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Meat-Tech Agrees to Acquire Cultured Fat Pioneer ‘Peace of Meat’ – PRNewswire

By Stell Cell Research

NESSZIONA,Israel, Dec. 8, 2020 /PRNewswire/ -- Meat-Tech 3D Ltd. (TASE: MEAT), today announced that it has signed an agreement to acquire 100% of the share capital of Peace of Meat PV, a pioneering Belgian producer of cultured avian products, for EUR 15 million in a combination of cash and Meat-Tech ordinary shares. The Company believes that it will be able to leverage Peace of Meat's technologies, including through novel hybrid food products, to expedite market entry while Meat-Tech develops an industrial process for cultivating and producing real meat using 3D bioprinting technology, without harming animals. The acquisition is expected to close in the coming weeks, subject to customary closing conditions.

Peace of Meat has developed a proprietary, stem-cell-based bioreactor technology for cultivating animal fats from chicken and ducks, without harming animals. It has conducted a number of taste tests, demonstrating the potential that its cultured fat has to enhance the taste of plant-based protein products. The technology's first expected application is in hybrid food products, combining plant-based protein with cultured animal fat, designed to provide meat analogues with qualities of "meatiness" (taste and texture) closer to that of conventional meat products. Meat-Tech estimates that the first hybrid products based on Peace of Meat technology could hit the market as early as 2022.

Pursuant to the acquisition agreement, Meat-Tech will pay half of the consideration immediately, with the payment of the balance subject to Peace of Meat complying with preset technological milestones over a period of two years, that were designed to scale up cultured fat production capabilities in preparation for market entry. To that end, it was agreed that Peace of Meat's management will continue in place to lead the development process.

This acquisition is consistent with Meat-Tech's growth strategy, aiming to streamline development processes and expand the Company's product range to penetrate cultured meat technology markets as quickly as possible. Meat-Tech is working to create synergy and added value for food manufacturers in the advanced production of cultured meat, while sustaining animal welfare and meeting the growing global demand for meat.

Sharon Fima, Meat-Tech's CEO: "Meat-Tech's novel technology for producing meat using 3D printing is gaining increasing international recognition. Boosted by our acquisition strategy, we believe we can turn Meat-Tech into a leading global center and home for innovative and groundbreaking cell-based food solutions that are both healthy and environmentally friendly. The combination of Peace of Meat's human capital and technology make this acquisition a significant step in that direction. I am pleased that both management teams share a common vision and strategy, and can join forces to advance the development of cultured food products with the potential to create real alternatives in the global meat market."

David Brandes and Dirk von Heinrichshorst, Co-Founders of Peace of Meat:"In an industry that is working towards a kinder, more sustainable planet, joining forces makes us stronger together. Peace of Meat has developed a powerful system for upscaled cultured biomass production and together with Meat-Tech we intend to accelerate product development toward commercialization.

"While Peace of Meat's core activity remains focused on the production of tasty, cultured fat as a B2B ingredient for meat alternatives, we see tremendous opportunity in jointly building a leading food-tech enterprise with Meat-Tech, based on a cellular platform.

"As entrepreneurs, we are excited about this acquisition as it poses a novel way of building and growing a company while significantly increasing the prospects of launching our product into the market."

About Peace of Meat:

Peace of Meat was established in Belgium in 2019 and is developing cultured chicken fat directly from animal cells without the need to grow or kill animals. The company believes that its innovative technology has the potential to support an industrial process for the production of cultured chicken fat. Peace Of Meat has entered into a number of scientific and commercial collaborations, in the process of positioning itself as a future B2B provider, with the potential to cover the entire value chain and to accelerate research and production processes in the industry, and has conducted taste tests for hybrid products it has developed.

About Meat-Tech:

Meat-Tech is developing a novel biological printing process designed to create living, edible meat tissue using cellular agriculture. Meat-Tech is developing technologies, processes and machines for cultivating, producing, and printing cultured meat. The company believes that it was the first in the world to use edible biological inks to 3D-print living tissue made up of various cells of bovine origin. The Company has the technology, knowledge and experience in applying tissue engineering practices for producing fat and muscle tissue for food consumption, as well as the ability to print, using a 3D bioprinter, a combination of live animal cells, growth factors and biological materials to produce living tissues that mimic the characteristics of natural tissue.

Forward-Looking Statements:

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the Company's development of the next generation of cultured meat food products by leveraging 3D digital printing technology, Peace of Meat's development of cultured fat products, the expected closing of the Company's acquisition of Peace of Meat and the expected post-closing synergies of the combined companies. These forward-looking statements include information about possible or assumed future results of the Company's business, financial condition, results of operations, liquidity, plans and objectives. In some cases, you can identify forward-looking statements by terminology such as "believe," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "expect," "predict," "potential," or the negative of these terms or other similar expressions. Forward-looking statements are based on information the Company has when those statements are made or management's current expectation and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking statements. Actual results could differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements after the date of this press release to conform these statements.

COMPANY / INVESTOR CONTACT:Eran Gabay, Partner, Director of Strategy Gelbart-Kahana Investor Relations: [emailprotected]

SOURCE Meat-Tech 3D Ltd.

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Meat-Tech Agrees to Acquire Cultured Fat Pioneer 'Peace of Meat' - PRNewswire

Actinium Reports 67 Percent Overall Response Rate in First Cohort in Actimab-A Venetoclax Combination Trial in Relapsed and Refractory AML at ASH -…

By Stell Cell Research

NEW YORK, Dec. 8, 2020 /PRNewswire/ --Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") today announced that first-in-human data from the first dose cohort of the Phase 1 portion of the Actimab-A venetoclax Phase 1/2 combination trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) were presented at the 62nd American Society of Hematology (ASH) annual meeting. The poster presentation highlighted results from the first three patients treated with the initial subtherapeutic dose level of 0.5 Ci/kg of Actimab-A and venetoclax.

