially strength-wise controlled by hard segment, elasticity controlled by soft segment. By combination of the high ratio of the hard and soft segment, you can achieve the properties you're looking for.

SPEAKER_06 27:43

So the degradation rate does not affect the mechanical property.

SPEAKER_03 27:48

No, degradation no is not going to affect.

SPEAKER_06 27:51

I think the yeah. Okay, I hope that answers your question, Rob. Um, all right. If we have no other questions, uh we are going to move on to our next speaker. Thank you so much, Needy and Raw. Please type your contact information, everyone. This applies to both the speakers and um the audiences. If you if you want to get in touch with people, feel free to share your social media link, your email, whatever you feel comfortable here. And I see we're we're not like a huge crowd here today, so I think everyone is safe. Uh so if you want to put them in the chat and also tell us who you are and where you're from. And I see a lot of new names that I don't recognize, so it would get to know to this community. Uh also when you put the chat, uh Nidi, you just put it in only two and I'm typing more. That's the wrong uh you have to make sure the chat is goes to everybody. All right. So let's move on to our next speaker. Uh, who is uh Monica Who. She just taught me how to say her last name, and again, I am she is from Asiform. Um she's heading the commercialization, right? Are you heading the commercialization? I'm looking out right now. Yeah. All right. Osiform uh used to be called Particle 3D, I remember, many years ago, but uh really transforming yourself now to a more mature biotech company. So Monica, the floor is yours.

3D Printed Ceramic Bone Substitutes

FDA Strategy And Reimbursement Reality

In Vivo Data And Research Products

SPEAKER_02 29:15

Yeah, thank you so much, Jenny. Um yeah, my name is Monica Vilayus, and I am the CCO of Ossieform, and uh we are a Denmark and UK-based uh medtech company. By 3D printing structural bone substitutes, we are working to reduce surgeons' reliance on permanent implant solutions and thereby improve patient outcomes and bring down complication rates in orthopedics and spine. We are currently working on getting our first orthopedic bone substitutes for extremities and pelvis surgery cleared by the FDA hopefully this summer. During the process of getting these medical devices to market, we also launched a line of research products back in 2021, and I'll tell you a bit more about the story behind this later. Meanwhile, we're developing a new generation of biointegrative spinal fusion devices as well as bone printing hubs for the point of care. So, Osiform was founded as a spin-out company from the University of Southern Denmark back in 2017. In collaboration with a local surgeon, our founders, who were medical engineering students at the time, um started investigating a new solution for 3D printing bone substitutes that could um that could restore patients' tissue to their former shape and structure. During the first years they formed uh they performed early in vivo validation and raised a series um seat around of uh approximately$800,000. And in 2019 they hired our CEO, Tia, and shortly after, in April 2019, they hired me as the first employee. And initially I was hired to take care of market research, communications, and marketing. But as it is in startups, um I was quickly involved in almost all areas of the company. I started establishing our network of clinical and industry partners, and I fell in love with the bone printing space. So today, more than 5 million bone grafting procedures are performed every year globally, and here autografting is still the clinical gold standard because surgeons need the biology to heal the bone. But it comes with several drawbacks, including limited supply, prolonged recovery, and pain. And this leads to a high demand for better bone graft substitutes. And now when surgeons want something that naturally integrates with the patient's bone, they can use grass from a donor, allographs, or ceramic graphs. But these are often associated with variable quality and tend to lack structural stability over time. So therefore surgeons are often highly reliant on costly metal implants because they need something more structural. And while a lot of progress has happened in this field to achieve better fusion into porous metal, it does still carry significant risk of tissue damage, infection, and patient concerns because the material is permanent, it's foreign to the human body, and because metal is much harder than bone. So we set out to create something structural but without the long-term risks of a permanent foreign body implantation or the variable quality of donor bone. And what we've done is we've taken the well-recognized ceramic material beta-tricalcium phosphate and developed a 3D printing technique to give it shape and structure. The material has been used clinically for the past 40 years, but primarily in non-structural forms like paste and also molded blocks. It's known to carry minimal risks of complications and our bodies recognize it as bone so it completely remodels into natural bone over time. So we leverage 3D printing and biomaterials to provide structural consistency while also allowing the defect side to completely regenerate. So more specifically, we mix the tricalcium phosphate powder with fatty acid to create a print, a paste that allows us to print with it. And when an implant has been printed, we then burn off the fatty acid again, and this leaves a pure ceramic part. And with this 3D printing technology, we can control the structure and the resorption rate of the bone substitute to match the specific demands of diversified applications. So not just the shape, but the trade-off between the porosity that enables good boning growth and ensures how fast the bone substitute resorbs, and the biomechanical factors that ensure structural stability throughout the healing process. So we knew that our bone substitute would be classified as a class II risk device in the US and be eligible for the 510K pathway, which typically does not require clinical evidence, but substantial equivalence in preclinical data to a predicate that has already been cleared by the FDA. Under the EU MDR, the same product is a class III implantable device coming with significantly higher clinical and regulatory burdens, both upfront and post-market. And this classification gap fundamentally shaped our market entry strategy. In the US, we can also validate real-world surgical workflows, outcomes, and market fit earlier. So we chose the US first to de-risk the technology, the products, and the evidence strategy before stepping into a class III environment. But the US market also comes with great challenges. First, one must be sure that there is a clear predicate and that equivalence can be proved to obtain the 510K clearance. Novel materials and architectures like those created with bioprinting can create challenges, which can potentially lead to additional test requirements or even a reclassification. Second, FDA clearance does not guarantee payment or commercial viability, especially not with the 510K pathway. So reimbursement strategy must be prioritized early. And third, US is very hard to enter commercially in general. There are also increasingly demanding requirements for new device adoption as decision making is being centralized and hospital supply chain and value analysis committees have become decisive in new device adoption. So you must be prepared to prove return on investment not only to surgeons but several other stakeholders as well. So there's a big strategic challenge here in designing the product and the claims tightly enough so that you stay within the 510K, but you also need to remain competitive and get paid. So towards this path, we have performed extensive preclinical testing and we have um initiated our regulatory process with the FDA. What we're working on right now is um the longer-term in vivo data in order to obtain the clearance of our first orthopedic devices. And as I mentioned, novel materials and architectures can create challenges and uh additional evidence requirements, and um we also experienced that we had to supply additional longer term in vivo data to the FDA. Um but now as we anticipate clearance this summer, we are poised to initiate uh first clinical use shortly thereafter. And um first we will start setting up a post-market study in the US to gather real-world evidence, both clinical and health economic, and from 2027 uh we will set up clinical investigations in Europe um in order to seek approval under the um MDR. So this data is from our latest in vivo study in uh femural uh rapid femural condyle defects showing uh bone ingrowth and uh bone substitute degradation over 26 weeks across our bone substitute uh in the top row, our predicate and the middle row, and an empty defect. The data shows equivalence in the trends of new bone growth and degradation uh between the ossiform bone and the predicate, uh which is also what we wanted to achieve. But the new bone that is uh generated looks different. The ossiform bone induced formation of um well organized lamilla bone. It underwent normal bone resorption followed by an overflow remodeling based bone formation, and the predicate induced more bone formation, but mainly as disorganized woven bone, and also the predicate um showed significant resorption of not only the implant material but also of newly formed bone past the 12-week study mark. So this and previous preclinical studies suggest that the 3D printed structure that we achieve enables balanced rates of bone in growth and bone substitute resorption, ultimately providing structural stability throughout the healing of the bone. Meanwhile, the MTDFEC control was unable to establish any meaningful uh reconstruction of the bone tissue, highlighting the need for bone void filling to facilitate healing. So uh during the process of getting our medical devices approved, uh we have launched a line of uh research products for research use only globally. These are bone mimicking 3D cell culture systems which are made from the same technology and the same material as our medical devices. With this research line, we have again valuable commercial uh experience while establishing collaborations with academia and further validating our technology. Among other things, we have uh produced this interesting uh video that you see in the corner showing osteoclasts in green naturally resorbing our scaffold, uh which is the red part. And uh furthermore, numerous studies have shown that cells behave naturally on our scaffolds, and in a direct comparison to bovine bone slices, uh we saw that they are comparable in terms of cell viability and collagen production uh among other things.

