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.

UCLA Researchers Create Skeletal Muscle From Stem Cells

Discovery is major step towards a stem cell replacement therapy for Duchenne Muscular Dystrophy

UCLA scientists have developed a new strategy to efficiently isolate, mature and transplant skeletal muscle cells created from human pluripotent stem cells, which can produce all cell types of the body. The findings are a major step towards developing a stem cell replacement therapy for muscle diseases including Duchenne Muscular Dystrophy, which affects approximately 1 in 5,000 boys in the U.S. and is the most common fatal childhood genetic disease.

The study was published in the journal Nature Cell Biology by senior author April Pyle, associate professor of microbiology, immunology and molecular genetics and member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. Using the natural human development process as a guide, the researchers developed ways to mature muscle cells in the laboratory to create muscle fibers that restore dystrophin, the protein that is missing in the muscles of boys with Duchenne.

Without dystrophin, muscles degenerate and become progressively weaker. Duchenne symptoms usually begin in early childhood; patients gradually lose mobility and typically die from heart or respiratory failure around age 20. There is currently no way to reverse or cure the disease.

For years, scientists have been trying different methods that direct human pluripotent stem cells to generate skeletal muscle stem cells that can function appropriately in living muscle and regenerate dystrophin-producing muscle fibers. However, the study led by Pyle found that the current methods are inefficient; they produce immature cells that are not appropriate for modeling Duchenne in the laboratory or creating a cell replacement therapy for the disease.

“We have found that just because a skeletal muscle cell produced in the lab expresses muscle markers, doesn’t mean it is fully functional,” said Pyle. “For a stem cell therapy for Duchenne to move forward, we must have a better understanding of the cells we are generating from human pluripotent stem cells compared to the muscle stem cells found naturally in the human body and during the development process.”

By analyzing human development, the researchers found a fetal skeletal muscle cell that is extraordinarily regenerative. Upon further analysis of these fetal muscle cells two new cell surface markers called ERBB3 and NGFR were discovered; this enabled the reserchers to precisely isolate muscle cells from human tissue and separate them from various cell types created using human pluripotent stem cells.

Once they were able to isolate  skeletal muscle cells using the newly identified surface markers, the research team matured those cells in the lab to create dystrophin-producing muscle fibers. The muscle fibers they created were uniformily muscle cells, but the fibers were still smaller than those found in real human muscle.

“We were missing another key component,” said Michael Hicks, lead author of the study. The skeletal muscle cells were not maturing properly, he explained. “We needed bigger, stronger muscle that also had the ability to contract.”

Once again, the team looked to the natural stages of human development for answers. Hicks discovered that a specific cell signaling pathway called TGF Beta needs to be turned off to enable generation of skeletal muscle fibers that contain the proteins that help muscles contract. Finally, the team tested their new method in a mouse model of Duchenne.

“Our long term goal is to develop a personalized cell replacement therapy using a patient’s own cells to treat boys with Duchenne,” said Hicks. “So, for this study we followed the same steps, from start to finish, that we’d follow when creating these cells for a human patient.”

First, the Duchenne patient cells were reprogrammed to become pluripotent stem cells. The researchers then removed the genetic mutation that causes Duchenne using the gene editing technology CRISPR-Cas9. Using the ERBB3 and NGFR surface markers, the skeletal muscle cells were isolated and then injected into mice at the same time a TGF Beta inhibitor was administered.

“The results were exactly what we’d hoped for,” said Pyle. “This is the first study to demonstrate that functional muscle cells can be created in a laboratory and restore dystrophin in animal models of Duchenne using the human development process as a guide.”

Further research will focus on generating skeletal muscle stem cells that can respond to continuous injury and regenerate new muscle long-term using the team’s new isolation and maturation strategy.

US FDA IND Allows for the Initiation of a US Clinical Trial of Novel Cell Pouch for the Treatment of Type 1 Diabetes backed by JDRF

Sernova Corp, a clinical stage company developing regenerative medicine technologies for the long-term treatment of diseases including diabetes and hemophilia, is pleased to announce it has received US Food and Drug Administration (FDA) notice of allowance for its IND for a new human clinical trial with the Cell Pouch System (TM) (CPS) in the United States.

Sernova plans to initiate the new clinical trial under this US IND to investigate the Cell Pouch for treatment of type 1 diabetes (T1D) in individuals with hypoglycemia unawareness. The trial is a Phase I/II prospective single arm study of islets transplanted into the subcutaneously implanted Cell Pouch. The primary objective of the study is to demonstrate safety and tolerability of islet transplantation into the Cell Pouch and the secondary objective is to assess efficacy through a series of defined measures.

JDRF has previously committed to provide Sernova up to $2.45 million USD to support the clinical trial.

“Hypoglycemia unawareness is a serious consequence of type 1 diabetes,” said Derek Rapp, President & CEO, JDRF International. “We are excited to see progress in this and other potentially life-saving JDRF-funded research, which could help prevent people with hypoglycemia unawareness from experiencing dangerous lows, as we strive to achieve our vision of a world without T1D.” JDRF is the leading global organization funding type 1 diabetes (T1D) research. The mission is to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications. To accomplish this, JDRF has invested nearly $2 billion in research funding since our inception.

JDRF is an organization built on a grassroots model of people connecting in their local communities, collaborating regionally for efficiency and broader fundraising impact, and uniting on a national stage to pool resources, passion, and energy. We collaborate with academic institutions, policymakers, and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D

“We are extremely enthusiastic about the promise of Sernova’s regenerative medicine platform to provide a new therapeutic option for diabetes patients with hypoglycemia unawareness. We believe Sernova’s multiple advancing cell based therapies have the potential to deliver significant improvement in the quality of life of patients suffering from diabetes and other debilitating diseases,” said Dr. Philip Toleikis, Sernova’s president & CEO.

The study is a Phase I/II single site, single arm, Company sponsored trial. Following approval by the Institutional Review Board, patients with hypoglycemia unawareness will be enrolled into the study under informed consent. Patients will then be implanted with the Cell Pouch including sentinel devices.  Following vascularized tissue development, a dose of purified islets under strict release criteria will be transplanted into the Cell Pouch and patients followed for safety and efficacy measures for approximately six months. At this point a decision will be made whether to transplant a second islet dose with subsequent safety and efficacy follow up. Patients will then be further followed for one year.