The enrolled patients had a median of 2 prior therapies (range 2-3) and a median bone marrow blast percentage of 30% (range 20 - >60). All 3 patients had poor risk disease with adverse cytogenetics, and each patient had an additional high-risk marker (FLT3-ITD+, antecedent JAK2+ myelofibrosis, or TP53 mutation). One patient who had multiple genetic mutations including IDH2, RUNX1, TP53 and others, achieved a complete remission with incomplete blood count recovery (CRi) after the first cycle of Actimab-A and venetoclax. Next generation sequencing at the end of the first cycle showed that patient was negative for the known IDH2 and RUNX1 mutations. This patient has continued treatment receiving the second cycle and their bone marrow remains normocellular with no excess blasts. In addition, another patient achieved a partial response after one cycle of Actimab-A and venetoclax. There were no Actimab-A related dose limiting toxicities or nonhematologic Grade 3 or greater related AEs reported in the first cohort. The trial has advanced to the second dose cohort of 1.0 Ci/kg of Actimab-A and venetoclax with patient enrollment ongoing.

Sandesh Seth, Actinium's Chairman and Chief Executive Officer, commented, "This ASH meeting, we are excited to highlight the promising data emerging from both our combination trials with Actimab-A in the R/R AML setting, namely the Actimab-A venetoclax and Actimab-A CLAG-M trials. Particularly compelling is the complete response reported in a patient with complex mutations like TP53 with Actimab-A and venetoclax and the high MRD negativity rate with Actimab-A and CLAG-M. The results clearly demonstrate that a superior clinical effect without adding meaningful toxicity is achievable using Ac-225 ARC's to precisely deliver powerful internal radiation and elicit a potentiating and synergistic treatment effect with chemotherapy and targeted agents. With this clinical validation in hand, we look forward to expanding our ARC combinations with other therapeutic modalities in AML and into additional indications to further establish our leadership position in the field by leveraging our enhanced R&D capabilities including new research facilities and key hires."

Dr. Mark Berger, Actinium's Chief Medical Officer, said, "We were thrilled to report a complete response in the Actimab-A venetoclax combination trial, in addition to the partial response previously highlighted in the abstract. Both responses occurred after just one cycle of a subtherapeutic dose of Actimab-A. These initial results, the one complete response and safety profile to date, support the potential mechanistic synergy of Actimab-A with venetoclax. As a single agent, venetoclax has produced low response rates of 19% in patients with R/R AML1 so we are pleased with the results seen in our first dose cohort. In addition, the clinical data from Actimab-A and Iomab-B presented at this year's ASH demonstrates our strong commitment to addressing the unmet needs of patients with R/R AML with our ARCs as best in class therapeutics, bridge to transplant and targeted conditioning for potentially curable bone marrow transplant. With this in mind, we look forward to guidance on Iomab-B expected from the ad-hoc DMC meeting before year-end."

This Phase 1/2 trial is a multicenter, open label trial of Actimab-A (lintuzumab-Ac225) added to venetoclax for patients with CD33 positive R/R AML. A Phase 2 trial studying Actimab-A as a single agent produced a 69% overall response rate in older unfit patients with newly diagnosed AML.In a poster presentation at the American Association of Cancer Research (AACR) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting MCL-1, a protein shown to mediate resistance to venetoclax. Further, the induction of direct AML cell death via double-stranded DNA breaks by Actimab-A provides a second mechanism for enhancing synergistic potency with venetoclax. Venetoclax is a B-Cell Lymphoma 2 (BCL-2) inhibitor that is jointly developed and marketed by AbbVie and Genentech and is approved for patients with AML, Chronic Lymphocytic Leukemia (CLL), and Small Lymphocytic Leukemia (SLL). Despite its approval in AML, venetoclax has produced low response rates of 19% as a single agent in R/R AML.1 This is due in part to the type of AML, risk factors, and cytogenetics of this patient population. The Phase 2 trial results, together with a synergistic mechanism of action with venetoclax demonstrated in pre-clinical studies, are driving this combination trial with an initial focus on the high unmet needs of R/R patients including those who have relapsed or do not respond to treatment with venetoclax based regimens.

1 Aldosset al. Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia. Haematologica2018.1888094.

About Actinium's CD33 Program

Actinium's CD33 program is evaluating the clinical utility of Actimab-A, an ARC comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as patients with multiple myeloma. The CD33 development program is driven by data from over one hundred treated patients, including a Phase 1/2 trial where Actimab-A produced a remission rate as high as 69% as a single agent. This clinical data is shaping a two-pronged approach for the CD33 program, where at low doses the Company is exploring its use for therapeutic purposes in combination with other modalities and at high doses for use for targeted conditioning prior to bone marrow transplant. Actinium currently has multiple clinical trials ongoing including the Phase 1 Actimab-A CLAG-M and Phase 1/2 Actimab-A venetoclax combination trials and is exploring additional CD33 ARC combinations with other therapeutic modalities such as chemotherapy, targeted agents or immunotherapy.

About Actinium Pharmaceuticals, Inc. (NYSE: ATNM)

Actinium Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing ARCs or Antibody Radiation-Conjugates, which combine the targeting ability of antibodies with the cell killing ability of radiation. Actinium's lead application for our ARCs is targeted conditioning, which is intended to selectively deplete a patient's disease or cancer cells and certain immune cells prior to a BMT or Bone Marrow Transplant, Gene Therapy or Adoptive Cell Therapy (ACT) such as CAR-T to enable engraftment of these transplanted cells with minimal toxicities. With our ARC approach, we seek to improve patient outcomes and access to these potentially curative treatments by eliminating or reducing the non-targeted chemotherapy that is used for conditioning in standard practice currently. Our lead product candidate, I-131 apamistamab (Iomab-B) is being studied in the ongoing pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory Acute Myeloid Leukemia (SIERRA) trial for BMT conditioning. The SIERRA trial is over seventy-five percent enrolled and positive single-agent, feasibility and safety data has been highlighted at ASH, TCT, ASCO and SOHO annual meetings. More information on this Phase 3 clinical trial can be found at http://www.sierratrial.com. I-131 apamistamab will also be studied as a targeted conditioning agent in a Phase 1 study with a CD19 CAR T-cell therapy and in a Phase 1/2 anti-HIV stem cell gene therapy with UC Davis. In addition, we are developing a multi-disease, multi-target pipeline of clinical-stage ARCs targeting the antigens CD45 and CD33 for targeted conditioning and as a therapeutic either in combination with other therapeutic modalities or as a single agent for patients with a broad range of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Ongoing combination trials include our CD33 ARC, Actimab-A, in combination with the salvage chemotherapy CLAG-M and the Bcl-2 targeted therapy venetoclax. Underpinning our clinical programs is our proprietary AWE (Antibody Warhead Enabling) technology platform. This is where our intellectual property portfolio of over 130 patents, know-how, collective research and expertise in the field are being leveraged to construct and study novel ARCs and ARC combinations to bolster our pipeline for strategic purposes. Our AWE technology platform is currently being utilized in a collaborative research partnership with Astellas Pharma, Inc. Website: https://www.actiniumpharma.com/

