StemCell Therapy

SINGAPORE, Dec. 14, 2020 /PRNewswire/ -- Hummingbird Bioscience, an innovative clinical-stage biotech company focused on developing revolutionary therapies for hard-to-drug targets, today announced a collaboration with Tempus, a leader in artificial intelligence and precision medicine, to drive the development of Hummingbird's lead clinical program, HMBD-001, as it advances into clinical trials in HER3-driven cancers, including those that harbor neuregulin 1 (NRG1) fusions. As part of the collaboration, Hummingbird will be leveraging Tempus' AI-enabled platform and proprietary data, as well as joining its TIME Trial Network, for rapid identification, site activation and efficient enrollment of cancer patients who have NRG1 fusions and meet eligibility criteria for HMBD-001 clinical trials.

NRG1 fusions are a rare genetic mutation that are increasingly recognized as a driver of multiple tumor malignancies, and an actionable target for HER3 targeted therapy. NRG1 fusions cause the overproduction of NRG1 ligands, resulting in increased HER3 activation and tumor growth. Up to 1% of all solid tumors harbor NRG1 fusions, therefore, it is important to identify this patient population and develop therapies that can treat them.[1]

HMBD-001 is a uniquely differentiated anti-HER3 neutralizing antibody that was developed using Hummingbird's proprietary Rational Antibody Discovery platform. HMBD-001 has been immune-engineered to bind with high affinity to the HER3 dimerization interface and block HER3 growth signals to the cancer. Most importantly, HMBD-001 uniquely blocks HER3 in both open and closed conformations, and in the presence or absence of high concentrations of NRG1.[2] Pre-clinical studies have shown that these differentiated properties of HMBD-001 lead to robust and sustained tumor growth inhibition in multiple HER3 cancer models, including those with NRG1-fusions.

"We are excited to collaborate with Tempus to leverage their just-in-time clinical trial program and apply Hummingbird's deep knowledge of disease driving protein mechanisms in order to identify patients with actionable genetic abnormalities," said Dr Piers Ingram, Co-founder and CEO of Hummingbird.

"We look forward to Hummingbird joining our TIME Trial Network, providing patients across the country access to its HMBD-001 clinical trial," said Amy Franzen, Vice President of Operations, Therapies, Tempus. "This collaboration is an opportunity to identify those patients who could benefit from this investigational therapy, and if they are eligible, rapidly open the trial just for them."

About NRG1 fusions

A subset of patients with cancer have recently been identified who possess abnormal NRG1 gene fusions, that is the hybridization of their NRG1 gene with any one of a number of genes to produce NRG1 proteins that overexpress the HER3-binding domains.[3] This results in increased HER3 binding and dimerization, which consequently leads to increased tumor growth. Less than 1% of all solid tumors harbor NRG1 fusions, and there are currently no approved therapies to treat this patient population.[1] Moreover, studies suggest that NRG1 fusions are mutually exclusive with other known molecular drivers of cancer, such as ALK, ROS, and RET gene fusions, meaning that NRG1 fusions are likely to be a distinct orphan indication in a discrete patient population.[1]

About HMBD-001

HMBD-001 represents a unique, highly-specific, anti-HER3 neutralizing antibody with a novel mechanism of action that offers significant potential for broad clinical benefit. Previous attempts to block the HER3 receptor, a key player in the signaling pathway that promotes cell division and tumor growth in cancer, have not proven to be efficacious. HER3 is activated by the binding of NRG1, which stabilizes a transient open conformation to allow it to form heterodimers with HER2/EGFR. In the presence of abundant HER2/EGFR, heterodimers can form without NRG1.

Pre-clinical models have shown that HMBD-001 is able to effectively and uniquely bind to a difficult-to-target region on HER3, blocking the heterodimerization of HER3 with HER2/EGFR independent of NRG1 binding. This potently inhibits the activation of the signaling pathway and consequently, stops tumor growth. Cancer Research UK has partnered with Hummingbird Bioscience to advance this novel antibody drug into clinical trials for the treatment of HER3-driven cancer.

About Hummingbird Bioscience

Hummingbird Bioscience is an innovative clinical-stage biotech company focused on developing revolutionary therapies against hard-to-drug targets for improved treatment outcomes. We harness the latest advances in systems biology and data science to better understand and solve the underlying causes of disease and guide development of our therapeutics.

Enabled by our proprietary Rational Antibody Discovery platform, we discover antibodies against optimal yet elusive epitopes on important targets that have not been successfully drugged, unlocking novel mechanisms of action. We are advancing a rich pipeline of first- and best-in-class drug candidates in oncology, autoimmune and infectious diseases, in collaboration with global partners in academia and industry.

Our highly experienced teams in Singapore and the US span antibody discovery, pharmacology, production and clinical development. Together we aim to accelerate the journey of new drugs from concept to clinical care. For more information, please visit http://www.hummingbirdbioscience.com, and follow Hummingbird on LinkedIn and Twitter (@hummingbirdbio).

About Tempus

Tempus is a technology company advancing precision medicine through the practical application of artificial intelligence in healthcare. With one of the world's largest libraries of clinical and molecular data, and an operating system to make that data accessible and useful, Tempus enables physicians to make real-time, data-driven decisions to deliver personalized patient care and in parallel facilitates discovery, development and delivery of optimal therapeutics. The goal is for each patient to benefit from the treatment of others who came before by providing physicians with tools that learn as the company gathers more data. For more information, visit tempus.com.

[1] Jonna S, Feldman RA, Swensen J, Gatalica Z, Korn WM, Borghaei H, Ma PC, Nieva JJ, Spira AI, Vanderwalde AM, Wozniak AJ, Kim ES, Liu SV.. Detection of NRG1 Gene Fusions in Solid Tumors. Clin Cancer Res. 2019; 25: 49664972. https://doi.org/10.1158/1078-0432.CCR-19-0160

[2] Thakkar D, Sancenon V, Taguiam MM, Guan S, Wu Z, Ng E, Paszkiewicz KH, Ingram PJ, Boyd-Kirkup JD. 10D1F, an Anti-HER3 Antibody that Uniquely Blocks the Receptor Heterodimerization Interface, Potently Inhibits Tumor Growth Across a Broad Panel of Tumor Models. Mol Cancer Ther. 2020; 19: 490501.

[3] Ruiz-Saenz A, Dreyer C, Campbell MR, Steri V, Gulizia N, Moasser MM. HER2 Amplification in Tumors Activates PI3K/Akt Signaling Independent of HER3. Cancer Res. 2018; 78: 36453658.

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Richard Kuhn: Traditionally, for viruses, we've either taken a virus and inactivated it, and used that as a vaccine, or we've taken a virus and made it less infectious that is, it's attentuated and made that a vaccine; or we've expressed proteins that are on the surface of a virus and used those proteins as stimulants for your immune system. These would be purified proteins that would be injected. The protein self-assembles into something that resembles the virus, but it doesn't have any of the components that allow the virus to replicate. So those are the standard, traditional vaccines.

The technology that Moderna and Pfizer are pushing right now is one in which you use the coding sequence, the information that codes for the viral protein that you're interested in. In the case of COVID-19, we're interested in a surface protein that we call the spike glycoprotein spike for short. This technology basically uses the genetic information that will make this spike protein when you put it into a cell. And that information is encoded in what we call messenger RNA mRNA. That's the vaccine, and it's packaged in a lipid nanoparticle for delivery purposes.

Serena Marshall: That's a ton of information, and I want to unpack it a little. Let's talk about the vaccines of days past, [in which we get] infected with a weakened version, an attenuated version, as you said. A lot of people think, Okay, so when I get this new COVID vaccine, am I going to be getting COVID? That's not the case here.

Richard Kuhn: That's absolutely correct. First of all, there's no infectious material being injected into an individual; you're only making a single protein, but it's the critical protein that your immune system will respond to.

What will happen is, that lipid nanoparticle will be able to enter cells in your body after you've been vaccinated. And that RNA, the messenger RNA, will make a protein, just like all the proteins your cells normally make. The only difference being that once it gets made, other cells are going to recognize it as foreign. And they're going to mount a response against it.

Serena Marshall: Why is it that this virus is able to have that protein and able to have that immune response?

Richard Kuhn: Well, this technology has been around for a few years. In fact, Moderna developed the technology initially against Zika virus. In the case of Zika virus, there was this massive expansion and infection of people in South and Central America, and everybody was very concerned, and then the virus died off. So Moderna had this technology but was never able to go to clinical trials because there was no Zika virus prevalent in the population.

Serena Marshall: So when we hear that this is a brand-new technology that's never been approved before, that's all true. But it's not new research; it actually, as you said, goes back to Zika. But also, [for] decades before they've been looking into this.

Richard Kuhn: The COVID-19 pandemic is the perfect situation for producing a messenger RNA vaccine, because it's very easy to produce in a large scale. Because it's synthetic, you don't have to grow anything in cells, which has been the traditional way that you produce vaccines. So it's very easy, it's very rapid. As soon as you have the genetic information of a virus or a pathogen, you can begin to develop a messenger RNA vaccine against it, which trims off years of very difficult work that we've previously had to do with the older vaccines.

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Track the Vax: What Do We Need to Know About the New Vaccines? - Everyday Health

Who do you think performs your medical laboratory tests for COVID-19 or any other test? If you answered my doctor or my nurse or a robot, you would be completely wrong.

To put it bluntly, your life is in the hands of medical laboratory professionals. We perform an estimated 13 billion laboratory tests in the United States each year. That means that laboratory testing is the single highest-volume medical activity in the lives of Americans.

Why should you care? Those 13 billion tests help drive approximately two-thirds of all medical decisions made by your doctor and other health care professionals from cradle to grave. There are only 337,800 practicing medical laboratory professionals for a population of just over 330 million people in the U.S.

Ive worked in public health and medical laboratories for three decades, specializing in the study of viruses and other microbes while also educating the next generation of medical laboratory scientists. In 2014, I coined the phrase the hidden profession that saves lives. With COVID-19, these unsung professionals are now in the limelight. Unfortunately, this pandemic has led to a nationwide burnout of these professionals, causing dangerous shortages in the U.S. health care infrastructure.

Medical laboratory testing is performed by highly skilled, rigorously educated, certified, licensed and dedicated medical laboratory professionals. You have probably never seen one of these medical scientists at work because they are rarely in public view unlike nurses, doctors and pharmacists.

In fact, without the test results we provide, your doctor or other health care professionals are flying blind. Dont get us wrong we have great respect and value for all health care professionals. We just want you to understand that we save lives every day even though you dont necessarily see us in the shadows of health care.

Since the beginning of the COVID-19 pandemic in the U.S., we have performed approximately 213 million tests and counting. And now we are tired. We hear the calls for more testing. Many of my former students, now colleagues in medical laboratories all over the country, are exhausted and dealing with burnout or thoughts of quitting.

The most common form of testing for COVID-19 and the gold standard is called a PCR test, which stands for polymerase chain reaction. Like most testing, PCR testing is largely invisible to patients once a nasal swab is taken. The purpose of this test is to detect the viruss genetic material called RNA in the cells collected on the swab.

