Stem Cell Clinic

Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease – Albany Times Union

By adminDecember 9, 2020Stell Cell Research

Mo Ebrahimkhani,University of Pittsburgh

Dec. 7, 2020Updated: Dec. 7, 2020 2:02p.m.

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

(THE CONVERSATION) Takeaways

Scientists have made progress growing human liver in the lab.

The challenge has been to direct stems cells to grow into a mature, functioning adult organ.

This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue.

When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.

Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patients cells.

Im a researcher working in this new field called synthetic biology focused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organs figuring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues.

The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery.

But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical.

Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs.

Tissues and organs made by genetic designs

I am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues.

I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicals like proteins or sugar in the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation.

To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ.

One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my students Jeremy Velazquez and Ryan LeGraw used genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells.

The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days.

Liver in a dish

I and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs.

We then used genetic engineering to tweak genes and the resulting proteins that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny several millimeters in width but more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies.

Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they arent perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.

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Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming.

The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bile a chemical important for digestion of food.

When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids designer organoids, as they are generated via a genetic design.

This article is republished from The Conversation under a Creative Commons license. Read the original article here: https://theconversation.com/genetic-engineering-transformed-stem-cells-into-working-mini-livers-that-extended-the-life-of-mice-with-liver-disease-151089.

Researchers Trace the Origin of Blood Cancer to Early Childhood, Decades before Diagnosis – PRNewswire

By adminDecember 9, 2020Stell Cell Research

WASHINGTON, Dec. 8, 2020 /PRNewswire/ --Genetic mutations linked with cancer can occur during childhood or even before birth and proliferate in the body for many years before causing cancer symptoms, according to a new study. The study, which traced the genetic origins of a blood cancer in 10 individuals, suggests there may be untapped opportunities to detect cancer warning signs much earlier and potentially intervene to prevent or slow cancer development.

"Our preliminary findings show these cancer driver mutations were often acquired in childhood, many decades before the cancer diagnosis," said senior study authorJyoti Nangalia, MD,of the Wellcome Sanger Institute and University of Cambridge. "Our results finally answer the common question posed by patients, 'How long has this cancer been growing?' as we were able to study how these particular cancers developed over the entire lifetime of individual patients."

The researchers analyzed bone marrow and blood samples from 10 people with Philadelphia-negative myeloproliferative neoplasms, a type of cancer that causes stem cells in the bone marrow to produce too many blood cells. In the majority of patients, this cancer is driven by a genetic mutation called JAK2V617F. By assessing JAK2V617F, other cancer-linked mutations and hundreds of thousands of other mutations that a person naturally acquires throughout life, the researchers were able to trace the ancestry of different blood cells and estimate the time at which each patient acquired JAK2V617F and other important mutations.

They determined that, in these 10 patients, the first cancer-linked mutations emerged as early as a few weeks after the start of life and up to the first decade of childhood despite clinical disease presenting many decades later in life.

"We were not expecting this," said Dr. Nangalia. "In fact, in one patient, the JAK2 mutation was acquired more than 50 years before their diagnosis."

While it is often assumed that most cancers are diagnosed within a few years of their emergence, the findings point to a more gradual, lifelong process in which a single cell acquires a cancer-linked mutation early in life and then slowly grows over decades, ultimately leading to cancer.

"Some of these cancer-linked mutations are found in healthy individuals as we get older, suggesting that aging causes them," said Dr. Nangalia. "However, aging per se doesn't drive such growth it simply takes a long time for the clones to grow." Sometimes, the growing clones pick up additional cancer-linked mutations along the way, accelerating their growth, researchers found.

"For these patients, we calculated how many of these cancer clones would have been present in the past, and our results suggest that these clones may have been detectable up to 10 to 40 years before diagnosis," said Dr. Nangalia. "In addition to detecting the mutations, the rate at which the mutated clones grew was also very important in determining whether, and when, cancer develops." The findings suggest that genetic testing could help identify people at risk for cancer much earlier than current methods allow, according to researchers.

The next steps would be to understand the factors that influence the different rates of cancer growth and determine whether there could be ways to intervene and slow the growth of cells with cancer-linked mutations. The researchers say their method for pinpointing the origin of this blood cancer could also be applied to other mutations and other blood cancers. "Understanding the timelines of development of different cancers is critical for efforts aimed at early cancer detection and prevention," said Dr. Nangalia.

