NeoStem, a provider of emerging cellular therapy, has entered into a definitive agreement to acquire California Stem Cell (CSC), an Irvine, Calif.-based stem cell biotechnology company. NeoStem plans to initiate a pivotal phase III trial of Melapuldencel-T, an autologous melanoma initiating (stem) cell immune-based therapy intended to eliminate the tumor cells capable of causing disease recurrence.

Since its founding in 2005, CSC has developed proprietary methods for the scalable production of high-purity human stem cells and their derivatives. CSC has been focused on the application of these cells in developing life changing therapies, including Melapuldencel-T, which has been the subject of compelling trial results for the treatment of metastatic melanoma. As a result, Melapuldencel-T has been approved to enter a phase III clinical trial with Special Protocol Assessment (SPA) and received Fast Track Designation for metastatic melanoma, as well as Orphan Drug Designation.

In a phase II randomized clinical trial of Melapuldencel-T (an irradiated autologous in vitro proliferating melanoma cell line loaded onto an autologous dendritic cell combined with granulocyte macrophage colony-stimulating factor [GM-CSF]), patients showed a significant improvement in two-year overall survival from 31% in controls to 72% in treated patients (p=0.007) with advanced melanoma (recurrent stage III and stage IV). The toxicity profile was favorable with no grade IV and only one grade III (allergic reaction) event in the study.

"NeoStem has been built upon a series of strategic acquisitions that created an infrastructure with strong development, regulatory and manufacturing expertise in cell therapy. By adding a late stage technology, such as Melapuldencel-T, we enhance our ability to add value for our shareholders," said Dr. Robin Smith, chairman and CEO of NeoStem. "We continue to lead the industry in the development of novel proprietary cellular therapies, and adding CSC's advanced immunotherapy technologies to our existing development pipeline and cGMP compliant cell therapy manufacturing facilities (PCT) brings us closer to our goal of delivering transformative cell based therapies to the market to help patients suffering from life-threatening medical conditions."

Dr. Hans Keirstead, current CEO of CSC said, "This transaction represents a major developmental step for our technology and tremendous hope for patients. We believe NeoStem's and PCT's deep expertise in scaled manufacturing, regulatory and clinical development will advance our programs significantly."

"Eliminating or neutralizing the tumor cells that are responsible for recurrence after medically induced tumor regression remains a seminal goal of cancer therapeutics. As such, these tumor initiating cells, so-called 'cancer stem cells,' appear to be ideal targets for therapeutic intervention that could lead to long term disease free survival, better overall survival and potential cures," said Dr. Robert Dillman, chief medical officer of CSC. "These cells express the repertoire of tumor-associated antigens for each individual patient that need to be recognized by the patient's immune system. As such, this is a patient-specific immunotherapy that addresses cancer heterogeneity and the origin of cancer recurrence, so it is potentially complementary to other cancer therapies, including other emerging enzyme-targeted agents and immunotherapies."

"T cells (a cell in your immune system) have always been thought to be capable of killing tumor cells, including autologous T cells of a patient with bulky cancer," said Dr. Andrew Pecora, chief visionary officer of NeoStem and chief innovations officer, professor and vice president of Cancer Services of the John Theurer Cancer Center at Hackensack University Medical Center. "It now is well established that tumors escape immune surveillance through inducing tolerance of autologous T cells. A new class of agent, so called T cell checkpoint inhibitors, has proven that unmasking tolerance allows autologous T cells to recognize and kill tumors in patients with a variety of tumor types including melanoma, lung cancer and renal cancer. However, even the best data presented to date combining two types of checkpoint inhibitors (e.g.: anti-CTLA-4 with anti-PD-1) in patients with melanoma did not improve outcomes for a significant percentage of patients treated and was associated with significant side effects. Lack of effect in part could be a result of insufficient targeting of melanoma initiating cells."

"Enhancement of immunologic targeting of melanoma initiating cells could significantly increase the incidence and durability of response as an immune-based therapy either alone or in combination with checkpoint inhibitors," said Dillman. "It is noteworthy that in the phase II randomized trial, Melapuldencel-T improved outcomes in a broad spectrum of advanced melanoma patients. This same inclusive population will be the target of the phase III program."

CSC's protocol to investigate the use of Melapuldencel-T in patients with stage III/IV melanoma has received SPA, indicating the FDA is in agreement with the design, clinical endpoints and planned clinical analyses of the phase III trial that will serve as the basis for a Biologics License Application.