NLA101: Providing a Bridge to Recovery

NLA101 is a universal donor, ex vivo expanded hematopoietic stem and progenitor cell product that provides bridging hematopoiesis to rapidly generate mature and functionally intact myeloid cells. These cells provide an immunity “boost” by preventing infection until the patient’s bone marrow can recover.

NLA101 is efficiently manufactured ahead of time, cryopreserved, and available for immediate use. A true off-the-shelf therapy, NLA101 is differentiated from other autologous or patient-specific allogeneic cell therapies as it does not require tissue matching. NLA101 is currently in Phase 2 development to improve treatment outcomes in patients receiving cord blood transplants and for patients receiving intensive chemotherapy.

NLA101 for Cord Blood Transplants

Widespread adoption of cord blood transplants is currently limited by the low cell dose provided in a cord blood graft. On average, a cord blood graft contains one tenth the number of stem and progenitor cells compared to other stem cell sources, specifically hematopoietic stem cell grafts from bone marrow or peripheral blood donors. As a result, patients receiving a cord blood transplant are at increased risk for significantly-delayed engraftment or graft failure and experience higher early transplant-related morbidity and mortality compared with patients receiving bone marrow or peripheral blood stem cell transplants.

NLA101 has the potential to address this limitation by instantly providing significantly-increased numbers of stem and progenitor cells capable of rapid production of blood and immune cells. Clinical results to date demonstrate that NLA101 may reduce morbidity and mortality associated with cord blood transplants and improve overall patient survival.

NLA101 following Intensive Chemotherapy

NLA101 is also in clinical development for patients receiving intensive chemotherapy. In these patients, life-threatening infections are very common, leading to lengthy hospitalization and increased reliance on supportive care.  Despite the use of growth factors and antibiotics, nearly 40% of patients treated with high-dose chemotherapy still experience infections, which can be life threatening. In addition, patients who experience serious infections are often required to delay the start of additional chemotherapy cycles or have their chemotherapy dose reduced to avoid ongoing complications. These delays or reductions in treatment may lessen chemotherapy’s effectiveness and its ability to induce long-term disease response.

NLA101 provides these patients with additional treatment options by reducing toxicities associated with intensive chemotherapy, allowing for earlier administration of chemotherapy which could lead to improved patient outcomes.

NLA101: Ongoing Clinical Trials

Nohla has advanced NLA101 into two large randomized, multi-center Phase 2 studies. The first is an ongoing Phase 2b study in the US for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia, myelodysplastic syndromes or chronic myelogenous leukemia undergoing a myeloablative cord blood transplant. Target enrollment for this trial is 160 patients. The goal of the trial is to determine whether adding NLA101 to standard donor cord blood transplant decreases the time to hematopoietic recovery, thereby reducing associated morbidities and mortality. More information can be found at clinicaltrials.gov.

The second Phase 2 global trial is intended to enroll 220 patients with AML who are at risk for myelosuppression following high dose chemotherapy. The primary objectives of this trial are to (a) evaluate the effect of NLA101 on the rate of Grade ≥ 3 bacterial and fungal infections associated with chemotherapy-induced neutropenia in adult subjects with AML and (b) obtain evidence about the lowest effective cell dose of NLA101 in reduction of infection. Site initiation is underway and patient enrollment is expected to begin before the end of 2017. More information can be found at clinicaltrials.gov.

NLA101: Clinical Results

Over 125 infusions of NLA101 have been administered across four clinical trials since 2009 with no unexpected safety issues to date. In a 15-patient pilot study in the setting of myeloablative cord blood transplant, no infusional toxicities were observed and no serious adverse events were attributed to treatment with NLA101. As compared with concurrent controls, subjects receiving NLA101 experienced a significantly reduced median time to platelet and neutrophil recovery. There was also no observation of treatment related mortality (TRM) or grade 3-4 acute GvHD in recipients of NLA101, representing a significant reduction in these outcomes (Milano et al, ASH December 2014).

In addition, a Phase 1 trial evaluating the safety and preliminary efficacy of infusing NLA101 following intensive chemotherapy was conducted in 29 adult patients with AML. NLA101 was administered after chemotherapy with clofarabine, cytarabine and G-CSF priming. A total of 42 infusions were administered to the 29 patients, with 13 patients going on to receive a second cycle of chemotherapy with NLA101. No unexpected toxicities, transfusion-associated GVHD, or NLA101-induced alloimmunization were observed. As compared with concurrent controls the rates of documented infections were significantly reduced, and no gram-negative rod bacteremia (for example, E. coli, which can rapidly progress in this setting from severe GI infection to sepsis) was observed in patients who received NLA101 (Delaney et al, Lancet Haematology 2016).