For patients suffering from blood cancers, an allogeneic hematopoietic stem cell transplantation (HSCT) is generally regarded as a potentially curative, yet high risk approach. During an HSCT treatment, the bone marrow, harboring the diseased cancer cells, is completely destroyed and subsequently replaced by stem cells in the graft from a healthy donor. After an HSCT treatment it usually takes the patient at least six to twelve months to recover to near-normal blood cell levels and immune cell functions. During this period, the patient is highly vulnerable to infections caused by bacteria, viruses and fungi but also to disease relapse.
ATIR101, administered as an adjunctive immunotherapeutic on top of HSCT, provides for a safe single dose donor lymphocyte infusion (DLI) with functional, mature immune cells from a partially matched (haploidentical) family member, with minimal risk of causing severe Graft-versus-Host-Disease (GVHD). The T-cells in ATIR101 will help fight infections and remaining tumor cells and thereby bridge the time until the immune system has fully re-grown from stem cells in the transplanted graft.
In ATIR101, T-cells that would cause GVHD are depleted from the donor lymphocytes using Kiadis Pharma’s photodepletion technology, minimizing the risk of GVHD and eliminating the need for prophylactic immune-suppression. At the same time, ATIR101 contains potential cancer killing T-cells from the donor that could eliminate residual cancer cells and help prevent relapse of the disease, known as the Graft-versus-Leukema (GVL) effect.
The Company estimates that approximately 35% of patients who are eligible and in urgent need of HSCT will not find a matching donor in time. A partially matched (haploidentical) family donor, however, will be available to over 95% of patients.
In 2013, Kiadis Pharma completed a Phase I/II dose escalation trial which demonstrated that ATIR101 can be safely administered up to high doses, without causing severe GVHD. Long-term follow-up demonstrated that up to 67% of high-risk leukemia patients treated with an efficacious dose of ATIR101 survived for at least five years.
Currently, ATIR101 is being tested using a single dose regimen in an open-label Phase II trial designed to confirm the safety of ATIR101 in patients with blood cancer, who have not found a matching donor and where a haploidentical family member is used as donor for HSCT. Kiadis Pharma announced full enrollment of this trial in July 2015. The primary endpoint of the trial was TRM within six months post-HSCT. The data of this primary endpoint, presented at EBMT 2016, confirmed that ATIR101 can be safely infused, does not cause acute grade III-IV GVHD and shows a significant reduction in TRM and a significant improvement in Overall Survival (OS) in comparison to a historical control group of patients undergoing a T-cell depleted haploidentical donor transplantation only. These data were corroborated in December 2016 at ASH, where the Company reported positive one-year data post-transplantation.
Based on these positive Phase II data, the Company decided to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for ATIR101. The Company is now compiling the MAA document.
In addition, Kiadis Pharma has initiated a transatlantic, Phase III trial to enroll patients with acute leukemia who will be randomized to receive a haploidentical allogeneic HSCT using either a single dose of ATIR101 or the post-transplant cyclophosphamide approach (also known as the Baltimore Protocol).
ATIR101 has been awarded Orphan Drug Designations in the US and Europe.
The European Medicines Agency (EMA) has issued and Advanced Therapy Medicinal Product (ATMP) certificate for manufacturing quality and non-clinical data to the Company. to date, Kiadis Pharma is one of only seven companies that have received such a certificate.