Monthly Archives: May 2020

The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non-animal approaches to health hazard assessment for ethical and practical reasons. Although non-animal approaches are becoming increasingly popular, there are almost no studies of side-by-side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air-liquid interface (ALI) cultures of donor-derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems. 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non-Animal Methods for...

CAMBRIDGE, Mass., April 29, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, will report first quarter 2020 financial results after the Nasdaq Global Market closes on Wednesday, May 6, 2020. Subsequently, at 4:30 p.m. E.T., the Company will host a conference call to discuss its first quarter 2020 financial results and to provide a corporate update.

The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 2553748. Please specify to the operator that you would like to join the "Sarepta First Quarter 2020 Earnings Call." The conference call will be webcast live under the investor relations section of Sarepta's website at http://www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

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Sarepta Therapeutics to Announce First Quarter 2020 Financial Results and Recent Corporate Developments on May 6, 2020 - GlobeNewswire

Personal Genome Diagnostics reached a key milestone in its effort to make genomic profiling of cancer available to patients and oncologists at the local level and its the first to do so for a product of its kind.

The Canton-based company received U.S. Food and Drug Administration clearance for its diagnostic kit, called PGDx elio tissue complete. Combining chemistry performed on a DNA sample and software that automates the data analysis process, the test can perform genomic profiling of a patients tissue sample in molecular labs in a hospital. That can open up access to a level of genomic analysis that currently requires sending samples out to a faraway lab.

Its also designed to provide actionable results: The information provided could help oncologists and patients make decisions about whether targeted therapies could be a treatment option, and potentially identify opportunities to participate in a clinical trial of a new kind of treatment.

If youre a patient you want as many answers as possible in the shortest amount of time possible that could inform your treatment decisions, said Megan Bailey, who was promoted as CEO of the Canton-based company last week. Now that can be a matter of days with complete answers out of a single sample.

For many companies seeking to bring advances in healthcare, regulatory approval from the FDA is an important step that signals a product is both safe and effective. It also means the product can enter the market.

In this case, PGDx received 510(K) clearance, which is used for medical devices. That required verification and validation studies to show results, as well as verifying that results were the same no matter where the test was run, said Dr. John Simmons, who is the companys VP of translational medicine. He added that this meant working with thousands of samples, and 15,000 hours of sequencing time.

PGDx elio kits, ready to head to local labs. (Courtesy photo)

It produced a standardized test that can analyze across 35 tumor types and nine organ systems seeking specific anomalies in DNA and gene expression in more than 500 genes. Now, it is cleared for advanced cancer patients with a solid tumor.

This is the first FDA-cleared next generation sequencing diagnostic that does all of those things, Simmons said. No previous test was that comprehensive in nature.

The companys path shows how Baltimores breakthroughs can have a commercial path. Founded by Johns Hopkins researchers Dr. Victor Velculescuand Dr. Luis Diaz,the company raised a$75 million investment roundin 2018 led byBristol-Myers SquibbandNEA,and has also expanded its footprint to a second location in Brewers Hill. Bailey said the company is very proud to be a fledgling company from Baltimore that became the first to receive clearance in the market.

Along the way, the team has been motivated throughout to meet the need among patients, as Bailey said less than 20% get a genomic-level profile.

Our mission here is to empower the fight against cancer, she said. Fighting is the best shot at beating it and thats why this clearance is so exciting and significant to us.

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PGDx received FDA clearance for its genomic cancer diagnostic kit. It's the first for a test of its kind - Technical.ly

SHANGHAI, April 29, 2020 /PRNewswire/ -- Bayer and OrigiMed (Shanghai) Co., Ltd. (referred to as "OrigiMed") today announced a strategic collaboration for the development and commercialization of NGS-based companion diagnostics in vitro diagnostic (CDx-IVD) in China for detection of NTRK gene fusions. This collaboration will focus on developing a CDx-IVD for larotrectinib (Vitrakvi) for the Chinese market, the first TRK inhibitor approved in US (2018) and Europe (2019) for adult and pediatrics with TRK fusion cancer and is currently developed globally, including in China.

