Yearly Archives: 2020


New Research On Brain Structure Highlights Cells Linked To Alzheimer’s And Autism – BioSpace

New insights into the architecture of the brain have been revealed by scientists at the Wellcome Sanger Institute, the Wellcome-MRC Cambridge Stem Cell Institute and their collaborators. The researchers discovered that cells in the cerebral cortex of mice, called astrocytes, are more diverse than previously thought, with distinct layers of astrocytes across the cerebral cortex that provide the strongest evidence to date of their specialization across the brain.

Published today (16 March) in Nature Neuroscience, the most in-depth study of its kind is set to change the way we think about the brain and the role of cells such as astrocytes. This knowledge will have with implications for the study of neurological disorders, such as Alzheimers, multiple sclerosis and autism.

In the past 20 years, research has shown glial cells to be key players in brain development and function, as well as promising targets for better understanding neurological disorders. Alzheimers causes around two thirds of dementia cases in the UK, which affects around 850,000 individuals at present*. MS is a neurological disorder that affects the central nervous system and impacts around 100,000 people in the UK**. Autism affects around one in every hundred people in the UK***.

Glial comes from the Greek word for glue or putty. At one time, glial cells were thought of as 'brain putty' functionally similar, passive cells whose only function was to fill the space around the all important neurons. However, new studies are showing their critical importance in regulating neuron functions^. Astrocytes are a type of glial cell, so called because of their star-shaped structure^^.

Despite the wealth of knowledge on neuronal function and the organisation of neurons into layers, prior to this study there had been little investigation into whether glial cells across different layers showed different cellular properties. To answer this question, the researchers developed a new methodological approach to provide a more detailed view of the organisation of astrocytes than ever before.

Nucleic acid imaging was carried out on mouse and human brain samples at the University of Cambridge to map how new genes are expressed within tissue. These maps were combined with single cell genomic data at the Wellcome Sanger Institute to extend the molecular description of astrocytes. These data sets were then combined to create a three-dimensional, high-resolution picture of astrocytes in the cerebral cortex.

The team discovered that astrocytes are not uniform as previously thought, but take distinct molecular forms depending on their location in the cerebral cortex. They found that astrocytes are also organised into multiple layers, but that the boundaries of astrocyte layers are not identical to the neuronal layers. Instead, astrocyte layers have less sharply defined edges and overlap the neuronal layers.

Dr Omer Bayraktar, Group Leader at the Wellcome Sanger Institute, said: The discovery that astrocytes are organised into layers that are similar, but not identical to, neuronal layers redefines our view of the structure of the mammalian brain. The structure of the cerebral cortex can no longer simply be seen as the structure of neurons. If you want to properly understand how our brains work, you have to consider how astrocytes are organised and what role they play.

As well as increasing our understanding of brain biology, the findings will have implications for the study and treatment of human neurological disorders. Over the past decade glial cells, rather than neurons, have been heavily implicated in diseases such as Alzheimers and multiple sclerosis.

Professor David Rowitch, senior author of the study and Head of Paediatrics at the University of Cambridge, said: This study shows that the cortical architecture is more complex than previously thought. It provides a basis to begin to understand the precise roles played by astrocytes, and how they are involved in human neurodevelopmental and neurodegenerative diseases.

ENDS

Contact details:Dr Matthew MidgleyPress OfficeWellcome Sanger InstituteCambridge, CB10 1SAPhone: 01223 494856Email: press.office@sanger.ac.uk

Notes to Editors:

In the cerebral cortex of the mammalian brain, neurons are the cells responsible for transmitting information throughout the body. It has long been recognised that the 10-14 billion neurons of the human cerebral cortex are organised into six layers, with distinct populations of neurons in each layer that correspond to their function https://www.dartmouth.edu/~rswenson/NeuroSci/chapter_11.html

* More information on Alzheimers disease can be found here: https://www.alzheimersresearchuk.org/about-dementia/types-of-dementia/alzheimers-disease/about/

**More information about MS can be found here: https://www.mssociety.org.uk/about-ms/what-is-ms

*** More Information on autism is available from the National Autistic Society: https://www.autism.org.uk/about/what-is/asd.aspx

^ An overview of the changing status of glial cells is available at: https://blogs.scientificamerican.com/brainwaves/know-your-neurons-meet-the-glia/

^^ Only half of the cells in the human cerebral cortex are neurons, the other half are glial cells, of which astrocytes are a type. The molecular signals that astrocytes provide are essential for forming synapses between neurons. They regulate synapse formation in the developing brain, as well as refining synapses in the maturing brain 'pruning' extra synapses to sculpt neuronal networks.

