Celularity: Productizing Placental-Derived Stem Cells for Any Patient

There have been some big biotech special purpose acquisition company (SPAC) deals over the past six months or so, including 23andMe, Sema4 and Tango Therapeutics. One such deal in early 2021 may not have generated the same headlines, but it has positioned Celularity to expand its role as a unique producer of stem cells for autoimmune and other diseases.

One of the biggest challenges cell therapy developers face is the human immune system—how do you make a cell-based treatment that the patient’s immune system does not reject as foreign?

The placenta is a material that normally possesses a low potential for provoking an immune response, which can be used to develop allogeneic cell therapies that can be used without the need for matching the patient to the donor. This normally discarded source material can be turned into potential therapeutics, with a single placenta capable of yielding hundreds to many thousands of doses, depending on the therapeutic.

Celularity is a clinical-stage biotechnology company focusing on the next evolution in cellular medicine by developing off-the-shelf placenta-derived allogeneic cell therapies, including genetically modified natural killer (NK) cells and T cells engineered with a chimeric antigen receptor (CAR-T cells) that target indications across cancer as well as infectious and degenerative diseases. By harnessing the placenta’s unique biology and ready availability, Celularity believes it will be able to develop therapeutic solutions that address a significant unmet global need for effective, accessible, and affordable therapeutics.

GEN Edge spoke with Robert Hariri, MD, PhD, the chairperson, founder, and CEO of Celularity, to discuss the company’s 20-year journey from inception to Celgene spinoff and, recently, a SPAC-funded, publicly traded entity.

GEN Edge: What were Celularity’s founding mission and vision?

Robert Hariri: Our mission was to lead the next evolution in cellular medicine, which is to create off-the-shelf, one-size-fits-all cellular products for immunotherapy and for what we call pro-regenerative activity. We leverage this platform of technology we discovered, which is to use the postpartum placenta as a source of cells that can be productized.

When stem cells first emerged as a research oddity, I was fascinated by the possibility that these cells, if harnessed, could serve as therapeutics to drive repair and regenerative processes that we often lose in our lifetime—in some cases because of a fundamental defect in the stem-cell populations or because there’s just not a sufficient quantity of material that can restore that regenerative process. I was convinced that for stem cells to have a meaningful role in medicine, someone was going to have to figure out a way to productize them so that doctors could write orders for them the way they do for biologics or small molecules.

When I first started, stem cells were being derived from embryonic material or the byproducts of abortion. I was convinced that just the moral ethical and cultural baggage associated with using those forced materials, in and of itself, could defeat success. More importantly, I realized that if you recover cells from an embryo that’s early in development or byproducts of an abortion that may take place in the first or second trimester, there’s no guarantee that the biology of that developing organism is of the quality necessary to be a useful therapeutic tool.

The placenta is designed to be nature’s universal donor tissue. A mother carries a fetus and its placenta for nine months, even though she’s only a 50% donor of the genetic material for that fetus and placenta. Though she’s an imperfect match, she doesn’t reject the placenta—and it doesn’t reject her. Consider surrogate pregnancy, where the mother’s not even related to the fetus.

We recognized that the opportunities in cellular medicines would lie both in cells for regenerative treatments of degenerative diseases as well as immunotherapeutic products. We took advantage of our deep expertise in the procurement qualification testing and processing of placentas to create methods to produce large quantities of high-quality cells as therapeutics. We’ve been fortunate to be the first company to look at the leftovers of a full-term healthy pregnancy—an organ that can be anywhere from 500–800 grams in size. The organ is a stem cell factory.

Our first foray into this area was a pluripotent stem cell from the placenta that we could mass-produce and have both immunomodulatory and pro-regenerative activities. From there, we discovered that the placenta was a source of a unique type of immune cell called NK cells that play an important role in the defense of the developing fetus. We developed methodologies to mass produce high-quality cells from these organs as therapeutics. Our capabilities go from using the cells as engineered unmodified versions of those cells to genetically modified or virally transfected that can express a specific kind of construct on their surface, like a CAR.

The company was about three years old when it entered into a research collaboration with Celgene, which acquired us back in 2002. We established the cell therapy division of the business that served as the basis for Bluebird’s autologous CAR-T program, as well as for the Juno Therapeutics transaction. But at a time when Celgene was maturing into a commercial powerhouse and not a development powerhouse, we took advantage of an opportunity to spin out as the only spin-off company of Celgene.

That’s what got us to be Celularity today. We’ve raised about $350 million thus far to get us where we are. We operate our own purpose-built-and-designed research development and manufacturing headquarters. We have one of the largest manufacturing footprints of any independent company in the world. We’ve got 15 independent GMP manufacturing suites, and we’re currently producing three different cell therapy products simultaneously as well as three different biomaterial products, which are currently on the market.

We take the best source of raw material for the field of cellular medicine. It’s an abundant resource. There are 130 million placentas thrown away a year in the world. It can be procured under rigorous conditions. You can ensure that this donor meets very high-quality standards before you invest in producing products. You can manage the logistics of procurement transport processing so that the minute the raw material hits our laboratory doors, it then goes into an assembly line where we extract cells, tissues, and byproducts of manufacturing like exosomes. From one procurement event, we’re producing several categories of therapeutic products.

The magic in our business is that we produce revenue-generating byproducts of manufacturing that are already on the market and easily can be grown aggressively while we’re taking unique cell therapy products all the way forward through to registration. It’s a very leverageable business model. We are not a typical early-stage cell therapy company because we’ve been around for quite some time. We invested $90 million in our current headquarters, including our biorepository. We’ve got deep expertise in manufacturing, and the biology of the cells we get from the placenta is extremely differentiated from any other cell type out there.

