MolMed S.p.A. (MLM.MI) announces the results of the contribution given by its investigational cell-based therapy TK to the treatment of haematologic malignancies through bone marrow transplantation from partially matched donors, presented at the Blood & Marrow Transplantation (BMT) Tandem Meetings, the combined annual meeting of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society of Blood & Marrow Transplantation (ASBMT), taking place in Salt Lake City (UT, U.S.).
The study concerns the overall intention to treat (ITT) analysis of 611 patients with high-risk haematologic malignancies (61% acute leukaemia) treated with bone marrow transplant from a healthy donor in a single centre, the San Raffaele Scientific Institute of Milan, in the past 8 years. The aim of the study was to assess the impact of transplants from partially compatible family donors (haplo-identical transplants), which were systematically offered to patients lacking a fully compatible donor, thus making the transplant option available to the largest number of patients within the time requested by disease progression.
In this patient population, which includes four treatment protocols conducted in parallel, the approach involving the use of TK cells produced by MolMed was previously tested in a Phase II trial (TK007) in patients with haematologic malignancies and currently in a pivotal Phase III trial (TK008) reserved for patients with high-risk acute leukaemia.
As of today, bone marrow transplantation from a matched donor represents the standard treatment option for patients suffering from acute leukaemia, however only about 50% of patients have a fully matched donor available in the family or in the volunteer donor registry. The analysis presented at the BMT Tandem Meetings reveals that, in this large patient population, results of transplants from partially matched (haploidentical) family donors are fully comparable in terms of overall survival and disease-free survival to those obtained with transplants from fully matched donors. These results are of particular relevance in light of the fact that this type of transplant is available for almost all patients: over 80% of the intention to treat population actually received a transplant. The contribution of TK to this patient population will continue through the centre’s participation in the randomized multicentre Phase III trial. Data available on the first 14 treated patients of this trial confirm the efficacy and safety profile of TK cells already observed in 123 patients treated in the Phase II and other previous studies.
MolMed is conducting an international pivotal randomised Phase III trial for high-risk leukaemia patients undergoing bone marrow transplants from haplo-identical family donors, ongoing in Europe and the United States. Moreover, based on cumulative efficacy and safety data and on the Orphan Drug designation related to the incidence of leukaemia, the Company expects to file a request for Conditional Marketing Authorisation of TK to the European Authority in mid-2013.
FROM GENES TO THERAPY
TK is a cell therapy product, based on the use of genetically engineered donor T cells administered to patients after haematopoietic stem cell transplants in order to improve anti-leukaemic activity of the graft and to accelerate immune reconstitution. The onset of reactions mediated by such lymphocytes against healthy tissues of the patients – known as Graft-versus-Host Disease (GvHD) – has been reported so far in 28 patients and has always been rapidly and completely controlled thanks to the TK technology, without posttransplant immune-suppression. No adverse events correlated to the use of TK cells were ever reported in these studies.
About Phase III trial TK008
TK008 is a pivotal randomised Phase III trial in adult patients affected by high-risk leukaemia undergoing transplant of haematopoietic stem cells collected from partially compatible (haplo-identical) family donors.
The trial design has disease-free survival as the primary end-point – which includes both transplant-related mortality and disease relapse – evaluated on a patient population of 170 patients. The trial will compare the outcome of haplo-transplants with or without TK add-backs, with a 3:1 randomisation ratio in favour of the TK arm. Secondary end-points include overall survival, reduction of transplant-related mortality, safety and patients’ quality of life. With the aim to provide additional clinical benefit to patients and to significantly increase the potential participation of centres in the trial, the Company implemented in 2012 two important changes in the protocol design of Phase III trial TK008. The first consists in broadening the enrolment criteria to include patients in leukaemic relapse, in addition to those in disease remission; the second change provides for the introduction of a further treatment option in the control arm, based on the use of an unmanipulated transplant followed by cyclophosphamide administration during the post-transplantation period.
This press release is written in compliance with public disclosure obligations established by CONSOB (Italian securities & exchange commission) resolution no. 11971 of 14 May 1999, as subsequently amended.
MolMed S.p.A. is a biotechnology company focused on research, development and clinical validation of novel anticancer therapies. MolMed’s pipeline includes two antitumour therapeutics in clinical development: TK, a cell-based therapy enabling bone marrow transplants from partially compatible donors, in absence of post-transplant immune-suppression, in Phase III in high-risk acute leukaemia; NGR-hTNF, a novel vascular targeting agent, in Phase III in malignant pleural mesothelioma and in Phase II in six more indications: colorectal, lung (small-cell and non-small-cell), liver and ovarian cancer, and soft tissue sarcomas. MolMed also offers top-level expertise in cell and gene therapy to third parties to develop, conduct and validate projects from preclinical to Phase III trials, including scale-up and cGMP production of clinical-grade viral vectors, and manufacturing of patient-specific genetically engineered cells. MolMed is headquartered at the San Raffaele Biomedical Science Park in Milan, Italy. The Company’s shares are listed on the main market (MTA) of the Milan Stock Exchange. (Ticker Reuters: MLMD.MI)