For laboratory professionals the first step is to convert any RNA from the virus into DNA. Then, using a series of chemical reactions and specialized equipment, the DNA is replicated millions of times so that it is easier to detect. If genetic material from SARS-CoV-2 is detected, then the patient is infected with the coronavirus.

The demands of such a precise test and meticulous process are putting a massive burden on this workforce.

Recently the American Society for Clinical Pathology conducted a survey of laboratory professionals and reported that 85.3% felt burnt out; 36.5% reported inadequate staffing; 31.5% complained of a heavy workload and pressure to complete all testing; and 14.9% cite a lack of recognition and respect.

Part of the weariness stems from the fact that in addition to COVID-19, we are also running tests for people who are having babies, heart attacks, cancer, antibiotic resistant infections, strep throat and other illness or diseases. These 13 billion tests are performed by a workforce that has vacancy rates of 7%-11% in almost every region of the country.

A medical, or clinical, laboratory science degree often requires an average of five years of college education. Medical laboratory scientists all have bachelors degrees and have certification or a license to practice. I, and many of my colleagues, have a masters degree, and also a doctorate. These complex qualifications are reflected in our education and clinical background.

A degree in medical laboratory testing requires mastery of several areas of medicine including the study of hematology, molecular diagnostics, immunology, urine analysis, microbiology, chemistry, parasitology, toxicology, immunohematology (blood banking), coagulation and transfusion, and laboratory safety and operation. I often tell my students that this degree is basically like having to complete four majors.

Our profession can also start toward a laboratory science career at an entry level with a bit less education and clinical training even as a technician, which requires only a 2-year associates medical laboratory technician degree. These technicians often move up the career ladder by obtaining other degrees. Like any health care professional degree, ours is externally accredited through the National Accreditation Agency for Clinical Laboratory Sciences.

Currently there are an estimated 337,800 employed medical laboratory professionals in the U.S., according to the Bureau of Labor Statistics. This is an estimate, because without licenses in every state, an accurate number of practicing laboratory professionals is not available. But the demand for these professionals is expected to grow by 25,000 between 2019 and 2029, according to the Bureau of Labor Statistics. But that doesnt include the number of jobs that will become vacant when workers retire or leave the profession during the pandemic.

What is frightening to me is that while the demand for clinical laboratory personnel is growing, the number of training programs actually is declining. Currently, there are 235 medical laboratory scientist and 240 medical laboratory technician training programs in the U.S. This is a 7% decline from the year 2000. In some states, there are no programs.

Fewer training programs, coupled with greater demand for laboratory professionals, could impact patient care, notes Jim Flanigan, executive vice president of the American Society for Clinical Laboratory Science. He is concerned by the lack of federal programs supporting medical laboratory education as compared to all other health programs. Vacancy rates are exceeding the number of medical laboratory scientist and medical laboratory technician graduates.

A number of other factors help explain our low workforce numbers. Training laboratory personnel is expensive, and there are few scholarship or loan programs available for prospective students. Salaries are also problematic. Compared to nursing, physical therapists or pharmacists, our professionals are paid 40%-60% less on average for annual salaries.

The American Society for Clinical Laboratory Science is calling for expansion of the Title VII health professions program which provides education and training opportunities in high-demand disciplines to include medical (clinical) laboratory science. The organization also supports efforts to improve visibility of the profession by engaging in community outreach opportunities and by partnering with middle and high school STEM programs to show young people that laboratory medicine is a viable career path.

Lastly, with competition for laboratory personnel intensifying over the last year, turnover rates for some categories of laboratory personnel now exceed 20%. Because of the difficulty in finding qualified staff, medical laboratories are increasingly turning to temporary staff to handle the patient testing workload. In a sense, the pandemic has exacerbated a free-agent effect for traveling medical laboratory professionals that hurts continuity and quality in health care.

We hope that you see us and hear us. Your life or that of a loved one depends on it.

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Who is doing all those COVID-19 tests? Why you should care about medical laboratory professionals - The Conversation US

Dec. 15, 2020 11:00 UTC

MENLO PARK, Calif.--(BUSINESS WIRE)-- Avellino announced today the appointment of three new members to its Board of Directors. In addition, the company announced a new Chief Executive Officer and President, and Chief Financial Officer and Treasurer. All appointments are effective December 2020.

The Board of Directors has been further strengthened by the appointment of Aimee S. Weisner, Esq.; Richard Gannotta, NP, DHA, FACHE; and William Stasior, MS, PhD. Joining the executive team is current Board member Jim Mazzo as CEO and President, and Cyril Allouche as CFO and Treasurer.

Avellino Group Chairman Gene Lee said, All of our newest Board members embody the spirit and ingenuity of Avellino and bring such broad talent, expertise, and energy to the table. We are very fortunate to have them by our side to help us continue to grow as a company. And with Jim moving into a senior executive leadership position, his immeasurable business experience with scientific acumen will enhance our ability to continue to lead the way in delivering best-in-class personalized genetic and molecular diagnostics, data, and therapeutics. Also, we are excited to welcome Cyril to our leadership team. His depth of business experience across multiple industries and preparing companies for entering public markets will be a perfect complement to the scientific expertise we have fostered at Avellino.

Board of Directors Appointments

Aimee S. Weisner, Esq. is an experienced independent director in the medical device, pharmaceutical and biotech spaces, and she brings significant expertise as a corporate medtech executive and attorney. Most recently, from 2011 to 2019, Ms. Weisner served as Corporate Vice President, General Counsel of Edwards Lifesciences Corporation.

Richard Gannotta, NP, DHA, FACHE is a recognized leader in the health sector with service in CEO / President and executive roles in some of the nations most prominent academic and public health systems and a leading global medical technology company. In addition, Dr. Gannotta is Senior Lecturer at the NYU Wagner Graduate School of Public Service where his area of focus is on the management of healthcare organizations and health policy.

William Stasior, MS, PhD has established himself as a creative innovator with technical expertise at Silicon Valleys most recognizable technology companies. Dr. Stasior currently serves as Corporate Vice President, Technology, and a member of the Office of the Chief Technology Officer at Microsoft. Prior to joining Microsoft, he was for many years the Vice President, Artificial Intelligence, at Apple and head of Apples Siri division. Among many of his career accomplishments, Dr. Stasior also served as the Vice President of Amazon Search and was CEO of Amazon Silicon Valley subsidiary A9.com. Prior to joining the Board, Mr. Stasior provided guidance to Avellino as part of the Executive Advisory Committee.

Chief Executive Officer and President

Avellino appoints Jim Mazzo as the new CEO and President. Mr. Mazzo is one of the ophthalmic industrys best known and most respected business leaders with over 38 years of proven experience. His global reputation for building and running world-class organizations is based on 22 years leading Allergans North American and European eye care organizations. His many accomplishments and contributions to the healthcare, business and educational communities include serving as Board Chairman for AdvaMed as well as Vice-Chairman and Trustee for Chapman University and the University of San Diego.

Chief Financial Officer and Treasurer

Avellino also welcomes Cyril Allouche to the executive team as its new Chief Financial Officer and Treasurer. Mr. Allouche brings to Avellino over 20 years of experience in finance leadership in both public and pre-IPO companies, including diagnostics and biopharmaceutical. He most recently served as CFO at Dermavant Sciences and held finance leadership roles at Revance Therapeutics and CareDx. He also spent over a decade at PricewaterhouseCoopers in Audit and Transaction services.

The inclusion of Aimee, Richard, and William provides expanded leadership and broader operational, digital, marketing, and commercialization expertise that will surely complement our executive team. Along with Cyrils deep and extensive experience in leading the financial operations of healthcare businesses, Avellino will continue to grow our genetic and molecular diagnostic tests pipeline and flourish as a company, said Avellino Group Chairman Gene Lee.

Added newly appointed CEO Jim Mazzo: Its exciting times here at Avellino, all of the additions to the boardroom along with the changes taking place at the senior executive level shows that we are set up for success with unlimited potential for tremendous growth. Considering this, and the positive impact Avellino has had in providing testing during the pandemic and their efforts to fight blindness since their inception, and the advances they will bring to healthcare in the future, joining the senior management team was an easy decision for me to make.

About Avellino

Avellino Lab USA, Inc. is a global leader in gene therapy and molecular diagnostics and is at the forefront of precision medicine for eye care. The company is a proud member of the California State COVID-19 Testing Taskforce, which is focused on the expansion of CoV2 testing and the reduction of testing turn-around times (TAT). Beyond the AvellinoCoV2 test, Avellino recently launched AvaGen, the worlds first DNA test to confirm the presence of genetic indicators that are positively associated with corneal dystrophies and keratoconus genetic risk factors. The company will also soon launch an infectious disease panel of diagnostic tests. Beyond diagnostics, the company is also pioneering CRISPR gene editing to manage and potentially cure inherited diseases. Avellino is headquartered in Silicon Valley, California, with operations in Korea, Japan, China, and the UK.

To learn more about Avellino, please visit http://www.avellino.com.

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Avellino Expands Its Board of Directors and Welcomes New Executive Management Members - BioSpace

Dublin, Dec. 03, 2020 (GLOBE NEWSWIRE) -- The "Global Next Generation Sequencing Market: Growth, Trends, Competitive Landscape, and Forecasts" report has been added to ResearchAndMarkets.com's offering.

The global next-generation sequencing market is expected to grow at a CAGR of around 17.5% during 2020-2026. Next-generation sequencing is also known as high-throughput sequencing. It is the process of determining the sequence of nucleotides in a section of the DNA. It includes procedures such as sequencing by ion semiconductor sequencing, synthesis (SBS), nanopore sequencing and single-molecule real-time (SMRT) sequencing. It is a cost-effective solution that offers precise results with high accuracy and speed. This enables the analysis of millions of DNA molecules simultaneously, which facilitates research in the fields of personalized and genetic medicines, agriculture and animal research, and clinical diagnostics.

Market Drivers

Market Challenges

Report's Scope

The global next-generation sequencing market report elucidates key industry trends, industry dynamics along with the quantitative analysis of the report. The report presents a clear picture of the global next-generation sequencing market by segmenting the market based on sequencing type, product type, technology, application, end user, and region. We believe that this report will aid the professionals and industry stakeholders in making informed decision.

