Placental Cells Significantly Inhibit Cancer Cell Growth in Newly Published Study

According to the peer-reviewed article in the journal Scientific Reports, placenta-derived cells called PLX cells, exhibit a strong inhibitory effect on various lines of breast, colorectal, kidney, liver, lung, muscle and skin cancers. The research was conducted over more than two years by Pluristem Therapeutics, Inc., a Haifa-based biotechnology company.

The article titled “Human Placental-Derived Adherent Stromal Cells Co-Induced with TNF‑a and IFN‑g Inhibit Triple-Negative Breast Cancer in Nude Mouse Xenograft Models” is based on studies which examined the effect of Pluristem Therapeutic‘s PLX cells that had been induced with tumor necrosis factor alpha (TNF-a) and interferon-gamma (IFN-g), on the proliferation of over 50 lines of human cancerous cells. The induction of the cells was carried out by adjusting their manufacturing process in order to transiently alter their secretion profile.

Data from the first study showed that the modified PLX cells exhibited an anti-proliferative effect on 45% of the tested cancer cell lines, with a strong inhibitory effect on various lines of breast, colorectal, kidney, liver, lung, muscle and skin cancers. Comprehensive bioinformatics analysis identified common characteristics of the cancer cell lines inhibited by PLX cells. This knowledge could potentially be used in the future for screening patients’ tumors to identify those patients most likely to show a positive response to treatment with PLX cells.

Based on these promising results, Pluristem conducted a pre-clinical study of female mice harboring human triple negative breast cancer (TNBC). TNBC is an aggressive form of breast cancer that does not respond to standard hormonal therapy due to a lack of estrogen and progesterone receptors. Current treatment for TNBC consists of a combination of surgery, radiation therapy, and chemotherapy, and yet the prognosis remains poor for patients with this type of breast cancer. In this study, weekly intramuscular (IM) injections of the induced PLX cells produced a statistically significant reduction (p= 0.025) in mean tumor size in the treated group compared with the untreated group, with 30% of the treated mice exhibiting complete tumor remission. In addition, a statistically significant reduction (p=0.003) was seen in the percentage of proliferating tumor cells as well as in the level of blood vessels within the tumors.

“The findings of this study published in a peer-reviewed journal are the outcome of over two years of research as well as the vast knowledge of PLX cell properties we have developed over the last 10 years. We believe the findings show promise for the utilization of our induced PLX cells in slowing and reversing the growth of cancer cells, particularly for some cancers that don’t have viable treatment options,” stated Zami Aberman, Chairman and Co-CEO of Pluristem. “The findings also confirm the effectiveness of IM administration and support a mechanism of action involving immunomodulation and inhibition of angiogenesis and cell proliferation in cancerous conditions. Our unique patented manufacturing platform allows us to alter our cells’ secretion profile in correlation with the targeted cancer cells, which may open new possibilities in the field of oncology to treat solid tumors and may also offer new paths to help millions of patients around the world. As in immunotherapy technology, PLX cells potentially have the ability to communicate with the body and to secrete biological components that enhance regeneration processes and support the body in fighting cancer cells.”

Pluristem has filed patent applications relating to the technology for the induction of PLX cells and the use of these cells for the treatment of cancer.

$8.7 Million Awarded to Support Phase III Femoral Neck Fracture Trial by EU Horizon 2020 Program

Pluristem Therapeutics Inc., a leading developer of placenta-based cell therapy products, announced today that its Phase III study of PLX-PAD cells to support recovery following surgery for femoral neck fracture has been awarded an $8.7 million (7.4 million Euro) non-dilutive grant from the Horizon 2020 program, the European Union’s largest research and innovation program. Final approval of the grant is subject to the finalization of the consortium and Horizon 2020 grant agreements.

