StemCell Therapy

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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Precedence Research is a worldwide market research and consulting organization. We give unmatched nature of offering to our customers present all around the globe across industry verticals. Precedence Research has expertise in giving deep-dive market insight along with market intelligence to our customers spread crosswise over various undertakings. We are obliged to serve our different client base present over the enterprises of medicinal services, healthcare, innovation, next-gen technologies, semi-conductors, chemicals, automotive, and aerospace & defense, among different ventures present globally.

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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.

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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

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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...

PHILADELPHIA, Nov. 09, 2020 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders, and Invitae (NYSE: NVTA), a leading medical genetics company, announce a collaboration to facilitate genetic testing and support early identification of GM1 gangliosidosis (GM1) through Invitaes Detect Lysosomal Storage Disorders (Detect LSDs). The two companies also are partnering to provide educational clinical trial information to clinicians and patients.

Early identification and intervention are crucial steps in providing effective treatment to patients with GM1, particularly in the infantile form where onset occurs within the first six months of a patients life, said Bruce Goldsmith, Ph.D, president and chief executive officer of Passage Bio. By combining Invitaes no-charge testing and counseling with information on clinical trials, clinicians will be able to intervene sooner and more efficiently, shortening the timeline to reliable diagnosis. As we plan to initiate our Phase 1/2 trial for PBGM01 soon, this partnership will be an important part of our support for patients and will also serve as a key resource to patients with GM1 and their families.

The Detect LSDs program offers genetic testing and genetic counseling at no charge to patients to encourage earlier diagnosis of lysosomal storage disorders like GM1 and, as a result, earlier access to clinical trials. In addition, Invitae provides clinical trial information and education to clinicians and patients who may benefit. Currently, the Detect LSDs program is available to patients within the United States and Canada.

Increasing access to genetic testing supports earlier diagnosis, enables clinical trials to develop new treatments and helps clinicians provide precision therapies sooner for better overall outcomes, said Robert Nussbaum, M.D., chief medical officer of Invitae. Were pleased Passage Bio has joined us in this effort.

Additional details, as well as terms and conditions of the Detect LSDs program, can be found at https://www.invitae.com/en/detectLSDs/.

About GM1

GM1 gangliosidosis (GM1) is a rare and often life-threatening monogenic recessive lysosomal storage disease caused by mutations in the GLB1 gene, which encodes lysosomal acid beta-galactosidase (-gal). Reduced -gal activity results in the accumulation of toxic levels of GM1 ganglioside in neurons throughout the brain, causing rapidly progressing neurodegeneration. GM1 manifests as a continuum of disease and is most severe in the Infantile form, which is characterized by onset in the first 6 months of life with hypotonia (reduced muscle tone), progressive CNS dysfunction, and rapid developmental regression. Life expectancy for infants with GM1 is two to four years, and infantile GM1 represents approximately 62.5% of the incidence of 0.5 to 1 in 100,000 live births. Currently, there are no approved disease-modifying therapies available.

About Passage Bio

At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming gene therapies for patients with rare, monogenic CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvanias Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. This provides our team with unparalleled access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at http://www.passagebio.com.

About Invitae

Invitae Corporation (NYSE: NVTA) is a leading medical genetics company whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website atinvitae.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including our planned IND submissions, initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators and partners ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, might, plan, potential, possible, will, would, and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

For further information, please contact:

Investors:Sarah McCabe and Zofia MitaStern Investor Relations, Inc.sarah.mccabe@sternir.com and zofia.mita@sternir.com

Media:Media:Gwen FisherPassage Bio215-407-1548gfisher@passagebio.com

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Passage Bio and Invitae Announce Collaboration to Facilitate Genetic Testing to Support Early Diagnosis and Greater Awareness of Clinical Trials for...

BEAM-201, an Off the Shelf Allogeneic CD7-Targeting CAR-T, Named as Development Candidate for Treatment of T-ALL; First Cell Therapy Featuring Four Simultaneous Genetic Edits; Demonstrates 96-99% On-target Editing and In Vivo Proof of Concept of Tumor Clearance

Multiple Upcoming Data Presentations Demonstrate Strength and Breadth of Base Editing Platform, Including First Preclinical Data from GSDIa Program

$135 Million in Capital Raised through Successful Follow-on Offering

CAMBRIDGE, Mass., Nov. 10, 2020 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today reported pipeline updates, recent business highlights and third quarter 2020 financial results.

