Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes.  Extramedullary involvement is frequent (central nervous system [CNS], lymph nodes, spleen, liver, and testis). Approximately 85% of ALLs are of precursor B-cells.  ALL accounts for .3% of all new cancer cases, and .3% of all cancer deaths.It is estimated that 6,660 new cases of ALL and 1,560 deaths related to the disease occurred in the US in 2022. ALL represents 12% of all leukemia cases progresses rapidly and is typically fatal within weeks or months if left untreated. 

The majority of newly diagnosed ALL patients are pediatric, however there are still a significant number of adults ALL patients. The goal of therapy is to lead patients into a long-enough remission so that an allogeneic hematopoietic stem cell transplantation (HSCT, the only curative approach) could be performed, leading to leukemia-free survival rates of 14% to 43%. There is an urgent need to develop new therapies for ALL for patients who are not candidates for HSCT or relapse after.

Cellectis’UCART22 is an allogeneic CAR T product that is being evaluated in the BALLI-01 study in adult patients with relapsed or refractory Acute lymphoblastic leukemia (r/r ALL). This product candidate has the potential to become an off-the-shelf available therapy for adult patients with r/r ALL that uniquely targets CD22. 

Non-Hodgkin Lymphoma (NHL) are a heterogeneous group of neoplasms that originate in any of the lymphoid cells: B-cells, T-cells, or NK-cells. NHLs encompass a spectrum of lymphoid malignancies, with 85% arising from B lymphocytes. (B-cell NHL). Non-Hodgkin lymphoma (NHL) is one of the most common cancers in the United States, accounting for about 4% of all cancers and one of the more common cancers among children teens, and  young adults. It is estimated that 80,470 new cases of NHL and 20,250 deaths related to the disease will occur in the US in 2022. The 5-year relative survival rate for people with NHL is 73%. 

Despite novel treatment approaches, challenges remain for patients with relapsed or refractory non-Hodgkin Lymphoma (r/r NHL). A significant proportion of patients relapse to CD19 CAR-T. There is an urgent need for new therapeutic modalities, addressing this patient population that represents a potential therapeutic alternative to CD19-directed therapies

UCART20x22 is Cellectis’ first dual allogeneic CAR T product candidate to enter clinical development in the NatHali-01 study in patients with r/r NHL. Dual targeting of CD20 and CD22, both validated targets in B-cell malignancies, has the potential to enhance tumor cell killing and increases the breadth of antigen targeting. These advantages may represent a potential therapeutic alternative to CD19-directed therapies.