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Archive for the ‘Genetic medicine’ Category

Co-Occurrence of the mcr-1.1 and mcr-3.7 Genes in a Multidrug-Resistan | IDR – Dove Medical Press

Thursday, October 22nd, 2020

Chongtao Du,1,* Yuyang Feng,1,* Guizhen Wang,2 Zhiyuan Zhang,1 Huimin Hu,1 Yu Yu,1 Jiayang Liu,1 Lihao Qiu,1 Hongtao Liu,1 Zhimin Guo,3 Jing Huang,3 Jiazhang Qiu1

1Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Peoples Republic of China; 2College of Food Engineering, Jilin Engineering Normal University, Changchun 130052, Peoples Republic of China; 3Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Jiazhang QiuCollege of Veterinary Medicine, Jilin University, No. 5333 Xian Road, Changchun 130062, Peoples Republic of ChinaEmail qiujz@jlu.edu.cnJing HuangDepartment of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, Peoples Republic of ChinaEmail huangj@jlu.edu.cn

Objective: A colistin-resistant Escherichia coli strain isolated from dog feces was characterized in this study.Methods and Results: A multiplex PCR assay was used to detect the presence of colistin-resistant mcr genes; it was found that E. coli QDFD216 co-harbored the mcr-1 and mcr-3 genes. Whole-genome sequencing and further bioinformatics analysis revealed that E. coli QDFD216 belonged to serotype O176:H11, fimH1311 type and ST132. The resistance genes blaCTX-M-14, mdfA, dfrA3, acrA, acrB, tolc, and sul3 were present in the chromosome. The mcr-1.1 and mcr-3.7 genes were located in two plasmids of different incompatibility groups. mcr-1.1 was carried by a IncX4-type plasmid within an typical IS 26-parA-mcr-1.1-pap2 cassette, while mcr-3.7 was encoded by an IncP1-type plasmid with a genetic structure of TnAs2-mcr-3.7-dgkA-IS 26. No additional antibiotic resistance genes were carried by either plasmid.Conclusion: This is the first report of an E. coli isolate co-harboring a mcr-1.1-carrying IncX4 plasmid and a mcr-3.7-carrying IncP1 plasmid. The evolution and mechanism of mcr gene co-existence need further study to assess its impact on public health.

Keywords: colistin resistance, whole-genome sequencing, mcr genes, mcr-1, mcr-3

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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The Prime Editing market to get on to the elliptical growth mode in the next decade – PharmiWeb.com

Thursday, October 22nd, 2020

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.

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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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Study reports chemical mechanism that boosts enzyme observed in cancer – IU Newsroom

Thursday, October 22nd, 2020

A new study led by scientists at IUPUI and Indiana University Bloomington is the first to describe a biochemical mechanism that increases the activity of a molecule whose presence is observed in many types of cancer.

The molecule, an enzyme called Pif1 helicase, plays a role in many important cellular processes in the body. Tightly regulating this protein is vital to genome stability because too little -- or too much -- activity can influence aging and age-related diseases, primarily cancer. A common cancer therapy, HDAC inhibitors, can also impact the mechanism that regulates this enzyme.

"We're currently giving people drugs that change the acetylation status of the cell without knowing how it affects many proteins that play a role in genome stability," said Lata Balakrishnan, an associate professor of biology in the School of Science at IUPUI, who is co-lead author on the study. "HDAC inhibitors upregulate certain tumor-suppression genes, and thus are used in combination therapies to treat specific cancers, but when it comes to their impact on other parts of the cell, we're basically operating in the dark."

The study's other lead author is Matthew Bochman, an associate professor in the IU Bloomington College of Arts and Sciences' Department of Molecular and Cellular Biochemistry. Other co-authors are Christopher Sausen and Onyekachi E. Ononye, Ph.D. students in Bochman's and Balakrishnan's labs, respectively, at the time of the study.

The effect of lysine acetylation on Pif1 is the mechanism described in the study. Lysine acetylation occurs when a small molecule called an acetyl group binds to lysine, an amino acid used to build common proteins in the body. This action transforms lysine from a positively charged molecule to a neutrally charged molecule. This neutralization can impact protein function, protein stability and protein-protein interaction in cells, among other things.

Helicases are known as the genetic "zippers" of cells because they pull apart DNA for the purpose of genetic replication and repair. They also help maintain telomeres, the structure at the end of chromosomes that shortens as people age.

In the new study, the researchers identified lysine acetylation on Pif1 helicase and showed the addition of the acetyl group increases the protein's activity -- as well as its "unzipping" function. They also found that lysine acetylation changes the shape -- or "conformation" -- of the Pif1 protein. They believe that this shape change increases the amount of Pif1 helicase.

"The dynamic interplay of the addition and removal of the acetyl group on lysine regulates a wide variety of proteins within the cell," Balakrishnan said. "Perturbations to this process can play a role in cancer, aging, inflammatory responses and even addiction-related behaviors."

"As a class, helicases are involved in a lot of processes necessary for genome integrity," Bochman added. "Any significant failure in these processes is generally carcinogenic."

The precise details of lysine acetylation in Pif1, its effect of the enzyme's shape and the resulting impact on helicase activity took nearly five years to observe and report. The study, carried out in parallel on two IU campuses, was made possible by the lead scientists' complementary expertise. As a biochemist who has previously studied lysine acetylation in other proteins, Balakrishnan was able to isolate Pif1 in vitro to observe its response to chemical reactions in a test tube. In contrast, as a geneticist working in yeast as a model organism to study Pif1, Bochman was able to modify cells in vivo to watch reactions play out in a living organism.

"The ability to observe these reactions in a living cell is often more relevant, but it's also a lot messier," Balakrishnan said. "Our experiments were constantly informing each other as to where to go next."

Looking to the future, Bochman said intricate knowledge of cellular processes -- such as lysine acetylation -- will increasingly play a role in personalized therapy.

"If you sequence a patient's tumor, you can fine-tune drugs to target very specific enzymes," he said. "Instead of a drug that broadly affects the whole cell, it will be possible to take a targeted approach that reduces potential side effects. This level of personalization is really the future of cancer biology and cancer medicine."

"Lysine Acetylation Regulates the Activity of Nuclear Pif1" is available online in advance of print in the Journal of Biological Chemistry. A perspective article on the work is also forthcoming in the journal Current Genetics.

This work was supported in part by the National Science Foundation, the National Institutes of Health and the American Cancer Society.

Indiana University's world-class researchers have driven innovation and creative initiatives that matter for 200 years. From curing testicular cancer to collaborating with NASA to search for life on Mars, IU has earned its reputation as a world-class research institution. Supported by $854 million last year from our partners, IU researchers are building collaborations and uncovering new solutions that improve lives in Indiana and around the globe.

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Making sense of genetic disease in dogs and cats – American Veterinary Medical Association

Thursday, October 15th, 2020

Understanding genetic disease in mixed-breed and purebred dogs and cats can bring about more effective treatments and better client service, says clinical geneticist and general practitioner Dr. Jerold Bell.

If we understand the genetic background of our patients, were better positioned to prevent, to mitigate, or to alter the expression of genetic disease, allowing our patients to be healthier in their lifetimes as well as to breed healthier dogs and cats, Dr. Bell said.

An adjunct professor at the Cummings School of Veterinary Medicine at Tufts University, Dr. Bell spoke about genetic diseases during the AVMA Virtual Convention 2020 this August. In addition to his teaching duties, Dr. Bell works as a solo practitioner, and he sees dogs and cats all day long and sees genetic disease in our patients all day long.