Publication:

Omer Ali Bayraktar, Theresa Bartels and Staffan Holmqvist et al. (2020). Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nature Neuroscience. https://doi.org/10.1038/s41593-020-0602-1

Funding:

The study was supported by the Dr Miriam and Sheldon G. Adelson Medical Research Foundation, National Institute of Health (1R01 MH109912; P01NS08351), NINDS Informatics Center for Neurogenetics and Neurogenomics (P30 NS062691), Wellcome and the European Research Council (281961).

Selected websites:

Wellcome - MRC Cambridge Stem Cell InstituteThe Wellcome - MRC Cambridge Stem Cell Institute is a world-leading centre for stem cell research with a mission to transform human health through a deep understanding of normal and pathological stem cell behaviour. Bringing together biological, clinical and physical scientists operating across a range of tissue types and at multiple scales, we explore the commonalities and differences in stem cell biology in a cohesive and inter-disciplinary manner. In 2019, we relocated to a new purpose-built home on the Cambridge Biomedical Campus. Housing over 350 researchers, including a critical mass of clinician scientists, the Institute integrates with neighbouring disease-focused research institutes and also serves as a hub for the wider stem cell community in Cambridge. https://www.stemcells.cam.ac.uk/

About the University of Cambridge

The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. To date, 107 affiliates of the University have won the Nobel Prize.

Founded in 1209, the University comprises 31 autonomous Colleges, which admit undergraduates and provide small-group tuition, and 150 departments, faculties and institutions. Cambridge is a global university. Its 19,000 student body includes 3,700 international students from 120 countries. Cambridge researchers collaborate with colleagues worldwide, and the University has established larger-scale partnerships in Asia, Africa and America.

The University sits at the heart of the Cambridge cluster, which employs 60,000 people and has in excess of 12 billion in turnover generated annually by the 4,700 knowledge-intensive firms in and around the city. The city publishes 341 patents per 100,000 residents. http://www.cam.ac.uk

The Wellcome Sanger InstituteThe Wellcome Sanger Institute is a world leading genomics research centre. We undertake large-scale research that forms the foundations of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared across the globe to advance science. Our ambition is vast we take on projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our findings are used to improve health and to understand life on Earth. Find out more at http://www.sanger.ac.uk or follow us on Twitter, Facebook, LinkedIn and on our Blog.

About WellcomeWellcome exists to improve health by helping great ideas to thrive. We support researchers, we take on big health challenges, we campaign for better science, and we help everyone get involved with science and health research. We are a politically and financially independent foundation. https://wellcome.ac.uk

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New Research On Brain Structure Highlights Cells Linked To Alzheimer's And Autism - BioSpace

Coriell Institute for Medical Research Awarded $8.6 Million Biobanking Contract from National Institute on Aging – Newswise

Newswise The National Institute on Aging (NIA) has extended its biobanking contract with the Coriell Institute for Medical Research for an additional five years.

The newly awarded $8.6 million funding keeps Coriell in place as the trusted steward of this collection and includes the addition of new innovative products to expand the collection. The NIA Aging Cell Repository was established at Coriell in 1974 and Coriell has continuously managed this unique resource ever since.

Coriells relationship with the NIA is among its oldest and most treasured, said Nahid Turan, Coriell's Chief Biobanking Officer. We at Coriell are committed to ensuring the success of this phenomenal collection of aging-related biospecimens, and we are thrilled at the opportunity to continue this important collaboration with NIA.

The NIA Aging Cell Repository contains a collection of high quality, well characterized human and animal cell line and DNA samples, representing aged human populations, age-related diseases, and animal models of aging and has seen significant changes in the last decade.

One major focus of the collection is now to generate valuable induced pluripotent stem cell (iPSC) lines, which can be used to model aging and perform disease in a dish experiments. These stem cells are created from skin or blood cells in the NIA collection, which were reverted into a stem cell state. From there, these cells can be coaxed into becoming nearly any other cell type in the body, including neuronal or nerve cells. Seven of these important iPSC lines have been added to the collection in the last three years, representing age related neurodegenerative disorders like Alzheimers disease as well as rare genetic diseases like Progeria and Werner Syndrome.

Late last year, the Repository also added more than 350 new cell lines collected from participants in a long-term study of aging known as The 90+ Study. Participants in this study all aged 90 years or older donated their DNA and agreed to answer questions over a period of time to help researchers better understand the lifestyle and biological factors which may contribute to advanced aging.