"Approved in various markets already, including the US and EU, larotrectinib is a first-of-its-kind treatment exclusively designed for adults and children with TRK fusion cancer. It is also the first compound that received its initial approval based on the molecular alteration (NTRK gene fusion) driving their cancer irrespective of the tumor site of origin," said Dr. Emmanuelle di Tomaso, Head of Oncology Precision Medicine, Bayer's Oncology Strategic Business Unit. "Cancer care is currently undergoing a paradigm shift, and as this new era of precision oncology treatment unfolds, we are continuing our effort of delivering innovative medicines such as larotrectinib, which can provide value to patients and their treating physicians around the world."

"As one of the first NGS companies to introduce NTRK gene fusion detection in China, we are looking forward to working with Bayer to jointly develop larotrectinib CDx-IVD, jointly support clinical trials of larotrectinib in mainland China and provide therapeutic benefits for more patients." The genomic testing and analysis of cancer patients to determine whether they are suitable for the treatment of larotrectinib is also a very urgent clinical need," said Dr. Wang Kai, CEO of OrigiMed.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to http://www.bayer.com.

About OrigiMed

OrigiMed is a medical science and technology transforming company and a partner of biopharmaceutical companies, who focuses on developing new technologies and clinical applications to help all types of cancer patients get access to precise treatment and to help accelerate biomarker-driven drug development. By carrying out more comprehensive and high-throughput methods, leveraging wholesome bioinformatics analysis and clinical annotation, to help match patients to approved targeted therapies, immunotherapies, and clinical trials-giving physicians and patients powerful actionable insights for navigating cancer care, ultimately aiming to fortify the evolution of cancer precision medicine. More information please visit http://www.origimed.com

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Bayer and OrigiMed reached a partnership to develop a next generation sequencing (NGS) based companion diagnostic-in vitro diagnostic (CDx-IVD)...

Friday, May 1, 2020

At least 2 billion people around the world have vision problems but how do you know if and when your pet is struggling with its own eyesight? Its a good question, especially in a year numbered 2020.

Dr. Wendy Townsend, associate professor of ophthalmology in Purdue Veterinary Medicines Department of Veterinary Clinical Sciences, has focused her career and research in veterinary medicine on diagnosing and treating eye conditions in animals. The most common question I get is if we fit animals with glasses, Dr. Townsend says. While thats not what we do, our goal is to help animals see better and improve their quality of life if theyre having issues.

Although her patients span a variety of species, her research is focused on a particular breed of dog that reigns as one of the most popular dog breeds in America: golden retrievers. Golden retriever pigmentary uveitis is a disease almost exclusively found in purebred golden retrievers. Its an inherited form of uveitis (inflammation of the uveal tract, which includes the iris). And though the disease is inherited, the onset and diagnosis usually occurs when the dogs are older.

The disease can often result in blindness due to cataracts and glaucoma, and there are no current methods to prevent or reverse it. Mild symptoms, such as redness and drainage, usually dont appear until the dog is around eight years old and can progress to an advanced stage before dogs see a veterinarian, Dr. Townsend says. The disease affects about 10% of senior golden retrievers.

Dr. Townsend is leading a study that is trying to identify the gene that causes the disease. If the gene can be identified, the disease can be detected earlier, and breeders will be able to identify which of their dogs might be carriers and how they can keep the disease from being passed on to future generations.

The problem breeders are facing right now is that even if theyre being responsible and making good decisions, they dont know their dog is affected, Dr. Townsend says. They can be several generations down their pedigree before they know theres a problem.

Dr. Townsend grew up owning golden retrievers and was completing her residency in veterinary ophthalmology when the disease was first recognized. It was bizarre because nobody could understand why it was happening in this specific breed, Dr. Townsend says. But since I loved golden retrievers and had a passion for ophthalmology, it seemed like a natural fit.

And although the disease presents itself primarily in purebred golden retrievers, Dr. Townsend explains that it can appear in some crossbreeds especially Labrador and golden retriever crosses. That becomes a concern because Labrador and golden crosses are frequently used as seeing-eye dogs, Dr. Townsend says. And because the disease doesnt show symptoms until these dogs are older, they could be struggling with their own vision and you might not even know.

Thats why Dr. Townsend says having dogs screened especially service dogs is critical. The earlier you can catch something, the better, Dr. Townsend says. That goes for all vision problems with any animal.