SPEAKER_01 41:54

So uh this is my final slide.

SPEAKER_02 41:58

Um I wanted to share with you that today we're in the fortunate situation that we have an established clean room production and uh ISO-certified um QMS as well. Uh our production is here at our facilities in Ulnse, where I'm sitting in Denmark. We have a worldwide patent portfolio, a highly experienced team, and collaborations with clinical key opinion leaders. Uh, being a rather small team, these uh clinical and industry partners that we have have been so important uh for us in validating our products and our value proposition. So early surgeon um collaboration and engagement has been really a key priority for us. Um we have raised eleven point eight million dollars so far through seed and a rounds, and um in the coming couple of years our pro priorities are to generate the clinical and health economic data and launch our first um products which are for food deformity correction into the US market uh as our first market.

SPEAKER_01 43:11

Um thank you so much for listening and let me know what questions you have for me.

SPEAKER_06 43:18

Thank you, Monica. That's an excellent presentation. You guys definitely made a lot of answers uh since I've last talked to you, uh especially in the regulatory space, it's such a kind of long and difficult, challenging path uh to get through regulatory. Um okay, let me see. Do we have any questions in the audience? Let me see. Um I have a question. Um in terms of what your product can do, um, you said you you're you're testing on the foot. Did I hear right? Like the first body parts. So is this low bearing, non low bearing? You know, what kind of bone defect can it do? Can it help?

SPEAKER_02 43:57

Yeah, good question. Uh these first products that we are bringing to market will be essentially uh bone-wide fillers for non-load-bearing indications, meaning that the surgeon will need to um fixate it with some kind of uh external fixation as well, like a uh compression plate or or stable um so um but we are also developing on a current area of R ⁇ D activity is combining the um implants with other materials uh both to make them more durable but also potentially to release additives in the longer run.

SPEAKER_06 44:36

Okay. And also like I think I remember many years ago when I talked to you guys uh you were focusing on uh cranial facial defects is that still a focus or it seems like it's there's a different it's a change.

SPEAKER_02 44:49

Yes it definitely has a funny story actually the the surgeon that our founder started working with back in the day was the then head of oral maxillofacial surgery at the hospital and um this was the initial uh focus and we're talking a lot about patient specific implants uh and this you know this is the clear uh obvious use of 3D printing but then we started speaking to more surgeons going to medical meetings in the US and we quickly learned that it's actually difficult to make it like really both profitable and scalable and uh we saw just a greater product market fit in orthopedics where they really need um they need products that are available off the shelf but they want something that is structurally tailored so that it fit perfect it fits perfectly not necessarily for each individual patient because even though we are different we are still very much the same most of us uh but they needed something um structural and more robust yeah and we just saw a clearer product market fit initially in uh the orthopedic space uh a very high need uh for new innovation because it's really dominated by metal solutions today uh but it's not like um we don't want to go that way it's definitely still on our radar and especially when we are looking into more custom or patient match solutions uh we also want to go into the oral maxillofacial space but it's um in the longer run yeah I think this is a good lesson for us all to learn is that the path from bench to bedside is not straight a lot of times it's a very torturous path and sometimes you have to pivot and uh I also I'm just trying to understand because I'm a common lay person I'm not in the space uh as much as you guys are uh the non-bearing bone defect in foot and ankle I'm assuming like what could that be?

SPEAKER_06 47:01

I mean usually you will want something to be load bearing don't you?

SPEAKER_02 47:05

Yes uh so specifically uh the two indications that we're targeting are osteotomies uh Evans osteotomy which is uh which you insert uh in the side of the foot to correct uh an outward splaying uh foot and the cotton osteotomy which is also for both are for uh flat foot uh reconstructions uh among other things and collapsing foot deformity and today uh the surgeons primarily use allographs the donor bone um and they are not very strong either um but it it's not necessary because then they they are often fixated or um the the patients are kept non-load bearing in the first six weeks and then that's fine. But uh the problem with these allographs that they use today is that they are often very weak and fragile but it it varies because obviously it's from a human donor so the quality does just vary.

SPEAKER_06 48:07

Very interesting how I've I would have never thought about that area to look into. So thank you very much Monica for sharing. Let's see do we have um any question from okay we have one question from Gavin do you have plans to incorporate biological material into your device through the 3D printing that's a very good question.

SPEAKER_02 48:28

Yes uh this was also an RD focus uh in the beginning uh from the very beginning actually our CTO uh was uh also uh he um made a research project uh showing that um pharmaceuticals like antibiotics could be released uh from the implants yeah because we have this fatty acid that we can keep in the implant or we can burn it off and if we don't burn it off through sintering the this fatty acid could potentially contain some kind of uh drugs um but uh currently it is uh at a very early stage of um RD activity but it's certainly interesting and um a potential for the future.

Cryobioprinting For Better Human Models

SPEAKER_06 49:21

I think more than one uh companies in 3D printing at least uh I know want to incorporate some kind of pharmaceuticals or biologics into their it's definitely the direction for the next generational implants. We'll see if that path actually moved through. Just like you know a lot of things that's very intuitive but when it comes to commercial it's uh not straightforward. Yeah regulatory that's a whole other uh world of uh sterilization that's like number one question I have is like now you have to change your sterilization strategy. Yeah uh if you can't burn off the fatty acid. Um all right cool Monica this is a really good conversation and thanks to the audience for engaging. Um also want to remind everybody just please put it in the QA boxes right now I'm managing like four different boxes right now to make sure I see all the questions. So if you can put it in the QA box that's that's that's helpful for me. All right so we're gonna move on to our next speaker. Uh thank you Monica come back for the panel discussion. All right so next speaker is the CEO and co-founder for Crocore very interesting bioprinting startup you guys are gonna see and this is um Carlos Enzio.