“Sernova’s FDA clearance to commence human clinical trials in the United States is an exciting step forward in diabetes research, initially focused to reduce the risk of hypoglycemia unawareness, a complication in which a patient is unaware of a deep drop in blood sugar that can have life threatening consequences,” said Dave Prowten, President and CEO of JDRF Canada. “This is also an example of the international collaboration fostered by JDRF-funded projects to accelerate transformative research to benefit the T1D community,” added Mr. Prowten.

The Cell Pouch is a novel, proprietary, scalable, implantable macroencapsulation device for the long-term survival and function of therapeutic cells (donor, stem cell derived cells and xenogeneic cells) which then release proteins and/or hormones as required to treat disease. The device is designed upon implantation to incorporate with tissue, forming highly vascularized tissue chambers for the transplantation and function of therapeutic cells. The device with therapeutic cells has been shown to provide long term safety and efficacy in small and large animal models of diabetes and has been proven to provide a biologically compatible environment for insulin producing cells in humans.

T1D is a life-threatening disease in which the body’s immune system mistakenly attacks and kills the pancreatic cells that produce insulin—a hormone that is essential for life because of its role to help the body use glucose. The existing standard of care for patients with TID is suboptimal.  To date, there is no cure for T1D, and people living with the disease are dependent on exogenous insulin therapy to help keep their blood-sugar levels from spiking too high, which can lead to long-term complications such as kidney and heart diseases or an acute, potentially deadly health crisis. Present-day insulin therapy is, however, an imperfect treatment method that requires people with T1D to carefully monitor their blood sugar throughout the day and take multiple, calculated doses of insulin based on food intake, exercise, stress, illness and other factors. A miscalculation or unexpected variable leading to high or low blood sugar episodes are daily threats, and only a third of people with T1D achieve their long-term blood glucose targets, placing them at risk for T1D-related health complications.

Sernova Corp is developing disruptive regenerative medical technologies using a medical device and immune protected therapeutic cells to improve the treatment and quality of life of people with chronic metabolic diseases such as insulin-dependent diabetes, blood disorders including hemophilia, and other diseases treated through replacement of proteins or hormones missing or in short supply within the body. For more information, please visit www.sernova.com

For more information, please visit jdrf.org or follow us on Twitter: @JDRF

Towards a safe and scalable cell therapy for type 1 diabetes by simplifying beta cell differentiation

More than 36 million people globally are affected by type 1 diabetes (T1D), a lifelong disorder where insulin producing cells are attacked and destroyed by the immune system resulting in deficient insulin production that requires daily blood glucose monitoring and administration of insulin. While successful outcomes from islet transplantations have been reported, very few patients can benefit from this therapeutic option due to limited access to cadaveric donor islets. Human pluripotent stem cell (hPSCs) could offer an unlimited and invariable source of insulin-producing beta cells for treatments of a larger population of T1D patients.

With the vision of providing a cell therapy for type 1 diabetes patients, scientists at the University of Copenhagen have identified a unique cell surface protein present on human pancreatic precursor cells providing for the first time a molecular handle to purify the cells whose fate is to become cells of the pancreas – including insulin producing cells. The work, outlined in a landmark study entitled ‘Efficient generation of glucose-responsive beta cells from isolated GP2+ human pancreatic progenitors’ has just been published in Cell Reports and is available here.

A biomarker to clearly separate cell populations is a holy grail of cell therapy research for the reasons of safety and end product consistency. By using this cell surface marker, the researchers have engineered a streamlined and simplified differentiation process to generate insulin-producing cells for future treatment of type 1 diabetes patients. The process enables cost-efficient manufacturing and exploits at its core an intermediate cell bank of purified pancreatic precursor cells.

The discovery of the new marker has also enabled the researchers to streamline and refine the process of producing hPSC-derived insulin cells.

“By starting with a purified population of pancreatic precursor cells instead of immature stem cells we eliminate the risk of having unwanted tumorigenic cells in the final cell preparation and thus generate a safer cell product for therapeutic purposes”, explains Assistant Professor Jacqueline Ameri, first author on the paper.

Professor Henrik Semb, Managing Director of the Danish stem cell centre (DanStem) explains:

“Although significant progress has been made towards making insulin producing beta cells in vitro (in the lab), we are still exploring how to mass-produce mature beta cells to meet the future clinical needs. Our current study contributes with valuable knowledge on how to address key technical challenges such as safety, purity and cost-effective manufacturing, aspects that if not confronted early on, could hinder stem cell therapy from becoming a clinically and commercially viable treatment in diabetes.”

Indeed, Semb’s group is among the first to directly address not only the therapeutic concept but to incorporate very early the manufacturing considerations in their process to ensure that future commercialization will be possible.

To translate the current findings into a potential treatment of type 1 diabetes, Ameri and Semb aim to commercialize their recent patent pending innovations by establishing the spin out company PanCryos. PanCryos has assembled a team with experts in stem cell biology, islet transplantations, business and regulatory guidance and is currently funded by a KU POC grant and a pre-seed funding from Novo Seeds.

“In parallel with other groups in this field, we have been working on a cell therapy for type 1 diabetes for many years. What is unique about our approach is the simplification of our protocol which acknowledges that eventually the process will need to be scaled up for manufacturing. PanCryos is being established to ensure the development of the first scalable allogenic cell therapy for type 1 diabetes so we can offer the route to an affordable therapy by providing a product that will not be too expensive to produce, as has occurred too often in the developing cell therapy field”, explains Jacqueline Ameri, co-founder and CEO for PanCryos.

T-cells lacking HDAC11 enzyme perform more effectively in destroying cancer cells

Researchers at the George Washington University (GW) Cancer Center have discovered a new role for the enzyme, histone deacetylase 11 (HDAC11), in the regulation of T-cell function.

T-cells can infiltrate tumors with the purpose of attacking the cancer cells. However, prior studies have found that the T-cells group around the tumor, but do not perform the job that they are meant to.

“The goal of the T-cell is to destroy the cancer tumor cells,” Eduardo M. Sotomayor, MD, director of the GW Cancer Center and senior author of the study, explained. “We wanted to look at and understand the mechanisms that allowed crosstalk between the tumor and the T-cells that stopped the T-cells from doing their job.”

The recent research, published in the journal Blood, centered on the discovery of “epigenetic checkpoints” in T-cell function in an effort to explain how and why these cells are modified to behave differently. The study found that when HDAC11 was removed the T-cells, they were more primed to attack the tumor.