2020 has been a year of significant progress for Beam, said John Evans, chief executive officer of Beam. Since the start of the year, weve named three development candidates from our portfolio, now including BEAM-201, our multiplex editing program for the treatment of T-cell acute lymphoblastic leukemia. We are also pleased to report that were on track to submit our first IND in the second half of 2021, with BEAM-101 for the treatment of sickle cell disease. The continued advancement of our pipeline is a testament to both the strength and breadth of our base editing platform and our exceptional team. Combined with the capital weve added to our balance sheet, we are well positioned to continue our strategy of advancing multiple programs to the clinic in parallel, in the hope of providing much-needed new treatment options for patients with serious diseases.

Base Editing Progress

Upcoming Base Editing Data Presentations

Beam will also report data during an oral presentation at AASLD from its Alpha-1 Antitrypsin Deficiency (Alpha-1) program. Details of the presentation are as follows:

Recent Business Highlights

Upcoming Investor Conference Presentation

John Evans, chief executive officer, will participate in a fireside chat during the Jefferies Virtual London Healthcare Conference on Thursday, November 19, 2020 at 4:25 p.m. GMT/11:25 a.m. ET.

The live webcast will be available in the investor section of the company's website at http://www.beamtx.com. The webcast will be archived for 60 days following the presentation.

Third Quarter 2020 Financial Results

About Beam Therapeutics

Beam Therapeutics(Nasdaq: BEAM) is a biotechnology company developing precision genetic medicines through the use of base editing. Beams proprietary base editors create precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This enables a wide range of potential therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs. Beam is a values-driven organization committed to its people, cutting-edge science, and a vision of providing life-long cures to patients suffering from serious diseases. For more information, visitwww.beamtx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements related to: the expected timing of filing investigational new drug applications; our ability to advance programs to the clinic; the sufficiency of our cash position; expected presentations at upcoming conferences; and the therapeutic applications and potential of our technology, including our ability to develop precision genetic medicines for patients through base editing. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including, without limitation, risks and uncertainties related to: our ability to develop, obtain regulatory approval for, and commercialize our product candidates, which may take longer or cost more than planned; our ability to raise additional funding, which may not be available; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the potential impact of the COVID-19 pandemic; that preclinical testing of our product candidates and preliminary or interim data from preclinical and clinical trials may not be predictive of the results or success of ongoing or later clinical trials; that enrollment of our clinical trials may take longer than expected; that our product candidates may experience manufacturing or supply interruptions or failures; risks related to competitive products; and the other risks and uncertainties identified under the heading Risk Factors in our Annual Report on Form 10-K for the year ended December 31, 2019, our Quarterly Report on Form 10-Q for the quarters ended March 31, 2020, June 30, 2020, and September 30, 2020, and in any subsequent filings with the Securities and Exchange Commission. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable law.

Contacts:

Investors:Chelcie ListerTHRUST Strategic Communicationschelcie@thrustsc.com

Media:Dan Budwick1ABdan@1abmedia.com

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Beam Therapeutics Announces Business and Pipeline Progress and Reports Third Quarter 2020 Financial Results - GlobeNewswire

DetailsCategory: DNA RNA and CellsPublished on Friday, 06 November 2020 17:53Hits: 894

- Marked Reductions in Phe Observed at Two Doses -

- Achieved Goal with Plans to Advance to Randomized, Concurrently Controlled Expansion Phase of Trial -

BEDFORD, MA, USA I November 06, 2020 I Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the presentation of positive data from the dose-escalation portion of the Phase 1/2 gene therapy pheNIX clinical trial for adults with phenylketonuria (PKU). The results showed that product candidate HMI-102 was generally well-tolerated, and resulted in marked reductions in phenylalanine (Phe) and the Phe-to-tyrosine (Tyr) ratio (Phe/Tyr ratio) at two doses. Phe is a registrable endpoint in PKU, and the Phe/Tyr ratio is a clinically relevant diagnostic measurement for PKU. With these positive results, Homology is progressing to the randomized, concurrently controlled expansion phase of the trial, which has the potential to be converted to a registrational trial.

