All right. Hello, everyone. Welcome back. I'm now joined by Pete O'Heeron and Hamid Khoja, the founder and CEO, and CSO, respectively, of FibroBiologics. This is an emerging player in cell therapy. It's a really exciting space, but what FibroBiologics is doing that's a bit different than everyone else, is they're advancing fibroblasts in place of the more traditional stem cells. These cells have many of the same properties, but with key advantages for fibroblasts in terms of cost, production, and potentially even potency. So I won't get too deep here, but with FibroBiologics, we see this as a potential opportunity to get in at the ground floor for a new cell type in regenerative medicine. And with that, Pete, Hamid, why don't you give us a quick two- to three-minute overview of what FibroBiologics does? Thank you, Michael, I appreciate it, and appreciate you having us here today. FibroBiologics, so it's almost kind of a stem cell 2.0. You know, there's two cells in the human body that you can use to regenerate tissue and cure chronic disease. There's a stem cell that everybody's heard about, and then there's a fibroblast, which almost nobody's heard about. The irony is that fibroblasts outnumber stem cells. They outnumber them 5,000 to one, the most common cell in the human body. They can do everything a stem cell can do, and they do it better. They're more robust, they're easier to harvest, easier to grow. They have more therapeutic potency, and we've just found them to outperform stem cells in all of our testing. So when we tell people and show them the data on how great fibroblasts are, most people say, "Well, I had no idea they had any therapeutic value at all. Why haven't we heard about them?" And we like to say that stem cells won the Nobel Prize in 2012 when Dr. Yamanaka created the first induced pluripotent stem cell. And of course, once that happens, you know, the media runs off with it, and a bunch of companies form, and so, you know, 20- 30 companies formed around stem cells. After that, it was Jim Allison won for immunotherapy for cancer, and you saw a bunch of immunotherapy companies form, and then most recently, Jennifer Doudna and Emmanuelle Charpentier won for CRISPR. So you can see that those Nobel Prizes really kind of steer the science in that direction. The second irony of the story is, the cell that Dr. Yamanaka used to create the first induced pluripotent stem cell, it was a fibroblast. So they asked someone in the lab why they didn't look at fibroblasts more carefully, and they said that they thought they'd been relegated to the evolutionary scrap heap of connective tissue. They thought they just held the body together with no therapeutic value. So we are excited about fibroblasts. We virtually own the market in intellectual property. We have more patents surrounding fibroblasts than the rest of the world combined. And you know, we like to say we've done the research and we've looked at big pharma and In the last 60 years of chemical compounds, they've never cured a chronic disease. I mean, think about that. We've spent billions, if not trillions of dollars, trying to cure chronic diseases with man-made chemical compounds. That will never happen. It will take a biologic process to cure a biologic defect. Creating a man-made external chemical compound and introducing it to the body will never cure a chronic disease. It will take a fibroblast, it will take cell therapy, immunotherapy, or gene therapy to cure that chronic disease. So I will turn it over to Hamid to give you just a quick overview on the science. Yeah, and I mean, as Pete has mentioned, quite a few of the characteristics of fibroblasts. We have to realize that fibroblasts are involved in every single step of wound healing, as well as immune modulation. If you think of it, it's one of the most prevalent cells in the human body, and they're involved in practically every aspect of tissue regeneration, tissue repair, et cetera. So it makes sense for them to be a good therapeutic potential therapeutic option. And just to give you an insight, we're probably the only company that is trying to utilize fibroblasts as a therapeutic for many chronic diseases. So I think in terms of the utility of the technology in the platform, I have great confidence that we can certainly offer some potential therapeutics going forward. Now, as you did mention, these are the most common cells in the human body, so could you talk a little bit about how you can actually take that and apply these as a therapeutic? Do you have to modify the cells? Is there anything that you have to do to them to make them therapeutically active? No, that's a good thing. Fibroblasts are very well studied, but as publications have indicated, there's about 16 different subtypes of fibroblasts. And of course, with having different subtypes, they have different functions. What we've been able to do is take and identify these different subsets based on their characteristics and use them accordingly towards whichever clinical indication we're targeting. For example, we have identified a subset of dermal fibroblasts that are very good in terms of being able to accommodate wound healing, in terms of their secretion and their surface markers, and that is the clone that we are targeting towards a therapeutic for diabetic foot ulcers. There's other subsets that are very good in modulating the immune system, and those subsets of the fibroblasts or subtypes of fibroblasts are the ones that we are targeting towards psoriasis, multiple sclerosis, or autoimmune disorders. So, no, we are