More importantly, this research highlights that HDAC11, which was the last of 11 HDAC to be discovered, should be treated as an immunotherapeutic target.

While the study focused on the T-cells around a lymphoma tumor, this research is pertinent to all types of cancer. The goal for the team was to find a way to activate the T-cells so that they could destroy the tumor. However, the process of cell activation does need to be refined and handled carefully.

“We don’t want T-cells to be easily activated, as they can cause harm to the host — the patient. So we want to look at possible methods and therapies to activate the T-cells when they need to work,” said Sotomayor.

“The next step is to perform preclinical studies with specific inhibitors of HDAC11 alone and in tandem with other existing immunotherapies, such as anti-PD1/anti-PDL1 antibodies, in order to find the most potent combination. Our goal is to make the T-cells better at destroying cancer tumors.”

This study represents a step forward in understanding the underlying mechanisms of T-cell function and epigenetic regulation of the HDAC11 enzyme.

Pioneering cancer gene therapy by Novartis backed by U.S. panel

(Reuters) – Novartis AG’s (NOVN.S) pioneering cancer drug won the backing of a federal advisory panel on Wednesday, paving the way for the first gene therapy to be approved in the United States.

An advisory panel to the Food and Drug Administration voted 10-0 that the drug, tisagenlecleucel, should be approved to treat patients with relapsed B-cell acute lymphoblastic leukemia (ALL), the most common form of U.S. childhood cancer.

The FDA is not obliged to follow the recommendations of its advisers but typically does so. The agency is expected to rule on the drug by the end of September.

Approval of tisagenlecleucel would have significant implications not only for Novartis but for companies developing similar treatments, including Kite Pharma Inc (KITE.O), Juno Therapeutics Inc (JUNO.O) and bluebird bio Inc (BLUE.O).

All four are developing chimeric antigen receptor T-cell therapies (CAR-T), which harness the body’s own immune cells to recognize and attack malignant cells.

If approved, the drugs, which are infused just once, are expected to cost up to $500,000 and generate billions of dollars for their developers. Success would also help advance a cancer-fighting technique that scientists have been trying to perfect for decades and lift the broader field of cell therapy.

“In the last five years there have been a significant number of cell therapy companies that have gone public or gotten investment in hopes of moving this type of therapy forward,” said Reni Benjamin, an analyst at Raymond James. “This is our first glimpse from a commercial and regulatory perspective about how the FDA is thinking about this space.”

A clinical trial of Novartis’s drug showed that 83 percent of patients who had relapsed or failed chemotherapy, achieved complete or partial remission three months post infusion. Patients with ALL who fail chemotherapy typically have only a 16 to 30 percent chance of survival.

Novartis is also testing the drug in diffuse large b-cell Lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, as is Kite. Part of the competitive landscape will include which company is best able to manufacture its product most efficiently and reliably.

The products are made by extracting and isolating a patient’s T cells, genetically engineering them to recognize and target specific cancer cells, and then infusing them back into the patient. Novartis said the entire process will take 22 days by the time it is launched.

More than half of patients experienced a serious complication known as cytokine release syndrome (CRS) which occurs when the body’s immune system goes into overdrive. Doctors were able to manage the condition and the syndrome caused no deaths.

The FDA expressed concern that the drug could cause new malignancies over the long term, but panelists generally felt that risk was low.

Reporting by Toni Clarke in Washington; Editing by Lisa Shumaker

Cardiac stem cells from heart disease patients may be harmful

Patients with severe and end-stage heart failure have few treatment options available to them apart from transplants and “miraculous” stem cell therapy. But a new Tel Aviv University study finds that stem cell therapy may, in fact, harm heart disease patients.

The research, led by Prof. Jonathan Leor of TAU’s Sackler Faculty of Medicine and Sheba Medical Center and conducted by TAU’s Dr. Nili Naftali-Shani, explores the current practice of using cells from the host patient to repair tissue — and contends that this can prove deleterious or toxic for patients. The study was recently published in the journal Circulation.

“We found that, contrary to popular belief, tissue stem cells derived from sick hearts do not contribute to heart healing after injury,” said Prof. Leor. “Furthermore, we found that these cells are affected by the inflammatory environment and develop inflammatory properties. The affected stem cells may even exacerbate damage to the already diseased heart muscle.”

Tissue or adult stem cells — “blank” cells that can act as a repair kit for the body by replacing damaged tissue — encourage the regeneration of blood vessel cells and new heart muscle tissue. Faced with a worse survival rate than many cancers, many heart failure patients have turned to stem cell therapy as a last resort.

“But our findings suggest that stem cells, like any drug, can have adverse effects,” said Prof. Leor. “We concluded that stem cells used in cardiac therapy should be drawn from healthy donors or be better genetically engineered for the patient.”

Hope for improved cardiac stem cell therapy

In addition, the researchers also discovered the molecular pathway involved in the negative interaction between stem cells and the immune system as they isolated stem cells in mouse models of heart disease. After exploring the molecular pathway in mice, the researchers focused on cardiac stem cells in patients with heart disease.

The results could help improve the use of autologous stem cells — those drawn from the patients themselves — in cardiac therapy, Prof. Leor said.

“We showed that the deletion of the gene responsible for this pathway can restore the original therapeutic function of the cells,” said Prof. Leor. “Our findings determine the potential negative effects of inflammation on stem cell function as they’re currently used. The use of autologous stem cells from patients with heart disease should be modified. Only stem cells from healthy donors or genetically engineered cells should be used in treating cardiac conditions.”

The researchers are currently testing a gene editing technique (CRISPER) to inhibit the gene responsible for the negative inflammatory properties of the cardiac stem cells of heart disease patients. “We hope our engineered stem cells will be resistant to the negative effects of the immune system,” said Prof. Leor.

Tissue Engineering Advance Reduces Heart Failure in Model of Heart Attack

Researchers have grown heart tissue by seeding a mix of human cells onto a 1-micron-resolution scaffold made with a 3-D printer. The cells organized themselves in the scaffold to create engineered heart tissue that beats synchronously in culture. When the human-derived heart muscle patch was surgically placed onto a mouse heart after a heart attack, it significantly improved heart function and decreased the amount of dead heart tissue.