As a veterinary ophthalmologist, Dr. Townsend says its not uncommon for her to see dogs from across the country affected by golden retriever pigmentary uveitis. In addition to those patients, she commonly sees animals with corneal ulcers (scratches on the eye), cataracts, and glaucoma. Her patients include mostly dogs, horses, and cats but she also has treated penguins, tigers, and other exotic species.

And although she doesnt fit animals with glasses, she has fitted a dog or two with contact lenses. Theyre usually dogs that participate in agility and have trouble focusing or struggle with nearsightedness.

Sometimes animals struggle with the same eye problems that people do. Theyre just not as good at telling us when something is wrong, Dr. Townsend says. She consistently encourages pet owners to be cognizant of their pets eye health for that very reason.

Animals are good at compensating when something isnt working right. So if one eye is bothering them, theyll just rely more heavily on the other eye, Dr. Townsend says. And most of our pets dont need to have super-sharp vision to lead normal everyday lives. But in some cases like with dogs that participate in agility being able to focus both near and far is important.

As Dr. Townsend continues her mission to solve the mystery behind golden retriever pigmentary uveitis in addition to seeing her patients she hopes she can build some awareness around the field of ophthalmology. The eye might be small, but its a powerful organ that we all use and it allows me to work across a wide variety of species, Dr. Townsend explains. I frequently have clients tell me, I had no idea this was an option, or, I didnt know there were eye doctors for dogs. The impact this field can have on our patients and their quality of life can be significant.

Dr. Townsends work is supported by the American Kennel Clubs Canine Health Foundation.

Writer(s): Abbey Nickel, Purdue News Service, and Kevin Doerr | pvmnews@purdue.edu

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More Than Meets the Eye: Veterinary Ophthalmologist Wendy Townsend Focuses on Animal Eye Conditions - Purdue Veterinary News

April 28, 2020

Rochester research into RNA structure and function provides key information for developing coronavirus treatments.

Viruses like the coronavirus that causes COVID-19 are able to unleash their fury because of a devious weapon: ribonucleic acid, also known as RNA.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. As COVID-19 continues to spread around the globe, RNA research provides an important foundation for developing antiviral drugs, vaccines, and other therapeutics to disrupt the virus and stop infections.

The Universitys website is a way to find guidance and critical information during a rapidly changing situation.

Find out what to do if you or a close contact have symptoms or think you may have been exposed.

Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA doesmake new virus that can infect more of our cells and also the cells of other human beings, says Lynne Maquat, professor of biochemistry and biophysics at the University of Rochester Medical Center and the director of Rochesters Center for RNA Biology.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, the RNA research world has exploded, Maquat says. The University of Rochester understood this.

In 2007, Maquat founded the Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

While much of the research across the University has been put on pause, labs that are involved in coronavirus research remain active.

Our strength as a university is our diversity of research expertise, combined with our highly collaborative nature, says Dragony Fu, an assistant professor of biology on the River Campus and a member of the Center for RNA Biology. We are surrounded by outstanding researchers who enhance our understanding of RNA biology, and a medical center that provides a translational aspect where the knowledge gained from RNA biology can be applied for therapeutics.

In mammals, such as humans, DNA contains genetic instructions that are transcribedor copiedinto RNA. While DNA remains in the cells nucleus, RNA carries the copies of genetic information to the rest of the cell by way of various combinations of amino acids, which it delivers to ribosomes. The ribosomes link the amino acids together to form proteins that then carry out functions within the human body.

Many diseases occur when these gene expressions go awry.

COVID-19, short for coronavirus disease 2019, is caused by the novel coronavirus SARS-CoV-2. Like many other viruses, SARS-CoV-2 is an RNA virus. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in RNA. The viral RNA is sneaky: its features cause the protein synthesis machinery of our cells to mistake it for RNA produced by our own DNA.

While SARS-CoV-2 is a new coronavirus, it likely replicates and functions similar to related coronaviruses that infect animals and humans, says Douglas Anderson, an assistant professor of medicine in the Aab Cardiovascular Research Institute and a member of the Center for RNA Biology, who studies how RNA mutations can give rise to human disease.