He explained that common genetic disorders are caused by ancient disease liability genes that preceded breed formation. Since these mutations occurred long before the separation of breeds, these diseases are seen across all breeds and in mixed breeds.

The most common hereditary diseases in dogs are allergies, followed by hip and elbow dysplasia; inherited cancers such as lymphoma, hemangiosarcoma, mast cell tumor, and osteosarcoma; patella luxation; nonstruvite bladder stones; hypothyroidism; mitral valve disease; inflammatory bowel disease; diabetes mellitus; retained testicles; and umbilical hernias.

In cats, the most prevalent genetic diseases are inflammatory cystitis, then feline urological syndrome, diabetes mellitus, lymphoplasmocytic gingivostomatitis, nonstruvite bladder stones, allergies, eosinophilic skin disease, and inflammatory bowel disease.

Disease is not a function of homozygosity, which happens when identical DNA sequences for a particular gene are inherited from both biological parents, nor is it a consequence of inbreeding. Rather, Dr. Bell explained, hereditary diseases are a result of the accumulation and propagation of specific disease liability genes. Breed-related deleterious genes accumulate in various ways, including direct selection for disease-associated phenotypes, linkage to selected traits, carriage by popular sires, genetic drift, andmost importantlythe absence of selection against deleterious phenotypes.

If we dont select for healthy parents to produce offspring, then we have no expectation of health in those offspring, Dr. Bell said. Not selecting for health is selecting for disease, and we need to understand that and pass that on to our breeder clients.

On the topic of disease and extreme phenotypes, Dr. Bell said brachycephalic obstructive airway syndrome is frequently diagnosed at veterinary clinics on account of the popularity of certain brachycephalic dog breeds, namely Pugs, French Bulldogs, and Bulldogs. Most breed standards do not call for the expression of extreme phenotypes, he said, nor do they select for the most extreme size or the most extreme brachycephalic trait.

Moderation away from extremes that cause disease should be the guiding principle in breeding, Dr. Bell noted, and in judging dog shows.

Common genetic diseases seen in mixed-breed dogs and cats occur randomly because of dispersed ancient liability genes, according to Dr. Bell. Uncommon and breed-specific recessive or complexly inherited disease is far less likely to occur in mixed-breed individuals.

Dr. Bell said designer-bred dogs and cats often have inherited diseases common in random-bred populations. They can also inherit disease liability genes shared by the parent breeds or parent species. So if youre breeding short-statured breeds together, it wouldnt be surprising to see patellar luxation, or in smaller toy size breeds, to see mitral valve disease, he said.

Hereditary disease manifests as a result of anatomical mismatch between parent breeds. We see a lot of this in dental disease, where we see crowding of teeth and malocclusions and misplaced teeth, Dr. Bell continued. Even in the musculoskeletal, if you breed two breeds with different body types together, we may see degenerative joint disease and poor joints. All of these things, all need to be monitored.

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

Thursday, October 15th, 2020

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

Thursday, October 15th, 2020

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

Thursday, October 15th, 2020

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.

Use of Forward-Looking Statements

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

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Identifying Genetic Variants, Matching With Targeted Therapies Serve as Next Great Challenge With Germline Testing in Oncology – OncLive

Thursday, October 15th, 2020

The revolution of genetic testing has led to more accurate and widespread assays for patients with cancer; however, as more genetic variants are identified, it has become a greater challenge to determine the optimal treatment for an individual patient, according to GouthamNarla, MD, PhD.

As we sequence more genes, we will have more information, which is a good thing, said Narla. Of course, we will also find more variants that, at this time, we don't know whether they're pathogenic or benign. They get lumped into the uncertain category, which creates uncertainty for patients and for providers, as well.

In an interview withOncLiveduring the 2020 Institutional Perspectives in Cancer (IPC) webinar on Precision Medicine, Narla, an associate professor in the Department of Medicine; chief of the Division of Genetic Medicine, Department of Medicine; and associate director of the Medical Scientist Training Program, University of Michigan, further discussed the utility of genomic testing and updates in next generation sequencing (NGS).

OncLive: Could you discuss the key advances in cancer genetics? What are some of the mechanisms that have driven its development?

Narla: A couple of major advancements we've seen in cancer genetics is the identification of additional disease-causing variants. It used to be when I first trained as a medical geneticist, we really only knew about BRCA1/2 and some of the mismatch repair genes. Now, we know about other genes, including PALB2, and other members and genes in that family. That has expanded the testing opportunities for our patients.

The other aspect that has been very exciting is now some of these gene variants are predictive of response to therapies. We have therapies that can be specifically used and work for patients who harbor some of these germline variants. That has really changed the way in which we have treated patients who carry these variants.

What are some of the recent developments in NGS?

Previously, we were doing single-gene testing, oftentimes by Sanger sequencing. Now, we can do large panels of genes depending upon the company and the panel; these comprise anywhere from 60 to 70 genesin some cases, several thousand genes. It has allowed us to collect vast amounts of sequencing information. Some of it will not be directly actionable now, but it still fuels research opportunities for us at major academic medical centers, and when more knowledge [is] gained, we go back to some of those sequencing results to see if, in fact, there was something that is now actionable based upon new knowledge.

How are we using this information to develop targeting strategies?

A lot of the approaches that we are using now may not involve the directly targeting the defective gene or protein, but they are leveraging knowledge about how that defective gene or protein causes activation of targetable pathways. For example, when it comes to BRCA1 loss, that creates a unique opportunity to use a PARP inhibitor in a synthetic lethal interaction, where those cells become highly dependent upon that enzyme. Then, you can inhibit with small molecules [or perhaps] approved PARP inhibitors, such as olaparib (Lynparza), and others for which there are now [a number of approved drugs that can target] a range of BRCA-deficient metastatic tumors.

How else has genomic testing evolved?

The evolution has been both in the number of individuals that we test, as well as how many genes we test. [For example, we used to] test families in which there are numbers of individuals who have cancer and we had a strong pretest probability that they would have a germline variant. Now, in fact, every patient with metastatic ovarian cancer, regardless of family history, gets tested. This is because we have PARP inhibitors for them. It not only has implications for their family but it also has implications for their treatment choices.

What guidelines have been helpful to your practice as it relates to genomic testing?

There are a number of organizations from the American Cancer Society to National Cancer Institute and the National Comprehensive Cancer Network (NCCN) that have very robust guidelines on who to test. There is also a little bit of subjectivity in making an appraisal with a genetics professional, meaning a genetic counselor or a medical geneticist, because not every family will fit the structure or will even know the entirety of their family history. There is some nuance to this, but there are definitely very established guidelines that exist and that we use when making these types of decisions.

However, the NCCN guidelines are very good and are used by [our institution. Then we apply our own nuances when we see the patient on a case by case basis. But, [in terms of] informing who should be tested and who should not, and which individual in the family should be [tested], the NCCN guidelines are a very good [resource].

What challenges could be addressed with future research?

I would like to see more of an effort to share data across all institutions and testing companies to reclassify these variants. I would like to see more basic science and translational science around what we call variant reclassification, so that we can really make definitive calls about the sequence changes that we see. The more genes we sequence, the more variants we find, and on larger panels, [we can see these uncertain variants in up to] 20% of patients. We're finding something in a gene, but we don't know whether it's good or bad for the patient.

Are there any new capabilities or technologies emerging that you find particularly exciting?

From a technology perspective, the last 10 years in sequencing has been a revolution; the cost of sequencing has come down and the accuracy has gone up. I'm not sure that we're going to see that much more of a revolution in the sequencing technology; it will be more efficient and more cost effective. We're [going to see] the identification of new genes associated with disease [and will therefore] it will be in the variant reclassification space.

