There is a global shortage of transplantable organs, from which have emerged two main approaches to solving this issue: xenotransplantation and bioengineering. With all the news in pig-to-human organ transplantation in recent months, it’s easy to overlook the progress made in the lab-grown organs—which are most likely more ethically sound. After all, wouldn’t you prefer to have an organ transplant made up of your own cells than that of another species?
Humacyte (Nasdaq: HUMA) is a clinical-stage biotechnology platform company developing universally implantable bioengineered human tissue at a commercial scale. Based in Durham, North Carolina, the company develops and manufactures acellular tissues to treat a wide range of diseases, injuries, and chronic conditions.
Their first product candidate, the human acellular vessels (HAV), is made by seeding human vascular cells from a qualified cell bank onto a biocompatible, biodegradable polymer mesh in a bioreactor bag. Over weeks, the cells grow and create new vascular tissue, forming a tube-shaped vessel structure while the polymer mesh degrades. The resulting bioengineered vessel is then decellularized to create the HAV: an extracellular matrix that retains the biomechanical properties of the vessel but is cleansed of cellular components that could induce an immune response. The HAV in the bioreactor bag can then be shipped, stored, and is immediately available when needed.
Humacyte’s HAVs are currently in late-stage clinical trials targeting multiple vascular applications, including vascular trauma, arteriovenous access for hemodialysis, and peripheral arterial disease. Preclinical development is also underway in coronary artery bypass grafting, pediatric heart surgery, treatment of type 1 diabetes, and multiple novel cell and tissue applications. Humacyte’s 6-mm HAV for arteriovenous (AV) access for hemodialysis was the first product candidate to receive the FDA’s Regenerative Medicine Advanced Therapy (RMAT) designation. The HAV technology received priority designation for the treatment of vascular trauma from the U.S. Secretary of Defense.
On August 26, 2021, Humacyte announced the successful completion of its business combination (the “Business Combination”) with Alpha Healthcare Acquisition Corp. (Nasdaq: AHAC), a special purpose acquisition company sponsored by Constellation Alpha Holdings.
GEN Edge met with founder, president, and CEO Laura E. Niklason, MD, PhD, to learn about Humacyte’s journey from clinical observation to commercial-scale tissue manufacturer and how the company plans on expanding its mission to help patients worldwide. Niklason is one of only a handful of women in history to found a biotechnology company that she also took public as the CEO, at a valuation exceeding $1 billion.
GEN Edge: What was the founding idea behind Humacyte?
Laura Niklason: Humacyte has developed methods to grow replacement human tissues at a commercial scale. What’s important about these tissues is that they can be implanted into any human recipient without rejection. After implantation into patients, these tissues repopulate with cells from the patient and essentially become new living tissues. They become tissues that are the patient’s own, over a period of months. That is potentially transformational for many areas of medicine. The tissues that we’re focusing on now are engineered blood vessels.
My work in this area began in the mid-1990s when I became interested in growing new blood vessels for patients and started working in the laboratory of Robert Langer at MIT— one of the pioneers in tissue engineering.
I’m also a physician. I’m an anesthesiologist and an intensive care unit physician. In medicine, you learn pretty quickly that a lot of disease and suffering are tied to failures of blood vessels. The arteries that supply the heart often need to be fixed or replaced in heart disease. It can be other types of vascular disease, like peripheral vascular disease, which can cause difficulty with walking. Microvascular disease causes problems in the kidneys; it causes kidney failure and can contribute to stroke. Diseases of the blood vessels and the need to replace blood vessels is a huge topic and a huge problem in medicine generally.
Because of that, I became interested while doing my medical training in Boston in using this new field of tissue engineering to use vascular cells, combined with what we understand about how new blood vessels grow, to make replacement vascular tissues. Essentially to take that knowledge and use these starting cells to create conditions in the laboratory where these vascular cells would be stimulated to form new blood vessels. That was kind of the initial platform that we developed. The overwhelming clinical need drove it. Once we developed the platform and the methods for taking vascular cells and creating new blood vessel tissues out of them. We’ve developed methods to grow tissues that are very mechanically robust and function at the time of implant.
Once you have that in hand, it opens doors to take the same technology and apply it to different clinical problems. In addition to vascular tissue, we anticipate growing airway replacement tracheas and using our blood vessels as delivery vehicles for therapeutic cells. We’re doing preclinical work right now where we use our engineered vessels essentially as a carrier to deliver a therapeutic number of islets to animals with diabetes.
The cells that we use to make our products are all human cells. We have cell banks at Humacyte, where we have recovered cells from tissue and organ donors. For example, when an organ donor dies and the liver and kidneys get sent to different places, Humacyte has worked with organ procurement organizations to obtain aortas or blood vessels from these organ donors. We’ve isolated cells from over 700 organ donors for more than a decade. We’ve screened these cells and put them through a large battery of tests, that have allowed us to identify a small subset of these donors that have produced cells that can replicate for long periods and have strong regenerative ability. When we put them in our bioreactor system, they’re very good at regenerating new arteries.
The tissues that we grow are all human. There are no animal products in the final tissues. After we grow the tissues, we decellularize them. The original donor cells that we start with are washed out of the final tissue. What’s delivered to a patient is engineered vascular tissue, but it has no cells. It consists entirely of a human vascular extracellular matrix— proteins like collagen and about 40–50 others.
GEN Edge: What advantages does having in-house manufacturing present Humacyte?
Niklason: Certainly, in the regenerative medicine and cell therapy space, product development and doing the basic science is challenging, but manufacturing is just as tricky. I can remember 20–30 years ago, as therapeutic proteins and antibodies were just coming into being, reading cynical articles saying that we would never figure out the manufacturing well enough to be able to make an antibody or a therapeutic protein efficiently because there were a lot of manufacturing hurdles at that time. For small molecules and even for therapeutic proteins, it’s now common to outsource that manufacturing because it’s become well-known in the industry.
