Celularity Gains FDA Orphan Drug Status on Strength of Placental Stem Cell Trials

On Tuesday, Celularity received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for its off-the-shelf natural killer cell therapy for malignant gliomas.

The news coincided with the American Association for Cancer Research (AACR) Annual Meeting 2021, where Celularity delivered an oral presentation and two posters. Each showcased the viability of that therapeutic compound, CYNK-001, as a treatment for multiple, disparate indications.

The presentations focused on CYNK-001 as an off-the-shelf therapeutic for both COVID-19 and for glioblastoma, but this non-genetically modified cryopreserved human placental hematopoietic stem cell-derived natural killer (NK) cell therapy also is being developed for leukemia. It is in Phase I trials for glioblastoma multiform (GBM), and was granted Fast Track designation by the FDA last month.

CYNK-001 is based on an earlier candidate, PNK-007, currently in trials for multiple myeloma and acute myeloid leukemia (AML). The difference between the two, Robert J. Hariri, M.D., Ph.D., founder, chair and CEO of Celularity, explained, is that “CYNK-001 is validated and cryopreserved.” Therefore, it may be an off-the-shelf allogeneic therapy with a long shelf-life.

The COVID-19 trial was the first time CYNK-001 was used for a non-cancer indication. The trial measured safety and efficacy. Results showed the infusions “generally were well-tolerated and three of four patients experienced improvements in oxygenation, inflammatory markers and radiographic findings,” according to the abstract.

In gastric cancer, the overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in about 20% of all cases and is linked to poor outcomes. Another compound, CYNK-101, showed synergistic anti-tumor antibody dependent cellular cytotoxicity when administered with Trastuzumab in vitro, ex vivo and in vivo.

Notably, “It is exactly the same candidate in each of those programs,” Hariri told BioSpace.

That one therapy has such diverse applications is possible because of its origin: placental stem cells.

“The biology of the placenta is remarkable,” Hariri said. “It’s nature’s stem cell factory. We originally thought it was merely a vascular interface between the baby and mother, but it’s actually a life-support system to create an environment for the proliferation and differentiation of stem cells that derive from the primordial stem cell created at fertilization.”

Specifically, “The placenta produces natural killer (NK) cells that are part of the innate immune system,” defending fetuses from infectious diseases and cancer. “One in one thousand women have cancer during pregnancy, yet the incidence of transfer is essentially non-existent,” he pointed out.

That’s because of the NK cells that, likewise, protect the baby from viral infections.

“Placental NK cells recognize stress antigen found on infected cells,” Hariri continued. “Adult-derived NK cells don’t express the same array or recognition markers found on placental cells, therefore, the youth of placental cells is important,” because of their unique characteristics.

“Stemness” is one example, he said. “Stemness is a characteristic of stem cells that is associated with their very versatile differentiality. They can access the entire genome of the stem cell to synthesize all the products the stem cell encodes for.” They also have “better proliferative performance, greater persistence and are immunologically naïve, so they haven’t yet developed the self-expression that lets them be targeted by a recipient’s immune system.

“Therefore, therapies derived from placental stem cells may be safer and more potent than those derived from ‘foreign’ cells.” Because the immune system doesn’t see these cells a ‘foreign,’ patients can be retreated as necessary “until you get the response you want.”

Placental stem cells can solve one of the challenges stem cell therapies face: access to raw material. Each post-partum placenta can produce hundreds to thousands of doses, making this a scalable, economic source of high-quality stem cells.

As Celularity looks to the future, “We are very cognizant of being thoughtful regarding the clinical indications we select. This is a very competitive landscape.”

It plans to produce its products inhouse and aims to be a world leader in the manufacture of cellular medicine.

“The key is consistency and reliability” Hariri said.

Because Celularity spun out from Celgene in 2017, its team has years of experience engineering and manufacturing NK cells and other cell types.

“Our headquarters houses GMP manufacturing capabilities with 15 independent production suites, so we can produce a range of products in parallel under rigorous regulatory guidelines,” he said.

Like every company in a dynamic industry, the probability of success determines access to capital. Celularity, a spinoff of Celgene, is well-positioned in that regard. Bristol Myers is a major stakeholder, and Celularity has raised hundreds of millions of dollars to pursue research and build infrastructure.

Its next step is to go public.

“We hope to close the GX Acquisition deal (announced in January) very soon,” Hariri said.

The capital raised from that transaction will help the company prosecute its clinical programs, and to grow both organically and transactionally.