Key Topics Covered:

1. Preface1.1 Report Description1.1.1 Objective of the Study1.1.2 Target Audience1.1.3 USP & Key Offerings1.2 Report's Scope1.3 Research Methodology1.3.1 Phase I - Secondary Research1.3.2 Phase II - Primary Research1.3.3 Phase III - Expert Interviews1.3.4 Assumptions

2. Executive Summary

3. Global Next Generation Sequencing Market3.1 Introduction3.2 Market Drivers & Challenges

4. Global Next Generation Sequencing Market Analysis4.1 Market Portraiture4.2 Market by Sequencing Type4.3 Market by Product Type4.4 Market by Technology4.5 Market by Application 4.6 Market by End User4.7 Market by Region 4.8 Impact of COVID-19

5. Global Next Generation Sequencing Market by Sequencing Type 5.1 Market Overview5.2 Whole Genome Sequencing5.3 Targeted Resequencing5.4 Whole Exome Sequencing5.5 RNA Sequencing5.6 CHIP Sequencing5.7 De Novo Sequencing5.8 Methyl Sequencing5.9 Others

6. Global Next Generation Sequencing Market by Product Type 6.1 Market Overview6.2 Instruments6.3 Reagents and Consumables6.4 Software and Services6.5 Others

7. Global Next Generation Sequencing Market by Technology Type 7.1 Market Overview7.2 Sequencing by Synthesis7.3 Ion Semiconductor Sequencing7.4 Single-Molecule Real-Time Sequencing7.5 Nanopore Sequencing7.6 Others

8. Global Next Generation Sequencing Market by Application8.1 Market Overview8.2 Drug Discovery and Personalized Medicine8.3 Genetic Screening8.4 Diagnostics8.5 Agriculture and Animal Research8.6 Bioinformatics8.7 Others

9. Global Next Generation Sequencing Market by End User9.1 Market Overview9.2 Academic Institutes & Research Centers9.3 Hospitals & Clinics9.4 Pharmaceutical & Biotechnology Companies9.5 Others

10. Global Next Generation Sequencing Market by Region10.1 Market Overview10.2 Europe10.2.1 Germany10.2.2 United Kingdom10.2.3 France10.2.4 Italy10.2.5 Spain10.2.6 Netherlands10.2.7 Russia10.2.8 Rest of the Europe10.3 North America10.3.1 United States10.3.2 Canada10.4 Asia Pacific10.4.1 China10.4.2 Japan10.4.3 South Korea10.4.4 Australia10.4.5 India10.4.6 Indonesia10.4.7 Rest of the Asia Pacific10.5 Latin America10.5.1 Mexico10.5.2 Brazil10.5.3 Argentina10.5.4 Rest of Latin America10.6 Middle East & Africa10.6.1 Saudi Arabia10.6.2 Turkey10.6.3 United Arab Emirates10.6.4 Rest of Middle East & Africa

11. SWOT Analysis

12. Porter's Five Forces

13. Market Value Chain Analysis

14. Competitive Landscape14.1 Competitive Scenario14.2 Company Profiles14.2.1 10x Genomics14.2.2 Agilent Technologies Inc.14.2.3 Becton Dickinson and Company14.2.4 BGI Group14.2.5 Eurofins Scientific14.2.6 F. Hoffmann-La Roche AG14.2.7 Illumina Inc.14.2.8 Genewiz14.2.9 Macrogen Inc.14.2.10 Oxford Nanopore Technologies14.2.11 Pacific Biosciences14.2.12 Perkinelmer Inc.14.2.13 Thermo Fisher Scientific Inc.14.2.14 Qiagen N.V.14.2.15 Genapsys Inc.

For more information about this report visit https://www.researchandmarkets.com/r/j561mc

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Continued here:
Global Next Generation Sequencing Market (2020 to 2026) - Growth, Trends, Competitive Landscape, and Forecasts - GlobeNewswire

Bottom Line: Among patients with lung cancer from Latin America, genomic and ancestry analyses revealed that Native American ancestry was associated with increased mutations in the EGFR gene, independent of smoking status.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research

Author: Matthew Meyerson, MD, PhD, director of the Center for Cancer Genomics at Dana-Farber Cancer Institute in Boston; professor of genetics and medicine at Dana-Farber Cancer Institute and Harvard Medical School; and an Institute Member of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts

Background: "Lung cancer is the leading cause of cancer mortality, both in the United States and globally, and understanding inherited risk factors for this disease may help us to identify populations that would benefit from increased screening efforts," said Meyerson.

"Previous work has demonstrated that EGFR-mutant lung cancer is more common among populations from East Asia compared with populations from North America or Europe, about 50 percent versus 10 percent of lung cancer cases, respectively," said Meyerson. "But it is not clear whether the ethnic difference in EGFR-mutant lung cancer is due to environmental or genetic factors," he added.

How the Study was Conducted & Results: Meyerson and colleagues analyzed samples from 1,153 patients with lung cancer from Latin America. Of them, 601 were from Mexico and 552 were from Colombia, and 499 patients self-reported as non-smokers. Through genomic analysis of tumor samples, the researchers identified somatic mutations in EGFR, KRAS, and other target genes.

Using a new method developed by Jian Carrot-Zhang, PhD, and Alexander Gusev, PhD, the researchers also performed ancestry analyses from tumor samples in this admixed population. Global ancestry analysis was performed to measure proportions of African, European, and Native American ancestry across the genome. Additionally, local ancestry analysis was performed, which evaluates genetic ancestry at a particular chromosomal location. Because local ancestry only evaluates a small portion of the genome, there is less potential for observed associations to be confounded by environmental exposures or socioeconomic status, which may be seen in global ancestry analyses, Meyerson explained.

Using the genomic and ancestry data, the researchers assessed the associations of somatic mutations in target genes and global ancestry groups within a single admixed population. After adjusting for a variety of factors, including self-reported smoking status and sample-specific tumor mutational burden, the researchers found that global Native American ancestry was positively correlated with mutations in the EGFR gene. Further, the researchers found that Native American ancestry was predominantly associated with oncogenic mutations in the EGFR gene, but not with non-oncogenic mutations.

Meyerson and colleagues then stratified patients by their self-reported smoking status and evaluated the association between global ancestry and mutations in target genes. In both never smokers and smokers, global Native American ancestry was associated with mutations in the EGFR gene, suggesting that the genomic differences associated with Native American ancestry are independent of smoking status.

"Smoking increases the risk for KRAS-mutant lung cancers, while patients with lung cancer who are non-smokers more often develop EGFR-mutant lung cancer," Meyerson said. "However, we show in our study that EGFR-mutant lung cancer is also elevated among smokers with Native American ancestry."

The researchers next developed a local Native American ancestry risk score to evaluate the association of ancestry with EGFR mutation frequency across multiple distinct sites in the genome. They found that the correlation between ancestry and increased mutation frequency in the EGFR gene was stronger at the local genome level than the global genome level. "These results suggest that germline genetics-in addition to environmental factors or socioeconomic status-may have an influence on the risk of EGFR-mutant lung cancer among those with Native American ancestry," Meyerson said.

The study was jointly led by Meyerson; by Gusev, an assistant professor of medicine at Dana-Farber and Harvard Medical School; by Andres F. Cardona, MD, of the Clinica del Country/Foundation for Clinical and Applied Cancer Research (FICMAC) in Bogota, Colombia; and by Oscar Arrieta, MD, head of Thoracic Oncology at the Instituto Nacional de Cancerologia in Mexico City. Carrot-Zhang, a postdoctoral research fellow at Dana-Farber Cancer Institute and Broad Institute, and first author of the study, developed computational methods with Gusev and performed the bulk of the computational analyses.

Author's Comments: "Many lung cancers are now treatable with targeted therapy or immunotherapy," Meyerson continued. "It is very important for patients with lung cancer to undergo somatic genetic testing to determine which treatments are most likely to be effective for their particular cancer."

Study Limitations: Limitations of the study include a small sample size, which Meyerson noted precluded the identification of the specific gene or site in the germline that is associated with increased somatic EGFR mutations among those with Native American ancestry. Further, the researchers only tested known hotspot mutations and protein truncating mutations in lung cancer driver genes, and future work is needed to comprehensively characterize lung cancer genomes from Latin American patients, Meyerson said.

Funding & Disclosures: This study was supported by a Translational Research Award from the Stuart Scott Memorial Fund of the V Foundation and by the National Cancer Institute. Meyerson is an American Cancer Society Research Professor.

Meyerson is the scientific advisory board chair of OrigiMed and an inventor of patents licensed to LabCorp for the diagnosis of mutations to the EGFR gene, with pending patent applications on EGFR inhibitors. Meyerson receives research funding from Bayer, Janssen, Novo Ventures, and Ono Pharmaceutical Co.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Native American Ancestry Associated With Increased EGFR Mutations - Technology Networks

OTTAWA, Nov. 30, 2020 (GLOBE NEWSWIRE) -- The global precision medicine market value surpassed USD 59.16 billion in 2019 and expected to reach USD 141.33 billion by 2027.

Precision medicine is an emerging approach of treatment and prevention of disease that takes into account the individual variability in environment, genes, and lifestyle for each person. This approach allows researchers and doctors to predict more precisely that which treatment and prevention strategies for a particular disease will work on the specified groups of people.

Although the term "precision medicine" is currently new to the consumers, the concept has been a part of healthcare industry for many years. For instance, a person who requires a blood transfusion is not given blood from any random donor; instead, the blood type of donor is matched with the recipient prior transfusion to reduce the risk of complications. Although examples can be found in various areas of medicine, the role of precision medicine in everyday healthcare is relatively limited. Researchers are significantly working to expand this approach in many areas of healthcare and health in the coming years.

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Growth Factors

The advent of precision medicine has significantly brought a paradigm shift in the drug delivery and diagnosis of the disease. The proliferation of sequencing methodologies, particularly Next Generation Sequencing (NGS), due to the increasing cost of sequencing and development of the Human Genome Project in the field of genomics is predicted to drive the market. NGS technology provides the data related to the patients genetic makeup along with response of drugs on the patient, thereby raising the development of precision medicine for the treatment of diseases. Moreover, NGS combined with Companion Diagnostics (CDx) is analyzed to play a significant role in the advancement of personalized therapeutics and diagnostics over the forecast period. Apart from the benefits offered by the precision medicine, they are highly expensive due to the application of high-end computational methods to examine individual genes projected to hinder the market growth.

Regional Snapshots

North America dominated the global precision medicine market with revenue share of nearly 40% in 2019 and expected to grow at an escalating pace during the forecast period. Technological advancement along with the presence of major players in the region contributes significantly towards the growth of the region. However, the Asia Pacific seeks to be the most opportunistic region in the precision medicine market owing to increasing cases of cancer and other diseases along with the health awareness among people.

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Report Highlights

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Key Players & Strategies

The global precision medicine market is highly competitive owing to the presence of major market participants. These market players are highly focused towards development and innovation of personalized products to upscale their position in the market. For instance, in October 2018, Qiagen announced to launch a novel RNA-seq library preparation solution for next-generation sequencing thereby expanding its user base and portfolio significantly. Similarly, other industry participants are also working prominently for advancement and innovation in the field of precision medicine.

Some of the key players operating in the market are Biocrates Life Sciences, TepnelPharma Services, Novartis, Qiagen, Quest Diagnostics, Menarini Silicon Biosystems, NanoString Technologies, Eagle Genomics, Pfizer, Intomics, Roche, and Teva Pharmaceutical among others.

Market Segmentation

By Technology

By Application

By End-Use

By Regional Outlook

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Precision Medicine Market Poised to Grow at 11.5% By 20227 - GlobeNewswire

Results include: Ethnicity estimate; Health predisposition reports; Carrier status reports; Wellness reports; Personal traits reports; Pharmacological compatibility

TellmeGen offers an ancestry plus health test that gives over 390 results. While the ancestry results arent as robust as competitors, the health component may be the most comprehensive at-home DNA test youll find. Youll receive information about your genetic predisposition to 100 diseases, carrier status for 88 inherited disorders, 150 characteristics of medication compatibility, and more than 50 personal traits. These personal traits are more meaningful than other tests that give information on hair growth or eye color; this test looks at likelihood of alcohol dependency, thyroid function, or preterm birth.

