Category Archives: Genetic medicine

PITTSBURGH, Oct. 13, 2020 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (NASDAQ: NBSE) (NeuBase or the Company), a biotechnology company accelerating the genetic revolution using a new class of synthetic medicines, announced the addition of Peter Nielsen, Ph.D. to its scientific advisory board. Dr. Nielsen, the primary inventor of peptide nucleic acid (PNA) technology, brings extensive experience in genetic medicine to NeuBase as the Company optimizes its PATrOL therapies and moves them towards the clinic.

We are honored to welcome Dr. Nielsen, a transformational leader in the field of genetics and genomic technologies, to the NeuBase scientific advisory board. His unique perspective gained over his distinctive career will undoubtedly provide valuable insight and complement our team of renowned experts, said Dietrich A. Stephan, Ph.D., chief executive officer of NeuBase. We believe that our new class of synthetic medicines, which relies on the elegant scaffold chemistry invented by Dr. Nielsen, has the potential to change the treatment landscape for many diseases, both common and rare. We look forward to leveraging his unparalleled knowledge as we continue to advance our PATrOL platform under the guidance of our outstanding group of scientific advisors.

Dr. Nielsen added, NeuBases PNA technology is among the first to be advanced through development for therapeutic applications, and I am thrilled to be part of the revolution the Company is leading. I look forward to working with the team and lending my guidance as NeuBase progresses its first-in-class medicines.

Dr. Peter Nielsen is a leading expert in gene targeting, RNA interference and chemical replication and translation and was one of the inventors of PNAs in 1991. He is currently a professor at the University of Copenhagen where his lab focuses on PNAs in regard to drug discovery, gene targeting, antisense principles, cellular and in vivo delivery and administration of biopharmaceuticals. He is the co-author of more than 400 scientific papers and reviews as well as over 20 patents and patent applications, and he serves on the advisory board of four scientific journals.In addition to his esteemed academic career, Dr. Nielsen is the co-founder of two biotech companies in Denmark and is a member of EMBO and the Danish Academy of Technical Sciences. He received his Ph.D. in 1980 from University of Copenhagen.

About NeuBase Therapeutics, Inc.NeuBase is accelerating the genetic revolution using a new class of synthetic medicines. NeuBases designer PATrOL therapies are centered around its proprietary drug scaffold to address genetic diseases at the source by combining the highly targeted approach of traditional genetic therapies with the broad organ distribution capabilities of small molecules. With an initial focus on silencing disease-causing mutations in debilitating neurological, neuromuscular and oncologic disorders, NeuBase is committed to redefining medicine for the millions of patients with both common and rare conditions. To learn more, visit http://www.neubasetherapeutics.com.

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This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements are distinguished by use of words such as "will," "would," "anticipate," "expect," "believe," "designed," "plan," or "intend," the negative of these terms, and similar references to future periods. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those risk factors contained in our filings with the U.S. Securities and Exchange Commission, may cause our actual results to differ from those expressed in forward-looking statements. The Company may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Because such statements deal with future events and are based on the Company's current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of the Company could differ materially from those described in or implied by the statements in this press release, including: the Company's plans to develop and commercialize its product candidates; the timing of initiation of the Company's planned clinical trials; the timing of the availability of data from the Company's clinical trials; the timing of any planned investigational new drug application or new drug application; the Company's plans to research, develop and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of the Company's product candidates; the Company's commercialization, marketing and manufacturing capabilities and strategy; global health conditions, including the impact of COVID-19; the Company's ability to protect its intellectual property position; and the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all, as well as those risk factors contained in our filings with the U.S. Securities and Exchange Commission. Except as otherwise required by law, the Company disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

NeuBase Investor Contact:Dan FerryManaging DirectorLifeSci Advisors, LLCDaniel@lifesciadvisors.comOP: (617) 430-7576

NeuBase Media Contact:Cait Williamson, Ph.D.LifeSci Communicationscait@lifescicomms.comOP: (646) 751-4366

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NeuBase Therapeutics Announces Addition of Peter Nielsen, Ph.D., Inventor of Peptide Nucleic Acid Technology, to Scientific Advisory Board - BioSpace

Researchers at the University of California, Davis, School of Veterinary Medicine have identified a genetic cause for the fatal condition equine familial isolated hypoparathyroidism (EFIH) in Thoroughbreds, marking the first genetic variant for hypoparathyroidism identified in any domestic animal species. Additionally, this is the first widely available genetic test for Thoroughbreds.

The study, led by Carrie Finno, DVM, PhD, Dipl. ACVIM, and Gary Magdesian, DVM, CVA, Dipl. ACVIM, ACVECC, ACVCP, wasreportedin the journalPLoS Genetics.Genetic testingcan now be performed at theUC Davis Veterinary Genetics Laboratoryto identify horses with the variant and avoid mating carriers that could produce affected foals.