What testing or sequencing studies are of particular interest?

One type of study that has read-out recently comprise the effectiveness of immunotherapy in patients who have mismatch repair deficient tumors. That has been really game-changing for those patients. The other major study is the use of PARP inhibitors in BRCA-mutant tumorsoriginally in the second- and third-line settings of ovarian cancer. [PARP inhibitors] have now moved to maintenance [therapy], pancreatic cancer, prostate cancer, and others. That has changed the management of patients with BRCA-positive tumors.

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Found: genes that sway the course of the coronavirus – Science

Thursday, October 15th, 2020

Science's COVID-19 coverage is supported by the Pulitzer Center.

It's one of the pandemic's 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 person's 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. It's really exciting. Each one provides a potential target for treatment, says genetic epidemiologist Priya Duggal of Johns Hopkins University.

Kenneth Baillie of the University of Edinburgh, an intensive care physician and geneticist, led the new study, which he discussed on 2 October at an online meeting of a data-pooling effort called the COVID-19 Host Genetics Initiative. He's hoping the results, also posted as a preprint on medRxiv, will speed treatments, although he cautions that any clinical trial inspired by the findings should wait for the study's acceptance in a peer-reviewed journal. Because the epidemic is progressing at such an alarming rate, even a few months of time saved will save lots of lives, Baillie says.

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.

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 genome-wide 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 person's 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 region's 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 severe COVID-19 cases (25 September, p. 155). 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 Baillie's 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 DPP9's enzyme for diabetes and baricitinib, which blocks TYK2's 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 person's 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 week's 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 don't 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 doesn't really help you, says geneticist Andre Franke of the Christian-Albrecht University of Kiel, a co-leader of the NEJM study.

Researchers expect to pin down more COVID-19 risk genesalready, after folding in the U.K. data plumbed by Baillie's team, the COVID-19 Host Genetics Initiative has found another hit, a gene called FOXP4 implicated in lung cancer. And in a new med-Rxiv 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 Baillie's, 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. team's could help reveal the underlying biology of the disease and inspire better treatments. I don't think genetics will lead us out of this. I think genetics may give us new opportunities, Duggal says.

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Proving The Value Of Preventive Genomics – Bio-IT World

Thursday, October 15th, 2020

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.

Editors Note: Even if you missed the start of the event, Bio-IT World Conference & Expo virtualis still live. Register nowfor on-demand presentations.

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

Thursday, October 15th, 2020

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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Larimar Therapeutics Announces Formation of Scientific Advisory Board – GlobeNewswire

Thursday, October 15th, 2020

BALA CYNWYD, Pa., Oct. 13, 2020 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (Nasdaq:LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases,today announced the formation of its Scientific Advisory Board (SAB). Larimars SAB is comprised of distinguished research scientists, professors and industry experts recognized as key opinion leaders in the fields of rare disease, pediatrics and mitochondrial disease.

Larimar is privileged to have this group of prestigious, multidisciplinary advisors who are committed to advancing the research and development of CTI-1601 for Friedreichs ataxia, said Nancy M. Ruiz, MD, FACP, FIDSA, Chief Medical Officer of Larimar Therapeutics. Their scientific perspectives will be invaluable to determine our strategic scientific pathway and support the development of other potential treatments for complex rare diseases to help fill unmet medical needs in this space.

Formalizing the SAB adds to our recent accomplishments, which include resuming our Phase 1 clinical trial of CTI-1601 for Friedreichs ataxia and receiving a positive opinion on orphan drug designation for CTI-1601 from the European Medicines Agencys Committee for Orphan Medicinal Products, said Carole Ben-Maimon, MD, President and Chief Executive Officer of Larimar Therapeutics. This progress helps position Larimar for success as we continue to execute our strategy of developing treatments for complex rare diseases.

The members of Larimars SAB are as follows:

About Larimar TherapeuticsLarimar Therapeutics, Inc. (Nasdaq:LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. The companys lead compound, CTI-1601, is currently being evaluated in a Phase 1 clinical program in the U.S. as a potential treatment for Friedreichs ataxia, a rare and progressive genetic disease. Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com.

Investor Contact:Joyce AllaireLifeSci Advisors, LLC(212) 915-2569jallaire@lifesciadvisors.com

Media Contact:Gina Cestari6 Degrees(917) 797-7904gcestari@6degreespr.com

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

Thursday, October 15th, 2020

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

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People with blood type O may have lower risk of COVID-19 infection and severe illness, studies suggest – WCVB Boston

Thursday, October 15th, 2020

People with blood type O may be less vulnerable to COVID-19 and have a reduced likelihood of getting severely ill, according to two studies published Wednesday. Experts say more research is needed.The research provides further evidence that blood type (also known as blood group) may play a role in a person's susceptibility to infection and their chance of having a severe bout of the disease. The reasons for this link aren't clear and more research is needed to say what implications, if any, it has for patients.Studies add to growing evidenceA Danish study found that among 7,422 people who tested positive for COVID-19, only 38.4% were blood type O even though, among a group of 2.2 million people who were not tested, that blood type made up 41.7% of the population.By contrast, 44.4% of group A tested positive, while in the wider Danish population that blood type makes up 42.4%.In the other study, researchers in Canada found that among 95 patients critically ill with COVID-19, a higher proportion with blood type A or AB 84% required mechanical ventilation compared with patients with blood group O or B, which was 61%.The Canadian study also found those with blood type A or AB had a longer stay in the intensive care unit, a median of 13.5 days, compared with those with blood group O or B, who had a median of nine days."As a clinician ... it is at the back of my mind when I look at patients and stratify them. But in terms of a definitive marker we need repeated findings across many jurisdictions that show the same thing," said Dr. Mypinder Sekhon, an intensive care physician at Vancouver General Hospital and an author of the Canadian study."I don't think this supersedes other risk factors of severity like age and co-morbities and so forth," added Sekhon, who is also a clinical assistant professor in the Division of Critical Care Medicine and Department of Medicine at the University of British Columbia."If one is blood group A, you don't need to start panicking. And if you're blood group O, you're not free to go to the pubs and bars."No need to worryMost humans fall into one of four blood groups: A, B, AB or O. In the United States, the most common blood groups are O and A.It makes very little difference to most people's daily lives unless you have to have a blood transfusion. Nor should people worry unduly about the link between blood type and COVID-19, said Dr. Torben Barington, the senior author of the Danish paper and a clinical professor at Odense University Hospital and the University of Southern Denmark."We do not know whether this is some kind of protection of group O, or whether it's some kind of vulnerability in the other blood groups," he said."I think this has scientific interest, and when we find out what the mechanism is, perhaps we're able to use that proactively in some way in regard to treatment."In the Danish study, researchers analyzed data on Danish individuals who were tested between February 27 and July 30, and the distribution of blood types among those people was compared with data from people who had not been tested. They found that blood group wasn't a risk factor for hospitalization or death from COVID-19.Both studies were published in the journal Blood Advances.While there are several theories, researchers don't yet know what mechanism could explain the link between different blood groups and COVID-19.Sekhon said it could be explained by people with blood type O having less of a key clotting factor making them less prone to coagulation problems in the blood. Clotting has been a major driver of the severity of COVID-19.Other possible explanations involve blood group antigens and how they affect the production of infection fighting antibodies. Or it could be linked to genes associated with blood types and their effect on receptors in the immune system."It's a repeated, interesting scientific observation that really warrants further mechanistic work," he said.'Important research question'The findings of the two new studies provide "more converging evidence that blood type may play a role in a person's susceptibility to COVID infection and their chance of having a severe bout of COVID-19," said Dr. Amesh Adalja, senior scholar at the Johns Hopkins University Center for Health Security in Baltimore, who was not involved in either of the studies.A separate study, published in The New England Journal of Medicine in June, found genetic data in some COVID-19 patients and healthy people suggesting that those with Type A blood had a higher risk of becoming infected, and those with type O blood were at a lower risk.That previous genetic study, paired with the two new studies in Blood Advances, are "suggestive that this is a real phenomenon that we're seeing," said Adalja, whose work is focused on emerging infectious disease."While we're not quite to the point where this is ironclad, it's clearly suggestive, and we have not seen anything inconsistent with this. The same pattern has been emerging with O blood type tending to be the one that's standing out," Adalja said.Adalja said that blood types and their susceptibility to various infections have been studied in the medical literature before. For instance, research suggests that people with blood type O appear to be more susceptible to norovirus infection.As for the novel coronavirus that causes COVID-19, "We need to figure out the mechanism and understand it at the molecular level to be able to say for sure how this is occurring that this is really the O blood type and not something that kind of tracks with O blood type," Adalja said."We're starting to see enough now that I think it's an important research question to answer," he said. "There's more science to be done here, but it seems to me that there's more evidence accumulating for this hypothesis."