Jyoti Nangalia, MBBChir,Wellcome Sanger Institute and University of Cambridge, will present this study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

SOURCE American Society of Hematology

http://www.hematology.org

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Researchers Trace the Origin of Blood Cancer to Early Childhood, Decades before Diagnosis - PRNewswire

Evotec and Sartorius Partner with Start-Up Curexsys on IPSC-Based Therapeutic Exosome Approach – BioSpace

By adminDecember 9, 2020Induced Pluripotent Stem Cells

HAMBURG, GERMANY / ACCESSWIRE / December 9, 2020 / Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and the life science company Sartorius announced today that they have entered into a partnership with the recently established Curexsys GmbH, a Goettingen, Germany-based technology leader specialising in the emerging field of therapeutic exosomes.

Curexsys delivers a proprietary isolation technology for exosomes based on a traceless immune-affinity process. This process is different from commonly used antibody-based processes and enables the company to overcome a key hurdle in exosome preparation, i.e. remaining antibodies in the final preparation. Curexsys is founded by Herbert Stadler, a serial biotech entrepreneur, and Jens Gruber, a former group leader of Medical RNA Biology who is going to lead Curexsys as Chief Scientific Officer.

Under the terms of the agreement, Evotec and Curexsys will collaborate with the production of Human Mesenchymal Stem Cells ("MSCs"), which serve as a source for exosomes. These are small vesicles that are naturally released from a cell. They contain proteins, nucleic acids and metabolites, which carry information from secreting to receiving cells. Exosomes have immunomodulatory and anti-inflammatory effects, which makes them a promising novel approach for innovative regenerative therapies, as therapeutics in age-related conditions, but also for diagnostic purposes. Curexsys aims to develop targeted approaches for a variety of diseases, initially focusing on Sicca Syndrome, commonly known as "dry eye", an inflammatory condition affecting 14% to 17% of the adult population for whom there is currently no effective treatment available.

The collaboration combines Evotec's industry-leading induced Pluripotent Stem Cell ("iPSC") platform with Curexsys' proprietary technology to selectively isolate exosomes. Sartorius will support Curexsys to set up a GMP-compliant and scalable manufacturing platform.

Furthermore, Evotec and Sartorius have formed a consortium to jointly invest in Curexsys' 8.2 m seed financing round with Evotec acquiring an equity stake of approx. 37% in Curexsys and Sartorius of approx. 21%.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "Therapeutic exosomes hold significant promise for regenerative medicine and beyond. Steadily increasing evidence suggests that exosomes derived from stem cells can aid tissue repair and engineering vesicles could carry drugs to diseased tissues. These efforts have been held back by a dearth of standardised methods to isolate and study vesicles. Combining Evotec's industrial-grade iPSC and PanOmics platforms with Curexsys' proprietary exosome isolation technology and Sartorius' ability to translate these into a fully GMP-compliant process is a unique opportunity to build the leading exosome company in the industry."

Dr Ren Faber, Head of Sartorius' Bioprocess Solutions Division, said: "With our integrated portfolio of manufacturing solutions Sartorius is the 'go-to' partner for developers of such new modalities when it comes to implementing GMP-compliant, flexible production processes. We are very much looking forward to contributing our proven and scalable technology platform to Curexsys process and help them achieve their next milestones faster."

Dr Jens Gruber, Chief Scientific Officer of Curexsys, added: "We are very happy that we were able to form such a consortium with industry leaders in their field. This unique constellation gives Curexsys an optimal starting position to advance our technologies for highly specific isolation of exosomes and to rapidly approach therapeutic applications."

About Exosomes and Curexsys Exosomes are extracellular, nanoscale vesicles that are actively secreted from cells to transfer information to neighbouring cells and distant tissues. Exosomes carry information of secreting to receiving cells utilising proteins, nucleic acids and metabolites. MSC-derived exosomes function as paracrine mediators that limit inflammation, reprogram immune cells, and activate endogenous repair pathways, recapitulating to a large extent the therapeutic effects of parental MSCs. Exosomes hold potential as diagnostics, as therapeutics and cosmeceuticals. More than 100 clinical trials involving exosomes are currently ongoing, demonstrating their broad therapeutic potential.

