Category Archives: Gene Medicine

Researchers have successfully used a DNA-editing technique to extend the lifespan of mice with the genetic variation associated with progeria, a rare genetic disease that causes extreme premature aging in children and can significantly shorten their life expectancy. The study was published in the journal Nature, and was a collaboration between the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; Broad Institute of Harvard and MIT, Boston; and the Vanderbilt University Medical Center, Nashville, Tennessee.

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Base editing for progeria treatmentProgeria is caused by a mutation in the nuclear lamin Agene in which one DNA base C is changed to a T. Researchers used the base editing method, which substitutes a single DNA letter for another without damaging the DNA, to reverse that change. Credit: Ernesto Del Aguila, NHGRI.

DNA is made up of four chemical bases A, C, G and T. Progeria, which is also known as Hutchinson-Gilford progeria syndrome, is caused by a mutation in the nuclear lamin A(LMNA) gene in which one DNA base C is changed to a T. This change increases the production of the toxic protein progerin, which causes the rapid aging process.

Approximately 1 in 4 million children are diagnosed with progeria within the first two years of birth, and virtually all of these children develop health issues in childhood and adolescence that are normally associated with old age, including cardiovascular disease (heart attacks and strokes), hair loss, skeletal problems, subcutaneous fat loss and hardened skin.

For this study, researchers used a breakthrough DNA-editing technique called base editing, which substitutes a single DNA letter for another without damaging the DNA, to study how changing this mutation might affect progeria-like symptoms in mice.

"The toll of this devastating illness on affected children and their families cannot be overstated," said Francis S. Collins, M.D., Ph.D., a senior investigator in NHGRI's Medical Genomics and Metabolic Genetics Branch, NIH director and a corresponding author on the paper. "The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research.

The toll of this devastating illness on affected children and their families cannot be overstated.The fact that a single specific mutation causes the disease in nearly all affected children made us realize that we might have tools to fix the root cause. These tools could only be developed thanks to long-term investments in basic genomics research.

The study follows another recent milestone for progeria research, as the U.S. Food and Drug Administration approved the first treatment for progeria in November 2020, a drug called lonafarnib. The drug therapy provides some life extension, but it is not a cure. The DNA-editing method may provide an additional and even more dramatic treatment option in the future.

David Liu, Ph.D., and his lab at the Broad Institute developed the base-editing method in 2016, funded in part by NHGRI.

"CRISPR editing, while revolutionary, cannot yet make precise DNA changes in many kinds of cells," said Dr. Liu, a senior author on the paper. "The base-editing technique we've developed is like a find-and-replace function in a word processor. It is extremely efficient in converting one base pair to another, which we believed would be powerful in treating a disease like progeria.

To test the effectiveness of their base-editing method, the team initially collaborated with the Progeria Research Foundation to obtain connective tissue cells from progeria patients. The team used the base editor on theLMNAgene within the patients cells in a laboratory setting. The treatment fixed the mutation in 90% of the cells.

The Progeria Research Foundation was thrilled to collaborate on this seminal study with Dr. Collinss group at the NIH and Dr. Lius group at Broad Institute, said Leslie Gordon, M.D., Ph.D., a co-author and medical director of The Progeria Research Foundation, which partially funded the study. These study results present an exciting new pathway for investigation into new treatments and the cure for children with progeria.

Following this success, the researchers tested the gene-editing technique by delivering a single intravenous injection of the DNA-editing mix into nearly a dozen mice with the progeria-causing mutation soon after birth. The gene editor successfully restored the normal DNA sequence of theLMNAgene in a significant percentage of cells in various organs, including the heart and aorta.

Many of the mice cell types still maintained the corrected DNA sequence six months after the treatment. In the aorta, the results were even better than expected, as the edited cells seemed to have replaced those that carried the progeria mutation and dropped out from early deterioration. Most dramatically, the treated mice's lifespan increased from seven months to almost 1.5 years. The average normal lifespan of the mice used in the study is two years.

As a physician-scientist, its incredibly exciting to think that an idea youve been working on in the laboratory might actually have therapeutic benefit, said Jonathan D. Brown, M.D., assistant professor of medicine in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. Ultimately our goal will be to try to develop this for humans, but there are additional key questions that we need to first address in these model systems.