“Our novel technique is the first to achieve resolution of 1 micrometer or less,” the researchers reported in the journal Circulation Research. This tissue engineering advance is an important step toward the goal of preventing heart failure after a heart attack. Such heart failures account for nearly half of the 7.3 million worldwide heart disease-related deaths each year.

The heart cannot regenerate muscle tissue after a heart attack has killed part of the muscle wall. That dead tissue can strain surrounding muscle, leading to a lethal heart enlargement. It has long been the dream of heart experts to create new tissue that could replace damaged muscle and protect the heart from dilatation after a heart attack.

The researchers, led by Jianyi “Jay” Zhang, M.D., Ph.D., the University of Alabama at Birmingham, and Brenda Ogle, Ph.D., the University of Minnesota, modeled the scaffold after a three-dimensional scan of the extracellular matrix of a piece of mouse myocardial tissue. Extracellular matrix is the collection of compounds secreted by cells that gives structural support and cushioning to hold the tissue together.

Using multiphoton three-dimensional printing, the team then created crosslinks among extracellular proteins dissolved in a photoreactive gelatin. When the uncrosslinked gelatin was washed away, the photopolymerized extracellular protein scaffold that remained replicated the shape of the extracellular matrix, with hollows where cells had been.

This native-like scaffold was seeded with a mix of 50,000 cardiomyocytes, smooth muscle cells and endothelial cells derived from human-induced pluripotent stem cells, or hiPSCs. This cardiac muscle patch, about four one-thousandths of an inch thick and eight one-hundredths of an inch square began beating within one day of seeding, and the speed and strength of contractions increased significantly over the next week.

Researchers found that the scaffold had aligned the muscle cells properly, similar to native heart tissue, and the cells showed a smooth wave of electrical signal moving across the patch, a vital part of the electrophysiology that propagates contraction of the heart across the atria or ventricles. It appeared that the native-like structure of the scaffold contributed to the healthy electrical and mechanical function of the cells.

When two of the patches were transplanted onto an infarcted mouse heart, there was significant improvement in measures of cardiac function, blood vessel density and cell proliferation, and reduced infarct size and programmed cell death, or apoptosis.

“Thus, the hiPSC-derived cardiac muscle patches produced for this report may represent an important step toward the clinical use of 3-D-printing technology,” Zhang, Ogle and colleagues wrote. They also said, “To our knowledge, this is the first time modulated raster scanning has ever been successfully used to control the fabrication of a tissue-engineered scaffold, and consequently, our results are particularly relevant for applications that require the fibrillar and mesh-like structures present in cardiac tissue.”

TapImmune’s T-Cell Cancer Vaccine for Worldwide Eradication of Women’s Cancers

Early proof of efficacy, scalability with cost effective manufacturing, and testability in large Phase III FDA trials are the reasons why TapImmune (TPIV) is the leading T-cell cancer vaccine company and will dominate this space. World class collaborators including the Mayo Clinic, AstraZeneca (AZN), Sloan Kettering and Phase II trial funding from the U.S. Department of Defense prove this point.

Vaccines have eradicated numerous infectious diseases. Cancer is vaccine’s next target, powered by T-cells. White blood cells that are responsible for detecting foreign or abnormal cells including cancerous ones, T-cells specialize in seeking, attaching to, and destroying cancer cells with the help of the rest of the immune system.

Cunning cancer cells often find ways to con the immune system though, making them invisible to T-cells. TapImmune’s effective T-cell cancer vaccine activates cytotoxic T cells and directs them to see and attack specific types of cancer.  TapImmune’s vaccines are superior to other T-cell based cancer treatment candidates due to their powerful and unique combination of proprietary peptide antigens.

Stimulating both killer T-cells (CD8) and helper T-cells (CD4) creates sustained and long lasting tumor cell killing.  Roche’s (ROG:VS) Herceptin, a monoclonal antibody isn’t even designed to kill tumor cells, but in a market desperate for a solution, it has become standard of care by merely slowing down tumor growth. 2015 Herceptin sales exceeded $6.6 billion. If slowing down cancer makes Herceptin a blockbuster, then TapImmune’s cancer killing T-cell vaccine should become an uber-blockbuster and command sales far higher than Herceptin.

Early efficacy results in Phase I trials conducted at the prestigious Mayo Clinic show immune response to TapImmune’s T-cell vaccine in between 75% and 100% of patients treated. These impressive data were published in the Journal of Clinical Oncology and presented at oncology’s top scientific conference, ASCO, as well as at the San Antonio Breast Cancer Symposium.

Beyond efficacy, off-the-shelf platform technology is what sets TapImmune apart in the market and gives its T-cell cancer vaccines the dominant position.

While other cancer vaccines have shown promise, they have for the most part been autologous – meaning doctors take tumor cells from a specific person, process those cells into a vaccine, and reinsert this one-person-specific vaccine into that same person. This kind of personalized medicine is very expensive and difficult to run through large Phase III studies given the way FDA trials are conducted today.

TapImmune’s T-cell vaccines have been specifically designed for high efficacy, high scalability, cost effectiveness, and are ideally suited for large scale FDA testing. This makes them more likely to get FDA approved and reimbursed once on the market.

Today, TapImmune is testing its lead cancer vaccine TPIV-200 in two Phase II studies and is set to begin enrollment any day in two more Phase II studies. Should any of these four trials show promise, TapImmune will charge into larger scale Phase IIIs, armed with an off-the-shelf, consistently manufactured, low cost cancer vaccine that can be used as a therapeutic and prophylactic (preventative).

Indications are ovarian cancer and triple negative breast cancer, two of the hardest women’s cancers to treat. The breast cancer treatment market will top $20 billion by 2024 and ovarian cancer will be $1.4 billion by 2021 according to Decision Resources.

Instead of creating a specific vaccine for each person, TapImmune has selected excellent cancer targets including folate receptor alpha and HER2/neu, which are expressed on the surface of majority of tumor target cells. Deploying TapImmune’s proprietary antigen expression system, these antigens were selected from immune responses in patients to broadly stimulate T-helper cells, T-killer cells and T-memory cells.

Blockbuster Herceptin can only be used in 15-20% of the HER2/neu positive breast cancer population. Besting this by far, TapImmune’s T-cell cancer vaccine is applicable to over 50% of the HER2/neu patient population.