For Thoroughbred owners and breeders, the loss of a foal has tremendous economic and emotional impacts, said first author Victor Rivas, who conducted the project as part of his undergraduate training in Finnos laboratory. It is important to promote safe and strategic breeding habits by actively breeding horses genetically screened not only for EFIH but for other diseases that may impact quality of life.

Foals affected with EFIH suffer from low blood calcium concentrations, resulting in involuntary muscle contractions, muscle stiffness that leads to a stiff gait and can progress to an inability to stand, seizures, fevers, and an abnormally fast pulse. Parathyroid hormone is typically produced to increase calcium levels in the body, but in these foals concentrations are low or inappropriately normal (i.e., they should be high due to the low calcium). Affected foals die or are euthanized due to poor prognosis. Necropsy results reveal underdeveloped or absent parathyroid glands.

Previously termed idiopathic hypocalcemia, EFIH has been observed in Thoroughbred foals up to 35 days of age. Disease onset and progression are likely determined by the amount of calcium in the diet early in life. This can vary based on dam milk calcium concentration and the amount of milk ingested.

In the current study, the researchers determined an autosomal recessive mode of inheritance and performed whole genome sequencing of two affected foals. A mutation in therap guanine nucleotide exchange factor 5(RAPGEF5) gene was present in two copies (homozygous) in both foals. They further analyzed the variant in a frog developmental model and demonstrated loss of function of the RAPGEF5 protein leading to aberrant development. Based on these data, the researchers hypothesize thatRAPGEF5might play a role in the derivation of the parathyroid gland during development.

Researchers have not identified the variant in individuals from 12 other breeds. The allele frequency for theRAPGEF5variant in an expanded set of 82 randomly selected, unaffected Thoroughbreds was 0.018. An unbiased allele frequency study has not been performed, so the allele frequency in the larger Thoroughbred population is currently unknown.

The next steps are to assess the allele frequency in a large population of randomly selected Thoroughbreds, said Finno. Additionally, we have discussed collaborating with Dr. Nathan Slovis at Hagyard Equine Medical Institute in Kentucky to test for the variant in cases of sudden death in Thoroughbred foals.

The clinical presentation of EFIH is similar to human familial hypoparathyroidism. Because theRAPGEF5gene is highly conserved across species, it is a potential new candidate gene for primary hypoparathyroidism in humans, the researchers said.

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Genetic Variant for EFIH in Thoroughbreds Found The Horse - TheHorse.com

A study of some of the sickest COVID-19 patients, such as those placed on ventilators, has identified gene variants that put people at greater risk of severe disease.

By Jocelyn KaiserOct. 13, 2020 , 1:25 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

Its one of the pandemics puzzles: Most people infected by SARS-CoV-2 never feel sick, whereas others develop serious symptoms or even end up in an intensive care unit clinging to life. Age and preexisting conditions, such as obesity, account for much of the disparity. But geneticists have raced to see whether a persons DNA also explains why some get hit hard by the coronavirus, and they have uncovered tantalizing leads.

Now, a U.K. group studying more than 2200 COVID-19 patients has pinned down common gene variants that are linked to the most severe cases of the disease, and that point to existing drugs that could be repurposed to help. Its really exciting. Each one provides a potential target for treatment, says genetic epidemiologist Priya Duggal of Johns Hopkins University.

In a standard approach to finding genes that influence a condition, geneticists scan the DNA of large numbers of people for millions of marker sequences, looking for associations between specific markers and cases of the disease. In June, one such genomewide association study in The New England Journal of Medicine (NEJM) found two hits linked to respiratory failure in 1600 Italian and Spanish COVID-19 patients: a marker within the ABO gene, which determines a persons blood type, and a stretch of chromosome 3 that holds a half-dozen genes. Those two links have also emerged in other groups data, including some from the DNA testing company 23andMe.

The new study confirmed the chromosome 3 regions involvement. And because 74% of its patients were so sick that they needed invasive ventilation, it had the statistical strength to reveal other markers, elsewhere in the genome, linked to severe COVID-19. One find is a gene called IFNAR2 that codes for a cell receptor for interferon, a powerful molecular messenger that rallies the immune defenses when a virus invades a cell. A variant of IFNAR2 found in one in four Europeans raised the risk of severe COVID-19 by 30%. Baillie says the IFNAR2 hit is entirely complementary to a finding reported in Science last month: very rare mutations that disable IFNAR2 and seven other interferon genes may explain about 4% of severeCOVID-19 cases. Both studies raise hopes for ongoing trials of interferons as a COVID-19 treatment.

A more surprising hit from the U.K. study points to OAS genes, which code for proteins that activate an enzyme that breaks down viral RNA. A change in one of those genes might impair this activation, allowing the virus to flourish. The U.K. data suggest there is a variant as common and influential on COVID-19 as the interferon genetic risk factor.

Other genes identified by Baillies team could ramp up the inflammatory responses to lung damage triggered by SARS-CoV-2, reactions that can be lethal to some patients. One, DPP9, codes for an enzyme known to be involved in lung disease; another, TYK2, encodes a signaling protein involved in inflammation. Drugs that target those two genes proteins are already in useinhibitors of DPP9s enzyme for diabetes and baricitinib, which blocks TYK2s product, for arthritis. Baricitinib is in early clinical testing for COVID-19, and the new data could push it up the priority list, Baillie says.