People with blood type O may be less vulnerable to COVID-19 and have a reduced likelihood of getting severely ill, according to two studies published Wednesday. Experts say more research is needed.

The research provides further evidence that blood type (also known as blood group) may play a role in a person's susceptibility to infection and their chance of having a severe bout of the disease. The reasons for this link aren't clear and more research is needed to say what implications, if any, it has for patients.

A Danish study found that among 7,422 people who tested positive for COVID-19, only 38.4% were blood type O even though, among a group of 2.2 million people who were not tested, that blood type made up 41.7% of the population.

By contrast, 44.4% of group A tested positive, while in the wider Danish population that blood type makes up 42.4%.

In the other study, researchers in Canada found that among 95 patients critically ill with COVID-19, a higher proportion with blood type A or AB 84% required mechanical ventilation compared with patients with blood group O or B, which was 61%.

The Canadian study also found those with blood type A or AB had a longer stay in the intensive care unit, a median of 13.5 days, compared with those with blood group O or B, who had a median of nine days.

"As a clinician ... it is at the back of my mind when I look at patients and stratify them. But in terms of a definitive marker we need repeated findings across many jurisdictions that show the same thing," said Dr. Mypinder Sekhon, an intensive care physician at Vancouver General Hospital and an author of the Canadian study.

"I don't think this supersedes other risk factors of severity like age and co-morbities and so forth," added Sekhon, who is also a clinical assistant professor in the Division of Critical Care Medicine and Department of Medicine at the University of British Columbia.

"If one is blood group A, you don't need to start panicking. And if you're blood group O, you're not free to go to the pubs and bars."

Most humans fall into one of four blood groups: A, B, AB or O. In the United States, the most common blood groups are O and A.

It makes very little difference to most people's daily lives unless you have to have a blood transfusion. Nor should people worry unduly about the link between blood type and COVID-19, said Dr. Torben Barington, the senior author of the Danish paper and a clinical professor at Odense University Hospital and the University of Southern Denmark.

"We do not know whether this is some kind of protection of group O, or whether it's some kind of vulnerability in the other blood groups," he said.

"I think this has scientific interest, and when we find out what the mechanism is, perhaps we're able to use that proactively in some way in regard to treatment."

In the Danish study, researchers analyzed data on Danish individuals who were tested between February 27 and July 30, and the distribution of blood types among those people was compared with data from people who had not been tested. They found that blood group wasn't a risk factor for hospitalization or death from COVID-19.

Both studies were published in the journal Blood Advances.

While there are several theories, researchers don't yet know what mechanism could explain the link between different blood groups and COVID-19.

Sekhon said it could be explained by people with blood type O having less of a key clotting factor making them less prone to coagulation problems in the blood. Clotting has been a major driver of the severity of COVID-19.

Other possible explanations involve blood group antigens and how they affect the production of infection fighting antibodies. Or it could be linked to genes associated with blood types and their effect on receptors in the immune system.

"It's a repeated, interesting scientific observation that really warrants further mechanistic work," he said.

The findings of the two new studies provide "more converging evidence that blood type may play a role in a person's susceptibility to COVID infection and their chance of having a severe bout of COVID-19," said Dr. Amesh Adalja, senior scholar at the Johns Hopkins University Center for Health Security in Baltimore, who was not involved in either of the studies.

A separate study, published in The New England Journal of Medicine in June, found genetic data in some COVID-19 patients and healthy people suggesting that those with Type A blood had a higher risk of becoming infected, and those with type O blood were at a lower risk.

That previous genetic study, paired with the two new studies in Blood Advances, are "suggestive that this is a real phenomenon that we're seeing," said Adalja, whose work is focused on emerging infectious disease.

"While we're not quite to the point where this is ironclad, it's clearly suggestive, and we have not seen anything inconsistent with this. The same pattern has been emerging with O blood type tending to be the one that's standing out," Adalja said.

Adalja said that blood types and their susceptibility to various infections have been studied in the medical literature before. For instance, research suggests that people with blood type O appear to be more susceptible to norovirus infection.

As for the novel coronavirus that causes COVID-19, "We need to figure out the mechanism and understand it at the molecular level to be able to say for sure how this is occurring that this is really the O blood type and not something that kind of tracks with O blood type," Adalja said.

"We're starting to see enough now that I think it's an important research question to answer," he said. "There's more science to be done here, but it seems to me that there's more evidence accumulating for this hypothesis."

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For PKU Research, Pigs Could Be the New Stand-In for People – UPMC

Thursday, October 15th, 2020

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Phenylketonuria (PKU) is a congenital disease in which patients lack an enzyme that breaks down the amino acid Phenylalanine (Phe). Untreated, PKU leads to intellectual disability, seizures and movement disorders.

Today, babies are typically diagnosed with PKU 3-5 days after birth, from a heel prick blood test. And the primary treatment sounds simple avoid foods that contain Phe. But thats easier said than done.

One of the problems with PKU, even though newborn screening and control of diet of young kids is good, the diet is bland and not too interesting. When kids become teens we know they want to be able to go out and have a meal with friends and they struggle to keep symptoms in check, said Dr. Rob Nicholls, professor of pediatrics and director of the Birth Defects Laboratories at the University of Pittsburgh School of Medicine.

Since Phe is an amino acid, its present in any food that contains a lot of protein steak, fish, tofu, beans, etc. so people with PKU end up purchasing Phe-free food to get the protein they need to grow and stay healthy.

But, besides being bland, this special food can also be quite expensive. Families often need help paying for it, since its not covered by health insurance.

There are a few gene therapies in the pipeline, as well as a drug that works for some, as well as enzyme substitution therapy that involves frequent painful injections, Nicholls said, but most people still end up with a prescription for a special diet.

A major roadblock for developing better treatments is the lack of a good animal model for PKU research.

Genetically engineered laboratory rodents the workhorse of preclinical research dont display PKU symptoms, and researchers have yet to establish another animal that does the job.

A PKU pig and its unaffected littermate at 2 months of age.

So, Nicholls and colleagues developed a pig model of PKU, which they describe in a paper published today in JCI Insight.

According to study coauthor Dr. Jerry Vockley, chief of medical genetics at UPMC Childrens Hospital of Pittsburgh, who sees many PKU patients and their families each year in the clinic, this new pig model of PKU will allow for the advancement of better treatment options beyond a difficult-to-sustain diet.