TapImmune vaccines cover about 85% of genotypes, offering broad population coverage from one easy to manufacture vaccine. With this effective formula, TapImmune can mass manufacture cancer vaccines that can be used on any person who needs it. No custom tailoring needed here.

HER2/neu is a valuable cancer target for both ovarian and colorectal cancer, both diseases where there are very few therapeutic options. In breast cancer as well, HER2/neu is overexpressed in ~ 30% of patients.

An equally powerful target is folate receptor alpha, overexpressed in 90% of ovarian cancer cells, over 80% of triple negative breast cancer, and 80% non-small cell lung cancer patients. In the US, approximately 30,000 ovarian cancer and 40,000 triple negative breast cancer patients are newly diagnosed every year. The only treatment options for these patients are surgery, radiation and chemotherapy. With time to recurrence being relatively short, survival prognosis is extremely poor after recurrence.

Fast Track and Orphan Drug designations have been granted by the U.S. FDA to TapImmune’s TPIV 200 in the treatment of ovarian cancer. There is every reason in the world for Fast Track to also be granted for a cancer vaccine to prevent recurrence in the breast cancer population.

Big pharma and the world’s leading medical institutions have independently vetted TapImmune’s technology.

A joint AstraZeneca-TapImmune Phase II ovarian cancer trial is now enrolling patients at the prestigious Sloan Kettering Institute. The trial is testing a combination therapy – TapImmune’s TPIV 200 and AstraZeneca’s durvalumab an anti-PD-L1 antibody, in 40 women who have high-grade ovarian cancer and have not been responsive to platinum chemotherapy, currently the standard of care for advanced ovarian cancer.

New stem cell delivery approach regenerates dental pulp-like tissue in a rodent model

When a tooth is damaged, either by severe decay or trauma, the living tissues that comprise the sensitive inner dental pulp become exposed and vulnerable to harmful bacteria. Once infection takes hold, few treatment options–primarily root canals or tooth extraction–are available to alleviate the painful symptoms.

Researchers at Tufts University School of Dental Medicine (TUSDM) now show that using a collagen-based biomaterial to deliver stem cells inside damaged teeth can regenerate dental pulp-like tissues in animal model experiments. The study, published online in the Journal of Dental Research on Dec. 15, supports the potential of this approach as part of a strategy for restoring natural tooth functionality.

“Endodontic treatment, such as a root canal, essentially kills a once living tooth. It dries out over time, becomes brittle and can crack, and eventually might have to be replaced with a prosthesis,” said senior study author Pamela Yelick, PhD, professor at TUSDM and director of its Division of Craniofacial and Molecular Genetics. “Our findings validate the potential of an alternative approach to endodontic treatment, with the goal of regenerating a damaged tooth so that it remains living and functions like any other normal tooth.”

Yelick and her colleagues, including lead study author Arwa Khayat, former graduate student in dental research at TUSDM, examined the safety and efficacy of gelatin methacrylate (GelMA)–a low-cost hydrogel derived from naturally occurring collagen–as a scaffold to support the growth of new dental pulp tissue. Using GelMA, the team encapsulated a mix of human dental pulp stem cells–obtained from extracted wisdom teeth–and endothelial cells, which accelerate cell growth. This mix was delivered into isolated, previously damaged human tooth roots, which were extracted from patients as part of unrelated clinical treatment and sterilized of remaining living tissue. The roots were then implanted and allowed to grow in a rodent animal model for up to eight weeks.

The researchers observed pulp-like tissue inside the once empty tooth roots after two weeks. Increased cell growth and the formation of blood vessels occurred after four weeks. At the eight-week mark, pulp-like tissue filled the entire dental pulp space, complete with highly organized blood vessels populated with red blood cells. The team also observed the formation of cellular extensions and strong adhesion into dentin–the hard, bony tissue that forms the bulk of a tooth. The team saw no inflammation at the site of implantation, and found no inflammatory cells inside implanted tooth roots, which verified the biocompatibility of GelMA.

Control experiments, which involved empty tooth roots or tooth roots with only GelMA and no encapsulated cells, showed significantly less growth, unorganized blood vessel formation, and poor or nonexistent dentin attachment.

The results support GelMA-encapsulated human dental stem cells and umbilical vein endothelial cells as part of a promising strategy to restore normal tooth function, according to the study authors. However, they note that the current study was limited to partial tooth roots and did not examine nerve formation in regenerated dental pulp tissue. They emphasize the need for additional safety and efficacy studies in larger animal models before human clinical trials can be considered.

“A significant amount of work remains to be done, but if we can extend and validate our findings in additional experimental models, this approach could become a clinically relevant therapy in the future,” said Yelick, who is also a member of the Cell, Molecular & Developmental Biology; Genetics; and Pharmacology & Experimental Therapeutics programs at the Sackler School of Graduate Biomedical Sciences at Tufts. “Our work is early stage, but we are excited for the possibility of someday giving patients the option of regenerating their own teeth.” Continue reading “New stem cell delivery approach regenerates dental pulp-like tissue in a rodent model”

Athersys Receives FDA Agreement Under Special Protocol Assessment for Phase 3 Study of Multistem® Treatment for Ischemic Stroke

Athersys, Inc.  announced that it has received agreement from the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the design and planned analysis of a Phase 3 clinical trial of Athersys’ novel MultiStem® cell therapy product for the treatment of ischemic stroke.  The SPA provides agreement from the FDA that the protocol design, clinical endpoints, planned conduct and statistical analyses encompassed in Athersys’ planned Phase 3 study are acceptable to support a regulatory submission for approval of the MultiStem product for treating ischemic stroke patients.  The results from the Phase 3 trial entitled, “MultiStem Administration for Stroke Treatment and Enhanced Recovery Study-2” (MASTERS-2), together with other available clinical data, would provide the foundation of the regulatory package to be submitted for marketing approval.

“This is a major accomplishment for Athersys, as it clearly defines the development and regulatory pathway for the approval of MultiStem cell therapy for the treatment of ischemic stroke,” stated Dr. Gil Van Bokkelen, Chairman and Chief Executive Officer of Athersys.  “We would like to thank the FDA for its engagement and guidance in this process, and the clinical investigators who have been critical to our development of this potential treatment for stroke.

