Celularity Tissue Factor Gene Knockout of Allogeneic Stromal Cells Significantly Lowers Thrombotic Effects; Study Highlights Critical Importance of Gene Editing Capability

Rhea-AI Summary

Celularity Inc. has published preclinical data demonstrating that CRISPR-mediated tissue factor gene knockout in allogeneic stromal cells leads to lower tissue factor expression and reduced thrombotic effects. This could improve the safety of ASC-based cell therapy. The study showed that efficient gene editing can significantly reduce tissue factor activity without affecting critical cell functions. Celularity plans to use this strategy to progress their genetically modified cell therapy candidate APPL-001 in various clinical indications.

Positive

• CRISPR-mediated tissue factor gene knockout in allogeneic stromal cells leads to lower tissue factor expression and reduced thrombotic effects, improving the safety of ASC-based cell therapy.
• Efficient gene editing can significantly reduce tissue factor activity without affecting critical cell functions.

Negative

• None.

Data published online in the journal Cytotherapy demonstrate that CRISPR-mediated tissue factor gene knockout (TFKO) in allogeneic stromal cells (ASCs) leads to significantly lower tissue factor (TF) expression, activity, and thrombotic effects, providing a feasible strategy potentially to improve the safety of ASC-based cell therapy

FLORHAM PARK, N.J., June 01, 2023 (GLOBE NEWSWIRE) -- Celularity Inc. (Nasdaq: CELU) (“Celularity”), a biotechnology company developing placental-derived allogeneic cell therapies and biomaterial products, announced today the online publication of preclinical data in Cytotherapy, the official journal of the International Society of Cell and Gene Therapy (ISCT).

The paper, “Characterization of CRISPR/Cas9-edited human placental allogenic stromal cells with low tissue factor expression and reduced thrombotic effects,” (Huang, et al.)¹ examined methods to reduce the tissue factor expressed by allogeneic stromal cells (ASCs), which has been regarded as a safety concern in clinical applications as it may trigger thrombosis when ASCs are administered intravenously.

Thrombogenic risk has been identified in association with intravenous administration of mesenchymal stem cells (MSCs), both allogeneic and autologous. These cells express procoagulant activity linked to the expression of tissue factor that, when in contact with blood, initiates coagulation. Mitigating thrombotic risk is of significant clinical importance.²

Placenta ASCs are MSC-like cells, cultured and expanded from full-term human placenta with a defined phenotype, demonstrate immunomodulation and pro-regenerative activities and have been investigated in clinical trials of Crohn’s disease, diabetic foot ulcer, and multiple sclerosis. The authors characterized and compared in vitro and in vivo activities of ASCs with CRISPR/Cas9-mediated TF gene knockout to non-edited ASCs with the goal of improving ASC clinical safety.

Using CRISPR gene editing of ASCs, the study demonstrated that efficient TFKO can be achieved, generating ASCs with significantly reduced TF activity without affecting the critical features and functions of the cells. The authors concluded that the TF gene knockout provides a feasible strategy which may improve the clinical safety features of ASC-based cell therapies.

“We are very encouraged by these results with an edited version of one of our cell therapy candidates,” said Robert J. Hariri, M.D., Ph.D., Celularity’s CEO, Chairman and Founder. “These data advance our understanding of the potential for ASCs to safely address human diseases. These data also are guiding our investment decision to progress our novel genetically modified allogeneic placental-derived mesenchymal-like adherent stromal cells (MLASCs), APPL-001, in diseases like Crohn’s disease, facioscapulohumeral muscular dystrophy (FSHD), and to explore a range of other clinical indications.”

About Celularity

Celularity Inc. (Nasdaq: CELU) headquartered in Florham Park, N.J., is a biotechnology company leading the next evolution in cellular and regenerative medicine by developing allogeneic cryopreserved off-the-shelf placental-derived cell therapies, including therapeutic programs using mesenchymal-like adherent stromal cells (MLASCs), T-cells engineered with CAR (CAR T-cells), and genetically modified and unmodified natural killer (NK) cells. These therapeutic programs target indications in autoimmune, infectious and degenerative diseases, and cancer. In addition, Celularity develops, manufactures, and commercializes innovative biomaterial products also derived from the postpartum placenta. Celularity believes that by harnessing the placenta’s unique biology and ready availability, it can develop therapeutic solutions that address significant unmet global needs for effective, accessible, and affordable therapies.

To learn more, visit celularity.com

Forward-Looking Statements

This press release includes “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995, as well as within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts are “forward-looking statements,” including those relating to future events. In some cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,” “can,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “forecast,” “intends,” “may,” “might,” “outlook,” “plan,” “possible,” “potential,” “predict,” “project,” “seek,” “should,” “strive,” “target,” “will,” “would” and the negative of terms like these or other comparable terminology, and other words or terms of similar meaning. The forward-looking statements in this press release include express or implied statements regarding Celularity’s approach to cellular medicine, the potential therapeutic benefit of gene edited MLASCs, and Celularity’s ability to progress APPL-001 into clinical studies for Crohn’s disease, among others. Many factors could cause actual results to differ materially from those described in these forward-looking statements, including but not limited to: the inherent risks in biotechnological development, including with respect to the development of novel biomaterial products and cellular therapies, and the clinical trial and regulatory approval process; and risks associated with Celularity’s current liquidity, as well as developments relating to Celularity’s competitors and industry, along with those risk factors set forth under the caption “Risk Factors” in Celularity’s annual report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 31, 2023, and other filings with the SEC. These risks and uncertainties may be amplified by current economic situations, including inflation, supply chain issues and overall economic uncertainty. If any of these risks materialize or underlying assumptions prove incorrect, actual results could differ materially from the results implied by these forward-looking statements. There may be additional risks that Celularity does not presently know, or that Celularity currently believes are immaterial, that could also cause actual results to differ from those contained in the forward-looking statements. In addition, these forward-looking statements reflect Celularity’s current expectations, plans, or forecasts of future events and views as of the date of this communication. Subsequent events and developments could cause assessments to change. Accordingly, forward-looking statements should not be relied upon as representing Celularity’s views as of any subsequent date, and Celularity undertakes no obligation to update forward-looking statements to reflect events or circumstances after the date hereof, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws.

¹ https://www.isct-cytotherapy.org/article/S1465-3249(23)00131-7/fulltext 
² Cells. 2019 Oct; 8(10): 1160. Coppin, et al

Celularity Contact:
Paul Graves, Chief Communications Officer
Celularity Inc.
paul.graves@celularity.com

FAQ

What did Celularity publish?

Celularity published preclinical data demonstrating that CRISPR-mediated tissue factor gene knockout in allogeneic stromal cells leads to lower tissue factor expression and reduced thrombotic effects.

What is the potential impact of this research?

The research suggests that this gene editing strategy could improve the safety of ASC-based cell therapy.

What did the study show about gene editing?

The study showed that efficient gene editing can significantly reduce tissue factor activity without affecting critical cell functions.

What is Celularity's plan for their cell therapy candidate?

Celularity plans to use this gene editing strategy to progress their genetically modified cell therapy candidate APPL-001 in various clinical indications.