Bringing Fibroblasts to the Spotlight: Q&A with FibroBiologics

Fibroblast
FibroBiologics

While many in the industry are focused on developing therapies derived from stem cells, FibroBiologics is taking a different approach. The Houston-based clinical stage biotech is focused on using fibroblast cells and fibroblast-derived materials to develop treatments for chronic diseases. Chief executive officer Pete O’Heeron and chief science officer Hamid Khoja, PhD, spoke with Pharmaceutical Executive at the BIO CEO & Investor Conference in NYC.

Pharmaceutical Executive: Can you discuss your technology platform and how you’re prioritizing your product candidates?
Pete O’Heeron:Yes, we look at it as cell therapy. There are really two cell types. You can use a stem cell or a fibroblast. Everyone's chasing stem cells. We're the only ones in fibroblasts that are looking at fibroblasts therapeutically.

When people say that they’re doing something that nobody else is doing, we actually are. We've just found a better cell source than stem cells that have higher potency to them. They also have higher therapeutic factors that make them easier to harness, grow, and shift.

Me and this group have worked on spheroids, which is a spherical cluster of about 3000 fibroblast cells, so it has more time on target when we use that delivery mechanism.

When we tell people that, they ask, “Why doesn’t everyone know about fibroblasts?” Our feeling is that since stem cells were the regenerative cell that won the Nobel Prize in 2012 when Dr Yamanaka created the first induced pluripotent stem cell, it set off a race, leaving the other regenerative cell type, fibroblasts, behind. More than 30 companies formed around stem cells.

Fibroblast
FibroBiologics

I look at Nobel prizes as a catalyst for the next 10 years of therapeutic research. The irony is that when Yamanaka won for the induced pluripotent stem cell (IPSC), he actually used a fibroblast to create the IPSC.

Fibroblasts really started the entire stem cell revolution. If someone asked about fibroblasts, the response was that they thought they'd been relegated to the evolutionary scrap of connective tissue. They thought of fibroblasts’ simply as a structural component of the body.. We look at it from the other angle. We find that, fibroblasts are involved in every biologic process.

With our clinical programs, each one has a little bit of secret sauce, a little bit of different approach. The core, however, is the fibroblast cell.

Take degenerative disc disease, for example. When you take a fibroblast cell and you put it into the nucleus of the disc, you get this pressure from the vertebrae above and below. That’s because the fibroblast wants to become a Chondrocyte, so it differentiates and regrows the disc.

In a lab setting, stem cells are inherently unstable. They want to be anything other than a stem cell. Fibroblasts are a more stable and potent platform to work with. We're thankful that everybody was chasing stem cells because it gave us the opportunity to build a portfolio of more intellectual property than the rest of the world combined in this space.

PE: You have clinical programs for a plethora on potential indications, including wound healing, multiple sclerosis, and others. Which one is your lead indication and how did you choose it?
Hamid Khoja, PhD: That’s a really good question: how do we prioritize our clinical indications? Our goal is to prioritize the clinical trials that are most efficient to complete. It is for that reason that we prioritized the diabetic foot ulcer treatment candidate because diabetic foot ulcer clinical trials will yield results faster due to the shorter clinical trial length requirements, about 12 weeks.

Multiple sclerosis, another clinical indication that we're targeting, is a much longer clinical trial. Typically lasting two years and is very expensive.

In this regard, wound care treatments are not only fast clinical trials but are also significantly cheaper. Our next clinical indication is for psoriasis, another autoimmune disorder that has dermatology physiology. We hope to complete all the pre-clinical studies this year, with the goal of submitting our IND at the end of the year or early in 2026.

As we mentioned, our candidate is topically administered. For all our products, we're not using single cells. Whereas with many stem cell therapeutics that have gone through phase one and even some that are in phase two are looking at single cells. Typically, these single cells have to be cultured for a period of time right before use. Instead, we utilize spheroids, which are significantly more viable and more robust.

If you think of a proposal for wound healing as something you administer on the surface of the wound, these spheroids migrate out on the surface of the wound. They release multiple growth factors and cytokines necessary for initiating the natural healing response for multiple sclerosis and other products. These spheroids release the products that are necessary for the immune system at a much slower pace. You have a longer potency and longer durability of the products.

That's something that has not been done with stem cells. Also, manufacturing stem cells is incredibly difficult. Once you're manufacturing for a phase two clinical trial, it's very difficult because they keep differentiating, and you have to have a mechanism of taking out those differentiated stem cells to get a better product for your clinical trial. That has proven very difficult, if not impossible, for quite a few clinical trials that were ended or that never went past phase one.

We don't have that limitation. Our cells are allogeneic. They can be utilized across different patient populations and are very easy to culture and remain highly stable.

PE: How many clinical trials do you currently have?
Khoja: We completed a clinical trial for multiple sclerosis at the end of 2021. That was a first-in-human, phase one clinical trial with a primary outcome of safety. For multiple sclerosis, we found no adverse events noted. The safety profile was excellent and very clean. We did see some efficacy, as we were monitoring and using several neurological assessment tools.

We have to do a larger phase I/II clinical trial that is better designed for efficacy.

When it comes to clinical trials, we like to combine phases because its less expensive and easier to do. In animal models for our multiple sclerosis treatment, we've been able to show that we can remyelinate, which is something that no one else has been able to show. We are not de-modulating the immune system, because our products do not penetrate the blood brain barrier. It's either direct secretion or a secondary secretion that gets past the blood brain barrier.

We've been also able to show independently, using three different assays, remyelination. It's not just looking at one assay and concluding that it's remyelinating. We've been able to use three independent assays to confirm that we actually do see remyelination.