Funding for the study was supported in part by NHGRI, the NIH Common Fund, the National Institute of Allergy and Infectious Diseases, the National Institute of Biomedical Imaging and Engineering, the National Institute of General Medical Sciences, the National Heart, Lung and Blood Institute and the National Center for Advancing Translational Sciences.

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DNA-editing method shows promise to treat mouse model of progeria - National Human Genome Research Institute

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Global Precision Medicine Market By Application (Diagnostics, Therapeutics and Others), Technologies (Pharmacogenomics, Point-of-Care Testing, Stem Cell Therapy, Pharmacoproteomics and Others), Indication (Oncology, Central Nervous System (CNS) Disorders, Immunology Disorders, Respiratory Disorders, Others), Drugs (Alectinib, Osimertinib, Mepolizumab,Aripiprazole lauroxil and Others), Route of Administration (Oral,Injectable), End- Users (Hospitals, Homecare, Specialty Clinics, Others), Geography (North America, South America, Europe, Asia-Pacific, Middle East and Africa) Industry Trends and Forecast to 2026

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Precision medicines is also known as personalized medicines is an innovative approach to the patient care for disease treatment, diagnosis and prevention base on the persons individual genes. It allows doctors or physicians to select treatment option based on the patients genetic understanding of their disease.

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Market Drivers

Market Restraints

Key Developments in the Market:

Competitive Analysis:

Global precision medicine market is highly fragmented and the major players have used various strategies such as new product launches, expansions, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of global precision medicine market for Global, Europe, North America, Asia-Pacific, South America and Middle East & Africa.

Key Market Players:

Few of the major competitors currently working in the global precision medicine market are Neon Therapeutics, Moderna, Inc, Merck & Co., Inc, Bayer AG, PERSONALIS INC, GENOCEA BIOSCIENCES, INC., F. Hoffmann-La Roche Ltd, CureVac AG, CELLDEX THERAPEUTICS, BIONTECH SE, Advaxis, Inc, GlaxoSmithKline plc, Bioven International Sdn Bhd, Agenus Inc., Immatics Biotechnologies GmbH, Immunovative Therapies, Bristol-Myers Squibb Company, Gritstone Oncology, NantKwest, Inc among others.

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By technology:- big data analytics, bioinformatics, gene sequencing, drug discovery, companion diagnostics, and others.

By application:- oncology, hematology, infectious diseases, cardiology, neurology, endocrinology, pulmonary diseases, ophthalmology, metabolic diseases, pharmagenomics, and others.

On the basis of end-users:- pharmaceuticals, biotechnology, diagnostic companies, laboratories, and healthcare it specialist.

On the basis of geography:- North America & South America, Europe, Asia-Pacific, and Middle East & Africa. U.S., Canada, Germany, France, U.K., Netherlands, Switzerland, Turkey, Russia, China, India, South Korea, Japan, Australia, Singapore, Saudi Arabia, South Africa, and Brazil among others.

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Global Precision Medicine Market 2020 Overview By Size, Share, Trends, Growth Factors and Leading Players With Detailed Analysis of Industry Structure...

Every drug, from morphine to ibuprofen, has a standard dose -- a sort of one-size-fits all recommendation. But a new study suggests that when it comes to drug doses, "one size fits all" rarely applies.

Stanford Medicine professor Russ Altman, MD, PhD, and a team of scientists found that almost everyone (99.5% of individuals) is likely to have an abnormal or "atypical" response to at least one therapeutic drug. This, at least, is the case for people in the United Kingdom, as the study's data came from the UK Biobank, a project that collects, studies and shares data.

The research found that nearly a quarter of the study's participants had been prescribed a drug for which they were predicted to have an atypical response, based on their genetic makeup. On average, participants were predicted to have an atypical response to 10 drugs.

"Ultimately, the hope is that we can show how pervasive drug response variability is and encourage more doctors to rethink the standard prescription protocols that are largely used today and use genetic testing to predict and adjust forthis variability," said Altman, who is an expert in pharmacogenetics, a field that studies the intersection of drugs and genetics.

An "atypical" drug response encompasses a lot of things; but generally speaking, it means a certain drug might not affect one person the way it does another.