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Coriell Institute for Medical Research Awarded $8.6 Million Biobanking Contract from National Institute on Aging - Newswise

His Immune System Went Out of Whack. The Usual Treatment Didnt Work. Why? – The New York Times

Jagasia was concerned that although G.V.H.D. was the most likely diagnosis, it might not be the right one. The patient had already been tested for the usual infections seen in immune-suppressed patients. So he looked for other possible causes of the patients diarrhea. He didnt find any. The patient lost another 15 pounds. When he looked in the mirror, he hardly recognized himself. Jagasia arranged for the patient to start getting intravenous nutrition and began tapering one immune-suppressing medication in order to start another.

The patients son was in medical school in another part of the state and called home frequently. When his father finally told him how sick he was, his son got scared. His father was a minimizer. If he was saying this, things must be bad.

When he got off the phone, the young man immediately turned to the internet. He typed in gastroenteritis after ... stem-cell transplant. The first results that came up referred to a paper in a medical journal, Clinical Infectious Diseases, published nearly a decade earlier that identified an unexpected culprit: norovirus.

Norovirus is one of the most common causes of gastroenteritis in the world. In the United States, its linked to an estimated 21 million cases of nausea and vomiting every year. Diarrhea can be present but is not typically as severe as other symptoms. In a normal host, the infection resolves on its own after 48 to 72 hours, thanks to the hard work of the immune system. Even so, norovirus was not a common cause of diarrhea in those who are immunosuppressed. But in the medical-journal paper, the first of its kind, 12 patients who had a stem-cell transplant and developed a persistent diarrheal illness were found to have norovirus. And of those 12, 11 were initially thought to have G.V.H.D. In most of those cases, it was only after the immune-suppressing medications were reduced that the patients own defenses could come to the rescue and vanquish the virus.

The son immediately sent the paper to his father. Had he been tested for norovirus? he asked. The patient wasnt sure. He forwarded the journal article to Jagasia and asked if hed had this test. He hadnt. Jagasia was 99 percent certain that this was a wild-goose chase. Hed never seen norovirus in patients with compromised immune systems. Still, testing was easy.

When the test came back positive, Jagasia was stunned. He repeated the test. Positive again. He immediately started to taper the immune-suppressing medications. As the doses came down, the diarrhea slowed, and after a few weeks, it stopped completely. With the help of the IV nutrition, and a slowly improving appetite, the patient began to gain back the weight he lost. From the patients point of view, his son saved his life.

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His Immune System Went Out of Whack. The Usual Treatment Didnt Work. Why? - The New York Times

China reports new progress in drug, therapies against Covid-19 – The Star Online

BEIJING: China has completed the clinical research of Favipiravir, an antiviral drug that has shown good clinical efficacy against the Covid-19 (coronavirus) outbreak, according to an official on Tuesday (March 17).

Favipiravir, the influenza drug which was approved for clinical use in Japan in 2014, has shown no obvious adverse reactions in the clinical trial, said Zhang Xinmin, director of the China National Center for Biotechnology Development under the Ministry of Science and Technology, at a press conference.

More than 80 patients have participated in the clinical trial in The Third People's Hospital of Shenzhen, south China's Guangdong Province, including 35 patients taking Favipiravir and 45 patients on a control group.

Results showed that patients receiving Favipiravir treatment turned negative for the virus in a shorter time compared with patients in the control group.

A multi-centred randomised clinical study led by the Zhongnan Hospital of Wuhan University also suggested that the therapeutic effect of Favipiravir is much better than that of the control group.

Favipiravir has been recommended to medical treatment teams and should be included in the diagnosis and treatment plan for Covid-19 as soon as possible, Zhang said.

A Chinese pharmaceutical company has been approved by the National Medical Products Administration to mass-produce the drug and ensure stable supply, Zhang added.

China is also pushing forward the utilization of some advanced technologies such as stem cell and artificial liver and blood purification in the treatment of severe cases.

Zhang said stem cell therapy proves effective in reducing severe inflammatory reactions caused by Covid-19, as well as reducing lung injury and pulmonary fibrosis in patients.

China has initiated several clinical research programs on stem cell therapy against Covid-19, including a stem cell drug that has been approved for clinical trial and a mesenchymal stem cell therapy.

Stem cell therapy has been used to treat 64 patients in severe and critical condition. Those patients' breathing difficulties were gradually relieved and they were generally cured in eight to 10 days.

The therapy also showed advantages in preventing pulmonary fibrosis and improving the long-term prognosis for patients.

The Chinese Society for Cell Biology and the Chinese Medical Association have jointly issued a guideline to standardize the clinical research and application of stem cell therapy against Covid-19.