“The SPA is important in clarifying and de-risking an accelerated development pathway for us because it means that the successful completion of the MASTERS-2 trial, together with other available clinical data, could enable us to apply for marketing approval in the United States,” continued Dr. Van Bokkelen. “With this goal now achieved, we will continue the process of engagement with the FDA, European and Canadian regulators, as well as the many sites that have expressed an interest in participating in the study, to complete other necessary activities prior to trial initiation.  We intend to be prepared to launch the trial in 2017 and will update our stockholders as we move forward with these plans.”

The MASTERS-2 clinical trial will be a randomized, double-blind, placebo-controlled clinical trial designed to enroll 300 patients in North America and Europe who have suffered moderate to moderate-severe ischemic stroke.  The enrolled subjects will receive either a single intravenous dose of MultiStem cell therapy or placebo, administered within 18-36 hours of the occurrence of the stroke, in addition to the standard of care. The primary endpoint will evaluate disability using modified Rankin Scale (mRS) scores at three months, comparing the distribution, or the “shift”, between the MultiStem treatment and placebo groups. The mRS shift analysis considers disability across the full spectrum, enabling recognition of large and small improvements in disability and differences in mortality and other serious outcomes, among strokes of different severities. The study will also assess Excellent Outcome (mRS ≤1, NIHSS ≤1, and Barthel Index ≥95) at three months and one year as key secondary endpoints.  Additionally, the study will consider other measures of functional recovery, biomarker data and clinical outcomes, including hospitalization, mortality and life-threatening adverse events, and post-stroke complications such as infection.  Recently, Athersys’ partner, HEALIOS KK, successfully completed a review from Japan’s Pharmaceutical and Medical Devices Agency of its Clinical Trial Notification, allowing it to commence a clinical trial evaluating the safety and efficacy of the administration of Athersys’ MultiStem cell therapy for the treatment of ischemic stroke in Japan.

Dr. David Hess, a lead clinical investigator in the planned MASTERS-2 trial, stroke specialist and Professor & Chairman of the Department of Neurology at the Medical College of Georgia at Augusta University, commented, “We were very encouraged by the results from the Phase 2 study, and we believe that MultiStem therapy has the potential to help many stroke patients who do not have access to or did not benefit from other therapies, such as tPA or mechanical thrombectomy.  We are excited to be a lead site in the MASTERS-2 trial and look forward to getting started. If the trial is successful, then MultiStem could represent a major advancement in stroke clinical care.”

MultiStem cell therapy is a patented regenerative medicine product that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of therapeutic factors produced in response to signals of inflammation and tissue damage.  MultiStem therapy’s potential for multidimensional therapeutic impact distinguishes it from traditional biopharmaceutical therapies focused on a single mechanism of benefit. The product represents a unique “off-the-shelf” stem cell product that can be manufactured in a scalable manner, may be stored for years in frozen form, and is administered without tissue matching or the need for immune suppression. Based upon its efficacy profile, its novel mechanisms of action, and a favorable and consistent safety profile demonstrated in both preclinical and clinical settings, MultiStem therapy could provide a meaningful benefit to patients, including those suffering from serious diseases and conditions with unmet medical need. Athersys has forged strategic partnerships and a broad network of collaborations to develop MultiStem cell therapy for a variety of indications, with an initial focus in the neurological, cardiovascular and inflammatory and immune disorder areas.

Stroke represents an area where the clinical need is particularly significant, since it is a leading cause of death and serious disability worldwide, with a substantially impaired quality of life for many stroke victims. Currently, there are nearly 17 million people that suffer a stroke globally and more than two million stroke victims each year in the United States, Europe and Japan, combined. Ischemic strokes, which represent the most common form of stroke, are caused by a blockage of blood flow in the brain that cuts off the supply of oxygen and nutrients and can result in long-term or permanent disability due to neurological damage. Unfortunately, current therapeutic options for ischemic stroke victims are limited, since the only available therapies, administration of the clot dissolving agent tPA, or “thrombolytic,” or surgical intervention using mechanical reperfusion to remove the clot, must be conducted within several hours of the occurrence of the stroke. As a consequence of this limited time window, only a small percentage of stroke victims are treated with the currently available therapy—most simply receive supportive or “palliative” care. The long-term costs of stroke are substantial, with many patients requiring extended hospitalization, extended physical therapy or rehabilitation (for those patients that are capable of entering such programs), and many require long-term institutional or family care.

Athersys Gets Nod from PMDA in Japan to Start Trial for the Treatment of Ischemic Stroke with MultiStem®

Athersys, Inc. got a major nod from Japan’s Pharmaceutical and Medical Devices Agency (PMDA) review of the Clinical Trial Notification (CTN), allowing the commencement by HEALIOS K.K. (Healios) of a confirmatory clinical trial evaluating the safety and efficacy of administration of MultiStem®, Athersys’ novel cell therapy product, for the treatment of ischemic stroke in Japan (also designated by Healios as HLCM051 in Japan).

In accordance with the regulatory system in Japan, a CTN is equivalent to an Investigational New Drug application, or IND, under the regulatory system used in the United States.  This clinical trial to be conducted in Japan is part of a partnership and license agreement between Healios and Athersys, focused on the development and commercialization in Japan of novel cellular therapies, including MultiStem, for the treatment of ischemic stroke and potentially other indications.  The study design was accepted as proposed to PMDA in the CTN.

“This announcement demonstrates exciting and important progress, achieved within less than eight months of launching the collaboration, and reflects the tremendous effort on the part of the teams at both organizations that are working together to advance this program in a highly focused and efficient manner,” said Gil Van Bokkelen, Ph.D., Chairman and Chief Executive Officer of Athersys.  “The development approach being taken by Healios and Athersys in Japan is consistent with the approach we plan to implement in a separate international study. Both studies are designed to provide the confirmatory evidence that we believe will put us in a strong position to obtain approval in one of the greatest areas of unmet clinical need in medicine today.”

The planned study will be a randomized, double-blind, placebo-controlled clinical trial conducted at hospitals in Japan that have extensive experience at providing care for stroke victims.  Based on the experience from the B01-02 study, subjects enrolled in the trial will receive either a single dose of MultiStem or placebo, administered within 18–36 hours of the occurrence of the stroke, in addition to standard of care.  As previously disclosed, the study will evaluate patient recovery through approximately 90 days following initial treatment based on Excellent Outcome and other neurological, functional and clinical endpoints.  Additional patient follow up will occur through one year, and other design elements of the Japan trial are consistent with a planned international Phase 3 study, and what has been described previously at the Stroke 2016 conference held in Sapporo earlier this year.