For instance, someone who has an atypical metabolic response might process that drug more efficiently, strengthening its initial effects but decreasing its efficacy over time. On the flip side, it could mean that that person is unable to metabolize the drug at all, leaving them without therapeutic aid, or even with dangerous side effects.

These differences in response to a drug are partially due to our genetics. Specific proteins -- workhorse molecules in the body -- break down drugs in order for the body to benefit from the therapeutic. Those proteins are regulated by a specific group of genes. Natural variation in those genes leads to differences in how an individual's body reacts to a given drug molecule.

Altman and his team, including graduate students and first authors of the study Greg McInnes and Adam Lavertu, analyzed data from nearly 500,000 participants.

For 230,000 participants in the study, the team had primary care data going back about 30 years. That includes which drugs had been prescribed, the dose, and all of the patient's different diagnoses. The researchers also had access to detailed genetic information about each patient. They paid special attention to genetic variations in a group of genes that are known to influence the human drug response.

By comparing an individual's genetics against the variations known to exist in the group of drug-response-associated genes, the researchers could predict how any given patient might respond to a drug.

"Pharmacogenetics as a field has been around for a long time, but it hasn't really been adopted into clinical use," McInnes told me. "It's been growing in the last few years as more people realize the impact that it could have on personalized health. For a long time, it's been this overlooked aspect of genetics that I think is actually one of the most clinically actionable advances that has come out of human genetics."

What's more, he said, the wide variability in the human drug response applies to common therapeutics most everyone has encountered or is familiar with -- ibuprofen, codeine, statins and beta blockers among others.

Moving forward, Lavertu says that the goal is to expand drug-gene variant interaction analyses into more diverse populations. The data from the UK Biobank provided critical insight, but it was largely only representative of a British population, where the majority shares European ancestry. A next step for the researchers is to investigate the same genes in the Million Veteran Program, a government research program with a more diverse study population, that is examining how genes, lifestyle and military exposures affect health and illness.

"Our hope is that doing more of these studies will help us find new relationships between genetic variants and drug response, so that pharmacogenetics can benefit more people," Lavertu said.

Photo byMicha Parzuchowski

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Based on genes, nearly everyone is likely to have an atypical response to at least one drug - Scope

Kathryn Anderson, a developmental biologist at the Memorial Sloan Kettering Cancer Center known for her work detailing the genetics of early embryogenesis, died November 30 at age 68.

Throughout her scientific career, Anderson used rigorous genetic screening assays to identify mutations suspected of disrupting cell division and differentiation in model systems. Having identified a gene of interest, she would then turn to a technique known as forward genetics, creating model organisms such as fruit flies and mice with a particular phenotype to better understand its molecular underpinnings. Using these tools, Anderson made important contributions to scientists understanding of several genetic pathwaysmost notably the Toll and Hedgehog pathwaysrequired for proper development of these animals.

Kathryn was fearless and very open-minded, Tatiana Omelchenko, a senior research scientist in Andersons lab who uses confocal microscopy to do live imaging of mouse embryos, tells The Scientist. Every lab has its own environment and its own mood, and when you stepped into Kathryns lab, you immediately felt very focused.

Born in La Jolla, California, in 1952, Anderson became interested in science at a young age, stemming back to an article in LIFEthat included a detailed image of a human fetus, according to an interview released shortly after her death. She attended the University of California, Berkeley, where she earned her undergraduate degree in biochemistry before heading to a graduate program in neurodevelopment at Stanford University in 1973.

Anderson left that program after only two years, earning a masters degree in neuroscience, and spent the next several years looking for her scientific niche. She enrolled briefly in medical school at the University of California, San Diego, an experience that led her to realize her love of basic research. The clinical work wasnt my cup of tea, Anderson shared in a 2005 biography. The lab was where I felt most at home.

Ultimately, Anderson landed at the University of California, Los Angeles, studying the developmental genetics of Drosophilaunder the guidance of biologist Judith Lengyel. For her PhD work, Anderson showed that in the first two hours after fertilization, the development of Drosophilaembryos remains under maternal control, with maternal RNA and proteins directing cell division and differentiation within the egg.