SPEAKER_04 50:32

Awesome thanks Jenny and great to be here thanks for the invite so let me share screen very quickly great hopefully everybody can see it there. Yeah so I'll I'll give a quick overview of some of the technologies and and things we've been working on and I'll try to really tackle or highlight this from a more scientific perspective to really take advantage of of the audience that is here and it's great I was looking at the the that the at the audience member it's good to see some familiar faces and those that are new uh very nice to meet you as well. So yeah I'll talk a little bit about first of all the the genesis of cryocore and and what we've been able to do. So really this the the cryo core stems the technology stems from the Shrike Sang lab which is affiliated with Harper Medical School and BWH here in the Boston area. And really uh with this lab is one of the pioneers in a lot of these biofabrication technologies, organs out chips, biomaterials and for the last six years with with Professor Shrike, you know we've we've been very happy about the technologies but we have this this itch that we can't really fully scratch and that itch is how taking into account the theme of today's conversation how can we continue to translate our technologies from the bench to the bedside towards broader and transformative applications. So we we had that itch and since the last year and a half or so we've been really focusing on how can we make this into something more viable and we've been fortunate enough to be able to continue to build out this vision with fundamental pillars right on the business side we have Jills Cotier on the science side and the biology side we we have a postdoc Salvador Collegos and then we're also beginning to incorporate some of the automation and machine learning tools with Rutrigo so we're we're a passionate team we're all in and I'm happy to show you some some of those aspects. But before I do let me just kind of like paint this macro perspective of of what is going on. You know what is the problem that we're really trying to tackle and this I'm sure we're all quite familiar with with which is that these regulatory mandates are pushing and urging the need for new approach meth methodologies, which are NAMs. And here we can kind of see it on the right hand side being like is illustrated with this timeline where we can see how in in recent years you have this huge surge of these mandates and frameworks that are being established by these governmental and regulatory agencies to push for new types of models. And we're talking about models used in preclinical drug development. So the rationale behind this push is that hey there's this huge translational gap as we see here between preclinical and clinical because the models that are currently being used don't replicate the human system. So if we can make new approach methodologies or more human relevant models then we will be able to bridge this translational gap. Ultimately this results in an improvement in time it improves like you have less economic loss and the the biggest gain and advantage and value capture here would be you're ultimately able to save lives. So that is the thought process here how can we create better models to enable the translation in a more efficient and efficacious way so before we continue just to establish the the same language right as a starting point here here here's how we define these models we go from left to right a 2D spheroid organoid Carlos I think we lost you a little bit your screen is frozen is everybody seeing what I'm seeing more recent technology is being being searched um the more um Carlos we we lost you for like two minutes oh just yeah from start are you able to hear me now or no yes yes now is back but you we kind of lost you know the the next slide actually you know if you can start from the two this one is yeah this one is fine this one's fine yeah okay so everybody what here was was everything clear?

SPEAKER_06 54:43

Yes.