The trial in Japan follows a Phase 2 study completed by Athersys, referred to as the B01-02 trial, which was conducted at 33 clinical sites in the United States and United Kingdom.  The study evaluated the safety and effectiveness of the intravenous administration of MultiStem cells within 24–48 hours after the occurrence of a moderate to severe stroke.  The evaluable patient population comprised 126 subjects who were treated with MultiStem therapy or placebo.

As disclosed previously, intravenous administration of MultiStem following an ischemic stroke was well tolerated, consistent with observations from other clinical trials evaluating the safety of MultiStem treatment.  Additionally, among all evaluable subjects in the B01-02 study, a greater percentage of subjects in the MultiStem group (15.4%) had an Excellent Outcome (mRS ≤1, NIHSS ≤1, and Barthel Index ≥95) at day 90 compared to the placebo group (6.6%) (p=0.10).  At one year, a greater percentage of subjects in the MultiStem group had an Excellent Outcome compared to the placebo group (23.1% vs. 8.2%, p=0.02). For the MultiStem subjects treated within 36 hours of the stroke (i.e. the target population in the planned Japan study), the difference in Excellent Outcome was even greater (e.g., at one year, 29.0% vs. 8.2%, p<0.01).  Likewise, other measures of functional recovery, including the mRS distribution or “shift” analysis, biomarker data and clinical outcomes, including shorter hospitalization, less time in the Intensive Care Unit, and lower rates of mortality and life threatening adverse events, suggest that MultiStem treated patients experienced an improved recovery from post-stroke neurological complications.

“We are excited about reaching this point and about the degree of enthusiasm expressed for the study at the clinical investigators meeting recently held in Tokyo.  With the CTN now in effect, the next steps in the process prior to the initiation of enrollment include obtaining Institutional Review Board approval and finalizing agreements with each of the participating clinical sites.  In the near term, Healios will be focusing on these activities, while Athersys provides support in other areas in preparation for the commencement of enrollment,” concluded Dr. Van Bokkelen.

Stroke represents an area where the clinical need is particularly significant, since it is a leading cause of death and serious disability worldwide, with a substantially impaired quality of life for many stroke victims. Currently, there are nearly 17 million people that suffer a stroke globally and more than two million stroke victims each year in the United States, Europe and Japan, combined. Ischemic strokes, which represent the most common form of stroke, are caused by a blockage of blood flow in the brain that cuts off the supply of oxygen and nutrients and can result in long-term or permanent disability due to neurological damage. Unfortunately, current therapeutic options for ischemic stroke victims are limited, since the only available therapies, administration of the clot dissolving agent tPA, or “thrombolytic,” or surgical intervention using mechanical reperfusion to remove the clot, must be conducted within several hours of the occurrence of the stroke. As a consequence of this limited time window, only a small percentage of stroke victims are treated with the currently available therapy—most simply receive supportive or “palliative” care. The long-term costs of stroke are substantial, with many patients requiring extended hospitalization, extended physical therapy or rehabilitation (for those patients that are capable of entering such programs), and many require long-term institutional or family care.

Novartis Dissolves Its Cell Therapy Unit; 120 Positions Eliminated

Novartis AG said it will fold its specialized cell and gene therapies unit into other parts of the company, leading to about 120 job cuts months before seeking approval for a new type of cancer treatment.

Cell and gene therapy development will no longer be housed in a separate division, the Basel, Switzerland-based company said Wednesday. The change won’t affect a plan to apply for U.S. approval early next year for a type of cell therapy, called a CAR-T, for children with an aggressive form of blood cancer, Novartis said. The therapy, known as CTL019, will be submitted for European approval later next year.

“Novartis is committed to the ongoing development of CAR-T therapies and remains well positioned to successfully launch CTL019,” the company wrote in a statement.

The Swiss drugmaker, Europe’s second-largest by sales, in May said it would create separate units for cancer treatments and for other medicines following the acquisition of oncology assets from GlaxoSmithKline Plc. While an isolated cell-therapy unit worked well under the previous structure, work on such medicines will be more efficient with the reorganization, Novartis said. Most of the affected jobs are in the U.S.

“Today’s news on Novartis is really a pattern seen with other bigger pharmaceuticals companies such as Pfizer.” stated Karine Kleinhaus, M.D., M.P.H., is Divisional Vice President, North America at Pluristem Therapeutics., a clinical-stage biotechnology company using placental cells

“Big pharma has found that focusing on licensing deals with smaller, focused biotechnology companies is the better route as these biotechs have focused their businesses, making them nimble and able to deal effectively with every aspect of the discovery and development of new therapies, including the complex manufacturing needed to produce highly sensitive biologics. With big pharma cutting down on R&D teams, smaller mid and late-stage firms like Pluristem, can step in with completed early R&D and commercial-grade manufacturing, as well as late-stage clinical trials that are under way,” add Dr. Kleinhaus.

Breakthrough in Understanding How Stem Cells Become Specialized

Scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) have made a major advance in understanding how the cells of an organism, which all contain the same genetic information, come to be so diverse. A study published today in Molecular Cell shows that a protein called OCT4 narrows down the range of cell types that stem cells can become. The findings could impact efforts to produce specific types of cells for future therapies to treat a broad range of diseases, as well as aid the understanding of which cells are affected by drugs that influence cell specialization.

“We found that the stem cell-specific protein OCT4 primes certain genes that, when activated, cause the cell to differentiate, or become more specialized,” said Laszlo Nagy, M.D., Ph.D., professor and director of the Genomic Control of Metabolism Program and senior author of the study. “This priming customizes stem cells’ responses to signals that induce differentiation and makes the underlying genetic process more efficient.”

Differentiation matters
As an organism—such as a human—develops from its simplest, earliest form into maturity, its cells transition from a highly flexible state—stem cells—to more specialized types that make up its tissues. Many labs are trying to recapitulate this process to generate specific types of cells that could be transplanted into patients to treat disease. For example, pancreatic beta cells could treat diabetes, and neurons that produce dopamine could treat Parkinson’s.

What OCT4 does
OCT4 is a transcription factor—a protein that regulates gene activity—that maintains stem cells’ ability to give rise to any tissue in the body. OCT4 works by sitting on DNA and recruiting factors that either help initiate or repress the reading of specific genes.