Development of this model of PKU for the first time allows us the opportunity to develop improved therapies and test them in a meaningful way, opening the door to a better life for patients, Vockley said.

To create a pig model of PKU, the researchers crossed a Yucatan mini pig which grows to about the size of a small human with a domestic pig and used CRISPR gene editing to cut out part of the gene for phenylalanine hydroxylase (PAH), the enzyme that breaks down Phe.

The animals were born at the University of Missouri, in collaboration with Dr. Randall Prather, Director of the National Swine Resource and Research Center.

During infancy, the PKU model pig, who was born with two copies of the edited PAH gene, was much smaller than a littermate with only one copy of the edited gene. There were also clear brain differences.

Blood Phe levels were much higher in the PKU pig than either PKU patients off their diet or mice engineered to lack the PAH gene. A completely Phe-free diet brought the animals levels down to normal, only to spike again with a diet of 50% Phe-free chow.

To verify that the gene editing protocol didnt accidentally clip off any adjacent genes, lead author Dr. Erik Koppes, a postdoctoral fellow in Nichollss lab, sequenced the genome of the PKU pig and verified that the edited segment was within the bounds of the gene known to cause PKU.

Koppes also looked for off-target mutations across the genome a common concern with CRISPR but didnt find any.

It took quite a bit of genetic detective work, Nicholls said.

Next, Nicholls plans to begin breeding PKU pigs for future studies. He hopes to one day move the animals to a nearby farm, where the operation can scale up at a lower cost, with the ultimate goal of making the pig the preferred model of preclinical PKU research.

This research was funded by the National PKU Alliance (NPKUA) and an IGNITE grant from the National Institute of Neurological Disorders and Stroke.

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Gemini Therapeutics and FS Development Corp. Announce Merger Agreement Creating Publicly Listed Precision Medicine Company Focused on Age-Related…

Thursday, October 15th, 2020

CAMBRIDGE, Mass. & SAN FRANCISCO--(BUSINESS WIRE)--Gemini Therapeutics, a clinical stage precision medicine company developing innovative treatments for genetically defined age-related macular degeneration (AMD), and FS Development Corp. (Nasdaq: FSDC), a special purpose acquisition company sponsored by Foresite Capital, today announced they have entered into a definitive merger agreement. Upon closing of the transaction, the company will be renamed Gemini Therapeutics, Inc. (Combined Company) and will be led by Jason Meyenburg, Chief Executive Officer of Gemini. The Combined Companys common stock is expected to be listed on Nasdaq.

In addition to the approximately $121 million held in FS Development Corp.s trust account (assuming no redemptions are effected), a group of premier healthcare investors has committed to participate in the transaction through a common stock PIPE of approximately $95 million at $10.00 per share. Investors in the PIPE include lead investor Foresite Capital, an affiliate of FS Development Corp.s sponsor, as well as Fidelity Management & Research Company LLC, Wellington Management, Boxer Capital of Tavistock Group, Alyeska Investment Group, L.P., Suvretta Capital Management, CVF, DAFNA Capital, and Acorn Bioventures, in addition to existing Gemini Therapeutics shareholders including Orbimed Healthcare Fund Management, Atlas Venture, Lightstone Ventures and Wu Capital.

This mornings announcement is important for the advancement of AMD research, as it ensures we have the necessary capital to advance our clinical programs and continue applying our insights in genetics and biology to pioneer first-in-class medicines to restore regulation of the complement system in the eye and throughout the body, bringing forward targeted precision therapies based on genetically defined populations, said Mr. Meyenburg. I would like to thank all those involved in making this transaction a success, particularly our new and existing blue chip investors, and the entire Gemini team.

Gemini embodies the type of company we had in mind when forming FSDC: a platform focused on the next generation of medicines utilizing genetics, said Jim Tananbaum, M.D., Chief Executive Officer of Foresite Capital and President and Chief Executive Officer of FS Development Corp. Gemini is developing treatments for patients losing their vision because of genetically driven macular degeneration. We are excited about the tremendous potential of this transaction, which we believe creates value for investors along with the potential to bring innovative new treatment options to patients.

Proceeds from the transaction are expected to provide Gemini with the capital needed to further develop its clinical programs and preclinical portfolio, including the following programs:

Post-closing of the transaction, Mr. Meyenburg and Dr. Tananbaum will be joined by board members from Gemini to form the seven-person board of directors.

Summary of Transaction

Current Gemini shareholders are converting 100% of their existing equity interests into common stock of the Combined Company. In addition to the approximately $121 million held in FSDCs trust account (assuming no redemptions are effected), an additional group of premier healthcare investors has committed to participate in the transaction through a common stock PIPE of approximately $95 million at $10 per share.

The Combined Company is expected to receive gross proceeds of approximately $216 million at the closing of the transaction (assuming no redemptions are effected), which is expected by January 2021. The close of this transaction is subject to approval of FSDCs shareholders and the satisfaction or waiver of certain other customary closing conditions.

Jefferies LLC and SVB Leerink acted as co-lead private placement agents for FS Development Corp. Jefferies LLC also acted as lead financial and capital markets advisor to FS Development Corp. Goldman Sachs & Co. LLC acted as lead financial advisor to Gemini in the transaction. Stifel acted as additional capital markets advisor to Gemini. Goodwin Procter LLP acted as legal counsel to Gemini. White & Case LLP acted as legal counsel to FS Development Corp.

The description of the business combination contained herein is only a high-level summary. Additional information about the transaction will be provided in a Current Report on Form 8-K that will contain an investor presentation to be filed by FS Development Corp. with the Securities and Exchange Commission (SEC) and will be available at http://www.sec.gov. In addition, FS Development Corp. intends to file a registration statement on Form S-4 with the SEC, which will include a proxy statement/prospectus, and will file other documents regarding the proposed transaction with the SEC.

In connection with the proposed business combination, FS Development Corp. intends to file a Registration Statement on Form S-4, including a preliminary proxy statement/prospectus and a definitive proxy statement/prospectus with the SEC. FS Development Corp.s stockholders and other interested persons are advised to read, when available, the preliminary proxy statement/prospectus and the amendments thereto and the definitive proxy statement/prospectus and documents incorporated by reference therein filed in connection with the proposed business combination, as these materials will contain important information about Gemini, FS Development Corp., and the proposed merger. When available, the definitive proxy statement/prospectus and other relevant materials for the proposed merger will be mailed to stockholders of FS Development Corp. as of a record date to be established for voting on the proposed business combination. Stockholders will also be able to obtain copies of the preliminary proxy statement/prospectus, the definitive proxy statement/prospectus, and other documents filed with the SEC that will be incorporated by reference therein, without charge, once available, at the SECs website at http://www.sec.gov, or by directing a request to press@foresitecapital.com.

Conference Call Information

Gemini and FS Development Corp. will host a conference call today, Thursday, October 15, 2020, at 10:30 a.m. Eastern Time, to discuss the proposed transaction. To access the conference call, please dial (888) 317-6003 (local) or (412) 317-6061 (international) at least 10 minutes prior to the start time and reference conference ID: 4983831.

About Gemini Therapeutics

Gemini Therapeutics is a clinical stage precision medicine company developing innovative treatments for age-related macular degeneration (AMD) by developing drugging strategies that are matched to specific genetic mutations found in patients with high clinical unmet need. Geminis lead clinical stage candidate, GEM103, is a recombinant form of the naturally occurring complement factor H protein currently in a Phase 2a trial in dry AMD patients with a complement factor H mutation. The company has generated a rich pipeline including recombinant proteins, gene therapies, and monoclonal antibodies. Geminis CLARITY natural history study is designed to provide unprecedented insight into the role of genetic risk in common retinal diseases and began in December 2018. Gemini was launched with funding from leading life science investors and powered by academic partnerships globally.