Case Studies In Complex Tissues

Cryocore Business Model And Access

SPEAKER_04 54:43

Nice perfect so I'll I'll start back on this one and thank thanks for the mention Jenny. So kind of here what we're trying to showcase is the the the types of models um and really establish like a baseline for how we define these models. We talk about 2D spheroid organoid organon chip and bioprinted tissues and what we're trying to do cry course technology and it's it's interesting because as you transition from left to right you have an increase in in the human relevance so they can create more complex types of structures but unfortunately you also have an increase in the complexity required to make these these models and these structures so if we hone in on bioprinting you have this technology that has the potential when done correctly to create these very complex and human relevant tissues and models. However the problem with bioprinting it is it has these these logistical and technical limitations which are are severely hindering its adoption and that's why when we look at the industry from like a preclinical drug development and pharma nobody's really talking about bioprinting as a widespread technology because it's so hard to implement it's so challenging. And this is really what Crocore focuses on how can we unlock the benefits of bioprinting to really create these new types of models to enable better translation from preclinical to clinical so here we'll we'll showcase this video that kind of allows us to visually showcase what are the challenges associated with bioprinting. So it encompasses a wide number of different areas and that's what makes it challenging from the biology making sure that your cells are happy the material optimization and creating the right environment for the cells making sure that you can print this material you go to the bioprinters themselves the operation the hardware the software the electronics scaling up is challenging throughput is challenging and not only that the shelf life is extremely limited. You can only use them when they're fresh so that me that that really complicates the logistics the distribution and overall adoption so what ends up happening is if you have this tool that scientists are very excited about using but they're unable to fully adopt it because of some of the the issues that we just mentioned. And it's not only happening in a centralized manner but it's really happening across the globe and in a widespread manner across the industry. These pharma companies are excited to use this technology but are unable to do so and this is what Cryo focuses on how can we unlock the potential of this bioprintate adoption so to address this challenge we came up with this technology called cryobioprinting and we are first going to look at this left hand side of the video and and here we have this material that is being deposited and we can see basically we combine bioprinting with in situ or instantaneous cryopreservation. So we can see in the video how as you're printing or depositing this material it's gonna transition from this bluish color to more like a white frozen type color and we design this material and we call those cryobinks that enable the cells to be happy during this crowd preservation process. And as we see on the right hand side of the video we can do this in an automated reproducible and scalable manner as well now this when you begin to really get fancy and creative with these types of structures then you can create some really beautiful 3D type of images um going from just more on the simple side like 2.5 D, these freeform structures some type of blood vessel different types of organs and tissues and and even multimaterial and freeform multimaterial structures so you really have leveraged all the benefits of bioprinting which is like this high spatial localization of different materials in this 3D format but what we can do as well is be able to integrate a wide number of cell sources right stem cells primary cells cell lines to create a multitude of tissue types from oncology to liver neuros so on and so forth and in a wide variety of formats such as like these 48 well plate formats into organs on chips reactors or just individual type of tissues um and and here we we in the last talk Monica was talking about this like the the the power of having these shelf ready models that it are are always available and that is what cryobioprinting enables you to do to have these to enable this long-term storage of your tissues of your models. So in this slide we showcase how we can take different types of cells like 3T3 and the Hubex endothelial cells we cryobioprint them after cryobioprinting we can store them in liquid nitrogen for three months after three months we can take them out thaw them culture for seven days and after seven days the cell viability is pretty good so it's upward of 80%. So this is now a powerful concept because what we're really trying to showcase here is you can take any type of cell any type of tissue fabricated in complex ways or customized personalized manner to create this human 3D model that is always available and that enables a lot of speed it also benefits with the reproducibility because you don't have batch to batch variation you can just have a stock or an inventory of these models and they're more human relevant. So that enables you to have better predictions. So this right here is a powerful concept that we believe will enable the adoption of our technology. Now I'm gonna showcase a little bit more on the technical side of things and and here we talk about this multi-cell uh compatibility so we were talking about like hey we have the potential to be able to really uh fabricate different types of tissues and here we showcase uh at a high level how we've been able to optimize different types of materials or different types of cryobio inks from C2C12, 3T3 hube breast cancer cells, MCF7, even uh human uh mesenchemo stem cells. So those we were able to cryobioprint and we can differentiate into into different states and conditions or cell types such as osteoblasts, chondrocytes and adipocytes and we see that when we differentiate and we can compare that to control samples or those that did not undergo this cryo process we see no significant trends uh significant differences in the trends of differentiation. So that is something that we're quite excited about because now we can begin to really play around with different cells and that's exactly what we're gonna showcase in the next couple slides. So I'll talk about a couple case studies. This first one is gonna be more on this uh neuromuscular or neurodegenerative type of avenue and and really again want to leverage the the the theme of today's conversation which is this like bench to bed site. So we we're showcasing here this in vivo translation for for a neuromuscular model where we can see in vivo these these images can kind of showcase how you have a specific patterning of these muscle cells and then you're gonna have some sort of junction within these like uh neurons connecting to these muscle cells. And what our technology can do and I'll I'll showcase how that is able to be achieved is we can pattern these muscle cells and then embed it with neurons to really begin to create these neuromuscular junction models and and and we'll showcase that a little bit further on. So before we talk about the alignment it one thing that is important for these type of neuromuscular uh applications is you need to be able to have a material that makes the cells happy. So in conventional printing it's very hard to print these very soft like materials and neurons like this soft material because as as we can see here on the left hand side when your material is like stiff the neurons don't have the the the the room and these astrocytes don't have the the room to grow to spread to kind of be happy so then when you make this material a little bit softer or significantly softer then the cells have the space to grow to be happy to to to really be in their environment because this is kind of how our brain structure is composed. And we see here the the challenges with printing these soft materials at room temperature it's almost like if you imagine like trying to print water obviously if if you deposit water it's just gonna go all over the place which is kind of what's happening here. So printing water in a reproducible way is extremely difficult right because you have no control over the shape. But then if we're freezing this water or this soft material as we're printing it then we can begin to pattern it and then we can begin to have control over the reproducibility and this enables us to create these highly complex structures in a reproducible format to have better readouts. So with that in mind then we're gonna transition as to how we're able to achieve the cell alignment that we previously talked about. So here another cool thing about cryo is that you can print these like vertical like pillars and structures because as you're printing you're freezing the material we can see that here in the in the video on the on the top left and you can kind of see the freezing process and that's kind of neat and we can also create these overarching structures which are quite nice and it'll freeze completely but another really interesting phenomena that is occurring or like this underlying mechanism is really aligning the cells so we see here like in conventional bioprinted and casting methods the cells are just there. You can't really control their organization they're they're there they're happy but no specific um architecture but then with this freezing process we can begin to align the cells and by tuning different parameters we can control how much they're aligned. And obviously we take into account the the benefits of bioprinting like printing different cell types such as muscle cells and neuronal cells we can create this junction to ultimately create muscle cells and neurons aligned to have promote their communication connectivity to create this neuromuscular junction model. I'll quickly go through these last couple of examples so the second case study basically here we're trying to do this pancreatic uh uh tumor stroma model where where we see here in in human or native tissues the way this tumor stroma or pancreatic PDAC model can be seen or represented is you have this tumor core and it's gonna be surrounded by these this stroma compartment. And if we kind of can think about it in more simple terms you have this stroma that acts as a barrier for the tumor core. So it kind of protects the tumor from other types of like the drugs or therapeutics because it it wants to promote the tumor to grow because it says like hey if you're happy I'm happy and if you grow I grow. So it kind of is is a barrier and they interplay and they're they're connected. So a lot of times what people are doing is like they only can print one type of material and they can print both in a reproducible way to really mimic how the the native tumor microenvironment is done. And what we've been able to achieve is really printing these two compartments and seeing how this barrier is acting to ultimately create better therapeutics or enable better drug development. So here I'll briefly uh glance over this but we really can optimize each one of these materials or compartments in this case the tumor compartment and have a specific cryobioink for the for for the Tumor pancreatic cells. And then on the flip side, for the stroma compartment, we have cancer associated fibroblast, and we can also optimize that cryobio ink specifically to promote the viability and the functionality and of course the morphology. So then we are able to put both of these materials together using the benefits of high spatial resolution, which bioprinting offers, to create this pancreatic tumor stroma model. And we've also done some proof of concept drug screening and are excited to be working in the early stages with some pharma companies to be able to continue to push this forward. And here I'll I'll just showcase very uh over the top uh some additional models of things that we're working on, such as this liver model, where you can have these beautiful types of stainings to see like cell-cell interactions, cell junctions, the matrix uh composition and the cell matrix uh ECM uh interactions. We can create this muscle vascular unit where we can have these cr uh vertical pillars and we can have the muscle cells and uh endothelial cells uh aligned. And lastly, we also are able to create with more precise deposition this endothelialized breast cancer model where we can have these MCF7 or these breast cancer cells, and we can lay down in specific patterning these hub eggs to create this this vasculature within your breast cancer model to really begin to recreate the complexities that is going on in the human system. So that's kind of uh at a quick glance what we've been doing. We're we're super excited to continue to push this forward, and yeah, if you have any questions, uh feel free to let me know. Thank you.

SPEAKER_06 1:07:36

Thank you, Carlos. Every time I learn something new from your presentation, fantastic presentation and beautiful slides. Um okay. Um do we have any questions from the audience? Please uh either just put them in the QA box or just chat. As I'm I'm gonna lose in my rules here because we don't have a whole lot of people to manage, so that's good. Um I I have I have just a side note, Carlos. Actually, I don't know if you probably don't maybe you do, that the co-storage inventory right now is actually kind of in the oversupply side of things. So that's actually to your benefit. If you want to freeze anything, you could do it cheaply. Um now my question is can people buy your printer and do it themselves or right now, or how do you how do people from all over the world access your technology? Because you said this is a global problem.

SPEAKER_04 1:08:27

Yeah, that's a great question. Thanks. So the way we from a business perspective, not from a technology perspective, is we don't really want to sell the hardware itself. We think that um is is in the long run, I mean, the way we see it, yes, you can sell the hardware and it potentially could have a great price point, like I don't know, a certain amount, thousands of dollars, but eventually, how many of these systems can you sell? And if you look at the form labs model, their business model, yes, they sell you the printer, but where they actually hook you is on the consumables themselves, like the these inks, the the the the the accessories, all that type of stuff. So right following that same train of thought, we want to be a consumable provider and just provide these well plates or these these tissues, these reactors, these chips, however you want to visualize it. But pretty much you have frozen bioprinted structures embedded within them that you can just have in the freezer, and whenever you want, you just take them out and use on demand. So it's kind of like this personalized and customized, as well as some standardized models that you want to say, hey, can you give me this XYZ and this type of weight and this type of structure? And we'll be like, no problem, how many do you want? A hundred, we'll ship them to you, and you'll always have them ready to go. So more faster iteration.

SPEAKER_06 1:09:42

Is there like a tier of pricing here? Like something that's like multimaterial, it's more complex, then it's more expensive, etc.

SPEAKER_04 1:09:51

Exactly. So we're working with, for example, this uh CRO and a more of a uh the a bio tool distributor, and for that it's gonna be a more standardized model, widespread, um, lower cost and lower price point as well. And it's more like standardized, as I was mentioning. But then we're working individually with these pharma companies on a one-to-one manner where it's gonna be more personalized, more complex, and higher costs and in higher price points. So depending on the application, it and that's there's some complexities involved with that in the in the business model, and it's been a fun exercise trying to think those out. But yes, we kind of see like we have to be since our technology is flexible, our business model and our pricing also has to be able to adapt to that.