Forward-Looking Statements for Actinium Pharmaceuticals, Inc.

This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.

Contacts:

Investors: Clayton Robertson Actinium Pharmaceuticals, Inc. [emailprotected]

Hans Vitzthum LifeSci Advisors, LLC [emailprotected](617) 430-9758

SOURCE Actinium Pharmaceuticals, Inc.

http://www.actiniumpharma.com/

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Actinium Reports 67 Percent Overall Response Rate in First Cohort in Actimab-A Venetoclax Combination Trial in Relapsed and Refractory AML at ASH -...

Tulane researcher shows enhanced therapeutic stem cell migration improves neurodegenerative disease – News from Tulane

By Induced Pluripotent Stem Cells

Jean-Pyo Lee, PhD, assistant professor in the Department of Physiology at Tulane School of Medicine, in collaboration with colleagues at Sanford Burnham Prebys Medical Discovery Institute and the University of California San Diego, has shown for the first time that injection of a synthetic drug that attracts stem cell migration can improve neurological outcome in a mouse model of neurodegenerative disease. (Photo provided)

Stem cell therapy, especially neural stem cells, offers great promise in treating brain injury. Neural stem cells exhibit a broad repertoire of potentially multiple therapeutic actions including functional neural replacement and acute and chronic anti-inflammatory action via the delivery of therapeutic gene products synthesized inherently by the stem cells in the disease environment.

For optimal stem cell therapy, neural stem cells should migrate quickly and extensively to the site of injury and neurodegeneration.

Jean-Pyo Lee, PhD, assistant professor in the Department of Physiology at Tulane School of Medicine, in collaboration with colleagues at Sanford Burnham Prebys Medical Discovery Institute and the University of California San Diego, has shown for the first time that injection of a synthetic agonist (drug),that attracts stem cell migration can improve neurological outcome in a mouse model of neurodegenerative disease. The research was recently published by the Proceedings of the National Academy of Sciences of the United States of America and can be viewed here: https://www.pnas.org/content/early/2020/11/19/1911444117.

The study addresses the important nature of tropism of stem cell migration using neural stem cells, Lee said. Chemokines and chemokine receptors found inneural stem cells can mediate this activity.

In this study, human neural stem cells derived from induced pluripotent stem cells were used. Transplantation of human induced pluripotent stem cell-derived neural stem cells in a mouse model of a prototypical neurodegenerative disease improves neurological function and increases the life span of neurodegenerative mice.

The study also found that a synthetic chemokineanalog attracts these neural stem cellsand increases the beneficial impact of these stem cells on neurological disorders, Lee said. When this analog is co-administered with transplanted neural stem cells, the agonist (drug) enhanced stem cell migration, dissemination and integration into the diseased brains. Considering the prevalence of neurological diseases and current limitations of stem cell therapy, the findings will contribute to advancing the stem cell field and will be of great interest to further neurodegenerative disease research.

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Tulane researcher shows enhanced therapeutic stem cell migration improves neurodegenerative disease - News from Tulane

Researchers restore lost sight in mice, offering clues to reversing aging – Science Magazine

By Induced Pluripotent Stem Cells

Researchers reversed damage to the mouse eye (shown in a microscope image of a healthy animal, above) by genetically reprogramming neurons that make up the optic nerve.

By Kelly ServickDec. 2, 2020 , 5:30 PM

Do old and damaged cells remember what it was like to be young? Thats the suggestion of new study, in which scientists reprogrammed neurons in mouse eyes to make them more resistant to damage and able to regrow after injurylike the cells of younger mice. The study suggests that hallmarks of aging, and possibly the keys to reversing it, lie in the epigenome, the proteins and other compounds that decorate DNA and influence what genes are turned on or off.

The idea that aging cells hold a memory of their young epigenome is very provocative, says Maximina Yun, a regenerative biologist at the Dresden University of Technology who was not involved in the work. The new study supports that [idea], but by no means proves it, she adds. If researchers can replicate these results in other animals and explain their mechanism, she says, the work could lead to treatments in humans for age-related disease in the eye and beyond.

Epigenetic factors influence our metabolism, our susceptibility to various diseases, and even the way emotional trauma is passed through generations. Molecular biologist David Sinclair of Harvard Medical School, who has long been on the hunt for antiaging strategies, has also looked for signs of aging in the epigenome.

The big question was, is there a reset button? he says. Would cells know how to become younger and healthier?

In the new study, Sinclair and his collaborators aimed to rejuvenate cells by inserting genes that encode reprogramming factors,which regulate gene expressionthe reading of DNA to make proteins. The team chose three of the four factors scientists have used for more than 10 years to turn adult cells into induced pluripotent stem cells, which resemble the cells of an early embryo. (Exposing animals to all four factors can cause tumors.)

The team focused specifically on neurons at the back of the eye called retinal ganglion cells. These cells relay information from light-sensitive photoreceptors to the brain using long tendrillike structures called axons, which make up the optic nerve. Theres a stark divide between youth and age in these cells: An embryonic or newborn mouse can regenerate the optic nerve if it gets severed, but that ability vanishes with time.