not modifying these fibroblasts, at least initially, for these clinical indications that we're targeting, but at, in terms of being able to modify fibroblasts towards a certain clinical indication, our IP does cover that. So if we need to, we certainly can do that. Got it. And just further, could you discuss some, sort of the differences, fibroblasts versus stem cells in regards to their signaling activities and, maybe further additionally, their potential applications in inflammatory conditions? Absolutely. I think, our data and as well as some publications have indicated that fibroblasts are more potent immune modulators than stem cells, and they're more consistent. Stem cells, as you very well know, are not designed to remain stem. They do differentiate. I think, I had a scientist once told me that if you look at them the wrong way, they differentiate. So, fibroblasts do not share that characteristics. They can differentiate, but you'll have to coax them to differentiate into another type of cells. Where in terms of immune modulation, at least our data has indicated that it is more potent than both bone marrow and adipose-derived stem cells in terms of immune modulation, in terms of their secretory patterns, in terms of their cytokine secretions and growth factors, which lead to immune modulation. We've seen a more potent, more durable immune modulation capability from fibroblasts than stem cells, and I think speaking of stem cells, they haven't been very successful in the last twenty years in reaching the clinic, and one of the major aspects has been manufacturing these at scale for clinical use, and even for the clinical trial use because they are very difficult and very expensive to culture and maintain. You don't have that difficulty with fibroblasts. Very, economical, and very easy to culture, maintain, store, and reuse. Yeah. So one thing that I would like to touch on is, why do you think it is that fibroblasts have a more potent immunomodulation, at least from what you've seen? Do you think this has to do with their innate role in that wound healing and injury repair response? Absolutely. I mean, if you think of it, fibroblasts are responsible for the secretion of the extracellular matrix, which is, in a sense, a protective layer. Right? It keeps the cells, tissues, and organs together. So when there is damage, signaling has to occur for that damage to be repaired, and fibroblasts are basically the first one in line, in terms of responding to damage. So I think they are designed to be able to modulate the immune system accordingly to repair damaged tissue. And stem cells, of course, play an important role. But if you look at wound healing per se, in terms of the stages of wound healing, stem cells are involved, but they come in much later. So whereas fibroblasts are some of the initial key responders to damaged tissue. Mm-hmm. And now this is a platform technology, right? This can be applied to many different indications. There's a ton of potential here. So can you talk about how you're prioritizing different indications and different avenues for development? Yes. In terms of clinical indications, our primary target at the moment is diabetic foot ulcer treatment. It is a short twelve-week clinical trial. We are on target in initiating that clinical trial in 2025, and we are planning on having all the necessary primary outcomes completed and reported by the end of 2025. And it is for that reason that we are targeting diabetic foot ulcer because it is a short clinical trial. Now, other clinical indications that we are targeting, multiple sclerosis as well as degenerative disc disease. We do have an IND that has been approved for degenerative disc disease. We have completed a phase I safety clinical trial for multiple sclerosis. However, those clinical trials are significantly longer. Typical clinical trials for multiple sclerosis and degenerative disc disease require at least a two-year follow-up. So it is for that reason that we are pushing diabetic foot ulcer treatment initially. Mm-hmm. Got it. And I just wanted to ask if you can talk a bit about the chronic wound care treatment landscape, which appears to be the significant near-term opportunity for FibroBiologics. And sort of what advantages does fibroblast therapy provide compared to existing treatments, particularly in terms of healing efficacy? Absolutely. Well, if we think of it, there's two key points in healing chronic wounds, right? One, you want to be able to heal it rapidly so that the risk of infection is lowered. Second, you want to be able to heal chronic wounds effectively and with high quality so that they don't recur. For example, diabetic foot ulcers, 40% recurrence rate within the first year, 70% recurrence rate at the same site within three years. And that happens because a lot of the therapeutics that are used in healing chronic wounds target more the accelerated wound healing rather than healing the wound in a quality manner. Our preclinical studies have indicated that we not only exceed in terms of accelerating the wound healing process as compared to Grafix, which is a FDA-approved product, but we also assess the quality using seven different metrics, and we exceed not only the control, but Grafix in all of those metrics that we have measured for quality wound healing. So therefore, our target is not just to accelerate and close the wound, but maintain that high-quality healed wound so it does not recur, or the probability of recurrence is significantly lowered. Now, this is relatively early stage and new technology, so could