A graphic created by the New York Times illustrates how the coronavirus that causes COVID-19 enters the body through the nose, mouth, or eyes and attaches to our cells. Once the virus is inside our cells, it releases its RNA. Our hijacked cells serve as virus factories, reading the viruss RNA and making long viral proteins to compromise the immune system. The virus assembles new copies of itself and spreads to more parts of the body andby way of saliva, sweat, and other bodily fluidsto other humans.

Once the virus is in our cells, the entire process of infection and re-infection depends on the viral RNA, Maquat says.

Researchers Douglas Anderson, Dragony Fu, and Lynne Maquat are among the scientists at the University of Rochester who study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. (University of Rochester photos / Matt Wittmeyer / J. Adam Fenster)

Maquat has been studying RNA since 1972 and was part of the earliest wave of scientists to realize the important role RNA plays in human health and disease.

Our cells have a number of ways to combat viruses in what can be viewed as an arms race between host and virus. One of the weapons in our cells arsenal is an RNA surveillance mechanism Maquat discovered called nonsense-mediated mRNA decay (NMD).

Nonsense-mediated mRNA decay protects us from many genetic mutations that could cause disease if NMD was not active to destroy the RNA harboring the mutation, she says.

Maquats discovery has contributed to the development of drug therapies for genetic disorders such as cystic fibrosis, and may be useful in developing treatments for coronavirus.

NMD also helps us combat viral infections, which is why many viruses either inhibit or evade NMD, she adds. The genome of the virus COVID-19 is a positive-sense, single-stranded RNA. It is well known that other positive-sense, single-stranded RNA viruses evade NMD by having RNA structures that prevent NMD from degrading viral RNAs.

Maquats lab is currently collaborating with a lab at Harvard University to test how viral proteins can inhibit the NMD machinery.

Like Maquat, Fu studies fundamental aspects of RNAand has found that his research on proteins may, too, be applicable to coronavirus research.

Fus lab analyzes enzymes and proteins that modify the chemical structure of RNA and how these chemical modifications impact the function of RNA. A research group at the University of California, San Francisco, recently identified an interaction between a protein made by the SARS-CoV-9 virus and a protein Fu studies.

This is an intriguing result, and we are currently thinking of ways this interaction could affect the host cell, Fu says. There is emerging evidence that RNA-based viruses undergo RNA modification, so we could use this knowledge to identify key links between the host and pathogen for development of a coronavirus vaccine or treatment.

One of the reasons viruses are such a challenge is that they change and mutate in response to drugs.

Targeting viral RNA, or the proteins it produces, is key for treating this disease.

That means novel virus treatments and vaccines have to be created each time a new strain of virus presents itself. Armed with innovative research on the fundamentals of RNA, scientists are better able to develop and test therapeutics that directly target the RNAs and processes critical to a viruss life cycle.

The University of Rochester Medical Center, for instance, is currently participating in a clinical trial to evaluate the safety and efficacy of a potential coronavirus treatment called remdesivir, an antiviral drug particularly tailored to attack RNA viruses. The drug inhibits RNA polymerase, an enzyme responsible for copying a DNA sequence into an RNA sequence.

Anderson has found that alternative therapeutics, such as the gene-editing technology CRISPR, may additionally usher in a new approach to how we target and combat infectious diseases, he says.

For the past few years, Andersons lab has developed tools and delivery systems that use the RNA-targeting CRISPR-Cas13 to treat human genetic diseases that affect muscle function. CRISPR-Cas13 is like a molecular pair of scissors that can target specific RNAs for degradation, using small, programmable guide RNAs.

When the health crisis first became apparent in Wuhan, China, researchers in Andersons lab turned their focus toward developing a CRISPR-Cas13 therapeutic aimed at SARS-CoV-2. Applying the knowledge already available about coronavirus RNA replication, they designed single CRISPR guide RNAs capable of targeting every viral RNA that is made within a SARS-CoV-2 infected cell. Using a novel cloning method developed in Andersons lab, multiple CRISPR guide-RNAs could be packaged into a single therapeutic vector (a genetically engineered carrier) to target numerous viral RNA sites simultaneously. The multi-pronged targeting strategy could be used as a therapy to safeguard against virus-induced cell toxicity and prevent escape of viruses which may have undergone mutation.