The Phase III trial of PLX-PAD cells in the treatment of femoral neck fracture will be a collaborative effort between Pluristem and an international consortium led by the Charité – Universitätsmedizin Berlin, under the leadership of Dr. Tobias Winkler, Principal Investigator at the Berlin-Brandenburg Center for Regenerative Therapies, Julius Wolff Institute and Center for Musculoskeletal Surgery. Dr. Winkler also served as Senior Scientist for Pluristem’s completed Phase I/II study of PLX-PAD for hip surgery. That trial demonstrated that patients treated with Pluristem’s PLX-PAD cells during total hip arthroplasty experienced significant muscle regeneration compared to the control group with an improvement in muscle force and in muscle volume six months after surgery.

This marks the second grant awarded to a Pluristem Phase III trial by Horizon 2020, following an $8 million (7.6 million Euro) award for its ongoing Phase III study of PLX-PAD cells in the treatment of Critical Limb Ischemia (CLI), which was awarded in August 2016.

Dr. Winkler commented, “Following the impressive results from the Phase I/II study of PLX-PAD cells in a similar orthopedic indication, we are excited to advance PLX-PAD cell therapy into a Phase III study to aid in muscle regeneration in patients recovering from femoral neck fracture. If similar results are achieved in this Phase III trial, it could show that PLX-PAD cells can improve outcomes in these procedures and change the way recovery is managed worldwide.”

Femoral neck fracture is the most common form of hip fracture, with mortality rates of up to 36%, and annual treatment costs estimated to be between $10-$15 billion in the U.S. alone. The number of surgeries performed annually to treat femoral neck fractures is increasing as populations age. Following surgery, many patients do not regain their baseline capabilities due to poor muscle healing and regeneration, which leads to significantly increased morbidity and a lower quality of life.

“We are honored to receive this second grant from the Horizon 2020 program,” stated Pluristem Chairman and Co-CEO Zami Aberman. “We believe this grant reflects a vote of confidence by the European Union and signals the need for cell therapy solutions to enable patients to lead healthier lives and to relieve health systems’ financial burdens. We are confident that this grant will help us move towards rapid entry into the European and U.S. markets.”

Pluristem’s PLX-PAD program is one of only a handful to be accepted into Europe’s Adaptive Pathway program, the purpose of which is to shorten the time it takes for innovative medicines to reach patients with serious conditions that lack adequate treatment options. Pluristem plans to enroll patients at clinical sites throughout Europe and the U.S. The study is expected to serve as a pivotal trial for regulatory approval in both regions.

The Berlin-Brandenburg Center for Regenerative Therapies (BCRT) was founded as a cooperative research institution of the Charité University Hospital in Berlin, which is one of the largest university hospitals in Europe, and Germany’s largest research association, the Helmholtz Association. The goal of the BCRT is to enhance endogenous regeneration by cells, biomaterials, and factors which can be used to develop and implement innovative therapies and products. The primary focus of the BCRT is on diseases of the immune system, the musculoskeletal system and the cardiovascular system for which currently only unsatisfactory treatment options are available.

Pluristem Therapeutics Inc. is a leading developer of placenta-based cell therapy products. The Company has reported robust clinical trial data in multiple indications for its patented PLX (PLacental eXpanded) cells, and is entering late-stage trials in several indications. PLX cell products release a range of therapeutic proteins in response to inflammation, ischemia, muscle trauma, hematological disorders, and radiation damage. The cells are grown using the Company’s proprietary three-dimensional expansion technology and can be administered to patients off-the-shelf, without tissue matching.

 

Leading Cell Therapy Company Pluristem to Partner with Japan’s Sosei for Commercialization of Regenerative Medicines in Japan

In a major global regenerative medicine deal, Israel-based Pluristem Therapeutics and Japan’s Sosei CVC, the venture capital arm of Japanese biopharma company Sosei Group, agreed to form a joint venture (JV) to commercialize Pluristem’s PLX-PAD cells in Japan. The deal marks Pluristem’s commercial entry into Japan and expands Sosei’s pipeline into regenerative medicines.