SPEAKER_06 1:10:34

And obviously, uh as I mentioned before, everybody when they think about bioprinting, they think about bioprinting an Oregon, and you did not mention that at all. Uh you're you're very practical talking about NAMS and business plans, blah. So are you thinking about that too eventually, or um do you have any um plans using this technology to create some kind of tissue similar?

SPEAKER_04 1:10:59

Yeah, uh for for the short term, being like the next two, three, four years, uh it it's it's I mean, bu if you can bioprint an organ, that's that's the gold mine. I mean that you you'll I mean who knows, you may get a like a noble like prize. I mean that that's that's jackpot. That's that's the gold standard, and that's the North Star. Um, but that is extremely difficult, and the stage that we're at, we don't have the capabilities to be able to focus on that. So as our technology matures and evolves, and we're able to get more resources, and that's why we see this um really collaboration with the Zhang Lab. Because I know from the Zhang Lab, we have projects where we are trying to print these organs, these full organ systems. So as our technology matures, with our capabilities matures, then we can eventually recombine these to like potentially crop preserve some of these organs or not even crop preserve, uh print them directly next to the patient. Um, so it it it's something that we are excited to to come, but that would be in five or ten years down the line.

SPEAKER_06 1:11:58

Thank you. I have one question from Matthew. How many cells can you pack into the the cryo inks? How critical is the material to cell ratio?

SPEAKER_04 1:12:08

Yeah, that's a beautiful question. And that's something that we're currently exploring, and we have explored. So we've tested with differ different concentrations to not give like the exact numbers because that's a bit too technical. Let's say on the lower end, on the medium end, and on the high end. And we've seen that on the lower end, it's not too great. Um on the medium end, we we kind of have a sweet spot and they're they're happy, they're good. But we have this new and we recently published that in in cell, this new type of biomaterial, which is like this is like this uh very high cell density material. And that is like pretty much all comprised of cells, and that we've also been able to showcase for some of these like uh crowd bar printing applications, and we have some ideas of how we can continue to push that type of material forward.

SPEAKER_06 1:12:53

Are you trying to using uh AI to help you speed up this uh try and error process?

SPEAKER_04 1:12:58

Yes, yes, 100%.

SPEAKER_06 1:13:00

By the way, I just want to shout out on your animation there. That that is completely AI generated. I I couldn't even do that. Um that's above and beyond.

unknown 1:13:09

Okay.

SPEAKER_04 1:13:10

For everything, for sure.

GLEND 3D With Natural Biopolymers

SPEAKER_06 1:13:12

Yeah. Awesome. Um, Carlos, thank you so much for the uh excellent presentation. We're gonna move on to our last speaker, but not the least. And then we can come back for a panel discussion. Hi, Joanna. So the next speaker is uh Joanna uh Zalas. Right? Is that right? Okay. And she is uh CEO and co-founder of uh Materialize Bio, a new startup, but uh very experienced uh executive team.