For more information, visit http://www.geminitherapeutics.com.

About FS Development Corp. (FSDC)

FS Development Corp., sponsored by Foresite Capital, is a blank check company formed for the purpose of effecting a business combination with one or more businesses in the biotechnology sector. The company is led by Jim Tananbaum, M.D., the CEO of Foresite Capital, an investment firm funding visionary healthcare entrepreneurs with approximately $3 billion in assets under management. The firm is headquartered in San Francisco.

Important Information About the Merger and Where to Find It

A full description of the terms of the business combination will be provided in a registration statement on Form S-4 to be filed with the SEC by FS Development Corp. that will include a prospectus with respect to the Combined Companys securities to be issued in connection with the business combination and a proxy statement with respect to the shareholder meeting of FS Development Corp. to vote on the business combination. FS Development Corp. urges its investors, shareholders and other interested persons to read, when available, the preliminary proxy statement/ prospectus as well as other documents filed with the SEC because these documents will contain important information about FS Development Corp., Gemini and the business combination. After the registration statement is declared effective, the definitive proxy statement/prospectus to be included in the registration statement will be mailed to shareholders of FS Development Corp. as of a record date to be established for voting on the proposed business combination. Once available, shareholders will also be able to obtain a copy of the S-4, including the proxy statement/prospectus, and other documents filed with the SEC without charge, by directing a request to: FS Development Corp., Attn: Secretary, 600 Montgomery Street, Suite 4500, San Francisco, California 94111. The preliminary and definitive proxy statement/prospectus to be included in the registration statement, once available, can also be obtained, without charge, at the SECs website (www.sec.gov).

Participants in the Solicitation

FS Development Corp. and Gemini Therapeutics and their respective directors and executive officers may be considered participants in the solicitation of proxies with respect to the proposed business combination described in this press release under the rules of the SEC. Information about the directors and executive officers of FS Development Corp. is set forth in FS Development Corp.s final prospectus filed with the SEC pursuant to Rule 424(b) of the Securities Act of 1933, as amended (the Securities Act) on August 13, 2020, and is available free of charge at the SECs website at http://www.sec.gov or by directing a request to: FS Development Corp., Attn: Secretary, 600 Montgomery Street, Suite 4500, San Francisco, California 94111. Information regarding the persons who may, under the rules of the SEC, be deemed participants in the solicitation of the FS Development Corp. shareholders in connection with the proposed business combination will be set forth in the registration statement containing the proxy statement/prospectus for the proposed business combination when it is filed with the SEC. These documents can be obtained free of charge from the sources indicated above.

Forward-Looking Statements

This press release contains forward-looking statements that are based on beliefs and assumptions and on information currently available. In some cases, you can identify forward-looking statements by the following words: may, will, could, would, should, expect, intend, plan, anticipate, believe, estimate, predict, project, potential, continue, ongoing or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties and other factors that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. Although we believe that we have a reasonable basis for each forward-looking statement contained in this press release, we caution you that these statements are based on a combination of facts and factors currently known by us and our projections of the future, about which we cannot be certain. Forward-looking statements in this press release include, but are not limited to, statements regarding the proposed business combination, including the timing and structure of the business combination, the proceeds of the business combination, the initial market capitalization of the Combined Company and the benefits of the business combination, as well as statements about the potential attributes and benefits of Geminis product candidates and the format and timing of Geminis product development activities and clinical trials. We cannot assure you that the forward-looking statements in this press release will prove to be accurate. These forward-looking statements are subject to a number of significant risks and uncertainties that could cause actual results to differ materially from expected results, including, among others, the ability to complete the business combination due to the failure to obtain approval from FS Development Corp.s shareholders or satisfy other closing conditions in the Merger Agreement, the occurrence of any event that could give rise to the termination of the Merger Agreement, the ability to recognize the anticipated benefits of the business combination, the outcome of any legal proceedings that may be instituted against FS Development Corp. or Gemini following announcement of the proposed business combination and related transactions, the impact of COVID-19 on Geminis business and/or the ability of the parties to complete the business combination, the ability to obtain or maintain the listing of FS Development Corp.s common stock on Nasdaq following the proposed business combination, costs related to the proposed business combination, changes in applicable laws or regulations, the possibility that FS Development Corp. or Gemini may be adversely affected by other economic, business, and/or competitive factors, and other risks and uncertainties, including those to be included under the header Risk Factors in the registration statement on Form S-4 to be filed by FS Development Corp. with the SEC and those included under the header Risk Factors in the final prospectus of FS Development Corp. related to its initial public offering. Most of these factors are outside of FS Development Corp.s and Geminis control and are difficult to predict. Furthermore, if the forward-looking statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all. The forward-looking statements in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release.

Non-Solicitation

This press release is not a proxy statement or solicitation of a proxy, consent or authorization with respect to any securities or in respect of the proposed business combination and shall not constitute an offer to sell or a solicitation of an offer to buy any securities nor shall there be any sale of securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. No offer of securities shall be made except by means of a prospectus meeting the requirements of the Securities Act.

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DNA Test Identifies Genetic Causes of Severe Fetal and Newborn Illness – UCSF News Services

Thursday, October 15th, 2020

A new study by University of California researchers shows the promise of high-throughput DNA-sequencing technologies to improve prenatal diagnosis and pregnancy outcomes for women who have experienced an abnormal prenatal ultrasound.

In the UC San Francisco-led study, scientists used a technique called exome sequencing to identify genetic diseases as the underlying cause in 37 of 127 cases of nonimmune hydrops fetalis (NIHF), a life-threatening condition in which the fetus is overloaded with fluid. The study was published online Oct. 7 in The New England Journal of Medicine (NEJM).

Corresponding author Teresa Sparks, MD, MAS, a UCSF assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, led the study with senior study author Mary Norton, MD, a professor in the same department. The cause of most cases of NIHF is not identified with standard testing, but when we apply exome sequencing, we find a genetic diagnosis in nearly 30 percent of cases of previously unknown cause, Sparks said.

NIHF affects about one in every 1,700 to 3,000 pregnancies in the United States and is associated with high risks of stillbirth, preterm birth, neonatal death and other complications. Although NIHF often leads to death, identifying the precise genetic cause is critical, as associated outcomes vary widely in severity.

NIHF can be a manifestation of many genetic diseases, but evidence of abnormal fluid accumulation in the fetus detected through an ultrasound exam whether it occurs under the skin, in the abdomen, or around the heart or lungs does not pinpoint an underlying cause.

Participants in the study were referred from throughout the United States after NIHF was identified with prenatal ultrasound but no underlying genetic disease was found using long established methods for detecting genetic abnormalities. These traditional genetic tests karyotype and chromosomal microarray analysis detect large abnormalities in chromosomes, not disorders caused by a defect in a single gene as are identified with exome sequencing.

Exome sequencing is the complete spelling out of the genetic code for DNA segments within the genome that serves as the blueprints for proteins. This has become possible to perform quickly and accurately in recent years, thanks to the continual refinement of technology that can sequence DNA strands that are thousands of nucleotide building blocks long, often in a massively parallel manner that helps ensure accurate results. Exome sequencing can identify even the smallest mutations, such as a change in a single building-block nucleotide base pair.