you talk about your existing data? Do you have anything in humans from the clinic, or is it mostly on the preclinical side that you've demonstrated? We only have preclinical data, and we just completed our preclinical IND-enabling studies. Our target is to have the first in-human, topically administered, fibroblast spheroids as a treatment for diabetic foot ulcer in 2025. Again, as Pete mentioned, this is a platform technology, and diabetic foot ulcers is the first target in terms of wound healing. There's VLUs, there's burn victim wounds, but also surgical wounds. We do have an extensive patent portfolio that covers the use of these fibroblast technologies for multiple types of chronic wounds and wound healing. Mm-hmm. So what about in multiple sclerosis? What have you shown in that so far? Yeah. Our preclinical studies in multiple sclerosis have been very encouraging. We've not only been able to show that it's a significant modulator of the immune system, and being that, it brings into equilibrium the dysregulated immune system that is the key player in multiple sclerosis and autoimmune disorder. But we've also been able to show remyelination. That's something that we have been very encouraged about. We can see remyelination occurring, oligodendrocyte expansion increase, which leads to remyelination increase, but we've also been able to show that microglia, which is the resident immune cells in the brain, are very well controlled and modulated. In multiple sclerosis, microglia expands really by quite a bit as compared to normal, which leads to the degradation of the myelin sheath by attacking the oligodendrocytes. We've been able to show a significant control and a reduction in microglia expansion as well. So I think those all those three attributes combined, I think, puts us in a very good standing to conducting a clinical trial for efficacy, hopefully in the near future. As I mentioned earlier, we have carried out a first-in-human five-patient safety clinical trial, and that we were able to show during the six-month follow-up for safety only, we were able to show that no adverse events noted. But also, at the same time, with the five patients, we did not see any recurrence or any MS attacks during that process, so during that time. So we're encouraged of its safety, but there are signs of efficacy, but we'll have to look at that at a larger patient set in the next clinical trial. Mm-hmm. In terms of those next steps, as you mentioned earlier, multiple sclerosis can be a fairly challenging indication to develop, especially for, you know, small and medium-sized biotechs. So, can you talk a little bit about your plans to move forward in this? Is this something where you would look to start in the next step trials on your own or seek a partner? We are definitely interested in seeking a partner. It is an expensive clinical trial, and I think, having a partner will certainly allow us to effectively and efficiently lead a phase I/II larger clinical trial. So I think, we're always open to collaboration and partnering in any of our clinical indication, including multiple sclerosis. Mm-hmm. Got it. And, you know, chronic lower back pain is one of the more popular indications for regenerative cell therapy. So why go after this, and what advantages may fibroblasts have over stem cell in an area with multiple other players? Yeah, there are multiple players like Mesoblast and DiscGenics that are looking at using cell therapy as a means of treating degenerative disc disease. However, I think I've seen some of the data. It looks encouraging, but I do have some questions on the clinical significance of some of the data that's been presented. I think what we have seen in our preclinical study, which has been published in two journals already, is that we have not only been able to show an improvement in disc height with fibroblast therapy, but we've also been able to show a reduction in systemic as well as local inflammation, which is responsible for some of the degeneration of the disc. And I think that's going to be very important in a clinical trial, not only to reduce the pain level, reduce the dependence on opioids, but rebuilding the tissue. I think one of the things that has not been shown in some of the other cell therapeutics is the rebuilding of the tissue. I think we can certainly in our preclinical studies we have indicated that we are rebuilding the tissue and the damaged cartilage. But one of the things that we have to see for some of these trials is that are they really rebuilding the tissue? And that remains to be seen. I think our preclinical studies have been very well presented in indicating that we are rebuilding tissue, and even in the lab, we have been able to very easily differentiate fibroblasts into chondrocyte-like cells. So I think that's very encouraging for us. Mm-hmm. It's a very easy, very, simple step of being able to do that. All right, and so I do want to follow up on something you touched on, because the FDA does seem to be turning around a bit when it comes to cell therapy. Mesoblast has their upcoming PDUFA date without the need for an additional trial. They seem to be encouraging accelerated filings. We've seen some good progress for Capricor as well, and to us, it looks like the current FDA seems to be more supportive of cell therapy. Is this something that you've also seen, and then could this create a more favorable environment for you guys with your development of fibroblasts? Absolutely. I mean, if we look at the therapeutics in the last year that have been approved that are