With TellmeGen, youll have access to a free medical forum where you can share your thoughts and ask questions of other users as well as the medical team. For an additional fee, you can request a consultation with a physician, genetic counselor, or nutritionist. Your results will be continually updated as new genetic science becomes available.

TellmeGen uses microarray technology (similar to 23andMe), which tests your DNA for certain variants of a gene known to be associated with a disease. The test doesnt give you information on every possible genetic variant that could cause the disease, only the most common. It is possible that you could have a genetic variant increasing your likelihood for the disease, even if the test report is negative.

Time to results: Four to six weeks

Price: $139

Information updates: Yes

Pros

Cons

Before you take a DNA test, ask yourself whether you really want to know some of the information that could become available to you.

People often find surprising information when they dig into their family historyinformation that affects not only themselves but their parents, siblings, or children. You may find a connection to a relative you didnt know existed or you could find that your genetic information is not linked to someone you thought was a blood relative. These could become issues you and your family grapple with for years to come.

Do you want to know if youre predisposed to an incurable disease such as Alzheimers or Parkinsons, or would you rather only know about diseases you can take action to prevent, such as Type II diabetes or high cholesterol? Depending on the type of test you choose, you may have to consider these questions as well, and your answer may affect your loved ones, too.

Make sure youre prepared for surprises and be certain you want to know the answers your test provides.

Originally posted here:
The Best At-Home DNA Test Kits for Ancestry and Health - Health.com

CAMBRIDGE, Mass. and EMERYVILLE, Calif., Dec. 3, 2020 /PRNewswire/ --Tevard Biosciences, a privately-held biotechnology company pioneering tRNA-based gene therapies, and Zogenix (Nasdaq: ZGNX), a global biopharmaceutical company developing and commercializing rare disease therapies, today announced that the companies have entered into a collaboration to identify and develop novel tRNA-based gene therapies for Dravet syndrome and other genetic epilepsies.

Under the collaboration, Tevard will utilize its two unique tRNA-based discovery platforms focused on mRNA Stabilization and Nonsense Codon Suppression to discover and advance novel drug candidates for the treatment of Dravet syndrome and other genetic epilepsies. Zogenix will further develop the candidates through advanced preclinical studies and clinical development, and be responsible for worldwide commercialization.

Zogenix is responsible for funding the collaboration and, under the terms of the agreement, Tevard will receive an initial collaboration payment of $10 million, of which approximately $5 million has previously been paid by Zogenix. Tevard will also receive $5 million in the form of a convertible note. Tevard is also eligible to receive additional development, regulatory and commercial-related milestone payments ranging from $70 million to $100 million for each program, as well as tiered royalties on future net global sales on any commercial products that result from the collaboration.

Tevard's unique tRNA technology platforms are designed to address underlying genetic mutations in a precise and regulated manner through the correction of nonsense mutations and the enhanced production of functional proteins. Together, these approaches hold promise to treat genetic disorders that are not well-suited to conventional gene replacement approaches.

"We are pleased to announce our collaboration with Zogenix, whose commitment to developing new treatments for Dravet syndrome and other genetic epilepsies is unparalleled," said Daniel E. Fischer, Co-founder, President, and Chief Executive Officer at Tevard Biosciences. "Tevard has assembled a team of leading experts focused on developing our breakthrough tRNA-based gene therapy platforms. Our collaboration with Zogenix will advance our mission to bring transformative gene therapy products to those living with Dravet and other rare and severe genetic disorders.

"We are thrilled to be working with an innovative company like Tevard to develop promising next-generation therapies," said Stephen J. Farr, Ph.D., President and Chief Executive Officer of Zogenix. "Through this important new collaboration, we have reinforced our long-term commitment to transforming the lives of rare epilepsy patients and their families, and look forward to sharing updates as our work together progresses."

About Dravet SyndromeDravet syndrome is a rare childhood-onset epilepsy marked by frequent debilitating seizures, lifelong developmental and motor impairments, and an increased risk of death (SUDEP). In addition to the catastrophic impact on the patient, the severity and unpredictability of the seizures, coupled with around-the-clock concern for the diagnosed child's safety and well-being, can present significant emotional and logistical challenges for parents and all members of the family.

About Tevard BiosciencesTevard Biosciences is a privately held biotechnology companypioneering tRNA-based gene therapiesto cure rare and severe genetic diseases with limited or no approved treatment options. Tevard was founded by MIT Professor and Whitehead InstituteFoundingMember Harvey Lodish, Ph.D., with life science entrepreneurs and executives Daniel Fischer and Warren Lammert, fathers of children with Dravet syndrome. The company is developing and applying two novel tRNA-based gene therapy platforms, co-invented by Professor Lodish with Johns Hopkins School of Medicine Professor Jeff Coller, Ph.D. and University of Iowa Professor Chris Ahern, Ph.D., for Dravet syndrome and other rare diseases caused by haploinsufficiency and/or nonsense mutations that are not amenable to traditional approaches to gene therapy. For more information, please visitwww.tevard.com.

About ZogenixZogenix is a global biopharmaceutical company committed to developing and commercializing therapies with the potential to transform the lives of patients and their families living with rare diseases. The company's first rare disease therapy, FINTEPLA (fenfluramine) oral solution has been approved by the U.S. FDA and received a positive CHMP opinion in Europe for the treatment of seizures associated with Dravet syndrome, a rare, severe childhood onset epilepsy. The company has two additional late-stage development programs underway: one for FINTEPLA for the treatment of seizures associated with Lennox-Gastaut syndrome, a different rare childhood-onset epilepsy and another for MT1621, an investigational novel substrate enhancement therapy for the treatment of TK2 deficiency, a rare genetic disorder. MT1621 is being developed through Modis Therapeutics, a Zogenix company.

Forward Looking Statements Zogenixcautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "intends," "potential," "suggests," "assuming," "designed," and similar expressions are intended to identify forward-looking statements. These statements include the potential that the use tRNA-based discovery platforms will result in the discovery and advancement novel drug candidates for the treatment of genetic epilepsies; and Zogenix's intention to develop any drug candidates discovered through tRNA-based discovery platforms. These statements are based on Zogenix's current beliefs and expectations. The inclusion of forward-looking statements should not be regarded as a representation byZogenixthat any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in Zogenix's business, including, uncertainties related to pharmaceutical product development, including whether any drug candidate will be discovered; results from preclinical or clinical studies may not support the continued development or commercialization of any discovered drug candidate; delays or disruptions in Zogenix's or Tevard's business operations due to the COVID-19 pandemic and other risks described in Zogenix's prior press releases as well as in public periodic filings with theU.S. Securities & Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, andZogenixundertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

CONTACTS:

Tevard BiosciencesInvestors and MediaKaren L. Bergman for Tevard+1 (650) 575-1509[emailprotected]

ZogenixMelinda BakerSenior Director, Corporate Communications+1 (510) 788-8732[emailprotected]

InvestorsBrian RitchieManaging Director, LifeSci Advisors LLC+1 (212) 915-2578[emailprotected]

MediaStefanie TuckVice President, Porter Novelli+1 (978) 390-1394[emailprotected]

SOURCE Tevard Biosciences

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Tevard Biosciences and Zogenix Announce Collaboration to Advance Novel Gene Therapies for Dravet Syndrome and Other Genetic Epilepsies - PRNewswire

Jacqueline Chu, M.D., considered the man with a negative coronavirus test on the other end of the phone, and knew, her heart dropping, that the test result was not enough to clear him for work.

The man was a grocery store clerkan essential workerand the sole earner for his family. A 14-day isolation period would put him at risk of getting fired or not having enough money to make rent that month. But he had just developed classic COVID-19 symptoms, and many others around him in Chelsea, Massachusetts, had confirmed cases. Even with the negative test, his chances of having the disease were too high to dismiss.

Accelerate Biologics, Gene and Cell Therapy Product Development partnering with GenScript ProBio

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For many Americans, including clinicians like Chu, who specializes in primary care and infectious disease at Massachusetts General Hospital, the pandemic has forced difficult conversations about the limits of medical tests. It has also revealed the catastrophic harms offailing to recognize those limits.

People think a positive test equals disease and a negative test equals not disease, said Deborah Korenstein, M.D., who heads the general medicine division at Memorial Sloan Kettering Cancer Center in New York City. Weve seen the damage of that in so many ways with COVID.

National COVID-19 test shortages have emphasized testings critical role in containing and mitigating the pandemic, but these inconvenient truths remain: A test result is rarely a definitive answer, but instead a single clue at one point in time, to be appraised alongside other clues like symptoms and exposure to those with confirmed cases. The result itself may be falsely positive or negative, or may show an abnormality that doesnt matter. And even an accurate, meaningful test result is useless (or worse) unless its acted on appropriately.

These lessons are not unique to COVID-19.

Last year, David Albanese logged in to the online patient portal for his primary care doctors office and discovered that his routine screening test for the hepatitis C virus showed a positive result.

I never considered myself somebody whos in a high-risk category, said the 34-year-old Boston-area college administrator and adjunct history professor. But I just know that for a couple of days, I was really, really anxious about this test. I didnt know if I should be behaving differently based on it.

Within days, a confirmatory test showed Albanese did not actually have the potentially severe yet curable liver infection. Still, the memory of that false positive result gave him a new perspective on testing writ large. He had been skeptical of recommendations shifting breast cancer screening to older ages to reduce the psychological toll of false positives, but he said they made more sense after his own testing drama.

Isnt it better to do the screening regardless? he said he used to think. Now, I realize it is a little more complicated.

These false positives are especially common for screening tests like hepatitis C antibody tests and mammograms that look for medical problems in healthy people without symptoms. They are designed to cast a wide net that catches more people with the disease, known as the tests sensitivity, but also risks catching some without it, which lowers what is known as the tests specificity.

Though some degree of uncertainty is inherent in all medical decisions, clinicians often fail to share this with patients because its complicated to explain and unsettling and leaves doctors vulnerable to seeming uninformed, said Korenstein. Whats more, doctors are trained to seek definitive answers and can themselves struggle to think in probabilities.

High-tech diagnostic testing has led to this mirage of certainty, said Korenstein. Back in the day before there were MRIs and what not, I think, doctors were more cognizant of how often they were uncertain.

Enter COVID-19. Coupled with genuine uncertainty about an emerging disease and a political environment that has sown misinformation and rendered science partisan, the nuances of testing are too often lost at a time when they are particularly crucial to convey.

Jasmine Marcelin, M.D., who specializes in infectious disease at the University of Nebraska Medical Center, was concerned to see Nebraskans tested at statewide facilities get inconsistent results without a lot of guidance or explanation about what these results might mean. When she offers COVID testing, she said, she approaches it as she does any other medical decision, starting with a simple question: What do you want to learn from this test?

To answer this, it helps to know something about how coronavirus tests work and how well they do their jobs.

Many of the available tests are meant to tell you whether youre infected right now. For example, polymerase chain reaction tests like the one Chus patient received detect small traces of genetic material from the virus. But by some estimates, those tests have a false negative rate of up to 30%, meaning three out of 10 people who truly have the infection will test negative. This rate also varies based on who collects the sample, from which part of the body and when in the course of a possible infection.

Antigen tests look for viral proteins and are faster to analyze than the PCR, but also less accurate.