Curexsys is a Goettingen, Germany-based start-up company founded by molecular biologist Dr Jens Gruber and the biochemist and serial entrepreneur Dr Herbert Stadler. With a scalable and semi-automated proprietary system for traceless immune-affinity cell sorting, Curexsys aims to become the leading supplier for clinical grade exosomes in regenerative medicine and anti-aging therapies.

About Evotec and iPSC Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

Evotec has built an industrialised iPSC infrastructure that represents one of the largest and most sophisticated iPSC platforms in the industry. Evotec's iPSC platform has been developed over the last years with the goal to industrialise iPSC-based drug screening in terms of throughput, reproducibility and robustness to reach the highest industrial standards, and to use iPSC-based cells in cell therapy approaches via the Company's proprietary EVOcells platform.

ABOUT SARTORIUS The Sartorius Group is a leading international partner of life science research and the biopharmaceutical industry. With innovative laboratory instruments and consumables, the Group's Lab Products & Services Division concentrates on serving the needs of laboratories performing research and quality control at pharma and biopharma companies and those of academic research institutes. The Bioprocess Solutions Division with its broad product portfolio focusing on single-use solutions helps customers to manufacture biotech medications and vaccines safely and efficiently. The Group has been annually growing by double digits on average and has been regularly expanding its portfolio by acquisitions of complementary technologies. In fiscal 2019, the company earned sales revenue of some 1.83 billion euros. At the end of 2019, more than 9,000 people were employed at the Group's approximately 60 manufacturing and sales sites, serving customers around the globe.

SARTORIUS CONTACT Petra Kirchhoff Head of Corporate Communications and Investor Relations +49 (0)551.308.3684 petra.kirchhoff@sartorius.com http://www.sartorius.com

ABOUT EVOTEC SE Evotec is a drug discovery alliance and development partnership company focused on rapidly progressing innovative product approaches with leading pharmaceutical and biotechnology companies, academics, patient advocacy groups and venture capitalists. We operate worldwide and our more than 3,400 employees provide the highest quality stand-alone and integrated drug discovery and development solutions. We cover all activities from target-to-clinic to meet the industry's need for innovation and efficiency in drug discovery and development (EVT Execute). The Company has established a unique position by assembling top-class scientific experts and integrating state-of-the-art technologies as well as substantial experience and expertise in key therapeutic areas including neuronal diseases, diabetes and complications of diabetes, pain and inflammation, oncology, infectious diseases, respiratory diseases, fibrosis, rare diseases and women's health. On this basis, Evotec has built a broad and deep pipeline of more than 100 co-owned product opportunities at clinical, pre-clinical and discovery stages (EVT Innovate). Evotec has established multiple long-term alliances with partners including Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CHDI, Novartis, Novo Nordisk, Pfizer, Sanofi, Takeda, UCB and others. For additional information please go to http://www.evotec.com and follow us on Twitter @Evotec.

FORWARD LOOKING STATEMENTS Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

SOURCE: Evotec AG via EQS Newswire

View source version on accesswire.com: https://www.accesswire.com/620112/Evotec-and-Sartorius-Partner-with-Start-Up-Curexsys-on-IPSC-Based-Therapeutic-Exosome-Approach

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Evotec and Sartorius Partner with Start-Up Curexsys on IPSC-Based Therapeutic Exosome Approach - BioSpace

Multiple gene edits and computer simulations could help treat rare genetic diseases – University of Wisconsin-Madison

By adminDecember 9, 2020Induced Pluripotent Stem Cells

The lab of KrisSaha at the University of WisconsinMadison has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders.

In proof-of-concept experiments, the labs researchers efficiently corrected multiple mutations responsible for a rare metabolic disorder, known as Pompe disease, in cells containing the disease-causing errors. They also used computer simulations to design the ideal gene-editing approach for treating human patients, a boon for rare disorders like Pompe disease that lack useful animal models.

Their promising platform advances the CRISPR genome-editing field and could lead to effective treatments for many diseases, not just Pompe disease.

The exact mutations seen in the Pompe patients are not in an existing animal model, so we cannot do all of the preclinical studies that we would like to do in order to evaluate the safety and efficacy of different genome editing strategies, says Saha, a professor of biomedical engineering at UWMadisons Wisconsin Institute for Discovery. We need a way to think about how we go from patient material to a therapy without having to build an animal model, a process that takes months to years and hundreds of thousands of dollars.