Dissolvable Ear Tubes And Pricing

SPEAKER_05 1:13:38

Thanks, Danny. Uh it's it's always great to be last because you get to hear everyone's presentation. Um and I I I hope I can tech can can contextualize and emphasize some of the really important things uh that have been shared so far from the co-panelists. But again, I'm Joanna Zilis. Um I'm the CEO and a co-founder of Materialized Bio. Materialized Bio is a medtech company, and we are building a new class of surgical tools using pure natural biopolymers. And we're doing that by taking a different approach to 3D manufacturing, which we call GLEND 3D, gravity-led engineering. And it has been optimized to be a tissue-friendly process that can create complex monolithic structures, um, maintaining their purity. But before I talk about materialized bio, I wanted to set some context on the topic of the panel about what bench to bedside really means for me. Uh I did my PhD at Tufts. Materialized bio was a tough is a tough spin-out, so this story comes full circle. But I've I've done a full transition from biomedical engineer, actually a tissue engineer, um, all the way to operator, um, the the true bench to bedside. And along the way of that journey for me, I've I've been able to experience firsthand uh what really important success factors are that go beyond having an amazing innovation, like you've seen of many companies and probably are building yourselves, um, and beyond FDA clearance into the commercialization phase. And so I'll I'll start with this one picture. It it's me uh in the pink surgical glasses on a surgical volunteer mission in Nicaragua. And I was invited to be part of the team, uh, it's almost 10 years ago now, by through my work embedded at the hospital at Matsane West St. Luke's through working at Integra Life Sciences as a clinical educator within their regenerative technologies portfolio. Uh, it was a moment for me where I realized that um great engineers can make great innovations, but that the path to actually translating innovation to patients represents the majority of a product's effort and um success. Because if it can get to clearance, but it can't get to the person who needs it most, um, you know, a lot of the innovation energy can be wasted. And so what I um that was just about four years after I graduated from Tufts. And there's no ignoring that, you know, an engineering degree or any type of engineering science studies tell you that fundamentals are very, very important, that you can't take shortcuts to great innovation. But when I was hired for my first job at Tissue Engineering Inc., which is a small company in South Boston that was building what we called the fanciest leather in the world, so a medical device made from fetal bovine skin. Um, they hired me to take really, really fancy pictures of their medical device integrating into the human body to differentiate it from the other collagen matrices that were available on the market. And when I was done with my first mission, I was put on tour with the sales team as an engineer, communicating the value of that medical device to surgeons and customers, patients, hospital systems, sometimes insurance companies, um, trying to show them that what we were developing was worth them adopting it into their facilities practice or coverage pipeline. Uh and I quickly learned that incremental improvements or just storytelling is not enough. And that preclinical work is just the first step in a value proposition that needs to be deeply developed in order to incite change for disruption and innovation. And it TEI was very effective at meeting some of those challenges. Uh the CEO at the time had planned for this. Uh, it's not something that you can react to last minute once you're on the market. You need to have things developing from the very beginning. And uh a few years later, we were bought by Integra Life Sciences and I was shuttled into a tremendously big regenerative tissue portfolio. It was like a candy shot for a biomedical engineer, um, and still focused my career on clinical education. And that's a point where I became a customer-obsessed uh engineer, not yet turn marketer. But I realized that at Integ uh at Integra, there was different divisions within a company: orthopedics, neuro, soft tissues, and different sales forces within a company. But when you looked at our end customers and our surgeons, take an orthopedic surgeon, for example, they had multiple reps calling on them and multiple products being sold from different people within the same company because the industry pipeline didn't true or structure didn't truly represent what the customer was doing every day. So that alignment and knowing that every market plays by different rules was also a very important uh revelation. When I left Integra and went to Conformis, it was my first exposure to 3D manufacturing. Uh Conformis, who was bought, I think a couple, I think it was 2023, um, by Restore 3D, was one of the first innovating on patient-specific implants. Uh, they were building um restorative patient PSI for total joints and and surgery guides associated with those. Uh and I think Monica, maybe Monica had said it, that uh that was a place where I learned that field information is very hard to operationalize. When you had to have surgeon approvals of your design requirements and MRIs collected from the space and deliver implants in fast enough timeframes to meet surgical um surgic surgery deadlines, things that are off the shelf sometimes can be in terms of of ease of use. Uh I I think then that message will and that lesson will stay with me for a long time. I um I joined Tissium backed into the soft tissue space shortly after. Uh having all of this insight. We were able to really develop a playbook. Tissium hired me, you know, I think it was five or six years before they were going commercial. And I think it shows planning early is really a a very smart thing to do and understanding all of the pillars of successful med tech translation uh and incorporating them into your product development pipeline. I saw Estelle Collins on the on the um on the audience, so shout out to Estelle. Uh she was one of the the engineers that led the development of the Tissium technology. Uh but we were there and we basically used our playbook to plan early, engage KOLs and surgeons in that development cycle and build the studies that are needed to successfully launch. They just gained clearance of their nerve co-optation device, which is a 3D printed biosynthetic scaffold, um, in June of uh of last of 2025, I think I think it was. But, anyways, uh so after Tissium, I uh was approached by David Kaplan, my PhD advisor, uh, who had been working for a number of years um with Glenn Young and Vincent Fitzpatrick, my co-founders at Materialize Bio. And they were built, they were very frustrated with their ability to bioprint silk or to build silk into a complex 3D structure. And I left Tissium because they had discovered a new manufacturing approach that we we have applied to many different biopolymers that struggle with meltability and with biosolidification, uh, as well as uh, you know, trade-offs between this viscosity or viscous inks as well as and end implant stress, uh, strength. And uh I I left TCM with a carve out, um, with a job at Brixton Biosciences, actually, with a carve out for materialize. And we worked for a a year or two on um building the story for materialized bio based on all of this entire recipe for reaching patients. So looking at what types of products could we build from this new manufacturing? What type of capabilities could we unlock? And what type of resources was it going to take for each one in terms of creation of a body of evidence? Um, what types of surgeon personalities, innovation, receptiveness to new products, to different surgeon surgeon specialties have? And how could we pick a problem that we could address with biopolymer technology or natural biopolymer technology, where we could hit on all of these important ingredients for the recipe for an innovation reaching patient success? And so uh in 2023, we founded Materialized Bio, but it was just about a year and a half later that we transitioned in the entire team uh to work on some of the first assets that I'll share with you today that we're building from this platform. So, as I mentioned before, um natural biopolymers, and I think we heard it from some of the other panelists, are difficult to work with. And I'm talking about things like silk, collagen, chitosan. Um, heat and high pressures can destroy their structures. Uh, the things that were made up today and nature is made up today just weren't designed to melt and resolidify like some biosynthetics or synthetics are designed to do. And when you process them with legacy manufacturing techniques, um you sometimes have to strengthen them with chemical cross links that or overprocess them, which leads to a loss of their function and it can lead to immunogenicity or uh and that can subsequently cascade into implant rejection and further a loss of true integration of a biomaterial implant with the human body. So revascularization, which can also uh have effects on susceptibility to infection risk. If something doesn't have your body living in it, your body can't protect it from infection. Um, bioprinting does force a trade-off right now between strength, structure, and scale for these natural biopolymers. Um, and when you have materials that have been lightly processed, this is the collagen mesh that we were working with at TEI. It's amazing it what if you keep the natural tissue properties of a natural tissue, what it can do when it's put in contact with the living thing. It can come back to life. This is the revascularization of a collagen matrix. Um and so what we're doing uh with Glen 3D is we have designed a tissue or uh an approach to make monolithic, complex 3D structures from bioinks of these materials that are highly viscous by using gravity and strategically designed molds uh to and with matched biosolidification steps uh to build a host or a portfolio of different pure natural uh biopolymer products. So here you're seeing sort of what's available on the medical device market today. This is a kitosan gel that's used as a nasal packing scent. Here's a collagen sheet and some silk and injectable gels. And here you're seeing what we can build now. This is a silk ear construct, um, some kitosan plates, uh multimaterial silk um constructs, and some tubes or stents, bifurcated and also with small flanges or circular mesh base. And these are millimeter scale, have micron resolution, so the resolution is limited to our mold, but also can be built into centimeter structures. At least that's what we've done so far in our lab. It potentially could scale bigger. So, what we've chosen to do first with this technology is to bring to widespread use chytosan, uh, which is a biopolym material. It's the second most bio-abundant biopolymer on earth, and it has a unique ability to be made with our process into a high-strength structure that can behave like a plastic, but is still susceptible to mild acidic solutions. We can use it in the body as a stent to hold something open, but then we can dissolve it away with some with an acid that's tissue-friendly or won't destroy or disrupt the rest of the environment. And that particular feature has a significant functional match to one of the top, the most common medical implant used in children in the United States, and one of the top five surgeries, uh, which is an ear tube surgery. 8% of kids have ear have had ear tubes in the United States. In Europe, the numbers are just as strong. And these tubes are designed to sit in a child's eardrum who is experiencing chronic ear infections, the most common reason kids go to the doctor and ventilate the middle ear space so that they experience less ear infections and you can deliver antibiotics locally instead of systemically. Um the reality is that these tubes don't always just naturally push out of the eardrum or just shut out marsupialized. Um repeat surgeries are common. The American Academy of Pediatrics recommends that after a few years, these tubes are surgically removed if they're still still persisting because they can cause permanent holes in the eardrum. And the numbers are quite um compelling. There's been a significant increase in the amount of tube insertions as we migrate away from systemic antibiotic use, um, going from 500,000 to more than 1.5 million in the US alone. Uh and unfortunately, with that comes increase in complications. And so by building a chitosin or biopolymer based tube that works exactly like a standard tube, but instead, when it's time for that tube to come out, that patient has the opportunity to instead of undergo a second surgery under general anesthesia, which for children carries carries rip a lot of risk. Um it's uh You can use Otic drops and just dissolve it away. And what that looks like here is our this is some of our work in chinchilla proof of concept studies compared to a silicone tube that has to be pulled out of the eardrum. We can see the hole that remains behind. Now, ear tubes have not been innovated on uh in uh almost 75 years. The same plastic and silicone tubes are being used. Um, it's really been commoditized uh into the operating room procedure. And so we're facing a business challenge where we're upgrading the category of implants in a very high volume space and we're going from a low-cost passitive implant to an outcomes-driven implant with a controlled removal feature. And so that means that when we think about introducing this into the commercial market, we have to price against the cost of removal surgery, not the cost of the tube, but ensure that the payment for these ear tube surgeries, which are broadly covered, um, still allows for that increase in cost. And so we've had to hit that sweet spot where we've validated with surgeons and facilities that that's something that they're willing to take on. And we have had to quantify the value that this represents to a system and in in terms of how this looks for an insurance company or an integrated system. Plus, we want to make sure that you know the the barriers to adoption in terms of clinical pathway have um been adequately refined and addressed and that there's no barriers or changes for surgeons who will be the ones driving uh the use of this, of this and the commercial of the adoption pathway for commercialization, during commercialization. So we have from day one, actually even before day one, day day minus one, engaged uh heavily with the ENT ecosystem. Um we have surgeons who've given um input into the design, um, the removal process. We've been to all of medical society meetings, we've gone through a mini version of the NSF I Corps through our phase one funding, and we are on the radar of leading surgeons in the space and are uh dovetailing actually with new AAO, so the Academy of Otolaryncology leadership in in their um ENT has historically been sort of an anti-industry space since uh since a Clarent came in, and there's been some sort of burn bridges that have had to be mended. Um and Roel Shaw, who's a pediatric ENT, has come in and has started to change, and so we're really um entering the space in a great time. If any of you are developing med tech products or plan to sell consumables, uh you should be aware of Acuity MD, which is uh a software that gives you access to procedure volumes, um, which is used on the commercial side to help sales teams tailor their growth. You can use it pre-commercially for understanding the fragmentation of your procedures, and we've definitely done that to help us plan our growth trajectory and our later stage funding targets and structures. Clinically, um, we are just planning uh our our first first in human feasibility study. We're doing it outside the US, and we're hoping to initiate that before the end of this year. Um, but we have also planned for post-market studies that we know are necessary to integrate our approach into uh clinical um guidance documents and and ensure broad market coverage and access. So, I mean, to wrap up really early alignment with the FCA, proof of concept have been front and foremost for us, but also understanding how to engage with societies, making sure we stay close to the patient and make and making sure that we're thinking about clinical data early and often are things that guide us today at Materialized Bio. Right now, we're um we're waiting the phase two program to come back online. We've we've been caught in the middle between phase one and phase two, but we're also raising a seed that will take us all the way through our commercialization or our market clearance objectives and enable us to have clinical data, um, feasibility data that we can soft launch with and um make us prime for growth capital that will enable us to truly commercialize this first asset uh and and successfully help patients um avoid complications that are common, too common to this implant category. Uh, this is our team. Um and I'd be happy to take any questions.