The new study shows that, at certain genes, OCT4 also collaborates with transcription factors that are activated by external signals, such as the retinoic acid (vitamin A) receptor (RAR) and beta-catenin, to turn on their respective genes. Vitamin A converts stem cells to neuronal precursors, and activation of beta-catenin by Wnt can either support pluripotency or promote non-neural differentiation, depending on what other signals are present. Recruitment of these factors ‘primes’ a subset of the genes that the signal-responsive factors can activate.

The big picture
“Our findings suggest a general principle for how the same differentiation signal induces distinct transitions in various types of cells,” added Nagy. “Whereas in stem cells, OCT4 recruits the RAR to neuronal genes, in bone marrow cells, another transcription factor would recruit RAR to genes for the granulocyte program. Which factors determine the effects of differentiation signals in bone marrow cells—and other cell types—remains to be determined.”

Next steps
“In a sense, we’ve found the code for stem cells that links the input—signals like vitamin A and Wnt—to the output—cell type,” said Nagy. “Now we plan to explore whether other transcription factors behave similarly to OCT4—that is, to find the code in more mature cell types.

“If other factors also have this dual function—both maintaining the current state and priming certain genes to respond to external signals—that would answer a key question in developmental biology and advance the field of stem cell research.”

Sanford Burnham Prebys Medical Discovery Institute (SBP) is an independent nonprofit medical research organization that conducts world-class, collaborative, biological research and translates its discoveries for the benefit of patients. SBP focuses its research on cancer, immunity, neurodegeneration, metabolic disorders and rare children’s diseases. The Institute invests in talent, technology and partnerships to accelerate the translation of laboratory discoveries that will have the greatest impact on patients.

Joint Research Collaboration Aims to Advance Human Clinical Trials for the Treatment of Hypoglycemic Unawareness Patients with Severe Type 1 Diabetes

A new research funding agreement between the Juvenile Diabetes Research Foundation (JDRF) and Sernova, a clinical-stage regenerative medicine biotech, aims to address people with severe type 1 diabetes (T1D) who are hypoglycemia unaware, a condition in which a person with diabetes does not experience the usual early warning symptoms of hypoglycemia (low blood sugar) following an insulin injection. The purpose of the funding is to advance human clinical trials of Sernova’s novel cell macroencapsulated implantable and scalable Cell Pouch System (CPS) with the hope to improve the quality of life and overall outcomes for these patients.

Type 1 diabetes is a disease in which the body’s immune system mistakenly attacks and kills the pancreatic cells that produce insulin—a hormone that is essential for life because of its role to help the body use glucose. People with diabetes who have hypoglycemia unawareness are at a higher risk of acute life threatening consequences that can lead to coma and death following an insulin injection that reduces blood glucose to dangerously low levels.

JDRF will provide Sernova $2.45 million USD to support a clinical trial at a major transplantation center in the United States. “JDRF has previously provided funding to advance the development of Sernova’s technologies through a preclinical collaboration with Massachusetts General Hospital, and we are proud to continue our support as Sernova’s technologies progress into new safety and efficacy clinical trials,” said Derek Rapp, JDRF President and CEO. “JDRF is excited about this collaboration, which advances research in encapsulated cell therapies, and will continue to drive progress toward our mission to accelerate life-changing breakthroughs to cure, prevent and treat T1D and its complications.”

“Sernova and JDRF are tightly aligned in our vision to see cell-based therapies developed to reduce disease burden and significantly increase the quality of life for people living with T1D,” remarked Dr. Philip Toleikis, Sernova’s President and CEO. “We see our work with JDRF on this important clinical trial as an exciting opportunity to more rapidly advance Sernova’s therapies to treat people with diabetes and address many of the shortcomings and challenges of current insulin therapy.”

Understanding Hypoglycemia Unawareness

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There is no cure for T1D, and people living with the disease are dependent on insulin therapy to help keep their blood-sugar levels from spiking too high, which can lead to long-term complications such as kidney and heart diseases or an acute, potentially deadly health crisis. Present-day insulin therapy is, however, an imperfect treatment method that requires people with T1D to monitor their blood sugar throughout the day and take multiple, calculated doses of insulin based on food intake, exercise, stress, illness and other factors. A miscalculation or unexpected variable leading to high or low blood sugar episodes are daily threats, and only a third of people with T1D achieve their long-term blood glucose targets, placing them at risk for T1D-related health complications.

Many patients with diabetes who experience insulin-induced drops in blood sugar levels which could reach acute dangerous levels have the typical early warning signs of hypoglycemia, which include sweating, trembling, butterflies in the stomach, tingling, numbness, and rapid pulse.

People with diabetes who have hypoglycemia unawareness don’t experience these symptoms in reaction to a severe drop in blood sugar levels. Instead, without warning, they can lapse into severe hypoglycemia, becoming confused or disoriented or falling unconscious into a coma followed by death. It has been shown that transplantation of new islets can reduce the incidence and severity of hypoglycemia unawareness.

“Sernova’s progression to human clinical trials is an incredible accomplishment in the global diabetes research agenda,” said Dave Prowten, President and CEO of JDRF Canada. “I am particularly proud of this trial being a part of the JDRF portfolio because it supports advancements of the best and brightest research minds in Canada at Sernova. Also, this is a shining example of the international collaboration fostered by projects funded by JDRF. Working together with our global partners, we can accelerate this type of transformative research and ensure it becomes available for the T1D community.”

Cell Pouch System Technology vs Existing Islet Transplant Technology

Currently, islet cell transplantation is a procedure that involves transplanting islet cells from a donor’s pancreas into a diabetic patient’s liver through a blood vessel, basically a “big injection” into the portal vein of the liver. In this procedure infused islets can result in toxicities such as liver hypertension resulting from blockage of small blood vessels where the islets lodge. In addition, a large proportion of infused islet cells die during or after the process often requiring multiple treatments to achieve efficacy. Because of these and other issues as well as the low number of available islet donors in addition to diminishing efficacy over time, the procedure is available to only a small fraction of the most severely ill T1D patients.

 “We hope with these trials to accomplish an improved quality of life for people with diabetes who also experience hypoglycemia unawareness, and to potentially increase the number of patients that could be treated,” remarked Dr. Toleikis. “This work will also lend important information as we continue our development of Cell Pouch System cell-based technologies to treat the broader T1D community.”