Looking to further her study of fruit flies, Anderson next traveled to the Max Planck Institute for Developmental Biology in Germany as a postdoc to work with Drosophilageneticist Christiane Nsslein-Volhard. In 1995, Nsslein-Volhard would share a Nobel Prize for her work using mass screenings to identify mutations that disrupt embryonic development, and Anderson would continue studying a handful of the genes identified in these early screens throughout her career.

One such gene, known as Toll, turned out to play an important role in dorsal-ventral (D-V) differentiationdictating, as Anderson said in her biography, how a fly embryo knows its back from its belly. In addition to probing the function of Toll,Anderson continued building out the wider Toll pathway after returning to the University of California, Berkeley, as an assistant professor in 1985, and later in her own lab at the Sloan Kettering Institute, which she launched in 1996 at Memorial Sloan Kettering. During this time, Anderson and her team identified roughly a dozen genes involved in cell differentiation along the D-V axis, and she used similar screening methods to better understand Tolls role in innate immunity of Drosophila. Her findings were noted by geneticists Jules Hoffmann and Bruce Beutler, whose study of Toll-like receptors in both fruit fly and mammalian immunity would later earn them a Nobel Prize.

Kathryn Anderson

Memorial Sloan Kettering Cancer Center

After her successes in fruit flies, Anderson began thinking about applying her same methods to the study of mice. She spent a year on sabbatical in the lab of Rosa Beddington at the National Institute for Medical Research in the UK, where she showed that Toll had no analogous role in the D-V differentiation of mammals. It demonstrated, she said in a 2016 interview with Development, that there are things about early mammalian development that you cant figure out by extrapolating from flies.

Back at the Sloan Kettering Institute, Anderson began once again using mass genetic screenings, this time to identify mutations of interest in mice, and then studying them in fine detail. These were lengthy experiments that often took years to yield results. I think her major contribution is discovering the functions and roles of genes through this mutagenesis screen, Omelchenko says. This is amazing because . . . the mouse embryo model is quite complex, but she did the work.

Anderson and her team screened more than 12,000 mutations, selecting roughly 40 that produce obvious phenotypic disruptions midway through gestation. Working diligently over many years, Anderson identified previously unknown pathways that have since prompted new research directions in the field of developmental biology.

Through her screening, for example, Anderson identified a previously unknown relationship between ciliamicroscopic, hairlike structures on the outside of some cellsand proper signaling of the Hedgehog pathway that dictates cell differentiation in mammalian embryos. Further research showed that components of this pathway are enriched in cilia, while mice with certain mutations in genes involved in Hedgehog signaling lacked cilia altogether in a structure called the node that directs gastrulation in vertebrate embryos. That turned out to be pretty amazing, actually: theres this whole organelle required for Hedgehog signaling in vertebrates, but not in flies, Anderson said in her Developmentinterview. Its a geneticists dream, but raises the question of why organize the genome like this: there are so many weak points in Hedgehog signalingand Hedgehog is so vital.

For her contributions to the field of developmental biology, Anderson was inducted into the National Academy of Sciences in 2002 and elected as a member of the Institute of Medicine of the National Academies in 2008. In addition, she was awarded the Thomas Hunt Morgan Medal for lifetime contributions to the science of genetics in 2012, the Federation of American Societies for Experimental Biologys Excellence in Science Award in 2014, and the Society for Developmental Biologys Edwin G. Conklin Medal for distinguished and sustained research in 2016, among other honors.

Prior to her death, Anderson had spoken about the possible extension of her research into human genetics, as disruptions in hedgehog signaling have since been linked both to birth defects and to a series of diseases referred to as ciliopathies. It was, however, a line of questioning she planned to leave to other scientists, content to continue her methodical work exploring mutations in mice.

Many scientists are very quiet people, but contemporary society requires you to be very loud [so] that people will listen to you, Omelchenko says. Kathryn is such a great example of being quiet, being a very deep thinker, and at the same time becoming a very successful and bright scientist. I think I will keep learning from her even though she has passed away.

Anderson is survived by her husband, Timothy Bestor, a geneticist at Columbia University.

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Developmental Biologist Kathryn Anderson Dies at 68 - The Scientist

ST. PAUL, Minn. & LAKE ZURICH, Ill.--(BUSINESS WIRE)--ScaleReady, a joint venture between Bio-Techne (NASDAQ: TECH), Fresenius Kabi, and Wilson Wolf, launches today. The new company brings together proven tools and technologies for cell culture, cell activation, gene editing, and cell processing from its founding partners.