Zhang said China is trying to use artificial liver and blood purification technology to treat critically ill patients. Patients receiving this treatment have seen reduced levels of inflammatory factors and improvement in chest imaging.

Their time on ventilator support has been decreased by an average of 7.7 days and the required ICU monitoring time has been shortened. - Xinhua/Asian News Network

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China reports new progress in drug, therapies against Covid-19 - The Star Online

Imfinzi in Combination with Standard-of-Care Chemotherapies Improves Survival in Lung Cancer – Curetoday.com

Final results of the phase 3 CASPIAN trial show that Imfinzi (durvalumab) in combination with a choice of standard-of-care chemotherapies demonstrates a sustained overall survival benefit in patients with extensive-stage small cell lung cancer.

We are pleased to see the sustained and meaningful survival benefit of Imfinzi for patients with small cell lung cancer after more than two years median follow up, Jose Baselga, executive vice president of oncology research and development at AstraZeneca, said in a company-issued press release. We have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin and remain on track for more approvals soon as we provide patients an important new first-line treatment option.

Imfinzi a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80 counters the tumor's immune-evading tactics and releases the inhibition of immune responses.

Previous results of the trial showed that Imfinzi plus etoposide and either carboplatin or cisplatin chemotherapy improved overall survival defined by the start of treatment until the time of patient death versus standard-of-care chemotherapy alone.

Safety and tolerability data for Imfinzi were similar to previous safety results and will be presented at a future medical conference.

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Imfinzi in Combination with Standard-of-Care Chemotherapies Improves Survival in Lung Cancer - Curetoday.com

What Are Drug Prevention and Treatment Options for COVID-19? – Pharmacy Times

COVID-19 has changed life as we know it.

There is no preventive vaccine or specific treatment available, according to the CDC.

Control measures and infection prevention should be implemented, and patients should receive supportive care, as needed.

Patients who have mild symptoms and seek advice should be advised to drink fluids, self-quarantine for 14 days, and take OTC medication for fever or other symptoms. They should also contact their doctor for further advice and guidance to see if a coronavirus test is available and/or needed.

Those with difficulty breathing or shortness of breath and high fevers should be seen and may be admitted into the hospital for oxygen. Some patients even need a ventilator. They should, if possible, first call their local emergency department for instruction.

All patients should focus on prevention and social distancing. These tips from the CDC are helpful.

Several pharmaceutical companies are racing to develop an effective treatment for the virus that is now a global pandemic. There are several classes of drugs in development, including antivirals, immunotherapies, vaccinations, as well as other investigational options. It is unknown whether a single drug could work or if a combination is needed, similar to HIV treatment. Below is a table outlining each area.

Note: corticosteroids should generally be avoided, because of their potential to prolong viral replication. In some cases, steroids may be indicated for other reasons.

Vaccines

Suzanne Soliman, PharmD, BCMAS, is the founder and president of the Pharmacist Moms Group.

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What Are Drug Prevention and Treatment Options for COVID-19? - Pharmacy Times

Orchard Therapeutics Appoints Company Founder and Gene Therapy Pioneer Bobby Gaspar, MD, Ph.D., as New Chief Executive Officer – BioSpace

BOSTON and LONDON, March 18, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that company founder and gene therapy pioneer Bobby Gaspar, M.D., Ph.D., has been named chief executive officer, effective immediately. Dr. Gaspar, previously president of research, chief scientific officer, and a member of the Orchard board of directors, succeeds Mark Rothera, who has served as the companys chief executive officer since 2017. As part of this transition process, Frank Thomas, Orchards chief operating officer and chief financial officer, will take on the role of president.

As a world-renowned scientist and physician, and accomplished strategic and organizational leader with more than 25 years of experience in medicine and biotechnology, Bobby Gaspar is uniquely qualified to lead Orchard into the future, said Jim Geraghty, chairman of the Orchard board of directors. In addition, Frank Thomas proven track record of success in leading operations, corporate finance and commercialization at a number of publicly traded life sciences companies will continue to be invaluable in his expanded role. On behalf of the entire Board of Directors, Id like to personally thank Mark for his many contributions to building Orchard into a leading gene therapy company over the last three years and wish him all the best in his future endeavors.

One of the companys principal scientific founders, Dr. Gaspar has served on Orchards board of directors and has driven its research, development and regulatory strategy since its inception. Over the course of his long career he has been a leading force in the development of hematopoietic stem cell (HSC) gene therapy bringing it from some of the first studies in patients to potential regulatory approvals. Dr. Gaspars unparalleled expertise, in addition to his deep relationships with key physicians and treatment centers around the world, will continue to be integral to efforts to identify and treat patients with metachromatic leukodystrophy (MLD) and other diseases through targeted disease education, early diagnosis and comprehensive newborn screening.