GEN Edge: What is Celularity’s plotted future trajectory?

Hariri: We’re actively enrolling in four different clinical programs. By year-end, we’re going to file three more INDs, and we should be in at least five actively enrolling either registration enabling or pivotal studies.

Our short-term goal is to get our lead candidate products, which are placental NK cells, both unmodified and genetically modified, and placental CAR T-cells. Our objective is to drive the fastest horse forward across the finish line as quickly as possible to validate the platform, because registration in any of those programs is highly leverageable into a broader range of diseases. Because our systems and process engineering team are experts at optimizing the productivity and the fidelity of cells that we manufacture in our cultivation environments, we believe that we will always be the quality and economic choice when choosing a cell therapy product.

By comparison, everything that the induced pluripotent stem cell (iPSC) companies have to do to induce pluripotency to produce an immune cell, that’s what our starting material comes with. Everything you need to do to create an iPSC already exists naturally in the pluripotent cell from the placenta. These cells are extremely amenable to all forms of modification in engineering, and because we collect so many of them and we’re starting with such a large starting bolus, our ability to create enormous scale is one of our strengths.

If we take a million hematopoietic regenerative cells into our cellular expansion manufacturing, we can produce hundreds of billions of NK cells. That means from one donor, we can produce many doses that can constitute a batch for an individual or multiple recipients of the therapeutic. We are getting better at process optimization and other methodologies to improve the yields from every donor placenta. Our placental CAR T-cell will be an off-the-shelf, one-size-fits-all product that’ll have both quality and economic advantages over other allogeneic or autologous approaches.

In the midterm, we intend to grow our business, not just by organic development of key programs but where we’re looking to be in a position to be a development partner of choice. We’re already deeply engaged in some of those relationships and are also identifying potential acquisition or other opportunities to buttress the technology we already have. We intend to build our revenue-generating business in the background as an engine to help drive the growth and performance of the overall company.

Unlike a company that’s making an NK cell for cancer and just focused on that linear program, we have all of the immunotherapy products that others have in the clinic that are produced from our proprietary platform. We’re producing revenue-generating products from the materials, and we also have programs for next-generation technologies like exosomes. All that occurs under one roof, which is unique in this industry.

GEN Edge: What are the obstacles to Celularity’s trajectory?

Hariri: There are several challenges in this industry. It’s about executing on a clinical program that gets you the best probability of a meaningful answer as quickly as possible. In the indications we’re going after, we’ve been successful at gaining access to abbreviated registration pathways. The challenges are making certain that the clinical relationships we have for programs, are both our boats operating at the tempo and the quality necessary to give us those important answers?

We want to make certain that we recognize early where we see fruitful opportunities and to accelerate those programs as quickly as possible in the longer term. We want to move, not just from immunotherapy, but also into the use of the placental cells in degenerative diseases and a range of other indications that have a much higher incidence and prevalence but have a longer regulatory cycle. The one thing about our products is that upon registration of any of these products, the ability to leverage that approval into other clinical areas creates a very abbreviated pathway to bolting on additional indications.

GEN Edge: Why did Celularity choose to go into a partnership with GX, and what do you look forward to from that partnership?

Hariri: We’ve been represented by investment banks since inception. Approximately one year ago, we were strongly moving towards a traditional crossover round followed by an IPO. One of the vice-chairmen of the board, John Sculley, the former CEO of Apple, introduced us to the GX team who had this SPAC. They were looking for a candidate company. That relationship got off to a very quick start. Everything fell into place.

The SPAC satisfied our objectives. It had roughly $300 million in the stack. We went out to raise an $80–100 million pipe, which we successfully raised. This will take us forward and leave us with around $300–400 million of proceeds, about a three-year runway for the company prosecuting all of its programs. The SPAC was just an efficient, rapid way to get into the public capital markets. If you go back a year, SPACs were increasingly popular in this biotech field. We were at the right place at the right time and met the right SPAC partners.

GEN Edge: What is your strategy behind being a publicly traded company?

Hariri: We’re in fairly advanced levels of development. We’ve got phase II programs that are in indications where you can get registration on phase II data. We also have several other programs, which are longer cycle programs, in the treatment of autoimmune diseases and certain degenerative diseases, all of which require reasonable access to capital to both accelerate and broaden the number of programs the company is involved in. Although we have many clinical development programs, we also have opportunities to raise capital at attractive valuations that allow us to even pursue a broader range of opportunities.

Our strategy is to grow the business fully exploiting the near-term revenue-generating [opportunities] to support activities. We’re also an ideal partner for co-development with big pharma companies. We have a large intellectual property portfolio, and many non-core assets are available to us for out-licensing to generate non-dilutive capital. We are putting the company on a strong financial footing. We have a very aggressive set of programs to prosecute, and we have a very big long-term opportunity in the more mainstream diseases.

Aside from all the fundamental, logistic characteristics, economic, and quality characteristics, the biology of cells from the placenta are so unique in their extremely augmented stemness characteristic, which is associated with better outcomes in treatment. We’re a company that produces a variety of cell therapy assets. We also produce products that can be used in conjunction with these cells as delivery vehicles to concentrate and sequester the active cells in different locations. We have that technology as well and long-term, we have great technology around byproducts of manufacturing—exosomes and other technologies—which can either be part of a common oral approach or independent therapeutics.