Importantly, many of the disorders identified in the study have not previously been reported in association with NIHF, so the findings broaden knowledge of genetic diseases that can present with the condition. Among the most common of 37 genetic disorders identified in the NEJM study were 11 cases affecting a key intracellular signaling pathway called RAS-MAPK, four cases of inborn errors of metabolism, four cases of musculoskeletal disorders, and three cases each of lymphatic, neurodevelopmental, cardiovascular and blood disorders. Many of these diagnoses would also have been missed by commercial gene panels, Sparks said.

Most mutations identified in the study newly arose in the fetus, but several were inherited, with the potential to affect future pregnancies with the same biologic mother or father.

There is a very wide range in genetic diagnoses underlying NIHF, and identifying the diagnosis is essential for families and healthcare providers, Sparks said. With advanced genetic testing, there is much more we can discover for families to help them understand the situation, for obstetricians and neonatologists to better take care of the pregnancy and anticipate the needs of the newborn, and ultimately to guide the development of novel prenatal management strategies such as in-utero therapies to improve health outcomes over the long term.

For some of the genetic disorders identified in the study, prenatal interventions that can improve or save lives already have been identified. For example, genetic causes of anemia in the fetus may be closely monitored, and the fetus may receive a blood transfusion if needed.

Similarly, for some of the inborn errors of metabolism identified in the study, enzyme therapies already are available after birth. Early diagnosis and treatment of these metabolic disorders leads to better outcomes. A co-author of the NEJM study, Tippi MacKenzie, MD, a professor with the UCSF Department of Surgery, is investigating in utero treatments for specific genetic disorders underlying NIHF in a new clinical trial. Sparks, Norton, and co-authors are also pursuing further investigations to identify additional genomic abnormalities underlying NIHF for the cases that remain unsolved.

Co-Authors: All co-authors of the NEJM study are affiliated with the University of California FetalMaternal Consortium or the UCSF Center for Maternal-Fetal Precision Medicine. Additional UCSF co-authors of the study include Billie Lianoglou, Sarah Downum, Sachi Patel, Amanda Faubel, Anne Slavotinek, Patrick Devine, Ugur Hodoglugil, Jessica Van Ziffle, and Stephan Sanders.

Funding: The study was funded by the UCSF Center for Maternal-Fetal Precision Medicine, the Fetal Health Foundation, the Brianna Marie Foundation, Ultragenyx, and the National Institutes of Health.

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.UCSF Health, which serves as UCSFs primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.

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PROfound Trial With Olaparib Shows Feasibility of Personalizing Care in mCRPC – OncLive

Thursday, October 15th, 2020

Olaparib (Lynparza) significantly improved overall survival (OS) versus enzalutamide (Xtandi) or abiraterone acetate (Zytiga) in patients with metastatic castration-resistant prostate cancer (mCRPC) who harbor BRCA1, BRCA2, and/or ATM aberrations, according to results from the final OS analysis of the pivotal phase 3 PROfound trial (NCT02987543).1

In the trial, patients with mCRPC who progressed on previous treatment with a new hormonal agent and harbored BRCA1, BRCA2, or ATM aberrations (n = 245; cohort A) or other alterations in the homologous recombination repair (HRR) pathway (n = 142; cohort B) were randomized 2:1 to receive either olaparib or enzalutamide or abiraterone acetate.

Final OS data from cohorts A and B were presented during the 2020 ESMO Virtual Scientific Program. Results showed that the median OS in cohort A was significantly longer with olaparib than with physicians choice (HR 0.69; 95% CI 0.50-0.97; P = .0175).1In cohort B, the median OS was 14.1 months with olaparib versus 11.5 months with the control (HR, 0.96; 95% CI, 0.63-1.49).

What is exciting about this particular trial is that it showed the feasibility of personalizing care and using precision medicine strategies to preselect patients to maximize the chance of benefit for those who are candidates for these treatments, said Maha H.A. Hussain, MD, FACP, FASCO.We can also help patients avoid unnecessary exposure to ineffective treatments.

Previously published data showed that olaparib resulted in a 66% reduction in the risk of disease progression or death compared with abiraterone or enzalutamide (HR, 0.34; 95% CI, 0.25-0.47;P<.0001).2 Based on these results, the FDA approved olaparib in May 2020 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR genemutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone.

In an interview with OncLive, Hussain, the Genevieve E. Teuton Professor of Medicine in the Department of Medicine of the Division of Hematology Oncology and the deputy director at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, further discussed the updated findings from the PROfound trial, its clinical significance in the treatment of patients with mCRPC paradigm, and the promise of precision medicine.

Hussain: PROfound is a randomized phase 3 clinical trial. It is one of the first precision medicine clinical trials to complete; patients were preselected based on specific genomic alterations and then randomized accordingly. Patients with mutations in the HRR genes or DNA damage repair genes were assigned to 2 different cohorts. The primary cohort was [comprised of] patients who had BRCA1/2 or ATM mutations, while cohort 2 included [those who harbored] other genes that are involved in the HRR pathway. Patients were randomized 2:1 to olaparib or standard of care per physicians choice of either abiraterone and prednisone or enzalutamide. The primary end point [of the trial] was radiographic progression-free survival (rPFS), which is a meaningful clinical end point, while OS was one of the several key secondary end points [examined].

Data from the Stand Up to Cancer highlighted the fact that over 20% of patients with mCRPC have significant mutations in the DNA repair pathway or the HRR genes. That [research] underscored the fact that this is a clinically relevant pathway to go after. At the time that [the PROfound trial was being designed] we saw evidence of benefit [with this approach] in other tumors [such as] breast and ovarian cancers, and then subsequently, in pancreatic cancer.

The specific pathway relevance is that both normal cells and cancer cells need to repair themselves when there is damage; the HRR pathway is involved in that repair process. However, are alterations or mutations [are present], the cells are not able to repair themselves and they fall back into a different pathway, which is the PARP pathway. Basically, PARP agents tend to inhibit that enzyme so that the [cancer] cells cannot repair themselves.

[Earlier data from the trial were previously published] this past summer. Johann de Bono, MB, ChB, PhD, of The Institute of Cancer Research was the first author on the publication in the New England Journal of Medicine, which highlighted [data regarding] the primary end point of rPFS. In this particular presentation delivered at the 2020 ESMO Virtual Congress, [investigators] reported OS [data from] cohorts A and B.

We saw that the benefit [with olaparib is] not only in terms of rPFS; the benefit translated into a median OS benefit of over 4 months between the arms, despite crossover from the control arm to the olaparib arm at time of progression. Additionally, the risk of death was reduced by 31%, which is very clinically significant. In [the cohort of patients who harbored the] other 12 genes, other than BRCA1/2 and ATM, we saw a trend in OS improvement but it was not statistically significant. The trend was about a little bit over 2 months of a difference. When adjusting for crossover, the trend improved although it was still not statistically significant. However, several patients in cohort B experienced clinical benefits from treatment. The primary benefit [with olaparib] still seems to be driven by BRCA primarily.

No; the overall safety was very much consistent with what was known about olaparib. The most common adverse effects observed included anemia, nausea, and fatigue. Most of these were low-grade events, aside from the anemia. Many of these patients were heavily pretreated; while they might have previously received abiraterone or enzalutamide, they would have also received chemotherapy and other potential anticancer treatment and be fairly advanced in the course of their disease. The findings, overall, are really not surprising and the safety profile very much consistent with what has been observed with the agent in other tumors.

We have reached a major benchmark in the management of this disease. Ever since the original observations regarding androgen deprivation [therapy] in prostate cancer and subsequent treatments, and certainly since the time I entered the field in the early 1990s, prostate cancer management has been more of a one-size-fits-all approach. In fact, when we give chemotherapy and hormone treatment we don't preselect [patients].