Dr. Gaspar commented: I am honored to become Orchards next CEO at a time of such opportunity for the company and for patients with severe genetic disorders. Through the consistent execution of our strategy, our talented team has advanced a leading portfolio of gene therapy candidates, expanding our R&D, manufacturing and commercial capabilities. We will now focus on driving continued innovation and growth, as well as strong commercial preparation and execution. I look forward to providing greater detail around our commercialization plan, pipeline prioritization and how we can realize the full potential of our HSC gene therapy platform, in the coming quarter.

Mr. Thomas commented: Im excited to be part of this next phase of Orchards evolution as a gene therapy leader as we look to refine our strategic priorities, ensure financial strength through improved operating efficiencies and prepare for a new cycle of growth, which includes our anticipated upcoming launch of OTL-200 in Europe. Im confident we will achieve long-term growth and value for our shareholders while turning groundbreaking innovation into potentially transformative therapies for patients suffering from devastating, often-fatal inherited diseases.

Mr. Rothera commented: It has been a great privilege to lead Orchard and this outstanding management team for the past three years. Orchard is poised to make a huge difference to the lives of patients worldwide living with devastating rare genetic conditions. Having worked closely with Bobby for the last several years, I know that he is tremendously talented, extremely passionate about the patient-centric mission, and fully prepared to lead Orchard as it enters its next phase as a company.

About OrchardOrchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically-modified blood stem cells and seeks to permanently correct the underlying cause of disease in a single administration. The company has one of the deepest gene therapy pipelines in the industry and is advancing seven clinical-stage programs across multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist, including inherited neurometabolic disorders, primary immune deficiencies and blood disorders.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (twitter.com/orchard_tx and http://www.linkedin.com/company/orchard-therapeutics), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-Looking Statements

This press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include express or implied statements relating to, among other things, the companys business strategy and goals, and the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, the risks and uncertainties include, without limitation: the impact of the COVID-19 virus on Orchards clinical and commercial programs, the risk that any one or more of Orchards product candidates, including the product candidate or candidates referred to in this release, will not be approved, successfully developed or commercialized, the risk of cessation or delay of any of Orchards ongoing or planned clinical trials, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates, the delay of any of Orchards regulatory submissions, the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates, the receipt of restricted marketing approvals, and the risk of delays in Orchards ability to commercialize its product candidates, if approved. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards annual report on Form 10-K for the year ended December 31, 2019, as filed with the U.S. Securities and Exchange Commission (SEC) on February 27, 2020, as well as subsequent filings and reports filed with the SEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

InvestorsRenee T. LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaChristine C. HarrisonVP, Public Affairs & Stakeholder Engagement+1 202-415-0137media@orchard-tx.com

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Orchard Therapeutics Appoints Company Founder and Gene Therapy Pioneer Bobby Gaspar, MD, Ph.D., as New Chief Executive Officer - BioSpace

Tessa Therapeutics to launch first CAR-T therapy for Hodgkin’s lymphoma (HL) – BSA bureau

TT11 will replace stem cell transplants as standard of care in Hodgkins lymphoma, says GlobalData

Tessa Therapeutics TT11 has become the first CAR-T therapy to receive the Food and Drug Administration (FDA) regenerative medicine advanced therapy (RMAT) designation and is set to become the leading cell-based therapy in Hodgkins lymphoma (HL), displacing the outdated stem cell transplants as the standard of care by 2024, says GlobalData, a leading data and analytics company.

Miguel Ferreira, MSc, Oncology and Hematology Analyst at GlobalData, comments: TT11, beingthe first CAR-T therapy to emerge from the HL pipeline, will benefit from being the first to market and with no other CAR-T therapies closing in, GlobalData expects TT11 to comfortably take the lead as the sole cell-based treatment for HL. This is further supported by key opinion leaders (KOLs) interviewed by GlobalData, who have shown preference for CAR-T clinical trials for their patients when possible.

Tessa Therapeutics TT11 became the 47th drug to receive RMAT designation, making it an ideal candidate to emerge from the HL pipeline. The data leading to this designation demonstrated a significant complete response (CR) rate of 66.7% in patients who had failed multiple lines of treatment which is a highly encouraging result. The pivotal Phase II trial is planned to take place in Q4 2020 and to run for two years. GlobalData believes that Tessa Therapeutics will discuss surrogate endpoints with the FDA to apply for regulatory approval based on the RMAT designation.