To test whether their treatment could bring back some of that resilience, Sinclair and colleagues crushed the optic nerves of mice using forceps and injected a harmless virus into the eye carrying the genes for the three reprogramming factors. The injection prevented some damaged retinal ganglion cells from dying and even prompted some to grow new axons reaching back to the brain, the team reports today in Nature.

When the researchers looked at methylation patternsthe DNA location of chemical tags called methyl groups that regulate gene expressionthey found that changes caused by the injury resembled those in aging mouse cells. In certain parts of the genome, the treatment reversed those changes. The researchers also found that the benefits of the introduced genes depended on cells ability to alter their methylation patterns: Mice lacking certain enzymes necessary to remove methyl groups from DNA saw no benefit to the treatment.

Thats really something special, says Leonard Levin, a visual neuroscientist at McGill University. The experiments suggest how the famous and well-studied reprogramming factors restore cells. But big questions remain, he says: How do these factors cause methyl groups to be added or removed? How does that process help retinal ganglion cells?

Sinclairs team also tested the approach in mice with a condition meant to mimic glaucoma, a leading cause of age-related blindness in humans. In glaucoma, the optic nerve gets damaged, often by a buildup of pressure in the eye. Sinclair and his colleagues injected tiny beads into the animals eyes that prevented normal drainage and increased pressure, which damaged retinal ganglion cells.

Four weeks later, the animals visual acuity had declined by about 25%, as measured by a vision test in which mice move their heads to track the movement of vertical bars displayed on computer monitors. But after the genetic treatment, the animals gained back roughly half of their lost acuitythe first demonstration of restored vision in mice after this glaucomalike injury.

Still, the improvement in acuity was small, Levin notes. And, he says, the treated mice were in a relatively early stage of damage, not the state of near or total blindness that people experience when glaucoma goes untreated for years. So its too early to say whether this approach could benefit people who have lost much of their vision. Levin adds that there are already very good treatments for early-stage glaucoma to prevent vision loss with medicated eye drops or surgery to lower eye pressure.

In a final set of experiments, Sinclair and colleagues injected the reprogramming-factor genes into the eyes of 1-year-old healthy mice, roughly the mouse equivalent of middle-age. By this stage, the animals had visual acuity scores about 15% lower than their 5-month-old counterparts. Four weeks after treatment, older mice had similar acuity scores to younger ones. In their cells, the researchers saw patterns of DNA methylation and gene expression resembling those of younger animals.

In the three sets of experiments, Sinclair says, the cells seemed to respond to the reprogramming factors by fine-tuning their gene expression to match a youthful state. He sees that behavior as a hint that cells keep a record of their epigenetic past, even though its not clear how that record is stored. A company Sinclair cofounded, Life Biosciences, is developing treatments for diseases associated with aging, including glaucoma, and he says hes now planning to test the safety of this gene therapy approach in larger animals.

Yun says that as a strategy for reversing aging or treating disease, resetting the epigenome is a very difficult one. Reprogramming cells to an earlier state carries a risk of prompting uncontrolled growth and cancer.Future studies should test how the three factors affect other types of cells and tissues and confirm that reprogrammed cells maintain their youthful state long-term, she says. There are a lot of roads to be traveled.

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Researchers restore lost sight in mice, offering clues to reversing aging - Science Magazine

Fate Therapeutics Reports Positive Interim Data from its Phase 1 Study of FT516 in Combination with Rituximab for B-cell Lymphoma | DNA RNA and Cells…

By Induced Pluripotent Stem Cells

Details Category: DNA RNA and Cells Published on Monday, 07 December 2020 09:38 Hits: 377

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

SAN DIEGO, CA, USA I December 04, 2020 I 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.

SOURCE: Fate Therapeutics

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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 | DNA RNA and Cells...

Bayer and Atara Biotherapeutics in CAR T-cell therapy deal – BioPharma-Reporter.com

By Induced Pluripotent Stem Cells

Atara is a pioneer in allogeneic T-cell immunotherapy with industry-leading allogeneic cell manufacturing processes and CAR T technologies.

Under the terms of the deal, that San Francisco-based innovator will receive an upfront payment of US60m, and up to a total of US$610m for development, regulatory and commercialization milestones, plus tiered royalties up to low double-digit percentage of net sales.

The collaboration will focus on Ataras off-the-shelf allogeneic T-cell immunotherapy, ATA3271, for high mesothelin-expressing tumors, and its autologous version, ATA2271, for high mesothelin-expressing tumors such as malignant pleural mesothelioma and non-small-cell lung cancer.Both therapies were developed in conjunction with Memorial Sloan Kettering Cancer Center (MSK).

Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors and is an attractive target for immune-based therapies, including CAR T therapy.

Both ATA2271 and ATA3271 are engineered for use in solid tumors as they incorporate Ataras novel inclusion of both a PD-1 DNR construct to overcome checkpoint inhibition and a 1XX costimulatory domain on the CAR (chimeric antigen receptor) to enhance expansion and functional persistence of the CAR T cells.

ATA3271, the allogeneic version of this CAR T, leverages Ataras EBV T-cell platform and is currently in IND-enabling studies. ATA2271, the autologous version, has enrolled the first patient in an open-label, single-arm Phase 1 clinical study in November 2020.

Bayer said the deal is a fundamental element of its new cell and 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 the pharma giants CGT unit.

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

Pascal Touchon, CEO of Atara, said Bayers proven track record in oncology global development and commercialization, and growing presence in cell and gene therapy, enhances Ataras capabilities and complements its leading allogeneic T-cell platform.

Atara is to lead the Investigational New Drug (IND)-enabling studies and process development for ATA3271 while Bayer will be responsible for submitting the IND and subsequent clinical development and commercialization. Atara will also continue to be responsible for the ongoing ATA2271 phase 1 study, for which an IND filing has been accepted and the clinical trial initiated.

As part of the deal, Atara will also provide translational and clinical manufacturing services to be reimbursed by Bayer. In addition, for a limited period of time, Bayer has a non-exclusive right to negotiate a license for additional Atara CAR T product candidates.