SPEAKER_06 1:32:31

Thank you so much, Joanna, uh, for an excellent presentation. And thank you so much for walking us through your journey. I wasn't expecting that. But it is so educational, though, because like I think a lot of people, especially part of a significant portion of our audience, is in academia who wants to go to the uh the best side. And you know, to know one person's example really walk you through the all the dramatic turns uh that you get there. So thank you very much for that. Um I actually have uh a couple of questions. One is I found the point that you you uh you mentioned about the the pricing strategy is is against the procedure, which you know, a lot of times like Charlie Monger always says, incentives. You always ask, what is incentives behind everything? I think that is actually a really key point. If the procedure of this, you know, the uh status quo is making a lot of money for the surgeons. I'm assuming I don't know what the overhead is and an overall you know take home is, but um, how do you, you know, your implant is, you know, assuming much cheaper and also less complication to the patient. How do you break down the equation to the doctor to say this is good for you and the patients both?

SPEAKER_05 1:33:47

It's it's very, it's a very hard, it's very hard to make everybody happy. Um and so you there's there's a couple of different factors. There's there's the site of service, so whether you're in the outpatient department, inpatient, or in the ASC, which all have different payment rates. And then within that, you have payments that go to the facility and payments that go to the physician. And so understanding the incentives of you know, where the push and pull is, you might bring something into an ASC and physicians are getting much better compensated individually, um, and the facility payment is much lower, or in the the hospital outpatient department, it's the opposite. So knowing those dynamics are really, is really, really important. The other thing though is that coverage is also something that's widely overlooked. Insurance, you could have payment structures that are in they appear incentivizing for a certain procedure. But if those are not, those are often rejected by insurance companies, they're not you you have to pay attention to that as well. So, so for example, if um you have a procedure that's very well paid, um, but uh 50% of the time it's denied versus a procedure that you could fit into that has half the payment, but it's covered 100% of the time, you you might be it might be better for you to design your technology and to think about your technology in the context of something that's reliable because clinics might care about that. And so that's what we've we've we've uh found a sweet spot for us. We're actually charging, we want to upgrade the category of ear tubes, whereas now they cost, you know,$50. We want to charge$500. And that means that that hits a facility cost. So we had to ensure that payments for ear tube procedures were big enough that that didn't represent, you know, uh 50% of the facility payment for that. And we also have a long-term coding strategy where we pay attention to how can we change codes to get more payment. And we work that into our commercial model.

SPEAKER_06 1:35:56

How long did it take you to figure that out? Because this is a really We're still figuring it out. This is a very important question for people who haven't really thought about it and are forming a company for MedTech or even biotech for reimbursement is how to get paid. It's it's you need to think this early before you even form the company to see if it's even a worthy end diver that can be commercially viable. But how like it takes a long time and lot, lots of twists and turns. So I'm just curious what your journey is like so far.

SPEAKER_05 1:36:27

Honestly, it's it's very it's difficult to I mean in the early stage of a development, you might have a certain landscape. And I always go back to, I don't know if you remember products called or or organogenesis first product and dermographed. So when I was at CEI, um, we were bringing that collagen matrix into the wound care space. It was prime, it was called Primatrix. And there was a big shakeup. Medicare said that they're going into this new reimbursement payment structure where they're gonna have a high bucket for technologies and a low bucket for technologies. And if you don't make the line, you're reimbursed$1,000 versus$200 for your tech. And it completely appended the market. Nobody could have predicted it. So it is, you do need a plan. And you, but uh I it know that it can change and it can accelerate your commercialization strategy, or it can put up a big barrier to your commercial commercialization strategy. And the the second thing I would also say about that is you need uh medical societies to back you no matter what's going on. Those surgeons, they have a voice and they have a voice on and creating new codes. Um, they have a voice, and you know, insurance companies go to them to understand. And so knowing staying close to medical societies and coding uh chairs uh and making relationships with those people and learning from them about what's gonna happen next and what the conversations are is key too.

SPEAKER_06 1:37:58

Yeah, the humans behind all this is really the true true driving force. I mean, either from pricing perspective or down the line uh market penetration. So thank you so much for this excellent conversation and presentation. All right, I'm gonna uh we're we're at the end of our webinar. I want to invite all the speakers back online.

SPEAKER_07 1:38:25

All right. Oh, actually, you know what?

SPEAKER_06 1:38:26

I just realized we missed a question down here. Um I have another question. Yeah, okay. Gavin naturally has a question for you, Joanna. What sort of unique challenges do you face using kitosin and other naturally occurring biopolymers?

SPEAKER_05 1:38:42

Um like it's a great question. And it's awesome, Gavin. If you work for Ken, you're on a good team. He's he Ken Gall's the best. Um I I mean, supply is is important and clean supply of in terms of kitesan, uh, you have really two choices. You can work with shrimp-based kitesan that comes from the shellfish industry as a byproduct, or mushroom-based kitosan, um, which is a newer product that's emerging that comes from cleaner sources. And so we we have to do significant validation of our lots that come in and ensure batch-to-batch consistency. And so we've had to do a lot of testing to make sure the natural sources don't affect the final performance of our products. I I think um that's just a given with biopolymers to making sure that the the conditions are right. But it's a very good and important point in terms of biomaterial supply chain.

SPEAKER_06 1:39:40

A really quick question. Is your material a hundred percent natural or is kind of modified?