The chromosome 3 region still stands out as the most powerful genetic actor: A single copy of the disease-associated variant more than doubles an infected persons odds of developing severe COVID-19. Evolutionary biologists reported last month in Nature that this suspicious region actually came from Neanderthals, through interbreeding with our species tens of thousands of years ago. It is now found in about 16% of Europeans and 50% of South Asians.

But the specific chromosome 3 gene or genes at play remain elusive. By analyzing gene activity data from normal lung tissue of people with and without the variant, the U.K. team homed in on CCR2, a gene that encodes a receptor for cytokine proteins that play a role in inflammation. But other data discussed at last weeks meeting point to SLC6Z20, which codes for a protein that interacts with the main cell receptor used by SARS-CoV-2 to enter cells. I dont think anyone at this point has a clear understanding of what are the underlying genes for the chromosome 3 link, says Andrea Ganna of the University of Helsinki, who co-leads the COVID-19 Host Genetics Initiative.

The U.K. genetics study did not confirm that the ABO variants affect the odds of severe disease. Some studies looking directly at blood type, not genetic markers, have reported that type O blood protects against COVID-19, whereas A blood makes a person more vulnerable. It may be that blood type influences whether a person gets infected, but not how sick they get, says Stanford University geneticist Manuel Rivas. In any case, O blood offers at best modest protection. There are a lot of people with O blood that have died of the disease. It doesnt really help you, says geneticist Andre Franke of the Christian-Albrecht University of Kiel, a coleader of the NEJM study.

Researchers expect to pin down more COVID-19 risk genesalready, after folding in the U.K. data plumbed by Baillies team, the COVID-19 Host Genetics Initiative has found another hit, a gene called FOXP4 implicated in lung cancer. And in a new medRxiv preprint posted last week, the company Ancestry.com reports that a gene previously connected to the effects of the flu may also boost COVID-19 susceptibility only in men, who are more likely to die of the disease than women.

Geneticists have had little luck so far identifying gene variants that explain why COVID-19 has hit Black people in the United States and United Kingdom particularly hard. The chromosome 3 variant is absent in most people of African ancestry. Researchers suspect that socioeconomic factors and preexisting conditions may better explain the increased risks. But several projects, including Baillies, are recruiting more people of non-European backgrounds to bolster their power to find COVID-19 gene links. And in an abstract for an online talk later this month at the American Society of Human Genetics annual meeting, the company Regeneron reports it has found a genome region that may raise the risk of severe disease mainly in people of African ancestry.

Even as more genetic risk factors are identified, their overall effect on infected people will be modest compared with other COVID-19 factors, Duggal says. But studies like the U.K. teams could help reveal the underlying biology of the disease and inspire better treatments. I dont think genetics will lead us out of this. I think genetics may give us new opportunities, Duggal says.

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Found: genes that sway the course of the coronavirus - Science Magazine

SAN DIEGO, Oct. 15, 2020 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) announced that a study led by scientists and clinicians from the Institute for Human Genetics at the UCSF School of Medicine and the Department of Pediatrics at the University of Colorado School of Medicine and published in bioRxiv used Bionanos proprietary genome imaging technology to identify novel disease causing variants in patients with three different genetic diseases and in a diverse control dataset of 154 individuals. The study found that Bionano's Saphyr System was able to comprehensively analyze complex genome structures called segmental duplications and helped identify several novel structural variations associated with each disease causing locus increasing the understanding of these diseases.

Segmental duplications are large segments of repetitive sequences tens to hundreds of thousands of base pairs in size. Short-read and long-read sequencing technologies cannot span these large segments of the genome. Only Bionanos optical mapping technology can image single molecules that are so long that they span the segmental duplications. These repetitive sequences can interact with each other when sperm or eggs are created and their rearrangement can cause severe genetic disease. Some of the most common of such diseases are microdeletions at 7q11.23, also known as Williams-Beuren syndrome (WBS), 15q13.3 microdeletion syndrome, 16p12.2 microdeletion syndrome and 22q11.2 deletion syndrome, also known as DiGeorge syndrome.

This study, published in bioRxiv, provides a population-level analysis of segmental duplications in 154 people and in patients with WBS, 15q13.3, and 16p12.2 microdeletion syndromes. Several novel SVs were detected for each locus, and the exact disease causing rearrangement was determined with much higher accuracy than was formerly possible without Saphyr. As previously announced, a recent publication in the journal Nature published on July 22, 2020 also discussed the unique contribution of Bionanos optical mapping technology to understanding the genetic causes of DiGeorge syndrome.