In order to build up its presence in the CGT sphere, Bayer said it is focused on strengthening its internal capabilities in that respect.

In parallel, it says it is pursuing external strategic collaborations, technology acquisitions and licensing. The goal is to build robust platforms with broad application across different therapeutic areas.

It outlined selected areas of CGT for its strategic focus including stem cell therapies with an emphasis on induced pluripotent cells or iPSCs - gene augmentation, gene editing and allogeneic cell therapies in different indications.

Leveraging external innovation together with the expertise of the teams at Bayer represents a key value-driver, especially in the highly dynamic and competitive field of CGT. Bayers operating model for CGT, where partners operate autonomously and are fully accountable to develop and progress their portfolio and technology, is essential for preserving their entrepreneurial culture and positions Bayer as a partner of choice.

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Bayer and Atara Biotherapeutics in CAR T-cell therapy deal - BioPharma-Reporter.com

Cord blood banks sell parents on promising stem cell research, but with no guarantees – The Arizona Republic

By Stem Cell Medicine

Stem cell treatment promise sells pregnant parents on cord blood banks Arizona Republic

Moments after Linda Buzans son Luca is born, her OB-GYN goes to work. She carefully cuts the white umbilical cord, then clamps it shut before any blood can escape. Once the cord is cleaned, she carefully inserts a needle with a long tube attached and lets the umbilical cord blood pump into a collection bag.

From there, the sample will travel in a labeled collection box to Tucson, where a laboratory for one of the oldest and biggest private cord blood banking companies nationwide is located. There, at the Cord Blood Registry laboratory, or CBR,baby Lucas umbilical cord blood will be frozen in a metal tank at less than minus 320 degrees, joining almost 900,000 other samples in storage,including that of his older sister, Lola.

Umbilical cord blood is full of stem cells, so it can be transplanted into patients to treat certain types of cancers, diseases and blood disorders. Umbilical cord blood works as an alternative for many patients who cant find bone marrow transplants.

Butthe odds that either Lola or Luca will develop a disease like cancer that would require an umbilical cord blood transplant are slim,about one in 1,000 or one in 2,000, according to University of Arizona umbilical cord blood stem cell researcher David Harris.

Its difficult to reconcile saving for yourself because youre afraid of cancer, Harris said. Do it based on facts, not fear.

Stem cells in umbilical cord blood could have another purpose: regenerative medicine. Current clinical trials show promise for the use of umbilical cord blood to treat a host of conditions such as neurological disorders, orthopedic injuriesand even diabetes. These potential usages are a new draw for parents to bank their childs umbilical cord blood.

The odds of use for these regenerative medicine applications is much, much higher, Harris said.

He estimates the odds of developing a disease that could be treated by umbilical cord blood stem cells is about one in ten.

Butthe science is still developing, which meanscompanies are selling parents ona product they may never be able to use.

In the past two decades, Harris has been involved with studies to treat kids with conditions like cerebral palsy, strokes, traumatic brain injuries and diabetes.

When you now start to talk about being able to treat a knee injury or a heart attack, or a stroke the ability to actually do that and then to see that it works is very exciting, he said. And thats really where the use of cord blood is going.

So far, Harris said hes seen the most success with orthopedic injuries and in treating children that have suffered from strokes.

With strokes, Harris said he observed children go from being completely paralyzed on one side to being fully functioning.

DONATIONS:Donated cord blood saved Sophie Lee's life, but most parents throw it away

Though some initial results show promise, Harris acknowledges that to move forward with any of these treatments, researchers need to demonstrate a good success rate.

The big question when it comes to using cord blood for regenerative medicine is when it will be incorporated into actual medical practice. For safety reasons, FDA approval for new treatments can take years,if not decades.

Currently, the only way to use umbilical cord blood stem cells for FDA-approved regenerative medicine is to qualify for and register in clinical trials to treat specific conditions. Harris has banked his owns sons cord blood on his belief that more and more umbilical cord blood treatments will become commercially available in the future. Buzan has done the same.

Brandon Buzan packages up his newborn son's umbilical cord blood to be shipped to the Cord Blood Registry lab for storage.(Photo: Amanda Morris)

Its not something that you want to say I wish I had done this, because you cant do it later.You have this one shot,"Buzan said."Even its like one percent of saving their life or helpingI mean for your child, youd do anything as a parent.

In Arizona, obstetrics health providers are required by law to educateexpectant parents about the options to publicly donate or privately bank cord blood. YetDr. Jaime Shamonki, the Chief Medical Officer of CBR, estimates that less than 5% of the population chooses to bank cord blood. A small percentage donate the blood, but a much larger percentage simply throws it away.

Kelly Helms, a Scottsdale-based OB-GYN, said the most common reasonher patients give for not banking their childs cord blood is the cost.

Buzan, who is one of her patients, said she got a discount to bank her childrens samples with CBR because of a connection her familyhad with the company. She paid a little over $1,000 for the initial processing and storage fee for both samples, and continues to pay an annual storage fee of about $120 for each one.

To bank one sample of cord blood and cord blood tissue, the initial cost is$2,830, according to CBR, with a $360 annual storage fee after that. To bank just the cord blood, not the tissue, the initial cost is $1,680, with a $180annual storage fee. Both cord blood and cord tissue have different types of stem cells that are thought to potentially repair the body in different ways.

The stem cells and potential treatments for both sources arent fully understood yet, so there are no guarantees that parents or children will actually be able to use the samplesthey pay to store.

Of the nearly 900,000 samples CBR keeps in storage, Shamonki estimates about 600 have been released for customers to use,representing a usage rate of less than 1 percent. According to Shamonki, the low sample release rate is due to FDA regulations, which stipulate that umbilical cord blood can only be used in approved treatments or clinical trials.

If we didnt have the FDA, then I would be able to release like thousands of units, she said. Its really a regulatory problem, its not a utility problem.

To boost usage of the samples, CBR maintains a registry to match eligible customers to clinical trials and has partnered with research institutions to sponsor clinical trials.