cell-based, it's been amazing, and I think if you look at the other therapeutics that are set to be approved, the cell-based therapeutics that are set to be approved in 2025, it looks very encouraging, so the FDA has been more receptive of accelerating cell-based therapeutics for multiple clinical indications, and I think that will have a positive impact even in our neck of the woods on using fibroblast as the therapeutic cell for multiple clinical indications. I think, as we will see in the next five years, we will see quite a bit more cell-based therapeutics going through the approval process, and I think that will pave the way for us, and it'll make it easier for us to get approval as well, so we're cheering all these people on, as they get approvals and go through the approval process for their cell-based products. Now, I would like to see if you could talk a little bit about the different platforms that you've had, because you have some IP surrounding different formulation, whether it's organoids or spheroids. Can you talk about how those might enable different applications of the cells? Absolutely. I mean, we have a very strong patent portfolio of over 160 different patents. Peter and I and our research team, we file probably about two to three patents a month. This is a new area, and so everything that we research, we find something new, and we want to make sure that we patent and secure that IP. But in terms of the ability of our product to reach a wider market, I think we should be able to do that. And it is a platform technology which could be used for multiple clinical indications. For example, as you've seen in some of the press releases, we have been able to develop an organoid, a pancreatic organoid that releases and secretes insulin while hiding from the immune system, and that's going to be important as a therapeutic for diabetes. But also, we've been able to develop an organoid that behaves as a we call it an artificial thymic organoid that behaves much like a thymus gland, a functioning thymus gland. So I think that's going to be very important because thymic involution has been linked as we age to an increase in autoimmune disorders, increase in cancer, reduced response to vaccination. So being able to reverse some of the losses that we see in the thymus over as we age will have a significant impact in the quality of life as we age. We've also been able to even generate an artificial bone marrow organoid that would be subcutaneous, most likely, that will function as a bone marrow, but outside of the bone marrow. So I think these all are part of our research findings, early research projects, and we're hoping to push those forward along with our other clinical indications. Yeah. No, that certainly creates an interesting opportunity. Essentially, does this allow you to not just follow where MSCs have gone, but also where iPSCs and differentiated cell transplant therapies have gone? Absolutely, because if you think of it, most, if not all of iPSCs are derived from fibroblasts, right? So I think the first step is using fibroblasts as to derive some of these iPSCs, and then differentiate them into other type of cells. We've taken a different approach in skipping the iPSC, I mean, granted, they will have an important part to play in cell therapy, but I think for the clinical indications that we're targeting, I think fibroblasts are the more practical and economical approach. All right. And so with that, we are up on our time here, but before we part ways, could you please give us a brief overview of what are the key upcoming events, milestones, and catalysts for FibroBiologics? Pete? Sure. Michael, appreciate that. What we have coming up, the near-term clinical trial for wound care. We'll be filing for an IND for multiple sclerosis next year, and you know, when Hamid talks about organoids, we have a virtual explosion of discovery going on right now in our lab every day. We tell our scientists, "It's like you're walking on Mars. Every step you take has never been taken by another human being." So we have while we have these clinical milestones that we're looking forward to, we're looking forward to it every single day something comes out of our lab. These organoids that Hamid and his team is perfecting can have a wide, encompassing impact on chronic disease treatment. Because like we said, the thymus, for example, we were looking at treating the thymus directly. No need, because we can create organoids that can perform a similar function to the thymus, and we can inject those sub-Q, and with these organoids, they really stay in place. There is more time on target with our wound care with these organoids, so I think that we have some exciting clinical programs coming up that we'll be seeing first in humans, but almost every day we're seeing discoveries coming out of the lab, and he talked about two patents a month. It may even be more than that when we're... Right now, we're working on another two patents. We just filed one this week, so everything we're doing almost on a daily basis is exciting. We will be presenting at BIO- Europe coming up. I believe it's November fourth or fifth. On Election Day, we'll be over in Europe, so we have that coming up, and we'll be at BIO, the Biotech Showcase in San Francisco in January. So we're out and about telling the story. All right. Well, Pete, Hamid, thank you so much for a very interesting conversation, and this, a really cool story, and just at the ground floor of what the potential these cells can do. Thank you. Thanks very much. Thank you very much, Michael.