Ferreira adds: The current landscape of second-line treatment in HL is only partially set in stone. Salvage treatment and stem cell transplants are the standard of care, though the toxicity and impact in quality of life of patients labels this approach as outdated and highly toxic despite response benefit. A new treatment that can displace or replace stem cell transplants to improve the response, quality of life, as well as treatable population in HL second line, has been highly anticipated.

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Tessa Therapeutics to launch first CAR-T therapy for Hodgkin's lymphoma (HL) - BSA bureau

Fate Therapeutics: Potential Catalysts Ahead – Seeking Alpha

Today, we will see why Fate Therapeutics (FATE) is an attractive pick in March 2020.

Fate Therapeutics is a clinical-stage biopharmaceutical company focused on the development of next-generation cellular immunotherapies for cancer and immune disorders. The company has pioneered proprietary iPSC (induced pluripotent stem cell) platform technology to develop off-the-shelf cell-based cancer immunotherapy products. Current patient-derived autologous and allogeneic cell therapies suffer from drawbacks such as high costs, manufacturing complexity, product heterogeneity, and high turnaround time. These methods, including patient and donor-derived approaches to cell therapy, also require batch-to-batch sourcing and engineering of millions of primary cells.

Fate Therapeutics aims to be the game-changer in cell-based cancer immunotherapy space by enabling the development of off-the-shelf cell products derived from master cell lines. The company aims to develop less costly, homogenous, and multi-dose or multi-cycle cell therapies with small turnaround time. The resultant cell therapy products are expected to be well-defined and uniform in the composition and can be mass-produced at a significant scale in a cost-effective manner and can be delivered off-the-shelf for broad patient accessibility.

The company's cell therapy pipeline comprises immune-oncology programs including off-the-shelf NK- and T-cell product candidates derived from master iPSC lines, and immuno-regulatory programs, including product candidates to prevent life-threatening complications in patients undergoing hematopoietic cell transplantation and to promote immune tolerance in patients with autoimmune disease.

Human-induced Pluripotent Stem cells are generated by reprogramming adult somatic cells to a pluripotent state. Fibroblasts are the most commonly used primary somatic cell type for the generation of induced pluripotent stem cells. They are reprogrammed using retroviruses. Pluripotent cells are capable of differentiating in all cell types that make up the body.

A single human iPSC can potentially differentiate into more than 200 cell types and provides a renewable source for making cells.

NK (natural killer) cells are the body's first line of defense against tumors and various pathogens. Fate Therapeutics is leveraging its iPSC platform to produce off-the-shelf NK cell therapy products.

FT500 is Fate Therapeutics' first off-the-shelf iPSC-derived NK-cell product candidate. The FT500 study is an open-label, multi-dose Phase 1 clinical trial designed to evaluate FT500 for the treatment of advanced solid tumors.

The dose-escalation stage of the study was originally designed to assess the safety and tolerability of three once-weekly doses of FT500, without IL-2 cytokine support, as a monotherapy and in combination with one of three FDA-approved ICI (immune checkpoint inhibitor) therapies in patients that have failed prior ICI therapy.

Data for the first 12 patients in the Phase 1 study has demonstrated clean safety for the iPSC platform. The cutoff date considered was November 28, 2019. It was seen that there were no reported dose-limiting toxicities, no FT500 related Grade 3 or greater adverse events or serious adverse events, and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease.

Further, the trial also involved the evaluation of a multi-dose treatment course consisting of outpatient lympho-conditioning followed by three once-weekly doses of FT500 over up to two 30-day treatment cycles. Here, based on patients' T-cell and antibody repertoire, no anti-product immune responses against FT500 were evident over the multi-dose treatment course.

A total of 62 doses of FT500 were administered to these 12 patients in a safe and well-tolerated manner. Initial clinical data thus provides strong evidence that multiple doses of iPSC-derived NK-cells can be delivered off-the-shelf without patient matching.

In December 2019, the company disclosed plans to amend the trial protocol by including IL-2 cytokine support with each dose of FT500 after completion of 300 million cells per dose cohort in the ICI combination arm. The company has commenced dose-expansion part of Phase 1 trial with 300 million cells per dose and is focusing on enrolling NSCLC patients who are refractory to or have relapsed following CBT. This tumor type is highly susceptible to NK-cell recognition and killing. The study is enrolling at three clinical sites in the U.S. Fate Therapeutics expects expansion data readout from the trial in the second half of 2020.