Despite FDA regulations, which Shamonki acknowledges are important to protect public health, she said CBR is releasing more and more units every year. Of the samples taken out, about 83% are used for regenerative medicine purposes, according to CBR.

What I know is that in the next fiveyears, next 10 years, there will be so many more opportunities, Shamonki said. So just because you dont have 100 different clinical trials you can sign up for tomorrow doesnt mean that these applications wont exist in fiveor 10 years, and your child might need it.

CBR is one of many companies that market cord blood banking to new parentsand is one of the biggest. Helms said she always recommends her patients to do their research and pick one of the larger, more established cord blood banking companies. Such companies might includeCBR, Cryo-cell, or ViaCord.

I've had patients lose their cord blood, privately banked blood, because they went with a small company and now they closed down, Helms said.

Even with some of the larger companies, the process of cord blood banking doesnt always run smoothly.

Although she couldn't have her daughter's cord blood stored, Chelsea Radford says she paid over $1,000 to ViaCord for processing fees.(Photo: Amanda Morris)

The first time Phoenix-resident Chelsea Radford heard about cord blood banking, she was already pregnant and facingmyriaddecisions that were sometimes overwhelming. She had never heard of it before reading some pamphlets from her gynecologist, but she was quickly sold on the idea of banking her daughters cord blood and tissue with ViaCord.

Radford has a history of Alzheimers disease in her family, and said she was initially interested in what potential treatments cord blood and tissue might offer for the disease. In 2015, one study suggested that human umbilical cord blood cells could have therapeutic benefitsin mice with Alzheimers disease.

In addition to researching studies, Radford said she spent hours looking at different cord blood banking companies and asking representatives questions about the process. Of all the companies, she found ViaCord to be the most responsive and willing to answer her questions in-depth.

Having the communication and the availability that is what sold me on ViaCord. But that really quickly ended there with the sale, she said.

On the day of her daughter Brylees birth in July2018,Radford went to a hospital that ViaCord had assured her was familiar with collecting cord blood. Soon after, she got a call from the company saying her sample couldnt be stored because not enough blood was collected. Shestill owed ViaCord over $1,000 for a lab processing fee.

Radford wanted more information before she would agree to pay, and said she spent monthscalling, leaving the company messages, and getting no response.

After the birth, nobody responds to anything, she said.

The company called her three months later to tell her that if she didnt pay her bill, they would send it to collections.

I got pissed! Radford said. The only thing they seem to care about is the moneythey dont care about is having a conversation with me about why and how this sample didnt turn out the way it shouldve. All they want to talk to me about is the money.

Still, Radford said she refused to pay a dime until she got an explanation. She contacted the doctor who delivered her baby and said she learned the doctor had never done a cord blood collection before and had never been trained on how to do one.

Finally, she spoke with a ViaCord representative, who she saidtold her this sometimes happens, butthe company wasnt responsible for the fact that the doctor who took her sample didnt take enough blood.

Frustrated and inundated with other responsibilities that come with caring for a newborn, Radford said she decided to pay the fee so that she could move on.

We paid a company to do nothing for us just to get them to leave us alone and not send a bill to collections that I dont feel like we shouldve had to foot in the first place, she said.

If she had a second child, Radford said she wouldnt choose to cord blood bank again, and doesnt recommend it to other moms.

You can still get stem cell help without using your own banked blood and tissueThis is just a costly option that is not a given that its going to work out 100% in your favor, she said. You could have a newborn and be responsible to pay thousands of dollars for nothing.

ViaCord did not respondto multiple requests for comment.

If parents decide to pay for private banking, Radford said they should be careful about making sure the doctors delivering their children know how to collect the samples. Shesaid blood banking companies should be more responsible in making sure that doctors are trained in blood collection.

While Helms is comfortable doing cord blood collection, she was never formally taught how to do it while studying and training to be an OB-GYN.

It was basically taught by the company, she said. Each kits a little different.

Helms said the procedure is fairly simple, but every once in a while, she comes across a company shes never heard of, and a kit she is unfamiliar with. Sometimes she needs to take on the extra responsibility of making sure she understands the directions for that particular kit.

Each company really should take on the responsibility, she said. I can't surf the Internet and look for every YouTube video on every cord blood banking company, she said.

Another potential complication in banking cord blood orblood tissue is that the blood or tissue can become infected.

Birth is not that clean of a process and ideally when you take that needle and you drain the umbilical cord, youll have cleaned that umbilical cord first and you hope that no bacteria get in to the cord blood unit, but its possible, it does happen on a number of occasions, Shamonki said.

Shamonki says CBR tests for any bacterial contamination before storing the tissue and works with parents who have infected samples to discuss possibilities of being able to use the unit in the future.

A Cord Blood Registry worker processes cord blood for storage in the company's Tucson laboratory.(Photo: Amanda Morris)

Nobody knows when regenerative medicine applications for cord blood will become readily available as FDA-approved mainstreamtreatments. New applications for cord blood are being tested every year and new technologies to expand and utilize stem cells in cord blood are constantly being developed.

We dont really know what the limits are, but there are limits to what (umbilical cord blood stem cells) can do, Harris said.

Because cord blood banking is so new it has only been around since 1989 its unclear how long samples can be stored and remain effective.

According to Harris, cord blood samples can still work after being stored for about two decades.

We recently took one out that was 24, 25 years old, he said.

He speculates that properly stored cord blood samples could probably work throughout a person's lifetime, if not longer.

Buzan is aware that stem cells and cord blood treatments are still a new science with no guarantees, but she also believes in the treatments future potential.

Every month, she and her husband receive email updates from CBR that explain some of the new clinical trials and research discoveries involving cord blood.

To be honest the most exciting thing is the unknown the unknown of what the cord blood could do, what theyre looking into now, thats fascinating, she said. Im just so glad we live in a time that where this is available to use this was not an option for my parents or my grandparents.

Amanda Morris covers all things bioscience, which includeshealth care,technology, new researchand the environment. Send her tips, story ideas, or dog memes at amorris@gannett.com and follow her on Twitter @amandamomorris for the latest bioscience updates.

Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.

Support local journalism.Subscribe to azcentral.com today.