To know if youve already had COVID-19, the closest you can get is the COVID-19 antibody test. But the too-common interpretation is black and white: I had COVID-19, or I didnt. Here, again, the reality is more nuanced. The test checks your blood for antibodiesyour immune systems soldiers in the fight against the coronavirus. A negative antibody test could mean you were never infected with SARS-CoV-2, or it could mean that youre currently infected but havent yet built up that army, or that these defenses have already faded away.

A positive test, on the other hand, may have mistakenly detected antibodies to another, similar-looking virus. And, even if the test correctly shows you had COVID-19, its not yet clear whether this means youre protected from reinfection.

Yet, these shades of gray are difficult to internalize. Roy Avellaneda, the 49-year-old president of the Chelsea City Council, got the antibody test out of curiosity and could not help but see his positive result as what he called an immunity pass. I can act a little bit cavalier with it now, he said. Yes, Ill continue to wear a mask and so forth, but the fear is gone.

Korenstein said thats a common though worrisome reaction. Its really hard to expect the public to have a more nuanced understanding when even doctors dont, she said.

Some of the uncertainty around COVID-19 testing has abated as researchers learn more about the new disease. Early in the pandemic, healthcare providers retested patients with confirmed cases, looking for a negative PCR test to prove they were no longer infectious. But soon, epidemiologists discovered that a COVID-19 patient rarely infected others 10 or more days after first developing symptoms (or 20, in severe cases), even if the PCR test was picking up traces of thepresumably deadvirus weeks or even months after initial infection. So the Centers for Disease Control and Prevention and health systems adjusted their policies to clear patients on the basis of time rather than a negative test.

But while the desire for certainty in coronavirus testing is magnified by the rampant uncertainty in other facets of pandemic life, this is simply not something most medical tests can provide.

Kaiser Health News(KHN) is a national health policy news service. It is an editorially independent program of theHenry J. Kaiser Family Foundationwhich is not affiliated with Kaiser Permanente.

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How COVID-19 highlights the uncertainty of medical testing - FierceBiotech

Novel agents that disrupt protein-protein interactions in the MLL network may be the key to unlocking new therapeutic avenues for patients with acute leukemias, which are characterized by diverse genetic and epigenetic alterations that are challenging to target, according to investigators.1

Early clinical data have demonstrated an antitumor effect of small molecule inhibitors directed at interactions of menin, a tumor suppressor protein, and MLL fusion proteins in acute myeloid leukemia (AML).2 One such agent, KO-539, is being investigated in 2 genetic subsets of AML: patients with rearrangements in KMT2A (also known as MLL1 or MLL) or with NPM1 mutations, which both promote leukemogenesis.

KMT2A(MLL) translocations are found in approximately 5% to 10% of patients with acute leukemias, including lymphoid, myeloid, or biphenotypic subtypes2; the 5-year survival rate for this population is approximately 35%.1 Over 30% of patients with AML have NPM1 mutations that, when they occur along with FLT3-ITD mutations, result in an overall survival rate of less than 50%.1

Investigators believe that menin is involved with a variety of cellular processes including aiding in the structural modification of MLL that stabilizes the bond between MLL and lens epithelium derived growth factor, a transcriptional coactivator believed to play a role in cancer.2 By causing a genetic disruption of the menin-MLL fusion protein interaction, they hypothesize, a novel agent could block the development of acute leukemia (Figure).3

In preclinical research, KO-539 prolonged survival compared with quizartinib, a FLT3 inhibitor, in 2 patient-derived xenograft models of NPM1/DNMT3/FLT3-mutant AML. In a confirmatory study, animals that were NPM1- and FLT3-mutant/DNMT3A wild-type and were treated with quizartinib relapsed by approximately day 35; those treated with KO-539 had no evidence of disease progression after 56 days.4

Although translocations of KMT2A(MLL) occur in approximately 3% of patients with AML, the mutational burden of these patients is far less than that of other cancer types; as a result, the translocations alone may result in the generation of the leukemic phenotype. Further, gene expression profiling has demonstrated overexpression of both HOXA9 and MEIS1, 2 oncoproteins thought to be critical for enhanced self-renewal in AML. Specifically, transcription of the HOXA9 and MEIS1 genes are dependent on KMT2A(MLL)-fusion protein binding to menin.5

The menin-MLL interaction seems to trigger the upregulation of certain leukemogenic or leukemia-promoting proteins, such as HOXA9 and MEIS1, said Amir T. Fathi, MD, in an interview with OncLive. [Developing] drugs that inhibit the leukemogenic signals can, in theory, lead to promotion of differentiation and maturation and response. Fathi is an associate professor of medicine at Harvard Medical School and director of the Leukemia Program at Massachusetts General Hospital, both in Boston.

Although KMT2A(MLL) and NPM1 alterations currently are the frontrunners as targets for in-human studies, Fathi suggested that, in time, investigators may learn more about efficacy in other subpopulations of patients with AML whose disease may be affected by epigenetic dysregulation from the menin-MLL interaction. If so, such findings may emerge as points of interest.

Other mutations that are seen in AML and myeloid malignancies, such as NPM1, DNMT3, EZH2, and others, appear to have their impact upstream from the menin-MLL, interaction, Fathi said. These alterations, too, can theoretically affect the menin-KMT2A interaction and complex and promote epigenetic dysregulation and leukemogenesis.

Because of the potential for broad efficacy, KO-539 is undergoing testing in a varied patient population in the phase 1 portion of the KOMET-001 trial (NCT04067336). We are assessing patients across a wide range of molecular subtypes to further define who may benefit from this class of targeted drug, explained Fathi, one of the leading investigators. We suspect that some patients with an NPM1 mutation or those with MLL rearrangements may be susceptible to response based on what we know from preclinical science, and we should study these populations carefully, but we are also assessing more broadly initially across AML to better characterize the other patient populations that may benefit.

KOMET-001 is the first in-human study of the menin-MLL inhibitor, which is being developed by Kura Oncology. The study will evaluate the safety and tolerability of escalating doses of KO-539 monotherapy for patients with relapsed and/or refractory AML.

Up until now, initial studies have been done extensively in preclinical models, said Eunice S. Wang, MD. If we extrapolate from some of our clinical models, we think that a dose of approximately 600 milligrams once per day would be effective, but because this is a first-in human study, we [followed] the typical phase 1 study design where we increase the dose.

Wang serves as chief of Leukemia Service, medical director of Infusion Services, at Roswell Park Comprehensive Cancer Center, and an associate professor in the Department of Medicine at Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo. She is scheduled to present preliminary data from the study during the 2020 American Society of Hematology Annual Meeting, which is being held in a virtual format December 5 to 8.

In an interview in advance of her presentation, Wang noted that investigators used a novel study design and started the first dose of KO-539 at 50 mg. KO-539 was administered orally once daily to patients in 28-continuous-day cycles and, as of data cutoff of August 10, 2020, 6 patients had proceeded through to the 200-mg dose. Following this, an expansion cohort of 3 patients at a 200 mg dose was initiated to better characterize the pharmacokinetics and exposure of KO-539.6

Early data show that KO-539 demonstrated biologic activity in 3 patients in the first 3 dose cohorts of 50 mg, 100 mg, and 200 mg. Tumor lysis syndrome was reported for 2 patients in the 50- and 200-mg cohorts. The patients had a KMT2A(MLL)-rearrangement and a TP53 mutation with a PICALM-AF10 fusion, respectively. The third patient treated at the 100-mg dose level had SETD2 and RUNX1 comutations and achieved a complete remission with confirmed negative minimal residual disease after 2 cycles of therapy. The patient remains on treatment.6

Although the study sample data are too small to reach conclusions, activity of the agent is promising. The complete remission data was very exciting, for a pill taken once a day for a patient who had multiple relapses, said Fathi. The responding patient did not have an MLL-translocation nor an NPM1-mutation, but there were other alterations that may have ultimate effects on the menin-MLL interaction and whose disease may thus have been susceptible to menin inhibition. It leaves open the door for the possibility to identify other groups of patients across AML who may benefit.

In safety data for 3 evaluable patients, no dose-limiting or dose-interrupting toxicities have been reported.6 Wang plans to present updated safety and efficacy data at the meeting.

Expansion cohorts are planned to further assess the safety and activity of KO-539 in an NPM1-mutant cohort and a KMT2A(MLL)-rearranged cohort. Right now, the expansion cohorts are designed to target subsets of patients with AML that have those specific mutations, said Wang. However, if we see evidence [of efficacy] in the early dose-escalation trials, we may consider trying to expand out [to other mutational subtypes] as well to a pool of patients with leukemia that are what we call mutation agnostic.

Theres still a lot of ground to go and patients to enroll, but there is a lot of opportunity to probe that signal a little bit more, to learn more, and to hopefully help these patients, Fathi said.

Another drug that aims to disrupt menin-MLL interactions is SNDX-5613, an oral inhibitor being developed by Syndax Pharmaceuticals under an FDA orphan drug designation for adults and pediatric patients with AML.7 The phase 1/2 AUGMENT-101 trial (NCT04065399) is testing the agent in patients with relapsed/refractory leukemias.

The study, which seeks to recruit 186 pediatric and adult patients, will evaluate escalating doses of SNDX-5613 monotherapy in phase 1. After the recommended dose is established, patients will be enrolled in 1 of 3 cohorts: acute lymphoblastic leukemia or mixed phenotype acute leukemia; KMT2A(MLL)-rearranged AML; and NPM1-mutant AML.8

Read more:
MLL Fusion Proteins Emerge as a Promising Target in AML - OncLive

Summary

Using cryo-electron microscopy, researchers at the Sloan Kettering Institute have gained an important insight into how cells repair broken DNA, a process fundamental to life that sometimes goes awry in cancer.

A landmark in cancer research was the discovery, in the early 1990s, of two cancer predisposition genes BRCA1 and BRCA2. When mutated, these genes increase a persons risk of developing several forms of cancer, including breast, ovarian, and prostate cancers. Since then, researchers around the world have been studying these genes and the proteins made from them to learn exactly how they increase the risk of cancer.

Many crucial breakthroughs in scientists understanding of this topic have come from research conducted at Memorial Sloan Kettering. In the late 1990s, Sloan Kettering Institute molecular biologist Maria Jasin showed that the BRCA2 protein was necessary for repairing a type of DNA damage called a double-strand break. When BRCA2 is mutated, it cant repair this damage well, and cancer is often the result.

In 2002, SKI structural biologist Nikola Pavletich determined the structure of the BRCA protein and showed that it binds to DNA. In a follow-up paper published in 2005, Dr. Pavletich showed that BRCA2 is required for DNA repair because it activates another protein, called Rad51, which is the actual machine that repairs double-strand breaks. In 2008, he showed how the bacterial version of Rad51, called RecA, starts the repair process by binding to one strand of the broken DNA.

Now, more than 12 years later, Dr. Pavletich has added yet another piece to the puzzle. In a report published October 14 in the journal Nature, he and his colleagues, including senior research scientist Haijuan Yang, describe the mechanism by which RecA and the broken DNA strand it carries search for the correct segment of a nearby DNA molecule to use as a repair template.

The findings cap a nearly 20-year quest, the pace of which has accelerated in recent years thanks to a new technology called cryo-electron microscopy (cryo-EM).