ScaleReady provides leading therapeutic developers with the most simple, scalable, and versatile manufacturing platform in the industry, enhancing the prospects of success for cell and gene therapy organizations. The new company will accelerate innovation in cell and gene therapy manufacturing, building on the R&D pipelines of its founding partners and through global technology partnerships with industry and academic leaders.

ScaleReadys mission is to accelerate the groundbreaking advances in cell and gene therapy by satisfying the longstanding need for a truly scalable, cost-effective and practical manufacturing platform, said Adam Bryan, General Manager of ScaleReady. Its exciting to see the commitment that our industry-leading partners have made to this mission. Their dedication to combine resources, expertise and decades of experience, position us to make a meaningful contribution to this industry now and in the future through rapid advancement of platform technologies that lead the industry to greater efficiency, practicality and simplicity.

Through this partnership, ScaleReady provides sales, marketing, and application support for tools and technologies used in cell and gene therapy manufacturing worldwide. Wilson Wolfs G-Rex cell culture technology, Fresenius Kabis Lovo and upcoming Cue cell processing systems, and Bio-Technes range of GMP proteins, reagents, media, and gene editing technologies, are all part of the ScaleReady manufacturing platform.

With this venture, Wilson Wolf is adding tremendous wherewithal in our quest to provide the field of cell and gene therapy with a disruptive manufacturing platform that cost-effectively accelerates the delivery of potential life-saving therapies to a wide segment of society, said John Wilson, Chief Executive Officer of Wilson Wolf. Our G-Rex technology is uniquely positioned to address the scale limitation issues facing the industry. Our partners at Bio-Techne and Fresenius Kabi share our common purpose and bring complementary technologies that will accelerate our work.

With cell and gene therapies showing great potential for a wide range of diseases, the need for reliable and consistent raw material supply has never been more important. At Bio-Techne, we recently opened a new large-scale GMP reagent facility, increasing manufacturing capacity for animal-free raw materials, including E. coli-derived recombinant proteins, to ensure sustainable supply for future needs, said David Eansor, President Protein Sciences Segment, at Bio-Techne.

Dean Gregory, President Global Commercial Operations, Transfusion Medicine and Cell Therapies at Fresenius Kabi added, Cell therapies hold promise for patients and are a major area of focus for Fresenius Kabi. Through the partnership represented by ScaleReady, we will be able to make a greater contribution to this field at an accelerated pace. We are thrilled to share our expertise in automated cell processing and closed-system development to this important collaboration.

ScaleReady is owned equally by the three partners Bio-Techne, Fresenius Kabi, and Wilson Wolf. Separately, the three companies do business globally and have combined revenues of more than $7 billion. No other financial terms were disclosed at this time.

About ScaleReady

ScaleReady is bringing the future of cell and gene therapies to life with the most powerful and versatile manufacturing platform in the industry. ScaleReady delivers rapid expansion of T-cells at scalereducing complexity and cost, while providing superior repeatability and cell quality. Founded in 2020, ScaleReady is a joint venture between Bio-Techne, Fresenius Kabi and Wilson Wolf that brings together tools and technologies for cell culture, cell activation, gene editing and cell processing from each founding partner. Learn more at http://www.scaleready.com.

About Bio-Techne

Bio-Techne Corporation (NASDAQ: TECH) is a global life sciences company providing innovative tools and bioactive reagents for the research and clinical diagnostic communities. Bio-Techne products assist scientific investigations into biological processes and the nature and progress of specific diseases. They aid in drug discovery efforts and provide the means for accurate clinical tests and diagnoses. With thousands of products in its portfolio, Bio-Techne generated approximately $739 million in net sales in fiscal 2020 and has over 2,300 employees worldwide. For more information on Bio-Techne and its brands, please visit http://www.bio-techne.com.

About Fresenius Kabi

Fresenius Kabi (www.fresenius-kabi.com/us) is a global health care company that specializes in medicines and technologies for infusion, transfusion and clinical nutrition. The companys products and services are used to help care for critically and chronically ill patients. The companys U.S. headquarters is in Lake Zurich, Illinois. The companys global headquarters is in Bad Homburg, Germany. Fresenius Kabi is part of Fresenius SE(ETR: FRE), a global health care group with more than 305,000 employees in more than 100 countries, and annual sales exceeding $30 billion.