Erik Holmlin, Ph.D., CEO of Bionano Genomics commented, The microdeletion and microduplication syndromes are common genetic disorders, yet the exact genomic structures that cause them have been difficult or impossible to characterize with current sequencing-based methods. Even though microdeletion syndromes are commonly represented by hallmark features, in many cases a wide variability in clinical features is observed. Being able to understand and measure the subtle structural differences in microdeletions among different patients could allow for better clinical or therapeutic management. An increasing number of studies have relied on Bionanos Saphyr system to characterize disease-causing structural variants that could not be correctly analyzed with other molecular techniques. We will continue to make our technology available to researchers everywhere who want to greatly expand the capabilities of their genomic analysis.

The publication is available at https://www.biorxiv.org/content/10.1101/2020.04.30.071449v1.full

About Bionano GenomicsBionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools, and genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visitwww.bionanogenomics.com or http://www.lineagen.com.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the contribution of Bionanos technology to the analysis or understandings of microdeletion syndromes and future development of better clinical or therapeutic management for such diseases; the effectiveness and utility of Bionanos technology in clinical settings; Saphyrs capabilities in comparison to other genome analysis technologies; the benefits of Bionanos optical mapping technology and its ability to facilitate genomic analysis in future studies; and Bionanos strategic plans. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated withour business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2019 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 (617) 430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, PhDLifeSci Communications+1 (617) 733-7668darren@lifescicomms.com

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Bionano Genomics' Saphyr System Shown to be Indispensable for the Analysis of Certain Genetic Disease Causing Variants - GlobeNewswire

PHILADELPHIA, Oct. 13, 2020 (GLOBE NEWSWIRE) -- Passage Bio, Inc. (NASDAQ: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders, today announced publication of data in a murine model of GM1 gangliosidosis (GM1) demonstrating that a single intracerebroventricular injection of an optimized adeno-associated virus (AAV) into the cerebral spinal fluid (CSF) resulted in significant expression of Beta-galactosidase (-gal) in the brain and peripheral tissues, and demonstrated dose-related reductions in neuronal lysosomal storage lesions, neurological impairment and improvement in survival. These data were published online ahead of print in the November issue of the peer-reviewed scientific journal Human Gene Therapy (HGT).

This study suggests that delivery of an AAV vector optimized to express b-gal directly into the CSF restored b-gal activity in the brain and, if further developed and tested in human clinical trials, may be effective in modifying and preventing the devastating effects of the genetic disease GM1, said James Wilson, M.D., Ph.D., director of the Gene Therapy Program at the University of Pennsylvania (Penn) and chief scientific advisor of Passage Bio. The AAV vector used in the study is the same as Passage Bios PBGM01 gene therapy, which is designed to deliver a functional human GLB1 gene into the brain and optimized to express -gal. These preclinical study data support the further development of PBGM01 as a potential therapy for patients suffering from GM1.

GM1 is a rare and often life-threatening monogenic lysosomal storage disease caused by mutations in the GLB1 gene, which encodes lysosomal acid -gal. Reduced -gal activity results in the accumulation of toxic levels of GM1 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 six 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 60 percent of the incidence of 0.5 to 1 in 100,000 live births. Currently, there are no approved disease-modifying therapies available.

Results of the PBGM01 preclinical study were reported in the paper titled, A single injection of an optimized AAV vector into cerebrospinal fluid corrects neurological disease in a murine model of GM1 gangliosidosis, by Christian Hinderer, M.D., Ph.D., and colleagues, including gene transfer pioneer Dr. Wilson, from the Gene therapy Program, Department of Medicine, University of Pennsylvania Perlman School of Medicine. The study in part was previously presented at the 22nd annual Meeting of the American Society for Cell and Gene Therapy (ASCGT) in 2019.

This research evaluated the impact of single intracerebroventricular administration of the human -gal containing AAV vector on -galactosidase enzyme activity in the murine brain and peripheral tissues, lysosomal storage lesions, neurological function (including neurological exams and gait analysis) and survival in mice lacking the -galactosidase gene. The mice received the single administration at age one month and were evaluated over 300 days. -gal activity was increased significantly in the cerebral spinal fluid and serum of the vector-treated mice compared to vehicle control-treated mice. Significant improvements in gait assessments as measured by stride length and hind paw print length and significant preservation of neurological function as measured by neurological exam scores were observed throughout the study period in the human -gal vector-treated mice. There were significant decreases in lysosomal storage lesions of vector-treated animals and by day 300 all animals that received the two highest doses were still alive, whereas none of the vehicle control-treated animals had survived.

Were excited about being able to soon advance PBGM01 into the clinic, and the potential promise it holds for patients with GM1, the majority of whom are infants and for whom there are no approved disease modifying treatments, said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. Our plan is to administer PBGM01 through intra-cisterna magna delivery into the brain, which we believe may offer several benefits in terms of safety, efficiency and distribution compared to other approaches.

Passage Bio expects to initiate dosing of PBGM01 in a Phase 1/2 trial late in the fourth quarter of 2020 or early in the first quarter of 2021 and remains on track to report initial 30-day safety and biomarker data late in the first half of 2021.

This research was supported by a research, collaboration and license agreement with Passage Bio. HGT is the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies. Click here to read the full-text article on the HGT website.