Fate Therapeutics is studying the second product candidate from iPSC product platform and off-the-shelf NK-cell cancer immunotherapy, FT516, in an open-label, multi-dose Phase 1 trial. This product has been engineered to augment antibody-dependent cellular cytotoxicity.

In December 2019, the company announced results for two patients dosed with FT516. FT516 was administered as a monotherapy to the first patient who was suffering from relapsed/refractory AML (acute myeloid leukemia). The company dosed FT516 in combination with rituximab to the second patient who was suffering from high-risk DLBCL (diffuse large B-cell lymphoma) and had relapsed after multiple rituximab combination regimens, autologous hematopoietic stem cell transplant, and CAR (chimeric antigen receptor) T-cell therapy. The patients had received a first treatment cycle consisting of outpatient lympho-conditioning, three once-weekly doses of FT516 and IL-2 to better promote NK-cell activity.

Initial clinical data based on bone marrow biopsy at day 42 demonstrated no morphologic evidence of leukemia. There was even evidence of hematopoietic recovery following the completion of the first FT516 treatment cycle in the AML patient. There was also no circulating leukemia cells in the patient's peripheral blood. The patient even reported the recovery of neutrophils without growth factor support. The data did not demonstrate dose-limiting toxicities, although serious adverse events were seen. Initial dose escalation data may be read out in the second half of 2020.

This initial clinical evidence highlights the high probability of engineered iPSC-derived NK-cells demonstrating anti-tumor activity in AML indication. Besides, there is a body of data that has demonstrated clinical proof-of-concept for donor-derived NK-cell therapy in relapsed refractory AML and relapsed refractory DLBCL.

In December 2019, FDA accepted FT516's second IND application for studying the product in combination with PDL1, PD1, EGFR and HER2-targeting monoclonal antibody therapies in solid tumor indications. Initially, the company plans to prioritize the combination of FT516 and avelumab in patients with advanced solid tumors who are refractory to or have relapsed following, at least one line of anti-PDL1 monoclonal antibody therapy. The company plans to initiate enrollment in a clinical trial for FT516 and avelumab in mid-2020.

Fate Therapeutics is studying off-the-shelf multi-antigen targeted CAR NK-cell product candidate, FT596, in solid tumor indications.

In December 2019, Fate Therapeutics reported favorable in vivo preclinical data for FT596.

Here, in humanized mouse models of lymphoma and leukemia, FT596's efficacy was comparable to that of primary CAR T-cells in promoting tumor clearance and extending survival. FT596 combined with rituximab also showed the enhanced killing of lymphoma cells in vivo as compared to rituximab alone. FT596 can thus emerge to be best-in-class off-the-shelf treatment in B-cell malignancies. Fate Therapeutics has started enrolling patients in the open-label Phase I study. Initial dose escalation data readout on FT596 is expected in the second half of 2020.

Fate Therapeutics has high hopes for FT596, considering that initial clinical data from a donor-derived CAR19 NK-cell program at MD Anderson, demonstrated a 73% overall response rate in patients with relapsed refractory non-Hodgkin's lymphoma and chronic lymphocytic leukemia with no major toxicities. Hence, while the efficacy seemed similar to CAR T therapy, the safety profile was differentiated in favor of CAR NK-cell therapies.

Although early, this data has highlighted CAR NK-cells' capacity to confer a high level of efficacy without the CAR-T cell therapy-related toxicities. Fate Therapeutics expects FT596 to effectively replace patient-specific and allogeneic CAR19 T-cell immunotherapies. The latter single-antigen specific and hence pose a risk of disease relapse due to antigen escape as well as cause significant toxicities due to off-target activity. FT596, on the other hand, has been engineered with three active anti-tumoral functional components.

Fate Therapeutics aims to be the first company to introduce off-the-shelf iPSC-derived CAR T-cell therapy to patients, FT819, by submitting IND in the second quarter of 2020. The company expects to file an IND application for off-the-shelf CRISPR-edited, iPSC-derived NK-cell product candidate, FT538, by early May 2020. The company has also planned IND submission for FT576 in the second half of 2020.

Although Fate Therapeutics is pioneering a revolutionary approach for mass production of off-shelf cell therapy products, its pipeline is very early stage. There has not been sufficient data from its clinical programs to make an informed estimate about the success probability of these programs. In this backdrop, the company is exposed to significant R&D failure risks. In case data readouts from FT500 and FT596 clinical programs do not match expectations, the company may witness increased share price volatility.

At the end of 2019, the company had cash worth $261 million on its balance sheet. The company spent cash worth $83.2 million on operating activities in 2019. This is a proxy for the 2019 cash burn rate. We assume that the annual cash burn rate in 2020 will be around $120 million, considering that three assets have entered in-human trials. Hence, the company seems to have cash that can sustain operations until the end of 2021. However, if cash is needed at a faster pace, the company may land up requiring more funds. This can lead to equity dilution.