The data were presented today in an oral presentation by Olaf Bodamer, M.D., Ph.D., FACMG, FAAP, Park Gerald Chair in Genetics & Genomics and Associate Chief of Genetics & Genomics at Boston Childrens Hospital, and principal investigator of the pheNIX trial, during the New England Consortium of Metabolic Programs (NECMP) annual meeting, which is focused on new research in metabolic disorders. NECMP includes metabolic clinics, healthcare providers, patient organizations and others dedicated to increasing knowledge of metabolic disorders and improving delivery of healthcare to patients.

This is the first-ever PKU gene therapy clinical trial, and I am excited to share these data with the PKU community as I believe they demonstrate the potential of HMI-102 to treat the underlying genetic cause and reduce the therapeutic burden for patients and their families, stated Dr. Bodamer. PKU is a challenging condition, and a treatment that establishes normal metabolism could change the prognosis for patients with this rare genetic disorder. We look forward to participating in the next phase of the study.

We are pleased to have met the goals of the dose-escalation portion of the trial, which were evaluation of safety and efficacy of a single I.V. administration of HMI-102 and dose determination for the expansion phase of the trial, stated Gabe Cohn, M.D., Chief Medical Officer of Homology Medicines. Even as many patients self-liberalized their diets, there were patients at the mid- and high-doses with plasma Phe values below 360 mol/L and/or 600 mol/L, and one of these patients achieved a Phe level within the normal range. This is the first time a genetic medicines approach has achieved these results in patients with PKU. We have learned a tremendous amount in the dose-escalation phase and are applying these learnings to the expansion phase of the trial, which we anticipate initiating in early 2021.

Dr. Cohn continued, We greatly appreciate the PKU community of patients, clinicians and caregivers who have participated in this first phase of the pheNIX trial, and we look forward to working together during the next phase.

As of the data cutoff date of October 19, 2020, six patients in the dose-escalation phase of the pheNIX trial had received gene therapy product candidate HMI-102 across three dose cohorts (low-dose Cohort 1, n=2; mid-dose Cohort 2, n=2; high-dose Cohort 3, n=2). Cohorts included males and females, with an age range of 21-49 and time in study ranging from 13 weeks to 52 weeks (end of study).

Safety ObservationsHMI-102 was generally well-tolerated, and there were no treatment-related serious adverse events (SAEs). There were no clinically significant changes in ECG or vital signs and no clinical signs of complement activation. The Grade 1 and 3* alanine aminotransferases (ALTs) observed in Cohorts 2 and 3, which is common in AAV-based gene therapy, were managed with increased steroids when necessary. The patients who experienced Grade 3 ALTs had pre-existing underlying immune conditions. An independent data monitoring committee, which provided guidance throughout the pheNIX trial, concluded that there were no safety concerns related to bilirubin, and that ALT elevations may be associated with reduced efficacy.

Updates to the expansion phase of the pheNIX trial, including key learnings related to patient selection, monitoring and steroid regimen, are being incorporated.

Efficacy Observations

Cohort 1 (Low-Dose)Through 52 weeks, patients in Cohort 1 continued to show no meaningful reductions in Phe.

Cohorts 2 and 3 (Mid- and High-Dose)The mean percent change from baseline in Phe observed in patients in Cohorts 2 and 3 were significant, compared to Cohort 1**. These Phe reductions occurred while patients self-liberalized their diets.

Through 48 weeks, one patient in Cohort 2 had Phe levels of <360 mol/L and/or <600 mol/L*** at multiple timepoints and had reached a minimum Phe level of 42 mol/L, compared with a baseline level of 1,010 mol/L. Through 13 weeks, one patient in Cohort 3 had a Phe level <360 mol/L and several Phe levels <600 mol/L at multiple timepoints and had reached a minimum Phe level of 303 mol/L, compared with a baseline level of 1,060 mol/L.

In Cohorts 2 and 3, Phe reductions were greater among patients with Grade 1 ALTs compared to patients with Grade 3 ALTs****; ALT elevations were managed with increased steroids when necessary. It appears higher ALT elevations may limit therapeutic activity, but can be managed with a modified steroid regimen, which is being incorporated into the expansion phase.