About PBGM01PBGM01 is an AAV-delivery gene therapy currently being developed for the treatment of infantile GM1, in which patients have mutations in the GLB1 gene causing little or no residual -gal enzyme activity and subsequent neurodegeneration. PBGM01 utilizes a next-generation AAVhu68 capsid administered through intra-cisterna magna (ICM) to deliver a functional GLB1 gene encoding -gal to the brain and peripheral tissues. By reducing the accumulation of GM1 gangliosides, PBGM01 has the potential to halt or prevent neuronal toxicity, thereby restoring developmental potential. In preclinical models, PBGM01 has demonstrated broad brain distribution and wide uptake of the -gal enzyme in both the central nervous system (CNS) and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1. The Company has received Orphan Drug and Rare Pediatric Disease designation for PBGM01 for patients with GM1 and expects to initiate dosing of its Phase 1/2 trial late in the fourth quarter of 2020 or early in the first quarter of 2021 and remains on track to report initial 30-day safety and biomarker data late in the first half of 2021.

About Passage BioPassage Bio is a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders with limited or no approved treatment options. The company is based in Philadelphia, PA and has a research, collaboration and license agreement with the University of Pennsylvania and its Gene Therapy Program (GTP). The GTP conducts discovery and IND-enabling preclinical work and Passage Bio conducts all clinical development, regulatory strategy and commercialization activities under the agreement. The company has a development portfolio of six product candidates, with the option to license eleven more, with lead programs in GM1 gangliosidosis, frontotemporal dementia and Krabbe disease.

University of Pennsylvania (Penn)Financial DisclosureDr. Wilson is a Penn faculty member and also a scientific collaborator, consultant and co-founder of Passage Bio. As such, he holds an equity stake in the company, receives sponsored research funding from Passage Bio, and as an inventor of certain Penn intellectual property that is licensed to Passage Bio, he may receive additional financial benefits under the license in the future. He is an inventor of intellectual property covering the technology described in paper published in HGT that is licensed from Penn to Passage Bio, and he may receive financial benefits under this license in the future. Penn also holds equity and licensing interests in Passage Bio.

Forward-Looking StatementsThis 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 theSecurities and Exchange Commission(SEC), and other reports as filed with theSEC. 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.212-362-1200sarah.mccabe@sternir.comzofia.mita@sternir.com

Media:Gwen FisherPassage Bio215.407.1548gfisher@passagebio.com

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Passage Bio Announces Publication of Preclinical Data That Show Single Injection of Optimized AAV Vector into Cerebral Spinal Fluid - BioSpace

By Deborah Borfitz

October 15, 2020| The Bio-IT World Conference & Expo closed out with a plenary keynote presentation on preventive genomics by Robert Green, M.D., professor of medicine at Harvard Medical School and a physician-scientist who directs the G2P Research Program at Brigham and Womens Hospital and the Broad Institute. Data-sharing difficulties were a recurring theme at this years conference but, as the COVID-19 Host Genetics Initiative has demonstrated, it is possible to combine genomic data to rapidly explore markers of disease, he says. But far more daily deaths are caused by cancer and cardiovascular diseasenot the pandemic virusand 59 of the causal genes are already known and actionable.

Genomic information is rarely incorporated into clinical care partly because labs, not care providers, are doing most of the testing and doctors are unclear if the benefits outweigh the costs and risks, says Green. The clinical value of DNA sequencing is also unproven, although its the central feature of personalized medicine programs that have been popping up around the country.

Green presented lessons learned from the MedSeq, exploring the impacts of incorporating genomic sequencing into everyday medicine for people with and without a suspected genetic cardiac disease, and BabySeq, testing methods for integrating sequencing into the care of newborns. Both are randomized trials funded by the National Institutes of Health.

MedSeq involved primary care physicians taking comprehensive family histories on participants with or without the addition of one-page genomic reports and following their outcomes. Reports from preventive genomic testing focused on defined, disease-specific variants with the highest clinical actionability, says Green, as distinct from indication-based testing looking at a wider universe of variants known or suspected of being pathogenic.

Notably, Green says, neither doctors nor patients experienced test-related anxietyeven when a monogenetic risk variant was discovered. In 100 individuals, 20% were found to carry a dominant mutation for a monogenetic condition. In fact, among the top four genetic mutations, sequencing often discovered ongoing disease that the healthcare system had missed.

Participating doctors, after only six hours of training, did not make any errors in communicating the results, adds Green. Healthcare spending six months post-disclosure was higher but not extraordinarily more. Two years later, 22% had been reclassified (e.g., variant of uncertain significance now likely benign or likely pathogenic variant now pathogenic).

In the smaller BabySeq Project, 11% of participants were identified as having monogenetic disease risk, Green says. As with MedSeq, a substantial number with genetic mutations already had phenotypic evidence of disease previously missed by their healthcare providers.

BabySeq additionally revealed no difference in bonding or vulnerability, says Green. Catastrophic distress is not an obstacle [to sequencing], as has often been suggested. The falling cost of genomic sequencing and interpretation should further improve the benefit-to-cost ratio.

