NLA101: Addressing Unmet Medical Needs

NLA101 is an ex-vivo expanded stem and progenitor cell graft derived from umbilical cord blood. The product was developed to improve treatment outcomes in patients receiving cord blood transplants, and in patients with hematologic malignancies at risk for chemotherapy induced neutropenia.

While HCT is a curative treatment option, patients require a matched related or unrelated donor genetically matched at multiple human leukocyte antigens (HLA) to avoid fatal outcomes from graft versus host disease. In contrast, patients undergoing a cord blood transplant (a form of HCT) require matching at fewer HLA loci between patient and cord blood donor, providing increased access to HCT for nearly all patients in need. However, widespread adoption of cord blood transplants as a treatment option is limited by the low cell dose provided by a cord blood graft. As a result, patients are at known risk of delayed engraftment or graft failure and higher early transplant related mortality as compared with other hematopoietic stem cell sources. NLA101 addresses this limitation by generating significantly increased numbers of stem and progenitor cells capable of rapid in vivo repopulation that provide robust early bridging engraftment until engraftment and hematopoietic recovery is achieved by the cord blood donor. As such, NLA101 is intended to reduce morbidity and mortality associated with HCT and improve long term survival. .

Another area of focus for the company is chemotherapy induced neutropenia (CIN) in patients with acute myelogenous leukemia (AML). Current AML chemotherapy approaches are aggressive and associated with significant morbidity and mortality due to prolonged severe neutropenia, thrombocytopenia and immunosuppression. As a result, life-threatening infections are very common in this AML population, leading to lengthy hospitalization and increased reliance on supportive care. Despite the use of growth factors and antibiotics, nearly 30% of patients with hematologic malignancies still experience CIN. To address this unmet medical need, Nohla is developing NLA101, a universal donor expanded progenitor cell product which overcomes the limitations of current standard of care for CIN by providing a donor cell source for rapid, transient, myelopoiesis until autologous recovery can occur. This may ultimately result in significantly improved disease control, reduced morbidity, and better overall patient survival.

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 leukemia, MDS or CML undergoing a myeloablative CBT. Target enrollment for this trial is 160 patients total. . The goal of the trial is to improve the kinetics of hematopoietic recovery and thereby reduce associated morbidities and mortality.

The second Phase 2 trial is a global study intended to enroll 220 patients with AML who are at risk for neutropenia following high dose chemotherapy. This is a multi-dose (?multi cycle) plus control arm study with the primary objective of identifying the minimally effective NLA101 cell dose in reduction of infections and infectious complications.

NLA101: Compelling 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 Phase 1 / 2 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, as well as reduced transplant-related mortality and improved disease-free survival. Furthermore, no grade 3-4 graft versus host disease (GVHD) was reported in patients receiving NLA101 (Milano et al, ASH December 2014) (see figures below).

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. No unexpected toxicities, transfusion-related GVHD, or NLA101-induced alloimmunization were observed. As compared with concurrent controls the rates of infections were significantly reduced, and no gram-negative rod bacteremia was observed in patients who received NLA101 (Delaney et al, Lancet Haematology 2016) (see figures below).

NLA101: A Strong Value Proposition

NLA101 therapy addresses a significant unmet need in patients with hematologic malignancies receiving myeloablative or high dose chemotherapy who are at risk for pancytopenia.

NLA101 can be efficiently manufactured, cryopreserved, and made available for immediate use. Unlike other treatment options, NLA101 does not require tissue matching or any patient-specific processing – a true, universal donor, off-the-shelf therapy. As a result, cost of goods is considerably lower compared to other personalized, patient-specific cell therapy products.