Infectious viruses and pandemics seemingly come out of nowhere, which has made it hard to rapidly develop and screen traditional small molecule therapeutics or vaccines, Anderson says. There is a clear need to develop alternative targeted therapeutics, such as CRISPR-Cas13, which have the ability to be rapidly reprogrammed to target new emerging pandemics.

While many new treatments for the novel coronavirus are being considered, there is one thing that is certain, Maquat says: Targeting viral RNA, or the proteins it produces, is key for treating this disease.

Tags: Arts and Sciences, Center for RNA Biology, COVID-19, Department of Biochemistry and Biophysics, Department of Biology, Douglas Anderson, Dragony Fu, featured-post, Lynne Maquat, medical center

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COVID-19: What's RNA research got to do with it? - University of Rochester

TEL AVIV & PARSIPPANY, N.J.--(BUSINESS WIRE)-- Teva Pharmaceuticals USA, Inc., an affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced that new data for AJOVY (fremanezumab-vfrm) injection and AUSTEDO (deutetrabenazine) tablets have appeared in an online supplement to Neurology. The data includes 23 abstracts that highlight a diverse set of data evaluating the efficacy and safety of AJOVY and AUSTEDO.

The abstracts were originally planned for presentation at the recently cancelled 2020 American Academy of Neurology (AAN) annual meeting. In addition to the online supplement, the abstracts are also available through the AAN online abstracts website.

We are pleased to have an opportunity to share this important data with the neurology community which build upon our understanding of the efficacy and safety of AJOVY and AUSTEDO across various patient populations, and further demonstrate Tevas commitment to the CNS space, said Denisa Hurtukova, MD, VP, Head of North America Medical Affairs. Teva is committed to ongoing evaluation of these significant therapies to help physicians, healthcare providers and most importantly, patients, make informed decisions about their treatments.

The featured abstracts include new AJOVY and AUSTEDO data, including results from an open-label extension of the FOCUS study, a Phase IIIb study that evaluated the efficacy and safety of quarterly and monthly treatment with AJOVY compared to placebo in adult patients with migraine and documented inadequate response to 2-4 classes of prior preventive treatments. Another analysis using the FDA Adverse Events Reporting System (FAERS) provides patient and healthcare professional insight into the real-world experience with CGRP pathway-targeted therapies. In addition, new data is available from a long-term, open-label extension study which examined the safety of AUSTEDO at higher doses beyond the approved maximum dose to treat chorea associated with Huntingtons disease, as well as the long-term experience with AUSTEDO in both younger and older patients with tardive dyskinesia.

The full list of Teva abstracts in the Neurology supplement includes:

AUSTEDO (deutetrabenazine) Tablets:

De Novo:

Encore:

AJOVY (fremanezumab-vfrm) Injection:

De Novo:

Encore:

About AJOVY (fremanezumab-vfrm) injection

AJOVY is available as a 225 mg/1.5 mL single dose injection in a prefilled syringe with two dosing options 225 mg monthly administered as one subcutaneous injection, or 675 mg every three months (quarterly), which is administered as three subcutaneous injections. AJOVY can be administered in office by a healthcare professional or at home by a patient or caregiver. No starting dose is required to begin treatment. The AJOVY autoinjector has been approved by the FDA and is available in the U.S. In addition to the U.S., the AJOVY autoinjector is currently available in Germany and should soon be available in other select European markets.

U.S. Important Safety Information about AJOVY (fremanezumab-vfrm) injection

Contraindications: AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients.

Hypersensitivity Reactions: Hypersensitivity reactions, including rash, pruritus, drug hypersensitivity, and urticaria were reported with AJOVY in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration. If a hypersensitivity reaction occurs, consider discontinuing AJOVY and institute appropriate therapy.

Adverse Reactions: The most common adverse reactions (5% and greater than placebo) were injection site reactions.

Please click here for full U.S. Prescribing Information for AJOVY (fremanezumab-vfrm) injection.

About AUSTEDO (deutetrabenazine)

AUSTEDO is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of tardive dyskinesia in adults and for the treatment of chorea associated with Huntingtons disease. Safety and effectiveness in pediatric patients have not been established.

AUSTEDO Indications and Usage

AUSTEDO is indicated for the treatment of chorea associated with Huntingtons disease and for the treatment of tardive dyskinesia in adults.