Expansion PhaseBased on the safety and efficacy results observed in the dose-escalation phase, Homology is advancing to the randomized, concurrently controlled, dose expansion phase of the pheNIX trial, which has the potential to be converted to a registrational trial.

All cohorts in the dose-escalation phase showed an acceptable safety profile and certain patients in Cohorts 2 and 3 showed marked Phe reductions. Based on these collective data, Homology has selected two doses for the expansion phase: the mid-dose from Cohort 2 and a dose between the doses in Cohorts 2 and 3. The Company believes the latter dose has the potential to improve Phe reductions while reducing steroid exposure that was required at the high-dose. The Company believes that advancing two doses in parallel provides the potential to convert to a registrational trial quickly with the optimal dose as the expansion phase does not include staggered dosing between patients.

Webcast/Conference Call Homology management and Dr. Bodamer will host a conference call and webcast today, Friday, November 6 at 4:30 p.m. ET. The webcast will be accessible on Homologys website in the Investors section, and the webcast replay will be available on the website for 90 days following the presentation. To access using the conference call line, dial (866) 244-8091 (U.S./Canada toll-free) or (602) 563-8623, with Conference ID 7394503.

About HMI-102HMI-102 is an investigational gene therapy in clinical development for the treatment of phenylketonuria (PKU) in adults. HMI-102 is designed to encode the PAH gene, which is mutated in people with PKU, delivered via the liver-tropic AAVHSC15 vector. Homology has received Fast Track Designation and orphan drug designation for HMI-102 from the U.S. Food and Drug Administration (FDA), and orphan drug designation from the European Medicines Agency (EMA).

About Phenylketonuria (PKU)PKU is a rare inborn error of metabolism caused by a mutation in thePAHgene. PKU results in a loss of function of the enzyme phenylalanine hydroxylase, which is responsible for the metabolism of phenylalanine (Phe), an amino acid obtained exclusively from the diet. If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease. According to the National PKU Alliance, PKU affects nearly 16,500 people in the U.S. with approximately 350 newborns diagnosed each year. The worldwide prevalence of PKU is estimated to be 50,000 people.

About Homology Medicines, Inc. Homology Medicines, Inc. is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homologys proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicinesin vivoeither through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visitwww.homologymedicines.com.

*ALT Grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5**P<0.004; Post-hoc comparison of Cohort 1 vs Cohorts 2&3 using repeated measures MANOVA/regression analysis***U.S. and EU PKU treatment guidelines described in: Vockley J et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genetics in Medicine 2014;16: 188-200.van Spronsen FJ et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 2017; 5: 74356.****P<0.05; Post-hoc comparison of Patients 3&6 vs Patients 4&5 using repeated measures MANOVA/regression analysis

SOURCE: Homology Medicines

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Homology Medicines Announces Presentation of Positive Data from the Dose-Escalation Phase of the pheNIX Gene Therapy Trial for Adults with PKU | DNA...

- IND for LB-001 in methylmalonic acidemia (MMA) cleared in August 2020, with first patient in Phase 1/2 SUNRISE trial expected to be enrolled in early 2021- Fast Track designation for LB-001 in MMA received in November 2020- First follow-on offering post-IPO closed in October 2020

LEXINGTON, Mass., Nov. 09, 2020 (GLOBE NEWSWIRE) -- LogicBio Therapeutics, Inc.(Nasdaq:LOGC) (LogicBio or the Company), a company dedicated to extending the reach of genetic medicine with pioneering targeted delivery platforms, today reported financial results for the quarter endedSeptember 30, 2020 and provided a business update.

LogicBio has recently marked several important achievements, which could set the stage for exciting news from our company in the quarters to come, said Frederic Chereau, President and CEO. Over the last several months, LogicBio made significant advances in its LB-001 program in methylmalonic acidemia (MMA), with the clearance of the IND and the receipt of Fast Track designation for LB-001 in MMA. Following our $48.3 million follow-on public offering in early October, we believe we are well-positioned financially to deliver on our upcoming milestones. Mr. Chereau continued, The Phase 1/2 SUNRISE trial is designed to treat MMA patients at a young age when gene editing could potentially make a meaningful, life-long difference. We continue to anticipate the enrollment of our first patient in the SUNRISE trial in early 2021, and we eagerly look forward to updating both the clinical community and investors of our progress as 2021 unfolds. Mr. Chereau concluded by saying, In addition to our exciting clinical program, we have extended our collaboration with the Childrens Medical Research Institute of Australia to continue to develop our Next Generation Capsid platform, which has already yielded novel liver-tropic capsids that we believe are superior to ones that are currently used in the clinic. We also anticipate sharing further data on our novel capsids in early 2021.