About Wilson Wolf

Based in St. Paul, Minnesota, Wilson Wolf (www.wilsonwolf.com) was founded in 1998 to pioneer the development of innovative cell culture technologies and has created patented products and protocols for numerous applications including monoclonal antibody production, corneal transplants, porcine heart valve testing, mesenchymal cell production, and islet transplants for type 1 diabetes. Over the last 5 years, its G-Rex product line has experienced an average annual sales growth rate of nearly 100%.

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ScaleReady Launches With the Mission to Revolutionize T Cell Therapy Manufacturing - Business Wire

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the HELIOS-A Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis, met its primary and both secondary endpoints at nine months in patients with hATTR amyloidosis with polyneuropathy. The primary endpoint was the change from baseline in the modified Neuropathy Impairment Score (mNIS+7) at 9 months as compared to historical placebo data from the APOLLO Phase 3 study of patisiran. The two secondary endpoints were changes in quality of life assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and gait speed assessed by the timed 10-meter walk test (10-MWT) compared to historical placebo. Vutrisiran met the primary endpoint (p less than 0.001) and achieved statistically significant results (p less than 0.001) for each of the Norfolk QoL-DN and 10-MWT secondary endpoints. In addition, vutrisiran treatment showed improvement compared to placebo on the exploratory cardiac biomarker endpoint, NT-proBNP (nominal p less than 0.05). Vutrisiran also demonstrated an encouraging safety and tolerability profile.

Based on these positive results, the Company plans to submit a New Drug Application (NDA) for vutrisiran with the U.S. Food and Drug Administration (FDA) in early 2021, and to follow with regulatory filings in additional countries, such as Brazil and Japan. The Company plans to submit a Marketing Authorisation Application (MAA) in the EU upon obtaining the results of the 18-month analysis expected in late 2021 as previously aligned with the European Medicines Agency (EMA).

We are excited to report positive topline results from the HELIOS-A study, which show that vutrisiran reduces neurologic impairment and improves quality of life in patients with hATTR amyloidosis with polyneuropathy as soon as 9 months, with an encouraging safety and tolerability profile. In addition, were very pleased to see evidence for reversal of polyneuropathy manifestations of disease and also favorable effects on the exploratory cardiac endpoint, NT-proBNP. We believe that vutrisiran, as a low-dose, once-quarterly, subcutaneously administered therapy, has the potential to be a highly attractive therapeutic option for patients living with this progressive, life-threatening, multi-system disease. We look forward to presenting the full 9-month results from HELIOS-A at a medical meeting in early 2021 and to announcing additional 18-month results, including additional exploratory cardiac endpoint data, in late 2021, said Akshay Vaishnaw, M.D., Ph.D., President of R&D at Alnylam. We would like to recognize and extend our profound gratitude to the patients, caregivers, investigators, and study staff who are participating in HELIOS-A and who, through their commitment during an especially difficult year, have helped make possible another potential advancement in the treatment of hATTR amyloidosis with polyneuropathy. We look forward to initiating our regulatory filings in early 2021 as we work to bring this investigational treatment one step closer to patients with this rare disease.

HELIOS-A (NCT03759379) is a Phase 3 global, randomized, open-label study to evaluate the efficacy and safety of vutrisiran. The study enrolled 164 patients with hATTR amyloidosis with polyneuropathy at 57 sites in 22 countries. Patients were randomized 3:1 to receive either 25mg of vutrisiran (N=122) via subcutaneous injection once every three months or 0.3 mg/kg of patisiran (N=42) via intravenous infusion once every three weeks (as a reference comparator) for 18 months. The primary endpoint is the change from baseline in mNIS+7 score at 9 months1, relative to historical placebo. Secondary endpoints at 9 months are the change from baseline in the Norfolk QoL-DN score and the timed 10-MWT, relative to historical placebo. Changes from baseline in NT-proBNP were evaluated as an exploratory endpoint at 9 months. The efficacy results of vutrisiran in HELIOS-A are compared to historical placebo control data from the landmark APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in a patient population similar to that studied in HELIOS-A. Additional secondary endpoints at 18 months will be evaluated in the HELIOS-A study, including change from baseline in mNIS+7, Norfolk QoL-DN, 10-MWT, modified body mass index (mBMI), Rasch-built Overall Disability Scale (R-ODS), and serum transthyretin (TTR) levels. Additional exploratory cardiac endpoint data at the 18-month time point will be evaluated, including NT-proBNP, echocardiographic measures and cardiac amyloid assessments with technetium scintigraphy imaging. Following the 18-month study period, all patients are eligible to receive vutrisiran for an additional 18 months as part of an open-label extension study. Full 9-month results will be presented at a medical conference in early 2021 and topline 18-month results, including further exploratory cardiac endpoint data, are expected to be announced in late 2021.