Pluristem has been active in the Japan market through discussions with, and applications to, Japan’s health regulatory agency, Pharmaceuticals and Medical Devices Agency (PMDA), seeking accelerated approval pathways for its PLX-PAD cells. The successful result is the PDMA’s acceptance of PLX-PAD cells into the accelerated pathways for regenerative medicine, making possible regulatory approval of PLX-PAD cells in the treatment of Critical Limb Ischemia (CLI) following just one 75-person clinical trial. This JV deal in Japan confirms Pluristem’s strategy of pursuing early approval pathways, as they also achieved in Europe.

Per the terms of the agreement between the two companies, an $11 million investment will be made by Sosei into the JV to fund a clinical trial of PLX-PAD for CLI that may directly lead to early conditional marketing approval and reimbursement based the PMDA’s accelerated regulatory pathway for regenerative medicine.  Pluristem gets 35% of the JV and its future profits. All proprietary rights related to PLX-PAD will be exclusively owned by Pluristem.

Sosei was likely compelled to partner with Pluristem based on the company’s advanced stem cell technology and its regulatory advantages in Japan. In addition to this JV with Pluristem, Sosei has partnerships with Novartis, AstraZeneca, MedIumme, and others. Pluristem and Sosei plan to enter into a definitive agreement no later than March 31, 2017.

Late Stage Critical Limb Ischemia Study using Placental Cell Therapy Snags $8 Million Grant from Europe’s Horizon 2020 Program

The European Union awarded an $8 million grant to cell therapy developer, Pluristem Therapeutics Inc., earmarked for a late stage trial in critical limb ischemia (CLI) program. The grant is part of the European Union’s Horizon 2020 program, which is its largest Research and Innovation program. The Phase III study of PLX-PAD in CLI will be a collaborative project carried out by an international consortium led by the Berlin-Brandenburg Center for Regenerative Therapies (BCRT) under the leadership of Prof. Hans-Dieter Volk and Prof. Petra Reinke together with Pluristem Therapeutics.

The consortium, which will include leading European research institutes and clinical sites, will undertake an extensive scientific program in parallel to the trial, using in-depth immunological, endocrine, and molecular analyses to better understand the mechanism of action of PLX-PAD in CLI.

As previously announced, Pluristem’s PLX-PAD development program has been selected for the EU’s Adaptive Pathways project, whose goal is to shorten the time it takes for innovative medicines to reach patients with serious conditions that lack adequate treatment options.

“We are honored to have been awarded this Horizon 2020 grant designed to support the manufacturing and development of our cell products for potential commercialization. This grant is a vote of confidence and an expression of hope by the European Union that we may be able to provide a regenerative therapy for millions of CLI patients around the world. Pluristem is committed to developing PLX-PAD for patients with peripheral artery disease, and this grant will help us move towards our goal of rapid entry into the European and U.S. markets, given positive results,” stated Pluristem Chairman and CEO Zami Aberman.

The pivotal study for Pluristem’s PLacental eXpanded (PLX) PAD cells in the treatment of CLI is a double blind, randomized, placebo controlled trial in an estimated 250 patients with CLI Rutherford Category 5 who are unsuitable candidates for revascularization. Patients will be treated with 300 million cells or placebo, injected twice intramuscularly (IM), with the second dose administered two months after the first. The primary endpoint will be time to amputation and death.

Patients will be enrolled in clinical sites located throughout Europe and the U.S. Pluristem’s intention is to utilize this study as a single pivotal trial for regulatory approval in both regions. PLX-PAD cells are designed to address the $12 billion global CLI market.

The Berlin-Brandenburg Center for Regenerative Therapies (BCRT) was founded as a cooperative research institution of the Charité University Hospital in Berlin, which is one of the largest university hospitals in Europe, and Germany’s largest research association, the Helmholtz Association. The goal of the BCRT is to enhance endogenous regeneration by cells, biomaterials, and factors which can be used to develop and implement innovative therapies and products. The primary focus of the BCRT is on diseases of the immune system, the musculoskeletal system and the cardiovascular system for which currently only unsatisfactory treatment options are available.