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Cord blood banks sell parents on promising stem cell research, but with no guarantees - The Arizona Republic

Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease – The Conversation US

By Stem Cell Medicine

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.

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.

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.

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Genetic engineering transformed stem cells into working mini-livers that extended the life of mice with liver disease - The Conversation US

Procyon Technologies LLC and Novo Nordisk A/S to Collaborate on the Development of a Stem-Cell Based Therapy for Type 1 Diabetes – PRNewswire

By Stem Cell Medicine

TUCSON, Ariz., Dec. 8, 2020 /PRNewswire/ --Procyon Technologies LLC today announced that it has entered into an exclusive research collaboration and license agreement with Novo Nordisk A/S to develop an implantable cell encapsulation device to be used in Novo Nordisk's development of a novel therapy for Type 1 diabetes.

The collaboration brings together Procyon Technologies' expertise with development of oxygen enabled implantable cell encapsulation devices and Novo Nordisk's expertise in stem cell-derived insulin-secreting cells.

The partners will work together to further optimize the device and cells for clinical testing and accelerate the path to First Human Dose with the joint vision of delivering a functional cure for people living with Type 1 diabetes.

Under the terms of the agreement, Procyon Technologies, a startup founded to commercialize innovations developed at the University of Arizona College of Medicine Tucson, will receive an upfront license fee and will be eligible for further payments relating to preclinical, clinical and regulatory milestones. In addition, Procyon Technologies will receive tiered sales milestones and royalties on the annual net sales of the products resulting from the collaboration.

Novo Nordisk will be responsible for the development, manufacturing and commercialization of the products resulting from the collaboration for Type 1 diabetes.

The right cells and the right device

Type 1 diabetes is an autoimmune disease in which insulin-producing beta cells in the pancreas are mistakenly destroyed by the body's immune system. For people with Type 1 diabetes, life-long daily administration of insulin to control their blood sugar and constant blood glucose monitoring is the burden of reality.

"If we are able to offer a treatment that safely and effectively replaces the insulin-producing cells that people with Type 1 diabetes have lost, we could essentially offer them a functional cure for their disease," said Jacob Sten Petersen,DMSc, corporate vice president and head of stem cell research and development for Novo Nordisk.

Since 2008, Novo Nordisk has invested in human stem cell technology and worked on generating a protocol for stem cell-derived insulin producing islet-like clusters for the treatment of Type 1 diabetes.

But having the right cells is only half the solution; the cells also need to be protected from the recipient's immune system to avoid rejection, as well as from the autoimmunity of Type 1 diabetes.

For the last two decades, Procyon Technologies co-founder Klearchos Papas, PhD, a professor in the Department of Surgery and director of the Institute for Cellular Transplantation at the University of Arizona College of Medicine Tucson, has been working on a solution to the second part of that challenge.

"As a pancreas transplant surgeon, the idea of replacing beta cell function in a diabetic patient to prevent progression of diabetic complications makes perfect sense," said Michael M.I. Abecassis, MD, MBA, dean of the UArizona College of Medicine Tucson and professor of surgery and immunobiology. "Therefore, the notion of doing this without the need for major surgery and without the need for anti-rejection drugs by leveraging the assets of academia with those of industry represents the next frontier in curing Type 1 diabetes and preventing its complications."

With support from JDRF International and the National Institute of Diabetes and Digestive and Kidney Diseases, and utilizing key University of Arizona facilities and infrastructure (such as the BIO5 Institute device prototyping lab), Dr. Papas and his team developed oxygen enabled implantable immuno-isolation device technology with a focus on safety, practicality, and the maintenance of viability and functionality of encapsulated cells.

"We are delighted and excited to join forces with Novo Nordisk and provide the 'implantable encapsulation device' part of the functional cure for people suffering from Type 1 diabetes. Novo Nordisk is a leader in the development of stem cell-derived insulin producing islet-like clusters, has demonstrated strong commitment, and has the capacity, infrastructure and most importantly, the shared vision and interest in seeking to bring this functional cure to patients," said Dr. Papas.

"The combination of the implantable encapsulation device with islet-like clusters provides a unique opportunity to develop a novel cell therapy for diabetes. This announcement reinforces the value of JDRF in supporting science and technologies that can be further advanced in partnerships," said Esther Latres, PhD, assistant vice president of research at JDRF.

"Dr. Papas' work exemplifies our research mission in the Department of Surgery. The collaboration between our investigators and clinicians allows for the development of innovative, cutting-edge solutions to the clinical problems we treat every day," said Taylor S. Riall, MD, PhD, chair of the UArizona Department of Surgery. "The partnership between Procyon Technologies and Novo Nordisk represents the culmination of years of hard work and will revolutionize the care of people with Type 1 diabetes."

A therapeutic implant

The Procyon cell encapsulation device is a small, flat, thin, highly durable, flexible implantable chamber. It mitigates foreign body response, promotes the formation of vascular structures on its surface enabling the rapid diffusion of nutrients to the cells inside and the rapid absorption of insulin (or other therapeutic molecules) secreted by the encapsulated cells while providing a barrier protecting them from attacks by the body's immune system without the need for immunosuppressive drugs. The Procyon technology, designed with practical clinical use as a driver, includes integration of oxygen delivery to the implantable device, which enables tighter packing of cells while maintaining their viability and functionality.

About Procyon Technologies LLC:

Procyon Technologies LLC (https://procyon-technologies.com) was founded in Arizona in 2016. Klearchos Papas, PhD, Allison F. Corkey, MS, Thomas Loudovaris, PhD, and Robert C. Johnson, PhD, are co-founders and worked with Tech Launch Arizona, the University of Arizona commercialization arm, to protect the intellectual property and license the platform technology suitable for the implantation of a variety of therapeutic cells aimed at treating a number of disorders. In addition to being highly respected researchers in the field of diabetes and encapsulation therapy for decades, Dr. Johnson, a part-time research professor in the Department of Surgery at the University of Arizona, has had Type 1 diabetes for nearly 51 years and Dr. Loudovaris is the father of two children with the disease.