Important Safety Information About AUSTEDO

Depression and Suicidality in Patients with Huntingtons Disease: AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntingtons disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO is contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.

Contraindications: AUSTEDO is contraindicated in patients with Huntingtons disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO is also contraindicated in: patients with hepatic impairment; patients taking reserpine or within 20 days of discontinuing reserpine; patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy; and patients taking tetrabenazine (Xenazine) or valbenazine (Ingrezza).

Clinical Worsening and Adverse Events in Patients with Huntingtons Disease: AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects.

QTc Prolongation: Tetrabenazine, a closely related VMAT2 inhibitor, causes an increase in the corrected QT (QTc) interval. A clinically relevant QT prolongation may occur in some patients treated with AUSTEDO who are CYP2D6 poor metabolizers or are co-administered a strong CYP2D6 inhibitor. Dose reduction may be necessary. The use of AUSTEDO in combination with other drugs known to prolong QTc may result in clinically significant QT prolongations. For patients requiring AUSTEDO doses greater than 24 mg per day who are using AUSTEDO with other drugs known to prolong QTc, assess the QTc interval before and after increasing the dose of AUSTEDO or the other drugs. AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported in association with drugs that reduce dopaminergic transmission, has been observed in patients receiving tetrabenazine. The risk may be increased by concomitant use of dopamine antagonists or antipsychotics. The management of NMS should include immediate discontinuation of AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems.

Akathisia, Agitation, and Restlessness: AUSTEDO may increase the risk of akathisia, agitation, and restlessness. The risk of akathisia may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops akathisia, the AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Parkinsonism: AUSTEDO may cause parkinsonism in patients with Huntingtons disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of AUSTEDO. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are on a maintenance dose of AUSTEDO and know how the drug affects them. Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.

Hyperprolactinemia: Tetrabenazine elevates serum prolactin concentrations in humans. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO.

Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to melanin-containing tissues and could accumulate in these tissues over time. Prescribers should be aware of the possibility of long-term ophthalmologic effects.

CYP2D6 Metabolism: In patients who are poor CYP2D6 metabolizers or are taking strong CYP2D6 inhibitors, the total daily dosage of AUSTEDO should not exceed 36 mg (maximum single dose of 18 mg).

Common Adverse Reactions: The most common adverse reactions for AUSTEDO (>8% and greater than placebo) in a controlled clinical study in patients with Huntingtons disease were somnolence, diarrhea, dry mouth, and fatigue. The most common adverse reactions for AUSTEDO (4% and greater than placebo) in controlled clinical studies in patients with tardive dyskinesia were nasopharyngitis and insomnia.

Please see accompanying full Prescribing Information, including Boxed Warning.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve peoples lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at http://www.tevapharm.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding AJOVY and AUSTEDO, which are based on managements current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to:

and other factors discussed in our Annual Report on Form 10-K for the year ended December 31, 2019, including in the sections captioned "Risk Factors and Forward Looking Statements. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200501005015/en/

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Recommendation for approval based on results from pivotal Phase 3 MEDALIST and BELIEVE studies

PRINCETON, NJ & CAMBRIDGE, MA, USA I April 30, 2020 IBristol Myers Squibb (NYSE: BMY) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion, recommending the approval of Reblozyl (luspatercept) for the treatment of:

This CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). If approved, Reblozyl would be the first erythroid maturation agent approved in the EU, representing a new class of therapy for eligible patients. The safety and efficacy results provided in the application are from the pivotal Phase 3 MEDALIST and BELIEVE studies, evaluating the ability of Reblozyl to effectively address anemia associated with MDS and beta thalassemia, respectively.

"Patients with myelodysplastic syndromes who experience anemia have limited treatment options, and some have been shown to not respond to available erythropoietin-based therapies," said Uwe Platzbecker, M.D., Head of Clinic and Policlinic for Hematology and Cell Therapy, Leipzig University Hospital and lead investigator of the MEDALIST study. If approved, the introduction of a new class of therapy in Reblozyl could provide a promising option to help relieve patients from the burden of regular transfusions to manage their disease.