Vutrisiran demonstrated an encouraging safety profile. There were two study discontinuations (1.6 percent) due to adverse events in the vutrisiran arm by Month 9, both due to deaths, neither of which was considered related to study drug. There were two serious adverse events (SAEs) deemed related to vutrisiran by the study investigator, consisting of dyslipidemia and urinary tract infection. Treatment emergent adverse events (AEs) occurring in 10 percent or more patients included diarrhea, pain in extremity, fall and urinary tract infections, with each of these events occurring at a similar or lower rate as compared with historical placebo. Injection site reactions (ISRs) were reported in five patients (4.1 percent) and were all mild and transient. There were no clinically significant changes in liver function tests (LFTs).

The HELIOS-A results reinforce our commitment to building an industry-leading franchise of medicines for the treatment of ATTR amyloidosis which began with the development and approval of ONPATTRO as a treatment for patients with hATTR amyloidosis with polyneuropathy. Indeed, the vutrisiran results from HELIOS-A now serve as a second example of the potential for RNAi therapeutics to have a meaningful impact for patients, showing the ability to halt and potentially even reverse polyneuropathy manifestations of the disease. Furthermore, our robust development program, including the APOLLO-B and HELIOS-B studies, investigates the potential of patisiran and vutrisiran, respectively, to treat the cardiac manifestations of disease across a broad spectrum of patients with ATTR amyloidosis, said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. We believe that our ATTR amyloidosis franchise will be a significant driver of Alnylams growth in the years to come, with the potential to position Alnylam as a top tier biopharma company.

Vutrisiran has been granted Orphan Drug Designation in the United States and the European Union for the treatment of ATTR amyloidosis. Vutrisiran has also been granted a Fast Track designation in the United States for the treatment of the polyneuropathy of hATTR amyloidosis in adults. The safety and efficacy of vutrisiran are being evaluated in the comprehensive HELIOS clinical development program and have not yet been evaluated by any health authority. The ongoing HELIOS-B Phase 3 clinical trial in patients with ATTR amyloidosis with cardiomyopathy was initiated in late 2019 and is currently enrolling at sites around the world. Together, the HELIOS-A and -B studies are intended to demonstrate the broad impact of vutrisiran across the multisystem manifestations of disease and the full spectrum of patients with ATTR amyloidosis.

Conference Call InformationAlnylam management will discuss the HELIOS-A results via conference call on Thursday, January 7, 2021, at 8:00 am ET. A webcast presentation will also be available on the Investors page of the Companys website, http://www.alnylam.com. To access the call, please dial 877-312-7507 (domestic) or +1-631-813-4828 (international) five minutes prior to the start time and refer to conference ID 4398564. A replay of the call will be available beginning at 11:00 am ET on the day of the call. To access the replay, please dial 855-859-2056 (domestic) or +1-404-537-3406 (international) and refer to conference ID 4398564.

About hATTR AmyloidosisHereditary transthyretin (TTR)-mediated amyloidosis (hATTR) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. TTR protein is primarily produced in the liver and is normally a carrier of vitamin A. Mutations in the TTR gene cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy, as well as other disease manifestations. hATTR amyloidosis, represents a major unmet medical need with significant morbidity and mortality affecting approximately 50,000 people worldwide. The median survival is 4.7 years following diagnosis, with a reduced survival (3.4 years) for patients presenting with cardiomyopathy.