Contact: Allison F. Corkey [emailprotected] 520-329-1425

SOURCE Procyon Technologies LLC

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Procyon Technologies LLC and Novo Nordisk A/S to Collaborate on the Development of a Stem-Cell Based Therapy for Type 1 Diabetes - PRNewswire

Hadassah Medical Center and Neurogenesis Announce Groundbreaking Results from a Phase 2 Study in Progressive Multiple Sclerosis treated with NG-01…

By Stem Cell Medicine

JERUSALEM, Dec. 8, 2020 /PRNewswire/ --NeuroGenesis, a clinical-stage biopharmaceutical company advancing innovative cell therapies to combat myelin-related neurodegenerative diseases, and Hadassah Medical Center announced today highly positive results from a placebo-controlled Phase 2 clinical trial, headed by Prof. Dimitrios Karussis, together with Dr. Petrou Panayiota and Dr. Ibrahim Kassis from Hadassah Medical Center in Jerusalem, assessing the impact of NG-01 autologous proprietary subpopulation of mesenchymal stem cells (MSCs) on patients with progressive multiple sclerosis (MS).

The results, recently published in Brain, a prestigious peer-reviewed journal published by Oxford University, and highlighted in the "Editor's Choice", show that:

"The treatment was well tolerated and the trial met all of its primary endpoints," said Professor Dimitrios Karussis, lead principle investigator and Director of MS Center at Hadassah Medical Center, Jerusalem. "The patients' improvement was in many cases quite remarkable and included regain of motor function and noticeable effects on their cognitive abilities."

Prof Karussis added, "Although we currently have several good treatment options for relapsing remitting MS, we fall short in providing effective treatment for progressive MS that could substantially suppress the progression of disability. This trial provides encouraging results and suggests a potential for a new approach that may not only slow down the progression of the disease but even induce improvement and promote repair mechanisms in progressive MS."

The technology is now further developed by NeuroGenesis, following a license from Hadasit, Hadassah Medical Center Technology Transfer Company.

Neurogenesis' technology entails collecting bone marrow from the patient. Then by utilizing a proprietary process, a unique subpopulation of bone marrow cells is identified, cultured and enhanced towards remyelinating biofactory cells (NG-01) that also possess neurotrophic immunolatory and neuroprotective properties. The NG-01 cell population is injected directly into the central nervoussystem (through the cerebrospinal fluid), where the cells home-in on the damaged area, take up residence and produce significant amounts of neurotrophic factors.

"Progressive MS is a chronic, debilitating disease with no satisfactory treatment to improve or reverse established disability," said Tal Gilat, CEO of NeuroGenesis. "We are therefore extremely pleased to witness the significant positive effect of our NG-01 cells. Following recent interactions with the FDA, we look forward to confirming and expanding these findings in a large multi-center MS trial, and continuing advanced studies in additional indications such as ALS."

About the Phase 2 trial of NG-01

The Phase 2, randomized, double-blind, placebo-controlled, clinical trial assessed the safety, tolerability and efficacy of transplantation of NG-01 in people with progressive MS. The study enrolled 48 participants with progressive MS which were randomized into 3 groups, receiving either an intrathecal or intravenous NG-01 injection, or a placebo injection.

The two predetermined primary endpoints of the trial were: (i) the safety of the intrathecal and intravenous NG-01 treatments assessed by incidence of adverse events versus those in the placebo-treated group; and (ii) the differences among the three groups in the Expanded Disability StatusScale(EDSS) score changes and the proportion of patients with treatment failure, as evidenced by an increase in EDSS (disease progression) score, at 6 and 12 months. Overall, the study duration was 14 months.

About Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease that causes damage in the myelin and the nerve cells of the central nervous system (demyelinating plaques in brain and spinal cord), resulting in cumulating neurological disability. The destruction of the myelin (the covering that protects nerves and promotes the efficient transmission of nerve impulses) causes secondary damage to the nerve cells and progressive atrophy. MS often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Motor problems are common in people with MS. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or paralysis of the muscles of the limbs, difficulty in walking, and poor sphincter control. The condition is also associated with visual problems, such as blurred or double vision or partial or complete vision loss. There is no known cure for multiple sclerosis.The existing treatments are mostly aimed to reduce the incidence of relapses of the disease and slow down the rate of neurological deterioration.

About NeuroGenesis

Neurogenesis is developing cell therapy for neurodegenerative diseases based on a unique approach for sustained delivery of high levels of remyelinating growth factors using the patient's own stem cells. The technology for this unique approach was licensed from Hadasit, theTechnology TransferCompany of Hadassah Medical Organization in Jerusalem, Israel. The Company's lead product is NG-01 for the treatment of progressive Multiple Sclerosis, (in which a placebo-controlled Phase 2 study has been completed and recently published). NG-01 were also tested in two successful Phase 2a trials in ALS patients. Up to today, more than 150 progressive MS and ALS patients from around the world have been treated with Neurogenesis'products via clinical trials (Phase 1 and Phase 2) and compassionate use treatments.

About Hadassah and Hadasit

For more than a century, Hadassah has set the standard of excellence for medical care and research in Israel. Our doctors and scientists are on the frontlines, uniquely positioned to pinpoint ever-evolving medical needs. Their experience and ingenuity have yielded new ideas with huge potential in all areas of medicine, including therapeutics, diagnostic medical devices, and digital health. Hadasit is the technology transfer company of Hadassah Medical Center in Jerusalem. We transform the cutting-edge research coming out of Hadassah into marketable medical technologies. We turn ground-breaking ideas into viable products and services that can change the world and better humanity.

NeuroGenesiscontact:Tsipi Haitovsky Global Media Liaison NeuroGenesis +972-52-5989-892 [emailprotected]

Hadassah contact:Hadar Elboim spokeswoman Hadassah Medical Organization + 972- 2-6776079 [emailprotected]

SOURCE NeuroGenesis

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Hadassah Medical Center and Neurogenesis Announce Groundbreaking Results from a Phase 2 Study in Progressive Multiple Sclerosis treated with NG-01...

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