Because DNA is so fundamental to life, cells have evolved a variety of means to preserve its integrity. When DNA is damaged say by UV light or x-rays there are several ways a cell can attempt to repair it. The most careful, error-free way is called homologous recombination. In this type of repair, a cell finds a segment of DNA on an intact chromosome that matches the broken region of the other and uses that as a template to fill in the gap. (Chromosomes come in pairs, one from mom, one from dad; these chromosomes are said to be homologous.)

From decades of work, it was clear that a single strand of broken DNA finds homologous DNA with the help of a protein called RecA. RecA and single-stranded DNA form a structure called a pre-synaptic filament. The filament binds to double-strand DNA, opens it up to expose its complementary strands, and then searches for homology along one of those strands.

The question we didnt understand was how its searching for homology between the single-stranded DNA that its carrying and the double-stranded DNA that it binds to, Dr. Pavletich says.

To investigate that question, they turned to cryo-EM. This relatively new form of microscopy, whose developers won the 2017 Nobel Prize in Chemistry, allows scientists to visualize the fine-grained structure of biological molecules at unparalleled resolution. MSK acquired a cryo-EM machine in 2017.

Before the advent of cryo-EM, the main way that biologists determined structures of proteins and other molecules was x-ray crystallography, a painstaking and time-consuming effort.

Weve spent a long time with crystallography trying to address these issues and it just did not work out, Dr. Pavletich says. Cryo-EM makes it much easier.

Part of the problem is that to really understand the mechanism, they needed to capture what the RecA protein looks like at various points during the DNA repair process; with x-ray crystallography, they were really only able to look at one point in time.

With cryo-EM, they are able to look at thousands and thousands of RecA proteins bound to DNA at various times points and from these many images piece together the entire sequence.

What we were able to determine is how RecA opens the double-stranded DNA and how one of the DNA strands is sequestered at a second secondary site in the RecA protein, Dr. Pavletich says.

This binding leaves the other DNA strand flipping around and hitting the single-stranded DNA that the filament was carrying, he adds. If there is homology, it stays there. If there are no homology it continues to float around.

Even if the team had had several x-ray crystal structures to work with, they wouldnt have been able to glean what they were able to using a million RecA-DNA particles. Thats the power of cryo-EM, he says. It took us 12 years to solve this, but if we had had cryo-EM in 2008 then it would have been much faster.

Homologous recombination is not only important in fixing mutations that can lead to cancer. Its also how genetic diversity is generated during the formation of sperm and egg: maternal and paternal chromosomes break along their lengths and swap segments before being repaired through homologous recombination. This genetic diversity is why you and your siblings look similar but not identical; you each got a different combination of maternal and paternal chromosomes.

Homologous recombination is also how the genome-editing tool CRISPR works. This technology, whose developers won the 2020 Nobel Prize in Chemistry, relies on the introduction of DNA double-strand breaks at specific locations in the genome and repair through homologous recombination.

Dr. Pavletich says he hopes the new insights into homologous recombination will ultimately help improve cancer care, as past discoveries have done. But he says thats not the primary goal of basic science research.

As scientists, we do what we do because we love the gratification of solving a problem, he says. And homologous recombination is one of those really longstanding and important biological problems to understand. So it feels really good to be able to make this contribution to science.

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Wielding Powerful Imaging Tools, MSK Researchers Decipher Process of DNA Repair - On Cancer - Memorial Sloan Kettering

A biobank is a storage facility for biological samples including blood, human tissue and/or DNA. They can then be used at any time for future medical research or pioneering methods.

The Managing Director of Estonian Biobank, Andres Metspalu, gives us some insight:

"I started the Estonian Biobank about 20 years ago. Our biobank is pretty large for a small country. We have around 20% of the entire Estonian population over the age of 18 included in our biobank; which equates to more than 200,000 individuals.

"They have all been analysed genetically, which is really remarkable. That is why we can do this genetic medicine not only for cancer, but also for other diseases.

"More than 3,000 people have already received their genetic risk (result) from the biobank.

"This is what keeps me busy every day, doing research and also facilitating the use of this information in healthcare".

"We are mainly talking about (predicting the risks of developing diseases like) cancer, cardiovascular diseases and type-2 diabetes. We also study melanoma, prostate cancer and lung cancer.

"We are also doing pharmacogenomics, drug response (how our bodies respond to drug intake).

"Not all drugs work on everyone as (pharmaceutical) companies believe or expect. Some drugs (can be) pretty harmful. You (can) get reactions and you (can) get side effects. You may end up in hospital after taking prescription drugs.

"Genetics can predict some serious events. It (genetics) should be used. This is what we are trying to introduce into everyday medical practice in Estonia".

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How genetics can help predict risks of cancer recurrence and improve treatment - Euronews

Here's a look at which companies are raking in cash this week in the biopharma industry.

Apollomics, Inc.

Committed tocombatting cancer with precision,Apollomics plans to use the$124.2 million Series Cfinancing to focusclinicalefforts on its lead programs: APL-101 and APL-106. APL-101 is an oral c-MET inhibitorcurrently involved in several ongoing clinical trials. TheSPARTA trialis in Phase II, targeting non-small cell lung cancer,glioblastomamultiforme and solid tumors with MET amplifications.APL-106 is a first-in-class targeted inhibitordesignedtoblockE-selectin, an adhesion molecule on cells in bone marrow,from binding with blood cancer cells.It has received Breakthrough Therapy Designation from the FDA in relapsed and refractory acute myeloid leukemia.In 2019,Apollomicsraised$100 million in a Series B round.

Decibel Therapeutics

Decibel Therapeutics made some noise this week with an oversubscribed Series D financing, raking in$82.2 million. The company will use the funds to advance DM-OTO, a gene therapy to restore hearing in children with congenital deafness due to a deficiency in the otoferlin gene.Clinical testing is expected to initiate in2022.DB-020 is already in a phase Ib study with cancer patients as apreventative treatment for the ototoxicityassociated with cisplatin-based chemotherapy.Hearing and balance disorders have historically been overlooked by the biopharma industry, even though they exact a devastating toll on the lives of hundreds of millions of people around the globe. At Decibel, we are dedicated to restoring hearing and balance with precision therapeutics designed to deliver the right genetic medicine specifically to the right cells in the ear, said Laurence Reid, Ph.D., Chief Executive Officer of Decibel.

Adagio Therapeutics

After launchingin Junewith $50 million, Adagio has pocketed another$80 million in a Series Bfinancing round to take its COVID-19 antibody into the clinic next year. Adagios neutralizing monoclonal antibodies are expected to provide broad protection against not onlyagainst SARS-CoV-2 and SARS-CoV-1, but also additional bat coronaviruses that have yet to cross the species barrier. Adagio got the green light from the FDA to proceed with their first-in-human study in early 2021.We were impressed by the thoughtful approach that Adagio took. By dealing with the broader coronavirus problem, we expect ADG20 to be more resistant to escape mutations and potentially cover future coronavirus pandemics, said Krishna Yeshwant, Managing Partner at GV. As a preventative agent, ADG20 holds the promise of providing the efficacy necessary to deliver greater protection against COVID-19. Given its unique combination of attributes, ADG20 could complement and supplement vaccines by providing rapid, durable antibody protection against current and future coronaviruses.

InmageneBiopharmaceuticals

Drug development companyInmagenehas its eye on being number one in immunology in China.The$21 million Series Bclosed this week will be pumped into conducting global clinical trials, research and development, and product in-licensing activities.Currently candidate IMG-020 is in a Phase II psoriasis trial, with a strong safety profile and clear clinical benefits giving it best-in-class potential. Manufactured inan E. coli system, IMG-020 is less than 1/20thof the average manufacturing cost of a typical antibody drug.The candidate is about to enter global registration trials formultiple indications.

Locus Biosciences

Its been a busy season for this CRISPR-engineer.In September,Locussigneda$144 million contract with BARDAto develop theirproduct targeting E. coli bacteria causing recurrent urinary tract infections. This week they closed a$14.4 million deal with CARB-Xto advance development of LBP-KP01, another CRISPR Cas3-enhanced bacteriophage (crPhage) product, targeting K. pneumoniae.The initial indication will be to target recurrent UTIs, then development for targeting lung infections (pneumonia), intra-abdominal infections (IAIs) and bacteremia.Together, the two cocktails have the potential to treat more than 90% of UTIs.Auniquedual mechanismof bacteria-hunting bacteriophages along with the DNA-targetingCRISPR-Cas3makesLocuscandidates significantly more effective at killing the targeted bacteria cells, regardless of whether they are resistant to antibiotics.Both the U.S. Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have identified antibiotic-resistant K. pneumoniaeas an urgent and serious public health threat requiring development of new treatments.

Memo Therapeutics

Swiss innovator Memo Therapeutics has raised over$15.3 million in a Series Bprimarilyto advance its COVID-19 antibody treatment.The company entered into a partnership with NorthwayBiotechpharmain August to manufactureMTX-COVAB, which is currently going through a fast-tracked development path as an immunotherapy and a preventative of the novel coronavirus. Memo plans to begin clinical studies in 2021. Proceeds will also be used to advance its neutralizing antibody MTX-005 against BK virus infection in renal transplant patients into Phase II studies."We believe Memo Therapeutics AG has taken innovation in the field of antibody discovery to the next level. Their ability to exploit the power of microfluidic single-cell molecular cloning could not only serve to move one step closer to conquer the COVID pandemic but also potentially other infectious diseases and cancer, said Dr. Robert Schier, Investment Director atSwisscantoInvest.

Trailhead Biosystems

Pushing the boundaries of dimensional testing, Trailhead is increasing the speed, lowering the cost and reducing the risk of developing cell therapies. A$6.6 millioninfusion of cash will expand the companys High Dimensional Design of Experiments platform (HD-DoE) to support the generation of multiple specialized human cells with therapeutic properties and theirpilotscalemanufacturing.Trailheads aim is to rapidly develop the capability to create highly pure, specialized human cell types for regenerative medicine and therapeutic purposes at an industrial scale. "Biology is complex, but conventional science is not," saysJan Jensen, Ph.D., Chief Executive Officer and founder of Trailhead Biosystems. "We created Trailhead Biosystems to address key limitations in the scientific process, unlocking a deeper understanding of biology that will enable us to better control it."

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Biopharma Money on the Move: November 4-10 - BioSpace

Eric Wang, Senior Photographer

Researchers at the Yale School of Medicine have identified genes that could be future targets for COVID-19 treatments.

In a partnership with the Broad Institute of MIT and Harvard, researchers at the School of Medicines Department of Immunology performed a genome-wide CRISPR screen, which evaluated each of the 20,000 preselected genes in the African green monkey genome that could affect coronavirus infections. This technique allowed researchers to quickly and effectively evaluate the genetic information from over a million modified cells.

According to assistant professor of laboratory medicine and immunobiology Craig Wilen, using a genetically modified virus called a CRISPR library, certain genes of interest were knocked out in the monkey cells in order to stop their products from being made and used in the cell. The cells were then infected with the coronavirus, and those that survived were analyzed to detect what genes were knocked out and could be affecting viral infection. The results pointed to over 25 possible host genes related to infection, but two specific hits for receptor and enzyme encoding genes seemed most promising as treatment targets.