The lab of Kris Saha (standing) has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders. Photo: Stephanie Precourt

Sahas team published its findings Dec. 8 in the journal Nature Communications.

In the first few months of life, an infant with Pompe disease becomes weaker and weaker as glycogen builds up in their muscles, their cells unable to break the complex sugar down. Multiple mutations in a gene calledGAAprevent their cells from correctly producing the proteins needed to make lysosomes, which turn glycogen into glucose, the fuel that powers cells. Left untreated, most patients with Pompe die within a year.

Developing effective therapies for such diseases can be difficult for a number of reasons. First, diseases like Pompe have no animal models in which to test treatments, a typical step in therapy development. And diseases like Pompe and many other inherited diseases are autosomal recessive, which means that mutations are present on both copies of a chromosome. Two sets of mutations require two successful gene-repair events for maximum effect. Further complicating the matter is the fact that many diseases are polygenic, resulting from mutations in two or more genes or multiple mutations spread across a single gene, as is the case for Pompe disease.

The Saha labs new approach uses precise gene-editing tools to edit both faulty alleles simultaneously within individual cells to restore function. In its new report, the research team used induced pluripotent stem cells derived from Pompe patients to reproduce the exactGAAmutations that cause the disease and to approximate the resulting tissue pathology.

To fix these Pompe mutations, the lab turned to a specially designed, ultra-precise genome-editing system described in aprevious studyled by Jared Carlson-Stevermer, who was at the time a graduate student in Sahas group. That report established an up to 18-fold increase in precision of gene edits by combining a DNA repair template with the cutting machinery of CRISPR in one particle.

In the current study, the researchers used the method to fix two mutations at once in Pompe-derived cells. By doing so, the researchers improved cell function dramatically, bringing lysosome protein production up to the level of healthy cells without any major adverse effects, which sometimes emerge from gene editing.

The research advances the CRISPR genome-editing field and could lead to effective treatments for many diseases.

But treating cells in the laboratory, while providing crucial insight, is not the same as creating a therapy for patients. A critical step in developing treatments usually involves testing on animal models to evaluate efficacy and safety, a major obstacle for Pompe disease and other genetic conditions that lack viable animal models.

To determine the best therapeutic strategy for polygenic diseases evaluating different doses, delivery mechanisms and timing, risks and other factors the research team instead built a computational model that allows it to predict the outcomes of various conditions.

This allows us to survey a wider scope of many different gene therapies during the design of a strategy, says coauthor Amritava Das, a postdoctoral associate at the Morgridge Institute for Research. The computational approach is critical when you dont have an animal model that resembles the human disease.

After pumping close to a million simulation conditions through the computational model, Das, Carlson-Stevermer and Saha have gained key insights about the delivery of gene editors into the livers of human infants with Pompe disease without having to subject a single patient to experimental treatments. And those insights establish that the multiple-correction genome-editing approach tested in stem cells may be an effective treatment for Pompe and other polygenic recessive disorders.

The computational model, which can be easily adapted for other polygenic conditions, is a big step for the development of therapies for diseases like Pompe and lays the groundwork for a bridge from laboratory studies to the clinic. And as more measurements are added to the model, it will gain more predictive power.

Its a very broad, adaptable platform, Das says about the combined stem cell model and computational tool, and a very different way of thinking about gene therapy.

This work was supported by the National Science Foundation (CBET-1350178, CBET-1645123), the National Institutes of Health (1R35GM119644-01), the Environmental Protection Agency (EPA-G2013 STAR-L1), the University of Wisconsin Carbone Cancer Center (P30 CA014520), the Wisconsin Alumni Research Foundation, and the Wisconsin Institute for Discovery.

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Multiple gene edits and computer simulations could help treat rare genetic diseases - University of Wisconsin-Madison

Cytovia Therapeutics announces plans to initiate in 2021 Clinical Development of Universal iPSC NK Cell Therapy for Hematological and Solid Tumors -…

By adminDecember 9, 2020Induced Pluripotent Stem Cells

December 08, 2020 09:04 ET | Source: Cytovia Therapeutics

CAMBRIDGE, Mass., Dec. 08, 2020 (GLOBE NEWSWIRE) -- Cytovia Therapeutics, an emerging NK cell therapeutics company, announced today that it plans to file with the FDAin 2021an Investigational New Drug (IND) application and initiate clinical trials in hematological and solid tumors with its Universal iPSC NK cell therapy (U-iNK).