SPEAKER_05 1:39:45

Yep, it's a hundred percent uh it's kaidesan, and we uh we we I should there's a there is a uh a 10% plasticizer, glycerol, to make it a bit um we've iterated on um to make it have properties of um that are closer to like a silicone bounce based on surgeon feedback.

SPEAKER_06 1:40:06

You know, um that it really brought us back to this whole webinar, even though, you know, I think there are a lot of different applications where everybody talked about some is for NEMS, other for implants, but there is a central core, is actually this is a modified biomaterial conference, really, is the material is playing uh is playing a key part in a lot of the technologies that we have mentioned here. Um and uh so I think the sh I I I'm just kind of curious is what do everybody expect in the next year or so in terms of development for your specific industry?

SPEAKER_07 1:40:41

It's just kind of general question outlook-wise.

SPEAKER_06 1:40:49

I mean, assuming the government is back to work and things are starting to open up again. I'm assuming.

SPEAKER_05 1:40:57

The med tech space is, I mean, for new companies at least at the seed stage, which I don't I mean, uh it it represents us. Um I think that it's been a very challenging fundraising environment. I think JP Morgan just put out a report um a couple weeks ago about med tech investments. And a lot of the the dollars have gone to growth stage companies, um, as well as like AI enabled tech. So if you can position yourself there, I think you you can accelerate. So I would I I think there's gonna be a a slowdown of of innovation, like good crossing the boundary of FDA to um commercialization uh because just because of the upstream funding challenges.

SPEAKER_06 1:41:39

And then yeah, the non-dilutive funding is also kind of put on put on hold. Yeah. Yeah. What about you, Carlos?

SPEAKER_04 1:41:46

Yeah, thanks. So I think uh that I was thinking about this the other day, actually, and you know, everybody talks about like the space wars and like who's gonna get to space first, or who I think there's this thing, and I don't have the right term for it yet, but like animal wars or nam wars, kind of like making that same analogy. But basically it's like there's a need for better models, and eventually in a year there's gonna be these like uh the the s there's gonna begin to be like major players that that are gonna like really begin to establish themselves. So there's a war to become one of these major players, like an arms race or a model race. So that's what we're we're rushing for, that's what we're pushing for to really try to establish ourselves at at the head of a pack or one of the leaders of the pack.

SPEAKER_06 1:42:31

Right, because there are now there's no no dominant player yet. So yeah, that that is a good forecast. Um Monica, what do you think? Next 12 months.

SPEAKER_02 1:42:43

Yeah, I can uh maybe um provide um commercial point of view um for the med tech industry at least, uh and I guess it applies to biotech as well, because um many institutions are under severe financial pressure and uh this is an ongoing process that has taken place for a long time. I I think we'll continue to see more consolidation of, for example, health systems. And that means like um ambulatory surgery centers that are no longer independent. It means uh lesser autonomy for many surgeons and um decision making, yeah, it's just being centralized to also uh administrators, financial decision makers and and value analysis committees, and that can really also slow down innovation or at least getting innovation to patients because small companies like ours often do not have the same resources to um generate the the data or the business cases that are required, and I I think we'll continue to see that uh as well.

SPEAKER_06 1:43:53

Yeah, tough times for a lot of companies for sure. Um but I am rooting for you guys all surviving this. Um uh okay. Um Niddy and Ra, do you guys have any comments about uh what do you think the next 12 what are you planning for the next 12 months?

SPEAKER_03 1:44:10

I we we think it is going to be a little difficult. Not uh having an NIH, NSF. We used to get a lot of funding from them. We find it very difficult to get them. Um I think it's going to be difficult at least at least a year or two. Uh I want to say, Joanne, I think your presentation is excellent. And the approach is fantastic. Um we do the other way. We develop something and look for in investors and you could an opposite direction. That's really a great thing you did. I want to ask you one more question. What uh what kind of a molecular weight use for quacky?

SPEAKER_05 1:44:52

Molecular weight. Uh that's I mean, I can't share our exact formulation, but uh I think that's exactly where um Glen3D shines uh you know in highly viscous, so higher molecular weight uh, you know, applications. So because biopolymers, I think we can't get them to flow well through printers, and we can't we have trouble biosolidifying biosolidifying them um as we build them up, right? Because they're not sensitive to, I mean, some collagens are like the formlapse collagen. You can play with temperature. And with Carlos's technology, you may actually open up and unlock different ways to freeze them as they grow. And so so I think fresh printing has tried to fit to fix that, but we've just said like, no more bioprinting. So let's let's go the other way and and build them into monolithic structures. And we we the advantage of monolithic structures or building them all at once in a volume is is that you have you don't have to, you're not limited by your Z direction and building that way.

SPEAKER_03 1:45:55

That's great. Good job.

SPEAKER_06 1:45:57

Good job. Yeah, I just uh I just want to say Jorana actually sneaked into this bioprinting conference, even though it was not a bioprinting conference. But uh 3D Heels, we have been expanding our horizon beyond just 3D printing, but more of an advanced manufacturing uh in general. And uh so yes, you qualify, Jorana. Don't feel bad about it.

SPEAKER_05 1:46:16

We do we do use to I mean we could not do what we do without our Form Labs printer. I mean, and or I mean we we we print, um, we prototype. We've we've we can prototype in in four hours. If we have a new design from a surgeon, we can we can CAD design it and we make it. And and that's how we build our structures. We just kind of reverse the process.

SPEAKER_06 1:46:39

It's okay. It's totally it's totally closure. It's fine. Um all right. Well, um, okay, we're at reaching the end of this webinar. I think we have learned a lot, even though everyone is so unique and different. Um uh I will uh our intern Peter and I will work together to create a highlight for this webinar so that uh people can watch it on YouTube. Check our YouTube channel for shorts and highlights. Um, and you can share the link of this webinar to all your friends and colleagues who you think might benefit, which I already thought was like, I need to share this with my entire pitch 3D company again because every time I organize a conference, I never knew who's gonna say what and what's gonna come out. The unpredictability is actually the fun part of it. But this this conference, even though you know we don't have a Nobel Prize people, although I do think Raw is deserving a Nobel Prize at some point. Um, but you know, it's very relevant to a lot of companies who are working or even struggling in the space. Um, so I think this is a very educational session for everyone. I hope the audience have the same uh feeling that I do. So thank you very much. We're gonna post process this on YouTube. You can see that short shortly. And you can also just directly ask people to register the link, and it's gonna be online for free for a couple weeks. So you have enough time. I think students like the postdoc in the lab who has like waiting for their cells to grow, like this this webinar is like the perfect opportunity to for that time to pass before you know you need to stimulate your cells again or something like that. Um, so alright, and I want to thank um also uh Bizwara Biomedical for sponsoring this event. Without our sponsors, it's very hard to keep this going. So thank you very much. And uh, I will see you next time, everyone. Thank you so much.

SPEAKER_03 1:48:35

Thank you again for all your looks too much.

SPEAKER_06 1:48:37

Thank you. We'll stay in touch. Okay, bye bye.

SPEAKER_03 1:48:41

Take care, bye.