– Data expand on previously described mechanism of action and validate use of UM171 to create improved hematopoietic stem cell (HSC) therapies, including UM171 Cell Therapy

– Company expects to initiate a Phase 3 study for UM171 Cell Therapy for the treatment of high and very high-risk acute leukemias and myelodysplasias in 2024

MONTREAL, February 1, 2024 – ExCellThera Inc. (ExCellThera), a world leader in enhanced blood stem cell therapies, announced today a publication in the journal Blood that further elucidates the UM171 mechanism of action and highlights the potential for UM171 to result in the efficient expansion of stem cells with preserved function for therapeutic use.

The manuscript is titled: KBTBD4-mediated Reduction of MYC Is Critical for Hematopoietic Stem Cell Expansion Upon UM171 Treatment

UM171 is a proprietary small molecule with a first-in-class mechanism of action that upregulates stem cell renewal and enhances graft compositions by selectively increasing primitive and immuno-modulatory cells while preserving cellular fitness and functionality. ExCellThera uses UM171 combined with blood stem cells to create UM171 Cell Therapy, which has shown positive clinical results in recent Phase 2 studies in patients with high-risk leukemias and myelodysplasias. The Company plans to initiate a Phase 3 study in high and very high-risk leukemias and myelodysplasias later this year.

Previous research revealed that UM171 promotes stem cell expansion and fitness through activation of the CRL3KBTBD4 E3 ubiquitin ligase, which targets the CoREST1 repressor complex for degradation. CoREST1 degradation promotes the expression of hematopoietic stem and progenitor cell transcriptional gene signatures that preserve HSC properties.

Publication Highlights

  • In addition to CoREST1, UM171 also reduces levels of chromatin-bound MYC, a protein involved in a wide range of cellular processes including cell-cycle control, metabolism, proteostasis, and self-renewal. Overexpression or amplification of MYC is associated with increased cell division, and several studies have also pointed to MYC having a critical role in HSC functions.
  • Similar to CoREST1 degradation, UM171-mediated MYC reduction was also found to be CRL3KBTBD4-dependent, and data suggest this reduction is important for UM171-induced HSC expansion and preservation.

“HSCs have significant therapeutic potential, especially for hematologic cancers, but a key challenge is being able to expand the number of cells ex vivo to the levels needed while also preserving their self-renewal and regenerative capacity for successful complication-free transplants,” said David Millette, Chief Executive Officer of ExCellThera. “Building upon previous mechanism of action studies, these new data further validate the use of UM171 to create improved HSCs, including our UM171 Cell Therapy that has shown promise in treating patients with high-risk leukemias and myelodysplasias. We are excited to continue advancing the development of UM171 Cell Therapy and bring this potentially transformative therapy to patients.”

About UM171 Cell Therapy

UM171 Cell Therapy has been evaluated in over 120 patients to treat hematologic malignancies in clinical trials in the United States, Europe and Canada. UM171 Cell Therapy has received orphan drug designation and regenerative medicine advanced therapy (RMAT) designation from the FDA as well as orphan medicinal product designation, advanced therapy medicinal product (ATMP) classification and priority medicines (PRIME) designation from the EMA.

A Phase 3 trial is planned for 2024. The use of UM171 Cell Therapy in other patient populations, including pediatric patients and patients with non-malignant hematological diseases, is also being explored.

UM171 Cell Therapy is an investigational cell therapy, and its safety and efficacy have not been established by the FDA, EMA, Health Canada or any other health authority.

About ExCellThera and UM171 Technology

ExCellThera is a world leader in enhanced blood stem cell therapies. ExCellThera’s proprietary EnhanceTM platform for cell expansion and metabolic fitness is designed to deliver a greater dose of functional therapeutic stem cells by expanding HSCs from any source and counteracting the effects of culture or gene editing induced stress. ExCellThera partners with biopharmas to help them develop best-in-class cell and gene therapies by leveraging the technologies that form the EnhanceTM platform, including the proprietary molecule UM171 which has a first-in-class mechanism of action for ex vivo expansion and metabolic fitness of HSCs. For additional information, visit excellthera.com, and follow us on LinkedIn.