Todays positive CHMP opinion of Reblozyl is an important milestone for adult beta thalassemia patients in the EU who have limited treatment options to address anemia, a serious consequence of the disease, said Maria Domenica Cappellini, M.D., Professor of Medicine, University of Milan, Fondazione IRCCS Ca Granda and lead investigator of the BELIEVE study. Reblozyl has the potential to significantly decrease the number of red blood cell transfusions patients need.

This decision by the CHMP is an important step towards making this first-in-class therapy an option for eligible patients with anemia due to beta thalassemia or myelodysplastic syndromes, said Diane McDowell, M.D., vice president, Hematology Global Medical Affairs, Bristol Myers Squibb. We, and our partners at Acceleron, look forward to the opportunity to make this treatment option available in the EU and are extremely appreciative of the patients, families and individuals who continue to help us progress important research in a range of serious diseases.

About MEDALIST

MEDALIST is a Phase 3, randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of luspatercept plus best supportive care (BSC) versus placebo plus BSC in adults with IPSS-R-defined very low-, low- or intermediate-risk non-del(5q) myelodysplastic syndromes (MDS). All patients were red blood cell (RBC) transfusion-dependent and were either refractory or intolerant to prior erythropoiesis stimulating agent (ESA) therapy, or were ESA nave and unlikely to respond due to endogenous serum erythropoietin levels of 200 U/L, and had no prior treatment with disease modifying agents. Results of the MEDALIST trial were first presented during the Plenary Session of the 2018 American Society of Hematology (ASH) Annual Meeting and were selected for the Best of ASH. The New England Journal of Medicine published the MEDALIST trial results in January 2020.

About MDS

MDS are a group of closely related blood cancers characterized by ineffective production of healthy red blood cells, white blood cells and platelets, which can lead to anemia and frequent or severe infections. People with MDS who develop anemia often require regular blood transfusions to increase the number of healthy red blood cells in circulation. Frequent transfusions are associated with an increased risk of iron overload, transfusion reactions and infections. There are approximately 50,000 patients with MDS in the EU5 countries.

About BELIEVE

BELIEVE is a Phase 3, randomized, double-blind, placebo-controlled multi-center study comparing luspatercept plus BSC versus placebo plus BSC in adults who require regular RBC transfusions (6-20 RBC units per 24 weeks with no transfusion-free period greater than 35 days during that period) due to beta thalassemia. Results of the BELIEVE trial were first presented at the 2018 ASH Annual Meeting and selected for the Best of ASH. The New England Journal of Medicine published the BELIEVE trial results in March 2020.

About Beta Thalassemia

Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy RBCs, often leading to severe anemia a condition that can be debilitating and can lead to more severe complications for patients as well as other serious health issues. Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of frequent RBC transfusions that have the potential to contribute to iron overload, which can cause serious complications such as organ damage. Across the United States, Germany, France, Italy, Spain and the United Kingdom, there are approximately 17,000 patients with beta thalassemia.

About Reblozyl

Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, promotes late-stage red blood cell maturation in animal models. Bristol Myers Squibb and Acceleron are jointly developing Reblozyl as part of a global collaboration. Reblozyl is currently approved in the U.S. for the treatment of:

Reblozyl is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.

Please see full Prescribing Information for REBLOZYL

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol-Myers Squibb Company and Juno Therapeutics, a Bristol-Myers Squibb Company.

About Acceleron

Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. The Company's leadership in the understanding of TGF-beta superfamily biology and protein engineering generates innovative compounds that engage the body's ability to regulate cellular growth and repair.

Acceleron focuses its research and development efforts in hematologic and pulmonary diseases. In hematology, Acceleron and its global collaboration partner, Bristol Myers Squibb, are co-promoting REBLOZYL (luspatercept-aamt), the first and only approved erythroid maturation agent, in the United States and are developing luspatercept for the treatment of chronic anemia in myelofibrosis. Acceleron is developing sotatercept for the treatment of pulmonary arterial hypertension, having recently reported positive topline results of the Phase 2 PULSAR trial and actively enrolling patients in the Phase 2 SPECTRA trial.

For more information, please visit http://www.acceleronpharma.com. Follow Acceleron on Social Media: @AcceleronPharma and LinkedIn.

SOURCE: Bristol-Myers Squibb

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Reblozyl (luspatercept) Receives Positive CHMP Opinion for the Treatment of Adults with Anemia in Beta Thalassemia and Myelodysplastic Syndromes |...