Cytovia's CEO, Dr. Daniel Teper commented: "Cytovia is among a select group of biotech companies developing Gene Edited iPSC NK and CAR NK cell therapeutics. We are aiming to be, in 2021, the second company to initiate clinical trials with an iPSC NK product. We are enthusiastic about the potential of U-iNK to prevent relapse in Acute Myeloid Leukemia, and in combination with PD1/ PDL-1 inhibitors and our own NK engager bispecific antibodies, to improve outcomes in solid tumors starting with hepatocellular carcinoma."

Cytovia will participate in the RBC Capital Markets Healthcare Private Company Conference on December 15-16, 2020. Daniel Teper, PharmD, CEO, Wei Li, PhD, CSO and Kaouthar Lbiati, MD, VP, Product Strategy will take part in a Fireside chat with RBC's Senior Analyst, Gregory Renza, MD, on December 16, 2020 at 10am ET. A link to the discussion will be available on Cytovias website and social media channels.

About Cytovia TherapeuticsCytovia Therapeutics Inc is an emerging biotechnology company that aims to accelerate patient access to transformational immunotherapies, addressing several of the most challenging unmet medical needs in cancer. Cytovia focuses on Natural Killer (NK) cell biology and is leveraging multiple advanced patented technologies, including an induced pluripotent stem cell (iPSC) platform for CAR (Chimeric Antigen Receptors) NK cell therapy, next-generation precision gene-editing to enhance targeting of NK cells, and NK engager multi-functional antibodies. Our initial product portfolio focuses on both hematological malignancies such as multiple myeloma and solid tumors including hepatocellular carcinoma and glioblastoma. The company partners with the University of California San Francisco (UCSF), the New York Stem Cell Foundation (NYSCF), the Hebrew University of Jerusalem, INSERM, and CytoImmune Therapeutics.

Learn more atwww.cytoviatx.comand follow Cytovia Therapeutics on Social MediaFacebook,LinkedIn,Twitter, Youtube

For more information, please contact:

Cytovia Therapeutics, Inc SophieBadr Vice President, Corporate Affairs sophie.badre@cytoviatx.com Cell: 1 (929) 317 1565

Anna Baran-Djokovic Vice President, Investor Relations anna@cytoviatx.com VP Investor Relations Cell: +44 7521083006

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Cytovia Therapeutics announces plans to initiate in 2021 Clinical Development of Universal iPSC NK Cell Therapy for Hematological and Solid Tumors -...

Fate Therapeutics Reports Positive Interim Data from its Phase 1 Study of FT516 in Combination with Rituximab for B-cell Lymphoma – GlobeNewswire

By adminDecember 9, 2020Induced Pluripotent Stem Cells

December 04, 2020 16:01 ET | Source: Fate Therapeutics, Inc.

3 of 4 Patients Evaluable for Efficacy in Dose Escalation Cohorts 2 and 3 Show Objective Response, with 2 Patients Achieving Complete Response

No Observed Events of Any Grade of Cytokine Release Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, or Graft-vs-Host Disease

Six Doses of FT516 were Well-tolerated with No FT516-related Grade 3 or Greater Adverse Events Reported by Investigators

Management to Host Virtual Event Entitled The Power of hnCD16 Today at 4:30 PM Eastern Time

SAN DIEGO, Dec. 04, 2020 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, today announced positive interim data from the Companys dose escalation Phase 1 study of FT516 in combination with rituximab for patients with relapsed / refractory B-cell lymphoma. FT516 is the Companys universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells.

We are highly encouraged by these Phase 1 data, which clearly demonstrate that off-the-shelf, iPSC-derived NK cells can drive complete responses for cancer patients and that our proprietary hnCD16 Fc receptor can effectively synergize with and enhance the mechanism of action of tumor-targeted antibodies, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Importantly, the safety profile of FT516 continues to suggest multiple doses of iPSC-derived NK cells can be administered in the outpatient setting, and supports potential use across multiple lines of therapy, including as part of early-line CD20-targeted monoclonal antibody regimens, for the treatment of B-cell lymphoma.

As of a November 16, 2020 data cutoff, three patients in the second dose cohort of 90 million cells per dose and one patient in the third dose cohort of 300 million cells per dose were available for assessment of safety and efficacy. All four patients were heavily pre-treated, having received at least two prior rituximab-containing regimens. Each patient received two 30-day treatment cycles, with each cycle consisting of fludarabine and cyclophosphamide lympho-conditioning followed by three once-weekly doses of FT516, IL-2 cytokine support, and rituximab.