Anticipated LogicBio Milestones for 2021:

LB-001 for MMA

Pipeline

Third Quarter 2020 Financial Results

Three Months Ended September 30, 2020 and 2019

About LogicBio Therapeutics

LogicBio Therapeuticsis dedicated to extending the reach of genetic medicine with pioneering targeted delivery platforms. LogicBios proprietary genome editing technology platform, GeneRide, enables the site-specific integration of a therapeutic transgene without nucleases or exogenous promoters by harnessing the native process of homologous recombination. LogicBio has received FDA clearance for the first-in-human clinical trial of LB-001, a wholly owned genome editing program leveraging GeneRide for the treatment of methylmalonic acidemia. Patient enrollment is expected to begin in early 2021. In addition, LogicBio has a collaboration withTakedato research and develop LB-301, an investigational therapy leveraging GeneRide for the treatment of the rare pediatric disease Crigler-Najjar syndrome.

LogicBio is also developing a Next Generation Capsid platform for use in gene editing and gene therapies. Data presented have shown that the capsids deliver highly efficient functional transduction of human hepatocytes with improved manufacturability with low levels of pre-existing neutralizing antibodies in human samples. Top-tier capsid candidates from this effort demonstrated significant improvements over benchmark AAVs currently in clinical development. LogicBio is developing these highly potent vectors for internal development candidates and potentially for business development collaborations.

LogicBio is headquartered inLexington, Mass. For more information, please visitwww.logicbio.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the federal securities laws, including those related to the Companys plans to initiate, advance and complete its planned Phase 1/2 SUNRISE clinical trial of LB-001 in MMA and the potential benefits to patients of LB-001; the timing, progress and results of the Companys research and development activities, including those related to the GeneRide technology platform and Next Generation Capsid Program; its plans for LB-301 in Crigler-Najjar; and the sufficiency of our cash on hand to fund our operating expenses and capital expenditures. These are not statements of historical facts and are based on managements beliefs and assumptions and on information currently available. They are subject to risks and uncertainties that could cause the actual results and the implementation of the Companys plans to vary materially, including the risks associated with the initiation, cost, timing, progress and results of the Companys current and future research and development activities and preclinical studies and potential future clinical trials. In particular, the impact of the COVID-19 pandemic on the Companys ability to progress with its research, development, manufacturing and regulatory efforts, including the Companys plans to initiate, advance and complete its Phase 1/2 clinical trial for LB-001 in MMA, and the value of and market for the Companys common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements inthe United Statesand in other countries, and the effectiveness of actions taken globally to contain and treat the disease. These risks are discussed in the Companys filings with theU.S. Securities and Exchange Commission(SEC), including, without limitation, the Companys Annual Report on Form 10-K filed onMarch 16, 2020with theSEC, the Companys Quarterly Report on Form 10-Q filed onMay 11, 2020, and the Companys subsequent Quarterly Reports on Form 10-Q and other filings with theSEC. Except as required by law, the Company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future.

LogicBio Therapeutics, Inc.Condensed Consolidated Balance Sheets(In Thousands)(Unaudited)

LogicBio Therapeutics, Inc.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(In thousands, except share and per share amounts)(unaudited)

Contact:

Matthias Jaffe Chief Financial Officer mjaffe@logicbio.com (617) 245-0399

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LogicBio Therapeutics Reports Third Quarter 2020 Financial Results and Provides Business Update - GlobeNewswire

LOS ANGELES, Calif.,November 11, 2020 In recognition of Veterans Day, the Prostate Cancer Foundation (PCF) today announced its new $5 million commitment to launch two new Centers of Excellence in collaboration with the VA Boston Healthcare System (VABHS), Dana-Farber Cancer Institute, the VA Portland Health Care System (VAPORHCS) and Oregon Health & Science University (OHSU) to deliver best-in-class precision oncology treatments to Veterans with prostate cancer.