According to finviz, the 12-month consensus target price of Fate Therapeutics is $37.94. On March 4, Citi analyst Yigal Nochomovitz reiterated the "Buy" rating and increased target price from $26 to $41. On March 4, Barclays analyst Peter Lawson also initiated coverage of Fate Therapeutics with an Overweight rating and $40 price target.

On March 3, BMO Capital analyst Do Kim raised the firm's price target on Fate Therapeutics to $28 from $22 and reiterated the "Market Perform" rating. On March 3, Guggenheim analyst Michael Schmidt reiterated the "Buy" rating and increased target price from $25 to $41. On March 3, Roth Capital analyst Tony Butler reiterated the "Neutral" rating but increased the target price from $20 to $30. On March 3, BTIG analyst Amanda Murphy reiterated the "Buy" rating and increased target price from $27 to $42. The analyst has also raised the estimated value of the company's iPSC platform from $740 million to $2.0 billion.

On March 3, Oppenheimer analyst Matthew Biegler reiterated the "Outperform" rating and increased the target price from $27 to $36. Piper Sandler analyst, Edward Tenthoff also reiterated the "Overweight" rating and raised the target price from $28 to $57.

In September 2019, Fate Therapeutics launched in-house GMP (Good Manufacturing Practices) manufacturing facility at headquarters in San Diego, California. This is custom designed to use clonal master iPSC lines as a renewable cell source for the consistent and scaled manufacture of off-the-shelf NK-cell and CAR T-cell products. The company has already produced hundreds of cryopreserved, infusion-ready doses of FT500, FT516, and FT596 at a low cost per dose. Currently stored in inventory, these doses are immediately available for use in the clinical settings.

The full control of cGMP production and the technical expertise to genetically engineer iPSCs and create qualified clonal master lines for clinical use implies that the company has operational expertise and redundancies required for the consistent cost-effective manufacturing and clinical supply of off-the-shelf cell products.

I believe that the 12-month target price of $30 fairly reflects the growth potential as well as risks associated with early-stage Fate Therapeutics. I consider this company to be a good pick for aggressive biotech investors with an investment horizon of at least one year.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Fate Therapeutics: Potential Catalysts Ahead - Seeking Alpha

Singapore formulates novel molecular therapy to treat leukaemia – BSA bureau

Researchers in Singapore find a common therapeutic vulnerability for a genetically diverse and deadly blast crisis chronic myeloid leukaemia

Scientists and clinicians from Duke-NUS Medical School, the Agency for Science, Technology and Researchs (A*STARs) Genome Institute of Singapore (GIS), and the Singapore General Hospital (SGH), have devised a novel drug combination that could treat a particularly deadly form of leukaemia, known as blast crisis (BC) chronic myeloid leukaemia (CML).

The team has also developed strategies that may identify patients with early-stage or chronic phase (CP) CML who are at increased risk of developing BC, and potentially preventing disease progression.

CML is a blood cancer that can be controlled by continuously taking an expensive type of medicine called a tyrosine kinase inhibitor (TKI). In almost all patients, stopping TKI treatment results in recurrence of CML.

While most CML patients respond well to life-long TKI usage, about 10 per cent of patients become resistant to TKIs, and progress to late-stage or blast crisis (BC) CML. Patients with BC almost always die from their disease. While many genetic mutations are known to be associated with BC progression, the mechanisms by which they and other factors cause BC remain largely unknown. This knowledge gap prevents clinicians from identifying which CML patients are at risk of BC progression, and treating BC when it occurs.

To fill these critical gaps, we employed the latest molecular approaches to establish that the so-called polycomb repressive complex, or PRC, alters the regulation of a set of genes which drive BC progression, said Dr Tun Kiat Ko, Research Fellow at Duke-NUS Cancer and Stem Cell Biology (CSCB) programme. He also added, We found that the consequences of altered PRC activity were common to the majority of BC cases, regardless of the different leukaemia-causing mutations we also found in them.

Using this increased understanding, the team devised novel drug combinations, which reverse the downstream effects of the PRC in BC. At the same time, they also developed methods to identify CML patients who were at increased risk of developing TKI-resistance and progressing to BC.

The team is currently working on approaches to identify CML patients who are at risk of BC transformation, and also to determine why the key PRC-related events occur in the first place.

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Singapore formulates novel molecular therapy to treat leukaemia - BSA bureau