Engineered tissues are not there yet. We have had to design, essentially from scratch, all of our bioreactor systems, all of the temperature control and the environmental controls and the automation. We’ve done all that ourselves. That’s required several years of investment and a fair bit of money and a large team of terrific people who are developing these manufacturing systems. We’ve kept them in-house because they’re complex and unique. Trying to farm this out and outsource this would undoubtedly be less efficient than us doing it ourselves because we’d still have to solve all the same problems, and then we would have to teach somebody else how to do it. It just made a lot more sense to keep it in-house.
Our current manufacturing capacity allows us to produce roughly 8,000 vessels per year, which we anticipate will be sufficient for the very early parts of our commercial launch. But we have enough room to build out our manufacturing capacity in the building because it’s a modular build-out. We have designed these units that we call Luna200 units, which can manufacture roughly a thousand vessels per year. And we have room for about 40 of these units in the building. This current facility that we’re in will allow us to manufacture up to roughly 40,000 vessels a year, which should take us well into a commercialization phase.
GEN Edge: What drove Humacyte’s decision to go public?
Niklason: We were very fortunate to go public in 2021. 2020 and 2021 were some of the most active for biotech IPOs and SPACs. We went public via a SPAC reverse merger in August 2021. A confluence of events made us decide to pull the trigger. One, the markets were open, and they were very receptive. Two, we had de-risked a lot of the story, which is important to do anytime you’re talking about a fundamentally new technology such as Humacyte’s. By early 2021, we had validated our commercial-scale manufacturing system. We’re using our commercial-scale manufacturing system to make the product used in our ongoing clinical trials.
We brought our manufacturing up to commercial scale capability, which was a big de-risking event when investors looked at the company. We also, at that time, had two late-stage clinical trials for our product in two different indications well underway. We are very far down the track on manufacturing and our clinical development. For investors looking at this exciting new company, having many of those milestones under our belt already made us a much more attractive investment. Between the overall investment environment for biotech at that time, and our de-risking events, we decided to take the plunge last year.
GEN Edge: How does Humacyte approach partnerships and licensing opportunities?
Niklason: In terms of commercial partnerships, we have a strong partnership with Fresenius Medical Care, one of the world’s largest kidney care companies. They supply dialysis services for nearly half of kidney failure patients in the U.S., Europe, and worldwide. Fresenius invested 150 million in Humacyte in 2018 because of our late-stage clinical trials using our engineered vessels in patients with kidney failure who need dialysis access. We have a strong corporate partnership with them. Together, we’re working on multiple initiatives around clinical development and looking at different indications for the product, both in the U.S. and Europe.
We have also developed research relationships with other smaller entities who produce, for example, stem cells that can serve as the basis for generating islets for our diabetes product that we’re working on. We’ve certainly formed working relationships with other entities to drive forward our products. Partnerships where someone has come to us and said, “We are interested in making tissue X, can you teach us how to make that or make that for us?” haven’t occurred yet, but we’re opportunistic. If something like that came along that made sense for the company and the technology, we would certainly look at it.
GEN Edge: How is Humacyte approaching the global market and associated challenges with manufacturing and regulatory approvals?
Niklason: It’s always interesting to ask a company that does its own manufacturing, “When do you build additional facilities, and where do you build those?” There is no clear answer. We have the one manufacturing facility in North Carolina right now. We will pursue a global strategy for gaining approvals and commercialization in the U.S., Europe, and eventually Asia. It is an open question of when it makes logistical, economic, and patient-care sense to expand operations and manufacturing to other sites overseas. When does it make sense to build a new facility in a geography like Europe? It’s certainly something we would possibly do in the future, particularly if our European market grew very quickly. That would be a significant investment. We will think about it in terms of the overall cash flow of the company and the size of the business in the U.S., Europe, and globally.
We hope to complete the enrollment of our two key late-stage clinical programs in dialysis access and vascular trauma during 2022. The endpoints in the trauma trial are fairly short-term endpoints. We still plan on filing our first biologics licensing application (BLA) for the trauma indication late in 2022, maybe early 2023. We hope to file a BLA amendment later in 2023, once we have one-year results from our dialysis access trial. Those are our current timelines regarding near-term regulatory filings and then, hopefully, approvals. We would hope to be on the market by 2023 with our first indication.
As far as going into other markets, our strategy right now is also to do similar filings in Europe. We’ve collected clinical data for the HAV on dialysis access and peripheral arterial disease at multiple European centers. And we would use that to support filings in Europe to gain approval there as well.
GEN Edge: What’s the biggest takeaway for you from this journey with Humacyte?
Niklason: Humacyte started as an idea, as a concept, and now it’s a building, a technology platform, and a product that helps patients. I know that we’ve saved limbs and lives with this product. I know that there are patients who are walking around who would not be if it weren’t for our product.
This is a journey. There’s a saying: If you want to go fast, go alone; but if you want to go far, go together. That’s an important lesson for taking a new idea or technology all the way. Coming up with the initial idea and trying to do a proof of principle can be done by yourself or a very small team, but it takes a village if you want to carry it through. We’ve been so fortunate that so many company members have been with us for a very long time and have seen the technology through.
At Humacyte, there is a mission of doing something fundamentally new, bringing that to patients, and then seeing that help those patients. It is a long journey, and I’m just very fortunate to be traveling with the team that I’m traveling with. It is exciting, but it’s a little bit like if you can imagine walking from California to New York—it’s a lot of steps and some steps are harder than others. It can take a lot longer than initially planned. And we’re almost done. We’re almost there in terms of seeking approval and getting on the market. It’s exciting and vindicating to have created something out of nothing.