About VutrisiranVutrisiran is an investigational, subcutaneously administered RNAi therapeutic in development for the treatment of ATTR amyloidosis, which encompasses both hereditary (hATTR) and wild-type (wtATTR) amyloidosis. It is designed to target and silence specific messenger RNA, blocking the production of wild-type and variant transthyretin (TTR) protein before it is made. Quarterly administration of vutrisiran may help to reduce deposition and facilitate the clearance of TTR amyloid deposits in tissues and potentially restore function to these tissues. Vutrisiran utilizes Alnylams Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, designed for increased potency and high metabolic stability that allows for infrequent subcutaneous injections. The safety and efficacy of vutrisiran have not been evaluated by the U.S. Food and Drug Administration, European Medicines Agency or any other health authority.

About RNAiRNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as a major scientific breakthrough that happens once every decade or so, and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylams RNAi therapeutic platform, function upstream of todays medicines by potently silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam PharmaceuticalsAlnylam (Nasdaq:ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylams commercial RNAi therapeutic products are ONPATTRO (patisiran), GIVLAARI (givosiran), OXLUMO (lumasiran), and, in Europe, Leqvio (inclisiran). Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam exceeded the goals first established in 2015 under its "Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit http://www.alnylam.com and engage with us on Twitter at @Alnylam or on LinkedIn.

Alnylam Forward Looking StatementsVarious statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, expectations regarding the direct or indirect effects on Alnylams business, activities and prospects as a result of the COVID-19 pandemic, or delays or interruptions resulting therefrom and the success of Alnylams mitigation efforts, Alnylam's views and plans with respect to the potential for RNAi therapeutics, including vutrisiran and patisiran, expectations regarding the safety and efficacy of vutrisiran as a treatment for hATTR amyloidosis with polyneuropathy, and its potential to have a meaningful impact on the course of this disease, expectations regarding the potential of vutrisiran and patisiran to treat the cardiac manifestations of ATTR amyloidosis across a broad spectrum of patients, Alnylams prospects for building an industry-leading ATTR amyloidosis franchise and to become a top-tier biopharma company, the expected timing for the filing of regulatory submissions for vutrisiran the presentation of full 9-month results and the announcement of 18-month topline results, including exploratory cardiac endpoint data, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic, such as the scope and duration of the outbreak, government actions and restrictive measures implemented in response, the availability of safe and effective vaccine(s), material delays in diagnoses of rare diseases, initiation or continuation of treatment for diseases addressed by Alnylam products, or in patient enrollment in clinical trials, potential supply chain disruptions, and other potential impacts to Alnylams business, the effectiveness or timeliness of steps taken by Alnylam to mitigate the impact of the pandemic, and Alnylams ability to execute business continuity plans to address disruptions caused by the COVID-19 or any future pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates, including vutrisiran; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates or its or its partner Novartis marketed products, including ONPATTRO, GIVLAARI, OXLUMO and Leqvio (in Europe); obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, including vutrisiran, and the success of its partner Novartis, in obtaining regulatory approval for inclisiran in the U.S. and elsewhere, and maintaining regulatory approval and obtaining pricing and reimbursement for its products, including ONPATTRO, GIVLAARI, and OXLUMO, as well as its partner Novartis success obtaining pricing and reimbursement for Leqvio; progress in continuing to establish an ex-United States infrastructure; successfully launching, marketing and selling its approved products globally, including ONPATTRO, GIVLAARI, and OXLUMO, and achieving net product revenues for ONPATTRO within its revised expected range during 2020; Alnylams ability to successfully expand the indication for ONPATTRO in the future; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's ability to manage its growth and operating expenses within the ranges of guidance provided by Alnylam through the implementation of further discipline in operations to moderate spend and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylams ability to establish and maintain strategic business alliances and new business initiatives; Alnylam's dependence on third parties, including Novartis for the continued development and commercialization of Leqvio, Regeneron for development, manufacture and distribution of certain products, including eye and CNS products, and Vir for the development of ALN-COV and other potential RNAi therapeutics targeting SARS-CoV-2 and host factors for SARS-CoV-2; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

1 In alignment with the EMA, the primary endpoint of change from baseline in mNIS+7 will be evaluated at 18 months to support an MAA.

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Alnylam Reports Positive Topline Results from HELIOS-A Phase 3 Study of Vutrisiran in Patients with hATTR Amyloidosis with Polyneuropathy - Business...