Safety Data All four relapsed / refractory patients were administered FT516 in an outpatient setting with no requirement for inpatient monitoring. No dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. The multi-dose, two-cycle treatment regimen was well-tolerated with no FT516-related grade 3 or greater adverse events reported by investigators. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without patient matching. All grade 3 or greater treatment emergent adverse events were not related to FT516 and were consistent with lympho-conditioning chemotherapy and underlying disease.

Activity Data Three of four relapsed / refractory patients achieved an objective response, including two complete responses (CR), following the second FT516 treatment cycle as assessed by PET-CT scan per Lugano 2014 criteria. A CR was achieved in one patient with diffuse large B-cell lymphoma (DLBCL) who was most recently refractory to a rituximab-containing treatment regimen, and a CR was achieved in one patient with follicular lymphoma (FL) who had previously been treated with four rituximab-containing treatment regimens. Notably, in one patient for which an interim tumor assessment showed a partial response following the first FT516 treatment cycle, the response deepened to a CR following administration of the second FT516 treatment cycle, suggesting that additional FT516 treatment cycles can confer clinical benefit.

M = million; CR = Complete Response; PR = Partial Response; PD = Progressive Disease As of November 16, 2020 database entry. Data subject to cleaning and source document verification. 1 Day 29 of the second FT516 treatment cycle as assessed per Lugano 2014 criteria

Dose escalation is continuing in the current dose cohort of 300 million cells per dose in combination with rituximab, and a fourth dose cohort of 900 million cells per dose in combination with rituximab is planned. The Company previously reported that two patients treated in the first dose cohort of 30 million cells per dose in combination with rituximab showed a protocol-defined response assessment of progressive disease. No events of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were observed in either patient.

About Fate Therapeutics iPSC Product Platform The Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

About FT516 FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Scientists from the Company have shown in a peer-reviewed publication (Blood. 2020;135(6):399-410) that hnCD16 iPSC-derived NK cells, compared to peripheral blood NK cells, elicit a more durable anti-tumor response and extend survival in combination with anti-CD20 monoclonal antibodies in an in vivo xenograft mouse model of human lymphoma. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for cancer and immune disorders. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology product candidates include natural killer (NK) cell and T-cell cancer immunotherapies, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens with chimeric antigen receptors (CARs). The Companys immuno-regulatory product candidates include ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease, and a myeloid-derived suppressor cell immunotherapy for promoting immune tolerance in patients with immune disorders. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Companys iPSC-derived NK cell product candidates, including FT516, its ongoing and planned clinical studies, and the expected clinical development plans for FT516. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that the Company may cease or delay clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties or delays in subject enrollment in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact: Christina Tartaglia Stern Investor Relations, Inc. 212.362.1200 christina@sternir.com

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Fate Therapeutics Reports Positive Interim Data from its Phase 1 Study of FT516 in Combination with Rituximab for B-cell Lymphoma - GlobeNewswire

Constantly Growing Applications and Innovations to Push Sales of Amniotic Membrane Market Up To ~US$2.4 Bn by 2027, Observes TMR – PRNewswire

By adminDecember 9, 2020Induced Pluripotent Stem Cells

ALBANY, N.Y, Dec. 8, 2020 /PRNewswire/ -- Transparency Market Research has published a new research report that provides detailed information about the global amniotic membrane market. The research report tried to shed light on different growth factors, prominent growth challenges, key segments, geographical outlook, and vendor landscape of the global amniotic membrane market. According to the research report, the amniotic membrane market is projected to reach a valuation worth US$2.4 Bn by the end of 2027. Initially, the valuation of the global market was around US$980 Mn, in 2018. In order to achieve such huge surge in terms of revenue, the market is projected to showcase a massive CAGR of ~10% over the course of the given period of assessment ranging from 2019 to 2027.

