Mesenchymal Stromal Cell Therapy Shows Potential in Affecting Crohn Disease Features

Mesenchymal‐like adherent stromal cell (MLASC) therapy altered gene and protein signatures associated with inflammation and fistula formation in patients with Crohn disease (CD) treated in Celularity’s phase 1 clinical trial (NCT01769755).¹

The legacy trial evaluated Celularity’s PDA001 MLASC therapy, although the company is now only developing the APPL-01 therapy for the indication, which is currently in investigational new drug application-enabling studies. The study evaluated mRNA gene expression data and proteomics data at early pretreatment, pretreatment baseline, early posttreatment, and at later post‐treatment.

“CD is a devastating condition for patients, and we believe these data help us begin to see the potential role that cell therapy may play in its treatment,” Robert J. Hariri, MD, PhD, CEO, chairman and founder, Celularity, said in a statement.¹ “Furthermore, these results validate our decision to progress our novel genetically modified allogeneic placental-derived MLASC, APPL-01, in CD, where this cell therapy candidate has the potential to make a significant difference. Celularity’s unique technology platform is grounded in our use of the post-partum placenta as the source of cells and biomaterials, enabling independent but complementary product opportunities in cellular and regenerative medicine.We’re moving forward with confidence to assess the potential immunomodulatory and pro-regenerative therapeutic benefits of MLASCs as we advance the development of therapeutic options for patients.”

READ MORE: First Patient With Crohn Disease Dosed in MSC-derived Therapy Trial

The analysis showed that MLASC treatment altered gene and protein signatures associated with inflammation and fistula formation and provided insight into pathways associated with severity of CD. The data also suggests that gene and protein profiling may be auseful tool to assess disease severity and treatment response. The biomarker responses validate the potential of MLASC therapy in managing CD and limiting fistula formation, which Celularity hopes to improve upon with the next generation APPL-01 therapy.

Celularity also recently released preclinical data that examined methods to reduce the tissue factor (TF) expressed by ASCs, which may trigger thrombosis in intravenous administrations of therapy.² CRISPR editing of ASCs demonstrated TF knockout that significantly reduced TF activity without altering the cells.

“We are very encouraged by these results with an edited version of one of our cell therapy candidates,” Hariri said.² “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 MLASCS, APPL-001, in diseases like Crohn’s disease, facioscapulohumeral muscular dystrophy (FSHD), and to explore a range of other clinical indications.”

REFERENCES

1. Celularity Announces Phase 1 Data Showing That MLASC Therapy in Patients With Crohn’s Disease May Be a Therapeutic Option to Manage Inflammatory Bowel Diseases and Prevent Fistula Formation. News release. Celularity. May 19, 2023. https://www.globenewswire.com/en/news-release/2023/05/19/2672795/0/en/Celularity-Announces-Phase-1-Data-Showing-That-MLASC-Therapy-in-Patients-With-Crohn-s-Disease-May-Be-a-Therapeutic-Option-to-Manage-Inflammatory-Bowel-Diseases-and-Prevent-Fistula-.html
2. Celularity Tissue Factor Gene Knockout Of Allogeneic Stromal Cells Significantly Lowers Thrombotic Effects; Study Highlights Critical Importance Of Gene Editing Capability. News release. June 1, 2023. https://celularity.com/celularity-tissue-factor-gene-knockout-of-allogeneic-stromal-cells-significantly-lowers-thrombotic-effects-study-highlights-critical-importance-of-gene-editing-capability-press-release/