PCF is committed to continuing to expand our partnership with the VA to advance cutting-edge research and care for Veterans with prostate cancer, said Jonathan W. Simons, MD, PCF president and CEO. Partnering with Dana-Farber and Oregon Health & Science University brings top expertise to our precision oncology efforts serving our nations Veterans. It is our duty to ensure that no Veteran is left behind when a medical breakthrough comes to the clinic.

More than 15,000 men in the Veterans Affairs (VA) health system are newly diagnosed with prostate cancer each year, making it the most frequently diagnosed cancer among Veterans. One in nine men and one in six African American men are diagnosed with prostate cancer each year, and four million men in the U.S. are living with the disease.

Precision medicine is individualized, based on gene sequencing a patients tumor, allowing for custom-tailored treatment that targets an individuals cancer by its unique biology and genetic signature. It is the key to ending deaths from prostate cancer. More than half the funds the PCF has committed have been used to launch its collaborative COE network at the forefront of precision oncology for prostate cancer. The PCF has also dedicated funding to the research of numerous VA physician scientists. The platform the PCF and VA have created is being used to build centers of excellence for other cancers, as well as to launch clinical studies in the fight against COVID-19.

With the addition of the new centers, the PCF has established 12 COEs to date, executing the ambitious mission of improving patient care for U.S. Veterans with prostate cancer. Located inBoston, MA, and Portland, OR, these new COEs join 10 other established Centers in cities across the U.S. in delivering advanced precision oncology treatments to save the lives of Veterans battling prostate cancer. The other centers are based inPhiladelphia, PA,Washington, DC,Durham, NC, Tampa Bay, FL, Seattle, WA,Chicago, IL,Bronx, NY,Los Angeles, CA,Manhattan, NY,andAnn Arbor, MI.

We are proud to partner with the PCF and the VA to launch this first PCF-VA Center of Excellence in New England, said Dana-Farber President and CEO Laurie H. Glimcher, MD. Our partnership will create better access to clinical trials and genomics for Veterans across all VA systems, and deliver the best possible care for Veterans diagnosed with prostate cancer.

The PCFs Veterans Health Initiative, which was established in 2016, is committed to investing$50 millionto deliver innovative, best-in-class prostate cancer care to Veterans, which includes expanding genomic data banking to provide improved prostate cancer treatment, greater access to clinical trials, and resources to develop better precision oncology care.

This award will make it possible for us to reach out to veterans throughout Oregon and Southwest Washington to offer genetic testing and sequencing for all patients with metastatic prostate cancer, said Julie Graff, M.D., Section Chief of Hematology/Oncology, VA Portland Health Care System and Associate Professor, Hematology & Medical Oncology, OHSU Knight Cancer Institute. Knowing more about each patients specific mutation(s) gives us the knowledge we need to explore more treatment and clinical trial options. Ultimately, we want Veterans to know they have access to leading treatment and clinical trials through the VA Portland Health Care System.

The Portland and Boston COEs were established with funding made possible through the Blavatnik Family Foundation and Rob and Cindy Citrone.

Members of the Blavatnik Family Foundation Precision Oncology

Center of Excellence (COE) at VABHS-Dana-Farber Boston include: Chong-xian Pan, MD, PhD, MS, Medicine faculty, Brigham and Womens Hospital, Harvard Medical School, staff physician, hematology/oncology, VABHS; Himisha Beltran, MD, Associate Professor of Medicine, Lank Center for Genitourinary Oncology Division of Molecular and Cellular Oncology, Dana-Farber, Director of Translational Research-Medical Oncology, Dana-Farber.

Members of the PCF Precision Oncology Center of Excellence (COE) at VAPORHCS-OHSU Portland team include: Julie Graff, MD, oncology (VAPORHCS, OHSU); Tomasz Beer, MD, oncology (OHSU, VAPORHCS); Jeremy Cetnar, MD, oncology (VAPORHCS, OHSU); Ryan Kopp, MD, urology (VAPORHCS); Mark Garzotto, MD, urology (VAPORHCS, OHSU); Amy Moran, PhD, immunology (OHSU); Reid Thompson, MD PhD, radiation oncology (VAPORHCS, OHSU); Rajan Kulkarni, MD PhD, dermatology (VAPORHCS, OHSU); Dean Fong, DO, pathology (VAPORHCS).