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Explore a report with detailed research, incisive insights, and in-depth country levels estimations. Gain business intelligence on global Amniotic Membrane Market by Product: Cryopreserved Amniotic Membrane, Lyophilization Amniotic Membrane; Application: Surgical Wounds, Ophthalmology, Others; End User: Hospitals, Ambulatory Surgical Centers, Specialized Clinics, and Research Centers & Laboratories at https://www.transparencymarketresearch.com/report-toc/42059

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Some of the notable names operating in the global amniotic membrane market are Amnio Technology, LLC, Katena Products, Inc., MiMedx, Skye Biologics, Inc., Integra LifeSciences, Applied Biologics, Human Regenerative Technologies, LLC, Tissue Tech, Osiris Therapeutics, Inc., and Stryker.

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Genetic Testing Services Market: According to the report, the global genetic testing services market was valued at US$ 41.2 Bn in 2018 and is anticipated to expand at a CAGR of 7.3% from 2019 to 2027, high incidence & prevalence of chronic diseases such as autoimmune, oncology, infectious and others are propelling the growth of global market

Bioprocess Technology Market: According to the report, the global bioprocess technology market was valued at US$ 21.9 Bn in 2018 and is anticipated to expand at a CAGR of 7.9% from 2019 to 2027, The global bioprocess technology market is driven by increase in prevalence of chronic pain, and rise in demand for home monitoring.

Oligonucleotide Synthesis Market: According to the report, the global oligonucleotide synthesis market was valued at US$ 1,966.2 Mn in 2018 and is anticipated to expand at a CAGR of 9.5% from 2019 to 2027, increasing use of synthesized oligonucleotides in diagnostics and research applications, and Technological advancements in synthetic chemistry are projected to drive the global market

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Constantly Growing Applications and Innovations to Push Sales of Amniotic Membrane Market Up To ~US$2.4 Bn by 2027, Observes TMR - PRNewswire

Stem cells: past, present, and future | Stem Cell Research …

By adminDecember 8, 2020Stell Cell Research

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Jasper Therapeutics Announces Data from First Transplant-naive Patient in Phase 1 Clinical Trial of JSP191 as Conditioning Agent in Patients with SCID…

By adminDecember 8, 2020Stell Cell Research

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, today announced clinical data from its ongoing multicenter Phase 1 clinical trial of JSP191, a first-in-class anti-CD117 monoclonal antibody, in patients with severe combined immune deficiency (SCID). The trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with SCID who are either transplant-naive or who received a prior stem cell transplant with a poor outcome.

Data from the first transplant-nave SCID patient in the Phase 1 trial, a 6-month-old infant, showed that a single dose of JSP191 administered prior to stem cell transplant was effective in establishing sustained donor chimerism followed by development of B, T and NK immune cells. No treatment-related adverse events were reported. The data were presented by primary investigator Rajni Agrawal-Hashmi, M.D., of Stanford University, at the 62nd American Society of Hematology (ASH) Annual Meeting & Exposition.

We have previously shown that JSP191 can be successfully used as a single conditioning agent in SCID patients who had failed a previous transplant, said Kevin N. Heller, M.D., Executive Vice President, Research and Development, of Jasper Therapeutics. This new data presented at ASH 2020 showing success in an infant with SCID undergoing a first transplant provides proof of concept of the safety and efficacy of the use of JSP191 as an alternative to genotoxic chemotherapies currently used to deplete stem cells prior to transplant.

Hematopoietic cell transplantation offers the only curative therapy for SCID, a severe genetic immune disorder that leaves patients without a functioning immune system. With this approach, standard-of-care chemotherapeutic conditioning regimens are given prior to transplant to reduce the number of blood stem cells in the bone marrow to make space for donor blood stem cells to engraft and cure the patient. JSP191 is designed to replace the need for chemotherapeutic conditioning agents, which are DNA-damaging and highly toxic.

Dr. Heller added, With our Phase 1 trials in SCID and hematologic disorders underway, we are planning to expand the development of JSP191 into additional indications, such as gene therapies, autoimmune diseases, Fanconis anemia and other rare disorders that can be cured by stem cell transplant.

The open-label, multicenter Phase 1 study is evaluating the safety, tolerability and efficacy of JSP191 as a conditioning agent in patients with SCID undergoing first or repeat hematopoietic cell transplantation. Up to three different doses of JSP191 are being assessed for dose-limiting toxicities. The trial is currently open for enrollment at Stanford University, the University of California, San Francisco, Memorial Sloan Kettering Cancer Center, the University of California, Los Angeles, and Cincinnati Childrens Hospital. Additional clinical trial sites in the United States will initiate enrollment in the coming weeks.