We think its possible that you could develop drugs that affect human targets, Wilen said. And the advantage there is it would be conserved and function across different coronaviruses.

Jin Wei, the studys primary author and a postdoctoral associate at Wilens lab, explained that he was directly involved in identifying the host genes critical to coronavirus infections.

According to Wei, the lab had prior experience in studying the modes of infections of RNA viruses such as MERS and other coronaviruses. This previous work meant they were uniquely prepared to study the genes that affect the SARS-CoV-2 virus infection which had never been done before.

We found there is no CRISPR screens for host genes for any coronaviruses, which may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis, Wei wrote in an email to the News. We leveraged our expertise with RNA virus pathogenesis and CRISPR screening to identify the host factors that are essential for SARS-CoV-2 infection.

Mia Madel Alfajaro, another postdoctoral associate at Wilens lab, explained that they found two important genes during their screening process that, when absent, helped cells survive the virus infection. One of them encodes the SARS-Cov-2 receptor, while the other is translated into an enzyme that aids the coronavirus in entering the cell.

Scientists at the Broad Institute provided the Yale researchers with the CRISPR library to be used in the monkey cells and the analyses they ran on the surviving cells genetic material.

Our group has significant expertise and capacity in terms of making CRISPR libraries, turning them from an idea into an actual test tube of particles, John Doench, an institute scientist at the Broad Institute, said.

Wei and Doench believe one of the main findings of the study comes from the comparison between SARS-CoV-2 and another coronavirus, MERS-CoV. These genetic hits that affect coronaviruses in general could be useful in finding pan-coronavirus treatments, according to Wilen.

According to Alfajaro, one of the limitations of this study is that there is no way to mimic exactly the behavior of a human beings lung cells, which means there are still many steps to be taken before a treatment is developed.

If we have [found] molecules, peptides or chemical inhibitors or COVID-19, that would be great, Alfajaro said. It will take time because some of the hits need to be developed.

Alfajaro believes drugs that are already approved by the FDA could be a possible focus for future research, since some of the drugs already on the market could affect the molecules found during the screening.

Doench does not believe that the main goal of the study was finding a drug that would end the pandemic. He argued that a future drug may be able to target the genes they found to create therapeutics for COVID-19, but that more work needs to be done.

From doing a genetic screen in a cell line in a monkey to having a drug target, there is so much science that needs to happen, he said.

According to Doench, the only way to stop the pandemic is through social distancing, wearing masks and eventually developing a vaccine.

The Broad Institute of MIT and Harvard was founded in 2004.

Beatriz Horta | beatriz.horta@yale.edu

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Yale scientists discover genes that could be COVID treatment targets - Yale Daily News

CAMBRIDGE, Mass., Nov. 10, 2020 (GLOBE NEWSWIRE) -- Generation Bio Co. (Nasdaq: GBIO) is an innovative genetic medicines company creating a new class of non-viral gene therapy. Today the company reported recent business highlights and third quarter financial results.

2020 continues to be a year of progress and execution for Generation Bio as we advance our non-viral gene therapy approach, said Geoff McDonough, M.D., president and chief executive officer of Generation Bio.Despite the challenges of the COVID-19 pandemic, we remain on-track to advance our lead programs into IND-enabling preclinical development next year. We believe our strong cash balance positions us well to execute on our ambitions into 2023.

Recent Business Highlights

This period marks an expansion of our focus beyond our platform to include preclinical development and readiness for the clinic. To support this effort, I am pleased to announce the appointment of Tracy Zimmermann to chief development officer. Tracy will lead our pre-clinical development programs across the portfolio, building on the excellent foundation she has created since joining Generation Bio in 2018. Tracys new role allows for Doug Kerr to focus on building our clinical development capabilities as chief medical officer. Together with Matt Stanton, our chief scientific officer, Tracy and Doug make a terrific, complementary leadership team for our R&D work, Dr. McDonough said. A summary of the leadership appointments follows.

Dr. McDonough continued, Separately, Mark Angelino, our chief operating officer and co-founder, will undertake a planned transition from Generation Bio to return to early stage company formation work in early 2021. Although too soon for farewells, we are indebted to Mark for his vision and leadership in forming and building our community here.

Selected Anticipated Company Milestones

Upcoming Investor Conference Presentations

Management will present at two upcoming investor conferences:

Live webcasts of the presentation and the fireside chat will be available in the investor section of the company's website atwww.generationbio.com. The webcasts will be archived for 60 days following the presentations.

Financial Results

About Generation Bio

Generation Bio is an innovative genetic medicines company focused on creating a new class of non-viral gene therapy to provide durable, redosable treatments for people living with rare and prevalent diseases. The companys non-viral platform incorporates a proprietary, high-capacity DNA construct called closed-ended DNA, or ceDNA; a cell-targeted lipid nanoparticle delivery system, or ctLNP; and an established, scalable capsid-free manufacturing process. The platform is designed to enable multi-year durability from a single dose of ceDNA and to allow titration and redosing if needed. The ctLNP is designed to deliver large genetic payloads, including multiple genes, to specific tissues to address a wide range of indications. The companys efficient, scalable manufacturing process supports Generation Bios mission to extend the reach of gene therapy to more people, living with more diseases, in more places around the world.

For more information, please visit http://www.generationbio.com.

Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about its strategic plans or objectives, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities, the initiation and completion of preclinical studies and clinical trials and clinical development of the Companys product candidates; uncertainties as to the availability and timing of results from preclinical studies and clinical trials; whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials; expectations for regulatory approvals to conduct trials or to market products; challenges in the manufacture of genetic medicine products; the Companys ability to obtain sufficient cash resources to fund the Companys foreseeable and unforeseeable operating expenses and capital expenditure requirements; the impact of the COVID-19 pandemic on the Companys business and operations; as well as the other risks and uncertainties set forth in the Risk Factors section of the Companys most recent quarterly report on Form 10-Q, and in subsequent filings the Company may make with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Companys views as of the date hereof. The Company anticipates that subsequent events and developments will cause the Companys views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Companys views as of any date subsequent to the date on which they were made.

Contacts:

InvestorsChelcie ListerTHRUST Strategic Communicationschelcie@thrustsc.com910-777-3049

MediaStephanie SimonTenBridge Communicationsstephanie@tenbridgecommunications.com617-581-9333

GENERATION BIO CO.CONSOLIDATED BALANCE SHEET DATA(unaudited)(in thousands)

GENERATION BIO CO.CONSOLIDATED STATEMENTS OF OPERATIONS(unaudited)(in thousands, except share and per share data)

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Generation Bio Reports Third Quarter 2020 Business Updates and Financial Results - GlobeNewswire

One of the biggest challenges that scientists and healthcare professionals are facing during the COVID-19 pandemic is the high rate of clinical variability. Whilst some patients present as asymptomatic, others are developing more severe symptoms such as pneumonia, and some cases are ultimately proving fatal. Why?The answer remains elusive; however, extensive research is exploring the possible contribution our genetics may be having. Genetic variation differences in the DNA sequences that make up our genome can impact our response to infectious diseases.

GoodCell uniquely measures and monitors inherited and acquired genetic variations in stem cells and other nucleated cells in our blood over time. Technology Networks recently spoke with Dr Salvatore Viscomi, chief medical officer at GoodCell, and attending physical at Baystate Health, to explore factors that might influence COVID-19 risk, and to discuss how the company is working to identify at-risk individuals through genetic variation analysis.

Molly Campbell (MC): For our readers that may be unfamiliar, can you discuss why medicine is moving towards a personalized approach, and why this is important considering genetic variation?Salvatore Viscomi (SV): Healthcare has traditionally taken the approach of one size fits all in defining individual risk for a disease and prescribing therapy for it. Understanding the differences between individuals on a molecular level optimizes assessment of an individuals susceptibility to a certain disease and predicting response to pharmacological therapy. Genomics plays the most important role in the emergence of personalized therapy. Identifying the inherited and acquired genetic variation will direct personalized screening and prevention plans and inform bespoke medical therapies.

MC: We know that there is high clinical variability across COVID-19 patients. How might genetic variation be contributing here, and what published evidence exists to support this?SV: Understanding immune response is critical to identifying individuals at high risk of severe morbidity and mortality. Emerging research suggests that accumulated genetic variation in our blood cells may be associated with a dysfunctional inflammatory response to COVID-19 leading to its pulmonary, cardiac and coagulopathic complications.

In a recent study published by JAMA Cardiology, researchers demonstrated an association between the presence of accumulated genetic change in our blood cells and a pro-inflammatory immune response that resembles the exaggerated cytokine release syndrome (CRS) manifested in COVID-19-positive patients. Direct evidence has emerged more recently; a study published in Cancers examined patients hospitalized with COVID-19 and found a significantly higher prevalence of accumulated genetic variation in all age groups compared to age-matched control groups.

MC: What impact might genetic variation in COVID-19 patients have on efforts to develop therapeutics or preventives, such as vaccines?SV: Identifying highly susceptible individuals through blood testing could have many applications. As an initial wave of vaccines move through Phase III trials and potentially come to market, we would have the data to determine prioritization of vaccinations when one is available. Business and government sectors need insight into risk factors that can inform inoculation strategies for societys most vulnerable, inform decisions around who should and should not be on the front lines, and give people more control when making personal decisions about how to mitigate individual risk. The broader field of genetics offers a window into the potential to correlate inherited and acquired gene mutations with immune response for the betterment of society, providing a more robust and accurate set of risk factors unique to every individual.

Furthermore, in high-risk individuals, targeting inflammation may be a clinical strategy to mitigate its clinical consequencesin COVID-19. For example, we may identify patients who are most responsive to pro-inflammatory inhibitors. Implementing measures intended to reduce subjects exposure to the infection or likelihood of contracting such infection through self-isolation, quarantine or social distancing may be advised.

MC: Can you explain the aims of GoodCell, and what the company does in terms of "banking blood for life"?SV: GoodCells mission is to extend and improve the quality of life through technology powered by our own cells. Blood is the author of our bodies, and can both cure as well as cause disease. Through our proprietary data aggregation and analytics technology platform, which aims to decode our blood cells and harness their insights to advance population and personal health, we empower individuals to identify, track and mitigate health risks. By getting ahead of their health risks, we enable the potential for a better life. In addition, through our personal biobanking service, long-term storage of your healthiest cells provides the opportunity for potential use in future therapeutics if you need them you are your best donor.

MC: Does GoodCell measure other "omics" parameters outside of genomics (DNA measurements and analysis), such as proteomics or metabolomics?SV: GoodCells platform leverages the power of blood to assess risk as such, we of course look at acquired and inherited genetic changes, but there are many more opportunities afforded by blood to understand and assess risk including routine blood chemistry tests, tests for biomarkers of disease, including emerging capabilities in liquid biopsy for earlier detection of solid tumor cancers. Ultimately, we are always looking to incorporate novel health and data insights into our product platform to better inform both an individuals health, as well as population-based health. Transcriptomics, epigenomics and metabolomics are but a few of the opportunities we are evaluating.

MC: What work is GoodCell currently conducting in the COVID-19 space?SV: GoodCell is currently engaged in a research collaboration with the New York Blood Center to evaluate how specific acquired and inherited genetic variation contribute to COVID-19 severity and recovery. We are analyzing genetic variation in asymptomatic/mildly symptomatic patients compared to hospitalized/ICU patients. GoodCell will evaluate the genetic variation in the collected samples using our proprietary assay platform to identify and validate their association with COVID-19 morbidity and mortality.