Exactly how often does sequencing reveal something important? Herere the stats from Green: 91% of the time for recessive mutations, 80% for atypical responses to medications, 15% for dominant mutation, and 50% for elevated polygenic risk specific to at least one condition such as diabetes or cancer.

Polarizing Topic

The Mass General Brigham Biobank, which looked for the 59 genes linked to disease, has identified such mutations in over 350 of the roughly 36,000 people it has sequenced. In 75% if those cases, the mutations were linked to either cardiovascular disease or cancer and the individuals had no idea they were carrying mutations, says Green.

A significant number did not even want to know of their risk, he adds. A similarly high number met National Comprehensive Cancer Center criteria for genetic testing but had never before been tested.

The Preventive Genomics Clinic at Brigham and Womens Hospital, staffed by genetics experts and counselors, offers individuals a menu of testing options (whole genome sequencing as well as smaller panels) and also gives patients the option of being seen via telemedicine. The heart-touching stories shared on its website include a man nudged by discovered mutations to finally get a colonoscopy, revealing two cancerous lesions that were subsequently extracted, and another with worsening heart disease who learned the underlying cause was Fabry diseasea rare but treatable condition.

Genomics is a notoriously polarizing subject, Green says. The challenge in convincing the skeptics is that genomics crosses multiple therapeutic domains and testing needs to be repeated over individuals lifetime.

The exceptionalism of genomics is sometimes misplaced, he later adds, referring to the disproportionate amount of fear about misuse of genetic information relative to psychological or infectious disease data. Its perfectly possible for large groups to share genomic data that is not identifiable. Its not full-proof, but its [technically] feasible.

Federal genetic privacy laws prevent genetics-based discrimination by employers and health insurers, Green says. In July, Florida became the first state in the nation to enact a DNA privacy law that also prohibits life, disability and long-term care insurance companies from using genetic tests for coverage purposes.

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Proving The Value Of Preventive Genomics - Bio-IT World

COPENHAGEN, Denmark, Oct. 13, 2020 /PRNewswire/ -- Novo Seeds, the early stage investment and company creation team of Novo Holdings, today announced an investment in Rappta Therapeutics ("Rappta"), an emerging biotech company focused on developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A). The investment is a part of a EUR 9M series A financing round.

PP2A is a critical enzyme regulating protein de-phosphorylation and a key tumor suppressor which to date has been very difficult to target pharmaceutically. Rappta has developed proprietary tools and a unique understanding of PP2A which allows it to therapeutically reactivate PP2A. As a result of PP2A's central role in the regulation of protein de-phosphorylation, Rappta's PP2A-reactivating technologies offer the potential to develop multiple lead compounds and build a platform for a new class of anti-cancer drugs.

Rappta has assembled a strong scientific, management and commercial team based in Finland and the US. Rappta's scientific team, led by CSO and co-founder, Professor Goutham Narla, Division Chief of Genetic Medicine at the University of Michigan, represents world-leading expertise in PP2A. The scientific team has published seminal papers onthe structural, functional and biological mechanisms of PP2A inactivation in human cancer. The team will be supported by the Scientific Advisory Board lead by Dr. William Hahn, a Professor of Medicine at the Harvard Medical School and the Chief Scientific Officer at the Dana-Farber Cancer Institute.

As a resut of the financing, Jeroen Bakker, Principal at Novo Seeds will join the Board.Other investors in the Series A round include Novartis Venture Fund ("NVF"), Advent Life Sciences ("Advent") and one family office.

Jeroen Bakker, Principal, Novo Seeds, said: "We are impressed by the team's pioneering work in PP2A-reactivating technologies. Novo Seeds' strategy is to back teams from all over the globe with world class science and attract other bluechip investors to help transform these entreprises into successful business in the Nordics. We are very pleased to see renowned investors such as NVF and Advent investing in the region. We look forward to working with them as we support Rappta's world-leading team translate their scientific and medical expertise in phosphatase biology into a clinical oncology biotech."

Mikko Mannerkoski, CEO and co-founder of Rappta Therapeutics, commented: "We are very pleased to attract such a strong syndicate of international investors which validates our approach to developing novel therapies to target the previously undruggable target protein PP2A. This funding will enable us to accelerate the development of our platform and advance the lead compounds towards clinical development."

The investment in Rappta follows recent Novo Seeds participation in Galecto's Series D and Chromologics seed financing rounds.

About Rappta Therapeutics

Rappta Therapeutics, based in Finland and the US, is developing first-in-class anti-cancer drugs activating protein phosphatase 2A (PP2A). It has developed proprietary tools and a unique understanding of PP2A which allows it to therapeutically reactivate PP2A, a critical enzyme regulating protein de-phosphorylation and tumor growth, with the potential to create a new class of anti-cancer drugs. Rappta has a strong scientific, management and commercial team. Its scientific team, led by CSO and co-founder, Professor Goutham Narla, Head of Cancer Research at the University of Michigan, represent world-leading expertise in PP2A. It is backed by blue-chip investors Advent Life Sciences, Novartis Venture Fund, Novo Seeds and one family office. For more information, go to http://www.rappta-therapeutics.com.

