SCIENCE
01
What is an allogenic hematopoietic stem cell transplantation and why does it represent a curative approach?
Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a powerful intervention with the potential to cure patients affected with aggressive hematologic malignancies or severe hereditary immunologic, metabolic, and hematologic diseases.
Through an allo-HSCT, the hematopoietic stem cells of the recipient are replaced by healthy donor stem cells and immune cells. Following engraftment, these will give rise to new blood cells, including leukocytes, thrombocytes, and erythrocytes, and establish a new immune system that will contribute to eliminate the residual neoplastic cells in patients with hematologic malignancies (graft-versus-leukemia effect).
02
How is allo-HSCT currently performed and what are its limitations?
A successful allo-HSCT entails three major phases: conditioning, transplantation, and regeneration.
The conditioning aims at (i) removing patient's own stem cells, thus creating space for donor’s cells, and (ii) eliminating residual neoplastic cells (minimal residual disease, MRD) in case of hematologic malignancies, thus improving patient's survival.
After application of the conditioning regimen, stem cells collected from a healthy donor will be infused intravenously and will localize in the bone marrow, where they will occupy the freed space and regenerate blood and immune cells.
The standard conditioning requires high doses of chemotherapy (±irradiation), which targets all dividing cells in the body in a non-specific manner, thus having multiple severe adverse effects. These include acute toxicity - with possible acute organ damage- and long terms complications (secondary malignancies, cardiovascular diseases, osteoporosis, infertility, endocrinal and metabolic dysfunctions). Furthermore, damaged tissues are prone to be targeted by the graft-derived immune cells that are ultimately responsible for the Graft versus Host Disease (GvHD). This can further impair tissue-damages resulting in organ dysfunction and, possibly, death. Therefore, immune-suppression is required after allo-HSCT and constitutes a risk factor for severe infections.
Taken together, the complications derived from the initial conditioning, the GvHD and the immunosuppression constitute a burdensome aspect of allo-HSCT, and high rates of non-relapse morbidity and mortality (i.e., due to transplantation) are reported in the western countries.
At ATLyphe we are dedicated to developing a targeted conditioning method for patients undergoing allogenic hematopoietic stem cell transplantation.
03
What is the mode of action behind ALY117, our CD117xCD3 bi-specific antibody?
ALY117 is a bi-specific antibody that specifically binds to two different proteins expressed on cell surfaces. On one side, it targets CD117 (tyrosine-protein kinase KIT), an antigen expressed by healthy stem cells and by pathological leukemic cells (leukemic blasts). On the other side, it binds to CD3e, a pan T cell surface-marker.
In this way, the CD117xCD3 bi-specific antibody links the T cells to CD117 positive cells, inducing T cell activation and T cell mediated killing (i.e., elimination) of target cells.
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The advantage of our precision approach is that only CD117-positive diseased (leukemic) and healthy stem cells are eliminated, while other, CD117-negative, healthy cells are spared.
04
What is the goal of ATLyphes’s conditioning method?
ATLyphe’s goal is to develop a safer conditioning that enables allogenic transplantation without causing severe side effects. This will ultimately (i) improve the outcome of transplantation routinely performed on “fit” subjects and (ii) make transplantation possible for patients who are currently non-eligible to undergo a curative allo-HSCT.
Furthermore, by introducing a new therapy that can specifically target malignant blasts, we aim at improving the elimination of residual neoplastic cells in patients who undergo transplantation due to an acute myeloid leukemia (AML) or myelodysplastic neoplasia (MDS), thus reducing the risk of relapse and improving survival-rates.
05
ATLyphe's Pipeline