Salvatore Viscomi was speaking to Molly Campbell, Science Writer, Technology Networks.

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Exploring Genetic Variation and COVID-19 Clinical Variability - Technology Networks

My lab, based at the University of Southern California Keck School of Medicine, uses zebrafish to model human birth defects affecting the face. When I tell people this, they are often skeptical that fish biology has any relevance to human health.

But zebrafish have backbones like us, contain by and large the same types of organs, and, critically for genetic research, share many genes in common. My group has exploited these genetic similarities to create zebrafish models for several human birth defects, including Saethre-Chotzen Syndrome, in which the bones of the skull abnormally fuse together, and early-onset arthritis.

Similar to fish, our bodies develop under the control of about 25,000 genes. The trick is finding out what each gene does. Stunning advances such as CRISPR-based molecular scissors, for which the Nobel Prize in chemistry was just awarded, allow us to precisely change genes, and designer chemicals can silence particular genes. In a recent study from our group published in Nature, however, we find that these tools are still far from perfect. Although CRISPR now allows us to efficiently generate lab animals that can pass human disease mutations onto the next generation, claims that simply injecting CRISPR into embryos or silencing genes with designer chemicals can accurately model human genetic disease are being questioned.

Finding the precise mutation that causes a particular birth defect or a late-onset disease can be tedious work. The human genome is made up of 3 billion building blocks called DNA nucleotides, and changing just one of these can cause devastating birth defects.

To figure out if we have identified the right disease-causing mutation in humans, we typically engineer the same change into the genome of a lab animal. We then breed these animals to generate babies with the disease mutation and look for the appearance of defects similar to those in human patients.

We study zebrafish because they are small, which means we can grow thousands of different genetically modified animals. We routinely use CRISPR to engineer fish that pass on a gene-breaking mutation to the next generation.

We then study the appearance of defects similar to those in humans lacking these genes in essence creating personalized zebrafish avatars of genetic disease. As zebrafish embryos are transparent and develop rapidly outside the mother, they are particularly useful for understanding how human disease mutations disrupt normal development.

Even in zebrafish, engineering animals to lack particular genes can be a time-consuming process. In my lab, we first create gene mutations in embryos, grow these fish to adulthood and then breed fish together to look at defects in the next generation.

This whole process can take a year or longer. Unsurprisingly, many labs are attempting shortcuts. Some are injecting large quantities of CRISPR molecular scissors into animals and then looking for defects in these same animals. Others are using chemicals to turn off, or silence, genes in the embryo rather than permanently changing the genes.

More and more frequently studies like this are calling into question the accuracy of these shortcuts. In animals that have been injected with CRISPR molecular scissors, not every cell is changed in the same way. And the chemicals used to silence genes appear to have unintended consequences, poisoning the embryo in a generic way.

For example, researchers in Spain recently reported that a gene called prrx1a was critical for the proper development of the heart. To figure this out, they silenced prrx1a in zebrafish with chemicals. Then, in a second experiment, they injected CRISPR molecular scissors into zebrafish embryos and examined them just one day later for heart defects.

In contrast, we completely removed the prrx1a gene and looked at generations of fish lacking this gene. Hearts in these mutant fish developed perfectly normally, showing that prrx1a was not critical for heart development. Instead, we showed that the heart defects seen upon chemical treatment in the Spanish study were due to a general poisoning of the embryos unrelated to the prrx1a gene. Animals simply injected with CRISPR also showed defects not seen upon complete removal of the prrx1a gene, although the exact reasons for these differences remain a source of active debate.

And not just our group has noticed these flaws. Using similar gene removal as we reported, the group led by Didier Stainier refuted a study that had used CRISPR injection and gene silencing to link the tek gene to blood vessel development. Given the number of studies relying on gene silencing in lab animals, as opposed to engineering the DNA mutations, the causative genes for many human diseases may need to be reevaluated.

The desire for speed in research must not come at a cost of accuracy and reproducibility.

The good news is that, with the ease of CRISPR, we now know how to engineer the right types of mutations in lab animals to validate human disease mutations. By creating lab animals such as zebrafish that have the mutations engineered into their genomes and then observing whether their offspring develop the same diseases as patients with the mutations, we can be confident in having identified the right human disease gene.

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Getting it right is important for accurately counseling prospective parents of their genetic risks for certain birth defects, as well as identifying the relevant genes that can be targeted to prevent or even reverse disease.

Science is constantly evolving. While the ability to engineer the genome with CRISPR is opening up endless possibilities for human genetics, researchers must also recognize the limitations of new technologies. Although rapid, directly injecting CRISPR or silencing genes with chemicals gives misleading results too often. In order to confidently identify causative mutations linked to human disease, we will need to continue to study lab animals engineered to carry and pass on the same DNA changes as found in human patients.

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Flaws emerge in modeling human genetic diseases in animals - The Conversation US

On Monday morning, when representatives from the drug company Pfizer said that its Covid-19 vaccine appears to be more than 90 percent effective, stocks soared, White House officials rushed to (falsely) claim credit, and sighs of relief went up all around the internet. Dear World. We have a vaccine! Best news since January 10, tweeted Florian Krammer, a virologist and vaccinologist at the Mount Sinai School of Medicine (who also happens to be a participant in the Pfizer Covid-19 vaccine trial).

Here's all the WIRED coverage in one place, from how to keep your children entertained to how this outbreak is affecting the economy.

But having a press release from a pharmaceutical company saying a vaccine works is very different from actually having a vaccine that works. Pfizer, and its German partner on the vaccine, BioNTech, have yet to release any data from their Phase III trial. The findings this week are based on the trials first interim analysis, conducted by an outside panel of experts after 94 of the 43,538 participants contracted the coronavirus. That analysis suggests that most of the people who became ill had received a placebo, instead of the vaccine. But it doesnt say much beyond that. (More on why that matters, later.)

And logistically, theres still a lot that has to happen before people who arent study subjects can start rolling up their sleeves. Pfizer researchers are now collecting at least two months worth of safety follow-up data. If those findings raise no red flags, the company could then apply for an emergency use authorization from the US Food and Drug Administration. Only then could execs start doling out the 50 million or so doses they expect to make by the end of the year, a process complicated by the fact that until its ready to be shot into someones arm, Pfizers vaccine needs to be kept at temperatures downwards of -80 degrees Fahrenheit, which is way colder than the usual vaccine cold chain. Completing the immunization also requires two doses given three weeks apart. Oh yeah, and states that at this moment are trying to do all the other things you have to do to prepare for such a complicated immunization pushhiring vaccinators, setting up digital registries, deciding who will get vaccine priorityare doing so without any extra money dedicated to the effort.

Those are a lot of caveats. But still, theres reason to be hopeful. If the results hold up, a Covid-19 vaccine thats 90 percent effective will have vastly exceeded the efficacy bar set by the FDA. That level of protection would put it up there with the measles shot, one of the most potent vaccines developed to date.

The arrival of an effective vaccine to fight SARS-CoV-2 less than a year after the novel coronavirus emerged would smash every record ever set by vaccine makers. Historic isnt even the right word, says Larry Corey of the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Center. A renowned virologist, Corey has spent the last three decades leading the search for a vaccine against the virus that causes AIDS. Hes never seen an inoculation developed for a new bug in under five years, let alone one. Its never happened before, never, not even close, he says. Its just an amazing accomplishment of science.

And perhaps even more monumental is the kind of vaccine that Pfizer and BioNTech are bringing across the finish line. The active ingredient inside their shot is mRNAmobile strings of genetic code that contain the blueprints for proteins. Cells use mRNA to get those specs out of hard DNA storage and into their protein-making factories. The mRNA inside Pfizer and BioNTechs vaccine directs any cells it reaches to run a coronavirus spike-building program. The viral proteins these cells produce cant infect any other cells, but they are foreign enough to trip the bodys defense systems. They also look enough like the real virus to train the immune system to recognize SARS-CoV-2, should its owner encounter the infectious virus in the future. Up until now, this technology has never been approved for use in people. A successful mRNA vaccine wont just be a triumph over the new coronavirus, itll be a huge leap forward for the science of vaccine making.

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Why Its a Big Deal If the First Covid Vaccine Is Genetic - WIRED

NEW YORK--(BUSINESS WIRE)--Genosity, Inc., an innovative biotechnology company that provides comprehensive software and laboratory solutions to enable precision medicine, announced today that it has entered into a strategic collaboration agreement with Igentify, a digital health technology company that has developed a digital genetic counselor assistant to improve provider interaction with patients for onboarding, enrollment, consenting, as well as facilitating counseling for personalized genetic testing results. Under the terms of agreement, Igentify will integrate its digital platform with Genositys Integrated Genomic Toolkit (IGT), and both companies will comarket the combined solution.

The integrated product, with an ability to interface with traditional EMR systems, is a complete solution for any health system offering genetic testing. This comprehensive platform enables a genomic testing order for a patient to be originated by a third-party health system, explained to the patient by a personalized and dynamic multimedia presentation which takes the patient through a genetic testing consent process and literacy assessment; processed in LIMS upon receipt of the patients specimen; the genomic data analyzed, interpreted and reported, and a full medical report communicated to the patient with customized, patient friendly PDF and video reports.

Our goal is to enable health systems to fully embrace precision medicine to the benefit of their patients which requires more than just performing or sending out a test. It is about enabling those who most directly touch patient lives. Our integrated system not only provides a solution for the operational aspects of all genetic testing, from patient enrollment to result report, but also enables our clients to build their data driven knowledge base that can help them advance research, improve patient care and engage in commercial collaborations. It is our pleasure to work with Igentify. Both executive teams have worked on solving operational challenges in genomics for a long time; this collaboration is the result of our work and experience in this critically important field, said Dr. Marc Grodman CEO and Cofounder of Genosity.

Dr. Doron Behar, CEO and Cofounder of Igentify, said, Genomic testing is a pillar of precision medicine which will affect the health of each individual worldwide and shape healthcare policies and prevention medicine practices. Demand for genetic testing is rising quickly, but a shortage of genetic counselors makes it impossible to scale up personal genetic counseling services, leaving health care providers unable to fulfill patient needs. Igentify is proud to combine our efforts with Genosity to allow the first of its kind comprehensive software solution that enables healthcare providers to establish genomic core centers of excellence comprising patient counseling, bioinformatics and a laboratory information management system for better patient care.

About Genosity:Genosity is a life science biotechnology company that employs its expertise, novel software solutions and laboratory services for both somatic and germline applications to enable its strategic partners to fully realize the value of precision medicine for both the research and clinical markets. For more information, please visit us at https://genosity.com.

About Igentify:Igentify is a digital health technology company with expertise in analyzing, interpreting and transforming complex genomic molecular results into medically supervised genetic reports. Igentify enables personalized genetic counseling services at scale. The mission of Igentify is to create accessible and actionable genomic data for all. For more information, please visit us at https://igentify.com.

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Genosity and Igentify Announce Strategic Collaboration to Integrate Their Offerings, Enabling Comprehensive and Holistic Precision Medicine Solution...