About Novo Holdings A/S

Novo Holdings A/S is a private limited liability company wholly owned by the Novo Nordisk Foundation. It is the holding and investment company of the Novo Group, comprising Novo Nordisk A/S and Novozymes A/S, and is responsible for managing the Novo Nordisk Foundation's assets.

Novo Holdings is recognized as a leading international life science investor, with a focus on creating long-term value. As a life science investor, Novo Holdings provides seed and venture capital to development-stage companies and takes significant ownership positions in growth and well-established companies. Novo Holdings also manages a broad portfolio of diversified financial assets. Further information: http://www.novoholdings.dk

SOURCE Novo Holdings

Excerpt from:
Novo Seeds co-leads Rappta Therapeutics Series A Financing for the Development of Phosphatase 2A drugs - PRNewswire

In a time already full of challenges and changes, some pregnant and postpartum women will also experience a rare but dangerous heart complication: an aortic dissection.

For a new investigation published in JAMA Cardiology, researchers studied the experiences of 29 participants in an international registry who were unexpectedly hospitalized for a dissection while pregnant. Most already had an underlying heart condition, although it was often not yet diagnosed.

SEE ALSO:Growth of Cardio-Obstetrics Care Presents Challenges, Opportunity

Aortic dissections only affect 3 in 100,000 people per year. They cause the layers of the aorta to tear, and blood to pool or leak instead of flowing normally. A patient needs a timely diagnosis and then urgent, life-saving medical attention.

Aortic diseases and conditions like Marfan syndrome or Loeys-Dietz syndrome are usually culprits in women who have a dissection while pregnant, the researchers say, although an association to high blood pressure, the most common risk factor in the general population, may exist, too.

Notably, the researchers found 19% of aortic dissections in women younger than 35 years old were associated with pregnancy. That means a woman already predisposed to have a dissection is more likely to have one during pregnancy, possibly due to hormones and changes to the body during pregnancy and postpartum.

Women in the cohort experienced dissections in all three trimesters of pregnancy in addition to within three months postpartum, although more cases occurred in the latter part of pregnancy and immediately following.

All of the participants who had a Type A aortic dissection, the most dangerous, underwent surgery to repair the dissection. Eighty-five percent of those women with a Type A dissection went into their pregnancies with a known diagnosis such as Marfan syndrome (the most common).

The participants who had a type B dissection were more likely to be given medication, although some received an open or minimally invasive heart surgery.

Given that aortic dissection is already rare, the ability to study a cohort of people who had the condition while pregnant provides an important opportunity, says senior author Kim Eagle, M.D., a director of the Michigan Medicine Frankel Cardiovascular Center and a professor of internal medicine.

Its important to understand what these women experienced, including their risk factors, underlying medical conditions and ultimate outcomes, in order to learn how best to care for others and to prevent future aortic dissections in this population, he says. Eagle started the International Registry of Acute Aortic Dissection, housed at Michigan Medicine, in 1996. Members include 57 active centers in 13 countries.

SEE ALSO:Registry Helps Move Aortic Dissection Care Forward

Twenty-eight of the 29 patients in the IRAD registry who had a dissection during pregnancy survived the hospitalization. The dissections studied in this publication occurred between 1998 and 2018 and the 29 women represent 1% of all women in the registry.

This is the 100th publication to come out of IRAD.

Twenty years ago, the seminal IRAD paper was published, aptly also in JAMA, detailing the first 454 patients, Eagle says. Over 10,000 patients and 24 years since data collection began, IRAD continues to influence our understanding and treatment of acute aortic dissection.

IRAD has been instrumental in characterizing the presentation of aortic dissection, along with better understanding its natural history and the impacts of different therapeutic approaches in the treatment of this very deadly disease, says Himanshu Patel, M.D., a cardiac surgeon and professor at Michigan Medicine. Patel leads adult cardiac surgery at the Frankel CVC, and co-leads the international cohort in IRAD.

Although aortic dissection is most often seen in older men, this cohort study underscores the importance of careful monitoring of cardiac conditions during pregnancy, researchers say.

Co-author Melinda Davis, M.D., part of the Cardio-Obstetrics team at Michigan Medicine with appointments in both cardiology and obstetrics and gynecology, says pre-pregnancy care for a woman with known aortic disease would include evaluation of maternal and fetal risk, counseling and possible genetic testing, followed by ongoing monitoring and testing.

IRAD is supported by R.L. Gore, Inc., the Ann and Bob Aikens Aortic Fund and The Tom Varbedian Fund for Aortic Research as well as grants from numerous participating IRAD aortic centers of excellence.

Paper cited: Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection. JAMA Cardiology. DOI: 10.1001/jamacardio.2020.4876.

