TCX-101 Program

BlueSphere’s TCX-101 program combines an engineered TCR T-cell therapy targeting a blood restricted antigen with allogeneic stem cell transplant. Our goal is to create a best-in-class HLA population coverage panel of novel TCR T-cell therapies for treatment of AML, ALL, and MDS.

Our first clinical candidate, BSB-1001, targets the blood restricted antigen HA-1, and we anticipate enrolling our first patient in 4Q2024.

Discovery

IND-ENABLING

PHASE 1

HEMATOLOGIC

Discovery

IND-Enabling

PHASE 1

BSB-1001: Blood Restricted #1 – HA-1
BSB-1001: Blood Restricted #1 – HA-1

IND Accepted

Discovery

IND-Enabling

PHASE 1

Blood Restricted #2
Blood Restricted #2

Discovery

IND-Enabling

PHASE 1

Blood Restricted #3
Blood Restricted #3

Discovery

IND-Enabling

PHASE 1

Blood Restricted #4
Blood Restricted #4

IND Submitted

The TCX-101 program used our TCXpressTM platform to identify novel TCRs targeting several different blood restricted antigens.  These TCRs are then engineered into T cells.

How does a TCR T-cell therapy work?
  • Unlike CAR-T cells, TCR T-cell therapy can target intracellular antigens.
  • T cells kill targeted cells by using their T cell receptor to identify fragments of antigens (peptides) presented by Human Leukocyte Antigens (HLA) molecules expressed by target cells. Think of this as a ‘lock and key’ system.
  • The TCR on the T cells acts as the key and the HLA-peptide on the target cell acts as the lock. If a T cell ‘key’ finds the right ‘lock’, it destroys the cell.
  • T cells can be engineered to have specific keys and given to patients as TCR T-cell therapy.  When given to patients that have cancerous cells with a corresponding lock, then the TCR T-cell therapy works to kill those cancerous cells.
  • HA-1 is an antigen presented only by a patient’s blood cells, including leukemia cells.
  • BSB-1001 are T cells engineered to kill any cell presenting the HA-1 antigen.
  • Evidence exists showing that HA-1 (and other ‘like’ antigens) directed T cells are responsible for anti-leukemia effect (Marijt, W., et al. PNAS 2003)
  • BSB-1001 expected NOT to target other tissues or cell types, minimizing the risk of off-tumor effects
  • BlueSphere has developed best-in-class population coverage by identifying TCRs targeting four different blood-restricted antigens
BSB-1001 T cell graphic
  • In order to provide the patient with replacement blood stem cells, the TCX-101 therapy is paired with a CD34+ (only stem cells) allogeneic stem cell transplant.
  • The stem cell transplant comes from a donor who does NOT present HA-1 on their blood cells, which allows the transplanted cells to escape being destroyed by the BSB-1001 therapy.
  • Allogeneic stem cell transplant (alloSCT) is the standard of care used to treat high-risk leukemias.
  • These transplants typically come from a mixture of donor cells, including both stem cells and T cells that are used to replace the patient’s entire blood system.
Stem Cell Transplant graphic
  • Unfortunately, while some of the T cells in the transplant can attack cancerous cells, leading to graft versus leukemia (GvL), the majority of the T cells give rise to graft versus host disease (GvHD), which is a serious side effect of stem cells transplant. This is where the donor T cells attack the patient’s healthy tissues.
  • However, some T cells are known to kill leukemia (graft v leukemia), which is the concept behind BSB-1001.
  • BlueSphere’s BSB-1001 therapy is comprised of modified T cells that can kill the patient’s blood cells, including any remaining leukemia cells, but that do not target other healthy cells, thereby enhancing GvL and minimizing GvHD.
  • The patients still receive the neutral stem cells (CD34+ alloSCT) to repopulate a healthy, cancer-free hematopoietic system.
Graft vs Leukemia | Donor immune cells attack recipient leukemia cells graphic
BSB 101 Illustration
  • BSB will treat patients who are currently eligible for transplant AND patients with ACTIVE leukemia, who are not typically eligible for transplant due to their high risk of recurrence.
  • BSB will treat patients on Day 0, at the same time as alloSCT. By doing this, we should achieve better T cell activation and less chance of residual leukemia presence, ultimately leading to better efficacy.
  • Because BSB deletes the native TCR (increased safety) and do a CD34 transplant (only donor stem cells without non-engineered T cells), BSB will not use immunosuppression. This allows for higher chance of killing leukemia and less chance of GVHD.

Contact us to hear more about our clinical programs and technology.