About SCID

Severe combined immune deficiency (SCID) is a group of rare disorders caused by mutations in genes involved in the development and function of infection-fighting immune cells. Infants with SCID appear healthy at birth but are highly susceptible to severe infections. The condition is fatal, usually within the first year or two of life, unless infants receive immune-restoring treatments, such as transplants of blood-forming stem cells, gene therapy or enzyme therapy.

About JSP191

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in animal models of SCID, myelodysplastic syndromes (MDS) and sickle cell disease (SCD). Treatment with JSP191 creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients.

JSP191 is currently being evaluated as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for severe combined immunodeficiency (SCID), which is potentially curable only by this type of treatment. JSP191 is also being evaluated in a Phase 1 study in patients with MDS or acute myeloid leukemia (AML) who are receiving hematopoietic cell transplant. For more information about the design of these clinical trials, visit http://www.clinicaltrials.gov (NCT02963064 and NCT04429191). Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The companys lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplant. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. For more information, please visit us at jaspertherapeutics.com.

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Jasper Therapeutics Announces Data from First Transplant-naive Patient in Phase 1 Clinical Trial of JSP191 as Conditioning Agent in Patients with SCID...

After boosting gene therapy focus, Bayer signs up to new cell therapy pact with Atara – FierceBiotech

By adminDecember 8, 2020Stell Cell Research

German pharma Bayer is moving into cell therapy R&D with its latest pact focusing on tough-to-treat lung cancers with Atara Biotherapeutics.

Bayer has been moving deeply into gene therapies over the past few years, but it's now entering the CAR-T research space in its Atara deal. CAR-T has been focused heavily on blood cancers, where there have been some amazing successes (but also serious safety worries), but this pact is focusing on a tougher area for cell therapy, namely solid tumors.

The deal focuses on off-the-shelf T-cell immunotherapy ATA3271 for high mesothelin-expressing tumors, with a focus on more rare and tough-to-treat high mesothelin-expressing tumors such as malignant pleural mesothelioma and non-small cell lung cancer.

At Parexel, we get the right people to you, so you can get the right treatment to your patients. Our functional service provider (FSP) outsourcing has evolved with biopharmas changing needs, so sponsors can efficiently manage operations through access to experts, resource flexibility, and reduced labor costs. Our latest whitepaper discusses the current FSP models and provides expert tips for choosing the right one.

The financials break down like this: Atara gets $60 million upfront, with up to $610 million on the table in biobucks. The biotech will lead IND-enabling studies and process development for ATA3271, while Bayer will be responsible for submitting the IND and then will take over R&D and sales work.

Atara will continue to be responsible for the ongoing ATA2271 phase 1 study, for which an IND filing has been accepted and a test already started.

RELATED: Bayer creates cell and gene therapy platform to support partners

For a limited time, Bayer also has a nonexclusive right to negotiate a license for additional Atara CAR-T product candidates.

This transaction is a fundamental element of Bayers new Cell & Gene Therapy strategy. It strengthens our development portfolio through allogeneic cell therapies and consolidates our emerging leadership in the field, said Wolfram Carius, head of Bayers Cell & Gene Therapy Unit.

We look forward to collaborating with Atara to develop off-the-shelf CAR T-cell therapies for patients with difficult-to-treat cancers.

Germanys Bayer has moved into cell and gene therapies on multiple fronts in recent years, buying up induced pluripotent stem cell specialist BlueRock Therapeutics and adeno-associated virus gene therapy player Asklepios BioPharmaceutical while investing in a clutch of other biotechs. The deals have given Bayer a pipeline of five advanced assets and more than 15 preclinical prospects.

It has backed other CAR-T players over the years, including CAR alternative player Triumvira and Century Therapeutics, but the Atara deal takes it further into directly working on a cell therapy.

This exciting collaboration between Atara and Bayer will accelerate the development of mesothelin-targeted CAR T-cell therapies for multiple solid tumors and helps us advance the power of our allogeneic cell therapy platform to patients as quickly as possible, added Pascal Touchon, president and CEO of Atara.

Bayers proven track record in oncology global development and commercialization, and growing presence in cell and gene therapy, enhances Ataras capabilities and complements our leading allogeneic T-cell platform.

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After boosting gene therapy focus, Bayer signs up to new cell therapy pact with Atara - FierceBiotech