Read more here:
Tied to Undiagnosed Aortic Disease, Aortic Dissection in Pregnancy Proves Difficult to Predict - Michigan Medicine

Children with chronic kidney disease spent about 30% longer in the hospital (an average of 2.8 days compared to 1.8 days for those without a chronic kidney disease) with nearly 60% more in hospital expenses ($8,755 per hospitalization compared to $5,016.)

Children with chronic kidney disease were also 50% more likely to die during hospitalization.

Data on in-hospital mortality for children with chronic illnesses is lacking, but we know that hospitalizations with a chronic kidney disease diagnosis have a higher mortality than those with other chronic condition diagnoses with the exception of heart failure, Modi says.

The fact that these children are potentially at higher risk of death while hospitalized should prompt providers to closely evaluate management strategies.

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That may mean bringing nephrologists in earlier if they are not already involved in patients care, making sure to avoid medications that could make kidney function worse as well as other steps that will improve care for these patients, Modi notes.

The high health care expenses for hospitalized pediatric patients with end-stage kidney disease, including dialysis, transplantation, and associated complications may be comparable to hospitalized heart failure patients, authors say.

Kidney disease may be associated with more medical complexities, authors say. The causes of chronic kidney disease in children include genetic disorders, congenital anomalies that may be part of a multi-organ system syndrome and systemic inflammatory disorders. A recent study from the UK reported that adult kidney disease patients also have a greater degree of medical complexity than patients seen by any other specialty.

Chronic kidney disease can be a devastating illness with many long-term consequences, Modi says. Some features of chronic kidney disease that start during childhood will have a significant impact on patients lives through adulthood.

We need further studies to better understand the health care needs and delivery of care to hospitalized children with chronic kidney disease in order to optimize health outcomes."

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Children with Chronic Kidney Disease Have Outsized Health Burden - Michigan Medicine

A new initiative at University of North Carolina at Chapel Hill is kicking off a genetic study of eating disorders that it says will be the largest of its kind.

If successful, the study, conducted by the Eating Disorders Genetic Initiative (EDGI), will be able to identify hundreds of genes that influence a person's likelihood of suffering from three prominent disorders: anorexia nervosa, bulimia nervosa and binge-eating disorder.

That knowledge could significantly improve the way those illnesses are treated, said Cynthia Bulik, a professor at the UNC School of Medicine and head of EDGI.

"It might help us with prediction and prevention in the future," Bulik said in a phone interview. "That is a direction we hope to go in help us identify those who are high risk."

Eating disorders affect a large number of people. About 9% of Americans, or 28.8 million, will have an eating disorder in their lifetime, according to the National Association of Anorexia Nervosa and Associated Disorders.

And that number could be increasing, as the coronavirus pandemic pushes the country into a mental health crisis as well. Bulik recently coauthored a study of individuals with eating disorders in the U.S. and the Netherlands that reported an increase in anxiety during the pandemic, which has disrupted the lives and routines of millions.

"We are clearly in the midst of a mental health pandemic," Bulik said. "The things (participants) talked about most was the lack of structure in their days ... (and) a lack of social support. Eating disorders thrive in isolation."

While there have been numerous psychiatric studies of eating disorders, the biologic underpinnings of the illness are still relatively unknown, and there are no medications to treat eating disorders

"Part of that is because we haven't understood the biology of eating disorders," she said.

EDGI is seeking 100,000 people across the world with a history of an eating disorder to volunteer as part of the genetic study. In the U.S., it is looking to reach 6,000 participants. In addition to genetics, EDGI will also survey participants from around the world to see how environmental factors influence the disorders.

Bulik said it will be important for EDGI to get a very diverse sample of volunteers. She hopes to complete the collection portion of the study by 2022.

The research is funded by the National Institute of Mental Health. The genetic samples will be collected via a saliva kit in the mail, and then be processed at a lab in Chapel Hill.

The study will build off a previous one that focused specifically on anorexia nervosa. Bulik said that study had transformational findings, identifying eight areas of the genome with significant associations with anorexia nervosa. Finding evidence for those associations, she said, helps reduce misunderstandings around the illness.

"These are serious illnesses with genetic bases, and we need to bust those myths about them being a choice," Bulik said. "One of the things that this research does is bust those myths. We can say with complete confidence that genes are involved."

That previous research only studied around 17,000 participants, and Bulik said the data would be much more reliable with a larger pool of volunteers.

By expanding the research to include other eating disorders, EDGI could determine if certain genetics predispose someone to multiple illnesses, or whether they all have unique causes.

"My gut says and preliminary information shows that there might be some shared genetic factors across all three disorders, but also unique genetic factors associated with them that decides the path (of treatment) you go down," she said. "There is not a clear demarcation between these disorders. People will toggle back and forth between anorexia and bulimia. They are not mutually exclusive."

EDGI is looking for participants who are 18 years or over and have, at any point in their lives, experienced anorexia nervosa, bulimia nervosa or binge-eating disorder. To volunteer or learn more, visit http://www.edgi.org.

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University is mapping the genetics of eating disorders to develop better treatments - yoursun.com