We still have [a lot of work to do]. Patients with metastatic castration-resistant disease continue to die from prostate cancer; they also suffer from pain and other factors involved with this disease. This [research] highlights the feasibility of performing precision medicine trials. It also shows us that meaningful clinical benefits could be achieved in these patients. I would hope that our partners across the spectrum will invest further in conducting more clinical trials.

The observation that we've seen with olaparib also opens up the door for potential combination clinical trials, both in castration-resistant disease and potentially in earlier stages of disease, where we might get a better return on investment from a clinical perspective.

Genomic profile evaluation for patients is critical moving forward, not only for the purpose of treatment for the patient. Conducting or counseling the patient regarding germline testing and tumor genomics evaluation in preparation for future treatment is also very critical. Obviously, genetic testing is associated with genetic counseling, [which may allow patients] and potential blood relatives [to get ahead of the game].

Tissue-based genomic evaluation will open the door for the patient to explore different treatments, and [certain] genomic alterations might qualify them for different clinical trials opportunities. [This work] underscores the hope for patients that their cancer can be managed better with genomically targeted treatments, specifically, in this case, the PARP inhibitor. [Now we can build on] these observations in terms of different treatment strategies and combinations.

Excerpt from:
PROfound Trial With Olaparib Shows Feasibility of Personalizing Care in mCRPC - OncLive

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Termination for medical reasons: Moms share TFMR stories – TODAY

Thursday, October 15th, 2020

Fifteen weeks into her second pregnancy, Katrina Villegas and her husband learned their baby girl had trisomy 13, a chromosomal disorder that causes severe disabilities and is usually fatal.

"Its really just a whirlwind situation for a few weeks," said Villegas, recalling how her baby's heart defects and other abnormalities began showing up on her ultrasounds. "We just tried to do as much research as we could about trisomy 13 and what that would mean for our daughter. At the end of the day we decided that we didnt want her suffering, so we ended up inducing the pregnancy early."

Villegas, who contributes to the TODAY Parenting Team, recalls feeling blindsided when she had to sign paperwork for a "medical abortion" prior to her induction.

"I lost it because it wasnt an abortion in my head," said Villegas. "This was a child that we wanted. We were making one of the hardest decisions you can make as a parent, which was to spare her pain."

In the face of fetal abnormalities that will cause death or severe suffering, it's not uncommon for a expectant mother to choose a termination for medical reasons (TFMR). Though it's not an official medical term, online loss support groups and parents who have been through it coined the term to describe their unique experience. The American College of Obstetricians and Gynecologists has released an official statement explaining that in some cases, abortion is a medical necessity.

Still, parents who choose TFMR often feel weighed down by feelings of guilt or secrecy, unsure how to grieve the loss and caught between identifying with having had a miscarriage or an abortion. Some don't tell friends and family for fear of judgment. Some feel unwelcome in pregnancy loss support groups.

On August 8, 2017, Villegas gave birth to her daughter, April Rey Villegas, who lived for 11 minutes before passing away in her mom's arms.

"She held my hand pretty much the entire time," the Germantown, Maryland, mom recalled. "Everybody in the family that wanted to come meet April got to do so and have a few special moments with her."

Villegas, who blogs about her loss at Terminations Remembered, says making the decision to end a pregnancy for medical reasons was isolating.

"When you think about coping with grief, one of the things people need to do is be able to process and talk, especially to the people they love and care about," said Villegas. "But often in this situation, parents dont tell the whole story and they dont talk about it openly even to people in their close circle because of the fear of judgment."

Wilmaris Soto-Ramos was 16 weeks into her first pregnancy when she received devastating news at an ultrasound appointment.

"Doctors came into the room and told me the extremities of our baby were really abnormal," Soto-Ramos told TODAY Parents. "Her feet were clubbed, her arms werent moving and she also had fluid in her brain."

Soto-Ramos and her partner were referred to a genetic counselor, who performed an amniocentesis, a procedure used to test for genetic abnormalities.

"In that amniocentesis they kind of found the same results," Soto-Ramos, who lives in Pawtucket, Rhode Island, shared. "The doctor looked at me and said, 'Most parents would terminate a pregnancy like this and you should, too,' which was really heartbreaking."

As she considered how to proceed with her own pregnancy, Soto-Ramos went on a quest for answers.

For the next five weeks Soto-Ramos visited specialists for more tests, until finally learning her daughter had a severe case of arthrogryposis, a rare genetic condition that affects the joints and muscles.

"Because it also affected her brain, she really wasnt viable," explained Soto-Ramos. "If she was to live, she would be wheelchair bound. She wouldnt be able to speak, talk, hear or eat. They also told me if I continued the pregnancy she would probably pass away regardless because of the fluid in her brain."

Soto-Ramos made the decision to end her pregnancy, allowing doctors to induce labor at 22 weeks gestation. On May 9, 2019, her daughter, Angelis Yawa Larbi, was delivered.

"She passed away in the birth canal as she was coming out," Soto-Ramos recalled. "Its something I really struggled with because I'm somebody who is pro-choice and, for me, this was a very-much-wanted pregnancy."

Dr. Christine Greves, an OB-GYN in Orlando, Florida, says it's the job of doctors to support, not judge, women who are faced with this devastating scenario.

"If a patient of mine was to come and talk to me about it, I would tell her there are different options and encourage her to find out more information," said Greves, who does not perform TFMR and typically refers patients to a maternal-fetal medicine specialist when abnormalities are detected in a pregnancy. "More knowledge can be helpful from the standpoint of providing peace with whatever decision they choose."

She said a doctor may suggest termination for medical reasons to a pregnant woman for two reasons: when a fetus is considered not viable due to a medical condition detected in utero or when a mother's life is at risk if she continues a pregnancy.

"When people get this sad news, their doctor tells them the possible outcome of carrying the pregnancy to term," explained Greves. "They explain what could happen either fully delivering the baby and then having the baby pass away, or as far as the maternal indication goes, making sure the patient is aware they could die if they go through with the pregnancy."

At the time of her daughter April's birth, Villegas' older daughter, Caroline, was two. Caroline asked to meet her baby sister after she was born, and has continued asking difficult questions about grief and loss in the years since her death. It's these conversations, combined with a desire to tell her 1-year-old son, William, about the sister that died before his birth, that led Villegas to write five children's books dealing with TFMR.

With titles like "Our Baby is Going to Die," and "The Baby Before You Died," the books explain both surgical termination and induction, and tackle difficult topics like expressing grief and remembering the baby who was lost.

Soto-Ramos says she's experienced isolation, even feeling excluded from some infant loss support groups because she chose to terminate her pregnancy. A licensed clinical social worker, Soto-Ramos is in the process of becoming a bereavement doula and hopes to help women cope with their grief and get the answers they need about their options.

"I found, especially for me being a woman of color, it was really difficult to get answers within the medical system and I had to go look for them, which was traumatizing on its own," said Soto-Ramos. "But Im glad I did because had I listened to the first doctor who told me to terminate my pregnancy without knowing what was going on, I would have always wondered, 'What if?'"

"I love my daughter so much and so deeply and know my decision was out of love, not out of fear about something a doctor told me," Soto-Ramos added. "It was because I loved her and knew what was going on."

Soto-Ramos kept trying to have a child, and she was pregnant when she talked to TODAY Parents for this story. On October 4, she gave birth to a healthy baby girl.

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Termination for medical reasons: Moms share TFMR stories - TODAY

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

Thursday, October 15th, 2020

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."

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

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