To learn more about clinical trials offered by the PCF-VA Centers of Excellence, Veterans should call (206)-277-3621. Information is also available atwww.PCF.org/veterans.

About the Prostate Cancer Foundation

The Prostate Cancer Foundation (PCF) is the worlds leading philanthropic organization dedicated to funding life-saving prostate cancer research. Founded in 1993 by Mike Milken, PCF has raised more than $830 million in support of cutting-edge research by more than 2,200 research projects at 220 leading cancer centers in 22 countries around the world. Thanks in part to PCFs commitment to ending death and suffering from prostate cancer, the death rate is down by 52% and countless more men are alive today as a result. The Prostate Cancer Foundation research now impacts more than 70 forms of human cancer by focusing onimmunotherapy, the microbiome, and food as medicine. Learn more at http://www.pcf.org.

Media Contact: Staci Vernick Prostate Cancer Foundationsvernick@pcf.org610-812-6092

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Prostate Cancer Foundation, Dana-Farber Cancer Institute and Oregon Health & Science University Partner to Adv - Prostate Cancer Foundation

Prime editing is the gene-editing method that can insert, delete and do base swapping accurately. Prime editing also termed as genetic word processor precisely select the target DNA and replace genetic code. Targeting 75,000 different mutations and correcting 89% of genetic defects will drive the demand for prime editing. In 2017, the first gene editing in the human body was attempted. Gene editing in a patient with Hunters syndrome was tested for safety and concluded reliable shreds of evidence. Superior target flexibility and editing precision with minimal errors make Prime editing first preference over the other conventional technique such as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). Application of prime editing in reversing Genetic disease will be a milestone in gene editing.

For more insights into the Market, request a sample of this report @https://www.persistencemarketresearch.com/samples/31691

Increasing prevalence of genetic disease creates a huge opportunity for prime editing market. Successful preliminary results with a genetic disease like Tay Sachs and Sickle cell anaemia will drive the prime editing market. Technological advancements providing minimal error with this technique will fuel the growth of prime editing. Decreased cost of DNA sequencing will propel prime editing market for research and commercialization. Arising ethical and safety concerns will make prime editing highly regulated sector. This may limit the scope and can restraint the growing market. Detrimental effect on Genetic diversity due to genetic engineering in one way may limit the market scope.

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The global Prime Editing market is classified on the basis of application and end user:

Based on application, Prime Editing Market is segmented into following:

Based on end user, Prime Editing Market is segmented into following:

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Prime Editing is the most recent invention has created a buzz in the market. Firms accessing conventional genome engineering technologies have rolled plans of transitioning to this new technology. The restructuring by the firms is either by building upon the technological capabilities or by merging or acquiring the firms which hold expertise in prime editing. Inscripta, one of the most innovative company has launched the worlds first benchtop platform for digital genome engineering. Inscriptas Onyx device that was launched in October 2019, will enable genome editing at an unprecedented scale and cheaper rate. In 2019, Beam Therapeutics collaborated with a premium start-up in prime editing segment Prime Medicine for Prime Editing Technology. Beam therapeutics holds expertise in precision genetic medicine using base editing technology. The market consolidation activities my giants depict that genome editing will be the largest revenue-generating segment for prime editing market.

North America will drive the market for Prime Editing due to high prevalence of genetic disease and technological advancement in the U.S. and Canada. One in every 27 Jews, is carrying Tay Sachs disease gene. After North America, Europe is leading in patient pool for genetic diseases such Hemophilia and Cystic fibrosis. The genetic disease pool will drive the adoption for Prime editing treatments in this region. Asia-Pacific will remain at steady growth for Prime Editing market due less disease prevalence and focus on other therapies. Latin America and Middle East and Africa region will boost the market owing to the disease prevalence.

Examples of some of the market participants in Prime Editing market identified across the value chain Beam Therapeutics Inc., Precision BioSciences, Inscripta, Inc, Horizon Discovery Ltd., Sangamo Therapeutics, Inc., CRISPR Therapeutics., Intellia Therapeutics, Inc.

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The Prime Editing market to witness elegant elevation in the next decade - Eurowire