Urgent Needs in Cancer

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is characterized by excessive proliferation of myeloid stem cells and their failure to properly differentiate into mature blood cells.1 There are an estimated 42,500 new diagnoses of AML each year in the United States, Europe and Japan.2, 3 The average five-year survival rate for patients with AML is less than 30%,4 but there are significant differences in prognosis depending on several factors, including the age of the patient at diagnosis.

For many of these patients, the only way to achieve durable remission or a cure is through hematopoietic stem cell transplant (HSCT), a procedure in which stem cells are obtained from matched healthy donors and administered following myeloablation to patients, resulting in reconstitution of the patient’s hematopoietic system with donor-derived cells. Over the past 20 years, there has been an increasing trend in allogeneic transplants for AML. There were over 16,000 allogeneic HSCT procedures performed in the United States between 2013 and 2017 for the treatment of AML. Despite this, approximately 40 percent of AML patients relapse within two years of their transplant and face an extremely poor prognosis, with two-year survival rates of less than 20%. Though targeted therapies are an effective treatment for many patients in transplant settings who relapse, these therapies are limited by toxicities resulting from the expression of the surface targets on healthy cells, including these new transplanted cells, which is referred to as on-target toxicity.

CD33 is an attractive target for the development of AML therapeutics based on preclinical and clinical results from third parties demonstrating the ability of anti-CD33 directed therapies to deplete tumor cells. However, CD33-directed therapeutic approaches have had limited impact in improving the prognosis of patients with AML due in part to on-target toxicity.

1. Leukemia – Acute Myeloid – AML: Statistics. Available at: https://www.cancer.net/cancer-types/leukemia-acute-myeloid-aml/statistics#:~:text=AML%20is%20the%20second%20most,of%20diagnosis%20is%20age%2068.
2. Cancer Stat Facts: Leukemia — Acute Myeloid Leukemia (AML). Available at: https://seer.cancer.gov/statfacts/html/amyl.html
3. O. Visser. Incidence, survival and prevalence of myeloid malignancies in Europe. EJC. Avaliable at: https://www.ejcancer.com/article/S0959-8049(12)00469-8/fulltext
4. Acute Myeloid Leukemia (AML) SEER Survival Rates by Time Since Diagnosis, 2000-2016. Available at: https://seer.cancer.gov/explorer/application.html?site=96&data_type=4&graph_type=6&compareBy=sex&chk_sex_1=1&chk_sex_3=3&chk_sex_2=2&race=1&age_range=1&hdn_stage=101&advopt_precision=1&advopt_display=2

Engineered Hematopoietic Stem Cells: VOR33

VOR33 is our lead eHSC product candidate designed to replace the standard of care in transplant settings. Once the VOR33 cells have engrafted, we believe that patients can be treated with anti-CD33 therapies, such as Mylotarg or VCAR33, with limited on-target toxicity, leading to durable anti-tumor activity and potential cures. In preclinical studies, we have observed that the removal of CD33 provided robust protection of these healthy donor HSCs from the cytotoxic effects of CD33-directed companion therapeutics yet had no deleterious effects on the differentiation or function of hematopoietic cells.


Licensed from the National Institutes of Health, VCAR33 is a CD33-directed chimeric antigen receptor T cell (CAR-T) therapy. VCAR33 is currently being investigated as an autologous monotherapy bridge-to-transplant for relapsed and/or refractory AML patients) in a multi-site, Phase 1 clinical trial in pediatric patients sponsored and overseen by the Center for International Blood and Marrow Transplant Research (CIBMTR).

Treatment System: VOR33/VCAR33

We believe VOR33 and VCAR33 could be highly synergistic as a Treatment System, potentially enabling prolonged remissions or cures in the post-transplant setting. We intend to investigate the VOR33/VCAR33 Treatment System, entailing VOR33 eHSC therapy followed by VCAR33 as a companion therapeutic, initially for transplant-eligible patients suffering from AML. We believe VCAR33 could be a potent anticancer therapy that, when combined with VOR33, could help obviate severe on-target myeloablative toxicities and unlock the efficacy potential of VCAR33. In addition, in this setting, VCAR33 T cells could be sourced from the same cell source as VOR33 (allogeneic cells), which may provide benefits such as a healthier, more abundant cell source alongside lower risk of host T cells attacking CAR-T cells, thereby potentially prolonging persistence. If our anticipated trials for the VOR33/VCAR33 Treatment System are successful, we will have the potential to provide a single-company solution for patients suffering from certain hematological malignancies.